Blocking the proliferation of human tumor cell lines by peptidase inhibitors from Bauhinia seeds.

Science.gov (United States)

Nakahata, Adriana Miti; Mayer, Barbara; Neth, Peter; Hansen, Daiane; Sampaio, Misako Uemura; Oliva, Maria Luiza Vilela

2013-03-01

In cancer tumors, growth, invasion, and formation of metastasis at a secondary site play a pivotal role, participating in diverse processes in the development of the pathology, such as degradation of extracellular matrix. Bauhinia seeds contain relatively large quantities of peptidase inhibitors, and two Bauhinia inhibitors were obtained in a recombinant form from the Bauhinia bauhinioides species, B. bauhinoides cruzipain inhibitor, which is a cysteine and serine peptidase inhibitor, and B. bauhinioides kallikrein inhibitor, which is a serine peptidase inhibitor. While recombinant B. bauhinoides cruzipain inhibitor inhibits human neutrophil elastase cathepsin G and the cysteine proteinase cathepsin L, recombinant B. bauhinioides kallikrein inhibitor inhibits plasma kallikrein and plasmin. The effects of recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor on the viability of tumor cell lines with a distinct potential of growth from the same tissue were compared to those of the clinical cytotoxic drug 5-fluorouracil. At 12.5 µM concentration, recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor were more efficient than 5-fluorouracil in inhibiting MKN-28 and Hs746T (gastric), HCT116 and HT29 (colorectal), SkBr-3 and MCF-7 (breast), and THP-1 and K562 (leukemia) cell lines. Additionally, recombinant B. bauhinoides cruzipain inhibitor inhibited 40 % of the migration of Hs746T, the most invasive gastric cell line, while recombinant B. bauhinioides kallikrein inhibitor did not affect cell migration. Recombinant B. bauhinioides kallikrein inhibitor and recombinant B. bauhinoides cruzipain inhibitor, even at high doses, did not affect hMSC proliferation while 5-fluorouracil greatly reduced the proliferation rates of hMSCs. Therefore, both recombinant B. bauhinoides cruzipain inhibitor and recombinant B. bauhinioides kallikrein inhibitor might be considered for further studies

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Czech Academy of Sciences Publication Activity Database

Sojka, D.; Hartmann, D.; Bartošová-Sojková, P.; Dvořák, Jan

2016-01-01

Roč. 32, č. 9 (2016), s. 708-723 ISSN 1471-4922 R&D Projects: GA ČR GA13-11043S; GA ČR(CZ) GAP302/11/1481 Institutional support: RVO:61388963 Keywords : aspartic peptidases * cathepsin D * hemoglobinolysis * parasites * vectors Subject RIV: CE - Biochemistry Impact factor: 6.333, year: 2016

Protective immune responses against Schistosoma mansoni infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase.

Directory of Open Access Journals (Sweden)

Hatem Tallima

2017-03-01

Full Text Available Schistosomiasis, a severe disease caused by parasites of the genus Schistosoma, is prevalent in 74 countries, affecting more than 250 million people, particularly children. We have previously shown that the Schistosoma mansoni gut-derived cysteine peptidase, cathepsin B1 (SmCB1, administered without adjuvant, elicits protection (>60% against challenge infection of S. mansoni or S. haematobium in outbred, CD-1 mice. Here we compare the immunogenicity and protective potential of another gut-derived cysteine peptidase, S. mansoni cathepsin L3 (SmCL3, alone, and in combination with SmCB1. We also examined whether protective responses could be boosted by including a third non-peptidase schistosome secreted molecule, glyceraldehyde 3-phosphate dehydrogenase (SG3PDH, with the two peptidases.While adjuvant-free SmCB1 and SmCL3 induced type 2 polarized responses in CD-1 outbred mice those elicited by SmCL3 were far weaker than those induced by SmCB1. Nevertheless, both cysteine peptidases evoked highly significant (P < 0.005 reduction in challenge worm burden (54-65% as well as worm egg counts and viability. A combination of SmCL3 and SmCB1 did not induce significantly stronger immune responses or higher protection than that achieved using each peptidase alone. However, when the two peptidases were combined with SG3PDH the levels of protection against challenge S. mansoni infection reached 70-76% and were accompanied by highly significant (P < 0.005 decreases in worm egg counts and viability. Similarly, high levels of protection were achieved in hamsters immunized with the cysteine peptidase/SG3PDH-based vaccine.Gut-derived cysteine peptidases are highly protective against schistosome challenge infection when administered subcutaneously without adjuvant to outbred CD-1 mice and hamsters, and can also act to enhance the efficacy of other schistosome antigens, such as SG3PDH. This cysteine peptidase-based vaccine should now be advanced to experiments in

Induction of Protective Immune Responses against Schistosomiasis Haematobium in Hamsters and Mice Using Cysteine Peptidase-Based Vaccine

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Hatem A M Tallima

2015-03-01

Full Text Available One of the major lessons we learned from the radiation-attenuated cercariae (RA vaccine studies is that protective immunity against schistosomiasis is dependent on the induction of T helper (Th1/Th2-related immune responses. Since most schistosome larval and adult-worm-derived molecules used for vaccination uniformly induce a polarized Th1 response, it was essential to include a type 2 immune responses-inducing molecule, such as cysteine peptidases, in the vaccine formula. Here we demonstrate that a single subcutaneous injection of Syrian hamsters with 200 microg active papain 1 h before percutaneous exposure to 150 cercariae of Schistosoma haematobium led to highly significant (P 50% in worm burden and worm egg counts in intestine. Immunization of hamsters with 20 microg recombinant glyceraldehyde 3-phosphate dehydrogenase (rSG3PDH and 20 ug 2-cys peroxiredoxin-derived peptide in a multiple antigen peptide construct (PRX MAP together with papain (20 microg/hamster as adjuvant led to considerable (64% protection against challenge S. haematobium infection, similar to the levels reported with irradiated cercariae. Cysteine peptidases-based vaccination was also effective in protecting outbred mice against a percutaneous challenge infection with S. haematobium cercariae. In two experiments, a mixture of Schistosoma mansoni cathepsin B1 (SmCB1 and Fasciola hepatica cathepsin L1 (FhCL1 led to highly significant (P < 0.005 reduction of 70% in challenge S. haematobium worm burden and 60% reduction in liver egg counts. Mice vaccinated with SmCB1/FhCL1/ rSG3PDH mixture and challenged with S. haematobium cercariae three weeks after the second immunization displayed highly significant (P < 0.005 reduction of 72% in challenge worm burden and no eggs in liver of 8-10 mice/group, as compared to unimmunized mice, associated with production of a mixture of type 1 and type 2-related cytokines and antibody responses.

Dipeptidyl peptidase expression during experimental colitis in mice

DEFF Research Database (Denmark)

Yazbeck, Roger; Sulda, Melanie L; Howarth, Gordon S

2010-01-01

We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection.......We have previously demonstrated that inhibition of dipeptidyl peptidase (DP) activity partially attenuates dextran sulfate sodium (DSS) colitis in mice. The aim of this study was to further investigate the mechanisms of this protection....

Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

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Chong-Yu Zhang

2015-02-01

Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

Lysosomal cysteine peptidases - Molecules signaling tumor cell death and survival.

Science.gov (United States)

Pišlar, Anja; Perišić Nanut, Milica; Kos, Janko

2015-12-01

Lysosomal cysteine peptidases - cysteine cathepsins - are general intracellular protein-degrading enzymes that control also a variety of specific physiological processes. They can trigger irreversible events leading to signal transduction and activation of signaling pathways, resulting in cell survival and proliferation or cell death. In cancer cells, lysosomal cysteine peptidases are involved in multiple processes during malignant progression. Their translocation from the endosomal/lysosomal pathway to nucleus, cytoplasm, plasma membrane and extracellular space enables the activation and remodeling of a variety of tumor promoting proteins. Thus, lysosomal cysteine peptidases interfere with cytokine/chemokine signaling, regulate cell adhesion and migration and endocytosis, are involved in the antitumor immune response and apoptosis, and promote cell invasion, angiogenesis and metastasis. Further, lysosomal cysteine peptidases modify growth factors and receptors involved in tyrosine kinase dependent pathways such as MAPK, Akt and JNK, thus representing key signaling tools for the activation of tumor cell growth and proliferation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Parasite Cathepsin D-Like Peptidases and Their Relevance as Therapeutic Targets

Czech Academy of Sciences Publication Activity Database

Sojka, Daniel; Hartmann, David; Bartošová-Sojková, Pavla; Dvořák, Jan

2016-01-01

Roč. 32, č. 9 (2016), s. 708-723 ISSN 1471-4922 R&D Projects: GA ČR GA14-33693S; GA ČR GA13-11043S; GA ČR(CZ) GAP302/11/1481 EU Projects: European Commission(XE) 248642 - SCHISTOSOMA PROTEASE Institutional support: RVO:60077344 ; RVO:68378050 Keywords : aspartic peptidases * cathepsin D * hemoglobinolysis * parasites * vectors Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 6.333, year: 2016

Selective chromogenic and fluorogenic peptide substrates for the assay of cysteine peptidases in complex mixtures.

Science.gov (United States)

Semashko, Tatiana A; Vorotnikova, Elena A; Sharikova, Valeriya F; Vinokurov, Konstantin S; Smirnova, Yulia A; Dunaevsky, Yakov E; Belozersky, Mikhail A; Oppert, Brenda; Elpidina, Elena N; Filippova, Irina Y

2014-03-15

This study describes the design, synthesis, and use of selective peptide substrates for cysteine peptidases of the C1 papain family, important in many biological processes. The structure of the newly synthesized substrates is Glp-Xaa-Ala-Y (where Glp=pyroglutamyl; Xaa=Phe or Val; and Y=pNA [p-nitroanilide], AMC [4-amino-7-methylcoumaride], or AFC [4-amino-7-trifluoromethyl-coumaride]). Substrates were synthesized enzymatically to guarantee selectivity of the reaction and optical purity of the target compounds, simplifying the scheme of synthesis and isolation of products. The hydrolysis of the synthesized substrates was evaluated by C1 cysteine peptidases from different organisms and with different functions, including plant enzymes papain, bromelain, ficin, and mammalian lysosomal cathepsins B and L. The new substrates were selective for C1 cysteine peptidases and were not hydrolyzed by serine, aspartic, or metallo peptidases. We demonstrated an application of the selectivity of the synthesized substrates during the chromatographic separation of a multicomponent set of digestive peptidases from a beetle, Tenebrio molitor. Used in combination with the cysteine peptidase inhibitor E-64, these substrates were able to differentiate cysteine peptidases from peptidases of other classes in midgut extracts from T. molitor larvae and larvae of the genus Tribolium; thus, they are useful in the analysis of complex mixtures containing peptidases from different classes. Published by Elsevier Inc.

Digestive peptidase evolution in holometabolous insects led to a divergent group of enzymes in Lepidoptera

KAUST Repository

Dias, Renata O.; Via, Allegra; Brandã o, Marcelo M.; Tramontano, Anna; Silva-Filho, Marcio C.

2015-01-01

© 2015 Elsevier Ltd. Trypsins and chymotrypsins are well-studied serine peptidases that cleave peptide bonds at the carboxyl side of basic and hydrophobic l-amino acids, respectively. These enzymes are largely responsible for the digestion of proteins. Three primary processes regulate the activity of these peptidases: secretion, precursor (zymogen) activation and substrate-binding site recognition. Here, we present a detailed phylogenetic analysis of trypsins and chymotrypsins in three orders of holometabolous insects and reveal divergent characteristics of Lepidoptera enzymes in comparison with those of Coleoptera and Diptera. In particular, trypsin subsite S1 was more hydrophilic in Lepidoptera than in Coleoptera and Diptera, whereas subsites S2-S4 were more hydrophobic, suggesting different substrate preferences. Furthermore, Lepidoptera displayed a lineage-specific trypsin group belonging only to the Noctuidae family. Evidence for facilitated trypsin auto-activation events were also observed in all the insect orders studied, with the characteristic zymogen activation motif complementary to the trypsin active site. In contrast, insect chymotrypsins did not seem to have a peculiar evolutionary history with respect to their mammal counterparts. Overall, our findings suggest that the need for fast digestion allowed holometabolous insects to evolve divergent groups of peptidases with high auto-activation rates, and highlight that the evolution of trypsins led to a most diverse group of enzymes in Lepidoptera.

Digestive peptidase evolution in holometabolous insects led to a divergent group of enzymes in Lepidoptera

KAUST Repository

Dias, Renata O.

2015-03-01

© 2015 Elsevier Ltd. Trypsins and chymotrypsins are well-studied serine peptidases that cleave peptide bonds at the carboxyl side of basic and hydrophobic l-amino acids, respectively. These enzymes are largely responsible for the digestion of proteins. Three primary processes regulate the activity of these peptidases: secretion, precursor (zymogen) activation and substrate-binding site recognition. Here, we present a detailed phylogenetic analysis of trypsins and chymotrypsins in three orders of holometabolous insects and reveal divergent characteristics of Lepidoptera enzymes in comparison with those of Coleoptera and Diptera. In particular, trypsin subsite S1 was more hydrophilic in Lepidoptera than in Coleoptera and Diptera, whereas subsites S2-S4 were more hydrophobic, suggesting different substrate preferences. Furthermore, Lepidoptera displayed a lineage-specific trypsin group belonging only to the Noctuidae family. Evidence for facilitated trypsin auto-activation events were also observed in all the insect orders studied, with the characteristic zymogen activation motif complementary to the trypsin active site. In contrast, insect chymotrypsins did not seem to have a peculiar evolutionary history with respect to their mammal counterparts. Overall, our findings suggest that the need for fast digestion allowed holometabolous insects to evolve divergent groups of peptidases with high auto-activation rates, and highlight that the evolution of trypsins led to a most diverse group of enzymes in Lepidoptera.

Extracellular peptidases of the cereal pathogen Fusarium graminearum.

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Rohan George Thomas Lowe

2015-11-01

Full Text Available The plant pathogenic fungus Fusarium graminearum (Fgr creates economic and health risks in cereals agriculture. Fgr causes head blight (or scab of wheat and stalk rot of corn, reducing yield, degrading grain quality and polluting downstream food products with mycotoxins. Fungal plant pathogens must secrete proteases to access nutrition and to breakdown the structural protein component of the plant cell wall. Research into the proteolytic activity of Fgr is hindered by the complex nature of the suite of proteases secreted. We used a systems biology approach comprising genome analysis, transcriptomics and label-free quantitative proteomics to characterise the peptidases deployed by Fgr during growth. A combined analysis of published microarray transcriptome datasets revealed seven transcriptional groupings of peptidases based on in vitro growth, in planta growth, and sporulation behaviours. An orbitrap MS/MS proteomics technique defined the extracellular proteases secreted by Fusarium graminearum. A meta-classification based on sequence characters and transcriptional/translational activity in planta and in vitro provides a platform to develop control strategies that target Fgr peptidases.

Novel structural mechanism of allosteric regulation of aspartic peptidases via evolutionary conserved exosite

Czech Academy of Sciences Publication Activity Database

Hánová, Iva; Brynda, Jiří; Hobizalová, Radka; Alam, N.; Sojka, Daniel; Kopáček, Petr; Marešová, Lucie; Vondrášek, Jiří; Horn, Martin; Schueler-Furman, O.; Mareš, Michael

2017-01-01

Roč. 284, Suppl 1 (2017), s. 300-301 ISSN 1742-464X. [FEBS Congress /42./ From Molecules to Cells and Back. 10.09.2017-14.09.2017, Jerusalem] Institutional support: RVO:61388963 ; RVO:60077344 Keywords : aspartic peptidases * exosite inhibition Subject RIV: CE - Biochemistry

Mycoplasma hyopneumoniae in vitro peptidase activities: identification and cleavage of kallikrein-kinin system-like substrates.

Science.gov (United States)

Moitinho-Silva, Lucas; Kondo, Marcia Y; Oliveira, Lilian C G; Okamoto, Debora N; Paes, Jéssica A; Machado, Mauricio F M; Veronez, Camila L; Motta, Guacyara; Andrade, Sheila S; Juliano, Maria A; Ferreira, Henrique B; Juliano, Luiz; Gouvea, Iuri E

2013-05-03

Bacterial proteases are important for metabolic processes and pathogenesis in host organisms. The bacterial swine pathogen Mycoplasma hyopneumoniae has 15 putative protease-encoding genes annotated, but none of them have been functionally characterized. To identify and characterize peptidases that could be relevant for infection of swine hosts, we investigated the peptidase activity present in the pathogenic 7448 strain of M. hyopneumoniae. Combinatorial libraries of fluorescence resonance energy transfer peptides, specific inhibitors and pH profiling were used to screen and characterize endopeptidase, aminopeptidase and carboxypeptidase activities in cell lysates. One metalloendopeptidase, one serine endopeptidase, and one aminopeptidase were detected. The detected metalloendopeptidase activity, prominent at neutral and basic pH ranges, was due to a thimet oligopeptidase family member (M3 family), likely an oligoendopeptidase F (PepF), which cleaved the peptide Abz-GFSPFRQ-EDDnp at the F-S bond. A chymotrypsin-like serine endopeptidase activity, possibly a subtilisin-like serine protease, was prominent at higher pH levels, and was characterized by its preference for a Phe residue at the P1 position of the substrate. The aminopeptidase P (APP) activity showed a similar profile to that of human membrane-bound APP. Genes coding for these three peptidases were identified and their transcription was confirmed in the 7448 strain. Furthermore, M. hyopneumoniae cell lysate peptidases showed effects on kallikrein-kinin system-like substrates, such as bradykinin-derived substrates and human high molecular weight kininogen. The M. hyopneumoniae peptidase activities, here characterized for the first time, may be important for bacterial survival strategies and thus represent possible targets for drug development against M. hyopneumoniae swine infections. Copyright © 2013 Elsevier B.V. All rights reserved.

Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type

Energy Technology Data Exchange (ETDEWEB)

Tomkinson, B.; Wernstedt, C.; Hellman, U.; Zetterqvist, Oe.

1987-11-01

The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with (/sup 3/H)diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residues 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases.

Fibrinogen and fibrin are novel substrates for Fasciola hepatica cathepsin L peptidases

NARCIS (Netherlands)

Mebius, Mirjam M.; Op Heij, Jody M J; Tielens, Aloysius G.M.; de Groot, Philip G; Urbanus, Rolf T; van Hellemond, Jaap J.

2018-01-01

Cathepsin peptidases form a major component of the secreted proteins of the blood-feeding trematodes Fasciola hepatica and Schistosoma mansoni. These peptidases fulfill many functions, from facilitating infection to feeding and immune evasion. In this study, we examined the Fasciola cathepsin L

Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

Energy Technology Data Exchange (ETDEWEB)

Wright, Helena [Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom); Kiss, András L.; Szeltner, Zoltán; Polgár, László [Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, H-1518 Budapest 112, PO Box 7 (Hungary); Fülöp, Vilmos, E-mail: vilmos@globin.bio.warwick.ac.uk [Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL (United Kingdom)

2005-10-01

Acylaminoacyl peptidase from porcine liver has been crystallized. Data were collected to 3.4 Å from native crystals and a search for heavy-atom derivatives is in progress. Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris–HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl{sub 2} and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 Å resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 Å and four molecules in the asymmetric unit.

Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase

International Nuclear Information System (INIS)

Wright, Helena; Kiss, András L.; Szeltner, Zoltán; Polgár, László; Fülöp, Vilmos

2005-01-01

Acylaminoacyl peptidase from porcine liver has been crystallized. Data were collected to 3.4 Å from native crystals and a search for heavy-atom derivatives is in progress. Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris–HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl 2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 Å resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 Å and four molecules in the asymmetric unit

Insecticidal effect of Canavalia ensiformis major urease on nymphs of the milkweed bug Oncopeltus fasciatus and characterization of digestive peptidases.

Science.gov (United States)

Defferrari, Marina S; Demartini, Diogo R; Marcelino, Thiago B; Pinto, Paulo M; Carlini, Celia R

2011-06-01

Jackbean (Canavalia ensiformis) ureases are entomotoxic upon the release of internal peptides by insect's digestive enzymes. Here we studied the digestive peptidases of Oncopeltus fasciatus (milkweed bug) and its susceptibility to jackbean urease (JBU). O. fasciatus nymphs fed urease showed a mortality rate higher than 80% after two weeks. Homogenates of midguts dissected from fourth instars were used to perform proteolytic activity assays. The homogenates hydrolyzed JBU in vitro, yielding a fragment similar in size to known entomotoxic peptides. The major proteolytic activity at pH 4.0 upon protein substrates was blocked by specific inhibitors of aspartic and cysteine peptidases, but not significantly affected by inhibitors of metallopeptidases or serine peptidases. The optimal activity upon N-Cbz-Phe-Arg-MCA was at pH 5.0, with complete blockage by E-64 in all pH tested. Optimal activity upon Abz-AIAFFSRQ-EDDnp (a substrate for aspartic peptidases) was detected at pH 5.0, with partial inhibition by Pepstatin A in the pH range 2-8. Fluorogenic substrates corresponding to the N- and C-terminal regions flanking a known entomotoxic peptide within urease sequence were also tested. While the midgut homogenate did not hydrolyze the N-terminal peptide, it cleaved the C-terminal peptide maximally at pH 4.0-5.0, and this activity was inhibited by E-64 (10 μM). The midgut homogenate was submitted to ion-exchange chromatography followed by gel filtration. A 22 kDa active fraction was obtained, resolved in SDS-PAGE (12%), the corresponding band was in-gel digested by trypsin, the peptides were analyzed by mass spectrometry, retrieving a cathepsin L protein. The purified cathepsin L was shown to have at least two possible cleavage sites within the urease sequence, and might be able to release a known insecticidal peptide in a single or cascade event. The results suggest that susceptibility of O. fasciatus nymphs to jackbean urease is, like in other insect models, due mostly

DapE Can Function as an Aspartyl Peptidase in the Presence of Mn2+

OpenAIRE

Broder, Daniel H.; Miller, Charles G.

2003-01-01

Extracts of a multiply peptidase-deficient (pepNABDPQTE iadA iaaA) Salmonella enterica serovar Typhimurium strain contain an aspartyl dipeptidase activity that is dependent on Mn2+. Purification of this activity followed by N-terminal sequencing of the protein suggested that the Mn2+-dependent peptidase is DapE (N-succinyl-l,l-diaminopimelate desuccinylase). A dapE chromosomal disruption was constructed and transduced into a multiply peptidase-deficient (MPD) strain. Crude extracts of this st...

Dipeptidyl peptidase-4 inhibitor induced angioedema - an overlooked and potentially lethal adverse drug reaction?

DEFF Research Database (Denmark)

Scott, Susanne Irene; Andersen, Michelle Fog; Aagaard, Lise

2018-01-01

to vasodilatation and increase in vascular permeability in the capillaries. Objective To assess the risk and pathomechanism of angioedema due to inhibition of dipeptidyl peptidase-4 inhibitors when used as monotherapy and in combination with angiotensin converting enzyme-inhibitors. Method PubMed, Embase......, the Cochrane Library, PubMed Central, Web of Science, Google Scholar and clinicaltrials.gov were searched using different combinations of keywords "angioedema", "dipeptidyl peptidase 4", "dipeptidyl peptidase 4 inhibitors", "gliptins", "bradykinin", "substance P" and "angiotensin converting enzyme...

DapE can function as an aspartyl peptidase in the presence of Mn2+.

Science.gov (United States)

Broder, Daniel H; Miller, Charles G

2003-08-01

Extracts of a multiply peptidase-deficient (pepNABDPQTE iadA iaaA) Salmonella enterica serovar Typhimurium strain contain an aspartyl dipeptidase activity that is dependent on Mn(2+). Purification of this activity followed by N-terminal sequencing of the protein suggested that the Mn(2+)-dependent peptidase is DapE (N-succinyl-L,L-diaminopimelate desuccinylase). A dapE chromosomal disruption was constructed and transduced into a multiply peptidase-deficient (MPD) strain. Crude extracts of this strain showed no aspartyl peptidase activity, and the strain failed to utilize Asp-Leu as a leucine source. The dapE gene was cloned into expression vectors in order to overproduce either the native protein (DapE) or a hexahistidine fusion protein (DapE-His(6)). Extracts of a strain carrying the plasmid overexpresssing native DapE in the MPD dapE background showed a 3,200-fold elevation of Mn(2+)-dependent aspartyl peptidase activity relative to the MPD dapE(+) strain. In addition, purified DapE-His(6) exhibited Mn(2+)-dependent peptidase activity toward aspartyl dipeptides. Growth of the MPD strain carrying a single genomic copy of dapE on Asp-Leu as a Leu source was slow but detectable. Overproduction of DapE in the MPD dapE strain allowed growth on Asp-Leu at a much faster rate. DapE was found to be specific for N-terminal aspartyl dipeptides: no N-terminal Glu, Met, or Leu peptides were hydrolyzed, nor were any peptides containing more than two amino acids. DapE is known to bind two divalent cations: one with high affinity and the other with lower affinity. Our data indicate that the form of DapE active as a peptidase contains Zn(2+) in the high-affinity site and Mn(2+) in the low-affinity site.

Bacillus thuringiensis Cry3Aa protoxin intoxication of Tenebrio molitor induces widespread changes in the expression of serine peptidase transcripts.

Science.gov (United States)

Oppert, Brenda; Martynov, Alexander G; Elpidina, Elena N

2012-09-01

The yellow mealworm, Tenebrio molitor, is a pest of stored grain products and is sensitive to the Bacillus thuringiensis (Bt) Cry3Aa toxin. As digestive peptidases are a determining factor in Cry toxicity and resistance, we evaluated the expression of peptidase transcripts in the midgut of T. molitor larvae fed either a control or Cry3Aa protoxin diet for 24 h (RNA-Seq), or in larvae exposed to the protoxin for 6, 12, or 24 h (microarrays). Cysteine peptidase transcripts (9) were similar to cathepsins B, L, and K, and their expression did not vary more than 2.5-fold in control and Cry3Aa-treated larvae. Serine peptidase transcripts (48) included trypsin, chymotrypsin and chymotrypsin-like, elastase 1-like, and unclassified serine peptidases, as well as homologs lacking functional amino acids. Highly expressed trypsin and chymotrypsin transcripts were severely repressed, and most serine peptidase transcripts were expressed 2- to 15-fold lower in Cry3Aa-treated larvae. Many serine peptidase and homolog transcripts were found only in control larvae. However, expression of a few serine peptidase transcripts was increased or found only in Cry3Aa-treated larvae. Therefore, Bt intoxication significantly impacted the expression of serine peptidases, potentially important in protoxin processing, while the insect maintained the production of critical digestive cysteine peptidases. Published by Elsevier Inc.

Reductive Evolution of the Mitochondrial Processing Peptidases of the Unicellular Parasites Trichomonas vaginalis and Giardia intestinalis

Czech Academy of Sciences Publication Activity Database

Šmíd, O.; Matušková, Anna; Harris, S. R.; Kučera, Tomáš; Novotný, M.; Horváthová, L.; Hrdý, I.; Kutejová, E.; Hirt, R. P.; Embley, T. M.; Janata, Jiří; Tachezy, J.

2008-01-01

Roč. 4, č. 12 (2008), s. 1-8 ISSN 1553-7366 R&D Projects: GA MŠk LC07032; GA AV ČR IAA501110631 Grant - others:CZ(CZ) B-Bio166/2006 (O.S.). S.H., R.P.H. Institutional research plan: CEZ:AV0Z50200510 Keywords : peptidases * mitochondria * human parasites Subject RIV: EE - Microbiology, Virology Impact factor: 9.125, year: 2008

Cuparane sesquiterpenes from Laurencia natalensis Kylin as inhibitors of alpha-glucosidase, dipeptidyl peptidase IV and xanthine oxidase

Czech Academy of Sciences Publication Activity Database

Rengasamy, K.R.R.; Poštová Slavětínská, Lenka; Kulkarni, M. G.; Stirk, W. A.; Van Staden, J.

2017-01-01

Roč. 25, Jul (2017), s. 178-183 ISSN 2211-9264 Institutional support: RVO:61388963 Keywords : 1-deoxyalgoane * dipeptidyl peptidase IV * diabetes * gout * Laurencia natalensis Subject RIV: CC - Organic Chemistry OBOR OECD: Organic chemistry Impact factor: 3.994, year: 2016

Kinetics and stereochemistry of hydrolysis of an N-(phenylacetyl)-α-hydroxyglycine ester catalyzed by serine β-lactamases and DD-peptidases.

Science.gov (United States)

Pelto, Ryan B; Pratt, R F

2012-09-28

The α-hydroxydepsipeptide 3-carboxyphenyl N-(phenylacetyl)-α-hydroxyglycinate (5) is a quite effective substrate of serine β-lactamases and low molecular mass DD-peptidases. The class C P99 and ampC β-lactamases catalyze the hydrolysis of both enantiomers of 5, although they show a strong preference for one of them. The class A TEM-2 and class D OXA-1 β-lactamases and the Streptomyces R61 and Actinomadura R39 DD-peptidases catalyze hydrolysis of only one enantiomer of at any significant rate. Experiments show that all of the above enzymes strongly prefer the same enantiomer, a surprising result since β-lactamases usually prefer L(S) enantiomers and DD-peptidases D(R). Product analysis, employing peptidylglycine α-amidating lyase, showed that the preferred enantiomer is D(R). Thus, it is the β-lactamases that have switched preference rather than the DD-peptidases. Molecular modeling of the P99 β-lactamase active site suggests that the α-hydroxyl 5 of may interact with conserved Asn and Lys residues. Both α-hydroxy and α-amido substituents on a glycine ester substrate can therefore enhance its productive interaction with the β-lactamase active site, although their effects are not additive; this may also be true for inhibitors.

Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for the management of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F; Holst, Jens J

2005-01-01

of appetite. Glucagon-like peptide-1 is, however, extremely rapidly inactivated by the serine peptidase, dipeptidyl peptidase IV, so that the native peptide is not useful clinically. A new approach to utilise the beneficial effects of glucagon-like peptide-1 in the treatment of type 2 diabetes has been...... the development of orally active dipeptidyl peptidase IV inhibitors. Preclinical studies have demonstrated that this approach is effective in enhancing endogenous levels of glucagon-like peptide-1, resulting in improved glucose tolerance in glucose-intolerant and diabetic animal models. In recent studies of 3......-12 months duration in patients with type 2 diabetes, dipeptidyl peptidase IV inhibitors have proved efficacious, both as monotherapy and when given in combination with metformin. Fasting and postprandial glucose concentrations were reduced, leading to reductions in glycosylated haemoglobin levels, while...

Extracellular peptidase hunting for improvement of protein production in plant cells and roots

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Jérôme eLallemand

2015-02-01

Full Text Available Plant-based recombinant protein production systems have gained an extensive interest over the past few years, because of their reduced cost and relative safety. Although the first products are now reaching the market, progress are still needed to improve plant hosts and strategies for biopharming. Targeting recombinant proteins toward the extracellular space offers several advantages in terms of protein folding and purification, but degradation events are observed, due to endogenous peptidases. This paper focuses on the analysis of extracellular proteolytic activities in two production systems: cell cultures and root-secretion (rhizosecretion, in Arabidopsis thaliana and Nicotiana tabacum. Proteolytic activities of extracellular proteomes (secretomes were evaluated in vitro against two substrate proteins: bovine serum albumin (BSA and human serum immunoglobulins G (hIgGs. Both targets were found to be degraded by the secretomes, BSA being more prone to proteolysis than hIgGs. The analysis of the proteolysis pH-dependence showed that target degradation was mainly dependent upon the production system: rhizosecretomes contained more peptidase activity than extracellular medium of cell suspensions, whereas variations due to plant species were smaller. Using class-specific peptidase inhibitors, serine and metallopeptidases were found to be responsible for degradation of both substrates. An in-depth in silico analysis of genomic and transcriptomic data from Arabidopsis was then performed and led to the identification of a limited number of serine and metallo-peptidases that are consistently expressed in both production systems. These peptidases should be prime candidates for further improvement of plant hosts by targeted silencing.

Introduction of peptidase genes from Lactobacillus delbrueckii subsp. lactis into Lactococcus lactis and controlled expression

NARCIS (Netherlands)

Wegmann, U.; Klein, J.R.; Drumm, I.; Kuipers, O.P.; Henrich, B.

Peptidases PepI, PepL, PepW, and PepG from Lactobacillus delbrueckii subsp, lactis, which have no counterparts in Lactococcus lactis, and peptidase PepQ were examined to determine their potential to confer new peptidolytic properties to lactococci, Controllable expression of the corresponding genes

High-level expression of nattokinase in Bacillus licheniformis by manipulating signal peptide and signal peptidase.

Science.gov (United States)

Cai, D; Wei, X; Qiu, Y; Chen, Y; Chen, J; Wen, Z; Chen, S

2016-09-01

Nattokinase is an enzyme produced by Bacillus licheniformis and has potential to be used as a drug for treating cardiovascular disease due to its beneficial effects of preventing fibrin clots etc. However, the low activity and titre of this protein produced by B. licheniformis often hinders its application of commercial production. The aim of this work is to improve the nattokinase production by manipulating signal peptides and signal peptidases in B. licheniformis. The P43 promoter, amyL terminator and AprN target gene were used to form the nattokinase expression vector, pHY-SP-NK, which was transformed into B. licheniformis and nattokinase was expressed successfully. A library containing 81 predicted signal peptides was constructed for nattokinase expression in B. licheniformis, with the maximum activity being obtained under the signal peptide of AprE. Among four type I signal peptidases genes (sipS, sipT, sipV, sipW) in B. licheniformis, the deletion of sipV resulted in a highest decrease in nattokinase activity. Overexpression of sipV in B. licheniformis led to a nattokinase activity of 35·60 FU ml(-1) , a 4·68-fold improvement over activity produced by the initial strain. This work demonstrates the potential of B. licheniformis for industrial production of nattokinase through manipulation of signal peptides and signal peptidases expression. This study has screened the signal peptides of extracellular proteins of B. licheniformis for nattokinase production. Four kinds of Type I signal peptidases genes have been detected respectively in B. licheniformis to identify which one played the vital role for nattokinase production. This study provided a promising strain for industry production of nattokinase. © 2016 The Society for Applied Microbiology.

β-delayed proton decay of 28S

International Nuclear Information System (INIS)

Pougheon, F.; Borrel, V.; Jacmart, J.C.; Bazin, D.; Del Moral, R.; Dufour, J.P.; Hubert, F.; Pravikoff, M.S.; Brown, B.A.

1989-01-01

β-delayed proton radioactivity has been observed for the 28 S isotope (T x = -2), produced by projectile fragmentation of 85 MeV/u 36 Ar. The measured half-life of 28 S is 125 ± 10 ms. Energy spectra of β-delayed protons have been measured. The lowest T = 2 state in the daughter nucleus 28 P has been located at an excitation energy of 5900 ± 21 keV. A comparison of the experimental data to the quadratic form of the isobaric multiplet mass equation shows that the energies of the five T = 2 states of the A = 28 quintet are well represented by that relation. Shell-model predictions for the half-life, location and decay properties of the lowest T = 2 state of 28 P are in good agreement with experimental data

Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade

Czech Academy of Sciences Publication Activity Database

Stremeňová, J.; Křepela, E.; Mareš, Vladislav; Trim, J.; Dbalý, V.; Marek, J.; Vaníčková, Z.; Lisá, Věra; Yea, Ch.; Šedo, A.

2007-01-01

Roč. 31, č. 4 (2007), s. 785-792 ISSN 1019-6439 R&D Projects: GA MZd NR8105 Institutional research plan: CEZ:AV0Z50110509 Keywords : Dipeptidyl peptidase-IV * human brain tumors * DASH molecules Subject RIV: FD - Oncology ; Hematology Impact factor: 2.295, year: 2007

Substrate specificity of low-molecular mass bacterial DD-peptidases.

Science.gov (United States)

Nemmara, Venkatesh V; Dzhekieva, Liudmila; Sarkar, Kumar Subarno; Adediran, S A; Duez, Colette; Nicholas, Robert A; Pratt, R F

2011-11-22

The bacterial DD-peptidases or penicillin-binding proteins (PBPs) catalyze the formation and regulation of cross-links in peptidoglycan biosynthesis. They are classified into two groups, the high-molecular mass (HMM) and low-molecular mass (LMM) enzymes. The latter group, which is subdivided into classes A-C (LMMA, -B, and -C, respectively), is believed to catalyze DD-carboxypeptidase and endopeptidase reactions in vivo. To date, the specificity of their reactions with particular elements of peptidoglycan structure has not, in general, been defined. This paper describes the steady-state kinetics of hydrolysis of a series of specific peptidoglycan-mimetic peptides, representing various elements of stem peptide structure, catalyzed by a range of LMM PBPs (the LMMA enzymes, Escherichia coli PBP5, Neisseria gonorrhoeae PBP4, and Streptococcus pneumoniae PBP3, and the LMMC enzymes, the Actinomadura R39 dd-peptidase, Bacillus subtilis PBP4a, and N. gonorrhoeae PBP3). The R39 enzyme (LMMC), like the previously studied Streptomyces R61 DD-peptidase (LMMB), specifically and rapidly hydrolyzes stem peptide fragments with a free N-terminus. In accord with this result, the crystal structures of the R61 and R39 enzymes display a binding site specific to the stem peptide N-terminus. These are water-soluble enzymes, however, with no known specific function in vivo. On the other hand, soluble versions of the remaining enzymes of those noted above, all of which are likely to be membrane-bound and/or associated in vivo and have been assigned particular roles in cell wall biosynthesis and maintenance, show little or no specificity for peptides containing elements of peptidoglycan structure. Peptidoglycan-mimetic boronate transition-state analogues do inhibit these enzymes but display notable specificity only for the LMMC enzymes, where, unlike peptide substrates, they may be able to effectively induce a specific active site structure. The manner in which LMMA (and HMM) DD-peptidases

A Diversity Doctor’s Best Lessons from the Campus

Directory of Open Access Journals (Sweden)

Kathy-Anne Jordan

2016-11-01

Full Text Available Review of the book: “Taking on Diversity: How We Can Move from Anxiety to Respect—A Diversity Doctor’s Best Lessons from the Campus.” By Rupert W. Nacoste. Amherst, NY: Prometheus Books, 2015. ISBN: 978-1-63388026-9

Dipeptidyl peptidase IV inhibitory activity of protein hydrolyzates ...

African Journals Online (AJOL)

Background: Type 2 diabetes is a chronic metabolic disorder. Recently, dipeptidyl peptidase IV (DPP-IV) inhibitors that protect incretin hormones from being cleaved by DPP-IV have been used as drugs to control glycemia. This study examined the potential hypoglycemic effect of amaranth grain storage protein hydrolyzates ...

Crystallization and preliminary crystallographic analysis of porcine acylaminoacyl peptidase.

Science.gov (United States)

Wright, Helena; Kiss, András L; Szeltner, Zoltán; Polgár, László; Fülöp, Vilmos

2005-10-01

Acylaminoacyl peptidase (also known as acylamino-acid-releasing enzyme or acylpeptide hydrolase; EC 3.4.19.1) is an unusual member of the prolyl oligopeptidase family catalysing the hydrolysis of an N-acylated peptide to an acylamino acid and a peptide with a free N-terminus. Acylaminoacyl peptidase purified from porcine liver has been crystallized in mother liquor containing 0.1 M Tris-HCl pH 7.0, 10%(w/v) polyethylene glycol 8000, 50 mM MgCl2 and 1%(w/v) CHAPS using the hanging-drop vapour-diffusion technique. A full data set to 3.4 A resolution was collected at ESRF beamline ID14-4 and space group C222 was assigned, with unit-cell parameters a = 84.8, b = 421.1, c = 212.0 A and four molecules in the asymmetric unit.

Three extracellular dipeptidyl peptidases found in Aspergillus oryzae show varying substrate specificities.

Science.gov (United States)

Maeda, Hiroshi; Sakai, Daisuke; Kobayashi, Takuji; Morita, Hiroto; Okamoto, Ayako; Takeuchi, Michio; Kusumoto, Ken-Ichi; Amano, Hitoshi; Ishida, Hiroki; Yamagata, Youhei

2016-06-01

Three extracellular dipeptidyl peptidase genes, dppB, dppE, and dppF, were unveiled by sequence analysis of the Aspergillus oryzae genome. We investigated their differential enzymatic profiles, in order to gain an understanding of the diversity of these genes. The three dipeptidyl peptidases were expressed using Aspergillus nidulans as the host. Each recombinant enzyme was purified and subsequently characterized. The enzymes displayed similar optimum pH values, but optimum temperatures, pH stabilities, and substrate specificities varied. DppB was identified as a Xaa-Prolyl dipeptidyl peptidase, while DppE scissile substrates were similar to the substrates for Aspergillus fumigatus DPPV (AfDPPV). DppF was found to be a novel enzyme that could digest both substrates for A. fumigatus DPPIV and AfDPPV. Semi-quantitative PCR revealed that the transcription of dppB in A. oryzae was induced by protein substrates and repressed by the addition of an inorganic nitrogen source, despite the presence of protein substrates. The transcription of dppE depended on its growth time, while the transcription of dppF was not affected by the type of the nitrogen source in the medium, and it started during the early stage of the fungal growth. Based on these results, we conclude that these enzymes may represent the nutrition acquisition enzymes. Additionally, DppF may be one of the sensor peptidases responsible for the detection of the protein substrates in A. oryzae environment. DppB may be involved in nitrogen assimilation control, since the transcription of dppB was repressed by NaNO3, despite the presence of protein substrates.

Optical signal processing up to 1.28 Tbits/s

DEFF Research Database (Denmark)

Mulvad, Hans Christian Hansen; Oxenløwe, Leif Katsuo; Galili, Michael

2009-01-01

Techniques for 640 Gbit/s optical signal processing are described, including demultiplexing, clock recovery, transmission, wavelength conversion, add-drop multiplexing, and timing-jitter tolerance. Demultiplexing at 1.28 Tbit/s is presented, with preliminary results for 1.28 Tbit/s transmission....

Production of aspartic peptidases by Aspergillus spp. using tuna ...

African Journals Online (AJOL)

The production of extracellular aspartic peptidase by the fungi Aspergillus niger and Aspergillus awamori was carried out in a shake flask and in stirred tank submerged fermentations using tuna cooked wastewater, an industrial effluent, as nitrogen source for culture medium. In stirred tank fermentation, biomass production ...

Profiling of proteolytic enzymes in the gut of the tick Ixodes ricinus reveals an evolutionarily conserved network of aspartic and cysteine peptidases

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Mareš Michael

2008-03-01

Full Text Available Abstract Background Ticks are vectors for a variety of viral, bacterial and parasitic diseases in human and domestic animals. To survive and reproduce ticks feed on host blood, yet our understanding of the intestinal proteolytic machinery used to derive absorbable nutrients from the blood meal is poor. Intestinal digestive processes are limiting factors for pathogen transmission since the tick gut presents the primary site of infection. Moreover, digestive enzymes may find practical application as anti-tick vaccine targets. Results Using the hard tick, Ixodes ricinus, we performed a functional activity scan of the peptidase complement in gut tissue extracts that demonstrated the presence of five types of peptidases of the cysteine and aspartic classes. We followed up with genetic screens of gut-derived cDNA to identify and clone genes encoding the cysteine peptidases cathepsins B, L and C, an asparaginyl endopeptidase (legumain, and the aspartic peptidase, cathepsin D. By RT-PCR, expression of asparaginyl endopeptidase and cathepsins B and D was restricted to gut tissue and to those developmental stages feeding on blood. Conclusion Overall, our results demonstrate the presence of a network of cysteine and aspartic peptidases that conceivably operates to digest host blood proteins in a concerted manner. Significantly, the peptidase components of this digestive network are orthologous to those described in other parasites, including nematodes and flatworms. Accordingly, the present data and those available for other tick species support the notion of an evolutionary conservation of a cysteine/aspartic peptidase system for digestion that includes ticks, but differs from that of insects relying on serine peptidases.

Interactions of "bora-penicilloates" with serine β-lactamases and DD-peptidases.

Science.gov (United States)

Dzhekieva, Liudmila; Adediran, S A; Pratt, R F

2014-10-21

Specific boronic acids are generally powerful tetrahedral intermediate/transition state analogue inhibitors of serine amidohydrolases. This group of enzymes includes bacterial β-lactamases and DD-peptidases where there has been considerable development of boronic acid inhibitors. This paper describes the synthesis, determination of the inhibitory activity, and analysis of the results from two α-(2-thiazolidinyl) boronic acids that are closer analogues of particular tetrahedral intermediates involved in β-lactamase and DD-peptidase catalysis than those previously described. One of them, 2-[1-(dihydroxyboranyl)(2-phenylacetamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid, is a direct analogue of the deacylation tetrahedral intermediates of these enzymes. These compounds are micromolar inhibitors of class C β-lactamases but, very unexpectedly, not inhibitors of class A β-lactamases. We rationalize the latter result on the basis of a new mechanism of boronic acid inhibition of the class A enzymes. A stable inhibitory complex is not accessible because of the instability of an intermediate on its pathway of formation. The new boronic acids also do not inhibit bacterial DD-peptidases (penicillin-binding proteins). This result strongly supports a central feature of a previously proposed mechanism of action of β-lactam antibiotics, where deacylation of β-lactam-derived acyl-enzymes is not possible because of unfavorable steric interactions.

Production and partial characterization of serine and metallo peptidases secreted by Aspergillus fumigatus Fresenius in submerged and solid state fermentation.

Science.gov (United States)

da Silva, Ronivaldo Rodrigues; de Freitas Cabral, Tatiana Pereira; Rodrigues, André; Cabral, Hamilton

2013-01-01

Enzyme production varies in different fermentation systems. Enzyme expression in different fermentation systems yields important information for improving our understanding of enzymatic production induction. Comparative studies between solid-state fermentation (SSF) using agro-industrial waste wheat bran and submerged fermentation (SmF) using synthetic media were carried out to determinate the best parameters for peptidase production by the fungus Aspergillus fumigatus Fresen. Variables tested include: the concentration of carbon and protein nitrogen sources, the size of the inoculum, the pH of the media, temperature, and the length of the fermentation process. The best peptidase production during SSF was obtained after 96 hours using wheat bran at 30 °C with an inoculum of 1 × 10(6) spores and yielded 1500 active units (U/mL). The best peptidase production using SmF was obtained after periods of 72 and 96 hours of fermentation in media containing 0.5% and 0.25% of casein, respectively, at a pH of 6.0 and at 30 °C and yielded 40 U/mL. We also found examples of catabolite repression of peptidase production under SmF conditions. Biochemical characterization of the peptidases produced by both fermentative processes showed optimum activity at pH 8.0 and 50 °C, and also showed that their proteolytic activity is modulated by surfactants. The enzymatic inhibition profile using phenylmethylsulfonyl fluoride (PMSF) in SmF and SSF indicated that both fermentative processes produced a serine peptidase. Additionally, the inhibitory effect of the ethylene-diaminetetraacetic acid (EDTA) chelating agent on the peptidase produced by SmF indicated that this fermentative process also produced a metallopeptidase.

Signaling domain of Sonic Hedgehog as cannibalistic calcium-regulated zinc-peptidase.

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Rocio Rebollido-Rios

2014-07-01

Full Text Available Sonic Hedgehog (Shh is a representative of the evolutionary closely related class of Hedgehog proteins that have essential signaling functions in animal development. The N-terminal domain (ShhN is also assigned to the group of LAS proteins (LAS = Lysostaphin type enzymes, D-Ala-D-Ala metalloproteases, Sonic Hedgehog, of which all members harbor a structurally well-defined Zn2+ center; however, it is remarkable that ShhN so far is the only LAS member without proven peptidase activity. Another unique feature of ShhN in the LAS group is a double-Ca2+ center close to the zinc. We have studied the effect of these calcium ions on ShhN structure, dynamics, and interactions. We find that the presence of calcium has a marked impact on ShhN properties, with the two calcium ions having different effects. The more strongly bound calcium ion significantly stabilizes the overall structure. Surprisingly, the binding of the second calcium ion switches the putative catalytic center from a state similar to LAS enzymes to a state that probably is catalytically inactive. We describe in detail the mechanics of the switch, including the effect on substrate co-ordinating residues and on the putative catalytic water molecule. The properties of the putative substrate binding site suggest that ShhN could degrade other ShhN molecules, e.g. by cleavage at highly conserved glycines in ShhN. To test experimentally the stability of ShhN against autodegradation, we compare two ShhN mutants in vitro: (1 a ShhN mutant unable to bind calcium but with putative catalytic center intact, and thus, according to our hypothesis, a constitutively active peptidase, and (2 a mutant carrying additionally mutation E177A, i.e., with the putative catalytically active residue knocked out. The in vitro results are consistent with ShhN being a cannibalistic zinc-peptidase. These experiments also reveal that the peptidase activity depends on pH.

Heterologous production of the stain solving peptidase PPP1 from Pleurotus pulmonarius.

Science.gov (United States)

Leonhardt, Robin-Hagen; Krings, Ulrich; Berger, Ralf G; Linke, Diana

2016-05-01

A novel stain solving subtilisin-like peptidase (PPP1) was identified from the culture supernatant of the agaricomycete Pleurotus pulmonarius. It was purified to homogeneity using a sequence of preparative isoelectric focusing, anion exchange and size exclusion chromatography. Peptides were identified by ab initio sequencing (nLC-ESI-QTOF-MS/MS), characterizing the enzyme as a member of the subtilase family (EC 3.4.21.X). An expression system was established featuring the pPIC9K vector, an alternative Kozak sequence, the codon optimized gene ppp1 gene without the native signal sequence with C-terminal hexa-histidine tag, and Pichia pastoris GS115 as expression host. Intracellular active enzyme was obtained from cultivations in shake flasks and in a five liter bioreactor. With reaction optima of 40 °C and a pH > 8.5, considerable bleaching of pre-stained fabrics (blood, milk and India ink), and the possibility of larger-scale production, the heterologous enzyme is well suitable for detergent applications, especially at lower temperatures as part of a more energy- and cost-efficient washing process. Showing little sequence similarity to other subtilases, this unique peptidase is the first subtilisin-like peptidase from Basidiomycota, which has been functionally produced in Pichia pastoris.

Mitochondrial intermediate peptidase: Expression in Escherichia coli and improvement of its enzymatic activity detection with FRET substrates

International Nuclear Information System (INIS)

Marcondes, Marcelo F.; Torquato, Ricardo J.S.; Assis, Diego M.; Juliano, Maria A.; Hayashi, Mirian A.F.; Oliveira, Vitor

2010-01-01

In the present study, soluble, functionally-active, recombinant human mitochondrial intermediate peptidase (hMIP), a mitochondrial metalloendoprotease, was expressed in a prokaryotic system. The hMIP fusion protein, with a poly-His-tag (6x His), was obtained by cloning the coding region of hMIP cDNA into the pET-28a expression vector, which was then used to transform Escherichia coli BL21 (DE3) pLysS. After isolation and purification of the fusion protein by affinity chromatography using Ni-Sepharose resin, the protein was purified further using ion exchange chromatography with a Hi-trap resource Q column. The recombinant hMIP was characterized by Western blotting using three distinct antibodies, circular dichroism, and enzymatic assays that used the first FRET substrates developed for MIP and a series of protease inhibitors. The successful expression of enzymatically-active hMIP in addition to the FRET substrates will contribute greatly to the determination of substrate specificity of this protease and to the development of specific inhibitors that are essential for a better understanding of the role of this protease in mitochondrial functioning.

A genetic study of various enzyme polymorphisms in Pleurodeles waltlii (Urodele Amphibian). II. Peptidases: demonstration of sex linkage.

Science.gov (United States)

Ferrier, V; Gasser, F; Jaylet, A; Cayrol, C

1983-06-01

The existence of four peptidases was demonstrated by starch gel electrophoresis in Pleurodeles waltlii: PEP-1, PEP-2, PEP-3, and PEP-4. Peptidases-3 and -4 are monomorphic, and peptidases-1 and -2 are polymorphic. The heredity of the polymorphisms was studied using individuals arising from crosses or of gynogenetic origin. Peptidase-1 is dimeric; its polymorphism depends on a pair of codominant alleles, Pep-1A and Pep-1B, which are situated on the Z and W sex chromosomes, respectively, in close proximity to, or even within, the sex differential segment. As the differential segment is very close to the centromere, the PEP-1 locus therefore also appears to be closely linked to it. Expression of the PEP-1 locus was shown to be independent of the sex hormone environment. This locus is the first case reported in amphibians of an enzyme marker linked to the genetic sex. It allows the sex of PLeurodeles to be determined before they reach sexual maturity. Peptidase-2 is monomeric. Its polymorphism depends on a pair of codominant alleles on an autosomal PEP-2 locus. The high proportion of heterozygous animals in the gynogenetic offspring of females heterozygous for the PEP-2 locus indicates segregation which is independent of the centromere. Analysis of the offspring of doubly heterozygous females (i.e., for two of the loci--LDH-B, G6PDH, PEP-1, and PEP-2) shows that the four loci are independent.

Expression of six peptidases from Lactobacillus helveticus in Lactococcus lactis.

Science.gov (United States)

Luoma, S; Peltoniemi, K; Joutsjoki, V; Rantanen, T; Tamminen, M; Heikkinen, I; Palva, A

2001-03-01

For development of novel starter strains with improved proteolytic properties, the ability of Lactococcus lactis to produce Lactobacillus helveticus aminopeptidase N (PepN), aminopeptidase C (PepC), X-prolyl dipeptidyl aminopeptidase (PepX), proline iminopeptidase (PepI), prolinase (PepR), and dipeptidase (PepD) was studied by introducing the genes encoding these enzymes into L. lactis MG1363 and its derivatives. According to Northern analyses and enzyme activity measurements, the L. helveticus aminopeptidase genes pepN, pepC, and pepX are expressed under the control of their own promoters in L. lactis. The highest expression level, using a low-copy-number vector, was obtained with the L. helveticus pepN gene, which resulted in a 25-fold increase in PepN activity compared to that of wild-type L. lactis. The L. helveticus pepI gene, residing as a third gene in an operon in its host, was expressed in L. lactis under the control of the L. helveticus pepX promoter. The genetic background of the L. lactis derivatives tested did not affect the expression level of any of the L. helveticus peptidases studied. However, the growth medium used affected both the recombinant peptidase profiles in transformant strains and the resident peptidase activities. The levels of expression of the L. helveticus pepD and pepR clones under the control of their own promoters were below the detection limit in L. lactis. However, substantial amounts of recombinant pepD and PepR activities were obtained in L. lactis when pepD and pepR were expressed under the control of the inducible lactococcal nisA promoter at an optimized nisin concentration.

Bacteriophage-Derived Peptidase CHAPK Eliminates and Prevents Staphylococcal Biofilms

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Mark Fenton

2013-01-01

Full Text Available New antibacterial agents are urgently needed for the elimination of biofilm-forming bacteria that are highly resistant to traditional antimicrobial agents. Proliferation of such bacteria can lead to significant economic losses in the agri-food sector. This study demonstrates the potential of the bacteriophage-derived peptidase, CHAPK, as a biocidal agent for the rapid disruption of biofilm-forming staphylococci, commonly associated with bovine mastitis. Purified CHAPK applied to biofilms of Staphylococcus aureus DPC5246 completely eliminated the staphylococcal biofilms within 4 h. In addition, CHAPK was able to prevent biofilm formation by this strain. The CHAPK lysin also reduced S. aureus in a skin decolonization model. Our data demonstrates the potential of CHAPK as a biocidal agent for prevention and treatment of biofilm-associated staphylococcal infections or as a decontaminating agent in the food and healthcare sectors.

Identification of Dipeptidyl-Peptidase (DPP5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis.

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Haruka Nishimata

Full Text Available Dipeptidyl peptidases (DPPs that liberate dipeptides from the N-terminal end of oligopeptides are crucial for the growth of Porphyromonas species, anaerobic asaccharolytic gram negative rods that utilize amino acids as energy sources. Porphyromonas endodontalis is a causative agent of periapical lesions with acute symptoms and Asp/Glu-specific DPP11 has been solely characterized in this organism. In this study, we identified and characterized two P. endodontalis DPPs, DPP5 and DPP7. Cell-associated DPP activity toward Lys-Ala-4-methylcoumaryl-7-amide (MCA was prominent in P. endodontalis ATCC 35406 as compared with the Porphyromonas gingivalis strains ATCC 33277, 16-1, HW24D1, ATCC 49417, W83, W50, and HNA99. The level of hydrolysis of Leu-Asp-MCA by DPP11, Gly-Pro-MCA by DPP4, and Met-Leu-MCA was also higher than in the P. gingivalis strains. MER236725 and MER278904 are P. endodontalis proteins belong to the S9- and S46-family peptidases, respectively. Recombinant MER236725 exhibited enzymatic properties including substrate specificity, and salt- and pH-dependence similar to P. gingivalis DPP5 belonging to the S9 family. However, the kcat/Km figure (194 µM-1·sec-1 for the most potent substrate (Lys-Ala-MCA was 18.4-fold higher as compared to the P. gingivalis entity (10.5 µM-1·sec-1. In addition, P. endodontalis DPP5 mRNA and protein contents were increased several fold as compared with those in P. gingivalis. Recombinant MER278904 preferentially hydrolyzed Met-Leu-MCA and exhibited a substrate specificity similar to P. gingivalis DPP7 belonging to the S46 family. In accord with the deduced molecular mass of 818 amino acids, a 105-kDa band was immunologically detected, indicating that P. endodontalis DPP7 is an exceptionally large molecule in the DPP7/DPP11/S46 peptidase family. The enhancement of four DPP activities was conclusively demonstrated in P. endodontalis, and remarkable Lys-Ala-MCA-hydrolysis was achieved by qualitative and

Identification of Dipeptidyl-Peptidase (DPP)5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis.

Science.gov (United States)

Nishimata, Haruka; Ohara-Nemoto, Yuko; Baba, Tomomi T; Hoshino, Tomonori; Fujiwara, Taku; Shimoyama, Yu; Kimura, Shigenobu; Nemoto, Takayuki K

2014-01-01

Dipeptidyl peptidases (DPPs) that liberate dipeptides from the N-terminal end of oligopeptides are crucial for the growth of Porphyromonas species, anaerobic asaccharolytic gram negative rods that utilize amino acids as energy sources. Porphyromonas endodontalis is a causative agent of periapical lesions with acute symptoms and Asp/Glu-specific DPP11 has been solely characterized in this organism. In this study, we identified and characterized two P. endodontalis DPPs, DPP5 and DPP7. Cell-associated DPP activity toward Lys-Ala-4-methylcoumaryl-7-amide (MCA) was prominent in P. endodontalis ATCC 35406 as compared with the Porphyromonas gingivalis strains ATCC 33277, 16-1, HW24D1, ATCC 49417, W83, W50, and HNA99. The level of hydrolysis of Leu-Asp-MCA by DPP11, Gly-Pro-MCA by DPP4, and Met-Leu-MCA was also higher than in the P. gingivalis strains. MER236725 and MER278904 are P. endodontalis proteins belong to the S9- and S46-family peptidases, respectively. Recombinant MER236725 exhibited enzymatic properties including substrate specificity, and salt- and pH-dependence similar to P. gingivalis DPP5 belonging to the S9 family. However, the kcat/Km figure (194 µM-1·sec-1) for the most potent substrate (Lys-Ala-MCA) was 18.4-fold higher as compared to the P. gingivalis entity (10.5 µM-1·sec-1). In addition, P. endodontalis DPP5 mRNA and protein contents were increased several fold as compared with those in P. gingivalis. Recombinant MER278904 preferentially hydrolyzed Met-Leu-MCA and exhibited a substrate specificity similar to P. gingivalis DPP7 belonging to the S46 family. In accord with the deduced molecular mass of 818 amino acids, a 105-kDa band was immunologically detected, indicating that P. endodontalis DPP7 is an exceptionally large molecule in the DPP7/DPP11/S46 peptidase family. The enhancement of four DPP activities was conclusively demonstrated in P. endodontalis, and remarkable Lys-Ala-MCA-hydrolysis was achieved by qualitative and quantitative

Dipeptidyl peptidase IV (DPPIV) activity in the tear fluid as an indicator of the severity of corneal injury: a histochemical and biochemical study

Czech Academy of Sciences Publication Activity Database

Čejková, Jitka; Zvárová, Jana; Čejka, Čestmír

2004-01-01

Roč. 19, - (2004), s. 669-676 ISSN 0213-3911 R&D Projects: GA ČR GA304/03/0419 Institutional research plan: CEZ:AV0Z5008914 Keywords : dipeptidyl peptidase IV Subject RIV: FF - HEENT, Dentistry Impact factor: 1.931, year: 2004

Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

Science.gov (United States)

2017-02-01

ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life -threatening... negative feedback loops within the pathway limit their effectiveness . For example, AKT inhibitors cause increased expression of IGF1R/ErbB3 and, as a...AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple- Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD

The crystal structure of an intermediate dimer of aspergilloglutamic peptidase that mimics the enzyme-activation product complex produced upon autoproteolysis.

Science.gov (United States)

Sasaki, Hiroshi; Kubota, Keiko; Lee, Woo C; Ohtsuka, Jun; Kojima, Masaki; Iwata, So; Nakagawa, Atsushi; Takahashi, Kenji; Tanokura, Masaru

2012-07-01

Aspergilloglutamic peptidase from Aspergillus niger var. macrosporus (AGP) is one of the so-called pepstatin-insensitive acid endopeptidases, which are distinct from the well-studied aspartic peptidases. Among the known homologues of the glutamic peptidases, AGP is a unique two-chain enzyme with a light chain and a heavy chain bound non-covalently with each other, and thus is an interesting target for protein structure-function relationship studies. In this article, we report the crystal structure of a dimeric form of the enzyme at a resolution of 1.6 Å. This form has a unique structure in which the C-terminal region of the light chain of one of the molecules binds to the active site cleft of the other molecule like a part of a substrate. This form mimics the enzyme-activation product complex produced upon autoproteolysis, and provides a structural clue that could help to clarify the activation mechanism. This type of dimeric structure of a peptidase is here reported for the first time.

Regulatory signals for intestinal amino acid transporters and peptidases

International Nuclear Information System (INIS)

Ferraris, R.P.; Kwan, W.W.; Diamond, J.

1988-01-01

Dietary protein ultimately regulates many processes involved in protein digestion, but it is often unclear whether proteins themselves, peptides, or amino acids (AAs) are the proximate regulatory signal. Hence the authors compared several processes involved in protein digestion in mice adapted to one of three rations, identical except for containing 54% of either casein, a partial hydrolysate of casein, or a free AA mixture simulating a complete hydrolysate of casein. The authors measured brush-border uptakes of seven AAs that variously serve as substrates for four AA transporters, and brush-border and cytosolic activities of four peptidases. The three rations yielded essentially the same AA uptake rates. Peptidase activities tended to be lower on the AA ration than on the protein ration. In other studies, all three rations yielded the same rates of brush-border peptide uptake; protein is only modestly more effective than AAs at inducing synthesis of pancreatic proteases; and, depending on the animal species, protein is either much less or much more effective than AAs at stimulating release of cholecystokinin and hence of pancreatic enzymes. Thus the regulators of each process involved in protein digestion are not necessarily that process's substrate

Arrabidaea chica Hexanic Extract Induces Mitochondrion Damage and Peptidase Inhibition on Leishmania spp.

Directory of Open Access Journals (Sweden)

Igor A. Rodrigues

2014-01-01

Full Text Available Currently available leishmaniasis treatments are limited due to severe side effects. Arrabidaea chica is a medicinal plant used in Brazil against several diseases. In this study, we investigated the effects of 5 fractions obtained from the crude hexanic extract of A. chica against Leishmania amazonensis and L. infantum, as well as on the interaction of these parasites with host cells. Promastigotes were treated with several concentrations of the fractions obtained from A. chica for determination of their minimum inhibitory concentration (MIC. In addition, the effect of the most active fraction (B2 on parasite’s ultrastructure was analyzed by transmission electron microscopy. To evaluate the inhibitory activity of B2 fraction on Leishmania peptidases, parasites lysates were treated with the inhibitory and subinhibitory concentrations of the B2 fraction. The minimum inhibitory concentration of B2 fraction was 37.2 and 18.6 μg/mL for L. amazonensis and L. infantum, respectively. Important ultrastructural alterations as mitochondrial swelling with loss of matrix content and the presence of vesicles inside this organelle were observed in treated parasites. Moreover, B2 fraction was able to completely inhibit the peptidase activity of promastigotes at pH 5.5. The results presented here further support the use of A. chica as an interesting source of antileishmanial agents.

Alogliptin, a potent and selective dipeptidyl peptidase-IV inhibitor for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F

2008-01-01

Takeda San Diego Inc is developing alogliptin, a small-molecule, orally available dipeptidyl peptidase IV (DPP IV) inhibitor, for the potential treatment of type 2 diabetes. In January 2008, Takeda announced that an NDA for alogliptin had been submitted to the FDA.......Takeda San Diego Inc is developing alogliptin, a small-molecule, orally available dipeptidyl peptidase IV (DPP IV) inhibitor, for the potential treatment of type 2 diabetes. In January 2008, Takeda announced that an NDA for alogliptin had been submitted to the FDA....

Glycine-rich loop of mitochondrial processing peptidase α-subunit is responsible for substrate recognition by a mechanism analogous to mitochondrial receptor Tom20

Czech Academy of Sciences Publication Activity Database

Dvořáková-Holá, Klára; Matušková, Anna; Kubala, M.; Otyepka, M.; Kučera, Tomáš; Večeř, J.; Heřman, P.; Parkhomenko, Natalia; Kutejová, E.; Janata, Jiří

2010-01-01

Roč. 396, č. 5 (2010), s. 1197-1210 ISSN 0022-2836 R&D Projects: GA AV ČR IAA501110631 Institutional research plan: CEZ:AV0Z50200510 Keywords : mitochondrial processing peptidase * presequence * substrate recognition Subject RIV: EE - Microbiology, Virology Impact factor: 4.008, year: 2010

The League of Nations and U.S. World Roles. Lesson Plan.

Science.gov (United States)

Romey, Barbara

1994-01-01

Asserts that the issue of U.S. participation in the League of Nations is usually presented as a failure by Woodrow Wilson and the Republicans to compromise. Presents a lesson that clarifies the choice confronting the United States in 1919-20 and interprets the league as a historic innovation. (CFR)

FORMING SCHOOLCHILD’S PERSONALITY IN COMPUTER STUDY LESSONS AT PRIMARY SCHOOL

Directory of Open Access Journals (Sweden)

Natalia Salan

2017-04-01

Full Text Available The influence of computer on the formation of primary schoolchildren’s personality and their implementing into learning activity are considered in the article. Based on the materials of state standards and the Law of Ukraine on Higher Education the concepts “computer”, “information culture” are defined, modern understanding of the concept “basics of computer literacy” is identified. The main task of school propaedeutic course in Computer Studies is defined. Interactive methods of activity are singled out. They are didactic games, designing, research, collaboration in pairs, and group interaction, etc. The essential characteristics of didactic game technologies are distinguished, the peculiarities of their use at primary school in Computer Study lessons are analyzed. Positive and negative aspects of using these technologies in Computer Study lessons are defined. The expediency of using game technologies while organizing students’ educational and cognitive activity in Computer Studies is substantiated. The idea to create a school course “Computer Studies at primary school” is caused by the wide introduction of computer technics into the educational system. Today’s schoolchild has to be able to use a computer as freely and easily as he can use a pen, a pencil or a ruler. That’s why it is advisable to start studying basics of Computer Studies at the primary school age. This course is intended for the pupils of the 2nd-4th forms. Firstly, it provides mastering practical skills of computer work and, secondly, it anticipates the development of children’s logical and algorithmic thinking styles. At these lessons students acquire practical skills to work with information on the computer. Having mastered the computer skills at primary school, children will be able to use it successfully in their work. In senior classes they will be able to realize acquired knowledge of the methods of work with information, ways of problem solving

HIV aspartyl peptidase inhibitors interfere with cellular proliferation, ultrastructure and macrophage infection of Leishmania amazonensis.

Directory of Open Access Journals (Sweden)

Lívia O Santos

Full Text Available BACKGROUND: Leishmania is the etiologic agent of leishmanisais, a protozoan disease whose pathogenic events are not well understood. Current therapy is suboptimal due to toxicity of the available therapeutic agents and the emergence of drug resistance. Compounding these problems is the increase in the number of cases of Leishmania-HIV coinfection, due to the overlap between the AIDS epidemic and leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: In the present report, we have investigated the effect of HIV aspartyl peptidase inhibitors (PIs on the Leishmania amazonensis proliferation, ultrastructure, interaction with macrophage cells and expression of classical peptidases which are directly involved in the Leishmania pathogenesis. All the HIV PIs impaired parasite growth in a dose-dependent fashion, especially nelfinavir and lopinavir. HIV PIs treatment caused profound changes in the leishmania ultrastructure as shown by transmission electron microscopy, including cytoplasm shrinking, increase in the number of lipid inclusions and some cells presenting the nucleus closely wrapped by endoplasmic reticulum resembling an autophagic process, as well as chromatin condensation which is suggestive of apoptotic death. The hydrolysis of HIV peptidase substrate by L. amazonensis extract was inhibited by pepstatin and HIV PIs, suggesting that an aspartyl peptidase may be the intracellular target of the inhibitors. The treatment with HIV PIs of either the promastigote forms preceding the interaction with macrophage cells or the amastigote forms inside macrophages drastically reduced the association indexes. Despite all these beneficial effects, the HIV PIs induced an increase in the expression of cysteine peptidase b (cpb and the metallopeptidase gp63, two well-known virulence factors expressed by Leishmania spp. CONCLUSIONS/SIGNIFICANCE: In the face of leishmaniasis/HIV overlap, it is critical to further comprehend the sophisticated interplays among Leishmania

Structural Basis for Specificity of Propeptide-Enzyme Interaction in Barley C1A Cysteine Peptidases

Science.gov (United States)

Cambra, Inés; Hernández, David; Diaz, Isabel; Martinez, Manuel

2012-01-01

C1A cysteine peptidases are synthesized as inactive proenzymes. Activation takes place by proteolysis cleaving off the inhibitory propeptide. The inhibitory capacity of propeptides from barley cathepsin L and B-like peptidases towards commercial and barley cathepsins has been characterized. Differences in selectivity have been found for propeptides from L-cathepsins against their cognate and non cognate enzymes. Besides, the propeptide from barley cathepsin B was not able to inhibit bovine cathepsin B. Modelling of their three-dimensional structures suggests that most propeptide inhibitory properties can be explained from the interaction between the propeptide and the mature cathepsin structures. Their potential use as biotechnological tools is discussed. PMID:22615948

Noncombatant Evacuation Operations: Department of State’s Lessons Learned Program

Science.gov (United States)

2016-06-10

means for utilizing the lessons learned, in some form of rehearsal or exercise, will 4 make the lessons learned meaningful. A lesson should only...required by DOS policy. The Department agreed with the recommendations to establish certain procedures to address the need to constantly 44 update...doctrine.31 Futch also explained that CALL is constantly seeking to expand training and educational efforts about the lessons learned process and

Administration of a dipeptidyl peptidase IV inhibitor enhances the intestinal adaptation in a mouse model of short bowel syndrome

DEFF Research Database (Denmark)

Okawada, Manabu; Holst, Jens Juul; Teitelbaum, Daniel H

2011-01-01

Glucagon-like peptide-2 induces small intestine mucosal epithelial cell proliferation and may have benefit for patients who suffer from short bowel syndrome. However, glucagon-like peptide-2 is inactivated rapidly in vivo by dipeptidyl peptidase IV. Therefore, we hypothesized that selectively inh...... inhibiting dipeptidyl peptidase IV would prolong the circulating life of glucagon-like peptide-2 and lead to increased intestinal adaptation after development of short bowel syndrome....

Sequence analysis and over-expression of ribosomal protein S28 ...

African Journals Online (AJOL)

RPS28 is a component of the 40S small ribosomal subunit encoded by RPS28 gene, which is specific to eukaryotes. The cDNA and the genomic sequence of RPS28 were cloned successfully from the Giant Panda using RT-PCR technology and Touchdown-PCR, respectively. Both sequences were analyzed preliminarily ...

Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.

Science.gov (United States)

Nagatsu, Toshiharu

2017-06-01

Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.

Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema

OpenAIRE

Byrd, James Brian; Touzin, Karine; Sile, Saba; Gainer, James V.; Yu, Chang; Nadeau, John; Adam, Albert; Brown, Nancy J.

2007-01-01

Angioedema is a potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors. Bradykinin and substance P, substrates of angiotensin-converting enzyme, increase vascular permeability and cause tissue edema in animals. Studies indicate that amino-terminal degradation of these peptides, by aminopeptidase P and dipeptidyl peptidase IV, may be impaired in individuals with angiotensin-converting enzyme inhibitor–associated angioedema. This case-control study tested the hy...

Inhibition of bacterial DD-peptidases (penicillin-binding proteins) in membranes and in vivo by peptidoglycan-mimetic boronic acids.

Science.gov (United States)

Dzhekieva, Liudmila; Kumar, Ish; Pratt, R F

2012-04-03

The DD-peptidases or penicillin-binding proteins (PBPs) catalyze the final steps of bacterial peptidoglycan biosynthesis and are inhibited by the β-lactam antibiotics. There is at present a question of whether the active site structure and activity of these enzymes is the same in the solubilized (truncated) DD-peptidase constructs employed in crystallographic and kinetics studies as in membrane-bound holoenzymes. Recent experiments with peptidoglycan-mimetic boronic acids have suggested that these transition state analogue-generating inhibitors may be able to induce reactive conformations of these enzymes and thus inhibit strongly. We have now, therefore, measured the dissociation constants of peptidoglycan-mimetic boronic acids from Escherichia coli and Bacillus subtilis PBPs in membrane preparations and, in the former case, in vivo, by means of competition experiments with the fluorescent penicillin Bocillin Fl. The experiments showed that the boronic acids bound measurably (K(i) DD-peptidase inhibitors are more or less effective in vivo than in homogeneous solution.

Synthesis and processing of escherichia-coli tem-beta-lactamase and bacillus-licheniformis alpha-amylase in escherichia-coli : The role of signal peptidase-i

NARCIS (Netherlands)

van Dijl, J M; Smith, H; Bron, Sierd; Venema, Gerard

A mutant of Escherichia coli, in which signal peptidase I synthesis can be regulated, was constructed. The mutant was used to study the effects of signal peptidase I limitation on the synthesis and efficiency of processing of two proteins: the periplasmic E. coli TEM-beta-lactamase and Bacillus

SYNTHESIS AND PROCESSING OF ESCHERICHIA-COLI TEM-BETA-LACTAMASE AND BACILLUS-LICHENIFORMIS ALPHA-AMYLASE IN ESCHERICHIA-COLI : THE ROLE OF SIGNAL PEPTIDASE-I

NARCIS (Netherlands)

van Dijl, J M; SMITH, H; BRON, S; VENEMA, G

A mutant of Escherichia coli, in which signal peptidase I synthesis can be regulated, was constructed. The mutant was used to study the effects of signal peptidase I limitation on the synthesis and efficiency of processing of two proteins: the periplasmic E. coli TEM-beta-lactamase and Bacillus

Lessons learned from the post-emergency TABLETOP exercise in Baton Rouge, Louisiana, on August 28 and September 18, 1990

International Nuclear Information System (INIS)

1991-07-01

On August 28 and September 18, 1990, Gulf States Utilities, the States of Louisiana and Mississippi, five local parishes, six Federal agencies, and the American Nuclear Insurers participated in a post-emergency TABLETOP exercise in Baton Rouge, Louisiana. The purpose of the exercise was to examine the post-emergency roles, responsibilities, and resources of utility, State, local, Federal and insurance organizations in response to a hypothetical accident at the River Bend Station in Louisiana resulting in a significant release of radiation to the environment. In pursuit of this goal, five major focus areas were addressed: (1) ingestion pathway response; (2) reentry, relocation and return; (3) decontamination of recovery; (4) indemnification of financial losses; and (5) deactivation of the emergency response. This report documents the lessons learned from that exercise

Isolation and purification of Bacillus thuringiensis var. israelensis IМV В-7465 peptidase with specificity toward elastin and collagen

Directory of Open Access Journals (Sweden)

N. А. Nidialkova

2016-06-01

Full Text Available Peptidase of Bacillus thuringiensis var. israelensis IМV В-7465 was isolated from culture supernatant using consecutive fractionations by an ammonium sulphate (60% saturation, ion-exchange chromatography and gel-filtration on the TSK-gels Toyoperl HW-55 and DEAE 650(M. Specific elastase (442 U∙mg of protein-1 and collagenase (212.7 U∙mg of protein-1 activities of the purified enzyme preparation were 8.0- and 6.1-fold, respectively higher than ones of the culture supernatant. Peptidase yields were 33.5% for elastase activity and 30.1% for collagenase activity. It was established that the enzyme is serine metal-dependent alkaline peptidase with Mr about 37 kDa. Maximal hydrolysis of elastin and collagen occurs at the optimum pH 8.0 and t° – 40 and 50 °С, respectively. The purified preparation has high stability at pH in the range of 7.0 to 10.0 and 40-50 °С.

A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized controlled trials

DEFF Research Database (Denmark)

Deacon, Carolyn F

2018-01-01

The first clinical study to investigate effects of dipeptidyl peptidase-4 (DPP-4) inhibition was published in 2002, and since then, numerous randomized controlled trials (RCTs) have shown that DPP-4 inhibitors are efficacious, safe and well-tolerated. This review will focus upon RCTs which have i...

Health disparities monitoring in the U.S.: lessons for monitoring efforts in Israel and other countries.

Science.gov (United States)

Abu-Saad, Kathleen; Avni, Shlomit; Kalter-Leibovici, Ofra

2018-02-28

Health disparities are a persistent problem in many high-income countries. Health policymakers recognize the need to develop systematic methods for documenting and tracking these disparities in order to reduce them. The experience of the U.S., which has a well-established health disparities monitoring infrastructure, provides useful insights for other countries. This article provides an in-depth review of health disparities monitoring in the U.S. Lessons of potential relevance for other countries include: 1) the integration of health disparities monitoring in population health surveillance, 2) the role of political commitment, 3) use of monitoring as a feedback loop to inform future directions, 4) use of monitoring to identify data gaps, 5) development of extensive cross-departmental cooperation, and 6) exploitation of digital tools for monitoring and reporting. Using Israel as a case in point, we provide a brief overview of the healthcare and health disparities landscape in Israel, and examine how the lessons from the U.S. experience might be applied in the Israeli context. The U.S. model of health disparities monitoring provides useful lessons for other countries with respect to documentation of health disparities and tracking of progress made towards their elimination. Given the persistence of health disparities both in the U.S. and Israel, there is a need for monitoring systems to expand beyond individual- and healthcare system-level factors, to incorporate social and environmental determinants of health as health indicators/outcomes.

Characterization of cDNA for human tripeptidyl peptidase II: The N-terminal part of the enzyme is similar to subtilisin

International Nuclear Information System (INIS)

Tomkinson, B.; Jonsson, A-K

1991-01-01

Tripeptidyl peptidase II is a high molecular weight serine exopeptidase, which has been purified from rat liver and human erythrocytes. Four clones, representing 4453 bp, or 90% of the mRNA of the human enzyme, have been isolated from two different cDNA libraries. One clone, designated A2, was obtained after screening a human B-lymphocyte cDNA library with a degenerated oligonucleotide mixture. The B-lymphocyte cDNA library, obtained from human fibroblasts, were rescreened with a 147 bp fragment from the 5' part of the A2 clone, whereby three different overlapping cDNA clones could be isolated. The deduced amino acid sequence, 1196 amino acid residues, corresponding to the longest open rading frame of the assembled nucleotide sequence, was compared to sequences of current databases. This revealed a 56% similarity between the bacterial enzyme subtilisin and the N-terminal part of tripeptidyl peptidase II. The enzyme was found to be represented by two different mRNAs of 4.2 and 5.0 kilobases, respectively, which probably result from the utilziation of two different polyadenylation sites. Futhermore, cDNA corresponding to both the N-terminal and C-terminal part of tripeptidyl peptidase II hybridized with genomic DNA from mouse, horse, calf, and hen, even under fairly high stringency conditions, indicating that tripeptidyl peptidase II is highly conserved

The Role of a Commander in Military Lessons Learned Systems

Directory of Open Access Journals (Sweden)

Zenon Waliński

2015-06-01

Full Text Available The aim of the paper is to investigate the role of a commander in military Lessons Learned systems. In order to achieve the aim, the paper presents (1 the architecture of the Lessons Learned capabilities in the U.S. Army, NATO and the Polish Armed Forces, (2 the commander’s role in the Lessons Learned process (3 the commander’s role in fostering Lessons Learned organisation culture. The paper is based on multiple case study analysis including Lessons Learned systems in NATO, the U.S. Army and the Polish Armed Forces.

Fluorescent turn-on determination of the activity of peptidases using peptide templated gold nanoclusters

International Nuclear Information System (INIS)

Luo, Junjun; Wang, Liqiang; Zeng, Ke; Shen, Congcong; Qian, Pin; Yang, Minghui; Rasooly, Avraham; Qu, Fengli

2016-01-01

The fluorescence intensity of gold nanoclusters (AuNCs) is inversely related to the length of a peptide immobilized on its surface. This finding has been exploited to design a turn-on fluorescent method for the determination of the activity of peptidase. The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) was chosen as a model peptidase. BACE1 cleaves the peptide substrates on AuNCs, and the fluorescence intensity of the AuNCs (at exCitation/emission wavelengths of 320/405 nm) carrying the rest of the cleaved peptide is significantly higher than that of the AuNCs with uncleaved peptide. Transmission electron microscopy revealed a decrease in the size of the AuNCs which is assumed cause fluorescence enhancement. The assay was applied to the determination of BACE1 activity in spiked cell lysates, and recoveries were between 96.9 and 104.0 %. (author)

The use of high impact practices (HIPs) on chemistry lesson design and implementation by pre-service teachers

Science.gov (United States)

Chamrat, Suthida; Apichatyotin, Nattaya; Puakanokhirun, Kittaporn

2018-01-01

The quality of lesson design is essential to learning effectiveness. Research shows some characteristics of lessons have strong effect on learning which were grouped into "High Impact Practices or HIPs. This research aims to examine the use of HIPs on chemistry lesson design as a part of Teaching Science Strand in Chemistry Concepts course. At the first round of lesson design and implementing in classroom, 14 chemistry pre-services teachers freely selected topics, designed and implemented on their own ideas. The lessons have been reflected by instructors and their peers. High Impact Practices were overtly used as the conceptual framework along with the After-Action Review and Reflection (AARR). The selected High Impact practice in this study consisted of 6 elements: well-designed lesson, vary cognitive demand/academic challenge, students center approach, opportunity of students to reflect by discussion or writing, the assignment of project based learning or task, and the lesson reflects pre-service teachers' Technological Pedagogical Content Knowledge (TPACK). The second round, pre-service teachers were encouraged to explicitly used 6 High Impact Practices in cooperated with literature review specified on focused concepts for bettering designed and implemented lessons. The data were collected from 28 lesson plans and 28 classroom observations to compare and discuss between the first and second lesson and implementation. The results indicated that High Impact Practices effect on the quality of delivered lesson. However, there are some elements that vary on changes which were detailed and discussed in this research article.

Sequence analysis and over-expression of ribosomal protein S28 ...

African Journals Online (AJOL)

STORAGESEVER

2009-06-03

Jun 3, 2009 ... protein S28 gene (RPS28) from the Giant Panda. Wan-ru Hou1* .... Materials. Skeletal muscle was collected from a dead Giant Panda at the Wo- ... synthesis. ... 72°C for 3 min in the first cycle and the anneal temperature decea- ..... laboratory manual 2nd ed., Cold Spring Harbor Laboratory Press, Cold.

The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of Polistes dominula venom.

Science.gov (United States)

Schiener, Maximilian; Hilger, Christiane; Eberlein, Bernadette; Pascal, Mariona; Kuehn, Annette; Revets, Dominique; Planchon, Sébastien; Pietsch, Gunilla; Serrano, Pilar; Moreno-Aguilar, Carmen; de la Roca, Federico; Biedermann, Tilo; Darsow, Ulf; Schmidt-Weber, Carsten B; Ollert, Markus; Blank, Simon

2018-01-22

Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients. Polistes dominula is an important elicitor of venom allergy in Southern Europe as well as in the United States. Due to its increased spreading to more moderate climate zones, Polistes venom allergy is likely to gain importance also in these areas. So far, only few allergens of Polistes dominula venom were identified as basis for component-resolved diagnostics. Therefore, this study aimed to broaden the available panel of important Polistes venom allergens. The 100 kDa allergen Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical relevance was supported by the potent activation of basophils from allergic patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and yellow jacket venom suggests the presence of exclusive as well as conserved IgE epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing component of Polistes venom, thus supporting its status as a major allergen of clinical relevance. Therefore, Pol d 3 might become a key element for proper diagnosis of Polistes venom allergy.

A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

Directory of Open Access Journals (Sweden)

Iana Parvanova

Full Text Available The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

Science.gov (United States)

Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

2017-01-01

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

Science.gov (United States)

Pinsky, C; Dua, A K; LaBella, F S

1982-07-15

Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

Safety and Mission Assurance for In-House Design Lessons Learned from Ares I Upper Stage

Science.gov (United States)

Anderson, Joel M.

2011-01-01

This viewgraph presentation identifies lessons learned in the course of the Ares I Upper Stage design and in-house development effort. The contents include: 1) Constellation Organization; 2) Upper Stage Organization; 3) Presentation Structure; 4) Lesson-Importance of Systems Engineering/Integration; 5) Lesson-Importance of Early S&MA Involvement; 6) Lesson-Importance of Appropriate Staffing Levels; 7) Lesson-Importance S&MA Team Deployment; 8) Lesson-Understanding of S&MA In-Line Engineering versus Assurance; 9) Lesson-Importance of Close Coordination between Supportability and Reliability/Maintainability; 10) Lesson-Importance of Engineering Data Systems; 11) Lesson-Importance of Early Development of Supporting Databases; 12) Lesson-Importance of Coordination with Safety Assessment/Review Panels; 13) Lesson-Implementation of Software Reliability; 14) Lesson-Implementation of S&MA Technical Authority/Chief S&MA Officer; 15) Lesson-Importance of S&MA Evaluation of Project Risks; 16) Lesson-Implementation of Critical Items List and Government Mandatory Inspections; 17) Lesson-Implementation of Critical Items List Mandatory Inspections; 18) Lesson-Implementation of Test Article Safety Analysis; and 19) Lesson-Importance of Procurement Quality.

Dipeptidyl-peptidase-IV inhibition augments postprandial lipid mobilization and oxidation in type 2 diabetic patients.

NARCIS (Netherlands)

Boschmann, M.; Engeli, S.; Dobberstein, K.; Budziarek, P.; Strauss, A.; Boehnke, J.; Sweep, F.C.; Luft, F.C.; He, Y.; Foley, J.E.; Jordan, J.

2009-01-01

CONTEXT: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity, resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extrapancreatic mechanisms. OBJECTIVE: We tested the hypothesis that DPP-4

Constellation Program Lessons Learned. Volume 2; Detailed Lessons Learned

Science.gov (United States)

Rhatigan, Jennifer; Neubek, Deborah J.; Thomas, L. Dale

2011-01-01

These lessons learned are part of a suite of hardware, software, test results, designs, knowledge base, and documentation that comprises the legacy of the Constellation Program. The context, summary information, and lessons learned are presented in a factual format, as known and described at the time. While our opinions might be discernable in the context, we have avoided all but factually sustainable statements. Statements should not be viewed as being either positive or negative; their value lies in what we did and what we learned that is worthy of passing on. The lessons include both "dos" and "don ts." In many cases, one person s "do" can be viewed as another person s "don t"; therefore, we have attempted to capture both perspectives when applicable and useful. While Volume I summarizes the views of those who managed the program, this Volume II encompasses the views at the working level, describing how the program challenges manifested in day-to-day activities. Here we see themes that were perhaps hinted at, but not completely addressed, in Volume I: unintended consequences of policies that worked well at higher levels but lacked proper implementation at the working level; long-term effects of the "generation gap" in human space flight development, the need to demonstrate early successes at the expense of thorough planning, and the consequences of problems and challenges not yet addressed because other problems and challenges were more immediate or manifest. Not all lessons learned have the benefit of being operationally vetted, since the program was cancelled shortly after Preliminary Design Review. We avoid making statements about operational consequences (with the exception of testing and test flights that did occur), but we do attempt to provide insight into how operational thinking influenced design and testing. The lessons have been formatted with a description, along with supporting information, a succinct statement of the lesson learned, and

Lesson Learned About FPOs from a Customer`s Perspective

Energy Technology Data Exchange (ETDEWEB)

Gray, C.J.

1998-12-31

Conoco has undertaken three FPSO (Floating Production Storage and Off-loading) projects in the 1990s, Ukpokiti offshore Nigeria, and MacCulloch and Banff in the UK sector of the North Sea. They are different in the technical and commercial solutions they employed. This presentation describes the key features of each project from a commercial and technical perspective and summarizes the good practices and those aspects that could have been improved. The key commercial areas covered include project strategy, contractor selection and leasing issues. The technical areas include facility selection, reservoir characterization, and operations. Lessons learned about Safety Management are also identified. The information about each project is limited to key features only

Biocatalytic ammonolysis of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester: preparation of an intermediate to the dipeptidyl peptidase IV inhibitor Saxagliptin.

Science.gov (United States)

Gill, Iqbal; Patel, Ramesh

2006-02-01

An efficient biocatalytic method has been developed for the conversion of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester (1) into the corresponding amide (5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid, 1-(1,1-dimethylethyl)ester (2), which is a critical intermediate in the synthesis of the dipeptidyl peptidase IV (DPP4) inhibitor Saxagliptin (3). Candida antartica lipase B mediates ammonolysis of the ester with ammonium carbamate as ammonia donor to yield up to 71% of the amide. The inclusion of Ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol byproducts, respectively, increases the yield to 98%, thereby offering an efficient and practical alternative to chemical routes which yield 57-64%.

Efficacy and safety of dipeptidyl peptidase-4 inhibitors as an add-on to insulin treatment in patients with Type 2 diabetes

DEFF Research Database (Denmark)

Frandsen, Christian S.; Madsbad, S

2014-01-01

diabetes. METHODS: We searched the MEDLINE and PubMed databases to identify all randomized controlled clinical trials evaluating dipeptidyl peptidase-4 inhibitors as an add-on to insulin in patients with Type 2 diabetes, which were selected for review. The abstracts and posters of the recent annual...... and placebo treatment. CONCLUSION: Adding a dipeptidyl peptidase-4 inhibitor treatment to insulin has a moderate effect on HbA1c , a weight-neutral effect and a good safety profile. The risk of hypoglycaemia is not increased despite a significant improvement in HbA1c ....

Analysing the integration of engineering in science lessons with the Engineering-Infused Lesson Rubric

Science.gov (United States)

Peterman, Karen; Daugherty, Jenny L.; Custer, Rodney L.; Ross, Julia M.

2017-09-01

Science teachers are being called on to incorporate engineering practices into their classrooms. This study explores whether the Engineering-Infused Lesson Rubric, a new rubric designed to target best practices in engineering education, could be used to evaluate the extent to which engineering is infused into online science lessons. Eighty lessons were selected at random from three online repositories, and coded with the rubric. Overall results documented the strengths of existing lessons, as well as many components that teachers might strengthen. In addition, a subset of characteristics was found to distinguish lessons with the highest level of engineering infusion. Findings are discussed in relation to the potential of the rubric to help teachers use research evidence-informed practice generally, and in relation to the new content demands of the U.S. Next Generation Science Standards, in particular.

Identification and characterization of a dipeptidyl peptidase IV inhibitor from aronia juice

Energy Technology Data Exchange (ETDEWEB)

Kozuka, Miyuki [Department of Health and Nutrition, Faculty of Human Science, Hokkaido Bunkyo University, Eniwa 061-1449 (Japan); Yamane, Takuya, E-mail: t-yamane@pharm.hokudai.ac.jp [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan); Nakano, Yoshihisa [Center for Research and Development Bioresources, Research Organization for University-Community Collaborations, Osaka Prefecture University, Sakai, Osaka 599-8570 (Japan); Nakagaki, Takenori [Institute of Food Sciences, Nakagaki Consulting Engineer Co., Ltd, Nishi-ku, Sakai 593-8328 (Japan); Ohkubo, Iwao [Department of Nutrition, School of Nursing and Nutrition, Tenshi College, Higashi-ku, Sapporo 065-0013 (Japan); Ariga, Hiroyoshi [Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812 (Japan)

2015-09-25

Aronia berries have many potential effects on health, including an antioxidant effect, effect for antimutagenesis, hepatoprotection and cardioprotection, an antidiabetic effect and inhibition of cancer cell proliferation. Previous human studies have shown that aronia juice may be useful for treatment of obesity disorders. In this study, we found that aronia juice has an inhibitory effect against dipeptidyl peptidase IV (DPP IV) (EC 3.4.14.5). DPP IV is a peptidase that cleaves the N-terminal region of incretins such as glucagon-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Inactivation of incretins by DPP IV induces reduction of insulin secretion. Furthermore, we identified that cyanidin 3, 5-diglucoside as the DPP IV inhibitor in aronia juice. DPP IV was inhibited more strongly by cyanidin 3, 5-diglucoside than by cyanidin and cyanidin 3-glucoside. The results suggest that DPP IV is inhibited by cyanidin 3, 5-diglucoside present in aronia juice. The antidiabetic effect of aronia juice may be mediated through DPP IV inhibition by cyanidin 3, 5-diglucoside. - Highlights: • DPP IV activity is inhibited by aronia juice. • DPP IV inhibitor is cyanidin 3, 5-diglucoside in aronia juice. • DPP IV is inhibited by cyanidin 3, 5-diglucoside more than cyanidin and cyanidin 3-glucoside.

DIPEPTIDYL PEPTIDASE 4 (DPP-4 INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS

Directory of Open Access Journals (Sweden)

Erna Kristin

2016-12-01

Diabetes mellitus (DM merupakan penyakit kronis yang menyebabkan sekitar 1,5 juta kematian pada tahun 2012 menurut Organisasi Kesehatan Dunia (WHO. DM tipe 2 (DMT2 banyaknya 90% dari keseluruhan DM di seluruh dunia. Prevalensi DMT2 meningkat karena obesitas. Pedoman klinis merekomendasikan penggunaan metformin sebagai pengobatan lini pertama kecuali ada kontraindikasi, maka bisa diikuti dengan penambahan 1 atau 2 OADs, seperti sulfonilurea (SU, inhibitor alpha-glucosidase, atau thiazolidinediones (TZD. Baru-baru ini, obat baru golongan dipeptidyl peptidase 4 (DPP-4 inhibitor telah ditambahkan ke algoritma pengobatan. Dipeptidyl peptidase 4 (DPP-4 inhibitor inhibitor adalah kelas obat antidiabetes oral yang menghambat DPP-4 enzim. Sitagliptin, saxagliptin, vildagliptin dan linagliptin yang merupakan golongan dipeptidyl peptidase-4 (DPP-4 inhibitor tersedia untuk pengobatan diabetes tipe 2 di Indonesia dan banyak negara lainnya. DPP-4 inhibitor memiliki khasiat glikemik yang setara. DPP-4 inhibitor menghasilkan peningkatan moderat hemoglobin terglikasi (A1C. Namun uji coba head-to-head jumlahnya terbatas, dan tidak ada data tentang penggunaan penggunaan jangka panjang (lebih dari dua tahun keamanan, kematian, komplikasi diabetes, atau kualitas-hidup pasien. Meskipun DPP-inhibitor tidak digunakan sebagai terapi awal untuk mayoritas pasien dengan diabetes tipe 2, DPP-4 inhibitor dapat digunakan sebagai terapi tambahan di tipe 2 pasien diabetes yang tidak toleran, ada kontraindikasi, atau tidak terkontrol dengan penggunaan metformin, sulfonilurea, atau thiazolidinediones. Peran sebenarnya dari DPP-4 inhibitor di antara beberapa obat lainnya untuk DMT2 tidak begitu jelas. Hanya ada sejumlah kecil studi jangka panjang pada DPP-4 inhibitor menilai penurunan glikemik, kemanjuran, kejadian kardiovaskular, kematian, atau keamanan. Pada pasien dengan gagal ginjal (perkiraan laju filtrasi glomerulus [eGFR] <30 mL / menit kronis dapat menggunakan DPP-4 inhibitor, linagliptin

Introduction of the U.S. Nuclear Regulatory Commission's Activities to Reflect Lessons Learned from Fukushima Nuclear Accident

Energy Technology Data Exchange (ETDEWEB)

Kim, Jongtae; Hong, Seong-Wan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Gun Hong [Kyungwon E-C Co., Seongnam (Korea, Republic of)

2014-10-15

The Charter requires the staff to highlight potential policy issues for the Commission and provide the Commission every 6 months an update on the review work conducted under the Charter. The recent status of NRC's activities and related program to reflect the lesson-learned from the Fukushima Daiichi nuclear power plant's severe accident are introduced in this paper. A wide variety of the U.S. NRC's activities to reflect lessons learned from the Fukushima nuclear accidents was investigated. From the investigation, it was found that most of NRC's activities, based on the Fukushima Near-Term Task Force (NTTF) recommendations, are being implemented in a comprehensive and systematic manner. The NRC staff initially prioritized the NTTF recommendations based on its judgment of the potential and relative safety enhancement which could be realized by each. As a result of the staff's prioritization and assessment process, the NTTF recommendations were prioritized into three tiers (i.e., Tier 1, 2 and 3). Tier 1 recommendations are which the staff determined should be started without unnecessary delay and for which sufficient resource flexibility, including availability of critical skill sets, exists. Tier 2 recommendations are which could not be initiated in the near term due to factors that include the need for further technical assessment and alignment, dependence on Tier 1 issues, or availability of critical skill sets. Tier 3 recommendations are that require further staff study to support a regulatory action, have an associated shorter term action that needs to be completed to inform the longer-term action, are dependent on the availability of critical skill sets, or are dependent on the resolution of NTTF Recommendation 1. Through the implementation of each tier activities, existing layers of defense in depth are expected to be gradually bolstered, and such a regulatory approach is much similar in the other countries. It was also found that

Introduction of the U.S. Nuclear Regulatory Commission's Activities to Reflect Lessons Learned from Fukushima Nuclear Accident

International Nuclear Information System (INIS)

Kim, Jongtae; Hong, Seong-Wan; Kim, Gun Hong

2014-01-01

The Charter requires the staff to highlight potential policy issues for the Commission and provide the Commission every 6 months an update on the review work conducted under the Charter. The recent status of NRC's activities and related program to reflect the lesson-learned from the Fukushima Daiichi nuclear power plant's severe accident are introduced in this paper. A wide variety of the U.S. NRC's activities to reflect lessons learned from the Fukushima nuclear accidents was investigated. From the investigation, it was found that most of NRC's activities, based on the Fukushima Near-Term Task Force (NTTF) recommendations, are being implemented in a comprehensive and systematic manner. The NRC staff initially prioritized the NTTF recommendations based on its judgment of the potential and relative safety enhancement which could be realized by each. As a result of the staff's prioritization and assessment process, the NTTF recommendations were prioritized into three tiers (i.e., Tier 1, 2 and 3). Tier 1 recommendations are which the staff determined should be started without unnecessary delay and for which sufficient resource flexibility, including availability of critical skill sets, exists. Tier 2 recommendations are which could not be initiated in the near term due to factors that include the need for further technical assessment and alignment, dependence on Tier 1 issues, or availability of critical skill sets. Tier 3 recommendations are that require further staff study to support a regulatory action, have an associated shorter term action that needs to be completed to inform the longer-term action, are dependent on the availability of critical skill sets, or are dependent on the resolution of NTTF Recommendation 1. Through the implementation of each tier activities, existing layers of defense in depth are expected to be gradually bolstered, and such a regulatory approach is much similar in the other countries. It was also found that

Fish skin gelatin hydrolysates produced by visceral peptidase and bovine trypsin: Bioactivity and stability.

Science.gov (United States)

Ketnawa, Sunantha; Benjakul, Soottawat; Martínez-Alvarez, Oscar; Rawdkuen, Saroat

2017-01-15

The peptidase from the viscera of farmed giant catfish was used for producing gelatin hydrolysates (HG) and compared with those produced from commercial bovine trypsin (HB). The degree of hydrolysis (DH) observed suggests that proteolytic cleavage rapidly occurred within the first 120min of incubation, and there was higher DH in HG than in HB. HG demonstrated the highest ACE-inhibitory activity, DPPH, ABTS radical scavenging activity, and FRAP. HB showed the highest FRAP activity. The DPPH radical scavenging activity of HG was quite stable over the pH range of 1-11, but it increased slightly when the heating duration time reached 240min at 100°C. The ACE-inhibitory activity of HG showed the highest stability at a pH of 7, and it remained very stable at 100°C for over 15-240min. The visceral peptidase from farmed giant catfish could be an alternative protease for generating protein hydrolysates with desirable bioactivities. The resulting hydrolysates showed good stability, making them potential functional ingredients for food formulations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Europe’s changing lessons from the past

NARCIS (Netherlands)

Sierp, Aline

2016-01-01

This special issue brings together scholars who concentrate on the way ‘lessons from the past’ have been framed in different national contexts in Central and Eastern Europe. In the wake of crisis in Europe, bits and pieces of the past are being resurrected as a means of understanding the present and

Strategic Program Planning Lessons Learned in Developing the LTS S&T Roadmap

Energy Technology Data Exchange (ETDEWEB)

Duane Hanson; Brent Dixon; Gretchen Matthern

2003-07-01

Technology roadmapping is a strategic planning method used by companies to identify and plan the development of technologies necessary for new products. The U.S. Department of Energy’s Office of Environmental Management has used this same method to refine requirements and identify knowledge and tools needed for completion of defined missions. This paper describes the process of applying roadmapping to clarify mission requirements and identify enhancing technologies for the Long-Term Stewardship (LTS) of polluted sites after site cleanup has been completed. The nature of some contamination problems is such that full cleanup is not achievable with current technologies and some residual hazards remain. LTS maintains engineered contaminant barriers and land use restriction controls, and monitors residual contaminants until they no longer pose a risk to the public or the environment. Roadmapping was used to clarify the breadth of the LTS mission, to identify capability enhancements needed to improve mission effectiveness and efficiency, and to chart out the research and development efforts to provide those enhancements. This paper is a case study of the application of roadmapping for program planning and technical risk management. Differences between the planned and actual application of the roadmapping process are presented along with lessons learned. Both the process used and lessons learned should be of interest for anyone contemplating a similar technology based planning effort.

Dipeptidyl-peptidase IV activity is correlated with colorectal cancer prognosis.

Directory of Open Access Journals (Sweden)

Gorka Larrinaga

Full Text Available Dipeptidyl-peptidase IV (EC 3.4.14.5 (DPPIV is a serine peptidase involved in cell differentiation, adhesion, immune modulation and apoptosis, functions that control neoplastic transformation. Previous studies have demonstrated altered expression and activity of tissue and circulating DPPIV in several cancers and proposed its potential usefulness for early diagnosis in colorectal cancer (CRC.The activity and mRNA and protein expression of DPPIV was prospectively analyzed in adenocarcinomas, adenomas, uninvolved colorectal mucosa and plasma from 116 CRC patients by fluorimetric, quantitative RT-PCR and immunohistochemical methods. Results were correlated with the most important classic pathological data related to aggressiveness and with 5-year survival rates. Results showed that: 1 mRNA levels and activity of DPPIV increased in colorectal neoplasms (Kruskal-Wallis test, p<0.01; 2 Both adenomas and CRCs displayed positive cytoplasmic immunostaining with luminal membrane reinforcement; 3 Plasmatic DPPIV activity was lower in CRC patients than in healthy subjects (Mann-U test, p<0.01; 4 Plasmatic DPPIV activity was associated with worse overall and disease-free survivals (log-rank p<0.01, Cox analysis p<0.01.1 Up-regulation of DPPIV in colorectal tumors suggests a role for this enzyme in the neoplastic transformation of colorectal tissues. This finding opens the possibility for new therapeutic targets in these patients. 2 Plasmatic DPPIV is an independent prognostic factor in survival of CRC patients. The determination of DPPIV activity levels in the plasma may be a safe, minimally invasive and inexpensive way to define the aggressiveness of CRC in daily practice.

Historical Lessons for Our Time : Italy’s Response to the Challenge of Terrorism

OpenAIRE

Drake, Richard

2016-01-01

During the so-called years of lead, Italy had the highest rate of terrorist violence in the industrialized world. Terrorist groups, descending ideologically from the country’s Marxist-Leninist and neo-fascist traditions, sought to destroy its democratic institutions. They failed. The success of the Italian government in ending this scourge merits careful study, for the lessons that might be gained in learning how we might cope with terrorism today.

An advanced system of the mitochondrial processing peptidase and core protein family in Trypanosoma brucei and multiple origins of the core I subunit in eukaryotes

Czech Academy of Sciences Publication Activity Database

Mach, J.; Poliak, Pavel; Matušková, Anna; Žárský, V.; Janata, Jiří; Lukeš, Julius; Tachezy, J.

2013-01-01

Roč. 5, č. 5 (2013), s. 860-875 ISSN 1759-6653 R&D Projects: GA ČR(CZ) GAP305/11/2179; GA ČR(CZ) GAP305/11/1061; GA MŠk(CZ) EE2.3.20.0055 Institutional support: RVO:60077344 ; RVO:61388971 Keywords : bc1 complex * evolution * mitochondrial processing peptidase * mitochondrial targeting sequence * trypanosome Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.532, year: 2013

Identification and Characterization of Noncovalent Interactions That Drive Binding and Specificity in DD-Peptidases and β-Lactamases.

Science.gov (United States)

Hargis, Jacqueline C; Vankayala, Sai Lakshmana; White, Justin K; Woodcock, H Lee

2014-02-11

Bacterial resistance to standard (i.e., β-lactam-based) antibiotics has become a global pandemic. Simultaneously, research into the underlying causes of resistance has slowed substantially, although its importance is universally recognized. Key to unraveling critical details is characterization of the noncovalent interactions that govern binding and specificity (DD-peptidases, antibiotic targets, versus β-lactamases, the evolutionarily derived enzymes that play a major role in resistance) and ultimately resistance as a whole. Herein, we describe a detailed investigation that elicits new chemical insights into these underlying intermolecular interactions. Benzylpenicillin and a novel β-lactam peptidomimetic complexed to the Stremptomyces R61 peptidase are examined using an arsenal of computational techniques: MD simulations, QM/MM calculations, charge perturbation analysis, QM/MM orbital analysis, bioinformatics, flexible receptor/flexible ligand docking, and computational ADME predictions. Several key molecular level interactions are identified that not only shed light onto fundamental resistance mechanisms, but also offer explanations for observed specificity. Specifically, an extended π-π network is elucidated that suggests antibacterial resistance has evolved, in part, due to stabilizing aromatic interactions. Additionally, interactions between the protein and peptidomimetic substrate are identified and characterized. Of particular interest is a water-mediated salt bridge between Asp217 and the positively charged N-terminus of the peptidomimetic, revealing an interaction that may significantly contribute to β-lactam specificity. Finally, interaction information is used to suggest modifications to current β-lactam compounds that should both improve binding and specificity in DD-peptidases and their physiochemical properties.

Free Trade Agreements With The United States: 8 Lessons For Prospective Parties From Australia’s Experience

OpenAIRE

Tully Stephen R.

2016-01-01

This article identifies 8 key lessons for those States contemplating a free trade agreement with the United States (U.S.) arising from Australia’s experience. The standards of intellectual property protection under the Australia-U.S. Free Trade Agreement and their impact on pharmaceutical prices in Australia are a particular focus. Prospective parties must first conduct a national interest self-assessment which reviews the desired strength of intellectual property protection under national la...

Cysteine peptidases of Eudiplozoon nipponicum: a broad repertoire of structurally assorted cathepsins L in contrast to the scarcity of cathepsins B in an invasive species of haematophagous monogenean of common carp

Czech Academy of Sciences Publication Activity Database

Jedličková, L.; Dvořáková, H.; Dvořák, J.; Kašný, M.; Ulrychová, Lenka; Vorel, J.; Žárský, V.; Mikeš, L.

2018-01-01

Roč. 11, Mar 6 (2018), č. článku 142. ISSN 1756-3305 R&D Projects: GA MŠk LO1302 Institutional support: RVO:61388963 Keywords : cysteine peptidase * protease * cathepsin * S2 subsite * haematophagy * blood digestion Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.080, year: 2016 https:// parasites andvectors.biomedcentral.com/ articles /10.1186/s13071-018-2666-2

Penicillin’s Discovery and Antibiotic Resistance: Lessons for the Future?

Science.gov (United States)


Lobanovska, Mariya; Pilla, Giulia

2017-01-01

Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s. Looking back at the history of penicillin might help us to relive this journey to find new treatments and antimicrobial agents. This is particularly relevant today as the emergence of multiple drug resistant bacteria poses a global threat, and joint efforts are needed to combat the rise and spread of resistance. PMID:28356901

Identification of diverse archaeal proteins with class III signal peptides cleaved by distinct archaeal prepilin peptidases

NARCIS (Netherlands)

Szabó, Zalán; Oliveira Stahl, Adriana; Albers, Sonja-V.; Kissinger, Jessica C.; Driessen, Arnold J.M.; Pohlschröder, Mechthild; Pohlschroder, M.

2007-01-01

Most secreted archaeal proteins are targeted to the membrane via a tripartite signal composed of a charged N terminus and a hydrophobic domain, followed by a signal peptidase-processing site. Signal peptides of archaeal flagellins, similar to class III signal peptides of bacterial type IV pilins,

Synthesis, kinetic evaluation, and utilization of a biotinylated dipeptide proline diphenyl phosphonate for the disclosure of dipeptidyl peptidase IV-like serine proteases.

Science.gov (United States)

Gilmore, Brendan F; Carson, Louise; McShane, Laura L; Quinn, Derek; Coulter, Wilson A; Walker, Brian

2006-08-18

In this study, we report on the synthesis, kinetic characterisation, and application of a novel biotinylated and active site-directed inactivator of dipeptidyl peptidase IV (DPP-IV). Thus, the dipeptide-derived proline diphenyl phosphonate NH(2)-Glu(biotinyl-PEG)-Pro(P)(OPh)(2) has been prepared by a combination of classical solution- and solid-phase methodologies and has been shown to be an irreversible inhibitor of porcine DPP-IV, exhibiting an over all second-order rate constant (k(i)/K(i)) for inhibition of 1.57 x 10(3) M(-1) min(-1). This value compares favourably with previously reported rates of inactivation of DPP-IV by dipeptides containing a P(1) proline diphenyl phosphonate grouping [B. Boduszek, J. Oleksyszyn, C.M. Kam, J. Selzler, R.E. Smith, J.C. Powers, Dipeptide phophonates as inhibitors of dipeptidyl peptidase IV, J. Med. Chem. 37 (1994) 3969-3976; B.F. Gilmore, J.F. Lynas, C.J. Scott, C. McGoohan, L. Martin, B. Walker, Dipeptide proline diphenyl phosphonates are potent, irreversible inhibitors of seprase (FAPalpha), Biochem, Biophys. Res. Commun. 346 (2006) 436-446.], thus demonstrating that the incorporation of the side-chain modified (N-biotinyl-3-(2-(2-(3-aminopropyloxy)-ethoxy)-ethoxy)-propyl) glutamic acid residue at the P(2) position is compatible with inhibitor efficacy. The utilisation of this probe for the detection of both purified dipeptidyl peptidase IV and the disclosure of a dipeptidyl peptidase IV-like activity from a clinical isolate of Porphyromonas gingivalis, using established electrophoretic and Western blotting techniques previously developed by our group, is also demonstrated.

Optical waveform sampling and error-free demultiplexing of 1.28 Tbit/s serial data in a silicon nanowire

DEFF Research Database (Denmark)

Ji, Hua; Hu, Hao; Galili, Michael

2010-01-01

We experimentally demonstrate 640 Gbit/s and 1.28 Tbit/s serial data optical waveform sampling and 640-to-10 Gbit/s and 1.28 Tbit/s-to-10 Gbit/s error-free demultiplexing using four-wave mixing in a 300nm$$450nm$$5mm silicon nanowire.......We experimentally demonstrate 640 Gbit/s and 1.28 Tbit/s serial data optical waveform sampling and 640-to-10 Gbit/s and 1.28 Tbit/s-to-10 Gbit/s error-free demultiplexing using four-wave mixing in a 300nm$$450nm$$5mm silicon nanowire....

Voys Lessons: Whirling Words in Chaucer’s “House of Rumour”

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Nicola Blake

2014-12-01

Full Text Available “Voys Lessons: Whirling Words in Chaucer’s ‘House of Rumour’” examines the lability of sound and its use in the dissemination, transposition, and authorship of stories within The House of Fame, a text exemplifying the mobility and flexibility of misused or unhinged words, as expressed through sound as opposed to text. By engaging the use and interpretation of sound in contrast to words, this new reading concentrates on the idea of narrative as material artifact with limited stasis. Geffrey’s pseudo-authorship, through his voyeuristic stance, engages the textuality of sounds and shows the related subtlety, elasticity, and democratic sociohistorical aspect of narrative construction. Chaucer’s dreamscape and use of authorial characters allows this argument to reposition the mobility and nature of sound, emphasizing its critical importance in the formation and corruption of stories, both written and oral.Keywords: sound, narrative, medieval, authorship, bricolage, authority, transposition, dissemination, context, Chaucer

A novel strategy to improve protein secretion via overexpression of the SppA signal peptide peptidase in Bacillus licheniformis.

Science.gov (United States)

Cai, Dongbo; Wang, Hao; He, Penghui; Zhu, Chengjun; Wang, Qin; Wei, Xuetuan; Nomura, Christopher T; Chen, Shouwen

2017-04-24

Signal peptide peptidases play an important role in the removal of remnant signal peptides in the cell membrane, a critical step for extracellular protein production. Although these proteins are likely a central component for extracellular protein production, there has been a lack of research on whether protein secretion could be enhanced via overexpression of signal peptide peptidases. In this study, both nattokinase and α-amylase were employed as prototypical secreted target proteins to evaluate the function of putative signal peptide peptidases (SppA and TepA) in Bacillus licheniformis. We observed dramatic decreases in the concentrations of both target proteins (45 and 49%, respectively) in a sppA deficient strain, while the extracellular protein yields of nattokinase and α-amylase were increased by 30 and 67% respectively in a strain overexpressing SppA. In addition, biomass, specific enzyme activities and the relative gene transcriptional levels were also enhanced due to the overexpression of sppA, while altering the expression levels of tepA had no effect on the concentrations of the secreted target proteins. Our results confirm that SppA, but not TepA, plays an important functional role for protein secretion in B. licheniformis. Our results indicate that the sppA overexpression strain, B. licheniformis BL10GS, could be used as a promising host strain for the industrial production of heterologous secreted proteins.

1.28-Tb/s Demultiplexing of an OTDM DPSK Data Signal Using a Silicon Waveguide

DEFF Research Database (Denmark)

Ji, Hua; Galili, Michael; Hu, Hao

2010-01-01

This letter demonstrates optical demultiplexing of a 1.28-Tb/s serial differential phase-shift-keying data signal using a nano-engineered silicon waveguide. We first present error-free performance at 640 Gb/s and then at 1.28 Tb/s with characterization of all 128 channels. Bit-error rates below $10...

Combating Ukraine’s Health Crisis : Lessons from Europe

OpenAIRE

Rekha Menon

2010-01-01

This knowledge brief synthesizes the important findings of a recent study. It spotlights key issues and challenges facing Ukraine's health sector and suggests strategies for improvement. To combat the current health crisis, Ukraine could look at the lessons learned by other European countries that have faced similar health crises.

A cathepsin F-like peptidase involved in barley grain protein mobilization, HvPap-1, is modulated by its own propeptide and by cystatins

Science.gov (United States)

Diaz, Isabel

2012-01-01

Among the C1A cysteine proteases, the plant cathepsin F-like group has been poorly studied. This paper describes the molecular and functional characterization of the HvPap-1 cathepsin F-like protein from barley. This peptidase is N-glycosylated and has to be processed to become active by its own propeptide being an important modulator of the peptidase activity. The expression pattern of its mRNA and protein suggest that it is involved in different proteolytic processes in the barley plant. HvPap-1 peptidase has been purified in Escherichia coli and the recombinant protein is able to degrade different substrates, including barley grain proteins (hordeins, albumins, and globulins) stored in the barley endosperm. It has been localized in protein bodies and vesicles of the embryo and it is induced in aleurones by gibberellin treatment. These three features support the implication of HvPap-1 in storage protein mobilization during grain germination. In addition, a complex regulation exerted by the barley cystatins, which are cysteine protease inhibitors, and by its own propeptide, is also described PMID:22791822

Functional analysis of C1 family cysteine peptidases in the larval gut of Tenebrio molitor and Tribolium castaneum

Science.gov (United States)

We studied protein digestion the tenebrionids Tenebrio molitor and Tribolium castaneum, pests of stored grains and grain products, to identify potential targets for biopesticide development. Tenebrionid larvae have highly compartmentalized guts, with primarily cysteine peptidases in the acidic anter...

Lessons from Early Medicaid Expansions Under Health Reform..

Data.gov (United States)

U.S. Department of Health & Human Services — Lessons from Early Medicaid Expansions Under Health Reform, Interviews with Medicaid Officials In a new study entitled Lessons from Early Medicaid Expansions Under...

Synthesis, QSAR, and Molecular Dynamics Simulation of Amidino-substituted Benzimidazoles as Dipeptidyl Peptidase III Inhibitors.

Science.gov (United States)

Rastija, Vesna; Agić, Dejan; Tomiš, Sanja; Nikolič, Sonja; Hranjec, Marijana; Grace, Karminski-Zamola; Abramić, Marija

2015-01-01

A molecular modeling study is performed on series of benzimidazol-based inhibitors of human dipeptidyl peptidase III (DPP III). An eight novel compounds were synthesized in excellent yields using green chemistry approach. This study is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of human DPP III activity using Quantitative Structure-Activity Relationship (QSAR) analysis, and to understand the mechanism of one of the most potent inhibitor binding into the active site of this enzyme, by molecular dynamics (MD) simulations. The best model obtained includes S3K and RDF045m descriptors which have explained 89.4 % of inhibitory activity. Depicted moiety for strong inhibition activity matches to the structure of most potent compound. MD simulation has revealed importance of imidazolinyl and phenyl groups in the mechanism of binding into the active site of human DPP III.

Frequency of Tabagism and N34S and P55S Mutations of Serine Peptidase Inhibitor, Kazal Type 1 (SPINK1) and R254W Mutation of Chymotrypsin C (CTRC) in Patients With Chronic Pancreatitis and Controls.

Science.gov (United States)

da Costa, Marianges Zadrozny Gouvêa; Pires, Júlia Glória Lucatelli; Nasser, Paulo Dominguez; Ferreira, Camila da Silva; Teixeira, Ana Cristina de Sá; Paranaguá-Vezozzo, Denise Cerqueira; Guarita, Dulce Reis; Carrilho, Flair José; Ono, Suzane Kioko

2016-10-01

This study aimed to investigate the association between chronic pancreatitis and smoking or genetic mutations. The study sample comprised 148 patients with chronic pancreatitis, 110 chronic alcoholic subjects without pancreatic disease, and 297 volunteer blood donors. Of the patients with chronic pancreatitis, 74% had alcoholic etiology and 26% had idiopathic pancreatitis. The frequency of smoking was 91.4% in patients with alcoholic pancreatitis, higher than 73.3% in alcoholic subjects without pancreatitis (P pancreatitis and blood donors. The N34S mutation of serine peptidase inhibitor, Kazal type 1 (SPINK1) was found in 2.7% of patients with chronic alcoholic pancreatitis, in 5.3% of patients with idiopathic pancreatitis, and in 0.4% of blood donors (P = 0.02). The P55S mutation of SPINK1 was found in 2.7% of patients with alcoholic pancreatitis and in 0.7% of blood donors (P = 0.12). The R254W mutation of chymotrypsin C was found in 0.9% of patients with alcoholic pancreatitis, in 0.9% of chronic alcoholic subjects without pancreatitis, and in 0.4% of blood donors (P = 0.75). In all cases, the mutations were heterozygous. Smoking and the N34S mutation of SPINK1 were positively correlated with chronic pancreatitis.

Dynamics of 28,30S i* compound nuclei formed at sub-barrier energies

Science.gov (United States)

Kaur, Manpreet; Singh, Bir Bikram; Kaur, Sarbjeet

2018-05-01

The decay of 28S i* and 30S i* compound nuclei (CN) formed at sub-barrier energies, in the reactions induced by stable projectile 16O and exotic projectile 18O, respectively, has been investigated within the quantum mechanical fragmentation theory based dynamical cluster-decay model (DCM). The collective potential energy surface shows that xα-type (x is an integer) clusters are minimized in the decay of 28S i* while in case of 30S i* in addition to xα-type clusters, np-xα (n, p are neutron and proton, respectively) type clusters are also minimized. These minimized fragments have more preformation probability P0, which is an important factor through which nuclear structure effects of decaying CN are probed, within DCM. The results show that light particles (LPs) are contributing mostly in the fusion cross-section, σfusion. In case of 30S i*, the contribution of 1n is highest and more compared to 4He in case of 28S i*, which seems to play an important role in fusion enhancement. The DCM calculated σfusion for both the CN formed with same Ec.m. = 7.0 MeV gives more value for σfusion of 30S i*, in agreement with the experimental data.

COMPLEXES OF BISCITRATOGERMANATES AND BISCITRATOSTANATES WITH METALS ARE MODIFIERS OF ACTIVITY OF Bacillus thuringiensis var. іsraelensis PEPTIDASES AND α-Penicillium canescens, Cladosporium cladosporioides AND Aspergillus niger GALACTOIDASES

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L. D. Varbanets

2016-06-01

Full Text Available The aim of the research was to study the effect of a number of coordination compounds of stanum and germanium (compounds 1‒8 as modifiers of activity of peptidases and α-galactosidases. The coordination compounds with the same type structure of were investigated as enzymes effectors. Two types of complexes: 1 [M(H2O6][Ge(НCitr2]4H2O (M = Mg(1, Mn(2, Co(3, Ni(4, Zn(5, containing biscitrate-stanate anion ([Ge(НCitr2]2-, and 2 [M(H2O6][Sn(НCitr2]4H2O (M = Mg(6, Co(7, Ni(8, containing biscitratostanate anion and various hexaaquacations ([M(H2O6]2+, М= Mg, Mn, Co, Ni, Zn were studied. It is shown that the compound 6 which is a biscitratostanate complex containing magnesium ions as metal, can be used for stimulation on 20‒25% of collagenase activity of B. thuringiensis var. israelensis IMV B-7465 peptidase 1 and peptidase 2. Compound 1 (biscitrate-stanate complex containing magnesium ions as metal and 7 (biscitratostanate complex containing cobalt ions as metal and compound 6 in a concentration of 0.001% are able to increase elastolytic activity of peptidase 1 on 55‒58%. However compound 7 has shown the greatest activating effect. It increased the elastolytic activity of peptidase 2 on 100‒140% (for both tested concentrations. This indicates that the compound 7 can further be used as of peptidase 2 elastolytic activity effector. In the study of effect of the considered coordination compounds on the activity of α-galactosidase of Penicillium canescens, Cladosporium cladosporioides and Aspergillus niger was found that when using a number of complexes (1‒2 and 4‒8, there is a slight increase on 12‒20% of enzyme activity of P. canescens, and the maximum effect (~20%, concentration 0.01% was provided by complex 6.

Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery.

Science.gov (United States)

Wagner, Leona; Wolf, Raik; Zeitschel, Ulrike; Rossner, Steffen; Petersén, Åsa; Leavitt, Blair R; Kästner, Florian; Rothermundt, Matthias; Gärtner, Ulf-Torsten; Gündel, Daniel; Schlenzig, Dagmar; Frerker, Nadine; Schade, Jutta; Manhart, Susanne; Rahfeld, Jens-Ulrich; Demuth, Hans-Ulrich; von Hörsten, Stephan

2015-12-01

The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P, secreted meprin-A (Mep-A), and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S, and tissue kallikrein could also be identified. The expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive angiotensin-converting enzyme inhibitors, while it ablates suspected hypertensive side effects of only antidiabetic DP4-inhibitors application. The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor selectivity by dipeptidyl peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids, and tissues revealed that most frequently DP4-like enzymes

Generation of Dipeptidyl Peptidase-IV-Inhibiting Peptides from β-Lactoglobulin Secreted by Lactococcus lactis

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Suguru Shigemori

2014-01-01

Full Text Available Previous studies showed that hydrolysates of β-lactoglobulin (BLG prepared using gastrointestinal proteases strongly inhibit dipeptidyl peptidase-IV (DPP-IV activity in vitro. In this study, we developed a BLG-secreting Lactococcus lactis strain as a delivery vehicle and in situ expression system. Interestingly, trypsin-digested recombinant BLG from L. lactis inhibited DPP-IV activity, suggesting that BLG-secreting L. lactis may be useful in the treatment of type 2 diabetes mellitus.

Novel aspects of cellular action of dipeptidyl peptidase IV/CD26.

Science.gov (United States)

Ansorge, Siegfried; Nordhoff, Karsten; Bank, Ute; Heimburg, Anke; Julius, Heiko; Breyer, Doreen; Thielitz, Anja; Reinhold, Dirk; Täger, Michael

2011-03-01

The cellular dipeptidyl peptidase IV (DPIV, E.C.3.4.14.5, CD26) is a type II membrane peptidase with various physio-logical functions. Our main knowledge on DPIV comes from studies of soluble DPIV which plays a role in regulation of glucose homeostasis by inactivation of the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic poly-peptide. It has been reported that membrane-bound DPIV plays a crucial role in the immune system and in other tissues and cells, but the knowledge on the action of cellular DPIV and its regulation is limited. In this study, we show particularly for immune cells that DPIV and not DP8 or DP9 is the most potent member of the DPIV family in regulating cellular immune functions. Moreover, we provide evidence that soluble and cellular DPIV differ in functions and hand-ling of substrates and inhibitors owing to the different accessibility of peptide substrates to the two access paths of DPIV. The different functions are based on the favored access path of the central pore of cellular DPIV and a special central pore binding site which assists substrate access to the active site of the enzyme. The newly discovered central pore binding site mediates an autosterical regulation of cellular DPIV and is its most crucial target site to regulate cellular functions such as growth and cytokine production. Neuropeptide Y (NPY) processing by cellular DPIV was found to be inhibited by ligands which interact with the central pore binding site. This finding suggests a crucial role of the immunosuppressive cytokine NPY in the function of DPIV in growth regulation.

Dipeptidyl peptidase IV inhibition enhances the intestinotrophic effect of glucagon-like peptide-2 in rats and mice

DEFF Research Database (Denmark)

Hartmann, B; Thulesen, J; Kissow, Hannelouise

2000-01-01

Glucagon-like peptide-2 (GLP-2) induces intestinal growth in mice; but in normal rats, it seems less potent, possibly because of degradation of GLP-2 by the enzyme dipeptidyl peptidase IV (DPP-IV). The purpose of this study was to investigate the survival and effect of GLP-2 in rats and mice afte...

Biosynthesis of intestinal microvillar proteins. Pulse-chase labelling studies on maltase-glucoamylase, aminopeptidase A and dipeptidyl peptidase IV

DEFF Research Database (Denmark)

Danielsen, E M; Sjöström, H; Norén, Ove

1983-01-01

The biogenesis of three intestinal microvillar enzymes, maltase-glucoamylase (EC 3.2.1.20), aminopeptidase A (aspartate aminopeptidase, EC 3.4.11.7) and dipeptidyl peptidase IV (EC 3.4.14.5), was studied by pulse-chase labelling of pig small-intestinal explants kept in organ culture. The earliest...

Development and analytical performance of a new ARCHITECT automated dipeptidyl peptidase-4 immunoassay

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Philip M. Hemken

2017-12-01

Full Text Available Background: Dipeptidyl peptidase-4 (DPP-4 may be a suitable biomarker to identify people with severe asthma who have greater activation of the interleukin-13 (IL-13 pathway and may therefore benefit from IL-13-targeted treatments. We report the analytical performance of an Investigational Use Only immunoassay and provide data on the biological range of DPP-4 concentrations. Methods: We assessed assay performance, utilising analyses of precision, linearity and sensitivity; interference from common endogenous assay interferents, and from asthma and anti-diabetic medications, were also assessed. The assay was used to measure the range of serum DPP-4 concentrations in healthy volunteers and subjects with diabetes and severe, uncontrolled asthma. Results: The total precision of DPP-4 concentration measurement (determined using percentage coefficient of variation was ≤5% over 20 days. Dilution analysis yielded linear results from 30 to 1305 ng/mL; the limit of quantitation was 19.2 ng/mL. No notable endogenous or drug interferences were observed at the expected therapeutic concentration. Median DPP-4 concentrations in healthy volunteers and subjects with asthma or Type 1 diabetes were assessed, with concentrations remaining similar in subjects with diabetes and asthma across different demographics. Conclusion: These analyses indicate that the ARCHITECT DPP-4 Immunoassay is a reliable and robust method for measuring serum DPP-4 concentration. Keywords: Asthma, Automated immunoassay, Biomarker, Dipeptidyl peptidase-4, IL-13

Animation with concurrent narration versus narration in physical education lesson

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Ioannou Panagiotis

2016-01-01

Full Text Available The purpose of the present study was to compare the effects of two different teaching methods on students' comprehension during Physical Education lesson: narration versus animation with concurrent narration, during teaching shot put event. Thirty primary school children (boys and girls volunteered to participate in this study. In experiment students listened (narration and viewed (animation with narration the presentation of two shot putting styles. A problem-solving and a retention test were used to evaluate students' comprehension. Results showed that students' comprehension was better when shot putting styles were presented through a mixed model (animation and narration group than a single (narration. The animation with concurrent narration group performed better than the narration group, in problem-solving (M = 4.91, SD = 1.36 and in retention test (M = 5.98, SD = 1.28 t(28 = 1.89 p<0.01. An instructional implication is that pictures with words is more effective way of teaching when they occur continuingly in time, than only words during Physical Education lesson.

[Phylogeny of protostome moulting animals (Ecdysozoa) inferred from 18 and 28S rRNA gene sequences].

Science.gov (United States)

Petrov, N B; Vladychenskaia, N S

2005-01-01

Reliability of reconstruction of phylogenetic relationships within a group of protostome moulting animals was evaluated by means of comparison of 18 and 28S rRNA gene sequences sets both taken separately and combined. Reliability of reconstructions was evaluated by values of the bootstrap support of major phylogenetic tree nodes and by degree of congruence of phylogenetic trees inferred by various methods. By both criteria, phylogenetic trees reconstructed from the combined 18 and 28S rRNA gene sequences were better than those inferred from 18 and 28S sequences taken separately. Results obtained are consistent with phylogenetic hypothesis separating protostome animals into two major clades, moulting Ecdysozoa (Priapulida + Kinorhyncha, Nematoda + Nematomorpha, Onychophora + Tardigrada, Myriapoda + Chelicerata, Crustacea + Hexapoda) and unmoulting Lophotrochozoa (Plathelminthes, Nemertini, Annelida, Mollusca, Echiura, Sipuncula). Clade Cephalorhyncha does not include nematomorphs (Nematomorpha). Conclusion was taken that it is necessary to use combined 18 and 28S data in phylogenetic studies.

The effectiveness of 28S and 16S molecular regions in resolving phylogeny of Malaysian microgastrinae (Hymenoptera: Braconidae)

Science.gov (United States)

Zuki, Ameyra Aman; Mohammed, Muhamad Azmi; Md-Zain, Badrul Munir; Yaakop, Salmah

2018-04-01

The phylogenetic relationships of Microgastrinae remains unclear though some studies have been conducted to resolve it. The function of Microgastrinae as endoparasitoids of Lepidopteran larvae makes this subfamily an ideal and potential species to be applied as biological control agent of infesting crops. In this study, a total of 13 microgastrine samples under 13 genera were collected from nine localities throughout Peninsular Malaysia. Two molecular regions, 28S nuclear marker and 16S mitochondrial marker were utilized in this study to examine the effectiveness of those regions in resolving the relationships within Microgastrinae. Total of 36 sequences were implemented in the analyses of NJ, MP and Bayesian for both markers. Results obtained from this study were supported by morphological and biological characters. Henceforth, the outcome from this study provides a proof of effectiveness of 28S and 16S molecular markers in studying the phylogenetic relationships of Microgastrinae from Malaysia exclusively and Oriental generally.

Refining MARGINS Mini-Lessons Using Classroom Observations

Science.gov (United States)

Iverson, E. A.; Manduca, C. A.; McDaris, J. R.; Lee, S.

2009-12-01

One of the challenges that we face in developing teaching materials or activities from research findings is testing the materials to determine that they work as intended. Traditionally faculty develop material for their own class, notice what worked and didn’t, and improve them the next year. However, as we move to a community process of creating and sharing teaching materials, a community-based process for testing materials is appropriate. The MARGINS project has piloted such a process for testing teaching materials and activities developed as part of its mini-lesson project (http://serc.carleton.edu/margins/index.html). Building on prior work developing mechanisms for community review of teaching resources (e.g. Kastens, 2002; Hancock and Manduca, 2005; Mayhew and Hall, 2007), the MARGINS evaluation team developed a structured classroom observation protocol. The goals of field testing are to a) gather structured, consistent feedback for the lesson authors based on classroom use; b) guide reviewers of these lessons to reflect on research-based educational practice as a framework for their comments; c) collect information on the data and observations that the reviewer used to underpin their review; d) determine which mini-lessons are ready to be made widely available on the website. The protocol guides faculty observations on why they used the activity, the effectiveness of the activity in their classroom, the success of the activity in leading to the desired learning, and what other faculty need to successfully use the activity. Available online (http://serc.carleton.edu/margins/protocol.html), the protocol can be downloaded and completed during instruction with the activity. In order to encourage review of mini-lessons using the protocol, a workshop focused on review and revision of activities was held in May 2009. In preparation for the workshop, 13 of the 28 participants chose to field test a mini-lesson prior to the workshop and reported that they found this

Saxagliptin: a new dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F; Holst, Jens J

2009-01-01

Saxagliptin is a potent and selective reversible inhibitor of dipeptidyl peptidase-4, which is being developed for the treatment of type 2 diabetes. It is absorbed rapidly after oral administration and has a pharmacokinetic profile compatible with once daily dosing. Saxagliptin is metabolized...... a neutral effect on body weight and dose adjustment because of age, gender, or hepatic impairment is not necessary. Saxagliptin is being co-developed by Bristol-Myers-Squibb (New York, NY, USA) and AstraZeneca (Cheshire, UK), and is currently undergoing regulatory review....

An updated systematic review and meta-analysis on the efficacy and tolerability of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes with moderate to severe chronic kidney disease

Directory of Open Access Journals (Sweden)

Devada Singh-Franco

2016-07-01

Full Text Available Objective: This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis. Methods: In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. Results: There were 2261 participants, 49–79 years of age, 49% men and 44% Caucasians. In seven placebo-comparator studies, reduction in hemoglobin A1c at weeks 12–24 was 0.55% (95% confidence interval: −0.68 to −0.43, P < 0.00001. In three sulfonylurea-comparator studies, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c at weeks 52–54 (−0.15% (95% confidence interval: −0.32 to 0.02. In one sitagliptin versus albiglutide study, albiglutide significantly reduced hemoglobin A1c in patients with moderate renal impairment (−0.51%. A similar reduction in hemoglobin A1c was seen with sitagliptin versus vildagliptin (−0.56% vs −0.54%. Compared with placebo or sulfonylurea, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c after 12 and 54 weeks in patients on dialysis. Hypoglycemia was reported by ~30% of patients in both dipeptidyl peptidase-4 inhibitors and placebo groups over 24–52 weeks. While hypoglycemia was more common with a sulfonylurea at 52–54 weeks (risk ratio: 0.46 (95% confidence interval: 0.18 to 1.18, there was significant heterogeneity (I2 = 87%. Limitations included high drop-out rate from most studies and small number of active-comparator studies. Conclusions: Dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease caused a modest reduction in hemoglobin A1c versus placebo, but not when compared with sulfonylureas or albiglutide, or when used in patients on dialysis. Additional active-comparator studies are needed to

Yellow Ducks Overboard! A Lesson in Geography and World Citizenship

Science.gov (United States)

Nagel, Paul; Beauboeuf, Donna

2012-01-01

This lesson was inspired by the book, "10 Little Rubber Ducks" by Eric Carle, which discusses ocean pollution. The book was inspired by an incident in 1992: A shipping container tumbled into the North Pacific Ocean, broke open, and 28,800 little rubber ducks (and other plastic bath toys) were lost at sea. The ducks were manufactured in China, and…

Lessons learned bulletin

International Nuclear Information System (INIS)

1994-05-01

During the past four years, the Department of Energy -- Savannah River Operations Office and the Westinghouse Savannah River Company (WSRC) Environmental Restoration (ER) Program completed various activities ranging from waste site investigations to closure and post closure projects. Critiques for lessons learned regarding project activities are performed at the completion of each project milestone, and this critique interval allows for frequent recognition of lessons learned. In addition to project related lessons learned, ER also performs lessons learned critiques. T'he Savannah River Site (SRS) also obtains lessons learned information from general industry, commercial nuclear industry, naval nuclear programs, and other DOE sites within the complex. Procedures are approved to administer the lessons learned program, and a database is available to catalog applicable lessons learned regarding environmental remediation, restoration, and administrative activities. ER will continue to use this database as a source of information available to SRS personnel

Peptidase-3 (Pep-3), dipeptidase variant in the rat homologous to mouse pep-3 (Dip-1) and human PEP-c.

Science.gov (United States)

Womack, J E; Cramer, D V

1980-10-01

Starch gel electrophoresis and histochemical staining with L-leucyl-L-tyrosine have revealed genetic variation for dipeptidase in Rattus norvegicus. The tissue distribution, substrate specificity, and heterozygous expression as a monmeric protein suggest homology of the variant peptidase to human PEP-C and mouse Pep-3 (Dip-1). We propose Peptidase-3 (Pep-3) as a name for this autosomal locus in the rat. The allele responsible for slower (less anodal) electrophoretic migration is designated Pep-3a and is characteristic of strain ACI/Pit. A faster (more anodal) electrophoretic mobility is the product of the Pep-3b allele in strain F344/Pit. Twenty-five additional inbred strains carry Pep-3a and 16 others carry Pep-3b. Wild rats trapped in Pittsburgh were polymorphic for this locus. Alleles at Pep-3 segregated independently of c (linkage group I), a (linkage group IV), RT2 and Es-1 (linkage group V), h (linkage group VI), and RTI (linkage group VIII).

Lessons Learned from Past and Ongoing Construction Projects

International Nuclear Information System (INIS)

Tabatabai, Omid

2011-01-01

Full text of publication follows: The nuclear industry in the U.S. faced many construction quality and design issues in the 1970's and 1980's. In 1984, the NRC issued NUREG-1055, 'Improving Quality and the Assurance of Quality in the Design and Construction of Nuclear Power Plants,' to document the lessons learned from nuclear power plant (NPP) construction in the U.S. In recent years, several countries have begun either planning for or actually constructing new NPPs. For instance, in the U.S., the nuclear industry has submitted several combined license and design certification applications to the NRC for licensing reviews and approval to build 30+ new NPP units. Latest construction experience from countries that are currently building new NPPs indicate that these countries are dealing with challenges that are similar to those issues that caused major quality assurance problems, delays, or even termination of several projects in U.S. in the 70's and 80's. The U.S. NRC is pro-actively taking measures to improve its regulatory programs as well as construction oversight activities before new NPPs construction begin in the U.S. In late 2007, the U.S. NRC's Office of New Reactors established a construction experience program (ConE) to obtain and evaluate construction and operating experience events and to identify the lessons learned from these events. In March 2009, the NRC published an Office Instruction to provide a process for incorporating the lessons learned and insights from the design, construction, and operation of the international and domestic NPPs into the licensing reviews, inspections, and construction of new reactors in the U.S. Additionally, the ConE program staff developed a Web-enabled database to store, manage, and make construction experience information available to all NRC technical reviewers as well as inspectors. Because this database contains information from other countries' regulators that are considered

[A novel dipeptidyl peptidase IV inhibitors developed through scaffold hopping and drug splicing strategy].

Science.gov (United States)

Wang, Shan-Chun; Zeng, Li-Li; Ding, Yu-Yang; Zeng, Shao-Gao; Song, Hong-Rui; Hu, Wen-Hui; Xie, Hui

2014-01-01

Though all the marketed drugs of dipeptidyl peptidase IV inhibitors are structurally different, their inherent correlation is worthy of further investigation. Herein we rapidly discovered a novel DPP-IV inhibitor 8g (IC50 = 4.9 nmol.L-1) which exhibits as good activity and selectivity as the market drugs through scaffold hopping and drug splicing strategies based on alogliptin and linagliptin. This study demonstrated that the employment of classic medicinal chemistry strategy to the marketed drugs with specific target is an efficient approach to discover novel bioactive molecules.

Glucagon-like peptide receptor agonists and dipeptidyl peptidase-4 inhibitors in the treatment of diabetes: a review of clinical trials

DEFF Research Database (Denmark)

Madsbad, Sten; Krarup, Thure; Deacon, Carolyn F

2008-01-01

-acting glucagon-like peptide-1 receptor agonists liraglutide and exenatide long-acting release reduce haemoglobin A1c by about 1.0-2.0% and have fewer gastrointestinal side-effects. The orally available dipeptidyl peptidase-4 inhibitors, that is sitagliptin and vildagliptin reduce haemoglobin A1c by 0...

Learning from Iraq and Afghanistan: Four Lessons for Building More Effective Coalitions

Directory of Open Access Journals (Sweden)

White Nathan

2016-06-01

Full Text Available Despite many tactical and operational successes by brave military and civilian personnel, post-9/11 operations by U.S. led coalitions in Iraq and Afghanistan did not achieve their intended outcomes. Although many efforts are underway by discrete organizations within coalition countries to identify and learn their own lessons from these conflicts, comparatively less attention is paid to broader lessons for successful coalitions. Given that the U.S. and its allies will most certainly form coalitions in the future for a range of different contingency scenarios, these lessons are equally deserving of close examination. This article identifies four interrelated lessons from Iraq and Afghanistan that can be utilized to inform more effective coalition development and employment.

Lessons from Zhu Xi’s Views on Inquiry and Learning for Contemporary Advanced Humanities Education and Research

Directory of Open Access Journals (Sweden)

Kirill Ole THOMPSON

2017-06-01

Full Text Available We are bearing witness to the rapid rise of a brave new world of education as flashy websites and interactive software replace individual study and classroom lectures. The expansion of college lecture halls has been stretched thin with video lessons and distance learning, and the siren call of massive open online courses (MOOCs by star Ivy League professors renders the traditional classroom barren in the eyes of savvy students who have the system pegged. Several questions arise in this context. Can the students of today receive a college education in the full sense? Does learning still have the same quality without close interactions with teachers and classmates in small to medium sized classrooms? Does research hold the same significance today when much of the work is done and so much information supplied by computers? What lessons do Zhu Xi’s teachings on inquiry and learning have for this educational world of e-texts and cyber-lessons? While not a Luddite tract, the present study raises questions and concerns about the goals and conduct of higher education today which, as Heisenberg avers, should not only aim at transmitting knowledge understood in set ways, but also at inculcating new ways of thinking and understanding. A college education, as Zhu Xi holds for “advanced learning”, is as much about cultivating a thoughtful, responsible person as producing a professional expert. Such education should include cultivating a student’s sensitivity, logic, and judgment, as well as knowledge about humanity, society, and the world. It is often forgotten that such sensitivity, logic, knowledge, and commitment not only make the student more thoughtful and responsible, in short more self-conscious, but also give her additional perspectives and enhance her professional expertise.

Improved heterologous protein production by a tripeptidyl peptidase gene (AosedD) disruptant of the filamentous fungus Aspergillus oryzae.

Science.gov (United States)

Zhu, Lin; Nemoto, Takeshi; Yoon, Jaewoo; Maruyama, Jun-ichi; Kitamoto, Katsuhiko

2012-01-01

Proteolytic degradation is one of the serious bottlenecks limiting the yields of heterologous protein production by Aspergillus oryzae. In this study, we selected a tripeptidyl peptidase gene AosedD (AO090166000084) as a candidate potentially degrading the heterologous protein, and performed localization analysis of the fusion protein AoSedD-EGFP in A. oryzae. As a result, the AoSedD-EGFP was observed in the septa and cell walls as well as in the culture medium, suggesting that AoSedD is a secretory enzyme. An AosedD disruptant was constructed to investigate an effect of AoSedD on the production level of heterologous proteins and protease activity. Both of the total protease and tripeptidyl peptidase activities in the culture medium of the AosedD disruptant were decreased as compared to those of the control strain. The maximum yields of recombinant bovine chymosin (CHY) and human lysozyme (HLY) produced by the AosedD disruptants showed approximately 2.9- and 1.7-fold increases, respectively, as compared to their control strains. These results suggest that AoSedD is one of the major proteases involved in the proteolytic degradation of recombinant proteins in A. oryzae.

Breathing Life into Engineering: A Lesson Study Life Science Lesson

Science.gov (United States)

Lawrence, Maria; Yang, Li-Ling; Briggs, May; Hession, Alicia; Koussa, Anita; Wagoner, Lisa

2016-01-01

A fifth grade life science lesson was implemented through a lesson study approach in two fifth grade classrooms. The research lesson was designed by a team of four elementary school teachers with the goal of emphasizing engineering practices consistent with the "Next Generation Science Standards" (NGSS) (Achieve Inc. 2013). The fifth…

NCBI nr-aa BLAST: CBRC-OANA-01-2119 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-OANA-01-2119 ref|ZP_01307403.1| Secreted/periplasmic Zn-dependent peptidase, insulina...se-like protein [Oceanobacter sp. RED65] gb|EAT11978.1| Secreted/periplasmic Zn-dependent peptidase, insulinase-like protein [Oceanobacter sp. RED65] ZP_01307403.1 0.40 28% ...

Loss of mitochondrial peptidase Clpp leads to infertility, hearing loss plus growth retardation via accumulation of CLPX, mtDNA and inflammatory factors

NARCIS (Netherlands)

Gispert, S.; Parganlija, D.; Klinkenberg, M.; Drose, S.; Wittig, I.; Mittelbronn, M.; Grzmil, P.; Koob, S.; Hamann, A.; Walter, M.; Buchel, F.; Adler, T.; Angelis, M. Hrabe de; Busch, D.H.; Zell, A.; Reichert, A.S.; Brandt, U.; Osiewacz, H.D.; Jendrach, M.; Auburger, G.

2013-01-01

The caseinolytic peptidase P (CLPP) is conserved from bacteria to humans. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder together with the chaperone CLPX. In spite of a known relevance for the mitochondrial unfolded protein response, its substrates

[Phylogenetic relationships among the genera of Taxodiaceae and Cupressaceae from 28S rDNA sequences].

Science.gov (United States)

Li, Chun-Xiang; Yang, Qun

2003-03-01

DNA sequences from 28S rDNA were used to assess relationships between and within traditional Taxodiaceae and Cupressaceae s.s. The MP tree and NJ tree generally are similar to one another. The results show that Taxodiaceae and Cupressaceae s.s. form a monophyletic conifer lineage excluding Sciadopitys. In the Taxodiaceae-Cupressaceae s.s. monophyletic group, the Taxodiaceae is paraphyletic. Taxodium, Glyptostrobus and Cryptomeria forming a clade(Taxodioideae), in which Glyptostrobus and Taxodium are closely related and sister to Cryptomeria; Sequoia, Sequoiadendron and Metasequoia are closely related to each other, forming another clade (Sequoioideae), in which Sequoia and Sequoiadendron are closely related and sister to Metasequoia; the seven genera of Cupressaceae s.s. are found to be closely related to form a monophyletic lineage (Cupressoideae). These results are basically similar to analyses from chloroplast gene data. But the relationships among Taiwania, Sequoioideae, Taxodioideae, and Cupressoideae remain unclear because of the slow evolution rate of 28S rDNA, which might best be answered by sequencing more rapidly evolving nuclear genes.

DCDM1: Lessons Learned from the World's Most Energy Efficient Data Center

Energy Technology Data Exchange (ETDEWEB)

Sickinger, David E [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Van Geet, Otto D [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Carter, Thomas [Johnson Controls

2018-05-03

This presentation discusses the holistic approach to design the world's most energy-efficient data center, which is located at the U.S. Department of Energy National Renewable Energy Laboratory (NREL). This high-performance computing (HPC) data center has achieved a trailing twelve-month average power usage effectiveness (PUE) of 1.04 and features a chiller-less design, component-level warm-water liquid cooling, and waste heat capture and reuse. We provide details of the demonstrated PUE and energy reuse effectiveness (ERE) and lessons learned during four years of production operation. Recent efforts to dramatically reduce the water footprint will also be discussed. Johnson Controls partnered with NREL and Sandia National Laboratories to deploy a thermosyphon cooler (TSC) as a test bed at NREL's HPC data center that resulted in a 50% reduction in water usage during the first year of operation. The Thermosyphon Cooler Hybrid System (TCHS) integrates the control of a dry heat rejection device with an open cooling tower.

Bovine pancreatic trypsin inhibitor immobilized onto sepharose as a new strategy to purify a thermostable alkaline peptidase from cobia (Rachycentron canadum) processing waste.

Science.gov (United States)

França, Renata Cristina da Penha; Assis, Caio Rodrigo Dias; Santos, Juliana Ferreira; Torquato, Ricardo José Soares; Tanaka, Aparecida Sadae; Hirata, Izaura Yoshico; Assis, Diego Magno; Juliano, Maria Aparecida; Cavalli, Ronaldo Olivera; Carvalho, Luiz Bezerra de; Bezerra, Ranilson Souza

2016-10-15

A thermostable alkaline peptidase was purified from the processing waste of cobia (Rachycentron canadum) using bovine pancreatic trypsin inhibitor (BPTI) immobilized onto Sepharose. The purified enzyme had an apparent molecular mass of 24kDa by both sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. Its optimal temperature and pH were 50°C and 8.5, respectively. The enzyme was thermostable until 55°C and its activity was strongly inhibited by the classic trypsin inhibitors N-ρ-tosyl-l-lysine chloromethyl ketone (TLCK) and benzamidine. BPTI column allowed at least 15 assays without loss of efficacy. The purified enzyme was identified as a trypsin and the N-terminal amino acid sequence of this trypsin was IVGGYECTPHSQAHQVSLNSGYHFC, which was highly homologous to trypsin from cold water fish species. Using Nα-benzoyl-dl-arginine ρ-nitroanilide hydrochloride (BApNA) as substrate, the apparent km value of the purified trypsin was 0.38mM, kcat value was 3.14s(-1), and kcat/km was 8.26s(-1)mM(-1). The catalytic proficiency of the purified enzyme was 2.75×10(12)M(-1) showing higher affinity for the substrate at the transition state than other fish trypsin. The activation energy (AE) of the BApNA hydrolysis catalyzed by this enzyme was estimated to be 11.93kcalmol(-1) while the resulting rate enhancement of this reaction was found to be approximately in a range from 10(9) to 10(10)-fold evidencing its efficiency in comparison to other trypsin. This new purification strategy showed to be appropriate to obtain an alkaline peptidase from cobia processing waste with high purification degree. According with N-terminal homology and kinetic parameters, R. canadum trypsin may gathers desirable properties of psychrophilic and thermostable enzymes. Copyright © 2016 Elsevier B.V. All rights reserved.

Examining the Effect of Lesson Study on Prospective Primary Teachers’ Knowledge of Lesson Planning [Ders İmecesinin Sınıf Öğretmeni Adaylarının Matematik Dersini Planlama Bilgilerine Etkisinin İncelenmesi

Directory of Open Access Journals (Sweden)

Müjgan Baki

2015-08-01

Full Text Available This article reflects a special part of a research conducted to examine the effect of lesson study on prospective classroom teachers’ mathematical pedagogical content knowledge (MPCK. In this article, the special part consists of prospective teachers’ knowledge of lesson planning including a mastery of planning an affective lesson taking into account student’s current knowledge, understanding and difficulties within mathematics. Therefore, the research question is how lesson study practices affect prospective classroom teachers’ knowledge of lesson planning as a sub component of MPCK. The research is conducted with 12 prospective classroom teachers, six of them have already assisted to lesson study and the others have not. Data collection tools consist of video records, class observations, field notes, interviews and lesson plans prepared and used by prospective teachers participated in lesson study. Findings indicated that the prospective classroom teachers who participated in lesson study improved their knowledge in terms of planning an affective lesson taking student’s current knowledge and understanding into consideration. They appeared to be aware of selecting and ordering appropriate activities related to the actual objectives of the mathematical topics. They also appeared to be better in lesson organization and lesson presentation comparing to the other group of prospective teachers who did not participated in lesson study. [Bu makale, Öğretmenlik Uygulaması derslerinde uygulanan ders imecesi modelinin sınıf öğretmeni adaylarının alanı öğretme bilgilerine etkisini izlemek amacıyla yapılan bir araştırmanın bir bölümünü yansıtmaktadır. Makalede alanı öğretme bilgisinin alt bileşenlerinden olan öğrenme-öğretme sürecini planlama boyutuna odaklanılarak ‘Ders imecesi uygulaması, sınıf öğretmeni adaylarının öğrenme öğretme sürecini planlama bilgilerinin gelişimini nasıl etkilemektedir

Dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes: A comparative review

DEFF Research Database (Denmark)

Deacon, Carolyn F.

2011-01-01

The dipeptidyl peptidase (DPP)-4 inhibitors are a new class of antihyperglycaemic agents which were developed for the treatment of type 2 diabetes by rational drug design, based on an understanding of the underlying mechanism of action and knowledge of the structure of the target enzyme. Although...... they differ in terms of their chemistry, they are all small molecules which are orally available. There are some differences between them in terms of their absorption, distribution, metabolism and elimination, as well as in their potency and duration of action, but their efficacy, both in terms of inhibiting...

28 CFR 0.10 - Attorney General's Advisory Committee of U.S. Attorneys.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Attorney General's Advisory Committee of... DEPARTMENT OF JUSTICE Office of the Attorney General § 0.10 Attorney General's Advisory Committee of U.S. Attorneys. (a) The Attorney General's Advisory Committee of United States Attorneys shall consist of an...

The Knitting Lesson.

Science.gov (United States)

Smith, Pamela

1987-01-01

Based on Jean-Francois Millet's 1869 painting, "The Knitting Lesson," this lesson's goal is to introduce students in grades seven through nine to genre (everyday life) painting the nineteenth century. The lesson is also designed to show that some aspects of genre may be timeless. (BSR)

Experiment data report for semiscale Mod-1 test S-28-2 (steam generator tube rupture test)

International Nuclear Information System (INIS)

Patton, M.L.; Sackett, K.E.

1977-10-01

Recorded test data are presented for Test S-28-2 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-2 was conducted from initial conditions of 15 936 kPa and 558 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. For Test S-28-2, accumulator injection into the intact loop hot leg was provided to simulate simulate the rupture of six steam generator tubes

Integrating UNESCO ICT-Based Instructional Materials in Chemistry Lessons

Directory of Open Access Journals (Sweden)

CHARLIE P. NACARIO

2014-08-01

Full Text Available This study determined the effectiveness of the lessons in Chemistry integrating UNESCO ICT-based instructional material on the achievement of Chemistry students at Central Bicol State University of Agriculture. It aimed to identify lessons that may be developed integrating UNESCO ICT-based instructional materials, determine the effect of the developed lessons using the material on: conceptual understanding; science process skills; and attitude towards chemistry and gather insights from the experiences of the students and teacher. The study used the single group pretest and posttest experimental design. Descriptive, quantitative and qualitative techniques were also utilized. Quantitative data were taken from the pretest-posttest results on the Test on Conceptual Understanding, Science Process Skills and Chemistry Attitudinaire. Qualitative data were drawn from the experts’ assessment of the developed lessons and research instruments, and the insights of students and teacher. The developed lessons integrating UNESCO ICT-based instructional materials were Atomic Model and Structure, Periodic Table of Elements, Chemical Bonding, and Balancing Chemical Equation. These lessons increased the conceptual understanding of the students by topic and skill from very low mastery to average mastery level. The students have slightly improved along the different science process skills. After teaching the lessons, the students’ attitude also improved. The students became more motivated and interested in Chemistry and the lessons were student centered and entailed teacher’s competence and flexibility in computer use.

Solid-State Lighting: Early Lessons Learned on the Way to Market

Energy Technology Data Exchange (ETDEWEB)

Sandahl, Linda J.; Cort, Katherine A.; Gordon, Kelly L.

2013-12-31

The purpose of this report is to document early challenges and lessons learned in the solid-state lighting (SSL) market development as part of the DOE’s SSL Program efforts to continually evaluate market progress in this area. This report summarizes early actions taken by DOE and others to avoid potential problems anticipated based on lessons learned from the market introduction of compact fluorescent lamps and identifies issues, challenges, and new lessons that have been learned in the early stages of the SSL market introduction. This study identifies and characterizes12 key lessons that have been distilled from DOE SSL program results.

The history of a lesson

DEFF Research Database (Denmark)

Rasmussen, Mikkel Vedby

2003-01-01

and emphasises the need to study the history of lessons rather than the lessons of history. This approach shows that Munich is the end point of a constitutive history that begins in the failure of the Versailles treaty to create a durable European order following the First World War. The Munich lesson is thus......The article investigates the concept of lessons in IR. By means of a constructivist critique of the 'lessons literature', the article analyses one of the most important of IR lessons: that of Munich. Examining how the Munich lesson came about, the article shows the praxeological nature of lessons...... one element of the lesson of Versailles, which is a praxeology that defines how the West is to make peace, and against whom peace must be defended. The lesson of Versailles has been, at least in part, constitutive of the outbreak of the Cold War, and it continues to define the Western conception...

Solid-State Lighting. Early Lessons Learned on the Way to Market

Energy Technology Data Exchange (ETDEWEB)

Sandahl, L. J.; Cort, K. A.; Gordon, K. L.

2014-01-01

Analysis of issues and lessons learned during the early stages of solid-state lighting market introduction in the U.S., which also summarizes early actions taken to avoid potential problems anticipated based on lessons learned from the market introduction of compact fluorescent lamps.

Recruitment Strategies and Lessons Learned from the Children’s Healthy Living Program Prevalence Survey

Directory of Open Access Journals (Sweden)

Julianne M. Power

2016-03-01

Full Text Available The US Affiliated Pacific region’s childhood obesity prevalence has reached epidemic proportions. To guide program and policy development, a multi-site study was initiated, in collaboration with partners from across the region, to gather comprehensive information on the regional childhood obesity prevalence. The environmental and cultural diversity of the region presented challenges to recruiting for and implementing a shared community-based, public health research program. This paper presents the strategies used to recruit families with young children (n = 5775 for children 2 – 8 years old for obesity-related measurement across eleven jurisdictions in the US Affiliated Pacific Region. Data were generated by site teams that provided summaries of their recruitment strategies and lessons learned. Conducting this large multi-site prevalence study required considerable coordination, time and flexibility. In every location, local staff knowledgeable of the community was hired to lead recruitment, and participant compensation reflected jurisdictional appropriateness (e.g., gift cards, vouchers, or cash. Although recruitment approaches were site-specific, they were predominantly school-based or a combination of school- and community-based. Lessons learned included the importance of organization buy-in; communication, and advance planning; local travel and site peculiarities; and flexibility. Future monitoring of childhood obesity prevalence in the region should consider ways to integrate measurement activities into existing organizational infrastructures for sustainability and cost-effectiveness, while meeting programmatic (e.g. study goals.

Lesson Learning at JPL

Science.gov (United States)

Oberhettinger, David

2011-01-01

A lessons learned system is a hallmark of a mature engineering organization A formal lessons learned process can help assure that valuable lessons get written and published, that they are well-written, and that the essential information is "infused" into institutional practice. Requires high-level institutional commitment, and everyone's participation in gathering, disseminating, and using the lessons

Review of the generic aging lessons learned (GALL) report for U.S. NPPs

International Nuclear Information System (INIS)

Gong Yi; Dou Yikang

2014-01-01

Generic aging lessons learned (GALL) report is a technical basis document issued by U.S. nuclear regulatory commission (NRC) for guiding the review of license renewal application (LRA) of its domestic nuclear power plants (NPPs). By form of tabulations, GALL report addresses the correlation among materials, environments, aging effects/mechanisms, and aging management programs (AMPs) from the level of specific structures and/or components. Based on literature investigation and analysis, the essential information of GALL report in the aspects of background, development history, content framework, and application was reviewed in this paper, which should be the first time in China and would have reference value for establishment of both the AMPs and the nuclear safety regulations of extending the lifetime of its NPPs. (authors)

Stimulation of Interleukin-10 Production by Acidic β-Lactoglobulin-Derived Peptides Hydrolyzed with Lactobacillus paracasei NCC2461 Peptidases

OpenAIRE

Prioult, Guénolée; Pecquet, Sophie; Fliss, Ismail

2004-01-01

We have previously demonstrated that Lactobacillus paracasei NCC2461 may help to prevent cow's milk allergy in mice by inducing oral tolerance to β-lactoglobulin (BLG). To investigate the mechanisms involved in this beneficial effect, we examined the possibility that L. paracasei induces tolerance by hydrolyzing BLG-derived peptides and liberating peptides that stimulate interleukin-10 (IL-10) production. L. paracasei peptidases have been shown to hydrolyze tryptic-chymotryptic peptides from ...

Finnish Students’ Engagement in Science Lessons

Directory of Open Access Journals (Sweden)

Janna Linnansaari

2015-05-01

Full Text Available The decreasing number of students who are engaged in science learning has been recognised as a problem. The pre-conditions of engagement and actual engagement were examined using a novel research method to obtain detailed information on Finnish students’ engagement in different situations and to gain a better understanding of this phenomenon. The study’s participants consisted of 68 students (31 girls, 37 boys from 9th grade and 67 students (46 girls, 21 boys from 1st grade in upper secondary school. The research aimed to answer the following question: How does Finnish students’ engagement occur in exact and life science lessons? Participants received smartphones equipped with a smartphone application that included an experience sampling method questionnaire. The smartphones were programmed to emit a signal during every science lesson and otherwise randomly during the day (from 8 am to 8 pm. The results reveal that situation and grade had significant effects on students’ pre-conditions of engagement and actual engagement. Our results also show that girls had the highest interest in life science lessons and boys in exact science lessons.

DSCOVR Contamination Lessons Learned

Science.gov (United States)

Graziani, Larissa

2015-01-01

The Triana observatory was built at NASA GSFC in the late 1990's, then placed into storage. After approximately ten years it was removed from storage and repurposed as the Deep Space Climate Observatory (DSCOVR). This presentation outlines the contamination control program lessons learned during the integration, test and launch of DSCOVR.

Sequencing and characterization of asclepain f: the first cysteine peptidase cDNA cloned and expressed from Asclepias fruticosa latex.

Science.gov (United States)

Trejo, Sebastián A; López, Laura M I; Caffini, Néstor O; Natalucci, Claudia L; Canals, Francesc; Avilés, Francesc X

2009-07-01

Asclepain f is a papain-like protease previously isolated and characterized from latex of Asclepias fruticosa. This enzyme is a member of the C1 family of cysteine proteases that are synthesized as preproenzymes. The enzyme belongs to the alpha + beta class of proteins, with two disulfide bridges (Cys22-Cys63 and Cys56-Cys95) in the alpha domain, and another one (Cys150-Cys201) in the beta domain, as was determined by molecular modeling. A full-length 1,152 bp cDNA was cloned by RT-RACE-PCR from latex mRNA. The sequence was predicted as an open reading frame of 340 amino acid residues, of which 16 residues belong to the signal peptide, 113 to the propeptide and 211 to the mature enzyme. The full-length cDNA was ligated to pPICZalpha vector and expressed in Pichia pastoris. Recombinant asclepain f showed endopeptidase activity on pGlu-Phe-Leu-p-nitroanilide and was identified by PMF-MALDI-TOF MS. Asclepain f is the first peptidase cloned and expressed from mRNA isolated from plant latex, confirming the presence of the preprocysteine peptidase in the latex.

Development of short Indonesian lesson plan to improve teacher performance

Science.gov (United States)

Yulianto, B.; Kamidjan; Ahmadi, A.; Asteria, P. V.

2018-01-01

The developmental research was motivated by the results of preliminary study through interviews, which revealed almost all of the teachers did not create lesson plan themselves. As a result of this load, the performance of the real learning in the classroom becomes inadequate. Moreover, when lesson plan was not made by teachers themselves, the learning process becomes ineffective. Therefore, this study designed to develop a prototype of the short lesson plan, in particular, Indonesian language teaching, and to investigate its effectiveness. The participants in the study were teachers who were trained through lesson study group to design short model’s lesson plan. Questionnaires and open-ended questions were used, and the quantitative and qualitative data obtained were analyzed accordingly. The analysis of the quantitative data, aided with SPSS, were frequency, percentage, and means, whereas the qualitative data were analyzed descriptively. The results showed that the teachers liked the model, and they were willing to design their own lesson plan. The observation data revealed that the classroom learning process became more interactive, and classroom atmosphere was more engaging and natural because the teachers did not stick to the lesson plan made by other teachers.

Japanese lesson study in mathematics its impact, diversity and potential for educational improvement

CERN Document Server

Isoda, Masami; Stephens, Max

2007-01-01

In Before It''s Too Late: A Report to the Nation from the National Commission on Mathematics and Science Teaching for the 21st Century (2000) in the US, the authors quote from James Stigler''s conclusions from various videotape research studies of mathematics teaching: "The key to long-term improvement [in teaching] is to figure out how to generate, accumulate, and share professional knowledge". Japanese Lesson Study has proved to be one successful means. This book supports the growing movement of lesson study to improve the quality of mathematics education from the original viewpoints of Japanese educators who have been engaging in lesson study in mathematics for professional development and curriculum implementation. This book also illustrates several projects related to lesson study in other countries.

Charismatic Leaders: A Lesson Plan.

Science.gov (United States)

Johns, Robert W.

1983-01-01

Focusing upon Franklin D. Roosevelt and Adolf Hitler, these lessons for high school students in U.S. or world history courses deal with what charismatic leadership is, what circumstances and personality factors generate charismatic movements, and the role, results, and dangers of charismatic leadership. (RM)

“I Felt Like My Life Had Been Given to Me to Start Over”: Alice Kaplan’s Language Memoir, French Lessons

Directory of Open Access Journals (Sweden)

Eleonora Rao

2016-06-01

Full Text Available Alice Kaplan’s memoir French Lessons (1993 is a story that deals as much with the issue of language learning as with that of cultural belonging(s. This “language memoir,” as it is typical of this sub-genre, is an intimate tale of the transition between languages and cultures. French Lessons recounts her evolving relationship with French language and culture in various phases of her life: starting from childhood, continuing through her graduate student years at Yale and finally as professor of French at Duke. Soon, however, in this unconventional Bildung, the second language turns out to be a verbal safe-house, an instant refuge when her first language and culture happen to be too uncomfortable. Ultimately, French provides a psychic space and a hiding place. Ultimately, however, as Derrida has shown, we are alienated from both the first and the second; we find ourselves to be more comfortable in one than in the other. This essay will analyze such processes with special attention to the part played by the body in Kaplan’s building as a student and eventually as a teacher. The analysis will be linked with the text’s peculiar narrative style: fast-paced, with simple, concise sentences, nevertheless extremely effective and moving.

Contribution of plasmid-encoded peptidase S8 (PrtP) to adhesion and transit in the gut of Lactococcus lactis IBB477 strain.

Science.gov (United States)

Radziwill-Bienkowska, Joanna Maria; Robert, Véronique; Drabot, Karolina; Chain, Florian; Cherbuy, Claire; Langella, Philippe; Thomas, Muriel; Bardowski, Jacek Karol; Mercier-Bonin, Muriel; Kowalczyk, Magdalena

2017-07-01

The ability of Lactococcus lactis to adhere to the intestinal mucosa can potentially prolong the contact with the host, and therefore favour its persistence in the gut. In the present study, the contribution of plasmid-encoded factors to the adhesive and transit properties of the L. lactis subsp. cremoris IBB477 strain was investigated. Plasmid-cured derivatives as well as deletion mutants were obtained and analysed. Adhesion tests were performed using non-coated polystyrene plates, plates coated with mucin or fibronectin and mucus-secreting HT29-MTX intestinal epithelial cells. The results indicate that two plasmids, pIBB477a and b, are involved in adhesion of the IBB477 strain. One of the genes localised on plasmid pIBB477b (AJ89_14230), which encodes cell wall-associated peptidase S8 (PrtP), mediates adhesion of the IBB477 strain to bare, mucin- and fibronectin-coated polystyrene, as well as to HT29-MTX cells. Interactions between bacteria and mucus secreted by HT29-MTX cells were further investigated by fluorescent staining and confocal microscopy. Confocal images showed that IBB477 forms dense clusters embedded in secreted mucus. Finally, the ability of IBB477 strain and its ΔprtP deletion mutant to colonise the gastrointestinal tract of conventional C57Bl/6 mice was determined. Both strains were present in the gut for up to 72 h. In summary, adhesion and persistence of IBB477 were analysed by in vitro and in vivo approaches, respectively. Our studies revealed that plasmidic genes encoding cell surface proteins are more involved in the adhesion of IBB477 strain than in the ability to confer a selective advantage in the gut.

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

International Nuclear Information System (INIS)

Baldwin, Michael; Russo, Crystal; Li, Xuerong; Chishti, Athar H.

2014-01-01

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

Energy Technology Data Exchange (ETDEWEB)

Baldwin, Michael; Russo, Crystal; Li, Xuerong [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Chishti, Athar H., E-mail: athar.chishti@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Sackler School of Graduate Biomedical Sciences, Programs in Physiology, Pharmacology, and Microbiology, Tufts University School of Medicine, Boston, MA 02111 (United States)

2014-08-08

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.

Lessons learned from case studies of inhalation exposures of workers to radioactive aerosols

Energy Technology Data Exchange (ETDEWEB)

Hoover, M.D.; Fencl, A.F.; Newton, G.J. [and others

1995-12-01

Various Department of Energy requirements, rules, and orders mandate that lessons learned be identified, evaluated, shared, and incorporated into current practices. The recently issued, nonmandatory DOE standard for Development of DOE Lessons Learned Program states that a DOE-wide lessons learned program will {open_quotes}help to prevent recurrences of negative experiences, highlight best practices, and spotlight innovative ways to solve problems or perform work more safely, efficiently, and cost effectively.{close_quotes} Additional information about the lessons learned program is contained in the recently issued DOE handbook on Implementing U.S. Department of Energy Lessons Learned Programs and in October 1995 DOE SAfety Notice on Lessons Learned Programs. This report summarizes work in progress at ITRI to identify lessons learned for worker exposures to radioactive aerosols, and describes how this work will be incorporated into the DOE lessons learned program, including a new technical guide for measuring, modeling, and mitigating airborne radioactive particles. Follow-on work is focusing on preparation of {open_quotes}lessons learned{close_quotes} training materials for facility designers, managers, health protection professionals, line supervisors, and workers.

Lessons learned from case studies of inhalation exposures of workers to radioactive aerosols

International Nuclear Information System (INIS)

Hoover, M.D.; Fencl, A.F.; Newton, G.J.

1995-01-01

Various Department of Energy requirements, rules, and orders mandate that lessons learned be identified, evaluated, shared, and incorporated into current practices. The recently issued, nonmandatory DOE standard for Development of DOE Lessons Learned Program states that a DOE-wide lessons learned program will open-quotes help to prevent recurrences of negative experiences, highlight best practices, and spotlight innovative ways to solve problems or perform work more safely, efficiently, and cost effectively.close quotes Additional information about the lessons learned program is contained in the recently issued DOE handbook on Implementing U.S. Department of Energy Lessons Learned Programs and in October 1995 DOE SAfety Notice on Lessons Learned Programs. This report summarizes work in progress at ITRI to identify lessons learned for worker exposures to radioactive aerosols, and describes how this work will be incorporated into the DOE lessons learned program, including a new technical guide for measuring, modeling, and mitigating airborne radioactive particles. Follow-on work is focusing on preparation of open-quotes lessons learnedclose quotes training materials for facility designers, managers, health protection professionals, line supervisors, and workers

Optical Waveform Sampling and Error-Free Demultiplexing of 1.28 Tb/s Serial Data in a Nanoengineered Silicon Waveguide

DEFF Research Database (Denmark)

Ji, Hua; Pu, Minhao; Hu, Hao

2011-01-01

This paper presents the experimental demonstrations of using a pure nanoengineered silicon waveguide for 1.28 Tb/s serial data optical waveform sampling and 1.28 Tb/s–10 Gb/s error free demultiplexing. The 330-fs pulses are resolved in each 780-fs time slot in waveform sampling. Error...

The Nonglycemic Actions of Dipeptidyl Peptidase-4 Inhibitors

Directory of Open Access Journals (Sweden)

Na-Hyung Kim

2014-01-01

Full Text Available A cell surface serine protease, dipeptidyl peptidase 4 (DPP-4, cleaves dipeptide from peptides containing proline or alanine in the N-terminal penultimate position. Two important incretin hormones, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic peptide (GIP, enhance meal-stimulated insulin secretion from pancreatic β-cells, but are inactivated by DPP-4. Diabetes and hyperglycemia increase the DPP-4 protein level and enzymatic activity in blood and tissues. In addition, multiple other functions of DPP-4 suggest that DPP-4 inhibitor, a new class of antidiabetic agents, may have pleiotropic effects. Studies have shown that DPP-4 itself is involved in the inflammatory signaling pathway, the stimulation of vascular smooth cell proliferation, and the stimulation of oxidative stress in various cells. DPP-4 inhibitor ameliorates these pathophysiologic processes and has been shown to have cardiovascular protective effects in both in vitro and in vivo experiments. However, in recent randomized clinical trials, DPP-4 inhibitor therapy in high risk patients with type 2 diabetes did not show cardiovascular protective effects. Some concerns on the actions of DPP-4 inhibitor include sympathetic activation and neuropeptide Y-mediated vascular responses. Further studies are required to fully characterize the cardiovascular effects of DPP-4 inhibitor.

Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Deacon, Carolyn F; Holst, Jens Juul

2013-01-01

INTRODUCTION: Dipeptidyl peptidase (DPP)-4 inhibitors belong to one class of drugs that have been approved for treatment of type 2 diabetes (T2D) based on the glucose-lowering actions of the gastrointestinal hormone glucagon-like peptide (GLP)-1. Several different compounds are now available...... of the different DPP-4 inhibitors, all are small orally active compounds with broadly similar HbA1c-lowering efficacy. They improve glycaemic control in T2D, without increasing the risk of hypoglycaemia or causing weight gain. They can be used as monotherapy or in combination with other anti-diabetic therapies......, and although their mechanism of action (inhibition of the catalytic activity of DPP-4) is the same, there are fundamental differences between them. AREAS COVERED: The authors discuss the differences between different DPP-4 inhibitors and review their therapeutic efficacy and key safety data. The literature...

Computer Directed Training System (CDTS), User’s Manual

Science.gov (United States)

1983-07-01

lessons, together with an estimate of the time required for completion. a. BSCOl0. This lesson in BASIC ( Beginners All Purpose Symbolic Instruction Code...A2-8 FIGURESj Figure A2-1. Training Systems Manager and Training Monitors Responsibility Flowchart ...training at the site. Therefore, the TSM must be knowledgeable in the various tasks required. Figure A2-1 illustrates the position in the flowchart . These

Hibiscus sabdariffa polyphenols alleviate insulin resistance and renal epithelial to mesenchymal transition: a novel action mechanism mediated by type 4 dipeptidyl peptidase.

Science.gov (United States)

Peng, Chiung-Huei; Yang, Yi-Sun; Chan, Kuei-Chuan; Wang, Chau-Jong; Chen, Mu-Lin; Huang, Chien-Ning

2014-10-08

The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE. In high glucose-stimulated tubular cells, HPE, like linagliptin, inhibited DPP-4 activation, thereby regulating vimentin (EMT marker) and IRS-1 (S307). IRS-1 knockdown revealed its essential role in mediating downstream EMT. In type 2 diabetic rats, pIRS-1 (S307) abundantly surrounds the tubular region, with increased vimentin in kidney. Both the expressions were reduced by HPE. In conclusion, HPE exerts effects similar to those of linagliptin, which improves insulin resistance and EMT, and could be an adjuvant to prevent diabetic nephropathy.

EBT-S 28-GHz, 200-kW, CW, mixed-mode, quasi-optical plasma heating system

International Nuclear Information System (INIS)

White, T.L.; Kimrey, H.D.; Bigelow, T.S.; Bates, D.D.; Eason, H.O.

1984-07-01

The ELMO Bumpy Torus-Scale (EBT-S) 28-GHz, 200-kW, cw, plasma heating system consists of a gyrotron oscillator, an oversized waveguide two-bend transmission system, and a quasi-optical mixed-mode microwave distribution manifold that feeds microwave power to the 24 plasma loads of the EBT-S fusion experiment. Balancing power to the 24 loads of the EBT-S fusion experiment. Balancing power to the 24 loads was achieved by adjusting the areas at 24 coupling irises. System performance is easily measured using system calorimetry. The distribution manifold mixed-mode power transmission, reflection, and loss coefficients are 89%, 6%, and 5%, respectively. The overall system efficiency (plasma power/gyrotron power) is 80%, but with some modifications to the distribution manifold we believe the ultimate efficiency can approach 90%. The system reliability is outstanding with a world's record 1 x 10 5 kW h of 28-GHz energy delivered to the EBT-S device with well over 1 x 10 3 operating hours

Lessons learned from the Three Mile Island Unit 2 Advisory Panel

International Nuclear Information System (INIS)

Lach, D.; Bolton, P.; Durbin, N.; Harty, R.

1994-08-01

In response to public concern about the cleanup of the Three Mile Island, Unit 2 (TMI-2) facility after an accident on March 28, 1979 involving a loss of reactor coolant and subsequent damage to the reactor fuel, twelve citizens were asked to serve on an independent Advisory Panel to consult with the Nuclear Regulatory Commission (NRC) on the decontamination and cleanup of the facility. The panel met 78 times over a period of thirteen years, holding public meetings in the vicinity of TMI-2 and meeting regularly with NRC Commissioners in Washington, DC. This report describes the results of a project designed to identify and describe the lessons learned from the Advisory Panel and place those lessons in the context of what we generally know about citizen advisory groups. A summary of the empirical literature on citizen advisory panels is followed by a brief history of the TMI-2 Advisory Panel. The body of the report contains the analysis of the lessons learned, preliminary conclusions about the effectiveness of the Panel, and implications for the NRC in the use of advisory panels. Data for the report include meeting transcripts and interviews with past and present Panel participants

Neurotensin analogs [D-TYR11] and [D-PHE11]neurotensin resist degradation by brain peptidases in vitro and in vivo

International Nuclear Information System (INIS)

Checler, F.; Vincent, J.P.; Kitabgi, P.

1983-01-01

The present study was designed to compare the susceptibility of neurotensin (NT), [ 3 H]NT, [D-Tyr11]NT and [D-Phe11]NT to degradation by 1) rat brain synaptic membranes in vitro and 2) after i.c.v. administration in the rat in vivo. Degradation was assessed by purifying the peptides using reverse phase high-performance liquid chromatography and by measuring the amount of radioactive or absorbing (OD 230) material under each peptide peak. In contrast to NT, [D-Tyr11]NT and [D-Phe11]NT were resistant to degradation by brain synaptic peptidases in vitro. Furthermore, NT was rapidly metabolized in brain tissues after i.c.v. administration, whereas [D-Tyr11]NT was metabolically stable. The present data confirm the central role of NT residue Tyr11 in the mechanisms of NT inactivation by brain synaptic peptidases. They account for the higher in vivo potency of [D-Tyr11]NT as compared with its in vitro potency. Finally, they explain, at least in part, the need to administer large doses of NT in the brain in order to observe neurobehavioral and neuropharmacological effects

Mycoplasma hyopneumoniae type I signal peptidase: expression and evaluation of its diagnostic potential.

Science.gov (United States)

Moitinho-Silva, Lucas; Heineck, Bianca L; Reolon, Luciano A; Paes, Jéssica A; Klein, Cátia S; Rebelatto, Raquel; Schrank, Irene S; Zaha, Arnaldo; Ferreira, Henrique B

2012-01-27

Type I signal peptidase (SPase I) is a membrane-anchored protease of the general secretory pathway, which is encoded by the sipS gene in Mycoplasma hyopneumoniae, the etiological agent of porcine enzootic pneumonia (PEP). In this study, the expression of the M. hyopneumoniae SPase I (MhSPase I) was analyzed in virulent and avirulent strains, and the recombinant protein (rMhSPase I), expressed in Escherichia coli, was evaluated regarding its potential as an immunodiagnostic antigen. It was demonstrated that the sipS coding DNA sequence (CDS) is most likely part of an operon, being co-transcribed along with four other CDSs. Quantitative reverse transcriptase PCR and immunoblot assays showed that MhSPase I is expressed by all three strains analyzed, with no transcriptional difference, but with evidence of a higher protein level in a pathogenic strain (7422), in comparison to another pathogenic (7448) and a non-pathogenic (J) strain. rMhSPase I was strongly immunogenic for mice, and the MhSPase I antigenicity was confirmed. Polyclonal serum anti-rMhSPase I presented no detectable cross-reaction with Mycoplasma flocculare and Mycoplasma hyorhinis. Moreover, phylogenetic analysis demonstrated a low conservation between MhSPase I and orthologous proteins from other porcine respiratory disease complex-related bacteria, Firmicutes and other Mycoplasma species. The potential of an rMhSPase I-based ELISA for PEP immunodiagnosis was demonstrated. Overall, we investigated the expression of sipS and the encoded MhSPase I in three M. hyopneumoniae strains and showed that this protein is a good antigen for use in PEP serodiagnosis and possibly vaccination, as well as a potential target for antibiotic development. Copyright © 2011 Elsevier B.V. All rights reserved.

The dipeptidyl peptidase-4 inhibitor vildagliptin does not affect ex vivo cytokine response and lymphocyte function in patients with type 2 diabetes mellitus

NARCIS (Netherlands)

Poppel, P.C.M. van; Gresnigt, M.S.; Smits, P.; Netea, M.G.; Tack, C.J.J.

2014-01-01

AIMS: The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in

Identification of Dipeptidyl-Peptidase (DPP)5 and DPP7 in Porphyromonas endodontalis, Distinct from Those in Porphyromonas gingivalis

OpenAIRE

Nishimata, Haruka; Ohara-Nemoto, Yuko; Baba, Tomomi T.; Hoshino, Tomonori; Fujiwara, Taku; Shimoyama, Yu; Kimura, Shigenobu; Nemoto, Takayuki K.

2014-01-01

Dipeptidyl peptidases (DPPs) that liberate dipeptides from the N-terminal end of oligopeptides are crucial for the growth of Porphyromonas species, anaerobic asaccharolytic gram negative rods that utilize amino acids as energy sources. Porphyromonas endodontalis is a causative agent of periapical lesions with acute symptoms and Asp/Glu-specific DPP11 has been solely characterized in this organism. In this study, we identified and characterized two P. endodontalis DPPs, DPP5 and DPP7. Cell-ass...

The dipeptidyl peptidase 4 inhibitor vildagliptin does not accentuate glibenclamide-induced hypoglycemia but reduces glucose-induced glucagon-like peptide 1 and gastric inhibitory polypeptide secretion

DEFF Research Database (Denmark)

El-Ouaghlidi, Andrea; Rehring, Erika; Holst, Jens Juul

2007-01-01

BACKGROUND/AIMS: Inhibition of dipeptidyl peptidase 4 by vildagliptin enhances the concentrations of the active form of the incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The present study asked whether vildagliptin accentuates glibenclamide-induced hy...

Dipeptidyl peptidase IV in two human glioma cell lines

Directory of Open Access Journals (Sweden)

A Sedo

2009-12-01

Full Text Available There is growing evidence that dipeptidyl peptidase IV [DPP-IV, EC 3.4.14.5] takes part in the metabolism of biologically active peptides participating in the regulation of growth and transformation of glial cells. However, the knowledge on the DPP-IV expression in human glial and glioma cells is still very limited. In this study, using histochemical and biochemical techniques, the DPP-IV activity was demonstrated in two commercially available human glioma cell lines of different transformation degree, as represented by U373 astrocytoma (Grade III and U87 glioblastoma multiforme (Grade IV lines. Higher total activity of the enzyme, as well as its preferential localisation in the plasma membrane, was observed in U87 cells. Compared to U373 population, U87 cells were morphologically more pleiomorphic, they were cycling at lower rate and expressing less Glial Fibrillary Acidic Protein. The data revealed positive correlation between the degree of transformation of cells and activity of DPP-IV. Great difference in expression of this enzyme, together with the phenotypic differences of cells, makes these lines a suitable standard model for further 57 studies of function of this enzyme in human glioma cells.

Lessons Learned for Decommissioning Planning

International Nuclear Information System (INIS)

Sohn, Wook; Kim, Young-gook; Kim, Hee-keun

2015-01-01

The purpose of this paper is to introduce the U.S. nuclear industrial's some key lessons learned especially for decommissioning planning based on which well informed decommissioning planning can be carried out. For a successful decommissioning, it is crucial to carry out a well-organized decommissioning planning before the decommissioning starts. This paper discussed four key factors which should be decided or considered carefully during the decommissioning planning period with introduction of related decommissioning lessons learned of U.S. nuclear industry. Those factors which have been discussed in this paper include the end state of a site, the overall decommissioning strategy, the management of the spent fuels, and the spent fuel pool island. Among them, the end state of a site should be decided first as it directs the whole decommissioning processes. Then, decisions on the overall decommissioning strategy (DECON vs. SAFSTOR) and the management of the spent fuels (wet vs. dry) should follow. Finally, the spent fuel pool island should be given due consideration because its implementation will result in much cost saving. Hopefully, the results of this paper would provide useful inputs to performing the decommissioning planing for the Kori unit 1

Dominating Duffer’s Domain: Lessons for the U.S. Marine corps Information Operations Practitioner

Science.gov (United States)

2017-01-01

has learned 26 hard -won lessons that readers may find useful for the future conduct and planning of IO. The principles espoused here were derived from...to be frank, it wasn’t that hard . I had done the ten-day Intermediate MAGTF (Marine Air Ground Task Force) Information Operations Practitioner...paragraph, with no phases. It was, however, beauti- fully formatted , and the task listing had everything: military deception, electronic warfare, OPSEC

Jackie Steals Home. Learning Page Lesson Plan.

Science.gov (United States)

Pulda, Arnold

In this lesson, students draw on their previous studies of American history and culture as they analyze primary sources from "Jackie Robinson and Other Baseball Highlights, 1860s-1960s" in the American Memory collection. A close reading of two documents relating to Jackie Robinson's breaking of the racial barrier in professional baseball…

Lessons Learned In Developing The VACIS Products

International Nuclear Information System (INIS)

Orphan, Victor J.

2011-01-01

SAIC's development of VACIS provides useful 'lessons learned' in bridging the gap from an idea to a security or contraband detection product. From a gamma densitometer idea for solving a specific Customs Service (CS) requirement (detection of drugs in near-empty tanker trucks) in mid-1990's, SAIC developed a broad line of vehicle and cargo inspections systems (over 500 systems deployed to date) based on a gamma-ray radiographic imaging technique. This paper analyzes the reasons for the successful development of VACIS and attempts to identify ''lessons learned'' useful for future security and contraband detection product developments.

Lessons from Fukushima: New Concerns for the Future

International Nuclear Information System (INIS)

Matsumura, Akio; Girard, Odile

2016-01-01

In this article, the author, former Japanese diplomat, expresses lessons he learned from the catastrophe. He outlines that several aspects of this crisis keep on affecting population's health and environmental safety. He outlines several aspects: experts as well as the public have been looking for technical solutions during the first two weeks, experts knew from the beginning that the crisis was largely beyond the current technical capacities. He states that, without the intervention of experts from different fields, important information would have remained in the government's and public operator's hands rather than been communicated to the public. According to him, the main lesson is that we are now living surrounded by new threats which have been actually present for ten years, and that Fukushima is a matter of new concerns about nuclear plants

Dipeptidyl peptidase-4 inhibition and narrow-band ultraviolet-B light in psoriasis (DINUP): study protocol for a randomised controlled trial.

LENUS (Irish Health Repository)

Lynch, Maeve

2016-01-15

Moderate to severe psoriasis is a systemic inflammatory disease associated with insulin resistance, obesity and type 2 diabetes (T2DM). Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycaemia and has a marketing authorisation for the treatment of T2DM. Non-immunosuppressive therapies that are effective for psoriasis and its associated comorbidities would be a significant advance in the treatment of this chronic disease.

Program of technical assistance to the Organization for the Prohibition of Chemical Weapons - lessons learned from the U.S. program of technical assistance to IAEA safeguards. Final report

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-06-01

The Defense Nuclear Agency is sponsoring a technical study of the requirements of a vehicle to meet the OPCW`s future needs for enhanced chemical weapons verification capabilities. This report provides information about the proven mechanisms by which the U.S. provided both short- and long-term assistance to the IAEA to enhance its verification capabilities. Much of the technical assistance has generic application to international organizations verifying compliance with disarmament treaties or conventions. In addition, some of the equipment developed by the U.S. under the existing arrangements can be applied in the verification of other disarmament treaties or conventions. U.S. technical assistance to IAEA safeguards outside of the IAEA`s regular budget proved to be necessary. The U.S. technical assistance was successful in improving the effectiveness of IAEA safeguards for its most urgent responsibilities and in providing the technical elements for increased IAEA {open_quotes}readiness{close_quotes} for the postponed responsibilities deemed important for U.S. policy objectives. Much of the technical assistance was directed to generic subjects and helped to achieve a system of international verification. It is expected that the capabilities of the Organization for the Prohibition of Chemical Weapons (OPCW) to verify a state`s compliance with the {open_quotes}Chemical Weapons Convention{close_quotes} will require improvements. This report presents 18 important lessons learned from the experience of the IAEA and the U.S. Program of Technical Assistance to IAEA Safeguards (POTAS), organized into three tiers. Each lesson is presented in the report in the context of the difficulty, need and history in which the lesson was learned. Only the most important points are recapitulated in this executive summary.

When do Armed Revolts Succeed: Lessons from Lanchester Theory

Science.gov (United States)

2011-10-01

When do Armed Revolts Succeed: Lessons from Lanchester Theory Michael P. Atkinson 1, Alexander Gutfraind 2, Moshe Kress 1 Abstract Major revolts have...classic Lanchester theory of combat. The model accounts for the split in the population between those loyal to the regime and those favoring the...Lessons from Lanchester Theory 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f

Impact of microencapsulated peptidase (Aspergillus oryzae) on cheddar cheese proteolysis and its biologically active peptide profile.

Science.gov (United States)

Seneweera, Saman; Kailasapathy, Kaila

2011-07-01

We investigated the delivery of calcium-alginate encapsulated peptidase (Flavourzyme(®), Aspergillus oryzae) on proteolysis of Cheddar cheese. Physical and chemical characteristics such as moisture, pH and fat content were measured, and no differences were found between control and experimental cheese at day 0. SDS-PAGE analysis clearly showed that proteolysis of α and k casein was significantly accelerated after three months of maturity in the experimental cheese. A large number of low molecular weight peptides were found in the water soluble fraction of the experimental cheeses and some of these peptides were new. N-terminal amino acid sequence analysis identified these as P(1), Leu-Thu-Glu; P(3), Asp-Val-Pro-Ser-Glu) and relatively abundant stable peptides P(2), P(4), Arg-Pro-Lys-His-Pro-Ile; P(5), Arg-Pro-Lys-His-Pro-Ile-Lys and P(6). These peptides were mainly originated from αs1-CN and β-CN. Three of the identified peptides (P(1), P(2), P(3) and P(4)) are known to biologically active and P(1) and P(3) were only present in experimental cheese suggesting that experimental cheese has improved health benefits.

Antimelanoma monoclonal antibody 225-28S. Evaluation of toxicity in man

Energy Technology Data Exchange (ETDEWEB)

Cascinelli, N; Attili, A; Belli, F; Buraggi, G; Turrin, A; Gasparini, M; Terno, G; Vaglini, M

1988-01-01

To investigate possible undesirable due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antybody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with /sup 131/I and F(ab')2 fragment with /sup 131/I, or /sup 123/I, or /sup 111/In or /sup 99/Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 ..mu..g, and the specific activity from 37.0 to 2116.4 MBqmg. The total radioactivity injected varied from 25.9 to 891.7 MBqmg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC WBC, platelet count, serum creatine, creatine clearence, plasma electrolyte levels, serum proteins, albuminglobulin ratio, serum bilirubin, SGOT, SgPT, /sub ..gamma../GT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reaction. None of the afore mentioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic.

Connecting polar research to NGSS STEM classroom lessons

Science.gov (United States)

Brinker, R.; Kast, D.

2016-12-01

Next Generation Science Standards (NGSS) are designed to bring consistent, rigorous science teaching across the United States. Topics are categorized as Performance Expectations (PE), Disciplinary Core Ideas (DCI), Cross-Cutting Concepts (CCC), and Science and Engineering Practices (SEP). NGSS includes a focus on environmental science and climate change across grade levels. Earth and planetary sciences are required at the high school level. Integrating polar science lessons into NGSS classrooms brings relevant, rigorous climate change curriculum across grade levels. Polar science provides opportunities for students to use current data during lessons, conduct their own field work, and collaborate with scientists. Polar science provides a framework of learning that is novel to most students. Inquiry and engagement are high with polar science lessons. Phenomenon related to polar science provide an excellent tool for science teachers to use to engage students in a lesson, stimulate inquiry, and promote critical thinking. When taught effectively, students see the connections between their community, polar regions and climate change, regardless of where on the planet students live. This presentation describes examples of how to effectively implement NGSS lessons by incorporating polar science lessons and field research. Examples of introductory phenomenon and aligned PEs, CCCs, DCIs, and SEPs are given. Suggested student activities, assessments, examples of student work, student research, labs, and PolarTREC fieldwork, use of current science data, and connections to scientists in the field are provided. The goals of the presentation are to give teachers a blueprint to follow when implementing NGSS lessons, and give scientists an understanding of the basics of NGSS so they may be better able to relate their work to U.S. science education and be more effective communicators of their science findings.

A systematic review and meta-analysis of moderate-to-vigorous physical activity levels in secondary school physical education lessons.

Science.gov (United States)

Hollis, Jenna L; Sutherland, Rachel; Williams, Amanda J; Campbell, Elizabeth; Nathan, Nicole; Wolfenden, Luke; Morgan, Philip J; Lubans, David R; Gillham, Karen; Wiggers, John

2017-04-24

Schools play an important role in physical activity promotion for adolescents. The systematic review aimed to determine the proportion of secondary (middle and high) school physical education (PE) lesson time that students spend in moderate to vigorous physical activity (MVPA), and to assess if MVPA was moderated by school level (middle and high school), type of physical activity measurement and type of PE activities. A systematic search of nine electronic databases was conducted (PROSPERO2014:CRD42014009649). Studies were eligible if they were published between 2005 and 2014; written in English; assessed MVPA in PE lessons of secondary (middle and high) school students; and used a quantitative MVPA measure (i.e., accelerometry, heart rate monitoring, pedometers or observational measures). Two reviewers examined the retrieved articles, assessed risk of bias, and performed data extraction. Random effects meta-analysis was used to calculate a pooled estimate of the percent of PE lesson time spent in MVPA and to assess moderator effects where data allowed. The search yielded 5,132 potentially relevant articles; 28 articles representing 25 studies (7 middle and 18 high school) from seven countries were included. Twelve studies measured MVPA through observational measures, seven used accelerometers, five used heart rate monitors and four used pedometers (including three studies using a mix of measures). Meta-analysis of 15 studies found that overall, students spent a mean (95% CI) of 40.5% (34.8-46.2%) of PE in MVPA. Middle school students spent 48.6% (41.3-55.9%) of the lesson in MVPA (n = 5 studies) and high school students 35.9% (28.3-43.6%) (n = 10 studies). Studies measuring MVPA using accelerometers (n = 5) showed that students spent 34.7% (25.1-44.4%) of the lesson in MVPA, while 44.4% (38.3-50.5%) was found for lessons assessed via observation (n = 9), 43.1% (24.3-61.9%) of the lesson for a heart rate based study, and 35.9% (31.0-40.8%) for a

Adapting Features from the SIOP Component: Lesson Delivery to English Lessons in a Colombian Public School

Directory of Open Access Journals (Sweden)

Rativa Murillo Hollman Alejandro

2013-04-01

Full Text Available Despite some school efforts to offer students the best second language learning, English language lessons are often taught with an overuse of the mother tongue. Hence, an action research project was conducted in order to discover how to adapt some features of the Sheltered Instruction Observation Protocol (SIOP component: Lesson delivery, for the teaching of English in sixth grade at a public school in Bogotá, Colombia. Data collection included observation checklists, field notes, surveys and artifacts. The findings demonstrated that the overuse of Spanish–the students’ mother tongue–was reduced when in addition to implementing the lesson delivery component, the teacher developed vocabulary activities. Finally, it was suggested that teachers have SIOP training for teaching content andto focus more on students needs.A pesar de algunos esfuerzos para ofrecer a los estudiantes un mejor aprendizaje de una segunda lengua, a menudo se recurre al uso excesivo de la lengua materna en las clases de inglés. Con el objetivo de hallar la forma de adaptar algunas características del componente del protocolo deobservación SIOP para la instrucción ‘Sheltered’: Desarrollo de clase, para la enseñanza de inglés en grado séptimo, se realiz�� un proyecto de investigación acción en un colegio público en Bogotá, Colombia. En la recolección de datos se emplearon formatos de observación, notas de campo,cuestionarios y evidencias documentales. Los resultados demostraron que el uso excesivo de español –la lengua materna de los estudiantes– se redujo porque además de la implementación del componente Desarrollo de clase, se llevaron a cabo actividades de vocabulario. Con esta investigación se sugiere que los profesores adquieran conocimientos acerca del citado modelo para la enseñanza de contenidos, y que se enfoquen más en las necesidades de los estudiantes.

PENGUASAAN KONSEP DAN KEMAMPUAN BERTANYA SISWA PADA MATERI HUKUM NEWTON MELALUI PEMBELAJARAN INQUIRY LESSON DENGAN STRATEGI LBQ

Directory of Open Access Journals (Sweden)

Alfiyah Nur Jannah

2016-03-01

Penelitian ini bertujuan untuk mengetahui penguasaan konsep dan kemampuan bertanya siswa pada materi hukum Newton dalam pembelajaran inquiry lesson dengan strategi LBQ, serta mengetahui respons siswa terhadap pembelajaran inquiry lesson dengan strategi LBQ. Jenis penelitian ini adalah Mixed Methods desain embedded experimental dengan subjek 36 siswa kelas X MIA 6 SMA Negeri 1 Krian. Analisis kuantitatif dilakukan untuk mengetahui data penguasaan konsep siswa dan data respons siswa terhadap pembelajaran. Analisis kualitatif dilakukan untuk mengetahui kemampuan bertanya siswa dan respons siswa terhadap pembelajaran. Hasil penelitian menunjukkan bahwa: siswa mampu mencapai indikator tertinggi pencapaian konsep yaitu level C6 dan sebagian besar siswa SMA memiliki penguasaan konsep pada level C5, kemampuan bertanya siswa meningkat pada setiap pertemuan dimana siswa menjadi lebih percaya diri untuk menyampaikan pertanyaan maupun pendapat saat mengikuti pengajaran fisika, dan siswa memberikan respons positif sebesar 65,28% terhadap pembelajaran inquiry lesson dengan strategi LBQ.

Treatment Discontinuation and Clinical Events in Type 2 Diabetes Patients Treated with Dipeptidyl Peptidase-4 Inhibitors or NPH Insulin as Third-Line Therapy

Directory of Open Access Journals (Sweden)

Cristiano S. Moura

2018-01-01

Full Text Available Objective. To compare dipeptidyl peptidase-4 (DPP-4 inhibitors with neutral protamine Hagedorn (NPH insulin, in terms of effectiveness and safety for the management of patients with type 2 diabetes mellitus (DM2 not controlled on metformin and sulfonylureas. Methods. A retrospective cohort study of individuals with DM2 newly dispensed with either DPP-4 inhibitors or NPH as third-line therapy, after metformin and sulfonylurea. Treatment discontinuation, macrovascular outcomes, and hypoglycemia were compared using multivariable Cox regression models, adjusted for sex, age, year of cohort entry, place of residence, hypertension, past history of hypoglycemia, diabetic ketoacidosis, comorbidities, and number of visits to emergency departments, outpatient physician, and hospitalizations. Results. Treatment discontinuation and hypoglycemia occurred more frequently with NPH than with DPP-4 inhibitor users. In the adjusted Cox model, the use of NPH compared to that of DPP-4 inhibitors was associated with a higher risk of discontinuation (HR: 1.33; 95% CI 1.27–1.40 and hypoglycemia (HR: 2.98; 95% CI 2.72–3.28. Risk of cardiovascular events was similar across groups. Conclusions. This real-world analysis suggests that DM2 patients initiating third-line therapy with NPH have poorer control of diabetes when compared to DPP-4 inhibitor initiators.

Developing children’s palliative care in Africa through beacon centres: lessons learnt

Science.gov (United States)

2013-01-01

Much progress has been made in the provision of palliative care across sub-Saharan Africa, however much still remains to be done, particularly in the area of children’s palliative care (CPC). The Beacon Centres programme was set up in 2009, aimed at improving access to CPC in South Africa, Uganda and Tanzania through more and better-trained health professionals and CPC clinical services of a high standard. Having identified sites in each country to develop into CPC Beacon Centres, Navigators were identified who would be the ‘champions’ for CPC in those sites and lead a programme of training, mentorship and support. Five navigators (2 in Uganda and Tanzania and 1 in South Africa) were trained between September and December 2009. Following this they undertook CPC needs assessments at the 3 centres and set up and delivered a six-month CPC training programme, providing mentorship and support to students to enable them to integrate CPC into their workplaces. To date, 188 participants have commenced the six-month course, with 80 having completed it. CPC has been integrated into the activities of the centres and a CPC virtual resource centre set up in South Africa. The achievements from the Beacon project have been great and the work of the navigators immense, but as in all projects it has not been without its challenges. Lessons learnt include issues around: the focus of the project; the length and nature of the training; assessment; accreditation; the choice of navigators; mentoring; administrative support; co-ordination; the choice of project sites; and the integration of CPC into services. The need for CPC is not going to go away and it is therefore important that models of scaling-up are found that are not only practical, feasible, affordable and sustainable, but that focus on the outcome of improved CPC for all those who need it. It is hoped that the lessons shared from the Beacon Project will help in developing and implementing such models. PMID:23419095

A Lesson about the Circular Flow. Active Learning Lessons. Economics International.

Science.gov (United States)

Landfried, Janet

This lesson plan was developed through "Economics International," an international program to help build economic education infrastructures in the emerging market economies. It provides a lesson description; appropriate grade level; economic concepts; content standards and benchmarks; related subjects; instructional objectives; time…

Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer.

Science.gov (United States)

Ross, Breyan; Krapp, Stephan; Augustin, Martin; Kierfersauer, Reiner; Arciniega, Marcelino; Geiss-Friedlander, Ruth; Huber, Robert

2018-02-13

Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 Å) and DPP9 (3.0 Å) unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively. Similar to DPP4, DPP8 and DPP9 molecules consist of one β-propeller and α/β hydrolase domain, forming a functional homodimer. However, they differ extensively in the ligand binding site structure. In intriguing contrast to DPP4, where liganded and unliganded forms are closely similar, ligand binding to DPP8/9 induces an extensive rearrangement at the active site through a disorder-order transition of a 26-residue loop segment, which partially folds into an α-helix (R-helix), including R160/133, a key residue for substrate binding. As vestiges of this helix are also seen in one of the copies of the unliganded form, conformational selection may contributes to ligand binding. Molecular dynamics simulations support increased flexibility of the R-helix in the unliganded state. Consistently, enzyme kinetics assays reveal a cooperative allosteric mechanism. DPP8 and DPP9 are closely similar and display few opportunities for targeted ligand design. However, extensive differences from DPP4 provide multiple cues for specific inhibitor design and development of the DPP family members as therapeutic targets or antitargets.

Sarcoid-like lung granulomas in a hemodialysis patient treated with a dipeptidyl peptidase-4 inhibitor.

Science.gov (United States)

Sada, Ken-Ei; Wada, Jun; Morinaga, Hiroshi; Tuchimochi, Shigeyuki; Uka, Mayu; Makino, Hirofumi

2014-04-01

It has been reported that the inhibition of dipeptidyl peptidase-4 (DPP-4)/CD26 on T-cells by DPP-4 enzymatic inhibitors suppresses lymphocyte proliferation and reduces the production of various cytokines, including tumor necrosis factor (TNF)-α. A 72-year-old female with diabetic nephropathy on hemodialysis developed multiple lung nodules following the administration of vildagliptin. A biopsy demonstrated the histology of granulomas without caseous necrosis. The discontinuation of vildagliptin resulted in the disappearance of the granulomas within 4 months. As granulomatosis often develops in patients under anti-TNF-α therapy, the accumulation of DPP-4 inhibitors or its metabolites is possibly linked to unrecognized complications, such as sarcoid-like lung granulomas.

Classroom Management and Lesson Planning(4)

Institute of Scientific and Technical Information of China (English)

2006-01-01

Lesson PlanningTask 1As teachers,we all need to plan our lessons before we teach.Make a list of things that you think need tobe included in a lesson plan.Then compare and discuss your list with another teacher.Also think about reasonswhy we need to plan our lessons.

SVMDLF: A novel R-based Web application for prediction of dipeptidyl peptidase 4 inhibitors.

Science.gov (United States)

Chandra, Sharat; Pandey, Jyotsana; Tamrakar, Akhilesh K; Siddiqi, Mohammad Imran

2017-12-01

Dipeptidyl peptidase 4 (DPP4) is a well-known target for the antidiabetic drugs. However, currently available DPP4 inhibitor screening assays are costly and labor-intensive. It is important to create a robust in silico method to predict the activity of DPP4 inhibitor for the new lead finding. Here, we introduce an R-based Web application SVMDLF (SVM-based DPP4 Lead Finder) to predict the inhibitor of DPP4, based on support vector machine (SVM) model, predictions of which are confirmed by in vitro biological evaluation. The best model generated by MACCS structure fingerprint gave the Matthews correlation coefficient of 0.87 for the test set and 0.883 for the external test set. We screened Maybridge database consisting approximately 53,000 compounds. For further bioactivity assay, six compounds were shortlisted, and of six hits, three compounds showed significant DPP4 inhibitory activities with IC 50 values ranging from 8.01 to 10.73 μm. This application is an OpenCPU server app which is a novel single-page R-based Web application for the DPP4 inhibitor prediction. The SVMDLF is freely available and open to all users at http://svmdlf.net/ocpu/library/dlfsvm/www/ and http://www.cdri.res.in/svmdlf/. © 2017 John Wiley & Sons A/S.

[Heritage Education Lesson Plans and Slide Presentations].

Science.gov (United States)

Van Buren, Maurie

Field tested in 27 schools and in grades four through twelve, this teaching unit stresses heritage education through the study of southern U.S. architectural styles for homes from the pioneer log structures to the 1950s ranch home. Each of the four lessons in this unit focuses around a slide presentation of 20 slides designed to fit into one…

Classroom Management and Lesson Planning(4)

Institute of Scientific and Technical Information of China (English)

2006-01-01

@@ Lesson Planning Task 1 As teachers,we all need to plan our lessons before we teach.Make a list of things that you think need to be included in a lesson plan.Then compare and discuss your list with another teacher.Also think about reasons why we need to plan our lessons.

Lesson Planning the Kodaly Way.

Science.gov (United States)

Boshkoff, Ruth

1991-01-01

Discusses the contribution of Zoltan Kodaly to music lesson planning. Emphasizes preparation, presentation, and practice as the three important strategies in teaching concepts and skills to be included in a lesson plan. Includes a sample lesson plan covering a semester and advice on choosing song material. (DK)

Lessons learned from the NREL village power program

Energy Technology Data Exchange (ETDEWEB)

Taylor, R.W. [National Renewable Energy Lab., Golden, CO (United States)

1998-09-01

Renewable energy solutions for village power applications can be economical, functional, and sustainable. Pilot projects are an appropriate step in the development of a commercially viable market for rural renewable energy solutions. Moreover, there are a significant number of rural electrification projects under way that employ various technologies, delivery mechanisms, and financing arrangements. These projects, if properly evaluated, communicated, and their lessons incorporated in future projects and programs, can lead the way to a future that includes a robust opportunity for cost-effective, renewable-based village power systems. This paper summarizes some of NREL`s recent experiences and lessons learned.

The Joint Lessons Learned System and Interoperability

Science.gov (United States)

1989-06-02

Learned: 1988-1989 As mentioned in the introduction to this chaoter, the Organizacion of the JcinC Chiefs cf Staff .OJCS) ueren significant transformatioi...Organization and Functions Manual . Washington, D.C.: HQDA, Office of the Deputy Chief 0f Staff for Operations and Plans, June 1984. ’..S. Army. Concept...U.S. Department of Defense. Joint Universal Lessons Learned System (JULLS) User’s Manual . Orlando, Florida: University of Central Florida, Institute

The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

DEFF Research Database (Denmark)

Balas, Bogdan; Baig, Muhammad R; Watson, Catherine

2007-01-01

AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However......, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo......-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP...

Error-free 5.1 Tbit/s data generation on a single-wavelength channel using a 1.28 Tbaud symbol rate

DEFF Research Database (Denmark)

Mulvad, Hans Christian Hansen; Galili, Michael; Oxenløwe, Leif Katsuo

2009-01-01

We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER......We demonstrate a record bit rate of 5.1 Tbit/s on a single wavelength using a 1.28 Tbaud OTDM symbol rate, DQPSK data-modulation, and polarisation-multiplexing. Error-free performance (BER...

With Interest It Comes To...Unconscionable Clauses in Sales Contracts. A Student's Lesson Plan [and] A Teacher's Lesson Plan [and] A Lawyer's Lesson Plan.

Science.gov (United States)

Howard, Estelle; And Others

One of a series of secondary level teaching units presenting case studies with pro and con analysis of particular legal problems, the document presents a student's lesson plan, a teacher's lesson plan, and a lawyer's lesson plan on unconscionable clauses in sales contracts. The unit acquaints students with the operation of sales contracts and…

Lessons learned related to packaging and transportation

International Nuclear Information System (INIS)

Wallen, C.

1995-01-01

The use of lessons learned as a tool for learning from past experiences is well established, especially by many organizations within the nuclear industry. Every person has, at some time, used the principles of lessons learned to adopt good work practices based on their own experiences or the experiences of others. Lessons learned can also help to avoid the recurrence of adverse practices, which is often an area that most lessons-learned programs tend to focus on. This paper will discuss how lessons learned relate to packaging and transportation issues and events experienced at Department of Energy (DOE) facilities. It will also discuss the role performed by the Office of Nuclear and Facility Safety's Office of Operating Experience Analysis and Feedback in disseminating lessons learned and operating experience feedback to the DOE complex. The central concept of lessons learned is that any organization should be able to learn from its own experiences and events. In addition, organizations should implement methodologies to scan external environments for lessons learned, to analyze and determine the relevance of lessons learned, and to bring about the necessary changes learned from these experiences. With increased concerns toward facility safety, the importance of utilizing the lessons-learned principles and the establishment of lessons-learned programs can not be overstated

Characterization of kallikrein-related peptidase 4 glycosylations.

Science.gov (United States)

Yamakoshi, Yasuo; Yamakoshi, Fumiko; Hu, Jan C-C; Simmer, James P

2011-12-01

Kallikrein-related peptidase 4 (KLK4) is a glycosylated serine protease that functions in the maturation (hardening) of dental enamel. Pig and mouse KLK4 contain three potential N-glycosylation sites. We isolated KLK4 from developing pig and mouse molars and characterized their N-glycosylations. N-glycans were enzymatically released by digestion with N-glycosidase F and fluorescently labeled with 2-aminobenzoic acid. Normal-phase high-performance liquid chromatography (NP-HPLC) revealed N-glycans with no, or with one, two, or three sialic acid attachments in pig KLK4 and with no, or with one or two sialic acid attachments in mouse KLK4. The labeled N-glycans were digested with sialidase to generate the asialo N-glycan cores that were fractionated by reverse-phase HPLC, and their retention times were compared with similarly labeled glycan standards. The purified cores were characterized by mass spectrometric and monosaccharide composition analyses. We determined that pig and mouse KLK4 have NA2 and NA2F biantennary N-glycan cores. The pig triantennary core is NA3. The mouse triantennary core is NA3 with a fucose connected by an α1-6 linkage, indicating that it is attached to the first N-acetyglucosamine (NA3F). We conclude that pig KLK4 has NA2, NA2F, and NA3 N-glycan cores with no, or with one, two, or three sialic acids. Mouse KLK4 has NA2, NA2F, and NA3F N-glycan cores with no, or with one or two sialic acids. © 2011 Eur J Oral Sci.

Macrocarpal C isolated from Eucalyptus globulus inhibits dipeptidyl peptidase 4 in an aggregated form.

Science.gov (United States)

Kato, Eisuke; Kawakami, Kazuhiro; Kawabata, Jun

2018-12-01

Dipeptidyl peptidase 4 (DPP-4) inhibitors are used for the treatment of type-2 diabetes mellitus. Various synthetic inhibitors have been developed to date, and plants containing natural DPP-4 inhibitors have also been identified. Here, 13 plant samples were tested for their DPP-4 inhibitory activity. Macrocarpals A-C were isolated from Eucalyptus globulus through activity-guided fractionation and shown to be DPP-4 inhibitors. Of these, macrocarpal C showed the highest inhibitory activity, demonstrating an inhibition curve characterised by a pronounced increase in activity within a narrow concentration range. Evaluation of macrocarpal C solution by turbidity, nuclear magnetic resonance spectroscopy and mass spectrometry indicated its aggregation, which may explain the characteristics of the inhibition curve. These findings will be valuable for further study of potential small molecule DPP-4 inhibitors.

E-LEARNING FROM NATURE THROUGH E-LESSONS

Directory of Open Access Journals (Sweden)

Anca Cristina COLIBABA

2017-08-01

Full Text Available The article is a study based on the e-Learning from Nature project (2015-1-IT02-KA201-015133 funded by the European Commission. The project’s main objectives are centred on improving students’ low achievement and stimulating secondary school students’ interest in science subjects. The article focuses on scientific education and its challenges and suggests an innovative approach which connects science with nature. It examines one of the most important project outputs: the e-lessons (short video lessons created within the European partnership and the way they can contribute to increasing students’ motivation to learn science. Participant teachers’ testimonials have also been considered in the general evaluation of this project output.

Understanding public sexual harassment : lesson plans and session guidance, key Stages 3 & 4.

OpenAIRE

Vera-Gray, F.; Bullough, J.

2017-01-01

These lesson plans have been written by Dr. Fiona Vera-Gray at Durham University and Jayne Bullough from Rape Crisis South London (RASASC). They were created through a partnership project with Doll’s Eye Theatre, Purple Drum, RASASC, Dr. Maria Garner, and Dr. Fiona Vera-Gray. Lessons on public sexual harassment were drawn from the work of Dr. Vera-Gray at Durham University. The project was made possible by Durham Law School’s Impact Acceleration Grant from the Economics and ...

USING LITERATURE IN GEOGRAPHY LESSONS

Directory of Open Access Journals (Sweden)

ROXANA HOBAI

2015-01-01

Full Text Available Including in a novel information about relief, climate, vegetation, fauna and various aspects of socio-economic life can make literature a real source of geographical information. Using realistic literary works in Geography lessons has multiple benefits, which are not limited only to geographical knowledge. In this paper there are some fragments from literature, suggestions of activities about how to integrate the fragments during Geography lessons and the results of these activities. The activities are from fifth to twelfth grade, passing through a first example of water pollution resulting from a Hercules labour, through the lyricism of the aurora borealis description, through the dramatic life of a refugee from Darfur, through the Dobrudgea winter landscape, through the grey urban landscape of Bucharest in the 90s and so on. Students were put into learning situations that stimulated their creativity, developed communication competencies and enriched their general knowledge.

Lessons for Teaching Art Criticism.

Science.gov (United States)

Barrett, Terry, Ed.; Clark, Gilbert, Ed.

This collection of lessons is meant to be a practical guide to help teachers engage children in art criticism. The lessons generally follow a similar format. Most suggest an age group but may be modified for use with younger or older students. Several authors suggest variations and extensions for lessons that include studio activities. A broad…

"Frankenstein." [Lesson Plan].

Science.gov (United States)

Simon, Melanie

Based on Mary Shelley's novel "Frankenstein," this lesson plan presents activities designed to help students understand that active readers interpret a novel (its characters, plot, setting, and theme) in different ways; and the great literature can be and has been adapted in many ways over time. The main activity of the lesson involves students…

Phagocytosis: history's lessons.

Science.gov (United States)

Garg, Manish; Chandawarkar, Rajiv Y

2013-01-01

The assimilation of lessons from the past is an essential component of education for scientists of tomorrow. These lessons are not easy to find. History books on science are few and usually highly dramatized and biographies of scientists tend to exaggerate the pomp of scientific discovery. Both underplay the hard and laborious work that is integral to any scientific pursuit. Here we illustrate one such example. A century ago, the Nobel Prize in Medicine was awarded to two scientists: Ilya Metchnikoff, a Russian zoologist, for the discovery ofphagocytosis-a cell-mediated ingestion ofmicrobes; and Paul Ehrlich, a distinguished physician-scientist, for discovering a highly antigen-specific serum-derived antibody-based immune defense. These two diametrically opposing views of the host-pathogen interaction set the stage for a strife that led to seminal advancements in immunology. Mirrored in this journey are important lessons for scientists today--ubiquitously as applicable to modern scientific life as they were a century ago. This commentaryhighlights these lessons--a fitting centenary to a well-deserved recognition.

Lessons Learned from Independent Technical Reviews of U.S. Department of Energy Low-Level Radioactive Waste Landfills/Disposal Facilities

International Nuclear Information System (INIS)

Adams, V.; Gupta, D.C.; Smegal, J.S.

2009-01-01

This paper describes the lessons learned from a series of independent technical reviews (ITRs) of waste management operations conducted at existing and proposed low-level radioactive waste landfills/disposal facilities at U.S. Department of Energy (DOE) sites. The evaluated waste disposal programs include those at Hanford, Idaho, Savannah River Site, Oak Ridge, Portsmouth, Paducah, and the Nevada Test Site. Based on these evaluations, cost-effective lessons learned were identified to improve reliability and effectiveness of DOE on-site disposal facilities. Key recommendations covered a wide range of issues, including the following: complex-wide applied research effort is needed to evaluate settlement behavior of DOE wastes and how they may affect cover performance; there is a need for unbiased assessment of relevance of liners for different climates and wastes to evaluate where and when liners should be used; there is a need to develop information to demonstrate attenuation capability of modern liner materials and to understand the attenuation capability of liners during performance assessment; a review of historical data on demolition volumes and logistics from past DOE projects can provide valuable insight that can be helpful in planning capacity of future on-site disposal facilities; and operating procedures need to be reviewed and updated on a regular basis so that procedures remain consistent with changes in requirements and take advantage of improvements in technology. The complex-wide independent reviews have assisted DOE sites in considering lessons learned regarding common technical, regulatory, and management issues. Facility management and their operating contractors have begun implementing the applicable recommendations within the context of the DOE Order 435.1, Radioactive Waste Management. (authors)

Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats

DEFF Research Database (Denmark)

Simonsen, Lotte; Pilgaard, Sofie; Orskov, Cathrine

2007-01-01

Long-term treatment with dipeptidyl peptidase IV inhibitors (DPPIV-I) or glucagon-like peptide (GLP)-1 analogs may potentially affect intestinal growth by down- or upregulating the intestinotrophic hormone GLP-2. This study compared the intestinotrophic effects of 12-wk administration of vehicle......, exendin-4 (Ex-4; 5 nmol/kg bid sc), or DPPIV-I (NN-7201, 10 mg/kg qd orally) in GK rats. Some animals were observed additionally for 9 wk after the end of treatment. Both treatments lowered glycated hemoglobin A1c at wk 12 vs. control (Ex-4, -0.8%; DPPIV-I, -0.4%). Body weight was reduced by Ex-4 compared...... with control (361 +/- 4 vs. 399 +/- 5 g; P weight was identical in all groups...

The purification and characterization of an 88-kDa Porphyromonas endodontalis 35406 protease.

Science.gov (United States)

Rosen, G; Shoshani, M; Naor, R; Sela, M N

2001-12-01

A Porphyromonas endodontalis ATCC 35406 protease was purified from Triton X-114 cell extracts by preparative SDS-PAGE followed by electroelution. The purified enzyme exhibits a molecular size of 88 kDa and was dissociated into two polypeptides of 43 and 41 kDa upon heating in the presence of sodium dodecyl sulfate with or without a reducing agent. The protease (pH optimum 7.5-8.0) degraded the extracellular matrix proteins fibrinogen and fibronectin. Collagen IV was also degraded at 37 degrees C but not at 28 degrees C. The protease also cleaved the bioactive peptide angiotensin at amino acid residue phenylalanine-8 and tyrosine-4 but failed to hydrolyze bradykinin, vasopressin and synthetic chromogenic substrates with phenylalanine or tyrosine at the P1 position. In addition, two peptidases were detected in P. endodontalis cells: a proline aminopeptidase that remained associated with the cell pellet after detergent extraction and peptidase/s that partitioned into the Triton X-114 phase after phase separation and degraded the bioactive peptides bradykinin and vasopressin. These P. endodontalis peptidases and proteases may play an important role in both the nutrition and pathogenicity of these assacharolytic microorganisms. The inactivation of bioactive peptides and degradation of extracellular matrix proteins by bacterial enzymes may contribute to the damage of host tissues accompanied with endodontic infections.

Collagenolytic activities of the major secreted cathepsin L peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica.

Directory of Open Access Journals (Sweden)

Mark W Robinson

Full Text Available BACKGROUND: The temporal expression and secretion of distinct members of a family of virulence-associated cathepsin L cysteine peptidases (FhCL correlates with the entry and migration of the helminth pathogen Fasciola hepatica in the host. Thus, infective larvae traversing the gut wall secrete cathepsin L3 (FhCL3, liver migrating juvenile parasites secrete both FhCL1 and FhCL2 while the mature bile duct parasites, which are obligate blood feeders, secrete predominantly FhCL1 but also FhCL2. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that FhCL1, FhCL2 and FhCL3 exhibit differences in their kinetic parameters towards a range of peptide substrates. Uniquely, FhCL2 and FhCL3 readily cleave substrates with Pro in the P2 position and peptide substrates mimicking the repeating Gly-Pro-Xaa motifs that occur within the primary sequence of collagen. FhCL1, FhCL2 and FhCL3 hydrolysed native type I and II collagen at neutral pH but while FhCL1 cleaved only non-collagenous (NC, non-Gly-X-Y domains FhCL2 and FhCL3 exhibited collagenase activity by cleaving at multiple sites within the α1 and α2 triple helix regions (Col domains. Molecular simulations created for FhCL1, FhCL2 and FhCL3 complexed to various seven-residue peptides supports the idea that Trp67 and Tyr67 in the S2 subsite of the active sites of FhCL3 and FhCL2, respectively, are critical to conferring the unique collagenase-like activity to these enzymes by accommodating either Gly or Pro residues at P2 in the substrate. The data also suggests that FhCL3 accommodates hydroxyproline (Hyp-Gly at P3-P2 better than FhCL2 explaining the observed greater ability of FhCL3 to digest type I and II collagens compared to FhCL2 and why these enzymes cleave at different positions within the Col domains. CONCLUSIONS/SIGNIFICANCE: These studies further our understanding of how this helminth parasite regulates peptidase expression to ensure infection, migration and establishment in host tissues.

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

Directory of Open Access Journals (Sweden)

Al-Balas QA

2014-01-01

Full Text Available Qosay A Al-Balas,1 Munia F Sowaileh,1 Mohammad A Hassan,1 Amjad M Qandil,1,2 Karem H Alzoubi,3 Nizar M Mhaidat,3 Ammar M Almaaytah,4 Omar F Khabour51Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 2Pharmaceutical Sciences Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanBackground: The dipeptidyl peptidase-IV (DPP-IV enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels.Methods: In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point.Results: Sixty

Alexander Technique Lessons or Acupuncture Sessions for Persons With Chronic Neck Pain: A Randomized Trial.

Science.gov (United States)

MacPherson, Hugh; Tilbrook, Helen; Richmond, Stewart; Woodman, Julia; Ballard, Kathleen; Atkin, Karl; Bland, Martin; Eldred, Janet; Essex, Holly; Hewitt, Catherine; Hopton, Ann; Keding, Ada; Lansdown, Harriet; Parrott, Steve; Torgerson, David; Wenham, Aniela; Watt, Ian

2015-11-03

Management of chronic neck pain may benefit from additional active self-care-oriented approaches. To evaluate clinical effectiveness of Alexander Technique lessons or acupuncture versus usual care for persons with chronic, nonspecific neck pain. Three-group randomized, controlled trial. (Current Controlled Trials: ISRCTN15186354). U.K. primary care. Persons with neck pain lasting at least 3 months, a score of at least 28% on the Northwick Park Questionnaire (NPQ) for neck pain and associated disability, and no serious underlying pathology. 12 acupuncture sessions or 20 one-to-one Alexander lessons (both 600 minutes total) plus usual care versus usual care alone. NPQ score (primary outcome) at 0, 3, 6, and 12 months (primary end point) and Chronic Pain Self-Efficacy Scale score, quality of life, and adverse events (secondary outcomes). 517 patients were recruited, and the median duration of neck pain was 6 years. Mean attendance was 10 acupuncture sessions and 14 Alexander lessons. Between-group reductions in NPQ score at 12 months versus usual care were 3.92 percentage points for acupuncture (95% CI, 0.97 to 6.87 percentage points) (P = 0.009) and 3.79 percentage points for Alexander lessons (CI, 0.91 to 6.66 percentage points) (P = 0.010). The 12-month reductions in NPQ score from baseline were 32% for acupuncture and 31% for Alexander lessons. Participant self-efficacy improved for both interventions versus usual care at 6 months (P neck pain and associated disability compared with usual care at 12 months. Enhanced self-efficacy may partially explain why longer-term benefits were sustained. Arthritis Research UK.

A role for nuclear translocation of tripeptidyl-peptidase II in reactive oxygen species-dependent DNA damage responses

Energy Technology Data Exchange (ETDEWEB)

Preta, Giulio; Klark, Rainier de [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

2009-11-27

Responses to DNA damage are influenced by cellular metabolism through the continuous production of reactive oxygen species (ROS), of which most are by-products of mitochondrial respiration. ROS have a strong influence on signaling pathways during responses to DNA damage, by relatively unclear mechanisms. Previous reports have shown conflicting data on a possible role for tripeptidyl-peptidase II (TPPII), a large cytosolic peptidase, within the DNA damage response. Here we show that TPPII translocated into the nucleus in a p160-ROCK-dependent fashion in response to {gamma}-irradiation, and that nuclear expression of TPPII was present in most {gamma}-irradiated transformed cell lines. We used a panel of nine cell lines of diverse tissue origin, including four lymphoma cell lines (T, B and Hodgkins lymphoma), a melanoma, a sarcoma, a colon and two breast carcinomas, where seven out of nine cell lines showed nuclear TPPII expression after {gamma}-irradiation. Further, this required cellular production of ROS; treatment with either N-acetyl-Cysteine (anti-oxidant) or Rotenone (inhibitor of mitochondrial respiration) inhibited nuclear accumulation of TPPII. The local density of cells was important for nuclear accumulation of TPPII at early time-points following {gamma}-irradiation (at 1-4 h), indicating a bystander effect. Further, we showed that the peptide-based inhibitor Z-Gly-Leu-Ala-OH, but not its analogue Z-Gly-(D)-Leu-Ala-OH, excluded TPPII from the nucleus. This correlated with reduced nuclear expression of p53 as well as caspase-3 and -9 activation in {gamma}-irradiated lymphoma cells. Our data suggest a role for TPPII in ROS-dependent DNA damage responses, through alteration of its localization from the cytosol into the nucleus.

Accident at Three Mile Island nuclear power plant and lessons learned

International Nuclear Information System (INIS)

Ashrafi, A.; Farnoudi, F.; Tochai, M.T.M.; Mirhabibi, N.

1986-01-01

On March 28, 1979, the TMI, unit 2 nuclear power plant experienced a loss of coolant accident (LOCA) which has had a major impact among the others, upon the safety of nuclear power plants. Although a small part of the reactor core melted in this accident, but due to well performance of the vital safety equipment, there was no serious radioactivity release to the environment, and the accident has had no impact on the basic safety goals. A brief scenario of the accident, its consequences and the lessons learned are discussed

Evaluation of the Teaching Methods Used in Secondary School Biology Lessons

Directory of Open Access Journals (Sweden)

Porozovs Juris

2015-06-01

Full Text Available The teacher’s skills in conducting the lesson and choice of teaching methods play an essential role in creating students’ interest in biology. The aim of the research was to study the opinion of secondary school students and biology teachers regarding the most successful teaching methods used in biology lessons and viable options to make biology lessons more interesting. The research comprised polling students and biology teachers from several schools, namely: 2 secondary schools in Jelgava, 2 in Riga and 1 in Vecumnieki. The responses revealed that 58% of students find biology lessons interesting. 56% of students indicated that their ability to focus attention during biology lessons depends on the task presented to them. Most of all they prefer watching the teacher’s presentations, listening to their teacher telling about the actual topic as well as performing laboratory work and group-work. Many students like participating in discussions, whereas a far smaller number would do various exercises, individual tasks, fill out worksheets or complete projects. Least of all students wish to work with the textbook. The methods most frequently applied by teachers are as follows: lecture, explanation, demonstration, and discussion. Teachers believe that their students prefer laboratory work and discussions as well as listening to their teacher and watching presentations or films. They also indicate at the necessity to link theory with practice and to involve information technologies. While teaching their subject biology teachers try to establish relationship between theory and real life in order to develop their students’ interest in natural processes.

How to Listen to Pachamama’s Testimonio: Lessons from Indigenous Voices

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Luis I Prádanos

2015-01-01

Full Text Available This article analyzes the collective, open-access, and modifiable publication El Vivir Bien como respuesta a la Crisis Global as a posthumanist testimonio or ecotestimonio intending to give voice to the biotic community of the Andes. Written by Quechua and Aymara people and presented to the United Nations by the Plurinational State of Bolivia, this document targets the global ecological, financial, and social crises from the perspective of Indigenous knowledges. This document also exemplifies the worldwide reemergence of Indigenous voices that are confronting the global ecological crisis and its environmental injustices through the revitalization of Indigenous worldviews and practices. This ecotestimonio conveys, among many timely lessons, the Indigenous teaching that humans must listen carefully to the non-human world to learn from Pachamama how to interrelate as humans and with non-humans to collaborate in ensuring the continuing vitality of the community of life. If we listen carefully to Pachamama ’s testimony, as Indigenous voices urge, doubt must be cast upon the viability of ideas celebrated by hegemonic Western modern discourses like "development," "progress," or ‘"economic growth." Instead, these voices invite us to rethink the place, functions, and responsibilities of humans as members of the web of life.

1.28 Tbit/s/channel single-polarization DQPSK transmission over 525 km using ultrafast time-domain optical Fourier transformation

DEFF Research Database (Denmark)

Guan, P.; Mulvad, Hans Christian Hansen; Tomiyama, Y.

2010-01-01

A single-channel 1.28 Tbit/s transmission over 525 km is demonstrated for the first time with a single-polarization DQPSK signal. Ultrafast time-domain optical Fourier transformation is successfully applied to DQPSK signals and results in improved performance and increased system margin.......A single-channel 1.28 Tbit/s transmission over 525 km is demonstrated for the first time with a single-polarization DQPSK signal. Ultrafast time-domain optical Fourier transformation is successfully applied to DQPSK signals and results in improved performance and increased system margin....

Lessons from History for Counter- Terrorism Strategic Communications

NARCIS (Netherlands)

Ingram, H.J.; Reed, A.G.

2016-01-01

Drawing on the Counter-terrorism Strategic Communication (CTSC) Project’s research paper “A Brief History of Propaganda during Conflict“, this Policy Brief lays out the key policy-relevant lessons for developing effective counter-terrorism strategic communications. It presents a framework of

Winning the Peace: Building a Strategic Level Lessons Learned Program

National Research Council Canada - National Science Library

French, Daniel L

2007-01-01

The U.S. military has developed a robust, comprehensive system to capture, analyze, and disseminate tactical-level and operational-level lessons learned from training events and ongoing conflict operations...

Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells

DEFF Research Database (Denmark)

Poulsen, Mona Dam; Hansen, Gert Helge; Dabelsteen, Erik

1993-01-01

Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part...... of the islets of Langerhans. The antigen is enzymatically active, as shown by enzyme histochemical analysis with a synthetic DP IV substrate. By immunoelectron microscopy (immunogold labeling), the labeling of DP IV in the islets was associated with the secretory granules of the A-cells, as identified by double...... labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein...

A Simple Method to Decode the Complete 18-5.8-28S rRNA Repeated Units of Green Algae by Genome Skimming.

Science.gov (United States)

Lin, Geng-Ming; Lai, Yu-Heng; Audira, Gilbert; Hsiao, Chung-Der

2017-11-06

Green algae, Chlorella ellipsoidea , Haematococcus pluvialis and Aegagropila linnaei (Phylum Chlorophyta) were simultaneously decoded by a genomic skimming approach within 18-5.8-28S rRNA region. Whole genomic DNAs were isolated from green algae and directly subjected to low coverage genome skimming sequencing. After de novo assembly and mapping, the size of complete 18-5.8-28S rRNA repeated units for three green algae were ranged from 5785 to 6028 bp, which showed high nucleotide diversity (π is around 0.5-0.6) within ITS1 and ITS2 (Internal Transcribed Spacer) regions. Previously, the evolutional diversity of algae has been difficult to decode due to the inability design universal primers that amplify specific marker genes across diverse algal species. In this study, our method provided a rapid and universal approach to decode the 18-5.8-28S rRNA repeat unit in three green algal species. In addition, the completely sequenced 18-5.8-28S rRNA repeated units provided a solid nuclear marker for phylogenetic and evolutionary analysis for green algae for the first time.

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Czech Academy of Sciences Publication Activity Database

Zavasnik-Bergant, T.; Vidmar, R.; Sekirnik, A.; Fonovic, M.; Salát, Jiří; Grunclová, Lenka; Kopáček, Petr; Turk, B.

2017-01-01

Roč. 7, JUN 30 (2017), č. článku 288. ISSN 2235-2988 R&D Projects: GA ČR GA13-11043S Institutional support: RVO:60077344 Keywords : cystatin OmC2 * tick saliva * cathepsin S * cathepsin C * lysosomal proteases * dpp1 * dipeptidyl peptidase 1 * dendritic cells Subject RIV: EC - Immunology OBOR OECD: Immunology Impact factor: 4.300, year: 2016

Development of a Single-Step Subtraction Method for Eukaryotic 18S and 28S Ribonucleic Acids

Directory of Open Access Journals (Sweden)

Marie J. Archer

2011-01-01

Full Text Available The abundance of mammalian 18S and 28S ribosomal RNA can decrease the detection sensitivity of bacterial or viral targets in complex host-pathogen mixtures. A method to capture human RNA in a single step was developed and characterized to address this issue. For this purpose, capture probes were covalently attached to magnetic microbeads using a dendrimer linker and the solid phase was tested using rat thymus RNA (mammalian components with Escherichia coli RNA (bacterial target as a model system. Our results indicated that random capture probes demonstrated better performance than specific ones presumably by increasing the number of possible binding sites, and the use of a tetrame-thylammonium-chloride (TMA-Cl- based buffer for the hybridization showed a beneficial effect in the selectivity. The subtraction efficiency determined through real-time RT-PCR revealed capture-efficiencies comparable with commercially available enrichment kits. The performance of the solid phase can be further fine tuned by modifying the annealing time and temperature.

Putting Gino's lesson to work: Actor-network theory, enacted humanity, and rehabilitation.

Science.gov (United States)

Abrams, Thomas; Gibson, Barbara E

2016-02-01

This article argues that rehabilitation enacts a particular understanding of "the human" throughout therapeutic assessment and treatment. Following Michel Callon and Vololona Rabeharisoa's "Gino's Lesson on Humanity," we suggest that this is not simply a top-down process, but is cultivated in the application and response to biomedical frameworks of human ability, competence, and responsibility. The emergence of the human is at once a materially contingent, moral, and interpersonal process. We begin the article by outlining the basics of the actor-network theory that underpins "Gino's Lesson on Humanity." Next, we elucidate its central thesis regarding how disabled personhood emerges through actor-network interactions. Section "Learning Gino's lesson" draws on two autobiographical examples, examining the emergence of humanity through rehabilitation, particularly assessment measures and the responses to them. We conclude by thinking about how rehabilitation and actor-network theory might take this lesson on humanity seriously. © The Author(s) 2016.

Lesson study in prospective mathematics teacher education: didactic and paradidactic technology in the post-lesson reflection

DEFF Research Database (Denmark)

Rasmussen, Klaus

2016-01-01

This paper presents a detailed analysis of the post-lesson reflection, carried out in the context of eight cases of lesson study conducted by teams of Danish, lower secondaryprospective teachers and their supervisors. The participants, representing different institutions, were all new to the less...... and concern to the whole profession of mathematics teachers and the analysis adds to our insight into the potential of lesson study in prospective education as a meeting place where pertinent actors contribute to the expansion and dissemination of shared professional knowledge......This paper presents a detailed analysis of the post-lesson reflection, carried out in the context of eight cases of lesson study conducted by teams of Danish, lower secondaryprospective teachers and their supervisors. The participants, representing different institutions, were all new to the lesson...... study format. Nevertheless, it is demonstrated how their interaction shape the development of discourse about mathematical learning. The anthropological theory of the didactic is employed as the theoretical approach to analyse the mathematical and primarily didactical praxeologies developed...

Low-Temperature Projects of the Department of Energy's Geothermal Technologies Program: Evaluation and Lessons Learned

Energy Technology Data Exchange (ETDEWEB)

Williams, Tom; Snyder, Neil; Gosnold, Will

2016-10-23

This paper discusses opportunities and challenges related to the technical and economic feasibility of developing power generation from geothermal resources at temperatures of 150 degrees C and lower. Insights from projects funded by the U.S. Department of Energy (DOE), Geothermal Technologies Office inform these discussions and provide the basis for some lessons learned to help guide decisions by DOE and the industry in further developing this resource. The technical basis for low-temperature geothermal energy is well established and the systems can be economic today in certain situations. However, these applications are far from a 'plug and play' product; successful development today requires a good knowledge of geothermal system design and operation.

Experiment data report for Semiscale Mod-1 test S-28-3 (steam generator tube rupture test)

International Nuclear Information System (INIS)

Gillins, R.L.; Sackett, K.E.

1977-10-01

Recorded test data are presented for Test S-28-3 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-3 was conducted from initial conditions of 15621 kPa and 555 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. Twelve steam generator tube ruptures were simulated by a controlled injection from a heated accumulator into the intact loop hot leg

Experiment data report for semiscale Mod-1 test S-28-4 (steam generator tube rupture test)

International Nuclear Information System (INIS)

Esparza, V.; Sackett, K.E.

1977-10-01

Recorded test data are presented for Test S-28-4 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-4 was conducted from initial conditions of 15 646 kPa and 557 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. Thirty steam generator tube ruptures were simulated by a controlled injection from a heated accumulator into the intact loop hot leg

Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer

DEFF Research Database (Denmark)

Ulmert, David; Vickers, Andrew J; Scher, Howard I

2012-01-01

The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase...... of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist....

U.S. Department of Energy Office of Legacy Management Legacy Uranium Mine Site Reclamation - Lessons Learned - 12384

Energy Technology Data Exchange (ETDEWEB)

Kilpatrick, Laura E. [U.S. Department of Energy Office of Legacy Management, Westminster, Colorado 80021 (United States); Cotter, Ed [S.M. Stoller Corporation, Grand Junction, Colorado 81503 (United States)

2012-07-01

The U.S. Department of Energy (DOE) Office of Legacy Management is responsible for administering the DOE Uranium Leasing Program (ULP) and its 31 uranium lease tracts located in the Uravan Mineral Belt of southwestern Colorado (see Figure 1). In addition to administering the ULP for the last six decades, DOE has also undertaken the significant task of reclaiming a large number of abandoned uranium (legacy) mine sites and associated features located throughout the Uravan Mineral Belt. In 1995, DOE initiated a 3-year reconnaissance program to locate and delineate (through extensive on-the-ground mapping) the legacy mine sites and associated features contained within the historically defined boundaries of its uranium lease tracts. During that same time frame, DOE recognized the lack of regulations pertaining to the reclamation of legacy mine sites and contacted the U.S. Bureau of Land Management (BLM) concerning the reclamation of legacy mine sites. In November 1995, The BLM Colorado State Office formally issued the United States Department of the Interior, Colorado Bureau of Land Management, Closure/Reclamation Guidelines, Abandoned Uranium Mine Sites as a supplement to its Solid Minerals Reclamation Handbook (H-3042-1). Over the next five-and-one-half years, DOE reclaimed the 161 legacy mine sites that had been identified on DOE withdrawn lands. By the late 1990's, the various BLM field offices in southwestern Colorado began to recognize DOE's experience and expertise in reclaiming legacy mine sites. During the ensuing 8 years, BLM funded DOE (through a series of task orders) to perform reclamation activities at 182 BLM mine sites. To date, DOE has reclaimed 372 separate and distinct legacy mine sites. During this process, DOE has learned many lessons and is willing to share those lessons with others in the reclamation industry because there are still many legacy mine sites not yet reclaimed. DOE currently administers 31 lease tracts (11,017 ha) that

Sodium-glucose cotransporter 2 inhibitors combined with dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: a review of current clinical evidence and rationale

Directory of Open Access Journals (Sweden)

Yassin SA

2017-03-01

Full Text Available Sayf A Yassin,1 Vanita R Aroda2 1MedStar Union Memorial Hospital, Baltimore, 2MedStar Health Research Institute, Hyattsville, MD, USA Abstract: Type 2 diabetes mellitus (T2DM is a progressive and multifactorial cardiometabolic disorder. Almost half of adults with diabetes fail to achieve their recommended glucose control target. This has prompted some clinicians to advocate the use of more intensive initial therapy, including the use of combination therapy to target multiple physiologic defects in diabetes with the goal of achieving and sustaining glucose control. Numerous options exist for combining the various classes of glucose-lowering agents in the treatment of T2DM. This report reviews the mechanism, rationale, and evidence from clinical trials for combining two of the newer drug classes, namely, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors, and considers the possible role of such dual therapy in the management of T2DM. Keywords: sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase-4 inhibitors, type 2 diabetes mellitus, combination therapy

The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis.

Directory of Open Access Journals (Sweden)

Jae Ho Seo

2016-07-01

Full Text Available Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating "stress" signals of 5' adenosine monophosphate-activated protein kinase (AMPK phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a "drugable" therapeutic target in cancer.

VLIV PROGRESIVNÍCH VYUČOVACÍCH JEDNOTEK TĚLESNÉ VÝCHOVY NA TĚLESNÉ ZATÍŽENÍ A CELKOVÉ HODNOCENÍ ADOLESCENTŮ S NIŽŠÍM A VYŠŠÍM SEBEHODNOCENÍM SPORTOVNÍ VÝKONNOSTI [THE INFLUENCE OF PROGRESSIVE PHYSICAL EDUCATION LESSONS ON PHYSICAL LOAD AND THEIR TOTAL EVALUATION BY ADOLESCENTS WITH LOWER AND HIGHER SELF-ASSESSMENT OF THEIR SPORT PERFORMANCE

Directory of Open Access Journals (Sweden)

Erik Sigmund

2009-12-01

Full Text Available Dlouhodobě pravidelná realizace pohybové aktivity (PA ve školní tělesné výchově (TV umožňuje formovat pozitivní postoje všech, i méně predisponovaných dětí, k pohybově aktivnímu a zdravému životnímu stylu. Celkem u 389 děvčat a 111 chlapců ve věku 13–17 let s nižším a vyšším sebehodnocením sportovní výkonnosti byl zjišťován vliv progresivních vyučovacích jednotek TV na jejich PA a celkové hodnocení v párovém srovnání s tradičními jednotkami TV. V tradičních vyučovacích jednotkách TV převažoval direktivní vyučovací styl a výkonové zaměření, zatímco pro progresivní vyučovací jednotky TV bylo typické řešení pohybových úkolů a diferenciace tělesného zatížení. Párově srovnávané progresivní i tradiční vyučovací jednotky TV byly nekoedukované a vedl je stejný vyučující. PA byla posuzována pomocí aktivního energetického výdeje z akcelerometru Caltrac (kcal/45min, kroků z pedometru Omron (počet/45min a průměrné srdeční frekvence (tepů/min ze sporttesteru Polar. Úroveň sportovní výkonnosti a celkového hodnocení účastníků vyučovacích jednotek TV byla zjišťována prostřednictvím standardizovaného Dotazníku k diagnostice vyučovací jednotky TV. Progresivní vyučovací jednotky TV snižují rozdíly v PA mezi studenty s nižším a vyšším sebehodnocením sportovní výkonnosti bez poklesu celkového hodnocení těchto jednotek. Děvčata s nižším sebehodnocením sportovní výkonnosti vykázala v progresivních vyučovacích jednotkách TV významně vyšší průměrné hodnoty aktivního energetického výdeje (o 17 kcal/45min; p=0,05; d=0,28 a množství kroků (o 398 počet/45min; p=0,007; d=0,36 při vyšším celkovém hodnocení (p=0,04 než v tradičních vyučovacích jednotkách TV. Progresivní vyučovací jednotky přispívají k vyšší PA v TV především u děvčat s nižším sebehodnocením sportovní v

NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

Science.gov (United States)

Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

2017-09-01

Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

75 FR 16492 - Agency Information Collection Activities: Form G-28, and Form G-28I, Revision of an Existing...

Science.gov (United States)

2010-04-01

... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services Agency Information... Attorney. OMB Control No. 1615-0105. The Department of Homeland Security, U.S. Citizenship and Immigration... of Homeland Security sponsoring the collection: Form G-28, and Form G-28I. U.S. Citizenship and...

Peptidases e lipases produzidas pelo fungo Fusarium oxysporum: caracterização e microencapsulação por spray drying

OpenAIRE

Tamara Angelo de Oliveira Santos

2012-01-01

Duas variações de resíduo agroindustrial foram analisadas como meio de cultura para o bioprocesso de fermentação semissólida pelo fungo Fusarium oxysporum, com o objetivo de obter a melhor produção de peptidases e lipases. Essas enzimas foram microencapsuladas por spray drying, visando garantir sua estabilidade e investigar outros prováveis benefícios obtidos pela técnica. A utilização de planejamento experimental permitiu analisar os efeitos e interações entre as variáveis operacionais do pr...

Lessons Learned in International Safeguards - Implementation of Safeguards at the Rokkasho Reprocessing Plant

International Nuclear Information System (INIS)

Ehinger, Michael H.; Johnson, Shirley

2010-01-01

The focus of this report is lessons learned at the Rokkasho Reprocessing Plant (RRP). However, the subject of lessons learned for application of international safeguards at reprocessing plants includes a cumulative history of inspections starting at the West Valley (New York, U.S.A.) reprocessing plant in 1969 and proceeding through all of the efforts over the years. The RRP is the latest and most challenging application the International Atomic Energy Agency has faced. In many ways the challenges have remained the same, timely inspection and evaluation with limited inspector resources, with the continuing realization that planning and preparations can never start early enough in the life cycle of a facility. Lessons learned over the years have involved the challenges of using ongoing advances in technology and dealing with facilities with increased throughput and continuous operation. This report will begin with a review of historical developments and lessons learned. This will provide a basis for a discussion of the experiences and lessons learned from the implementation of international safeguards at RRP.

The individual teacher in lesson study collaboration

DEFF Research Database (Denmark)

Skott, Charlotte Krog; Møller, Hanne

2017-01-01

used in lesson study research. Design/methodology/approach The authors use collective case studies. By being participant observers the authors provide detailed descriptions of two selected teachers’ lived experiences of lesson study collaboration. In addition to gain first-hand insights, the authors...... in the participation of each of the two teachers during a two-year lesson study project. By comparing these shifts the authors identify significant conditions for their individual learning. Research limitations/implications Although the study is small scale, both the insights into the different ways in which teachers...... participated and the theoretical insights might be valuable for other lesson study research approaches. Practical implications This paper provides valuable insights into conditions that might influence teachers’ participation in lesson study activities, especially in cultures with little experience of lesson...

A rabies lesson improves rabies knowledge amongst primary school children in Zomba, Malawi

Science.gov (United States)

Burdon Bailey, Jordana L.; Gamble, Luke; Gibson, Andrew D.; Bronsvoort, Barend M. deC.; Handel, Ian G.; Mellanby, Richard J.; Mazeri, Stella

2018-01-01

Rabies is an important neglected disease, which kills around 59,000 people a year. Over a third of these deaths are in children less than 15 years of age. Almost all human rabies deaths in Africa and Asia are due to bites from infected dogs. Despite the high efficacy of current rabies vaccines, awareness about rabies preventive healthcare is often low in endemic areas. It is therefore common for educational initiatives to be conducted in conjunction with other rabies control activities such as mass dog vaccination, however there are few examples where the efficacy of education activities has been assessed. Here, primary school children in Zomba, Malawi, were given a lesson on rabies biology and preventive healthcare. Subsequently, a mass dog vaccination programme was delivered in the same region. Knowledge and attitudes towards rabies were assessed by a questionnaire before the lesson, immediately after the lesson and 9 weeks later to assess the impact the lesson had on school children’s knowledge and attitudes. This assessment was also undertaken in children who were exposed to the mass dog vaccination programme but did not receive the lesson. Knowledge of rabies and how to be safe around dogs increased following the lesson (both prabies and how to be safe around dogs was greater amongst school children who had received the lesson compared to school children who had not received the lesson, but had been exposed to a rabies vaccination campaign in their community (both prabies can improve short and medium-term rabies knowledge and attitudes of Malawian schoolchildren. PMID:29522517

Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma

International Nuclear Information System (INIS)

Tamat, S.R.; Moore, D.E.; Patwardhan, A.; Hersey, P.

1989-01-01

The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a bridge to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC

What Happens at the Lesson Start?

Science.gov (United States)

Saloviita, Timo

2016-01-01

Transitional periods, such as lesson starts, are necessary steps from one activity to another, but they also compete with time for actual learning. The aim of the present study was to replicate a previous pilot study on lesson starts and explore possible disturbances. In total, 130 lesson starts in Finnish basic education in grades 1-9 were…

Development and evaluation of a 28S rRNA gene-based nested PCR assay for P. falciparum and P. vivax

Science.gov (United States)

Pakalapati, Deepak; Garg, Shilpi; Middha, Sheetal; Acharya, Jyoti; Subudhi, Amit K; Boopathi, Arunachalam P; Saxena, Vishal; Kochar, Sanjay K; Kochar, Dhanpat K; Das, Ashis

2013-01-01

The 28S rRNA gene was amplified and sequenced from P. falciparum and P. vivax isolates collected from northwest India. Based upon the sequence diversity of the Plasmodium 28SrRNA gene in comparison with its human counterpart, various nested polymerase chain reaction (PCR) primers were designed from the 3R region of the 28SrRNA gene and evaluated on field isolates. This is the first report demonstrating the utility of this gene for species-specific diagnosis of malaria for these two species, prevalent in India. The initial evaluation on 363 clinical isolates indicated that, in comparison with microscopy, which showed sensitivity and specificity of 85.39% and 100% respectively, the sensitivity and specificity of the nested PCR assay was found to be 99.08% and 100% respectively. This assay was also successful in detecting mixed infections that are undetected by microscopy. Our results demonstrate the utility of the 28S rRNA gene as a diagnostic target for the detection of the major plasmodial species infecting humans. PMID:23816509

Lesson study i Danmark?

DEFF Research Database (Denmark)

Mogensen, Arne

2009-01-01

Der beskrives et japansk lesson study forløb, og det diskuteres i hvilket omfang, de gode japanske erfaringer kan overføres til dansk matematikundervisning.......Der beskrives et japansk lesson study forløb, og det diskuteres i hvilket omfang, de gode japanske erfaringer kan overføres til dansk matematikundervisning....

Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme.

Science.gov (United States)

Matteucci, E; Giampietro, O

2009-01-01

Dipeptidyl peptidase-4 (DPP4) or adenosine deaminase complexing protein 2 (ADCP 2) or T-cell activation antigen CD26 (EC 3.4.14.5.) is a serine exopeptidase belonging to the S9B protein family that cleaves X-proline dipeptides from the N-terminus of polypeptides, such as chemokines, neuropeptides, and peptide hormones. The enzyme is a type II transmembrane glycoprotein, expressed on the surface of many cell types, whose physiological functions are largely unknown. Protein dimerisation should be required for catalytic activity and glycosylation of the enzyme could impact on its physiological functions. The dimeric glycoprotein ADCP has been found linked to adenosine deaminase (ADA) whose relationship with lymphocyte maturation-differentiation is well-established. Since implicated in the regulation of the biological activity of hormones and chemokines, such as glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, DPP4 inhibition offers a new potential therapeutic approach for type 2 diabetes mellitus, as monotherapy and adjunct therapy to other oral agents. The clinical use of presently available orally active inhibitors of DPP4, however, has been associated with side effects that have been in part attributed to the inhibition of related serine proteases, such as DPP8 and DPP9. Indeed, it is noteworthy that CD26 has a key role in immune regulation as a T cell activation molecule and in immune-mediated disorder. All-cause infections were increased after sitagliptin treatment. It is noteworthy that the effects of DPP4 inhibition on the immune system have not been extensively investigated. So far, only routine laboratory safety variables have been measured in published randomised controlled trials. The review summarises present knowledge in the field and suggests some potential directions of future research.

Decay properties of exotic N ≅ 28 S and Cl nuclei and the 48Ca/46Ca abundance ratio

International Nuclear Information System (INIS)

Sorlin, O.; Guillemaud-Mueller, D.; Mueller, A.C.; Borrel, V.; Dogny, S.; Pougheon, F.; Anne, R.; Lewitowicz, M.; Saint-Laurent, M.G.; Borcea, C.; Fifield, L.K.; Bazin, D.; Thielemann, F.K.; Hillebrandt, W.

1992-01-01

Beta-decay half-lives and β-delayed neutron-emission probabilities of the very neutron-rich nuclei 44 S and 45-47 Cl have been measured. These isotopes, which lie at or close to the N=28 magic shell were produced in interactions of a 60 MeV/u 48 Ca beam from GANIL (Grand Accelerateur National d'Ions Lourds) with a 64 Ni target and were separated by the doubly achromatic spectrometer LISE (Ligne d'Ions Super Epluches). Their decay was studied by a β-n time correlation measurement. The results are compared to recent model predictions and indicate a rapid weakening of the N=28 shell effect below 48 20 Ca 28 . The nuclear structure effects reflected in the decay properties of the exotic S and Cl isotopes may be the clue for the astrophysical understanding of the unusual 48 Ca/ 46 Ca abundance ratio measured in the solar system as well as the Ca-Ti-Cr anomalies observed in EK-inclusions of the Allende meteorite

St. Louis FUSRAP Lessons Learned

International Nuclear Information System (INIS)

Eberlin, J.; Williams, D.; Mueller, D.

2003-01-01

The purpose of this paper is to present lessons learned from fours years' experience conducting Remedial Investigation and Remedial Action activities at the St. Louis Downtown Site (SLDS) under the Formerly Utilized Sites Remedial Action Program (FUSRAP). Many FUSRAP sites are experiencing challenges conducting Remedial Actions within forecasted volume and budget estimates. The St. Louis FUSRAP lessons learned provide insight to options for cost effective remediation at FUSRAP sites. The lessons learned are focused on project planning (budget and schedule), investigation, design, and construction

A Relevant Lesson: Hitler Goes to the Mall

Science.gov (United States)

Gerwin, David

2003-01-01

A "Motivation" eliciting the "Aim" of each lesson initiates each lesson in the orthodox "developmental lesson-plan" that has dominated classroom instruction in NYC public schools for at least the past half-century. An action-research study of 38 lesson-plans (over 5 each from 5 teachers) drawn from student-teaching…

Electricity reform in Argentina: Lessons for developing countries

Energy Technology Data Exchange (ETDEWEB)

Pollitt, Michael [Judge Business School and ESRC Electricity Policy Research Group, University of Cambridge (United Kingdom)

2008-07-15

Argentina was one of the first countries in the world to implement a comprehensive reform of its electricity sector. Among developing countries only Chile has had a comparably comprehensive and successful reform. This paper traces the history of the Argentine reform, which began in 1992, and assesses its progress and its lessons. We conclude that the reform was very successful prior to the collapse of the Argentine peso in early 2002. We suggest lessons for the generation, transmission and distribution (and retailing) sectors, as well as the economic regulation of electricity and the general institutional environment. We note that the achievements of the sector have been severely strained by the government's poor energy policy since the crisis. (author)

DoD’s Response When Psychological Health is Failing: Lessons Learned from Suicide Experiences. A survivor and clinician’s perspective on how suicide prevention efforts can be enhanced within the Department

Science.gov (United States)

2011-01-26

When Psychological Health is Failing: Lessons Learned from Suicide Experiences January 26, 2011 COL George D. Patrin, MD, FACHE, FAAP T e Quadruple...26 JAN 2011 2. REPORT TYPE 3. DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE DoD’s Response When Psychological Health is Failing...provider)  Family Hx of multiple severe mental health diagnoses - depression, bipolar, schizophrenia, bulimia , alcoholism, autism  Social Hx

The Role of Content in Inquiry-Based Elementary Science Lessons: An Analysis of Teacher Beliefs and Enactment

Science.gov (United States)

Furtak, Erin Marie; Alonzo, Alicia C.

2010-05-01

The Trends in International Mathematics and Science Study (TIMSS) Video Study explored instructional practices in the United States (US) in comparison with other countries that ranked higher on the 1999 TIMSS assessment, and revealed that 8th grade science teachers in the US emphasize activities over content during lessons (Roth et al. 2006). This study applies the content framework from the TIMSS Video Study to a sample of 28 3rd grade teachers enacting an inquiry-based unit on floating and sinking, and seeks a deeper understanding of teachers’ practices through analysis of interviews with those teachers. Transcripts of observed lessons were coded according to the TIMSS framework for types of content, and transcripts of teacher interviews were coded to capture the ways in which teachers described their role in and purposes for teaching science, particularly with respect to the floating and sinking unit. Results indicate that teachers focused more on canonical, procedural and experimental knowledge during lessons than on real-world connections and the nature of science; however, none of the types of content received major emphasis in a majority of the classrooms in the sample. During interviews, teachers described their practice in ways that prioritized helping students to like science over specific content outcomes. The study suggests that elementary school teachers’ emphasis on doing and feeling during inquiry-based lessons may interfere with teaching of content.

Dipeptidyl peptidase IV inhibitors derived from a mangrove flora Rhizophora mucronata: An in silico approach

Directory of Open Access Journals (Sweden)

Selvaraj Gurudeeban

2012-08-01

Full Text Available Dipeptidyl peptidase IV (DPP IV is responsible for conversion of glucose tolerance (GLP-1, into inactive form. The inhibition of DPP IV would be beneficial in the treatment of diabetes mellitus. Therefore, the aim of the present study was to isolate and evaluate cystine, phenyl acetic acid, acrylamide, caprylone and oleic acid from Rhizophora mucronata inhibitory action on DPP IV inhibitors using in silico approach. In silico analysis of cystine, phenyl acetic acid, acrylamide, caprylone and oleic acid on human apo DPP IV protein was done by using Autodoc 4.0. Among the five compounds cysteine acts as an inhibitor with binding energy -5.89 kcal/mol, seven hydrogen bond interactions at residues VAL459, VAL 459, GLU408, GLU206, ARG358, GLU205 and SER209 to suppresses the action of DPP IV protein.

Identification of Dh/+ and Dh/Dh embryos through close linkage of Dh and peptidase-3.

Science.gov (United States)

Holmes, L B

1986-12-01

The close linkage between the genes Dominant hemimelia (Dh) and peptidase-3 (Pep-3) has been determined in 65 informative matings with the recombination frequency of 3.8%. Progeny testing showed that nonpenetrance does occur in Dh/+ adults. The presence of the "slow" and "fast" variants of Pep-3 can be determined in homogenates of kidney tissue as well as in a portion of the day 10 and 11 embryos. In a litter of embryos born to an informative mating, those which are Dh/Dh, Dh/+, and +/+ can be distinguished by the presence of the Pep-3 allele known to be in coupling with the Dh gene. This technique makes it possible to identify and to study the limb malformations and other phenotypic effects of Dh during their development and before the limb deformity is visible.

Kenya’s Life Lessons through the Lived Experience of Rural Caregivers

Directory of Open Access Journals (Sweden)

Amy Cappiccie

2017-11-01

Full Text Available This qualitative research study used a phenomenological lens to examine the perspectives of familial caregivers in the Laikipia Region of Kenya. Through the narrative of the caregivers’ lived experience, key factors identified included social supports, rewards of caregiving, and lessons to others. Overarching basic themes centered on food insecurity, disease, rejection, lack of support, education challenges, inadequate land ownership, the absence of male support and neglect issues. These unique perspectives can contribute towards our understanding of policy and programming needs for orphaned children and familial caregivers in rural Kenya and within the rural areas of the East African context.

Global polio eradication initiative: lessons learned and legacy.

Science.gov (United States)

Cochi, Stephen L; Freeman, Andrew; Guirguis, Sherine; Jafari, Hamid; Aylward, Bruce

2014-11-01

The world is on the verge of achieving global polio eradication. During >25 years of operations, the Global Polio Eradication Initiative (GPEI) has mobilized and trained millions of volunteers, social mobilizers, and health workers; accessed households untouched by other health initiatives; mapped and brought health interventions to chronically neglected and underserved communities; and established a standardized, real-time global surveillance and response capacity. It is important to document the lessons learned from polio eradication, especially because it is one of the largest ever global health initiatives. The health community has an obligation to ensure that these lessons and the knowledge generated are shared and contribute to real, sustained changes in our approach to global health. We have summarized what we believe are 10 leading lessons learned from the polio eradication initiative. We have the opportunity and obligation to build a better future by applying the lessons learned from GPEI and its infrastructure and unique functions to other global health priorities and initiatives. In so doing, we can extend the global public good gained by ending for all time one of the world's most devastating diseases by also ensuring that these investments provide public health dividends and benefits for years to come. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

19 CFR 111.28 - Responsible supervision.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Responsible supervision. 111.28 Section 111.28 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY CUSTOMS BROKERS Duties and Responsibilities of Customs Brokers § 111.28 Responsible supervision. (a) General. Every individual broker...

Beautiful Beads: A Lesson in Making Beads with Friendly Clay. AMACO[R] Lesson.

Science.gov (United States)

Gamble, Harriet; Gamble, David

This lesson resource includes a brief summary of the history of bead making and historic fascination with beads as adornment. A focus on design elements, color theory, craftsmanship, and technical skill in bead making is encouraged. The plan includes lesson goals and objectives; background preparation; a glossary of terms; a list of supplies; and…

Lesson study on 2nd grader of elementary school to improve the student’s numeracy skill

Science.gov (United States)

Prabowo, A.; Asih; Jumardi

2018-03-01

The purpose of this research is to find the most appropriate learning media of multiplication and division for the 2nd graders of elementary school. The study used the steps in the lesson study, Plan-Do-See. Data were taken using observation instruments, video documentation, and learning evaluation tools. Initially, teachers used gravel as media of multiplication and division. Students can solve numeracy problems when they learn by those media. In test, 80% of students were failure when the teacher evaluates them. By involving experts and partner teachers at school, classroom teachers can solve problems by discover multiplication and division media with the drawing media created by the students themselves. At the end of the lesson, 100% of students have mastered multiplication and division with the media.

Low-Temperature Projects of the Department of Energy's Geothermal Technologies Program: Evaluation and Lessons Learned: Preprint

Energy Technology Data Exchange (ETDEWEB)

Williams, Tom; Snyder, Neil; Gosnold, Will

2016-12-01

This paper discusses opportunities and challenges related to the technical and economic feasibility of developing power generation from geothermal resources at temperatures of 150 degrees C and lower. Insights from projects funded by the U.S. Department of Energy (DOE), Geothermal Technologies Office inform these discussions and provide the basis for some lessons learned to help guide decisions by DOE and the industry in further developing this resource. The technical basis for low-temperature geothermal energy is well established and the systems can be economic today in certain situations. However, these applications are far from a 'plug and play' product; successful development today requires a good knowledge of geothermal system design and operation.

Albumin Redhill (-1 Arg, 320 Ala → Thr): A glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site

International Nuclear Information System (INIS)

Brennan, S.O.; Myles, T.; Peach, R.J.; George, P.M.; Donaldson, D.

1990-01-01

Albumin Redhill is an electrophoretically slow genetic variant of human serum albumin that does not bind 63 Ni 2+ and has a molecular mass 2.5 kDa higher than normal albumin. Its inability to bind Ni 2+ was explained by the finding of an additional residue of Arg at position -1. This did not explain the molecular basis of the genetic variation or the increase in apparent molecular mass. Fractionation of tryptic digests on concanavalin A-Sepharose followed by peptide mapping of the bound and unbound fractions and sequence analysis of the glycopeptides identified a mutation of 320 Ala → Thr. This introduces as Asn-Tyr-Thr oligosaccharide attachment sequence centered on Asn-318 and explains the increase in molecular mass. This, however, did not satisfactorily explain the presence of the additional Arg residue at position -1. DNA sequencing of polymerase chain reaction-amplified genomic DNA encoding the prepro sequence of albumin indicated an additional mutation of -2 Arg → Cys. The authors propose that the new Phe-Cys-Arg sequence in the propeptide is an aberrant signal peptidase cleavage site and that the signal peptidase cleaves the propeptide of albumin Redhill in the lumen of the endoplasmic reticulum before it reaches the Golgi vesicles, the site of the diarginyl-specific proalbumin convertase

Lessons Learned

Directory of Open Access Journals (Sweden)

Amanda Phelan BNS, MSc, PhD

2015-03-01

Full Text Available The public health nurses’ scope of practice explicitly includes child protection within their role, which places them in a prime position to identify child protection concerns. This role compliments that of other professions and voluntary agenices who work with children. Public health nurses are in a privileged position as they form a relationship with the child’s parent(s/guardian(s and are able to see the child in its own environment, which many professionals cannot. Child protection in Ireland, while influenced by other countries, has progressed through a distinct pathway that streamlined protocols and procedures. However, despite the above serious failures have occurred in the Irish system, and inquiries over the past 20 years persistently present similar contributing factors, namely, the lack of standardized and comprehensive service responses. Moreover, poor practice is compounded by the lack of recognition of the various interactional processes taking place within and between the different agencies of child protection, leading to psychological barriers in communication. This article will explore the lessons learned for public health nurses practice in safeguarding children in the Republic of Ireland.

Experiment data report for Semiscale Mod-1 Test S-28-1 (steam generator tube rupture test series)

International Nuclear Information System (INIS)

Collins, B.L.; Coppin, C.E.; Sackett, K.E.

1977-10-01

Recorded test data are presented for Test S-28-1 of the Semiscale Mod-1 steam generator tube rupture test series. These tests are among several Semiscale Mod-1 experiments conducted to investigate the thermal and hydraulic phenomena accompanying a hypothesized loss-of-coolant accident in a pressurized water reactor (PWR) system. Test S-28-1 was conducted from initial conditions of 15 767 kPa and 557 K to investigate the response of the Semiscale Mod-1 system to a depressurization and reflood transient following a simulated double-ended offset shear of the broken loop cold leg piping. During the test, cooling water was injected into the cold leg of the intact and broken loops to simulate emergency core coolant injection in a PWR. Sixty steam generator tube ruptures were simulated by a controlled injection from a heated accumulator into the intact loop hot leg

Microencapsulate Aspergillus niger peptidases from agroindustrial waste wheat bran: spray process evaluation and stability.

Science.gov (United States)

Cabral, T P F; Bellini, N C; Assis, K R; Teixeira, C C C; Lanchote, A D; Cabral, H; Freitas, L A P

2017-09-01

The aim of this work was to obtain microencapsulated stable Aspergillus niger peptidases by post fermentation spray drying. The enzymatic extract was evaluated before and after spray drying microencapsulation to verify the effects of five different process parameters on the extract enzymatic activity, i.e. air flow, extract feed rate, drying temperature, homogenising time and weight ratio of extract to encapsulation material. The optimal conditions were determined by desirability functions and experimentally confirmed. Additionally, the stability of the microparticles was assessed during 60 days at 4 °C, 25 °C and 40 °C. The results revealed that the microparticles stored at 4 °C retained approximately 100% of their proteolytic activity at nine days of storage. Considering the industrial adaptation of the bioprocess and the prospect of commercial application of the proteases, the evaluation of different parameters for drying enzymes is required as a valuable alternative to obtain biotechnological products with high added value.

Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium.

Science.gov (United States)

Morikawa, Toshio; Ninomiya, Kiyofumi; Akaki, Junji; Kakihara, Namiko; Kuramoto, Hiroyuki; Matsumoto, Yurie; Hayakawa, Takao; Muraoka, Osamu; Wang, Li-Bo; Wu, Li-Jun; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi

2015-10-01

A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC50 = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V-VII (2-4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2-4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2'-O-β-D-glucopyranoside (16, IC50 = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

MAP kinase-signaling controls nuclear translocation of tripeptidyl-peptidase II in response to DNA damage and oxidative stress

Energy Technology Data Exchange (ETDEWEB)

Preta, Giulio; Klark, Rainier de; Chakraborti, Shankhamala [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden); Glas, Rickard, E-mail: rickard.glas@ki.se [Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm (Sweden)

2010-08-27

Research highlights: {yields} Nuclear translocation of TPPII occurs in response to different DNA damage inducers. {yields} Nuclear accumulation of TPPII is linked to ROS and anti-oxidant enzyme levels. {yields} MAPKs control nuclear accumulation of TPPII. {yields} Inhibited nuclear accumulation of TPPII decreases DNA damage-induced {gamma}-H2AX expression. -- Abstract: Reactive oxygen species (ROS) are a continuous hazard in eukaroytic cells by their ability to cause damage to biomolecules, in particular to DNA. Previous data indicated that the cytosolic serine peptidase tripeptidyl-peptidase II (TPPII) translocates into the nucleus of most tumor cell lines in response to {gamma}-irradiation and ROS production; an event that promoted p53 expression as well as caspase-activation. We here observed that nuclear translocation of TPPII was dependent on signaling by MAP kinases, including p38MAPK. Further, this was caused by several types of DNA-damaging drugs, a DNA cross-linker (cisplatinum), an inhibitor of topoisomerase II (etoposide), and to some extent also by nucleoside-analogues (5-fluorouracil, hydroxyurea). In the minority of tumor cell lines where TPPII was not translocated into the nucleus in response to DNA damage we observed reduced intracellular ROS levels, and the expression levels of redox defense systems were increased. Further, treatment with the ROS-inducer {gamma}-hexa-chloro-cyclohexane ({gamma}-HCH, lindane), an inhibitor of GAP junctions, restored nuclear translocation of TPPII in these cell lines upon {gamma}-irradiation. Moreover, blocking nuclear translocation of TPPII in etoposide-treated cells, by using a peptide-derived inhibitor (Z-Gly-Leu-Ala-OH), attenuated expression of {gamma}-H2AX in {gamma}-irradiated melanoma cells. Our results indicated a role for TPPII in MAPK-dependent DNA damage signaling.

Progress and Lessons Learned in Transuranic Waste Disposition at The Department of Energy's Advanced Mixed Waste Treatment Project

Energy Technology Data Exchange (ETDEWEB)

J.D. Mousseau; S.C. Raish; F.M. Russo

2006-05-18

This paper provides an overview of the Department of Energy's (DOE) Advanced Mixed Waste Treatment Project (AMWTP) located at the Idaho National Laboratory (INL) and operated by Bechtel BWXT Idaho, LLC(BBWI) It describes the results to date in meeting the 6,000-cubic-meter Idaho Settlement Agreement milestone that was due December 31, 2005. The paper further describes lessons that have been learned from the project in the area of transuranic (TRU) waste processing and waste certification. Information contained within this paper would be beneficial to others who manage TRU waste for disposal at the Waste Isolation Pilot Plant (WIPP).

Lessons Learned from a Decade of Sudden Oak Death in California: Evaluating Local Management

Science.gov (United States)

Alexander, Janice; Lee, Christopher A.

2010-09-01

Sudden Oak Death has been impacting California’s coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California’s wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks.

Analysing the Integration of Engineering in Science Lessons with the Engineering-Infused Lesson Rubric

Science.gov (United States)

Peterman, Karen; Daugherty, Jenny L.; Custer, Rodney L.; Ross, Julia M.

2017-01-01

Science teachers are being called on to incorporate engineering practices into their classrooms. This study explores whether the Engineering-Infused Lesson Rubric, a new rubric designed to target best practices in engineering education, could be used to evaluate the extent to which engineering is infused into online science lessons. Eighty lessons…

Lesson plan profile of senior high school biology teachers in Subang

Science.gov (United States)

Rohayati, E.; Diana, S. W.; Priyandoko, D.

2018-05-01

Lesson plan have important role for biology teachers in teaching and learning process. The aim of this study was intended to gain an overview of lesson plan of biology teachers’ at Senior High Schools in Subang which were the members of biology teachers association in Subang. The research method was descriptive method. Data was collected from 30 biology teachers. The result of study showed that lesson plan profile in terms of subject’s identity had good category with 83.33 % of average score. Analysis on basic competence in fair category with 74.45 % of average score. The compatibility of method/strategy was in fair category with average score 72.22 %. The compatibility of instrument, media, and learning resources in fair category with 71.11 % of average score. Learning scenario was in good category with 77.00 % of average score. The compatibility of evaluation was in low category with 56.39 % of average score. It can be concluded that biology teachers in Subang were good enough in making lesson plan, however in terms of the compatibility of evaluation needed to be fixed. Furthermore, teachers’ training for biology teachers’ association was recommended to increasing teachers’ skill to be professional teachers.

Lessons learned from Spain's nuclear program

International Nuclear Information System (INIS)

Garcia Rodriguez, A.

1993-01-01

The commercial nuclear program in Spain dates back to the beginning of the 1960s. There are currently nine units in operation, one more has been decommissioned and a further five are in different phases of construction but under nuclear moratorium since 1983. This article gives a general overview of the program, the criteria applied, what it has meant to and required of the industry and, finally, what lessons have been learned. (author) 2 figs

ISO 50001 for Commercial Buildings: Lessons Learned From U.S. DOE Pilot Project: Preprint

Energy Technology Data Exchange (ETDEWEB)

Deru, M.; Field, K.; Punjabi, S.

2014-08-01

In the U.S., the ISO 50001 Standard, which establishes energy management systems (EnMSs) and processes, has shown uptake primarily in the industrial sector. The U.S. Department of Energy (DOE) undertook a pilot program to explore ISO 50001 implementation in commercial buildings. Eight organizations participated as pilots, with technical assistance provided by DOE, the National Renewable Energy Laboratory (NREL), the Lawrence Berkeley National Laboratory (LBNL), and the Georgia Institute of Technology (Georgia Tech). This paper shares important lessons learned from the pilot. Staff time was the most critical resource required to establish effective EnMSs in commercial buildings. The pilot also revealed that technical support and template/example materials were essential inputs. Crucial activities included evaluating performance, identifying goals, making connections, communicating operational controls, and tracking/reviewing progress. Benefits realized included enhanced intra-organizational connections, greater energy awareness, increased process efficiencies, and improved ability to make business cases. Incremental benefits for ISO 50001 certification were greater accountability, assurance of best practices, public relations opportunities, and potential to unlock verified savings credits or incentive money. Incremental certification costs included more staff/consultant time, money for certification, and a tendency to limit EnMS scope in order to ensure favorable audit results. Five best practices were identified - utilizing expert technical assistance, training, and other resources; focusing on implementation over documentation; keeping top management involved; considering organizational structure when selecting EnMS scope; and matching the implementation level to an EnMS's scope and scale. The last two practices are particularly relevant to the commercial buildings sector.

The Fernald Closure Project: Lessons Learned

International Nuclear Information System (INIS)

Murphy, Cornelius M.; Carr, Dennis

2008-01-01

For nearly 37 years, the U.S. Department of Energy site at Fernald - near Cincinnati, Ohio - produced 230,000 metric tons (250,000 short tons) of high-purity, low-enriched uranium for the U.S. Defense Program, generating more than 5.4 million metric tons (6 million short tons) of liquid and solid waste as it carried out its Cold War mission. The facility was shut down in 1989 and clean up began in 1992, when Fluor won the contract to clean up the site. Cleaning up Fernald and returning it to the people of Ohio was a $4.4 billion mega environmental-remediation project that was completed in October 2006. Project evolved through four phases: - Conducting remedial-investigation studies to determine the extent of damage to the environment and groundwater at, and adjacent to, the production facilities; - Selecting cleanup criteria - final end states that had to be met that protect human health and the environment; - Selecting and implementing the remedial actions to meet the cleanup goals; - Executing the work in a safe, compliant and cost-effective manner. In the early stages of the project, there were strained relationships - in fact total distrust - between the local community and the DOE as a result of aquifer contamination and potential health effects to the workers and local residents. To engage citizens and interested stakeholders groups in the decision-making process, the DOE and Fluor developed a public-participation strategy to open the channels of communication with the various parties: site leadership, technical staff and regulators. This approach proved invaluable to the success of the project, which has become a model for future environmental remediation projects. This paper will summarize the history and shares lessons learned: the completion of the uranium-production mission to the implementation of the Records of Decision defining the cleanup standards and the remedies achieved. Lessons learned fall into ten categories: - Regulatory approach with end

MODIS Science Algorithms and Data Systems Lessons Learned

Science.gov (United States)

Wolfe, Robert E.; Ridgway, Bill L.; Patt, Fred S.; Masuoka, Edward J.

2009-01-01

For almost 10 years, standard global products from NASA's Earth Observing System s (EOS) two Moderate Resolution Imaging Spectroradiometer (MODIS) sensors are being used world-wide for earth science research and applications. This paper discusses the lessons learned in developing the science algorithms and the data systems needed to produce these high quality data products for the earth sciences community. Strong science team leadership and communication, an evolvable and scalable data system, and central coordination of QA and validation activities enabled the data system to grow by two orders of magnitude from the initial at-launch system to the current system able to reprocess data from both the Terra and Aqua missions in less than a year. Many of the lessons learned from MODIS are already being applied to follow-on missions.

4. 7s nearly periodic oscillations superimposed on the solar microwave great burst of 28 March 1976

Energy Technology Data Exchange (ETDEWEB)

Kaufmann, P; Piazza, L R; Raffaelli, J C [Universidade Mackenzie, Sao Paulo (Brazil). Centro de Radio-Astronomia e Astrofisica

1977-09-01

An unusual fast oscillation was found superimposed on the solar great burst on 28 March 1976, as measured at 7 GHz. The period of the oscillation was 4.7 +- 0.9 s, defined over the entire duration of the event. The amplitude of the oscillation was proportional to the flux density in the range 50<S<3000 solar flux units. The degree of circular polarization has not shown any fast periodic time structure.

Molecular systematic of three species of Oithona (Copepoda, Cyclopoida from the Atlantic Ocean: comparative analysis using 28S rDNA.

Directory of Open Access Journals (Sweden)

Georgina D Cepeda

Full Text Available Species of Oithona (Copepoda, Cyclopoida are highly abundant, ecologically important, and widely distributed throughout the world oceans. Although there are valid and detailed descriptions of the species, routine species identifications remain challenging due to their small size, subtle morphological diagnostic traits, and the description of geographic forms or varieties. This study examined three species of Oithona (O. similis, O. atlantica and O. nana occurring in the Argentine sector of the South Atlantic Ocean based on DNA sequence variation of a 575 base-pair region of 28S rDNA, with comparative analysis of these species from other North and South Atlantic regions. DNA sequence variation clearly resolved and discriminated the species, and revealed low levels of intraspecific variation among North and South Atlantic populations of each species. The 28S rDNA region was thus shown to provide an accurate and reliable means of identifying the species throughout the sampled domain. Analysis of 28S rDNA variation for additional species collected throughout the global ocean will be useful to accurately characterize biogeographical distributions of the species and to examine phylogenetic relationships among them.

Lessons from Queer Bioethics: A Response to Timothy F. Murphy.

Science.gov (United States)

Richie, Cristina

2016-06-01

'Bioethics still has important work to do in helping to secure status equality for LGBT people' writes Timothy F. Murphy in a recent Bioethics editorial. The focus of his piece, however, is much narrower than human rights, medical care for LGBT people, or ending the HIV/AIDS pandemic. Rather, he is primarily concerned with sexuality and gender identity, and the medical intersections thereof (i.e. DSM diagnosis; access to SrS or ARTs). It is the objective of this response to provide an alternate account of bioethics from a Queer perspective. I will situate Queer bioethics within Queer studies, and offer three 'lessons' that bioethics can derive from this perspective. These are not definitive rules for Queer bioethics, since it is a field which fundamentally opposes categorizations, favoring pastiche over principles. These lessons are exploratory examples, which both complement and contradict LGBT bioethics. My latter two lessons - on environmental bioethics and disability - overlap with some of Murphy's concerns, as well as other conceptions of LGBT bioethics. However, the first lesson takes an antithetical stance to Murphy's primary focus by resisting all forms of heteroconformity and disavowing reproduction as consonant with Queer objectives and theory. The first lesson, which doubles as a primer in Queer theory, does heavy philosophical lifting for the remainder of the essay. This response to Timothy F. Murphy, whose work is certainly a legacy in bioethics, reveals the multiplicity of discourses in LGBT/Queer studies, many of which are advantageous - even essential - to other disciplines like bioethics. © 2016 John Wiley & Sons Ltd.

Decade of War: Applying Past Lessons to the Counter-ISIS Campaign

Science.gov (United States)

2017-05-22

then-Chairman of the Joint Chiefs of Staff General Martin Dempsey called for the U.S. military to “learn the lessons from the past decade of operations...1 Executive summary In 2012, then-Chairman of the Joint Chiefs of Staff General Martin Dempsey called for the U.S. military to “learn

The value teleradiology represents for Europe: A study of lessons learned in the U.S

International Nuclear Information System (INIS)

Pechet, Tiron C.M.; Girard, Greg; Walsh, Brent

2010-01-01

Pathology and demography have combined to fuel exponential demand for advanced medical imaging. To support this demand, radiology must move beyond traditional department or modality-based picture archiving and communication systems (PACS) to solutions that ensure access regardless of location. This article delineates underlying reasons for the growth in demand for access to medical imaging in both Europe and the United States. It explains why teleradiology/PACS is critical to support this growth in Europe. It discusses the benefits of and barriers to its widespread implementation as discovered in Canada and the U.S. and how these lessons learned relate to Europe. The article establishes the technological imperatives for teleradiology/PACS and presents three real-world case studies of successful data sharing and shared workflow models via single imaging implementations. CML HealthCare: Geographically spanning Canada and the United States with 129 sites performing nearly 5 million plus annual exams. Shields MRI: 29 facilities, including 3 Radiation Oncology centers, across an area 4 times the size of Switzerland. MRA/Novant: 40 radiologists working in a complete subspecialty reporting environment. Finally, it provides a high-level list of selection criteria for teleradiology/PACS and examines how industry trends affecting the U.S. are important baseline considerations to the success of teleradiology/PACS in Europe.

Why Germany's 'Messy' energy transition should be a lesson to other nations

Energy Technology Data Exchange (ETDEWEB)

Shepherd, John [nuclear 24, Brighton (United Kingdom)

2015-03-15

Germany's so-called ''energy transition'' (''Energiewende'') is increasingly drawing the intention of the international community - but it seems for all the wrong reasons. US Senator Lamar Alexander said recently that German energy policy is one of the reasons the US should not abandon nuclear, but actually encourage increased investment in nuclear power plants. Alexander's remarks were made in an article published by the US Nuclear Energy Institute, in which he outlined his reasons why the US should not follow Germany's lead. Alexander rightly pointed out that the cost of attempting to replace nuclear power with wind, solar, and accompanying infrastructure is estimated by the German government at some 1.2 trillion US dollars (about 1 trillion Euros). The senator also made the point that Germany ''does not produce enough reliable, baseload energy for an important manufacturing economy''. He also expressed concern at Germany's reliance on buying natural gas from Russia. While Germany has been forcing the closure of nuclear power plants others, including the oil-rich United Arab Emirates (UAE), have been investing in new nuclear, Alexander said. Judging from Alexander's remarks, it seems that Germany's energy transition experience will, after all, have a long-lasting legacy. That legacy will be a valuable lesson to other major industrialised nations in why they should not follow Germany's lead in abandoning a sensible energy mix, if they wish to maintain and develop economic and industrial productivity while keeping to international commitments to tackle climate change.

The Date That Lives in Infamy: Pearl Harbor Lesson Plans.

Science.gov (United States)

Department of the Navy, Washington, DC.

This lesson plan can help teachers and students understand what happened on December 7, 1941, beginning with the first U.S. treaty with Japan in 1854 through the attacks in 1941. Students use primary sources to synthesize information and draw conclusions about the role of the U.S. Navy in foreign policy and to understand how people in 1941 reacted…

Feedback suppression of meal-induced glucagon-like peptide-1 (GLP-1) secretion mediated through elevations in intact GLP-1 caused by dipeptidyl peptidase-4 inhibition

DEFF Research Database (Denmark)

Baranov, Oleg; Kahle, Melanie; Deacon, Carolyn F

2016-01-01

AIM: To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by dipeptidyl peptidase (DPP-4) inhibition. METHODS: A total of 24 patients (12 on a diet/exercise re......AIM: To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L-cell feedback inhibition induced by dipeptidyl peptidase (DPP-4) inhibition. METHODS: A total of 24 patients (12 on a diet....../exercise regimen, 12 on metformin) were treated, in randomized order, for 7-9 days, with either vildagliptin (50 mg twice daily = 100 mg/d), sitagliptin (100 mg once daily in those on diet, 50 mg twice daily in those on metformin treatment = 100 mg/d) or placebo (twice daily). A mixed-meal test was performed....... RESULTS: Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide concentrations were doubled by both DPP-4 inhibitors. Meal-related total GLP-1 responses were reduced by vildagliptin and sitagliptin treatment alike in the majority of patients (vildagliptin: p = 0...

Production and characterization of two major Aspergillus oryzae secreted prolyl endopeptidases able to efficiently digest proline-rich peptides of gliadin.

Science.gov (United States)

Eugster, Philippe J; Salamin, Karine; Grouzmann, Eric; Monod, Michel

2015-12-01

Prolyl endopeptidases are key enzymes in the digestion of proline-rich proteins. Fungal extracts rich in prolyl endopeptidases produced by a species such as Aspergillus oryzae used in food fermentation would be of particular interest for the development of an oral enzyme therapy product in patients affected by intolerance to gluten. Two major A. oryzae secreted prolyl endopeptidases of the MEROPS S28 peptidase family, AoS28A and AoS28B, were identified when this fungus was grown at acidic pH in a medium containing soy meal protein or wheat gliadin as the sole source of nitrogen. AoS28B was produced by 12 reference A. oryzae strains used in food fermentation. AoS28A was secreted by six of these 12 strains. This protease is the orthologue of the previously characterized Aspergillus fumigatus (AfuS28) and Aspergillus niger (AN-PEP) prolyl endopeptidases which are encoded by genes with a similar intron-exon structure. Large amounts of secreted AoS28A and AoS28B were obtained by gene overexpression in A. oryzae. AoS28A and AoS28B are endoproteases able to cleave N-terminally blocked proline substrates. Both enzymes very efficiently digested the proline-rich 33-mer of gliadin, the most representative immunotoxic peptide deriving from gliadin, with some differences in terms of specificity and optimal pH. Digestion of the gliadin peptide in short peptides with both enzymes was found to occur from its N terminus.

Structural and computational analysis of peptide recognition mechanism of class-C type penicillin binding protein, alkaline D-peptidase from Bacillus cereus DF4-B

OpenAIRE

Nakano, Shogo; Okazaki, Seiji; Ishitsubo, Erika; Kawahara, Nobuhiro; Komeda, Hidenobu; Tokiwa, Hiroaki; Asano, Yasuhisa

2015-01-01

Alkaline D-peptidase from Bacillus cereus DF4-B, called ADP, is a D-stereospecific endopeptidase reacting with oligopeptides containing D-phenylalanine (D-Phe) at N-terminal penultimate residue. ADP has attracted increasing attention because it is useful as a catalyst for synthesis of D-Phe oligopeptides or, with the help of substrate mimetics, L-amino acid peptides and proteins. Structure and functional analysis of ADP is expected to elucidate molecular mechanism of ADP. In this study, the c...

Automated Reasoning Across Tactical Stories to Derive Lessons Learned

Directory of Open Access Journals (Sweden)

J. Wesley Regian

2008-06-01

Full Text Available The Military Analogical Reasoning System (MARS is a performance support system and decision aid for commanders in Tactical Operations Centers. MARS enhances and supports the innate human ability for using stories to reason about tactical goals, plans, situations, and outcomes. The system operates by comparing many instances of stored tactical stories, determining which have analogous situations and lessons learned, and then returning a description of the lessons learned. The description of the lessons learned is at a level of abstraction that can be generalized to an appropriate range of tactical situations. The machine-understandable story representation is based on a military operations data model and associated tactical situation ontology. Thus each story can be thought of, and reasoned about, as an instance of an unfolding tactical situation. The analogical reasoning algorithm is based on Gentner's Structure Mapping Theory. Consider the following two stories. In the first, a U.S. platoon in Viet Nam diverts around a minefield and subsequently comes under ambush from a large hill overlooking their new position. In the second, a U.S. task force in Iraq diverts around a biochemical hazard and subsequently comes under ambush from the roof of an abandoned building. MARS recognizes these stories as analogical, and derives the following abstraction: When enemy-placed obstacles force us into an unplanned route, beware of ambush from elevation or concealment. In this paper we describe the MARS interface, military operations data model, tactical situation ontology, and analogical reasoning algorithm.

Implementation of lesson study in physics teaching by group of teachers in Solok West Sumatera

Science.gov (United States)

Yurnetti, Y.

2018-04-01

This article based of collaborative classroom action research with science teachers group or MGMP at Solok West Sumatera; based on their willingness to implementation of lesson study by this group. The study started by discussing some problems according to the implementation of the lesson study, establishing the teaching materials, developing learning tools, defining the model teachers, conducting classroom activities, and reflecting by discussions. The preparation of this study includes some learning material according to temperature and heat; the observation form that led by observer teachers; teachers’s model impression and open questionnaire implementation of lesson study that applied to the students and teachers. This research got some information about the strengths and weaknesses of learning using lesson study from the students involved. To conclude, the implementation of lesson study should be able to support the principle of collaborative in learning. The challenge of this study is how to make a condition to gather some teachers in one school at a certain time because they have the schedule at their own school.

Simple and Practical Efficiency Lessons

Science.gov (United States)

Kolpin, Van

2018-01-01

The derivation of conditions necessary for Pareto efficient production and exchange is a lesson frequently showcased in microeconomic theory textbooks. Traditional delivery of this lesson is, however, limited in its scope of application and can be unnecessarily convoluted. The author shows that the universe of application is greatly expanded and a…

Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

Science.gov (United States)

Dasari, Suvarna; Kölling, Ralf

2016-07-01

We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

Challenging Gender in Single-Sex Spaces: Lessons from a Feminist

OpenAIRE

Buzuvis, Erin

2018-01-01

Published: Erin E. Buzuvis, Challenging Gender in Single-Sex Spaces: Lessons from a Feminist, 80 L. & CONTEMP. PROBS. 155 (2017). This Article explores transgender inclusion within adult recreational women’s leagues by using the example of the Mary Vazquez Women’s Softball League (MVWSL), in Northampton, Massachusetts. A MVWSL policy addressing transgender inclusion became necessary due to a noticeable increase in gender-identity diversity. The resultant policy respects the league’s core ...

Planning geometry lessons with learning platforms

DEFF Research Database (Denmark)

Tamborg, Andreas Lindenskov

mathematics teachers’ joint planning of a lesson in geometry with a learning platform called Meebook is analyzed using the instrumental approach. It is concluded that the interface in Meebook orients the teachers work toward what the students should do rather than what they should learn, although the latter......This paper investigates how mathematics teachers plan lessons with a recently implemented Danish learning platform designed to support teachers in planning lessons in line with a recent objective-oriented curriculum. Drawing on data from observations of and interviews with teachers, three...... is a key intention behind the implementation of the platform. It is also concluded that when the teachers succeed in using learning objectives actively in their planning, the objectives support the teachers in designing lessons that correspond with their intentions. The paper concludes with a discussion...

Effect of tailored on-road driving lessons on driving safety in older adults: A randomised controlled trial.

Science.gov (United States)

Anstey, Kaarin J; Eramudugolla, Ranmalee; Kiely, Kim M; Price, Jasmine

2018-06-01

We evaluated the effectiveness of individually tailored driving lessons compared with a road rules refresher course for improving older driver safety. Two arm parallel randomised controlled trial, involving current drivers aged 65 and older (Mean age 72.0, 47.4% male) residing in Canberra, Australia. The intervention group (n = 28) received a two-hour class-based road rules refresher course, and two one-hour driving lessons tailored to improve poor driving skills and habits identified in a baseline on-road assessment. The control group (n = 29) received the road rules refresher course only. Tests of cognitive performance, and on-road driving were conducted at baseline and at 12-weeks. Main outcome measure was the Driver safety rating (DSR) on the on-road driving test. The number of Critical Errors made during the on-road was also recorded. 55 drivers completed the trial (intervention group: 27, control group: 28). Both groups showed reduction in dangerous/hazardous driver errors that required instructor intervention. From baseline to follow-up there was a greater reduction in the number of critical errors made by the intervention group relative to the control group (IRR = 0.53, SE = 0.1, p = .008). The intervention group improved on the DSR more than the control group (intervention mean change = 1.07 SD = 2.00, control group mean change = 0.32 SD = 1.61). The intervention group had 64% remediation of unsafe driving, where drivers who achieved a score of 'fail' at baseline, 'passed' at follow-up. The control group had 25% remediation. Tailored driving lessons reduced the critical driving errors made by older adults. Longer term follow-up and larger trials are required. Copyright © 2018 Elsevier Ltd. All rights reserved.

A bacterial acyl aminoacyl peptidase couples flexibility and stability as a result of cold adaptation.

Science.gov (United States)

Brocca, Stefania; Ferrari, Cristian; Barbiroli, Alberto; Pesce, Alessandra; Lotti, Marina; Nardini, Marco

2016-12-01

Life in cold environments requires an overall increase in the flexibility of macromolecular and supramolecular structures to allow biological processes to take place at low temperature. Conformational flexibility supports high catalytic rates of enzymes in the cold but in several cases is also a cause of instability. The three-dimensional structure of the psychrophilic acyl aminoacyl peptidase from Sporosarcina psychrophila (SpAAP) reported in this paper highlights adaptive molecular changes resulting in a fine-tuned trade-off between flexibility and stability. In its functional form SpAAP is a dimer, and an increase in flexibility is achieved through loosening of intersubunit hydrophobic interactions. The release of subunits from the quaternary structure is hindered by an 'arm exchange' mechanism, in which a tiny structural element at the N terminus of one subunit inserts into the other subunit. Mutants lacking the 'arm' are monomeric, inactive and highly prone to aggregation. Another feature of SpAAP cold adaptation is the enlargement of the tunnel connecting the exterior of the protein with the active site. Such a wide channel might compensate for the reduced molecular motions occurring in the cold and allow easy and direct access of substrates to the catalytic site, rendering transient movements between domains unnecessary. Thus, cold-adapted SpAAP has developed a molecular strategy unique within this group of proteins: it is able to enhance the flexibility of each functional unit while still preserving sufficient stability. Structural data are available in the Protein Data Bank under the accession number 5L8S. © 2016 Federation of European Biochemical Societies.

Masterwork Art Lesson: Kandinsky Watercolors.

Science.gov (United States)

LiPira, Michael

2003-01-01

Presents an art lesson used with sixth-grade students which also can be used with other grade levels. Explains that the artwork of Wassily Kandinsky served as inspiration for this lesson. Explains that the students learned about abstract art and used watercolors to create their own paintings in the style of Kandinsky. (CMK)

Bead Game Simulation. Lesson Plan.

Science.gov (United States)

Ripp, Ken

This lesson plan offers students the opportunity to participate in the three basic economic systems (market, command, and tradition). By working in each of the systems, students will internalize the fundamental values present in each system and will gain insights into the basic advantages and disadvantages of each system. The lesson plan provides…

U.S. DOE’s Energy Treasure Hunt Exchange In-Plant Trainings – DOE Resources, Early Results and Lessons Learned

Energy Technology Data Exchange (ETDEWEB)

Nimbalkar, Sachin U. [ORNL; Brockway, Walter F. [ORNL; Lung, Bruce [U.S. Department of Energy (DOE); Thirumaran, Kiran [ORNL; Wenning, Thomas J. [ORNL

2017-06-01

The primary objective of the Department of Energy’s (DOE) Energy Treasure Hunt In-Plant Training (INPLT) is to train Better Plants partner employees to lead and conduct future energy efficiency Treasure Hunts within their facilities without DOE assistance. By taking a “learning-by-doing” approach, this INPLT, like other DOE INPLT trainings, has the added benefit of uncovering real energy and cost-saving opportunities. This INPLT leverages DOE and Better Plants technical staff, resources and tools and the EPA “Energy Treasure Hunt Guide: Simple Steps to Finding Energy Savings” process. While Treasure Hunts are a relatively well-known approach to identifying energy-savings in manufacturing plants, DOE is adding several additional elements in its Treasure Hunt Exchanges. The first element is technical assistance and methodology. DOE provides high-quality technical resources, such as energy efficiency calculators, fact sheets, source books etc., to facilitate the Treasure Hunt process and teaches four fundamentals: 1) how to profile equipment, 2) how to collect data, and 3), data & ROI calculation methodologies. Another element is the “train the trainer” approach wherein the training facilitator will train at least one partner employee to facilitate future treasure hunts. Another element is that DOE provides energy diagnostic equipment and teaches the participants how to use them. Finally, DOE also offers partners the opportunity to exchange teams of employees either within a partners’ enterprise or with other partners to conduct the treasure hunt in each other’s facilities. This exchange of teams is important because each team can bring different insights and uncover energy-saving opportunities that would otherwise be missed. This paper will discuss DOE methodology and the early results and lessons learned from DOE’S Energy Treasure Hunt In-Plant Trainings at Better Plants Partner facilities.

Implementing US Department of Energy lessons learned programs. Volume 2

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-08-01

The DOE Lessons Learned Handbook is a two-volume publication developed to supplement the DOE Lessons Learned Standard (DOE-STD-7501-95) with information that will organizations in developing or improving their lessons learned programs. Volume 1 includes greater detail than the Standard in areas such as identification and documentation of lessons learned; it also contains sections on specific processes such as training and performance measurement. Volume 2 (this document) contains examples of program documents developed by existing lessons learned programs as well as communications material, functional categories, transmittal documents, sources of professional and industry lessons learned, and frequently asked questions about the Lessons Learned List Service.

Lessons learned from application of the Swedish regulations for decommissioning of nuclear facilities - The regulator's perspective

International Nuclear Information System (INIS)

Efraimsson, Henrik; Amft, Martin; Leisvik, Mathias

2016-01-01

The paper presents an overview of the Swedish regulations for decommissioning of nuclear facilities. It describes some of the experiences that the Swedish Radiation Safety Authority has gained from the application of these regulations. The focus of the present paper lies on administrative aspects of the care and maintenance operation and on the safety related documentation that has to be prepared before dismantling commences. Lessons learned during recent years will be considered when revising the regulations for decommissioning. Also these lessons learned will help to streamline the administration of the large NPP decommissioning projects that are anticipated to commence in Sweden in the near future. (authors)

Physically active academic lessons in elementary children.

Science.gov (United States)

Bartholomew, John B; Jowers, Esbelle M

2011-06-01

Although schools are an ideal location to conduct interventions that target children, the emphasis on standardized testing makes it difficult to implement interventions that do not directly support academic instruction. In response, physically active academic lessons have been developed as a strategy to increase physical activity while also addressing core educational goals. Texas I-CAN! is one incarnation of this approach. We will review the on-going research on the impact of these active lessons on: teacher implementation, child step count, child attention control, and academic performance. The collected studies support the impact of physically active academic lessons on each area of interest. If these data can be replicated, it suggests that teachers might find these lessons of benefit to their primary role as educators, which should ease dissemination of these and other physically active lessons in elementary schools. Copyright © 2011 Elsevier Inc. All rights reserved.

The biomass energy industry of northern New England: Lessons for America

Energy Technology Data Exchange (ETDEWEB)

Connors, J.F. [Maine State Planning Office, Augusta, ME (United States); Keeney, N.H. III [New Hampshire Governor`s Office of Energy and Community Services, Concord, NH (United States)

1993-12-31

The successful development of biomass energy for electricity generation in northern New England (Maine, New Hampshire) was launched by new innovative public policies and the relative competitive advantages of ample supplies of wood residues and forest biomass. Since 1980 over 600 megawatts of wood-fired capacity has been developed, and generates nearly 20% of the two state electricity supply. What are the factors that account for this dramatic development, and what are the lessons for the rest of the America`s? This paper summarizes the influences of public policies, the importance of extensive resources, the power needs of the utilities, the business/investment opportunities for IPP`s, and native strengths in fuel procurement and wood combustion experience. Conclusions are drawn in the form of lessons for other regions, and jurisdictions concerned with attaining the benefits of biomass energy development.

Lesson Study and History Education

Science.gov (United States)

Halvorsen, Anne-Lise; Kesler Lund, Alisa

2013-01-01

This article examines the experiences of a group of fifth-grade teachers who used lesson study, a teacher-driven form of professional development, to teach history in a project supported by a Teaching American History Grant. The project addressed the following questions: What does a lesson study cycle for history education look like? What…

49 CFR 28.152-28.159 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.152-28.159 Section 28.152-28.159 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.152-28.159 [Reserved] ...

49 CFR 28.171-28.999 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.171-28.999 Section 28.171-28.999 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.171-28.999 [Reserved] ...

49 CFR 28.132-28.139 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.132-28.139 Section 28.132-28.139 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.132-28.139 [Reserved] ...

49 CFR 28.161-28.169 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.161-28.169 Section 28.161-28.169 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.161-28.169 [Reserved] ...

49 CFR 28.141-28.148 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.141-28.148 Section 28.141-28.148 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.141-28.148 [Reserved] ...

49 CFR 28.104-28.109 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.104-28.109 Section 28.104-28.109 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.104-28.109 [Reserved] ...

49 CFR 28.112-28.129 - [Reserved

Science.gov (United States)

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false [Reserved] 28.112-28.129 Section 28.112-28.129 Transportation Office of the Secretary of Transportation ENFORCEMENT OF NONDISCRIMINATION ON THE BASIS OF HANDICAP IN PROGRAMS OR ACTIVITIES CONDUCTED BY THE DEPARTMENT OF TRANSPORTATION §§ 28.112-28.129 [Reserved] ...

Value pricing pilot program : lessons learned

Science.gov (United States)

2008-08-01

This "Lessons Learned Report" provides a summary of projects sponsored by the Federal Highway Administration's (FHWA's) Congestion and Value Pricing Pilot Programs from 1991 through 2006 and draws lessons from a sample of projects with the richest an...

"It is the antigen(s), stupid" and other lessons from over a decade of vaccitherapy of human cancer.

Science.gov (United States)

Buckwalter, Matthew R; Srivastava, Pramod K

2008-10-01

The lessons are: (a) human cancers certainly respond to immunological manipulations. Efforts at human cancer immunotherapy are therefore worthwhile. (b) Prophylaxis is very different from therapy of pre-existing disease, and hence much enthusiasm should not be derived from successful prophylaxis studies. Even in case of infectious agents against which robust prophylaxis is routinely achieved, therapy is nearly impossible once the disease has established. (c) Studies with appropriate cancer models of mice and rats are useful. The notion that it is easy to cure cancers in mice is generally advanced the most confidently by those who have never cured a mouse of cancer by immunotherapy. (d) With a nod to James Carville, it is the antigen(s), stupid! We still do not know the identity of protective tumor antigens. If any lesson can be drawn at all, it may well be that cancer immunotherapy must move away from the one-shoe-fits-all therapeutic models of chemotherapy and must move to individualized approaches. (e) All targets are equal, but some are more equal than others. The key is specificity for cancer. That does not necessarily mean specificity for cancer cells. (f) Vaccitherapy must be attempted preferably in the minimal residual disease setting, even though this is certain to be time-taking and expensive. In the setting of bulky disease, vaccitherapy must be combined with blockade of inhibitory signals, or depletion of down-regulatory T cells. Inhibition of effector level suppression of immune response is a key. Vaccitherapy alone or immuno-modulation alone is unlikely to succeed in therapy of bulky metastatic disease.

Dynasting Theory: Lessons in learning grounded theory

Directory of Open Access Journals (Sweden)

Johnben Teik-Cheok Loy, MBA, MTS, Ph.D.

2011-06-01

Full Text Available This article captures the key learning lessons gleaned from the author’s experience learning and developing a grounded theory for his doctoral dissertation using the classic methodology as conceived by Barney Glaser. The theory was developed through data gathered on founders and successors of Malaysian Chinese family-own businesses. The main concern for Malaysian Chinese family businesses emerged as dynasting . the building, maintaining, and growing the power and resources of the business within the family lineage. The core category emerged as dynasting across cultures, where founders and successors struggle to transition from traditional Chinese to hybrid cultural and modernized forms of family business from one generation to the next. The key learning lessons were categorized under five headings: (a sorting through different versions of grounded theory, (b educating and managing research stakeholders, (c embracing experiential learning, (d discovering the core category: grounded intuition, and (e recognizing limitations and possibilities.Keywords: grounded theory, learning, dynasting, family business, Chinese

Students’ motivation in a disc golf-lesson and a soccer-lesson: An experimental study in the Physical Education setting

Directory of Open Access Journals (Sweden)

Kristian Vernegaard

2017-09-01

Full Text Available One of the purposes of physical education (PE in both Norway and Denmark is that PE should inspire to a lifelong active lifestyle. Based on the self-determination theory, the aim of the present study was to compare students’ intrinsic motivation, extrinsic motivation, and perceived competence in a lifestyle sport inspired PE-lesson (disc golf to a traditional PE-lesson (soccer and general PE. In addition, we aimed to investigate whether differences in motivation and perceived competence were conditional of the students’ relative attitude toward PE. The result of the study revealed that perceived competence was higher in the disc golf-lesson compared to the soccer-lesson and general PE. No overall differences in intrinsic motivation were found. However, when investigating differences in intrinsic motivation according to the students’ relative attitude toward PE, the results indicated that the students with a negative attitude toward PE was significantly more intrinsically motivated in disc golf-lesson compared to soccer-lesson and general PE. The findings may be seen as further recommendations to physical educators to vary the activity choices in physical education classes.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl-peptidase IV.

Science.gov (United States)

Herlihy, Sarah E; Tang, Yu; Phillips, Jonathan E; Gomer, Richard H

2017-03-01

Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV-like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. © 2016 The Protein Society.

Functional similarities between the dictyostelium protein AprA and the human protein dipeptidyl‐peptidase IV

Science.gov (United States)

Herlihy, Sarah E.; Tang, Yu; Phillips, Jonathan E.

2017-01-01

Abstract Autocrine proliferation repressor protein A (AprA) is a protein secreted by Dictyostelium discoideum cells. Although there is very little sequence similarity between AprA and any human protein, AprA has a predicted structural similarity to the human protein dipeptidyl peptidase IV (DPPIV). AprA is a chemorepellent for Dictyostelium cells, and DPPIV is a chemorepellent for neutrophils. This led us to investigate if AprA and DPPIV have additional functional similarities. We find that like AprA, DPPIV is a chemorepellent for, and inhibits the proliferation of, D. discoideum cells, and that AprA binds some DPPIV binding partners such as fibronectin. Conversely, rAprA has DPPIV‐like protease activity. These results indicate a functional similarity between two eukaryotic chemorepellent proteins with very little sequence similarity, and emphasize the usefulness of using a predicted protein structure to search a protein structure database, in addition to searching for proteins with similar sequences. PMID:28028841

Dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes: safety, tolerability, and efficacy

Directory of Open Access Journals (Sweden)

Mary Elizabeth Cox

2010-01-01

Full Text Available Mary Elizabeth Cox1, Jennifer Rowell1, Leonor Corsino1, Jennifer B Green1,21Department of Medicine, Division of Endocrinology, Metabolism, and Nutrition. Duke University Medical Center, Durham, NC, USA; 2Department of Medicine, Division of Endocrinology, Durham Veterans Affairs Medical Center, Durham, NC, USAAbstract: Although glycemic control is an important and effective way to prevent and minimize the worsening of diabetes-related complications, type 2 diabetes is a progressive disease which often proves difficult to manage. Most affected patients will eventually require therapy with multiple medications in order to reach appropriate glycemic targets. The dipeptidyl peptidase-4 (DPP-4 inhibitors constitute a relatively new class of oral medications for the treatment of type 2 diabetes, which has become widely incorporated into clinical practice. This review summarizes the available data on the efficacy, safety, and tolerability of these medications.Keywords: type 2 diabetes, pharmacotherapy, DPP-4 inhibitor, sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin

Lessons learned from the shut down, planning, and the preparatory activities of decommissioning the research reactor VVR-S Magurele, Bucharest

International Nuclear Information System (INIS)

Dragusin, M.; Copaciu, V.

2006-01-01

The nuclear research reactor type VVR was shut down in December 1997 after forty years of operation. The main characteristics of this reactor are: Thermal power 2 MW, Thermal energy - 9.59 GWhd, Average flux of thermal neutrons-10 13 n/cm 2 .s, nine horizontal channels, sixteen vertical exposure channels, three biological channels, reactor type tank, water used as a moderator, coolant and reflector. The reactor was used in research and radioisotope production. The reactor has been permanently shut down since April 2002, when the decommissioning was officially announced. Discussions regarding funding mechanisms for the conservation phase, and decommissioning (planning, preparatory activities, spent nuclear fuel management), have taken place since five years ago when the final decision of permanent shut down was taken. Quality management includes procedures for recording and archiving the lessons learned. The planning of decommissioning started in 1990 when the reactor was still operational. After fifteen years the regulatory body has not yet approved the decommissioning plan for the reactor. In this paper the following aspects are discussed: decommissioning strategy from safe enclosure to immediate dismantling, specific features of the site (treatment of radioactive waste near reactor) and state of decommissioning, use of the lessons learned in the planning of decommissioning for the other two small nuclear facilities situated in the same area with VVR-reactor: Sub critical Assembly 'HELEN' and Zero Power Critical Reactor RP-0, AFR ponds for spent nuclear fuel, other radiological facilities for radioisotopes production facilities radiation processing and accelerators. Preparatory activities for decommissioning have included: elaboration of a plan (inter alia, justification of the selected strategy, management of the radioactive waste in accordance with the waste acceptance criteria), reactor storage in parallel with the removal of the equipment and materials used in

11C-PBR28 binding to translocator protein increases with progression of Alzheimer’s disease

OpenAIRE

Kreisl, William C.; Lyoo, Chul Hyoung; Liow, Jeih-San; Wei, Monica; Snow, Joseph; Page, Emily; Jenko, Kimberly J.; Morse, Cheryl L.; Zoghbi, Sami S.; Pike, Victor W.; Turner, R. Scott; Innis, Robert B.

2016-01-01

This longitudinal study sought to determine whether the 18 kDa translocator protein (TSPO), a marker of neuroinflammation, increases over time in Alzheimer’s disease. Positron emission tomography (PET) imaging with the TSPO radioligand 11C-PBR28 imaging was performed at baseline and after a median follow-up of 2.7 years in 14 amyloid-positive patients and eight amyloid-negative controls. Patients had a greater increase in TSPO binding than controls in inferior parietal lobul...

Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

DEFF Research Database (Denmark)

Herman, Gary A; Bergman, Arthur; Stevens, Catherine

2006-01-01

CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

Regulating “big data education” in Europe: lessons learned from the US

Directory of Open Access Journals (Sweden)

Yoni Har Carmel

2016-03-01

Full Text Available European schools are increasingly relying on vendors to collect, process, analyse, and even make decisions based on a considerable amount of student data through big data tools and methods. Consequently, portions of school’s power are gradually shifting from traditional public schools to the hands of for-profit organisations. This article discusses the current and forthcoming European Union (EU data protection regime with respect to the protection of student rights from the potential risk of outsourcing student data utilisation in Kindergarten-12th grade (K-12 educational systems. The article identifies what lessons can be drawn from recent developments in the United States (US “student data affair”. These lessons can provide a new perspective for designing a balanced policy for regulating the shift in school’s power.

Treatment of both native and deamidated gluten peptides with an endo-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease

DEFF Research Database (Denmark)

Toft-Hansen, Henrik; Rasmussen, Karina Søndergård; Nielsen, Anne Staal

2014-01-01

the proliferative response by a gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to protease-digested gluten peptides. A proline-specific endo-peptidase from Aspergillus niger (AnP2), was particularly efficient at diminishing proliferation after stimulation with cleaved antigen, and could...

Learning to observe mathematical learning in lesson studies

DEFF Research Database (Denmark)

Rasmussen, Klaus; Østergaard, Camilla Hellsten; Foss, Kristian Kildemoes

2016-01-01

This poster deals with lesson study (LS) in pre-service teacher education. In particular how to prepare for, carry out, and reflect upon, observations of pupil learning. Observation is of crucial importance to the lesson study process, and here we present a study of observation features which ena...... enable or hinder fruitful lesson study. While substantial research has been carried out in the general field of bserving pupils’ learning processes and teachers’ pedagogical practice, little is known about this in the particular setting of lesson study....

28 CFR 0.28 - General functions.

Science.gov (United States)

2010-07-01

... Affairs § 0.28 General functions. The Office of Public Affairs is headed by a Director of Public Affairs who shall: (a) Handle matters pertaining to relations with the public generally. (b) Disseminate... 28 Judicial Administration 1 2010-07-01 2010-07-01 false General functions. 0.28 Section 0.28...

Chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26

International Nuclear Information System (INIS)

Cutler, Murray J.; Lowthers, Erica L.; Richard, Cynthia L.; Hajducek, Dagmar M.; Spagnuolo, Paul A.; Blay, Jonathan

2015-01-01

Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12. We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays. 5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations. Our results indicate that conventional anticancer agents may act to inhibit chemokine-mediated migration through eradication of CXCR4+ cells and attenuation of

Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

International Nuclear Information System (INIS)

Wu, C.-M.; Chang, Margaret Dah-Tsyr

2004-01-01

Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

Sequencing Analysis of Mutant Allele $cdc$28-$srm$ of Protein Kinase CDC28 and Molecular Dynamics Study of Glycine-Rich Loop in Wild-Type and Mutant Allele G16S of CDK2 as Model

CERN Document Server

Koltovaya, N A; Kholmurodov, Kh T; Kretov, D A

2005-01-01

The central role that cyclin-dependent kinases play in the timing of cell division and the high incidence of genetic alteration of CDKs or deregulation of CDK inhibitors in a number of cancers make CDC28 of the yeast \\textit{Saccharomyces cerevisiae }very attractive model for studies of mechanisms of CDK regulation. Earlier it was found that certain gene mutations including \\textit{cdc28-srm} affect cell cycle progression, maintenance of different genetic structures and increase cell sensitivity to ionizing radiation. A~\\textit{cdc28-srm} mutation is not temperature-sensitive mutation and differs from the known \\textit{cdc28-ts }mutations because it has the evident phenotypic manifestations at 30 $^{\\circ}$C. Sequencing analysis of \\textit{cdc28-srm} revealed a single nucleotide substitution G20S. This is a third glycine in a conserved sequence GxGxxG in the G-rich loop positioned opposite the activation T-loop. Despite its demonstrated importance, the role of the G-loop has remained unclear. The crystal stru...

Thomas Edison's Inventions in the 1900s and Today: From "New" to You! [Lesson Plan].

Science.gov (United States)

2002

The purpose of this lesson is to familiarize students with life and technology around 1900 so that they can better understand how Thomas Edison and his many inventions influenced both. Without some understanding of Edison's time, it is unclear just how significant an impact Edison had on the world, both then and now. While the incandescent light…

Keiko, Killer Whale. [Lesson Plan].

Science.gov (United States)

Discovery Communications, Inc., Bethesda, MD.

This lesson plan presents activities designed to help students understand that Keiko, the killer whale, lived for a long time in an aquarium and had to be taught to live independently; and that computer users can get updates on how Keiko is doing. The main activity of the lesson involves middle school students working in small groups to produce a…

Introduction to Animal Nutrition. Instructor Guide [and] Student Reference. Volume 28, Number 7 [and] Volume 28, Number 8.

Science.gov (United States)

Peiter, Andrea; And Others

This instructor guide and the corresponding student reference contain five lessons about animal science for inclusion in Vocational Instructional Management System (VIMS) agricultural education courses. The lessons cover these topics: the monogastric digestive system, the ruminant digestive system, the importance of meeting nutritional needs, how…

Efficacy of melflufen, a peptidase targeted therapy, and dexamethasone in an ongoing open-label phase 2a study in patients with relapsed and relapsed-refractory multiple myeloma (RRMM) including an initial report on progression free survival

DEFF Research Database (Denmark)

Voorhees, P. M.; Magarotto, V.; Sonneveld, P.

2015-01-01

to DNA or is readily metabolized by intracellular peptidases into hydrophilic alkylating metabolites. With targeted delivery of alkylating metabolites to tumor cells in vitro (such as multiple myeloma that are rich in activating peptidase), melflufen exerts a 20-100 fold higher anti-tumor potency...... and produces a 20 fold higher intracellular concentration of alkylating moieties compared with melphalan. Methods: Melflufen is evaluated in combination with dexamethasone (dex) 40 mg weekly in an ongoing Phase 1/2a study. RRMM patients with measurable disease and at least 2 prior lines of therapy are eligible......%) and constipation and epistaxis (13%). Treatment-related Grade 3 or 4 AEs were reported in 27 patients (87%). Those occurring in >5% of patients were thrombocytopenia (68%), neutropenia (55%), anemia (42%), leukopenia (32%) and febrile neutropenia, fatigue, pyrexia, asthenia and hyperglycemia each occurred in 6...

Job Oriented Training ’Lessons Learned’

Science.gov (United States)

2008-11-01

Job Oriented Training ’Lessons Learned’ Job Oriented Training (JOT), een vorm van trainen waarbij de cursist zelfstandig, zonder theorie vooraf...39 77 lnfo-DenV@tno.nl TNO-rapportnummer TNO-DV 2008 A447 Opdrachtnummer Datum november 2008 Auteur (s) drs. H.E. Stubbe dr. A.H. van der...onderlinge discussie over achterliggende overwegingen te stimuleren. Zij hebben op dat moment nog geen theorie aangeboden gekregen en zijn niet op de hoogte

Lessons Learned from FUSRAP

Energy Technology Data Exchange (ETDEWEB)

Castillo, Darina [U.S. Department of Energy, Office of Legacy Management; Carpenter, Cliff [U.S. Department of Energy, Office of Legacy Management; Miller, Michele [Navarro Research and Engineering

2016-03-06

The US DOE Office of Legacy Management (LM) is the long-term steward for 90 sites remediated under numerous regulatory regimes including the Formerly Utilized Sites Remedial Action Program (FUSRAP) sites. In addition, LM holds considerable historical information, gathered in the 1970s, to determine site eligibility for remediation under FUSRAP. To date, 29 FUSRAP sites are in LM’s inventory of sites for long-term surveillance and maintenance (LTS&M), and 25 are with the US Army Corps of Engineers (USACE) for remediation or in the process of being transitioned to LM. It is forecasted that 13 FUSRAP sites will transfer from the USACE to LM over the next 10 years; however, the timing of the transfers is strongly dependent upon federal funding of the ongoing remedial actions. Historically, FUSRAP sites were generally cleaned up for “unrestricted” industrial use or remediated to the “cleanup standards” at that time, and their use remained unchanged. Today, these sites as well as the adjacent properties are now changing or envisioned to have changes in land use, typically from industrial to commercial or residential uses. The implication of land-use change affects DOE’s LTS&M responsibility for the sites under LM stewardship as well as the planning for the additional sites scheduled to transition in time. Coinciding with land-use changes at or near FUSRAP sites is an increased community awareness of these sites. As property development increases near FUSRAP sites, the general public and interested stakeholders regularly inquire about the sufficiency of cleanups that impact their neighborhoods and communities. LM has used this experience to address a series of lessons learned to improve our program management in light of the changing conditions of our sites. We describe these lessons learned as (1) improved stakeholder relations, (2) enhanced LTS&M requirements for the sites, and (3) greater involvement in the transition process.

System 80+{trademark} standard design incorporates radiation protection lessons learned

Energy Technology Data Exchange (ETDEWEB)

Crom, T.D.; Naugle, C.L. [Duke Engineering & Services, Inc., Charlotte, NC (United States); Turk, R.S. [ABB Combustion Engineering Nuclear Power, Windsor, CT (United States)

1995-03-01

Many lessons have been learned from the current generation of nuclear plants in the area of radiation protection. The following paper will outline how the lessons learned have been incorporated into the design and operational philosophy of the System 80+{trademark} Standard Design currently under development by ABB Combustion Engineering (ABB-CE) with support from Duke Engineering and Services, Inc. and Stone and Webster Engineering Corporation in the Balance-of-Plant design. The System 80+{trademark} Standard Design is a complete nuclear power plant for national and international markets, designed in direct response to utility needs for the 1990`s, and scheduled for Nuclear Regulatory Commission (NRC) Design Certification under the new standardization rule (10 CFR Part 52). System 80+{trademark} is a natural extension of System 80{sup R} technology, an evolutionary change based on proven Nuclear Steam Supply System (NSSS) in operation at Palo Verde in Arizona and under construction at Yonggwang in the Republic of Korea. The System 80+{trademark} Containment and much of the Balance of Plant design is based upon Duke Power Company`s Cherokee Plant, which was partially constructed in the late 1970`s, but, was later canceled (due to rapid declined in electrical load growth). The System 80+{trademark} Standard Design meets the requirements given in the Electric Power Research Institute (EPRI) Advanced Light Water Reactor (ALWR) Requirements Document. One of these requirements is to limit the occupational exposure to 100 person-rem/yr. This paper illustrates how this goal can be achieved through the incorporation of lessons learned, innovative design, and the implementation of a common sense approach to operation and maintenances practices.

Phylogenetic position of Loricifera inferred from nearly complete 18S and 28S rRNA gene sequences.

Science.gov (United States)

Yamasaki, Hiroshi; Fujimoto, Shinta; Miyazaki, Katsumi

2015-01-01

Loricifera is an enigmatic metazoan phylum; its morphology appeared to place it with Priapulida and Kinorhyncha in the group Scalidophora which, along with Nematoida (Nematoda and Nematomorpha), comprised the group Cycloneuralia. Scarce molecular data have suggested an alternative phylogenetic hypothesis, that the phylum Loricifera is a sister taxon to Nematomorpha, although the actual phylogenetic position of the phylum remains unclear. Ecdysozoan phylogeny was reconstructed through maximum-likelihood (ML) and Bayesian inference (BI) analyses of nuclear 18S and 28S rRNA gene sequences from 60 species representing all eight ecdysozoan phyla, and including a newly collected loriciferan species. Ecdysozoa comprised two clades with high support values in both the ML and BI trees. One consisted of Priapulida and Kinorhyncha, and the other of Loricifera, Nematoida, and Panarthropoda (Tardigrada, Onychophora, and Arthropoda). The relationships between Loricifera, Nematoida, and Panarthropoda were not well resolved. Loricifera appears to be closely related to Nematoida and Panarthropoda, rather than grouping with Priapulida and Kinorhyncha, as had been suggested by previous studies. Thus, both Scalidophora and Cycloneuralia are a polyphyletic or paraphyletic groups. In addition, Loricifera and Nematomorpha did not emerge as sister groups.

Mini-Lessons on Language (The Round Table).

Science.gov (United States)

English Journal, 1993

1993-01-01

Describes several successful lessons that provide students with new awareness of the English language. Includes lessons focusing on language change, onomatopoeia, slang, word origin, dialect, and language functions. (MM)

The 2015 Nepal Earthquake(s): Lessons Learned From the Disability and Rehabilitation Sector's Preparation for, and Response to, Natural Disasters.

Science.gov (United States)

Landry, Michel D; Sheppard, Phillip S; Leung, Kit; Retis, Chiara; Salvador, Edwin C; Raman, Sudha R

2016-11-01

The frequency of natural disasters appears to be mounting at an alarming rate, and the degree to which people are surviving such traumatic events also is increasing. Postdisaster survival often triggers increases in population and individual disability-related outcomes in the form of impairments, activity limitations, and participation restrictions, all of which have an important impact on the individual, his or her family, and their community. The increase in postdisaster disability-related outcomes has provided a rationale for the increased role of the disability and rehabilitation sector's involvement in emergency response, including physical therapists. A recent major earthquake that has drawn the world's attention occurred in the spring of 2015 in Nepal. The response of the local and international communities was large and significant, and although the collection of complex health and disability issues have yet to be fully resolved, there has been a series of important lessons learned from the 2015 Nepal earthquake(s). This perspective article outlines lessons learned from Nepal that can be applied to future disasters to reduce overall disability-related outcomes and more fully integrate rehabilitation in preparation and planning. First, information is presented on disasters in general, and then information is presented that focuses on the earthquake(s) in Nepal. Next, field experience in Nepal before, during, and after the earthquake is described, and actions that can and should be adopted prior to disasters as part of disability preparedness planning are examined. Then, the emerging roles of rehabilitation providers such as physical therapists during the immediate and postdisaster recovery phases are discussed. Finally, approaches are suggested that can be adopted to "build back better" for, and with, people with disabilities in postdisaster settings such as Nepal. © 2016 American Physical Therapy Association.

Introduction to Animal Reproduction. Instructor Guide [and] Student Reference. Volume 28, Number 5 [and] Volume 28, Number 6.

Science.gov (United States)

Peiter, Andrea; And Others

This instructor guide and the corresponding student reference contain seven lessons about animal reproduction for inclusion in Vocational Instructional Management System (VIMS) agricultural education courses. The lessons cover the following topics: the male and female reproductive systems, puberty and the estrous cycle, conception and gestation,…

Systemwide Deployment of Medical Team Training: Lessons Learned in the Department of Defense

National Research Council Canada - National Science Library

King, Heidi B; Kohsin, Beth; Salisbury, Mary

2005-01-01

.... Lessons learned within the U.S. Department of Defense indicate that for teamwork initiatives to be effective, they must possess a clear blueprint defining the solid steps for building the desired culture...

Improving Mathematics Teaching as Deliberate Practice through Chinese Lesson Study

Science.gov (United States)

Huang, Rongjin; Prince, Kyle M.; Barlow, Angela T.

2017-01-01

This study examined how a ninth grade teacher improved an Algebra I lesson through a lesson study approach. We used multiple data sources to investigate the improvement of the lesson towards student-centered mathematics instruction, perceived benefits of the teacher, and factors associated with the improvement of teaching. The lesson group…

Craft Lessons: Teaching Writing K-8. Second Edition

Science.gov (United States)

Fletcher, Ralph; Portalupi, JoAnn

2007-01-01

Since its publication in 1998 Craft Lessons has become a mainstay of writing teachers, both new and experienced. Practical lessons--each printed on one page--and the instructional language geared to three grade-level groupings: K-2, 3-4, and 5-8 are contained in this book. In the decade since Craft Lessons' publication the world has changed in…

Anticipating students' reasoning and planning prompts in structured problem-solving lessons

Science.gov (United States)

Vale, Colleen; Widjaja, Wanty; Doig, Brian; Groves, Susie

2018-02-01

Structured problem-solving lessons are used to explore mathematical concepts such as pattern and relationships in early algebra, and regularly used in Japanese Lesson Study research lessons. However, enactment of structured problem-solving lessons which involves detailed planning, anticipation of student solutions and orchestration of whole-class discussion of solutions is an ongoing challenge for many teachers. Moreover, primary teachers have limited experience in teaching early algebra or mathematical reasoning actions such as generalising. In this study, the critical factors of enacting the structured problem-solving lessons used in Japanese Lesson Study to elicit and develop primary students' capacity to generalise are explored. Teachers from three primary schools participated in two Japanese Lesson Study teams for this study. The lesson plans and video recordings of teaching and post-lesson discussion of the two research lessons along with students' responses and learning are compared to identify critical factors. The anticipation of students' reasoning together with preparation of supporting and challenging prompts was critical for scaffolding students' capacity to grasp and communicate generality.

Safety Requirements / Design Criteria for SFR. Lessons Learned from the Fukushima Dai-ichi Accident

International Nuclear Information System (INIS)

Yllera, Javier

2013-01-01

After the Fukushima event (March 2011) the IAEA has started an action to review and revise, if necessary, all Safety Standards to take into consideration the lessons learned from the accident. The Safety Standards that need to be revised have been identified. A Prioritization Approach has been established: The first priority is to review safety guides applicable for NPPs and spent fuel storage with focus on the measures for the prevention and mitigation of severe accident due to external hazards - ● Regulatory framework, Safety assessment, Management system, Radiation protection and Emergency Preparedness and response; ● Sitting, Design, Operation of NPPs ● Decommissioning and Waste Management. Original sources for lessons learned: IAE fact Finding Mission, Japan´s report to the Ministerial Conference, INSAG Report, etc. Later, other lesson sources considered

Countering the al-Shabaab Insurgency in Somalia: Lessons for U.S. Special Operations Forces

Science.gov (United States)

2014-02-01

correctly, that such an esteemed lineage is apocryphal, it is still an important founding myth for the Somali people and an indicator of their wish to...urban elites. Flush with money and with access to the halls of power, they used land registration laws (backed with a healthy dollop of armed...node/108486. 345. Nagl, John A. Learning to Eat Soup with a Knife: Counterinsurgency Lessons from Malaya and Vietnam. Paperback ed. Chicago: University

Isolation of a cdc28 mutation that abrogates the dependence of S ...

Indian Academy of Sciences (India)

We have isolated a mutation in the budding yeast Saccharomyces cerevisisae CDC28 gene that allows cdc13 cells, carrying damaged DNA, to continue with the cell division cycle. While cdc13 mutant cells are arrested as large-budded cells at the nonpermissive temperature 37°C, the cdc13 cdc28 double mutant culture ...

The first structure in a family of peptidase inhibitors reveals an unusual Ig-like fold [v2; ref status: indexed, http://f1000r.es/1nx

Directory of Open Access Journals (Sweden)

Daniel J Rigden

2013-08-01

Full Text Available We report the crystal structure solution of the Intracellular Protease Inhibitor (IPI protein from Bacillus subtilis, which has been reported to be an inhibitor of the intracellular subtilisin Isp1 from the same organism. The structure of IPI is a variant of the all-beta, immunoglobulin (Ig fold. It is possible that IPI is important for protein-protein interactions, of which inhibition of Isp1 is one. The intracellular nature of ISP is questioned, because an alternative ATG codon in the ipi gene would produce a protein with an N-terminal extension containing a signal peptide. It is possible that alternative initiation exists, producing either an intracellular inhibitor or a secreted form that may be associated with the cell surface.  Homologues of the IPI protein from other species are multi-domain proteins, containing signal peptides and domains also associated with the bacterial cell-surface. The cysteine peptidase inhibitors chagasin and amoebiasin also have Ig-like folds, but their topology differs significantly from that of IPI, and they share no recent common ancestor. A model of IPI docked to Isp1 shows similarities to other subtilisin:inhibitor complexes, particularly where the inhibitor interacts with the peptidase active site.

Finland as a Knowledge Economy 2.0: Lessons on Policies and Governance

DEFF Research Database (Denmark)

in the 1950’s into one of the leading innovation-driven, knowledge-based economies and high-tech producers in the twenty-first century. The development was rapid, and involved determined action and sometimes drastic decisions by the government and other key actors. Today, at the end of 2013, Finland is facing...... new types of challenges both domestically and internationally in efforts to maintain its societal sustainability and economic competitiveness. Finland Knowledge Economy 2.0 presents some of the key policies, elements, initiatives and decisions behind Finland’s path into the Knowledge Economy of today....... The authors hope to provide the readers inspiration, new ideas, and novel insights. Hopefully some of the lessons learned may prove valuable in another context. Based on this account of the development of Finnish Knowledge Economy, the authors have identified six areas of lessons, each described in detail...

Professor's Page: Do Demonstration Lessons Work?

Science.gov (United States)

Clarke, Doug

2011-01-01

As part of a large research and professional development project funded by the Catholic Education Office Melbourne (CEOM), called "Contemporary Teaching and Learning of Mathematics," the ACU team has been leading demonstration lessons. There is certainly not universal agreement on the worth of demonstration lessons in the mathematics…

Dipeptidyl peptidase-IV activity and/or structure homologues (DASH) in transformed neuroectodermal cells

Czech Academy of Sciences Publication Activity Database

Malík, Radek; Bušek, P.; Mareš, Vladislav; Ševčík, J.; Kleibl, Z.; Šedo, A.

2003-01-01

Roč. 524, - (2003), s. 95-102 ISSN 0065-2598. [International Conference on Dipeptidyl Aminopeptidases. Berlin, 26.09.2002-28.09.2002] R&D Projects: GA ČR GA301/02/0962 Grant - others:GA UK(CZ) 7/2002/C Institutional research plan: CEZ:AV0Z5011922 Keywords : DASH molecules * DPP-IV activity * glioma cells Subject RIV: FD - Oncology ; Hematology

Characterization of a new M13 metallopeptidase from deep-sea Shewanella sp. E525-6 and mechanistic insight into its catalysis

Directory of Open Access Journals (Sweden)

Jin-Yu eYang

2016-01-01

Full Text Available Bacterial extracellular peptidases are important for bacterial nutrition and organic nitrogen degradation in the ocean. While many peptidases of the M13 family from terrestrial animals and bacteria are studied, there has been no report on M13 peptidases from marine bacteria. Here, we characterized an M13 peptidase, PepS, from the deep-sea sedimentary strain Shewanella sp. E525-6, and investigated its substrate specificity and catalytic mechanism. The gene pepS cloned from strain E525-6 contains 2085 bp and encodes an M13 metallopeptidase. PepS was expressed in Escherichia coli and purified. Among the characterized M13 peptidases, PepS shares the highest sequence identity (47% with Zmp1 from Mycobacterium tuberculosis, indicating that PepS is a new member of the M13 family. PepS had the highest activity at 30°C and pH 8.0. It retained 15% activity at 0°C. Its half life at 40°C was only 4 min. These properties indicate that PepS is a cold-adapted enzyme. The smallest substrate for PepS is pentapeptide, and it is probably unable to cleave peptides of more than 30 residues. PepS prefers to hydrolyze peptide bonds with P1’ hydrophobic residues. Structural and mutational analyses suggested that His531, His535 and Glu592 coordinate the catalytic zinc ion in PepS, Glu532 acts as a nucleophile, and His654 is probably involved in the transition state stabilization. Asp538 and Asp596 can stablize the orientations of His531 and His535, and Arg660 can stablize the orientation of Asp596. These results help in understanding marine bacterial peptidases and organic nitrogen degradation.

The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose

DEFF Research Database (Denmark)

Utzschneider, Kristina M; Tong, Jenny; Montgomery, Brenda

2007-01-01

OBJECTIVE: To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: A total of 22 subjects with IFG (11 female and 11 male, mean +/- SD...... age 59.6 +/- 11.5 years) were treated orally with 100 mg vildagliptin once daily in a single-blind study. Subjects received placebo for 2 weeks (run-in) followed by vildagliptin for 6 weeks (treatment) and then placebo for 2 weeks (washout). A frequently sampled intravenous glucose tolerance test....... RESULTS: Fasting plasma glucose did not change after 6 weeks of vildagliptin treatment. With treatment, mean +/- SEM AIR(g) increased from 224 +/- 44 to 286 +/- 52 pmol/l (P

A Novel Dynamic Model Describing the Spread of the MERS-CoV and the Expression of Dipeptidyl Peptidase 4

Directory of Open Access Journals (Sweden)

Siming Tang

2017-01-01

Full Text Available The Middle East respiratory syndrome (MERS coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4, is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed. Our results show that the spread of MERS-CoV can also be controlled by decreasing the expression rate of DPP4.

Defense Language Institute Russian Basic Course. Volumes XXVIII, Lessons 131-140. Volume XXX, Lessons 151-159.

Science.gov (United States)

Defense Language Inst., Washington, DC.

The 19 lessons in these two volumes are intended for the advanced phase of a 159-lesson intensive audiolingual basic Russian course developed recently by the Defense Language Institute to train native speakers of English to a Level 3 second language proficiency. These third and fifth volumes contain such features as (1) texts on the Russian Civil…

Social support and child protection: Lessons learned and learning.

Science.gov (United States)

Thompson, Ross A

2015-03-01

Social support has been a topic of research for nearly 50 years, and its applications to prevention and intervention have grown significantly, including programs advancing child protection. This article summarizes the central conclusions of the 1994 review of research on social support and the prevention of child maltreatment prepared for the U.S. Advisory Board on Child Abuse and Neglect, and surveys advances in the field since its publication. Among the lessons learned twenty years ago are (a) the diversity of the social support needs of at-risk families and their association with child endangerment, (b) the need to supplement the emotionally affirmative aspects of social support with efforts to socialize parenting practices and monitor child well-being, (c) the desirability of integrating formal and informal sources of social support for recipients, and (d) the importance of considering the complex recipient reactions to receiving support from others. The lessons we are now learning derive from research exploring the potential of online communication to enhance social support, the neurobiology of stress and its buffering through social support, and the lessons of evaluation research that are identifying the effective ingredients of social support interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Children's Satisfaction with Private Music Lessons.

Science.gov (United States)

Rife, Nora A.; Shnek, Zachary M.; Lauby, Jennifer L.; Lapidus, Leah Blumberg

2001-01-01

Determines the language children use to express their feelings of satisfaction with private music lessons. Offers a list of statements from children about private music lessons to be used to assess those feelings. Discusses the effects of age, gender, and musical instruments on satisfaction for music educators. Includes references. (DAJ)

Human Spaceflight Conjunction Assessment: Lessons Learned

Science.gov (United States)

Smith, Jason T.

2011-01-01

This viewgraph presentation reviews the process of a human space flight conjunction assessment and lessons learned from the more than twelve years of International Space Station (ISS) operations. Also, the application of these lessons learned to a recent ISS conjunction assessment with object 84180 on July 16, 2009 is also presented.

Free Trade and Tariffs: Level III, Unit 2, Lesson 1; Capitalism, Communism, Socialism: Lesson 2; Nationalism vs. Internationalism: Lesson 3. Advanced General Education Program. A High School Self-Study Program.

Science.gov (United States)

Manpower Administration (DOL), Washington, DC. Job Corps.

This self-study program for high-school level contains lessons on: Free Trade and Tariffs; Capitalism, Communism, Socialism; and Nationalism vs. Internationalism. Each of the lessons concludes with a Mastery Test to be completed by the student. (DB)

Lessons learned from accidents in radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Ortiz-Lopez, P [International Atomic Energy Agency, Vienna (Austria). Div. of Nuclear Safety; Novotny, J [University Hospital St. Rafael, Leuven (Belgium); Haywood, J [South Cleveland Hospital (United Kingdom). Cleveland Medical Physics Unit

1996-08-01

Radiotherapy is the only application of radiation which intentionally delivers very high doses to humans. A gross deviation from the prescribed dose or dose distribution can have severe, or even fatal consequences. Since the patient is placed directly in the beam or sources are inserted in the body, any mistake made with the beam or the sources leads almost certainly to an accidental exposure. Lessons learned from previous incidents can be used to test the vulnerability of a given facility, provided that these are adequately disseminated. The purpose of this paper is to present a summary of the lessons learned from a relatively large sample of events. The analysis has been presented as a short description followed by an identification of the triggering event and the contributing factors. These have been grouped as follows: errors in commissioning or calibration machines and sources affecting many patients; mistakes affecting individual patients such as irradiating the wrong patient, the wrong, field or site, and mistakes when entering data into or reading from the patient`s chart; error due to unusual treatments or situations; equipment failure and human machine problems, including maintenance. (author). 1 ref.

Crowdfunding in Emerging Markets : Lessons from East African Startups

OpenAIRE

World Bank Group

2015-01-01

The purpose of this paper is to capture lessons learned from East African entrepreneurs who were some of crowdfunding’s first adopters. Their experiences can serve as a practical guide for entrepreneurs looking to more effectively utilize crowdfunding across all emerging markets. In order to gather this data, the World Bank conducted interviews with a number of East African technology entr...

Bruce A restart (execution and lessons-learned)

International Nuclear Information System (INIS)

Soini, J.

2011-01-01

Lessons learned with the Bruce Units 3 and 4 restart have been incorporated into the current refurbishment of Units 1 and 2. In addition, lessons learned on the lead unit (U2) are aggressively applied on the lagging unit (U1) to maximize efficiency and productivity. There will be a discussion on how this internal OPEX, along with external lessons learned, are used to continuously improve all aspects of the Bruce A Restart project management cycle, from scope selection, through planning and scheduling, to execution.

The physical education lesson in Turkish primary schools: Affective ...

African Journals Online (AJOL)

In the study students' affective entry characteristics related to Physical Education lessons were examined based on three dimensions: interest towards the lesson, level of motivation in the lesson and educational gains. The study further aimed to investigate how these three dimensions were affected by the gender factor.

Inductive & Deductive Science Thinking: A Model for Lesson Development

Science.gov (United States)

Bilica, Kim; Flores, Margaret

2009-01-01

Middle school students make great learning gains when they participate in lessons that invite them to practice their developing scientific reasoning skills; however, designing developmentally appropriate, clear, and structured lessons about scientific thinking and reasoning can be difficult. This challenge can be met through lessons that teach…

Phylogenetic analysis of the spider mite sub-family Tetranychinae (Acari: Tetranychidae based on the mitochondrial COI gene and the 18S and the 5' end of the 28S rRNA genes indicates that several genera are polyphyletic.

Directory of Open Access Journals (Sweden)

Tomoko Matsuda

Full Text Available The spider mite sub-family Tetranychinae includes many agricultural pests. The internal transcribed spacer (ITS region of nuclear ribosomal RNA genes and the cytochrome c oxidase subunit I (COI gene of mitochondrial DNA have been used for species identification and phylogenetic reconstruction within the sub-family Tetranychinae, although they have not always been successful. The 18S and 28S rRNA genes should be more suitable for resolving higher levels of phylogeny, such as tribes or genera of Tetranychinae because these genes evolve more slowly and are made up of conserved regions and divergent domains. Therefore, we used both the 18S (1,825-1,901 bp and 28S (the 5' end of 646-743 bp rRNA genes to infer phylogenetic relationships within the sub-family Tetranychinae with a focus on the tribe Tetranychini. Then, we compared the phylogenetic tree of the 18S and 28S genes with that of the mitochondrial COI gene (618 bp. As observed in previous studies, our phylogeny based on the COI gene was not resolved because of the low bootstrap values for most nodes of the tree. On the other hand, our phylogenetic tree of the 18S and 28S genes revealed several well-supported clades within the sub-family Tetranychinae. The 18S and 28S phylogenetic trees suggest that the tribes Bryobiini, Petrobiini and Eurytetranychini are monophyletic and that the tribe Tetranychini is polyphyletic. At the genus level, six genera for which more than two species were sampled appear to be monophyletic, while four genera (Oligonychus, Tetranychus, Schizotetranychus and Eotetranychus appear to be polyphyletic. The topology presented here does not fully agree with the current morphology-based taxonomy, so that the diagnostic morphological characters of Tetranychinae need to be reconsidered.

31 CFR 28.630 - Judicial review.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Judicial review. 28.630 Section 28.630 Money and Finance: Treasury Office of the Secretary of the Treasury NONDISCRIMINATION ON THE BASIS... Judicial review. Action taken pursuant to 20 U.S.C. 1682 is subject to judicial review as provided in 20 U...

A Qualitative Study on Primary School Mathematics Lesson Evaluation

Science.gov (United States)

Zhao, Dongchen; Ma, Yunpeng

2009-01-01

Through the qualitative interviews of five implementers of primary school mathematics curriculum, this study addresses the ways in which mathematics lessons are evaluated. Results show that each evaluator recognizes different aspects of a "good lesson," however, among all criteria, the design of the lesson plan, realization of the lesson…

"Elements of Astronomy": A Television Course of 30 Lessons

Science.gov (United States)

Perez, J. P. D.; Del Pozo, E. P. G.; Rodriguez, R. R. T.; Mendez, A. M. B.; Rodriguez, E. R. F.; Gamez, R. G. D.

2006-08-01

It was broadcasted to all Cuba from March to December 2005, one lesson per week, transmitting three times each lesson, this means 90 hours of broadcasting. It was one of the courses of the Program "University for All", that Educative Channel produced. The Thematic: Sky Coordinates and Constellations; Astronomical Instruments; Solar System; Planets and their Moons; Comets, Asteroids and Meteoroids; Sun; Cosmic Environment and Space Weather; Stars; Galaxy and Quasars; Observable Universe; Life, Intelligent Life and Civilizations in the Universe; and History of Astronomy in Cuba. The professor staff was a group of 5 researchers of the Astronomy Department. They did an effort that each lesson had the best information level with a minimum of mathematical expressions. And were used more than 60 slides and various astronomical films fragments per lesson. To make one lesson was analyzed several astronomical films, selected a group of fragments and pre-edited into various blocks with the TV specialists, later a power point presentation was conformed using all available information on-line and bibliography. Then the lesson was recorded by the TV specialist at the Educative Channel and latter reviewed and improved by one AVID edition. The Course groundwork began in April 2003, with the first list of 12 lessons, later in June was increased to18 lessons, and started the work of "Tabloide" making; it is a journal-type book of 32 pages, equivalent to about 120 normal pages including 64 illustrations. At December 2004 the Course was increased to 30 lessons and the "Tabloide" was send to editor, later 200,000 exemplars was published. Many people followed Course and "Tabloide" was shopped in some months.

Technological and Genomic Analysis of Roles of the Cell-Envelope Protease PrtS in Yoghurt Starter Development

Directory of Open Access Journals (Sweden)

Hui Tian

2018-04-01

Full Text Available The cell-envelope protease PrtS was proved to be efficient in optimal bacterial growth and fast acidification in pure culture, while its positive effect on the performance of mixed-cultures in milk fermentation was not defined. The aim was to analyze effects of the PrtS on the symbiosis between strains during yoghurt production and cold storage. Two Streptococcus thermophilus strains, KLDS3.1012 and KLDS SM, and two different proteolytic strains of Lactobacillus delbrueckii subsp. Bulgaricus, L7 and L12, were used. Technological properties (viability, acid production, and proteolysis were determined. Comparative genomics was used to analyze the proteolytic system (cell-envelope protease, transport system, intracellular peptidase of Streptococcus thermophilus strains. S. thermophilus KLDS SM possesses an intact gene encoding PrtS (A9497_00420, which was not found in the genome of S. thermophilus KLDS3.1012. This gene is the main difference in the proteolytic system between the two genomes. PrtS endowed KLDS SM high levels of viability during fermentation and cold storage. When combined with a weaker lactobacillus strain during fermentation, the acceleration of acid production of mixed-culture by KLDS SM would start at an earlier time. KLDS SM increased the post-acidification of yoghurts during cold storage, but the pH was steadily maintained during 14–28 days. Results suggest that strains of Streptococcus thermophilus with strong proteolytic ability could be used in a wide range of dairy production. The present study provided data for yoghurt starter development from the point of view of proteolysis.

Lessons learned from accidents investigations

Energy Technology Data Exchange (ETDEWEB)

Zuniga-Bello, P. [Consejo Nacional de Ciencia y Tecnologia (CONACYT), Mexico City (Mexico); Croft, J. [National Radiological Protection Board (United Kingdom); Glenn, J

1997-12-31

Accidents from three main practices: medical applications, industrial radiography and industrial irradiators are used to illustrate some common causes of accidents and the main lessons to be learned. A brief description of some of these accidents is given. Lessons learned from the described accidents are approached by subjects covering: safety culture, quality assurance, human factors, good engineering practice, defence in depth, security of sources, safety assessment and monitoring and verification compliance. (author)

Lessons learned from accident investigations

International Nuclear Information System (INIS)

Zuniga-Bello, P.; Croft, J.R.; Glenn, J.

1998-01-01

Accidents in three main practices - medical applications, industrial radiography and industrial irradiators - are used to illustrate some common causes of accidents and the main lessons to be learned from them. A brief description of some of these accidents is given. Lessons learned from the accidents described are approached bearing in mind: safety culture, quality assurance, human factors, good engineering practice, defence in depth, security of sources, safety assessment and monitoring and verification compliance. (author)

Free Trade Agreements With The United States: 8 Lessons For Prospective Parties From Australia’s Experience

Directory of Open Access Journals (Sweden)

Tully Stephen R.

2016-12-01

Full Text Available This article identifies 8 key lessons for those States contemplating a free trade agreement with the United States (U.S. arising from Australia’s experience. The standards of intellectual property protection under the Australia-U.S. Free Trade Agreement and their impact on pharmaceutical prices in Australia are a particular focus. Prospective parties must first conduct a national interest self-assessment which reviews the desired strength of intellectual property protection under national law and their preference for using flexibilities available to them under the existing international intellectual property rights framework. The United States negotiates free trade agreements in light of previous ones, negotiating outcomes obtained in other fora and the decisions of international trade tribunals. Negotiations typically occur behind closed doors, which is a process having adverse implications for transparent decision-making, public consultation periods and contributions from interested non-governmental actors. A concluded agreement will build on prior treaties and influence the course of future international arrangements. But the impact of a United States free trade agreement is not always clear, including because of a lack of reliable data, and the extent of national legal change is a contested issue given existing reform agendas and external influences. The United States seek to redesign national health care systems in its own image and had little success in Australia’s case. National legal systems need not be harmonised: although there can be some convergence in intellectual property rights regimes, significant differences may also remain. Negotiators must reconcile competing cultures, philosophies and perspectives between States for a free trade agreement to be worthwhile.

Supporting teachers' technology integration in lesson plans

NARCIS (Netherlands)

Janssen, Noortje

2017-01-01

Lesson planning offers rich opportunities for teachers to consider and implement technology in the classroom. This dissertation investigated the design and effectiveness of supplementary information to assist pre-service teachers during the lesson planning process. Based on the Technological,

28 CFR 2.21 - Reparole consideration guidelines.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Reparole consideration guidelines. 2.21....21 Reparole consideration guidelines. (a)(1) If revocation is based upon administrative violation(s... analogy with listed federal offense behaviors. (b) The guidelines for parole consideration specified at 28...

Transforming Past Lessons to Mold the Future: A Case Study on Operation NICKEL GRASS

National Research Council Canada - National Science Library

Riney, Thomas J

2003-01-01

...?" In this case, the specific lessons from the 1973 airlift operation supporting Israel, Operation NICKEL GRASS, were analyzed and generalized using the Tenets of Operations described in U.S. Army field manuals...

Aspects of 17th century Binding Medium: inclusions in Rembrandt’s Anatomy Lesson of Dr Nicolaes Tulp

DEFF Research Database (Denmark)

Noble, Petria; Wadum, Jørgen; Groen, Karin

2000-01-01

During the recent restoration of Rembrandt's Anatomy Lesson of Dr. Nicolaes Tulp minuscule crater-like holes, which cover the surface of the painting, were studied. Whitish material within the holes was identified as lead chloride hydroxide and a variety of lead soaps. These inclusions, which...

Identification of dipeptidyl peptidase-IV inhibitory peptides from mare whey protein hydrolysates.

Science.gov (United States)

Song, J J; Wang, Q; Du, M; Ji, X M; Mao, X Y

2017-09-01

Inhibition of dipeptidyl peptidase-IV (DPP-IV) activity is a promising strategy for treatment of type 2 diabetes. In the current study, DPP-IV inhibitory peptides were identified from mare whey protein hydrolysates obtained by papain. The results showed that all the mare whey protein hydrolysates obtained at various hydrolysis durations possessed more potent DPP-IV inhibitory activity compared with intact whey protein. The 4-h hydrolysates showed the greatest DPP-IV inhibitory activity with half-maximal inhibitory concentration of 0.18 mg/mL. The 2 novel peptides from 4-h hydrolysate fractions separated by successive chromatographic steps were characterized by liquid chromatography-electrospray ionization tandem mass spectrometry. The novel peptides Asn-Leu-Glu-Ile-Ile-Leu-Arg and Thr-Gln-Met-Val-Asp-Glu-Glu-Ile-Met-Glu-Lys-Phe-Arg, which corresponded to β-lactoglobulin 1 f(71-77) and β-lactoglobulin 1 f(143-155), demonstrated DPP-IV inhibitory activity with half-maximal inhibitory concentrations of 86.34 and 69.84 μM, respectively. The DPP-IV inhibitory activity of the 2 peptides was retained or even improved after simulated gastrointestinal digestion in vitro. Our findings indicate that mare whey protein-derived peptides may possess potential as functional food ingredients in the management of type 2 diabetes. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Asymmetric synthesis of a potent, aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV inhibitor.

Science.gov (United States)

Xu, Feng; Corley, Edward; Zacuto, Michael; Conlon, David A; Pipik, Brenda; Humphrey, Guy; Murry, Jerry; Tschaen, David

2010-03-05

A practical asymmetric synthesis of a novel aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV (DPP-4) inhibitor 1 has been developed. Application of a unique three-component cascade coupling with chiral nitro diester 7, which is easily accessed via a highly enantioselective Michael addition of dimethyl malonate to a nitrostyrene, allows for the assembly of the functionalized piperidinone skeleton in one pot. Through a base-catalyzed, dynamic crystallization-driven process, the cis-piperidionone 16a is epimerized to the desired trans isomer 16b, which is directly crystallized from the crude reaction stream in high yield and purity. Isomerization of the allylamide 16b in the presence of RhCl(3) is achieved without any epimerization of the acid/base labile stereogenic center adjacent to the nitro group on the piperidinone ring, while the undesired enamine intermediate is consumed to <0.5% by utilizing a trace amount of HCl generated from RhCl(3). The amino lactam 4, obtained through hydrogenation and hydrolysis, is isolated as its crystalline pTSA salt from the reaction solution directly, as such intramolecular transamidation has been dramatically suppressed via kinetic control. Finally, a Cu(I) catalyzed coupling-cyclization allows for the formation of the tricyclic structure of the potent DPP-4 inhibitor 1. The synthesis, which is suitable for large scale preparation, is accomplished in 23% overall yield.

Identification of novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides in camel milk protein hydrolysates.

Science.gov (United States)

Nongonierma, Alice B; Paolella, Sara; Mudgil, Priti; Maqsood, Sajid; FitzGerald, Richard J

2018-04-01

Nine novel dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (FLQY, FQLGASPY, ILDKEGIDY, ILELA, LLQLEAIR, LPVP, LQALHQGQIV, MPVQA and SPVVPF) were identified in camel milk proteins hydrolysed with trypsin. This was achieved using a sequential approach combining liquid chromatography tandem mass spectrometry (LC-MS/MS), qualitative/quantitative structure activity relationship (QSAR) and confirmatory studies with synthetic peptides. The most potent camel milk protein-derived DPP-IV inhibitory peptides, LPVP and MPVQA, had DPP-IV half maximal inhibitory concentrations (IC 50 ) of 87.0 ± 3.2 and 93.3 ± 8.0 µM, respectively. DPP-IV inhibitory peptide sequences identified within camel and bovine milk protein hydrolysates generated under the same hydrolysis conditions differ. This was linked to differences in enzyme selectivity for peptide bond cleavage of camel and bovine milk proteins as well as dissimilarities in their amino acid sequences. Camel milk proteins contain novel DPP-IV inhibitory peptides which may play a role in the regulation of glycaemia in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation of an observation tool to assess physical activity-promoting physical education lessons in high schools: SOFIT.

Science.gov (United States)

Fairclough, Stuart J; Weaver, R Glenn; Johnson, Siobhan; Rawlinson, Jack

2018-05-01

SOFIT+ is an observation tool to measure teacher practices related to moderate-to-vigorous physical activity (MVPA) promotion during physical education (PE). The objective of the study was to examine the validity of SOFIT+ during high school PE lessons. This cross-sectional, observational study tested the construct validity of SOFIT+ in boys' and girls' high school PE lessons. Twenty-one PE lessons were video-recorded and retrospectively coded using SOFIT+. Students wore hip-mounted accelerometers during lessons as an objective measure of MVPA. Multinomial logistic regression was used to estimate the likelihood of students engaging in MVPA during different teacher practices represented by observed individual codes and a combined SOFIT+ index-score. Fourteen individual SOFIT+ variables demonstrated a statistically significant relationship with girls' and boys' MVPA. Observed lesson segments identified as high MVPA-promoting were related to an increased likelihood of girls engaging in 5-10 (OR=2.86 [95% CI 2.41-3.40]), 15-25 (OR=7.41 [95% CI 6.05-9.06]), and 30-40 (OR=22.70 [95% CI 16.97-30.37])s of MVPA. For boys, observed high-MVPA promoting segments were related to an increased likelihood of engaging in 5-10 (OR=1.71 [95% CI 1.45-2.01]), 15-25 (OR=2.69 [95% CI 2.31-3.13]) and 30-40 (OR=4.26 [95% CI 3.44-5.29])s of MVPA. Teacher practices during high school PE lessons are significantly related to students' participation in MVPA. SOFIT+ is a valid and reliable tool to examine relationships between PE teacher practices and student MVPA during PE. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Lessons Learned in Software Testing A Context-Driven Approach

CERN Document Server

Kaner, Cem; Pettichord, Bret

2008-01-01

Decades of software testing experience condensed into the most important lessons learned.The world's leading software testing experts lend you their wisdom and years of experience to help you avoid the most common mistakes in testing software. Each lesson is an assertion related to software testing, followed by an explanation or example that shows you the how, when, and why of the testing lesson. More than just tips, tricks, and pitfalls to avoid, Lessons Learned in Software Testing speeds you through the critical testing phase of the software development project without the extensive trial an

Lesson Planning with the Common Core

Science.gov (United States)

Estes, Linda A.; McDuffie, Amy Roth; Tate, Cathie

2014-01-01

Planning a lesson can be similar to planning a road trip--a metaphor the authors use to describe how they applied research and theory to their lesson planning process. A map and mode of transportation, the Common Core State Standards for Mathematics (CCSSM) and textbooks as resources, can lead to desired destinations, such as students engaging in…

Genetics of Alzheimer’s Disease: Lessons Learned in Two Decades

Directory of Open Access Journals (Sweden)

Nilüfer Ertekin Taner

2010-03-01

Full Text Available Alzheimer’s disease (AD is the most common type of dementia. It is estimated that more than 35 million people worldwide will suffer from dementia in 2010. Without effective therapies, this epidemic is expected to affect more than 115 million patients worldwide by 2050. Genetic studies can help us understand the disease pathophysiology, thereby providing potential therapeutic, presymptomatic predictive and preventative avenues. Since 1990, there has been evidence for a substantial genetic component underlying the risk for AD. Three genes with autosomal dominant mutations lead to early-onset familial AD, which explains less than 1% of all AD. Apolipoprotein ε4, the only widely accepted genetic risk factor for late-onset AD, accounts for only a portion of this risk. Genetic linkage and association studies have identified multiple candidate gene regions, although many resulting candidate genes suffer from lack of replication, at least partially due to underpowered studies in the setting of genetic heterogeneity and small-tomoderate effect size. Genome-wide association studies that assess hundreds of thousands of single-nucleotide polymorphisms (SNPs in thousands of subjects have been viewed as a potentially powerful approach in uncovering common risk variations for genetically complex diseases such as AD. To date, 11 independent genome-wide association studies have been completed in late-onset AD (LOAD that led to candidate regions and genes for follow-up. These studies provide evidence for novel, plausible genetic risk factors for AD, but still fail to account for all of the estimated risk. Additional genetic risk factors of even smaller effect size, rare variants and/or structural DNA polymorphisms may exist, which may escape detection by conventional methods. Alternative approaches such as nextgeneration sequencing, use of quantitative endophenotypes, copy number variation analyses, and meta-analyses may be required. This review summarizes the

Genetics of Alzheimer’s Disease: Lessons Learned in Two Decades

Directory of Open Access Journals (Sweden)

Nilüfer Ertekin Taner

2010-03-01

Full Text Available Alzheimer’s disease (AD is the most common type of dementia. It is estimated that more than 35 million people worldwide will suffer from dementia in 2010. Without effective therapies, this epidemic is expected to affect more than 115 million patients worldwide by 2050. Genetic studies can help us understand the disease pathophysiology, thereby providing potential therapeutic, presymptomatic predictive and preventative avenues. Since 1990, there has been evidence for a substantial genetic component underlying the risk for AD. Three genes with autosomal dominant mutations lead to early-onset familial AD, which explains less than 1% of all AD. Apolipoprotein ε4, the only widely accepted genetic risk factor for late-onset AD, accounts for only a portion of this risk. Genetic linkage and association studies have identified multiple candidate gene regions, although many resulting candidate genes suffer from lack of replication, at least partially due to underpowered studies in the setting of genetic heterogeneity and small-tomoderate effect size. Genome-wide association studies that assess hundreds of thousands of single-nucleotide polymorphisms (SNPs in thousands of subjects have been viewed as a potentially powerful approach in uncovering common risk variations for genetically complex diseases such as AD. To date, 11 independent genome-wide association studies have been completed in late-onset AD (LOAD that led to candidate regions and genes for follow-up. These studies provide evidence for novel, plausible genetic risk factors for AD, but still fail to account for all of the estimated risk. Additional genetic risk factors of even smaller effect size, rare variants and/or structural DNA polymorphisms may exist, which may escape detection by conventional methods. Alternative approaches such as nextgeneration sequencing, use of quantitative endophenotypes, copy number variation analyses, and meta-analyses may be required. This review summarizes the

Opportunities for Grid Modernization Collaboration: U.K.-U.S. Grid Modernization Workshop Report, February 28 - March 2, 2017

Energy Technology Data Exchange (ETDEWEB)

2017-06-28

This report captures the discussions and takeaways from the U.K.-U.S. Grid Modernization Workshop on February 28-March 2, 2017 at the National Renewable Energy Laboratory. Speakers from across the United States and Europe convened to discuss the challenges associated with grid modernization for the 21st century, while identifying transatlantic solutions and opportunities for collaboration.

[Economics] Introductory Lesson (Begin Day One). Lesson Plan.

Science.gov (United States)

Lewin, Roland

This introductory lesson on teaching economics concepts contains sections on the following: purpose; objectives; time; materials needed; and step-by-step classroom procedures. The focus is on the economic problem of scarcity and opportunity costs. Attached is an original skit, "There's no such thing as a free lunch," and a chart that…

Regional Stability & Lessons Learned in Regional Peace Building

DEFF Research Database (Denmark)

Vestenskov, David; Johnsen, Anton Asklund

, as none of the countries is able to deal with the intrastate and interstate conflicts on its own. The conference Regional Stability & Lessons Learned in Regional Peace Building was the result of comprehensive cooperation between Pakistan’s National Defence University and the Royal Danish Defence College......The NATO-led intervention in Afghanistan is coming to an end, and the necessity of regional peace building solutions for the region’s security issues seems more exigent than ever before. Regional states have to come to terms with each other in some ways if violent extremists are to be countered...

English language-in-education: A lesson planning model for subject ...

African Journals Online (AJOL)

English language-in-education: A lesson planning model for subject teachers. ... lack of critical academic language skills in English as the Language of Learning and ... process of lesson design and the 'forward' process of lesson presentation.

AGOR 28

Science.gov (United States)

2015-12-18

and transporting them to a vendor in Seattle for measurements . The measuring will take place between the 28th and 30th. • Steering Hydraulics...the suction lower down on the hull. • CTD Handling Device – The cylinder has been reinstalled and tested. The repaired sensor is now measuring rod...Communications – FCC Station license applied for and approved. FBB activated. Iridium SIM Card in route from service provider. Inmarsat C’s and

Evolutionary insight on localization of 18S, 28S rDNA genes on homologous chromosomes in Primates genomes

Science.gov (United States)

Mazzoleni, Sofia; Rovatsos, Michail; Schillaci, Odessa; Dumas, Francesca

2018-01-01

Abstract We explored the topology of 18S and 28S rDNA units by fluorescence in situ hybridization (FISH) in the karyotypes of thirteen species representatives from major groups of Primates and Tupaia minor (Günther, 1876) (Scandentia), in order to expand our knowledge of Primate genome reshuffling and to identify the possible dispersion mechanisms of rDNA sequences. We documented that rDNA probe signals were identified on one to six pairs of chromosomes, both acrocentric and metacentric ones. In addition, we examined the potential homology of chromosomes bearing rDNA genes across different species and in a wide phylogenetic perspective, based on the DAPI-inverted pattern and their synteny to human. Our analysis revealed an extensive variability in the topology of the rDNA signals across studied species. In some cases, closely related species show signals on homologous chromosomes, thus representing synapomorphies, while in other cases, signal was detected on distinct chromosomes, leading to species specific patterns. These results led us to support the hypothesis that different mechanisms are responsible for the distribution of the ribosomal DNA cluster in Primates. PMID:29416829

Evolutionary insight on localization of 18S, 28S rDNA genes on homologous chromosomes in Primates genomes

Directory of Open Access Journals (Sweden)

Sofia Mazzoleni

2018-01-01

Full Text Available We explored the topology of 18S and 28S rDNA units by fluorescence in situ hybridization (FISH in the karyotypes of thirteen species representatives from major groups of Primates and Tupaia minor (Günther, 1876 (Scandentia, in order to expand our knowledge of Primate genome reshuffling and to identify the possible dispersion mechanisms of rDNA sequences. We documented that rDNA probe signals were identified on one to six pairs of chromosomes, both acrocentric and metacentric ones. In addition, we examined the potential homology of chromosomes bearing rDNA genes across different species and in a wide phylogenetic perspective, based on the DAPI-inverted pattern and their synteny to human. Our analysis revealed an extensive variability in the topology of the rDNA signals across studied species. In some cases, closely related species show signals on homologous chromosomes, thus representing synapomorphies, while in other cases, signal was detected on distinct chromosomes, leading to species specific patterns. These results led us to support the hypothesis that different mechanisms are responsible for the distribution of the ribosomal DNA cluster in Primates.

Nuclear Security Summit and Workshop 2015: Preventing, Understanding and Recovering from Nuclear Accidents lessons learned from Chernobyl and Fukushima

Science.gov (United States)

2016-09-01

Workshop 2015 "Preventing, Understanding and Recovering from Nuclear Accidents"--lessons learned from Chernobyl and Fukushima Distribution Statement...by the factor to get the U.S. customary unit. “Preventing, Understanding and Recovering from Nuclear Accidents” – lessons learned from Chernobyl ...and Fukushima NUCLEAR SECURITY SUMMIT & WORKSHOP 2015 2 Background The 1986 Chernobyl and the 2011 Fukushima accidents provoked world-wide concern

Feedback of safety - related operational experience: Lessons learned

Energy Technology Data Exchange (ETDEWEB)

Elias, D [Commonwealth Edison Co. (United States)

1997-09-01

The presentation considers the following aspects of feedback of safety-related operational experience: lessons learned program, objectives, personnel characteristics; three types of documents for transmitting lessons learned issues.

Feedback of safety - related operational experience: Lessons learned

International Nuclear Information System (INIS)

Elias, D.

1997-01-01

The presentation considers the following aspects of feedback of safety-related operational experience: lessons learned program, objectives, personnel characteristics; three types of documents for transmitting lessons learned issues

Role of intestinal brush border peptidases in the simulated digestion of milk proteins.

Science.gov (United States)

Picariello, Gianluca; Miralles, Beatriz; Mamone, Gianfranco; Sánchez-Rivera, Laura; Recio, Isidra; Addeo, Francesco; Ferranti, Pasquale

2015-05-01

This study aimed to assess the impact of the "often neglected" intestinal brush border membranes (BBMs) hydrolases on dietary peptides, exploring the possibility that the disintegration of proteins progressed in the small intestine up to a "core" of intrinsically stable oligopeptides, persisting independently on the up-stream breakdown. Samples of sodium caseinate, skim milk powder, and whey protein isolate were submitted to in vitro simulated gastropancreatic digestion using two different procedures: (i) a simplified model involving the main compartmental specific proteases; (ii) a static digestion method based on a frameset of parameters inferred from in vivo. The gastroduodenal digesta were further hydrolyzed with peptidases from porcine jejunal BBM. The peptidomes arising from the two digestion models, characterized by combined HPLC and MS techniques, differed to some extent. However, only specific protein domains survived digestion, among which are potential bioactive or immunogenic (food allergy) peptides. The degree of hydrolysis (DH) after BBM digestion (70-77%) practically did not differ between the digestion models and significantly increased the DH after duodenal steps. Any in vitro digestion model should be supplemented with a jejunal phase to realistically determine the bioaccessibility and bioavailability of dietary peptides. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.

Science.gov (United States)

Walus, Mariusz; Kida, Elizabeth; Golabek, Adam A

2010-06-01

There are 35 missense mutations among 68 different mutations in the TPP1 gene, which encodes tripeptidyl peptidase I (TPPI), a lysosomal aminopeptidase associated with classic late-infantile neuronal ceroid lipofuscinosis (CLN2 disease). To elucidate the molecular mechanisms underlying TPPI deficiency in patients carrying missense mutations and to test the amenability of mutant proteins to chemical chaperones and permissive temperature treatment, we introduced individually 14 disease-associated missense mutations into human TPP1 cDNA and analyzed the cell biology of these TPPI variants expressed in Chinese hamster ovary cells. Most TPPI variants displayed obstructed transport to the lysosomes, prolonged half-life of the proenzyme, and residual or no enzymatic activity, indicating folding abnormalities. Protein misfolding was produced by mutations located in both the prosegment (p.Gly77Arg) and throughout the length of the mature enzyme. However, the routes of removal of misfolded proteins by the cells varied, ranging from their efficient degradation by the ubiquitin/proteasome system to abundant secretion. Two TPPI variants demonstrated enhanced processing in response to folding improvement treatment, and the activity of one of them, p.Arg447His, showed a fivefold increase under permissive temperature conditions, which suggests that folding improvement strategies may ameliorate the function of some misfolding TPPI mutant proteins.

A compilation of information on the {sup 31}P(p,{alpha}){sup 28}Si reaction and properties of excited levels in the compound nucleus {sup 32}S

Energy Technology Data Exchange (ETDEWEB)

Miller, R.E.; Smith, D.L. [Argonne National Lab., IL (United States). Technology Development Div.

1997-11-01

This report documents a survey of the literature, and provides a compilation of data contained therein, for the {sup 31}P(p,{alpha}){sup 28}Si reaction. Attention is paid here to resonance states in the compound-nuclear system {sup 32}S formed by {sup 31}P + p, with emphasis on the alpha-particle decay channels, {sup 28}Si + {alpha} which populate specific levels in {sup 28}Si. The energy region near the proton separation energy for {sup 32}S is especially important in this context for applications in nuclear astrophysics. Properties of the excited states in {sup 28}Si are also considered. Summaries of all the located references are provided and numerical data contained in them are compiled in EXFOR format where applicable.

Drug fever and acute inflammation from hypercytokinemia triggered by dipeptidyl peptidase-4 inhibitor vildagliptin.

Science.gov (United States)

Anno, Takatoshi; Kaneto, Hideaki; Kawasaki, Fumiko; Shigemoto, Ryo; Aoyama, Yumi; Kaku, Kohei; Okimoto, Niro

2018-04-01

A 69-year-old man started taking the dipeptidyl peptidase-4 inhibitor, vildagliptin. One week later, C-reactive protein and plasma immunoglobulin E levels were markedly elevated, and the vildagliptin was stopped. After the patient's laboratory findings were normalized, we decided to restart vildagliptin with the patient's agreement. The next day, he had a high fever, and C-reactive protein and procalcitonin levels were elevated. Although we failed to find a focus of infection, we started antibiotics therapy. Two days later, the high fever had improved, and the C-reactive protein level had decreased. A drug lymphocyte stimulation test showed a positive result for vildagliptin. We examined various kinds of cytokine and infection markers just before and after the treatment with vildagliptin. Finally, we diagnosed the patient with vildagliptin-induced drug fever, probably based on the increase of various inflammatory cytokine levels and the response to this. Taken together, we should be aware of the possibility of vildagliptin inducing drug fever and/or acute inflammation. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

[Research progress of dipeptidyl peptidase 4 inhibitors on healing of chronic diabetic foot ulcers].

Science.gov (United States)

Gao, Yunyi; Liang, Yujie; Ran, Xingwu

2018-05-01

To review the effect of dipeptidyl peptidase 4 (DPP-4) inhibitors on the wound healing and its mechanisms in chronic diabetic foot ulcers. The latest literature concerning DPP-4 inhibitors for chronic diabetic foot ulcers was extensively reviewed, as well as the potential benefit and mechanism of DPP-4 inhibitors on wound healing of diabetic foot ulcers was analyzed thoroughly. DPP-4 inhibitors can accelerated the ulcer healing. The mechanisms probably include inhibiting the expression of the matrix metalloproteinase (MMP) and restoring the balance of the wound MMP and the tissue inhibitors of MMP; promoting recruitment of endothelial progenitor cells and augmenting angiogenesis; optimizing extracellular matrix construction and the immune response to persistent hypoxia in chronic diabetes wounds, and so on. At present, clinical researches show that DPP-4 inhibitors may be considered as an adjuvant treatment for chronic diabetic foot ulcers. DPP-4 inhibitors show promise in the local wound healing of chronic diabetic foot ulcers. However, more strictly designed, adequately powered, long-term follow-up, and high-quality randomized control trials are needed to further verify their efficacy and safety for chronic diabetic foot ulcers.

Driver. D530.2 – Tools for the Lessons Learned Framework

NARCIS (Netherlands)

Schaik, M.G. van; et al

2016-01-01

In this deliverable D530.2 “Tools for the Lessons Learned Framework” the overall lessons learned framework will be clarified based on the delivery D53.1 “Lessons Learned Framework Concept” and aligned with the deliverable D52.1 “Harmonized competence framework”. The Tools for the Lessons Learned

Synthetic (+)-antroquinonol exhibits dual actions against insulin resistance by triggering AMP kinase and inhibiting dipeptidyl peptidase IV activities.

Science.gov (United States)

Hsu, C Y; Sulake, R S; Huang, P-K; Shih, H-Y; Sie, H-W; Lai, Y-K; Chen, C; Weng, C F

2015-01-01

The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity. Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo. The results showed that of (+)-antroquinonol (100 μM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice. Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity. © 2014 The British Pharmacological Society.

UNLEARNED LESSONS OF CONTEMPORARY HISTORY

Directory of Open Access Journals (Sweden)

А Н Данилов

2017-12-01

Full Text Available The article considers the complex geopolitical situation in the global world at the end of the second decade of the 21st century as determined by the consequences of the collapse of the Soviet Union and by the new world order. The author seeks to answer the questions who will define the current geopolitical situation, whose aims it will reflect, what will become the basis of new geopolitical realities, the basis of moral solidarity of humankind, and the spiritual basis of future civilizations. The new challenges give rise to a desperate struggle for different scenarios for building a happy life. Moreover, it is not clear which ideal of the future world will be widely supported as a development guideline. The recognition as such of the standard of living and development of the strongest ones becomes a real threat to the new civilization for it leads to the loss of national interests of sovereign states, and to the loss of an independent future. Today, there is an active search for new theories and concepts that will adequately explain con-temporary global processes. In this thematic context, the author identifies main lessons not learned by the world political elites. The first lesson: new states are not born in an empty place, their common history is a great advantage ensuring prospects for the further development of interstate cooperation. The second lesson: the widespread falsification of history has a negative impact on national, cultural and social-group identity in transforming societies. The third lesson: after the collapse of the Soviet Union, the post-war balance of power was destroyed together with the system of checks and balances in world politics (a bipolar model of the world. The fourth lesson: under radical social transformations, the moral system of the population devaluates with numerous crisis consequences.

Laying the Groundwork: Lessons Learned from the Telecommunications Industry for Distributed Generation; Preprint

Energy Technology Data Exchange (ETDEWEB)

Wise, A. L.

2008-05-01

The telecommunications industry went through growing pains in the past that hold some interesting lessons for the growing distributed generation (DG) industry. The technology shifts and stakeholders involved with the historic market transformation of the telecommunications sector mirror similar factors involved in distributed generation today. An examination of these factors may inform best practices when approaching the conduits necessary to accelerate the shifting of our nation's energy system to cleaner forms of generation and use. From a technical perspective, the telecom industry in the 1990s saw a shift from highly centralized systems that had no capacity for adaptation to highly adaptive, distributed network systems. From a management perspective, the industry shifted from small, private-company structures to big, capital-intensive corporations. This presentation will explore potential correlation and outline the lessons that we can take away from this comparison.

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage.

Science.gov (United States)

Azpurua, Jorge; Ke, Zhonghe; Chen, Iris X; Zhang, Quanwei; Ermolenko, Dmitri N; Zhang, Zhengdong D; Gorbunova, Vera; Seluanov, Andrei

2013-10-22

The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.

The East Asian Development Experience: Policy Lessons, Implications, and Recommendations for Sub-Saharan Africa (SSA) Global Competitiveness

OpenAIRE

Ashford C. Chea

2012-01-01

The paper looks at the development experience of East Asia and draws lessons for Sub-Saharan Africa in building global competitiveness. It starts with a historical perspective of both regions’ developmental trajectories. This is followed by an analysis of the causes of East Asia’s superior economic performance and development and SSA underdevelopment. The article also draws policy lessons from East Asia development strategies for SSA global competitiveness. The paper ends with a presentation ...

The implementation of school-based lesson study at elementary school

Directory of Open Access Journals (Sweden)

Purnomo Purnomo

2017-07-01

Full Text Available This study aims to describe and interpret the implementation of school-based lesson study in SDN I Kretek. This study uses the qualitative research. The data were collected through in-depth interviews, participant observation, field notes, and documentation. The data validity was determined through sources and techniques triangulation. The data were analyzed using the Interactive Analysis Model from Miles and Huberman. The results show: (1 the planning of school-based lesson study program at SDN 1 Kretek has been implemented from the beginning of the school year 2014/2015 by establishing school-based lesson study team. This team is responsible for planning, managing, and evaluating school-based lesson study program at SDN 1 Kretek, (2 school-based lesson study at SDN 1 Kretek is implemented in three phases, namely planning, implementation, and reflection, and (3 The evaluation of lesson study is conducted by each teacher who has conducted the open class and conducted thoroughly with a meeting by a team of school-based lesson study SDN 1 Kretek at the end of the school year.

Nuclear critics and nuclear controversy: Lessons for the next 50 years

International Nuclear Information System (INIS)

Perkins, B.

1992-01-01

For more than a decade, nuclear electric power was at the center of one of the most widespread and passionate controversies in the United States. A combination of local community groups and a sophisticated national opposition seriously delayed nuclear plants being built in state after state, contributing to major cost increases and, in some instances, project cancellations. According to plans of the US government and electric power industry, new nuclear power plants will be ordered by the mid-1990s and will be in operation around the turn of the century. The success of these plans will depend in part on how well the government and industry learned the lessons of the years of controversy - how well they can rally public support despite the inevitable opposition of nuclear critics. This paper is based on a review of the national nuclear controversy of the 1970s and early 1980s. It analyzes the key lessons to be learned from those experiences and projects them onto the new societal and political setting of the 1990s, reflecting more recent research into effective siting procedures, public participation, risk communications, and other disciplines related to the development of public acceptance for nuclear power plants

NCBI nr-aa BLAST: CBRC-MMUR-01-1497 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-MMUR-01-1497 ref|ZP_02478000.1| fimbrial leader peptidase [Haemophilus parasui...s 29755] gb|EDS24927.1| fimbrial leader peptidase [Haemophilus parasuis 29755] ZP_02478000.1 9.4 26% ...

Histone H3 Serine 28 Is Essential for Efficient Polycomb-Mediated Gene Repression in Drosophila

Directory of Open Access Journals (Sweden)

Philip Yuk Kwong Yung

2015-06-01

Full Text Available Trimethylation at histone H3K27 is central to the polycomb repression system. Juxtaposed to H3K27 is a widely conserved phosphorylatable serine residue (H3S28 whose function is unclear. To assess the importance of H3S28, we generated a Drosophila H3 histone mutant with a serine-to-alanine mutation at position 28. H3S28A mutant cells lack H3S28ph on mitotic chromosomes but support normal mitosis. Strikingly, all methylation states of H3K27 drop in H3S28A cells, leading to Hox gene derepression and to homeotic transformations in adult tissues. These defects are not caused by active H3K27 demethylation nor by the loss of H3S28ph. Biochemical assays show that H3S28A nucleosomes are a suboptimal substrate for PRC2, suggesting that the unphosphorylated state of serine 28 is important for assisting in the function of polycomb complexes. Collectively, our data indicate that the conserved H3S28 residue in metazoans has a role in supporting PRC2 catalysis.

Plant Identification Characteristics for Deciduous Trees & Shrubs. Lesson Plans.

Science.gov (United States)

Burkholder, Kathy

This manual contains a group of lesson plans designed for use with a slide series (not included here). Its purpose is to introduce students to the basic concepts and terminology used in the identification of deciduous trees and shrubs. The manual is composed of 12 lesson plans. The first lesson is an introduction to plant identification. The…

How to Make Lesson Study Work in America and Worldwide: A Japanese Perspective on the Onto-Cultural Basis of (Teacher) Education

Science.gov (United States)

Rappleye, Jeremy; Komatsu, Hikaru

2017-01-01

Lesson Study is a Japanese approach to teacher development borrowed by American researchers in the late 1990s seeking to break from top-down, "best practice" approaches. Two decades later, Lesson Study has gained a strong foothold in American policy circles. Seeking to contribute to the growing research base, this article looks deeper…

Considerations for implementing an organizational lessons learned process.

Energy Technology Data Exchange (ETDEWEB)

Fosshage, Erik D

2013-05-01

This report examines the lessons learned process by a review of the literature in a variety of disciplines, and is intended as a guidepost for organizations that are considering the implementation of their own closed-loop learning process. Lessons learned definitions are provided within the broader context of knowledge management and the framework of a learning organization. Shortcomings of existing practices are summarized in an attempt to identify common pitfalls that can be avoided by organizations with fledgling experiences of their own. Lessons learned are then examined through a dual construct of both process and mechanism, with emphasis on integrating into organizational processes and promoting lesson reuse through data attributes that contribute toward changed behaviors. The report concludes with recommended steps for follow-on efforts.

Towards a lessons learned system for critical software

International Nuclear Information System (INIS)

Andrade, J.; Ares, J.; Garcia, R.; Pazos, J.; Rodriguez, S.; Rodriguez-Paton, A.; Silva, A.

2007-01-01

Failure can be a major driver for the advance of any engineering discipline and Software Engineering is no exception. But failures are useful only if lessons are learned from them. In this article we aim to make a strong defence of, and set the requirements for, lessons learned systems for safety-critical software. We also present a prototype lessons learned system that includes many of the features discussed here. We emphasize that, apart from individual organizations, lessons learned systems should target industrial sectors and even the Software Engineering community. We would like to encourage the Software Engineering community to use this kind of systems as another tool in the toolbox, which complements or enhances other approaches like, for example, standards and checklists

Towards a lessons learned system for critical software

Energy Technology Data Exchange (ETDEWEB)

Andrade, J. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: jag@udc.es; Ares, J. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: juanar@udc.es; Garcia, R. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: rafael@udc.es; Pazos, J. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: jpazos@fi.upm.es; Rodriguez, S. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: santi@udc.es; Rodriguez-Paton, A. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: arpaton@fi.upm.es; Silva, A. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: asilva@fi.upm.es

2007-07-15

Failure can be a major driver for the advance of any engineering discipline and Software Engineering is no exception. But failures are useful only if lessons are learned from them. In this article we aim to make a strong defence of, and set the requirements for, lessons learned systems for safety-critical software. We also present a prototype lessons learned system that includes many of the features discussed here. We emphasize that, apart from individual organizations, lessons learned systems should target industrial sectors and even the Software Engineering community. We would like to encourage the Software Engineering community to use this kind of systems as another tool in the toolbox, which complements or enhances other approaches like, for example, standards and checklists.

Lessons from Goiania

International Nuclear Information System (INIS)

Nazari Alves, R.

2000-01-01

The lessons learned from the radiological accident of Goiania in 1987 derived from the observations from the Regulatory Agency which was in charge of the decontamination tasks may be consolidated into four classes: Preventive Actions, characterised as those that aim to minimise the probability of occurrence of a radiological accident; Minimisation of time between the moment of the accident occurrence and the beginning of intervention, in case a radiological accident does occur, despite all preventive measures; Intervention, which is correlated to the type of installation, its geographical location, the social classes involved and their contamination vectors; and Follow up, for which well established rules to allow continuing monitoring of the victims and rebuilding of homes are necessary. The greatest lesson of all was the need for integration of the professionals involved, from all organizations. (author)

Lessons learned on digital systems safety

International Nuclear Information System (INIS)

Sivertsen, Terje

2005-06-01

A decade ago, in 1994, lessons learned from Halden research activities on digital systems safety were summarized in the reports HWR-374 and HWR-375, under the title 'A Lessons Learned Report on Software Dependability'. The reports reviewed all activities made at the Halden Project in this field since 1977. As such, the reports provide a wealth of information on Halden research. At the same time, the lessons learned from the different activities are made more accessible to the reader by being summarized in terms of results, conclusions and recommendations. The present report provides a new lessons learned report, covering the Halden Project research activities in this area from 1994 to medio 2005. As before, the emphasis is on the results, conclusions and recommendations made from these activities, in particular how they can be utilized by different types of organisations, such as licensing authorities, safety assessors, power companies, and software developers. The contents of the report have been edited on the basis of input from a large number of Halden work reports, involving many different authors. Brief summaries of these reports are included in the last part of the report. (Author)

Lesson Study-Building Communities of Learning Among Pre-Service Science Teachers

Science.gov (United States)

Hamzeh, Fouada

Lesson Study is a widely used pedagogical approach that has been used for decades in its country of origin, Japan. It is a teacher-led form of professional development that involves the collaborative efforts of teachers in co-planning and observing the teaching of a lesson within a unit for evidence that the teaching practices used help the learning process (Lewis, 2002a). The purpose of this research was to investigate if Lesson Study enables pre-service teachers to improve their own teaching in the area of science inquiry-based approaches. Also explored are the self-efficacy beliefs of one group of science pre-service teachers related to their experiences in Lesson Study. The research investigated four questions: 1) Does Lesson Study influence teacher preparation for inquiry-based instruction? 2) Does Lesson Study improve teacher efficacy? 3) Does Lesson Study impact teachers' aspiration to collaborate with colleagues? 4) What are the attitudes and perceptions of pre-service teachers to the Lesson Study idea in Science? The 12 participants completed two pre- and post-study surveys: STEBI- B, Science Teaching Efficacy Belief Instrument (Enochs & Riggs, 1990) and ASTQ, Attitude towards Science Teaching. Data sources included student teaching lesson observations, lesson debriefing notes and focus group interviews. Results from the STEBI-B show that all participants measured an increase in efficacy throughout the study. This study added to the body of research on teaching learning communities, professional development programs and teacher empowerment.

Reflection after teaching a lesson: Experiences of secondary school science teachers

Science.gov (United States)

Halstead, Melissa A.

Secondary science teachers spend most of their time planning, collaborating, and teaching, but spend little time reflecting after teaching a single lesson. The theoretical framework of the adult learning theory and the transformative learning theory was the basis of this study. This qualitative research study was conducted to understand the reflective experiences of secondary science educators after teaching a single or several lessons. The collection of data consisted of interviews from a group of purposefully selected secondary science teachers who met the criteria set forth by the researcher. Through a qualitative analysis of interviews and field notes, the researcher determined that the secondary science teachers in this study shared similar as well as different experiences regarding collaborative and individual reflection after teaching a single or several lessons. The findings from this study also suggested that secondary science educators prefer to collaboratively reflect and then reflect alone to allow for further thought. Additionally, a supportive school culture increases the secondary science teacher’s desire to engage in collaborative as well as individual reflection. The information from this study could be used to close the gaps that exist in the teacher professional development programs.

Teen worker safety training: methods used, lessons taught, and time spent.

Science.gov (United States)

Zierold, Kristina M

2015-05-01

Safety training is strongly endorsed as one way to prevent teens from performing dangerous tasks at work. The objective of this mixed methods study was to characterize the safety training that teenagers receive on the job. From 2010 through 2012, focus groups and a cross-sectional survey were conducted with working teens. The top methods of safety training reported were safety videos (42 percent) and safety lectures (25 percent). The top lessons reported by teens were "how to do my job" and "ways to spot hazards." Males, who were more likely to do dangerous tasks, received less safety training than females. Although most teens are getting safety training, it is inadequate. Lessons addressing safety behaviors are missing, training methods used are minimal, and the time spent is insignificant. More research is needed to understand what training methods and lessons should be used, and the appropriate safety training length for effectively preventing injury in working teens. In addition, more research evaluating the impact of high-quality safety training compared to poor safety training is needed to determine the best training programs for teens. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Lessons of nuclear robot history

International Nuclear Information System (INIS)

Oomichi, Takeo

2014-01-01

Severe accidents occurred at Fukushima Daiichi Nuclear Power Station stirred up people's great expectation of nuclear robot's deployment. However unexpected nuclear disaster, especially rupture of reactor building caused by core meltdown and hydrogen explosion, made it quite difficult to introduce nuclear robot under high radiation environment to cease accidents and dispose damaged reactor. Robotics Society of Japan (RSJ) set up committee to look back upon lessons learned from 50 year's past experience of nuclear robot development and summarized 'Lessons of nuclear robot history', which was shown on the home page website of RSJ. This article outlined it with personal comment. History of nuclear robot developed for inspection and maintenance at normal operation and for specific required response at nuclear accidents was reviewed with many examples at home and abroad for TMI, Chernobyl and JCO accidents. Present state of Fukushima accident response robot's introduction and development was also described with some comments on nuclear robot development from academia based on lessons. (T. Tanaka)

PENERAPAN PEMBELAJARAN KOOPERATIF TIPE JIGSAW BERBASIS LESSON STUDY UNTUK MENINGKATAN AKTIVITAS KOLABORATIF MAHASISWA PGSD PADA MATA KULIAH PENDIDIKAN MATEMATIKA I

Directory of Open Access Journals (Sweden)

Ratih Purnamasari

2016-09-01

Full Text Available Abstrak. Penelitian ini bertujuan mengetahui peningkatan aktivitas kolaboratif mahasiswa pada mata kuliah pendidikan matematika I dengan menerapkan pembelajaran kooperatif tipe jigsaw berbasis lesson study. Penelitian dilakukan dengan tahapan-tahapan yang berlaku dalam pembelajaran berbasis lesson study yang terdiri dari plan, do dan see. Lokasi penelitian di FKIP UNPAK dengan waktu pelaksanaan antara bulan Mei-Juni 2013. Subyek penelitian mahasiswa S1 Prodi Pendidikan Guru Sekolah Dasar (PGSD semester VI yang mengambil mata kuliah pendidikan matematika I. Pengumpulan data dengan teknik dokumentasi, observasi, wawancara dan angket. Instrumen meliputi : lembar observasi, pedoman wawancara dan angket. Data hasil observasi dianalisis secara deskriptif kualitatif untuk mengetahui peningkatan aktivitas kolaboratif mahasiswa dalam kerja kelompok. Hasil penelitian menunjukkan penerapan pembelajaran kooperatif tipe jigsaw berbasis lesson study dapat meningkatkan aktivitas kolaboratif mahasiswa dalam kerja kelompok pada mata kuliah pendidikan matematika I, khususnya pada materi KPK, FPB dan pecahan. Hal ini dapat dilihat dari peningkatan ketercapaian indikator kegiatan lesson study di setiap siklusnya, serta hasil angket respon mahasiswa yang mayoritas menyatakan positif terhadap proses pembelajaran yang dilakukan. Selain itu, hasil wawancara terhadap mahasiswa juga menunjukkan bahwa pembelajaran kooperatif tipe jigsaw ternyata dapat meningkatkan motivasi mahasiswa untuk belajar secara berkolaborasi. Alangkah baiknya jika para dosen dalam membelajarkan mata kuliah pendidikan matematika 1 mencoba menggunakan pembelajaran kooperatif tipe jigsaw berbasis lesson study. Kata Kunci: Aktivitas Kolaboratif, Jigsaw, Lesson Study  Abstract. This study aimed to increase collaborative activities of students in the subject of Pendidikan Matematika I by implementing cooperative learning jigsaw-based lesson study. Research carried out by stages that apply in lesson

Karyological characterization and identification of four repetitive element groups (the 18S – 28S rRNA gene, telomeric sequences, microsatellite repeat motifs, Rex retroelements) of the Asian swamp eel (Monopterus albus)

Science.gov (United States)

Suntronpong, Aorarat; Thapana, Watcharaporn; Twilprawat, Panupon; Prakhongcheep, Ornjira; Somyong, Suthasinee; Muangmai, Narongrit; Surin Peyachoknagul; Srikulnath, Kornsorn

2017-01-01

Abstract Among teleost fishes, Asian swamp eel (Monopterus albus Zuiew, 1793) possesses the lowest chromosome number, 2n = 24. To characterize the chromosome constitution and investigate the genome organization of repetitive sequences in M. albus, karyotyping and chromosome mapping were performed with the 18S – 28S rRNA gene, telomeric repeats, microsatellite repeat motifs, and Rex retroelements. The 18S – 28S rRNA genes were observed to the pericentromeric region of chromosome 4 at the same position with large propidium iodide and C-positive bands, suggesting that the molecular structure of the pericentromeric regions of chromosome 4 has evolved in a concerted manner with amplification of the 18S – 28S rRNA genes. (TTAGGG)n sequences were found at the telomeric ends of all chromosomes. Eight of 19 microsatellite repeat motifs were dispersedly mapped on different chromosomes suggesting the independent amplification of microsatellite repeat motifs in M. albus. Monopterus albus Rex1 (MALRex1) was observed at interstitial sites of all chromosomes and in the pericentromeric regions of most chromosomes whereas MALRex3 was scattered and localized to all chromosomes and MALRex6 to several chromosomes. This suggests that these retroelements were independently amplified or lost in M. albus. Among MALRexs (MALRex1, MALRex3, and MALRex6), MALRex6 showed higher interspecific sequence divergences from other teleost species in comparison. This suggests that the divergence of Rex6 sequences of M. albus might have occurred a relatively long time ago. PMID:29093797

PENERAPAN LESSON STUDY UNTUK MENINGKATAN KEMAMPUAN MENGAJAR MAHASISWA CALON GURU FISIKA

Directory of Open Access Journals (Sweden)

Rif’ati Dina Handayani

2015-02-01

ABSTRAK Lesson study merupakan suatu model pengembangan kemampuan mengajar melalui pengkajian pembelajaran secara kolaboratif dan berkelanjutan. Lesson study dilaksanakan dalam tiga tahapan, yaitu plan, do, see yang dilaksanakan secara terstruktur, bersiklus dan berkelanjutan. Dalam penelitian ini subjek dari pelaksanaan lesson study adalah empat orang  mahasiswa calon guru fisika yang sedang melaksanakan PPL di salah satu SMP Negeri di Bondowoso. Hasil penelitian menunjukkan bahwa penerapan lesson study dapat meningkatkan kemampuan mengajar mahasiswa calon guru fisika dari kriteria kurang baik menjadi kriteria sangat baik. Kata kunci: Calon guru fisika, Lesson Study, Kemampuan Mengajar

LESSONS LEARNED Biosurveillance Mobile App Development Intern Competition (Summer 2013)

Energy Technology Data Exchange (ETDEWEB)

Noonan, Christine F. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Henry, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Corley, Courtney D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2014-01-14

The purpose of the lessons learned document for the BEOWulf Biosurveillance Mobile App Development Intern Competition is to capture the project’s lessons learned in a formal document for use by other project managers on similar future projects. This document may be used as part of new project planning for similar projects in order to determine what problems occurred and how those problems were handled and may be avoided in the future. Additionally, this document details what went well with the project and why, so that other project managers may capitalize on these actions. Project managers may also use this document to determine who the project team members were in order to solicit feedback for planning their projects in the future. This document will be formally communicated with the organization and will become a part of the organizational assets and archives.

Constellation Program: Lessons Learned. Volume 1; Executive Summary

Science.gov (United States)

Rhatigan, Jennifer L. (Editor)

2011-01-01

This document (Volume I) provides an executive summary of the lessons learned from the Constellation Program. A companion Volume II provides more detailed analyses for those seeking further insight and information. In this volume, Section 1.0 introduces the approach in preparing and organizing the content to enable rapid assimilation of the lessons. Section 2.0 describes the contextual framework in which the Constellation Program was formulated and functioned that is necessary to understand most of the lessons. Context of a former program may seem irrelevant in the heady days of new program formulation. However, readers should take some time to understand the context. Many of the lessons would be different in a different context, so the reader should reflect on the similarities and differences in his or her current circumstances. Section 3.0 summarizes key findings developed from the significant lessons learned at the program level that appear in Section 4.0. Readers can use the key findings in Section 3.0 to peruse for particular topics, and will find more supporting detail and analyses in Section 4.0 in a topical format. Appendix A contains a white paper describing the Constellation Program formulation that may be of use to readers wanting more context or background information. The reader will no doubt recognize some very similar themes from previous lessons learned, blue-ribbon committee reviews, National Academy reviews, and advisory panel reviews for this and other large-scale human spaceflight programs; including Apollo, Space Shuttle, Shuttle/Mir, and the ISS. This could represent an inability to learn lessons from previous generations; however, it is more likely that similar challenges persist in the Agency structure and approach to program formulation, budget advocacy, and management. Perhaps the greatest value of these Constellation lessons learned can be found in viewing them in context with these previous efforts to guide and advise the Agency and its

Do Lessons in Nature Boost Subsequent Classroom Engagement? Refueling Students in Flight

Directory of Open Access Journals (Sweden)

Ming Kuo

2018-01-01

Full Text Available Teachers wishing to offer lessons in nature may hold back for fear of leaving students keyed up and unable to concentrate in subsequent, indoor lessons. This study tested the hypothesis that lessons in nature have positive—not negative—aftereffects on subsequent classroom engagement. Using carefully matched pairs of lessons (one in a relatively natural outdoor setting and one indoors, we observed subsequent classroom engagement during an indoor instructional period, replicating these comparisons over 10 different topics and weeks in the school year, in each of two third grade classrooms. Pairs were roughly balanced in how often the outdoor lesson preceded or followed the classroom lesson. Classroom engagement was significantly better after lessons in nature than after their matched counterparts for four of the five measures developed for this study: teacher ratings; third-party tallies of “redirects” (the number of times the teacher stopped instruction to direct student attention back onto the task at hand; independent, photo-based ratings made blind to condition; and a composite index each showed a nature advantage; student ratings did not. This nature advantage held across different teachers and held equally over the initial and final 5 weeks of lessons. And the magnitude of the advantage was large. In 48 out of 100 paired comparisons, the nature lesson was a full standard deviation better than its classroom counterpart; in 20 of the 48, the nature lesson was over two standard deviations better. The rate of “redirects” was cut almost in half after a lesson in nature, allowing teachers to teach for longer periods uninterrupted. Because the pairs of lessons were matched on teacher, class (students and classroom, topic, teaching style, week of the semester, and time of day, the advantage of the nature-based lessons could not be attributed to any of these factors. It appears that, far from leaving students too keyed up to concentrate

Sarcopenia in Elderly Diabetic Patients: Role of Dipeptidyl Peptidase 4 Inhibitors.

Science.gov (United States)

Rizzo, Maria Rosaria; Barbieri, Michelangela; Fava, Ilaria; Desiderio, Manuela; Coppola, Carla; Marfella, Raffaele; Paolisso, Giuseppe

2016-10-01

Our study aimed to investigate the effect of dipeptidyl peptidase 4 inhibitors (DPP4-I) on sarcopenic parameters in elderly type 2 diabetic patients. All elderly diabetic patients were invited to present themselves at our outpatient Geriatric Centre to undergo to evaluation of glycemic, inflammatory, and sarcopenic parameters and to perform a meal test for glucagon-like peptide-1 analogue (GLP-1) activity evaluation. According to European Working Group on Sarcopenia in Older People (EWGSOP) criteria, sarcopenic parameters were assessed by bioelectrical impedance analysis (BIA) and Kern dynamometer and 4-m gait speed tests. All patients received standardized meals for the assessment of postprandial levels of GLP-1 activity. Data of 80 elderly diabetic patients treated with oral glucose-lowering drugs (DPP4-I or Sulfonylureas Group) for at least 24 months before enrollment were analyzed. The DPP4-I Group showed appropriate glycemic control, lower levels of inflammatory parameters, a significant and greater increase, during interprandial periods, of GLP-1 activity, and better sarcopenic parameters (fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed) compared with the Sulfonylureas Group. Univariate analysis showed that sarcopenic parameters correlated with glycemic control and with GLP-1 area under the curve values. Multivariate analysis confirms these relationships. The results are consistent with the hypothesis that DPP4-I use might have a positive effect on the loss of muscle mass and its function. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Dipeptidyl peptidase-II from probiotic Pediococcus acidilactici: Purification and functional characterization.

Science.gov (United States)

Gandhi, Dimpi; Chanalia, Preeti; Attri, Pooja; Dhanda, Suman

2016-12-01

Dipeptidylpeptidase-II (DPP-II, E.C. 3.4.14.2), an exopeptidase was purified 15.4 fold with specific activity and yield of 15.4U/mg/mL and 14.68% respectively by a simple two step procedure from a probiotic Pediococcus acidilactici. DPP-II is 38.7KDa homodimeric serine peptidase with involvement of His and subunit mass of 18.9KDa. The enzyme exhibited optimal activity at pH 7.0 and 37°C with activation energy of 24.97kJ/mol. The enzyme retained more than 90% activity upto 50°C thus adding industrial importance. DPP-II hydrolysed Lys-Ala-4mβNA with K M of 50μM and V max of 30.8nmol/mL/min. In-silico characterization studies of DPP-II on the basis of peptide fragments obtained by MALDI-TOF revealed an evolutionary relationship between DPP-II of prokaryotes and phosphate binding proteins. Secondary and three-dimensional structure of enzyme was also deduced by in-silico approach. Functional studies of DPP-II by TLC and HPLC-analysis of collagen degraded products revealed that enzyme action released free amino acids and other metabolites. Microscopic and SDS-PAGE analysis of enzyme treated analysis of chicken's chest muscle (meat) hydrolysis revealed change and hydrolysis of myofibrils. This may affect the flavor and texture of meat thereby suggesting its role in meat tenderization. Being a protein of LAB (Lactic acid bacteria), it is also expected to be safe. Copyright © 2016 Elsevier B.V. All rights reserved.

Inspiring Creativity in Urban School Leaders: Lessons from the Performing Arts

Science.gov (United States)

Kaimal, Girija; Drescher, Jon; Fairbank, Holly; Gonzaga, Adele; White, George P.

2014-01-01

This paper presents an analysis of how guided engagement with the arts can provide leadership lessons for school leaders and administrators. The study was conducted as part of two projects funded by the School Leadership Program (SLP) grants from the U.S. Department of Education. The principal interns and practicing school leaders participated in…

From the School Newsroom to the Courtroom. Lessons on the Hazelwood Case and Free Expression Policy Making in the Public Schools.

Science.gov (United States)

Rosenblum, Warren; And Others

The purpose of this lesson packet is to raise issues about student rights of free expression in public schools. Included are preparatory reading material and two classroom simulation activities. The lessons are based on the U.S. Supreme Court case of Hazelwood v. Kuhlmeier, in which a Missouri high school principal and school district were sued by…

Pacemaker Primary Curriculum; Lesson Book Level B.

Science.gov (United States)

Ross, Dorothea M.; Ross, Sheila A.

This lesson book, which is the second in a four-level program for young children with learning difficulties, describes the purpose of and equipment and procedures for teaching lessons in the following subjects areas on the primary grade level: arithmetic, reading, vocabulary, listening, planning, problem solving, social behavior, art, music, and…

Pacemaker Primary Curriculum; Lesson Book Level A.

Science.gov (United States)

Ross, Dorothea M.; Ross, Sheila A.

This lesson book, which is the first in a four-level program for young children with learning difficulties, describes the purpose of and equipment and procedures for teaching lessons in the following subject areas on the kindergarten level: arithmetic concepts, number concepts, reading readiness, vocabulary, language, listening, social behavior,…

Pacemaker Primary Curriculum; Lesson Book Level C.

Science.gov (United States)

Ross, Dorothea M.; Ross, Sheila A.

This lesson book, which is the third in a four-level program for young children with learning difficulties, describes the purpose of and equipment and procedures for teaching lessons in the following subject areas on the primary grade level: arithmetic, reading, vocabulary, spelling, printing, listening, planning, problem solving, social behavior,…

Pacemaker Primary Curriculum; Lesson Book Level D.

Science.gov (United States)

Ross, Dorothea M.; Ross, Sheila A.

This lesson book, which is the last in a four-level program for young children with learning difficulties, describes the purpose of and equipment and procedures for teaching lessons in the following subject areas on the primary level: arithmetic, reading, vocabulary, spelling, printing, listening, planning and problem solving, social behavior,…

Lessons from World War I

Directory of Open Access Journals (Sweden)

John Scales Avery

2014-05-01

Full Text Available The history of World War I is reviewed, starting with a discussion of the development of nationalist movements in Europe. It is pointed out that the global disaster started with a seemingly small operation by Austria, which escalated uncontrollably into an all-destroying conflagration. A striking feature of the war was that none of the people who started it had any idea of what it would be like. Technology had changed the character of war, but old patterns of thought remained in place. We also examine the roots of the war in industrial and colonial competition, and in an arms race. Finally, parallels with current events, and the important lessons for today’s world are discussed.

Lessons Learned In Aerosol Monitoring With The RASA

International Nuclear Information System (INIS)

Forrester, Joel B.; Bowyer, Ted W.; Carty, Fitz; Comes, Laura; Eslinger, Paul W.; Greenwood, Lawrence R.; Haas, Derek A.; Hayes, James C.; Kirkham, Randy R.; Lepel, Elwood A.; Litke, Kevin E.; Miley, Harry S.; Morris, Scott J.; Schrom, Brian T.; Van Davelaar, Peter; Woods, Vincent T.

2011-01-01

The Radionuclide Aerosol Sampler/Analyzer (RASA) is an automated aerosol collection and analysis system designed by Pacific Northwest National Laboratory (PNNL) in the 1990's and is deployed in several locations around the world as part of the International Monitoring System (IMS) required under the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The RASA operates unattended, save for regularly scheduled maintenance, iterating samples through a three-step process on a 24-hour interval. In its 15-year history, much has been learned from the operation and maintenance of the RASA that can benefit engineering updates or future aerosol systems. On 11 March 2011, a 9.0 magnitude earthquake and tsunami rocked the eastern coast of Japan, resulting in power loss and cooling failures at the Daiichi nuclear power plants in Fukushima Prefecture. Aerosol collections were conducted with the RASA in Richland, WA. We present a summary of the lessons learned over the history of the RASA, including lessons taken from the Fukushima incident, regarding the RASA IMS stations operated by the United States.

Teaching Norwegian to Beginners: Six Principles to Guide Lesson Planning

Directory of Open Access Journals (Sweden)

Anna Krulatz

2014-01-01

Full Text Available Teaching a foreign language is no simple task. There are several factors to consider, from curriculum design, to material selection and lesson implementation, to assessment. The challenge, however, is even greater, if you are teaching a less commonly taught language such as Norwegian – a language spoken by fewer than six million native speakers, used almost exclusively in one country, and with a limited number of available pedagogical materials. Under such circumstances, the task of preparing high quality communicative lessons is immense, even for an experienced language instructor. The goal of this article is to present how a successful language lesson can be developed even if one is using a textbook that does not foster communicative competence. As an example, I am using a unit from a Norwegian textbook for beginners: På vei, often used in Norwegian as a second language course for adults in Norway. The lesson focuses on routines and times of the day, and it concludes with the students comparing and contrasting their daily routines with a partner. Prior to this lesson, students have learned to provide basic information about themselves (where they come from, what languages they speak, what they do for work, expressions for greetings and goodbyes, basic verbs relating to daily activities such as ‘snakker’ (to speak, ‘kjører’ (to drive, ‘kjøpper’ (to buy, ‘jobber’ (to work, ‘leser’ (to read, ‘scriver’ (to write, ordinal numerals, meals, some food items, some basic prepositions and locations, words for family members, and subject and object pronouns for all persons. If you were to closely follow the textbook in teaching this unit, you would begin by teaching the students how to tell time, then briefly go over some verbs to express daily routines, listen to and read a text titled ‘Jeg står opp klokka seks,’ a narrative about Monica’s day (Monica is one of the characters in the book, and finally ask the students

The Decay of Bound Isobaric Analogue States in {sup 28}Si and {sup 32}S Using (d, n{gamma}) Reactions

Energy Technology Data Exchange (ETDEWEB)

Nilsson, L; Nilsson, A; Bergqvist, I

1970-03-15

A method has been developed for recording coincidences between neutrons and gamma - rays produced in (d, n{gamma}) reactions. Neutron energies were measured by time-of-flight techniques and a large Nal(Tl) crystal was used to determine gamma - ray energies and intensities. The neutron detector was placed in the forward direction to emphasize the excitation of l{sub P} = 0 levels in the residual nuclei. The method was applied to the {sup 27}Al (d, n{gamma}) {sup 28}Si and {sup 31}P (d, n{gamma}) {sup 32}S reactions at the deuteron energy 4.0 MeV. The gamma - ray decay of a number of levels below 12 MeV in {sup 28}Si and below 9 MeV in {sup 32}S was studied. The isobaric analogue levels are prominently populated by the (d, n) reaction. The method is in particular suitable for studies of the decay of these levels.

Knowledge and Cognitive Process Dimensions of Technology Teachers' Lesson Objectives

Science.gov (United States)

Mathumbu, David; Rauscher, Willem; Braun, Max

2014-01-01

A clearly stated lesson objective is considered an essential component of a well-planned lesson. Many teachers of Technology, a relatively new subject in South African schools, teach Technology with rather limited training both in content and methodological approaches. This study sought to investigate and classify lesson objectives framed or…

Public Heath in Colonial and Post-Colonial Ghana: Lesson-Drawing for The Twenty-First Century

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Adu-Gyamfi, Samuel

2017-06-01

Full Text Available Public health in twenty-first century Ghana is mired with several issues ranging from the inadequacy of public health facilities, improper settlement planning, insanitary conditions, and the inadequacy of laws and their implementation. This situation compared to the colonial era is a direct contradiction. Development in the pre-colonial era to the colonial era sought to make the prevention of diseases a priority in the colonial administration. This was begun with the establishment of the health branch in 1909 as a response to the bubonic plague that was fast spreading in the colony. From here public health policies and strategies were enacted to help the diseases prevention cause. Various public health boards, the medical research institute or the laboratory branch, the waste management department, the use of preventive medicine and maintenance of good settlement planning and sanitation were public health measures in the colonial era. This research seeks to analyse the public health system in the colonial era so as to draw basic lessons for twenty-first century Ghana. Archival data and other secondary sources are reviewed and analysed to help draw these lessons. Richard Rose’s lesson-drawing approach was used to draw the lessons.

Effective Lesson Planning: Field Trips in the Science Curriculum

Science.gov (United States)

Rieger, C. R.

2010-10-01

Science field trips can positively impact and motivate students. However, if a field trip is not executed properly, with appropriate preparation and follow-up reinforcement, it can result in a loss of valuable educational time and promote misconceptions in the students. This study was undertaken to determine if a classroom lesson before an out-of-the-classroom activity would affect learner gain more or less than a lesson after the activity. The study was based on the immersive theater movie ``Earth's Wild Ride'' coupled with a teacher-led Power Point lesson. The participants in the study were students in a sixth grade physical science class. The order of lessons showed no detectable effect on final learner outcomes. Based on pre- and post-testing, improvement in mean learning gain came from the teacher-led lesson independent of the movie. The visit to the immersive theater, however, had significant positive effects that did not show up in the quantitative results of the testing.

Behavioral Characteristics of Ubiquitin-Specific Peptidase 46-Deficient Mice

Science.gov (United States)

Imai, Saki; Kano, Makoto; Nonoyama, Keiko; Ebihara, Shizufumi

2013-01-01

We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST) and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92), and mice with this mutation (MT mice), as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA) receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT) or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system. PMID:23472206

Behavioral characteristics of ubiquitin-specific peptidase 46-deficient mice.

Directory of Open Access Journals (Sweden)

Saki Imai

Full Text Available We have previously identified Usp46, which encodes for ubiquitin-specific peptidase 46, as a quantitative trait gene affecting the immobility time of mice in the tail suspension test (TST and forced swimming test. The mutation that we identified was a 3-bp deletion coding for lysine (Lys 92, and mice with this mutation (MT mice, as well as Usp46 KO mice exhibited shorter TST immobility times. Behavioral pharmacology suggests that the gamma aminobutyric acid A (GABAA receptor is involved in regulating TST immobility time. In order to understand how far Usp46 controls behavioral phenotypes, which could be related to mental disorders in humans, we subjected Usp46 MT and KO mice to multiple behavioral tests, including the open field test, ethanol preference test, ethanol-induced loss of righting reflex test, sucrose preference test, novelty-suppressed feeding test, marble burying test, and novel object recognition test. Although behavioral phenotypes of the Usp46 MT and KO mice were not always identical, deficiency of Usp46 significantly affected performance in all these tests. In the open field test, activity levels were lower in Usp46 KO mice than wild type (WT or MT mice. Both MT and KO mice showed lower ethanol preference and shorter recovery times after ethanol administration. Compared to WT mice, Usp46 MT and KO mice exhibited decreased sucrose preference, took longer latency periods to bite pellets, and buried more marbles in the sucrose preference test, novelty-suppressed feeding test, and marble burying test, respectively. In the novel object recognition test, neither MT nor KO mice showed an increase in exploration of a new object 24 hours after training. These findings indicate that Usp46 regulates a wide range of behavioral phenotypes that might be related to human mental disorders and provides insight into the function of USP46 deubiquitinating enzyme in the neural system.

Proceedings of a U.S. Geological Survey pressure-sensor Workshop, Denver, Colorado, July 28-31, 1992

Science.gov (United States)

Wilbourn, Sammy L.

1994-01-01

The U.S. Geological Survey (USGS) conducted a Pressure Sensor Workshop, oriented toward the measurement of stage in surface waters, in Denver, Colorado, July 28-31, 1992. Twenty attendees from the U.S. Geological Survey and the National Oceanic and Atmospheric Administration gave presentations concerning their experiences with the use of pressure sensors in hydrologic investigations. This report is a compilation of the abstracts of the presentations made at the workshop. Workshop participants concluded that each of the sensors evaluated by the U.S. Geological Survey has strengths and weaknesses. Personnel contemplating the use of pressure sensors discussed at this workshop should contact workshop attendees and consult with them about their experiences with those sensors. The attendees preferred to use stilling wells with float-operated water-level sensors as the primary means for monitoring water levels. However, pressure sensor systems were favored as replacements for mercury manometers and as alternatives to stilling wells at sites where stilling wells are not practical or cost effective.

Leadership in American Indian Communities: Winter Lessons

Science.gov (United States)

Metoyer, Cheryl A.

2010-01-01

Winter lessons, or stories told in the winter, were one of the ways in which tribal elders instructed and directed young men and women in the proper ways to assume leadership responsibilities. Winter lessons stressed the appropriate relationship between the leader and the community. The intent was to remember the power and purpose of that…

Comparing U.S. Army suicide cases to a control sample: initial data and methodological lessons.

Science.gov (United States)

Alexander, Cynthia L; Reger, Mark A; Smolenski, Derek J; Fullerton, Nicole R

2014-10-01

Identification of risk and protective factors for suicide is a priority for the United States military, especially in light of the recent steady increase in military suicide rates. The Department of Defense Suicide Event Report contains comprehensive data on suicides for active duty military personnel, but no analogous control data is available to permit identification of factors that differentially determine suicide risk. This proof-of-concept study was conducted to determine the feasibility of collecting such control data. The study employed a prospective case-control design in which control cases were randomly selected from a large Army installation at a rate of four control participants for every qualifying Army suicide. Although 111 Army suicides were confirmed during the study period, just 27 control soldiers completed the study. Despite the small control sample, preliminary analyses comparing suicide cases to controls identified several factors more frequently reported for suicide cases, including recent failed intimate relationships, outpatient mental health history, mood disorder diagnosis, substance abuse history, and prior self-injury. No deployment-related risk factors were found. These data are consistent with existing literature and form a foundation for larger control studies. Methodological lessons learned regarding study design and recruitment are discussed to inform future studies. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

The roles of lesson study in the development of mathematics learning instrument based on learning trajectory

Science.gov (United States)

Misnasanti; Dien, C. A.; Azizah, F.

2018-03-01

This study is aimed to describe Lesson Study (LS) activity and its roles in the development of mathematics learning instruments based on Learning Trajectory (LT). This study is a narrative study of teacher’s experiences in joining LS activity. Data collecting in this study will use three methods such as observation, documentations, and deep interview. The collected data will be analyzed with Milles and Huberman’s model that consists of reduction, display, and verification. The study result shows that through LS activity, teachers know more about how students think. Teachers also can revise their mathematics learning instrument in the form of lesson plan. It means that LS activity is important to make a better learning instruments and focus on how student learn not on how teacher teach.

Object lessons: notes on geometry in Norman Allison Calkins’ textbook (Brazil, end of nineteenth century, beginning of twentieth century

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Maria Laura Magalhães Gomes

2011-12-01

Full Text Available Primary object lessons, by Norman Allison Calkins, ranslated by Rui Barbosa, a book that was widely disseminated in Brazil during the final years of the 19th century and the beginning of the 20th century, presents object teaching as a general method to be used in every subject or primary school. This article analyses Calkins’ book according to its presentation of mathematical content, focusing particularly on geometry lessons. It also iscusses five features of the approach adopted by Calkins: the presentation of plane geometry before geometry in space, the several materials necessary to the teaching of geometry, the drawing lessons associated with the lessons on shape, the sequence of presentation of the contents and the relations between geometry teaching and children’s pleasure and curiosity. Comments about the utilization and circulation of Calkins’ manual in geometry teaching in Brazil are also provided.

Mathematics teachers’ reflective practice within the context of adapted lesson study

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Barbara Posthuma

2012-11-01

Full Text Available There seems to be paucity of research in South Africa on mathematics teachers’ reflective practice. In order to study this phenomenon, the context of lesson study (in an adapted form was introduced to five mathematics teachers in a rural school in the Free State. The purpose was to investigate their reflective practice whilst they collaboratively planned mathematics lessons and reflected on the teaching of the lessons. Data were obtained through interviews, video-recorded lesson observations, field notes taken during the lesson study group meetings and document analyses (lesson plans and reflective writings. The adapted lesson study context provided a safe space for teachers to reflect on their teaching and they reported an increase in self-knowledge and finding new ways of teaching mathematics to learners. This finding has some potential value for planning professional learning programmes in which teachers are encouraged to talk about their classroom experiences, share their joys and challenges with one another and strive to build a community of reflective practitioners to enhance their learners’ understanding of mathematics.

Lessons learned from MELOX plant operation and support to design of new MOX fuel fabrication plants

International Nuclear Information System (INIS)

Tourre, Joel; Gattegno, Robert; Guay, Philippe; Bariteau, Jean-Pierre

2005-01-01

AREVA is participating in the design of the US MOX Fuel Fabrication Facility (MFFF). To support this project and allow the U.S. Department of Energy (DOE) client to reap full benefit from the MELOX operating experience, AREVA, through COGEMA and its engineering subsidiary SGN have implemented a rigorous process to prudently apply MELOX Lessons Learned to the MFFF design. This paper describes the Lessons Learned process, how the process supports the advancement of fuel fabrication technology and, how the results of the process are benefiting the client. (author)

The accident at TEPCO's Fukushima-Daiichi Nuclear Power Station: What went wrong and what lessons are universal?

Energy Technology Data Exchange (ETDEWEB)

Omoto, Akira, E-mail: akira.omoto@mac.com

2013-12-11

After a short summary of the nuclear accident at the Fukushima Daiichi Nuclear Power Station, this paper discusses “what went wrong” by illustrating the problems of the specific layers of defense-in-depth (basic strategy for assuring nuclear safety) and “what lessons are universal.” Breaches in the multiple layers of defense were particularly significant in respective protection (a) against natural disasters (first layer of defense) as well as (b) against severe conditions, specifically in this case, a complete loss of AC/DC power and isolation from the primary heat sink (fourth layer of defense). Confusion in crisis management by the government and insufficient implementation of offsite emergency plans revealed problems in the fifth layer of defense. By taking into consideration managerial and safety culture that might have relevance to this accident, in the author's view, universal lessons are as follows: a)Resilience: the need to enhance organizational capabilities to respond, monitor, anticipate, and learn in changing conditions, especially to prepare for the unexpected. This includes increasing distance to cliff edge by knowing where it exists and how to increase safety margin. b)Responsibility: the operator is primarily responsible for safety, and the government is responsible for protecting public health and environment. For both, their right decisions are supported by competence, knowledge, and an understanding of the technology, as well as humble attitudes toward the limitations of what we know and what we can learn from others. c)Social license to operate: the need to avoid, as much as possible regardless of its probability of occurrence, the reasonably anticipated environmental impact (such as land contamination), as well as to build public confidence/trust and a renewed liability scheme.

Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa.

Science.gov (United States)

van West, D; Monteleone, P; Di Lieto, A; De Meester, I; Durinx, C; Scharpe, S; Lin, A; Maj, M; Maes, M

2000-01-01

The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders.

Biomarkers in chronic fatigue syndrome: evaluation of natural killer cell function and dipeptidyl peptidase IV/CD26.

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Mary A Fletcher

2010-05-01

Full Text Available Chronic Fatigue Syndrome (CFS studies from our laboratory and others described decreased natural killer cell cytotoxicity (NKCC and elevated proportion of lymphocytes expressing the activation marker, dipeptidyl peptidase IV (DPPIV also known as CD26. However, neither these assays nor other laboratory tests are widely accepted for the diagnosis or prognosis of CFS. This study sought to determine if NKCC or DPPIV/CD26 have diagnostic accuracy for CFS.Subjects included female and male CFS cases and healthy controls. NK cell function was measured with a bioassay, using K562 cells and (51Cr release. Lymphocyte associated DPPIV/CD26 was assayed by qualitative and quantitative flow cytometry. Serum DPPIV/CD26 was measured by ELISA. Analysis by receiver operating characteristic (ROC curve assessed biomarker potential. Cytotoxic function of NK cells for 176 CFS subjects was significantly lower than in the 230 controls. According to ROC analysis, NKCC was a good predictor of CFS status. There was no significant difference in NK cell counts between cases and controls. Percent CD2+ lymphocytes (T cells and NK cells positive for DPPIV/C26 was elevated in CFS cases, but there was a decrease in the number of molecules (rMol of DPPIV/C26 expressed on T cells and NK cells and a decrease in the soluble form of the enzyme in serum. Analyses by ROC curves indicated that all three measurements of DPPIV/CD26 demonstrated potential as biomarkers for CFS. None of the DPPIV/C26 assays were significantly correlated with NKCC.By ROC analysis, NKCC and three methods of measuring DPPIV/C26 examined in this study had potential as biomarkers for CFS. Of these, NKCC, %CD2+CD26+ lymphocytes and rMol CD26/CD2+ lymphocyte, required flow cytometry, fresh blood and access to a high complexity laboratory. Soluble DPPIV/C26 in serum is done with a standard ELISA assay, or with other soluble factors in a multiplex type of ELISA. Dipeptidyl peptidase IV on lymphocytes or in serum was

SOCAP: Lessons learned in applying SIPE-2 to the military operations crisis action planning domain

Science.gov (United States)

Desimone, Roberto

1992-01-01

This report describes work funded under the DARPA Planning and Scheduling Initiative that led to the development of SOCAP (System for Operations Crisis Action Planning). In particular, it describes lessons learned in applying SIPE-2, the underlying AI planning technology within SOCAP, to the domain of military operations deliberate and crisis action planning. SOCAP was demonstrated at the U.S. Central Command and at the Pentagon in early 1992. A more detailed report about the lessons learned is currently being prepared. This report was presented during one of the panel discussions on 'The Relevance of Scheduling to AI Planning Systems.'

Lessons learned -- NREL Village Power Program

Energy Technology Data Exchange (ETDEWEB)

Flowers, L.

1998-07-01

In 1993, a workshop was convened at the National Renewable Energy Laboratory (NREL) to discuss the issues of applying renewable energy in a sustainable manner to international rural development. One of the summary recommendations was that NREL could assist in the renewable energy for rural electrification effort by developing and supplying six related activities: resource assessment, comparative analysis and modeling, performance monitoring and analysis, pilot project development, internet-based project data, communications, and training. In response to this recommendation, NREL launched its Village Power Program consisting of these activities that cut across NREL technologies and disciplines. Currently NREL is active in 20 countries, with pilot projects in 12 of those countries. At this time the technologies include photovoltaics, wind, biomass, and hybrids. The rural applications include home lighting and communications, water pumping, schools and health posts, battery charging stations, ecotourism, and village systems. These pilot projects are central to the renewable energy village power development through the demonstration of three aspects critical to replication and implementation of the projects on a significant scale. The three aspects are technical functionality, economic competitiveness, and institutional sustainability. It is important to note that the pilot projects from which NREL's experience has been gained were funded and, in many cases, developed by other organizations and agencies. NREL's role has been one of technical assistance or project management or both. The purpose of this paper is to describe the lessons NREL staff has gleaned from their participation in the various pilot projects. The author hopes that these lessons will help the Renewable Energy-Based Rural Electrification (RERE) community in implementing sustainable projects that lead to replication.

Project management lessons learned from building the Wendelstein 7-x stellerator fusion research reactor

Energy Technology Data Exchange (ETDEWEB)

Freire-Gormaly, M.; Gittens, A.; Zhang, L., E-mail: m.freire.gormaly@utoronto.ca, E-mail: antonio.gittens@mail.utoronto.ca, E-mail: lavender.zhang@outlook.com [University of Toronto, Toronto, ON (Canada)

2015-07-01

Wendelstein 7-X (W7-X) is the world's largest 'stellerator' nuclear fusion reactor being commissioned in Greifswald, Germany. It will inform the international fusion energy test device (ITER). The complexity of W7- X added challenges since industrial expertise to manufacture components did not exist. The construction was completed eight years behind schedule and almost 100% over budget. Key take-away lessons in project management were revealed from W7-X which can be applied to any nuclear project. These lessons are aligned with the project management knowledge areas of schedule, stakeholder, procurement, scope, schedule, cost, communication, risk, quality, human resources and procurement management. (author)

Summary of Planned Implementation for the HTGR Lessons Learned Applicable to the NGNP

International Nuclear Information System (INIS)

Mckirdy, Ian

2011-01-01

This document presents a reconciliation of the lessons learned during a 2010 comprehensive evaluation of pertinent lessons learned from past and present high temperature gas-cooled reactors that apply to the Next Generation Nuclear Plant Project along with current and planned activities. The data used are from the latest Idaho National Laboratory research and development plans, the conceptual design report from General Atomics, and the pebble bed reactor technology readiness study from AREVA. Only those lessons related to the structures, systems, and components of the Next Generation Nuclear Plant (NGNP), as documented in the recently updated lessons learned report are addressed. These reconciliations are ordered according to plant area, followed by the affected system, subsystem, or component; lesson learned; and finally an NGNP implementation statement. This report (1) provides cross references to the original lessons learned document, (2) describes the lesson learned, (3) provides the current NGNP implementation status with design data needs associated with the lesson learned, (4) identifies the research and development being performed related to the lesson learned, and (5) summarizes with a status of how the lesson learned has been addressed by the NGNP Project.

Gross Domestic Pizza. Active Learning Lessons. Economics International.

Science.gov (United States)

Zaleskiene, Irena; Venger, Anatoly; MacDonald, Rich; Davis, Debbie

This lesson plan was developed through "Economics International," an international program to help build economic education infrastructures in the emerging market economies. It provides a lesson description; appropriate age level; economic concepts; content standards and benchmarks; related subject areas; instructional objectives; time…

The information society and its consequences: lessons from the past.

OpenAIRE

Duquenoy, Penny; Holvast, Jan; Whitehouse, Diane

2005-01-01

Without doubt the year 1976 was an important year for the discussion on Computers and Society. In that year Joseph Weizenbaum’s Computer Power and Human Reason was published and IFIP’s TC 9 on Computers and Society was founded. In this contribution we want to give a short overview of the history since then and answer the question “what lessons can be learned from the past twenty-five years?” Following a review of the vigorous debate on the development of computers in society that has taken pl...

Raising the temperature of the UK heat pump market: Learning lessons from Finland

International Nuclear Information System (INIS)

Hannon, Matthew J.

2015-01-01

Heat pumps play a central role in decarbonising the UK's buildings sector as part of the Committee on Climate Change's (CCC) updated abatement scenario for meeting the UK's fourth carbon budget. However, the UK has one of the least developed heat pump markets in Europe and renewable heat output from heat pumps will need to increase by a factor of 50 over the next 15 years to be in line with the scenario. Therefore, this paper explores what lessons the UK might learn from Finland to achieve this aim considering that its current level of heat pump penetration is comparable with that outlined in the CCC scenario for 2030. Despite the two countries’ characteristic differences we argue they share sufficient similarities for the UK to usefully draw some policy-based lessons from Finland including: stimulating new-build construction and renovation of existing stock; incorporating renewable heat solutions in building energy performance standards; and bringing the cost of heat pumps in-line with gas fired heating via a combination of subsidies, taxes and energy RD&D. Finally, preliminary efforts to grow the heat pump market could usefully focus on properties unconnected to the gas-grid, considering these are typically heated by relatively expensive oil or electric heating technologies. -- Highlights: •Heat pumps are expected to play a key role in meeting the UK's 4th carbon budget. •Today, heat pump deployment per capita in the UK is one of the lowest in Europe. •Finland offers some policy lessons given its high level of heat pump deployment. •Policies: raising build rates, building standards and heat pump cost-effectiveness. •Deployment efforts should focus on buildings not heated by relatively low-cost gas

A phylogenetic framework for root lesion nematodes of the genus Pratylenchus (Nematoda): Evidence from 18S and D2-D3 expansion segments of 28S ribosomal RNA genes and morphological characters.

Science.gov (United States)

Subbotin, Sergei A; Ragsdale, Erik J; Mullens, Teresa; Roberts, Philip A; Mundo-Ocampo, Manuel; Baldwin, James G

2008-08-01

The root lesion nematodes of the genus Pratylenchus Filipjev, 1936 are migratory endoparasites of plant roots, considered among the most widespread and important nematode parasites in a variety of crops. We obtained gene sequences from the D2 and D3 expansion segments of 28S rRNA partial and 18S rRNA from 31 populations belonging to 11 valid and two unidentified species of root lesion nematodes and five outgroup taxa. These datasets were analyzed using maximum parsimony and Bayesian inference. The alignments were generated using the secondary structure models for these molecules and analyzed with Bayesian inference under the standard models and the complex model, considering helices under the doublet model and loops and bulges under the general time reversible model. The phylogenetic informativeness of morphological characters is tested by reconstruction of their histories on rRNA based trees using parallel parsimony and Bayesian approaches. Phylogenetic and sequence analyses of the 28S D2-D3 dataset with 145 accessions for 28 species and 18S dataset with 68 accessions for 15 species confirmed among large numbers of geographical diverse isolates that most classical morphospecies are monophyletic. Phylogenetic analyses revealed at least six distinct major clades of examined Pratylenchus species and these clades are generally congruent with those defined by characters derived from lip patterns, numbers of lip annules, and spermatheca shape. Morphological results suggest the need for sophisticated character discovery and analysis for morphology based phylogenetics in nematodes.

Building Accessible Educational Web Sites: The Law, Standards, Guidelines, Tools, and Lessons Learned

Science.gov (United States)

Liu, Ye; Palmer, Bart; Recker, Mimi

2004-01-01

Professional education is increasingly facing accessibility challenges with the emergence of webbased learning. This paper summarizes related U.S. legislation, standards, guidelines, and validation tools to make web-based learning accessible for all potential learners. We also present lessons learned during the implementation of web accessibility…

Innovative Work Practices and Lessons Learned at the N Area Deactivation Project

International Nuclear Information System (INIS)

Day, R.S.

1999-01-01

This report identifies many of the lessons learned, innovations,and effective work practices that derived from activities supporting the N Area Deactivation Project at the U.S. Department of Energy's (DOE) Hanford Site. The work practices discussed in this report may be applicable and beneficial to similar projects throughout the DOE complex

Changing State-University Relations: The Experiences of Japan and Lessons for Malaysia

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Sirat, Morshidi; Kaur, Sarjit

2010-01-01

This article investigates the changing state-university relations in Japan and Malaysia. Its main objective is to identify and examine possible lessons for Malaysia, based on the Japanese experience. Notably, since the late 1970s, Malaysia has been looking towards Japan as a model for socio-economic development (the "look-east" Policy)…

Medical faculty members' attitude on lesson planning Semnan University of Medical Sciences

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Masomeh Saberian

2003-01-01

Full Text Available Background: Lesson planning has a distinct role in enhancing education quality, as well as maintaining the friendly and dynamic atmosphere of the academic environment and increasing student's initiatives for achieving better educational attainments. Lesson planning is a process for defining the goals, understanding the needs, and specifying available tools and possible limitations. Lesson planning is a written description of this process, which shows the materials, the route, the time, and the place of instructions, as well as a method for evaluating students. Purpose: to identify the attitudes of Semnan University of Medical Sciences (SUMS on lesson planning. Methods: Fifty-three faculty members of the SUMS participated in this study. A questionnaire was used, which contained 8 demographic questions, and 24 r questions for identification the faculty members' attitude. Questionnaires were distributed among the faculty members in sealed envelopes, without denoting their names. The questionnaires were gathered after being completed. Results were analyzed by calculating the mean, standard deviation, absolute and relative frequencies, and using Chi-square and Fischer exact test at the level of 5%. Results: II was shown that 88% of faculty members favoured lesson planning before the beginning of the semester. But they found lesson planning a difficult task, because of their heavy workload. Of the faculty members, 60.4% organized their teaching classes according to a designed lesson plan, and believed that it did affect the quality of their teaching, but 49.1% disagreed with distributing the designed lesson plan among the students. Discussion: Although professor favoured lesson planning and find it necessary to work according to such a plan, workload and lack of knowledge are defined as two main obstacles in doing so. It is believed that by decreasing the professor's workload and provision of lesson planning workshops, these problems could be solved

Lessons learned from AU PSO-missions in Africa

DEFF Research Database (Denmark)

Mandrup, Thomas

The paper deals with the lessons learned from AU's PSO since 2002, and what that entails for the design of future PSO.......The paper deals with the lessons learned from AU's PSO since 2002, and what that entails for the design of future PSO....

Biotech Business Lessons for Defense Acquisition

Science.gov (United States)

2016-01-01

repudiates what func- tional personnel hold dear—that their hurdles are vital to some moral or ethical responsibility to protect or safeguard...94 Strategic Studies Quarterly ♦ Summer 2016 Biotech Business Lessons for Defense Acquisition Col David L. Peeler Jr., USAF Abstract The desire to...examples and lessons from private business sectors would serve DOD interests well. ✵ ✵ ✵ ✵ ✵ Acquisition reform! No other two words so stress or trouble

Improving the primary school science learning unit about force and motion through lesson study

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Phaikhumnam, Wuttichai; Yuenyong, Chokchai

2018-01-01

The study aimed to develop primary school science lesson plan based on inquiry cycle (5Es) through lesson study. The study focused on the development of 4 primary school science lesson plans of force and motion for Grade 3 students in KKU Demonstration Primary School (Suksasart), first semester of 2015 academic year. The methodology is mixed method. The Inthaprasitha (2010) lesson study cycle was implemented in group of KKU Demonstration Primary School. Instruments of reflection of lesson plan developing included participant observation, meeting and reflection report, lesson plan and other document. The instruments of examining students' learning include classroom observation and achievement test. Data was categorized from these instruments to find the issues of changing and improving the good lesson plan of Thai primary school science learning. The findings revealed that teachers could develop the lesson plans through lesson study. The issues of changing and improving were disused by considering on engaging students related to societal issues, students' prior knowledge, scientific concepts for primary school students, and what they learned from their changing. It indicated that the Lesson Study allowed primary school science teachers to share ideas and develop ideas to improve the lesson. The study may have implications for Thai science teacher education through Lesson Study.

ELPSA AS A LESSON DESIGN FRAMEWORK

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Tom Lowrie

2015-07-01

Full Text Available This paper offers a framework for mathematics lesson design that is consistent with the way we learn about, and discover, most things in life. In addition, the framework provides a structure for identifying how mathematical concepts and understanding are acquired and developed. This framework is called ELPSA and represents five learning components, namely: Experience, Language, Pictorial, Symbolic and Applications. This framework has been used in developing lessons and teacher professional programs in Indonesia since 2012 in cooperation with the World Bank. This paper describes the theory that underlines the framework in general and in relation to each inter-connected component. Two explicit learning sequences for classroom practice are described, associated with Pythagoras theorem and probability. This paper then concludes with recommendations for using ELPSA in various institutional contexts.Keywords: ELPSA, lesson design framework, Pythagoras theorem, probability DOI: dx.doi.org/10.22342/jme.62.77

Pro-apoptotic effect of a Mycoplasma hyopneumoniae putative type I signal peptidase on PK(15) swine cells.

Science.gov (United States)

Paes, Jéssica A; Virginio, Veridiana G; Cancela, Martín; Leal, Fernanda M A; Borges, Thiago J; Jaeger, Natália; Bonorino, Cristina; Schrank, Irene S; Ferreira, Henrique B

2017-03-01

Mycoplasma hyopneumoniae is an economically significant swine pathogen that causes porcine enzootic pneumonia (PEP). Important processes for swine infection by M. hyopneumoniae depend on cell surface proteins, many of which are secreted by secretion pathways not completely elucidated so far. A putative type I signal peptidase (SPase I), a possible component of a putative Sec-dependent pathway, was annotated as a product of the sipS gene in the pathogenic M. hyopneumoniae 7448 genome. This M. hyopneumoniae putative SPase I (MhSPase I) displays only 14% and 23% of sequence identity/similarity to Escherichia coli bona fide SPase I, and, in complementation assays performed with a conditional E. coli SPase I mutant, only a partial restoration of growth was achieved with the heterologous expression of a recombinant MhSPase I (rMhSPase I). Considering the putative surface location of MhSPase I and its previously demonstrated capacity to induce a strong humoral response, we then assessed its potential to elicit a cellular and possible immunomodulatory response. In assays for immunogenicity assessment, rMhSPase I unexpectedly showed a cytotoxic effect on murine splenocytes. This cytotoxic effect was further confirmed using the swine epithelial PK(15) cell line in MTT and annexin V-flow cytometry assays, which showed that rMhSPase I induces apoptosis in a dose dependent-way. It was also demonstrated that this pro-apoptotic effect of rMhSPase I involves activation of a caspase-3 cascade. The potential relevance of the rMhSPase I pro-apoptotic effect for M. hyopneumoniae-host interactions in the context of PEP is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.