Optical mapping and sequencing of the Escherichia coli KO11 genome reveal extensive chromosomal rearrangements, and multiple tandem copies of the Zymomonas mobilis pdc and adhB genes.

PubMed

Turner, Peter C; Yomano, Lorraine P; Jarboe, Laura R; York, Sean W; Baggett, Christy L; Moritz, Brélan E; Zentz, Emily B; Shanmugam, K T; Ingram, Lonnie O

2012-04-01

Escherichia coli KO11 (ATCC 55124) was engineered in 1990 to produce ethanol by chromosomal insertion of the Zymomonas mobilis pdc and adhB genes into E. coli W (ATCC 9637). KO11FL, our current laboratory version of KO11, and its parent E. coli W were sequenced, and contigs assembled into genomic sequences using optical NcoI restriction maps as templates. E. coli W contained plasmids pRK1 (102.5 kb) and pRK2 (5.4 kb), but KO11FL only contained pRK2. KO11FL optical maps made with AflII and with BamHI showed a tandem repeat region, consisting of at least 20 copies of a 10-kb unit. The repeat region was located at the insertion site for the pdc, adhB, and chloramphenicol-resistance genes. Sequence coverage of these genes was about 25-fold higher than average, consistent with amplification of the foreign genes that were inserted as circularized DNA. Selection for higher levels of chloramphenicol resistance originally produced strains with higher pdc and adhB expression, and hence improved fermentation performance, by increasing the gene copy number. Sequence data for an earlier version of KO11, ATCC 55124, indicated that multiple copies of pdc adhB were present. Comparison of the W and KO11FL genomes showed large inversions and deletions in KO11FL, mostly enabled by IS10, which is absent from W but present at 30 sites in KO11FL. The early KO11 strain ATCC 55124 had no rearrangements, contained only one IS10, and lacked most accumulated single nucleotide polymorphisms (SNPs) present in KO11FL. Despite rearrangements and SNPs in KO11FL, fermentation performance was equal to that of ATCC 55124.

Metabolic engineering for improved production of ethanol by Corynebacterium glutamicum.

PubMed

Jojima, Toru; Noburyu, Ryoji; Sasaki, Miho; Tajima, Takahisa; Suda, Masako; Yukawa, Hideaki; Inui, Masayuki

2015-02-01

Recombinant Corynebacterium glutamicum harboring genes for pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adhB) can produce ethanol under oxygen deprivation. We investigated the effects of elevating the expression levels of glycolytic genes, as well as pdc and adhB, on ethanol production. Overexpression of four glycolytic genes (pgi, pfkA, gapA, and pyk) in C. glutamicum significantly increased the rate of ethanol production. Overexpression of tpi, encoding triosephosphate isomerase, further enhanced productivity. Elevated expression of pdc and adhB increased ethanol yield, but not the rate of production. Fed-batch fermentation using an optimized strain resulted in ethanol production of 119 g/L from 245 g/L glucose with a yield of 95% of the theoretical maximum. Further metabolic engineering, including integration of the genes for xylose and arabinose metabolism, enabled consumption of glucose, xylose, and arabinose, and ethanol production (83 g/L) at a yield of 90 %. This study demonstrated that C. glutamicum has significant potential for the production of cellulosic ethanol.

Two Novel Anoxia-Induced Ethylene Response Factors That Interact with Promoters of Deastringency-Related Genes from Persimmon

PubMed Central

Min, Ting; Fang, Fang; Ge, Hang; Shi, Yan-na; Luo, Zheng-rong; Yao, Yun-cong; Grierson, Donald; Yin, Xue-ren; Chen, Kun-song

2014-01-01

A hypoxic environment is generally undesirable for most plants and stimulates anaerobic metabolism. It is a beneficial treatment, however, for the removal of astringency from persimmon to improve the fruit quality after harvest. High soluble tannins (SCTs) content is one of most important causes of astringency. High CO2 (95%) treatment effectively reduced SCTs in both “Mopan” and “Gongcheng-shuishi” persimmon fruit by causing increases in acetaldehyde. Using RNA-seq and realtime PCR, twelve ethylene response factor genes (DkERF11-22) were isolated and characterized, to determine those responsive to high CO2 treatment. Only two genes, DkERF19 and DkERF22, showed trans-activation effects on the promoters of deastringency-related genes pyruvate decarboxylase genes (DkPDC2 and DkPDC3) and the transcript levels of these genes was enhanced by hypoxia. Moreover, DkERF19 and the previously isolated DkERF9 had additive effects on activating the DkPDC2 promoter. Taken together, these results provide further evidence that transcriptome changes in the level of DkERF mRNAs regulate deastringency-related genes and their role in the mechanism of persimmon fruit deastringency is discussed. PMID:24805136

OptSSeq: High-throughput sequencing readout of growth enrichment defines optimal gene expression elements for homoethanologenesis

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

Ghosh, Indro Neil; Landick, Robert

The optimization of synthetic pathways is a central challenge in metabolic engineering. OptSSeq (Optimization by Selection and Sequencing) is one approach to this challenge. OptSSeq couples selection of optimal enzyme expression levels linked to cell growth rate with high-throughput sequencing to track enrichment of gene expression elements (promoters and ribosomebinding sites) from a combinatorial library. OptSSeq yields information on both optimal and suboptimal enzyme levels, and helps identify constraints that limit maximal product formation. Here we report a proof-of-concept implementation of OptSSeq using homoethanologenesis, a two-step pathway consisting of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) that converts pyruvate tomore » ethanol and is naturally optimized in the bacterium Zymomonas mobilis. We used OptSSeq to determine optimal gene expression elements and enzyme levels for Z. mobilis Pdc, AdhA, and AdhB expressed in Escherichia coli. By varying both expression signals and gene order, we identified an optimal solution using only Pdc and AdhB. We resolved current uncertainty about the functions of the Fe 2+-dependent AdhB and Zn 2+- dependent AdhA by showing that AdhB is preferred over AdhA for rapid growth in both E. coli and Z. mobilis. Finally, by comparing predictions of growth-linked metabolic flux to enzyme synthesis costs, we established that optimal E. coli homoethanologenesis was achieved by our best pdc-adhB expression cassette and that the remaining constraints lie in the E. coli metabolic network or inefficient Pdc or AdhB function in E. coli. Furthermore, OptSSeq is a general tool for synthetic biology to tune enzyme levels in any pathway whose optimal function can be linked to cell growth or survival.« less

OptSSeq: High-throughput sequencing readout of growth enrichment defines optimal gene expression elements for homoethanologenesis

DOE PAGES

Ghosh, Indro Neil; Landick, Robert

2016-07-16

The optimization of synthetic pathways is a central challenge in metabolic engineering. OptSSeq (Optimization by Selection and Sequencing) is one approach to this challenge. OptSSeq couples selection of optimal enzyme expression levels linked to cell growth rate with high-throughput sequencing to track enrichment of gene expression elements (promoters and ribosomebinding sites) from a combinatorial library. OptSSeq yields information on both optimal and suboptimal enzyme levels, and helps identify constraints that limit maximal product formation. Here we report a proof-of-concept implementation of OptSSeq using homoethanologenesis, a two-step pathway consisting of pyruvate decarboxylase (Pdc) and alcohol dehydrogenase (Adh) that converts pyruvate tomore » ethanol and is naturally optimized in the bacterium Zymomonas mobilis. We used OptSSeq to determine optimal gene expression elements and enzyme levels for Z. mobilis Pdc, AdhA, and AdhB expressed in Escherichia coli. By varying both expression signals and gene order, we identified an optimal solution using only Pdc and AdhB. We resolved current uncertainty about the functions of the Fe 2+-dependent AdhB and Zn 2+- dependent AdhA by showing that AdhB is preferred over AdhA for rapid growth in both E. coli and Z. mobilis. Finally, by comparing predictions of growth-linked metabolic flux to enzyme synthesis costs, we established that optimal E. coli homoethanologenesis was achieved by our best pdc-adhB expression cassette and that the remaining constraints lie in the E. coli metabolic network or inefficient Pdc or AdhB function in E. coli. Furthermore, OptSSeq is a general tool for synthetic biology to tune enzyme levels in any pathway whose optimal function can be linked to cell growth or survival.« less

Novel Approaches to Preventing Urinary Tract Infection in Women

DTIC Science & Technology

1999-09-01

throughput analysis of differential gene expression of in vitro urothelium exposed to uropathogenic Escherichia colj pDC-1. Program and abstracts of...chip" analysis of in vitro urothelium exposed to uropathogenic Escherichia coli pDC-1. Presented at the annual meeting of the American Academy of

Hepatitis B Virus Lacks Immune Activating Capacity, but Actively Inhibits Plasmacytoid Dendritic Cell Function

PubMed Central

Woltman, Andrea M.; Shi, Cui C.; Janssen, Harry L. A.

2011-01-01

Chronic hepatitis B virus (HBV) infection is caused by inadequate anti-viral immunity. Activation of plasmacytoid dendritic cells (pDC) leading to IFNα production is important for effective anti-viral immunity. Hepatitis B virus (HBV) infection lacks IFNα induction in animal models and patients and chronic HBV patients display impaired IFNα production by pDC. Therefore, HBV and HBV-derived proteins were examined for their effect on human pDC in vitro. In addition, the in vitro findings were compared to the function of pDC derived from chronic HBV patients ex vivo. In contrast to other viruses, HBV did not activate pDC. Moreover, HBV and HBsAg abrogated CpG-A/TLR9-induced, but not Loxoribine/TLR7-induced, mTOR-mediated S6 phosphorylation, subsequent IRF7 phosphorylation and IFNα gene transcription. HBV/HBsAg also diminished upregulation of co-stimulatory molecules, production of TNFα, IP-10 and IL-6 and pDC-induced NK cell function, whereas TLR7-induced pDC function was hardly affected. In line, HBsAg preferentially bound to TLR9-triggered pDC demonstrating that once pDC are able to bind HBV/HBsAg, the virus exerts its immune regulatory effect. HBV not only directly interfered with pDC function, but also indirectly by interfering with monocyte-pDC interaction. Also HBeAg diminished pDC function to a certain extent, but via another unknown mechanism. Interestingly, patients with HBeAg-positive chronic hepatitis B displayed impaired CpG-induced IFNα production by pDC without significant alterations in Loxoribine-induced pDC function compared to HBeAg-negative patients and healthy controls. The lack of activation and the active inhibition of pDC by HBV may both contribute to HBV persistence. The finding that the interaction between pDC and HBV may change upon activation may aid in the identification of a scavenging receptor supporting immunosuppressive effects of HBV and also in the design of novel treatment strategies for chronic HBV. PMID:21246041

Rapamycin has suppressive and stimulatory effects on human plasmacytoid dendritic cell functions

PubMed Central

Boor, P P C; Metselaar, H J; Mancham, S; van der Laan, L J W; Kwekkeboom, J

2013-01-01

Plasmacytoid dendritic cells (PDC) are involved in innate immunity by interferon (IFN)-α production, and in adaptive immunity by stimulating T cells and inducing generation of regulatory T cells (Treg). In this study we studied the effects of mammalian target of rapamycin (mTOR) inhibition by rapamycin, a commonly used immunosuppressive and anti-cancer drug, on innate and adaptive immune functions of human PDC. A clinically relevant concentration of rapamycin inhibited Toll-like receptor (TLR)-7-induced IFN-α secretion potently (−64%) but TLR-9-induced IFN-α secretion only slightly (−20%), while the same concentration suppressed proinflammatory cytokine production by TLR-7-activated and TLR-9-activated PDC with similar efficacy. Rapamycin inhibited the ability of both TLR-7-activated and TLR-9-activated PDC to stimulate production of IFN-γ and interleukin (IL)-10 by allogeneic T cells. Surprisingly, mTOR-inhibition enhanced the capacity of TLR-7-activated PDC to stimulate naive and memory T helper cell proliferation, which was caused by rapamycin-induced up-regulation of CD80 expression on PDC. Finally, rapamycin treatment of TLR-7-activated PDC enhanced their capacity to induce CD4+forkhead box protein 3 (FoxP3)+ regulatory T cells, but did not affect the generation of suppressive CD8+CD38+lymphocyte activation gene (LAG)-3+ Treg. In general, rapamycin inhibits innate and adaptive immune functions of TLR-stimulated human PDC, but enhances the ability of TLR-7-stimulated PDC to stimulate CD4+ T cell proliferation and induce CD4+FoxP3+ regulatory T cell generation. PMID:23968562

Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.

PubMed

Loures, Flávio V; Röhm, Marc; Lee, Chrono K; Santos, Evelyn; Wang, Jennifer P; Specht, Charles A; Calich, Vera L G; Urban, Constantin F; Levitz, Stuart M

2015-02-01

Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.

Expression and localization of a novel phosducin-like protein from amphioxus Branchiostoma belcheri

NASA Astrophysics Data System (ADS)

Saren, Gaowa; Zhao, Yonggang

2009-05-01

A full length amphioxus cDNA, encoding a novel phosducin-like protein ( Amphi-PhLP), was identified for the first time from the gut cDNA library of Branchiostoma belcheri. It is comprised of 1 550 bp and an open reading frame (ORF) of 241 amino acids, with a predicted molecular mass of approximately 28 kDa. In situ hybridization histochemistry revealed a tissue-specific expression pattern of Amphi-PhLP with the high levels in the ovary, and at a lower level in the hind gut and testis, hepatic caecum, gill, endostyle, and epipharyngeal groove, while it was absent in the muscle, neural tube and notochord. In the Chinese Hamster Ovary (CHO) cells transfected with the expression plasmid pEGFP-N1/ Amphi-PhLP, the fusion protein was targeted in the cytoplasm of CHO cells, suggesting that Amphi-PhLP is a cytosolic protein. This work may provide a framework for further understanding of the physiological function of Amphi-PhLP in B. belcheri.

Functional Interaction between Phosducin-like Protein 2 and Cytosolic Chaperonin Is Essential for Cytoskeletal Protein Function and Cell Cycle Progression

PubMed Central

Stirling, Peter C.; Srayko, Martin; Takhar, Karam S.; Pozniakovsky, Andrei; Hyman, Anthony A.

2007-01-01

The C haperonin Containing Tcp1 (CCT) maintains cellular protein folding homeostasis in the eukaryotic cytosol by assisting the biogenesis of many proteins, including actins, tubulins, and regulators of the cell cycle. Here, we demonstrate that the essential and conserved eukaryotic phosducin-like protein 2 (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity. Consistent with this functional interaction, temperature-sensitive alleles of Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We uncovered several high-copy suppressors of the plp2 alleles, all of which are associated with G1/S cell cycle progression but which do not appreciably affect cytoskeletal protein function or fully rescue the growth defects. Our data support a model in which Plp2p modulates the biogenesis of several CCT substrates relating to cell cycle and cytoskeletal function, which together contribute to the essential function of PLP2. PMID:17429077

Triolein-based polycation lipid nanocarrier for efficient gene delivery: characteristics and mechanism

PubMed Central

Zhang, Zhiwen; Fang, Xiaoling; Hao, Junguo; Li, Yajuan; Sha, Xianyi

2011-01-01

We proposed to develop a polycation lipid nanocarrier (PLN) with higher transfection efficiency than our previously described polycation nanostrucutred lipid nanocarrier (PNLC). PLN was composed of triolein, cetylated low-molecular-weight polyethylenimine, and dioleoyl phosphatidylethanolamine. The physicochemical properties of PLN and the PLN/DNA complexes (PDC) were characterized. The in vitro transfection was performed in human lung adenocarcinoma (SPC-A1) cells, and the intracellular mechanism was investigated as well. The measurements indicated that PLN and PDC are homogenous nanometer-sized particles with a positive charge. The transfection efficiency of PDC significantly increased with the content of triolein and was higher than that of PNLC and commercial Lipofectamine™ 2000. In particular, the transfection of PLN in the presence of 10% serum was more effective than that in its absence. With the help of specific inhibitors of chlorpromazine and filipin, the clathrin-dependent endocytosis pathway was determined to be the main contributor to the successful transfection mediated by PLN in SPC-A1 cells. The captured images verified that the fluorescent PDC was localized in the lysosomes and nuclei after endocytosis. Thus, PLN represents a novel efficient nonviral gene delivery vector. PMID:22114487

Triolein-based polycation lipid nanocarrier for efficient gene delivery: characteristics and mechanism.

PubMed

Zhang, Zhiwen; Fang, Xiaoling; Hao, Junguo; Li, Yajuan; Sha, Xianyi

2011-01-01

We proposed to develop a polycation lipid nanocarrier (PLN) with higher transfection efficiency than our previously described polycation nanostrucutred lipid nanocarrier (PNLC). PLN was composed of triolein, cetylated low-molecular-weight polyethylenimine, and dioleoyl phosphatidylethanolamine. The physicochemical properties of PLN and the PLN/DNA complexes (PDC) were characterized. The in vitro transfection was performed in human lung adenocarcinoma (SPC-A1) cells, and the intracellular mechanism was investigated as well. The measurements indicated that PLN and PDC are homogenous nanometer-sized particles with a positive charge. The transfection efficiency of PDC significantly increased with the content of triolein and was higher than that of PNLC and commercial Lipofectamine 2000. In particular, the transfection of PLN in the presence of 10% serum was more effective than that in its absence. With the help of specific inhibitors of chlorpromazine and filipin, the clathrin-dependent endocytosis pathway was determined to be the main contributor to the successful transfection mediated by PLN in SPC-A1 cells. The captured images verified that the fluorescent PDC was localized in the lysosomes and nuclei after endocytosis. Thus, PLN represents a novel efficient nonviral gene delivery vector.

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells

PubMed Central

Lamote, Jochen A. S.; Kestens, Manon; Van Waesberghe, Cliff; Delva, Jonas; De Pelsmaeker, Steffi; Devriendt, Bert

2017-01-01

ABSTRACT Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-α response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity. IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines. PMID:28122975

The Pseudorabies Virus Glycoprotein gE/gI Complex Suppresses Type I Interferon Production by Plasmacytoid Dendritic Cells.

PubMed

Lamote, Jochen A S; Kestens, Manon; Van Waesberghe, Cliff; Delva, Jonas; De Pelsmaeker, Steffi; Devriendt, Bert; Favoreel, Herman W

2017-04-01

Plasmacytoid dendritic cells (pDC) play a central role in the antiviral immune response, both in the innate response and in shaping the adaptive response, mainly because of their ability to produce massive amounts of type I interferon (TI-IFN). Here, we report that cells infected with the live attenuated Bartha vaccine strain of porcine alphaherpesvirus pseudorabies virus (PRV) trigger a dramatically increased TI-IFN response by porcine primary pDC compared to cells infected with wild-type PRV strains (Becker and Kaplan). Since Bartha is one of the relatively few examples of a highly successful alphaherpesvirus vaccine, identification of factors that may contribute to its efficacy may provide insights for the rational design of other alphaherpesvirus vaccines. The Bartha vaccine genome displays several mutations compared to the genome of wild-type PRV strains, including a large deletion in the unique short (US) region, encompassing the glycoprotein E (gE), gI, US9, and US2 genes. Using recombinant PRV Becker strains harboring the entire Bartha US deletion or single mutations in the four affected US genes, we demonstrate that the absence of the viral gE/gI complex contributes to the observed increased IFN-α response. Furthermore, we show that the absence of gE leads to an enhanced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in pDC, which correlates with a higher TI-IFN production by pDC. In conclusion, the PRV Bartha vaccine strain triggers strongly increased TI-IFN production by porcine pDC. Our data further indicate that the gE/gI glycoprotein complex suppresses TI-IFN production by pDC, which represents the first alphaherpesvirus factor that suppresses pDC activity. IMPORTANCE Several alphaherpesviruses, including herpes simpex virus, still lack effective vaccines. However, the highly successful Bartha vaccine has contributed substantially to eradication of the porcine alphaherpesvirus pseudorabies virus (PRV) in several countries. The impact of Bartha on the immune response is still poorly understood. Type I interferon (TI-IFN)-producing plasmacytoid dendritic cells (pDC) may play an important role in vaccine development. Here, we show that Bartha elicits a dramatically increased type I interferon (TI-IFN) response in primary porcine pDC compared to wild-type strains. In addition, we found that the gE/gI complex, which is absent in Bartha, inhibits the pDC TI-IFN response. This is the first description of an immune cell type that is differentially affected by Bartha versus wild-type PRV and is the first report describing an alphaherpesvirus protein that inhibits the TI-IFN response by pDC. These data may therefore contribute to the rational design of other alphaherpesvirus vaccines. Copyright © 2017 American Society for Microbiology.

Dendritic cell fate is determined by BCL11A

PubMed Central

Ippolito, Gregory C.; Dekker, Joseph D.; Wang, Yui-Hsi; Lee, Bum-Kyu; Shaffer, Arthur L.; Lin, Jian; Wall, Jason K.; Lee, Baeck-Seung; Staudt, Louis M.; Liu, Yong-Jun; Iyer, Vishwanath R.; Tucker, Haley O.

2014-01-01

The plasmacytoid dendritic cell (pDC) is vital to the coordinated action of innate and adaptive immunity. pDC development has not been unequivocally traced, nor has its transcriptional regulatory network been fully clarified. Here we confirm an essential requirement for the BCL11A transcription factor in fetal pDC development, and demonstrate this lineage-specific requirement in the adult organism. Furthermore, we identify BCL11A gene targets and provide a molecular mechanism for its action in pDC commitment. Embryonic germ-line deletion of Bcl11a revealed an absolute cellular, molecular, and functional absence of pDCs in fetal mice. In adults, deletion of Bcl11a in hematopoietic stem cells resulted in perturbed yet continued generation of progenitors, loss of downstream pDC and B-cell lineages, and persisting myeloid, conventional dendritic, and T-cell lineages. Challenge with virus resulted in a marked reduction of antiviral response in conditionally deleted adults. Genome-wide analyses of BCL11A DNA binding and expression revealed that BCL11A regulates transcription of E2-2 and other pDC differentiation modulators, including ID2 and MTG16. Our results identify BCL11A as an essential, lineage-specific factor that regulates pDC development, supporting a model wherein differentiation into pDCs represents a primed “default” pathway for common dendritic cell progenitors. PMID:24591644

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency

PubMed Central

Pliss, Lioudmila; Hausknecht, Kathryn A.; Stachowiak, Michal K.; Dlugos, Cynthia A.; Richards, Jerry B.; Patel, Mulchand S.

2013-01-01

Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH−. The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice. PMID:23840713

Beneficial effect of feeding a ketogenic diet to mothers on brain development in their progeny with a murine model of pyruvate dehydrogenase complex deficiency.

PubMed

Pliss, Lioudmila; Jatania, Urvi; Patel, Mulchand S

2016-06-01

Pyruvate dehydrogenase complex (PDC) deficiency is a major inborn error of oxidative metabolism of pyruvate in the mitochondria causing congenital lactic acidosis and primarily structural and functional abnormalities of the central nervous system. To provide an alternate source of acetyl-CoA derived from ketone bodies to the developing brain, a formula high in fat content is widely employed as a treatment. In the present study we investigated efficacy of a high-fat diet given to mothers during pregnancy and lactation on lessening of the impact of PDC deficiency on brain development in PDC-deficient female progeny. A murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene was employed in this study. Maternal consumption of a high-fat diet during pregnancy and lactation had no effect on number of live-birth, body growth, tissue PDC activity levels, as well as the in vitro rates of glucose oxidation and fatty acid biosynthesis by the developing brain of PDC-deficient female offspring during the postnatal age 35 days, as compared to the PDC-deficient progeny born to dams on a chow diet. Interestingly, brain weight was normalized in PDC-deficient progeny of high fat-fed mothers with improvement in impairment in brain structure deficit whereas brain weight was significantly decreased and was associated with greater cerebral structural defects in progeny of chow-fed mothers as compared to control progeny of mothers fed either a chow or high fat diet. The findings provide for the first time experimental support for beneficial effects of a ketogenic diet during the prenatal and early postnatal periods on the brain development of PDC-deficient mammalian progeny.

Recognition of Aspergillus fumigatus Hyphae by Human Plasmacytoid Dendritic Cells Is Mediated by Dectin-2 and Results in Formation of Extracellular Traps

PubMed Central

Loures, Flávio V.; Röhm, Marc; Lee, Chrono K.; Santos, Evelyn; Wang, Jennifer P.; Specht, Charles A.; Calich, Vera L. G.; Urban, Constantin F.; Levitz, Stuart M.

2015-01-01

Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation. PMID:25659141

Does the cycad genotoxin MAM implicated in Guam ALS-PDC induce disease-relevant changes in mouse brain that includes olfaction?

PubMed

Kisby, Glen; Palmer, Valerie; Lasarev, Mike; Fry, Rebecca; Iordanov, Mihail; Magun, Eli; Samson, Leona; Spencer, Peter

2011-11-01

Western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC), a prototypical neurodegenerative disease (tauopathy) affecting distinct genetic groups with common exposure to neurotoxic chemicals in cycad seed, has many features of Parkinson's and Alzheimer's diseases (AD), including early olfactory dysfunction. Guam ALS-PDC incidence correlates with cycad flour content of cycasin and its aglycone methylazoxymethanol (MAM), which produces persistent DNA damage (O(6)-methylguanine) in the brains of mice lacking O(6)-methylguanine methyltransferase (Mgmt(-/-)). We described in Mgmt(-/-)mice up to 7 days post-MAM treatment that brain DNA damage was linked to brain gene expression changes found in human neurological disease, cancer, and skin and hair development. This addendum reports 6 months post-MAM treatment- related brain transcriptional changes as well as elevated mitogen activated protein kinases and increased caspase-3 activity, both of which are involved in tau aggregation and neurofibrillary tangle formation typical of ALS-PDC and AD, plus transcriptional changes in olfactory receptors. Does cycasin act as a "slow (geno)toxin" in ALS-PDC?

DkPK Genes Promote Natural Deastringency in C-PCNA Persimmon by Up-regulating DkPDC and DkADH Expression

PubMed Central

Guan, Changfei; Du, Xiaoyun; Zhang, Qinglin; Ma, Fengwang; Luo, Zhengrong; Yang, Yong

2017-01-01

The astringency of Chinese pollination-constant non-astringent (C-PCNA) persimmon (Diospyros kaki Thunb.) can be naturally removed on the tree. This process is controlled by a single locus and is dominant against other types of persimmons; therefore, this variant is an important candidate for commercial cultivation and the breeding of PCNA cultivars. In our previous study, six full-length coding sequences (CDS) for pyruvate kinase genes (DkPK1-6) were isolated, and DkPK1 is thought to be involved in the natural deastringency of C-PCNA persimmon fruit. Here, we characterize the eight other DkPK genes (DkPK7-14) from C-PCNA persimmon fruit based on transcriptome data. The transcript changes in DkPK7-14 genes and correlations with the proanthocyanidin (PA) content were investigated during different fruit development stages in C-PCNA, J-PCNA, and non-PCNA persimmon; DkPK7 and DkPK8 exhibited up-regulation patterns during the last developmental stage in C-PCNA persimmon that was negatively correlated with the decrease in soluble PAs. Phylogenetic analysis and subcellular localization analysis revealed that DkPK7 and DkPK8 are cytosolic proteins. Notably, DkPK7 and DkPK8 were ubiquitously expressed in various persimmon organs and abundantly up-regulated in seeds. Furthermore, transient over-expression of DkPK7 and DkPK8 in persimmon leaves led to a significant decrease in the content of soluble PAs but a significant increase in the expression levels of the pyruvate decarboxylase (DkPDC) and alcohol dehydrogenase genes (DkADH), which are closely related to acetaldehyde metabolism. The accumulated acetaldehyde that results from the up-regulation of the DkPDC and DkADH genes can combine with soluble PAs to form insoluble PAs, resulting in the removal of astringency from persimmon fruit. Thus, we suggest that both DkPK7 and DkPK8 are likely to be involved in natural deastringency via the up-regulation of DkPDC and DkADH expression during the last developmental stage in C-PCNA persimmon. PMID:28243247

[Preliminary analysis of retinal gene expression profile of diabetic rat].

PubMed

Mei, Yan; Zhou, Hong-ying; Xiang, Tao; Lu, You-guang; Li, Ai-dong; Tang, En-jie; Yang, Hui-jun

2005-10-01

Establishing the retinal gene expression profiles of non-diabetic rat and diabetic rat and comparing the profiles in order to analyze the possible genes related with diabetic retinopathy. The whole retinal transcriptional fragments of non-diabetic rat and 8-week diabetic rat were obtained by restriction fragments differential display-PCR (RFDD-PCR). Bioinformatic analysis of retinal gene expression was performed using soft wares, including Fragment Analysis. After comparison of the expression profiles, the related gene fragments of diabetic retinopathy were initially selected as the target gene of further approach. A total of 3639 significant fragments were obtained. By means of more than 3-fold contrast of fluorescent intensity as the differential expression standard, the authors got 840 differential fragments, accounting for 23.08% of the expressed numbers and including 5 visual related genes, 13 excitatory neruotransmitter genes and 3 inhibitory neurotransmitter genes. At the 8th week, the expression of Rhodopsin kinase, beta-arrestin, Phosducinìrod photoreceptor cGMP-gated channel and Rpe65 as well as iGlu R1-4 were down-regulated. mGluRs and GABA-Rs were all up-regulated, whereas the expression of GlyR was unchanged. These results prompt again that the changes in retinal nervous layer of rat have occurred at an early stage of diabetes. The genes expression pattern of visual related genes and excitatory and inhibitory neurotransmitters in rat diabetic retina have been involved in neuro-dysfunctions of diabetic retina.

Downregulation of a putative plastid PDC E1α subunit impairs photosynthetic activity and triacylglycerol accumulation in nitrogen-starved photoautotrophic Chlamydomonas reinhardtii

PubMed Central

Shtaida, Nastassia; Khozin-Goldberg, Inna; Solovchenko, Alexei; Chekanov, Konstantin; Didi-Cohen, Shoshana; Leu, Stefan; Cohen, Zvi; Boussiba, Sammy

2014-01-01

The chloroplast pyruvate dehydrogenase complex (cpPDC) catalyses the oxidative decarboxylation of pyruvate forming acetyl-CoA, an immediate primer for the initial reactions of de novo fatty acid (FA) synthesis. Little is known about the source of acetyl-CoA in the chloroplasts of photosynthetic microalgae, which are capable of producing high amounts of the storage lipid triacylglycerol (TAG) under conditions of nutrient stresses. We generated Chlamydomonas reinhardtii CC-1618 mutants with decreased expression of the PDC2_E1α gene, encoding the putative chloroplast pyruvate dehydrogenase subunit E1α, using artificial microRNA. A comparative study on the effects of PDC2_E1α silencing on FAs and TAG production in C. reinhardtii, grown photoautotrophically and mixotrophically, with and without a nitrogen source in the nutrient medium, was carried out. Reduced expression of PDC2 _E1α led to a severely hampered photoautotrophic growth phenotype with drastic impairment in TAG accumulation under nitrogen deprivation. In the presence of acetate, downregulation of PDC2_E1α exerted little to no effect on TAG production and photosynthetic activity. In contrast, under photoautotrophic conditions, especially in the absence of a nitrogen source, a dramatic decline in photosynthetic oxygen evolution and photosystem II quantum yield against a background of the apparent over-reduction of the photosynthetic electron chain was recorded. Our results suggest an essential role of cpPDC in the supply of carbon precursors for de novo FA synthesis in microalgae under conditions of photoautotrophy. A shortage of this supply is detrimental to the nitrogen-starvation-induced synthesis of storage TAG, an important carbon and energy sink in stressed Chlamydomonas cells, thereby impairing the acclimation ability of the microalga. PMID:25210079

Overexpression of pyruvate decarboxylase in the yeast Hansenula polymorpha results in increased ethanol yield in high-temperature fermentation of xylose.

PubMed

Ishchuk, Olena P; Voronovsky, Andriy Y; Stasyk, Oleh V; Gayda, Galina Z; Gonchar, Mykhailo V; Abbas, Charles A; Sibirny, Andriy A

2008-11-01

Improvement of xylose fermentation is of great importance to the fuel ethanol industry. The nonconventional thermotolerant yeast Hansenula polymorpha naturally ferments xylose to ethanol at high temperatures (48-50 degrees C). Introduction of a mutation that impairs ethanol reutilization in H. polymorpha led to an increase in ethanol yield from xylose. The native and heterologous (Kluyveromyces lactis) PDC1 genes coding for pyruvate decarboxylase were expressed at high levels in H. polymorpha under the control of the strong constitutive promoter of the glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH). This resulted in increased pyruvate decarboxylase activity and improved ethanol production from xylose. The introduction of multiple copies of the H. polymorpha PDC1 gene driven by the strong constitutive promoter led to a 20-fold increase in pyruvate decarboxylase activity and up to a threefold elevation of ethanol production.

Pyruvate Decarboxylase Catalyzes Decarboxylation of Branched-Chain 2-Oxo Acids but Is Not Essential for Fusel Alcohol Production by Saccharomyces cerevisiae

PubMed Central

ter Schure, Eelko G.; Flikweert, Marcel T.; van Dijken, Johannes P.; Pronk, Jack T.; Verrips, C. Theo

1998-01-01

The fusel alcohols 3-methyl-1-butanol, 2-methyl-1-butanol, and 2-methyl-propanol are important flavor compounds in yeast-derived food products and beverages. The formation of these compounds from branched-chain amino acids is generally assumed to occur via the Ehrlich pathway, which involves the concerted action of a branched-chain transaminase, a decarboxylase, and an alcohol dehydrogenase. Partially purified preparations of pyruvate decarboxylase (EC 4.1.1.1) have been reported to catalyze the decarboxylation of the branched-chain 2-oxo acids formed upon transamination of leucine, isoleucine, and valine. Indeed, in a coupled enzymatic assay with horse liver alcohol dehydrogenase, cell extracts of a wild-type Saccharomyces cerevisiae strain exhibited significant decarboxylation rates with these branched-chain 2-oxo acids. Decarboxylation of branched-chain 2-oxo acids was not detectable in cell extracts of an isogenic strain in which all three PDC genes had been disrupted. Experiments with cell extracts from S. cerevisiae mutants expressing a single PDC gene demonstrated that both PDC1- and PDC5-encoded isoenzymes can decarboxylate branched-chain 2-oxo acids. To investigate whether pyruvate decarboxylase is essential for fusel alcohol production by whole cells, wild-type S. cerevisiae and an isogenic pyruvate decarboxylase-negative strain were grown on ethanol with a mixture of leucine, isoleucine, and valine as the nitrogen source. Surprisingly, the three corresponding fusel alcohols were produced in both strains. This result proves that decarboxylation of branched-chain 2-oxo acids via pyruvate decarboxylase is not an essential step in fusel alcohol production. PMID:9546164

Combined cytotoxic activity of an infectious, but non-replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells

PubMed Central

Thomann, Sabrina; Boscheinen, Jan B; Vogel, Karin; Knipe, David M; DeLuca, Neal; Gross, Stefanie; Schuler-Thurner, Beatrice; Schuster, Philipp; Schmidt, Barbara

2015-01-01

Malignant melanoma is an aggressive tumour of the skin with increasing incidence, frequent metastasis and poor prognosis. At the same time, it is an immunogenic type of cancer with spontaneous regressions. Most recently, the tumoricidal effect of plasmacytoid dendritic cells (pDC) and their capacity to overcome the immunosuppressive tumour microenvironment are being investigated. In this respect, we studied the effect of the infectious, but replication-deficient, herpes simplex virus 1 (HSV-1) d106S vaccine strain, which lacks essential immediate early genes, in pDC co-cultures with 11 melanoma cell lines. We observed a strong cytotoxic activity, inducing apoptotic and necrotic cell death in most melanoma cell lines. The cytotoxic activity of HSV-1 d106S plus pDC was comparable to the levels of cytotoxicity induced by natural killer cells, but required only a fraction of cells with effector : target ratios of 1 : 20 (P < 0·05). The suppressive activity of cell-free supernatants derived from virus-stimulated pDC was significantly neutralized using antibodies against the interferon-α receptor (P < 0·05). In addition to type I interferons, TRAIL and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a minor extent. UV-irradiated viral stocks were significantly less active than infectious particles, both in the absence and presence of pDC (P < 0·05), indicating that residual activity of HSV-1 d106S is a major component and sensitizes the tumour cells to interferon-producing pDC. Three leukaemic cell lines were also susceptible to this treatment, suggesting a general anti-tumour effect. In conclusion, the potential of HSV-1 d106S for therapeutic vaccination should be further evaluated in patients suffering from different malignancies. PMID:26194553

Downregulation of a putative plastid PDC E1α subunit impairs photosynthetic activity and triacylglycerol accumulation in nitrogen-starved photoautotrophic Chlamydomonas reinhardtii.

PubMed

Shtaida, Nastassia; Khozin-Goldberg, Inna; Solovchenko, Alexei; Chekanov, Konstantin; Didi-Cohen, Shoshana; Leu, Stefan; Cohen, Zvi; Boussiba, Sammy

2014-12-01

The chloroplast pyruvate dehydrogenase complex (cpPDC) catalyses the oxidative decarboxylation of pyruvate forming acetyl-CoA, an immediate primer for the initial reactions of de novo fatty acid (FA) synthesis. Little is known about the source of acetyl-CoA in the chloroplasts of photosynthetic microalgae, which are capable of producing high amounts of the storage lipid triacylglycerol (TAG) under conditions of nutrient stresses. We generated Chlamydomonas reinhardtii CC-1618 mutants with decreased expression of the PDC2_E1α gene, encoding the putative chloroplast pyruvate dehydrogenase subunit E1α, using artificial microRNA. A comparative study on the effects of PDC2_E1α silencing on FAs and TAG production in C. reinhardtii, grown photoautotrophically and mixotrophically, with and without a nitrogen source in the nutrient medium, was carried out. Reduced expression of PDC2 _E1α led to a severely hampered photoautotrophic growth phenotype with drastic impairment in TAG accumulation under nitrogen deprivation. In the presence of acetate, downregulation of PDC2_E1α exerted little to no effect on TAG production and photosynthetic activity. In contrast, under photoautotrophic conditions, especially in the absence of a nitrogen source, a dramatic decline in photosynthetic oxygen evolution and photosystem II quantum yield against a background of the apparent over-reduction of the photosynthetic electron chain was recorded. Our results suggest an essential role of cpPDC in the supply of carbon precursors for de novo FA synthesis in microalgae under conditions of photoautotrophy. A shortage of this supply is detrimental to the nitrogen-starvation-induced synthesis of storage TAG, an important carbon and energy sink in stressed Chlamydomonas cells, thereby impairing the acclimation ability of the microalga. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Starmerella bombicola influences the metabolism of Saccharomyces cerevisiae at pyruvate decarboxylase and alcohol dehydrogenase level during mixed wine fermentation

PubMed Central

2012-01-01

Background The use of a multistarter fermentation process with Saccharomyces cerevisiae and non-Saccharomyces wine yeasts has been proposed to simulate natural must fermentation and to confer greater complexity and specificity to wine. In this context, the combined use of S. cerevisiae and immobilized Starmerella bombicola cells (formerly Candida stellata) was assayed to enhance glycerol concentration, reduce ethanol content and to improve the analytical composition of wine. In order to investigate yeast metabolic interaction during controlled mixed fermentation and to evaluate the influence of S. bombicola on S. cerevisiae, the gene expression and enzymatic activity of two key enzymes of the alcoholic fermentation pathway such as pyruvate decarboxylase (Pdc1) and alcohol dehydrogenase (Adh1) were studied. Results The presence of S. bombicola immobilized cells in a mixed fermentation trial confirmed an increase in fermentation rate, a combined consumption of glucose and fructose, an increase in glycerol and a reduction in the production of ethanol as well as a modification in the fermentation of by products. The alcoholic fermentation of S. cerevisiae was also influenced by S. bombicola immobilized cells. Indeed, Pdc1 activity in mixed fermentation was lower than that exhibited in pure culture while Adh1 activity showed an opposite behavior. The expression of both PDC1 and ADH1 genes was highly induced at the initial phase of fermentation. The expression level of PDC1 at the end of fermentation was much higher in pure culture while ADH1 level was similar in both pure and mixed fermentations. Conclusion In mixed fermentation, S. bombicola immobilized cells greatly affected the fermentation behavior of S. cerevisiae and the analytical composition of wine. The influence of S. bombicola on S. cerevisiae was not limited to a simple additive contribution. Indeed, its presence caused metabolic modifications during S. cerevisiae fermentation causing variation in the gene expression and enzymatic activity of alcohol deydrogenase and pyruvate decarboxilase. PMID:22305374

Ethanol production by Escherichia coli strains co-expressing Zymomonas PDC and ADH genes

DOEpatents

Ingram, Lonnie O.; Conway, Tyrrell; Alterthum, Flavio

1991-01-01

A novel operon and plasmids comprising genes which code for the alcohol dehydrogenase and pyruvate decarboxylase activities of Zymomonas mobilis are described. Also disclosed are methods for increasing the growth of microorganisms or eukaryotic cells and methods for reducing the accumulation of undesirable metabolic products in the growth medium of microorganisms or cells.

Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment

PubMed Central

Kim, Seung Tae; Kim, Sun Young; Kim, Nayoung K.D.; Jang, Jiryeon; Kang, Mihyun; Jang, Hyojin; Ahn, Soomin; Kim, Seok Hyeong; Park, Yoona; Cho, Yong Beom; Heo, Jeong Wook; Lee, Woo Yong; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Park, Woong-Yang; Lee, Jeeyun; Kim, Hee Cheol

2016-01-01

Background We aimed to establish a prospectively enrolled colorectal cancer (CRC) cohort for targeted sequencing of primary tumors from CRC patients. In parallel, we established collateral PDC models from the matched primary tumor tissues, which may be later used as preclinical models for genome-directed targeted therapy experiments. Results In all, we identified 27 SNVs in the 6 genes such as PIK3CA (N = 16), BRAF (N = 6), NRAS (N = 2), and CTNNB1 (N = 1), PTEN (N = 1), and ERBB2 (N = 1). RET-NCOA4 translocation was observed in one out of 105 patients (0.9%). PDC models were successfully established from 62 (55.4%) of the 112 samples. To confirm the genomic features of various tumor cells, we compared variant allele frequency results of the primary tumor and progeny PDCs. The Pearson correlation coefficient between the variants from primary tumor cells and PDCs was 0.881. Methods Between April 2014 and June 2015, 112 patients with CRC who underwent resection of the primary tumor were enrolled in the SMC Oncology Biomarker study. The PDC culture protocol was performed for all eligible patients. All of the primary tumors from the 112 patients who provided written informed consent were genomically sequenced with targeted sequencing. In parallel, PDC establishment was attempted for all sequenced tumors. Conclusions We have prospectively sequenced a CRC cohort of 105 patients and successfully established 62 PDC in parallel. Each genomically characterized PDCs can be used as a preclinical model especially in rare genomic alteration event. PMID:26909603

Bcl-2 antagonists kill plasmacytoid dendritic cells from lupus-prone mice and dampen interferon-α production.

PubMed

Zhan, Yifan; Carrington, Emma M; Ko, Hyun-Ja; Vikstrom, Ingela B; Oon, Shereen; Zhang, Jian-Guo; Vremec, David; Brady, Jamie L; Bouillet, Philippe; Wu, Li; Huang, David C S; Wicks, Ian P; Morand, Eric F; Strasser, Andreas; Lew, Andrew M

2015-03-01

Interferon-α (IFNα)-producing plasmacytoid dendritic cells (PDCs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). IFNα-related genes are highlighted among SLE susceptibility alleles and are characteristically expressed in the blood of patients with SLE, while in mouse models of lupus, PDC numbers and IFNα production are increased. This study was undertaken to investigate the effects of inhibitors that selectively target different antiapoptotic molecules on the survival of PDCs. PDC numbers, in vitro survival, and expression of antiapoptotic molecules were evaluated in lupus-prone (NZB × NZW)F1 (NZB/NZW) mice. The impact of Bcl-2 antagonists and glucocorticoids on PDCs was evaluated in vitro and in vivo. IFNα production by NZB/NZW mice was evaluated before and after treatment with Bcl-2 antagonists. PDCs, but not lymphoid tissue-resident conventional DCs, largely relied on the antiapoptotic protein Bcl-2 for survival. The enlarged PDC compartment in NZB/NZW mice was associated with selectively prolonged survival and increased Bcl-2 transcription. Functionally, this resulted in enhanced production of IFNα. Bcl-2 inhibitors selectively killed mouse and human PDCs, including PDCs from SLE patients, but not conventional DCs, dampened IFNα production by PDCs, and synergized with glucocorticoids to kill activated PDCs. Enhanced PDC survival is a likely contributing factor to enhanced IFNα production by lupus PDCs. Bcl-2 antagonists potently and selectively kill PDCs and reduce IFNα production. Thus, we believe that they are attractive candidates for treating PDC-associated diseases. Copyright © 2015 by the American College of Rheumatology.

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment.

PubMed

Santos, Fátima Milhano; Gaspar, Leonor Mesquita; Ciordia, Sergio; Rocha, Ana Sílvia; Castro E Sousa, João Paulo; Paradela, Alberto; Passarinha, Luís António; Tomaz, Cândida Teixeira

2018-04-11

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses.

iTRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment

PubMed Central

Gaspar, Leonor Mesquita; Ciordia, Sergio; Rocha, Ana Sílvia; Castro e Sousa, João Paulo; Paradela, Alberto

2018-01-01

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses. PMID:29641463

Extended causal modeling to assess Partial Directed Coherence in multiple time series with significant instantaneous interactions.

PubMed

Faes, Luca; Nollo, Giandomenico

2010-11-01

The Partial Directed Coherence (PDC) and its generalized formulation (gPDC) are popular tools for investigating, in the frequency domain, the concept of Granger causality among multivariate (MV) time series. PDC and gPDC are formalized in terms of the coefficients of an MV autoregressive (MVAR) model which describes only the lagged effects among the time series and forsakes instantaneous effects. However, instantaneous effects are known to affect linear parametric modeling, and are likely to occur in experimental time series. In this study, we investigate the impact on the assessment of frequency domain causality of excluding instantaneous effects from the model underlying PDC evaluation. Moreover, we propose the utilization of an extended MVAR model including both instantaneous and lagged effects. This model is used to assess PDC either in accordance with the definition of Granger causality when considering only lagged effects (iPDC), or with an extended form of causality, when we consider both instantaneous and lagged effects (ePDC). The approach is first evaluated on three theoretical examples of MVAR processes, which show that the presence of instantaneous correlations may produce misleading profiles of PDC and gPDC, while ePDC and iPDC derived from the extended model provide here a correct interpretation of extended and lagged causality. It is then applied to representative examples of cardiorespiratory and EEG MV time series. They suggest that ePDC and iPDC are better interpretable than PDC and gPDC in terms of the known cardiovascular and neural physiologies.

Chitosan-bound pyridinedicarboxylate Ni(II) and Fe(III) complex biopolymer films as waste water decyanidation agents.

PubMed

Adewuyi, Sheriff; Jacob, Julianah Modupe; Olaleye, Oluwatoyin Omolola; Abdulraheem, Taofiq Olanrewaju; Tayo, Jubril Ayopo; Oladoyinbo, Fatai Oladipupo

2016-10-20

Chitosan is a biopolymer with immense structural advantage for chemical and mechanical modifications to generate novel properties, functions and applications. This work depicts new pyridinedicarboxylicacid (PDC) crosslinked chitosan-metal ion films as veritable material for cyanide ion removal from aqueous solution. The PDC-crosslinked chitosan-metal films (PDC-Chit-Ni(II) and PDC-Chit-Fe(III)) were formed by complexing PDC-crosslinked chitosan film with anhydrous nickel(II) and iron(III) chloride salts respectively. The PDC-Chit and its metal films were characterized employing various analytical and spectroscopic techniques. The FT-IR, UV-vis and the XRD results confirm the presence of the metal ions in the metal coordinated PDC-crosslinked chitosan film. The surface morphological difference of PDC-Chit-Ni(II) film before and after decyanidation was explored with scanning electron microscopy. Furthermore, the quantitative amount of nickel(II) and iron(III) present in the complex were determined using Atomic Absorption Spectrophotometer as 32.3 and 37.2μg/g respectively which portends the biopolymer film as a good complexing agent. Removal of cyanide from aqueous solution with PDC-Chit, PDC-Chit-Ni(II) and PDC-Chit-Fe(III) films was studied with batch equilibrium experiments. At equilibrium, decyanidation capacity (DC) followed the order PDC-Chit-Ni (II)≈PDC-Chit-Fe(III)>PDC-Chit. PDC-Chit-Ni(II) film gave 100% CN(-) removal within 40min decyanidation owing to favorable coordination geometry. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low-level HIV infection of plasmacytoid dendritic cells: onset of cytopathic effects and cell death after PDC maturation.

PubMed

Schmidt, Barbara; Scott, Iain; Whitmore, Robert G; Foster, Hillary; Fujimura, Sue; Schmitz, Juergen; Levy, Jay A

2004-11-24

Plasmacytoid dendritic cells (PDC), the natural type-1 interferon (IFN) producing cells, are part of the innate immune defense against human immunodeficiency virus (HIV). PDC numbers are reduced in advanced stages of infection. These cells can be infected in vivo by HIV since highly purified PDC showed evidence of infectious HIV. Moreover, when PDC derived from uninfected donors were exposed to high-titered HIV isolates, productive infection occurred although with low-level replication. Using real-time amplification, PDC and unstimulated CD4+ cells were found equally susceptible to HIV infection; however, HIV replication was considerably limited in the PDC. Virus replication was enhanced after PDC treatment with CD40L and antibodies against IFN-alpha, most likely reflecting the reduction in IFN-alpha activity. On maturation, the infected PDC showed multinuclear cell syncytia formation and death. These findings indicate that PDC can be reservoirs for HIV dissemination and that HIV infection of PDC can contribute to their decline.

Corrected and Republished from: BCL11A Is a Critical Component of a Transcriptional Network That Activates Recombinase Activating Gene Expression and V(D)J Recombination

PubMed Central

Lee, Baeck-Seung; Lee, Bum-Kyu; Iyer, Vishwanath R.; Sleckman, Barry P.; Shaffer, Arthur L.; Ippolito, Gregory C.

2017-01-01

ABSTRACT Recombination activating gene 1 (RAG1) and RAG2 are critical enzymes for initiating variable-diversity-joining [V(D)J] segment recombination, an essential process for antigen receptor expression and lymphocyte development. The BCL11A transcription factor is required for B cell and plasmacytoid dendritic cell (pDC) development, but its molecular function(s) in early B cell fate specification and commitment is unknown. We show here that the major B cell isoform, BCL11A-XL, binds directly to the RAG1 promoter as well as directly to regulatory regions of transcription factors previously implicated in both B cell and pDC development to activate RAG1 and RAG2 gene transcription in pro- and pre-B cells. We employed BCL11A overexpression with recombination substrates to demonstrate direct consequences of BCL11A/RAG modulation on V(D)J recombination. We conclude that BCL11A is a critical component of a transcriptional network that regulates B cell fate by controlling V(D)J recombination. PMID:29038163

PDC-TREM, a plasmacytoid dendritic cell-specific receptor, is responsible for augmented production of type I interferon.

PubMed

Watarai, Hiroshi; Sekine, Etsuko; Inoue, Sayo; Nakagawa, Ryusuke; Kaisho, Tsuneyasu; Taniguchi, Masaru

2008-02-26

Type I interferons (IFNs) derived from plasmacytoid dendritic cells (PDCs) are critical for antiviral responses; however, the mechanisms underlying their production remain unclear. We have identified a receptor, PDC-TREM, which is associated with Plexin-A1 (PlxnA1) on the PDC cell surface and is preferentially expressed after TLR-stimulation. Limited TLR signals induced PDC-TREM expression but failed to induce IFN-alpha production. However, when coupled with Sema6D, a ligand for Plexin-A1, limited TLR-stimulation resulted in PDC-TREM-mediated DAP12-dependent phosphorylation of phosphoinositide 3-kinase (PI3K) and extracellular regulated kinase (Erk) 1/2 at 6-9 h, and IFN-alpha was produced. Inhibition of PDC-TREM expression by pdctrem-shRNA, blocking of PDC-TREM-binding with PlxnA1 by PDC-TREM mAb, and DAP12 deficiency all resulted in greatly reduced PDC-TREM-dependent activation of signaling molecules and IFN-alpha production. Thus, PDC-TREM is responsible for IFN-alpha production, whereas TLR signals are essential for PDC-TREM expression.

Quantum key distribution with entangled photon sources

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

Ma Xiongfeng; Fung, Chi-Hang Fred; Lo, H.-K.

2007-07-15

A parametric down-conversion (PDC) source can be used as either a triggered single-photon source or an entangled-photon source in quantum key distribution (QKD). The triggering PDC QKD has already been studied in the literature. On the other hand, a model and a post-processing protocol for the entanglement PDC QKD are still missing. We fill in this important gap by proposing such a model and a post-processing protocol for the entanglement PDC QKD. Although the PDC model is proposed to study the entanglement-based QKD, we emphasize that our generic model may also be useful for other non-QKD experiments involving a PDCmore » source. Since an entangled PDC source is a basis-independent source, we apply Koashi and Preskill's security analysis to the entanglement PDC QKD. We also investigate the entanglement PDC QKD with two-way classical communications. We find that the recurrence scheme increases the key rate and the Gottesman-Lo protocol helps tolerate higher channel losses. By simulating a recent 144-km open-air PDC experiment, we compare three implementations: entanglement PDC QKD, triggering PDC QKD, and coherent-state QKD. The simulation result suggests that the entanglement PDC QKD can tolerate higher channel losses than the coherent-state QKD. The coherent-state QKD with decoy states is able to achieve highest key rate in the low- and medium-loss regions. By applying the Gottesman-Lo two-way post-processing protocol, the entanglement PDC QKD can tolerate up to 70 dB combined channel losses (35 dB for each channel) provided that the PDC source is placed in between Alice and Bob. After considering statistical fluctuations, the PDC setup can tolerate up to 53 dB channel losses.« less

Adaptation of oxidative phosphorylation to photoperiod-induced seasonal metabolic states in migratory songbirds.

PubMed

Trivedi, Amit Kumar; Malik, Shalie; Rani, Sangeeta; Kumar, Vinod

2015-06-01

Eukaryotic cells produce chemical energy in the form of ATP by oxidative phosphorylation of metabolic fuels via a series of enzyme mediated biochemical reactions. We propose that the rates of these reactions are altered, as per energy needs of the seasonal metabolic states in avian migrants. To investigate this, blackheaded buntings were photoperiodically induced with non-migratory, premigratory, migratory and post-migratory phenotypes. High plasma levels of free fatty acids, citrate (an intermediate that begins the TCA cycle) and malate dehydrogenase (mdh, an enzyme involved at the end of the TCA cycle) confirmed increased availability of metabolic reserves and substrates to the TCA cycle during the premigratory and migratory states, respectively. Further, daily expression pattern of genes coding for enzymes involved in the oxidative decarboxylation of pyruvate to acetyl-CoA (pdc and pdk) and oxidative phosphorylation in the TCA cycle (cs, odgh, sdhd and mdh) was monitored in the hypothalamus and liver. Reciprocal relationship between pdc and pdk expressions conformed with the altered requirements of acetyl-CoA for the TCA cycle in different metabolic states. Except for pdk, all genes had a daily expression pattern, with high mRNA expression during the day in the premigratory/migratory phenotypes, and at night (cs, odhg, sdhd and mdh) in the nonmigratory phenotype. Differences in mRNA expression patterns of pdc, sdhd and mdh, but not of pdk, cs and odgh, between the hypothalamus and liver indicated a tissue dependent metabolism in buntings. These results suggest the adaptation of oxidative phosphorylation pathway(s) at gene levels to the seasonal alternations in metabolism in migratory songbirds. Copyright © 2015 Elsevier Inc. All rights reserved.

Fluorescence studies on the interaction of choline-binding domain B of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.

PubMed

Damai, Rajani S; Anbazhagan, V; Rao, K Babu; Swamy, Musti J

2009-12-01

The microenvironment and accessibility of the tryptophan residues in domain B of PDC-109 (PDC-109/B) in the native state and upon ligand binding have been investigated by fluorescence quenching, time-resolved fluorescence and red-edge excitation shift (REES) studies. The increase in the intrinsic fluorescence emission intensity of PDC-109/B upon binding to lysophosphatidylcholine (Lyso-PC) micelles and dimyristoylphosphatidylcholine (DMPC) membranes was considerably less as compared to that observed with the whole PDC-109 protein. The degree of quenching achieved by different quenchers with PDC-109/B bound to Lyso-PC and DMPC membranes was significantly higher as compared to the full PDC-109 protein, indicating that membrane binding afforded considerably lesser protection to the tryptophan residues of domain B as compared to those in the full PDC-109 protein. Finally, changes in red-edge excitation shift (REES) seen with PDC-109/B upon binding to DMPC membranes and Lyso-PC micelles were smaller that the corresponding changes in the REES values observed for the full PDC-109. These results, taken together suggest that intact PDC-109 penetrates deeper into the hydrophobic parts of the membrane as compared to domain B alone, which could be the reason for the inability of PDC-109/B to induce cholesterol efflux, despite its ability to recognize choline phospholipids at the membrane surface.

Efficient sensing of avian influenza viruses by porcine plasmacytoid dendritic cells.

PubMed

Bel, Michael; Ocaña-Macchi, Manuela; Liniger, Matthias; McCullough, Kenneth C; Matrosovich, Mikhail; Summerfield, Artur

2011-04-01

H5N1 influenza A virus (IAV) infections in human remain rare events but have been associated with severe disease and a higher mortality rate compared to infections with seasonal strains. An excessive release of pro-inflammatory cytokine together with a greater virus dissemination potential have been proposed to explain the high virulence observed in human and other mammalian and avian species. Among the cells involved in the cytokine storm, plasmacytoid dendritic cells (pDC) could play an important role considering their unique capacity to secrete massive amounts of type I interferon (IFN). Considering the role of IFN as a major component of antiviral responses as well as in priming inflammatory responses, we aimed to characterize the induction of IFN-α release upon infection with IAV originating from various avian and mammalian species in a comparative way. In our porcine pDC model, we showed that the viral components triggering IFN responses related to the ability to hemagglutinate, although virosomes devoid of viral RNA were non-stimulatory. Heat-treatment at 65 °C but not chemical inactivation destroyed the ability of IAV to stimulate pDC. All IAV tested induced IFN-α but at different levels and showed different dose-dependencies. H5 and H7 subtypes, in particular H5N1, stimulated pDC at lower doses when compared to mammalian IAV. At high viral doses, IFN-α levels reached by some mammalian IAV surpassed those induced by avian isolates. Although sialic acid-dependent entry was demonstrated, the α-2,3 or α-2,6 binding specificity alone did not explain the differences observed. Furthermore, we were unable to identify a clear role of the hemagglutinin, as the IFN-α doses-response profiles did not clearly differ when viruses with all genes of identical avian origin but different HA were compared. This was found with IAV bearing an HA derived from either a low, a high pathogenic H5N1, or a human H3. Stimulation of pDC was associated with pDC depletion within the cultures. Taken together and considering the efficient sensing of H5N1 at low dose, pDC on one side may play a role in the cytokine storm observed during severe disease, on the other hand could participate in early antiviral responses limiting virus replication.

Efficient Sensing of Avian Influenza Viruses by Porcine Plasmacytoid Dendritic Cells

PubMed Central

Bel, Michael; Ocaña-Macchi, Manuela; Liniger, Matthias; McCullough, Kenneth C.; Matrosovich, Mikhail; Summerfield, Artur

2011-01-01

H5N1 influenza A virus (IAV) infections in human remain rare events but have been associated with severe disease and a higher mortality rate compared to infections with seasonal strains. An excessive release of pro-inflammatory cytokine together with a greater virus dissemination potential have been proposed to explain the high virulence observed in human and other mammalian and avian species. Among the cells involved in the cytokine storm, plasmacytoid dendritic cells (pDC) could play an important role considering their unique capacity to secrete massive amounts of type I interferon (IFN). Considering the role of IFN as a major component of antiviral responses as well as in priming inflammatory responses, we aimed to characterize the induction of IFN-α release upon infection with IAV originating from various avian and mammalian species in a comparative way. In our porcine pDC model, we showed that the viral components triggering IFN responses related to the ability to hemagglutinate, although virosomes devoid of viral RNA were non-stimulatory. Heat-treatment at 65 °C but not chemical inactivation destroyed the ability of IAV to stimulate pDC. All IAV tested induced IFN-α but at different levels and showed different dose-dependencies. H5 and H7 subtypes, in particular H5N1, stimulated pDC at lower doses when compared to mammalian IAV. At high viral doses, IFN-α levels reached by some mammalian IAV surpassed those induced by avian isolates. Although sialic acid-dependent entry was demonstrated, the α-2,3 or α-2,6 binding specificity alone did not explain the differences observed. Furthermore, we were unable to identify a clear role of the hemagglutinin, as the IFN-α doses-response profiles did not clearly differ when viruses with all genes of identical avian origin but different HA were compared. This was found with IAV bearing an HA derived from either a low, a high pathogenic H5N1, or a human H3. Stimulation of pDC was associated with pDC depletion within the cultures. Taken together and considering the efficient sensing of H5N1 at low dose, pDC on one side may play a role in the cytokine storm observed during severe disease, on the other hand could participate in early antiviral responses limiting virus replication. PMID:21994734

Bioethanol production by heterologous expression of Pdc and AdhII in Streptomyces lividans.

PubMed

Lee, Jae Sun; Chi, Won-Jae; Hong, Soon-Kwang; Yang, Ji-Won; Chang, Yong Keun

2013-07-01

Two genes from Zymomonas mobilis that are responsible for ethanol production, pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adhII), were heterologously expressed in the Gram-positive bacterium Streptomyces lividans TK24. An examination of carbon distribution revealed that a significant portion of carbon metabolism was switched from biomass and organic acid biosynthesis to ethanol production upon the expression of pdc and adhII. The recombinant S. lividans TK24 produced ethanol from glucose with a yield of 23.7% based on the carbohydrate consumed. The recombinant was able to produce ethanol from xylose, L-arabinose, mannose, L-rhamnose, galactose, ribose, and cellobiose with yields of 16.0, 25.6, 21.5, 33.6, 30.6, 14.6, and 33.3%, respectively. Polymeric substances such as starch and xylan were directly converted to ethanol by the recombinant with ethanol yields of 18.9 and 8.8%, respectively. The recombinant S. lividans TK24/Tpet developed in this study is potentially a useful microbial resource for ethanol production from various sources of biomasses, especially microalgae.

Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection.

PubMed

Blasius, Amanda L; Krebs, Philippe; Sullivan, Brian M; Oldstone, Michael B; Popkin, Daniel L

2012-09-01

Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.

Investigation of PDC bit failure base on stick-slip vibration analysis of drilling string system plus drill bit

NASA Astrophysics Data System (ADS)

Huang, Zhiqiang; Xie, Dou; Xie, Bing; Zhang, Wenlin; Zhang, Fuxiao; He, Lei

2018-03-01

The undesired stick-slip vibration is the main source of PDC bit failure, such as tooth fracture and tooth loss. So, the study of PDC bit failure base on stick-slip vibration analysis is crucial to prolonging the service life of PDC bit and improving ROP (rate of penetration). For this purpose, a piecewise-smooth torsional model with 4-DOF (degree of freedom) of drilling string system plus PDC bit is proposed to simulate non-impact drilling. In this model, both the friction and cutting behaviors of PDC bit are innovatively introduced. The results reveal that PDC bit is easier to fail than other drilling tools due to the severer stick-slip vibration. Moreover, reducing WOB (weight on bit) and improving driving torque can effectively mitigate the stick-slip vibration of PDC bit. Therefore, PDC bit failure can be alleviated by optimizing drilling parameters. In addition, a new 4-DOF torsional model is established to simulate torsional impact drilling and the effect of torsional impact on PDC bit's stick-slip vibration is analyzed by use of an engineering example. It can be concluded that torsional impact can mitigate stick-slip vibration, prolonging the service life of PDC bit and improving drilling efficiency, which is consistent with the field experiment results.

Coordination properties of tridentate (N,O,O) heterocyclic alcohol (PDC) with Cu(II). Mixed ligand complex formation reactions of Cu(II) with PDC and some bio-relevant ligands.

PubMed

El-Sherif, Ahmed A; Shoukry, Mohamed M

2007-03-01

The formation equilibria of copper(II) complexes and the ternary complexes Cu(PDC)L (PDC=2,6-bis-(hydroxymethyl)-pyridine, HL=amino acid, amides or DNA constituents) have been investigated. Ternary complexes are formed by a simultaneous mechanism. The results showed the formation of Cu(PDC)L, Cu(PDC, H(-1))(L) and Cu(PDC, H(-2))(L) complexes. The concentration distribution of the complexes in solution is evaluated as a function of pH. The effect of dioxane as a solvent on the protonation constant of PDC and the formation constants of Cu(II) complexes are discussed. The thermodynamic parameters DeltaH degrees and DeltaS degrees calculated from the temperature dependence of the equilibrium constants are investigated.

Plasmacytoid Dendritic Cell Dynamics Tune Interferon-Alfa Production in SIV-Infected Cynomolgus Macaques

PubMed Central

Bruel, Timothée; Dupuy, Stéphanie; Démoulins, Thomas; Rogez-Kreuz, Christine; Dutrieux, Jacques; Corneau, Aurélien; Cosma, Antonio; Cheynier, Rémi; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Vaslin, Bruno

2014-01-01

IFN-I production is a characteristic of HIV/SIV primary infections. However, acute IFN-I plasma concentrations rapidly decline thereafter. Plasmacytoid dendritic cells (pDC) are key players in this production but primary infection is associated with decreased responsiveness of pDC to TLR 7 and 9 triggering. IFNα production during primary SIV infection contrasts with increased pDC death, renewal and dysfunction. We investigated the contribution of pDC dynamics to both acute IFNα production and the rapid return of IFNα concentrations to pre-infection levels during acute-to-chronic transition. Nine cynomolgus macaques were infected with SIVmac251 and IFNα-producing cells were quantified and characterized. The plasma IFN-I peak was temporally associated with the presence of IFNα+ pDC in tissues but IFN-I production was not detectable during the acute-to-chronic transition despite persistent immune activation. No IFNα+ cells other than pDC were detected by intracellular staining. Blood-pDC and peripheral lymph node-pDC both lost IFNα− production ability in parallel. In blood, this phenomenon correlated with an increase in the counts of Ki67+-pDC precursors with no IFNα production ability. In tissues, it was associated with increase of both activated pDC and KI67+-pDC precursors, none of these being IFNα+ in vivo. Our findings also indicate that activation/death-driven pDC renewal rapidly blunts acute IFNα production in vivo: pDC sub-populations with no IFNα-production ability rapidly increase and shrinkage of IFNα production thus involves both early pDC exhaustion, and increase of pDC precursors. PMID:24497833

Impaired plasmacytoid dendritic cell (PDC)-NK cell activity in viremic human immunodeficiency virus infection attributable to impairments in both PDC and NK cell function.

PubMed

Conry, Sara J; Milkovich, Kimberly A; Yonkers, Nicole L; Rodriguez, Benigno; Bernstein, Helene B; Asaad, Robert; Heinzel, Frederick P; Tary-Lehmann, Magdalena; Lederman, Michael M; Anthony, Donald D

2009-11-01

Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections impair plasmacytoid dendritic cell (PDC) and natural killer (NK) cell subset numbers and functions, though little is known about PDC-NK cell interactions during these infections. We evaluated PDC-dependent NK cell killing and gamma interferon (IFN-gamma) and granzyme B production, using peripheral blood mononuclear cell (PBMC)-based and purified cell assays of samples from HCV- and HIV-infected subjects. CpG-enhanced PBMC killing and IFN-gamma and granzyme B activity (dependent on PDC and NK cells) were impaired in viremic HIV infection. In purified PDC-NK cell culture experiments, CpG-enhanced, PDC-dependent NK cell activity was cell contact and IFN-alpha dependent, and this activity was impaired in viremic HIV infection but not in HCV infection. In heterologous PDC-NK cell assays, impaired PDC-NK cell killing activity was largely attributable to an NK cell defect, while impaired PDC-NK cell IFN-gamma-producing activity was attributable to both PDC and NK cell defects. Additionally, the response of NK cells to direct IFN-alpha stimulation was defective in viremic HIV infection, and this defect was not attributable to diminished IFN-alpha receptor expression, though IFN-alpha receptor and NKP30 expression was closely associated with killer activity in viremic HIV infection but not in healthy controls. These data indicate that during uncontrolled HIV infection, PDC-dependent NK cell function is impaired, which is in large part attributable to defective IFN-alpha-induced NK cell activity and not to altered IFN-alpha receptor, NKP30, NKP44, NKP46, or NKG2D expression.

Improvement of ethanol yield from glycerol via conversion of pyruvate to ethanol in metabolically engineered Saccharomyces cerevisiae.

PubMed

Yu, Kyung Ok; Jung, Ju; Ramzi, Ahmad Bazli; Kim, Seung Wook; Park, Chulhwan; Han, Sung Ok

2012-02-01

The conversion of low-priced glycerol to higher value products has been proposed as a way to improve the economic viability of the biofuels industry. In a previous study, the conversion of glycerol to ethanol in a metabolically engineered strain of Saccharomyces cerevisiae was accomplished by minimizing the synthesis of glycerol, the main by-product in ethanol fermentation processing. To further improve ethanol production, overexpression of the native genes involved in conversion of pyruvate to ethanol in S. cerevisiae was successfully accomplished. The overexpression of an alcohol dehydrogenase (adh1) and a pyruvate decarboxylase (pdc1) caused an increase in growth rate and glycerol consumption under fermentative conditions, which led to a slight increase of the final ethanol yield. The overall expression of the adh1 and pdc1 genes in the modified strains, combined with the lack of the fps1 and gpd2 genes, resulted in a 1.4-fold increase (about 5.4 g/L ethanol produced) in fps1Δgpd2Δ (pGcyaDak, pGupCas) (about 4.0 g/L ethanol produced). In summary, it is possible to improve the ethanol yield by overexpression of the genes involved in the conversion of pyruvate to ethanol in engineered S. cerevisiae using glycerol as substrate.

IL-27 Production and STAT3-Dependent Upregulation of B7-H1 Mediate Immune Regulatory Functions of Liver Plasmacytoid DC1

PubMed Central

Matta, Benjamin M.; Raimondi, Giorgio; Rosborough, Brian R.; Sumpter, Tina L.; Thomson, Angus W.

2012-01-01

Plasmacytoid (p) dendritic cells (DC) are highly-specialized APC that, in addition to their well-recognized role in anti-viral immunity, also regulate immune responses. Liver-resident pDC are considerably less immunostimulatory than those from secondary lymphoid tissues and are equipped to promote immune tolerance/regulation through various mechanisms. IL-27 is an IL-12-family cytokine that regulates the function of both APC and T cells, although little is known about its role in pDC immunobiology. In this study, we show that mouse liver pDC express higher levels of IL-27p28 and EBV-induced protein (Ebi)3 compared to splenic pDC. Both populations of pDC express the IL-27Rα/WSX-1; however, only liver pDC significantly upregulate expression of the co-regulatory molecule B7 homolog-1 (B7-H1) in response to IL-27. Inhibition of STAT3 activation completely abrogates IL-27-induced upregulation of B7-H1 expression on liver pDC. Liver pDC treated with IL-27 increase the percentage of CD4+Foxp3+ T cells in MLR, which is dependent upon expression of B7-H1. pDC from Ebi3-deficient mice lacking functional IL-27, show increased capacity to stimulate allogeneic T cell proliferation and IFN-γ production in MLR. Liver but not spleen pDC suppress delayed-type hypersensitivity responses to OVA, an effect that is lost with Ebi3−/− and B7-H1−/− liver pDC compared to wild-type (WT) liver pDC. These data suggest that IL-27 signaling in pDC promotes their immunoregulatory function and that IL-27 produced by pDC contributes to their capacity to regulate immuneresponses in vitro and in vivo. PMID:22508931

An Evaluation of the Performance Diagnostic Checklist-Human Services (PDC-HS) Across Domains.

PubMed

Wilder, David A; Lipschultz, Joshua; Gehrman, Chana

2018-06-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to assess the environmental variables that contribute to poor employee performance in human service settings. Although the PDC-HS has been shown to effectively identify variables contributing to problematic performance, interventions based on only two of the four PDC-HS domains have been evaluated to date. In addition, the extent to which PDC-HS-indicated interventions are more effective than nonindicated interventions for two domains remains unclear. In the current study, we administered the PDC-HS to supervisors to assess the variables contributing to infrequent teaching of verbal operants and use of a timer by therapists at a center-based autism treatment program. Each of the four PDC-HS domains was identified as contributing to poor performance for at least one therapist. We then evaluated PDC-HS-indicated interventions for each domain. In addition, to assess the predictive validity of the tool, we evaluated various nonindicated interventions prior to implementing a PDC-HS-indicated intervention for two of the four domains. Results suggest that the PDC-HS-indicated interventions were effective across all four domains and were more effective than the nonindicated interventions for the two domains for which they were evaluated. Results are discussed in terms of the utility of the PDC-HS to identify appropriate interventions to manage therapist performance in human service settings.

Associations of Frequency and Duration of Patient-Doctor Contact in Hemodialysis Facilities with Mortality

PubMed Central

Karaboyas, Angelo; Robinson, Bruce M.; Li, Yun; Fukuhara, Shunichi; Bieber, Brian A.; Rayner, Hugh C.; Andreucci, Vittorio E.; Pisoni, Ronald L.; Port, Friedrich K.; Morgenstern, Hal; Akizawa, Tadao; Saran, Rajiv

2013-01-01

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7±5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis. PMID:23886592

PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

PubMed

McHugh, Anna; Robe, Amanda J; Palmer, Jeremy M; Jones, David E J

2006-05-01

Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression. Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects. T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1

Plasmacytoid Dendritic Cell Infection and Sensing Capacity during Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infection

PubMed Central

Jochems, Simon P.; Jacquelin, Beatrice; Chauveau, Lise; Huot, Nicolas; Petitjean, Gaël; Lepelley, Alice; Liovat, Anne-Sophie; Ploquin, Mickaël J.; Cartwright, Emily K.; Bosinger, Steven E.; Silvestri, Guido; Barré-Sinoussi, Françoise; Lebon, Pierre; Schwartz, Olivier

2015-01-01

ABSTRACT Human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques (MAC) lead to chronic inflammation and AIDS. Natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM), are protected against SIV-induced chronic inflammation and AIDS. Here, we report that AGM plasmacytoid dendritic cells (pDC) express extremely low levels of CD4, unlike MAC and human pDC. Despite this, AGM pDC efficiently sensed SIVagm, but not heterologous HIV/SIV isolates, indicating a virus-host adaptation. Moreover, both AGM and SM pDC were found to be, in contrast to MAC pDC, predominantly negative for CCR5. Despite such limited CD4 and CCR5 expression, lymphoid tissue pDC were infected to a degree similar to that seen with CD4+ T cells in both MAC and AGM. Altogether, our finding of efficient pDC infection by SIV in vivo identifies pDC as a potential viral reservoir in lymphoid tissues. We discovered low expression of CD4 on AGM pDC, which did not preclude efficient sensing of host-adapted viruses. Therefore, pDC infection and efficient sensing are not prerequisites for chronic inflammation. The high level of pDC infection by SIVagm suggests that if CCR5 paucity on immune cells is important for nonpathogenesis of natural hosts, it is possibly not due to its role as a coreceptor. IMPORTANCE The ability of certain key immune cell subsets to resist infection might contribute to the asymptomatic nature of simian immunodeficiency virus (SIV) infection in its natural hosts, such as African green monkeys (AGM) and sooty mangabeys (SM). This relative resistance to infection has been correlated with reduced expression of CD4 and/or CCR5. We show that plasmacytoid dendritic cells (pDC) of natural hosts display reduced CD4 and/or CCR5 expression, unlike macaque pDC. Surprisingly, this did not protect AGM pDC, as infection levels were similar to those found in MAC pDC. Furthermore, we show that AGM pDC did not consistently produce type I interferon (IFN-I) upon heterologous SIVmac/HIV type 1 (HIV-1) encounter, while they sensed autologous SIVagm isolates. Pseudotyping SIVmac/HIV-1 overcame this deficiency, suggesting that reduced uptake of heterologous viral strains underlays this lack of sensing. The distinct IFN-I responses depending on host species and HIV/SIV isolates reveal the host/virus species specificity of pDC sensing. PMID:25903334

[Clinical aspects, imaging and neuropathology of Kii ALS/PDC].

PubMed

Kokubo, Yasumasa

2007-11-01

During 1996 and 2006, we examined clinically 37 patients and neuropathologically 13 autopsy cases with amyotrophic lateral sclerosis/parkinsonism-dementia complex of the Kii peninsula (Kii ALS/PDC). The ages of onset were between 52 years and 74 years (mean age: 65.3 years). The male to female ratio was 1:1.85. The ratio of positive family history where ALS or PDC occurred within the fourth degree of the relatives was 78.4% in the patients with Kii ALS/PDC. The average duration of the illness was 6.47 years. Kii ALS/PDC was divided into five clinical subtypes, pure ALS form, ALS with dementia form, PDC with parkinsonism predominant form, PDC with dementia predominant form (that is called late-life dementia in Guam) and PDC with ALS features form. Unique pigmentary retinopathy was found in 33.3% of the patients with Kii ALS/PDC. CT/MRI images showed atrophy of the frontal and temporal lobes and SPECT images showed a decrease in the blood flow of the frontal and temporal lobes. The cardiac 123I-MIBG uptake was decreased in 4 out of 8 patients with ALS/PDC and the decrease in uptake correlated with the modified Hoehn-Yahr staging. The cardinal neuropathological features of Kii ALS/PDC were abundant neurofibrillary tangles (NFTs) associated with loss of nerve cells in the cerebral cortex and the brain stem, and findings of ALS neuropathology. Ultrastructurally, NFTs consisted of paired helical filaments. Tau protein, a main component of NFTs, was consisted of 3R and 4R tau isoforms, and phosphoryrated at 18 sites of tau phosphoryrated sites. The neurons of dentate gyrus of hippocampus and anterior horn cells were stained with anti-TDP-43 antibody. The clinical and neuropathological aspects of Kii ALS/PDC are regarded as being identical with those of Guam ALS/PDC.

Peoria Disposal Co.`s PDC Laboratories: Analyzing and cleaning up -- Literally

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

McAdams, C.L.

1995-10-01

In the early 1980s, says Royal Coulter, president and CEO of Peoria Disposal Co. (PDC, Peoria, IL), many PDC customers were unfamiliar with the methods required for the proper characterization of then newly regulated hazardous wastes. So in early 1981, to expedite permitting and, ultimately, acceptance of waste by PDC, a lab was set up so the company could step in and provide the needed services. By focusing on the delivery of quality services in the analysis of groundwater, wastewater, and solid waste for PDC, Coulter says, the laboratory soon developed into a successful and independent commercial operation. In Julymore » of 1981, PDC Laboratories was incorporated as an independent environmental analytical laboratory. PDC Labs is a subsidiary of PDC Technical Services, Inc., which provides environmental consulting and site remediation services, and is itself a wholly-owned subsidiary of Coulter Companies, Inc. Peoria Disposal offers solid waste disposal, industrial waste water treatment, waste stabilization, transportation services, and brokerage services.« less

Type I interferon regulates pDC maturation and Ly49Q expression.

PubMed

Toma-Hirano, Makiko; Namiki, Sahori; Miyatake, Shoichiro; Arai, Ken-Ichi; Kamogawa-Schifter, Yumiko

2007-10-01

Ly49Q is expressed on peripheral mouse plasmacytoid dendritic cells (pDC). Immature Ly49Q-negative pDC precursors acquire Ly49Q in the bone marrow and then migrate into the periphery. While searching for molecules that regulate pDC maturation, we found that type I interferon (IFN) inhibited Ly49Q acquisition in vitro. Infections that induce type I IFN production by cells other than pDC (a condition mimicked by poly(I:C) injection in vivo) increase the prevalence of Ly49Q(-) pDC in the bone marrow and peripheral lymphoid organs in wild-type but not IFN-alpha/beta receptor knockout BALB/c mice. Moreover, in vivo exposure to type I IFN causes some Ly49Q(-), but not Ly49Q(+), pDC to convert to conventional DC, defined as B220(-) CD11c(+) CD11b(+) cells. These data suggest that type I IFN regulates pDC development and affects their distribution in the body.

The Use of the Performance Diagnostic Checklist-Human Services to Assess and Improve the Job Performance of Individuals with Intellectual Disabilities.

PubMed

Smith, Madison; Wilder, David A

2018-06-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to identify the variables responsible for performance problems. To date, the PDC-HS has not been examined with individuals with intellectual disabilities. In the current study, two supervisors with intellectual disabilities completed the PDC-HS to assess the productivity of two supervisees with disabilities who performed a pricing task in a thrift store. The PDC-HS suggested that performance deficits were due to a lack of training; a PDC-HS-indicated intervention was effective to increase accurate pricing. • The PDC-HS is an informant-based tool designed to identify the variables responsible for employee performance problems in human service settings. • The PDC-HS can be completed by some individuals with intellectual disabilities in a supervisory position to identify the variables responsible for problematic job performance among their supervisees. • A PDC-HS indicated intervention was demonstrated to be effective to improve the job performance of individuals with disabilities. • The PDC-HS may be a useful tool to support performance improvement and job maintenance among individuals with intellectual disabilities.

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus

PubMed Central

2013-01-01

Background The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). Results A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6–9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. Conclusions This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance. PMID:23902280

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus.

PubMed

Shah, Neethu; Gaupp, Rosmarie; Moriyama, Hideaki; Eskridge, Kent M; Moriyama, Etsuko N; Somerville, Greg A

2013-07-31

The Per-Arnt-Sim (PAS) domain represents a ubiquitous structural fold that is involved in bacterial sensing and adaptation systems, including several virulence related functions. Although PAS domains and the subclass of PhoQ-DcuS-CitA (PDC) domains have a common structure, there is limited amino acid sequence similarity. To gain greater insight into the evolution of PDC/PAS domains present in the bacterial kingdom and staphylococci in specific, the PDC/PAS domains from the genomic sequences of 48 bacteria, representing 5 phyla, were identified using the sensitive search method based on HMM-to-HMM comparisons (HHblits). A total of 1,007 PAS domains and 686 PDC domains distributed over 1,174 proteins were identified. For 28 Gram-positive bacteria, the distribution, organization, and molecular evolution of PDC/PAS domains were analyzed in greater detail, with a special emphasis on the genus Staphylococcus. Compared to other bacteria the staphylococci have relatively fewer proteins (6-9) containing PDC/PAS domains. As a general rule, the staphylococcal genomes examined in this study contain a core group of seven PDC/PAS domain-containing proteins consisting of WalK, SrrB, PhoR, ArlS, HssS, NreB, and GdpP. The exceptions to this rule are: 1) S. saprophyticus lacks the core NreB protein; 2) S. carnosus has two additional PAS domain containing proteins; 3) S. epidermidis, S. aureus, and S. pseudintermedius have an additional protein with two PDC domains that is predicted to code for a sensor histidine kinase; 4) S. lugdunensis has an additional PDC containing protein predicted to be a sensor histidine kinase. This comprehensive analysis demonstrates that variation in PDC/PAS domains among bacteria has limited correlations to the genome size or pathogenicity; however, our analysis established that bacteria having a motile phase in their life cycle have significantly more PDC/PAS-containing proteins. In addition, our analysis revealed a tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance.

Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer.

PubMed

Stacpoole, Peter W

2017-11-01

The mitochondrial pyruvate dehydrogenase complex (PDC) irreversibly decarboxylates pyruvate to acetyl coenzyme A, thereby linking glycolysis to the tricarboxylic acid cycle and defining a critical step in cellular bioenergetics. Inhibition of PDC activity by pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation has been associated with the pathobiology of many disorders of metabolic integration, including cancer. Consequently, the PDC/PDK axis has long been a therapeutic target. The most common underlying mechanism accounting for PDC inhibition in these conditions is post-transcriptional upregulation of one or more PDK isoforms, leading to phosphorylation of the E1α subunit of PDC. Such perturbations of the PDC/PDK axis induce a "glycolytic shift," whereby affected cells favor adenosine triphosphate production by glycolysis over mitochondrial oxidative phosphorylation and cellular proliferation over cellular quiescence. Dichloroacetate is the prototypic xenobiotic inhibitor of PDK, thereby maintaining PDC in its unphosphorylated, catalytically active form. However, recent interest in the therapeutic targeting of the PDC/PDK axis for the treatment of cancer has yielded a new generation of small molecule PDK inhibitors. Ongoing investigations of the central role of PDC in cellular energy metabolism and its regulation by pharmacological effectors of PDKs promise to open multiple exciting vistas into the biochemical understanding and treatment of cancer and other diseases. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Demonstration of PDC-E1 subunits as major antigens in the complement-fixing fraction M4 and re-evaluation of PDC-E1-specific antibodies in PBC patients.

PubMed

Berg, Christoph P; Stein, Gerburg M; Klein, Reinhild; Pascu, Maria; Berg, Thomas; Kammer, Winfried; Priemer, Martin; Nordheim, Alfred; Schulze-Osthoff, Klaus; Gregor, Michael; Wesselborg, Sebastian; Berg, Peter A

2006-09-01

Primary biliary cirrhosis (PBC) is characterized by the presence of antimitochondrial antibodies (AMA). Autoantibodies specific for the mitochondrial M4 antigen can be detected by a complement fixation test (CFT) but not by immunoblotting. The aim of this study was to elucidate the identity of the M4 antigen. M4 proteins were purified by affinity chromatography using IgG fractions of PBC marker sera being CFT positive (n=5) or negative (n=5) and identified by Western blotting, silver staining and sequence analysis. Further, a cohort of 57 PBC patients was tested for the reactivity to M4 and pyruvate dehydrogenase complex (PDC). Two AMA patterns of the marker sera were visualized: CFT-positive sera were defined as PDC-E2(+)/E1(+) and the CFT-negative sera as PDC-E2(+)/E1(-). The major proteins in the M4 fraction could be related to the PDC-E1 subunits. A clear-cut association between anti-M4 reactivity in the CFT and the reactivity to both PDC subunits could also be documented in the cohort of 57 PBC patients showing anti-PDC-E1alpha and E1beta antibodies at a frequency of 74% and 67%. CFT reactivity against M4 antigens could be preferentially identified as a reaction against PDC-E1. As PDC-E1 subunits as compared with PDC-E2 lack lipoyl-binding sites, they probably have to be considered as an independent and important target.

Plasmacytoid Dendritic Cells Suppress HIV-1 Replication but Contribute to HIV-1 Induced Immunopathogenesis in Humanized Mice

PubMed Central

Li, Guangming; Cheng, Menglan; Nunoya, Jun-ichi; Cheng, Liang; Guo, Haitao; Yu, Haisheng; Liu, Yong-jun; Su, Lishan; Zhang, Liguo

2014-01-01

The role of plasmacytoid dendritic cells (pDC) in human immunodeficiency virus type 1 (HIV-1) infection and pathogenesis remains unclear. HIV-1 infection in the humanized mouse model leads to persistent HIV-1 infection and immunopathogenesis, including type I interferons (IFN-I) induction, immune-activation and depletion of human leukocytes, including CD4 T cells. We developed a monoclonal antibody that specifically depletes human pDC in all lymphoid organs in humanized mice. When pDC were depleted prior to HIV-1 infection, the induction of IFN-I and interferon-stimulated genes (ISGs) were abolished during acute HIV-1 infection with either a highly pathogenic CCR5/CXCR4-dual tropic HIV-1 or a standard CCR5-tropic HIV-1 isolate. Consistent with the anti-viral role of IFN-I, HIV-1 replication was significantly up-regulated in pDC-depleted mice. Interestingly, the cell death induced by the highly pathogenic HIV-1 isolate was severely reduced in pDC-depleted mice. During chronic HIV-1 infection, depletion of pDC also severely reduced the induction of IFN-I and ISGs, associated with elevated HIV-1 replication. Surprisingly, HIV-1 induced depletion of human immune cells including T cells in lymphoid organs, but not the blood, was reduced in spite of the increased viral replication. The increased cell number in lymphoid organs was associated with a reduced level of HIV-induced cell death in human leukocytes including CD4 T cells. We conclude that pDC play opposing roles in suppressing HIV-1 replication and in promoting HIV-1 induced immunopathogenesis. These findings suggest that pDC-depletion and IFN-I blockade will provide novel strategies for treating those HIV-1 immune non-responsive patients with persistent immune activation despite effective anti-retrovirus treatment. PMID:25077616

Production of indole antibiotics induced by exogenous gene derived from sponge metagenomes.

PubMed

Takeshige, Yuya; Egami, Yoko; Wakimoto, Toshiyuki; Abe, Ikuro

2015-05-01

Sponge metagenomes are accessible genetic sources containing genes and gene clusters responsible for the biosynthesis of sponge-derived bioactive natural products. In this study, we obtained the clone pDC112, producing turbomycin A and 2,2-di(3-indolyl)-3-indolone, based on the functional screening of the metagenome library derived from the marine sponge Discodermia calyx. The subcloning experiment identified ORF 25, which is homologous to inosine 5'-monophosphate dehydrogenase and required for the production of 2,2-di(3-indolyl)-3-indolone in Escherichia coli.

New PDC bit optimizes drilling performance

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

Besson, A.; Gudulec, P. le; Delwiche, R.

1996-05-01

The lithology in northwest Argentina contains a major section where polycrystalline diamond compact (PDC) bits have not succeeded in the past. The section consists of dense shales and cemented sandstone stringers with limestone laminations. Conventional PDC bits experienced premature failures in the section. A new generation PDC bit tripled rate of penetration (ROP) and increased by five times the potential footage per bit. Recent improvements in PDC bit technology that enabled the improved performance include: the ability to control the PDC cutter quality; use of an advanced cutter lay out defined by 3D software; using cutter face design code formore » optimized cleaning and cooling; and, mastering vibration reduction features, including spiraled blades.« less

PDC expressing CD36, CD61 and IL-10 may contribute to propagation of immune tolerance.

PubMed

Parcina, Marijo; Schiller, Martin; Gierschke, Aline; Heeg, Klaus; Bekeredjian-Ding, Isabelle

2009-05-01

Human plasmacytoid dendritic cells (PDC) are blood dendritic cell antigen 2 (BDCA2) and blood dendritic cell antigen 4 (BDCA4) positive leukocytes that do not express common lineage markers. They have been described as proinflammatory innate immune cells and are the major source of alphaIFN in the human body. PDC-derived secretion of type I IFNs upon triggering of nucleic acid-sensing toll-like receptors (TLR) primes immune cells to rapidly respond to microbial stimuli and promotes a Th1 response. Here, we report that human PDC express CD36 and CD61 (beta3 integrin), both involved in uptake of apoptotic cells and in induction of tolerance. Freshly isolated PDC and PDC within human blood leukocytes constitutively express IL-10. Thus, PDC may possess a so far neglected role in propagation of immune tolerance.

Antimicrobial activity and mechanism of PDC213, an endogenous peptide from human milk

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

Sun, Yazhou; Nanjing Maternal and Child Health Medical Institute, Nanjing Maternal and Child Health Hospital, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing; Zhou, Yahui

Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and diskmore » diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation. - Highlights: • PDC213 is an endogenous peptide presenting higher levels in preterm milk. • PDC213 showed obvious antimicrobial against S. aereus and Y. enterocolitica. • PDC213 can permeabilize bacterial membranes and cell walls to kill bacterias. • PDC213 is a novel type of antimicrobial peptides worthy further investigation.« less

Top-down mass spectrometry reveals new sequence variants of the major bovine seminal plasma protein PDC-109.

PubMed

Laitaoja, Mikko; Sankhala, Rajeshwer S; Swamy, Musti J; Jänis, Janne

2012-07-01

The major protein of bovine seminal plasma, PDC-109, is a 109-residue polypeptide that exists as a polydisperse aggregate under native conditions. The oligomeric state of this aggregate varies with ionic strength and the presence of lipids. Binding of PDC-109 to choline phospholipids on the sperm plasma membrane results in an efflux of cholesterol and choline phospholipids, which is an important step in sperm capacitation. In this study, Fourier transform ion cyclotron resonance mass spectrometry was used to analyze PDC-109 purified from bovine seminal plasma. In addition to the previously known PDC-109 variants, four new sequence variants were identified by top-down mass spectrometry. For example, a protein variant containing point mutations P10L and G14R was identified along with another form having a 14-residue truncation in the N-terminal region. Two other minor variants could also be identified from the affinity-purified PDC-109. These results demonstrate that PDC-109 is naturally produced as a mixture of several protein forms, most of which have not been detected in previous studies. Native mass spectrometry revealed that PDC-109 is exclusively monomeric at low protein concentrations, suggesting that the protein oligomers are weakly bound and can easily be disrupted. Ligand binding to PDC-109 was also investigated, and it was observed that two molecules of O-phosphorylcholine bind to each PDC-109 monomer, consistent with previous reports. Copyright © 2012 John Wiley & Sons, Ltd.

Novel tannin-based Si, P co-doped carbon for supercapacitor applications

NASA Astrophysics Data System (ADS)

Ramasahayam, Sunil Kumar; Nasini, Udaya B.; Shaikh, Ali U.; Viswanathan, Tito

2015-02-01

Increasing environmental pollution and population compounded by a decrease in the availability of non-renewable resources and fossil fuels has propelled the need for sustainable alternate energy storage technologies particularly in the last two decades. An attempt to meet this crisis was carried out by a unique, microwave-assisted method which has enabled the generation of a novel Si, P co-doped carbon (SiPDC) for supercapacitor applications. The microwave-assisted method is useful in developing SiPDC at a rapid and economical fashion that does not employ any inert or reducing gases, but is high yielding. Varying proportions of precursor materials were utilized to generate four SiPDCs (SiPDC-1, SiPDC-2, SiPDC-3 and SiPDC-4) with varying contents of dopants as evidenced by X-ray photoelectron spectroscopic (XPS) results. Surface area and pore size analysis revealed that SiPDC-2 has a surface area of 641.51 m2 g-1, abundant micropores, mesopores and macropores which are critical for electrical double layer capacitance (EDLC). Of all the SiPDCs, SiPDC-2 exhibited highest capacitance of 276 F g-1 in 1 M H2SO4 and 244 F g-1 in 6 M KOH at a scan rate of 5 mV s-1. Galvanostatic charge-discharge studies performed in 6 M KOH establish the high capacitance of SiPDC-2. SiPDC-2 also exhibited excellent electrochemical stability in 1 M H2SO4 and 6 M KOH.

Type III IFNs are produced by and stimulate human plasmacytoid dendritic cells1

PubMed Central

Yin, Zhiwei; Dai, Jihong; Deng, Jing; Sheikh, Faruk; Natalia, Mahwish; Shih, Tiffany; Lewis-Antes, Anita; Amrute, Sheela B.; Garrigues, Ursula; Doyle, Sean; Donnelly, Raymond P; Kotenko, Sergei V; Fitzgerald-Bocarsly, Patricia

2012-01-01

Plasmacytoid dendritic cells (pDC) are rare cells found in peripheral blood and lymphoid tissues. pDC are considered to be “professional” type I interferon (IFN) producing cells and produce 10–100-fold more IFN-α than other cell types in response to enveloped viruses or synthetic TLR-7 and -9 agonists. In this study, purified pDC were found to express high levels of IFN-λ receptor mRNA as well as cell-surface IFN-λ receptor. We have developed intracellular flow cytometry assays using antibodies to IFN-λ1/3 or -λ2 to assess the expression of IFN-λ proteins by pDC. We observed that a subset of human pDC expresses only intracellular IFN-α while another subset produces both IFN-α and IFN-λ after stimulation with virus or the TLR9 agonist, CpGA; the cells that co-expressed IFN-α and IFN-λ were the cells with the highest levels of IFN-α expression. Antibody cross-linking of CD4 or BDCA-2 molecules on pDC inhibited both HSV-induced IFN-λ and IFN-α production. Like the production of IFN-α, the HSV-induced IFN-λ production in pDC was mediated through TLR9 and independent of virus replication. Exogenous IFN-λ treatment of pDC resulted in increased virus-induced expression of both IFN-α and IFN-λ. In addition, both exogenous IFN-λ and –α inhibited dexamethasone-induced apoptosis of pDC. We conclude that pDC are major producers of IFN-λ1 and –λ2 in response to viral stimulation and also express functional receptors for this cytokine. Thus, IFN-λ can serve as an autocrine signal to strengthen the antiviral response of pDC by increasing IFN-α and IFN-λ production, resulting in prolonged pDC survival. PMID:22891284

Paramagnetic nanoparticles to track and quantify in vivo immune human therapeutic cells

NASA Astrophysics Data System (ADS)

Aspord, Caroline; Laurin, David; Janier, Marc F.; Mandon, Céline A.; Thivolet, Charles; Villiers, Christian; Mowat, Pierre; Madec, Anne-Marie; Tillement, Olivier; Perriat, Pascal; Louis, Cédric; Bérard, Frédéric; Marche, Patrice N.; Plumas, Joël; Billotey, Claire

2013-11-01

This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies.This study aims to investigate gadolinium-based nanoparticles (Gd-HNP) for in vitro labeling of human plasmacytoid dendritic cells (HuPDC) to allow for in vivo tracking and HuPDC quantifying using magnetic resonance imaging (MRI) following parenteral injection. Human plasmacytoid DC were labeled (LabHuPDC) with fluorescent Gd-HNP (Gd-FITC-HNP) and injected via intraperitoneal and intravenous routes in 4-5 NOD-SCID β2m-/-mice (treated mice = TM). Control mice (CM) were similarly injected with unlabeled HuPDC. In vivo 7 T MRI was performed 24 h later and all spleens were removed in order to measure Gd and fluorescence contents and identify HuPDC. Gd-FITC-HNP efficiently labeled HuPDC (0.05 to 0.1 pg per cell), without altering viability and activation properties. The magnetic resonance (MR) signal was exclusively due to HuPDC. The normalized MR splenic intensity for TM was significantly higher than for CM (p < 0.024), and highly correlated with the spleen Gd content (r = 0.97), and the number of HuPDC found in the spleen (r = 0.94). Gd-FITC-HNP allowed for in vivo tracking and HuPDC quantifying by means of MRI following parenteral injection, with very high sensitivity (<3000 cells per mm3). The safety of these new nanoparticle types must be confirmed via extensive toxicology tests including in vivo stability and biodistribution studies. Corresponding address: Service de Médecine Nucléaire, Hôpital, Nord - CHU Saint-Etienne, Avenue Albert Raimond, 42270 Saint-Priest-en-Jarez, France. E-mail: claire.billotey@chu-st-etienne.fr

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles

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

Long, Ling; Cai, Xiaodong; Guo, Ruomi

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect ofmore » Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region. - Highlights: • MRI-guided focused ultrasound enhances gene transfection into the brain of rats. • Increased Nrf2 expression protects neurons in the rat model of PD. • Nrf2 protects neurons in PD by inhibiting ROS production.« less

The switch from fermentation to respiration in Saccharomyces cerevisiae is regulated by the Ert1 transcriptional activator/repressor.

PubMed

Gasmi, Najla; Jacques, Pierre-Etienne; Klimova, Natalia; Guo, Xiao; Ricciardi, Alessandra; Robert, François; Turcotte, Bernard

2014-10-01

In the yeast Saccharomyces cerevisiae, fermentation is the major pathway for energy production, even under aerobic conditions. However, when glucose becomes scarce, ethanol produced during fermentation is used as a carbon source, requiring a shift to respiration. This adaptation results in massive reprogramming of gene expression. Increased expression of genes for gluconeogenesis and the glyoxylate cycle is observed upon a shift to ethanol and, conversely, expression of some fermentation genes is reduced. The zinc cluster proteins Cat8, Sip4, and Rds2, as well as Adr1, have been shown to mediate this reprogramming of gene expression. In this study, we have characterized the gene YBR239C encoding a putative zinc cluster protein and it was named ERT1 (ethanol regulated transcription factor 1). ChIP-chip analysis showed that Ert1 binds to a limited number of targets in the presence of glucose. The strongest enrichment was observed at the promoter of PCK1 encoding an important gluconeogenic enzyme. With ethanol as the carbon source, enrichment was observed with many additional genes involved in gluconeogenesis and mitochondrial function. Use of lacZ reporters and quantitative RT-PCR analyses demonstrated that Ert1 regulates expression of its target genes in a manner that is highly redundant with other regulators of gluconeogenesis. Interestingly, in the presence of ethanol, Ert1 is a repressor of PDC1 encoding an important enzyme for fermentation. We also show that Ert1 binds directly to the PCK1 and PDC1 promoters. In summary, Ert1 is a novel factor involved in the regulation of gluconeogenesis as well as a key fermentation gene. Copyright © 2014 by the Genetics Society of America.

Correlation of membrane binding and hydrophobicity to the chaperone-like activity of PDC-109, the major protein of bovine seminal plasma.

PubMed

Sankhala, Rajeshwer S; Damai, Rajani S; Swamy, Musti J

2011-03-08

The major protein of bovine seminal plasma, PDC-109 binds to choline phospholipids present on the sperm plasma membrane upon ejaculation and plays a crucial role in the subsequent events leading to fertilization. PDC-109 also shares significant similarities with small heat shock proteins and exhibits chaperone-like activity (CLA). Although the polydisperse nature of this protein has been shown to be important for its CLA, knowledge of other factors responsible for such an activity is scarce. Since surface exposure of hydrophobic residues is known to be an important factor which modulates the CLA of chaperone proteins, in the present study we have probed the surface hydrophobicity of PDC-109 using bisANS and ANS. Further, effect of phospholipids on the structure and chaperone-like activity of PDC-109 was studied. Presence of DMPC was found to increase the CLA of PDC-109 significantly, which could be due to the considerable exposure of hydrophobic regions on the lipid-protein recombinants, which can interact productively with the nonnative structures of target proteins, resulting in their protection. However, inclusion of DMPG instead of DMPC did not significantly alter the CLA of PDC-109, which could be due to the lower specificity of PDC-109 for DMPG as compared to DMPC. Cholesterol incorporation into DMPC membranes led to a decrease in the CLA of PDC-109-lipid recombinants, which could be attributed to reduced accessibility of hydrophobic surfaces to the substrate protein(s). These results underscore the relevance of phospholipid binding and hydrophobicity to the chaperone-like activity of PDC-109.

The lipid composition modulates the influence of the bovine seminal plasma protein PDC-109 on membrane stability.

PubMed

Tannert, Astrid; Töpfer-Petersen, Edda; Herrmann, Andreas; Müller, Karin; Müller, Peter

2007-10-16

The bovine seminal plasma protein PDC-109 exerts an essential influence on the sperm cell plasma membrane during capacitation. However, by any mechanism, it has to be ensured that this function of the protein on sperm cells is not initiated too early, that is, upon ejaculation when PDC-109 and sperm cells come into first contact, but rather at later stages of sperm genesis in the female genital tract. To answer the question of whether changes of the bovine sperm lipid composition can modulate the effect of PDC-109 on sperm membranes, we have investigated the influence of PDC-109 on the integrity of (i) differently composed lipid vesicles and of (ii) membranes from human red blood cells and bovine spermatozoa. PDC-109 most effectively disturbed lipid membranes composed of choline-containing phospholipids and in the absence of cholesterol. The impact of the protein on lipid vesicles was attenuated in the presence of cholesterol or of noncholine-containing phospholipids, such as phosphatidylethanolamine or phosphatidylserine. An extraction of cholesterol from lipid or biological membranes using methyl-beta-cyclodextrin caused an increased membrane perturbation by PDC-109. Our results argue for a oppositional effect of PDC-109 during sperm cell genesis. We hypothesize that the lipid composition of ejaculated bull sperm cells allows a binding of PDC-109 without leading to an impairment of the plasma membrane. At later stages of sperm cell genesis upon release of cholesterol from sperm membranes, PDC-109 triggers a destabilization of the cells.

The role of FOXO and PPAR transcription factors in diet-mediated inhibition of PDC activation and carbohydrate oxidation during exercise in humans and the role of pharmacological activation of PDC in overriding these changes.

PubMed

Constantin-Teodosiu, Dumitru; Constantin, Despina; Stephens, Francis; Laithwaite, David; Greenhaff, Paul L

2012-05-01

High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We aimed to reveal molecular changes underpinning this process in resting and exercising humans. We also tested whether pharmacological activation of PDC overrides these diet-induced changes. Healthy males consumed a control diet (CD) and on two further occasions an isocaloric high-fat diet (HFD). After each diet, subjects cycled for 60 min after intravenous infusion with saline (CD and HFD) or dichloroacetate (HFD+DCA). Quadriceps muscle biopsies obtained before and after 10 and 60 min of exercise were used to estimate CHO use, PDC activation, and mRNAs associated with insulin, fat, and CHO signaling. Compared with CD, HFD increased resting pyruvate dehydrogenase kinase 2 (PDK2), PDK4, forkhead box class O transcription factor 1 (FOXO1), and peroxisome proliferator-activated receptor transcription factor α (PPARα) mRNA and reduced PDC activation. Exercise increased PDC activation and whole-body CHO use in HFD, but to a lower extent than in CD. Meanwhile PDK4 and FOXO1, but not PPARα or PDK2, mRNA remained elevated. HFD+DCA activated PDC throughout and restored whole-body CHO use during exercise. FOXO1 appears to play a role in HFD-mediated muscle PDK4 upregulation and inhibition of PDC and CHO oxidation in humans. Also, pharmacological activation of PDC restores HFD-mediated inhibition of CHO oxidation during exercise.

Decreased frequency and function of circulating plasmocytoid dendritic cells (pDC) in hepatitis B virus infected humans.

PubMed

Duan, Xue-Zhang; Wang, Min; Li, Han-Wei; Zhuang, Hui; Xu, Dongping; Wang, Fu-Sheng

2004-11-01

The Type 2 precursor plasmacytoid dendritic cells (pDC) represent the most important cell type in antiviral innate immunity. To understand the function of pDC during hepatitis B virus infection, the frequency and function of circulating pDC were analyzed by flow cytometric analysis, and IFN-alpha secretion of total PBMCs was determined by ELISA assay in 25 healthy subjects and 116 patients at various stages of chronic hepatitis B virus infection (CHB). The number of circulating pDC was found to be significantly lower in patients with CHB and associated liver cirrhosis (LC). The ability of PBMCs to secrete IFN-alpha also decreased significantly. There was a corresponding decrease of circulating NK cells and CD8+ T cells. We observed that lamuvidine antiviral therapy restored the number of circulating pDC and there was a reversal of pDC frequency with the control of HBV replication in chronic HBV patients, indicating these subjects are unlikely to be totally immunocompromised. The decrease of pDC was found to be related to nosocomial infections in LC patients. Our results suggest that CHB patients probably have a quantitative and qualitative impairment of circulating pDC or NK cells, which may be associated with HBV persistent infection as well as the nosocomial infections that arise in LC patients.

Identification of PDC-109-like protein(s) in buffalo seminal plasma.

PubMed

Harshan, Hiron M; Sankar, Surya; Singh, L P; Singh, Manish Kumar; Sudharani, S; Ansari, M R; Singh, S K; Majumdar, A C; Joshi, P

2009-10-01

The FN-2 family of seminal plasma proteins represents the major protein fraction of bovine seminal plasma. These proteins also constitute the major seminal plasma proteins fraction in horse, goat and bison seminal plasma and are present in pig, rat, mouse, hamster and human seminal plasma. BSP-A1 and BSP-A2, the predominant proteins of the FN-2 family, are collectively termed as PDC-109. Fn-2 proteins play an important role in fertilization, including sperm capacitation and formation of oviductal sperm reservoirs. Significantly, BSP proteins were also shown to have negative effects in the context of sperm storage. No conclusive evidence for the presence of buffalo seminal plasma protein(s) similar to PDC-109 exists. Studies with buffalo seminal plasma indicated that isolation and identification of PDC-109-like protein(s) from buffalo seminal plasma by conventional methods might be difficult. Thus, antibodies raised against PDC-109 isolated, and purified from cattle seminal plasma, were used for investigating the presence of PDC-109-like protein(s) in buffalo seminal plasma. Buffalo seminal plasma proteins were resolved on SDS-PAGE, blotted to nitro cellulose membranes and probed for the presence of PDC-109-like protein(s) using the PDC-109 antisera raised in rabbits. A distinct immunoreactive band well below the 20-kDa regions indicated the presence of PDC-109-like protein(s) in buffalo seminal plasma.

Relationship between the maxillary transverse dimension and palatally displaced canines: A cone-beam computed tomographic study.

PubMed

Hong, Wei-Hsin; Radfar, Rebecca; Chung, Chun-Hsi

2015-05-01

To examine the relationship between palatally displaced maxillary canines (PDC) and the maxillary transverse dimension using cone-beam computed tomography (CBCT). Thirty-three patients (11 males and 22 females, mean age 18.2 years) with PDC were matched to 66 patients (22 males and 44 females, mean age 18.1 years) without PDC (control) by gender, age, and posterior occlusion. A CBCT image was taken on all the patients prior to any orthodontic treatment. For each patient the maxillary basal bone widths and interdental widths at the maxillary first molars and first and second premolars were measured on axial and coronal sections of CBCT images. In addition, the presence of permanent tooth agenesis and the widths of maxillary incisors were recorded. Similar maxillary transverse dimensions, both skeletally and dentally, were found between the PDC and control groups. In the PDC group, the number of patients with permanent tooth agenesis was six times higher than in the control group. In addition, the maxillary lateral incisors on PDC-affected sides were smaller than those of control group (P < .05). The maxillary transverse dimension, both skeletally and dentally, had no effect on the occurrence of PDC. The higher prevalence of permanent tooth agenesis was found in the PDC group. Moreover, the mean mesiodistal width of maxillary lateral incisors in the PDC group was significantly smaller than in the control group (P < .05).

The bovine seminal plasma protein PDC-109 extracts phosphorylcholine-containing lipids from the outer membrane leaflet.

PubMed

Tannert, Astrid; Kurz, Anke; Erlemann, Karl-Rudolf; Müller, Karin; Herrmann, Andreas; Schiller, Jürgen; Töpfer-Petersen, Edda; Manjunath, Puttaswamy; Müller, Peter

2007-04-01

The bovine seminal plasma protein PDC-109 modulates the maturation of bull sperm cells by removing lipids, mainly phosphatidylcholine and cholesterol, from their cellular membrane. Here, we have characterized the process of extraction of endogenous phospholipids and of their respective analogues. By measuring the PDC-109-mediated release of fluorescent phospholipid analogues from lipid vesicles and from biological membranes (human erythrocytes, bovine epididymal sperm cells), we showed that PDC-109 extracts phospholipids with a phosphorylcholine headgroup mainly from the outer leaflet of these membranes. The ability of PDC-109 to extract endogenous phospholipids from epididymal sperm cells was followed by mass spectrometry, which allowed us to characterize the fatty acid pattern of the released lipids. From these cells, PDC-109 extracted phosphatidylcholine and sphingomyelin that contained an enrichment of mono- and di-unsaturated fatty acids as well as short-chain and lyso-phosphatidylcholine species. Based on the results, a model explaining the phospholipid specificity of PDC-109-mediated lipid release is presented.

Plasmacytoid pre-dendritic cells (pDC): from molecular pathways to function and disease association.

PubMed

Alculumbre, Solana; Raieli, Salvatore; Hoffmann, Caroline; Chelbi, Rabie; Danlos, François-Xavier; Soumelis, Vassili

2018-02-19

Plasmacytoid pre-dendritic cells (pDC) are a specialized DC population with a great potential to produce large amounts of type I interferon (IFN). pDC are involved in the initiation of antiviral immune responses through their interaction with innate and adaptive immune cell populations. In a context-dependent manner, pDC activation can induce their differentiation into mature DC able to induce both T cell activation or tolerance. In this review, we described pDC functions during immune responses and their implication in the clearance or pathogenicity of human diseases during infection, autoimmunity, allergy and cancer. We discuss recent advances in the field of pDC biology and their implication for future studies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Snare coupling of the pre-pectoral pacing lead delivery catheter to the femoral transseptal apparatus for endocardial cardiac resynchronization therapy : mid-term results.

PubMed

Patel, Mehul B; Worley, Seth J

2013-04-01

Limitations imposed by the coronary sinus venous anatomy triggered the transseptal approach for endocardial LV lead placement. The alignment of the interatrial septum (IAS) and its neighborhood anatomy does not favor transseptal puncture from the pre-pectoral area. Locating and advancing a pre-pectoral LV lead delivery catheter (PDC) through an opening created in the IAS via femoral transseptal puncture (FTP) is time consuming and technically difficult. We describe a method where the PDC is snare coupled to the femoral transseptal apparatus (FTA). When the FTA is advanced into the left atrium (LA) the coupled PDC follows. The catheter of a 25-mm loop snare kit is replaced with the PDC (SelectSite®). The snare loop is positioned in the right common iliac vein from the pre-pectoral access. The PDC is coupled to the FTA by advancing the transseptal apparatus through the open snare loop. After conventional FTP, the FTA is withdrawn back into the right atrium (RA) over an extra support wire positioned in the LA. The PDC with open snare loop is pulled over the FTA up to the RA. The PDC is advanced to close the snare loop on the extra support wire immediately distal to the tip of the dilator close to the puncture site. The PDC is deflected to align with the FTA. The snare coupled catheters are gently advanced across the IAS into the LA. The PDC is released from the FTA by advancing the snare and opening the loop; the snare is then removed from the PDC. The PDC is deflected and advanced into the left ventricle (LV). After positioning the 4.1 Fr lumen less LV lead, the PDC is sliced and removed. The PDC snare coupled to the FTA was advanced into the LA in all five patients, however, access was lost during catheter manipulation in the one right-sided case. Endocardial LV lead was successfully positioned in all five patients. Snare coupling the pre-pectoral SelectSite® catheter to the FTA is technically simple, reliable and a safe method for transseptal endocardial LV lead placement for left pre-pectoral implantation.

PDC cutters improve drilling in harsh environments

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

Mensa-Wilmot, G.

2000-02-01

Improvements in polycrystalline diamond compact (PDC) cutter technology have contributed immensely to the industry's acceptance of PDC bits as effective drilling tools. These cutters are being engineered to address the needs and requirements of different drilling programs. Extensive research and developments efforts have been dedicated to the analysis of the diamond table/tungsten carbide interface. The paper describes PDC cutter development, operational challenges, offset performance, and field experiences.

DNA Hairpins Containing the Cytidine Analog Pyrrolo-dC: Structural, Thermodynamic, and Spectroscopic Studies

PubMed Central

Zhang, Xu; Wadkins, Randy M.

2009-01-01

Structures formed by single-strand DNA have become increasingly interesting because of their roles in a number of biological processes, particularly transcription and its regulation. Of particular importance is the fact that antitumor drugs such as Actinomycin D can selectively bind DNA hairpins over fully paired, double-strand DNA. A new fluorescent base analog, pyrrolo-deoxycytidine (PdC), can now be routinely incorporated into single-strand DNA. The fluorescence of PdC is particularly useful for studying the formation of single-strand DNA in regions of double-strand DNA. The fluorescence is quenched when PdC is paired with a complementary guanine residue, and thus is greatly enhanced upon formation of single-strand DNA. Hence, any process that results in melting or opening of DNA strands produces an increase in the fluorescence intensity of this base analog. In this study we measured the structural effects of incorporating PdC into DNA hairpins, and the effect of this incorporation on the binding of the hairpins by a fluorescent analog of the drug Actinomycin D. Two hairpin DNAs were used: one with PdC in the stem (basepaired) and one with PdC in the loop (unpaired). The thermal stability, 7-aminoactinomycin D binding, and three-dimensional structures of PdC incorporated into these DNA hairpins were all quite similar as compared to the hairpins containing an unmodified dC residue. Fluorescence lifetime measurements indicate that two lifetimes are present in PdC, and that the increase in fluorescence of the unpaired PdC residue compared to the basepaired PdC is due to an increase in the contribution of the longer lifetime to the average fluorescence lifetime. Our data indicate that PdC can be used effectively to differentiate paired and unpaired bases in DNA hairpin secondary structures, and should be similarly applicable for related structures such as cruciforms and quadruplexes. Further, our data indicate that PdC can act as a fluorescence resonance energy transfer donor for the fluorescent drug 7-aminoactinomycin D. PMID:19254547

DNA hairpins containing the cytidine analog pyrrolo-dC: structural, thermodynamic, and spectroscopic studies.

PubMed

Zhang, Xu; Wadkins, Randy M

2009-03-04

Structures formed by single-strand DNA have become increasingly interesting because of their roles in a number of biological processes, particularly transcription and its regulation. Of particular importance is the fact that antitumor drugs such as Actinomycin D can selectively bind DNA hairpins over fully paired, double-strand DNA. A new fluorescent base analog, pyrrolo-deoxycytidine (PdC), can now be routinely incorporated into single-strand DNA. The fluorescence of PdC is particularly useful for studying the formation of single-strand DNA in regions of double-strand DNA. The fluorescence is quenched when PdC is paired with a complementary guanine residue, and thus is greatly enhanced upon formation of single-strand DNA. Hence, any process that results in melting or opening of DNA strands produces an increase in the fluorescence intensity of this base analog. In this study we measured the structural effects of incorporating PdC into DNA hairpins, and the effect of this incorporation on the binding of the hairpins by a fluorescent analog of the drug Actinomycin D. Two hairpin DNAs were used: one with PdC in the stem (basepaired) and one with PdC in the loop (unpaired). The thermal stability, 7-aminoactinomycin D binding, and three-dimensional structures of PdC incorporated into these DNA hairpins were all quite similar as compared to the hairpins containing an unmodified dC residue. Fluorescence lifetime measurements indicate that two lifetimes are present in PdC, and that the increase in fluorescence of the unpaired PdC residue compared to the basepaired PdC is due to an increase in the contribution of the longer lifetime to the average fluorescence lifetime. Our data indicate that PdC can be used effectively to differentiate paired and unpaired bases in DNA hairpin secondary structures, and should be similarly applicable for related structures such as cruciforms and quadruplexes. Further, our data indicate that PdC can act as a fluorescence resonance energy transfer donor for the fluorescent drug 7-aminoactinomycin D.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

PubMed

Schütz, C; Inselmann, S; Sausslele, S; Dietz, C T; Mu Ller, M C; Eigendorff, E; Brendel, C A; Metzelder, S K; Bru Mmendorf, T H; Waller, C; Dengler, J; Goebeler, M E; Herbst, R; Freunek, G; Hanzel, S; Illmer, T; Wang, Y; Lange, T; Finkernagel, F; Hehlmann, R; Huber, M; Neubauer, A; Hochhaus, A; Guilhot, J; Xavier Mahon, F; Pfirrmann, M; Burchert, A

2017-04-01

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86 + pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86 + pDC (n=12). This suggested that low CD86 + pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6-47.9) for patients with >95 CD86 + pDC per 10 5 lymphocytes, but 70.0% (95% CI 59.3-78.3) for patients with <95 CD86 + pDC (hazard ratio (HR) 3.4, 95% - CI: 1.9-6.0; P<0.0001). Moreover, only patients with <95 CD86 + pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1-0.8; P=0.0263). High CD86 + pDC counts significantly correlated with leukemia-specific CD8 + T - cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21-0.92; P=0.0098). Our data demonstrate that CML patients with high CD86 + pDC counts have a higher risk of relapse after TKI discontinuation.

Correlation of Membrane Binding and Hydrophobicity to the Chaperone-Like Activity of PDC-109, the Major Protein of Bovine Seminal Plasma

PubMed Central

Sankhala, Rajeshwer S.; Damai, Rajani S.; Swamy, Musti J.

2011-01-01

The major protein of bovine seminal plasma, PDC-109 binds to choline phospholipids present on the sperm plasma membrane upon ejaculation and plays a crucial role in the subsequent events leading to fertilization. PDC-109 also shares significant similarities with small heat shock proteins and exhibits chaperone-like activity (CLA). Although the polydisperse nature of this protein has been shown to be important for its CLA, knowledge of other factors responsible for such an activity is scarce. Since surface exposure of hydrophobic residues is known to be an important factor which modulates the CLA of chaperone proteins, in the present study we have probed the surface hydrophobicity of PDC-109 using bisANS and ANS. Further, effect of phospholipids on the structure and chaperone-like activity of PDC-109 was studied. Presence of DMPC was found to increase the CLA of PDC-109 significantly, which could be due to the considerable exposure of hydrophobic regions on the lipid-protein recombinants, which can interact productively with the nonnative structures of target proteins, resulting in their protection. However, inclusion of DMPG instead of DMPC did not significantly alter the CLA of PDC-109, which could be due to the lower specificity of PDC-109 for DMPG as compared to DMPC. Cholesterol incorporation into DMPC membranes led to a decrease in the CLA of PDC-109-lipid recombinants, which could be attributed to reduced accessibility of hydrophobic surfaces to the substrate protein(s). These results underscore the relevance of phospholipid binding and hydrophobicity to the chaperone-like activity of PDC-109. PMID:21408153

Patient-Doctor Contact Interval and Clinical Outcomes in Continuous Ambulatory Peritoneal Dialysis Patients.

PubMed

Yi, Chunyan; Guo, Qunying; Lin, Jianxiong; Li, Jianying; Yu, Xueqing; Yang, Xiao

2017-01-01

The optimal patient-doctor contact (PDC) interval remains unknown in peritoneal dialysis (PD) patients. The aim was to investigate the association between PDC interval and clinical outcomes in continuous ambulatory PD (CAPD) patients. In this retrospective cohort study, CAPD patients who resided in Guangzhou city between January 2006 and December 2012 were included. According to receiver operating characteristic curve analysis, all patients were classified as high (PDC interval ≤2 months) and low (PDC interval >2 months) PDC frequency groups. Biochemical data, clinical events, and clinical outcomes during the follow-up period were compared. Of 433 CAPD patients, the mean age was 51.3 ± 15.7 years, 54.3% of patients were male, and 29.1% with diabetes. The median vintage of PD was 45.8 (26.3-69.1) months. Patients with high PDC frequency (n = 233) had better patient-survival rates (99.6, 87.7, and 76.5% vs. 92.7, 76.5, and 58.7% at 1, 3, and 5 years; p < 0.001), lower peritonitis rate (0.17 vs. 0.23 episodes per patient-year; p < 0.001), and hospitalization rate (0.49 vs. 0.67 episodes per patient-year; p < 0.001) than those in the low PDC frequency group (n = 200). After adjustment for confounders, PDC interval of no more than 2 months was independently associated with better patient survival (hazard ratio 0.60, 95% CI 0.42-0.86, p = 0.006). A PDC interval of 2 months or less was associated with better clinical outcomes in CAPD patients. This indicates that a shorter PDC interval should be encouraged for them to achieve better clinical outcomes. © 2017 S. Karger AG, Basel.

PDC-bit performance under simulated borehole conditions

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

Anderson, E.E.; Azar, J.J.

1993-09-01

Laboratory drilling tests were used to investigate the effects of pressure on polycrystalline-diamond-compact (PDC) drill-bit performance. Catoosa shale core samples were drilled with PDC and roller-cone bits at up to 1,750-psi confining pressure. All tests were conducted in a controlled environment with a full-scale laboratory drilling system. Test results indicate, that under similar operating conditions, increases in confining pressure reduce PDC-bit performance as much as or more than conventional-rock-bit performance. Specific energy calculations indicate that a combination of rock strength, chip hold-down, and bit balling may have reduced performance. Quantifying the degree to which pressure reduces PDC-bit performance will helpmore » researchers interpret test results and improve bit designs and will help drilling engineers run PDC bits more effectively in the field.« less

Sidechain biology and the immunogenicity of PDC-E2, the major autoantigen of primary biliary cirrhosis.

PubMed

Mao, Tin K; Davis, Paul A; Odin, Joseph A; Coppel, Ross L; Gershwin, M Eric

2004-12-01

The E2 component of mitochondrial pyruvate dehydrogenase complex (PDC-E2) is the immunodominant autoantigen of primary biliary cirrhosis. Whereas lipoylation of PDC-E2 is essential for enzymatic activity and predominates under normal conditions, other biochemical systems exist that also target the lysine residue, including acylation of fatty acids or xenobiotics and ubiquitinylation. More importantly, the immunogenicity can be affected by derivatization of the lysine residue, as the recognition of lipoylated PDC-E2 by patient autoantibodies is enhanced compared with octanoylated PDC-E2. Furthermore, our laboratory has shown that various xenobiotic modifications of a peptide representing the immunodominant region of PDC-E2 are immunoreactive against patient sera. The only purported regulatory system that prevents the accumulation of potentially autoreactive PDC-E2 is glutathionylation, in which the lysine-lipoic acid moiety is further modified with glutathione during apoptosis. Interestingly, this system is found in several cell lines, including HeLa, Jurkat, and Caco-2 cells, but not in cholangiocytes and salivary gland epithelial cells, both of which are targets for destruction in primary biliary cirrhosis. Hence, the failure of this or other regulatory system(s) may overwhelm the immune system with immunogenic PDC-E2 that can initiate the breakdown of tolerance in a genetically susceptible individual. In this review the authors survey the data available on the biochemical life of PDC-E2, with particular emphasis on the lysine residue and its known interactions with machinery involved in various posttranslational modifications.

Application of microalgae hydrolysate as a fermentation medium for microbial production of 2-pyrone 4,6-dicarboxylic acid.

PubMed

Htet, April N; Noguchi, Mana; Ninomiya, Kazuaki; Tsuge, Yota; Kuroda, Kosuke; Kajita, Shinya; Masai, Eiji; Katayama, Yoshihiro; Shikinaka, Kazuhiro; Otsuka, Yuichiro; Nakamura, Masaya; Honda, Ryo; Takahashi, Kenji

2018-06-01

Actual biomass of microalgae was tested as a fermentation substrate for microbial production of 2-pyrone 4,6-dicarboxylic acid (PDC). Acid-hydrolyzed green microalgae Chlorella emersonii (algae hydrolysate) was diluted to adjust the glucose concentration to 2 g/L and supplemented with the nutrients of Luria-Bertani (LB) medium (tryptone 10 g/L and yeast extract 5 g/L). When the algae hydrolysate was used as a fermentation source for recombinant Escherichia coli producing PDC, 0.43 g/L PDC was produced with a yield of 20.1% (mol PDC/mol glucose), whereas 0.19 g/L PDC was produced with a yield of 8.6% when LB medium supplemented with glucose was used. To evaluate the potential of algae hydrolysate alone as a fermentation medium for E. coli growth and PDC production, the nutrients of LB medium were reduced from the algae hydrolysate medium. Interestingly, 0.17 g/L PDC was produced even without additional nutrient, which was comparable to the case using pure glucose medium with nutrients of LB medium. When using a high concentration of hydrolysate without additional nutrients, 1.22 g/L PDC was produced after a 24-h cultivation with the yield of 16.1%. Overall, C. emersonii has high potential as cost-effective fermentation substrate for the microbial production of PDC. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Resolving Phenylalanine Metabolism Sheds Light on Natural Synthesis of Penicillin G in Penicillium chrysogenum

PubMed Central

Veiga, Tânia; Solis-Escalante, Daniel; Romagnoli, Gabriele; ten Pierick, Angela; Hanemaaijer, Mark; Deshmuhk, Amit; Wahl, Aljoscha; Pronk, Jack T.

2012-01-01

The industrial production of penicillin G by Penicillium chrysogenum requires the supplementation of the growth medium with the side chain precursor phenylacetate. The growth of P. chrysogenum with phenylalanine as the sole nitrogen source resulted in the extracellular production of phenylacetate and penicillin G. To analyze this natural pathway for penicillin G production, chemostat cultures were switched to [U-13C]phenylalanine as the nitrogen source. The quantification and modeling of the dynamics of labeled metabolites indicated that phenylalanine was (i) incorporated in nascent protein, (ii) transaminated to phenylpyruvate and further converted by oxidation or by decarboxylation, and (iii) hydroxylated to tyrosine and subsequently metabolized via the homogentisate pathway. The involvement of the homogentisate pathway was supported by the comparative transcriptome analysis of P. chrysogenum cultures grown with phenylalanine and with (NH4)2SO4 as the nitrogen source. This transcriptome analysis also enabled the identification of two putative 2-oxo acid decarboxylase genes (Pc13g9300 and Pc18g01490). cDNAs of both genes were cloned and expressed in the 2-oxo-acid-decarboxylase-free Saccharomyces cerevisiae strain CEN.PK711-7C (pdc1 pdc5 pdc6Δ aro10Δ thi3Δ). The introduction of Pc13g09300 restored the growth of this S. cerevisiae mutant on glucose and phenylalanine, thereby demonstrating that Pc13g09300 encodes a dual-substrate pyruvate and phenylpyruvate decarboxylase, which plays a key role in an Ehrlich-type pathway for the production of phenylacetate in P. chrysogenum. These results provide a basis for the metabolic engineering of P. chrysogenum for the production of the penicillin G side chain precursor phenylacetate. PMID:22158714

Auxin production by the plant trypanosomatid Phytomonas serpens and auxin homoeostasis in infected tomato fruits.

PubMed

Ienne, Susan; Freschi, Luciano; Vidotto, Vanessa F; De Souza, Tiago A; Purgatto, Eduardo; Zingales, Bianca

2014-09-01

Previously we have characterized the complete gene encoding a pyruvate decarboxylase (PDC)/indolepyruvate decarboxylase (IPDC) of Phytomonas serpens, a trypanosomatid highly abundant in tomato fruits. Phylogenetic analyses indicated that the clade that contains the trypanosomatid protein behaves as a sister group of IPDCs of γ-proteobacteria. Since IPDCs are key enzymes in the biosynthesis of the plant hormone indole-3-acetic acid (IAA), the ability for IAA production by P. serpens was investigated. Similar to many microorganisms, the production of IAA and related indolic compounds, quantified by high performance liquid chromatography, increased in P. serpens media in response to amounts of tryptophan. The auxin functionality was confirmed in the hypocotyl elongation assay. In tomato fruits inoculated with P. serpens the concentration of free IAA had no significant variation, whereas increased levels of IAA-amide and IAA-ester conjugates were observed. The data suggest that the auxin produced by the flagellate is converted to IAA conjugates, keeping unaltered the concentration of free IAA. Ethanol also accumulated in P. serpens-conditioned media, as the result of a PDC activity. In the article we discuss the hypothesis of the bifunctionality of P. serpens PDC/IPDC and provide a three-dimensional model of the enzyme.

Effect of pH in a Pd-based ethanol membraneless air breathing nanofluidic fuel cell with flow-through electrodes

NASA Astrophysics Data System (ADS)

López-Rico, C. A.; Galindo-de-la-Rosa, J.; Ledesma-García, J.; Arriaga, L. G.; Guerra-Balcázar, M.; Arjona, N.

2015-12-01

In this work, a nanofluidic fuel cell (NFC) in which streams flow through electrodes was used to investigate the role of pH in the cell performance using ethanol as fuel and two Pd nanoparticles as electrocatalysts: one commercially available (Pd/C from ETEK) and other synthesized using ionic liquids (Pd/C IL). The cell performances for both electrocatalysts in acid/acid (anodic/cathodic) streams were of 18.05 and 9.55 mW cm-2 for Pd/C ETEK and Pd/C IL. In alkaline/alkaline streams, decrease to 15.94 mW cm-2 for Pd/C ETEK and increase to 15.37 mW cm-2 for Pd/C IL. In alkaline/acidic streams both electrocatalysts showed similar cell voltages (up to 1 V); meanwhile power densities were of 87.6 and 99.4 mW cm-2 for Pd/C ETEK and Pd/C IL. The raise in cell performance can be related to a decrease in activation losses, the combined used of alkaline and acidic streams and these high values compared with flow-over fuel cells can be related to the enhancement of the cathodic mass transport by using three dimensional porous electrodes and two sources of oxygen: from air and from a saturated solution.

Enhanced optical and electrochemical properties of polyaniline/cobalt oxide nano composite

NASA Astrophysics Data System (ADS)

Niranjana, M.; Yesappa, L.; Ashokkumar, S. P.; Vijeth, H.; Basappa, M.; Devendrappa, H.

2018-05-01

Polyaniline and its composites at different wt. % of Cobalt oxide nano (PDC1, PDC2 and PDC5) were prepared by in-situ chemical reaction method The optical property was carried out using UV-Vis. Absorption Spectroscopy. The electrochemical property like cyclic voltammetry and galvonostatic charging-discharging was carried out for PANI and PDC nanocomposite electrode materials. A specific capacitance of 212.08 F/g and 336.41 F/g with scan rates 100 and 200 mV/s at 0.4 A/g current density respectively. These results are suggesting PDC composite is a prominent candidate for supercapacitor properties applications.

Plasmacytoid Dendritic Cells Promote Host Defense Against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway

PubMed Central

Davidson, Sophia; Kaiko, Gerard; Loh, Zhixuan; Lalwani, Amit; Zhang, Vivian; Spann, Kirsten; Foo, Shen Yun; Hansbro, Nicole; Uematsu, Satoshi; Akira, Shizuo; Matthaei, Klaus I.; Rosenberg, Helene F.; Foster, Paul S.; Phipps, Simon

2012-01-01

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants. In human infants, plasmacytoid dendritic cells (pDC) are recruited to the nasal compartment during infection and initiate host defense through the secretion of type I IFN, IL-12 and IL-6. However, RSV-infected pDCs are refractory to TLR7-mediated activation. Here, we used the rodent-specific pathogen, pneumonia virus of mice (PVM), to determine the contribution of pDC and TLR7-signaling to the development of the innate inflammatory and early adaptive immune response. In wild-type (WT) but not TLR7- or myeloid differentiation protein 88 (MyD88)-deficient mice, PVM inoculation led to a marked infiltration of pDCs and increased expression of type I, II and III IFNs. The delayed induction of IFNs in the absence of TLR7 or MyD88 was associated with a diminished innate inflammatory response and augmented virus recovery from lung tissue. In the absence of TLR7, PVM-specific CD8+ T cell cytokine production was abrogated. The adoptive transfer of TLR7-sufficient but not TLR7-deficient pDC to TLR7-gene-deleted mice recapitulated the antiviral responses observed in WT mice and promoted virus clearance. In summary, TLR7-mediated signaling by pDC is required for appropriate innate responses to acute pneumovirus infection. It is conceivable that as-yet-unidentified defects in the TLR7 signaling pathway may be associated with elevated levels of RSV-associated morbidity and mortality among otherwise healthy human infants. PMID:21482736

Plasmacytoid Dendritic Cells Die by the CD8 T Cell-Dependent Perforin Pathway during Acute Nonviral Inflammation.

PubMed

Mossu, Adrien; Daoui, Anna; Bonnefoy, Francis; Aubergeon, Lucie; Saas, Philippe; Perruche, Sylvain

2016-09-01

Regulation of the inflammatory response involves the control of dendritic cell survival. To our knowledge, nothing is known about the survival of plasmacytoid dendritic cells (pDC) in such situation. pDC are specialized in type I IFN (IFN-I) secretion to control viral infections, and IFN-I also negatively regulate pDC survival during the course of viral infections. In this study, we asked about pDC behavior in the setting of virus-free inflammation. We report that pDC survival was profoundly reduced during different nonviral inflammatory situations in the mouse, through a mechanism independent of IFN-I and TLR signaling. Indeed, we demonstrated that during inflammation, CD8(+) T cells induced pDC apoptosis through the perforin pathway. The data suggest, therefore, that pDC have to be turned down during ongoing acute inflammation to not initiate autoimmunity. Manipulating CD8(+) T cell response may therefore represent a new therapeutic opportunity for the treatment of pDC-associated autoimmune diseases, such as lupus or psoriasis. Copyright © 2016 by The American Association of Immunologists, Inc.

DOD Inventory of Contracted Services: Actions Needed to Help Ensure Inventory Data Are Complete and Accurate

DTIC Science & Technology

2015-11-01

for Personnel and Readiness NAVSEA Naval Sea Systems Command OFPP Office of Federal Procurement Policy OMB Office of Management and Budget PDC ...Documentation of Contractors ( PDC ) process is delegated to the manpower and programing functions at the commands. The PDC process collects information from...review results. Army’s PDC tool, used to inform the inventory review, tracks by location and functional requirement—such as administrative or

Proper nozzle location, bit profile, and cutter arrangement affect PDC-bit performance significantly

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

Garcia-Gavito, D.; Azar, J.J.

1994-09-01

During the past 20 years, the drilling industry has looked to new technology to halt the exponentially increasing costs of drilling oil, gas, and geothermal wells. This technology includes bit design innovations to improve overall drilling performance and reduce drilling costs. These innovations include development of drag bits that use PDC cutters, also called PDC bits, to drill long, continuous intervals of soft to medium-hard formations more economically than conventional three-cone roller-cone bits. The cost advantage is the result of higher rates of penetration (ROP's) and longer bit life obtained with the PDC bits. An experimental study comparing the effectsmore » of polycrystalline-diamond-compact (PDC)-bit design features on the dynamic pressure distribution at the bit/rock interface was conducted on a full-scale drilling rig. Results showed that nozzle location, bit profile, and cutter arrangement are significant factors in PDC-bit performance.« less

Interaction of mammalian seminal plasma protein PDC-109 with cholesterol: implications for a putative CRAC domain.

PubMed

Scolari, Silvia; Müller, Karin; Bittman, Robert; Herrmann, Andreas; Müller, Peter

2010-10-26

Seminal plasma proteins of the fibronectin type II (Fn2) family modulate mammalian spermatogenesis by triggering the release of the lipids phosphatidylcholine and cholesterol from sperm cells. Whereas the specific interaction of these proteins with phosphatidylcholine is well-understood, their selectivity for cholesterol is unknown. To characterize the interaction between the bovine Fn2 protein PDC-109 and cholesterol, we have investigated the effect of PDC-109 on the dynamics of fluorescent cholesterol analogues in lipid vesicles by time-resolved fluorescence anisotropy. The data show that PDC-109 decreases the rotational mobility of cholesterol within the membrane and that the extent of this impact depends on the cholesterol structure, indicating a specific influence of PDC-109 on cholesterol. We propose that the cholesterol recognition/interaction amino acid consensus (CRAC) regions of PDC-109 are involved in the interaction with cholesterol.

Plasmacytoid Dendritic Cells: Neglected Regulators of the Immune Response to Staphylococcus aureus

PubMed Central

Bekeredjian-Ding, Isabelle; Greil, Johann; Ammann, Sandra; Parcina, Marijo

2014-01-01

Plasmacytoid dendritic cells (pDC) are a rare subset of leukocytes equipped with Fcγ and Fcε receptors, which exert contrary effects on sensing of microbial nucleic acids by endosomal Toll-like receptors. In this article, we explain how pDC contribute to the immune response to Staphylococcus aureus. Under normal circumstances the pDC participates in the memory response to the pathogen: pDC activation is initiated by uptake of staphylococcal immune complexes with IgG or IgE. However, protein A-expressing S. aureus strains additionally trigger pDC activation in the absence of immunoglobulin. In this context, staphylococci exploit the pDC to induce antigen-independent differentiation of IL-10 producing plasmablasts, an elegant means to propagate immune evasion. We further discuss the role of type I interferons in infection with S. aureus and the implications of these findings for the development of immune based therapies and vaccination. PMID:24904586

Overexpression of miR-183/-96/-182 triggers neuronal cell fate in Human Retinal Pigment Epithelial (hRPE) cells in culture.

PubMed

Davari, Maliheh; Soheili, Zahra-Soheila; Samiei, Shahram; Sharifi, Zohreh; Pirmardan, Ehsan Ranaei

2017-01-29

miR-183 cluster, composed of miR-183/-96/-182 genes, is highly expressed in the adult retina, particularly in photoreceptors. It involves in development, maturation and normal function of neuroretina. Ectopic overexpression of miR-183/-96/-182 genes was performed to assess reprogramming of hRPE cells. They were amplified from genomic DNA and cloned independently or in tandem configuration into pAAV.MCS vector. hRPE cells were then transfected with the recombinant constructs. Real-Time PCR was performed to measure the expression levels of miR-183/-96/-182 and that of several retina-specific neuronal genes such as OTX2, NRL, PDC and DCT. The transfected cells also were immunocytochemically examined for retina-specific neuronal markers, including Rhodopsin, red opsin, CRX, Thy1, CD73, recoverin and PKCα, to determine the cellular fate of the transfected hRPE cells. Data showed that upon miR-183/-96/-182 overexpression in hRPE cultures, the expression of neuronal genes including OTX2, NRL, PDC and DCT was also upregulated. Moreover, miR-183 cluster-treated hRPE cells were immunoreactive for neuronal markers such as Rhodopsin, red opsin, CRX and Thy1. Both transcriptional and translational upregulation of neuronal genes in miR-183 cluster-treated hRPE cells suggests that in vitro overexpression of miR-183 cluster could trigger reprogramming of hRPE cells to retinal neuron fate. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of Gene Expression and Proteomic Profiles of Clonal Genotypes from Theobroma cacao Subjected to Soil Flooding

PubMed Central

Bertolde, Fabiana Z.; Almeida, Alex-Alan F.; Pirovani, Carlos P.

2014-01-01

Soil flooding causes changes in gene transcription, synthesis and degradation of proteins and cell metabolism. The main objective of this study was to understand the biological events of Theobroma cacao during soil flooding-induced stress, using the analyses of gene expression and activity of key enzymes involved in fermentation, as well as the identification of differentially expressed proteins by mass spectrometry in two contrasting genotypes for flooding tolerance (tolerant - TSA-792 and susceptible - TSH-774). Soil anoxia caused by flooding has led to changes in the expression pattern of genes associated with the biosynthesis of alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC) and lactate dehydrogenase (LDH) in leaves and roots of the two evaluated genotypes. Significant differences were observed between the enzyme activities of the two genotypes. Leaves and roots of the TSA-792 genotype showed higher ADH activity as compared to the TSH-774 genotype, whereas the activities of PDC and LDH have varied over the 96 h of soil flooding, being higher for TSA-792 genotype, at the initial stage, and TSH-774 genotype, at the final stage. Some of the identified proteins are those typical of the anaerobic metabolism-involved in glycolysis and alcoholic fermentation-and different proteins associated with photosynthesis, protein metabolism and oxidative stress. The ability to maintain glycolysis and induce fermentation was observed to play an important role in anoxia tolerance in cacao and may also serve to distinguish tolerant and susceptible genotypes in relation to this stressor. PMID:25289700

Analysis of gene expression and proteomic profiles of clonal genotypes from Theobroma cacao subjected to soil flooding.

PubMed

Bertolde, Fabiana Z; Almeida, Alex-Alan F; Pirovani, Carlos P

2014-01-01

Soil flooding causes changes in gene transcription, synthesis and degradation of proteins and cell metabolism. The main objective of this study was to understand the biological events of Theobroma cacao during soil flooding-induced stress, using the analyses of gene expression and activity of key enzymes involved in fermentation, as well as the identification of differentially expressed proteins by mass spectrometry in two contrasting genotypes for flooding tolerance (tolerant - TSA-792 and susceptible - TSH-774). Soil anoxia caused by flooding has led to changes in the expression pattern of genes associated with the biosynthesis of alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC) and lactate dehydrogenase (LDH) in leaves and roots of the two evaluated genotypes. Significant differences were observed between the enzyme activities of the two genotypes. Leaves and roots of the TSA-792 genotype showed higher ADH activity as compared to the TSH-774 genotype, whereas the activities of PDC and LDH have varied over the 96 h of soil flooding, being higher for TSA-792 genotype, at the initial stage, and TSH-774 genotype, at the final stage. Some of the identified proteins are those typical of the anaerobic metabolism-involved in glycolysis and alcoholic fermentation-and different proteins associated with photosynthesis, protein metabolism and oxidative stress. The ability to maintain glycolysis and induce fermentation was observed to play an important role in anoxia tolerance in cacao and may also serve to distinguish tolerant and susceptible genotypes in relation to this stressor.

The In-Situ One-Step Synthesis of a PDC Macromolecular Pro-Drug and the Fabrication of a Novel Core-Shell Micell.

PubMed

Yu, Cui-Yun; Yang, Sa; Li, Zhi-Ping; Huang, Can; Ning, Qian; Huang, Wen; Yang, Wen-Tong; He, Dongxiu; Sun, Lichun

2016-01-01

The development of slow release nano-sized carriers for efficient antineoplastic drug delivery with a biocompatible and biodegradable pectin-based macromolecular pro-drug for tumor therapy has been reported in this study. Pectin-doxorubicin conjugates (PDC), a macromolecular pro-drug, were prepared via an amide condensation reaction, and a novel amphiphilic core-shell micell based on a PDC macromolecular pro-drug (PDC-M) was self-assembled in situ, with pectin as the hydrophilic shell and doxorubicin (DOX) as the hydrophobic core. Then the chemical structure of the PDC macromolecular pro-drug was identified by both Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy ((1)H-NMR), and proved that doxorubicin combined well with the pectin and formed macromolecular pro-drug. The PDC-M were observed to have an unregularly spherical shape and were uniform in size by scanning electron microscopy (SEM). The average particle size of PDC-M, further measured by a Zetasizer nanoparticle analyzer (Nano ZS, Malvern Instruments), was about 140 nm. The encapsulation efficiency and drug loading were 57.82% ± 3.7% (n = 3) and 23.852% ±2.3% (n = 3), respectively. The in vitro drug release behaviors of the resulting PDC-M were studied in a simulated tumor environment (pH 5.0), blood (pH 7.4) and a lysosome media (pH 6.8), and showed a prolonged slow release profile. Assays for antiproliferative effects and flow cytometry of the resulting PDC-M in HepG2 cell lines demonstrated greater properties of delayed and slow release as compared to free DOX. A cell viability study against endothelial cells further revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX. Hemolysis activity was investigated in rabbits, and the results also demonstrated that the PDC-M has greater compatibility in comparison with free DOX. This shows that the resulting PDC-M can ameliorate the hydrophobicity of free DOX. This work proposes a novel strategy for in-situ one-step synthesis of macromolecular pro-drugs and fabrication of a core-shell micelle, demonstrating great potential for cancer chemotherapy.

Modeling and Analysis of Gated, Pulsed RFI and Its Effect on GPS Receivers: Analysis of Average Cycle Slip Rate and Average Bit Error Probability

DTIC Science & Technology

2014-04-01

as a function of the pulse duty cycle PDC is [1]: ∆C/N0 = 20 log(1 − PDC ) (1) PDC , PW × PRF (2) where PW represents the pulse width (sec) and PRF is...corresponding degradation in C/N0 should now be modeled as ∆C/N0 = 20 log(1 − PDCLIM) (3) PDCLIM , PDC τobs TTC . (4) The degradation model of Eqn. 3 and 4...cycle that is the product of the duty cycle of the pulsed waveform ( PDC ) and the duty cycle of the of the gating waveform (τobs/TTC). While such a model

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

PubMed

Sepehry, Amir A; Lee, Philip E; Hsiung, Ging-Yuek R; Beattie, B Lynn; Feldman, Howard H; Jacova, Claudia

2017-01-01

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis.

PubMed

Bellucci, Roberto; Oertelt, Sabine; Gallagher, Meagan; Li, Sigui; Zorn, Emmanuel; Weller, Edie; Porcheray, Fabrice; Alyea, Edwin P; Soiffer, Robert J; Munshi, Nikhil C; Gershwin, M Eric; Ritz, Jerome

2007-03-01

A unique characteristic of the autoimmune liver disease primary biliary cirrhosis (PBC) is the presence of high-titer and extremely specific autoantibodies to the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Autoantibodies to PDC-E2 antigen have only been detected in patients with disease or in those who subsequently develop PBC. One exception has been a subgroup of patients with multiple myeloma (MM) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received donor lymphocyte infusions (DLIs) after transplantation. These patients developed high-titer antibodies to a variety of myeloma-associated antigens, including PDC-E2, coincident with rejection of myeloma cells in vivo. To examine the specificity of autoantibodies to PDC in these patients, we screened sera from patients with MM, chronic leukemias, monoclonal gammopathy of unknown significance (MGUS), PBC, and healthy donors. Three of 11 patients with MM (27%) and 2 of 6 patients with chronic leukemias (33%) developed anti-PDC-E2 antibodies in association with DLI response; 2 of 12 (17%) patients in the MGUS pretreatment control population also had detectable anti-PDC responses. Interestingly, the epitope specificity of these PDC-E2 autoantibodies was distinctive, suggesting that the mechanisms leading to loss of tolerance in the transplantation patients are distinct from PBC.

Pyroclastic density current dynamics and associated hazards at ice-covered volcanoes

NASA Astrophysics Data System (ADS)

Dufek, J.; Cowlyn, J.; Kennedy, B.; McAdams, J.

2015-12-01

Understanding the processes by which pyroclastic density currents (PDCs) are emplaced is crucial for volcanic hazard prediction and assessment. Snow and ice can facilitate PDC generation by lowering the coefficient of friction and by causing secondary hydrovolcanic explosions, promoting remobilisation of proximally deposited material. Where PDCs travel over snow or ice, the reduction in surface roughness and addition of steam and meltwater signficantly changes the flow dynamics, affecting PDC velocities and runout distances. Additionally, meltwater generated during transit and after the flow has come to rest presents an immediate secondary lahar hazard that can impact areas many tens of kilometers beyond the intial PDC. This, together with the fact that deposits emplaced on ice are rarely preserved means that PDCs over ice have been little studied despite the prevalence of summit ice at many tall stratovolcanoes. At Ruapehu volcano in the North Island of New Zealand, a monolithologic welded PDC deposit with unusually rounded clasts provides textural evidence for having been transported over glacial ice. Here, we present the results of high-resolution multiphase numerical PDC modeling coupled with experimentaly determined rates of water and steam production for the Ruapehu deposits in order to assess the effect of ice on the Ruapehu PDC. The results suggest that the presence of ice significantly modified the PDC dynamics, with implications for assessing the PDC and associated lahar hazards at Ruapehu and other glaciated volcanoes worldwide.

Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency.

PubMed

Shin, Ha Kyung; Grahame, George; McCandless, Shawn E; Kerr, Douglas S; Bedoyan, Jirair K

2017-11-01

Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidemia in children. Prompt and correct diagnosis of PDC deficiency and differentiating between specific vs generalized, or secondary deficiencies has important implications for clinical management and therapeutic interventions. Both genetic and enzymatic testing approaches are being used in the diagnosis of PDC deficiency. However, the diagnostic efficacy of such testing approaches for individuals affected with PDC deficiency has not been systematically investigated in this disorder. We sought to evaluate the diagnostic sensitivity and variability of the various PDC enzyme assays in females and males at the Center for Inherited Disorders of Energy Metabolism (CIDEM). CIDEM data were filtered by lactic acidosis and functional PDC deficiency in at least one cell/tissue type (blood lymphocytes, cultured fibroblasts or skeletal muscle) identifying 186 subjects (51% male and 49% female), about half were genetically resolved with 78% of those determined to have a pathogenic PDHA1 mutation. Assaying PDC in cultured fibroblasts in cases where the underlying genetic etiology is PDHA1, was highly sensitive irrespective of gender; 97% (95% confidence interval [CI]: 90%-100%) and 91% (95% CI: 82%-100%) in females and males, respectively. In contrast to the fibroblast-based testing, the lymphocyte- and muscle-based testing were not sensitive (36% [95% CI: 11%-61%, p=0.0003] and 58% [95% CI: 30%-86%, p=0.014], respectively) for identifying known PDC deficient females with pathogenic PDHA1 mutations. In males with a known PDHA1 mutation, the sensitivity of the various cell/tissue assays (75% lymphocyte, 91% fibroblast and 88% muscle) were not statistically different, and the discordance frequency due to the specific cell/tissue used for assaying PDC was 0.15±0.11. Based on this data, a practical diagnostic algorithm is proposed accounting for current molecular approaches, enzyme testing sensitivity, and variability due to gender, cell/tissue type used for testing, and successive repeat testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions.

PubMed

Saas, Philippe; Varin, Alexis; Perruche, Sylvain; Ceroi, Adam

2017-01-01

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases, as well as in tumor immune escape mechanisms. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. The kinetics of glycolysis after TLR7/9 triggering may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR. This could explain a delayed glycolysis in mouse PDC. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statin or LXR agonist treatment) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

PubMed Central

Saas, Philippe; Varin, Alexis; Perruche, Sylvain; Ceroi, Adam

2017-01-01

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases, as well as in tumor immune escape mechanisms. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. The kinetics of glycolysis after TLR7/9 triggering may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR. This could explain a delayed glycolysis in mouse PDC. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statin or LXR agonist treatment) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role. PMID:28580131

Directional connectivity of resting state human fMRI data using cascaded ICA-PDC analysis.

PubMed

Silfverhuth, Minna J; Remes, Jukka; Starck, Tuomo; Nikkinen, Juha; Veijola, Juha; Tervonen, Osmo; Kiviniemi, Vesa

2011-11-01

Directional connectivity measures, such as partial directed coherence (PDC), give us means to explore effective connectivity in the human brain. By utilizing independent component analysis (ICA), the original data-set reduction was performed for further PDC analysis. To test this cascaded ICA-PDC approach in causality studies of human functional magnetic resonance imaging (fMRI) data. Resting state group data was imaged from 55 subjects using a 1.5 T scanner (TR 1800 ms, 250 volumes). Temporal concatenation group ICA in a probabilistic ICA and further repeatability runs (n = 200) were overtaken. The reduced data-set included the time series presentation of the following nine ICA components: secondary somatosensory cortex, inferior temporal gyrus, intracalcarine cortex, primary auditory cortex, amygdala, putamen and the frontal medial cortex, posterior cingulate cortex and precuneus, comprising the default mode network components. Re-normalized PDC (rPDC) values were computed to determine directional connectivity at the group level at each frequency. The integrative role was suggested for precuneus while the role of major divergence region may be proposed to primary auditory cortex and amygdala. This study demonstrates the potential of the cascaded ICA-PDC approach in directional connectivity studies of human fMRI.

Histone deacetylase inhibitor valproic acid affects plasmacytoid dendritic cells phenotype and function.

PubMed

Arbez, Jessy; Lamarthée, Baptiste; Gaugler, Béatrice; Saas, Philippe

2014-08-01

Plasmacytoid dendritic cells (PDC) represent a rare subset of dendritic cells specialized in the production of type I IFN in response to microbial pathogens. Recent data suggested that histone deacetylase (HDAC) inhibitors possess potent immunomodulatory properties both in vitro and in vivo. In this study, we assayed the ability of the HDAC inhibitor, valproic acid (VPA), to influence the phenotype and functional properties of human PDC isolated from peripheral blood. We showed that VPA inhibited the production of IFN-α and the proinflammatory cytokines TNF-α and IL-6 by CpG-activated PDC. VPA also affected the phenotype of PDC by reducing the expression of costimulatory molecules induced by CpG activation. Moreover, VPA reduced the capacity of CpG-stimulated PDC to promote CD4(+) T cell proliferation and IFN-γ production, while enhancing the proportion of IL-10 positive T cells. These results suggest that HDAC inhibition by VPA alters essential human PDC functions, highlighting the need for monitoring immune functions in cancer patients receiving HDAC inhibitors, but also making these drugs attractive therapies in inflammatory, and autoimmune diseases implicating PDC. Copyright © 2014 Elsevier GmbH. All rights reserved.

Wear and performance: An experimental study on PDC bits

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

Villa, O.; Azar, J.J.

1997-07-01

Real-time drilling data, gathered under full-scale conditions, was analyzed to determine the influence of cutter dullness on PDC-bit rate of penetration. It was found that while drilling in shale, the cutters` wearflat area was not a controlling factor on rate of penetration; however, when drilling in limestone, wearflat area significantly influenced PDC bit penetration performance. Similarly, the presence of diamond lips on PDC cutters was found to be unimportant while drilling in shale, but it greatly enhanced bit performance when drilling in limestone.

Bovine seminal PDC-109 protein: an overview of biochemical and functional properties.

PubMed

Srivastava, N; Jerome, A; Srivastava, S K; Ghosh, S K; Kumar, Amit

2013-04-01

Although long-term storage of bovine semen is desirable for wider use, successful cryopreservation depends on several factors, including various proteins present in seminal plasma. One such group of proteins, viz. bovine seminal plasma (BSP) proteins represents the major protein fraction in bovine seminal plasma. They constitute three major heparin-binding (HB-) acidic proteins secreted by seminal vesicles, viz. BSP-A1/-A2 (PDC-109), BSP-A3 and BSP-30-kDa. By purification studies it was deduced that PDC-109 is a polypeptide of 109 amino acids and contains two tandem repeating fibronectin type-II (Fn-II) domains, preceded by a 23 residue N-terminal domain. Though BSP-A1 and BSP-A2 are biochemically similar they differ only in glycosylation and their mixture is called PDC-109 or gonadostatins. PDC-109 exists as a polydisperse, multimeric self-associated molecule and possesses multifunctional properties, viz. binding to the surface of plasma membrane of spermatozoa causing conformational change in the sperm surface proteins and enhances motility. Besides binding, PDC-109 protein provokes cholesterol efflux from sperm membrane and promotes sperm reservoir by interacting with oviductal membrane. Interaction of sperm with PDC-109 protein induces sperm capacitation and acrosome reaction. However, prolonged exposure of spermatozoa with free floating PDC-109 protein as during processing for preservation, increases cholesterol efflux from spermatozoa. The efflux of sperm membrane cholesterol and disturbance in cholesterol:phospholipids ratio causes destabilization of plasma membrane thereby inducing cryoinjury to the sperm. In this review, the biochemical, functional properties of PDC-109 protein and its role during semen cryopreservation is summarized. Copyright © 2013 Elsevier B.V. All rights reserved.

The major protein of bovine seminal plasma, PDC-109, is a molecular chaperone.

PubMed

Sankhala, Rajeshwer Singh; Swamy, Musti J

2010-05-11

The major protein of bovine seminal plasma, PDC-109, binds to choline phospholipids on the sperm plasma membrane and induces the efflux of cholesterol and choline phospholipids, which is an important step in sperm capacitation. The high abundance, polydisperse nature and reversibility of thermal unfolding of PDC-109 suggest significant similarities to chaperone-like proteins such as spectrin, alpha-crystallin, and alpha-synuclein. In the present study, biochemical and biophysical approaches were employed to investigate the chaperone-like activity of PDC-109. The effect of various stress factors such as high temperature, chemical denaturant (urea), and acidic pH on target proteins such as lactate dehydrogenase, alcohol dehydrogenase, and insulin were studied in both the presence and absence of PDC-109. The results obtained indicate that PDC-109 exhibits chaperone-like activity, as evidenced by its ability to suppress the nonspecific aggregation of target proteins and direct them into productive folding. Atomic force microscopic studies demonstrate that PDC-109 effectively prevents the fibrillation of insulin, which is of considerable significance since amyloidogenesis has been reported to be a serious problem during sperm maturation in certain species. Binding of phosphorylcholine or high ionic strength in the medium inhibited the chaperone-like activity of PDC-109, suggesting that most likely the aggregation state of the protein is important for the chaperone function. These observations show that PDC-109 functions as a molecular chaperone in vitro, suggesting that it may assist the proper folding of proteins involved in the bovine sperm capacitation pathway. To the best of our knowledge, this is the first study reporting chaperone-like activity of a seminal plasma protein.

Pre-Departure Clearance (PDC): An Analysis of Aviation Safety Reporting System Reports Concerning PDC Related Errors

NASA Technical Reports Server (NTRS)

Montalyo, Michael L.; Lebacqz, J. Victor (Technical Monitor)

1994-01-01

Airlines operating in the United States are required to operate under instrument flight rules (EFR). Typically, a clearance is issued via voice transmission from clearance delivery at the departing airport. In 1990, the Federal Aviation Administration (FAA) began deployment of the Pre-Departure Clearance (PDC) system at 30 U.S. airports. The PDC system utilizes aeronautical datalink and Aircraft Communication and Reporting System (ACARS) to transmit departure clearances directly to the pilot. An objective of the PDC system is to provide an immediate reduction in voice congestion over the clearance delivery frequency. Participating airports report that this objective has been met. However, preliminary analysis of 42 Aviation Safety Reporting System (ASRS) reports has revealed problems in PDC procedures and formatting which have caused errors in the proper execution of the clearance. It must be acknowledged that this technology, along with other advancements on the flightdeck, is adding more responsibility to the crew and increasing the opportunity for error. The present study uses these findings as a basis for further coding and analysis of an additional 82 reports obtained from an ASRS database search. These reports indicate that clearances are often amended or exceptions are added in order to accommodate local ATC facilities. However, the onboard ACARS is limited in its ability to emphasize or highlight these changes which has resulted in altitude and heading deviations along with increases in ATC workload. Furthermore, few participating airports require any type of PDC receipt confirmation. In fact, 35% of all ASRS reports dealing with PDC's include failure to acquire the PDC at all. Consequently, this study examines pilots' suggestions contained in ASRS reports in order to develop recommendations to airlines and ATC facilities to help reduce the amount of incidents that occur.

New PDC bit design reduces vibrational problems

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

Mensa-Wilmot, G.; Alexander, W.L.

1995-05-22

A new polycrystalline diamond compact (PDC) bit design combines cutter layout, load balancing, unsymmetrical blades and gauge pads, and spiraled blades to reduce problematic vibrations without limiting drilling efficiency. Stabilization improves drilling efficiency and also improves dull characteristics for PDC bits. Some PDC bit designs mitigate one vibrational mode (such as bit whirl) through drilling parameter manipulation yet cause or excite another vibrational mode (such as slip-stick). An alternative vibration-reducing concept which places no limitations on the operational environment of a PDC bit has been developed to ensure optimization of the bit`s available mechanical energy. The paper discusses bit stabilization,more » vibration reduction, vibration prevention, cutter arrangement, load balancing, blade layout, spiraled blades, and bit design.« less

A Novel Coordination Polymer Constructed by Hetero-Metal Ions and 2,3-Pyridine Dicarboxylic Acid: Synthesis and Structure of [NiNa2(PDC)2(μ-H2O)(H2O)2] n

NASA Astrophysics Data System (ADS)

Dou, Ming-Yu; Lu, Jing

2017-12-01

A novel coordination polymer containing hetero-metal ions, [NiNa2(PDC)2(μ-H2O)(H2O)2] n , where PDC is 2,3-pyridine dicarboxylate ion, has been synthesized. In the structure, the PDC ligand chelates and bridges two Ni(II) and two Na(I) centers. Two kinds of metal centers are connected by μ4-PDC and μ2-H2O to form 2D coordination layers. Hydrogen bonds between coordination water molecules and carboxylate oxygen atoms further link these 2D coordination layers to form 3D supramolecular network.

Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan

PubMed Central

Hata, Yukiko; Ma, Ning; Yoneda, Misao; Morimoto, Satoru; Okano, Hideyuki; Murayama, Shigeo; Kawanishi, Shosuke; Kuzuhara, Shigeki; Kokubo, Yasumasa

2018-01-01

Objective: The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Methods: Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Results: Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Conclusion: Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC. PMID:29403345

Identification of HLA-A2–restricted CD8+ Cytotoxic T Cell Responses in Primary Biliary Cirrhosis

PubMed Central

Kita, Hiroto; Lian, Zhe-Xiong; Van de Water, Judy; He, Xiao-Song; Matsumura, Shuji; Kaplan, Marshall; Luketic, Velimir; Coppel, Ross L.; Ansari, Aftab A.; Gershwin, M. Eric

2002-01-01

Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4+ and CD8+ T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4+ T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2–restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159–167 of PDC-E2, induces specific MHC class I–restricted CD8+ CTL lines from 10/12 HLA-A2+ PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2–specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2–specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2–specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen–immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease. PMID:11781370

Nitrative Stress and Tau Accumulation in Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC) in the Kii Peninsula, Japan.

PubMed

Hata, Yukiko; Ma, Ning; Yoneda, Misao; Morimoto, Satoru; Okano, Hideyuki; Murayama, Shigeo; Kawanishi, Shosuke; Kuzuhara, Shigeki; Kokubo, Yasumasa

2017-01-01

Objective: The Kii Peninsula of Japan is known to be a high incidence area of amyotrophic lateral sclerosis/parkinsonism-dementia complex (Kii ALS/PDC) with tauopathy. Nitrative stress and oxidative stress on ALS/PDC and their relationship to tau pathology were clarified. Methods: Seven patients with Kii ALS/PDC (3 males and 4 females, average age 70.7 years, 3 with ALS, 2 with ALS with dementia, and 2 with PDC) were analyzed in this study. Five patients with Alzheimer's disease and five normal aged subjects were used as controls. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded temporal lobe sections (the hippocampal area including hippocampus, prosubiculum, subiculum, presubiculum, and parahippocampal gyri) using antibodies to detect phosphorylated tau (anti-AT-8), nitrated guanine (anti-8-NG), anti-iNOS, anti-NFκB, and oxidized guanine (anti-8-OHdG) antibodies. Results: Most hippocampal neurons of Kii ALS/PDC patients were stained with anti-8-NG, anti-iNOS, anti-NFκB, and anti-8-OHdG antibodies and some AT-8 positive neurons were co-stained with anti-8-NG antibody. The numbers of 8-NG positive neurons and 8-OHdG positive neurons were greater than AT-8 positive neurons and the number of 8-NG positive neurons was larger in patients with Kii ALS/PDC than in controls. Conclusion: Nitrative and oxidative stress may take priority over tau accumulation and lead to the neurodegeneration in Kii ALS/PDC.

Parabolic Dish Concentrator (PDC-2) Development

NASA Technical Reports Server (NTRS)

Rafinejad, D.

1984-01-01

The design of the Parabolic Dish Concentrator (PDC-2) is described. The following five subsystems of the concentrator are discussed: (1) reflective surface subsystem, (2) support structure subsystem, (3) foundation, (4) drive subsystem, and (5) electrical and control subsystem. The status of the PDC-2 development project is assessed.

PDC bits break ground with advanced vibration mitigation

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

NONE

1995-10-01

Advancements in PDC bit technology have resulted in the identification and characterization of different types of vibrational modes that historically have limited PDC bit performance. As a result, concepts have been developed that prevent the initiation of vibration and also mitigate its damaging effects once it occurs. This vibration-reducing concept ensures more efficient use of the energy available to a PDC bit performance. As a result, concepts have been developed that prevent the imitation of vibration and also mitigate its damaging effects once it occurs. This vibration-reducing concept ensures more efficient use of the energy available to a PDC bit,more » thereby improving its performance. This improved understanding of the complex forces affecting bit performance is driving bit customization for specific drilling programs.« less

Estimating time-varying drug adherence using electronic records: extending the proportion of days covered (PDC) method.

PubMed

Bijlsma, Maarten J; Janssen, Fanny; Hak, Eelko

2016-03-01

Accurate measurement of drug adherence is essential for valid risk-benefit assessments of pharmacologic interventions. To date, measures of drug adherence have almost exclusively been applied for a fixed-time interval and without considering changes over time. However, patients with irregular dosing behaviour commonly have a different prognosis than patients with stable dosing behaviour. We propose a method, based on the proportion of days covered (PDC) method, to measure time-varying drug adherence and drug dosage using electronic records. We compare a time-fixed PDC method with the time-varying PDC method through detailed examples and through summary statistics of 100 randomly selected patients on statin therapy. We demonstrate that time-varying PDC method better distinguishes an irregularly dosing patient from a stably dosing patient and demonstrate how the time-fixed method can result in a biassed estimate of drug adherence. Furthermore, the time-varying PDC method may be better used to reduce certain types of confounding and misclassification of exposure. The time-varying PDC method may improve longitudinal and time-to-event studies that associate adherence with a clinical outcome or (intervention) studies that seek to describe changes in adherence over time. Copyright © 2015 John Wiley & Sons, Ltd.

Biophysical investigations on the interaction of the major bovine seminal plasma protein, PDC-109, with heparin.

PubMed

Sankhala, Rajeshwer S; Damai, Rajani S; Anbazhagan, V; Kumar, C Sudheer; Bulusu, Gopalakrishnan; Swamy, Musti J

2011-11-10

PDC-109, the major bovine seminal plasma protein, binds to sperm plasma membrane and modulates capacitation in the presence of heparin. In view of this, the PDC-109/heparin interaction has been investigated employing various biophysical approaches. Isothermal titration calorimetric studies yielded the association constant and changes in enthalpy and entropy for the interaction at 25 °C (pH 7.4) as 1.92 (±0.2) × 10(5) M(-1), 18.6 (±1.6) kcal M(-1), and 86.5 (±5.1) cal M(-1) K(-1), respectively, whereas differential scanning calorimetric studies indicated that heparin binding results in a significant increase in the thermal stability of PDC-109. The affinity decreases with increase in pH and ionic strength, consistent with the involvement of electrostatic forces in this interaction. Circular dichroism spectroscopic studies indicated that PDC-109 retains its conformational features even up to 70-75 °C in the presence of heparin, whereas the native protein unfolds at about 55 °C. Atomic force microscopic studies demonstrated that large oligomeric structures are formed upon binding of PDC-109 to heparin, indicating an increase in the local density of the protein, which may be relevant to the ability of heparin to potentiate PDC-109 induced sperm capacitation.

Spermine and spermidine act as chemical chaperones and enhance chaperone-like and membranolytic activities of major bovine seminal plasma protein, PDC-109.

PubMed

Singh, Bhanu Pratap; Saha, Ishita; Nandi, Indrani; Swamy, Musti J

2017-12-02

The major bovine seminal plasma protein, PDC-109, binds to choline phospholipids of the sperm plasma membrane and induces an efflux of cholesterol and choline phospholipids (cholesterol efflux), which is crucial for sperm capacitation. PDC-109 also exhibits chaperone-like activity and protects target proteins against various kinds of stress. Here we show that the polyamines spermine and spermidine, present in high concentration in the seminal plasma of various mammals, increase the ability of PDC-109 to perturb membrane structure as well as its chaperone-like activity. Interestingly, spermine/spermidine alone did not perturb membrane structure but exhibited chaperone-like activity by protecting target proteins against thermal and oxidative stress. When spermine/spermidine was used along with PDC-109, the observed chaperone-like activity was considerably higher than that expected for a simple additive effect, suggesting that PDC-109 and the polyamines act in a synergistic fashion. These results indicate that at the high concentrations present in the seminal plasma spermine/spermidine exhibit a positive modulatory effect on the chaperone-like activity of PDC-109 and may also function as chemical chaperones and protect other seminal plasma proteins from various kinds of stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolation and characterization of cDNA clones for carrot extensin and a proline-rich 33-kDa protein

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

Chen, J.; Varner, J.E.

1985-07-01

Extensins are hydroxyproline-rich glycoproteins associated with most dicotyledonous plant cell walls. To isolate cDNA clones encoding extensin, the authors started by isolating poly(A) RNA from carrot root tissue, and then translating the RNA in vitro, in the presence of tritiated leucine or proline. A 33-kDa peptide was identified in the translation products as a putative extensin precursor. From a cDNA library constructed with poly(A) RNA from wounded carrots, one cDNA clone (pDC5) was identified that specifically hybridized to poly(A) RNA encoding this 33-kDa peptide. They isolated three cDNA clones (pDC11, pDC12, and pDC16) from another cDNA library using pCD5 asmore » a probe. DNA sequence data, RNA hybridization analysis, and hybrid released in vitro translation indicate that the cDNA clones pDC11 encodes extensin and that cDNA clones pDC12 and pDC16 encode the 33-kDa peptide, which as yet has an unknown identity and function. The assumption that the 33-kDa peptide was an extensin precursor was invalid. RNA hybridization analysis showed that RNA encoded by both clone types is accumulated upon wounding.« less

An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae

PubMed Central

2012-01-01

Background Pyruvate-decarboxylase negative (Pdc-) strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc-S. cerevisiae an interesting platform for efficient conversion of glucose towards pyruvate-derived products without formation of ethanol as a by-product. However, Pdc- strains cannot grow on high glucose concentrations and require C2-compounds (ethanol or acetate) for growth under conditions with low glucose concentrations, which hitherto has limited application in industry. Results Genetic analysis of a Pdc- strain previously evolved to overcome these deficiencies revealed a 225bp in-frame internal deletion in MTH1, encoding a transcriptional regulator involved in glucose sensing. This internal deletion contains a phosphorylation site required for degradation, thereby hypothetically resulting in increased stability of the protein. Reverse engineering of this alternative MTH1 allele into a non-evolved Pdc- strain enabled growth on 20 g l-1 glucose and 0.3% (v/v) ethanol at a maximum specific growth rate (0.24 h-1) similar to that of the evolved Pdc- strain (0.23 h-1). Furthermore, the reverse engineered Pdc- strain grew on glucose as sole carbon source, albeit at a lower specific growth rate (0.10 h-1) than the evolved strain (0.20 h-1). The observation that overexpression of the wild-type MTH1 allele also restored growth of Pdc-S. cerevisiae on glucose is consistent with the hypothesis that the internal deletion results in decreased degradation of Mth1. Reduced degradation of Mth1 has been shown to result in deregulation of hexose transport. In Pdc- strains, reduced glucose uptake may prevent intracellular accumulation of pyruvate and/or redox problems, while release of glucose repression due to the MTH1 internal deletion may contribute to alleviation of the C2-compound auxotrophy. Conclusions In this study we have discovered and characterised a mutation in MTH1 enabling Pdc- strains to grow on glucose as the sole carbon source. This successful example of reverse engineering not only increases the understanding of the glucose tolerance of evolved Pdc-S. cerevisiae, but also allows introduction of this portable genetic element into various industrial yeast strains, thereby simplifying metabolic engineering strategies. PMID:22978798

Insights into Proximal-Medial Pyroclastic Density Current Deposits at a High-Risk Glaciated Volcano: Mt Ruapehu, New Zealand

NASA Astrophysics Data System (ADS)

Cowlyn, J.; Kennedy, B.; Gravley, D. M.; Cronin, S. J.; Pardo, N.; Wilson, T. M.; Leonard, G.; Townsend, D.; Dufek, J.

2014-12-01

Pyroclastic density currents (PDCs) are a destructive volcanic hazard. Quantifying the types, frequency and magnitudes of PDC events in the geological record is essential for effective risk management. However small-medium volume valley-confined PDC deposits have low preservation potential, especially when emplaced in active drainages or onto snow or ice. Where PDC deposits are preserved they can be difficult to distinguish from other surficial deposits and are frequently misinterpreted or overlooked. This is the case at Mt. Ruapehu; a much visited, high-risk active volcano in New Zealand with no historical PDCs. Through systematic field observations we identified several young proximal-medial andesitic PDC deposits exposed on Ruapehu's eastern flanks. The oldest deposits (Ohinewairua PDCs, <13.6 ka) are massive pumice-rich deposits that are preserved at least 7km from source (North Crater) and correlate with Ruapehu's largest plinian eruptions. Overlying these, the pumice-rich Pourahu PDC deposit reaches >10km from source (South Crater) and correlates with Ruapehu's last known plinian eruption (~11.6 ka). Several younger locally preserved PDC deposits (Tukino PDCs) with denser juvenile clasts represent proximal PDCs from smaller eruptions at South Crater. Finally, a variably welded, bedded deposit containing clasts of welded spatter is interpreted to represent multiple failures of near-vent (North Ruapehu) accumulations of erupted material. Here, PDC initiation appears to have been controlled by the topographic gradient and deposition rate, without requiring a collapsing eruption column. The Ruapehu deposits highlight the limited preservation of PDC deposits, which appears to be favoured at PDC margins. Lateral and vertical flow stratification means the resulting deposits may not then represent the bulk flow. Additionally, deposit textures, distributions, and associations with moraines indicate that many of Ruapehu's PDCs encountered glacial ice during transport. This affected their distribution, mobility and preservation, and has implications for assessing the PDC hazard at Ruapehu and other glaciated volcanoes. The deposits reinforce that hazardous PDCs threatening life and infrastructure may be generated even from small eruptions and across a wide range of eruption styles.

Identification of target genes to control acetate yield during aerobic fermentation with Saccharomyces cerevisiae.

PubMed

Curiel, José Antonio; Salvadó, Zoel; Tronchoni, Jordi; Morales, Pilar; Rodrigues, Alda Joao; Quirós, Manuel; Gonzalez, Ramón

2016-09-15

Aerobic fermentation of grape must, leading to respiro-fermentative metabolism of sugars, has been proposed as way of reducing alcohol content in wines. Two factors limit the usefulness of Saccharomyces cerevisiae for this application, the Crabtree effect, and excess volatile acidity under aerobic conditions. This work aimed to explore the impact on ethanol acetate production of different S. cerevisiae strains deleted for genes previously related with the Crabtree phenotype. Recombinant strains were constructed on a wine industrial genetic background, FX10. All yeast strains, including FX10, showed respiro-fermentative metabolism in natural grape must under aerobic conditions, as well as a concomitant reduction in ethanol yield. This indicates that the Crabtree effect is not a major constrain for reaching relevant respiration levels in grape must. Indeed, only minor differences in ethanol yield were observed between the original and some of the recombinant strains. In contrast, some yeast strains showed a relevant reduction of acetic acid production. This was identified as a positive feature for the feasibility of alcohol level reduction by respiration. Reduced acetic acid production was confirmed by a thorough analysis of these and some additional deletion strains (involving genes HXK2, PYK1, REG1, PDE2 and PDC1). Some recombinant yeasts showed altered production of glycerol and pyruvate derived metabolites. REG1 and PDC1 deletion strains showed a strong reduction of acetic acid yield in aerobic fermentations. Since REG1 defective strains may be obtained by non-GMO approaches, these gene modifications show good promise to help reducing ethanol content in wines.

Neuropsychological study of amyotrophic lateral sclerosis and parkinsonism-dementia complex in Kii peninsula, Japan

PubMed Central

2014-01-01

Background The Kii peninsula of Japan is one of the foci of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS/PDC) in the world. The purpose of this study is to clarify the neuropsychological features of the patients with ALS/PDC of the Kii peninsula (Kii ALS/PDC). Methods The medical interview was done on 13 patients with Kii ALS/PDC, 12 patients with Alzheimer’s disease, 10 patients with progressive supranuclear palsy, 10 patients with frontotemporal lobar degeneration and 10 patients with dementia with Lewy bodies. These patients and their carer/spouse were asked to report any history of abulia-apathy, hallucination, personality change and other variety of symptoms. Patients also underwent brain magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and neuropsychological tests comprising the Mini Mental State Examination, Raven’s Colored Progressive Matrices, verbal fluency, and Paired-Associate Word Learning Test and some of them were assessed with the Frontal Assessment Battery (FAB). Results All patients with Kii ALS/PDC had cognitive dysfunction including abulia-apathy, bradyphrenia, hallucination, decrease of extraversion, disorientation, and delayed reaction time. Brain MRI showed atrophy of the frontal and/or temporal lobes, and SPECT revealed a decrease in cerebral blood flow of the frontal and/or temporal lobes in all patients with Kii ALS/PDC. Disorientation, difficulty in word recall, delayed reaction time, and low FAB score were recognized in Kii ALS/PDC patients with cognitive dysfunction. Conclusions The core neuropsychological features of the patients with Kii ALS/PDC were characterized by marked abulia-apathy, bradyphrenia, and hallucination. PMID:25041813

Minimally invasive fluoroscopic percutaneous peritoneal dialysis catheter salvage.

PubMed

Narayan, Rajeev; Fried, Terrance; Chica, Gerardo; Schaefer, Mathew; Mullins, Daniel

2014-06-01

Peritoneal dialysis catheter (PDC) dysfunction can often be treated fluoroscopically by manipulation with wire, balloon or stiff stylet, saving surgical intervention for refractory cases. We describe an enhanced percutaneous approach to PDC salvage that can lead to a more definitive intervention and salvage for cases refractory to fluoroscopic manipulation. In five cases of PD catheter malfunction, the deep cuff was dissected free after a 0.035 hydrophilic wire was passed into the peritoneum through the PDC. Only the intraperitoneal portion of the PDC was explanted. The PDC was cleared of obstruction and omentum. The intraperitoneal portion of the PDC was reimplanted over wire via a peel-away sheath and the deep cuff sutured. Omental entrapment was present in three of five patients and fibrin occlusion in four of the five cases. All catheters were repaired successfully by the described technique. Post procedure, 3-5 days of lower volume, recumbent PD exchanges were performed prior to full-dose PD. No perioperative complications or leaks were noted. All PDCs were patent at 6 months. One patient required laparoscopy for recurrent omental wrapping 3 months post intervention. PDC salvage in this manner is a cost-effective alternative to laparoscopic repair of PDCs failing catheter manipulation. The infection barrier afforded by the original superficial cuff and subcutaneous tunnel is maintained. PD can be resumed immediately. Only refractory cases need laparoscopy. This procedure allows for a more definitive correction of catheter migration and obstruction, avoids placement of a new PDC or temporary hemodialysis, is cost-effective and expands percutaneous options for dysfunctional PD catheters.

The Proliferation of PDC-Type Environments in Industry and Universities

NASA Technical Reports Server (NTRS)

Shishko, R.

2000-01-01

JPL's Project Design Cenger (PDC), opened in 1994, has become a model for other facilities of the same type in the aerospace industry. More recently, PDC-type environments have been adopted by some university aerospace departments as an educational tool. This paper discusses some of these facilities and their possible future direction.

Mathematical modeling of PDC bit drilling process based on a single-cutter mechanics

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

Wojtanowicz, A.K.; Kuru, E.

1993-12-01

An analytical development of a new mechanistic drilling model for polycrystalline diamond compact (PDC) bits is presented. The derivation accounts for static balance of forces acting on a single PDC cutter and is based on assumed similarity between bit and cutter. The model is fully explicit with physical meanings given to all constants and functions. Three equations constitute the mathematical model: torque, drilling rate, and bit life. The equations comprise cutter`s geometry, rock properties drilling parameters, and four empirical constants. The constants are used to match the model to a PDC drilling process. Also presented are qualitative and predictive verificationsmore » of the model. Qualitative verification shows that the model`s response to drilling process variables is similar to the behavior of full-size PDC bits. However, accuracy of the model`s predictions of PDC bit performance is limited primarily by imprecision of bit-dull evaluation. The verification study is based upon the reported laboratory drilling and field drilling tests as well as field data collected by the authors.« less

Study on the Effect of Diamond Grain Size on Wear of Polycrystalline Diamond Compact Cutter

NASA Astrophysics Data System (ADS)

Abdul-Rani, A. M.; Che Sidid, Adib Akmal Bin; Adzis, Azri Hamim Ab

2018-03-01

Drilling operation is one of the most crucial step in oil and gas industry as it proves the availability of oil and gas under the ground. Polycrystalline Diamond Compact (PDC) bit is a type of bit which is gaining popularity due to its high Rate of Penetration (ROP). However, PDC bit can easily wear off especially when drilling hard rock. The purpose of this study is to identify the relationship between the grain sizes of the diamond and wear rate of the PDC cutter using simulation-based study with FEA software (ABAQUS). The wear rates of a PDC cutter with a different diamond grain sizes were calculated from simulated cuttings of cutters against granite. The result of this study shows that the smaller the diamond grain size, the higher the wear resistivity of PDC cutter.

Independent of plasmacytoid dendritic cell (pDC) infection, pDC triggered by virus-infected cells mount enhanced type I IFN responses of different composition as opposed to pDC stimulated with free virus.

PubMed

Frenz, Theresa; Graalmann, Lukas; Detje, Claudia N; Döring, Marius; Grabski, Elena; Scheu, Stefanie; Kalinke, Ulrich

2014-09-01

Upon treatment with vesicular stomatitis virus (VSV) particles, plasmacytoid dendritic cells (pDC) are triggered to mount substantial type I IFN responses, whereas myeloid DC (mDC) are only minor producers. Interestingly, bone marrow-derived (BM-)mDC were more vulnerable to infection with enhanced GFP (eGFP)-expressing VSV (VSVeGFP) than BM-pDC. BM-pDC stimulated with wild-type VSV mounted TLR-dependent IFN responses that were independent of RIG-I-like helicase (RLH) signaling. In contrast, in BM-pDC the VSV variant M2 induced particularly high IFN responses triggered in a TLR- and RLH-dependent manner, whereas BM-mDC stimulation was solely RLH-dependent. Importantly, VSVeGFP treatment of BM-pDC derived from IFN-β yellow fluorescent protein (YFP) reporter mice (messenger of IFN-β) resulted in YFP(+) and eGFP(+) single-positive cells, whereas among messenger of IFN-β-BM-mDC most YFP(+) cells were also eGFP(+). This observation indicated that unlike mDC, direct virus infection was not required to trigger IFN responses of pDC. VSV-infected BM-mDC triggered BM-pDC to mount significantly higher IFN responses than free virus particles. Stimulation with infected cells enhanced the percentages of pDC subsets expressing either IFN-β(+) or IFN-α6(+) plus IFN-β(+). Irrespective of whether stimulated with free virus or infected cells, IFN induction was dependent on autophagy of pDC, whereas autophagy of the infected mDC was dispensable. Collectively, these results indicated that productive VSV infection was needed to trigger IFN responses of mDC, but not of pDC, and that IFN responses were primarily induced by virus-infected cells that stimulated pDC in a TLR-dependent manner. Copyright © 2014 by The American Association of Immunologists, Inc.

Molecular recognition modes between adenine or adeniniun(1+) ion and binary M(II)(pdc) chelates (MCoZn; pdc=pyridine-2,6-dicarboxylate(2-) ion).

PubMed

Del Pilar Brandi-Blanco, María; Choquesillo-Lazarte, Duane; Domínguez-Martín, Alicia; Matilla-Hernández, Antonio; González-Pérez, Josefa María; Castiñeiras, Alfonso; Niclós-Gutiérrez, Juan

2013-10-01

Mixed ligand M(II)-complexes (MCoZn) with pyridine-2,6-dicarboxylate(2-) chelator (pdc) and adenine (Hade) have been synthesized and studied by X-ray diffraction and other spectral and thermal methods: [Cu(pdc)(H(N9)ade)(H2O)] (1), [Cu2(pdc)2(H2O)2(μ2-N3,N7-H(N9)ade)]·3H2O (2), trans-[M(pdc)(H(N9)ade)(H2O)2]·nH2O for MCo (3-L, 3-M, 3-H) or Zn (4-L, 4-H), where n is 0, 1 or 3 for the 'lowest' (L), 'medium' (M) and 'highest' (H) hydrated forms, and the salt trans-[Ni(pdc)(H2(N1,N9)ade)(H2O)2]Cl·2H2O (5). In all the nine compounds, both neutral and cationic adenine exist as their most stable tautomer and the molecular recognition pattern between the metal-pdc chelates and the adenine or adeninium(1+) ligands involves the MN7 bond in cooperation with an intra-molecular N6H⋯O(coordinated carboxylate) interligand interaction. In addition the dinuclear copper(II) compound (2) has the CuN3 bond and the N9H⋯O(coord. carboxylate) interaction. The structures of mononuclear ternary complexes proved that the molecular recognition pattern is the same irrespective of (a) the coordination geometry of the complex molecule, (b) the different hydrated forms of crystals with Co or Zn, and (c) the neutral of cationic form of the adenine ligand. These features are related to the mer-NO2 chelating ligand conformation (imposed by the planar rigidity of pdc) as a driving force for the observed metal binding mode. Copyright © 2013 Elsevier Inc. All rights reserved.

Random phage mimotopes recognized by monoclonal antibodies against the pyruvate dehydrogenase complex-E2 (PDC-E2).

PubMed Central

Cha, S; Leung, P S; Van de Water, J; Tsuneyama, K; Joplin, R E; Ansari, A A; Nakanuma, Y; Schatz, P J; Cwirla, S; Fabris, L E; Neuberger, J M; Gershwin, M E; Coppel, R L

1996-01-01

Dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex (PDC-E2), is the autoantigen most commonly recognized by autoantibodies in primary biliary cirrhosis (PBC). We identified a peptide mimotope(s) of PDC-E2 by screening a phage-epitope library expressing random dodecapeptides in the pIII coat protein of fd phage using C355.1, a murine monoclonal antibody (mAb) that recognizes a conformation-dependent epitope in the inner lipoyl domain of PDC-E2 and uniquely stains the apical region of bile duct epithelium (BDE) only in patients with PBC. Eight different sequences were identified in 36 phage clones. WMSYPDRTLRTS was present in 29 clones; WESYPFRVGTSL, APKTYVSVSGMV, LTYVSLQGRQGH, LDYVPLKHRHRH, AALWGVKVRHVS, KVLNRIMAGVRH and GNVALVSSRVNA were singly represented. Three common amino acid motifs (W-SYP, TYVS, and VRH) were shared among all peptide sequences. Competitive inhibition of the immunohistochemical staining of PBC BDE was performed by incubating the peptides WMSYPDRTLRTS, WESYPDRTLRTS, APKTYVSVSGMV, and AALWGVKVRHVS with either C355.1 or a second PDC-E2-specific mAb, C150.1. Both mAbs were originally generated to PDC-E2 but map to distinct regions of PDC-E2. Two of the peptides, although selected by reaction with C355.1, strongly inhibited the staining of BDE by C150.1, whereas the peptide APKTYVSVSGMV consistently inhibited the staining of C355.1 on biliary duct epithelium more strongly than the typical mitochondrial staining of hepatocytes. Rabbit sera raised against the peptide WMSYPDRTLRTS stained BDE of livers and isolated bile duct epithelial cells of PBC patients more intensively than controls. The rabbit sera stained all size ducts in normals, but only small/medium-sized ductules in PBC livers. These studies provide evidence that the antigen present in BDE is a molecular mimic of PDC-E2, and not PDC-E2 itself. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8855289

Use of alternating and pulsed direct current electrified fields for zebra mussel control

USGS Publications Warehouse

Luoma, James A.; Dean, Jan C.; Severson, Todd J.; Wise, Jeremy K.; Barbour, Matthew

2017-01-01

Alternatives to chemicals for controlling dreissenid mussels are desirable for environmental compatibility, but few alternatives exist. Previous studies have evaluated the use of electrified fields for stunning and/or killing planktonic life stages of dreissenid mussels, however, the available literature on the use of electrified fields to control adult dreissenid mussels is limited. We evaluated the effects of sinusoidal alternating current (AC) and 20% duty cycle square-wave pulsed direct current (PDC) exposure on the survival of adult zebra mussels at water temperatures of 10, 15, and 22 °C. Peak voltage gradients of ~ 17 and 30 Vp/cm in the AC and PDC exposures, respectively, were continuously applied for 24, 48, or 72 h. Peak power densities ranged from 77,999 to 107,199 µW/cm3 in the AC exposures and 245,320 to 313,945 µW/cm3 in the PDC exposures. The peak dose ranged from 6,739 to 27,298 Joules/cm3 and 21,306 to 80,941 Joules/cm3 in the AC and PDC exposures, respectively. The applied power ranged from 16.6 to 68.9 kWh in the AC exposures and from 22.2 to 86.4 kWh in the PDC exposures. Mortality ranged from 2.7 to 92.7% in the AC exposed groups and from 24.0 to 98.7% in PDC exposed groups. Mortality increased with corresponding increases in water temperature and exposure duration, and we observed more zebra mussel mortality in the PDC exposures. Exposures conducted with AC required less of a peak dose (Joules/cm3) but more applied power (kWh) to achieve the same level of adult zebra mussel mortality as corresponding PDC exposures. The results demonstrate that 20% duty cycle square-wave PDC requires less energy than sinusoidal AC to inducing the same level of adult zebra mussel mortality.

PDC bits: What`s needed to meet tomorrow`s challenge

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

Warren, T.M.; Sinor, L.A.

1994-12-31

When polycrystalline diamond compact (PDC) bits were introduced in the mid-1970s they showed tantalizingly high penetration rates in laboratory drilling tests. Single cutter tests indicated that they had the potential to drill very hard rocks. Unfortunately, 20 years later we`re still striving to reach the potential that these bits seem to have. Many problems have been overcome, and PDC bits have offered capabilities not possible with roller cone bits. PDC bits provide the most economical bit choice in many areas, but their limited durability has hampered their application in many other areas.

The dynamics of photoinduced defect creation in amorphous chalcogenides: The origin of the stretched exponential function

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

Freitas, R. J.; Shimakawa, K.; Department of Electrical and Electronic Engineering, Gifu University, Gifu 501-1193

The article discusses the dynamics of photoinduced defect creations (PDC) in amorphous chalcogenides, which is described by the stretched exponential function (SEF), while the well known photodarkening (PD) and photoinduced volume expansion (PVE) are governed only by the exponential function. It is shown that the exponential distribution of the thermal activation barrier produces the SEF in PDC, suggesting that thermal energy, as well as photon energy, is incorporated in PDC mechanisms. The differences in dynamics among three major photoinduced effects (PD, PVE, and PDC) in amorphous chalcogenides are now well understood.

31P NMR and AFM studies on the destabilization of cell and model membranes by the major bovine seminal plasma protein, PDC-109.

PubMed

Damai, Rajani S; Sankhala, Rajeshwer S; Anbazhagan, Veerappan; Swamy, Musti J

2010-11-01

The effect of PDC-109 binding to dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles (MLVs) and supported membranes was investigated by (31)P NMR spectroscopy and atomic force microscopy. Additionally, the effect of cholesterol on the binding of PDC-109 to phosphatidylcholine (PC) membranes was studied. Binding of PDC-109 to MLVs of DMPC and DPPG induced the formation of an isotropic signal in their (31)P NMR spectra, which increased with increasing protein/lipid ratio and temperature, consistent with protein-induced disruption of the MLVs and the formation of small unilamellar vesicles or micelles but not inverse hexagonal or cubic phases. Incorporation of cholesterol in the DMPC MLVs afforded a partial stabilization of the lamellar structure, consistent with previous reports of membrane stabilization by cholesterol. AFM results are consistent with the above findings and show that addition of PDC-109 leads to a complete breakdown of PC membranes. The fraction of isotropic signal in (31)P NMR spectra of DPPG in the presence of PDC-109 was less than that of DMPC under similar conditions, suggesting a significantly higher affinity of the protein for PC. Confocal microscopic studies showed that addition of PDC-109 to human erythrocytes results in a disruption of the plasma membrane and release of hemoglobin into the solution, which was dependent on the protein concentration and incubation time.

Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

PubMed Central

Tokita, Daisuke; Sumpter, Tina L.; Raimondi, Giorgio; Zahorchak, Alan F.; Wang, Zhiliang; Nakao, Atsunori; Mazariegos, George V.; Abe, Masanori; Thomson, Angus W.

2008-01-01

Background/Aims The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC),- innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-reated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally-occurring regulatory T cells (Treg). Results While IL-10 production was greater for freshly-isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4+ T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4+CD25+ regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusion The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity. PMID:18926588

New PDC cutters improve drilling efficiency

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

Mensa-Wilmot, G.

1997-10-27

New polycrystalline diamond compact (PDC) cutters increase penetration rates and cumulative footage through improved abrasion, impact, interface strength, thermal stability, and fatigue characteristics. Studies of formation characterization, vibration analysis, hydraulic layouts, and bit selection continue to improve and expand PDC bit applications. The paper discusses development philosophy, performance characteristics and requirements, Types A, B, and C cutters, and combinations.

Causes of wear of PDC bits and ways of improving their wear resistance

NASA Astrophysics Data System (ADS)

Timonin, VV; Smolentsev, AS; Shakhtorin, I. O.; Polushin, NI; Laptev, AI; Kushkhabiev, AS

2017-02-01

The scope of the paper encompasses basic factors that influence PDC bit efficiency. Feasible ways of eliminating the negatives are illustrated. The wash fluid flow in a standard bit is modeled, the resultant pattern of the bit washing is analyzed, and the recommendations are made on modification of the PDC bit design.

Risk of developing palatally displaced canines in patients with early detectable dental anomalies: a retrospective cohort study

PubMed Central

GARIB, Daniela Gamba; LANCIA, Melissa; KATO, Renata Mayumi; OLIVEIRA, Thais Marchini; NEVES, Lucimara Teixeira das

2016-01-01

ABSTRACT The early recognition of risk factors for the occurrence of palatally displaced canines (PDC) can increase the possibility of impaction prevention. Objective To estimate the risk of PDC occurrence in children with dental anomalies identified early during mixed dentition. Material and Methods The sample comprised 730 longitudinal orthodontic records from children (448 females and 282 males) with an initial mean age of 8.3 years (SD=1.36). The dental anomaly group (DA) included 263 records of patients with at least one dental anomaly identified in the initial or middle mixed dentition. The non-dental anomaly group (NDA) was composed of 467 records of patients with no dental anomalies. The occurrence of PDC in both groups was diagnosed using panoramic and periapical radiographs taken in the late mixed dentition or early permanent dentition. The prevalence of PDC in patients with and without early diagnosed dental anomalies was compared using the chi-square test (p<0.01), relative risk assessments (RR), and positive and negative predictive values (PPV and NPV). Results PDC frequency was 16.35% and 6.2% in DA and NDA groups, respectively. A statistically significant difference was observed between groups (p<0.01), with greater risk of PDC development in the DA group (RR=2.63). The PPV and NPV was 16% and 93%, respectively. Small maxillary lateral incisors, deciduous molar infraocclusion, and mandibular second premolar distoangulation were associated with PDC. Conclusion Children with dental anomalies diagnosed during early mixed dentition have an approximately two and a half fold increased risk of developing PDC during late mixed dentition compared with children without dental anomalies. PMID:28076458

Technical advance: Generation of human pDC equivalents from primary monocytes using Flt3-L and their functional validation under hypoxia.

PubMed

Sekar, Divya; Brüne, Bernhard; Weigert, Andreas

2010-08-01

The division of labor between DC subsets is evolutionarily well-defined. mDC are efficient in antigen presentation, whereas pDC act as rheostats of the immune system. They activate NK cells, cause bystander activation of mDC, and interact with T cells to induce tolerance. This ambiguity positions pDC at the center of inflammatory diseases, such as cancer, arthritis, and autoimmune diseases. The ability to generate human mDC ex vivo made it possible to engineer them to suit therapy needs. Unfortunately, a similar, easily accessible system to generate human pDC is not available. We describe a method to generate human pDC equivalents ex vivo, termed mo-pDC from peripheral blood monocytes using Flt3-L. mo-pDC showed a characteristic pDC profile, such as high CD123 and BDCA4, but low CD86 and TLR4 surface expression and a low capacity to induce autologous lymphocyte proliferation and to phagocytose apoptotic debris in comparison with mDC. Interestingly, mo-pDC up-regulated the pDC lineage-determining transcription factor E2-2 as well as expression of BDCA2, which is under the transcriptional control of E2-2 but not its inhibitor ID2, during differentiation. mo-pDC produced high levels of IFN-alpha when pretreated overnight with TNF-alpha. Under hypoxia, E2-2 was down-regulated, and ID2 was induced in mo-pDC, whereas surface expression of MHCI, CD86, and BDCA2 was decreased. Furthermore, mo-pDC produced high levels of inflammatory cytokines when differentiated under hypoxia compared with normoxia. Hence, mo-pDC can be used to study differentiation and functions of human pDC under microenvironmental stimuli.

Two enzymatic reaction pathways in the formation of pyropheophorbide a.

PubMed

Suzuki, Yasuyo; Doi, Michio; Shioi, Yuzo

2002-01-01

The demethoxycarbonyl reaction of pheophorbide a in plants and algae was investigated. Two types of enzyme that catalyze alternative reactions in the formation of pyropheophorbide a were found. One enzyme, designated 'pheophorbidase (Phedase)', was purified nearly to homogeneity from cotyledons of radish (Raphanus sativus). This enzyme catalyzes the conversion of pheophorbide a to a precursor of pyropheophorbide a, C-13(2)-carboxylpyropheophorbide a, by demethylation, and then the precursor is decarboxylated non-enzymatically to yield pyropheophorbide a. The activity of Phedase was inhibited by the reaction product, methanol. The other enzyme, termed 'pheophorbide demethoxycarbonylase (PDC)', was highly purified from the Chl b-less mutant NL-105 of Chlamydomonas reinhardtii. This enzyme had produced no intermediate as shown in the Phedase reaction, indicating that it converts pheophorbide a directly into pyropheophorbide a, probably by nucleophilic reaction. Phedase and PDC consisted of both senescence-induced and constitutive enzymes. The molecular weight of both Phedases was 113 000 and of senescence-induced PDC was 170 000. The K (m) values against pheophorbide a for both Phedases were 14-15 muM and 283 muM for senescence-induced PDC. The activity of both Phedases was inhibited by the reaction product, methanol, whereas methanol had no specific effect on senescence-induced PDC. Phenylmethylsulfonic fluoride and N-ethylmaleimide inhibited the senescence-induced Phedase and PDC, respectively. Among the 23 species from 15 different families tested, Phedase activity was found in 10 species from three families. PDC activity was not detected in plants lacking Phedase activity, except for Chlamydomonas. Based on these findings, a likely conclusion is that at least two alternative pathways that are catalyzed by two different enzymes, Phedase and PDC, exist for the formation of pyropheophorbide a.

Comparison of the dental anomalies found in maxillary canine-first premolar transposition cases with those in palatally displaced canine cases.

PubMed

Scerri, Erica Sultana; McDonald, Fraser; Camilleri, Simon

2016-02-01

To compare the developmental dental anomalies associated with maxillary canine-first premolar (MxCP1) transposition and those of palatally displaced canine (PDC) with each other and with the background prevalence in the Maltese population in order to elucidate whether the two conditions have similar or differing genetic backgrounds. Dental records of 477 subjects with PDC, 57 subjects with MxCP1, and a control group of 500 subjects with no history of a PDC or tooth transposition were compared for canine eruption anomalies and hypodontia. A high frequency of bilateral occurrence was present for both canine malpositions and when unilateral, a trend to right-sided occurrence was evident. The occurrence of transpositions in the PDC group and of PDC in the MxCP1 group was higher than expected. The prevalence of incisor hypodontia was significantly higher in subjects with PDC and MxCP1, as compared to the control group. The size of the MxCP1 group is relatively small. The study population is a small isolated Caucasian population and the results may not be applicable to other populations. There is no significant difference between the MxCP1 and PDC groups in the prevalence or distribution of hypodontia and each of these groups exhibits a higher prevalence of the other canine anomaly. These findings support the theory that PDC and MxCP1 form part of a group of interrelated dental anomalies that share a common genetic basis. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effect of polysaccharide of dendrobium candidum on proliferation and apoptosis of human corneal epithelial cells in high glucose

PubMed Central

Li, Qiangxiang; Chen, Jing; Li, Yajia; Chen, Ting; Zou, Jing; Wang, Hua

2017-01-01

Abstract Background: The aim of the study was to observe the effect of polysaccharide of dendrobium candidum (PDC) and high glucose on proliferation, apoptosis of human corneal epithelial cells (HCEC). Methods: The MTT method was used to screen and take the optimal high-glucose concentration, treatment time, and PDC concentration using HCEC and divide it into 4 groups: control group (C), high glucose group (HG), PDC group, and HG + PDC group. We observed and compared the effect of the 4 groups on HCEC proliferation by MTT, apoptosis by Annexin V-FITC/PI double fluorescent staining and flow cytometry (FCM), and expression of bax mRNA and bcl-2 mRNA by RT-qPCR. Results: Compared with the control group, proliferative activity of HCEC cells was reduced; the cells apoptosis ratio was increased; the expression of bax mRNA was increased, and the expression of bcl-2 mRNA was reduced in the HG group. Proliferative activity of HCEC cells in the PDC group was increased, and the expression of bcl-2 mRNA was increased but that of bax mRNA was decreased. Proliferative activity of HCEC cells in the HG + PDC group was increased, but it could not restore to the normal level; the expression of bax mRNA was significantly decreased but the expression of bcl-2 mRNA was significantly increased. Conclusions: Our results demonstrate that high glucose can inhibit proliferative activity and induce apoptosis of HCEC. PDC can improve the proliferative activity of HCEC cells under the high glucose environment and reduce the apoptosis of cells by regulating the expression of bax and bcl-2. PDC play a very important role on protecting and repairing of corneal epithelial cells damage in high glucose. PMID:28796073

[Lessons from Guam ALS/PDC study].

PubMed

Asao, Hirano

2007-11-01

An extraordinarily high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) affecting the native population was discovered on the island of Guam a half century ago. Guam ALS is identical to classic ALS clinically and pathologically while PDC is marked by progressive parkinsonism and dementia. The unusual histological finding in these fetal neurodegenerative diseases is the presence of numerous neurofibrillary tangles in a selective topographic distribution unassociated with senile plaques. There have been remarkable advances in field of age-associated neurodegenerative disease after our initial study of Guam cases. Four noteworthy topics are presented in this communication. 1) Clinically, the coexistence of parkinsonism and dementia was frequently recognized in Parkinson disease and Alzheimer disease. Some other new disease entities characterized by coexistence of parkinsonism and dementia have been reported. These include progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17. 2) Neuropathologically, abundant neurofibrillary tangles unassociated with senile plaques were demonstrated in many diseases such as aftermath of boxing and tangle-only dementia. Furthermore, tau-positive structures were recognized not only in neurons but in glial cells in certain diseases. Tauopathy is one of the current hot research subjects. 3) Familial aggregation of Guam ALS patients provoked investigation of familial ALS elsewhere. Familial motor neuron disease with SOD1 mutation is the target of worldwide intense investigation at the present time. SOD1 gene mutation is, however, not found in Guam ALS. 4) The most striking findings of the Guam study is the gradual decline in the incidence of ALS on Guam during a quarter century and virtual disappearance of new patients. This may be linked to a remarkable change in environment and life style of the Chamorro population. The etiology of ALS is still unknown and no new treatment is available. Guam ALS/PDC is certainly one of the most mysterious riddles among age-associated neurodegenerative diseases during the last half a century.

Effects of high CO₂ levels on fermentation, peroxidation, and cellular water stress in Fragaria vesca stored at low temperature in conditions of unlimited O₂.

PubMed

Blanch, Maria; Rosales, Raquel; Mateos, Raquel; Perez-Gago, María B; Sanchez-Ballesta, Maria T; Escribano, María I; Merodio, Carmen

2015-01-28

To better understand the tolerance of strawberries (Fragaria vesca L.) to high CO2 in storage atmospheres, fermentation and cellular damage were investigated. Fruits were stored for 3 and 6 days at 0 °C in the presence of different CO2 levels (0, 20, or 40%) with 20% O2. Changes in pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH) gene expression and in fermentative metabolites, as well as in bound water and malondialdehyde (MDA) concentrations, were analyzed. In strawberries stored without added CO2, up-regulation of PDC and ADH was not associated with an increase in fermentative metabolites. By contrast, moderate ethanol fermentation in fruits exposed to 20% CO2 seems to be essential to maintain fruit metabolism, reducing both lipid peroxidation and cellular water stress. However, if the CO2 concentration increases (40%), the excess acetaldehyde and ethanol produced were closely correlated with a decrease in bound water and production of MDA.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 1: Findings from the PDC Implementation Study.

ERIC Educational Resources Information Center

Smith, Allen G.; And Others

This third year interim report, one of a series of documents on the evaluation of Project Developmental Continuity (PDC), presents findings from three major analyses of program implementation; measurement of the extent each program has implemented the basic PDC Guidelines; a description of patterns of that implementation; and analysis of some…

A Process Evaluation of Project Developmental Continuity: Final Report of the PDC Feasibility Study, 1974-1977.

ERIC Educational Resources Information Center

Love, John M.; And Others

This is the final report of the 3-year feasibility phase of a projected 7-year longitudinal evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Chapter I gives an overview of the PDC program…

Natural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement

PubMed Central

Smith, Nikaïa; Pietrancosta, Nicolas; Davidson, Sophia; Dutrieux, Jacques; Chauveau, Lise; Cutolo, Pasquale; Dy, Michel; Scott-Algara, Daniel; Manoury, Bénédicte; Zirafi, Onofrio; McCort-Tranchepain, Isabelle; Durroux, Thierry; Bachelerie, Françoise; Schwartz, Olivier; Münch, Jan; Wack, Andreas; Nisole, Sébastien; Herbeuval, Jean-Philippe

2017-01-01

Plasmacytoid dendritic cells (pDC) are specialized in secretion of type I interferon in response to pathogens. Here we show that natural monoamines and synthetic amines inhibit pDC activation by RNA viruses. Furthermore, a synthetic analogue of histamine reduces type I interferon production in a mouse model of influenza infection. We identify CXC chemokine receptor 4 (CXCR4) as a receptor used by amines to inhibit pDC. Our study establishes a functional link between natural amines and the innate immune system and identifies CXCR4 as a potential ‘on-off' switch of pDC activity with therapeutic potential. PMID:28181493

Antiwhirl PDC bits increased penetration rates in Alberta drilling. [Polycrystalline Diamond Compact

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

Bobrosky, D.; Osmak, G.

1993-07-05

The antiwhirl PDC bits and an inhibitive mud system contributed to the quicker drilling of the time-sensitive shales. The hole washouts in the intermediate section were dramatically reduced, resulting in better intermediate casing cement jobs. Also, the use of antirotation PDC-drillable cementing plugs eliminated the need to drill out plugs and float equipment with a steel tooth bit and then trip for the PDC bit. By using an antiwhirl PDC bit, at least one trip was eliminated in the intermediate section. Offset data indicated that two to six conventional bits would have been required to drill the intermediate hole interval.more » The PDC bit was rebuildable and therefore rerunnable even after being used on five wells. In each instance, the cost of replacing chipped cutters was less than the cost of a new insert roller cone bit. The paper describes the antiwhirl bits; the development of the bits; and their application in a clastic sequence, a carbonate sequence, and the Shekilie oil field; the improvement in the rate of penetration; the selection of bottom hole assemblies; washout problems; and drill-out characteristics.« less

Induction of tolerance to poison ivy urushiol in the guinea pig by epicutaneous application of the structural analog 5-methyl-3-n-pentadecylcatechol.

PubMed

Stampf, J L; Benezra, C; Byers, V; Castagnoli, N

1986-05-01

Previous studies have established that epicutaneous application of 5-methyl-3-n-pentadecylcatechol (5-Me-PDC), a synthetic analog of a poison ivy urushiol component, leads to immune tolerance to 3-n-pentadecylcatechol (PDC) in mice. The induction of tolerance by 5-Me-PDC may be mediated by a protein conjugate formed via selective reaction of thiol nucleophiles present on the carrier macromolecule with the corresponding o-quinone derived from the parent catechol. In order to examine further the tolerogenic properties of 5-Me-PDC, we have extended our studies to the guinea pig, the generally accepted experimental species for the study of contact allergy. The results have established that specific immune tolerance to poison ivy urushiol is induced following 2 epicutaneous applications of the PDC analog. Furthermore, we were able to show that the treated animals remained tolerant for at least 6 weeks, a period of time comparable to that observed following the intravenous administration of the O,O-bis-acetyl derivative of PDC. The data point to the possibility of developing a therapeutically effective topical tolerogen for poison ivy contact dermatitis.

Antimicrobial activity and mechanism of PDC213, an endogenous peptide from human milk.

PubMed

Sun, Yazhou; Zhou, Yahui; Liu, Xiao; Zhang, Fan; Yan, Linping; Chen, Ling; Wang, Xing; Ruan, Hongjie; Ji, Chenbo; Cui, Xianwei; Wang, Jiaqin

2017-02-26

Human milk has always been considered an ideal source of elemental nutrients to both preterm and full term infants in order to optimally develop the infant's tissues and organs. Recently, hundreds of endogenous milk peptides were identified in human milk. These peptides exhibited angiotensin-converting enzyme inhibition, immunomodulation, or antimicrobial activity. Here, we report the antimicrobial activity and mechanism of a novel type of human antimicrobial peptide (AMP), termed PDC213 (peptide derived from β-Casein 213-226 aa). PDC213 is an endogenous peptide and is present at higher levels in preterm milk than in full term milk. The inhibitory concentration curve and disk diffusion tests showed that PDC213 had obvious antimicrobial against S. aureus and Y. enterocolitica, the common nosocomial pathogens in neonatal intensive care units (NICUs). Fluorescent dye methods, electron microscopy experiments and DNA-binding activity assays further indicated that PDC213 can permeabilize bacterial membranes and cell walls rather than bind intracellular DNA to kill bacteria. Together, our results suggest that PDC213 is a novel type of AMP that warrants further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial transcription factor A serves as a danger signal by augmenting plasmacytoid dendritic cell responses to DNA.

PubMed

Julian, Mark W; Shao, Guohong; Bao, Shengying; Knoell, Daren L; Papenfuss, Tracey L; VanGundy, Zachary C; Crouser, Elliott D

2012-07-01

Plasmacytoid dendritic cells (pDC) are potent APCs known to regulate immune responses to self-Ags, particularly DNA. The mitochondrial fraction of necrotic cells was found to most potently promote human pDC activation, as reflected by type I IFN release, which was dependent upon the presence of mitochondrial DNA and involved TLR9 and receptors for advanced glycation end products. Mitochondrial transcription factor A (TFAM), a highly abundant mitochondrial protein that is functionally and structurally homologous to high mobility group box protein 1, was observed to synergize with CpG-containing oligonucleotide, type A, DNA to promote human pDC activation. pDC type I IFN responses to TFAM and CpG-containing oligonucleotide, type A, DNA indicated their engagement with receptors for advanced glycation end products and TLR9, respectively, and were dependent upon endosomal processing and PI3K, ERK, and NF-κB signaling. Taken together, these results indicate that pDC contribute to sterile immune responses by recognizing the mitochondrial component of necrotic cells and further incriminate TFAM and mitochondrial DNA as likely mediators of pDC activation under these circumstances.

Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response

PubMed Central

Hemann, Emily A.; Sjaastad, Louisa E.; Langlois, Ryan A.

2015-01-01

ABSTRACT Following influenza A virus (IAV) infection, development of a robust IAV-specific CD8 T cell response is required for clearance of primary infection and enhances memory protection. Following IAV infection, plasmacytoid dendritic cells (pDC) or CD8α+ DC regulate pulmonary effector CD8 T cell responses within the lung. Without this DC-T cell interaction, insufficient effector CD8 T cells are maintained in the lungs, leading to enhanced morbidity and mortality. Previous studies have demonstrated that pDC are capable of classical presentation or cross-presentation of IAV antigens and could potentially regulate IAV-specific CD8 T cell responses through either mechanism. Our results demonstrate that pDC from the lungs of donor mice infected with an IAV that is not able to replicate in hematopoietic cells (142t-IAV), unlike donor pDC isolated from the lungs of control infected mice, are not able to rescue the host IAV-specific CD8 T cell response from apoptosis. This indicates that pDC must utilize the direct presentation pathway for this rescue. This inability of pDC from 142t-IAV donors to rescue the IAV-specific CD8 T cell response is not due to differences in the overall ability of 142t-IAV to replicate within the lungs or generate defective viral genomes or to differences in levels of costimulatory molecules required for this interaction. We further demonstrate that bypassing the antigen presentation pathway by coating the 142t-IAV pDC with IAV peptide epitopes restores their ability to rescue the IAV-specific CD8 T cell response. IMPORTANCE IAV continues to be a global health burden, infecting 5 to 20% of the global population annually. Continued investigation into the mechanisms that mediate protective immune responses against IAV is important to improving current vaccination and antiviral strategies antagonistic toward IAV. Our findings presented herein demonstrate a key requirement for pDC promotion of effector CD8 T cell survival: that rather than utilizing cross-presentation, pDC must be infected and utilize the endogenous pathway for presentation of antigens to CD8 T cells during in vivo IAV infections. This suggests that targeting presentation via the endogenous pathway in pDC could be important for the development of unique antiviral cellular therapies. PMID:26719269

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Estrogen Receptor α Deficiency Modulates TLR Ligand-Mediated PDC-TREM Expression in Plasmacytoid Dendritic Cells in Lupus-Prone Mice.

PubMed

Scott, Jennifer L; Cunningham, Melissa A; Naga, Osama S; Wirth, Jena R; Eudaly, Jackie G; Gilkeson, Gary S

2015-12-15

Female lupus-prone NZM2410 estrogen receptor α (ERα)-deficient mice are protected from renal disease and have prolonged survival compared with wild-type littermates; however, the mechanism of protection is unknown. Plasmacytoid dendritic cells (pDCs) and type I IFN drive lupus pathogenesis. Estrogen acting via ERα enhances both pDC development and IFN production. The objectives for this study were to determine if ERα modulates pDC function and IFN activity in predisease NZM2410 mice as a possible protective mechanism of ERα deficiency in lupus-prone mice. We measured the effect of ERα deficiency on spleen pDC frequency, number, maturation, and activation state. ERα deficiency reduced type I IFN activity and the frequency of MHC class II(+) pDCs in the spleen without altering overall pDC frequency, number, or maturation state. Additionally, ERα-deficient NZM2410 mice had a significantly decreased frequency of pDCs expressing PDC-TREM, a modulator of TLR-mediated IFN production. After in vitro TLR9 stimulation, ERα deficiency significantly reduced the expression of PDC-TREM on pDCs from both NZM2410 and C57BL/6 mice. Thus, we have identified a significant effect of ERα deficiency on pDCs in predisease NZM2410 mice, which may represent a mechanism by which ERα deficiency protects NZM2410 mice from lupuslike disease. Copyright © 2015 by The American Association of Immunologists, Inc.

Estrogen receptor alpha deficiency modulates TLR ligand mediated PDC-TREM expression in plasmacytoid dendritic cells in lupus prone mice

PubMed Central

Scott, Jennifer L; Cunningham, Melissa A; Naga, Osama S; Wirth, Jena R; EuDaly, Jackie G; Gilkeson, Gary S

2016-01-01

Female lupus prone NZM2410 estrogen receptor alpha (ERα) deficient mice are protected from renal disease and have prolonged survival compared to wild type (WT) littermates, however the mechanism of protection is unknown. Plasmacytoid dendritic cells (pDCs) and type I interferon (IFN) drive lupus pathogenesis. Estrogen acting via ERα enhances both pDC development and IFN production. The objectives for this study were to determine if ERα modulates pDC function and IFN activity in pre-disease NZM2410 mice as a possible protective mechanism of ERα deficiency in lupus prone mice. We measured the effect of ERα deficiency on spleen pDC frequency, number, maturation, and activation state. ERα deficiency reduced type I IFN activity and the frequency of MHCII+ pDCs in the spleen without altering overall pDC frequency, number, or maturation state. Additionally, ERα deficient NZM2410 mice had a significantly decreased frequency of pDCs expressing PDC-TREM, a modulator of toll-like receptor (TLR) mediated IFN production. After in vitro TLR9 stimulation, ERα deficiency significantly reduced the expression of PDC-TREM on pDCs from both NZM2410 and C57BL/6 mice. Thus, we have identified a significant effect of ERα deficiency on pDCs in pre-disease NZM2410 mice, which may represent a mechanism by which ERα deficiency protects NZM2410 mice from lupus like disease. PMID:26553076

Epstein-Barr Virus Promotes Interferon-α Production by Plasmacytoid Dendritic Cells

PubMed Central

Quan, Timothy E.; Roman, Robert M.; Rudenga, Benjamin J.; Holers, V. Michael; Craft, Joe

2010-01-01

Objective Epstein-Barr virus (EBV) infection has been linked to systemic lupus erythematosus (SLE) as demonstrated by the presence of increased seroprevalence and elevated viral loads, but the mechanism of this linkage has not been elucidated. Increased IFN-α levels and signatures, associated with innate immune responses, have been found in patients with SLE. Plasmacytoid dendritic cells (pDC) are innate immune cells that mediate viral immunity by producing large quantities of interferon alpha (IFN-α), but the role they play during infection with EBV remains unclear. To address this issue, we investigated the ability of EBV to promote IFN-α production by pDC in healthy subjects. Methods Human pDC were sorted and cultured in the presence of EBV, EBV small RNA (EBER), and EBV double-stranded DNA (dsDNA). IFN-α production by pDC was measured by enzyme-linked immunosorbent assay (ELISA), with activation of these cells measured by flow cytometry. Results We demonstrate that EBV DNA and RNA promote IFN-α production by human pDC through engagement of Toll-like receptor (TLR) 9 and TLR7, respectively, with initial viral recognition by pDC mediated by binding to major histocompatibility (MHC) class II molecules. Conclusion These data demonstrate that MHC class II-specific engagement by virus and subsequent viral nucleic acid recognition mediates IFN-α production by pDC. Our results suggest that elevated levels of IFN-α found in lupus patients may be a result of aberrantly controlled chronic viral infection. PMID:20178121

Risk of developing palatally displaced canines in patients with early detectable dental anomalies: a retrospective cohort study.

PubMed

Garib, Daniela Gamba; Lancia, Melissa; Kato, Renata Mayumi; Oliveira, Thais Marchini; Neves, Lucimara Teixeira das

2016-01-01

To estimate the risk of PDC occurrence in children with dental anomalies identified early during mixed dentition. The sample comprised 730 longitudinal orthodontic records from children (448 females and 282 males) with an initial mean age of 8.3 years (SD=1.36). The dental anomaly group (DA) included 263 records of patients with at least one dental anomaly identified in the initial or middle mixed dentition. The non-dental anomaly group (NDA) was composed of 467 records of patients with no dental anomalies. The occurrence of PDC in both groups was diagnosed using panoramic and periapical radiographs taken in the late mixed dentition or early permanent dentition. The prevalence of PDC in patients with and without early diagnosed dental anomalies was compared using the chi-square test (p<0.01), relative risk assessments (RR), and positive and negative predictive values (PPV and NPV). PDC frequency was 16.35% and 6.2% in DA and NDA groups, respectively. A statistically significant difference was observed between groups (p<0.01), with greater risk of PDC development in the DA group (RR=2.63). The PPV and NPV was 16% and 93%, respectively. Small maxillary lateral incisors, deciduous molar infraocclusion, and mandibular second premolar distoangulation were associated with PDC. Children with dental anomalies diagnosed during early mixed dentition have an approximately two and a half fold increased risk of developing PDC during late mixed dentition compared with children without dental anomalies.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model.

PubMed

Salama, Abeer; Hegazy, Rehab; Hassan, Azza

2016-01-01

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

PubMed Central

Salama, Abeer; Hassan, Azza

2016-01-01

Chromium (Cr) is used in many industries and it is widely distributed in the environment. Exposure to Cr dust has been reported among workers at these industries. Beside its hazardous effects on the lungs, brain injury could be induced, as the absorption of substances through the nasal membrane has been found to provide them a direct delivery to the brain. We investigated the distribution and the effects of Cr in both brain and lung following the intranasal instillation of potassium dichromate (inPDC) in rats. Simultaneously, we used the common intraperitoneal (ipPDC) rat model of acute Cr-toxicity for comparison. Thirty male Wistar rats were randomly allocated into five groups (n = 6); each received a single dose of saline, ipPDC (15 mg/kg), or inPDC in three dose levels: 0.5, 1, or 2 mg/kg. Locomotor activity was assessed before and 24 h after PDC administration, then, the lungs and brain were collected for biochemical, histopathological, and immunohistochemical investigations. Treatment of rats with ipPDC resulted in a recognition of 36% and 31% of the injected dose of Cr in the brain and lung tissues, respectively. In inPDC-treated rats, targeting the brain by Cr was increased in a dose-dependent manner to reach 46% of the instilled dose in the group treated with the highest dose. Moreover, only this high dose of inPDC resulted in a delivery of a significant concentration of Cr, which represented 42% of the instilled dose, to the lungs. The uppermost alteration in the rats locomotor activity as well as in the brain and lung histopathological features and contents of oxidative stress biomarkers, interleukin-1β (IL-1β), phosphorylated protein kinase B (PKB), and cyclooxygenase 2 (COX-2) were observed in the rats treated with inPDC (2 mg/kg). The findings revealed that these toxic manifestations were directly proportional to the delivered concentration of Cr to the tissue. In conclusion, the study showed that a comparably higher concentrations of Cr and more elevated levels of oxidative stress and inflammatory markers were observed in brain and lung tissues of rats subjected to inPDC in a dose that is just 0.13 that of ipPDC dose commonly used in Cr-induced toxicity studies. Therefore, the study suggests a high risk of brain-targeting injury among individuals environmentally or occupationally exposed to Cr dust, even in low doses, and an additional risk of lung injury with higher Cr concentrations. Moreover, the study introduces inPDC (2 mg/kg)-instillation as a new experimental animal model suitable to study the acute brain and lung toxicities induced by intranasal exposure to Cr compounds. PMID:27997619

β-Cell-specific pyruvate dehydrogenase deficiency impairs glucose-stimulated insulin secretion

PubMed Central

Srinivasan, Malathi; Choi, Cheol S.; Ghoshal, Pushpankur; Pliss, Lioudmila; Pandya, Jignesh D.; Hill, David; Cline, Gary

2010-01-01

Glucose-stimulated insulin secretion (GSIS) by β-cells requires the generation of ATP from oxidation of pyruvate as well as generation of coupling factors involving three different pyruvate cycling shuttles. The roles of several key enzymes involved in pyruvate cycling in β-cells have been documented using isolated islets and β-cell clonal lines. To investigate the role of the pyruvate dehydrogenase (PDH) complex (PDC) in GSIS, a murine model of β-cell-specific PDH deficiency (β-PDHKO) was created. Pancreatic insulin content was decreased in 1-day-old β-PDHKO male pups and adult male mice. The plasma insulin levels were decreased and blood glucose levels increased in β-PDHKO male mice from neonatal life onward. GSIS was reduced in isolated islets from β-PDHKO male mice with about 50% reduction in PDC activity. Impairment in a glucose tolerance test and in vivo insulin secretion during hyperglycemic clamp was evident in β-PDHKO adults. No change in the number or size of islets was found in pancreata from 4-wk-old β-PDHKO male mice. However, an increase in the mean size of individual β-cells in islets of these mice was observed. These findings show a key role of PDC in GSIS by pyruvate oxidation. This β-PDHKO mouse model represents the first mouse model in which a mitochondrial oxidative enzyme deletion by gene knockout has been employed to demonstrate an altered GSIS by β-cells. PMID:20841503

Overexpression of the genes PDC1 and ADH1 activates glycerol conversion to ethanol in the thermotolerant yeast Ogataea (Hansenula) polymorpha.

PubMed

Kata, Iwona; Semkiv, Marta V; Ruchala, Justyna; Dmytruk, Kostyantyn V; Sibirny, Andriy A

2016-08-01

Conversion of byproduct from biodiesel production glycerol to high-value compounds is of great importance. Ethanol is considered a promising product of glycerol bioconversion. The methylotrophic thermotolerant yeast Ogataea (Hansenula) polymorpha is of great interest for this purpose as the glycerol byproduct contains methanol and heavy metals as contaminants, and this yeast utilizes methanol and is relatively resistant to heavy metals. Besides, O. polymorpha shows robust growth on glycerol and produces ethanol from various carbon sources. The thermotolerance of this yeast is an additional advantage, allowing increased fermentation temperature to 45-48 °C, leading to increased rate of the fermentation process and a fall in the cost of distillation. The wild-type strain of O. polymorpha produces insignificant amounts of ethanol from glycerol (0.8 g/l). Overexpression of PDC1 coding for pyruvate decarboxylase enhanced ethanol production up to 3.1 g/l, whereas simultaneous overexpression of PDC1 and ADH1 (coding for alcohol dehydrogenase) led to further increase in ethanol production from glycerol. Moreover, the increased temperature of fermentation up to 45 °C stimulated the production of ethanol from glycerol used as the only carbon source up to 5.0 g/l, which exceeds the data obtained by methylotrophic yeast strains reported so far. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A Process Evaluation of Project Developmental Continuity, Interim Report VII, Volume 3: Assessment of Program Impact Through the Head Start Year.

ERIC Educational Resources Information Center

Granville, Arthur C.; And Others

This interim report, part of a series of documents examining the feasibility of the longitudinal evaluation of Project Developmental Continuity (PDC), presents the results of an analysis of PDC impact at the Head Start level, using Spring 1977 data. PDC is a Head Start Demonstration Program aimed at providing educational and developmental…

Distribution of Pseudomonas-Derived Cephalosporinase and Metallo-β-Lactamases in Carbapenem-Resistant Pseudomonas aeruginosa Isolates from Korea.

PubMed

Cho, Hye Hyun; Kwon, Gye Cheol; Kim, Semi; Koo, Sun Hoe

2015-07-01

The emergence of carbapenem resistance among Pseudomonas aeruginosa is an increasing problem in many parts of the world. In particular, metallo-β-lactamases (MBLs) and AmpC β- lactamases are responsible for high-level resistance to carbapenem and cephalosporin. We studied the diversity and frequency of β-lactamases and characterized chromosomal AmpC β- lactamase from carbapenem-resistant P. aeruginosa isolates. Sixty-one carbapenem-resistant P. aeruginosa isolates were collected from patients in a tertiary hospital in Daejeon, Korea, from January 2011 to June 2014. Minimum inhibitory concentrations (MICs) of four antimicrobial agents were determined using the agar-dilution method. Polymerase chain reaction and sequencing were used to identify the various β-lactamase genes, class 1 integrons, and chromosomally encoded and plasmid-mediated ampC genes. In addition, the epidemiological relationship was investigated by multilocus sequence typing. Among 61 carbapenem-resistant P. aeruginosa isolates, 25 isolates (41.0%) were MBL producers. Additionally, 30 isolates producing PDC (Pseudomonas-derived cephalosporinase)-2 were highly resistant to ceftazidime (MIC50 = 256 μg/ml) and cefepime (MIC50 = 256 μg/ml). Of all the PDC variants, 25 isolates harboring MBL genes showed high levels of cephalosporin and carbapenem resistance, whereas 36 isolates that did not harbor MBL genes revealed relatively low-level resistance (ceftazidime, p < 0.001; cefepime, p < 0.001; imipenem, p = 0.003; meropenem, p < 0.001). The coexistence of MBLs and AmpC β-lactamases suggests that these may be important contributing factors for cephalosporin and carbapenem resistance. Therefore, efficient detection and intervention to control drug resistance are necessary to prevent the emergence of P. aeruginosa possessing this combination of β-lactamases.

The application of advanced PDC concepts proves effective in south Texas

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

Dahlem, J.S.; Baxter, R.L.; Dunn, K.E.

1996-12-01

Over the years, a variety of problems with polycrystalline diamond compact (PDC) bit design and application has been documented, with bit whirl being identified as the cause of many inherent problems. The goal of most PDC manufacturers, and the subject of this paper, is development of a better-performing, whirl-resistant PDC bit design. Similarly, the goal for most operators is the lower cost resulting from effective application of such bits. Toward those ends, a cooperative development effort between operators and a manufacturer was undertaken to apply advanced concepts effectively to the design, manufacture, and application of a new series of PDCmore » bits in south Texas. Adoption of design concepts, such as force-balanced cutting structures, asymmetric blade layouts, spiral blade designs, and tracking cutter arrangements, proved effective in countering the destructive effects of bit whirl, and allowed PDC bits to be used in harder formations. Summaries of both operational and economic performance confirm the success of the undertaking.« less

A Survey on Personal Data Cloud

PubMed Central

Wang, Jiaqiu; Wang, Zhongjie

2014-01-01

Personal data represent the e-history of a person and are of great significance to the person, but they are essentially produced and governed by various distributed services and there lacks a global and centralized view. In recent years, researchers pay attention to Personal Data Cloud (PDC) which aggregates the heterogeneous personal data scattered in different clouds into one cloud, so that a person could effectively store, acquire, and share their data. This paper makes a short survey on PDC research by summarizing related papers published in recent years. The concept, classification, and significance of personal data are elaborately introduced and then the semantics correlation and semantics representation of personal data are discussed. A multilayer reference architecture of PDC, including its core components and a real-world operational scenario showing how the reference architecture works, is introduced in detail. Existing commercial PDC products/prototypes are listed and compared from several perspectives. Five open issues to improve the shortcomings of current PDC research are put forward. PMID:25165753

Lipid Raft, Regulator of Plasmodesmal Callose Homeostasis.

PubMed

Iswanto, Arya Bagus Boedi; Kim, Jae-Yean

2017-04-03

A bstract: The specialized plasma membrane microdomains known as lipid rafts are enriched by sterols and sphingolipids. Lipid rafts facilitate cellular signal transduction by controlling the assembly of signaling molecules and membrane protein trafficking. Another specialized compartment of plant cells, the plasmodesmata (PD), which regulates the symplasmic intercellular movement of certain molecules between adjacent cells, also contains a phospholipid bilayer membrane. The dynamic permeability of plasmodesmata (PDs) is highly controlled by plasmodesmata callose (PDC), which is synthesized by callose synthases (CalS) and degraded by β-1,3-glucanases (BGs). In recent studies, remarkable observations regarding the correlation between lipid raft formation and symplasmic intracellular trafficking have been reported, and the PDC has been suggested to be the regulator of the size exclusion limit of PDs. It has been suggested that the alteration of lipid raft substances impairs PDC homeostasis, subsequently affecting PD functions. In this review, we discuss the substantial role of membrane lipid rafts in PDC homeostasis and provide avenues for understanding the fundamental behavior of the lipid raft-processed PDC.

Development and testing of a Mudjet-augmented PDC bit.

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

Black, Alan; Chahine, Georges; Raymond, David Wayne

2006-01-01

This report describes a project to develop technology to integrate passively pulsating, cavitating nozzles within Polycrystalline Diamond Compact (PDC) bits for use with conventional rig pressures to improve the rock-cutting process in geothermal formations. The hydraulic horsepower on a conventional drill rig is significantly greater than that delivered to the rock through bit rotation. This project seeks to leverage this hydraulic resource to extend PDC bits to geothermal drilling.

Comparison of pulsating DC and DC power air-water plasma jet: A method to decrease plume temperature and increase ROS

NASA Astrophysics Data System (ADS)

Liu, K.; Hu, H.; Lei, J.; Hu, Y.; Zheng, Z.

2016-12-01

Most air-water plasma jets are rich in hydroxyl radicals (•OH), but the plasma has higher temperatures, compared to that of pure gas, especially when using air as working gas. In this paper, pulsating direct current (PDC) power was used to excite the air-water plasma jet to reduce plume temperature. In addition to the temperature, other differences between PDC and DC plasma jets are not yet clear. Thus, comparative studies of those plasmas are performed to evaluate characteristics, such as breakdown voltage, temperature, and reactive oxygen species. The results show that the plume temperature of PDC plasma is roughly 5-10 °C lower than that of DC plasma in the same conditions. The •OH content of PDC is lower than that of DC plasma, whereas the O content of PDC plasma is higher. The addition of water leads in an increase in the plume temperature and in the production of •OH with two types of power supplies. The production of O inversely shows a declining tendency with higher water ratio. The most important finding is that the PDC plasma with 100% water ratio achieves lower temperature and more abundant production of •OH and O, compared with DC plasma with 0% water ratio.

Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.

PubMed

Halim, Nader D; Mcfate, Thomas; Mohyeldin, Ahmed; Okagaki, Peter; Korotchkina, Lioubov G; Patel, Mulchand S; Jeoung, Nam Ho; Harris, Robert A; Schell, Michael J; Verma, Ajay

2010-08-01

Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria, and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons versus astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture, but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDH alpha). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorylated PDH alpha. Dephosphorylation of astrocytic PDH alpha restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed. (c) 2010 Wiley-Liss, Inc.

Plasmacytoid dendritic cells (PDC) are the major DC subset innately producing cytokines in human lymph nodes.

PubMed

Cox, Karina; North, Margaret; Burke, Michael; Singhal, Hemant; Renton, Sophie; Aqel, Nayef; Islam, Sabita; Knight, Stella C

2005-11-01

Plasmacytoid dendritic cells (PDC) constitute a distinct subset of DC found in human peripheral lymph nodes (LN), but little is known about their function. Cell suspensions were prepared from tumor draining LN (n=20) and control LN (n=11) of women undergoing surgical resection for primary breast cancer and elective surgery for benign conditions, respectively. Using four-color flow cytometry, human leukocyte antigen-DR+ DC subsets were identified phenotypically. The proportions and numbers of cells innately producing interleukin (IL)-4, IL-10, IL-12, and interferon-gamma (IFN-gamma) were also measured from intracellular accumulation of cytokine after blocking with monensin. All flow cytometry data were collected without compensation and were compensated off-line using the Winlist algorithm (Verity software). This package also provided the subtraction program to calculate percentage positive cells and intensity of staining. PDC (CD11c-, CD123+) expressed more cytokines than did myeloid DC (CD11c+) or CD1a+ putative "migratory" DC (P<0.001). LN PDC from patients with a good prognosis (px; n=11) demonstrated a relative increase in IL-12 and IFN-gamma expression (median IL-10:IL-12 ratio=0.78 and median IL-4:IFN-gamma ratio=0.7), and PDC from LN draining poor px cancer (n=9) showed a relative increase in IL-10 and IL-4 expression (median IL-10:IL-12 ratio=1.31 and median IL-4:IFN-gamma ratio=2.6). The difference in IL-4:IFN-gamma expression between good and poor px cancer groups was significant (P<0.05). Thus, PDC innately producing cytokines were identified in cell suspensions from human LN, and the character of PDC cytokine secretion may differ between two breast cancer prognostic groups. We speculate that a shift towards PDC IL-10 and IL-4 expression could promote tumor tolerance in LN draining poor px breast cancer.

Cortical metabolism in pyruvate dehydrogenase deficiency revealed by ex vivo multiplet 13C-NMR of the adult mouse brain

PubMed Central

Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Malloy, Craig R.; Patel, Mulchand S.; Pascual, Juan M.

2013-01-01

The pyruvate dehydrogenase complex (PDC), required for complete glucose oxidation, is essential for brain development. Although PDC deficiency is associated with a severe clinical syndrome, little is known about its effects on either substrate oxidation or synthesis of key metabolites such as glutamate and glutamine. Computational simulations of brain metabolism indicated that a 25% reduction in flux through PDC and a corresponding increase in flux from an alternative source of acetyl-CoA would substantially alter the 13C NMR spectrum obtained from brain tissue. Therefore, we evaluated metabolism of [1,6-13C2]glucose (oxidized by both neurons and glia) and [1,2-13C2]acetate (an energy source that bypasses PDC) in the cerebral cortex of adult mice mildly and selectively deficient in brain PDC activity, a viable model that recapitulates the human disorder. Intravenous infusions were performed in conscious mice and extracts of brain tissue were studied by 13C NMR. We hypothesized that mice deficient in PDC must increase the proportion of energy derived from acetate metabolism in the brain. Unexpectedly, the distribution of 13C in glutamate and glutamine, a measure of the relative flux of acetate and glucose into the citric acid cycle, was not altered. The 13C labeling pattern in glutamate differed significantly from glutamine, indicating preferential oxidation of [1,2-13C]acetate relative to [1,6-13C]glucose by a readily discernible metabolic domain of the brain of both normal and mutant mice, presumably glia. These findings illustrate that metabolic compartmentation is preserved in the PDC-deficient cerebral cortex, probably reflecting intact neuron-glia metabolic interactions, and that a reduction in brain PDC activity sufficient to induce cerebral dysgenesis during development does not appreciably disrupt energy metabolism in the mature brain. PMID:22884585

Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response.

PubMed

Hemann, Emily A; Sjaastad, Louisa E; Langlois, Ryan A; Legge, Kevin L

2015-12-30

Following influenza A virus (IAV) infection, development of a robust IAV-specific CD8 T cell response is required for clearance of primary infection and enhances memory protection. Following IAV infection, plasmacytoid dendritic cells (pDC) or CD8α(+) DC regulate pulmonary effector CD8 T cell responses within the lung. Without this DC-T cell interaction, insufficient effector CD8 T cells are maintained in the lungs, leading to enhanced morbidity and mortality. Previous studies have demonstrated that pDC are capable of classical presentation or cross-presentation of IAV antigens and could potentially regulate IAV-specific CD8 T cell responses through either mechanism. Our results demonstrate that pDC from the lungs of donor mice infected with an IAV that is not able to replicate in hematopoietic cells (142t-IAV), unlike donor pDC isolated from the lungs of control infected mice, are not able to rescue the host IAV-specific CD8 T cell response from apoptosis. This indicates that pDC must utilize the direct presentation pathway for this rescue. This inability of pDC from 142t-IAV donors to rescue the IAV-specific CD8 T cell response is not due to differences in the overall ability of 142t-IAV to replicate within the lungs or generate defective viral genomes or to differences in levels of costimulatory molecules required for this interaction. We further demonstrate that bypassing the antigen presentation pathway by coating the 142t-IAV pDC with IAV peptide epitopes restores their ability to rescue the IAV-specific CD8 T cell response. IAV continues to be a global health burden, infecting 5 to 20% of the global population annually. Continued investigation into the mechanisms that mediate protective immune responses against IAV is important to improving current vaccination and antiviral strategies antagonistic toward IAV. Our findings presented herein demonstrate a key requirement for pDC promotion of effector CD8 T cell survival: that rather than utilizing cross-presentation, pDC must be infected and utilize the endogenous pathway for presentation of antigens to CD8 T cells during in vivo IAV infections. This suggests that targeting presentation via the endogenous pathway in pDC could be important for the development of unique antiviral cellular therapies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Fermentation of xylose to ethanol by genetically modified enteric bacteria

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

Tolan, J.S.

1987-01-01

This thesis describes the fermentation of D-xylose by wild type and recombinant Klebsiella planticola ATCC 33531 and Erwinia chrysanthemi B374. The recombinant strains bear multi-copy plasmids containing the pdc gene inserted from Zymomonas mobilis. Expression of the gene in K. planticola markedly increased the yield of ethanol, up to 1.3 mole/mole xylose, or 25.1 g/L. Concurrently, there were significant decreases in the yields of formation acetate, lactate, and butanediol. Transconjugant Klebsiella grew almost as fast as the wild type and tolerated up to 4% ethanol. The plasmid was retained by the cells during at least one batch culture, even inmore » the absence of selective pressure by antibiotics to maintain the plasmid. The cells produced 31.6 g/L ethanol from 79.6 g/L of a D-glucose-D-xylose-L-arabinose mixture designed to simulate hydrolyzed hemicellulose. The physiology of the wild type K. planticola is described in more detail than in the original report of its isolation. E. chrysanthemi PDC transconjugants also produced ethanol in high yield (up to 1.45 mole/mole xylose). However, transconjugant E. chrysanthemi grew only 1/4 as rapidly as the wild type and tolerated only 2% ethanol. The plasmid PZM15 apparently exhibits pleiotropic effects when inserted into K. planticola and into E. chrysanthemi.« less

Syntheses, structures and properties of 3D inorganic-organic hybrid frameworks constructed from lanthanide polymer and Keggin-type tungstosilicate

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

Gao Yuanzhe; College of Chemistry and Material Science, Hebei Normal University, Shijiazhuang, Hebei 050016; Xu Yanqing, E-mail: xyq@bit.edu.c

2010-05-15

Inorganic-organic hybrid frameworks, namely [Ce(H{sub 2}O){sub 3}(pdc)]{sub 4}[SiW{sub 12}O{sub 40}].6H{sub 2}O 1, [M(H{sub 2}O){sub 4}(pdc)]{sub 4}[SiW{sub 12}O{sub 40}].2H{sub 2}O (M=Ce for 2a, La for 2b, Nd for 2c; H{sub 2}pdc=pyridine-2,6-dicarboxylic acid) were assembled through incorporation of Keggin-type heteropolyanion [SiW{sub 12}O{sub 40}]{sup 4-} within the voids of lanthanides-pdc network as pillars or guests under hydrothermal condition. Single-crystal X-ray analyses of these crystals reveal that compound 1 presents 3D pillar-layered framework with the [SiW{sub 12}O{sub 40}]{sup 4-} anions located on the square voids of the two-dimensional Ce-pdc bilayer. Compounds 2a-c are isostructural and constructed from 3D Ln-pdc-based metal-organic framework (MOF) incorporating noncoordinatingmore » guests Keggin structure [SiW{sub 12}O{sub 40}]{sup 4-}. Solid-state properties of compounds 1 and 2a-c such as thermal stability and photoluminescence have been further investigated. - Graphical abstract: Two types of new inorganic-organic hybrid frameworks through incorporation of Keggin-type heteropolyanion [SiW{sub 12}O{sub 40}]{sup 4-} within the voids of lanthanides-pdc network as pillars or guests under hydrothermal condition were successfully assembled. Solid-state properties of compounds 1 and 2a such as thermal stability and photoluminescence have been further investigated.« less

Supraspinal and spinal effects of L-trans-PDC, an inhibitor of glutamate transporter, on the micturition reflex in rats.

PubMed

Honda, Masashi; Yoshimura, Naoki; Hikita, Katsuya; Hinata, Nobuyuki; Muraoka, Kuniyasu; Saito, Motoaki; Chancellor, Michael B; Takenaka, Atsushi

2013-09-01

Glutamate is a major excitatory transmitter in the central nervous system, controlling lower urinary tract function. Five types of glutamate transporters such as GLAST (EAAT1), GLT-1 (EAAT2), EAAC-1 (EAAT3), EAAT4, and EAAT5 have been cloned so far. In the current study we tested whether L-trans-pyrrolidine-2,4-dicarboxylic acid (L-trans-PDC), a non-selective inhibitor of glutamate transporters that increases endogenous glutamate concentration, can affect the micturition reflex in urethane anesthetized rats. Continuous cystometrograms (CMG, 0.04 ml/min infusion rate) were performed in two groups of urethane-anesthetized rats. A group of 18 rats was used for intrathecal administration of 1-10 µg of L-trans-PDC via an intrathecal catheter. In the second group of 18 rats, 1-10 µg of L-trans-PDC were administered intracerebroventricularly via a catheter inserted into the lateral ventricle. Micturition parameters were recorded and compared before and after drug administration. Intrathecal administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested. Intracerebroventricular administration of L-trans-PDC at 1, 3, and 10 µg (n = 6 per dose) also increased intercontraction intervals in dose dependent fashion, but did not affect postvoid residual or basal pressure at any doses tested. The current results show that, in urethane-anesthetized rats, suppression of glutamate transporters by L-trans-PDC has an inhibitory effect on the micturition reflex at supraspinal and spinal sites, possibly via activation of glutamate-mediated inhibitory pathways. Copyright © 2012 Wiley Periodicals, Inc.

Haloacetic Acid Water Disinfection Byproducts Affect Pyruvate Dehydrogenase Activity and Disrupt Cellular Metabolism.

PubMed

Dad, Azra; Jeong, Clara H; Wagner, Elizabeth D; Plewa, Michael J

2018-02-06

The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as byproducts of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic, and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown. In this study, we evaluated the effects of mono-, di-, and tri-HAAs on cellular GAPDH enzyme kinetics, cellular ATP levels, and pyruvate dehydrogenase complex (PDC) activity. Here, treatments conducted in Chinese hamster ovary (CHO) cells revealed differences among mono-, di-, and triHAAs in their molecular targets. The monoHAAs, iodoacetic acid and bromoacetic acid, were the strongest inhibitors of GAPDH and greatly reduced cellular ATP levels. Chloroacetic acid, diHAAs, and triHAAs were weaker inhibitors of GAPDH and some increased the levels of cellular ATP. HAAs also affected PDC activity, with most HAAs activating PDC. The primary finding of this work is that mono- versus multi-HAAs address different molecular targets, and the results are generally consistent with a model in which monoHAAs activate the PDC through GAPDH inhibition-mediated disruption in cellular metabolites, including altering ATP-to-ADP and NADH-to-NAD ratios. The monoHAA-mediated reduction in cellular metabolites results in accelerated PDC activity by way of metabolite-ratio-dependent PDC regulation. DiHAAs and triHAAs are weaker inhibitors of GAPDH, but many also increase cellular ATP levels, and we suggest that they increase PDC activity by inhibiting pyruvate dehydrogenase kinase.

Structures of pseudechetoxin and pseudecin, two snake-venom cysteine-rich secretory proteins that target cyclic nucleotide-gated ion channels: implications for movement of the C-terminal cysteine-rich domain

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

Suzuki, Nobuhiro; Department of Biochemistry, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki 305-8602; Yamazaki, Yasuo

2008-10-01

The structures of pseudechetoxin and pseudecin suggest that both proteins bind to cyclic nucleotide-gated ion channels in a manner in which the concave surface occludes the pore entrance. Cyclic nucleotide-gated (CNG) ion channels play pivotal roles in sensory transduction by retinal photoreceptors and olfactory neurons. The elapid snake toxins pseudechetoxin (PsTx) and pseudecin (Pdc) are the only known protein blockers of CNG channels. These toxins belong to a cysteine-rich secretory protein (CRISP) family containing an N-terminal pathogenesis-related proteins of group 1 (PR-1) domain and a C-terminal cysteine-rich domain (CRD). PsTx and Pdc are highly homologous proteins, but their blocking affinitiesmore » on CNG channels are different: PsTx blocks both the olfactory and retinal channels with ∼15–30-fold higher affinity than Pdc. To gain further insights into their structure and function, the crystal structures of PsTx, Pdc and Zn{sup 2+}-bound Pdc were determined. The structures revealed that most of the amino-acid-residue differences between PsTx and Pdc are located around the concave surface formed between the PR-1 domain and the CRD, suggesting that the concave surface is functionally important for CNG-channel binding and inhibition. A structural comparison in the presence and absence of Zn{sup 2+} ion demonstrated that the concave surface can open and close owing to movement of the CRD upon Zn{sup 2+} binding. The data suggest that PsTx and Pdc occlude the pore entrance and that the dynamic motion of the concave surface facilitates interaction with the CNG channels.« less

Site-specific tumor grading system in colorectal cancer: multicenter pathologic review of the value of quantifying poorly differentiated clusters.

PubMed

Ueno, Hideki; Hase, Kazuo; Hashiguchi, Yojiro; Shimazaki, Hideyuki; Tanaka, Masafumi; Miyake, Ohki; Masaki, Tadahiko; Shimada, Yoshifumi; Kinugasa, Yusuke; Mori, Yoshiyuki; Kishimoto, Mitsuo; Kameoka, Shingo; Sato, Yu; Matsuda, Keiji; Nakadoi, Koichi; Shinto, Eiji; Nakamura, Takahiro; Sugihara, Kenichi

2014-02-01

The study aimed to determine the value of a novel site-specific grading system based on quantifying poorly differentiated clusters (PDC; Grade(PDC)) in colorectal cancer (CRC). A multicenter pathologic review involving 12 institutions was performed on 3243 CRC cases (stage I, 583; II, 1331; III, 1329). Cancer clusters of ≥5 cancer cells and lacking a gland-like structure (PDCs) were counted under a ×20 objective lens in a field containing the maximum clusters. Tumors with <5, 5 to 9, and ≥10 PDCs were classified as grades G1, G2, and G3, respectively. According to Grade(PDC), 1594, 1005, and 644 tumors were classified as G1, G2, and G3 and had 5-year recurrence-free survival rates of 91.6%, 75.4%, and 59.6%, respectively (P<0.0001). Multivariate analysis showed that Grade exerted an influence on prognostic outcome independently of TNM staging; approximately 20% and 46% of stage I and II patients, respectively, were selected by Grade(PDC) as a population whose survival estimate was comparable to or even worse than that of stage III patients. Grade(PDC) surpassed TNM staging in the ability to stratify patients by recurrence-free survival (Akaike information criterion, 2915.6 vs. 2994.0) and had a higher prognostic value than American Joint Committee on Cancer (AJCC) grading (Grade(AJCC)) at all stages. Regarding judgment reproducibility of grading tumors, weighted κ among the 12 institutions was 0.40 for Grade(AJCC) and 0.52 for Grade(PDC). Grade(PDC) has a robust prognostic power and promises to be of sufficient clinical value to merit implementation as a site-specific grading system in CRC.

A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

USGS Publications Warehouse

Chernoff, Neil; Hill, D. J.; Diggs, D. L.; Faison, B. D.; Francis, B. M.; Lang, J. R.; Larue, M. M.; Le, T.-T.; Loftin, Keith A.; Lugo, J. N.; Schmid, J. E.; Winnik, W. W.

2017-01-01

The compound BMAA (β-N-methylamino-L-alanine) has been postulated to play a significant role in four serious neurological human diseases: Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) found on Guam, and ALS, Parkinsonism, and dementia that occur globally. ALS/PDC with symptoms of all three diseases first came to the attention of the scientific community during and after World War II. It was initially associated with cycad flour used for food because BMAA is a product of symbiotic cycad root-dwelling cyanobacteria. Human consumption of flying foxes that fed on cycad seeds was later suggested as a source of BMAA on Guam and a cause of ALS/PDC. Subsequently, the hypothesis was expanded to include a causative role for BMAA in other neurodegenerative diseases including Alzheimer’s disease (AD) through exposures attributed to proximity to freshwaters and/or consumption of seafood due to its purported production by most species of cyanobacteria. The hypothesis that BMAA is the critical factor in the genesis of these neurodegenerative diseases received considerable attention in the medical, scientific, and public arenas. This review examines the history of ALS/PDC and the BMAA-human disease hypotheses; similarities and differences between ALS/PDC and the other diseases with similar symptomologies; the relationship of ALS/PDC to other similar diseases, studies of BMAA-mediated effects in lab animals, inconsistencies and data gaps in the hypothesis; and other compounds and agents that were suggested as the cause of ALS/PDC on Guam. The review concludes that the hypothesis of a causal BMAA neurodegenerative disease relationship is not supported by existing data.

Spectrum of neurological and survival outcomes in pyruvate dehydrogenase complex (PDC) deficiency: lack of correlation with genotype.

PubMed

DeBrosse, Suzanne D; Okajima, Kazuki; Zhang, Shulin; Nakouzi, Ghunwa; Schmotzer, Christine L; Lusk-Kopp, Marilyn; Frohnapfel, Mary Beth; Grahame, George; Kerr, Douglas S

2012-11-01

Pyruvate dehydrogenase complex (PDC) deficiency is a relatively common mitochondrial disorder that primarily presents with neurological manifestations and lactic acidemia. We analyzed the clinical outcomes and neurological features of 59 consented symptomatic subjects (27 M, 32 F), who were confirmed to have PDC deficiency with defined mutations in one of the genes of PDC (PDHA1, n = 53; PDHB, n = 4; DLAT, n = 2), including 47 different mutations, of which 22 were novel, and for whom clinical records and/or structured interviews were obtained. 39% of these subjects (23/59) have died. Of these, 91% (21/23) died before age 4 years, 61% (14/23) before 1 year, and 43% (10/23) before 3 months. 56% of males died compared with 25% of females. Causes of death included severe lactic acidosis, respiratory failure, and infection. In subjects surviving past 6 months, a broad range of intellectual outcomes was observed. Of 42 subjects whose intellectual abilities were professionally evaluated, 19% had normal or borderline intellectual ability (CQ/IQ ≥ 70), 10% had mild intellectual disability (ID) (CQ/IQ 55-69), 17% had moderate ID (CQ/IQ 40-54), 24% had severe ID (CQ/IQ 25-39) and 33% had profound ID (CQ/IQ<25). Assessment by parents was comparable. Of 10 subjects who reached age 12 years, 9 had had professional IQ assessments, and only 4 had IQs ≥ 70 (only 2 of these 4 had assessments after age 12 years). The average outcome for females was severe-to-profound ID, whereas that of males was mild-to-moderate ID. Of subjects for whom specific neurological data were available, the majority had hypotonia (89%), and hypertonia or mixed hyper-/hypotonia (49%) were common. Seizures (57%), microcephaly (49%), and structural brain abnormalities including ventriculomegaly (67%) and agenesis, dysgenesis, or hypoplasia of the corpus callosum (55%) were common. Leigh syndrome was found in only 35%. Structural brain abnormalities were more common in females, and Leigh syndrome was more common in males. In a subgroup of 16 ambulatory subjects >3.5 years in whom balance was evaluated, ataxia was found in 13. Peripheral neuropathy was documented in 2 cases but not objectively evaluated in most subjects. Outcomes of this population with genetically confirmed PDC deficiency are heterogeneous and not distinctive. Correlations between specific genotypes and outcomes were not established. Although more females survive, related to the prevalence of X-linked PDHA1 mutations, symptomatic surviving females are generally more severely impaired cognitively and have a different pattern of neurological impairment compared to males. Neonatal or infant onset of symptoms was associated with poor outcomes. Males with PDHA1 mutations and low fibroblast PDC activity were less likely to survive beyond infancy. Recurrence rate in siblings of subjects with PDHA1 mutation was less than 5%. Paradoxically, in this retrospective review, potential factors considered possibly relevant to development, such as in vitro PDC activity, specific mutations, use of ketogenic diets, supplements, or medications, were generally not confirmed to be significantly correlated with objective outcomes of survival or neuro-cognitive function. Therefore, the basis of variability of these outcomes remains largely undetermined. Copyright © 2012 Elsevier Inc. All rights reserved.

Hydrogenolysis of α-methylbenzyl alcohol to ethylbenzene over Pd/C catalyst

NASA Astrophysics Data System (ADS)

Feng, J.; Zhong, Y. H.; Dai, S. H.

2018-01-01

The hydrogenolysis of α-methylbenzyl alcohol (MBA) to ethylbenzene (EB) over Pd/C catalyst was studied. The XRD and TEM results show that Pd nanoparticles are well dispersed on the carbon support with good crystallinity. There is no 1-cyclohexylethanol or ethylcyclohexane in the products, indicating that Pd/C is excellent for inhibiting the hydrogenation of the aromatic ring. Alcohol solvents are beneficial to increase the catalytic activity because of their strong polarity and good solubility.

HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-alpha.

PubMed

Hardy, Andrew W; Graham, David R; Shearer, Gene M; Herbeuval, Jean-Philippe

2007-10-30

Plasmacytoid dendritic cells (pDC) are key players in viral immunity and produce IFN-alpha after HIV-1 exposure, which in turn regulates TNF-related apoptosis-inducing ligand (TRAIL) expression by CD4(+) T cells. We show here that infectious and noninfectious HIV-1 virions induce activation of pDC into TRAIL-expressing IFN-producing killer pDC (IKpDC). IKpDC expressed high levels of activation markers (HLA-DR, CD80, CD83, and CD86) and the migration marker CCR7. Surprisingly, CXCR4 and CCR5 were down-regulated on IKpDC. We also show that HIV-1-induced IKpDC depended on Toll-like receptor 7 (TLR7) activation. HIV-1 or TLR7 agonistexposed IKpDC induced apoptosis of the CD4(+) T cell line SupT1 via the TRAIL pathway. Furthermore, IFN-alpha produced after HIV-induced TLR7 stimulation was responsible for TRAIL expression and the down-regulation of both CXCR4 and CCR5 by IKpDC. In contrast, activation and migration markers were not regulated by IFN-alpha. Finally, IFN-alpha increased the survival of IKpDC. We characterized a subset of pDC with a killer activity that is activated by endosomal-associated viral RNA and not by infection.

Fluorescent Zn-PDC/Tb3+ Coordination Polymer Nanostructure: A Candidate for Highly Selective Detections of Cefixime Antibiotic and Acetone in Aqueous System.

PubMed

Pan, Hong; Wang, Sufan; Dao, Xiaoyao; Ni, Yonghong

2018-02-05

Tb 3+ -doped zinc-based coordination polymer nanospindle bundles (Zn-PDC/Tb 3+ , or [Zn(2,5-PDC)(H 2 O) 2 ]·H 2 O/Tb 3+ ) were synthesized by a simple solution precipitation route at room temperature, employing Zn(NO 3 ) 2 , Tb(NO 3 ) 3 , and 2,5-Na 2 PDC as the initial reactants, and a mixture of water and ethanol with the volume ratio of 10:10 as the solvent. The as-obtained nanostructures presented strong fluorescent emission under the excitation of 298 nm light, which was attributed to the characteristic emission of the Tb 3+ ion. It was found that the above-mentioned strong fluorescence of the nanostructures could be selectively quenched by cefixime (CFX) in aqueous solution. The other common antibiotics hardly interfered. Thus, as-obtained Zn-PDC/Tb 3+ nanostructures could be prepared as a highly sensitive fluorescence probe for selective detection of CFX in an aqueous system. The corresponding detection limit reached 72 ppb. The theoretic calculation and UV-vis absorption experiments confirmed that the fluorescence quenching of Zn-PDC/Tb 3+ nanostructures toward CFX should be attributed to the electron transfer and the fluorescence inner filter effect between the fluorescent matter and the analyte. In addition, the strong fluorescence of the nanostructures could also be selectively quenched by acetone in the water system.

Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

PubMed

Gelber, C; Gemmell, L; McAteer, D; Homola, M; Swain, P; Liu, A; Wilson, K J; Gefter, M

1997-03-01

Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.

Comparative study on catalytic hydrodehalogenation of halogenated aromatic compounds over Pd/C and Raney Ni catalysts

NASA Astrophysics Data System (ADS)

Ma, Xuanxuan; Liu, Sujing; Liu, Ying; Gu, Guodong; Xia, Chuanhai

2016-04-01

Catalytic hydrodehalogenation (HDH) has proved to be an efficient approach to dispose halogenated aromatic compounds (HACs). Liquid-phase HDH of single and mixed halobenzenes/4-halophenols with H2 over 5% Pd/C and Raney Ni catalyst are investigated and compared. For liquid-phase HDH of single HACs, hydrogenolytic scission reactivity of C-X bonds decreases in order of C-Br > C-Cl > C-I > C-F over Pd/C catalyst, and in order of C-I > C-Br > C-Cl > C-F over Raney Ni catalyst. To clarify the reason why hydrogenolytic scission reactivity of C-X bonds over Pd/C and Raney Ni catalysts exhibits different trends, liquid-phase HDH of mixed HACs over Pd/C and Raney Ni catalysts were studied, and catalysts are characterized by SEM, EDX, and XRD techniques. It was found that the high adsorption of iodoarenes on Pd/C catalyst caused the HDH reactivity of iodoarenes to be lower than that of chloroarenes and bromoarenes in the HDH of single HACs. Moreover, the adsorption of in situ produced iodine ion (I-) to catalyst surface would result in the decline of catalytic activity, which might be the main reason why the HDH reactivity of HACs in the presence of NaI is rather low.

Fat tissue after lipolysis of lipomas: a histopathological and immunohistochemical study.

PubMed

Bechara, Falk G; Sand, Michael; Hoffmann, Klaus; Sand, Daniel; Altmeyer, Peter; Stücker, Markus

2007-07-01

Injections with Lipostabil, a phosphatidylcholine (PDC) containing substance, have become a popular technique to treat localized fat accumulation and lipomas for aesthetic reasons. Despite its frequent use, the mechanism of action of PDC and histological changes of treated fat tissue still remain unclear. To investigate the histological changes of lipomas after treatment with PDC. In all, fourteen lipomas (n = 14) in five patients presenting with multiple lipomas were treated with intralesional injections of PDC (Lipostabil, Nettermann, Germany). Histological changes with immunohistochemical analysis of the inflammatory process were evaluated 4, 10, 24, 48 h, 10 days, 30 days and 60 days after lipolysis. Between 4 and 48 h after injection, histology shows a lobular neutrophilic infiltrate with partially destroyed fat cells. At day 10 the inflammatory process is accompanied by an infiltration of T-lymphocytes. After 60 days formation of macrophages with foam cells are visible, accompanied by thickened septa and capsula. Lipolysis with PDC results in a distinct inflammatory reaction of affected fat tissue, similar to factitial panniculitis. Early destruction of fat cells may suggest the involvement of detergent or osmotic mechanisms in the process.

CD4- and dynamin-dependent endocytosis of HIV-1 into plasmacytoid dendritic cells

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

Pritschet, Kathrin; Donhauser, Norbert; Schuster, Philipp

Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p

cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells

PubMed Central

Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

2016-01-01

Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID:27058035

Turbodrills and innovative PDC bits economically drilled hard formations

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

Boudreaux, R.C.; Massey, K.

1994-03-28

The use of turbodrills and polycrystalline diamond compact (PDC) bits with an innovative, tracking cutting structure has improved drilling economics in medium and hard formations in the Gulf of Mexico. Field results have confirmed that turbodrilling with trackset PDC bits reduced drilling costs, compared to offset wells. The combination of turbodrills and trackset bits has been used successfully in a broad range of applications and with various drilling parameters. Formations ranging from medium shales to hard, abrasive sands have been successfully and economically drilled. The tools have been used in both water-based and oil-based muds. Additionally, the turbo-drill and tracksetmore » PDC bit combination has been stable on directional drilling applications. The locking effect of the cutting structure helps keep the bit on course.« less

Mild Deoxygenation of Aromatic Ketones and Aldehydes over Pd/C Using Polymethylhydrosiloxane as the Reducing Agent**

PubMed Central

Volkov, Alexey; Gustafson, Karl P J; Tai, Cheuk-Wai; Verho, Oscar; Bäckvall, Jan-E; Adolfsson, Hans

2015-01-01

Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol % Pd/C catalyst to furnish the corresponding deoxygenated product in 93 % yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions. PMID:25728614

A new product for photon-limited imaging

NASA Astrophysics Data System (ADS)

Gonsiorowski, Thomas

1986-01-01

A new commercial low-light imaging detector, the Photon Digitizing Camera (PDC), is based on the PAPA detector developed at Harvard University. The PDC generates (x, y, t)-coordinate data of each detected photoevent. Because the positional address computation is performed optically, very high counting rates are achieved even at full spatial resolution. Careful optomechanical and electronic design results in a compact, rugged detector with superb performance. The PDC will be used for speckle imaging of astronomical sources and other astronomical and low-light applications.

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production.

PubMed

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production.

Ribavirin Contributes to Hepatitis C Virus Suppression by Augmenting pDC Activation and Type 1 IFN Production

PubMed Central

Wang, Yang; McGivern, David R; Cheng, Liang; Li, Guangming; Lemon, Stanley M; Niu, Junqi; Su, Lishan; Reszka-Blanco, Natalia J

2015-01-01

Ribavirin is used as a component of combination therapies for the treatment of chronic hepatitis C virus (HCV) infection together with pegylated interferon and/or direct-acting antiviral drugs. Its mechanism of action, however, is not clear. Direct antiviral activity and immunomodulatory functions have been implicated. Plasmacytoid dendritic cells (pDCs) are the principal source of type 1 interferon during viral infection. The interaction of pDCs with HCV-infected hepatocytes is the subject of intense recent investigation, but the effect of ribavirin on pDC activation has not been evaluated. In this study we showed that ribavirin augments toll-like receptors 7 and 9-mediated IFNα/β expression from pDCs and up-regulated numerous interferon-stimulated genes. Using the H77S.3 HCV infection and replication system, we showed that ribavirin enhanced the ability of activated pDCs to inhibit HCV replication, correlated with elevated induction of IFNα. Our findings provide novel evidence that ribavirin contributes to HCV inhibition by augmenting pDCs-derived type 1 IFN production. PMID:26274905

78 FR 69408 - Combined Notice of Filings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-19

....m. ET 11/18/13. Docket Numbers: RP14-154-000. Applicants: PDC Energy, Inc., Alliance Petroleum Corporation. Description: Joint Petition of PDC Energy, Inc. and Alliance Petroleum Corporation for Limited...

Succinyl-CoA synthetase (SUCLA2) deficiency in two siblings with impaired activity of other mitochondrial oxidative enzymes in skeletal muscle without mitochondrial DNA depletion.

PubMed

Huang, Xiaoping; Bedoyan, Jirair K; Demirbas, Didem; Harris, David J; Miron, Alexander; Edelheit, Simone; Grahame, George; DeBrosse, Suzanne D; Wong, Lee-Jun; Hoppel, Charles L; Kerr, Douglas S; Anselm, Irina; Berry, Gerard T

2017-03-01

Mutations in SUCLA2 result in succinyl-CoA ligase (ATP-forming) or succinyl-CoA synthetase (ADP-forming) (A-SCS) deficiency, a mitochondrial tricarboxylic acid cycle disorder. The phenotype associated with this gene defect is largely encephalomyopathy. We describe two siblings compound heterozygous for SUCLA2 mutations, c.985A>G (p.M329V) and c.920C>T (p.A307V), with parents confirmed as carriers of each mutation. We developed a new LC-MS/MS based enzyme assay to demonstrate the decreased SCS activity in the siblings with this unique genotype. Both siblings shared bilateral progressive hearing loss, encephalopathy, global developmental delay, generalized myopathy, and dystonia with choreoathetosis. Prior to diagnosis and because of lactic acidosis and low activity of muscle pyruvate dehydrogenase complex (PDC), sibling 1 (S1) was placed on dichloroacetate, while sibling 2 (S2) was on a ketogenic diet. S1 developed severe cyclic vomiting refractory to therapy, while S2 developed Leigh syndrome, severe GI dysmotility, intermittent anemia, hypogammaglobulinemia and eventually succumbed to his disorder. The mitochondrial DNA contents in skeletal muscle (SM) were normal in both siblings. Pyruvate dehydrogenase complex, ketoglutarate dehydrogenase complex, and several mitochondrial electron transport chain (ETC) activities were low or at the low end of the reference range in frozen SM from S1 and/or S2. In contrast, activities of PDC, other mitochondrial enzymes of pyruvate metabolism, ETC and, integrated oxidative phosphorylation, in skin fibroblasts were not significantly impaired. Although we show that propionyl-CoA inhibits PDC, it does not appear to account for decreased PDC activity in SM. A better understanding of the mechanisms of phenotypic variability and the etiology for tissue-specific secondary deficiencies of mitochondrial enzymes of oxidative metabolism, and independently mitochondrial DNA depletion (common in other cases of A-SCS deficiency), is needed given the implications for control of lactic acidosis and possible clinical management. Copyright © 2016 Elsevier Inc. All rights reserved.

Voltage Drop Compensation Method for Active Matrix Organic Light Emitting Diode Displays

NASA Astrophysics Data System (ADS)

Choi, Sang-moo; Ryu, Do-hyung; Kim, Keum-nam; Choi, Jae-beom; Kim, Byung-hee; Berkeley, Brian

2011-03-01

In this paper, the conventional voltage drop compensation methods are reviewed and the novel design and driving scheme, the advanced power de-coupled (aPDC) driving method, is proposed to effectively compensate the voltage IR drop of active matrix light emitting diode (AMOLED) displays. The advanced PDC driving scheme can be applied to general AMOLED pixel circuits that have been developed with only minor modification or without requiring modification in pixel circuit. A 14-in. AMOLED panel with the aPDC driving scheme was fabricated. Long range uniformity (LRU) of the 14-in. AMOLED panel was improved from 43% without the aPDC driving scheme, to over 87% at the same brightness by using the scheme and the layout complexity of the panel with new design scheme is less than that of the panel with the conventional design scheme.

Characterization of pore structure in cement-based materials using pressurization-depressurization cycling mercury intrusion porosimetry (PDC-MIP)

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

Zhou Jian, E-mail: Jian.Zhou@tudelft.n; Ye Guang, E-mail: g.ye@tudelft.n; Magnel Laboratory for Concrete Research, Department of Structural Engineering, Ghent University, Technologiepark-Zwijnaarde 904 B-9052, Ghent

2010-07-15

Numerous mercury intrusion porosimetry (MIP) studies have been carried out to investigate the pore structure in cement-based materials. However, the standard MIP often results in an underestimation of large pores and an overestimation of small pores because of its intrinsic limitation. In this paper, an innovative MIP method is developed in order to provide a more accurate estimation of pore size distribution. The new MIP measurements are conducted following a unique mercury intrusion procedure, in which the applied pressure is increased from the minimum to the maximum by repeating pressurization-depressurization cycles instead of a continuous pressurization followed by a continuousmore » depressurization. Accordingly, this method is called pressurization-depressurization cycling MIP (PDC-MIP). By following the PDC-MIP testing sequence, the volumes of the throat pores and the corresponding ink-bottle pores can be determined at every pore size. These values are used to calculate pore size distribution by using the newly developed analysis method. This paper presents an application of PDC-MIP on the investigation of the pore size distribution in cement-based materials. The experimental results of PDC-MIP are compared with those measured by standard MIP. The PDC-MIP is further validated with the other experimental methods and numerical tool, including nitrogen sorption, backscanning electron (BSE) image analysis, Wood's metal intrusion porosimetry (WMIP) and the numerical simulation by the cement hydration model HYMOSTRUC3D.« less

Isothermal titration calorimetric studies on the interaction of the major bovine seminal plasma protein, PDC-109 with phospholipid membranes.

PubMed

Anbazhagan, V; Sankhala, Rajeshwer S; Singh, Bhanu Pratap; Swamy, Musti J

2011-01-01

The interaction of the major bovine seminal plasma protein, PDC-109 with lipid membranes was investigated by isothermal titration calorimetry. Binding of the protein to model membranes made up of diacyl phospholipids was found to be endothermic, with positive values of binding enthalpy and entropy, and could be analyzed in terms of a single type of binding sites on the protein. Enthalpies and entropies for binding to diacylphosphatidylcholine membranes increased with increase in temperature, although a clear-cut linear dependence was not observed. The entropically driven binding process indicates that hydrophobic interactions play a major role in the overall binding process. Binding of PDC-109 with dimyristoylphosphatidylcholine membranes containing 25 mol% cholesterol showed an initial increase in the association constant as well as enthalpy and entropy of binding with increase in temperature, whereas the values decreased with further increase in temperature. The affinity of PDC-109 for phosphatidylcholine increased at higher pH, which is physiologically relevant in view of the basic nature of the seminal plasma. Binding of PDC-109 to Lyso-PC could be best analysed in terms of two types of binding interactions, a high affinity interaction with Lyso-PC micelles and a low-affinity interaction with the monomeric lipid. Enthalpy-entropy compensation was observed for the interaction of PDC-109 with phospholipid membranes, suggesting that water structure plays an important role in the binding process.

Isothermal Titration Calorimetric Studies on the Interaction of the Major Bovine Seminal Plasma Protein, PDC-109 with Phospholipid Membranes

PubMed Central

Anbazhagan, V.; Sankhala, Rajeshwer S.; Singh, Bhanu Pratap; Swamy, Musti J.

2011-01-01

The interaction of the major bovine seminal plasma protein, PDC-109 with lipid membranes was investigated by isothermal titration calorimetry. Binding of the protein to model membranes made up of diacyl phospholipids was found to be endothermic, with positive values of binding enthalpy and entropy, and could be analyzed in terms of a single type of binding sites on the protein. Enthalpies and entropies for binding to diacylphosphatidylcholine membranes increased with increase in temperature, although a clear-cut linear dependence was not observed. The entropically driven binding process indicates that hydrophobic interactions play a major role in the overall binding process. Binding of PDC-109 with dimyristoylphosphatidylcholine membranes containing 25 mol% cholesterol showed an initial increase in the association constant as well as enthalpy and entropy of binding with increase in temperature, whereas the values decreased with further increase in temperature. The affinity of PDC-109 for phosphatidylcholine increased at higher pH, which is physiologically relevant in view of the basic nature of the seminal plasma. Binding of PDC-109 to Lyso-PC could be best analysed in terms of two types of binding interactions, a high affinity interaction with Lyso-PC micelles and a low-affinity interaction with the monomeric lipid. Enthalpy-entropy compensation was observed for the interaction of PDC-109 with phospholipid membranes, suggesting that water structure plays an important role in the binding process. PMID:22022488

Sensing of Porcine Reproductive and Respiratory Syndrome Virus-Infected Macrophages by Plasmacytoid Dendritic Cells

PubMed Central

García-Nicolás, Obdulio; Auray, Gaël; Sautter, Carmen A.; Rappe, Julie C. F.; McCullough, Kenneth C.; Ruggli, Nicolas; Summerfield, Artur

2016-01-01

Porcine reproductive and respiratory syndrome virus (PRRSV) represents a macrophage (MØ)-tropic virus which is unable to induce interferon (IFN) type I in its target cells. Nevertheless, infected pigs show a short but prominent systemic IFN alpha (IFN-α) response. A possible explanation for this discrepancy is the ability of plasmacytoid dendritic cells (pDC) to produce IFN-α in response to free PRRSV virions, independent of infection. Here, we show that the highly pathogenic PRRSV genotype 1 strain Lena is unique in not inducing IFN-α production in pDC, contrasting with systemic IFN-α responses found in infected pigs. We also demonstrate efficient pDC stimulation by PRRSV Lena-infected MØ, resulting in a higher IFN-α production than direct stimulation of pDC by PRRSV virions. This response was strain-independent, required integrin-mediated intercellular contact, intact actin filaments in the MØ and was partially inhibited by an inhibitor of neutral sphingomyelinase. Although infected MØ-derived exosomes stimulated pDC, an efficient delivery of the stimulatory component was dependent on a tight contact between pDC and the infected cells. In conclusion, with this mechanism the immune system can efficiently sense PRRSV, resulting in production of considerable quantities of IFN-α. This is adding complexity to the immunopathogenesis of PRRSV infections, as IFN-α should alert the immune system and initiate the induction of adaptive immune responses, a process known to be inefficient during infection of pigs. PMID:27458429

Co-C and Pd-C Eutectic Fixed Points for Radiation Thermometry and Thermocouple Thermometry

NASA Astrophysics Data System (ADS)

Wang, L.

2017-12-01

Two Co-C and Pd-C eutectic fixed point cells for both radiation thermometry and thermocouple thermometry were constructed at NMC. This paper describes details of the cell design, materials used, and fabrication of the cells. The melting curves of the Co-C and Pd-C cells were measured with a reference radiation thermometer realized in both a single-zone furnace and a three-zone furnace in order to investigate furnace effect. The transition temperatures in terms of ITS-90 were determined to be 1324.18 {°}C and 1491.61 {°}C with the corresponding combined standard uncertainty of 0.44 {°}C and 0.31 {°}C for Co-C and Pd-C, respectively, taking into account of the differences of two different types of furnaces used. The determined ITS-90 temperatures are also compared with that of INRIM cells obtained using the same reference radiation thermometer and the same furnaces with the same settings during a previous bilateral comparison exercise (Battuello et al. in Int J Thermophys 35:535-546, 2014). The agreements are within k=1 uncertainty for Co-C cell and k = 2 uncertainty for Pd-C cell. Shapes of the plateaus of NMC cells and INRIM cells are compared too and furnace effects are analyzed as well. The melting curves of the Co-C and Pd-C cells realized in the single-zone furnace are also measured by a Pt/Pd thermocouple, and the preliminary results are presented as well.

Esterification of oil adsorbed on palm decanter cake into methyl ester using sulfonated rice husk ash as heterogeneous acid catalyst

NASA Astrophysics Data System (ADS)

Hindryawati, Noor; Erwin, Maniam, Gaanty Pragas

2017-02-01

Palm Decanter cake (PDC) which is categorized as the waste from palm oil mill has been found to contain residual crude palm oil. The oil adsorbed on the PDC (PDC-oil) can be extracted and potentially used as feedstock for biodiesel production. Feedstock from waste like PDC-oil is burdened with high free fatty acids (FFAs) which make the feedstock difficult to be converted into biodiesel using basic catalyst. Therefore, in this study, a solid acid, RHA-SO3H catalyst was synthesized by sulfonating rice husk ash (RHA) with concentrated sulfuric acid. The RHA-SO3H prepared was characterized with TGA, FTIR, BET, XRD, FE-SEM, and Hammett indicators (methyl red, bromophenol blue, and crystal violet). PDC was found to have about 11.3 wt. % oil recovered after 1 hour extraction using ultrasound method. The presence of sulfonate group was observed in IR spectrum, and the surface area of RHA-SO3H was reduced to 37 m2.g-1 after impregnation of sulfonate group. The RHA-SO3H catalyst showed that it can work for both esterification of free fatty acid which is present in PDC-oil, and transesterification of triglycerides into methyl ester. The results showed highest methyl ester content of 70.2 wt.% at optimal conditions, which was 6 wt.% catalyst amount, methanol to oil molar ratio of 17:1 for 5 hours at 120 °C.

Lectin-Binding Specificity of the Fertilization-Relevant Protein PDC-109 by Means of Surface Plasmon Resonance and Carbohydrate REcognition Domain EXcision-Mass Spectrometry.

PubMed

Defaus, Sira; Avilés, Manuel; Andreu, David; Gutiérrez-Gallego, Ricardo

2018-04-04

Seminal plasma proteins are relevant for sperm functionality and some appear responsible for establishing sperm interactions with the various environments along the female genital tract towards the oocyte. In recent years, research has focused on characterizing the role of these proteins in the context of reproductive biology, fertility diagnostics and treatment of related problems. Herein, we focus on the main protein of bovine seminal plasma, PDC-109 (BSP-A1/-A2), which by virtue of its lectin properties is involved in fertilization. By means of surface plasmon resonance, the interaction of PDC-109 with a panel of the most relevant glycosidic epitopes of mammals has been qualitatively and quantitatively characterized, and a higher affinity for carbohydrates containing fucose has been observed, in line with previous studies. Additionally, using the orthogonal technique of Carbohydrate REcognition Domain EXcision-Mass Spectrometry (CREDEX-MS), the recognition domain of the interaction complexes between PDC-109 and all fucosylated disaccharides [(Fuc-α1,(3,4,6)-GlcNAc)] has been defined, revealing the specific glycotope and the peptide domain likely to act as the PDC-109 carbohydrate binding site.

Inhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis.

PubMed

Go, Younghoon; Jeong, Ji Yun; Jeoung, Nam Ho; Jeon, Jae-Han; Park, Bo-Yoon; Kang, Hyeon-Ji; Ha, Chae-Myeong; Choi, Young-Keun; Lee, Sun Joo; Ham, Hye Jin; Kim, Byung-Gyu; Park, Keun-Gyu; Park, So Young; Lee, Chul-Ho; Choi, Cheol Soo; Park, Tae-Sik; Lee, W N Paul; Harris, Robert A; Lee, In-Kyu

2016-10-01

Hepatic steatosis is associated with increased insulin resistance and tricarboxylic acid (TCA) cycle flux, but decreased ketogenesis and pyruvate dehydrogenase complex (PDC) flux. This study examined whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities. Wild-type mice fed a high-fat diet exhibited hepatic steatosis, insulin resistance, and increased levels of pyruvate, TCA cycle intermediates, and malonyl-CoA but reduced ketogenesis and PDC activity due to PDK2 induction. Hepatic PDC activation by PDK2 inhibition attenuated hepatic steatosis, improved hepatic insulin sensitivity, reduced hepatic glucose production, increased capacity for β-oxidation and ketogenesis, and decreased the capacity for lipogenesis. These results were attributed to altered enzymatic capacities and a reduction in TCA anaplerosis that limited the availability of oxaloacetate for the TCA cycle, which promoted ketogenesis. The current study reports that increasing hepatic PDC activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease. © 2016 by the American Diabetes Association.

Measurement and analysis of chatter in a compliant model of a drillstring equipped with a PDC bit

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

Elsayed, M.A.; Raymond, D.W.

1999-11-09

Typical laboratory testing of Polycrystalline Diamond Compact (PDC) bits is performed on relatively rigid setups. Even in hard rock, PDC bits exhibit reasonable life using such testing schemes. Unfortunately, field experience indicates otherwise. In this paper, the authors show that introducing compliance in testing setups provides better simulation of actual field conditions. Using such a scheme, they show that chatter can be severe even in softer rock, such as sandstone, and very destructive to the cutters in hard rock, such as sierra white granite.

NOK mediates glycolysis and nuclear PDC associated histone acetylation.

PubMed

Shi, Wei-Ye; Yang, Xiao; Huang, Bo; Shen, Wen H; Liu, Li

2017-06-01

NOK is a potent oncogene that can transform normal cells to cancer cells. We hypothesized that NOK might impact cancer cell metabolism and histone acetylation. We show that NOK localizes in the mitochondria, and while it minimally impacts tricarboxylic acid (TCA) cycle, it markedly inhibits the process of electron transport and oxidative phosphorylation processes and dramatically enhances aerobic glycolysis in cancer cells. NOK promotes the mitochondrial-nuclear translocation of pyruvate dehydrogenase complex (PDC), and enhances histone acetylation in the nucleus. Together, these findings show that NOK mediates glycolysis and nuclear PDC associated histone acetylation.

Lethal neonatal case and review of primary short-chain enoyl-CoA hydratase (SCEH) deficiency associated with secondary lymphocyte pyruvate dehydrogenase complex (PDC) deficiency.

PubMed

Bedoyan, Jirair K; Yang, Samuel P; Ferdinandusse, Sacha; Jack, Rhona M; Miron, Alexander; Grahame, George; DeBrosse, Suzanne D; Hoppel, Charles L; Kerr, Douglas S; Wanders, Ronald J A

2017-04-01

Mutations in ECHS1 result in short-chain enoyl-CoA hydratase (SCEH) deficiency which mainly affects the catabolism of various amino acids, particularly valine. We describe a case compound heterozygous for ECHS1 mutations c.836T>C (novel) and c.8C>A identified by whole exome sequencing of proband and parents. SCEH deficiency was confirmed with very low SCEH activity in fibroblasts and nearly absent immunoreactivity of SCEH. The patient had a severe neonatal course with elevated blood and cerebrospinal fluid lactate and pyruvate concentrations, high plasma alanine and slightly low plasma cystine. 2-Methyl-2,3-dihydroxybutyric acid was markedly elevated as were metabolites of the three branched-chain α-ketoacids on urine organic acids analysis. These urine metabolites notably decreased when lactic acidosis decreased in blood. Lymphocyte pyruvate dehydrogenase complex (PDC) activity was deficient, but PDC and α-ketoglutarate dehydrogenase complex activities in cultured fibroblasts were normal. Oxidative phosphorylation analysis on intact digitonin-permeabilized fibroblasts was suggestive of slightly reduced PDC activity relative to control range in mitochondria. We reviewed 16 other cases with mutations in ECHS1 where PDC activity was also assayed in order to determine how common and generalized secondary PDC deficiency is associated with primary SCEH deficiency. For reasons that remain unexplained, we find that about half of cases with primary SCEH deficiency also exhibit secondary PDC deficiency. The patient died on day-of-life 39, prior to establishing his diagnosis, highlighting the importance of early and rapid neonatal diagnosis because of possible adverse effects of certain therapeutic interventions, such as administration of ketogenic diet, in this disorder. There is a need for better understanding of the pathogenic mechanisms and phenotypic variability in this relatively recently discovered disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

PDC Bit Testing at Sandia Reveals Influence of Chatter in Hard-Rock Drilling

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

RAYMOND,DAVID W.

1999-10-14

Polycrystalline diamond compact (PDC) bits have yet to be routinely applied to drilling the hard-rock formations characteristic of geothermal reservoirs. Most geothermal production wells are currently drilled with tungsten-carbide-insert roller-cone bits. PDC bits have significantly improved penetration rates and bit life beyond roller-cone bits in the oil and gas industry where soft to medium-hard rock types are encountered. If PDC bits could be used to double current penetration rates in hard rock geothermal well-drilling costs could be reduced by 15 percent or more. PDC bits exhibit reasonable life in hard-rock wear testing using the relatively rigid setups typical of laboratorymore » testing. Unfortunately, field experience indicates otherwise. The prevailing mode of failure encountered by PDC bits returning from hard-rock formations in the field is catastrophic, presumably due to impact loading. These failures usually occur in advance of any appreciable wear that might dictate cutter replacement. Self-induced bit vibration, or ''chatter'', is one of the mechanisms that may be responsible for impact damage to PDC cutters in hard-rock drilling. Chatter is more severe in hard-rock formations since they induce significant dynamic loading on the cutter elements. Chatter is a phenomenon whereby the drillstring becomes dynamically unstable and excessive sustained vibrations occur. Unlike forced vibration, the force (i.e., weight on bit) that drives self-induced vibration is coupled with the response it produces. Many of the chatter principles derived in the machine tool industry are applicable to drilling. It is a simple matter to make changes to a machine tool to study the chatter phenomenon. This is not the case with drilling. Chatter occurs in field drilling due to the flexibility of the drillstring. Hence, laboratory setups must be made compliant to observe chatter.« less

C9orf72 hexanucleotide repeat expansion and Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complex.

PubMed

Dombroski, Beth A; Galasko, Douglas R; Mata, Ignacio F; Zabetian, Cyrus P; Craig, Ulla-Katrina; Garruto, Ralph M; Oyanagi, Kiyomitsu; Schellenberg, Gerard D

2013-06-01

High-prevalence foci of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC) exist in Japanese on the Kii Peninsula of Japan and in the Chamorros of Guam. Clinical and neuropathologic similarities suggest that the disease in these 2 populations may be related. Recent findings showed that some of the Kii Peninsula ALS cases had pathogenic C9orf72 repeat expansions, a genotype that causes ALS in Western populations. To perform genotyping among Guam residents to determine if the C9orf72 expanded repeat allele contributes to ALS-PDC in this population and to evaluate LRRK2 for mutations in the same population. Case-control series from neurodegenerative disease research programs on Guam that screened residents for ALS, PDC, and dementia. Study participants included 24 with ALS and 22 with PDC and 43 older control subjects with normal cognition ascertained between 1956 and 2006. All but one participant were Chamorro, the indigenous people of Guam. A single individual of white race/ethnicity with ALS was ascertained on Guam during the study. Participants were screened for C9orf72 hexanucleotide repeat length. Participants with repeat numbers in great excess of 30 were considered to have pathogenic repeat expansions. LRRK2 was screened for point mutations by DNA sequencing. We found a single individual with an expanded pathogenic hexanucleotide repeat. This individual of white race/ethnicity with ALS was living on Guam at the time of ascertainment but had been born in the United States. All Chamorro participants with ALS and PDC and control subjects had normal repeats, ranging from 2 to 17 copies. No pathogenic LRRK2 mutations were found. Unlike participants with ALS from the Kii Peninsula, C9orf72 expansions do not cause ALS-PDC in Chamorros. Likewise, LRRK2 mutations do not cause Guam ALS-PDC.

Silicon-containing polymer-derived ceramic nanocomposites (PDC-NCs): preparative approaches and properties.

PubMed

Ionescu, Emanuel; Kleebe, Hans-Joachim; Riedel, Ralf

2012-08-07

Composites consist by definition of at least two materials (Gibbsian phases) with rather different properties. They exhibit a heterogeneous microstructure and possess improved properties with respect to their components. Furthermore, the design of their microstructure allows for tailoring their overall properties. In the last decades, intense work was performed on the synthesis of nanocomposites, which have the feature that at least one of their components is nanoscaled. However, the microstructure-property relationship of nanocomposite materials is still a challenging topic. This tutorial review paper deals with a special class of nanocomposites, i.e. polymer-derived ceramic nanocomposites (PDC-NCs), which have been shown to be promising materials for various structural and functional applications. Within this context, different preparative approaches for PDC-NCs as well as some of their properties will be presented and discussed. Furthermore, recent results concerning the relationship between the nano/microstructure of PDC-NCs and their properties will be highlighted.

Parametric down-conversion with nonideal and random quasi-phase-matching

NASA Astrophysics Data System (ADS)

Yang, Chun-Yao; Lin, Chun; Liljestrand, Charlotte; Su, Wei-Min; Canalias, Carlota; Chuu, Chih-Sung

2016-05-01

Quasi-phase-matching (QPM) has enriched the capacity of parametric down-conversion (PDC) in generating biphotons for many fundamental tests and advanced applications. However, it is not clear how the nonidealities and randomness in the QPM grating of a parametric down-converter may affect the quantum properties of the biphotons. This paper intends to provide insights into the interplay between PDC and nonideal or random QPM structures. Using a periodically poled nonlinear crystal with short periodicity, we conduct experimental and theoretical studies of PDC subject to nonideal duty cycle and random errors in domain lengths. We report the observation of biphotons emerging through noncritical birefringent-phasematching, which is impossible to occur in PDC with an ideal QPM grating, and a biphoton spectrum determined by the details of nonidealities and randomness. We also observed QPM biphotons with a diminished strength. These features are both confirmed by our theory. Our work provides new perspectives for biphoton engineering with QPM.

Detection of periodicity based on independence tests - III. Phase distance correlation periodogram

NASA Astrophysics Data System (ADS)

Zucker, Shay

2018-02-01

I present the Phase Distance Correlation (PDC) periodogram - a new periodicity metric, based on the Distance Correlation concept of Gábor Székely. For each trial period, PDC calculates the distance correlation between the data samples and their phases. PDC requires adaptation of the Székely's distance correlation to circular variables (phases). The resulting periodicity metric is best suited to sparse data sets, and it performs better than other methods for sawtooth-like periodicities. These include Cepheid and RR-Lyrae light curves, as well as radial velocity curves of eccentric spectroscopic binaries. The performance of the PDC periodogram in other contexts is almost as good as that of the Generalized Lomb-Scargle periodogram. The concept of phase distance correlation can be adapted also to astrometric data, and it has the potential to be suitable also for large evenly spaced data sets, after some algorithmic perfection.

Spatiotemporal structure of biphoton entanglement in type-II parametric down-conversion

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

Brambilla, E.; Caspani, L.; Lugiato, L. A.

2010-07-15

We investigate the spatiotemporal structure of the biphoton correlation in type-II parametric down-conversion (PDC). As in type-I PDC [Phys. Rev. Lett. 102, 223601 (2009)], we find that the correlation is nonfactorizable in space and time. Differently from type I, the type-II correlation in the spontaneous regime displays an asymmetric V-shaped structure in any cross section including time and one transverse dimension. This asymmetry along the temporal coordinate originates from the signal-idler group velocity mismatch and tends to disappear as the parametric gain is raised. We observe a progressive transition toward a symmetric X-shaped geometry similar to that found in typemore » I when stimulated PDC becomes dominant. We also give quantitative evaluations of the localization in space and in time of the correlation, analyze its behavior for different crystal tuning angles, and underline qualitative differences with respect to type-I PDC.« less

PDC bit hydraulics design, profile are key to reducing balling

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

Hariharan, P.R.; Azar, J.J.

1996-12-09

Polycrystalline diamond compact (PDC) bits with a parabolic profile and bladed hydraulic design have a lesser tendency to ball during drilling of reactive shales. PDC bits with ribbed or open-face hydraulic designs and those with flat or rounded profiles tended to ball more often in the bit balling experiments conducted. Experimental work also indicates that PDC hydraulic design seems to have a greater influence on bit balling tendency compared to bit profile design. There are five main factors that affect bit balling: formation type, drilling fluid, drilling hydraulics, bit design, and confining pressures. An equation for specific energy showed thatmore » it could be used to describe the efficiency of the drilling process by examining the amount of energy spent in drilling a unit volume of rock. This concept of specific energy has been used herein to correlate with the parameter Rd, a parameter to quantify the degree of balling.« less

Probabilistic Asteroid Impact Risk Assessment for the Hypothetical PDC17 Impact Exercise

NASA Technical Reports Server (NTRS)

Wheeler, Lorien; Mathias, Donovan

2017-01-01

Performing impact risk assessment for the 2017 Planetary Defense Conference (PDC17) hypothetical impact exercise, to take place at the PDC17 conference, May 15-20, 2017. Impact scenarios and trajectories are developed and provided by NASA's Near Earth Objects Office at JPL (Paul Chodas). These results represent purely hypothetical impact scenarios, and do not reflect any known asteroid threat. Risk assessment was performed using the Probabilistic Asteroid Impact Risk (PAIR) model developed by the Asteroid Threat Assessment Project (ATAP) at NASA Ames Research Center. This presentation includes sample results that may be presented or used in discussions during the various stages of the impact exercisecenter dot Some cases represent alternate scenario options that may not be used during the actual impact exercise at the PDC17 conference. Updates to these initial assessments and/or additional scenario assessments may be performed throughout the impact exercise as different scenario options unfold.

Orbital angular momentum modes of high-gain parametric down-conversion

NASA Astrophysics Data System (ADS)

Beltran, Lina; Frascella, Gaetano; Perez, Angela M.; Fickler, Robert; Sharapova, Polina R.; Manceau, Mathieu; Tikhonova, Olga V.; Boyd, Robert W.; Leuchs, Gerd; Chekhova, Maria V.

2017-04-01

Light beams with orbital angular momentum (OAM) are convenient carriers of quantum information. They can also be used for imparting rotational motion to particles and providing high resolution in imaging. Due to the conservation of OAM in parametric down-conversion (PDC), signal and idler photons generated at low gain have perfectly anti-correlated OAM values. It is interesting to study the OAM properties of high-gain PDC, where the same OAM modes can be populated with large, but correlated, numbers of photons. Here we investigate the OAM spectrum of high-gain PDC and show that the OAM mode content can be controlled by varying the pump power and the configuration of the source. In our experiment, we use a source consisting of two nonlinear crystals separated by an air gap. We discuss the OAM properties of PDC radiation emitted by this source and suggest possible modifications.

Quantitative and functional analysis of PDC-E2–specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis

PubMed Central

Kita, Hiroto; Matsumura, Shuji; He, Xiao-Song; Ansari, Aftab A.; Lian, Zhe-Xiong; Van de Water, Judy; Coppel, Ross L.; Kaplan, Marshall M.; Gershwin, M. Eric

2002-01-01

While the pathologic mechanisms responsible for organ-specific tissue damage in primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile ducts. Previously, we have documented that there is 100-fold enrichment in the frequency of CD4+ autoreactive T cells in the liver that are specific for peptides encoded by the E2 components of the pyruvate dehydrogenase complexes (PDC-E2). We have also recently characterized the first MHC class I–restricted epitope for PDC-E2, namely amino acid 159–167, a region very similar to the epitope recognized by MHC class II–restricted CD4+ cells and by autoantibodies. The effector functions of these PDC-E2159-167–specific CD8+ cytotoxic T lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer technology and report herein that there is tenfold increase in the frequency of PDC-E2159-167–specific CTLs in the liver as compared with the blood in PBC. In addition, the precursor frequency of the CTLs in blood was significantly higher in early-stage PBC. Of interest was the fact that, upon stimulation with the peptide, the response of PDC-E2159-167 tetramer-positive cells is heterogeneous with respect to IFN-γ synthesis. These data, we believe for the first time, document the enrichment of autoantigen-specific CD8+ T cells in the PBC liver, suggesting that CD8+ T cells play a significant role in the immunopathogenesis of PBC. PMID:11994412

A predictive risk model for electroshock-induced mortality of the endangered Cape Fear shiner

USGS Publications Warehouse

Holliman, F.M.; Reynolds, J.B.; Kwak, T.J.

2003-01-01

We evaluated the effects of a single electroshock on injury and mortality of hatchery-reared Cape Fear shiners Notropis mekistocholas (N = 517), an endangered cyprinid. Groups of 18-22 Cape Fear shiners were exposed to DC, 120-Hz pulsed DC (PDC), or 60-Hz PDC at voltage gradients of 1.1, 1.9, or 2.7 V/cm for 3 s. Mortality occurred only among fish exposed to 120-Hz PDC (25%) and DC (38%) applied at 2.7 V/cm. Because no mortality occurred in Cape Fear shiners exposed to 60-Hz PDC, this waveform was selected for further study of electroshock duration (3, 6, 12, 24, or 48 s) and voltage gradient (0.9, 1.6, or 2.3 V/cm). Most fish electroshocked in the experiments were immobilized (ceased swimming motion). No physical injury was detected by necropsy or radiography in any fish. Electroshock-induced mortality of Cape Fear shiners showed a strong multivariable relationship to voltage gradient, electroshock duration, and fish length. Fish subjected to 60-Hz PDC at 0.9 or 1.6 V/cm for 6 s experienced low mortality (<10%). Our results demonstrate that Cape Fear shiners can be immobilized by 60-Hz PDC electroshock without injury or significant risk of mortality. We propose that electrofishing may be safely used to sample similar small cyprinids, imperiled or otherwise, when electrofishers select an appropriate waveform (DC pulsed at 60-Hz or less) and use it judiciously (minimal exposure at, or below, the immobilization threshold).

Cu-PDC-bpa solid coordination frameworks (PDC=2,5-pyrindinedicarboxylate; bpa=1,2-DI(4-pyridil)ethane)): 2D and 3D structural flexibility producing a 3-c herringbone array next to ideal

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

Llano-Tomé, Francisco, E-mail: francisco.llano@ehu.eus; Bazán, Begoña, E-mail: bego.bazan@ehu.eus; BCMaterials Parque Tecnológico de Zamudio, Ibaizabal Bidea, Edificio 500–Planta 1, 48160 Derio

Combination of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce solid coordination frameworks (SCF) which are crystalline materials based on connections between metal ions through organic ligands. In this context, this work is focused on two novel Cu{sup II}-based SCFs exhibiting PDC (2,5-pyridinedicarboxylate) and bpa (1,2-di(4-pyridyl)ethane), being the first structures reported in literature containing both ligands. Chemical formula are [Cu{sub 2}[(PDC){sub 2}(bpa)(H{sub 2}O){sub 2}]·3H{sub 2}O·DMF (1), and [Cu{sub 2}(PDC){sub 2}(bpa)(H{sub 2}O){sub 2}]·7H{sub 2}O (2), where DMF is dimethylformamide. Compounds 1 and 2 have been characterized by means of X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric (TG) analysis,more » differential thermal analysis (DTA) and dielectric measurements. The crystallographic analysis revealed that compounds 1 and 2 can be described as herringbone-type layers formed by helicoidal Cu-PDC-Cu chains connected through bpa ligands. Solvent molecules are crystallized between the layers, providing the inter-layer connections through hydrogen bonds. Differences between both compounds are attributable to the flexibility of bpa (in 2D) as well as to the 3D packing of the layers which is solvent dependent. This fact results in the fact that compound 2 is the most regular 3-c herringbone array reported so far. The structural dynamism of these networks is responsible for the crystalline to-amorphous to-crystalline (CAC) transformation from compound 1 to compound 2. Crystallochemical features for both compounds have also been studied and compared to similar 3-connected herringbone-arrays. - Graphical abstract: Cu-PDC-bpa 3-c herringbone arrays. - Highlights: • The most ideal herringbone array reported so far is a Cu-PDC-bpa SCF. • Conformational freedom of bpa results in 2D and 3D flexibility of the SCFs. • The flexibility of the SCFs is related to a phase transformation. • Dielectric measurements confirm the mobility of guest solvent molecules.« less

Ab-initio study of high temperature lattice dynamics of BCC zirconium (β-Zr) and uranium (γ-U)

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

Ghosh, Partha S., E-mail: parthasarathi13@gmail.com; Arya, A., E-mail: parthasarathi13@gmail.com; Dey, G. K., E-mail: parthasarathi13@gmail.com

2014-04-24

Using self consistent ab-initio lattice dynamics calculations, we show that bcc structures of Zr and U phases become stable at high temperature by phonon-phonon interactions. The calculated temperature dependent phonon dispersion curve (PDC) of β-Zr match excellently with experimental PDC. But the calculated PDC for γ-U shows negative phonon frequencies even at solid to liquid transition temperature. We show that this discrepancy is due to an overestimation of instability depth of bcc U phase which is removed by incorporation of spin-orbit coupling in the electronic structure calculations.

International Workshop on Condensed Matter Theories (13th) Held in Campos do Jordao, Brazil on August 1989

DTIC Science & Technology

1990-01-01

Pdc(rlr 2 r)][Pc-(r’) + Pdco (rr.rl)] (2) The two- and three-point irreducible exchange functions Paf, and Pa.- are clas- sified according to the...r, r2r’) l(ri rI )PdCI(rI r~r’) + Perde(r r2r’ ) + PVdc(r r’ ) grter,) - VPd(rl r2 r’ ) Pdco (r’ r 2 ri) - vPCC(r)Pdc.(r’r2r,) - vPc(r’)Pdc(r~r2r’)I

[Methodology of determination of the time of death and outlooks for the further development].

PubMed

Novikov, P I; Vlasov, A Iu; Shved, E F; Natsentov, E O; Korshunov, N V; Belykh, S A

2004-01-01

A methodological analysis of diagnosing the prescription of death coming (PDC) is described in the paper. Key philosophic fundamentals for further novel and more effective methods of PDC determination are elucidated. Main requirement applicable to postmortem diagnosis are defined. Different methods of modeling the postmortem process are demonstrated by the example of cadaver cooling, i.e. in real time, by analogue computer systems and by mathematic modeling. The traditional empiric and the adaptive approaches are comparatively analyzed in modeling the postmortem processes for the PDC diagnosis. A variety of promising trends for further related research is outlined.

Peripheral blood CD4 T-cell and plasmacytoid dendritic cell (pDC) reactivity to herpes simplex virus 2 and pDC number do not correlate with the clinical or virologic severity of recurrent genital herpes.

PubMed

Moss, Nicholas J; Magaret, Amalia; Laing, Kerry J; Kask, Angela Shaulov; Wang, Minna; Mark, Karen E; Schiffer, Joshua T; Wald, Anna; Koelle, David M

2012-09-01

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals.

Confined compressive strength analysis can improve PDC bit selection. [Polycrystalline Diamond Compact

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

Fabain, R.T.

1994-05-16

A rock strength analysis program, through intensive log analysis, can quantify rock hardness in terms of confined compressive strength to identify intervals suited for drilling with polycrystalline diamond compact (PDC) bits. Additionally, knowing the confined compressive strength helps determine the optimum PDC bit for the intervals. Computing rock strength as confined compressive strength can more accurately characterize a rock's actual hardness downhole than other methods. the information can be used to improve bit selections and to help adjust drilling parameters to reduce drilling costs. Empirical data compiled from numerous field strength analyses have provided a guide to selecting PDC drillmore » bits. A computer analysis program has been developed to aid in PDC bit selection. The program more accurately defines rock hardness in terms of confined strength, which approximates the in situ rock hardness downhole. Unconfined compressive strength is rock hardness at atmospheric pressure. The program uses sonic and gamma ray logs as well as numerous input data from mud logs. Within the range of lithologies for which the program is valid, rock hardness can be determine with improved accuracy. The program's output is typically graphed in a log format displaying raw data traces from well logs, computer-interpreted lithology, the calculated values of confined compressive strength, and various optional rock mechanic outputs.« less

Utilizing a Pediatric Disaster Coalition Model to Increase Pediatric Critical Care Surge Capacity in New York City.

PubMed

Frogel, Michael; Flamm, Avram; Sagy, Mayer; Uraneck, Katharine; Conway, Edward; Ushay, Michael; Greenwald, Bruce M; Pierre, Louisdon; Shah, Vikas; Gaffoor, Mohamed; Cooper, Arthur; Foltin, George

2017-08-01

A mass casualty event can result in an overwhelming number of critically injured pediatric victims that exceeds the available capacity of pediatric critical care (PCC) units, both locally and regionally. To address these gaps, the New York City (NYC) Pediatric Disaster Coalition (PDC) was established. The PDC includes experts in emergency preparedness, critical care, surgery, and emergency medicine from 18 of 25 major NYC PCC-capable hospitals. A PCC surge committee created recommendations for making additional PCC beds available with an emphasis on space, staff, stuff (equipment), and systems. The PDC assisted 15 hospitals in creating PCC surge plans by utilizing template plans and site visits. These plans created an additional 153 potential PCC surge beds. Seven hospitals tested their plans through drills. The purpose of this article was to demonstrate the need for planning for disasters involving children and to provide a stepwise, replicable model for establishing a PDC, with one of its primary goals focused on facilitating PCC surge planning. The process we describe for developing a PDC can be replicated to communities of any size, setting, or location. We offer our model as an example for other cities. (Disaster Med Public Health Preparedness. 2017;11:473-478).

Correntropy-based partial directed coherence for testing multivariate Granger causality in nonlinear processes

NASA Astrophysics Data System (ADS)

Kannan, Rohit; Tangirala, Arun K.

2014-06-01

Identification of directional influences in multivariate systems is of prime importance in several applications of engineering and sciences such as plant topology reconstruction, fault detection and diagnosis, and neurosciences. A spectrum of related directionality measures, ranging from linear measures such as partial directed coherence (PDC) to nonlinear measures such as transfer entropy, have emerged over the past two decades. The PDC-based technique is simple and effective, but being a linear directionality measure has limited applicability. On the other hand, transfer entropy, despite being a robust nonlinear measure, is computationally intensive and practically implementable only for bivariate processes. The objective of this work is to develop a nonlinear directionality measure, termed as KPDC, that possesses the simplicity of PDC but is still applicable to nonlinear processes. The technique is founded on a nonlinear measure called correntropy, a recently proposed generalized correlation measure. The proposed method is equivalent to constructing PDC in a kernel space where the PDC is estimated using a vector autoregressive model built on correntropy. A consistent estimator of the KPDC is developed and important theoretical results are established. A permutation scheme combined with the sequential Bonferroni procedure is proposed for testing hypothesis on absence of causality. It is demonstrated through several case studies that the proposed methodology effectively detects Granger causality in nonlinear processes.

Integrative proteomics and biochemical analyses define Ptc6p as the Saccharomyces cerevisiae pyruvate dehydrogenase phosphatase.

PubMed

Guo, Xiao; Niemi, Natalie M; Coon, Joshua J; Pagliarini, David J

2017-07-14

The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue ∼50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S. cerevisiae has not been conclusively defined. Here, using comparative mitochondrial phosphoproteomics, analyses of protein-protein interactions by affinity enrichment-mass spectrometry, and in vitro biochemistry, we define Ptc6p as the primary PDC phosphatase in S. cerevisiae Our analyses further suggest additional substrates for related S. cerevisiae phosphatases and describe the overall phosphoproteomic changes that accompany mitochondrial respiratory dysfunction. In summary, our quantitative proteomics and biochemical analyses have identified Ptc6p as the primary-and likely sole- S. cerevisiae PDC phosphatase, closing a key knowledge gap about the regulation of yeast mitochondrial metabolism. Our findings highlight the power of integrative omics and biochemical analyses for annotating the functions of poorly characterized signaling proteins. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

PdRu/C catalysts for ethanol oxidation in anion-exchange membrane direct ethanol fuel cells

NASA Astrophysics Data System (ADS)

Ma, Liang; He, Hui; Hsu, Andrew; Chen, Rongrong

2013-11-01

Carbon supported PdRu catalysts with various Pd:Ru atomic ratios were synthesized by impregnation method, and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), electrochemical half-cell tests, and the anion-exchange membrane direct ethanol fuel cell (AEM-DEFC) tests. XRD results suggest that the PdRu metal exists on carbon support in an alloy form. TEM study shows that the bimetallic PdRu/C catalysts have slightly smaller average particle size than the single metal Pd/C catalyst. Lower onset potential and peak potential and much higher steady state current for ethanol oxidation in alkaline media were observed on the bimetallic catalysts (PdxRuy/C) than on the Pd/C, while the activity for ethanol oxidation on the pure Ru/C was not noticeable. By using Pd/C anode catalysts and MnO2 cathode catalysts, AEM-DEFCs free from the expensive Pt catalyst were assembled. The AEM DEFC using the bimetallic Pd3Ru/C anode catalyst showed a peak power density as high as 176 mW cm-2 at 80 °C, about 1.8 times higher than that using the single metal Pd/C catalyst. The role of Ru for enhancing the EOR activity of Pd/C catalysts is discussed.

Peripheral Blood CD4 T-Cell and Plasmacytoid Dendritic Cell (pDC) Reactivity to Herpes Simplex Virus 2 and pDC Number Do Not Correlate with the Clinical or Virologic Severity of Recurrent Genital Herpes

PubMed Central

Moss, Nicholas J.; Magaret, Amalia; Laing, Kerry J.; Kask, Angela Shaulov; Wang, Minna; Mark, Karen E.; Schiffer, Joshua T.; Wald, Anna

2012-01-01

Leukocytes participate in the immune control of herpes simplex virus (HSV). Data from HIV coinfections, germ line mutations, and case reports suggest involvement of CD4 T cells and plasmacytoid dendritic cells (pDC). We investigated the relationships between these cells and recurrent genital herpes disease severity in the general population. Circulating CD4 T-cell responses to HSV-2 were measured in specimens from 67 immunocompetent individuals with measured genital lesion and HSV shedding rates. Similarly, pDC number and functional responses to HSV-2 were analyzed in 40 persons. CD4 responses and pDC concentrations and responses ranged as much as 100-fold between persons while displaying moderate within-person consistency over time. No correlations were observed between these immune response parameters and genital HSV-2 severity. Cytomegalovirus (CMV) coinfection was not correlated with differences in HSV-2-specific CD4 T-cell responses. The CD4 T-cell response to HSV-2 was much more polyfunctional than was the response to CMV. These data suggest that other immune cell subsets with alternate phenotypes or anatomical locations may be responsible for genital herpes control in chronically infected individuals. PMID:22761381

Conformational dynamics and ligand binding in the multi-domain protein PDC109.

PubMed

Kim, Hyun Jin; Choi, Moo Young; Kim, Hyung J; Llinás, Miguel

2010-02-18

PDC109 is a modular multi-domain protein with two fibronectin type II (Fn2) repeats joined by a linker. It plays a major role in bull sperm binding to the oviductal epithelium through its interactions with phosphorylcholines (PhCs), a head group of sperm cell membrane lipids. The crystal structure of the PDC109-PhC complex shows that each PhC binds to the corresponding Fn2 domain, while the two domains are on the same face of the protein. Long timescale explicit solvent molecular dynamics (MD) simulations of PDC109, in the presence and absence of PhC, suggest that PhC binding strongly correlates with the relative orientation of choline-phospholipid binding sites of the two Fn2 domains; unless the two domains tightly bind PhCs, they tend to change their relative orientation by deforming the flexible linker. The effective PDC109-PhC association constant of 28 M(-1), estimated from their potential of mean force is consistent with the experimental result. Principal component analysis of the long timescale MD simulations was compared to the significantly less expensive normal mode analysis of minimized structures. The comparison indicates that difference between relative domain motions of PDC109 with bound and unbound PhC is captured by the first principal component in the principal component analysis as well as the three lowest normal modes in the normal mode analysis. The present study illustrates the use of detailed MD simulations to clarify the energetics of specific ligand-domain interactions revealed by a static crystallographic model, as well as their influence on relative domain motions in a multi-domain protein.

Interaction of the major protein from bovine seminal plasma, PDC-109 with phospholipid membranes and soluble ligands investigated by fluorescence approaches.

PubMed

Anbazhagan, V; Damai, Rajani S; Paul, Aniruddha; Swamy, Musti J

2008-06-01

The major protein from bovine seminal plasma, PDC-109 binds selectively to choline phospholipids on the sperm plasma membrane and plays a crucial role in priming spermatozoa for fertilization. The microenvironment and accessibility of tryptophans of PDC-109 in the native state, in the presence of phosphorylcholine (PrC) and phospholipid membranes as well as upon denaturation have been investigated by fluorescence approaches. Quenching of the protein intrinsic fluorescence by different quenchers decreased in the order: acrylamide>succinimide>Cs(+)>I(-). Ligand binding afforded considerable protection from quenching, with shielding efficiencies following the order: dimyristoylphosphatidylcholine (DMPC)>lysophosphatidylcholine (Lyso-PC)>PrC. This has been attributed to a partial penetration of the protein into the DMPC membranes and Lyso-PC micelles, as well as a further stabilization of the binding due to the interaction of PDC-109 with lipid acyl chains and the resulting tightening of the protein structure, leading to a decreased accessibility of the tryptophan residues. Red-edge excitation shift (REES) studies yielded REES values of 4 nm for both native and denatured PDC-109, whereas reduced and denatured protein gave a REES of only 0.5 nm, clearly indicating that the structural and dynamic features of the microenvironment around the tryptophan residues are retained even after denaturation, presumably due to the constraints imposed on the protein structure by disulfide bonds. Upon binding of PDC-109 to DMPC membranes and Lyso-PC micelles the REES values were reduced to 2.5 and 1.0 nm, respectively, which could be due to the penetration of some parts of the protein, especially the segment containing Trp-90 into the membrane interior, where the red-edge effects are considerably reduced.

Sequestration of PDC-109 protein by specific antibodies and egg yolk cryoprotects bull spermatozoa.

PubMed

Srivastava, N; Srivastava, S K; Ghosh, S K; Jerome, A; Das, G K; Mehrotra, S

2013-10-01

PDC-109, one of the most abundant proteins in bovine seminal plasma, has detrimental effect on spermatozoa in a time- and concentration-dependent manner. Therefore, we hypothesized that sequestration of detrimental protein from ejaculates would be beneficial following cryopreservation of sperm cells. To this aim, we evaluated the effect of sequestration of PDC-109 either by anti-PDC-109 antibodies (Ab) or egg yolk (EY) alone or by the synergistic action of EY + Ab in minimizing cryoinjury to bull spermatozoa. PDC-109 protein was purified by applying two-step chromatography procedures. The purified protein was injected in rabbits to raise antibodies which were isolated using ion-exchange chromatography. After checking the Ab cross-reactivity, they were quantitated and added to ejaculates, either alone or in addition to EY in Tris-glycerol (TG) extender. Thus, ejaculates were processed in extender containing EY + TG (group I), Ab + TG (group II) or EY + Ab + TG (group III). Semen quality parameters (SQPs) viz. viability and acrosome integrity (FITC-PSA), cryoinjury to spermatozoa (chlortetracycline, CTC assay) and in vitro fertility of protein-sequestered-semen (zona-penetration assay) were evaluated. A significant (p < 0.05) improvement in post-thaw SQPs as well as in non-capacitated spermatozoa observed at pre-freeze and post-thaw stages of cryopreservation in group III compared with other groups indicated reduction in protein-mediated cryoinjury. From this study, it can be concluded that sequestration of PDC-109 by synergistic action of EY+Ab as compared to either of them alone significantly improve sperm quality and minimize cryoinjury to bull spermatozoa upon storage at ultra-low temperatures. © 2013 Blackwell Verlag GmbH.

The effects of vent location, event scale and time forecasts on pyroclastic density current hazard maps at Campi Flegrei caldera (Italy)

NASA Astrophysics Data System (ADS)

Bevilacqua, Andrea; Neri, Augusto; Bisson, Marina; Esposti Ongaro, Tomaso; Flandoli, Franco; Isaia, Roberto; Rosi, Mauro; Vitale, Stefano

2017-09-01

This study presents a new method for producing long-term hazard maps for pyroclastic density currents (PDC) originating at Campi Flegrei caldera. Such method is based on a doubly stochastic approach and is able to combine the uncertainty assessments on the spatial location of the volcanic vent, the size of the flow and the expected time of such an event. The results are obtained by using a Monte Carlo approach and adopting a simplified invasion model based on the box model integral approximation. Temporal assessments are modelled through a Cox-type process including self-excitement effects, based on the eruptive record of the last 15 kyr. Mean and percentile maps of PDC invasion probability are produced, exploring their sensitivity to some sources of uncertainty and to the effects of the dependence between PDC scales and the caldera sector where they originated. Conditional maps representative of PDC originating inside limited zones of the caldera, or of PDC with a limited range of scales are also produced. Finally, the effect of assuming different time windows for the hazard estimates is explored, also including the potential occurrence of a sequence of multiple events. Assuming that the last eruption of Monte Nuovo (A.D. 1538) marked the beginning of a new epoch of activity similar to the previous ones, results of the statistical analysis indicate a mean probability of PDC invasion above 5% in the next 50 years on almost the entire caldera (with a probability peak of 25% in the central part of the caldera). In contrast, probability values reduce by a factor of about 3 if the entire eruptive record is considered over the last 15 kyr, i.e. including both eruptive epochs and quiescent periods.

Pasture v. standard dairy cream in high-fat diet-fed mice: improved metabolic outcomes and stronger intestinal barrier.

PubMed

Benoit, Bérengère; Plaisancié, Pascale; Géloën, Alain; Estienne, Monique; Debard, Cyrille; Meugnier, Emmanuelle; Loizon, Emmanuelle; Daira, Patricia; Bodennec, Jacques; Cousin, Olivier; Vidal, Hubert; Laugerette, Fabienne; Michalski, Marie-Caroline

2014-08-28

Dairy products derived from the milk of cows fed in pastures are characterised by higher amounts of conjugated linoleic acid and α-linolenic acid (ALA), and several studies have shown their ability to reduce cardiovascular risk. However, their specific metabolic effects compared with standard dairy in a high-fat diet (HFD) context remain largely unknown; this is what we determined in the present study with a focus on the metabolic and intestinal parameters. The experimental animals were fed for 12 weeks a HFD containing 20 % fat in the form of a pasture dairy cream (PDC) or a standard dairy cream (SDC). Samples of plasma, liver, white adipose tissue, duodenum, jejunum and colon were analysed. The PDC mice, despite a higher food intake, exhibited lower fat mass, plasma and hepatic TAG concentrations, and inflammation in the adipose tissue than the SDC mice. Furthermore, they exhibited a higher expression of hepatic PPARα mRNA and adipose tissue uncoupling protein 2 mRNA, suggesting an enhanced oxidative activity of the tissues. These results might be explained, in part, by the higher amounts of ALA in the PDC diet and in the liver and adipose tissue of the PDC mice. Moreover, the PDC diet was found to increase the proportions of two strategic cell populations involved in the protective function of the intestinal epithelium, namely Paneth and goblet cells in the small intestine and colon, compared with the SDC diet. In conclusion, a PDC HFD leads to improved metabolic outcomes and to a stronger gut barrier compared with a SDC HFD. This may be due, at least in part, to the protective mechanisms induced by specific lipids.

JAK-inhibitor tofacitinib suppresses interferon alfa production by plasmacytoid dendritic cells and inhibits arthrogenic and antiviral effects of interferon alfa.

PubMed

Boor, Patrick P C; de Ruiter, Petra E; Asmawidjaja, Patrick S; Lubberts, Erik; van der Laan, Luc J W; Kwekkeboom, Jaap

2017-10-01

Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections. Using in vitro culture models with human cells, we studied the effects of tofacitinib on PDC survival and IFNα production, and on arthrogenic and antiviral effects of IFNα. Tofacitinib inhibited the expression of antiapoptotic BCL-A1 and BCL-XL in human PDC and induced PDC apoptosis. TLR7 stimulation upregulated the levels of antiapoptotic Bcl-2 family members and prevented the induction of PDC apoptosis by tofacitinib. However, tofacitinib robustly inhibited the production of IFNα by toll like receptor-stimulated PDC. In addition, tofacitinib profoundly suppressed IFNα-induced upregulation of TLR3 on synovial fibroblasts, thereby inhibiting their cytokine and protease production in response to TLR3 ligation. Finally, tofacitinib counteracted the suppressive effects of IFNα on viral replication. Tofacitinib inhibits PDC survival and IFNα production and suppresses arthrogenic and antiviral effects of IFNα signaling. Inhibition of the IFNα pathway at 2 levels may contribute to the beneficial effects of tofacitinib in autoimmune diseases and explain the increased viral infection rates observed during tofacitinib treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Cu-PDC-bpa solid coordination frameworks (PDC=2,5-pyrindinedicarboxylate; bpa=1,2-DI(4-pyridil)ethane)): 2D and 3D structural flexibility producing a 3-c herringbone array next to ideal

NASA Astrophysics Data System (ADS)

Llano-Tomé, Francisco; Bazán, Begoña; Urtiaga, Miren-Karmele; Barandika, Gotzone; Antonia Señarís-Rodríguez, M.; Sánchez-Andújar, Manuel; Arriortua, María-Isabel

2015-10-01

Combination of polycarboxylate anions and dipyridyl ligands is an effective strategy to produce solid coordination frameworks (SCF) which are crystalline materials based on connections between metal ions through organic ligands. In this context, this work is focused on two novel CuII-based SCFs exhibiting PDC (2,5-pyridinedicarboxylate) and bpa (1,2-di(4-pyridyl)ethane), being the first structures reported in literature containing both ligands. Chemical formula are [Cu2[(PDC)2(bpa)(H2O)2]·3H2O·DMF (1), and [Cu2(PDC)2(bpa)(H2O)2]·7H2O (2), where DMF is dimethylformamide. Compounds 1 and 2 have been characterized by means of X-ray diffraction (XRD), infrared spectroscopy (IR), thermogravimetric (TG) analysis, differential thermal analysis (DTA) and dielectric measurements. The crystallographic analysis revealed that compounds 1 and 2 can be described as herringbone-type layers formed by helicoidal Cu-PDC-Cu chains connected through bpa ligands. Solvent molecules are crystallized between the layers, providing the inter-layer connections through hydrogen bonds. Differences between both compounds are attributable to the flexibility of bpa (in 2D) as well as to the 3D packing of the layers which is solvent dependent. This fact results in the fact that compound 2 is the most regular 3-c herringbone array reported so far. The structural dynamism of these networks is responsible for the crystalline to-amorphous to-crystalline (CAC) transformation from compound 1 to compound 2. Crystallochemical features for both compounds have also been studied and compared to similar 3-connected herringbone-arrays.

Exploring sequence requirements for C₃/C₄ carboxylate recognition in the Pseudomonas aeruginosa cephalosporinase: Insights into plasticity of the AmpC β-lactamase.

PubMed

Drawz, Sarah M; Taracila, Magdalena; Caselli, Emilia; Prati, Fabio; Bonomo, Robert A

2011-06-01

In Pseudomonas aeruginosa, the chromosomally encoded class C cephalosporinase (AmpC β-lactamase) is often responsible for high-level resistance to β-lactam antibiotics. Despite years of study of these important β-lactamases, knowledge regarding how amino acid sequence dictates function of the AmpC Pseudomonas-derived cephalosporinase (PDC) remains scarce. Insights into structure-function relationships are crucial to the design of both β-lactams and high-affinity inhibitors. In order to understand how PDC recognizes the C₃/C₄ carboxylate of β-lactams, we first examined a molecular model of a P. aeruginosa AmpC β-lactamase, PDC-3, in complex with a boronate inhibitor that possesses a side chain that mimics the thiazolidine/dihydrothiazine ring and the C₃/C₄ carboxylate characteristic of β-lactam substrates. We next tested the hypothesis generated by our model, i.e. that more than one amino acid residue is involved in recognition of the C₃/C₄ β-lactam carboxylate, and engineered alanine variants at three putative carboxylate binding amino acids. Antimicrobial susceptibility testing showed that the PDC-3 β-lactamase maintains a high level of activity despite the substitution of C₃/C₄ β-lactam carboxylate recognition residues. Enzyme kinetics were determined for a panel of nine penicillin and cephalosporin analog boronates synthesized as active site probes of the PDC-3 enzyme and the Arg349Ala variant. Our examination of the PDC-3 active site revealed that more than one residue could serve to interact with the C₃/C₄ carboxylate of the β-lactam. This functional versatility has implications for novel drug design, protein evolution, and resistance profile of this enzyme. Copyright © 2011 The Protein Society.

Cloning and sequencing of pyruvate decarboxylase (PDC) genes from bacteria and uses therefor

DOEpatents

Maupin-Furlow, Julie A [Gainesville, FL; Talarico, Lee Ann [Gainesville, FL; Raj, Krishnan Chandra [Tamil Nadu, IN; Ingram, Lonnie O [Gainesville, FL

2008-02-05

The invention provides isolated nucleic acids molecules which encode pyruvate decarboxylase enzymes having improved decarboxylase activity, substrate affinity, thermostability, and activity at different pH. The nucleic acids of the invention also have a codon usage which allows for high expression in a variety of host cells. Accordingly, the invention provides recombinant expression vectors containing such nucleic acid molecules, recombinant host cells comprising the expression vectors, host cells further comprising other ethanologenic enzymes, and methods for producing useful substances, e.g., acetaldehyde and ethanol, using such host cells.

A proteomics study of barley powdery mildew haustoria.

PubMed

Godfrey, Dale; Zhang, Ziguo; Saalbach, Gerhard; Thordal-Christensen, Hans

2009-06-01

A number of fungal and oomycete plant pathogens of major economic importance feed on their hosts by means of haustoria, which they place inside living plant cells. The underlying mechanisms are poorly understood, partly due to difficulty in preparing haustoria. We have therefore developed a procedure for isolating haustoria from the barley powdery mildew fungus (Blumeria graminis f.sp. hordei, Bgh). We subsequently aimed to understand the molecular mechanisms of haustoria through a study of their proteome. Extracted proteins were digested using trypsin, separated by LC, and analysed by MS/MS. Searches of a custom Bgh EST sequence database and the NCBI-NR fungal protein database, using the MS/MS data, identified 204 haustoria proteins. The majority of the proteins appear to have roles in protein metabolic pathways and biological energy production. Surprisingly, pyruvate decarboxylase (PDC), involved in alcoholic fermentation and commonly abundant in fungi and plants, was absent in our Bgh proteome data set. A sequence encoding this enzyme was also absent in our EST sequence database. Significantly, BLAST searches of the recently available Bgh genome sequence data also failed to identify a sequence encoding this enzyme, strongly indicating that Bgh does not have a gene for PDC.

78 FR 20665 - Pediatric Device Consortia Grant Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... population (neonates, infants, children, and adolescents) includes patients who are 21 years of age or... of the Office of Orphan Products Development (OOPD) Pediatric Device Consortia (PDC) Grant Program. The goal of the PDC Grant Program is to facilitate the development, production, and distribution of...

pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation

PubMed Central

Duraes, Fernanda V.; Lippens, Carla; Steinbach, Karin; Dubrot, Juan; Brighouse, Dale; Bendriss-Vermare, Nathalie; Issazadeh-Navikas, Shohreh; Merkler, Doron; Hugues, Stephanie

2016-01-01

Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation. PMID:26341385

Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state.

PubMed

Swiecki, M; Miller, H L; Sesti-Costa, R; Cella, M; Gilfillan, S; Colonna, M

2017-07-01

Plasmacytoid dendritic cells (pDCs) detect viruses initiating antiviral type I interferon responses. The microbiota is known to shape immune responses, but whether it influences pDC homeostasis and/or function is poorly understood. By comparing pDCs in germ-free and specific pathogen-free mice, we found that the microbiota supports homeostatic trafficking by eliciting constitutive levels of the chemokine CCL2 that engages CCR2. Mononuclear phagocytes were required for tonic CCL2 levels. CCL2 was particularly important for trafficking of a CCR2 hi subset of pDCs that produced proinflammatory cytokines and was prone to apoptosis. We further demonstrated that CCR2 was also essential for pDC migration during inflammation. Wild-type (WT):Ccr2 -/- mixed bone marrow chimeras revealed that CCR2 promotes pDC migration in a cell-intrinsic manner. Overall, we identify a novel role for the microbiota in shaping immunity, which includes induction of CCL2 levels that control homeostatic trafficking of pDCs.

The Regulation of Pyruvate Dehydrogenase Activity in Pea Leaf Mitochondria (The Effect of Respiration and Oxidative Phosphorylation).

PubMed

Moore, A. L.; Gemel, J.; Randall, D. D.

1993-12-01

The regulation of the pea (Pisum sativum) leaf mitochondrial pyruvate dehydrogenase complex by respiratory rate and oxidative phosphorylation has been investigated by measuring the respiratory activity, the redox poise of the quinone pool (Q-pool), and mitochondrial pyruvate dehydrogenase (mtPDC) activity under various metabolic conditions. It was found that, under state 4 conditions, mtPDC activity was unaffected by either the addition of succinate, 2-oxoglutarate, or glycine or the overall respiratory rate and redox poise of the Q-pool but was partially inhibited by NADH due to product inhibition. In the presence of ADP significant inactivation of PDC, which was sensitive to oligomycin, was observed with all substrates, apart from pyruvate, suggesting that inactivation was due to ATP formation. Inactivation of PDC by ADP addition was observed even in the presence of carboxyatractyloside, an inhibitor of the ATP/ADP translocator, suggesting that other mechanisms to facilitate the entry of adenylates, in addition to the adenylate carrier, must exist in plant mitochondria.

Pyruvate Decarboxylase, the Target for Omeprazole in Metronidazole-Resistant and Iron-Restricted Tritrichomonas foetus

PubMed Central

Sutak, Róbert; Tachezy, Jan; Kulda, Jaroslav; Hrdý, Ivan

2004-01-01

The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 μg/ml [63 μM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 μg/ml). Metronidazole-susceptible T. foetus, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells, T. foetus cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation. PMID:15155220

Tumor Budding and PDC Grade Are Stage Independent Predictors of Clinical Outcome in Mismatch Repair Deficient Colorectal Cancer.

PubMed

Ryan, Éanna; Khaw, Yi Ling; Creavin, Ben; Geraghty, Robert; Ryan, Elizabeth J; Gibbons, David; Hanly, Ann; Martin, Sean T; O'Connell, P Ronan; Winter, Desmond C; Sheahan, Kieran

2018-01-01

Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.

A controlled trial of Partners in Dementia Care: veteran outcomes after six and twelve months

PubMed Central

2014-01-01

Introduction “Partners in Dementia Care” (PDC) tested the effectiveness of a care-coordination program integrating healthcare and community services and supporting veterans with dementia and their caregivers. Delivered via partnerships between Veterans Affairs medical centers and Alzheimer’s Association chapters, PDC targeted both patients and caregivers, distinguishing it from many non-pharmacological interventions. Hypotheses posited PDC would improve five veteran self-reported outcomes: 1) unmet need, 2) embarrassment about memory problems, 3) isolation, 4) relationship strain and 5) depression. Greater impact was expected for more impaired veterans. A unique feature was self-reported research data collected from veterans with dementia. Methods and Findings Five matched communities were study sites. Two randomly selected sites received PDC for 12 months; comparison sites received usual care. Three structured telephone interviews were completed every 6 months with veterans who could participate. Results Of 508 consenting veterans, 333 (65.6%) completed baseline interviews. Among those who completed baseline interviews, 263 (79.0%) completed 6-month follow-ups and 194 (58.3%) completed 12-month follow-ups. Regression analyses showed PDC veterans had significantly less adverse outcomes than those receiving usual care, particularly for more impaired veterans after 6 months, including reduced relationship strain (B = −0.09; p = 0.05), depression (B = −0.10; p = 0.03), and unmet need (B = −0.28; p = 0.02; and B = −0.52; p = 0.08). PDC veterans also had less embarrassment about memory problems (B = −0.24; p = 0.08). At 12 months, more impaired veterans had further reductions in unmet need (B = −0.96; p < 0.01) and embarrassment (B = −0.05; p = 0.02). Limitations included use of matched comparison sites rather than within-site randomization and lack of consideration for variation within the PDC group in amounts and types of assistance provided. Conclusions Partnerships between community and health organizations have the potential to meet the dementia-related needs and improve the psychosocial functioning of persons with dementia. Trial Registry NCT00291161 PMID:24764496

A controlled trial of Partners in Dementia Care: veteran outcomes after six and twelve months.

PubMed

Bass, David M; Judge, Katherine S; Snow, A Lynn; Wilson, Nancy L; Morgan, Robert O; Maslow, Katie; Randazzo, Ronda; Moye, Jennifer A; Odenheimer, Germaine L; Archambault, Elizabeth; Elbein, Richard; Pirraglia, Paul; Teasdale, Thomas A; McCarthy, Catherine A; Looman, Wendy J; Kunik, Mark E

2014-01-01

"Partners in Dementia Care" (PDC) tested the effectiveness of a care-coordination program integrating healthcare and community services and supporting veterans with dementia and their caregivers. Delivered via partnerships between Veterans Affairs medical centers and Alzheimer's Association chapters, PDC targeted both patients and caregivers, distinguishing it from many non-pharmacological interventions. Hypotheses posited PDC would improve five veteran self-reported outcomes: 1) unmet need, 2) embarrassment about memory problems, 3) isolation, 4) relationship strain and 5) depression. Greater impact was expected for more impaired veterans. A unique feature was self-reported research data collected from veterans with dementia. Five matched communities were study sites. Two randomly selected sites received PDC for 12 months; comparison sites received usual care. Three structured telephone interviews were completed every 6 months with veterans who could participate. Of 508 consenting veterans, 333 (65.6%) completed baseline interviews. Among those who completed baseline interviews, 263 (79.0%) completed 6-month follow-ups and 194 (58.3%) completed 12-month follow-ups. Regression analyses showed PDC veterans had significantly less adverse outcomes than those receiving usual care, particularly for more impaired veterans after 6 months, including reduced relationship strain (B = -0.09; p = 0.05), depression (B = -0.10; p = 0.03), and unmet need (B = -0.28; p = 0.02; and B = -0.52; p = 0.08). PDC veterans also had less embarrassment about memory problems (B = -0.24; p = 0.08). At 12 months, more impaired veterans had further reductions in unmet need (B = -0.96; p < 0.01) and embarrassment (B = -0.05; p = 0.02). Limitations included use of matched comparison sites rather than within-site randomization and lack of consideration for variation within the PDC group in amounts and types of assistance provided. Partnerships between community and health organizations have the potential to meet the dementia-related needs and improve the psychosocial functioning of persons with dementia. NCT00291161.

The incidence and prognosis of true duodenal carcinomas.

PubMed

Buchbjerg, T; Fristrup, C; Mortensen, M B

2015-06-01

Primary duodenal carcinoma (PDC) is a rare gastrointestinal tumor. The difficult distinction between PDC and other types of carcinoma (e.g. within the periampullary region) is reflected in the scarce literature on true duodenal carcinomas. However, this distinction may be important in relation to the overall prognosis as well as in the choice of adjuvant or palliative treatment strategies. The aim of this study was to evaluate the incidence, management and prognosis of patients with true PDC within a well-defined geographical area. Retrospective analysis of all patients diagnosed with true PDC from 1997 to 2012 within the Region of Southern Denmark. Only patients where the surgeon and the pathologist agreed on the tumor being classified as originating from the duodenum were included. Seventy-one patients (43 M, 28 F) with a mean age of 67 years (range 35-87) met the criteria for true PDC. The incidence was 5.4 per 1,000,000, and the pathological classification was: Adenocarcinoma 87%, mucinous adenocarcinoma 7%, carcinoma 4% and signet ring cell carcinoma 1%. Intended curative resection was performed in 28 patients (39%) (22 Whipple procedures and 6 local resections), and all but one patient had negative resection margins. Thirteen patients (46%) had lymph node metastasis. Twenty-nine (67%) of the palliative treated patients had a single (n = 24) or double by-pass procedure (n = 5). The median and 5-year survival for the resected patients were 23 months (CI 7-44) and 27% (CI 10-44). The median survival in the palliative group was 5 months (CI 2-11), and none of the patients were alive after three years. The incidence of true PDC within a geographical and histopathologically completely monitored area was 5.4 per 1,000,000. Less than 40% of the patients could be resected and they had a median survival of 23 month and an estimated 5-year survival of 27%. The prognosis of true PDC seemed lower than expected according to previously published data. Copyright © 2015 Elsevier Ltd. All rights reserved.

Uncovering dispersion properties in semiconductor waveguides to study photon-pair generation

NASA Astrophysics Data System (ADS)

Laiho, K.; Pressl, B.; Schlager, A.; Suchomel, H.; Kamp, M.; Höfling, S.; Schneider, C.; Weihs, G.

2016-10-01

We investigate the dispersion properties of ridge Bragg-reflection waveguides to deduce their phasematching characteristics. These are crucial for exploiting them as sources of parametric down-conversion (PDC). In order to estimate the phasematching bandwidth we first determine the group refractive indices of the interacting modes via Fabry-Perot experiments in two distant wavelength regions. Second, by measuring the spectra of the emitted PDC photons, we gain access to their group index dispersion. Our results offer a simple approach for determining the PDC process parameters in the spectral domain, and provide important feedback for designing such sources, especially in the broadband case.

Inactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam.

PubMed

Barnes, Melissa D; Bethel, Christopher R; Alsop, Jim; Becka, Scott A; Rutter, Joseph D; Papp-Wallace, Krisztina M; Bonomo, Robert A

2018-05-01

Pseudomonas aeruginosa is a prevalent and life-threatening Gram-negative pathogen. Pseudomonas -derived cephlosporinase (PDC) is the major inducible cephalosporinase in P. aeruginosa In this investigation, we show that relebactam, a diazabicyclooctane β-lactamase inhibitor, potently inactivates PDC-3, with a k 2 / K of 41,400 M -1 s -1 and a k off of 0.00095 s -1 Relebactam restored susceptibility to imipenem in 62% of multidrug-resistant P. aeruginosa clinical isolates, while only 21% of isolates were susceptible to imipenem-cilastatin alone. Relebactam promises to increase the efficacy of imipenem-cilastatin against P. aeruginosa . Copyright © 2018 American Society for Microbiology.

Project Developmental Continuity: PDC Classroom Observation Manual.

ERIC Educational Resources Information Center

Meece, Judy; And Others

This classroom observation manual (Fall 1976) was developed for use in the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. The manual provides detailed instructions for the observer on…

CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis.

PubMed

Shimoda, Shinji; Miyakawa, Hiroshi; Nakamura, Minoru; Ishibashi, Hiromi; Kikuchi, Kentaro; Kita, Hiroto; Niiro, Hiroaki; Arinobu, Youjirou; Ono, Nobuyuki; Mackay, Ian R; Gershwin, M Eric; Akashi, Koichi

2008-09-01

Approximately 5% of patients with primary biliary cirrhosis (PBC) lack characteristic anti-mitochondrial antibodies (AMA). Yet clinically AMA+ and AMA- patients are similar. Using both AMA+ and AMA- patients, we quantitated the frequency of autoreactive T cells that respond to the major CD4 T-cell epitope, PDC-E2 163-176, using limiting dilution assays and quantitation of IFN-gamma, IL-10 and IL-4. Further, based on data that both PBC patients and healthy subjects have CD4+ T cells that recognize PDC-E2 163-176 but with differing costimulation requirements, assays were performed using two different antigen-presenting cell (APC) systems: either autologous peripheral blood mononuclear cells (PBMC) or HLA DR53 transfected mouse fibroblast cell lines (L-DR53). When costimulation-incompetent L-DR53 were used as APCs, the PDC-E2 CD4 T-cell frequency and capacity for IFN-gamma production were equivalent in both AMA+ and AMA- patients but the frequencies of such cells were significantly lower in normals, with IL-10 production similar in all three groups. Thus, in PBC there is 'universal' autoreactive CD4+ T-cell immune responsiveness to the critical autoantigen, PDC-E2. These observations emphasize that the mitochondrial autoreactivity in PBC is a multi-lineage response and hence, AMA-negative PBC may be an anachronism that refers only to sera autoantibodies.

Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.

PubMed

Braun, Sandra; Berg, Christoph; Buck, Sandra; Gregor, Michael; Klein, Reinhild

2010-02-28

To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC). Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore, the inner lipoyl peptide 167-184 was used in an unlipoylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA positive PBC patients, 63 patients with other liver disorders and 22 healthy blood donors served as controls. Of the 95 PBC-sera, 74% reacted with the peptide 475-499 and 58% with the peptide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylated and lipoylated peptide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera, respectively; using ovalbumin-coupled peptides, the incidence increased up to 57% (unlipoylated form). Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodominant epitopes recognized by AMA in PBC.

Unsteady specific work and isentropic efficiency of a radial turbine driven by pulsed detonations

NASA Astrophysics Data System (ADS)

Rouser, Kurt P.

There has been longstanding government and industry interest in pressure-gain combustion for use in Brayton cycle based engines. Theoretically, pressure-gain combustion allows heat addition with reduced entropy loss. The pulsed detonation combustor (PDC) is a device that can provide such pressure-gain combustion and possibly replace typical steady deflagration combustors. The PDC is inherently unsteady, however, and comparisons with conventional steady deflagration combustors must be based upon time-integrated performance variables. In this study, the radial turbine of a Garrett automotive turbocharger was coupled directly to and driven, full admission, by a PDC in experiments fueled by hydrogen or ethylene. Data included pulsed cycle time histories of turbine inlet and exit temperature, pressure, velocity, mass flow, and enthalpy. The unsteady inlet flowfield showed momentary reverse flow, and thus unsteady accumulation and expulsion of mass and enthalpy within the device. The coupled turbine-driven compressor provided a time-resolved measure of turbine power. Peak power increased with PDC fill fraction, and duty cycle increased with PDC frequency. Cycle-averaged unsteady specific work increased with fill fraction and frequency. An unsteady turbine efficiency formulation is proposed, including heat transfer effects, enthalpy flux-weighted total pressure ratio, and ensemble averaging over multiple cycles. Turbine efficiency increased with frequency but was lower than the manufacturer reported conventional steady turbine efficiency.

Functions of TGF-β-exposed plasmacytoid dendritic cells.

PubMed

Saas, Philippe; Perruche, Sylvain

2012-01-01

Plasmacytoid dendritic cells (pDCs) belong to the family of dendritic cells and possess specific features that distinguish them from conventional dendritic cells. For instance, pDC are the main interferon-alpha-secreting cells. Plasmacytoid dendritic cells exert both proinflammatory and regulatory functions. This is attested by the involvement of pDC through interferon-alpha secretion in several autoimmune diseases, and by the implication of pDC in tolerance. The same is true for TGF-β that plays a dual role in inflammation. In this review, we discuss recent data on pDC and TGF-β interactions. As with many cell types, pDCs are able to respond to TGF-β using the classic Smad signaling pathway. In addition, pDCs are capable to secrete TGF-β, in particular in response to TGF-β exposure. Exposure of pDCs to TGF-β prevents type I interferon secretion in response to TLR7/9 ligands. In contrast, the consequences of TGF-β on the antigen-presenting cell capacities of pDC are less clear, since TGF-β-exposed pDCs may lead to both regulatory T-cell and interleukin-17-secreting cell polarization. Here, we discuss the factors that may influence this polarization. We also discuss how pDCs exposed to TGF-β may participate in tolerance induction and maintenance, or, on the contrary, in autoimmune diseases.

Formocresol versus calcium hydroxide direct pulp capping of human primary molars: two year follow-up.

PubMed

Aminabadi, Naser Asl; Farahani, Ramin Mostofi Zadeh; Oskouei, Sina Ghertasi

2010-01-01

Clinical and radiographic evaluation of the premedicated direct pulp capping using formocresol (PDC) versus conventional direct pulp capping using calcium hydroxide (CDC) in human carious primary molars. A total of 120 vital primary molars with pinpoint exposure during caries removal in 84 patients aged 4-5 years were selected. In the PDC group (n = 60), 20% Buckley's formocresol solution, and in the CDC group (n = 60), calcium hydroxide powder were applied to the exposure sites followed by placement of zinc oxide-eugenol base. Teeth were restored with preformed stainless steel crowns. Clinical and radiographic evaluations of the treatment outcomes were performed at regular intervals of 6 and 12 months, respectively, for two years post-operatively. The prevalence of spontaneous pain, sensitivity on percussion, and fistula were significantly higher in the CDC group compared to the PDC group (P < 0.05). The number of teeth exhibiting periapical/furcal radiolucency or external/internal root resorption was also higher in the CDC group (P < 0.05). The clinical success rate of the PDC was 90% compared to the 61.7% of the CDC (P < 0.05). The radiographic success rates of the PDC and CDC groups were 85% and 53.3%, respectively (P < 0.05). It seems formocresol premedicated direct pulp capping could safely be used as a substitute for conventional direct pulp capping.

[CCT chaperonins and their cochaperons].

PubMed

Bregier, Cezary; Kupikowska, Barbara; Fabczak, Hanna; Fabczak, Stanisław

2008-01-01

Chaperonins are large oligomers consisting of two superimposed rings, each enclosing a cavity used for the folding of other proteins. They have been divided into two groups. Chaperonins of type I were identified in mitochondria and chloroplasts (Hsp60) or bacterial cytosol (GroEL) as well. Chaperonins type II were found in Archea and the eukaryotic cell cytosol (CCT). Protein folding occurs in the chaperonin after its conformational changes induced upon ATP binding. Mechanism of the protein folding, although still poorly defined, clearly differs from the one established for GroEL. Although CCT with prefoldin seems to be mainly involved in the folding of actin and tubulin, other substrates engaged in various cellular processes are beginning to be characterized, including proteins possessing WD40-repeats. Moreover, several lines of evidence suggest that beside prefoldin, CCT may work in concert with phosducin-like proteins (PhLPs).

Project Developmental Continuity Evaluation: Final Report. Executive Summary.

ERIC Educational Resources Information Center

Bond, James T.; Rosario, Jose

This executive summary presents the major results of the longitudinal evaluation of Project Developmental Continuity (PDC). A Head Start demonstration project initiated by the Administration for Children, Youth and Families (ACYF) in 1974, the PDC aimed to stimulate the development and implementation of comprehensive programs linking Head Start…

Project Developmental Continuity Evaluation: Site Visitors' Manual.

ERIC Educational Resources Information Center

Morris, Mary; Smith, Allen

This site visitors' manual is part of a series of documents on the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. The PDC evaluation documents and analyzes the process of program…

Does PDC Belong in Facilities Management?

ERIC Educational Resources Information Center

Dessoff, Alan

2012-01-01

Whether planning, design, and construction (PDC) of buildings should be part of facilities management, with its traditional operations and maintenance functions, or separated from it, has been a divisive question on many campuses for a long time. Now, although it is not happening everywhere, facilities managers at a number of institutions, public…

Plasmonic diabolo cavity enhanced spin pumping

NASA Astrophysics Data System (ADS)

Qian, Jie; Gou, Peng; Gui, Y. S.; Hu, C. M.; An, Zhenghua

2017-09-01

Low spin-current generation efficiency has impeded further progress in practical spin devices, especially in the form of wireless excitation. To tackle this problem, a unique Plasmonic Diabolo Cavity (PDC) is proposed to enhance the spin pumping (SP) signal. The SP microwave photovoltage is enhanced ˜22-fold by PDC at ferromagnetic resonance (FMR). This improvement owes to the localization of the microwave magnetic field, which drives the spin precession process to more effectively generate photovoltage at the FMR condition. The in-plane anisotropy of spin pumping is found to be suppressed by PDC. Our work suggests that metamaterial resonant structures exhibit rich interactions with spin dynamics and could potentially be applied in future high-frequency spintronics.

Implementation of the Sun Position Calculation in the PDC-1 Control Microprocessor

NASA Technical Reports Server (NTRS)

Stallkamp, J. A.

1984-01-01

The several computational approaches to providing the local azimuth and elevation angles of the Sun as a function of local time and then the utilization of the most appropriate method in the PDC-1 microprocessor are presented. The full algorithm, the FORTRAN form, is felt to be very useful in any kind or size of computer. It was used in the PDC-1 unit to generate efficient code for the microprocessor with its floating point arithmetic chip. The balance of the presentation consists of a brief discussion of the tracking requirements for PPDC-1, the planetary motion equations from the first to the final version, and the local azimuth-elevation geometry.

Project Developmental Continuity Evaluation: Final Report. Volume II: The Process of Program Implementation in PDC.

ERIC Educational Resources Information Center

Wacker, Sally; And Others

The second of two volumes, this document continues the final evaluation report of Project Developmental Continuity (PDC), a Head Start demonstration project initiated in 1974 to develop program models which enhance children's social competence by fostering developmental continuity from preschool through the early elementary grades. In particular,…

Project Developmental Continuity Evaluation: Final Report. Volume I: Outcomes of the PDC Intervention.

ERIC Educational Resources Information Center

Bond, James T.; And Others

The first of two volumes, this document reports an evaluation of Project Developmental Continuity (PDC), a Head Start demonstration project initiated in 1974 to develop program models which enhance children's social competence by fostering developmental continuity from preschool through the early elementary years. In general, the impact of program…

Partners in Dementia Care: A Care Coordination Intervention for Individuals with Dementia and Their Family Caregivers

ERIC Educational Resources Information Center

Judge, Katherine S.; Bass, David M.; Snow, A. Lynn; Wilson, Nancy L.; Morgan, Robert; Looman, Wendy J.; McCarthy, Catherine; Kunik, Mark E.

2011-01-01

Purpose: This article provides a detailed description of a telephone-based care coordination intervention, Partners in Dementia Care (PDC), for veterans with dementia and their family caregivers. Essential features of PDC included (a) formal partnerships between Veterans Affairs (VA) medical centers and Alzheimer's Association Chapters; (b) a…

Evaluating the Performance Diagnostic Checklist-Human Services to Assess Incorrect Error-Correction Procedures by Preschool Paraprofessionals

ERIC Educational Resources Information Center

Bowe, Melissa; Sellers, Tyra P.

2018-01-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) has been used to assess variables contributing to undesirable staff performance. In this study, three preschool teachers completed the PDC-HS to identify the factors contributing to four paraprofessionals' inaccurate implementation of error-correction procedures during discrete trial…

Plasmacytoid dendritic cells control dengue and Chikungunya virus infections via IRF7-regulated interferon responses

PubMed Central

Zafirova, Biljana; This, Sébastien; Coléon, Séverin; Décembre, Elodie; Paidassi, Helena; Bouvier, Isabelle; Joubert, Pierre-Emmanuel; Duffy, Darragh; Walzer, Thierry

2018-01-01

Type I interferon (IFN-I) responses are critical for the control of RNA virus infections, however, many viruses, including Dengue (DENV) and Chikungunya (CHIKV) virus, do not directly activate plasmacytoid dendritic cells (pDCs), robust IFN-I producing cells. Herein, we demonstrated that DENV and CHIKV infected cells are sensed by pDCs, indirectly, resulting in selective IRF7 activation and IFN-I production, in the absence of other inflammatory cytokine responses. To elucidate pDC immunomodulatory functions, we developed a mouse model in which IRF7 signaling is restricted to pDC. Despite undetectable levels of IFN-I protein, pDC-restricted IRF7 signaling controlled both viruses and was sufficient to protect mice from lethal CHIKV infection. Early pDC IRF7-signaling resulted in amplification of downstream antiviral responses, including an accelerated natural killer (NK) cell-mediated type II IFN response. These studies revealed the dominant, yet indirect role of pDC IRF7-signaling in directing both type I and II IFN responses during arbovirus infections. PMID:29914621

Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

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

Kato, Masato; Wynn, R. Max; Chuang, Jacinta L.

2009-09-11

We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-{alpha} (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-{alpha} prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-{alpha}, whichmore » nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.« less

Drilling plastic formations using highly polished PDC cutters

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

Smith, R.H.; Lund, J.B.; Anderson, M.

1995-12-31

Highly plastic and over-pressured formations are troublesome for both roller cone and PDC bits. Thus far, attempts to increase penetration rates in these formations have centered around re-designing the bit or modifying the cutting structure. These efforts have produced only moderate improvements. This paper presents both laboratory and field data to illustrate the benefits of applying a mirror polished surface to the face of PDC cutters in drilling stressed formations. These cutters are similar to traditional PDC cutters, with the exception of the reflective mirror finish, applied to the diamond table surfaces prior to their installation in the bit. Resultsmore » of tests conducted in a single point cutter apparatus and a full-scale drilling simulator will be presented and discussed. Field results will be presented that demonstrate the effectiveness of polished cutters, in both water and oil-based muds. Increases in penetration rates of 300-400% have been observed in the Wilcox formation and other highly pressured shales. Typically, the beneficial effects of polished cutters have been realized at depths greater than 7000 ft, and with mud weights exceeding 12 ppg.« less

pDC therapy induces recovery from EAE by recruiting endogenous pDC to sites of CNS inflammation.

PubMed

Duraes, Fernanda V; Lippens, Carla; Steinbach, Karin; Dubrot, Juan; Brighouse, Dale; Bendriss-Vermare, Nathalie; Issazadeh-Navikas, Shohreh; Merkler, Doron; Hugues, Stephanie

2016-02-01

Plasmacytoid dendritic cells (pDCs) exhibit both innate and adaptive functions. In particular they are the main source of type I IFNs and directly impact T cell responses through antigen presentation. We have previously demonstrated that during experimental autoimmune encephalomyelitis (EAE) initiation, myelin-antigen presentation by pDCs is associated with suppressive Treg development and results in attenuated EAE. Here, we show that pDCs transferred during acute disease phase confer recovery from EAE. Clinical improvement is associated with migration of injected pDCs into inflamed CNS and is dependent on the subsequent and selective chemerin-mediated recruitment of endogenous pDCs to the CNS. The protective effect requires pDC pre-loading with myelin antigen, and is associated with the modulation of CNS-infiltrating pDC phenotype and inhibition of CNS encephalitogenic T cells. This study may pave the way for novel pDC-based cell therapies in autoimmune diseases, aiming at specifically modulating pathogenic cells that induce and sustain autoimmune inflammation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evidence of erosional self-channelization of pyroclastic density currents revealed by ground-penetrating radar imaging at Mount St. Helens, Washington (USA)

NASA Astrophysics Data System (ADS)

Gase, Andrew C.; Brand, Brittany D.; Bradford, John H.

2017-03-01

The causes and effects of erosion are among the least understood aspects of pyroclastic density current (PDC) dynamics. Evidence is especially limited for erosional self-channelization, a process whereby PDCs erode a channel that confines the body of the eroding flow or subsequent flows. We use ground-penetrating radar imaging to trace a large PDC scour and fill from outcrop to its point of inception and discover a second, larger PDC scour and fill. The scours are among the largest PDC erosional features on record, at >200 m wide and at least 500 m long; estimated eroded volumes are on the order of 106 m3. The scours are morphologically similar to incipient channels carved by turbidity currents. Erosion may be promoted by a moderate slope (5-15°), substrate pore pressure retention, and pulses of increased flow energy. These findings are the first direct evidence of erosional self-channelization by PDCs, a phenomenon that may increase flow velocity and runout distance through confinement and substrate erosion.

Some Aspects of PDC Electrolysis

NASA Astrophysics Data System (ADS)

Poláčik, Ján; Pospíšil, Jiří

2016-10-01

In this paper, aspects of pulsed direct current (PDC) water splitting are described. Electrolysis is a simple and well-known method to produce hydrogen. The efficiency is relatively low in normal conditions using conventional DC. PDC in electrolysis brings about many advantages. It increases efficiency of hydrogen production, and performance of the electrolyser may be smoothly controlled without compromising efficiency of the process. In our approach, ultra-short pulses are applied. This method enhances efficiency of electrical energy in the process of decomposition of water into hydrogen and oxygen. Efficiency depends on frequency, shape and width of the electrical pulses. Experiments proved that efficiency was increased by 2 to 8 per cent. One of the prospects of PDC electrolysis producing hydrogen is in increase of efficiency of energy storage efficiency in the hydrogen. There are strong efforts to make the electrical grid more efficient and balanced in terms of production by installing electricity storage units. Using hydrogen as a fuel decreases air pollution and amount of carbon dioxide emissions in the air. In addition to energy storage, hydrogen is also important in transportation and chemical industry.

Presearch data conditioning in the Kepler Science Operations Center pipeline

NASA Astrophysics Data System (ADS)

Twicken, Joseph D.; Chandrasekaran, Hema; Jenkins, Jon M.; Gunter, Jay P.; Girouard, Forrest; Klaus, Todd C.

2010-07-01

We describe the Presearch Data Conditioning (PDC) software component and its context in the Kepler Science Operations Center (SOC) Science Processing Pipeline. The primary tasks of this component are to correct systematic and other errors, remove excess flux due to aperture crowding, and condition the raw flux light curves for over 160,000 long cadence (~thirty minute) and 512 short cadence (~one minute) stellar targets. Long cadence corrected flux light curves are subjected to a transiting planet search in a subsequent pipeline module. We discuss science algorithms for long and short cadence PDC: identification and correction of unexplained (i.e., unrelated to known anomalies) discontinuities; systematic error correction; and removal of excess flux due to aperture crowding. We discuss the propagation of uncertainties from raw to corrected flux. Finally, we present examples from Kepler flight data to illustrate PDC performance. Corrected flux light curves produced by PDC are exported to the Multi-mission Archive at Space Telescope [Science Institute] (MAST) and are made available to the general public in accordance with the NASA/Kepler data release policy.

Measurements of multiple gas parameters in a pulsed-detonation combustor using time-division-multiplexed Fourier-domain mode-locked lasers.

PubMed

Caswell, Andrew W; Roy, Sukesh; An, Xinliang; Sanders, Scott T; Schauer, Frederick R; Gord, James R

2013-04-20

Hyperspectral absorption spectroscopy is being used to monitor gas temperature, velocity, pressure, and H(2)O mole fraction in a research-grade pulsed-detonation combustor (PDC) at the Air Force Research Laboratory. The hyperspectral source employed is termed the TDM 3-FDML because it consists of three time-division-multiplexed (TDM) Fourier-domain mode-locked (FDML) lasers. This optical-fiber-based source monitors sufficient spectral information in the H(2)O absorption spectrum near 1350 nm to permit measurements over the wide range of conditions encountered throughout the PDC cycle. Doppler velocimetry based on absorption features is accomplished using a counterpropagating beam approach that is designed to minimize common-mode flow noise. The PDC in this study is operated in two configurations: one in which the combustion tube exhausts directly to the ambient environment and another in which it feeds an automotive-style turbocharger to assess the performance of a detonation-driven turbine. Because the enthalpy flow [kilojoule/second] is important in assessing the performance of the PDC in various configurations, it is calculated from the measured gas properties.

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

Desai, S.; Ruff, V.; DuBrul, E.F.

The pyruvate dehydrogenase complex (PDC) plays a pivotal role in the anaerobic metabolism of Ascaris suum mitochondria. They have initiated a series of studies on the in vitro synthesis and mitochondrial import of PDC. PDC has been purified from adult Ascaris body wall muscle, fully phosphorylated in vitro, and separated into its component subunits on SDS/PAGE. The individual components were electroeluted from the gels and used to immunize rabbits. IgG's to the individual subunits were prepared from antisera and their specificities were verified by immuno-blotting. Each IgG identified a single specific band at the appropriate location in extracts of adultmore » Ascaris body wall muscle mitochondria. Poly A/sup +/-RNA was prepared from body wall muscle and translated in a reticylocyte lysate system using /sup 35/S-methionine. Translation products were immunoprecipitated with specific IgG's, electrophoresed, and fluorographed. Each immunoprecipitation gave rise to a single radioactive polypeptide that was slightly larger than the specific PDC subunit isolated from the adult mitochondria. This system has demonstrated its feasibility for the study of mitochondrial import of a multienzyme complex that is critical for the anaerobic mitochondrial metabolism of Ascaris suum.« less

Pyrrolo-dC modified duplex DNA as a novel probe for the sensitive assay of base excision repair enzyme activity.

PubMed

Lee, Chang Yeol; Park, Ki Soo; Park, Hyun Gyu

2017-12-15

We develop a novel approach to determine formamidopyrimidine DNA glycosylase (Fpg) activity by taking advantage of the unique fluorescence property of pyrrolo-dC (PdC) positioned opposite to 8-oxoguanine (8-oxoG) in duplex DNA. In its initial state, PdC in duplex DNA undergoes the efficient stacking and collisional quenching interactions, showing the low fluorescence signal. In contrast, the presence of Fpg, which specifically removes 8-oxoG and incises resulting apurinic (AP) site, transforms duplex DNA into single-stranded (ss) DNAs. As a result, the intrinsic fluorescence signal of PdC in ssDNA is recovered to exhibit the significantly enhanced fluorescence signal. Based on this Fpg-dependent fluorescence response of PdC, we could reliably determine Fpg activity down to 1.25U/ml with a linear response from 0 to 50U/ml. In addition, the diagnostic capability of this strategy was successfully demonstrated by reliably assaying Fpg activity in human blood serum, showing its great potential in the practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of normalization of Partial Directed Coherence on the statistical assessment of connectivity patterns: a simulation study.

PubMed

Toppi, J; Petti, M; Vecchiato, G; Cincotti, F; Salinari, S; Mattia, D; Babiloni, F; Astolfi, L

2013-01-01

Partial Directed Coherence (PDC) is a spectral multivariate estimator for effective connectivity, relying on the concept of Granger causality. Even if its original definition derived directly from information theory, two modifies were introduced in order to provide better physiological interpretations of the estimated networks: i) normalization of the estimator according to rows, ii) squared transformation. In the present paper we investigated the effect of PDC normalization on the performances achieved by applying the statistical validation process on investigated connectivity patterns under different conditions of Signal to Noise ratio (SNR) and amount of data available for the analysis. Results of the statistical analysis revealed an effect of PDC normalization only on the percentages of type I and type II errors occurred by using Shuffling procedure for the assessment of connectivity patterns. No effects of the PDC formulation resulted on the performances achieved during the validation process executed instead by means of Asymptotic Statistic approach. Moreover, the percentages of both false positives and false negatives committed by Asymptotic Statistic are always lower than those achieved by Shuffling procedure for each type of normalization.

Presearch Data Conditioning in the Kepler Science Operations Center Pipeline

NASA Technical Reports Server (NTRS)

Twicken, Joseph D.; Chandrasekaran, Hema; Jenkins, Jon M.; Gunter, Jay P.; Girouard, Forrest; Klaus, Todd C.

2010-01-01

We describe the Presearch Data Conditioning (PDC) software component and its context in the Kepler Science Operations Center (SOC) pipeline. The primary tasks of this component are to correct systematic and other errors, remove excess flux due to aperture crowding, and condition the raw flux light curves for over 160,000 long cadence (thirty minute) and 512 short cadence (one minute) targets across the focal plane array. Long cadence corrected flux light curves are subjected to a transiting planet search in a subsequent pipeline module. We discuss the science algorithms for long and short cadence PDC: identification and correction of unexplained (i.e., unrelated to known anomalies) discontinuities; systematic error correction; and excess flux removal. We discuss the propagation of uncertainties from raw to corrected flux. Finally, we present examples of raw and corrected flux time series for flight data to illustrate PDC performance. Corrected flux light curves produced by PDC are exported to the Multi-mission Archive at Space Telescope [Science Institute] (MAST) and will be made available to the general public in accordance with the NASA/Kepler data release policy.

Mild deoxygenation of aromatic ketones and aldehydes over Pd/C using polymethylhydrosiloxane as the reducing agent.

PubMed

Volkov, Alexey; Gustafson, Karl P J; Tai, Cheuk-Wai; Verho, Oscar; Bäckvall, Jan-E; Adolfsson, Hans

2015-04-20

Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol % Pd/C catalyst to furnish the corresponding deoxygenated product in 93 % yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Hippocampal sclerosis in the parkinsonism-dementia complex of Guam: quantitative examination of neurons, neurofibrillary tangles, and TDP-43 immunoreactivity in CA1.

PubMed

Oyanagi, Kiyomitsu; Yamazaki, Mineo; Hashimoto, Tomoyo; Asakawa, Mika; Wakabayashi, Koichi; Takahashi, Hitoshi

2015-06-01

The cornu ammonis 1 (CA1) area in the hippocampus of the parkinsonism-dementia complex (PDC) of Guam was examined quantitatively with special references to the number of neurons, intraneuronal (i) and extracellular (e) neurofibirillary tangles (NFTs), and TDP-43 (43-kDa trans-activation-responsive region DNA-binding protein)-immunopositive structures, in 24 Chamorro patients with PDC of Guam and seven control Chamorro Guamanians (both groups having no ischemic or anoxic complications). The results were that: (i) in the patients with mildly involved PDC, total numbers of neurons, iNFTs and eNFTs were almost the same as those of neurons of controls; (ii) in patients severely involved, total numbers of neurons, iNFTs and eNFTs decreased markedly; (iii) the decrease of the number of pyramidal neurons in CA1 with positive nuclear TDP-43 was intimately correlated with the decrease in total neuron numbers; (iv) whereas the numbers of neurons and TDP-43-immunopositive intracytoplasmic aggregation in the CA1 area were inversely correlated; and (v) depression of nuclear TDP-43 immuonostainability was not affected by the presence or absence of NFTs. In conclusion, hippocampal sclerosis exists in PDC; there is a possibility of elimination of eNFTs which appeared in the CA1 in patients with PDC and loss of the neurons correlates with disappearance of nuclear TDP-43, but not with appearance of intraneurocytoplasmic TDP-43 aggregation or iNFTs. © 2015 Japanese Society of Neuropathology.

Improving outcomes for people with progressive cancer: interrupted time series trial of a needs assessment intervention.

PubMed

Waller, Amy; Girgis, Afaf; Johnson, Claire; Lecathelinais, Christophe; Sibbritt, David; Forstner, Dion; Liauw, Winston; Currow, David C

2012-03-01

Improving the effectiveness of cancer care delivery has become a major focus of research. This study assessed the uptake and impact of the Palliative Care Needs Assessment Guidelines and Needs Assessment Tool: Progressive Disease--Cancer (NAT: PD-C) on the outcomes of people with advanced cancer. Given widely varying survival in people with advanced cancer, an interrupted time series design was used, with data on unmet needs, depression, anxiety, and quality of life collected from 195 patients using telephone interviews every two months, for up to 18 months. Patients completed at least two baseline interviews before health professionals were academically detailed in the use of the Palliative Care Needs Assessment Guidelines and NAT: PD-C. Health professionals completed the NAT: PD-C with patients approximately monthly for the remainder of the study. Changes in patients' outcomes were compared prior to and following the introduction of the NAT: PD-C using general estimating equations. Moderate to high needs across all domains were frequently seen in the preintervention phase. The use of the NAT: PD-C was associated with a significant reduction in health system and information and patient care and support needs. These resources have the potential as an efficient and acceptable strategy for supporting needs-based cancer care. Further work is required to determine their unique contribution to improvements in patient outcomes. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Patient adherence to transdermal rivastigmine after switching from oral donepezil: a retrospective claims database study.

PubMed

Tian, Haijun; Abouzaid, Safiya; Chen, Wei; Kahler, Kristijan H; Kim, Edward

2013-01-01

To examine patient adherence before and after switching from donepezil to the rivastigmine patch. This retrospective cohort study used the MarketScan Commercial and Medicare data sets (2004 to 2009). Patients with a diagnosis of Alzheimer disease who were new donepezil users and were subsequently switched to the rivastigmine patch were included. The proportion of days covered (PDC) and PDC difference between donepezil and the rivastigmine patch were calculated from the time of initiation to the switch, capped at 1 year after the first respective claim. PDC was calculated as the number of days with drugs available divided by the number of days in the respective follow-up periods. The sample included 772 patients (mean age 77 y; 58% female). The mean time between switching from donepezil to the rivastigmine patch was 579 (SD=317.3) days. The mean PDC for the rivastigmine patch was highest among patients who switched within 3 months (80.4% vs. 90.7%; P=0.04) and within 7 to 9 months (61.3% vs. 71.0%; P=0.05) of initiating donepezil. When adherence was analyzed in increments of 1 year, patients who switched to the rivastigmine patch within the first year of treatment had significantly greater adherence to rivastigmine compared with those who were on donepezil (PDC 69.3% vs. 60.6%; P=0.0004). Switching from donepezil to the rivastigmine patch seems to be associated with increased adherence, especially in patients who switched within the first year of initiating donepezil.

Suitability of energy cone for probabilistic volcanic hazard assessment: validation tests at Somma-Vesuvius and Campi Flegrei (Italy)

NASA Astrophysics Data System (ADS)

Tierz, Pablo; Sandri, Laura; Costa, Antonio; Zaccarelli, Lucia; Di Vito, Mauro Antonio; Sulpizio, Roberto; Marzocchi, Warner

2016-11-01

Pyroclastic density currents (PDCs) are gravity-driven hot mixtures of gas and volcanic particles which can propagate at high speed and cover distances up to several tens of kilometers around a given volcano. Therefore, they pose a severe hazard to the surroundings of explosive volcanoes able to produce such phenomena. Despite this threat, probabilistic volcanic hazard assessment (PVHA) of PDCs is still in an early stage of development. PVHA is rooted in the quantification of the large uncertainties (aleatory and epistemic) which characterize volcanic hazard analyses. This quantification typically requires a big dataset of hazard footprints obtained from numerical simulations of the physical process. For PDCs, numerical models range from very sophisticated (not useful for PVHA because of their very long runtimes) to very simple models (criticized because of their highly simplified physics). We present here a systematic and robust validation testing of a simple PDC model, the energy cone (EC), to unravel whether it can be applied to PVHA of PDCs. Using past PDC deposits at Somma-Vesuvius and Campi Flegrei (Italy), we assess the ability of EC to capture the values and variability in some relevant variables for hazard assessment, i.e., area of PDC invasion and maximum runout. In terms of area of invasion, the highest Jaccard coefficients range from 0.33 to 0.86 which indicates an equal or better performance compared to other volcanic mass-flow models. The p values for the observed maximum runouts vary from 0.003 to 0.44. Finally, the frequencies of PDC arrival computed from the EC are similar to those determined from the spatial distribution of past PDC deposits, with high PDC-arrival frequencies over an ˜8-km radius from the crater area at Somma-Vesuvius and around the Astroni crater at Campi Flegrei. The insights derived from our validation tests seem to indicate that the EC is a suitable candidate to compute PVHA of PDCs.

Sequestration of PDC-109 protein improves freezability of crossbred bull spermatozoa.

PubMed

Srivastava, N; Srivastava, S K; Ghosh, S K; Singh, L P; Prasad, J K; Kumar, Amit; Perumal, P; Jerome, A; Thamizharasan, A

2012-03-01

A study was carried out to assess the effect of sequestration of PDC-109 protein, a majority constituent of heparin binding proteins (HBP) of seminal plasma, on freezability and in vitro fertilizing ability of crossbred bull spermatozoa after cryopreservation. The study consisted of isolation and characterization of PDC-109 protein to raise anti-sera against it in rabbits. Following which, raised antibodies against PDC-109 protein was quantitated and coated in tubes used for collection of ejaculates. Semen ejaculates thus collected were cryopreserved using EYTG extender. Physico-morphological characteristics, viz. motility, viability, acrosomal integrity and HOS response as an indicator of freezability of cryopreserved spermatozoa were determined at pre freeze as well as post thaw stage. At pre freeze stage, a significant (p<0.05) improvement in viability (83.83 ± 2.18 vs 75.17 ± 2.42) and acrosome integrity (81.33 ± 2.38 vs 72.83 ± 2.39) in antibodies treated group than control was observed. Similarly, increase in HOS responsive spermatozoa was highly significant (p<0.01) than control (78.83 ± 1.69 vs 67.5 ± 1.75). At post thaw stage, significant (p<0.05) improvement in viability (69.50 ± 2.16 vs 60.33 ± 2.19) and HOS responsive spermatozoa (68.67 ± 1.62 vs 58.50 ± 1.32) and highly significant (p<0.01) increase in individual motility (56.17 ± 1.83 vs 47.00 ± 1.86) and acrosome integrity (75.17 ± 2.38 vs 61.83 ± 2.1) was observed in antibodies treated group when compared to control was observed. The results from the study revealed that sequestration of PDC-109 protein from semen samples leads to significant improvement in pre-freeze and post-thaw values of above parameters in cryopreserved spermatozoa. It is thus concluded that sequestration of PDC-109 protein from ejaculates improves freezability of crossbred bull spermatozoa. Copyright © 2012 Elsevier B.V. All rights reserved.

A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals

PubMed Central

Ayehunie, Seyoum; Snell, Maureen; Child, Matthew; Klausner, Mitchell

2009-01-01

A predictive allergenicity test system for assessing the contact allergenicity of chemicals is needed by the cosmetic and pharmaceutical industry to monitor product safety in the marketplace. Development of such non-animal alternative assay systems for skin sensitization and hazard identification has been pursued by policy makers and regulatory agencies. We investigated whether phenotypic and functional changes to a subset of dendritic cells (DC), plasmacytoid DC (pDC), could be used to identify contact allergens. To achieve this goal, normal human DC were generated from CD34+ progenitor cells and cryopreserved. Frozen DC were thawed and the pDC fraction (CD123+/CD11c-) was harvested using FACS sorting. The pDC were cultured, expanded, and exposed to chemical allergens (N=26) or non-allergens (N=22). Concentrations of each chemical that resulted in >50% viability was determined using FACS analysis of propidium iodide stained cells using pDC from 2-5 donors. Expression of the surface marker, CD86, which has been implicated in dendritic cell maturation, was used as a marker of allergenicity. CD86 expression increased (≥ 1.5 fold) for 25 of 26 allergens (sensitivity = 96%) but did not increase for 19 of 22 non-allergens (specificity = 86%). In a direct comparison to historical data for the regulatory approved, mouse local lymph node assay (LLNA) for 23 allergens and 22 non-allergens, the pDC method had sensitivity and specificity of 96% and 86%, respectively, while the sensitivity and specificity of the LLNA assay was 83% and 82%, respectively. In conclusion, CD86 expression in pDC appears to be a sensitive and specific indicator to identify contact allergenicity. Such an assay method utilizing normal human cells will be useful for high throughput screening of chemicals for allergenicity. PMID:19665512

Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response.

PubMed

Charbonnier, Anne-Sophie; Hammad, Hamida; Gosset, Philippe; Stewart, Geoffrey A; Alkan, Sefik; Tonnel, André-Bernard; Pestel, Joël

2003-01-01

Although reports suggest that dendritic cells (DC) are involved in the allergic reaction characterized by a T helper cell type 2 (Th2) profile, the role of myeloid (M-DC) and plasmacytoid DC (P-DC), controlling the balance Th1/Th2, remains unknown. Here, we showed that in Dermatophagoides pteronyssinus (Dpt)-sensitized allergic patients and in healthy donors, M-DC displayed a higher capacity to capture Der p 1, a major allergen of Dpt, than did P-DC. However, Der p 1-pulsed M-DC from healthy subjects overexpressed CD80 and secreted interleukin (IL)-10, whereas M-DC from allergic patients did not. In contrast, with Der p 1-pulsed P-DC from both groups, no increase in human leukocyte antigen-DR, CD80, and CD86 and no IL-10 secretion were detected. When cocultured with allogeneic naive CD4(+) T cells from healthy donors, Der p 1-pulsed M-DC from allergic patients favored a Th1 profile [interferon (IFN)-gamma(high)/IL-4(low)] and Der p 1-pulsed P-DC, a Th2 profile (IFN-gamma(low)/IL-4(high)). In healthy donors, no T cell polarization (IFN-gamma(low)/IL-4(low)) was induced by Der p 1-pulsed M-DC or P-DC, but in response to Der p 1-pulsed M-DC, T cells secreted IL-10. The neutralization of IL-10 produced by Der p 1-pulsed M-DC from healthy donors led to an inhibition of IL-10 production by T cells and a polarization toward a type 1. Thus, IL-10 produced by M-DC might be an essential mediator controlling the balance between tolerance and allergic status. In addition, P-DC could contribute to the steady state in healthy donors or to the development of a Th2 response in allergic donors.

Inactivation of a class A and a class C β-lactamase by 6β-(hydroxymethyl)penicillanic acid sulfone

PubMed Central

Papp-Wallace, Krisztina M.; Bethel, Christopher R.; Gootz, Thomas D.; Shang, Wenchi; Stroh, Justin; Lau, William; McLeod, Dale; Price, Loren; Marfat, Anthony; Distler, Anne; Drawz, Sarah M.; Chen, Hansong; Harry, Emily; Nottingham, Micheal; Carey, Paul R.; Buynak, John D.; Bonomo, Robert A.

2012-01-01

β-Lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) contribute significantly to the longevity of the β-lactam antibiotics used to treat serious infections. In the quest to design more potent compounds and to understand the mechanism of action of known inhibitors, 6β-(hydroxymethyl)penicillanic acid sulfone (6β-HM-sulfone) was tested against isolates expressing the class A TEM-1 β-lactamase and a clinically important variant of the AmpC cephalosporinase of Pseudomonas aeruginosa, PDC-3. The addition of the 6β-HM-sulfone inhibitor to ampicillin was highly effective. 6β-HM-sulfone inhibited TEM-1 with an IC50 of 12 ± 2 nM and PDC-3 with an IC50 of 180 ± 36 nM, and displayed lower partition ratios than commercial inhibitors, with partition ratios (kcat/kinact) equal to 174 for TEM-1 and 4 for PDC-3. Measured for 20 h, 6β-HM-sulfone demonstrated rapid, first-order inactivation kinetics with the extent of inactivation being related to the concentration of inhibitor for both TEM-1 and PDC-3. Using mass spectrometry to gain insight into the intermediates of inactivation of this inhibitor, 6β-HM-sulfone was found to form a major adduct of +247 ± 5 Da with TEM-1 and +245 ± 5 Da with PDC-3, suggesting that the covalently bound, hydrolytically stabilized acyl-enzyme has lost a molecule of water (H–O–H). Minor adducts of +88 ± 5 Da with TEM-1 and +85 ± 5 Da with PDC-3 revealed that fragmentation of the covalent adduct can result but appeared to occur slowly with both enzymes. 6β-HM-sulfone is an effective and versatile β-lactamase inhibitor of representative class A and C enzymes. PMID:22155308

A break-even analysis for dementia care collaboration: Partners in Dementia Care.

PubMed

Morgan, Robert O; Bass, David M; Judge, Katherine S; Liu, C F; Wilson, Nancy; Snow, A Lynn; Pirraglia, Paul; Garcia-Maldonado, Maurilio; Raia, Paul; Fouladi, N N; Kunik, Mark E

2015-06-01

Dementia is a costly disease. People with dementia, their families, and their friends are affected on personal, emotional, and financial levels. Prior work has shown that the "Partners in Dementia Care" (PDC) intervention addresses unmet needs and improves psychosocial outcomes and satisfaction with care. We examined whether PDC reduced direct Veterans Health Administration (VHA) health care costs compared with usual care. This study was a cost analysis of the PDC intervention in a 30-month trial involving five VHA medical centers. Study subjects were veterans (N = 434) 50 years of age and older with dementia and their caregivers at two intervention (N = 269) and three comparison sites (N = 165). PDC is a telephone-based care coordination and support service for veterans with dementia and their caregivers, delivered through partnerships between VHA medical centers and local Alzheimer's Association chapters. We tested for differences in total VHA health care costs, including hospital, emergency department, nursing home, outpatient, and pharmacy costs, as well as program costs for intervention participants. Covariates included caregiver reports of veterans' cognitive impairment, behavior problems, and personal care dependencies. We used linear mixed model regression to model change in log total cost post-baseline over a 1-year follow-up period. Intervention participants showed higher VHA costs than usual-care participants both before and after the intervention but did not differ significantly regarding change in log costs from pre- to post-baseline periods. Pre-baseline log cost (p ≤ 0.001), baseline cognitive impairment (p ≤ 0.05), number of personal care dependencies (p ≤ 0.01), and VA service priority (p ≤ 0.01) all predicted change in log total cost. These analyses show that PDC meets veterans' needs without significantly increasing VHA health care costs. PDC addresses the priority area of care coordination in the National Plan to Address Alzheimer's Disease, offering a low-cost, structured, protocol-driven, evidence-based method for effectively delivering care coordination.

Systematic review with meta-analysis of studies comparing primary duct closure and T-tube drainage after laparoscopic common bile duct exploration for choledocholithiasis.

PubMed

Podda, Mauro; Polignano, Francesco Maria; Luhmann, Andreas; Wilson, Michael Samuel James; Kulli, Christoph; Tait, Iain Stephen

2016-03-01

With advances in laparoscopic instrumentation and acquisition of advanced laparoscopic skills, laparoscopic common bile duct exploration (LCBDE) is technically feasible and increasingly practiced by surgeons worldwide. Traditional practice of suturing the dochotomy with T-tube drainage may be associated with T-tube-related complications. Primary duct closure (PDC) without a T-tube has been proposed as an alternative to T-tube placement (TTD) after LCBDE. The aim of this meta-analysis was to evaluate the safety and effectiveness of PDC when compared to TTD after LCBDE for choledocholithiasis. A systematic literature search was performed using PubMed, EMBASE, MEDLINE, Google Scholar, and the Cochrane Central Register of Controlled Trials databases for studies comparing primary duct closure and T-tube drainage. Studies were reviewed for the primary outcome measures: overall postoperative complications, postoperative biliary-specific complications, re-interventions, and postoperative hospital stay. Secondary outcomes assessed were: operating time, median hospital expenses, and general complications. Sixteen studies comparing PDC and TTD qualified for inclusion in our meta-analysis, with a total of 1770 patients. PDC showed significantly better results when compared to TTD in terms of postoperative biliary peritonitis (OR 0.22, 95% CI 0.06-0.76, P = 0.02), operating time (WMD, -22.27, 95% CI -33.26 to -11.28, P < 0.00001), postoperative hospital stay (WMD, -3.22; 95% CI -4.52 to -1.92, P < 0.00001), and median hospital expenses (SMD, -1.37, 95% CI -1.96 to -0.77, P < 0.00001). Postoperative hospital stay was significantly decreased in the primary duct closure with internal biliary drainage (PDC + BD) group when compared to TTD group (WMD, -2.68; 95% CI -3.23 to -2.13, P < 0.00001). This comprehensive meta-analysis demonstrates that PDC after LCBDE is feasible and associated with fewer complications than TTD. Based on these results, primary duct closure may be considered as the optimal procedure for dochotomy closure after LCBDE.

Associations among sella turcica bridging, atlas arcuate foramen (ponticulus posticus) development, atlas posterior arch deficiency, and the occurrence of palatally displaced canine impaction.

PubMed

Haji Ghadimi, Mona; Amini, Fariborz; Hamedi, Shayesteh; Rakhshan, Vahid

2017-03-01

Head and neck skeletal anomalies or normal variants might predict the occurrence of palatally displaced impacted maxillary canines. Despite their clinical importance, studies in this regard are rare, especially when it comes to vertebral anomalies. This case-control study was performed on cephalographs of 35 orthodontic patients (11 male, 24 female) with palatally displaced canines (PDC) and 75 patients without them (29 male, 46 female). PDC were diagnosed on panoramic and lateral cephalographs and from clinical reports. The occurrence and severity of sella turcica bridge and the atlas ponticulus posticus, and deficiency of the posterior atlas arch were evaluated twice on lateral cephalographs. The associations between the occurrence and level of these skeletal anomalies and variations of PDC occurrence as well as additional correlations were assessed using multivariable and bivariate statistics (α = 0.05; β ≤0.2). The patients' mean age was 18.4 ± 1.9 years. In the control and patient groups, 23 (30.7%) and 21 subjects (60%) had sella turcica bridging, respectively (chi-square, P = 0.003). Ponticulus posticus was observed in 14 (18.7%) controls and 15 (42.9%) patients (chi-square, P = 0.007). Posterior atlas arch deficiency was observed in 4 (5.3%) controls and 5 (14.3%) patients (chi-square, P = 0.111). The presence of ponticulus posticus and sella turcica bridging might be associated with increased odds of PDC occurrence for about odds ratios of 3.1 and 3.5 times, respectively (binary logistic regression). PDC is positively associated with the occurrence and severity of sella turcica bridging and ponticulus posticus. The association between PDC and posterior atlas arch deficiency was inconclusive. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Genetic improvement of Escherichia coli for ethanol production: Chromosomal integration of Zymomonas mobilis genes encoding pyruvate decarboxylase and alcohol dehydrogenase II

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

Ohta, Kazuyoshi; Beall, D.S.; Mejia, J.P.

1991-04-01

Zymomonas mobilis genes for pyruvate decarboxylase (pdc) and alcohol dehydrogenase II (adhB) were integrated into the Escherichia coli chromosome within or near the pyruvate formate-lyase gene (pfl). Integration improved the stability of the Z. mobilis genes in E. coli, but further selection was required to increase expression. Spontaneous mutants were selected for resistance to high levels of chloramphenicol that also expressed high levels of the Z. mobilis genes. Analogous mutants were selected for increased expression of alcohol dehydrogenase on aldehyde indicator plates. These mutants were functionally equivalent to the previous plasmid-based strains for the fermentation of xylose and glucose tomore » ethanol. Ethanol concentrations of 54.4 and 41.6 g/liter were obtained from 10% glucose and 8% xylose, respectively. The efficiency of conversion exceeded theoretical limits (0.51 g of ethanol/g of sugar) on the basis of added sugars because of the additional production of ethanol from the catabolism of complex nutrients. Further mutations were introduced to inactivate succinate production (frd) and to block homologous recombination (recA).« less

A Process Evaluation of Project Developmental Continuity, Interim Report VI: Recommendations for Continuing the Impact Study.

ERIC Educational Resources Information Center

Granville, Arthur; And Others

This interim report re-examines data on instrument suitability, comparability of groups, and adequacy of sample size in Year III of the process evaluation of Project Developmental Continuity (PDC) and offers preliminary recommendations concerning the feasibility of continuing the impact study. PDC is a Head Start demonstration program aimed at…

Development and Initial Testing of a Measure of Person-Directed Care

ERIC Educational Resources Information Center

White, Diana L.; Newton-Curtis, Linda; Lyons, Karen S.

2008-01-01

Purpose: The purpose of the study was to empirically test items of a new measure designed to assess person-directed care (PDC) practices in long-term care. Design and Methods: After reviewing the literature, we identified five areas related to PDC: personhood, comfort care, autonomy, knowing the person, and support for relationships. We also…

The Diogene 4 pi detector at Saturne

NASA Technical Reports Server (NTRS)

Alard, J. P.; Arnold, J.; Augerat, J.; Babinet, R.; Bastid, N.; Brochard, F.; Costilhes, J. P.; Crouau, M.; De Marco, N.; Drouet, M.;

IFN-α regulates Blimp-1 expression via miR-23a and miR-125b in both monocytes-derived DC and pDC.

PubMed

Parlato, Stefania; Bruni, Roberto; Fragapane, Paola; Salerno, Debora; Marcantonio, Cinzia; Borghi, Paola; Tataseo, Paola; Ciccaglione, Anna Rita; Presutti, Carlo; Romagnoli, Giulia; Bozzoni, Irene; Belardelli, Filippo; Gabriele, Lucia

2013-01-01

Type I interferon (IFN-I) have emerged as crucial mediators of cellular signals controlling DC differentiation and function. Human DC differentiated from monocytes in the presence of IFN-α (IFN-α DC) show a partially mature phenotype and a special capability of stimulating CD4+ T cell and cross-priming CD8+ T cells. Likewise, plasmacytoid DC (pDC) are blood DC highly specialized in the production of IFN-α in response to viruses and other danger signals, whose functional features may be shaped by IFN-I. Here, we investigated the molecular mechanisms stimulated by IFN-α in driving human monocyte-derived DC differentiation and performed parallel studies on peripheral unstimulated and IFN-α-treated pDC. A specific miRNA signature was induced in IFN-α DC and selected miRNAs, among which miR-23a and miR-125b, proved to be negatively associated with up-modulation of Blimp-1 occurring during IFN-α-driven DC differentiation. Of note, monocyte-derived IFN-α DC and in vitro IFN-α-treated pDC shared a restricted pattern of miRNAs regulating Blimp-1 expression as well as some similar phenotypic, molecular and functional hallmarks, supporting the existence of a potential relationship between these DC populations. On the whole, these data uncover a new role of Blimp-1 in human DC differentiation driven by IFN-α and identify Blimp-1 as an IFN-α-mediated key regulator potentially accounting for shared functional features between IFN-α DC and pDC.

IFN-α Regulates Blimp-1 Expression via miR-23a and miR-125b in Both Monocytes-Derived DC and pDC

PubMed Central

Parlato, Stefania; Salerno, Debora; Marcantonio, Cinzia; Borghi, Paola; Tataseo, Paola; Ciccaglione, Anna Rita; Presutti, Carlo; Romagnoli, Giulia; Bozzoni, Irene; Belardelli, Filippo; Gabriele, Lucia

2013-01-01

Type I interferon (IFN-I) have emerged as crucial mediators of cellular signals controlling DC differentiation and function. Human DC differentiated from monocytes in the presence of IFN-α (IFN-α DC) show a partially mature phenotype and a special capability of stimulating CD4+ T cell and cross-priming CD8+ T cells. Likewise, plasmacytoid DC (pDC) are blood DC highly specialized in the production of IFN-α in response to viruses and other danger signals, whose functional features may be shaped by IFN-I. Here, we investigated the molecular mechanisms stimulated by IFN-α in driving human monocyte-derived DC differentiation and performed parallel studies on peripheral unstimulated and IFN-α-treated pDC. A specific miRNA signature was induced in IFN-α DC and selected miRNAs, among which miR-23a and miR-125b, proved to be negatively associated with up-modulation of Blimp-1 occurring during IFN-α-driven DC differentiation. Of note, monocyte-derived IFN-α DC and in vitro IFN-α-treated pDC shared a restricted pattern of miRNAs regulating Blimp-1 expression as well as some similar phenotypic, molecular and functional hallmarks, supporting the existence of a potential relationship between these DC populations. On the whole, these data uncover a new role of Blimp-1 in human DC differentiation driven by IFN-α and identify Blimp-1 as an IFN-α-mediated key regulator potentially accounting for shared functional features between IFN-α DC and pDC. PMID:23977359

The Development of a Competency Based Train-the-Trainer Course for the Certification of Professional Development Center Instructors.

ERIC Educational Resources Information Center

Rudasill, Susann E.

A competency-based training course was designed to prepare Professional Development Center (PDC) instructors for the certification process. After an exhaustive review of the literature, it was determined that a relevant training course that would specifically reflect the needs of the PDC was not available. The decision was then made to design a…

A Process Evaluation of Project Developmental Continuity. Interim Report III, Executive Summary: Preliminary Recommendations for the Study of Child Impact.

ERIC Educational Resources Information Center

Granville, Arthur C.; And Others

This executive summary presents the major findings of Interim Report III, which reports preliminary evaluation of Project Developmental Continuity (PDC). A Head Start demonstration program, PDC is aimed at promoting greater educational and developmental continuity as children make the transition from preschool to school. The report addresses three…

A Process Evaluation of Project Developmental Continuity. Interim Report II, Part A: Program Case Studies. Volume 2.

ERIC Educational Resources Information Center

Spencer, Lynn, Ed.

These 7 case studies are part of a series of documents on the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Each case study reviews the planning year at a PDC demonstration site in one…

Chemokine and lymph node homing receptor expression on pDC vary by graft source.

PubMed

Hosoba, Sakura; Harris, Wayne Ac; Lin, Kaifeng L; Waller, Edmund K

2014-11-01

A randomized clinical trial of BM vs. blood stem cell transplants from unrelated donors showed that more plasmacytoid dendritic cells (pDCs) in BM grafts was associated with better post-transplant survival. Here, we describe differences in homing-receptor expression on pDC to explain observed differences following BM vs. blood stem cell transplantation.

A Process Evaluation of Project Developmental Continuity. Interim Report II, Part A: Program Case Studies. Volume I.

ERIC Educational Resources Information Center

Spencer, Lynn, Ed.

These 8 case studies are part of a series of documents on the evaluation of Project Developmental Continuity (PDC), a Head Start demonstration program aimed at providing educational and developmental continuity between children's Head Start and primary school experiences. Each case study reviews the planning year at a PDC demonstration site in one…

Psychometric Properties of a Korean Measure of Person-Directed Care in Nursing Homes

ERIC Educational Resources Information Center

Choi, Jae-Sung; Lee, Minhong

2014-01-01

Objective: This study examined the validity and reliability of a person-directed care (PDC) measure for nursing homes in Korea. Method: Managerial personnel from 223 nursing homes in 2010 and 239 in 2012 were surveyed. Results: Item analysis and exploratory factor analysis for the first sample generated a 33-item PDC measure with eight factors.…

The Use of the Performance Diagnostic Checklist to Guide Intervention Selection in an Independently Owned Coffee Shop

ERIC Educational Resources Information Center

Pampino, Ralph N.; Heering, Paul W.; Wilder, David A.; Barton, Carolyn G.; Burson, Liberty

2004-01-01

The utility of the Performance Diagnostic Checklist (PDC) (Austin, 2000) as an assessment tool to design an intervention for increasing maintenance tasks in an independently owned coffee shop was examined. The PDC, which was administered to four employees, identified a lack of appropriate antecedents and consequences as areas in need of…

Numerical simulation study on the optimization design of the crown shape of PDC drill bit.

PubMed

Ju, Pei; Wang, Zhenquan; Zhai, Yinghu; Su, Dongyu; Zhang, Yunchi; Cao, Zhaohui

The design of bit crown is an important part of polycrystalline diamond compact (PDC) bit design, although predecessors have done a lot of researches on the design principles of PDC bit crown, the study of the law about rock-breaking energy consumption according to different bit crown shape is not very systematic, and the mathematical model of design is over-simplified. In order to analyze the relation between rock-breaking energy consumption and bit crown shape quantificationally, the paper puts forward an idea to take "per revolution-specific rock-breaking work" as objective function, and analyzes the relationship between rock properties, inner cone angle, outer cone arc radius, and per revolution-specific rock-breaking work by means of explicit dynamic finite element method. Results show that the change law between per revolution-specific rock-breaking work and the radius of gyration is similar for rocks with different properties, it is beneficial to decrease rock-breaking energy consumption by decreasing inner cone angle or outer cone arc radius. Of course, we should also consider hydraulic structure and processing technology in the optimization design of PDC bit crown.

Efficient Sensing of Infected Cells in Absence of Virus Particles by Blasmacytoid Dendritic Cells Is Blocked by the Viral Ribonuclease Erns

PubMed Central

Python, Sylvie; Gerber, Markus; Suter, Rolf; Ruggli, Nicolas; Summerfield, Artur

2013-01-01

Plasmacytoid dendritic cells (pDC) have been shown to efficiently sense HCV- or HIV-infected cells, using a virion-free pathway. Here, we demonstrate for classical swine fever virus, a member of the Flaviviridae, that this process is much more efficient in terms of interferon-alpha induction when compared to direct stimulation by virus particles. By employment of virus replicon particles or infectious RNA which can replicate but not form de novo virions, we exclude a transfer of virus from the donor cell to the pDC. pDC activation by infected cells was mediated by a contact-dependent RNA transfer to pDC, which was sensitive to a TLR7 inhibitor. This was inhibited by drugs affecting the cytoskeleton and membrane cholesterol. We further demonstrate that a unique viral protein with ribonuclease activity, the viral Erns protein of pestiviruses, efficiently prevented this process. This required intact ribonuclease function in intracellular compartments. We propose that this pathway of activation could be of particular importance for viruses which tend to be mostly cell-associated, cause persistent infection, and are non-cytopathogenic. PMID:23785283

Prescription drug coupons: evolution and need for regulation in direct-to-consumer advertising.

PubMed

Mackey, Tim K; Yagi, Nozomi; Liang, Bryan A

2014-01-01

Pharmaceutical marketing in the United States had undergone a shift from largely exclusively targeting physicians to considerable efforts in targeting patients through various forms of direct-to-consumer advertising ("DTCA"). This includes the use of DTCA in prescription drug coupons ("PDCs"), a new form of DTCA that offers discounts and rebates directly to consumers to lower costs of drug purchasing. Our examination of PDCs reveals that the use and types of PDC programs is expanding and includes promotion of the vast majority of top grossing pharmaceuticals. However, controversy regarding this emerging form of DTCA has given rise to health policy concerns about their overall impact on prescription drug expenditures for consumers, payers, and the health care system, and whether they lead to optimal long-term utilization of pharmaceuticals. In response to these concerns and the growing popularity of PDCs, what we propose here are clearer regulation and regulatory guidance for PDC DTCA use. This would include review for appropriate disclosure of marketing claims, increased transparency in PDC use for pharmaceutical pricing, and leveraging potential positive benefits of PDC use for vulnerable or underserved patient populations. Copyright © 2014 Elsevier Inc. All rights reserved.

[Discovery of the target genes inhibited by formic acid in Candida shehatae].

PubMed

Cai, Peng; Xiong, Xujie; Xu, Yong; Yong, Qiang; Zhu, Junjun; Shiyuan, Yu

2014-01-04

At transcriptional level, the inhibitory effects of formic acid was investigated on Candida shehatae, a model yeast strain capable of fermenting xylose to ethanol. Thereby, the target genes were regulated by formic acid and the transcript profiles were discovered. On the basis of the transcriptome data of C. shehatae metabolizing glucose and xylose, the genes responsible for ethanol fermentation were chosen as candidates by the combined method of yeast metabolic pathway analysis and manual gene BLAST search. These candidates were then quantitatively detected by RQ-PCR technique to find the regulating genes under gradient doses of formic acid. By quantitative analysis of 42 candidate genes, we finally identified 10 and 5 genes as markedly down-regulated and up-regulated targets by formic acid, respectively. With regard to gene transcripts regulated by formic acid in C. shehatae, the markedly down-regulated genes ranking declines as follows: xylitol dehydrogenase (XYL2), acetyl-CoA synthetase (ACS), ribose-5-phosphate isomerase (RKI), transaldolase (TAL), phosphogluconate dehydrogenase (GND1), transketolase (TKL), glucose-6-phosphate dehydrogenase (ZWF1), xylose reductase (XYL1), pyruvate dehydrogenase (PDH) and pyruvate decarboxylase (PDC); and a declining rank for up-regulated gens as follows: fructose-bisphosphate aldolase (ALD), glucokinase (GLK), malate dehydrogenase (MDH), 6-phosphofructokinase (PFK) and alcohol dehydrogenase (ADH).

Model-independent position domain sliding mode control for contour tracking of robotic manipulator

NASA Astrophysics Data System (ADS)

Yue, W. H.; Pano, V.; Ouyang, P. R.; Hu, Y. Q.

2017-01-01

In this paper, a new position domain feedback type sliding mode control (PDC-SMC) law is proposed for contour tracking control of multi-DOF (degree of freedom) nonlinear robotic manipulators focusing on the improvement of contour tracking performances. One feature of the proposed control law is its model-independent control scheme that can avoid calculation of the feedforward part in a standard SMC. The new control law takes the advantages of the high contour tracking performance of PD type feedback position domain control (PDC) and the robustness of SMC. Stability analysis is performed using the Lyapunov stability theory, and simulation studies are conducted to verify the effectiveness of the developed PDC-SMC control system. In addition, the effects of control parameters of the SMC on system performances are studied.

Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants.

PubMed

Wang, Jennifer P; Zhang, Lei; Madera, Rachel F; Woda, Marcia; Libraty, Daniel H

2012-07-06

Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge. Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy.

Ethylene and 1-MCP regulate major volatile biosynthetic pathways in apple fruit.

PubMed

Yang, Xiaotang; Song, Jun; Du, Lina; Forney, Charles; Campbell-Palmer, Leslie; Fillmore, Sherry; Wismer, Paul; Zhang, Zhaoqi

2016-03-01

The effects of ethylene and 1-methylcyclopropene (1-MCP) on apple fruit volatile biosynthesis and gene expression were investigated. Statistical analysis identified 17 genes that changed significantly in response to ethylene and 1-MCP treatments. Genes encoding branched-chain amino acid aminotransferase (BCAT), aromatic amino acid aminotransferase (ArAT) and amino acid decarboxylases (AADC) were up-regulated during ripening and further enhanced by ethylene treatment. Genes related to fatty acid synthesis and metabolism, including acyl-carrier-proteins (ACPs), malonyl-CoA:ACP transacylase (MCAT), acyl-ACP-desaturase (ACPD), lipoxygenase (LOX), hydroperoxide lyase (HPL), alcohol dehydrogenase (ADH), pyruvate decarboxylase (PDC2), β-oxidation, acyl-CoA synthetase (ACS), enoyl-CoA hydratase (ECHD), acyl-CoA dehydrogenase (ACAD), and alcohol acyltransferases (AATs) also increased during ripening and in response to ethylene treatment. Allene oxide synthase (AOS), alcohol dehydrogenase 1 (ADH1), 3-ketoacyl-CoA thiolase and branched-chain amino acid aminotransferase 2 (BCAT2) decreased in ethylene-treated fruit. Treatment with 1-MCP and ethylene generally produced opposite effects on related genes, which provides evidence that regulation of these genes is ethylene dependent. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Truncation of a mannanase from Trichoderma harzianum improves its enzymatic properties and expression efficiency in Trichoderma reesei.

PubMed

Wang, Juan; Zeng, Desheng; Liu, Gang; Wang, Shaowen; Yu, Shaowen

2014-01-01

To obtain high expression efficiency of a mannanase gene, ThMan5A, cloned from Trichoderma harzianum MGQ2, both the full-length gene and a truncated gene (ThMan5AΔCBM) that contains only the catalytic domain, were expressed in Trichoderma reesei QM9414 using the strong constitutive promoter of the gene encoding pyruvate decarboxylase (pdc), and purified to homogeneity, respectively. We found that truncation of the gene improved its expression efficiency as well as the enzymatic properties of the encoded protein. The recombinant strain expressing ThMan5AΔCBM produced 2,460 ± 45.1 U/ml of mannanase activity in the culture supernatant; 2.3-fold higher than when expressing the full-length ThMan5A gene. In addition, the truncated mannanase had superior thermostability compared with the full-length enzyme and retained 100 % of its activity after incubation at 60 °C for 48 h. Our results clearly show that the truncated ThMan5A enzyme exhibited improved characteristics both in expression efficiency and in its thermal stability. These characteristics suggest that ThMan5AΔCBM has potential applications in the food, feed, paper, and pulp industries.

A new device for continuous assessment of gut perfusion: proof of concept on a porcine model of septic shock

PubMed Central

2014-01-01

Introduction We evaluate an innovative device consisting of an enteral feeding tube equipped with a photoplethysmography (PPG) sensor in contact with the duodenal mucosa. This study aims to determine if the PPG signal, composed of a continuous (PDC) and a pulsatile part (PAC), is a reliable method to assess gut perfusion in a porcine model of septic shock. Method Fourteen piglets were anesthetized and mechanically ventilated. They were randomly assigned to two groups: the nonseptic (NS) group received an infusion of Ringer’s lactate solution (RL) alone, the septic (S) group received in addition a suspension of live Pseudomonas aeruginosa. Heart rate (HR), pulse oximetry (SpO2), mean arterial pressure (MAP), cardiac index (CI) and serum lactates were recorded and gut microcirculation (GM) was monitored with a laser Doppler probe applied on the duodenal serosa. PDC and PAC were given by the PPG probe inserted in the duodenum. Data was collected every 15 minutes (t0, t15…) during 150 minutes (t150). After administration of the bacteria suspension (t0), resuscitation maneuvers were performed following a defined algorithm. GM PAC, and PDC were expressed as variation from baseline (GMvar, PACvar, PDCvar). Analysis of variance (ANOVA) with repeated measures was performed to compare hemodynamic variables, with Bonferroni correction as post hoc analysis on t0, t60 and t150. Results One piglet was withdrawn from analysis due to a defective probe. S group (six piglets) received resuscitation therapy while NS group (seven piglets) did not. A significant group effect was found for the all parameters except HR. Post hoc analysis found a significant decrease for GM and PAC at t60. The correlation between PAC, PDC and microcirculatory parameters were as follows: rPACvar-GMvar = 0.496, P <0.001, rPDCvar-GMvar = 0.244; P = 0.002. In the septic group, correlations were as follows: rPAC-lactate = -0.772, P <0.001; rPDC-lactate = -0.681, P <0.01). At the onset of shock, a decrease of PAC, PDC and GM occurred before the alteration of MAP. Conclusions PAC and PDC decreased at the onset of shock and were correlated with GM and lactate. These results confirm that PPG signal reliably reflects the early perfusion alteration of the gut. Further studies should assess the clinical use of this device. PMID:25030376

Thermal interactions of the AD79 Vesuvius pyroclastic density currents and their deposits at Villa dei Papiri (Herculaneum archaeological site, Italy)

NASA Astrophysics Data System (ADS)

Giordano, G.; Zanella, E.; Trolese, M.; Baffioni, C.; Vona, A.; Caricchi, C.; De Benedetti, A. A.; Corrado, S.; Romano, C.; Sulpizio, R.; Geshi, N.

2018-05-01

Pyroclastic density currents (PDCs) can have devastating impacts on urban settlements, due to their dynamic pressure and high temperatures. Our degree of understanding of the interplay between these hot currents and the affected infrastructures is thus fundamental not only to implement our strategies for risk reduction, but also to better understand PDC dynamics. We studied the temperature of emplacement of PDC deposits that destroyed and buried the Villa dei Papiri, an aristocratic Roman edifice located just outside the Herculaneum city, during the AD79 plinian eruption of Mt Vesuvius (Italy) by using the thermal remanent magnetization of embedded lithic clasts. The PDC deposits around and inside the Villa show substantial internal thermal disequilibrium. In areas affected by convective mixing with surface water or with collapsed walls, temperatures average at around 270 °C (min 190 °C, max 300 °C). Where the deposits show no evidence of mixing with external material, the temperature is much higher, averaging at 350 °C (min 300 °C; max 440 °C). Numerical simulations and comparison with temperatures retrieved at the very same sites from the reflectance of charcoal fragments indicate that such thermal disequilibrium can be maintained inside the PDC deposit for time-scales well over 24 hours, i.e. the acquisition time of deposit temperatures for common proxies. We reconstructed in detail the history of the progressive destruction and burial of Villa dei Papiri and infer that the rather homogeneous highest deposit temperatures (average 350 °C) were carried by the ash-sized fraction in thermal equilibrium with the fluid phase of the incoming PDCs. These temperatures can be lowered on short time- (less than hours) and length-scales (meters to tens of meters) only where convective mixing with external materials or fluids occurs. By contrast, where the Villa walls remained standing the thermal exchange was only conductive and very slow, i.e. negligible at 50 cm distance from contact after 24 hours. We then argue that the state of conservation of materials buried by PDC deposits largely depends on the style of the thermal interactions. Here we also suggest that PDC deposit temperatures are excellent proxies for the temperatures of basal parts of PDCs close to their depositional boundary layer. This general conclusion stresses the importance of mapping of deposit temperatures for the understanding of thermal processes associated with PDC flow dynamics and during their interaction with the affected environment.

JPL Facilities and Software for Collaborative Design: 1994 - Present

NASA Technical Reports Server (NTRS)

DeFlorio, Paul A.

2004-01-01

The viewgraph presentation provides an overview of the history of the JPL Project Design Center (PDC) and, since 2000, the Center for Space Mission Architecture and Design (CSMAD). The discussion includes PDC objectives and scope; mission design metrics; distributed design; a software architecture timeline; facility design principles; optimized design for group work; CSMAD plan view, facility design, and infrastructure; and distributed collaboration tools.

Simply pyroclastic currents

NASA Astrophysics Data System (ADS)

Palladino, Danilo M.

2017-07-01

Gravity-driven, ground-hugging gas-pyroclast mixtures produced during explosive volcanic eruptions define a full spectrum of particle concentration, flow regime and particle support mechanisms. To describe these phenomena, the term "pyroclastic density current" (PDC) has become increasingly popular in the last few tens of years. Here, I question the general application of the term PDC to the whole flow spectrum and, instead, I propose the simpler term "pyroclastic current".

Modeling of Compaction Wave Behavior in Confined Granular Energetic Material

DTIC Science & Technology

1990-08-01

Compacted 65% TMD Aggregate Melamine Compaction Wave Microwave DIAGNOSTICS: Interferometry (a) Microwave Interferometry (b) 3 Wall-Mounted Pressure...involved 65% TMD melamine but was run very recently (Dec 1989) The value of compaction wave speed (from the microwave data) just after impact is...47 B. Simulation of PDC-M34 / 65% TMD Melamine (Inert Material) ........ 54 C. Influence of Energy Release / PDC Experiment

An Evaluation of the Performance Diagnostic Checklist-Human Services to Assess an Employee Performance Problem in a Center-Based Autism Treatment Facility

ERIC Educational Resources Information Center

Ditzian, Kyle; Wilder, David A.; King, Allison; Tanz, Jeanine

2015-01-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to assess the environmental variables that contribute to poor employee performance in human services settings. We administered the PDC-HS to 3 supervisors to assess the variables that contributed to poor performance by 4 staff members when securing…

Synthesis of 4-(5-iodo-3-methylpyrazolyl) phenylsulfonamide and its elaboration to a COX II inhibitor library by solution-phase suzuki coupling using Pd/C as a solid-supported catalyst.

PubMed

Organ, Michael G; Mayer, Stanislas

2003-01-01

An effective synthesis of 4-(5-iodo-3-methylpyrazolyl) phenylsulfonamide has been developed. This aromatic iodide template served as an efficient oxidative addition partner for the preparation of a solution-phase library of Celecoxib analogues via Suzuki coupling using Pd/C, a readily filterable catalyst.

Use of the Performance Diagnostic Checklist to Select an Intervention Designed to Increase the Offering of Promotional Stamps at Two Sites of a Restaurant Franchise

ERIC Educational Resources Information Center

Rodriguez, Manuel; Wilder, David A.; Therrien, Kelly; Wine, Byron; Miranti, Reylissa; Daratany, Kenneth; Salume, Gloria; Baranovsky, Greg; Rodriquez, Matias

2006-01-01

The performance diagnostic checklist (PDC) was administered to examine the variables influencing the offering of promotional stamps by employees at two sites of a restaurant franchise. PDC results suggested that a lack of appropriate antecedents, equipment and processes, and consequences were responsible for the deficits. Based on these results,…

Geochemistry of the July 2015 pyroclastic flow at Volcán de Colima

NASA Astrophysics Data System (ADS)

Atlas, Z. D.; Long, E.; Macorps, E.; Garcia Hernandez, M.; Charbonnier, S. J.; Varley, N. R.

2016-12-01

We investigated the geochemical variation of the July 2015 pyroclastic density current (PDC) from Volcán de Colima, Mexico. This important eruption produced a highly mobile PDC, with the largest run-out since 1913 (10.7 km). The eruptive mechanism is still unclear and geochemical characterization is critical to determine its origin. Normalized major element concentrations define differentiation trends and concentrations similar to 1998-2000 lava, consistent with earlier volcanic products. SiO2 ranges from 59.9 to 61.0 wt.% with low Mg# (0.48-0.51), moderate K2O (1.35-1.42 wt.%) and higher total alkalis (6.95-7.66 wt.%). The PDC is characterized by high Sr, Ba, Nb and U, low Ba/Nb and Sc/Y ratios. Higher Sr can be attributed to abundant plagioclase, however high Ba, Nb and U must be attributed to other minerals. U is compatible in apatite or ilmenite but due to the incompatible behavior P2O5 with SiO2 apatite contribution is unlikely. Nb is partitioned into ilmenite but also biotite, while Ba strongly partitions to biotite/phlogopite, known from scoria cone lamprophyre magma erupted next to Volcán de Colima. Our data suggest that U along with some Nb is partitioned to Ti-Fe oxide or to ilmentie. Covariation of U and Nb with Ba suggests that biotite +/- ilmenite may be involved in the generation of the 2015 PDC magma. The lack of an Eu anomaly and overall REE patterns suggest that excess plagioclase likely comes from fragments of previously emplaced lava and that the source and overall generation of the PDC is similar to recent eruptive products. LILE along with high Nb is unlike 1913 but are more similar to 1869 and 1880 rocks, lower K melt inclusions of Reubi & Blundy (2008) and unit N from Crummy et al. (2014) erupted 7000 Ybp and represent a sharp departure from the pre-1999 eruptive products. Our results indicate that the PDC chemistry must have some influence from the addition of a biotite bearing gabbrotic endmember in accord with previous studies.

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention for Newly Diagnosed and Treatment-Naive Atrial Fibrillation Patients: An Update Using 2013–2014 Data

PubMed Central

Brown, Joshua D.; Shewale, Anand R.; Talbert, Jeffery C.

2017-01-01

BACKGROUND Few studies have assessed adherence to non-vitamin K antagonist oral anticoagulants (NOACs), especially using contemporary data now that multiple NOACs are available. OBJECTIVE To compare adherence and treatment patterns among NOACs for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). METHODS Incident and treatment-naive NVAF patients were identified during 2013–2014 from a large claims database in this retrospective cohort study. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Adherence to the index medication and adherence to any oral anticoagulant was assessed using the proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence. RESULTS Dabigatran had lower adherence (PDC = 0.76, 0.64, 0.57) compared with rivaroxaban (PDC = 0.83, 0.73, 0.66; P < 0.001) and apixaban (PDC = 0.82, 0.72, 0.66; P < 0.001) at 3, 6, and 9 months of follow-up and twice the number of switches to either other anticoagulants or antiplatelet therapy. Adherence was higher overall as stroke risk increased, and dabigatran had consistently lower adherence compared with the other NOACs. Multivariable logistic regression predicting PDC ≥ 0.80 showed rivaroxaban users with higher odds of high adherence compared with dabigatran or rivaroxaban across all time periods. Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. CONCLUSIONS In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable unadjusted adherence profiles compared with dabigatran, while rivaroxaban users had higher odds of high adherence (PDC ≥ 0.80) among the NOACs in adjusted analyses. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes and quality assessment. PMID:28854077

Renoprotective Effect of Lactoferrin against Chromium-Induced Acute Kidney Injury in Rats: Involvement of IL-18 and IGF-1 Inhibition.

PubMed

Hegazy, Rehab; Salama, Abeer; Mansour, Dina; Hassan, Azza

2016-01-01

Hexavalent chromium (CrVI) is a heavy metal widely used in more than 50 industries. Nephrotoxicity is a major adverse effect of chromium poisoning. The present study investigated the potential renoprotective effect of lactoferrin (Lf) against potassium dichromate (PDC)-induced acute kidney injury (AKI) in rats. Beside, because previous studies suggest that interlukin-18 (IL-18) and insulin-like growth factor-1 (IGF-1) play important roles in promoting kidney damage, the present work aimed to evaluate the involvement of these two cytokines in PDC model of AKI and in the potential renoprotective effect of lactoferrin. Adult male albino Wistar rats were pretreated with Lf (200 mg/kg/day, p.o.) or (300 mg/kg/day, p.o.); the doses that are usually used in the experiment studies, for 14 days followed by a single dose of PDC (15 mg/kg, s.c.). PDC caused significant increase in serum urea, creatinine, and total protein levels. This was accompanied with decreased renal glutathione content, and increased renal malondialdehyde, IL-18, IL-4, nuclear factor kappa B (NFκB), IGF-1, and the phosphorylated form of forkhead box protein O1 (FoxO1) levels. Moreover, normal expression IFN-γ mRNA and enhanced expression of TNF-α mRNA was demonstrated in renal tissues. Histopathological investigations provoked deleterious changes in the renal tissues. Tubular epithelial hyperplasia and apoptosis were demonstrated immunohistochemically by positive proliferating cell nuclear antigen (PCNA), Bax, and Caspase-3 expression, respectively. Pretreatment of rats with Lf in both doses significantly corrected all previously mentioned PDC-induced changes with no significant difference between both doses. In conclusion, the findings of the present study demonstrated the involvement of oxidative stress, inflammatory reactions, tubular hyperplasia and apoptosis in PDC-induced AKI. It suggested a role of IL-18 through stimulation of IL-4-induced inflammatory pathway, and IGF-1 through triggering FoxO1-induced cell proliferation. Moreover, the study revealed that Lf protected the kidney against Cr-induced AKI in rats and significantly showed antioxidant, anti-inflammatory, and anti-proliferative properties with down-regulation of IL-18 and IGF-1.

Pyroclastic density currents at Etna volcano, Italy: The 11 February 2014 case study

NASA Astrophysics Data System (ADS)

Andronico, Daniele; Di Roberto, Alessio; De Beni, Emanuela; Behncke, Boris; Bertagnini, Antonella; Del Carlo, Paola; Pompilio, Massimo

2018-05-01

On 11 February 2014, a considerable volume (0.82 to 1.29 × 106 m3) of unstable and hot rocks detached from the lower-eastern flank of the New Southeast Crater (NSEC) at Mt. Etna, producing a pyroclastic density current (PDC). This event was by far the most extensive ever recorded at Mt. Etna since 1999 and has attracted the attention of the scientific community and civil protection to this type of volcanic phenomena, usually occurring without any clear volcanological precursor and especially toward the mechanisms which led to the crater collapse, the PDC flow dynamics and the related volcanic hazard. We present here the results of the investigation carried out on the 11 February 2014 collapse and PDC events; data were obtained through a multidisciplinary approach which includes the analysis of photograph, images from visible and thermal surveillance cameras, and the detailed stratigraphic, textural and petrographic investigations of the PDC deposits. Results suggest that the collapse and consequent PDC was the result of a progressive thermal and mechanical weakening of the cone by repeated surges of magma passing through it during the eruptive activity prior to the 11 February 2014 events, as well as pervasive heating and corrosion by volcanic gas. The collapse of the lower portion of the NSEC was followed by the formation of a relatively hot (up to 750 °C) dense flow which travelled about 2.3 km from the source, stopping shortly after the break of the slope and emplacing the main body of the deposit which ranges between 0.39 and 0.92 × 106 m3. This flow was accompanied a relatively hot cloud of fine ash that dispersed over a wider area. The results presented may contribute to the understanding of this very complex type of volcanic phenomena at Mt. Etna and in similar volcanic settings of the world. In addition, results will lay the basis for the modeling of crater collapse and relative PDC events and consequently for the planning of hazard assessment strategies aimed at reducing the potential risks to scientists and tens of thousands of tourists visiting Etna's summit areas every year.

Exploring the effects of temperature and grain size on plumes associated with PDCs through analogue experimentation

NASA Astrophysics Data System (ADS)

Mitchell, S. J.; Eychenne, J.; Rust, A.

2015-12-01

Pyroclastic density currents (PDCs) often loft upwards into convective, buoyant co-PDC plumes. Recent analogue experiments using a unimodal grain size of 22 ± 6 μm (Andrews & Manga, 2012) have established that plume generation is aided by PDC interaction with a topographic barrier. Here, we have simulated the onset of co-PDC plumes from the collapse of concentrated particle-gas mixtures comprised of unimodal or bimodal grain size distributions (GSD) of glass beads, using combinations of lognormal populations with modes of 35, 195 and 590 μm. The collapse of a mixture, with constant mass 2950 ± 150 g, induced the propagation of a gravity current channelized down a 13° sloping tank; a barrier in the tank caused the gravity current to produce a plume of particles. Experiments were recorded with high speed visible and thermal-infrared cameras. Initial GSD and temperature of the mixture were varied to assess the effects of the addition of a coarser component on plume generation. Analogue co-PDC plumes were only produced when a proportion of fine grains (35 μm) was present in the initial granular mixture. Sampling of the particles entrained in the co-PDC plumes revealed that fine grains (35 μm) are preferentially lofted, although a few coarser particles (195 or 590 μm) are also entrained in the co-PDC plumes and settle closer to the area of uplift. Increasing the initial temperature of the mixture increases plume height measured at 1 and 2s after onset; this is supported by repeat experiments at specific conditions. Bimodal mixtures containing both fine (35 μm) and coarser (195 or 590 μm) grains result in plume heights and initial flow velocities higher than observed in unimodal fine-grained experiments of the same total mass of particles. Repeat experiments identify the natural variability in plume generation under the same nominal conditions, which is likely due to the combined variations of momentum during flow propagation and heat-driven buoyancy, as well as the homogeneity of the initial particle mixture.

Seminal PDC-109 protein vis-à-vis cholesterol content and freezability of buffalo spermatozoa.

PubMed

Singh, Mahak; Ghosh, S K; Prasad, J K; Kumar, Anuj; Tripathi, R P; Bhure, S K; Srivastava, N

2014-01-10

Advancements in reproductive technologies have shown seminal plasma (SP) as a nutritive-protective medium for spermatozoa metabolism, function and transport. At the same time quality variables and thus freezability of spermatozoa are influenced by SP proteins originating from male reproductive tract. One such protein, viz. PDC-109 is reported to influence freezability of spermatozoa in cattle. Thus the present investigation was designed to evaluate effect of seminal PDC-109 protein concentration on post-thaw cholesterol content and semen quality variables (SQP) as an indicator of membrane integrity and freezability, respectively of buffalo spermatozoa. Ejaculates (n=42) selected on the basis of mass activity and individual motility were divided into three parts, first part for SP proteins isolation, second for cholesterol estimation and third part was cryo-preserved to evaluate freezability based on post-thaw SQP, viz. individual progressive motility, viability and acrosome integrity of spermatozoa. A total of 28 (66.7%) and 14 (33.3%) ejaculates from four bulls were found as freezable or non-freezable, respectively. Though total seminal plasma protein (TSPP) concentration was found similar in freezable and non-freezable ejaculates, the heparin binding proteins (HBP) content in non-freezable semen was greater (P<0.01) than freezable ejaculates. There was a similar trend for the PDC-109 protein content in respective ejaculates. Cholesterol content of spermatozoa and SQP were greater (P<0.05 and 0.01, respectively) in freezable as compared to non-freezable ejaculates of each bull at post-thaw stage. This study showed that concentrations of HBP and PDC-109 in non-freezable semen might be responsible for greater cryo-damage reflecting in poor freezability of buffalo spermatozoa. Copyright © 2013 Elsevier B.V. All rights reserved.

A contribution to the hazards assessment at Copahue volcano (Argentina-Chile) by facies analysis of a recent pyroclastic density current deposit

NASA Astrophysics Data System (ADS)

Balbis, C.; Petrinovic, I. A.; Guzmán, S.

2016-11-01

We recognised and interpreted a recent pyroclastic density current (PDC) deposit at the Copahue volcano (Southern Andes), through a field survey and a sedimentological study. The relationships between the behaviour of the PDCs, the morphology of the Río Agrio valley and the eruptive dynamics were interpreted. We identified two lithofacies in the deposit that indicate variations in the eruptive dynamics: i) the opening of the conduit and the formation of a highly explosive eruption that formed a diluted PDC through the immediate collapse of the eruptive column; ii) a continued eruption which followed immediately and records the widening of the conduit, producing a dense PDC. The eruption occurred in 2000 CE, was phreatomagmatic (VEI ≤ 2), with a vesiculation level above 4000 m depth and fragmentation driven by the interaction of magma with an hydrothermal system at ca. 1500 m depth. As deduced from the comparison between the accessory lithics of this deposit and those of the 2012 CE eruption, the depth of onset of vesiculation and fragmentation level in this volcano is constant in depth. In order to reproduce the distribution pattern of this PDC's deposit and to simulate potential PDC's forming-processes, we made several computational modelling from "denser" to "more diluted" conditions. The latter fairly reproduces the distribution of the studied deposit and represents perhaps one of the most dangerous possible scenarios of the Copahue volcanic activity. PDCs occurrence has been considered in the last volcanic hazards map as a low probability process; evidences found in this contribution suggest instead to include them as more probable and thus very important for the hazards assessment of the Copahue volcano.

Plasmacytoid DC from Aged Mice Down-Regulate CD8 T Cell Responses by Inhibiting cDC Maturation after Encephalitozoon cuniculi Infection

PubMed Central

Gigley, Jason P.; Khan, Imtiaz A.

2011-01-01

Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations. PMID:21695169

Structure and catalytic mechanism of LigI: insight into the amidohydrolase enzymes of cog3618 and lignin degradation.

PubMed

Hobbs, Merlin Eric; Malashkevich, Vladimir; Williams, Howard J; Xu, Chengfu; Sauder, J Michael; Burley, Stephen K; Almo, Steven C; Raushel, Frank M

2012-04-24

LigI from Sphingomonas paucimobilis catalyzes the reversible hydrolysis of 2-pyrone-4,6-dicarboxylate (PDC) to 4-oxalomesaconate and 4-carboxy-2-hydroxymuconate in the degradation of lignin. This protein is a member of the amidohydrolase superfamily of enzymes. The protein was expressed in Escherichia coli and then purified to homogeneity. The purified recombinant enzyme does not contain bound metal ions, and the addition of metal chelators or divalent metal ions to the assay mixtures does not affect the rate of product formation. This is the first enzyme from the amidohydrolase superfamily that does not require a divalent metal ion for catalytic activity. The kinetic constants for the hydrolysis of PDC are 340 s(-1) and 9.8 × 10(6) M(-1) s(-1) (k(cat) and k(cat)/K(m), respectively). The pH dependence on the kinetic constants suggests that a single active site residue must be deprotonated for the hydrolysis of PDC. The site of nucleophilic attack was determined by conducting the hydrolysis of PDC in (18)O-labeled water and subsequent (13)C nuclear magnetic resonance analysis. The crystal structures of wild-type LigI and the D248A mutant in the presence of the reaction product were determined to a resolution of 1.9 Å. The C-8 and C-11 carboxylate groups of PDC are coordinated within the active site via ion pair interactions with Arg-130 and Arg-124, respectively. The hydrolytic water molecule is activated by the transfer of a proton to Asp-248. The carbonyl group of the lactone substrate is activated by electrostatic interactions with His-180, His-31, and His-33.

Frequency distribution of causal connectivity in rat sensorimotor network: resting-state fMRI analyses.

PubMed

Shim, Woo H; Baek, Kwangyeol; Kim, Jeong Kon; Chae, Yongwook; Suh, Ji-Yeon; Rosen, Bruce R; Jeong, Jaeseung; Kim, Young R

2013-01-01

Resting-state functional MRI (fMRI) has emerged as an important method for assessing neural networks, enabling extensive connectivity analyses between multiple brain regions. Among the analysis techniques proposed, partial directed coherence (PDC) provides a promising tool to unveil causal connectivity networks in the frequency domain. Using the MRI time series obtained from the rat sensorimotor system, we applied PDC analysis to determine the frequency-dependent causality networks. In particular, we compared in vivo and postmortem conditions to establish the statistical significance of directional PDC values. Our results demonstrate that two distinctive frequency populations drive the causality networks in rat; significant, high-frequency causal connections clustered in the range of 0.2-0.4 Hz, and the frequently documented low-frequency connections <0.15 Hz. Frequency-dependence and directionality of the causal connection are characteristic between sensorimotor regions, implying the functional role of frequency bands to transport specific resting-state signals. In particular, whereas both intra- and interhemispheric causal connections between heterologous sensorimotor regions are robust over all frequency levels, the bilaterally homologous regions are interhemispherically linked mostly via low-frequency components. We also discovered a significant, frequency-independent, unidirectional connection from motor cortex to thalamus, indicating dominant cortical inputs to the thalamus in the absence of external stimuli. Additionally, to address factors underlying the measurement error, we performed signal simulations and revealed that the interactive MRI system noise alone is a likely source of the inaccurate PDC values. This work demonstrates technical basis for the PDC analysis of resting-state fMRI time series and the presence of frequency-dependent causality networks in the sensorimotor system.

Calibration methodology application of kerma area product meters in situ: Preliminary results

NASA Astrophysics Data System (ADS)

Costa, N. A.; Potiens, M. P. A.

2014-11-01

The kerma-area product (KAP) is a useful quantity to establish the reference levels of conventional X-ray examinations. It can be obtained by measurements carried out with a KAP meter on a plane parallel transmission ionization chamber mounted on the X-ray system. A KAP meter can be calibrated in laboratory or in situ, where it is used. It is important to use one reference KAP meter in order to obtain reliable quantity of doses on the patient. The Patient Dose Calibrator (PDC) is a new equipment from Radcal that measures KAP. It was manufactured following the IEC 60580 recommendations, an international standard for KAP meters. This study had the aim to calibrate KAP meters using the PDC in situ. Previous studies and the quality control program of the PDC have shown that it has good function in characterization tests of dosimeters with ionization chamber and it also has low energy dependence. Three types of KAP meters were calibrated in four different diagnostic X-ray equipments. The voltages used in the two first calibrations were 50 kV, 70 kV, 100 kV and 120 kV. The other two used 50 kV, 70 kV and 90 kV. This was related to the equipments limitations. The field sizes used for the calibration were 10 cm, 20 cm and 30 cm. The calibrations were done in three different cities with the purpose to analyze the reproducibility of the PDC. The results gave the calibration coefficient for each KAP meter and showed that the PDC can be used as a reference instrument to calibrate clinical KAP meters.

Validation of Montgomery-Åsberg Rating Scale and Cornell Scale for Depression in Dementia in Brazilian elderly patients.

PubMed

Portugal, Maria da Glória; Coutinho, Evandro Silva Freire; Almeida, Cloyra; Barca, Maria Lage; Knapskog, Anne-Brita; Engedal, Knut; Laks, Jerson

2012-08-01

There are few studies on validation of depression scales in the elderly in Latin America. This study aimed to assess the validity of Montgomery-Åsberg. Depression Rating Scale (MADRS) and Cornell Scale for Depression in Dementia (CSDD) in Brazilian elderly outpatients. A convenience sample of 95 outpatients was diagnosed for dementia and depression according to DSM-IV-TR, ICD-10, and PDC-dAD criteria. Receiver Operating Curves (ROC) were used to calculate the area under the curve (AUC) and to assess MADRS and CSDD cut-offs for each diagnostic criterion. Dementia was diagnosed in 71 of 95 patients. Depression was diagnosed in 35, 30, and 51 patients by ICD-10, DSM-IV, and PDC-dAD, respectively. MADRS cut-off score of 10 correctly diagnosed 67.4% and 66.3% patients as depressed according to DSM-IV and ICD-10. A cut-off of 9 correctly identified 74.7% by PDC-dAD criteria; a CSDD cut-off score of 13 best recognized depression according to DSM-IV and ICD-10. A score of 11 diagnosed depression according to PDC-dAD, while MADRS = 9 recognized depression in dementia. CSDD was more efficient in showing depression in mild than in moderate/severe dementia according to DSM-IV/ICD-10. PDC-dAD behaved nicely for any severity stage. MADRS and CSDD cut-offs of 10 and 13 were the optimal ones to diagnose depression in elderly, respectively. CSDD cut-offs are higher than those found in other countries. Other Latin American studies are needed to compare results with our study.

Retrospective interrupted time series examining hypertension and diabetes medicines usage following changes in patient cost sharing in the 'Farmácia Popular' programme in Brazil.

PubMed

Emmerick, Isabel Cristina Martins; Campos, Monica Rodrigues; Luiza, Vera Lucia; Chaves, Luisa Arueira; Bertoldi, Andrea Dâmaso; Ross-Degnan, Dennis

2017-11-03

'Farmácia Popular' (FP) programme was launched in 2004, expanded in 2006 and changed the cost sharing for oral hypoglycaemic (OH) and antihypertensive (AH) medicines in 2009 and in 2011. This paper describes patterns of usage and continuity of coverage for OH and AH medicines following changes in patient cost sharing in the FP. Interrupted time series study using retrospective administrative data. Monthly programme participation (PP) and proportion of days covered (PDC) were the two outcome measures. The open cohort included all patients with two or more dispensings for a given study medicine in 2008-2012. The interventions were an increase in patient cost sharing in 2009 and zero patient cost sharing for key medicines in 2011. A total of 3.6 and 9.5 million patients receiving treatment for diabetes and hypertension, respectively, qualified for the study. Before the interventions, PP was growing by 7.3% per month; median PDC varied by medicine from 50% to 75%. After patient cost sharing increased in 2009, PP reduced by 56.5% and PDC decreased for most medicines (median 60.3%). After the 2011 free medicine programme, PP surged by 121 000 new dispensings per month and PDC increased for all covered medicines (80.7%). Cost sharing was found to be a barrier to continuity of treatment in Brazil's private sector FP programme. Making essential medicines free to patients appear to increase participation and continuity of treatment to clinically beneficial levels (PDC >80%). © 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.

Pyruvate dehydrogenase complexes from the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum, helminths exhibiting anaerobic mitochondrial metabolism.

PubMed

Diaz, F; Komuniecki, R W

1994-10-01

The pyruvate dehydrogenase complex (PDC) has been purified to apparent homogeneity from 2 parasitic helminths exhibiting anaerobic mitochondrial metabolism, the equine nematode, Parascaris equorum, and the canine cestode, Dipylidium caninum. The P. equorum PDC yielded 7 major bands when separated by SDS-PAGE. The bands of 72, 55-53.5, 41 and 36 kDa corresponded to E2, E3, E1 alpha and E1 beta, respectively. The complex also contained additional unidentified proteins of 43 and 45 kDa. Incubation of the complex with [2-14C]pyruvate resulted in the acetylation of only E2. These results suggest that the P. equorum PDC lacks protein X and exhibits an altered subunit composition, as has been described previously for the PDC of the related nematode, Ascaris suum. In contrast, the D. caninum PDC yielded only four major bands after SDS-PAGE of 59, 58, 39 and 34 kDa, which corresponded to E3, E2, E1 alpha and E1 beta, respectively. Incubation of the D. caninum complex with [2-14C]pyruvate resulted in the acetylation of E2 and a second protein which comigrated with E3, suggesting that the D. caninum complex contained protein X and had a subunit composition similar to PDCs from other eukaryotic organisms. Both helminth complexes appeared less sensitive to inhibition by elevated NADH/NAD+ ratios than complexes isolated from aerobic organisms, as would be predicted for PDCs from organisms exploiting microaerobic habitats. These results suggest that although these helminths have similar anaerobic mitochondrial pathways, they contain significantly different PDCs.

Plasmacytoid DC from aged mice down-regulate CD8 T cell responses by inhibiting cDC maturation after Encephalitozoon cuniculi infection.

PubMed

Gigley, Jason P; Khan, Imtiaz A

2011-01-01

Age associated impairment of immune function results in inefficient vaccination, tumor surveillance and increased severity of infections. Several alterations in adaptive immunity have been observed and recent studies report age related declines in innate immune responses to opportunistic pathogens including Encephalitozoon cuniculi. We previously demonstrated that conventional dendritic cells (cDC) from 9-month-old animals exhibit sub-optimal response to E. cuniculi infection, suggesting that age associated immune senescence begins earlier than expected. We focused this study on how age affects plasmacytoid DC (pDC) function. More specifically how aged pDC affect cDC function as we observed that the latter are the predominant activators of CD8 T cells during this infection. Our present study demonstrates that pDC from middle-aged mice (12 months) suppress young (8 week old) cDC driven CD8 T cell priming against E. cuniculi infection. The suppressive effect of pDC from older mice decreased maturation of young cDC via cell contact. Aged mouse pDC exhibited higher expression of PD-L1 and blockade of their interaction with cDC via this molecule restored cDC maturation and T cell priming. Furthermore, the PD-L1 dependent suppression of cDC T cell priming was restricted to effector function of antigen-specific CD8 T cells not their expansion. To the best of our knowledge, the data presented here is the first report highlighting a cell contact dependent, PD-L1 regulated, age associated defect in a DC subpopulation that results in a sub-optimal immune response against E. cuniculi infection. These results have broad implications for design of immunotherapeutic approaches to enhance immunity for aging populations.

The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions.

PubMed

Shrank, William H; Hoang, Tuyen; Ettner, Susan L; Glassman, Peter A; Nair, Kavita; DeLapp, Dee; Dirstine, June; Avorn, Jerry; Asch, Steven M

2006-02-13

A large proportion of Americans are enrolled in 3-tier pharmacy benefit plans. We studied whether patients enrolled in such plans who receive generic or preferred brand-name agents when initiating chronic therapy were more adherent to treatment than those who received nonpreferred brand-name medications. We analyzed pharmacy claims filled between October 1, 2001, and October 1, 2003, from a large health plan for 6 classes of chronic medications: 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, calcium channel blockers, oral contraceptives, orally inhaled corticosteroids, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors. We measured adherence as the proportion of days covered (PDC) in each drug class during the first year of therapy. We evaluated how the formulary status of the initial prescription (generic, preferred, or nonpreferred) influenced PDC and adequate adherence, defined as PDC greater than 80%, over the subsequent year. A total of 7532 new prescriptions were filled in 1 of the classes evaluated: 1747 (23.2%) for nonpreferred medications, 4376 (58.1%) for preferred drugs, and 1409 (18.7%) for generic drugs. After controlling for patient sociodemographic characteristics and drug class, PDC was 12.6% greater for patients initiated on generic medications vs nonpreferred medications (58.8% vs 52.2%; P<.001). The PDC was 8.8% greater for patients initiated on preferred vs nonpreferred medications (56.8% vs 52.2%; P<.001). Patients initiated on generic and preferred medications had 62% and 30% greater odds, respectively, of achieving adequate adherence compared with those who received nonpreferred medications. In 3-tier pharmacy benefit plans, prescribing generic or preferred medications within a therapeutic class is associated with improvements in adherence to therapy.

Pd/C Synthesized with Citric Acid: An Efficient Catalyst for Hydrogen Generation from Formic Acid/Sodium Formate

PubMed Central

Wang, Zhi-Li; Yan, Jun-Min; Wang, Hong-Li; Ping, Yun; Jiang, Qing

2012-01-01

A highly efficient hydrogen generation from formic acid/sodium formate aqueous solution catalyzed by in situ synthesized Pd/C with citric acid has been successfully achieved at room temperature. Interestingly, the presence of citric acid during the formation and growth of the Pd nanoparticles on carbon can drastically enhance the catalytic property of the resulted Pd/C, on which the conversion and turnover frequency for decomposition of formic acid/sodium formate system can reach the highest values ever reported of 85% within 160 min and 64 mol H2 mol−1 catalyst h−1, respectively, at room temperature. The present simple, low cost, but highly efficient CO-free hydrogen generation system at room temperature is believed to greatly promote the practical application of formic acid system on fuel cells. PMID:22953041

Plasmacytoid dendritic cell interferon-α production to R-848 stimulation is decreased in male infants

PubMed Central

2012-01-01

Background Sex differences in response to microbial infections, especially viral ones, may be associated with Toll-like receptor (TLR)-mediated responses by plasmacytoid dendritic cells (pDCs). Results In this study, we identified sex differences in human infant pDC interferon-α production following challenge with the TLR7/8 agonist R-848. Male pDC responses were significantly lower than those of females during early infancy. This difference may be attributed to the androgen surge experienced by males during the early infancy period. Pretreatment of human pDCs with dihydrotestosterone produced a significant reduction in interferon-α production following R-848 challenge. Conclusions Androgen-mediated regulation of pDC TLR7-driven innate immune responses may contribute to the observed sex differences in response to infections during early infancy. PMID:22769054

Position statement: introduction, methods, and participants. The Writing Group for the International Society for Clinical Densitometry (ISCD) Position Development Conference.

PubMed

2004-01-01

Following publication of the proceedings from the first Position Development Conference (PDC) of the International Society for Clinical Densitometry (ISCD), members of the ISCD Scientific Advisory Committee (SAC) addressed additional topics of interest in the field of bone densitometry. These topics were addressed at a subsequent PDC, which was held in Cincinnati, Ohio, July 25-27, 2003. Five topics were chosen for discussion: (1) the diagnosis of osteoporosis in men, premenopausal women, and children; (2) technical standardization for dual-energy X-ray absorptiometry (DXA); (3) indications for bone densitometry; (4) reporting of bone density results; and (5) nomenclature and decimal places for bone densitometry. This report describes the methodology used for the development, presentation, and finalization of PDC positions. These positions are discussed in the following papers.

Initiation Mechanisms of Low-loss Swept-ramp Obstacles for Deflagration to Detonation Transition in Pulse Detonation Combustors

DTIC Science & Technology

2009-12-01

minimal pressure losses. 15. NUMBER OF PAGES 113 14. SUBJECT TERMS Pulse Detonation Combustors, PDC, Pulse Detonation Engines, PDE , PDE ...Postgraduate School PDC Pulse Detonation Combustor PDE Pulse Detonation Engine RAM Random Access Memory RDT Research, Design and Test RPL...inhibiting the implementation of this advanced propulsion system. The primary advantage offered by pulse detonation engines ( PDEs ) is the high efficiency

Plasmacytoid dendritic cells: no longer an enigma and now key to transplant tolerance?

PubMed Central

Rogers, NM; Isenberg, JS; Thomson, AW

2014-01-01

Plasmacytoid (p) dendritic cells (DC) are a specialized subset of DC whose primary role was initially defined by the production of type I interferons in response to viral infection. They are now known to also possess a repertoire of functions capable of determining T cell fate and activation. Under homeostatic conditions, non-lymphoid tissue-resident pDC play a critical role in the regulation of mucosal immunity, as well as the development of central and peripheral tolerance. Although these cells display a number of characteristics that differ from conventional DC, particularly altered costimulatory molecule expression and poor allostimulatory capacity when interacting with T cells, this phenotype favors the generation of alloantigen-specific regulatory CD4+ or CD8+ T cells critical to the development of graft tolerance. In this minireview we discuss pDC ontogeny, functional biology and the emerging data that demonstrate the importance of pDC in the induction of tolerance, as well as recent studies that define mechanisms underlying pDC-mediated tolerance to both solid organ and hematopoietic stem cell transplantats. We also highlight their use in clinical settings and the potential of pDC both as targets and cellular therapeutic agents to improve the outcome of organ transplantation. PMID:23617754

Electrofishing for crappies: Electrical settings influence immobilization efficiency, injury, and mortality

USGS Publications Warehouse

Dolan, C.R.; Miranda, L.E.; Henry, T.B.

2002-01-01

Continuous direct current (DC) and pulsed DC (PDC) of varying frequency and pulse period are commonly used to immobilize and collect crappies Pomoxis spp. in freshwater. However, little information is available about the minimum electrical-setting thresholds required for immobilization or how the settings relate to incidence of injury. We investigated the effect of increasing power densities on the immobilization and injury of black crappies P. nigromaculatus (average total length = 154 mm) treated with DC and various PDC settings. Forced swimming toward the electrodes was observed in black crappies exposed to DC, but that was less apparent for PDC. The minimum peak power densities required to immobilize black crappies ranged from 0.10 to 6.5 mW/cm3 and depended on pulse frequency and period. The incidence of hemorrhaging ranged from 0% to 50% and that of spinal damage from 9% to 45%. However, the severity of injury also depended on pulse frequency and period. No fish suffered mortality at or below the immobilization thresholds, but mortality ranged from 0% to 15% at settings above the thresholds. Mortality was observed with PDC settings of 15 Hz only. Fish that were tetanized following electrical treatment were more prone to injury than those that exhibited narcosis.

Interplay of foot-and-mouth disease virus, antibodies and plasmacytoid dendritic cells: virus opsonization under non-neutralizing conditions results in enhanced interferon-alpha responses

PubMed Central

2012-01-01

Foot-and-mouth disease virus (FMDV) is a highly infectious member of the Picornaviridae inducing an acute disease of cloven-hoofed species. Vaccine-induced immune protection correlates with the presence of high levels of neutralizing antibodies but also opsonising antibodies have been proposed as an important mechanism of the immune response contributing to virus clearance by macrophages and leading to the production of type-I interferon (IFN) by plasmacytoid dendritic cells (pDC). The present study demonstrates that the opsonising antibody titres mediating enhanced IFN-α responses in pDC were similar to neutralizing titres, when antigenically related viruses from the same serotype were employed. However, sera cross-reacted also with non-neutralized isolates of multiple serotypes, when tested in this assay. Both uncomplexed virus and immune complexed virus stimulated pDC via Toll-like receptor 7. An additional finding of potential importance for strain-specific differences in virulence and/or immunogenicity was that pDC activation by FMDV strongly differed between viral isolates. Altogether, our results indicate that opsonising antibodies can have a broader reactivity than neutralizing antibodies and may contribute to antiviral responses induced against antigenically distant viruses. PMID:22934974

Quantitative analysis of biomedical samples using synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ektessabi, Ali; Shikine, Shunsuke; Yoshida, Sohei

2001-07-01

X-ray fluorescence (XRF) using a synchrotron radiation (SR) microbeam was applied to investigate distributions and concentrations of elements in single neurons of patients with neurodegenerative diseases. In this paper we introduce a computer code that has been developed to quantify the trace elements and matrix elements at the single cell level. This computer code has been used in studies of several important neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and parkinsonism-dementia complex (PDC), as well as in basic biological experiments to determine the elemental changes in cells due to incorporation of foreign metal elements. The substantial nigra (SN) tissue obtained from the autopsy specimens of patients with Guamanian parkinsonism-dementia complex (PDC) and control cases were examined. Quantitative XRF analysis showed that neuromelanin granules of Parkinsonian SN contained higher levels of Fe than those of the control. The concentrations were in the ranges of 2300-3100 ppm and 2000-2400 ppm respectively. On the contrary, Zn and Ni in neuromelanin granules of SN tissue from the PDC case were lower than those of the control. Especially Zn was less than 40 ppm in SN tissue from the PDC case while it was 560-810 ppm in the control. These changes are considered to be closely related to the neuro-degeneration and cell death.

Robust Nonlinear Causality Analysis of Nonstationary Multivariate Physiological Time Series.

PubMed

Schack, Tim; Muma, Michael; Feng, Mengling; Guan, Cuntai; Zoubir, Abdelhak M

2018-06-01

An important research area in biomedical signal processing is that of quantifying the relationship between simultaneously observed time series and to reveal interactions between the signals. Since biomedical signals are potentially nonstationary and the measurements may contain outliers and artifacts, we introduce a robust time-varying generalized partial directed coherence (rTV-gPDC) function. The proposed method, which is based on a robust estimator of the time-varying autoregressive (TVAR) parameters, is capable of revealing directed interactions between signals. By definition, the rTV-gPDC only displays the linear relationships between the signals. We therefore suggest to approximate the residuals of the TVAR process, which potentially carry information about the nonlinear causality by a piece-wise linear time-varying moving-average model. The performance of the proposed method is assessed via extensive simulations. To illustrate the method's applicability to real-world problems, it is applied to a neurophysiological study that involves intracranial pressure, arterial blood pressure, and brain tissue oxygenation level (PtiO2) measurements. The rTV-gPDC reveals causal patterns that are in accordance with expected cardiosudoral meachanisms and potentially provides new insights regarding traumatic brain injuries. The rTV-gPDC is not restricted to the above problem but can be useful in revealing interactions in a broad range of applications.

A Critical Assessment of Vector Control for Dengue Prevention

PubMed Central

Achee, Nicole L.; Gould, Fred; Perkins, T. Alex; Reiner, Robert C.; Morrison, Amy C.; Ritchie, Scott A.; Gubler, Duane J.; Teyssou, Remy; Scott, Thomas W.

2015-01-01

Recently, the Vaccines to Vaccinate (v2V) initiative was reconfigured into the Partnership for Dengue Control (PDC), a multi-sponsored and independent initiative. This redirection is consistent with the growing consensus among the dengue-prevention community that no single intervention will be sufficient to control dengue disease. The PDC's expectation is that when an effective dengue virus (DENV) vaccine is commercially available, the public health community will continue to rely on vector control because the two strategies complement and enhance one another. Although the concept of integrated intervention for dengue prevention is gaining increasingly broader acceptance, to date, no consensus has been reached regarding the details of how and what combination of approaches can be most effectively implemented to manage disease. To fill that gap, the PDC proposed a three step process: (1) a critical assessment of current vector control tools and those under development, (2) outlining a research agenda for determining, in a definitive way, what existing tools work best, and (3) determining how to combine the best vector control options, which have systematically been defined in this process, with DENV vaccines. To address the first step, the PDC convened a meeting of international experts during November 2013 in Washington, DC, to critically assess existing vector control interventions and tools under development. This report summarizes those deliberations. PMID:25951103

Retention of the cyanobacterial neurotoxin beta-N-methylamino-l-alanine in melanin and neuromelanin-containing cells--a possible link between Parkinson-dementia complex and pigmentary retinopathy.

PubMed

Karlsson, Oskar; Berg, Cecilia; Brittebo, Eva B; Lindquist, Nils Gunnar

2009-02-01

beta-N-methylamino-l-alanine (BMAA), a neurotoxic amino acid produced by cyanobacteria, has been suggested to be involved in the etiology of a neurodegenerative disease complex which includes Parkinson-dementia complex (PDC). In PDC, neuromelanin-containing neurons in substantia nigra are degenerated. Many PDC patients also have an uncommon pigmentary retinopathy. The aim of this study was to investigate the distribution of (3)H-BMAA in mice and frogs, with emphasis on pigment-containing tissues. Using autoradiography, a distinct retention of (3)H-BMAA was observed in melanin-containing tissues such as the eye and neuromelanin-containing neurons in frog brain. Analysis of the binding of (3)H-BMAA to Sepia melanin in vitro demonstrated two apparent binding sites. In vitro-studies with synthetic melanin revealed a stronger interaction of (3)H-BMAA with melanin during synthesis than the binding to preformed melanin. Long-term exposure to BMAA may lead to bioaccumulation in melanin- and neuromelanin-containing cells causing high intracellular levels, and potentially changed melanin characteristics via incorporation of BMAA into the melanin polymer. Interaction of BMAA with melanin may be a possible link between PDC and pigmentary retinopathy.

Assessment of Program Impact Through First Grade, Volume I: The Context, Conceptual Approach and Methods of the Evaluation. An Evaluation of Project Developmental Continuity. Interim Report X.

ERIC Educational Resources Information Center

Rosario, Jose; And Others

This volume is the first of a series reporting evaluation findings on the impact of Project Developmental Continuity (PDC) on institutions, classroom staff, parents and children from the time the children entered Head Start through the first grade. PDC was begun in 1974 with the purpose of ensuring that disadvantaged children receive continuous…

An Assessment-based Solution to a Human-Service Employee Performance Problem

PubMed Central

Wilder, David A.; Majdalany, Lina; Mathisen, David; Strain, Leigh Ann

2013-01-01

The PDC-HS implicated a lack of proper training on participant duties and a lack of performance feedback as contributors to the performance problems. As a result, an intervention targeting training on participant duties and performance feedback was implemented across eight treatment rooms; the intervention increased performance in all rooms. This preliminary validation study suggests the PDC-HS may prove useful in solving performance problems in human-service settings. PMID:25729505

A cross-sectional view of the current state of treatment of youth with type 2 diabetes in the USA: Enrollment data from the Pediatric Diabetes Consortium type 2 diabetes registry

USDA-ARS?s Scientific Manuscript database

To describe the clinical characteristics, treatment approaches, clinical outcomes, and co-morbidities of youth with type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium (PDC) T2D Registry. PDC enrolled 598 youth <21 yr of age with T2D from February 2012 to July 2015 at eight centers. ...

Redesigned PDC bit solves low hydraulic hp problems

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

NONE

1996-06-01

A new PDC bit design was created to solve a problem a drilling contractor had due to hydraulic horsepower limitations on rigs used in a particular geographical area. The new bit design, which arose from a formal alliance between Exeter Drilling Co. and Hughes Christensen Co. has greatly improved bit cleaning and overall drilling efficiency in applications where only low hydraulic hp is available. The new design has been run successfully in the Denver-Julesburg (D-J) basin of Colorado. The development was described in detail in paper IADC/SPE 35109, ``Unique PDC bit configuration dramatically improves hole cleaning, drilling efficiency in lowmore » hydraulic applications,`` presented by G.J. Hertzler III, Exeter Drilling Co. and J.T. Wankier, Hughes Christensen Co., at the 1996 IADC/SPE Drilling Conference, New Orleans, La., March 12--15. This article is an abstract of that paper, which contains significantly more technical data.« less

Ceramic Nanocomposites from Tailor-Made Preceramic Polymers

PubMed Central

Mera, Gabriela; Gallei, Markus; Bernard, Samuel; Ionescu, Emanuel

2015-01-01

The present Review addresses current developments related to polymer-derived ceramic nanocomposites (PDC-NCs). Different classes of preceramic polymers are briefly introduced and their conversion into ceramic materials with adjustable phase compositions and microstructures is presented. Emphasis is set on discussing the intimate relationship between the chemistry and structural architecture of the precursor and the structural features and properties of the resulting ceramic nanocomposites. Various structural and functional properties of silicon-containing ceramic nanocomposites as well as different preparative strategies to achieve nano-scaled PDC-NC-based ordered structures are highlighted, based on selected ceramic nanocomposite systems. Furthermore, prospective applications of the PDC-NCs such as high-temperature stable materials for thermal protection systems, membranes for hot gas separation purposes, materials for heterogeneous catalysis, nano-confinement materials for hydrogen storage applications as well as anode materials for secondary ion batteries are introduced and discussed in detail. PMID:28347023

Development and testing of Parabolic Dish Concentrator No. 1

NASA Technical Reports Server (NTRS)

Dennison, E. W.; Thostesen, T. O.

1984-01-01

Parabolic Dish Concentrator No. 1 (PDC-1) is a 12-m-diameter prototype concentrator with low life-cycle costs for use with thermal-to-electric energy conversion devices. The concentrator assembly features panels made of a resin transfer molded balsa core/fiberglass sandwich with plastic reflective film as the reflective surface and a ribbed framework to hold the panels in place. The concentrator assembly tracks in azimuth and elevation on a base frame riding on a circular track. It is shown that the panels do not exhibit the proper parabolic contour. However, thermal gradients were discovered in the panels with daily temperature changes. The PDC-1 has sufficient optical quality to operate satisfactorily in a dish-electric system. The PDC-1 development provides the impetus for creating innovative optical testing methods and valuable information for use in designing and fabricating concentrators of future dish-electric systems.

Enhanced Mobility in Concentrated Pyroclastic Density Currents: An Examination of a Self-Fluidization Mechanism

NASA Astrophysics Data System (ADS)

Breard, Eric C. P.; Dufek, Josef; Lube, Gert

2018-01-01

Pyroclastic density currents (PDCs) are a significant volcanic hazard. However, their dominant transport mechanisms remain poorly understood, in part because of the large variability of PDC types and deposits. Here we combine field data with experimental and numerical simulations to illuminate the twofold fate of particles settling from an ash cloud to form the dense PDC basal flow. At solid fractions >1 vol %, heterogeneous drag leads to formation of mesoscale particle clusters that favor rapid particle settling and result in a mobile dense layer with significant bed weight support. Conversely, at lower concentrations the absence of particle clusters typically leads to formation of poorly mobile dense beds that deposit massive layers. Based on this transport dichotomy, we present a numerical dense-dilute parameter that allows a PDC's dominant transport mechanism to be determined directly from the deposit geometry and grainsize characteristics.

Low-profile wireless passive resonators for sensing

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

Gong, Xun; An, Linan

A resonator for sensing a physical or an environmental parameter includes a support having a top surface that provides a ground plane, and a polymer-derived ceramic (PDC) element positioned on the top surface including a PDC layer, and a metal patch on the PDC layer. The metal patch is electrically isolated from all surrounding structure, and the resonator has a resonant frequency that changes as a function of the physical or environmental parameter. A system for wirelessly sensing a physical or environmental parameter includes at least one resonator and a wireless RF reader located remotely from the resonator for transmittingmore » a wide-band RF interrogation signal that excites the resonator. The wireless RF reader detects a sensing signal retransmitted by the resonator and includes a processor for determining the physical or environmental parameter at the location of the resonator from the sensing signal.« less

The January 21, 1951 Blast of Mount Lamington in Papua New Guinea: Sequence of Events and Characteristics of the Deposits

NASA Astrophysics Data System (ADS)

Belousova, M.; Belousov, A.; Patia, H.; Hoblitt, R. P.

2011-12-01

We present the results of a detailed reinvestigation of deposits of the famous 1951 eruption of Mount Lamington which was originally studied by T. Taylor (1958). We found that the climactic phase of the eruption was triggered by a relatively small gravitational collapse of the old intracrater lava dome (debris avalanche V=0.02-0.04 cub. km; L=8.5 km; H/L=0.14). The collapse was followed by vertical explosive fountain which was not buoyant and formed a pyroclastic density current (PDC). This PDC completely devastated an area of 230 sq. km, traveling maximum distance of 15 km in N direction; 3500 people were killed by the eruption. The PDC deposit, which is still well-preserved, was studied in 2 profiles, which are parallel to the longest axis of the surge propagation. The deposit consists of mostly juvenile rock fragments (80-85%) represented by poorly vesicular (4 - 40%) highly crystalline dacite; bombs with poorly developed bread crust surfaces are common in proximal areas. The deposit is in general normally graded and consists of lapilli and coarse ash fining upward into fine ash. The base of the deposit is mixed with soil in proximal areas. Stratigraphic characteristics of the deposit demonstrate strong local fluctuations, but have clear trends with distance from the volcano. At distances from 3 to 12 km from the volcano the maximum deposit thickness decreases from 55 to 5 cm, and the average size of the 10 largest clasts decreases from 4.5 cm to 0.5 cm; Md diameter decreases from -1.5 to 4.5 phi; sorting improves from 3 to 0.7 phi. The surge produced spectacular tree blow-down in the devastated area. Aerial photographs taken one month after eruption show that the PDC was strongly channelized even by small (tens meters) topographic features; the front of the moving PDC was frequently split into multiple small tongues which were variously deflected by topography. The deposit and the tree blow-down features demonstrate many similarities with those of blast-generated PDCs of Bezymianny in 1956 and Mount St. Helens in 1980. A notable difference however is that although some layering similar to the classic A, B, C stratigraphy is present in the proximal deposits of Lamington, the layers are not so clearly distinguished by grain size characteristics and lack the sharp contacts that are common in classic blast deposits. We attribute this difference to the fact that, unlike the St. Helens and Bezymianny examples, the Lamington blast cloud first ascended vertically before collapsing and producing a PDC. Consequently the Lamington PDC ingested more air and was more dilute than those at St. Helens and Bezymianny.

Thermophilic Gram-Positive Biocatalysts for Biomass Conversion to Ethanol

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

Shanmugam, K.T.; Ingram, L.O.; Maupin-Furlow, J.A.

2003-12-01

Production of energy from renewable sources is receiving increased attention due to the finite nature of fossil fuels and the environmental impact associated with the continued large scale use of fossil energy sources. Biomass, a CO2-neutral abundant resource, is an attractive alternate source of energy. Biomass-derived sugars, such as glucose, xylose, and other minor sugars, can be readily fermented to fuel ethanol and commodity chemicals. Extracellular cellulases produced by fungi are commercially developed for depolymerization of cellulose in biomass to glucose for fermentation by appropriate biocatalysts in a simultaneous saccharification and fermentation (SSF) process. Due to the differences in themore » optimum conditions for the activity of the fungal cellulases and the growth and fermentation characteristics of the current industrial biocatalysts, SSF of cellulose is envisioned at conditions that are not optimal for the fungal cellulase activity leading to higher than required cost of cellulase in SSF. We have isolated bacterial biocatalysts whose growth and fermentation requirements match the optimum conditions for commercial fungal cellulase activity (pH 5.0 and 50 deg. C). These isolates fermented both glucose and xylose, major components of cellulose and hemicellulose, respectively, to L(+)-lactic acid. Xylose was metabolized through the pentose-phosphate pathway by these organisms as evidenced by the fermentation profile and analysis of the fermentation products of 13C1-xylose by NMR. As expected for the metabolism of xylose by the pentose-phosphate pathway, 13C-lactate accounted for more than 90% of the total 13C-labeled products. All three strains fermented crystalline cellulose to lactic acid with the addition of fungal cellulase (Spezyme CE) (SSF) at an optimum of about 10 FPU/g cellulose. These isolates also fermented cellulose and sugar cane bagasse hemicellulose acid hydrolysate simultaneously. Based on fatty acid profile and 16S rRNA sequence, these isolates cluster with Bacillus coagulans although B. coagulans type strain, ATCC 7050, failed to utilize xylose as a carbon source. For successful production of ethanol from pyruvate, both pyruvate decarboxylase (PDC) and alcohol dehydrogenase (AHD) need to be produced at optimal levels in these biocatalysts. A plasmid containing the S. ventriculi pdc gene and the adh gene from geobacillus stearothermophilus was constructed using plasmid pWH1520 that was successfully used for expression of pdc in B. megaterium. The resulting portable ethanol (PET) plasmid, pJAM423, was transformed into B. megaterium. After xylose induction, a significant fraction of cell cytoplasm was composed of the S. ventriculi PDC and G. stearothermophilus ADH proteins. In preliminary experiments, the amount of ethanol produced by b. megaterium with plasmid pJAM423 was about twice (20 mM) of the bacterium without the plasmid. These results show that the PET operon is functional in B. megaterium but high level ethanol production needs further genetic and metabolic engineering. A genetic transfer system for the second generation biocatalysts needs to be developed for transferring the plasmid pJAM423 and its derivatives for engineering these organisms for ethanol production from biomass derived sugars and cellulose to ethanol. One of the new biocatalysts, strain P4-102B was found to be transformable with plasmids and the method for introducing plasmid pJAM423 into this strain and expression of the encoded DNA is being optimized. These new second generation biocatalysts have the potential to reduce the cost of SSF by minimizing the amount of fungal cellulases, a significant cost component in the use of biomass as a renewable resource for production of fuels and chemicals.« less

Synthesis and Structural Characterization of Magnesium Based Coordination Networks in Different Solvents

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

D Banerjee; J Finkelstein; A Smirnov

2011-12-31

Three magnesium based metal-organic frameworks, Mg{sub 3}(3,5-PDC){sub 3}(DMF){sub 3} {center_dot} DMF [1], Mg(3,5-PDC)(H{sub 2}O) {center_dot} (H{sub 2}O) [3], and Mg{sub 4}(3,5-PDC){sub 4}(DMF){sub 2}(H{sub 2}O){sub 2} {center_dot} 2DMF {center_dot} 4.5H{sub 2}O [4], and a 2-D coordination polymer, [Mg(3,5-PDC)(H{sub 2}O){sub 2}] [2] [PDC = pyridinedicarboxylate], were synthesized using a combination of DMF, methanol, ethanol, and water. Compound 1 [space group P2{sub 1}/n, a = 12.3475(5) {angstrom}, b = 11.1929(5) {angstrom}, c = 28.6734(12) {angstrom}, {beta} = 98.8160(10){sup o}, V = 3916.0(3) {angstrom}{sup 3}] consists of a combination of isolated and corner-sharing magnesium octahedra connected by the organic linkers to form a 3-Dmore » network with a 12.2 {angstrom} x 4.6 {angstrom} 1-D channel. The channel contains coordinated and free DMF molecules. In compound 2 [space group C2/c, a = 9.964(5) {angstrom}, b = 12.0694(6) {angstrom}, c = 7.2763(4) {angstrom}, {beta} = 106.4970(6){sup o}, V = 836.70(6) {angstrom}{sup 3}], PDC connects isolated seven coordinated magnesium polyhedra into a layered structure. Compound 3 [space group P6{sub 1}22, a = 11.479(1) {angstrom}, c = 14.735(3) {angstrom}, V = 1681.7(4) {angstrom}{sup 3}] (previously reported) contains isolated magnesium octahedra connected by the organic linker with each other forming a 3D network. Compound 4 [space group P2{sub 1}/c, a = 13.7442(14) {angstrom}, b = 14.2887(15) {angstrom}, c = 14.1178(14) {angstrom}, {beta} = 104.912(2){sup o}, V = 2679.2(5) {angstrom}{sup 3}] also exhibits a 3D network based on isolated magnesium octahedra with square cavities containing both disordered DMF and water molecules. The structural topologies originate due to the variable coordination ability of solvent molecules with the metal center. Water molecules coordinate with the magnesium metal centers preferably over other polar solvents (DMF, methanol, ethanol) used to synthesize the coordination networks. Despite testing multiple desolvation routes, we were unable to measure BET surface areas greater than 51.9 m{sup 2}/g for compound 1.« less

Erosional self-channelization of pyroclastic density currents - Evidence from ground-penetrating radar imaging at Mt. St. Helens, Washington (USA)

NASA Astrophysics Data System (ADS)

Gase, A.; Brand, B. D.; Bradford, J.

2016-12-01

The causes and consequences of substrate erosion are among the least understood attributes of pyroclastic density current (PDC) dynamics. Field evidence of substrate erosion is often limited by the location and quality of exposed PDC deposits. Here we present evidence for one of the most spatially extensive cases of PDC erosion to date, found within the 18 May 1980 deposits of Mt. St. Helens, Washington (USA). An 8 m deep and 300 m wide PDC scour and fill feature, which extends into PDC deposits from earlier in the eruption, is exposed along a distal outcrop of the shallow-dipping (<15º) pumice plain. Near surface geophysical techniques allow us to investigate the nature, extent, and cause of this large scour. We used 50 MHz ground-penetrating radar to track the distal scour from outcrop toward its source. Beginning 700 m up-flow from the large scour and fill exposure, the feature progressively widens from 205 m to 280 m and deepens from 10 m to 13 m, suggesting the PDCs became more erosive along the length of the scour. We extended our transects across the pumice plain to locate additional scours and to establish the topography at the time of erosion. We found a second 420 m wide and 11 m deep scour that extends at least 500 m from its inception point. Apparent dips of the sides of both channels are asymmetrical, due to pronounced erosion on the up-slope side of the flow in cross-section. Our data show no evidence of subsurface topographic irregularities or high slope angles up-flow from either erosional feature. These features imply large PDCs from semi-sustained or fluctuating eruptions can self-channelize by erosional mechanisms. Our findings suggest that (1) concentrated PDCs are capable of producing large scours on shallow slopes with negligible surface roughness, analogous to the erosional channels of submarine turbidity currents, (2) substrate properties, including partial fluidization of fresh PDC deposits, may facilitate substrate erosion during semi-sustained eruptions, and (3) large PDCs can undergo self-channelization, whereby axial zones of high flow energy erode channels that confine subsequent flows. Erosion and self-channelization of this nature is not accounted for in models of concentrated PDCs, which may result in underestimates of run-out distance.

Oral Health Disparities and Unmet Dental Needs among Preschool Children in Chelsea, MA: Exploring Mechanisms, Defining Solutions

PubMed Central

Isong, Inyang; Dantas, Laila; Gerard, Macda; Kuhlthau, Karen

2014-01-01

Background Significant disparities exist in children’s receipt of preventive dental care (PDC) in the United States. Many of the children at greatest risk of dental disease do not receive timely PDC; when they do receive dental care, it is often more for relief of dental pain. Chelsea is a low-income, diverse Massachusetts community with high rates of untreated childhood caries. There are various dental resources available in Chelsea, yet many children do not access dental care at levels equivalent to their needs. Objective Using Chelsea as a case-study, to explore factors contributing to forgone PDC (including the age 1 dental visit) in an in-depth way. Methods We used a qualitative study design that included semi-structured interviews with parents of preschool children residing in Chelsea, and Chelsea-based providers including pediatricians, dentists, a dental hygienist and early childhood care providers. We examined: a) parents’ dental attitudes and oral health cultural beliefs; b) parents’ and providers’ perspectives on facilitators and barriers to PDC, reasons for unmet needs, and proposed solutions to address the problem. We recorded, transcribed and independently coded all interviews. Using rigorous, iterative qualitative data analyses procedures, we identified emergent themes. Results Factors perceived to facilitate receipt of PDC included Head-Start oral health policies, strong pediatric primary care/dental linkages, community outreach and advertising, and parents’ own oral health experiences. Most parents and providers perceived there to be an adequate number of accessible dental services and resources in Chelsea, including for Medicaid enrollees. However, several barriers impeded children from receiving timely PDC, the most frequently cited being insurance related problems for children and adults. Other barriers included limited dental services for children <2 years, perceived poor quality of some dental practices, lack of emphasis on prevention-based dental care, poor care-coordination, and insufficient culturally-appropriate care. Important family-level barriers included parental oral health literacy, cultural factors, limited English proficiency and competing priorities. Several solutions were proposed to address identified barriers. Conclusion Even in a community with a considerable number of dental resources, various factors may preclude access to these services by preschool-aged children. Opportunities exist to address modifiable factors through strategic oral health policies, community outreach and improved care coordination between physicians, dentists and early childhood care providers. PMID:25614878

Oral Health Disparities and Unmet Dental Needs among Preschool Children in Chelsea, MA: Exploring Mechanisms, Defining Solutions.

PubMed

Isong, Inyang; Dantas, Laila; Gerard, Macda; Kuhlthau, Karen

Significant disparities exist in children's receipt of preventive dental care (PDC) in the United States. Many of the children at greatest risk of dental disease do not receive timely PDC; when they do receive dental care, it is often more for relief of dental pain. Chelsea is a low-income, diverse Massachusetts community with high rates of untreated childhood caries. There are various dental resources available in Chelsea, yet many children do not access dental care at levels equivalent to their needs. Using Chelsea as a case-study, to explore factors contributing to forgone PDC (including the age 1 dental visit) in an in-depth way. We used a qualitative study design that included semi-structured interviews with parents of preschool children residing in Chelsea, and Chelsea-based providers including pediatricians, dentists, a dental hygienist and early childhood care providers. We examined: a) parents' dental attitudes and oral health cultural beliefs; b) parents' and providers' perspectives on facilitators and barriers to PDC, reasons for unmet needs, and proposed solutions to address the problem. We recorded, transcribed and independently coded all interviews. Using rigorous, iterative qualitative data analyses procedures, we identified emergent themes. Factors perceived to facilitate receipt of PDC included Head-Start oral health policies, strong pediatric primary care/dental linkages, community outreach and advertising, and parents' own oral health experiences. Most parents and providers perceived there to be an adequate number of accessible dental services and resources in Chelsea, including for Medicaid enrollees. However, several barriers impeded children from receiving timely PDC, the most frequently cited being insurance related problems for children and adults. Other barriers included limited dental services for children <2 years, perceived poor quality of some dental practices, lack of emphasis on prevention-based dental care, poor care-coordination, and insufficient culturally-appropriate care. Important family-level barriers included parental oral health literacy, cultural factors, limited English proficiency and competing priorities. Several solutions were proposed to address identified barriers. Even in a community with a considerable number of dental resources, various factors may preclude access to these services by preschool-aged children. Opportunities exist to address modifiable factors through strategic oral health policies, community outreach and improved care coordination between physicians, dentists and early childhood care providers.

Pulsed direct and constant direct currents in the pilocarpine iontophoresis sweat chloride test.

PubMed

Gomez, Carla Cristina Souza; Servidoni, Maria de Fatima; Marson, Fernando Augusto de Lima; Canavezi, Paulo Jose Coelho; Vinagre, Adriana Mendes; Costa, Eduardo Tavares; Ribeiro, Antonio Fernando; Ribeiro, Maria Angela Gonçalves de Oliveira; Toro, Adyleia Aparecida Dalbo Contrera; Pavan, Celia Regina; Rondon, Michelle Vivine Sá Dos Santos; Lorena, Sonia Leticia Silva; Vieria, Francisco Ubaldi; Ribeiro, Jose Dirceu

2014-12-13

The classic sweat test (CST) is the golden standard for cystic fibrosis (CF) diagnosis. Then, our aim was compare the production and volume of sweat, and side effects caused by pulsed direct current (PDC) and constant direct current (CDC). To determine the optimal stimulation time (ST) for the sweat collection. To verify the PDC as CF diagnosis option. Prospective study with cross-sectional experimental intervention. Experiment 1 (right arm): PDC and CDC. ST at 10 min and sweat collected at 30 min. Currents of 0.5; 0.75; 1.0 and 1.5 mA and frequencies of 0, 200, 1,000 and 5,000 Hz applied. Experiment 2 (left arm): current of 1.0 mA, ST at 5 and 10 min and sweat collected at 15 and 30 min with frequencies of 0; 200; 1,000 and 5,000 Hz applied Experiments 1 and 2 were performed with current density (CD) from 0.07 to 0.21 mA/cm2. Experiment 3: PDC was used in typical CF patients with two CFTR mutations screened and or with CF diagnosis by rectal biopsy and patients with atypical CF. 48 subjects (79.16% female) with average of 29.54 ± 8.87 years old were enrolled. There was no statistical difference between the interaction of frequency and current in the sweat weight (p = 0.7488). Individually, positive association was achieved between weight sweat and stimulation frequency (p = 0.0088); and current (p = 0.0025). The sweat production was higher for 10 min of stimulation (p = 0.0023). The sweat collection was better for 30 min (p = 0.0019). The skin impedance was not influenced by ST and sweat collection (p > 0.05). The current frequency was inversely associated with the skin impedance (p < 0.0001). The skin temperature measured before stimulation was higher than after (p < 0.0001). In Experiment 3 (29 subjects) the PDC showed better kappa index compared to CDC (0.9218 versus 0.5205, respectively). The performance of the CST with CDC and PDC with CD of 0.14 to 0.21 mA/cm2 showed efficacy in steps of stimulation and collection of sweat, without side effects. The optimal stimulation time and sweat collection were, respectively, 10 and 30 min.

Synthesis and Structural Characterization of Magnesium Based Coordination Networks in Different Solvents

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

Banerjee, Debasis; Finkelstein, Jeffrey; Smirnov, A.

2015-10-15

Three magnesium based metal-organic frameworks, Mg{sub 3}(3,5-PDC){sub 3}(DMF){sub 3} {center_dot} DMF [1], Mg(3,5-PDC)(H{sub 2}O) {center_dot} (H{sub 2}O) [3], and Mg4(3,5-PDC)4(DMF){sub 2}(H{sub 2}O){sub 2} {center_dot} 2DMF {center_dot} 4.5H{sub 2}O [4], and a 2-D coordination polymer, [Mg(3,5-PDC)(H{sub 2}O){sub 2}] [2] [PDC = pyridinedicarboxylate], were synthesized using a combination of DMF, methanol, ethanol, and water. Compound 1 [space group P2{sub 1}/n, a = 12.3475(5) {angstrom}, b = 11.1929(5) {angstrom}, c = 28.6734(12) {angstrom}, {beta} = 98.8160(10){sup o}, V = 3916.0(3) {angstrom}{sup 3}] consists of a combination of isolated and corner-sharing magnesium octahedra connected by the organic linkers to form a 3-D network withmore » a 12.2 {angstrom} x 4.6 {angstrom} 1-D channel. The channel contains coordinated and free DMF molecules. In compound 2 [space group C2/c, a = 9.964(5) {angstrom}, b = 12.0694(6) {angstrom}, c = 7.2763(4) {angstrom}, {beta} = 106.4970(6){sup o}, V = 836.70(6) {angstrom}{sup 3}], PDC connects isolated seven coordinated magnesium polyhedra into a layered structure. Compound 3 [space group P6{sub 1}22, a = 11.479(1) {angstrom}, c = 14.735(3) {angstrom}, V = 1681.7(4) {angstrom}{sup 3}] (previously reported) contains isolated magnesium octahedra connected by the organic linker with each other forming a 3D network. Compound 4 [space group P2{sub 1}/c, a = 13.7442(14) {angstrom}, b = 14.2887(15) {angstrom}, c = 14.1178(14) {angstrom}, {beta} = 104.912(2){sup o}, V = 2679.2(5) {angstrom}{sup 3}] also exhibits a 3D network based on isolated magnesium octahedra with square cavities containing both disordered DMF and water molecules. The structural topologies originate due to the variable coordination ability of solvent molecules with the metal center. Water molecules coordinate with the magnesium metal centers preferably over other polar solvents (DMF, methanol, ethanol) used to synthesize the coordination networks. Despite testing multiple desolvation routes, we were unable to measure BET surface areas greater than 51.9 m{sup 2}/g for compound 1.« less

Panamanian Politics: The Legacy of Torrijismo and Prospects for Demilitarization

DTIC Science & Technology

1991-06-01

Arias 1 15"Comptroller General Views Military Corruption," on Circuito RPC Television in Spanish 31 January 1990, reported in Foreign Broadcast...for the PDC to 13 0Catto, William, p. 1. 131"PDC Calls for Change in Endara Government," Circuito RPC Television in Spanish 1 August 1990, reported...With President Endara," on Circuito RPC Television in Spanish 8 January 1990, reported in Foreign Broadcast Information Service, Latin America, p. 39

Effect of PDC bit design and confining pressure on bit-balling tendencies while drilling shale using water base mud

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

Hariharan, P.R.; Azar, J.J.

1996-09-01

A good majority of all oilwell drilling occurs in shale and other clay-bearing rocks. In the light of relatively fewer studies conducted, the problem of bit-balling in PDC bits while drilling shale has been addressed with the primary intention of attempting to quantify the degree of balling, as well as to investigate the influence of bit design and confining pressures. A series of full-scale laboratory drilling tests under simulated down hole conditions were conducted utilizing seven different PDC bits in Catoosa shale. Test results have indicated that the non-dimensional parameter R{sub d} [(bit torque).(weight-on-bit)/(bit diameter)] is a good indicator ofmore » the degree of bit-balling and that it correlated well with Specific-Energy. Furthermore, test results have shown bit-profile and bit-hydraulic design to be key parameters of bit design that dictate the tendency of balling in shales under a given set of operating conditions. A bladed bit was noticed to ball less compared to a ribbed or open-faced bit. Likewise, related to bit profile, test results have indicated that the parabolic profile has a lesser tendency to ball compared to round and flat profiles. The tendency of PDC bits to ball was noticed to increase with increasing confining pressures for the set of drilling conditions used.« less

Observer-Based Non-PDC Control for Networked T-S Fuzzy Systems With an Event-Triggered Communication.

PubMed

Peng, Chen; Ma, Shaodong; Xie, Xiangpeng

2017-02-07

This paper addresses the problem of an event-triggered non-parallel distribution compensation (PDC) control for networked Takagi-Sugeno (T-S) fuzzy systems, under consideration of the limited data transmission bandwidth and the imperfect premise matching membership functions. First, a unified event-triggered T-S fuzzy model is provided, in which: 1) a fuzzy observer with the imperfect premise matching is constructed to estimate the unmeasurable states of the studied system; 2) a fuzzy controller is designed following the same premise as the observer; and 3) an output-based event-triggering transmission scheme is designed to economize the restricted network resources. Different from the traditional PDC method, the synchronous premise between the fuzzy observer and the T-S fuzzy system are no longer needed in this paper. Second, by use of Lyapunov theory, a stability criterion and a stabilization condition are obtained for ensuring asymptotically stable of the studied system. On account of the imperfect premise matching conditions are well considered in the derivation of the above criteria, less conservation can be expected to enhance the design flexibility. Compared with some existing emulation-based methods, the controller gains are no longer required to be known a priori. Finally, the availability of proposed non-PDC design scheme is illustrated by the backing-up control of a truck-trailer system.

Spacecraft Mission Design for the Mitigation of the 2017 PDC Hypothetical Asteroid Threat

NASA Technical Reports Server (NTRS)

Barbee, Brent W.; Sarli, Bruno V.; Lyzhoft, Joshua; Chodas, Paul W.; Englander, Jacob A.

2017-01-01

This paper presents a detailed mission design analysis results for the 2017 Planetary Defense Conference (PDC) Hypothetical Asteroid Impact Scenario, documented at https://cneos.jpl.nasa.gov/ pd/cs/pdc17/. The mission design includes campaigns for both reconnaissance (flyby or rendezvous) of the asteroid (to characterize it and the nature of the threat it poses to Earth) and mitigation of the asteroid, via kinetic impactor deflection, nuclear explosive device (NED) deflection, or NED disruption. Relevant scenario parameters are varied to assess the sensitivity of the design outcome, such as asteroid bulk density, asteroid diameter, momentum enhancement factor, spacecraft launch vehicle, and mitigation system type. Different trajectory types are evaluated in the mission design process from purely ballistic to those involving optimal midcourse maneuvers, planetary gravity assists, and/or lowthrust solar electric propulsion. The trajectory optimization is targeted around peak deflection points that were found through a novel linear numerical technique method. The optimization process includes constrain parameters, such as Earth departure date, launch declination, spacecraft/asteroid relative velocity and solar phase angle, spacecraft dry mass, minimum/maximum spacecraft distances from Sun and Earth, and Earth/spacecraft communications line of sight. Results show that one of the best options for the 2017 PDC deflection is solar electric propelled rendezvous mission with a single spacecraft using NED for the deflection

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells.

PubMed

Garnache-Ottou, Francine; Chaperot, Laurence; Biichle, Sabeha; Ferrand, Christophe; Remy-Martin, Jean-Paul; Deconinck, Eric; de Tailly, Patrick Darodes; Bulabois, Bénédicte; Poulet, Jacqueline; Kuhlein, Emilienne; Jacob, Marie-Christine; Salaun, Véronique; Arock, Michel; Drenou, Bernard; Schillinger, Françoise; Seilles, Estelle; Tiberghien, Pierre; Bensa, Jean-Claude; Plumas, Joel; Saas, Philippe

2005-02-01

A new entity of acute leukemia coexpressing CD4(+)CD56(+) markers without any other lineage-specific markers has been identified recently as arising from lymphoid-related plasmacytoid dendritic cells (pDCs). In our laboratory, cells from a patient with such CD4(+)CD56(+) lineage-negative leukemia were unexpectedly found to also express the myeloid marker CD33. To confirm the diagnosis of pDC leukemia despite the CD33 expression, we demonstrated that the leukemic cells indeed exhibited pDC phenotypic and functional properties. In 7 of 8 other patients with CD4(+)CD56(+) pDC malignancies, we were able to confirm that the tumor cells expressed CD33 although with variable expression levels. CD33 expression was shown by flow cytometry, reverse transcriptase-polymerase chain reaction, and immunoblot analysis. Furthermore, CD33 monoclonal antibody stimulation of purified CD4(+)CD56(+) leukemic cells led to cytokine secretion, thus confirming the presence of a functional CD33 on these leukemic cells. Moreover, we found that circulating pDCs in healthy individuals also weakly express CD33. Overall, our results demonstrate that the expression of CD33 on CD4(+)CD56(+) lineage-negative cells should not exclude the diagnosis of pDC leukemia and underline that pDC-specific markers should be used at diagnosis for CD4(+)CD56(+) malignancies.

Overexpression, purification, crystallization and preliminary structural studies of p-coumaric acid decarboxylase from Lactobacillus plantarum

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

Rodríguez, Héctor; Rivas, Blanca de las; Muñoz, Rosario

2007-04-01

The enzyme p-coumaric acid decarboxylase (PDC) from L. plantarum has been recombinantly expressed, purified and crystallized. The structure has been solved at 2.04 Å resolution by the molecular-replacement method. The substrate-inducible p-coumaric acid decarboxylase (PDC) from Lactobacillus plantarum has been overexpressed in Escherichia coli, purified and confirmed to possess decarboxylase activity. The recombinant His{sub 6}-tagged enzyme was crystallized using the hanging-drop vapour-diffusion method from a solution containing 20%(w/v) PEG 4000, 12%(w/v) 2-propanol, 0.2 M sodium acetate, 0.1 M Tris–HCl pH 8.0 with 0.1 M barium chloride as an additive. Diffraction data were collected in-house to 2.04 Å resolution. Crystals belongedmore » to the tetragonal space group P4{sub 3}, with unit-cell parameters a = b = 43.15, c = 231.86 Å. The estimated Matthews coefficient was 2.36 Å{sup 3} Da{sup −1}, corresponding to 48% solvent content, which is consistent with the presence of two protein molecules in the asymmetric unit. The structure of PDC has been determined by the molecular-replacement method. Currently, the structure of PDC complexed with substrate analogues is in progress, with the aim of elucidating the structural basis of the catalytic mechanism.« less

Fe2P as a novel efficient catalyst promoter in Pd/C system for formic acid electro-oxidation in fuel cells reaction

NASA Astrophysics Data System (ADS)

Wang, Fulong; Xue, Huaiguo; Tian, Zhiqun; Xing, Wei; Feng, Ligang

2018-01-01

Developing catalyst promoter for Pd/C catalyst is significant for the catalytic ability improvement in energy transfer related electrochemical reactions. Herein, we demonstrate Fe2P as an efficient catalyst promoter in Pd/C catalyst system for formic acid electro-oxidation in fuel cells reactions. Adding Fe2P in the Pd/C catalyst system greatly increases the performances for formic acid oxidation by 3-4 times; the CO stripping technique displays two kinds of active sites formation in the Pd-Fe2P/C catalyst system coming from the interaction of Pd, Fe2P and Pd oxide species and both are more efficient for formic acid and CO-species electrooxidation. The smaller charge transfer resistance and Tafel slope for formic acid oxidation indicate the improvements in kinetics by Fe2P in the Pd-Fe2P/C system. The nanostructured hybrid units of Pd, Fe2P and carbon are evidently visible in the high resolution microscopy images and XPS technique confirmes the electronic effect in the catalyst system. The promotion effect of Fe2P in the catalyst system arising from the structure, composition and electronic effect changes is discussed with the help from multiple physical and electrochemical techniques. It is concluded that Fe2P as a significant catalyst promoter will have potential application in energy transfer related electrochemical reactions.

Cerebrovascular recovery after stroke with individual and combined losartan and captopril treatment of SHRsp.

PubMed

Smeda, John S; Daneshtalab, Noriko

2017-09-01

We assessed whether the superior restoration of cerebrovascular function after hemorrhagic stroke by losartan versus captopril treatment was due to better BP, uremia, uricaemia, or aldosterone control in Kyoto Wistar stroke-prone-hypertensive rats and evaluated whether elevated angiotensin II (A2) levels enhanced the effectiveness of losartan treatment. Constriction was studied in the middle cerebral arteries (MCAs) using a pressure myograph. Post-stroke survival increased from 21 to 310 and 189days respectively with losartan and captopril treatment. Neither treatment reduced BP, both reversed uremia and hyperaldosteronism equally after 7days. Plasma uric acid remained low. At stroke, MCA constriction to pressure (PDC), protein kinase C (PKC) activation, depolarization, and sarcoplasmic Ca 2+ were attenuated. Endothelial-dependent-vasodilation by bradykinin and endogenous NO release were lost. Both treatments recovered these functions within 7days. These functions deteriorated after 116days of captopril but not losartan treatment. Inhibiting A2 formation during losartan treatment didn't alter BP or vascular recovery. The superior recovery of PDC by losartan over captopril was not produced by better BP, uremia or aldosterone control or elevated A2. PDC recovery was associated with improved PKC function and enhanced basal NO release. The re-establishment of PDC could reduce cerebrovascular over-perfusion and hematoma expansion after stroke. Copyright © 2017 Elsevier Inc. All rights reserved.

Long-term Safety of Dichloroacetate in Congenital Lactic Acidosis

PubMed Central

Abdelmalak, Monica; Lew, Alicia; Ramezani, Ryan; Shroads, Albert L.; Coats, Bonnie S.; Langaee, Taimour; Shankar, Meena N.; Neiberger, Richard E.; Subramony, S.H.; Stacpoole, Peter W.

2013-01-01

We followed 8 patients (4 males) with biochemically and/or molecular genetically proven deficiencies of the E1α subunit of the pyruvate dehydrogenase complex (PDC; 3 patients) or respiratory chain complexes I (1 patient), IV (3 patients) or I+IV (1 patient) who received oral dichloroacetate (DCA; 12.5 mg/kg/12 hours) for 9.7 to 16.5 years. All subjects originally participated in randomized controlled trials of DCA and were continued on an open-label chronic safety study. Patients (1 adult) ranged in age from 3.5 to 40.2 years at the start of DCA administration and are currently aged 16.9 to 49.9 years (mean ± SD: 23.5 ± 10.9 years). Subjects were either normal or below normal body weight for age and gender. The 3 PDC deficient patients did not consume high fat (ketogenic) diets. DCA maintained normal blood lactate concentrations, even in PDC deficient children on essentially unrestricted diets. Hematological, electrolyte, renal and hepatic status remained stable. Nerve conduction either did not change or decreased modestly and led to reduction or temporary discontinuation of DCA in 3 patients, although symptomatic worsening of peripheral neuropathy did not occur. We conclude that chronic DCA administration is generally well-tolerated in patients with congenital causes of lactic acidosis and is effective in maintaining normal blood lactate levels, even in PDC-deficient children not consuming strict ketogenic diets. PMID:23611579

Human Pyruvate Dehydrogenase Complex E2 and E3BP Core Subunits: New Models and Insights from Molecular Dynamics Simulations.

PubMed

Hezaveh, Samira; Zeng, An-Ping; Jandt, Uwe

2016-05-19

Targeted manipulation and exploitation of beneficial properties of multienzyme complexes, especially for the design of novel and efficiently structured enzymatic reaction cascades, require a solid model understanding of mechanistic principles governing the structure and functionality of the complexes. This type of system-level and quantitative knowledge has been very scarce thus far. We utilize the human pyruvate dehydrogenase complex (hPDC) as a versatile template to conduct corresponding studies. Here we present new homology models of the core subunits of the hPDC, namely E2 and E3BP, as the first time effort to elucidate the assembly of hPDC core based on molecular dynamic simulation. New models of E2 and E3BP were generated and validated at atomistic level for different properties of the proteins. The results of the wild type dimer simulations showed a strong hydrophobic interaction between the C-terminal and the hydrophobic pocket which is the main driving force in the intertrimer binding and the core self-assembly. On the contrary, the C-terminal truncated versions exhibited a drastic loss of hydrophobic interaction leading to a dimeric separation. This study represents a significant step toward a model-based understanding of structure and function of large multienzyme systems like PDC for developing highly efficient biocatalyst or bioreaction cascades.

Spatial imaging of carbon reactivity centers in Pd/C catalytic systems† †Electronic supplementary information (ESI) available: Detailed experimental procedures and FE-SEM images. See DOI: 10.1039/c5sc00802f

PubMed Central

Pentsak, E. O.; Kashin, A. S.; Polynski, M. V.; Kvashnina, K. O.; Glatzel, P.

2015-01-01

Gaining insight into Pd/C catalytic systems aimed at locating reactive centers on carbon surfaces, revealing their properties and estimating the number of reactive centers presents a challenging problem. In the present study state-of-the-art experimental techniques involving ultra high resolution SEM/STEM microscopy (1 Å resolution), high brilliance X-ray absorption spectroscopy and theoretical calculations on truly nanoscale systems were utilized to reveal the role of carbon centers in the formation and nature of Pd/C catalytic materials. Generation of Pd clusters in solution from the easily available Pd2dba3 precursor and the unique reactivity of the Pd clusters opened an excellent opportunity to develop an efficient procedure for the imaging of a carbon surface. Defect sites and reactivity centers of a carbon surface were mapped in three-dimensional space with high resolution and excellent contrast using a user-friendly nanoscale imaging procedure. The proposed imaging approach takes advantage of the specific interactions of reactive carbon centers with Pd clusters, which allows spatial information about chemical reactivity across the Pd/C system to be obtained using a microscopy technique. Mapping the reactivity centers with Pd markers provided unique information about the reactivity of the graphene layers and showed that >2000 reactive centers can be located per 1 μm2 of the surface area of the carbon material. A computational study at a PBE-D3-GPW level differentiated the relative affinity of the Pd2 species to the reactive centers of graphene. These findings emphasized the spatial complexity of the carbon material at the nanoscale and indicated the importance of the surface defect nature, which exhibited substantial gradients and variations across the surface area. The findings show the crucial role of the structure of the carbon support, which governs the formation of Pd/C systems and their catalytic activity. PMID:29511504

Profiling of sperm proteins and association of sperm PDC-109 with bull fertility.

PubMed

Somashekar, Lakshminarayana; Selvaraju, Sellappan; Parthipan, Sivashanmugam; Ravindra, Janivara Parameswaraiah

2015-01-01

The composition of sperm proteins influences the fertilizing ability of sperm and hence the present study was conducted (i) to profile sperm proteins expression patterns in bulls of differing fertility index and (ii) to identify and relate the abundant sperm proteins with bull fertility. The semen samples were collected from Holstein-Friesian bulls (n = 12) varying in conception rate (CR) (high/low). The frozen semen straws (three ejaculates, from each bull) were used to study (a) sperm kinetic parameters, (b) plasmalemma integrity, (c) mitochondrial membrane potential, and (d) chromatin distribution. Three bulls were randomly selected from each group (n = 3) and the neat sperm pellets were subjected to percoll purification, followed by protein isolation using 0.1% Triton X100. The sperm kinetic parameters, plasmalemma integrity, mitochondrial membrane potential, and the chromatin distribution did not differ significantly between groups. The number of acidic (pI; 3.1-5.6, 37%) and basic (pI; 7.9-10.0, 27%) proteins and their pattern of expression varied significantly (p < 0.05) between high and low fertile bulls. The abundant sperm protein spots in 2D-gel electrophoresis (2DE) were identified as seminal plasma protein PDC-109 (i.e., protein with N-terminus aspartic acid, D and carboxy terminus cystine, having 109 amino acids) and its isoform and spermadhesin-1 (SPADH1). The western blot analysis confirmed the presence of PDC-109 isoform proteins at 15.4 kDa (pI 5.3 and 5.5). The seminal plasma protein PDC-109 was abundant in the low fertile when compared to the high fertile group (p < 0.05). This study suggests that the imbalance in acidic and basic sperm proteins may influence sperm fertility and sperm PDC-109 levels above a certain threshold affects bull fertility.

Sensing of Immature Particles Produced by Dengue Virus Infected Cells Induces an Antiviral Response by Plasmacytoid Dendritic Cells

PubMed Central

Hillaire, Marine L. B.; Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Screaton, Gavin R.; Davidson, Andrew D.; Dreux, Marlène

2014-01-01

Dengue virus (DENV) is the leading cause of mosquito-borne viral illness and death in humans. Like many viruses, DENV has evolved potent mechanisms that abolish the antiviral response within infected cells. Nevertheless, several in vivo studies have demonstrated a key role of the innate immune response in controlling DENV infection and disease progression. Here, we report that sensing of DENV infected cells by plasmacytoid dendritic cells (pDCs) triggers a robust TLR7-dependent production of IFNα, concomitant with additional antiviral responses, including inflammatory cytokine secretion and pDC maturation. We demonstrate that unlike the efficient cell-free transmission of viral infectivity, pDC activation depends on cell-to-cell contact, a feature observed for various cell types and primary cells infected by DENV, as well as West Nile virus, another member of the Flavivirus genus. We show that the sensing of DENV infected cells by pDCs requires viral envelope protein-dependent secretion and transmission of viral RNA. Consistently with the cell-to-cell sensing-dependent pDC activation, we found that DENV structural components are clustered at the interface between pDCs and infected cells. The actin cytoskeleton is pivotal for both this clustering at the contacts and pDC activation, suggesting that this structural network likely contributes to the transmission of viral components to the pDCs. Due to an evolutionarily conserved suboptimal cleavage of the precursor membrane protein (prM), DENV infected cells release uncleaved prM containing-immature particles, which are deficient for membrane fusion function. We demonstrate that cells releasing immature particles trigger pDC IFN response more potently than cells producing fusion-competent mature virus. Altogether, our results imply that immature particles, as a carrier to endolysosome-localized TLR7 sensor, may contribute to regulate the progression of dengue disease by eliciting a strong innate response. PMID:25340500

Pyroclastic flow hazard assessment at Somma-Vesuvius based on the geological record

NASA Astrophysics Data System (ADS)

Gurioli, L.; Sulpizio, R.; Cioni, R.; Sbrana, A.; Santacroce, R.; Luperini, W.; Andronico, D.

2010-11-01

During the past 22 ka of activity at Somma-Vesuvius, catastrophic pyroclastic density currents (PDCs) have been generated repeatedly. Examples are those that destroyed the towns of Pompeii and Ercolano in AD 79, as well as Torre del Greco and several circum-Vesuvian villages in AD 1631. Using new field data and data available from the literature, we delineate the area impacted by PDCs at Somma-Vesuvius to improve the related hazard assessment. We mainly focus on the dispersal, thickness, and extent of the PDC deposits generated during seven plinian and sub-plinian eruptions, namely, the Pomici di Base, Greenish Pumice, Pomici di Mercato, Pomici di Avellino, Pompeii Pumice, AD 472 Pollena, and AD 1631 eruptions. We present maps of the total thickness of the PDC deposits for each eruption. Five out of seven eruptions dispersed PDCs radially, sometimes showing a preferred direction controlled by the position of the vent and the paleotopography. Only the PDCs from AD 1631 eruption were influenced by the presence of the Mt Somma caldera wall which stopped their advance in a northerly direction. Most PDC deposits are located downslope of the pronounced break-in slope that marks the base of the Somma-Vesuvius cone. PDCs from the Pomici di Avellino and Pompeii Pumice eruptions have the most dispersed deposits (extending more than 20 km from the inferred vent). These deposits are relatively thin, normally graded, and stratified. In contrast, thick, massive, lithic-rich deposits are only dispersed within 7 to 8 km of the vent. Isopach maps and the deposit features reveal that PDC dispersal was strongly controlled by the intensity of the eruption (in terms of magma discharge rate), the position of the vent area with respect to the Mt Somma caldera wall, and the pre-existing topography. Facies characteristics of the PDC deposits appear to correlate with dispersal; the stratified facies are consistently dispersed more widely than the massive facies.

Directly assessing interpersonal RSA influences in the frequency domain: An illustration with generalized partial directed coherence.

PubMed

Liu, Siwei; Gates, Kathleen M; Blandon, Alysia Y

2018-06-01

Despite recent research indicating that interpersonal linkage in physiology is a common phenomenon during social interactions, and the well-established role of respiratory sinus arrhythmia (RSA) in socially facilitative physiological regulation, little research has directly examined interpersonal influences in RSA, perhaps due to methodological challenges in analyzing multivariate RSA data. In this article, we aim to bridge this methodological gap by introducing a new method for quantifying interpersonal RSA influences. Specifically, we show that a frequency-domain statistic, generalized partial directed coherence (gPDC), can be used to capture lagged relations in RSA between social partners without first estimating RSA for each person. We illustrate its utility by examining the relation between gPDC and marital conflict in a sample of married couples. Finally, we discuss how gPDC complements existing methods in the time domain and provide guidelines for choosing among these different statistical techniques. © 2018 Society for Psychophysiological Research.

The Dox-pDC - A murine conditionally immortalized plasmacytoid dendritic cell line with native immune profile

PubMed Central

Wiedemuth, Ralf; Binner, Aline; Navratiel, Katrin; Anastassiadis, Konstantinos; Brenner, Sebastian

2018-01-01

Plasmacytoid dendritic cells (pDC) constitute a very rare blood cell population and play a significant role in immune response and immune-mediated disorders. Investigations on primary pDCs are hindered not only due to their rarity but also because they represent a heterogeneous cell population which is difficult to culture ex vivo. We generated a conditionally immortalized pDC line (Dox-pDC) from mice with Doxycycline-inducible SV40 Large T Antigen with a comparable immune profile to primary pDCs. The Dox-pDC secrete pro- and anti-inflammatory cytokines upon Toll-like receptor 9 stimulation and upregulate their MHCI, MHCII and costimulatory molecules. Further, the Dox-pDC activate and polarize naïve T cells in vivo and in vitro in response to the model antigen Ovalbumin. Due to their long-term culture stability and their robust proliferation Dox-pDC represent a reliable alternative to primary mouse pDC. PMID:29489861

Investigating the effects of PDC cutters geometry on ROP using the Taguchi technique

NASA Astrophysics Data System (ADS)

Jamaludin, A. A.; Mehat, N. M.; Kamaruddin, S.

2017-10-01

At times, the polycrystalline diamond compact (PDC) bit’s performance dropped and affects the rate of penetration (ROP). The objective of this project is to investigate the effect of PDC cutter geometry and optimize them. An intensive study in cutter geometry would further enhance the ROP performance. The relatively extended analysis was carried out and four significant geometry factors have been identified that directly improved the ROP. Cutter size, back rake angle, side rake angle and chamfer angle are the stated geometry factors. An appropriate optimization technique that effectively controls all influential geometry factors during cutters manufacturing is introduced and adopted in this project. By adopting L9 Taguchi OA, simulation experiment is conducted by using explicit dynamics finite element analysis. Through a structure Taguchi analysis, ANOVA confirms that the most significant geometry to improve ROP is cutter size (99.16% percentage contribution). The optimized cutter is expected to drill with high ROP that can reduce the rig time, which in its turn, may reduce the total drilling cost.

The Dox-pDC - A murine conditionally immortalized plasmacytoid dendritic cell line with native immune profile.

PubMed

Thieme, Sebastian; Holzbaur, Alexander; Wiedemuth, Ralf; Binner, Aline; Navratiel, Katrin; Anastassiadis, Konstantinos; Brenner, Sebastian; Richter, Cornelia

2018-01-01

Plasmacytoid dendritic cells (pDC) constitute a very rare blood cell population and play a significant role in immune response and immune-mediated disorders. Investigations on primary pDCs are hindered not only due to their rarity but also because they represent a heterogeneous cell population which is difficult to culture ex vivo. We generated a conditionally immortalized pDC line (Dox-pDC) from mice with Doxycycline-inducible SV40 Large T Antigen with a comparable immune profile to primary pDCs. The Dox-pDC secrete pro- and anti-inflammatory cytokines upon Toll-like receptor 9 stimulation and upregulate their MHCI, MHCII and costimulatory molecules. Further, the Dox-pDC activate and polarize naïve T cells in vivo and in vitro in response to the model antigen Ovalbumin. Due to their long-term culture stability and their robust proliferation Dox-pDC represent a reliable alternative to primary mouse pDC.

Pyruvate decarboxylase provides growing pollen tubes with a competitive advantage in petunia.

PubMed

Gass, Nathalie; Glagotskaia, Tatiana; Mellema, Stefan; Stuurman, Jeroen; Barone, Mario; Mandel, Therese; Roessner-Tunali, Ute; Kuhlemeier, Cris

2005-08-01

Rapid pollen tube growth places unique demands on energy production and biosynthetic capacity. The aim of this work is to understand how primary metabolism meets the demands of such rapid growth. Aerobically grown pollen produce ethanol in large quantities. The ethanolic fermentation pathway consists of two committed enzymes: pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH). Because adh mutations do not affect male gametophyte function, the obvious question is why pollen synthesize an abundant enzyme if they could do just as well without. Using transposon tagging in Petunia hybrida, we isolated a null mutant in pollen-specific Pdc2. Growth of the mutant pollen tubes through the style is reduced, and the mutant allele shows reduced transmission through the male, when in competition with wild-type pollen. We propose that not ADH but rather PDC is the critical enzyme in a novel, pollen-specific pathway. This pathway serves to bypass pyruvate dehydrogenase enzymes and thereby maintain biosynthetic capacity and energy production under the unique conditions prevailing during pollen-pistil interaction.

Oral hyposensitization to poison ivy and poison oak.

PubMed

Marks, J G; Trautlein, J J; Epstein, W L; Laws, D M; Sicard, G R

1987-04-01

We evaluated the safety and efficacy of a 1:1 mixture of pentadecylcatechol (PDC) and heptadecylcatechol (HDC) diacetate in reducing hypersensitivity to poison ivy and poison oak. The study was double-blind, parallel, randomized, and placebo controlled. The 44 subjects receiving the active drug ingested a cumulative dose of 306.5 mg over a five-week period. Subsequently, 14 patients were continued on a maintenance phase, ingesting an additional 960 mg of drug. The PDC-HDC diacetate was well tolerated, with no significant side effects. Evaluation of efficacy compared poststudy and prestudy reactions to patch tests using urushiol in doses of 0.025, 0.05, 0.125, 0.25, and 0.5 micrograms applied to the forearm. The results indicated that the induction phase as well as the maintenance phase did not induce a statistically significant hyposensitivity to urushiol, and we were thus unable to decrease sensitivity to poison ivy and poison oak in humans using orally ingested PDC-HDC diacetate.

Technology Development and Field Trials of EGS Drilling Systems at Chocolate Mountain

DOE Data Explorer

Steven Knudsen

2012-01-01

Polycrystalline diamond compact (PDC) bits are routinely used in the oil and gas industry for drilling medium to hard rock but have not been adopted for geothermal drilling, largely due to past reliability issues and higher purchase costs. The Sandia Geothermal Research Department has recently completed a field demonstration of the applicability of advanced synthetic diamond drill bits for production geothermal drilling. Two commercially-available PDC bits were tested in a geothermal drilling program in the Chocolate Mountains in Southern California. These bits drilled the granitic formations with significantly better Rate of Penetration (ROP) and bit life than the roller cone bit they are compared with. Drilling records and bit performance data along with associated drilling cost savings are presented herein. The drilling trials have demonstrated PDC bit drilling technology has matured for applicability and improvements to geothermal drilling. This will be especially beneficial for development of Enhanced Geothermal Systems whereby resources can be accessed anywhere within the continental US by drilling to deep, hot resources in hard, basement rock formations.

Performance assessment study of the balloon-borne astronomical soft gamma-ray polarimeter PoGOLite

NASA Astrophysics Data System (ADS)

Arimoto, M.; Kanai, Y.; Ueno, M.; Kataoka, J.; Kawai, N.; Tanaka, T.; Yamamoto, K.; Takahashi, H.; Mizuno, T.; Fukazawa, Y.; Axelsson, M.; Kiss, M.; Marini Bettolo, C.; Carlson, P.; Klamra, W.; Pearce, M.; Chen, P.; Craig, B.; Kamae, T.; Madejski, G.; Ng, J. S. T.; Rogers, R.; Tajima, H.; Thurston, T. S.; Saito, Y.; Takahashi, T.; Gunji, S.; Bjornsson, C.-I.; Larsson, S.; Ryde, F.; Bogaert, G.; Varner, G.

2007-12-01

Measurements of polarization play a crucial role in the understanding of the dominant emission mechanism of astronomical sources. Polarized Gamma-ray Observer-Light version (PoGOLite) is a balloon-borne astronomical soft gamma-ray polarimeter at the 25 80 keV band. The PoGOLite detector consists of a hexagonal close-packed array of 217 Phoswich detector cells (PDCs) and side anti-coincidence shields (SASs) made of BGO crystals surrounding PDCs. Each PDC consists of a slow hollow scintillator, a fast scintillator and a BGO crystal that connects to a photomultiplier tube at the end. To examine the PoGOLite's capability and estimate the performance, we conducted experiments with the PDC using radioisotope 241Am. In addition, we compared this result with performance expected by Monte Carlo simulation with Geant4. As a result, we found that the actual PDC has the capability to detect a 100 m Crab source until 80 keV.

Cathode buffer composed of fullerene-ethylenediamine adduct for an organic solar cell

NASA Astrophysics Data System (ADS)

Kimoto, Yoshinori; Akiyama, Tsuyoshi; Fujita, Katsuhiko

2017-02-01

We developed a fullerene-ethylenediamine adduct (C60P-DC) for a cathode buffer material in organic bulk heterojunction solar cells, which enhance the open-circuit voltage (V oc). The evaporative spray deposition using ultra dilute solution (ESDUS) technique was employed to deposit the buffer layer onto the organic active layer to avoid damage during the deposition. By the insertion of a C60P-DC buffer layer, V oc and power conversion efficiency (PCE) were increased from 0.41 to 0.57 V and from 1.65 to 2.10%, respectively. The electron-only device with the C60P-DC buffer showed a much lower current level than that without the buffer, indicating that the V oc increase is caused not by vacuum level shift but by hole blocking. The curve fitting of current density-voltage (J-V) characteristics to the equivalent circuit with a single diode indicated that the decrease in reversed saturation current by hole blocking increased caused the V oc.

Detection and Correction of Step Discontinuities in Kepler Flux Time Series

NASA Technical Reports Server (NTRS)

Kolodziejczak, J. J.; Morris, R. L.

2011-01-01

PDC 8.0 includes an implementation of a new algorithm to detect and correct step discontinuities appearing in roughly one of every 20 stellar light curves during a given quarter. The majority of such discontinuities are believed to result from high-energy particles (either cosmic or solar in origin) striking the photometer and causing permanent local changes (typically -0.5%) in quantum efficiency, though a partial exponential recovery is often observed [1]. Since these features, dubbed sudden pixel sensitivity dropouts (SPSDs), are uncorrelated across targets they cannot be properly accounted for by the current detrending algorithm. PDC detrending is based on the assumption that features in flux time series are due either to intrinsic stellar phenomena or to systematic errors and that systematics will exhibit measurable correlations across targets. SPSD events violate these assumptions and their successful removal not only rectifies the flux values of affected targets, but demonstrably improves the overall performance of PDC detrending [1].

Synthesis and characterization of heterometallic uranyl pyridinedicarboxylate compounds

NASA Astrophysics Data System (ADS)

Jayasinghe, Ashini S.; Payne, Maurice K.; Forbes, Tori Z.

2017-10-01

The incorporation of transition metals into hybrid uranyl materials can result in more diverse structural topologies and variations in physical and chemical properties. To explore the impact of transition metals on the uranyl cation, five uranium containing bimetallic chain compounds, [(UO2)M(PDC)2(H2O)4]·4(H2O) (PDC = 2,6 pyridinedicarboxylate; M = Ni2+, Co2+, Fe2+, Zn2+, and Cu2+) were synthesized by evaporation of aqueous solutions at room temperature. The uranyl cation is complex by two PDC ligands and the transition metal cations bond to the complex to form a one-dimensional chain topology. The presence of the transition metal leads to the presence of a stronger uranyl oxo bonds as shown by the single-crystal X-ray diffraction data and the Raman spectra. Solid state diffuse reflectance UV/Visible spectra confirmed the presence of the transition metals in the structure by the broad bands that appeared at relevant wavelengths.

Bacterial synthesis of N-hydroxycinnamoyl phenethylamines and tyramines.

PubMed

Sim, Geun Young; Yang, So-Mi; Kim, Bong Gyu; Ahn, Joong-Hoon

2015-10-13

Hydroxycinnamic acids (HCAs) including cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, are C6-C3 phenolic compounds that are synthesized via the phenylpropanoid pathway. HCAs serve as precursors for the synthesis of lignins, flavonoids, anthocyanins, stilbenes and other phenolic compounds. HCAs can also be conjugated with diverse compounds including quinic acid, hydroxyl acids, and amines. Hydroxycinnamoyl (HC) amine conjugates such as N-HC tyramines and N-HC phenethylamines have been considered as potential starting materials to develop antiviral and anticancer drugs. We synthesized N-HC tyramines and N-HC phenethylamines using three different approaches in Escherichia coli. Five N-HC phenethylamines and eight N-HC tyramines were synthesized by feeding HCAs and phenethylamine or tyramine to E. coli harboring 4CL (encoding 4-coumarate CoA:ligase) and either SHT (encoding phenethylamine N-HC transferase) or THT (encoding tyramine N-HC transferase). Also, N-(p-coumaroyl) phenethylamine and N-(p-coumaroyl) tyramine were synthesized from p-coumaric acid using E. coli harboring an additional gene, PDC (encoding phenylalanine decarboxylase) or TDC (encoding tyrosine decarboxylase). Finally, we synthesized N-(p-coumaroyl) phenethylamine and N-(p-coumaroyl) tyramine from glucose by reconstructing the metabolic pathways for their synthesis in E. coli. Productivity was maximized by optimizing the cell concentration and incubation temperature. We reconstructed the metabolic pathways for synthesis of N-HC tyramines and N-HC phenethylamines by expressing several genes including 4CL, TST or SHT, PDC or TDC, and TAL (encoding tyrosine ammonia lyase) and engineering the shikimate metabolic pathway to increase endogenous tyrosine concentration in E. coli. Approximately 101.9 mg/L N-(p-coumaroyl) phenethylamine and 495.4 mg/L N-(p-coumaroyl) tyramine were synthesized from p-coumaric acid. Furthermore, 152.5 mg/L N-(p-coumaroyl) phenethylamine and 94.7 mg/L N-(p-coumaroyl) tyramine were synthesized from glucose.

Mass budget partitioning during explosive eruptions: insights from the 2006 paroxysm of Tungurahua volcano, Ecuador

NASA Astrophysics Data System (ADS)

Bernard, Julien; Eychenne, Julia; Le Pennec, Jean-Luc; Narváez, Diego

2016-08-01

How and how much the mass of juvenile magma is split between vent-derived tephra, PDC deposits and lavas (i.e., mass partition) is related to eruption dynamics and style. Estimating such mass partitioning budgets may reveal important for hazard evaluation purposes. We calculated the volume of each product emplaced during the August 2006 paroxysmal eruption of Tungurahua volcano (Ecuador) and converted it into masses using high-resolution grainsize, componentry and density data. This data set is one of the first complete descriptions of mass partitioning associated with a VEI 3 andesitic event. The scoria fall deposit, near-vent agglutinate and lava flow include 28, 16 and 12 wt. % of the erupted juvenile mass, respectively. Much (44 wt. %) of the juvenile material fed Pyroclastic Density Currents (i.e., dense flows, dilute surges and co-PDC plumes), highlighting that tephra fall deposits do not depict adequately the size and fragmentation processes of moderate PDC-forming event. The main parameters controlling the mass partitioning are the type of magmatic fragmentation, conditions of magma ascent, and crater area topography. Comparisons of our data set with other PDC-forming eruptions of different style and magma composition suggest that moderate andesitic eruptions are more prone to produce PDCs, in proportions, than any other eruption type. This finding may be explained by the relatively low magmatic fragmentation efficiency of moderate andesitic eruptions. These mass partitioning data reveal important trends that may be critical for hazard assessment, notably at frequently active andesitic edifices.

New horizons in microbiological food safety: Photodynamic Decontamination based on a curcumin derivative.

PubMed

Glueck, Michael; Schamberger, Barbara; Eckl, Peter; Plaetzer, Kristjan

2017-12-06

Outbreaks of foodborne diseases are regularly reported worldwide. In particular, uncooked plant food is considered risky in terms of microbiological safety. Food is also the most important transmission route for resistant microorganisms from animals to humans. Photodynamic Decontamination (PDc) of foodstuff was recently introduced as a novel approach for increasing microbiological food safety. We investigated the efficiency of PDc on plant food with different geometries (flat, spherical and complex) using a two-dimensional LED array as a light source (435 nm, 33.8 J cm -2 ) and the cationic curcumin derivative SACUR-3 as a photosensitiser. A photoantibacterial effect (>3 log 10 CFU reduction) was achieved on all flat substrates (slices of cucumber, tomato and lettuce) with 10 μM, 50 μM or 100 μM SACUR-3. The maximal photokilling with a relative inactivation of 5.6 log 10 was measured on lettuce using 50 μM of the photoactive compound. Phototreatment of non-germinated fenugreek seeds and mung beans was successful if the spherical objects were rotated while under illumination (antibacterial effect at 100 μM SACUR-3). The decontamination of mung bean germlings with a more complex geometry using the PDc approach was ineffective with the two-dimensional light source. In conclusion, PDc based on the cationic curcumin derivative SACUR-3 is very effective at improving the microbiological safety of plant food with a flat or spherical geometry. More complex objects will require the development of novel illumination devices.

Effect of Foot-and-Mouth Disease Virus Infection on the Frequency, Phenotype and Function of Circulating Dendritic Cells in Cattle

PubMed Central

Sei, Janet J.; Waters, Ryan A.; Kenney, Mary; Barlow, John W.; Golde, William T.

2016-01-01

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that causes one of the most devastating diseases in cloven-hoofed animals. Disease symptoms develop within 2 to 3 days of exposure and include fever and vesicular lesions on the tongue and hooves. Dendritic cells (DC) play an essential role in protective immune responses against pathogens. Therefore, investigating their role during FMDV infection would lead to a better understanding of host-pathogen interactions. In this study, following infection of cattle with FMDV, we investigated the frequency and function of conventional (cDC) and plasmacytoid DC (pDC) in blood by using multi-color flow cytometry. We show that the frequency of cDC and pDC increased following FMDV infection and peaked 3 to 4 days post-infection. During peak viremia, the cattle became lymphopenic, the expression of MHC class II molecules on cDC and pDC was dramatically down-regulated, the processing of exogenous antigen by cDC and pDC was impaired, and there was an increase in IL-10 production by DC and monocytes. Notably, after clearance of FMDV from the blood, MHC class II expression returned to pre-infection levels. Altogether, our study demonstrates that in cattle, FMDV inhibits the function of DC, thereby retarding the initiation of adaptive immune responses, potentially enhancing virus shedding during the acute phase of infection. PMID:27008425

Predialysis Cardiovascular Disease Medication Adherence and Mortality After Transition to Dialysis.

PubMed

Molnar, Miklos Z; Gosmanova, Elvira O; Sumida, Keiichi; Potukuchi, Praveen K; Lu, Jun Ling; Jing, Jennie; Ravel, Vanessa A; Soohoo, Melissa; Rhee, Connie M; Streja, Elani; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2016-10-01

Medication nonadherence is a known risk factor for adverse outcomes in the general population. However, little is known about the association of predialysis medication adherence among patients with advanced chronic kidney disease and mortality following their transition to dialysis. Observational study. 32,348 US veterans who transitioned to dialysis during 2007 to 2011. Adherence to treatment with cardiovascular drugs, ascertained from pharmacy database records using proportion of days covered (PDC) and persistence during the predialysis year. Post-dialysis therapy initiation all-cause and cardiovascular mortality, using Cox models with adjustment for confounders. Mean age of the cohort was 72±11 (SD) years; 96% were men, 74% were white, 23% were African American, and 69% had diabetes. During a median follow-up of 23 (IQR, 9-36) months, 18,608 patients died. Among patients with PDC>80%, there were 14,006 deaths (mortality rate, 283 [95% CI, 278-288]/1,000 patient-years]); among patients with PDC>60% to 80%, there were 3,882 deaths (mortality rate, 294 [95% CI, 285-304]/1,000 patient-years); among patients with PDC≤60%, there were 720 deaths (mortality rate, 291 [95% CI, 271-313]/1,000 patient-years). Compared with patients with PDC>80%, the adjusted HR for post-dialysis therapy initiation all-cause mortality for patients with PDC>60% to 80% was 1.12 (95% CI, 1.08-1.16), and for patients with PDC≤60% was 1.21 (95% CI, 1.11-1.30). In addition, compared with patients showing medication persistence, adjusted HR risk for post-dialysis therapy initiation all-cause mortality for patients with nonpersistence was 1.11 (95% CI, 1.05-1.16). A similar trend was detected for cardiovascular mortality and in subgroup analyses. Large number of missing values; results may not be generalizable to women or the general US population. Predialysis cardiovascular medication nonadherence is an independent risk factor for postdialysis mortality in patients with advanced chronic kidney disease transitioning to dialysis therapy. Further studies are needed to assess whether interventions targeting adherence improve survival after dialysis therapy initiation. Published by Elsevier Inc.

Using machine learning to examine medication adherence thresholds and risk of hospitalization.

PubMed

Lo-Ciganic, Wei-Hsuan; Donohue, Julie M; Thorpe, Joshua M; Perera, Subashan; Thorpe, Carolyn T; Marcum, Zachary A; Gellad, Walid F

2015-08-01

Quality improvement efforts are frequently tied to patients achieving ≥80% medication adherence. However, there is little empirical evidence that this threshold optimally predicts important health outcomes. To apply machine learning to examine how adherence to oral hypoglycemic medications is associated with avoidance of hospitalizations, and to identify adherence thresholds for optimal discrimination of hospitalization risk. A retrospective cohort study of 33,130 non-dual-eligible Medicaid enrollees with type 2 diabetes. We randomly selected 90% of the cohort (training sample) to develop the prediction algorithm and used the remaining (testing sample) for validation. We applied random survival forests to identify predictors for hospitalization and fit survival trees to empirically derive adherence thresholds that best discriminate hospitalization risk, using the proportion of days covered (PDC). Time to first all-cause and diabetes-related hospitalization. The training and testing samples had similar characteristics (mean age, 48 y; 67% female; mean PDC=0.65). We identified 8 important predictors of all-cause hospitalizations (rank in order): prior hospitalizations/emergency department visit, number of prescriptions, diabetes complications, insulin use, PDC, number of prescribers, Elixhauser index, and eligibility category. The adherence thresholds most discriminating for risk of all-cause hospitalization varied from 46% to 94% according to patient health and medication complexity. PDC was not predictive of hospitalizations in the healthiest or most complex patient subgroups. Adherence thresholds most discriminating of hospitalization risk were not uniformly 80%. Machine-learning approaches may be valuable to identify appropriate patient-specific adherence thresholds for measuring quality of care and targeting nonadherent patients for intervention.

An Industry/DOE Program to Develop and Benchmark Advanced Diamond Product Drill Bits and HP/HT Drilling Fluids to Significantly Improve Rates of Penetration

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

TerraTek

2007-06-30

A deep drilling research program titled 'An Industry/DOE Program to Develop and Benchmark Advanced Diamond Product Drill Bits and HP/HT Drilling Fluids to Significantly Improve Rates of Penetration' was conducted at TerraTek's Drilling and Completions Laboratory. Drilling tests were run to simulate deep drilling by using high bore pressures and high confining and overburden stresses. The purpose of this testing was to gain insight into practices that would improve rates of penetration and mechanical specific energy while drilling under high pressure conditions. Thirty-seven test series were run utilizing a variety of drilling parameters which allowed analysis of the performance ofmore » drill bits and drilling fluids. Five different drill bit types or styles were tested: four-bladed polycrystalline diamond compact (PDC), 7-bladed PDC in regular and long profile, roller-cone, and impregnated. There were three different rock types used to simulate deep formations: Mancos shale, Carthage marble, and Crab Orchard sandstone. The testing also analyzed various drilling fluids and the extent to which they improved drilling. The PDC drill bits provided the best performance overall. The impregnated and tungsten carbide insert roller-cone drill bits performed poorly under the conditions chosen. The cesium formate drilling fluid outperformed all other drilling muds when drilling in the Carthage marble and Mancos shale with PDC drill bits. The oil base drilling fluid with manganese tetroxide weighting material provided the best performance when drilling the Crab Orchard sandstone.« less

Theoretical studies of chemisorption and dimer model systems: Moller-Plesset and configuration interaction calculations on PdH, PdC, PdO, PdF, Pd sub 2 , and PdCO

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

Schwerdtfeger, P.; McFeaters, J.S.; Moore, J.J.

1991-01-01

Ab initio SCF studies have been performed to study the molecular properties of several single-bonded palladium compounds, PdH, PdC, PdO, PdF, Pd{sub 2}, and PdCO, which are important in surface and materials science. Electron correlation effects were evaluated by a second- and third-order Moller-Plesset (MP) perturbation theory and a size-consistency-corrected configuration interaction with single and double substitutions (CISC). Relativistic effects were investigated for PdH and PdF. The ground state of PdC has been calculated at the CISC level to be a {sup 3}{Pi} state which is only 0.26 eV below the {sup 3}{Sigma}{sup {minus}} state (previously assigned ground state) andmore » 0.51 eV below the {sup 1}{Sigma}{sup +} state. PdC is predicted to be stable in the gas phase, and the possibility of preparing this compound is investigated. The bonding in CO chemisorbed on palladium is studied by using the model Pd-CO system. The effect of d{sub {pi}}-{pi}{sup *} back-bonding, discussed at the Hartree-Fock and CI level, is compared with results from multiple-scattering {Chi}{alpha} calculations. The C-O stretching frequency shift for CO on palladium was analyzed at various levels of theory, and the results indicated that the decrease in the CO force constant associated with chemisorption is not solely the result of d{sub {pi}}-{pi}{sup *} back-bonding.« less

A Novel Methodology to Validate the Accuracy of Extraoral Dental Scanners and Digital Articulation Systems.

PubMed

Ellakwa, A; Elnajar, S; Littlefair, D; Sara, G

2018-05-03

The aim of the current study is to develop a novel method to investigate the accuracy of 3D scanners and digital articulation systems. An upper and a lower poured stone model were created by taking impression of fully dentate male (fifty years old) participant. Titanium spheres were added to the models to allow for an easily recognisable geometric shape for measurement after scanning and digital articulation. Measurements were obtained using a Coordinate Measuring Machine to record volumetric error, articulation error and clinical effect error. Three scanners were compared, including the Imetric 3D iScan d104i, Shining 3D AutoScan-DS100 and 3Shape D800, as well as their respective digital articulation software packages. Stoneglass Industries PDC digital articulation system was also applied to the Imetric scans for comparison with the CMM measurements. All the scans displayed low volumetric error (p⟩0.05), indicating that the scanners themselves had a minor contribution to the articulation and clinical effect errors. The PDC digital articulation system was found to deliver the lowest average errors, with good repeatability of results. The new measuring technique in the current study was able to assess the scanning and articulation accuracy of the four systems investigated. The PDC digital articulation system using Imetric scans was recommended as it displayed the lowest articulation error and clinical effect error with good repeatability. The low errors from the PDC system may have been due to its use of a 3D axis for alignment rather than the use of a best fit. Copyright© 2018 Dennis Barber Ltd.

Increase the risk of intellectual disability in children with scabies: A nationwide population-based cohort study.

PubMed

Liu, Jui-Ming; Hsu, Ren-Jun; Chang, Fung-Wei; Yeh, Chia-Lun; Huang, Chun-Fa; Chang, Shu-Ting; Chiu, Nan-Chang; Chang, Hung-Yang; Chi, Hsin; Lin, Chien-Yu

2017-06-01

Scabies is a common and distressing disease caused by the mite Sarcoptes scabiei var. hominis. Psychiatric disorder in childhood is an important disease and easily neglected. There are several similarities in scabies and psychiatric disorders in childhood (PDC). Both of them may present with pruritus. They are relatively common in patients with lower socioeconomic status and crowded environment. Furthermore, immune-mediated inflammatory processes play a role in the pathophysiology in both diseases. An association between scabies and psychiatric disorders may exist. This nationwide population-based cohort study utilized data from the National Health Insurance Research Database to investigate the relationship between scabies and PDC. A total of 2137 children with scabies were identified as the study group and 8548 age- and sex-matched children were selected as the control group. A total of 607 (5.68%) children developed PDC during the 7-year follow-up period. The overall incidences of PDC are similar but patients with scabies had a higher risk of developing intellectual disability (ID) (scabies group vs control group: 1.3% vs 0.6%, adjusted hazard ratio: 2.04 and 95% confidence interval: 1.25-3.32). The immune-mediated inflammatory processes of both diseases were reviewed and may contribute to the 104% increased risk of interleukin in patients with scabies. We suggest a more comprehensive management in treating patients with scabies or ID. Early and comprehensive treatment of scabies and other risk factors may decrease the risk of subsequent ID. When we approach patients with ID, concurrent evaluation of scabies and other risk factors may contribute to successful management.

Increase the risk of intellectual disability in children with scabies

PubMed Central

Liu, Jui-Ming; Hsu, Ren-Jun; Chang, Fung-Wei; Yeh, Chia-Lun; Huang, Chun-Fa; Chang, Shu-Ting; Chiu, Nan-Chang; Chang, Hung-Yang; Chi, Hsin; Lin, Chien-Yu

2017-01-01

Abstract Scabies is a common and distressing disease caused by the mite Sarcoptes scabiei var. hominis. Psychiatric disorder in childhood is an important disease and easily neglected. There are several similarities in scabies and psychiatric disorders in childhood (PDC). Both of them may present with pruritus. They are relatively common in patients with lower socioeconomic status and crowded environment. Furthermore, immune-mediated inflammatory processes play a role in the pathophysiology in both diseases. An association between scabies and psychiatric disorders may exist. This nationwide population-based cohort study utilized data from the National Health Insurance Research Database to investigate the relationship between scabies and PDC. A total of 2137 children with scabies were identified as the study group and 8548 age- and sex-matched children were selected as the control group. A total of 607 (5.68%) children developed PDC during the 7-year follow-up period. The overall incidences of PDC are similar but patients with scabies had a higher risk of developing intellectual disability (ID) (scabies group vs control group: 1.3% vs 0.6%, adjusted hazard ratio: 2.04 and 95% confidence interval: 1.25–3.32). The immune-mediated inflammatory processes of both diseases were reviewed and may contribute to the 104% increased risk of interleukin in patients with scabies. We suggest a more comprehensive management in treating patients with scabies or ID. Early and comprehensive treatment of scabies and other risk factors may decrease the risk of subsequent ID. When we approach patients with ID, concurrent evaluation of scabies and other risk factors may contribute to successful management. PMID:28591057

Enhancement of oxidation resistance of graphite foams by polymer derived-silicon carbide coating for concentrated solar power applications

DOE PAGES

Kim, T.; Singh, D.; Singh, M.

2015-05-01

Graphite foam with extremely high thermal conductivity has been investigated to enhance heat transfer of latent heat thermal energy storage (LHTES) systems. However, the use of graphite foam for elevated temperature applications (>600 °C) is limited due to poor oxidation resistance of graphite. In the present study, oxidation resistance of graphite foam coated with silicon carbide (SiC) was investigated. A pre-ceramic polymer derived coating (PDC) method was used to form a SiC coating on the graphite foams. Post coating deposition, the samples were analyzed by scanning electron microscopy and energy dispersive spectroscopy. The oxidation resistance of PDC-SiC coating was quantifiedmore » by measuring the weight of the samples at several measuring points. The experiments were conducted under static argon atmosphere in a furnace. After the experiments, oxidation rates (%/hour) were calculated to predict the lifetime of the graphite foams. The experimental results showed that the PDC-SiC coating could prevent the oxidation of graphite foam under static argon atmosphere up to 900 °C.« less

Hybrid NiCoOx adjacent to Pd nanoparticles as a synergistic electrocatalyst for ethanol oxidation

NASA Astrophysics Data System (ADS)

Wang, Wei; Yang, Yan; Liu, Yanqin; Zhang, Zhe; Dong, Wenkui; Lei, Ziqiang

2015-01-01

To improve the electrocatalytic activity of Pd for ethanol oxidation, hybrid NiCoOx adjacent to Pd catalyst (Pd-NiCoOx/C) is successfully synthesized. Physical characterization shows NiCoOx is closely adjacent to Pd nanoparticles in Pd-NiCoOx/C catalyst, which leads to Strong Metal-Support Interactions (SMSI) between the NiCoOx and Pd nanoparticles, in favor of the electrocatalytic properties. The Pd-NiCoOx/C catalyst is estimated to own larger electrochemically active surface area than Pd/C and Pd-NiO/C catalysts. Moreover, compared to Pd/C catalyst, the onset potential of Pd-NiCoOx/C catalyst is negative 40 mV for ethanol oxidation. Noticeably, the current density of Pd-NiCoOx/C catalyst is 2.05 and 1.43 times higher contrasted to Pd/C and Pd-NiO/C catalysts accordingly. Importantly, the Pd-NiCoOx/C catalyst exhibits better stability during ethanol oxidation, which is a promising electrocatalyst for application in direct alkaline alcohol fuel cells.

Pyruvate Decarboxylase Provides Growing Pollen Tubes with a Competitive Advantage in PetuniaW⃞

PubMed Central

Gass, Nathalie; Glagotskaia, Tatiana; Mellema, Stefan; Stuurman, Jeroen; Barone, Mario; Mandel, Therese; Roessner-Tunali, Ute; Kuhlemeier, Cris

2005-01-01

Rapid pollen tube growth places unique demands on energy production and biosynthetic capacity. The aim of this work is to understand how primary metabolism meets the demands of such rapid growth. Aerobically grown pollen produce ethanol in large quantities. The ethanolic fermentation pathway consists of two committed enzymes: pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH). Because adh mutations do not affect male gametophyte function, the obvious question is why pollen synthesize an abundant enzyme if they could do just as well without. Using transposon tagging in Petunia hybrida, we isolated a null mutant in pollen-specific Pdc2. Growth of the mutant pollen tubes through the style is reduced, and the mutant allele shows reduced transmission through the male, when in competition with wild-type pollen. We propose that not ADH but rather PDC is the critical enzyme in a novel, pollen-specific pathway. This pathway serves to bypass pyruvate dehydrogenase enzymes and thereby maintain biosynthetic capacity and energy production under the unique conditions prevailing during pollen–pistil interaction. PMID:15994907

Facile Aqueous Phase Synthesis of Pd3Cu-B/C Nanocatalyst for Glucose Electrooxidation

NASA Astrophysics Data System (ADS)

Chai, Dan; Lu, Haibin; Wang, Yaqian; Hua, Xiuwen; Ren, Na; Zhang, Xiongwen

2018-01-01

A novel Pd3Cu-B/C nanocatalyst was facilely synthesized through an aqueous phase process. And it was developed for use in the glucose electrooxidation reaction in fuel cells. Cyclic voltammetry shown that the electrochemical surface area of Pd3Cu-B/C is 2.25 times that of Pd/C. Glucose electrooxidation curves revealed that peak current on the Pd3Cu-B/C is actually 1.73 times of the Pd/C. This high performance of Pd3Cu-B/C could be ascribed to the synergistic effect between Pd, Cu and B.

Highly Unsaturated Platinum and Palladium Carbenes PtC 3 and PdC 3 Isolated and Characterized in the Gas Phase

DOE PAGES

Bittner, Dror M.; Zaleski, Daniel P.; Tew, David P.; ...

2016-02-16

Carbenes of platinum and palladium, PtC 3 and PdC 3 , were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and abinitio calculations confirm that both molecules are linear. The geometry of PtC 3 was accurately determined by fitting to the experimental moments of inertia of twenty-six isotopologues. In conclusion, the results are consistent with the proposal of an autogenic isolobal relationship between O, Au + , and Ptatoms.

Ash aggregation during the 11 February 2010 partial dome collapse of the Soufrière Hills Volcano, Montserrat

NASA Astrophysics Data System (ADS)

Burns, F. A.; Bonadonna, C.; Pioli, L.; Cole, P. D.; Stinton, A.

2017-04-01

On 11 February 2010, Soufrière Hills Volcano, Montserrat, underwent a partial dome collapse ( 50 × 106 m3) and a short-lived Vulcanian explosion towards the end. Three main pyroclastic units were identified N and NE of the volcano: dome-collapse pyroclastic density current (PDC) deposits, fountain-collapse PDC deposits formed by the Vulcanian explosion, and tephra-fallout deposits associated with elutriation from the dome-collapse and fountain-collapse PDCs (i.e. co-PDC fallout deposit). The fallout associated with the Vulcanian explosion was mostly dispersed E and SE by high altitude winds. All units N and NE of the volcano contain variable amounts and types of particle aggregates, although the co-PDC fallout deposit is associated with the largest abundance (i.e. up to 24 wt%). The size of aggregates found in the co-PDC fallout deposit increases with distance from the volcano and proximity to the sea, reaching a maximum diameter of 12 mm about 500 m from the coast. The internal grain size of all aggregates have nearly identical distributions (with Mdϕ ≈ 4-5), with particles in the size categories > 3 ϕ (i.e. < 250 μm) being distributed in similar proportions within the aggregates but in different proportions within distinct internal layers. In fact, most aggregates are characterized by a coarse grained central core occupying the main part of the aggregate, coated by a thin layer of finer ash (single-layer aggregates), while others have one or two additional layers accreted over the core (multiple-layer aggregates). Calculated aggregate porosity and settling velocity vary between 0.3 and 0.5 and 11-21 m s- 1, respectively. The aggregate size shows a clear correlation with both the core size and the size of the largest particles found in the core. The large abundance of aggregates in the co-PDC fallout deposits suggests that the buoyant plumes elutriated above PDCs represent an optimal environment for the formation (particle collision) and development (aggregate layering) of particle aggregates. However, specific conditions are required, including i) a large availability of water (in this case provided by the steam plumes associated with the entrance of PDCs into the ocean), ii) presence of plume regions with different grain-size features (i.e. both median size and sorting) that allows for the development of multiple layers, iii) strong turbulence that permits both particle collision and the transition of the aggregates through different plume regions, iv) presence of hot regions (e.g. PDCs) that promote aggregate preservation (in this case also facilitated by the presence of sea salt).

Field-trip guide for exploring pyroclastic density current deposits from the May 18, 1980, eruption of Mount St. Helens, Washington

USGS Publications Warehouse

Brand, Brittany D.; Pollock, Nicholas; Sarocchi, Damiano; Dufek, Josef; Clynne, Michael A.

2017-07-05

Pyroclastic density currents (PDCs) are one of the most dangerous phenomena associated with explosive volcanism. To help constrain damage potential, a combination of field studies, laboratory experiments, and numerical modeling are used to establish conditions that influence PDC dynamics and depositional processes, including runout distance. The objective of this field trip is to explore field relations that may constrain PDCs at the time of emplacement.The PDC deposits from the May 18, 1980, eruption of Mount St. Helens are well exposed along the steep flanks (10–30° slopes) and across the pumice plain (5–12° slopes) as far as 8 km north of the volcano. The pumice plain deposits represent deposition from a series of concentrated PDCs and are primarily thick (3–12 m), massive, and poorly sorted. In contrast, the steep east-flank deposits are stratified to cross-stratified, suggesting deposition from PDCs where turbulence strongly influenced transport and depositional processes.The PDCs that descended the west flank were largely nondepositional; they maintained a higher flow energy and carrying capacity than PDCs funneled through the main breach, as evidenced by the higher concentration of large blocks in their deposits. The PDC from the west flank collided with PDCs funneled through the breach at various points along the pumice plain. Evidence for flow collision will be explored and debated throughout the field trip.Evidence for substrate erosion and entrainment is found (1) along the steep eastern flank of the volcano, which has a higher degree of rough, irregular topography relative to the west flanks where PDCs were likely nonerosive, (2) where PDCs encountered debris-avalanche hummocks across the pumice plain, and (3) where PDCs eroded and entrained material deposited by PDCs produced during earlier phases of the eruption. Two features interpreted as large-scale (tens of meters wide) levees and a large (~200 m wide) channel scour-and-fill feature provide the first evidence of self-channelization within PDCs sustained for minutes to tens of minutes (total volume of deposits is ~0.12 km3; area covered is ~15.5 km2; Rowley and others, 1981).Our ability to interpret the deposits of PDCs is critical for understanding transport and depositional processes that control PDC dynamics. The results of extensive work on the May 18, 1980, PDC deposits show that slope and irregular topography strongly influence PDC flow path, dynamics, criticality (for example, supercritical versus subcritical), carrying capacity, and erosive capacity. However, the influence of these conditions on ultimate flow runout and damage potential warrants further exploration through the combination of field, experimental, and numerical approaches.

Monascus ruber as cell factory for lactic acid production at low pH.

PubMed

Weusthuis, Ruud A; Mars, Astrid E; Springer, Jan; Wolbert, Emil Jh; van der Wal, Hetty; de Vrije, Truus G; Levisson, Mark; Leprince, Audrey; Houweling-Tan, G Bwee; Pha Moers, Antoine; Hendriks, Sjon Na; Mendes, Odette; Griekspoor, Yvonne; Werten, Marc Wt; Schaap, Peter J; van der Oost, John; Eggink, Gerrit

2017-07-01

A Monascus ruber strain was isolated that was able to grow on mineral medium at high sugar concentrations and 175g/l lactic acid at pH 2.8. Its genome and transcriptomes were sequenced and annotated. Genes encoding lactate dehydrogenase (LDH) were introduced to accomplish lactic acid production and two genes encoding pyruvate decarboxylase (PDC) were knocked out to subdue ethanol formation. The strain preferred lactic acid to glucose as carbon source, which hampered glucose consumption and therefore also lactic acid production. Lactic acid consumption was stopped by knocking out 4 cytochrome-dependent LDH (CLDH) genes, and evolutionary engineering was used to increase the glucose consumption rate. Application of this strain in a fed-batch fermentation resulted in a maximum lactic acid titer of 190g/l at pH 3.8 and 129g/l at pH 2.8, respectively 1.7 and 2.2 times higher than reported in literature before. Yield and productivity were on par with the best strains described in literature for lactic acid production at low pH. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Chronic Exposure to Dietary Sterol Glucosides is Neurotoxic to Motor Neurons and Induces an ALS-PDC Phenotype

PubMed Central

Tabata, R. C.; Wilson, J. M. B.; Ly, P.; Zwiegers, P.; Kwok, D.; Van Kampen, J. M.; Cashman, N.; Shaw, C. A.

2008-01-01

Epidemiological studies of the Guamanian variants of amyotrophic lateral sclerosis (ALS) and parkinsonism, amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC), have shown a positive correlation between consumption of washed cycad seed flour and disease occurrence. Previous in vivo studies by our group have shown that the same seed flour induces ALS and PDC phenotypes in out bred adult male mice. In vitro studies using isolated cycad compounds have also demonstrated that several of these are neurotoxic, specifically, a number of water insoluble phytosterol glucosides of which β-sitosterol β-d-glucoside (BSSG) forms the largest fraction. BSSG is neurotoxic to motor neurons and other neuronal populations in culture. The present study shows that an in vitro hybrid motor neuron (NSC-34) culture treated with BSSG undergoes a dose-dependent cell loss. Surviving cells show increased expression of HSP70, decreased cytosolic heavy neurofilament expression, and have various morphological abnormalities. CD-1 mice fed mouse chow pellets containing BSSG for 15 weeks showed motor deficits and motor neuron loss in the lumbar and thoracic spinal cord, along with decreased glutamate transporter labelling, and increased glial fibrillary acid protein reactivity. Other pathological outcomes included increased caspase-3 labelling in the striatum and decreased tyrosine-hydroxylase labelling in the striatum and substantia nigra. C57BL/6 mice fed BSSG-treated pellets for 10 weeks exhibited progressive loss of motor neurons in the lumbar spinal cord that continued to worsen even after the BSSG exposure ended. These results provide further support implicating sterol glucosides as one potential causal factor in the motor neuron pathology previously associated with cycad consumption and ALS-PDC. PMID:18196479

Pyruvate Dehydrogenase Kinase-4 Structures Reveal a Metastable Open Conformation Fostering Robust Core-free Basal Activity

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

Wynn, R. Max; Kato, Masato; Chuang, Jacinta L.

2008-10-21

Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4. PDK4 is overexpressed in skeletal muscle in type 2 diabetes, resulting in impaired glucose utilization. Here we show that human PDK4 has robust core-free basal activity, which is considerably higher than activity levels of other PDK isoforms stimulated by the PDC core. PDK4 binds the L3 lipoyl domain, but its activity is not significantly stimulated by any individual lipoyl domains or the core of PDC. The 2.0-{angstrom} crystal structures of the PDK4 dimer with bound ADP reveal an open conformation with a wider active-site cleft, comparedmore » with that in the closed conformation epitomized by the PDK2-ADP structure. The open conformation in PDK4 shows partially ordered C-terminal cross-tails, in which the conserved DW (Asp{sup 394}-Trp{sup 395}) motif from one subunit anchors to the N-terminal domain of the other subunit. The open conformation fosters a reduced binding affinity for ADP, facilitating the efficient removal of product inhibition by this nucleotide. Alteration or deletion of the DW-motif disrupts the C-terminal cross-tail anchor, resulting in the closed conformation and the nearly complete inactivation of PDK4. Fluorescence quenching and enzyme activity data suggest that compounds AZD7545 and dichloroacetate lock PDK4 in the open and the closed conformational states, respectively. We propose that PDK4 with bound ADP exists in equilibrium between the open and the closed conformations. The favored metastable open conformation is responsible for the robust basal activity of PDK4 in the absence of the PDC core.« less

Electrophile-modified lipoic derivatives of PDC-E2 elicits anti-mitochondrial antibody reactivity.

PubMed

Naiyanetr, Phornnop; Butler, Jeffrey D; Meng, Liping; Pfeiff, Janice; Kenny, Thomas P; Guggenheim, Kathryn G; Reiger, Roman; Lam, Kit; Kurth, Mark J; Ansari, Aftab A; Coppel, Ross L; López-Hoyos, Marcos; Gershwin, M Eric; Leung, Patrick S C

2011-11-01

Our laboratory has hypothesized that xenobiotic modification of the native lipoyl moiety of the major mitochondrial autoantigen, the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), may lead to loss of self-tolerance in primary biliary cirrhosis (PBC). This thesis is based on the finding of readily detectable levels of immunoreactivity of PBC sera against extensive panels of protein microarrays containing mimics of the inner lipoyl domain of PDC-E2 and subsequent quantitative structure-activity relationships (QSARs). Importantly, we have demonstrated that murine immunization with one such mimic, 2-octynoic acid coupled to bovine serum albumin (BSA), induces anti-mitochondrial antibodies (AMAs) and cholangitis. Based upon these data, we have focused on covalent modifications of the lipoic acid disulfide ring and subsequent analysis of such xenobiotics coupled to a 15mer of PDC-E2 for immunoreactivity against a broad panel of sera from patients with PBC and controls. Our results demonstrate that AMA-positive PBC sera demonstrate marked reactivity against 6,8-bis(acetylthio)octanoic acid, implying that chemical modification of the lipoyl ring, i.e. disruption of the S-S disulfide, renders lipoic acid to its reduced form that will promote xenobiotic modification. This observation is particularly significant in light of the function of the lipoyl moiety in electron transport of which the catalytic disulfide constantly opens and closes and, thus, raises the intriguing thesis that common electrophilic agents, i.e. acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs), may lead to xenobiotic modification in genetically susceptible individuals that results in the generation of AMAs and ultimately clinical PBC. Copyright © 2011 Elsevier Ltd. All rights reserved.

History of psychosis and mania, and outcomes after kidney transplantation - a retrospective study.

PubMed

Molnar, Miklos Z; Eason, James D; Gaipov, Abduzhappar; Talwar, Manish; Potukuchi, Praveen K; Joglekar, Kiran; Remport, Adam; Mathe, Zoltan; Mucsi, Istvan; Novak, Marta; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

2018-05-01

History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients. © 2018 Steunstichting ESOT.

Dendritic cells in uninfected infants born to hepatitis B virus-positive mothers.

PubMed

Koumbi, Lemonica J; Papadopoulos, Nikolaos G; Anastassiadou, Vassiliki; Machaira, Maria; Kafetzis, Dimitris A; Papaevangelou, Vassiliki

2010-07-01

Plasmacytoid dendritic cells (pDCs) play a central role in antiviral immunity, detecting viruses via Toll-like receptors (TLR) and producing in response vast amounts of type I interferons (IFNs). Hepatitis B virus (HBV) causes chronic infection after vertical transmission. This study investigated whether an HBV-infected maternal environment might influence DC numbers and pDC function in uninfected infants. Blood was collected from inactive HBsAg carrier and control mothers and their infants at birth and 1 and 6 months of age. HBV DNA was measured in maternal and neonatal perinatal sera using real-time PCR. The circulating frequencies of myeloid DCs (mDCs) and pDCs were determined in the babies by flow cytometry. Peripheral blood mononuclear cells (PBMCs) and cord blood pDCs were stimulated with resiquimod, and alpha interferon (IFN-alpha) production and the pDC phenotype were assessed. The effect of the common-cold virus, rhinovirus (RV), on resiquimod stimulation was also determined. HBV DNA was detected in 62.3% of the mothers and 41% of their infants. DC numbers and pDC functions were similar between subjects and controls and were not correlated with maternal or neonatal viremia. RV infection did not induce pDC maturation until the age of 6 months, and it reduced TLR7-dependent resiquimod-induced IFN-alpha production similarly in both groups. Although the DC system is immature at birth, DCs of uninfected neonates of HBV-positive mothers are competent to initiate and maintain T-cell responses. RV is a weak inducer of IFN-alpha production until the age of 6 months and inhibits IFN-alpha responses triggered by the TLR7 pathway.

Co-C and Pd-C Fixed Points for the Evaluation of Facilities and Scales Realization at INRIM and NMC

NASA Astrophysics Data System (ADS)

Battuello, M.; Wang, L.; Girard, F.; Ang, S. H.

2014-04-01

Two hybrid cells for realizing the Co-C and Pd-C fixed points and constructed at Istituto Nazionale di Ricerca Metrologica (INRIM) were used for an evaluation of facilities and procedures adopted by INRIM and National Metrology Institute of Singapore (NMC) for the realization of the solid-liquid phase transitions of high-temperature fixed points and for determining their transition temperatures. Four different furnaces were used for the investigations, i.e., two single-zone furnaces, one of them of the direct-heating type, and two identical three-zone furnaces. The transition temperatures were measured at both institutes by adopting different procedures for realizing the radiation scales, i.e., at INRIM a scheme based on the extrapolation of fixed-point interpolated scales and an International Temperature Scale of 1990 (ITS-90) approach at NMC. The point of inflection (POI) of the melting curves was determined and assumed as a practical representation of the melting temperature. Different methods for deriving the POI were used, and differences as large as some hundredths of a kelvin were found with the different approaches. The POIs of the different melting curves were analyzed with respect to the different possible operative conditions with the aim of deriving reproducibility figures to improve the estimated uncertainty. As regard to the institutes inter-comparison, differences of 0.13 K and 0.29 K were found between INRIM and NMC determinations at the Co-C and Pd-C points, respectively. Such differences are compatible with the combined standard uncertainties of the comparison, which are estimated to be 0.33 K and 0.36 K at the Co-C and Pd-C points, respectively.

Caregiver outcomes of partners in dementia care: effect of a care coordination program for veterans with dementia and their family members and friends.

PubMed

Bass, David M; Judge, Katherine S; Snow, A Lynn; Wilson, Nancy L; Morgan, Robert; Looman, Wendy J; McCarthy, Catherine A; Maslow, Katie; Moye, Jennifer A; Randazzo, Ronda; Garcia-Maldonado, Maurilio; Elbein, Richard; Odenheimer, Germaine; Kunik, Mark E

2013-08-01

The objective is to test the effectiveness of Partners in Dementia Care (PDC), a care-coordination program that integrates and improves access to medical and nonmedical services, while strengthening the informal care network and providing information, coaching, and emotional support. PDC was delivered via a partnership between Veterans Affairs (VA) Medical Centers (VAMCs) and Alzheimer's Association chapters, for caregivers of veterans with dementia living in the community and receiving primary care from the VA. The initial sample was 486 caregivers of 508 veterans with diagnosed dementia. Outcomes were evaluated for 394 and 324 caregivers who completed 6- and 12- month follow-up, respectively. PDC had a standardized protocol that included assessment and reassessment, action planning, and ongoing monitoring. It was delivered by telephone and e-mail for cost efficiency and the ability to handle caseloads of 100 to 125. Care coordinators from VAMCs and Alzheimer's Association chapters worked as a team using a shared computerized record. A variety of caregiver outcomes was measured after 6 and 12 months. Intervention group caregivers had significant improvements in outcomes representing unmet needs, three types of caregiver strains, depression, and two support resources. Most improvements were evident after 6 months, with more-limited improvements from Months 6 to 12. Some outcomes improved for all caregivers, whereas some improved for caregivers experiencing more initial difficulties or caring for veterans with more-severe impairments. PDC is a promising model that improves linkages between healthcare services and community services, which is a goal of several new national initiatives such as the National Plan to Address Alzheimer's Disease and a proposed amendment to the Older Americans Act. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Tracking the time-varying cortical connectivity patterns by adaptive multivariate estimators.

PubMed

Astolfi, L; Cincotti, F; Mattia, D; De Vico Fallani, F; Tocci, A; Colosimo, A; Salinari, S; Marciani, M G; Hesse, W; Witte, H; Ursino, M; Zavaglia, M; Babiloni, F

2008-03-01

The directed transfer function (DTF) and the partial directed coherence (PDC) are frequency-domain estimators that are able to describe interactions between cortical areas in terms of the concept of Granger causality. However, the classical estimation of these methods is based on the multivariate autoregressive modelling (MVAR) of time series, which requires the stationarity of the signals. In this way, transient pathways of information transfer remains hidden. The objective of this study is to test a time-varying multivariate method for the estimation of rapidly changing connectivity relationships between cortical areas of the human brain, based on DTF/PDC and on the use of adaptive MVAR modelling (AMVAR) and to apply it to a set of real high resolution EEG data. This approach will allow the observation of rapidly changing influences between the cortical areas during the execution of a task. The simulation results indicated that time-varying DTF and PDC are able to estimate correctly the imposed connectivity patterns under reasonable operative conditions of signal-to-noise ratio (SNR) ad number of trials. An SNR of five and a number of trials of at least 20 provide a good accuracy in the estimation. After testing the method by the simulation study, we provide an application to the cortical estimations obtained from high resolution EEG data recorded from a group of healthy subject during a combined foot-lips movement and present the time-varying connectivity patterns resulting from the application of both DTF and PDC. Two different cortical networks were detected with the proposed methods, one constant across the task and the other evolving during the preparation of the joint movement.

Pyruvate dehydrogenase kinase-4 structures reveal a metastable open conformation fostering robust core-free basal activity.

PubMed

Wynn, R Max; Kato, Masato; Chuang, Jacinta L; Tso, Shih-Chia; Li, Jun; Chuang, David T

2008-09-12

Human pyruvate dehydrogenase complex (PDC) is down-regulated by pyruvate dehydrogenase kinase (PDK) isoforms 1-4. PDK4 is overexpressed in skeletal muscle in type 2 diabetes, resulting in impaired glucose utilization. Here we show that human PDK4 has robust core-free basal activity, which is considerably higher than activity levels of other PDK isoforms stimulated by the PDC core. PDK4 binds the L3 lipoyl domain, but its activity is not significantly stimulated by any individual lipoyl domains or the core of PDC. The 2.0-A crystal structures of the PDK4 dimer with bound ADP reveal an open conformation with a wider active-site cleft, compared with that in the closed conformation epitomized by the PDK2-ADP structure. The open conformation in PDK4 shows partially ordered C-terminal cross-tails, in which the conserved DW (Asp(394)-Trp(395)) motif from one subunit anchors to the N-terminal domain of the other subunit. The open conformation fosters a reduced binding affinity for ADP, facilitating the efficient removal of product inhibition by this nucleotide. Alteration or deletion of the DW-motif disrupts the C-terminal cross-tail anchor, resulting in the closed conformation and the nearly complete inactivation of PDK4. Fluorescence quenching and enzyme activity data suggest that compounds AZD7545 and dichloroacetate lock PDK4 in the open and the closed conformational states, respectively. We propose that PDK4 with bound ADP exists in equilibrium between the open and the closed conformations. The favored metastable open conformation is responsible for the robust basal activity of PDK4 in the absence of the PDC core.

Relationship between medication synchronization and antiretroviral adherence.

PubMed

Ghassemi, Emily; Smith, Jennifer; Owens, Laura; Herring, Charles; Holland, Melissa

2018-06-12

To compare antiretroviral adherence (measured as the proportion of days covered [PDC]) and change in viral load in insured, HIV-infected, adult outpatients enrolled and not enrolled in a medication synchronization program. This was a multicenter, retrospective, pilot cohort study. Fifty-eight insured, HIV-infected, outpatients at least 18 years of age receiving antiretroviral therapy (ART) for at least 3 months as of August 2015 were included. PDC, viral load, PDC dichotomized into adherent or nonadherent, and viral load dichotomized into detectable or undetectable were collected for each patient. Study data were compared in those with (enrolled) and without (not enrolled or control) medication synchronization. The study end points were analyzed between the 2 groups retrospectively after 3 months. PDC in patients undergoing medication synchronization was significantly higher than in control patients: mean ± SD 96 ± 9% versus 71 ± 27%, respectively (P < 0.0001). The medication synchronization group was also more likely to be adherent to ART than the control group (odds ratio 10.67, 95% confidence interval 2.63-43.31). In the medication synchronization group, 75.9% of patients had an undetectable baseline viral load, and 83.3% had an undetectable viral load at study completion. In the control group, 62.1% and 64.7% had an undetectable viral load at baseline and completion, respectively. No statistically significant change in viral load was observed between groups (P = 0.34). In insured, HIV-infected, adult outpatients, implementation of a medication synchronization program was associated with improved ART adherence. Future studies are needed to better assess the impact of medication synchronization on clinical outcomes. Copyright © 2018 American Pharmacists Association®. All rights reserved.

The multifaceted biology of plasmacytoid dendritic cells

PubMed Central

Swiecki, Melissa; Colonna, Marco

2015-01-01

Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that specializes in the production of type I interferons (IFNs). pDCs promote antiviral immune responses and have been implicated in the pathogenesis of autoimmune diseases characterized by a type I IFN signature. However, pDCs can also induce tolerogenic immune responses. Here, we review recent progress from the field of pDC biology, focusing on: the molecular mechanisms that regulate pDC development and functions; the pathways involved in their sensing of pathogens and endogenous nucleic acids; the function of pDCs at mucosal sites; and their roles in infections, autoimmunity and cancer. PMID:26160613

Highly Unsaturated Platinum and Palladium Carbenes PtC3 and PdC3 Isolated and Characterized in the Gas Phase

PubMed Central

Bittner, Dror M.; Zaleski, Daniel P.; Tew, David P.

2016-01-01

Abstract Carbenes of platinum and palladium, PtC3 and PdC3, were generated in the gas phase through laser vaporization of a metal target in the presence of a low concentration of a hydrocarbon precursor undergoing supersonic expansion. Rotational spectroscopy and ab initio calculations confirm that both molecules are linear. The geometry of PtC3 was accurately determined by fitting to the experimental moments of inertia of twenty‐six isotopologues. The results are consistent with the proposal of an autogenic isolobal relationship between O, Au+, and Pt atoms. PMID:26879473

Study of pyruvate decarboxylase and thiamine kinase from brewer's yeast by SERS

NASA Astrophysics Data System (ADS)

Maskevich, Sergei A.; Chernikevich, Ivan P.; Gachko, Gennedy A.; Kivach, Leonid N.; Strekal, Nataliya D.

1993-06-01

The Surface Enhanced Raman Scattering (SERS) spectra of holopyruvate decarboxylase (PDC) and thiamine kinase (ThK) adsorbed on silver electrode were obtained. In contrast to the Raman, the SERS spectrum of PDC contained no modes of tryptophan residues, it indicates a removal of this moiety from the surface. In the SERS spectrum of ThK the bands belonging to ligands bound to the protein were observed. A correlation between the SERS signal intensity and the enzymatic activity of the ThK separate fraction and found. The influence of amino acids on SERS spectra of thiamine (Th) was studied to determine the possible composition on microsurrounding of coenzyme.

CD4 Receptor is a Key Determinant of Divergent HIV-1 Sensing by Plasmacytoid Dendritic Cells

PubMed Central

Wilen, Craig; Gopal, Ramya; Huq, Rumana; Wu, Vernon; Sunseri, Nicole; Bhardwaj, Nina

2016-01-01

Plasmacytoid dendritic cells (pDC) are innate immune cells that sense viral nucleic acids through endosomal Toll-like receptor (TLR) 7/9 to produce type I interferon (IFN) and to differentiate into potent antigen presenting cells (APC). Engagement of TLR7/9 in early endosomes appears to trigger the IRF7 pathway for IFN production whereas engagement in lysosomes seems to trigger the NF-κB pathway for maturation into APC. We showed previously that HIV-1 (HIV) localizes predominantly to early endosomes, not lysosomes, and mainly stimulate IRF7 rather than NF-κB signaling pathways in pDC. This divergent signaling may contribute to disease progression through production of pro-apoptotic and pro-inflammatory IFN and inadequate maturation of pDCs. We now demonstrate that HIV virions may be re-directed to lysosomes for NF-κB signaling by either pseudotyping HIV with influenza hemagglutinin envelope or modification of CD4 mediated-intracellular trafficking. These data suggest that HIV envelope-CD4 receptor interactions drive pDC activation toward an immature IFN producing phenotype rather than differentiation into a mature dendritic cell phenotype. PMID:27082754

Rock Drilling Performance Evaluation by an Energy Dissipation Based Rock Brittleness Index

NASA Astrophysics Data System (ADS)

Munoz, H.; Taheri, A.; Chanda, E. K.

2016-08-01

To reliably estimate drilling performance both tool-rock interaction laws along with a proper rock brittleness index are required to be implemented. In this study, the performance of a single polycrystalline diamond compact (PDC) cutter cutting and different drilling methods including PDC rotary drilling, roller-cone rotary drilling and percussive drilling were investigated. To investigate drilling performance by rock strength properties, laboratory PDC cutting tests were performed on different rocks to obtain cutting parameters. In addition, results of laboratory and field drilling on different rocks found elsewhere in literature were used. Laboratory and field cutting and drilling test results were coupled with values of a new rock brittleness index proposed herein and developed based on energy dissipation withdrawn from the complete stress-strain curve in uniaxial compression. To quantify cutting and drilling performance, the intrinsic specific energy in rotary-cutting action, i.e. the energy consumed in pure cutting action, and drilling penetration rate values in percussive action were used. The results show that the new energy-based brittleness index successfully describes the performance of different cutting and drilling methods and therefore is relevant to assess drilling performance for engineering applications.

Experimental Study on Longmaxi Shale Breaking Mechanism with Micro-PDC Bit

NASA Astrophysics Data System (ADS)

Wang, Teng; Xiao, Xiaohua; Zhu, Haiyan; Zhao, Jingying; Li, Yuheng; Lu, Ming

2017-10-01

China has abundant shale gas resource, but its geological conditions are complicated. This work sought to find the shale breaking mechanism with the polycrystalline diamond compact (PDC) bit when drilling the shale that is rich in stratification. Therefore, a laboratory-scale drilling device based on a drilling machine is developed. The influences of Longmaxi shale stratification on drilling parameters in the drilling process with micro-PDC bit are investigated. Six groups of drilling experiments with six inclination angles ( β = 0°, 15°, 30°, 45°, 60° and 90°), total thirty-six groups, are carried out. The weight on bit reaches the maximum value at β = 30° and reaches the minimum value at β = 0°. The biggest torque value is at β = 30°, and the smaller torque values are at β = 15°, β = 45° and β = 60°. When the inclination angle is between 30° and 60°, the shale fragmentation volume is larger. The inclination angle β = 0° is beneficial, and β = 15° and β = 60° are detrimental to controlling the drilling direction in the Longmaxi shale gas formation.

Steroidal 5-en-3-ones, intermediates of the transformation of steroidal 5-en-3 beta-ols to steroidal 4-en-3,6-diones oxidized by pyridinium dichromate and pyridinium chlorochromate.

PubMed

Li, S H; Li, T S

1998-02-01

Oxidation of cholesterol (1a) or pregnenolone (1b) with pyridinium dichromate (PDC) in dimethylformamide (DMF) or in dichloromethane (DCM) and pyridinium chlorochromate (PCC) in DCM provided cholest-4-en-3,6-dione (2a) or pregn-4-en-3,6,20-trione (2b). TLC monitoration of the reactions implied that cholest-5-en-3-one (3a) or pregn-5-en-3,20-dione (3b) and cholest-4-en-3-one (4a) or pregn-4-en-3,20-dione (4b) might be intermediates. Individual oxidation of 3a or 3b with PDC and PCC could give 2a or 2b, but 4a or 4b remained unchanged. Further investigation indicated that 4a or 4b was an isomerization product of 3a or 3b on silica gel TLC plate rather than really existence in the reaction mixture. These results shown steroidal 5-en-3-ones were intermediates of the transformation of steroidal 5-en-3 beta-ols to steroidal 4-en-3,6-diones oxidized by PDC and PCC.

CD22 expression on blastic plasmacytoid dendritic cell neoplasms and reactivity of anti-CD22 antibodies to peripheral blood dendritic cells.

PubMed

Reineks, Edmunds Z; Osei, Ebenezer S; Rosenberg, Arlene; Auletta, Jeffrey; Meyerson, Howard J

2009-07-01

We identified CD22 expression on a blastic plasmacytoid dendritic cell (pDC) neoplasm presenting as a leukemia in a child. CD22 expression, as determined by the antibody s-HCL-1, was also noted on the neoplastic cells from three additional patients with blastic pDC tumors identified at our institution. Subsequently we determined that peripheral blood pDCs react with the s-HCL-1 antibody demonstrating that normal pDCs express CD22. Evaluation of five additional anti-CD22 antibodies indicated that staining of pDCs with these reagents was poor except for s-HCL-1. Therefore, the detection of CD22 on pDCs is best demonstrated with the use of this specific antibody clone. All anti-CD22 antibodies stained conventional DCs. We also evaluated the reactivity of the anti-CD22 antibodies with basophils and noted that the pattern of staining was similar to that seen with pDCs. The studies demonstrate that normal DCs and pDC neoplasms express CD22, and highlight clone specific differences in anti-CD22 antibody reactivity patterns on pDCs and basophils. (c) 2009 Clinical Cytometry Society.

Dramatically Enhanced Spin Dynamo with Plasmonic Diabolo Cavity.

PubMed

Gou, Peng; Qian, Jie; Xi, Fuchun; Zou, Yuexin; Cao, Jun; Yu, Haochi; Zhao, Ziyi; Yang, Le; Xu, Jie; Wang, Hengliang; Zhang, Lijian; An, Zhenghua

2017-07-13

The applications of spin dynamos, which could potentially power complex nanoscopic devices, have so far been limited owing to their extremely low energy conversion efficiencies. Here, we present a unique plasmonic diabolo cavity (PDC) that dramatically improves the spin rectification signal (enhancement of more than three orders of magnitude) under microwave excitation; further, it enables an energy conversion efficiency of up to ~0.69 mV/mW, compared with ~0.27 μV/mW without a PDC. This remarkable improvement arises from the simultaneous enhancement of the microwave electric field (~13-fold) and the magnetic field (~195-fold), which cooperate in the spin precession process generates photovoltage (PV) efficiently under ferromagnetic resonance (FMR) conditions. The interplay of the microwave electromagnetic resonance and the ferromagnetic resonance originates from a hybridized mode based on the plasmonic resonance of the diabolo structure and Fabry-Perot-like modes in the PDC. Our work sheds light on how more efficient spin dynamo devices for practical applications could be realized and paves the way for future studies utilizing both artificial and natural magnetism for applications in many disciplines, such as for the design of future efficient wireless energy conversion devices, high frequent resonant spintronic devices, and magnonic metamaterials.

A Novel Strategy for Selection and Validation of Reference Genes in Dynamic Multidimensional Experimental Design in Yeast

PubMed Central

Cankorur-Cetinkaya, Ayca; Dereli, Elif; Eraslan, Serpil; Karabekmez, Erkan; Dikicioglu, Duygu; Kirdar, Betul

2012-01-01

Background Understanding the dynamic mechanism behind the transcriptional organization of genes in response to varying environmental conditions requires time-dependent data. The dynamic transcriptional response obtained by real-time RT-qPCR experiments could only be correctly interpreted if suitable reference genes are used in the analysis. The lack of available studies on the identification of candidate reference genes in dynamic gene expression studies necessitates the identification and the verification of a suitable gene set for the analysis of transient gene expression response. Principal Findings In this study, a candidate reference gene set for RT-qPCR analysis of dynamic transcriptional changes in Saccharomyces cerevisiae was determined using 31 different publicly available time series transcriptome datasets. Ten of the twelve candidates (TPI1, FBA1, CCW12, CDC19, ADH1, PGK1, GCN4, PDC1, RPS26A and ARF1) we identified were not previously reported as potential reference genes. Our method also identified the commonly used reference genes ACT1 and TDH3. The most stable reference genes from this pool were determined as TPI1, FBA1, CDC19 and ACT1 in response to a perturbation in the amount of available glucose and as FBA1, TDH3, CCW12 and ACT1 in response to a perturbation in the amount of available ammonium. The use of these newly proposed gene sets outperformed the use of common reference genes in the determination of dynamic transcriptional response of the target genes, HAP4 and MEP2, in response to relaxation from glucose and ammonium limitations, respectively. Conclusions A candidate reference gene set to be used in dynamic real-time RT-qPCR expression profiling in yeast was proposed for the first time in the present study. Suitable pools of stable reference genes to be used under different experimental conditions could be selected from this candidate set in order to successfully determine the expression profiles for the genes of interest. PMID:22675547

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

Korinko, P.; Howard, S.; Maxwell, D.

During final preparations for start of the PDCF Inner Can (IC) qualification effort, welding was performed on an automated weld system known as the PICN. During the initial weld, using a pedigree canister and plug, a weld defect was observed. The defect resulted in a hole in the sidewall of the canister, and it was observed that the plug sidewall had not been consumed. This was a new type of failure not seen during development and production of legacy Bagless Transfer Cans (FB-Line/Hanford). Therefore, a team was assembled to determine the root cause and to determine if the process couldmore » be improved. After several brain storming sessions (MS and T, R and D Engineering, PDC Project), an evaluation matrix was established to direct this effort. The matrix identified numerous activities that could be taken and then prioritized those activities. This effort was limited by both time and resources (the number of canisters and plugs available for testing was limited). A discovery process was initiated to evaluate the Vendor's IC fabrication process relative to legacy processes. There were no significant findings, however, some information regarding forging/anneal processes could not be obtained. Evaluations were conducted to compare mechanical properties of the PDC canisters relative to the legacy canisters. Some differences were identified, but mechanical properties were determined to be consistent with legacy materials. A number of process changes were also evaluated. A heat treatment procedure was established that could reduce the magnetic characteristics to levels similar to the legacy materials. An in-situ arc annealing process was developed that resulted in improved weld characteristics for test articles. Also several tack welds configurations were addressed, it was found that increasing the number of tack welds (and changing the sequence) resulted in decreased can to plug gaps and a more stable weld for test articles. Incorporating all of the process improvements for the actual can welding process, however, did not result in an improved weld geometry. Several possibilities for the lack of positive response exist, some of which are that (1) an insufficient number of test articles were welded under prototypic conditions, (2) the process was not optimized so that significant improvements were observable over the 'noise', and (3) the in-situ arc anneal closed the gap down too much so the can was unable to exhaust pressure ahead of the weld. Several operational and mechanical improvements were identified. The weld clamps were changed to a design consistent with those used in the legacy operations. A helium puff operation was eliminated; it is believed that this operation was the cause of the original weld defect. Also, timing of plug mast movement was found to correspond with weld irregularities. The timing of the movement was changed to occur during weld head travel between tacks. In the end a three sequential tack weld process followed by a pulse weld at the same current and travel speed as was used for the legacy processes was suggested for use during the IC qualification effort. Relative to legacy welds, the PDC IC weld demonstrates greater fluctuation in the region of the weld located between tack welds. However, canister weld response (canister to canister) is consistent and with the aid of the optical mapping system (for targeting the cut position) is considered adequate. DR measurements and METs show the PDC IC welds to have sufficient ligament length to ensure adequate canister pressure/impact capacity and to ensure adequate stub function. The PDC welding process has not been optimized as a result of this effort. Differences remain between the legacy BTC welds and the PDC IC weld, but these differences are not sufficient to prevent resumption of the current PDC IC qualification effort. During the PDC IC qualification effort, a total of 17 cans will be welded and a variety of tests/inspections will be performed. The extensive data collected during that qualification effort should be of a sufficient population to determine if additional weld process optimization is necessary prior to production release.« less

The banana fruit Dof transcription factor MaDof23 acts as a repressor and interacts with MaERF9 in regulating ripening-related genes

PubMed Central

Feng, Bi-hong; Han, Yan-chao; Xiao, Yun-yi; Kuang, Jian-fei; Fan, Zhong-qi; Chen, Jian-ye; Lu, Wang-jin

2016-01-01

The DNA binding with one finger (Dof) proteins, a family of plant-specific transcription factors, are involved in a variety of plant biological processes. However, little information is available on their involvement in fruit ripening. We have characterized 25 MaDof genes from banana fruit (Musa acuminata), designated as MaDof1–MaDof25. Gene expression analysis in fruit subjected to different ripening conditions revealed that MaDofs were differentially expressed during different stages of ripening. MaDof10, 23, 24, and 25 were ethylene-inducible and nuclear-localized, and their transcript levels increased during fruit ripening. Moreover, yeast two-hybrid and bimolecular fluorescence complementation analyses demonstrated a physical interaction between MaDof23 and MaERF9, a potential regulator of fruit ripening reported in a previous study. We determined that MaDof23 is a transcriptional repressor, whereas MaERF9 is a transcriptional activator. We suggest that they might act antagonistically in regulating 10 ripening-related genes, including MaEXP1/2/3/5, MaXET7, MaPG1, MaPME3, MaPL2, MaCAT, and MaPDC, which are associated with cell wall degradation and aroma formation. Taken together, our findings provide new insight into the transcriptional regulation network controlling banana fruit ripening. PMID:26889012

Electronic availability of microgravity experiments safety and integration requirements documents

NASA Technical Reports Server (NTRS)

Hogan, Jean M.

1995-01-01

This follow-on to NASA Contractor Report 195447, Microgravity Experiments Safety and Integration Requirements Document Tree, provides the details for accessing the systems that contain the official, electronic versions of the documents initially researched in NASA Contractor Report 195447. The data in this report serves as a valuable information source for the NASA Lewis Research Center Project Documentation Center (PDC), as well as for all developers of space experiments. The PDC has acquired the hardware, software, ID's, and passwords necessary to access most of these systems and is now able to provide customers with current document information as well as immediate delivery of available documents in either electronic or hard copy format.

Investigating the change of causality in emerging property markets during the financial tsunami

NASA Astrophysics Data System (ADS)

Hui, Eddie C. M.; Chen, Jia

2012-08-01

In this paper, we employ the multivariate CUSUM (cumulative sum) test for covariance structure as well as the renormalized partial directed coherence (PDC) method to capture the structural causality change of real estate stock indices of five emerging Asian countries and regions (i.e., Thailand, Malaysia, South Korea, PR China, and Taiwan). Meanwhile, we develop a method to make the comparison of renormalized PDC more intuitive and a set of criteria to measure the result. One of our findings indicates that the regional influence of the Chinese real estate stock market on the causality structure of the five markets has arisen under the effect of the financial tsunami.

Liquid Hydrogenation of Maleic Anhydride with Pd/C Catalyst at Low Pressure and Temperature in Batch Reactor.

PubMed

Kim, Ji Sun; Baek, Jae Ho; Ryu, Young Bok; Hong, Seong-Soo; Lee, Man Sig

2015-01-01

Succinic acid (SA) produced from hydrogenation of maleic anhydride (MAN) is used widely in manufacturing of pharmaceuticals, agrochemicals, surfactants and detergent, green solvent and biodegradable plastic. In this study, we performed that liquid hydrogenation of MAN to SA with 5 wt% Pd supported on activated carbon (Pd/C) at low pressure and temperature. The synthesis of SA was performed in aqueous solution while varying temperature, pressure, catalytic amount and agitation speed. We confirmed that the composition of the products consisting of SA, maleic acid (MA), fumaric acid (FA) and malic acid (MLA) depends on the process. The catalytic characteristics were analyzed by TGA, TEM.

Functional and Structural Analysis of Phenazine O-Methyltransferase LaPhzM from Lysobacter antibioticus OH13 and One-Pot Enzymatic Synthesis of the Antibiotic Myxin.

PubMed

Jiang, Jiasong; Guiza Beltran, Daisy; Schacht, Andrew; Wright, Stephen; Zhang, Limei; Du, Liangcheng

2018-04-20

Myxin is a well-known antibiotic that had been used for decades. It belongs to the phenazine natural products that exhibit various biological activities, which are often dictated by the decorating groups on the heteroaromatic three-ring system. The three rings of myxin carry a number of decorations, including an unusual aromatic N5, N10-dioxide. We previously showed that phenazine 1,6-dicarboxylic acid (PDC) is the direct precursor of myxin, and two redox enzymes (LaPhzS and LaPhzNO1) catalyze the decarboxylative hydroxylation and aromatic N-oxidations of PDC to produce iodinin (1.6-dihydroxy- N5, N10-dioxide phenazine). In this work, we identified the LaPhzM gene from Lysobacter antibioticus OH13 and demonstrated that LaPhzM encodes a SAM-dependent O-methyltransferase converting iodinin to myxin. The results further showed that LaPhzM is responsible for both monomethoxy and dimethoxy formation in all phenazine compounds isolated from strain OH13. LaPhzM exhibits relaxed substrate selectivity, catalyzing O-methylation of phenazines with non-, mono-, or di- N-oxide. In addition, we demonstrated a one-pot biosynthesis of myxin by in vitro reconstitution of the three phenazine-ring decorating enzymes. Finally, we determined the X-ray crystal structure of LaPhzM with a bound cofactor at 1.4 Å resolution. The structure provided molecular insights into the activity and selectivity of the first characterized phenazine O-methyltransferase. These results will facilitate future exploitation of the thousands of phenazines as new antibiotics through metabolic engineering and chemoenzymatic syntheses.

Expression Plasmids for Use in Candida glabrata

PubMed Central

Zordan, Rebecca E.; Ren, Yuxia; Pan, Shih-Jung; Rotondo, Giuseppe; Peñas, Alejandro De Las; Iluore, Joseph; Cormack, Brendan P.

2013-01-01

We describe a series of CEN/ARS episomal plasmids containing different Candida glabrata promoters, allowing for a range of constitutive or regulated expression of proteins in C. glabrata. The set of promoters includes three constitutive promoters (EGD2pr, HHT2pr, PDC1pr), two macrophage/phagocytosis-induced promoters (ACO2pr, LYS21pr), and one nutritionally regulated promoter (MET3pr). Each promoter was cloned into two plasmid backbones that differ in their selectable marker, URA3, or the dominant-selectable NAT1 gene, which confers resistance to the drug nourseothricin. Expression from the 12 resulting plasmids was assessed using GFP as a reporter and flow cytometry or quantitative reverse-transcription polymerase chain reaction to assess expression levels. Together this set of plasmids expands the toolkit of expression vectors available for use with C. glabrata. PMID:23934995

Geometry and material choices govern hard-rock drilling performance of PDC drag cutters.

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

Wise, Jack LeRoy

2005-06-01

Sandia National Laboratories has partnered with industry on a multifaceted, baseline experimental study that supports the development of improved drag cutters for advanced drill bits. Different nonstandard cutter lots were produced and subjected to laboratory tests that evaluated the influence of selected design and processing parameters on cutter loads, wear, and durability pertinent to the penetration of hard rock with mechanical properties representative of formations encountered in geothermal or deep oil/gas drilling environments. The focus was on cutters incorporating ultrahard PDC (polycrystalline diamond compact) overlays (i.e., diamond tables) on tungsten-carbide substrates. Parameter variations included changes in cutter geometry, material composition,more » and processing conditions. Geometric variables were the diamond-table thickness, the cutting-edge profile, and the PDC/substrate interface configuration. Material and processing variables for the diamond table were, respectively, the diamond particle size and the sintering pressure applied during cutter fabrication. Complementary drop-impact, granite-log abrasion, linear cutting-force, and rotary-drilling tests examined the response of cutters from each lot. Substantial changes in behavior were observed from lot to lot, allowing the identification of features contributing major (factor of 10+) improvements in cutting performance for hard-rock applications. Recent field demonstrations highlight the advantages of employing enhanced cutter technology during challenging drilling operations.« less

Purpose-built PDC bit successfully drills 7-in liner equipment and formation: An integrated solution

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

Puennel, J.G.A.; Huppertz, A.; Huizing, J.

1996-12-31

Historically, drilling out the 7-in, liner equipment has been a time consuming operation with a limited success ratio. The success of the operation is highly dependent on the type of drill bit employed. Tungsten carbide mills and mill tooth rock bits required from 7.5 to 11.5 hours respectively to drill the pack-off bushings, landing collar, shoe track and shoe. Rates of penetration dropped dramatically when drilling the float equipment. While conventional PDC bits have drilled the liner equipment successfully (averaging 9.7 hours), severe bit damage invariably prevented them from continuing to drill the formation at cost-effective penetration rates. This papermore » describes the integrated development and application of an IADC M433 Class PDC bit, which was designed specifically to drill out the 7-in. liner equipment and continue drilling the formation at satisfactory penetration rates. The development was the result of a joint investigation There the operator and bit/liner manufacturers shared their expertise in solving a drilling problem, The heavy-set bit was developed following drill-off tests conducted to investigate the drillability of the 7-in. liner equipment. Key features of the new bit and its application onshore The Netherlands will be presented and analyzed.« less

Spacecraft Mission Design for the Mitigation of the 2017 PDC Hypothetical Asteroid Threat

NASA Technical Reports Server (NTRS)

Barbee, Brent W.; Sarli, Bruno V.; Lyzhoft, Josh; Chodas, Paul W.; Englander, Jacob A.

2017-01-01

This paper presents a detailed mission design analysis results for the 2017 Planetary Defense Conference (PDC) Hypothetical Asteroid Impact Scenario, documented at https:cneos.jpl.nasa.govpdcspdc17. The mission design includes campaigns for both reconnaissance (flyby or rendezvous) of the asteroid (to characterize it and the nature of the threat it poses to Earth) and mitigation of the asteroid, via kinetic impactor deflection, nuclear explosive device (NED) deflection, or NED disruption. Relevant scenario parameters are varied to assess the sensitivity of the design outcome, such as asteroid bulk density, asteroid diameter, momentum enhancement factor, spacecraft launch vehicle, and mitigation system type. Different trajectory types are evaluated in the mission design process from purely ballistic to those involving optimal midcourse maneuvers, planetary gravity assists, and/or low-thrust solar electric propulsion. The trajectory optimization is targeted around peak deflection points that were found through a novel linear numerical technique method. The optimization process includes constrain parameters, such as Earth departure date, launch declination, spacecraft, asteroid relative velocity and solar phase angle, spacecraft dry mass, minimum/maximum spacecraft distances from Sun and Earth, and Earth-spacecraft communications line of sight. Results show that one of the best options for the 2017 PDC deflection is solar electric propelled rendezvous mission with a single spacecraft using NED for the deflection.

The effects of poststroke captopril and losartan treatment on cerebral blood flow autoregulation in SHRsp with hemorrhagic stroke.

PubMed

Smeda, John S; Daneshtalab, Noriko

2011-02-01

The ability of captopril and losartan treatment to restore cerebral blood flow (CBF) autoregulation after intracerebral hemorrhagic stroke (HS) was assessed in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp). Laser Doppler techniques assessed CBF autoregulation in the middle cerebral artery (MCA) perfusion domain and a pressure myograph was used to measure pressure-dependent constriction (PDC) in isolated MCAs before and after stroke and after 13, 33, and 63 days of poststroke captopril or losartan treatment. The treatments did not lower blood pressure (BP) and equally suppressed plasma aldosterone after HS. The HS development was associated with the loss of CBF autoregulation, high CBF, increased CBF conductance to elevations in BP, and the loss of PDC in the MCAs. Both treatments restored these functions to prestroke levels within 13 days. The PDC and CBF autoregulation subsequently deteriorated after 63 days of captopril treatment while being maintained at prestroke levels over all durations of losartan treatment. The SHRsp subjected to 35 days of poststroke losartan treatment exhibited less blood-brain barrier (BBB) disruption and brain herniation than captopril-treated SHRsp. The superior ability of losartan to restore CBF autoregulation and myogenic function may have contributed to the more effective attenuation of cerebral damage after HS.

The effects of poststroke captopril and losartan treatment on cerebral blood flow autoregulation in SHRsp with hemorrhagic stroke

PubMed Central

Smeda, John S; Daneshtalab, Noriko

2011-01-01

The ability of captopril and losartan treatment to restore cerebral blood flow (CBF) autoregulation after intracerebral hemorrhagic stroke (HS) was assessed in Kyoto–Wistar stroke-prone hypertensive rats (SHRsp). Laser Doppler techniques assessed CBF autoregulation in the middle cerebral artery (MCA) perfusion domain and a pressure myograph was used to measure pressure-dependent constriction (PDC) in isolated MCAs before and after stroke and after 13, 33, and 63 days of poststroke captopril or losartan treatment. The treatments did not lower blood pressure (BP) and equally suppressed plasma aldosterone after HS. The HS development was associated with the loss of CBF autoregulation, high CBF, increased CBF conductance to elevations in BP, and the loss of PDC in the MCAs. Both treatments restored these functions to prestroke levels within 13 days. The PDC and CBF autoregulation subsequently deteriorated after 63 days of captopril treatment while being maintained at prestroke levels over all durations of losartan treatment. The SHRsp subjected to 35 days of poststroke losartan treatment exhibited less blood–brain barrier (BBB) disruption and brain herniation than captopril-treated SHRsp. The superior ability of losartan to restore CBF autoregulation and myogenic function may have contributed to the more effective attenuation of cerebral damage after HS. PMID:20648036

Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type

PubMed Central

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC. PMID:20978318

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2010-01-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC. genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

Genetic profile of adenoid cystic carcinomas (ACC) with high-grade transformation versus solid type.

PubMed

Costa, Ana Flávia; Altemani, Albina; Vékony, Hedy; Bloemena, Elisabeth; Fresno, Florentino; Suárez, Carlos; Llorente, José Luis; Hermsen, Mario

2011-08-01

ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features, and to compare results to solid ACC. Genome wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, four with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), and five solid ACC. In addition, Ki67 index and p53 immunopositivity was assessed. ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component. ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.

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

Nikolau, Basil J; Wurtele, Eve S; Oliver, David J

The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method ofmore » producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.alpha. subunit of pPDH, the E1.beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyruvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.alpha. pPDH, E1.beta. pPDH, E2 pPDH, mtPDH or ALDH.« less

Synthesis, spectroscopic studies and electrochemistry of palladium (II) macrocyclic complexes derived from a new tetraazahalogen substituted ligands by template method and their antimicrobial and pesticidal activities

NASA Astrophysics Data System (ADS)

Masih, Iffat; Fahmi, Nighat

2011-09-01

A new series of Pd(II) macrocyclic complexes have been synthesized by template condensation of bis(benzil)4-chloro 1,2-phenylenediamine (ML 1) and bis(benzil)4-fluro 1,2-phenylenediamine (ML 2) respectively, with appropriate diamine i.e. 1,2-phenylenediamine, 4-chloro 1,2-phenylenediamine and 4-fluro 1,2-phenylenediamine in the presence of PdCl 2 to form complexes of the type [Pd(C 40H 26N 4ClF)]Cl 2, [Pd(C 40H 27N 4X)]Cl 2 and [Pd(C 40H 26N 4X 2)]Cl 2, where X = Cl, F. The complexes have been characterized with the help of elemental analysis, IR, 1H NMR, electronic spectra, conductance measurement, magnetic susceptibility, cyclic voltammetry and X-ray powder diffraction studies. On the basis of these studies a square planar geometry has been proposed around the metal ion. The newly synthesized ligands and their complexes have been screened for antimicrobial and pesticidal activities. The results obtained from bioassays indicate that this class of compounds can be utilized for the design of new substance with pesticidal activity and promising antimicrobial activity.

Respiratory syncytial virus induced type I IFN production by pDC is regulated by RSV-infected airway epithelial cells, RSV-exposed monocytes and virus specific antibodies.

PubMed

Schijf, Marcel A; Lukens, Michael V; Kruijsen, Debby; van Uden, Nathalie O P; Garssen, Johan; Coenjaerts, Frank E J; Van't Land, Belinda; van Bleek, Grada M

2013-01-01

Innate immune responses elicited upon virus exposure are crucial for the effective eradication of viruses, the onset of adaptive immune responses and for establishing proper immune memory. Respiratory syncytial virus (RSV) is responsible for a high disease burden in neonates and immune compromised individuals, causing severe lower respiratory tract infections. During primary infections exuberant innate immune responses may contribute to disease severity. Furthermore, immune memory is often insufficient to protect during RSV re-exposure, which results in frequent symptomatic reinfections. Therefore, identifying the cell types and pattern recognition receptors (PRRs) involved in RSV-specific innate immune responses is necessary to understand incomplete immunity against RSV. We investigated the innate cellular response triggered upon infection of epithelial cells and peripheral blood mononuclear cells. We show that CD14(+) myeloid cells and epithelial cells are the major source of IL-8 and inflammatory cytokines, IL-6 and TNF-α, when exposed to live RSV Three routes of RSV-induced IFN-α production can be distinguished that depend on the cross-talk of different cell types and the presence or absence of virus specific antibodies, whereby pDC are the ultimate source of IFN-α. RSV-specific antibodies facilitate direct TLR7 access into endosomal compartments, while in the absence of antibodies, infection of monocytes or epithelial cells is necessary to provide an early source of type I interferons, required to engage the IFN-α,β receptor (IFNAR)-mediated pathway of IFN-α production by pDC. However, at high pDC density infection with RSV causes IFN-α production without the need for a second party cell. Our study shows that cellular context and immune status are factors affecting innate immune responses to RSV. These issues should therefore be addressed during the process of vaccine development and other interventions for RSV disease.

Low-health literacy flashcards & mobile video reinforcement to improve medication adherence in patients on oral diabetes, heart failure, and hypertension medications.

PubMed

Yeung, Denise L; Alvarez, Kristin S; Quinones, Marissa E; Clark, Christopher A; Oliver, George H; Alvarez, Carlos A; Jaiyeola, Adeola O

To design and investigate a pharmacist-run intervention using low health literacy flashcards and a smartphone-activated quick response (QR) barcoded educational flashcard video to increase medication adherence and disease state understanding. Prospective, matched, quasi-experimental design. County health system in Dallas, Texas. Sixty-eight primary care patients prescribed targeted heart failure, hypertension, and diabetes medications INTERVENTION: Low health literacy medication and disease specific flashcards, which were also available as QR-coded online videos, were designed for the intervention patients. The following validated health literacy tools were conducted: Newest Vital Sign (NVS), Rapid Estimate of Adult Literacy Medicine-Short Form, and Short Assessment of Health Literacy-50. The primary outcome was the difference in medication adherence at 180 days after pharmacist intervention compared with the control group, who were matched on the basis of comorbid conditions, targeted medications, and medication class. Medication adherence was measured using a modified Pharmacy Quality Alliance proportion of days covered (PDC) calculation. Secondary outcomes included 90-day PDC, improvement of greater than 25% in baseline PDC, and final PDC greater than 80%. Linear regression was performed to evaluate the effect of potential confounders on the primary outcome. Of the 34 patients receiving the intervention, a majority of patients scored a high possibility of limited health literacy on the NVS tool (91.2%). The medication with the least adherence at baseline was metformin, followed by angiotensin-converting enzyme inhibitors and beta blockers. At 180 days after intervention, patients in the intervention group had higher PDCs compared with their matched controls (71% vs. 44%; P = 0.0069). The use of flashcards and QR-coded prescription bottles for medication and disease state education is an innovative way of improving adherence to diabetes, hypertension, and heart failure medications in a low-health literacy patient population. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Respiratory Syncytial Virus Induced Type I IFN Production by pDC Is Regulated by RSV-Infected Airway Epithelial Cells, RSV-Exposed Monocytes and Virus Specific Antibodies

PubMed Central

Schijf, Marcel A.; Lukens, Michael V.; Kruijsen, Debby; van Uden, Nathalie O. P.; Garssen, Johan; Coenjaerts, Frank E. J.; van’t Land, Belinda; van Bleek, Grada M.

2013-01-01

Innate immune responses elicited upon virus exposure are crucial for the effective eradication of viruses, the onset of adaptive immune responses and for establishing proper immune memory. Respiratory syncytial virus (RSV) is responsible for a high disease burden in neonates and immune compromised individuals, causing severe lower respiratory tract infections. During primary infections exuberant innate immune responses may contribute to disease severity. Furthermore, immune memory is often insufficient to protect during RSV re-exposure, which results in frequent symptomatic reinfections. Therefore, identifying the cell types and pattern recognition receptors (PRRs) involved in RSV-specific innate immune responses is necessary to understand incomplete immunity against RSV. We investigated the innate cellular response triggered upon infection of epithelial cells and peripheral blood mononuclear cells. We show that CD14+ myeloid cells and epithelial cells are the major source of IL-8 and inflammatory cytokines, IL-6 and TNF-α, when exposed to live RSV Three routes of RSV-induced IFN-α production can be distinguished that depend on the cross-talk of different cell types and the presence or absence of virus specific antibodies, whereby pDC are the ultimate source of IFN-α. RSV-specific antibodies facilitate direct TLR7 access into endosomal compartments, while in the absence of antibodies, infection of monocytes or epithelial cells is necessary to provide an early source of type I interferons, required to engage the IFN-α,β receptor (IFNAR)-mediated pathway of IFN-α production by pDC. However, at high pDC density infection with RSV causes IFN-α production without the need for a second party cell. Our study shows that cellular context and immune status are factors affecting innate immune responses to RSV. These issues should therefore be addressed during the process of vaccine development and other interventions for RSV disease. PMID:24303065

Low–health literacy flashcards & mobile video reinforcement to improve medication adherence in patients on oral diabetes, heart failure, and hypertension medications

PubMed Central

Yeung, Denise L.; Alvarez, Kristin S.; Quinones, Marissa E.; Clark, Christopher A.; Oliver, George H.; Alvarez, Carlos A.; Jaiyeola, Adeola O.

2017-01-01

Objective To design and investigate a pharmacist-run intervention using low health literacy flashcards and a smartphone-activated quick response (QR) barcoded educational flashcard video to increase medication adherence and disease state understanding. Design Prospective, matched, quasi-experimental design. Setting County health system in Dallas, Texas. Participants Sixty-eight primary care patients prescribed targeted heart failure, hypertension, and diabetes medications Intervention Low health literacy medication and disease specific flashcards, which were also available as QR-coded online videos, were designed for the intervention patients. The following validated health literacy tools were conducted: Newest Vital Sign (NVS), Rapid Estimate of Adult Literacy Medicine–Short Form, and Short Assessment of Health Literacy–50. Main outcome measures The primary outcome was the difference in medication adherence at 180 days after pharmacist intervention compared with the control group, who were matched on the basis of comorbid conditions, targeted medications, and medication class. Medication adherence was measured using a modified Pharmacy Quality Alliance proportion of days covered (PDC) calculation. Secondary outcomes included 90-day PDC, improvement of greater than 25% in baseline PDC, and final PDC greater than 80%. Linear regression was performed to evaluate the effect of potential confounders on the primary outcome. Results Of the 34 patients receiving the intervention, a majority of patients scored a high possibility of limited health literacy on the NVS tool (91.2%). The medication with the least adherence at baseline was metformin, followed by angiotensin-converting enzyme inhibitors and beta blockers. At 180 days after intervention, patients in the intervention group had higher PDCs compared with their matched controls (71% vs. 44%; P = 0.0069). Conclusion The use of flashcards and QR-coded prescription bottles for medication and disease state education is an innovative way of improving adherence to diabetes, hypertension, and heart failure medications in a low-health literacy patient population. PMID:27816544

Comparison of Adherence to Rivaroxaban Versus Apixaban Among Patients With Atrial Fibrillation.

PubMed

McHorney, Colleen A; Peterson, Eric D; Laliberté, François; Germain, Guillaume; Nelson, Winnie W; Crivera, Concetta; Schein, Jeffrey; Lefebvre, Patrick

2016-11-01

Non-vitamin K antagonist oral anticoagulant medications are increasingly used for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF). This study aimed to compare adherence with rivaroxaban and apixaban among patients with NVAF in routine clinical practice. Using pharmacy and medical claims from Truven Health Analytics MarketScan databases, we identified NVAF patients aged ≥18 years treated with rivaroxaban or apixaban. Baseline demographic and clinical features were balanced using 1:1 propensity score matching. Adherence to therapy was measured at 90 and 180 days post-index date and was defined by the proportion of days covered (PDC) ≥0.80 and PDC ≥0.90. "Gaps in care," defined as those with 10 or more day gaps in supply, were also evaluated. Between June 2012 and April 2014, 11,477 rivaroxaban and 2992 apixaban users were identified. Baseline characteristics for rivaroxaban and apixaban users were well matched. Relative to apixaban users, rivaroxaban users were more likely to have a PDC ≥0.80 at both 90 days (85.3% vs 79.9%; P < 0.001) and 180 days (75.8% vs 72.2%; P = 0.001). Similar results were observed with PDC ≥0.90. The proportion of patients with at least one 5+ and 10+ day gap in prescriptions was significantly lower in the rivaroxaban versus apixaban cohorts: 54.2% versus 62.4% (P < 0.001) and 40.0% versus 49.2% (P < 0.001), respectively. Adherence to non-vitamin K antagonist oral anticoagulants among NVAF patients is less than ideal, and gaps in treatment are common. Those on once-a-day rivaroxaban had significantly higher adherence and fewer gaps in treatment compared with twice-a-day apixaban. Future studies are needed to explore whether these treatment differences affect comparative patient outcomes. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Relating the physical properties of volcanic rocks to the characteristics of ash generated by experimental abrasion

NASA Astrophysics Data System (ADS)

Buckland, Hannah M.; Eychenne, Julia; Rust, Alison C.; Cashman, Katharine V.

2018-01-01

Interactions between clasts in pyroclastic density currents (PDCs) generate volcanic ash that can be dispersed to the atmosphere in co-PDC plumes, and due to its small size, is far-travelled. We designed a series of experiments to determine the effects of pyroclast vesicularity and crystal content on the efficiency and type of ash generated by abrasion. Two different pyroclastic materials were used: (1) basaltic-andesite pyroclasts from Fuego volcano (Guatemala) with 26-46% vesicularity and high groundmass crystallinity and (2) tephri-phonolite Avellino pumice (Vesuvius, Italy) with 55-75% vesicularity and low groundmass crystallinity. When milled, both clast types produced bimodal grain size distributions with fine ash modes between 4 and 5φ (32-63 μm). Although the vesicular Avellino pumice typically generated more ash than the denser Fuego pyroclasts, the ash-generating potential of a single pyroclast was independent of density, and instead governed by heterogeneous crystal and vesicle textures. One consequence of these heterogeneities was to cause the vesicular Avellino clasts to split in addition to abrading, which further enhanced abrasion efficiency. The matrix characteristics also affected ash shape and componentry, which will influence the elutriation and transport properties of ash in the atmosphere. The experimental abrasion successfully replicated some of the characteristics of natural co-PDC ash samples, as shown by similarities in the Adherence Factor, which measures the proportion of attached matrix on phenocrysts, of both the experimentally generated ash and natural co-PDC ash samples. Our results support previous studies, which have shown that abrasion is an effective mechanism for generating fine ash that is similar in size ( 5φ; 30 μm) to that found in co-PDC deposits. We further show that both the abundance and nature (shape, density, components, size distribution) of those ash particles are strongly controlled by the matrix properties of the abraded pyroclasts.

Antifungal Activity of Plasmacytoid Dendritic Cells and the Impact of Chronic HIV Infection.

PubMed

Maldonado, Samuel; Fitzgerald-Bocarsly, Patricia

2017-01-01

Due to the effectiveness of combined antiretroviral therapy, people living with HIV can control viral replication and live longer lifespans than ever. However, HIV-positive individuals still face challenges to their health and well-being, including dysregulation of the immune system resulting from years of chronic immune activation, as well as opportunistic infections from pathogenic fungi. This review focuses on one of the key players in HIV immunology, the plasmacytoid dendritic cell (pDC), which links the innate and adaptive immune response and is notable for being the body's most potent producer of type-I interferons (IFNs). During chronic HIV infection, the pDC compartment is greatly dysregulated, experiencing a substantial depletion in number and compromise in function. This immune dysregulation may leave patients further susceptible to opportunistic infections. This is especially important when considering a new role for pDCs currently emerging in the literature: in addition to their role in antiviral immunity, recent studies suggest that pDCs also play an important role in antifungal immunity. Supporting this new role, pDCs express C-type lectin receptors including dectin-1, dectin-2, dectin-3, and mannose receptor, and toll-like receptors-4 and -9 that are involved in recognition, signaling, and response to a wide variety of fungal pathogens, including Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans , and Pneumocystis jirovecii . Accordingly, pDCs have been demonstrated to recognize and respond to certain pathogenic fungi, measured via activation, cytokine production, and fungistatic activity in vitro , while in vivo mouse models indicated a strikingly vital role for pDCs in survival against pulmonary Aspergillus challenge. Here, we discuss the role of the pDC compartment and the dysregulation it undergoes during chronic HIV infection, as well as what is known so far about the role and mechanisms of pDC antifungal activity.

Hydrothermal synthesis of Bismuth(III) coordination polymer and its transformation to nano α-Bi{sub 2}O{sub 3} for photocatalytic degradation

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

Huang, Ya-Jing; Zheng, Yue-Qing, E-mail: zhengnbu@163.com; Zhu, Hong-Lin

A new Bi(III) coordination polymer Bi{sub 2}(Hpdc){sub 2}(pdc){sub 2}·2H{sub 2}O (H{sub 2}pdc=pyridine-2,6-dicarboxylic acid) was synthesized by hydrothermal method. Solid state thermal decomposition of this complex under 500 °C for 1 h led to the foliated Bi{sub 2}O{sub 3} nanoparticles, which were then characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Comparative study on their photocatalytic activity toward the degradation of rhodamine B (RhB), methylene blue (MB) and methyl orange (MO) in polluted water was explored, and the mechanism of these photocatalytic degradation was discussed. These results provided some interesting insights into their photocatalytic applications. - Graphical abstract: Wemore » regard Bi{sub 2}(Hpdc){sub 2}(pdc){sub 2}·2H{sub 2}O with 1D chain structures as the precursor, then calcinate the complex to prepare nano-powder α-Bi{sub 2}O{sub 3}. The photochemical experiment indicates that Bi{sub 2}(Hpdc){sub 2}(pdc){sub 2}·2H{sub 2}O can be used as an efficient photocatalyst for the degradation of RhB and MB. Interestingly, nano α-Bi{sub 2}O{sub 3} shows higher activity than the commercial Bi{sub 2}O{sub 3} for the degradation of RhB, MB or MO. Display Omitted - Highlights: • A novel dinuclear Bi(III) coordination polymer is hydrothermally synthesized. • Calcinating the precursor Bi-CP will result in the nano Bi{sub 2}O{sub 3} with foliated morphology. • Nano Bi{sub 2}O{sub 3} shows higher activity than the commercial Bi{sub 2}O{sub 3} for the degradation of dyes.« less

Moving branded statins to lowest copay tier improves patient adherence.

PubMed

Chen, Shih-Yin; Shah, Sonali N; Lee, Yuan-Chi; Boulanger, Luke; Mardekian, Jack; Kuznik, Andreas

2014-01-01

Statins are efficacious in reducing the risk of major cardiovascular events for both primary and secondary prevention, yet long-term adherence is poor. Their effectiveness could be compromised in actual practice when patients are not adherent to the treatments. Higher copayments have been shown to be associated with lower adherence to statins. To assess the effect on patient adherence of moving branded atorvastatin and rosuvastatin from the second to the first tier by a Medicare Part D plan sponsor. Pharmacy claims and eligibility records between July 1, 2009, and July 31, 2011, of Medicare Part D members not receiving the low-income subsidy were analyzed. New atorvastatin and rosuvastatin users in January 2010 (2010 cohort) were compared with those in January 2011 (2011 cohort) after this formulary tier change (tier-reduction group). Adherence was defined by the proportion of days covered (PDC) over 6 months. The impact of tier reduction on adherence was evaluated via logistic regression for binary outcome (PDC≥0.8) and generalized linear regression for continuous PDC by comparing the 2011 cohort with the 2010 cohort, adjusting for demographic and clinical characteristics. Other statin users (97% on generic statins) were also analyzed, serving as a nontier-reduction comparator group. We identified 12,437 members in the tier-reduction group. Between the 2010 and 2011 cohorts, mean PDC increased from 0.77 to 0.83, and the proportion of members with high adherence increased from 62.0% to 72.9% (both P < 0.001). After regression adjustment, members in the 2011 cohort were more likely to be adherent (OR=1.68; 95% CI=1.55-1.82) and had a 5.9% increase in PDC (P < 0.05). There was no significant increase in adherence observed in the comparator nontier-reduction group. Findings from this study suggest that financial incentives may improve medication adherence. Future studies should evaluate whether such formulary strategies improve long-term adherence and patient outcomes.

Stratigraphy, paleoenvironment and emplacement mechanisms of the Koko fissure craters, O'ahu, Hawai'i

NASA Astrophysics Data System (ADS)

Skilling, I. P.; Bluth, J.; Simoneau, E.

2011-12-01

The Koko fissure craters are aligned and nested basanitic tuff cones and rings at the SE corner of O'ahu, Hawai'i. There are no published studies of their stratigraphy, emplacement mechanisms or depositional paleoenvironments. This study focuses on a tuff cone complex (Koko Crater) and a younger adjacent nested tuff ring (Hanauma Bay). A detailed stratigraphy with logged sections for both Koko Crater and the Hanauma Bay craters are presented and discussed. Koko Crater is dominated by wet fallout deposits on steep proximal slopes, commonly resedimented by hot (vesiculated) and cold (unvesiculated) debris flows, slumps and slides, but with an increasing percentage of wet (low temperature) low concentration PDC deposits preserved in the shallowly-dipping flanking apron deposits, and in the uppermost proximal deposits. At least two earlier cone or ring rims are preserved along its southern margin. The deposits of Hanauma Bay overlie the Koko deposits and are dominated by a mix of wet low concentration PDC, wet fallout and synchronous PDC, and fallout deposits in proximal settings, and by low concentration, probably drier, PDC deposits in more distal settings. The Hanauma Bay rings were emplaced before the Koko Crater tephra was consolidated, as steep-sided rills incised into Koko tephra are locally filled with tephra of mixed Koko and Hanauma sources. The onset of Hanauma Bay eruptions is marked by a horizon that is very rich in rounded coral sand clasts. Discontinuous horizons and lenses of coral block fallout are also very common in the Hanauma tephra. Coral sand is absent and coral blocks are much rarer in the Koko tephra. These observations, and probably also the dominance of wet fallout at Koko, imply that Koko was erupted in deeper water than the nearshore coral beach environment of the Hanauma rings. A faster rate of water recharge into the conduit in deeper open water is probably the most important factor in the generation of a cone rather than a ring at this locality.

Impact of Nonadherence to Inhaled Corticosteroid/LABA Therapy on COPD Exacerbation Rates and Healthcare Costs in a Commercially Insured US Population

PubMed Central

Davis, Jill R.; Wu, Bingcao; Kern, David M.; Tunceli, Ozgur; Fox, Kathleen M.; Horton, John; Legg, Randall F.; Trudo, Frank

2017-01-01

Background Evidence of poor patient adherence to medications for chronic obstructive pulmonary disease (COPD) is well-documented, but its impact on disease exacerbation rates and associated healthcare costs remains unclear. Objective To assess the association between adherence levels to different inhaled corticosteroid/long-acting ß2-adrenergic agonist (LABA) and COPD exacerbation rates and costs in a commercially insured population. Methods In this observational cohort study, patients with COPD (aged ≥40 years) who were treatment-naïve to inhaled corticosteroid/LABA and were initiating budesonide plus formoterol or fluticasone plus salmeterol between March 1, 2009, and January 31, 2014, were identified in a national representative claims database and were followed for up to 12 months. The date of the first prescription fill for either drug was defined as the index date. Patients were divided into 4 cohorts based on adherence to the index therapy, which was measured by proportion of days covered (PDC); the cohorts were classified as adherent (PDC ≥0.8), mildly nonadherent (0.5 ≤ PDC <0.8), moderately nonadherent (0.3 ≤ PDC <0.5), and highly nonadherent (PDC <0.3). Each nonadherent group was matched in a 1:1 ratio to the adherent group independently, based on prognostically important variables, using propensity score analyses. Exacerbation rates and healthcare costs were analyzed for 1 year after treatment initiation. Results During the study period, 13,657 eligible patients with COPD initiated inhaled corticosteroid/LABA; of these, only 1898 (13.9%) patients were adherent during follow-up. Group matching resulted in 1572 patients per group for comparison 1 (adherent vs mildly nonadherent), 1604 patients for comparison 2 (adherent vs moderately nonadherent), and 1755 patients for comparison 3 (adherent vs highly nonadherent). The moderately and highly nonadherent cohorts had higher exacerbation rates than the adherent patients (comparison 2: rate ratio [RR], 1.11; 95% confidence interval [CI], 1.01–1.21; P = .03; comparison 3: RR, 1.11; 95% CI, 1.01–1.21; P = .02). Adherent patients incurred significantly lower healthcare costs than all the nonadherent groups (comparison 1, $22,671 vs $25,545; P <.01; comparison 2, $22,508 vs $24,303; P <.01; comparison 3, $22,460 vs $25,148; P <.01). Conclusions Patients adhered to their inhaled corticosteroid/LABA treatments had lower COPD exacerbation rates and lower healthcare costs compared with the moderately and highly nonadherent patients. Better adherence to maintenance therapies may help to reduce the clinical and economic burdens of COPD. PMID:28626506

Effects of volcano profile on dilute pyroclastic density currents: Numerical simulations

NASA Astrophysics Data System (ADS)

Doronzo, D. M.; Valentine, G. A.; Dellino, P.; de Tullio, M. D.

2012-04-01

Explosive activity and lava dome collapse at stratovolcanoes can lead to pyroclastic density currents (PDCs; mixtures of volcanic gas, air, and volcanic particles) that produce complex deposits and pose a hazard to surrounding populations. Two-dimensional numerical simulations of dilute PDCs (characterized by a turbulent suspended load and deposition through a bed load) are carried out with the Euler-Lagrange approach of multiphase physics. The fluid phase is modeled as a dusty gas (1.88 kg/m3 dense), and the solid phase is modeled as discrete particles (1 mm, 5 mm, and 10 mm; 1500 kg/m3 dense and irregularly-shaped), which are two-way coupled to the gas, i.e. they affect the fluid turbulence. The initial PDC, which enters a volcano domain 5 km long and 1.9 km high, has the following characteristics: thickness of 200 m, velocity of 20 m/s, temperature of 573 K, turbulence of 5 %, and sediment concentration of 3 % by volume. The actual physics of flow boundary zone is simulated at the PDC base, by monitoring the sediment flux toward the substrate, which acts through the flow boundary zone, and the grain-size distribution. Also, the PDC velocity and dynamic pressure are calculated. The simulations show that PDC transport, deposition, and hazard potential are sensitive to the shape of the volcano slope (profile) down which they flow. In particular, three generic volcano profiles, straight, concave-upward, and convex-upward are focused on. Dilute PDCs that flow down a constant slope gradually decelerate over the simulated run-out distance (5 km in the horizontal direction) due to a combination of sedimentation, which reduces the density of the PDC, and mixing with the atmosphere. However, dilute PDCs down a concave-upward slope accelerate high on the volcano flanks and have less sedimentation until they begin to decelerate over the shallow lower slopes. A convex-upward slope causes dilute PDCs to lose relatively more of their pyroclast load on the upper slopes of a volcano, and although they accelerate as they reach the lower, steeper slopes, the acceleration is reduced because of the upstream loss of pyroclasts (lower density contrast with the atmosphere). The dynamic pressure, a measure of the damage that can be caused by PDCs, reflects these complex relations. Details are found in Valentine et al. (2011). Reference Valentine G.A., Doronzo D.M., Dellino P., de Tullio M.D. (2011), Effects of volcano profile on dilute pyroclastic density currents: Numerical simulations, Geology, 39, 947-950.

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention in Incident, Treatment-Naïve Nonvalvular Atrial Fibrillation.

PubMed

Brown, Joshua D; Shewale, Anand R; Talbert, Jeffery C

2016-11-01

Non-vitamin K antagonist oral anticoagulants (NOACs) are widely used for prevention of stroke secondary to nonvalvular atrial fibrillation (NVAF). Increased use of NOACs is partially a result of simplified regimens compared with warfarin, which has been associated with poor adherence and persistence to therapy. Few studies have assessed adherence to NOACs, especially using contemporary data now that multiple NOACs are available. To evaluate adherence to NOACs in a cohort of newly diagnosed NVAF patients who are commercially insured. Incident, treatment-naïve NVAF patients were identified in 2013 from a large claims database. Patients were included who initiated rivaroxaban, dabigatran, or apixaban within 30 days after diagnosis. Subjects were required to have 12 months of pre-index information to assess demographic and clinical characteristics (comorbidities, CHA 2 DS 2 -VASc, and HAS-BLED scores). Adherence to the index medication and adherence to any oral anticoagulant was assessed using proportion of days covered (PDC) at 3, 6, and 9 months. The number of switches and gaps in therapy were also evaluated. Analyses were stratified by stroke risk scores, and a logistic regression model was used to control for factors that may predict high adherence (PDC ≥ 0.80). A total of 3,455 rivaroxaban, 1,264 dabigatran, and 504 apixaban users were included with no major clinical or demographic differences between groups. At 3, 6, and 9 months of follow-up, dabigatran had lower adherence (PDC = 0.77, 0.67, and 0.62) compared with rivaroxaban (PDC = 0.84, 0.75, and 0.70; P < 0.001) and apixaban (PDC = 0.82, 0.75, and 0.71; P < 0.001), as well as nearly twice the number of switches to either other anticoagulants or antiplatelet therapy. At 9 months, 55.0% of rivaroxaban initiators had PDC ≥ 0.80, which was comparable with 56.8% for apixaban and significantly greater than 46.7% for dabigatran (P < 0.001). Adherence was higher overall as stroke risk increased and showed dabigatran had consistently lower adherence compared with the other NOACs. Overall adherence to any oral anticoagulants, allowing for switches to another NOAC or warfarin, was not dependent on the index medication (9-month PDC = 0.74, 0.71, and 0.74 for rivaroxaban, dabigatran, and apixaban initiators). Adjusted analyses showed that increasing age and comorbid hypertension and diabetes were associated with higher adherence. Compared with rivaroxaban, dabigatran initiators had nearly 30% lower odds of being adherent to their index medication, and no differences were observed between apixaban and rivaroxaban. At 9 months, there were no differences between NOACs for overall adherence to oral anticoagulants. In this real-world analysis of adherence to NOACs, rivaroxaban and apixaban had favorable profiles compared with dabigatran, and rivaroxaban appeared to have higher overall adherence among the NOACs. Clinicians and managed care organizations should consider the implications of lower adherence on clinical outcomes as well as quality assessment. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Brown reports receiving a training fellowship from Human and Pfizer. Study concept and design were contributed by Brown and Shewale. Talbert took the lead in data collection, along with Brown, and data interpretation was primarily performed by Brown, along with Shewale. The manuscript was written primarily by Brown, along with Shewale, and revised by all the authors.

Multiphoton correlations in parametric down-conversion and their measurement in the pulsed regime

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

Ivanova, O A; Iskhakov, T Sh; Penin, A N

2006-10-31

We consider normalised intensity correlation functions (CFs) of different orders for light emitted via parametric down-conversion (PDC) and their dependence on the number of photons per mode. The main problem in measuring such correlation functions is their extremely small width, which considerably reduces their contrast. It is shown that if the radiation under study is modulated by a periodic sequence of pulses that are short compared to the CF width, no decrease in the contrast occurs. A procedure is proposed for measuring normalised CFs of various orders in the pulsed regime. For nanosecond-pulsed PDC radiation, normalised second-order CF is measuredmore » experimentally as a function of the mean photon number. (nonlinear optical phenomena)« less

Alkanes from Bioderived Furans by using Metal Triflates and Palladium-Catalyzed Hydrodeoxygenation of Cyclic Ethers.

PubMed

Song, Hai-Jie; Deng, Jin; Cui, Min-Shu; Li, Xing-Long; Liu, Xin-Xin; Zhu, Rui; Wu, Wei-Peng; Fu, Yao

2015-12-21

Using a metal triflate and Pd/C as catalysts, alkanes were prepared from bioderived furans in a one-pot hydrodeoxygenation (HDO) process. During the reaction, the metal triflate plays a crucial role in the ring-opening HDO of furan compounds. The entire reaction process has goes through two major phases: at low temperatures, saturation of the exocyclic double bond and furan ring are catalyzed by Pd/C; at high temperatures, the HDO of saturated furan compounds is catalyzed by the metal triflate. The reaction mechanism was verified by analyzing the changes of the intermediates during the reaction. In addition, different metal triflates, solvents, and catalyst recycling were also investigated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethanol production by engineered thermophiles.

PubMed

Olson, Daniel G; Sparling, Richard; Lynd, Lee R

2015-06-01

We compare a number of different strategies that have been pursued to engineer thermophilic microorganisms for increased ethanol production. Ethanol production from pyruvate can proceed via one of four pathways, which are named by the key pyruvate dissimilating enzyme: pyruvate decarboxylase (PDC), pyruvate dehydrogenase (PDH), pyruvate formate lyase (PFL), and pyruvate ferredoxin oxidoreductase (PFOR). For each of these pathways except PFL, we see examples where ethanol production has been engineered with a yield of >90% of the theoretical maximum. In each of these cases, this engineering was achieved mainly by modulating expression of native genes. We have not found an example where a thermophilic ethanol production pathway has been transferred to a non-ethanol-producing organism to produce ethanol at high yield. A key reason for the lack of transferability of ethanol production pathways is the current lack of understanding of the enzymes involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.

PubMed

Schlitzer, Andreas; Heiseke, Alexander F; Einwächter, Henrik; Reindl, Wolfgang; Schiemann, Matthias; Manta, Calin-Petru; See, Peter; Niess, Jan-Hendrik; Suter, Tobias; Ginhoux, Florent; Krug, Anne B

2012-06-21

The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.

Intratumoral CpG-B promotes anti-tumoral neutrophil, cDC, and T cell cooperation without reprograming tolerogenic pDC.

PubMed

Humbert, Marion; Guery, Leslie; Brighouse, Dale; Lemeille, Sylvain; Hugues, Stephanie

2018-03-27

Cancer immunotherapies utilize distinct mechanisms to harness the power of the immune system to eradicate cancer cells. Therapeutic vaccines, aimed at inducing active immune responses against an existing cancer, are highly dependent on the immunological microenvironment, where many immune cell types display high levels of plasticity and, depending on the context, promote very different immunological outcomes. Among them, plasmacytoid dendritic cells (pDC), known to be highly immunogenic upon inflammation, are maintained in a tolerogenic state by the tumor microenvironment. Here we report that intratumoral (i.t.) injection of established solid tumors with CpG oligonucleotides-B (CpG-B) inhibits tumor growth. Interestingly, control of tumor growth was independent of tumor-associated (TA) pDC, which remained refractory to CpG-B stimulation and whose depletion did not alter the efficacy of the treatment. Instead, tumor growth inhibition subsequent to i.t. CpG-B injection depended on the recruitment of neutrophils into the milieu, resulting in the activation of conventional dendritic cells (cDC), subsequent increased anti-tumor T cell priming in draining lymph nodes, and enhanced effector T cell infiltration in the tumor microenvironment. These results reinforce the concept that intratumoral delivery of TLR9 agonists alters the tumor microenvironment by improving the anti-tumor activity of both innate and adaptive immune cells. Copyright ©2018, American Association for Cancer Research.

Impact of HIV-specialized pharmacies on adherence to medications for comorbid conditions.

PubMed

DuChane, Janeen; Clark, Bobby; Hou, John; Fitzner, Karen; Pietrandoni, Glen; Duncan, Ian

2014-01-01

To determine if patients using human immunodeficiency virus (HIV)-specialized pharmacies have greater adherence to drugs used to treat comorbid conditions and HIV compared with patients who use traditional pharmacies. Retrospective cohort study, with patients' propensity matched based on pharmacy use: HIV-specialized versus traditional. Nationwide pharmacy chain. Adult patients who filled at least two prescriptions for an antiretroviral therapy (ART). Patients also needed to have at least two prescriptions for an angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) or a statin for analyses examining comorbid conditions. Proportion of days covered (PDC). The adherence analyses for ART, ACE inhibitors/ARBs, and statins included 14,278, 1,484, and 1,372 pairs, respectively. The mean PDC for ART patients using HIV-specialized pharmacies was higher than that for patients using traditional pharmacies (86.20% vs. 81.87%; P <0.0001). Patients taking ACE inhibitors/ARBs in the specialized group also had a higher mean PDC compared with patients in the traditional group (82.61 vs. 79.66; P = 0.0002), as did specialized pharmacy users in the statin group (83.77 vs. 81.29; P = 0.0009). HIV patients managed by an HIV-specialized pharmacy have significantly higher adherence to medication for comorbid conditions compared with patients using traditional pharmacies. Patients of HIV-specialized pharmacies also have significantly higher adherence to ART compared with peers using traditional pharmacies.

Materials and methods for the alteration of enzyme and acetyl CoA levels in plants

DOEpatents

Nikolau, Basil J.; Wurtele, Eve S.; Oliver, David J.; Behal, Robert; Schnable, Patrick S.; Ke, Jinshan; Johnson, Jerry L.; Allred, Carolyn C.; Fatland, Beth; Lutziger, Isabelle; Wen, Tsui-Jung

2005-09-13

The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method of producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.alpha. subunit of pPDH, the E1.beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyruvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.alpha. pPDH, E1.beta. pPDH, E2 pPDH, mtPDH or ALDH.

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

Nikolau, Basil J.; Wurtele, Eve S.; Oliver, David J.

The present invention provides nucleic acid and amino acid sequences of acetyl CoA synthetase (ACS), plastidic pyruvate dehydrogenase (pPDH), ATP citrate lyase (ACL), Arabidopsis pyruvate decarboxylase (PDC), and Arabidopsis aldehyde dehydrogenase (ALDH), specifically ALDH-2 and ALDH-4. The present invention also provides a recombinant vector comprising a nucleic acid sequence encoding one of the aforementioned enzymes, an antisense sequence thereto or a ribozyme therefor, a cell transformed with such a vector, antibodies to the enzymes, a plant cell, a plant tissue, a plant organ or a plant in which the level of an enzyme has been altered, and a method ofmore » producing such a plant cell, plant tissue, plant organ or plant. Desirably, alteration of the level of enzyme results in an alteration of the level of acetyl CoA in the plant cell, plant tissue, plant organ or plant. In addition, the present invention provides a recombinant vector comprising an antisense sequence of a nucleic acid sequence encoding pyruvate decarboxylase (PDC), the E1.sub..alpha. subunit of pPDH, the E1.sub..beta. subunit of pPDH, the E2 subunit of pPDH, mitochondrial pyurvate dehydrogenase (mtPDH) or aldehyde dehydrogenase (ALDH) or a ribozyme that can cleave an RNA molecule encoding PDC, E1.sub..alpha. pPDH, E1.sub..beta. pPDH, E2 pPDH, mtPDH or ALDH.« less

Directed blasts and blast-generated pyroclastic density currents: a comparison of the Bezymianny 1956, Mount St Helens 1980, and Soufrière Hills, Montserrat 1997 eruptions and deposits

USGS Publications Warehouse

Belousov, Alexander; Voight, Barry; Belousova, Marina

2007-01-01

We compare eruptive dynamics, effects and deposits of the Bezymianny 1956 (BZ), Mount St Helens 1980 (MSH), and Soufrière Hills volcano, Montserrat 1997 (SHV) eruptions, the key events of which included powerful directed blasts. Each blast subsequently generated a high-energy stratified pyroclastic density current (PDC) with a high speed at onset. The blasts were triggered by rapid unloading of an extruding or intruding shallow magma body (lava dome and/or cryptodome) of andesitic or dacitic composition. The unloading was caused by sector failures of the volcanic edifices, with respective volumes for BZ, MSH, and SHV c. 0.5, 2.5, and 0.05 km3 . The blasts devastated approximately elliptical areas, axial directions of which coincided with the directions of sector failures. We separate the transient directed blast phenomenon into three main parts, the burst phase, the collapse phase, and the PDC phase. In the burst phase the pressurized mixture is driven by initial kinetic energy and expands rapidly into the atmosphere, with much of the expansion having an initially lateral component. The erupted material fails to mix with sufficient air to form a buoyant column, but in the collapse phase, falls beyond the source as an inclined fountain, and thereafter generates a PDC moving parallel to the ground surface. It is possible for the burst phase to comprise an overpressured jet, which requires injection of momentum from an orifice; however some exploding sources may have different geometry and a jet is not necessarily formed. A major unresolved question is whether the preponderance of strong damage observed in the volcanic blasts should be attributed to shock waves within an overpressured jet, or alternatively to dynamic pressures and shocks within the energetic collapse and PDC phases. Internal shock structures related to unsteady flow and compressibility effects can occur in each phase. We withhold judgment about published shock models as a primary explanation for the damage sustained at MSH until modern 3D numerical modeling is accomplished, but argue that much of the damage observed in directed blasts can be reasonably interpreted to have been caused by high dynamic pressures and clast impact loading by an inclined collapsing fountain and stratified PDC. This view is reinforced by recent modeling cited for SHV. In distal and peripheral regions, solids concentration, maximum particle size, current speed, and dynamic pressure are diminished, resulting in lesser damage and enhanced influence by local topography on the PDC. Despite the different scales of the blasts (devastated areas were respectively 500, 600, and >10 km2 for BZ, MSH, and SHV), and some complexity involving retrogressive slide blocks and clusters of explosions, their pyroclastic deposits demonstrate strong similarity. Juvenile material composes >50% of the deposits, implying for the blasts a dominantly magmatic mechanism although hydrothermal explosions also occurred. The character of the magma fragmented by explosions (highly viscous, phenocryst-rich, variable microlite content) determined the bimodal distributions of juvenile clast density and vesicularity. Thickness of the deposits fluctuates in proximal areas but in general decreases with distance from the crater, and laterally from the axial region. The proximal stratigraphy of the blast deposits comprises four layers named A, B, C, D from bottom to top. Layer A is represented by very poorly sorted debris with admixtures of vegetation and soil, with a strongly erosive ground contact; its appearance varies at different sites due to different ground conditions at the time of the blasts. The layer reflects intense turbulent boundary shear between the basal part of the energetic head of the PDC and the substrate. Layer B exhibits relatively well-sorted fines depleted debris with some charred plant fragments; its deposition occurred by rapid suspension sedimentation in rapidly waning, high-concentration conditions. Layer C is mainly a poorly sorted massive layer enriched by fines with its uppermost part laminated, created by rapid sedimentation under moderate-concentration, weakly tractive conditions, with the uppermost laminated part reflecting a dilute depositional regime with grain-by-grain traction deposition. By analogy to laboratory experiments, mixing at the flow head of the PDC created a turbulent dilute wake above the body of a gravity current, with layer B deposited by the flow body and layer C by the wake. The uppermost layer D of fines and accretionary lapilli is an ash fallout deposit of the finest particles from the high-rising buoyant thermal plume derived from the sediment-depleted pyroclastic density current. The strong similarity among these eruptions and their deposits suggests that these cases represent similar source, transport and depositional phenomena.

Low-pH production of D-lactic acid using newly isolated acid tolerant yeast Pichia kudriavzevii NG7.

PubMed

Park, Hyun Joo; Bae, Jung-Hoon; Ko, Hyeok-Jin; Lee, Sun-Hee; Sung, Bong Hyun; Han, Jong-In; Sohn, Jung-Hoon

2018-06-13

Lactic acid is a platform chemical for the sustainable production of various materials. To develop a robust yeast platform for low-pH production of D-lactic acid, an acid-tolerant yeast strain was isolated from grape skins and named Pichia kudriavzevii NG7 by ribosomal RNA sequencing. This strain was able to grow at pH 2.0 and 50°C. For the commercial application of P. kudriavzevii NG7 as a lactic acid producer, the ethanol fermentation pathway was redirected to lactic acid by replacing pyruvate decarboxylase 1 gene (PDC1) with D-lactate dehydrogenase gene (D-LDH) derived from Lactobacillus plantarum. To enhance lactic acid tolerance, this engineered strain was adapted to high lactic acid concentrations, and a new transcriptional regulator, PAR1, responsible for acid tolerance, was identified by whole-genome resequencing. The final engineered strain produced 135 g/L and 154 g/L of D-lactic acid with productivity over 3.66 g/L/h at pH 3.6 and 4.16 g/L/h at pH 4.7, respectively. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Direct fermentation of Jerusalem artichoke tuber powder for production of l-lactic acid and d-lactic acid by metabolically engineered Kluyveromyces marxianus.

PubMed

Bae, Jung-Hoon; Kim, Hyun-Jin; Kim, Mi-Jin; Sung, Bong Hyun; Jeon, Jae-Heung; Kim, Hyun-Soon; Jin, Yong-Su; Kweon, Dae-Hyuk; Sohn, Jung-Hoon

2018-01-20

An efficient production system for optically pure l- and d-lactic acid (LA) from Jerusalem artichoke tuber powder (JAP) was developed by metabolic engineering of Kluyveromyces marxianus. To construct LA-producing strains, the ethanol fermentation pathway of K. marxianus was redirected to LA production by disruption of KmPDC1 and expression of l- and d-lactate dehydrogenase (LDH) genes derived from Lactobacillus plantarum under the control of the K. marxianus translation elongation factor 1α promoter. To further increase the LA titer, the l-LA and d-LA consumption pathway of host strains was blocked by deletion of the oxidative LDH genes KmCYB2 and KmDLD1. The recombinant strains produced 130g/L l-LA and 122g/L d-LA by direct fermentation from 230g/L JAP containing 140g/L inulin, without pretreatment or nutrient supplementation. The conversion efficiency and optical purity were ≫>95% and ≫>99%, respectively. This system using JAP and the inulin-assimilating yeast K. marxianus could lead to a cost-effective process for the production of LA. Copyright © 2017 Elsevier B.V. All rights reserved.

VizieR Online Data Catalog: Possible planets around A stars (Balona, 2014)

NASA Astrophysics Data System (ADS)

Balona, L. A.

2015-02-01

The Kepler Input Catalogue (KIC; Brown et al., 2011, Cat. V/133) provides estimates of effective temperature, surface gravity and radii for practically all stars in the Kepler field from ground-based multicolour photometry. The light curves for all Kepler A stars, i.e. stars with effective temperatures, Teff, in the range 7500

Risk Factors, Health Care Resource Utilization, and Costs Associated with Nonadherence to Antiretrovirals in Medicaid-Insured Patients with HIV.

PubMed

Dunn, Keith; Lafeuille, Marie-Hélène; Jiao, Xiaolong; Romdhani, Hela; Emond, Bruno; Woodruff, Kimberly; Pesa, Jacqueline; Tandon, Neeta; Lefebvre, Patrick

2018-06-07

Adherence to antiretrovirals (ARVs) is critical to achieving durable virologic suppression. To investigate risk factors of poor adherence and the effect of suboptimal adherence on health care resource utilization (HCRU) and costs in Medicaid patients. A retrospective longitudinal study was conducted using Medicaid data. Adults (aged ≥ 18 years) with human immunodeficiency virus (HIV)-1 initiating selected ARVs (index date) were identified. Adherence was measured using medication possession ratio (MPR) and proportion of days covered (PDC) at 6 and 12 months post-index. Risk factors of poor adherence (PDC < 80%) were assessed using a logistic regression. HCRU and costs were compared between suboptimal (80% ≤ PDC < 95%) and optimal (PDC ≥ 95%) adherence groups using Poisson and ordinary least square models, respectively. In total, 3,477 patients were identified. Using MPR, 1,282 (39.0%) of the evaluable patients had poor adherence; 667 (20.2%) had suboptimal adherence; and 1,342 (40.8%) had optimal adherence versus 1,342 (51.1%), 509 (19.0%), and 804 (30.0%), respectively, using PDC at 6 months. PDC at 12 months was even lower. Younger age (OR = 1.58; 95% CI = 1.18-2.11; P = 0.002), noncapitated coverage (OR = 1.40; 95% CI = 1.16-1.69; P < 0.001), dual Medicaid/Medicare coverage (OR = 5.98; 95% CI = 4.39-8.16; P < 0.001), no baseline ARV treatment (OR = 1.98; 95% CI = 1.62-2.41; P < 0.001), and baseline asymptomatic HIV (OR = 1.37; 95% CI = 1.13-1.68; P = 0.002) were associated with higher risk of poor adherence. Suboptimal adherence patients had higher total number of days spent in a hospital (incidence rate ratio [IRR] = 1.62; 95% CI = 1.13-2.19; P = 0.008), total number of long-term care admissions (IRR = 3.11; 95% CI = 1.26-7.39; P = 0.008), total medical costs (mean monthly cost difference = $339; 95% CI = $153-$536; P < 0.001), and inpatient costs (mean monthly cost difference = $259; 95% CI = $122-$418; P < 0.001) compared with patients with optimal adherence. Nonadherence to ARVs was observed in 60%-80% of Medicaid patients, depending on the adherence measure used, and was associated with incremental HCRU and costs. Age, insurance type and coverage, previous ARV treatment, and HIV symptoms were predictors of adherence. Treatment options that enhance adherence and prevent developing virologic failure with drug resistance should be considered for HIV patients. This study was supported by Janssen Scientific Affairs, which was involved in the study design, data collection, data analysis, manuscript preparation, and publication decisions. Emond, Lafeuille, Romdhani, and Lefebvre are employees of Analysis Group, a consulting company that received research grants from Janssen Scientific Affairs to conduct this study. Dunn, Woodruff, Pesa, and Tandon are current employees and stockholders of Johnson & Johnson, owner of Janssen Scientific Affairs. Jiao was an employee of Janssen at the time of the study. Emond has received grants from Novartis, Regeneron, Aegerion, Lundbeck, Bristol-Myers Squibb, Bayer, Millennium, Allergan, AbbVie, and GlaxoSmithKline unrelated to this study. Part of the material in this study was presented at the Academy of Managed Care Pharmacy 2017 Annual Meeting, March 27-30, 2017, in Denver, Colorado, and at the 9th International AIDS Society Conference, July 23-26, 2017, in Paris, France.