Drug resistance is conferred on the model yeast Saccharomyces cerevisiae by expression of full-length melanoma-associated human ATP-binding cassette transporter ABCB5.

Science.gov (United States)

Keniya, Mikhail V; Holmes, Ann R; Niimi, Masakazu; Lamping, Erwin; Gillet, Jean-Pierre; Gottesman, Michael M; Cannon, Richard D

2014-10-06

ABCB5, an ATP-binding cassette (ABC) transporter, is highly expressed in melanoma cells, and may contribute to the extreme resistance of melanomas to chemotherapy by efflux of anti-cancer drugs. Our goal was to determine whether we could functionally express human ABCB5 in the model yeast Saccharomyces cerevisiae, in order to demonstrate an efflux function for ABCB5 in the absence of background pump activity from other human transporters. Heterologous expression would also facilitate drug discovery for this important target. DNAs encoding ABCB5 sequences were cloned into the chromosomal PDR5 locus of a S. cerevisiae strain in which seven endogenous ABC transporters have been deleted. Protein expression in the yeast cells was monitored by immunodetection using both a specific anti-ABCB5 antibody and a cross-reactive anti-ABCB1 antibody. ABCB5 function in recombinant yeast cells was measured by determining whether the cells possessed increased resistance to known pump substrates, compared to the host yeast strain, in assays of yeast growth. Three ABCB5 constructs were made in yeast. One was derived from the ABCB5-β mRNA, which is highly expressed in human tissues but is a truncation of a canonical full-size ABC transporter. Two constructs contained full-length ABCB5 sequences: either a native sequence from cDNA or a synthetic sequence codon-harmonized for S. cerevisiae. Expression of all three constructs in yeast was confirmed by immunodetection. Expression of the codon-harmonized full-length ABCB5 DNA conferred increased resistance, relative to the host yeast strain, to the putative substrates rhodamine 123, daunorubicin, tetramethylrhodamine, FK506, or clorgyline. We conclude that full-length ABCB5 can be functionally expressed in S. cerevisiae and confers drug resistance.

The Yeast Plasma Membrane ATP Binding Cassette (ABC) Transporter Aus1

Science.gov (United States)

Marek, Magdalena; Milles, Sigrid; Schreiber, Gabriele; Daleke, David L.; Dittmar, Gunnar; Herrmann, Andreas; Müller, Peter; Pomorski, Thomas Günther

2011-01-01

The ATP binding cassette (ABC) transporter Aus1 is expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and is required for sterol uptake. These observations suggest that Aus1 promotes the translocation of sterols across membranes, but the precise transport mechanism has yet to be identified. In this study, an extraction and purification procedure was developed to characterize the Aus1 transporter. The detergent-solubilized protein was able to bind and hydrolyze ATP. Mutagenesis of the conserved lysine to methionine in the Walker A motif abolished ATP hydrolysis. Likewise, ATP hydrolysis was inhibited by classical inhibitors of ABC transporters. Upon reconstitution into proteoliposomes, the ATPase activity of Aus1 was specifically stimulated by phosphatidylserine (PS) in a stereoselective manner. We also found that Aus1-dependent sterol uptake, but not Aus1 expression and trafficking to the plasma membrane, was affected by changes in cellular PS levels. These results suggest a direct interaction between Aus1 and PS that is critical for the activity of the transporter. PMID:21521689

Rice Stomatal Closure Requires Guard Cell Plasma Membrane ATP-Binding Cassette Transporter RCN1/OsABCG5.

Science.gov (United States)

Matsuda, Shuichi; Takano, Sho; Sato, Moeko; Furukawa, Kaoru; Nagasawa, Hidetaka; Yoshikawa, Shoko; Kasuga, Jun; Tokuji, Yoshihiko; Yazaki, Kazufumi; Nakazono, Mikio; Takamure, Itsuro; Kato, Kiyoaki

2016-03-07

Water stress is one of the major environmental stresses that affect agricultural production worldwide. Water loss from plants occurs primarily through stomatal pores. Here, we report that an Oryza sativa half-size ATP-binding cassette (ABC) subfamily G protein, RCN1/OsABCG5, is involved in stomatal closure mediated by phytohormone abscisic acid (ABA) accumulation in guard cells. We found that the GFP-RCN1/OsABCG5-fusion protein was localized at the plasma membrane in guard cells. The percentage of guard cell pairs containing both ABA and GFP-RCN1/OsABCG5 increased after exogenous ABA treatment, whereas they were co-localized in guard cell pairs regardless of whether exogenous ABA was applied. ABA application resulted in a smaller increase in the percentage of guard cell pairs containing ABA in rcn1 mutant (A684P) and RCN1-RNAi than in wild-type plants. Furthermore, polyethylene glycol (drought stress)-inducible ABA accumulation in guard cells did not occur in rcn1 mutants. Stomata closure mediated by exogenous ABA application was strongly reduced in rcn1 mutants. Finally, rcn1 mutant plants had more rapid water loss from detached leaves than the wild-type plants. These results indicate that in response to drought stress, RCN1/OsABCG5 is involved in accumulation of ABA in guard cells, which is indispensable for stomatal closure. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Maltose-binding protein effectively stabilizes the partially closed conformation of the ATP-binding cassette transporter MalFGK2

KAUST Repository

Weng, Jingwei; Gu, Shuo; Gao, Xin; Huang, Xuhui; Wang, Wenning

2017-01-01

Maltose transporter MalFGK2 is a type-I importer in the ATP-binding cassette (ABC) transporter superfamily. Upon the binding of its periplasmic binding protein, MalE, the ATPase activity of MalFGK2 can be greatly enhanced. Crystal structures of the MalFGK2-MalE-maltose complex in a so-called

Maltose-binding protein effectively stabilizes the partially closed conformation of the ATP-binding cassette transporter MalFGK2

KAUST Repository

Weng, Jingwei

2017-02-23

Maltose transporter MalFGK2 is a type-I importer in the ATP-binding cassette (ABC) transporter superfamily. Upon the binding of its periplasmic binding protein, MalE, the ATPase activity of MalFGK2 can be greatly enhanced. Crystal structures of the MalFGK2-MalE-maltose complex in a so-called

Molecular Events Involved in a Single Cycle of Ligand Transfer from an ATP Binding Cassette Transporter, LolCDE, to a Molecular Chaperone, LolA*

OpenAIRE

Taniguchi, Naohiro; Tokuda, Hajime

2008-01-01

An ATP binding cassette transporter LolCDE complex releases lipoproteins from the inner membrane of Escherichia coli in an ATP-dependent manner, leading to the formation of a complex between a lipoprotein and a periplasmic chaperone, LolA. LolA is proposed to undergo a conformational change upon the lipoprotein binding. The lipoprotein is then transferred from the LolA-lipoprotein complex to the outer membrane via LolB. Unlike most ATP binding cassette transporters med...

Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology.

Science.gov (United States)

Tournier, Nicolas; Declèves, Xavier; Saubaméa, Bruno; Scherrmann, Jean-Michel; Cisternino, Salvatore

2011-01-01

Some of the ATP-binding cassette (ABC) transporters like P-glycoprotein (P-gp; ABCB1, MDR1), BCRP (ABCG2) and MRPs (ABCCs) that are present at the blood-brain barrier (BBB) influence the brain pharmacokinetics (PK) of their substrates by restricting their uptake or enhancing their clearance from the brain into the blood, which has consequences for their CNS pharmacodynamics (PD). Opioid drugs have been invaluable tools for understanding the PK-PD relationships of these ABC-transporters. The effects of morphine, methadone and loperamide on the CNS are modulated by P-gp. This review examines the ways in which other opioid drugs and some of their active metabolites interact with ABC transporters and suggests new mechanisms that may be involved in the variability of the response of the CNS to these drugs like carrier-mediated system belonging to the solute carrier (SLC) superfamily. Exposure to opioids may also alter the expression of ABC transporters. P-gp can be overproduced during morphine treatment, suggesting that the drug has a direct or, more likely, an indirect action. Variations in cerebral neurotransmitters during exposure to opioids and the release of cytokines during pain could be new endogenous stimuli affecting transporter synthesis. This review concludes with an analysis of the pharmacotherapeutic and clinical impacts of the interactions between ABC transporters and opioids.

The Role of ATP-Binding Cassette Transporters in Neuro-Inflammation: Relevance for Bioactive Lipids

OpenAIRE

Kooij, Gijs; van Horssen, Jack; Bandaru, Veera Venkata Ratnam; Haughey, Norman J.; de Vries, Helga E.

2012-01-01

ATP-binding cassette (ABC) transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB). These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS). Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within th...

Genome-wide identification, characterization and phylogenetic analysis of 50 catfish ATP-binding cassette (ABC) transporter genes.

Science.gov (United States)

Liu, Shikai; Li, Qi; Liu, Zhanjiang

2013-01-01

Although a large set of full-length transcripts was recently assembled in catfish, annotation of large gene families, especially those with duplications, is still a great challenge. Most often, complexities in annotation cause mis-identification and thereby much confusion in the scientific literature. As such, detailed phylogenetic analysis and/or orthology analysis are required for annotation of genes involved in gene families. The ATP-binding cassette (ABC) transporter gene superfamily is a large gene family that encodes membrane proteins that transport a diverse set of substrates across membranes, playing important roles in protecting organisms from diverse environment. In this work, we identified a set of 50 ABC transporters in catfish genome. Phylogenetic analysis allowed their identification and annotation into seven subfamilies, including 9 ABCA genes, 12 ABCB genes, 12 ABCC genes, 5 ABCD genes, 2 ABCE genes, 4 ABCF genes and 6 ABCG genes. Most ABC transporters are conserved among vertebrates, though cases of recent gene duplications and gene losses do exist. Gene duplications in catfish were found for ABCA1, ABCB3, ABCB6, ABCC5, ABCD3, ABCE1, ABCF2 and ABCG2. The whole set of catfish ABC transporters provide the essential genomic resources for future biochemical, toxicological and physiological studies of ABC drug efflux transporters. The establishment of orthologies should allow functional inferences with the information from model species, though the function of lineage-specific genes can be distinct because of specific living environment with different selection pressure.

G3.5 PAMAM dendrimers enhance transepithelial transport of SN38 while minimizing gastrointestinal toxicity.

Science.gov (United States)

Goldberg, Deborah S; Vijayalakshmi, Nirmalkumar; Swaan, Peter W; Ghandehari, Hamidreza

2011-03-30

Poly(amido amine) (PAMAM) dendrimers have shown promise in oral drug delivery. Conjugation of SN38 to PAMAM dendrimers has the potential to improve its oral absorption while minimizing gastrointestinal toxicity. In this work we evaluated G3.5 PAMAM dendrimer-SN38 conjugates with ester-linked glycine and β-alanine spacers for their suitability in oral therapy of hepatic colorectal cancer metastases. G3.5-βAlanine-SN38 was mostly stable while G3.5-Glycine-SN38 showed 10%, 20%, and 56% SN38 release in simulated gastric, intestinal and liver environments for up to 6, 24 and 48 hours, respectively. Short-term treatment of Caco-2 cells with G3.5-SN38 conjugates did not reduce cell viability, while comparable concentrations of SN38 caused significant cytotoxicity. G3.5-Glycine-SN38 and G3.5-βAlanine-SN38 showed IC₅₀ values of 0.60 and 3.59 μM, respectively, in HT-29 cells treated for 48 h, indicating the efficacy of the drug delivery system in colorectal cancer cells with longer incubation time. Both conjugates increased SN38 transepithelial transport compared to the free drug. Transport of G3.5-Glycine-SN38 was highly concentration-dependent whereas transport of G3.5-βAlanine-SN38 was concentration-independent, highlighting the influence of drug loading and spacer chemistry on transport mechanism. Together these results show that PAMAM dendrimers have the potential to improve the oral bioavailability of potent anti-cancer drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

Drugs, ionophoric peptides, and steroids as substrates of the yeast multidrug transporter Pdr5p

NARCIS (Netherlands)

Kolaczkowski, M; vanderRest, M; CybularzKolaczkowska, A; Soumillion, JP; Konings, WN; Goffeau, A

1996-01-01

Pdr5p is the yeast Saccharomyces cerevisiae ATP-binding cassette transporter conferring resistance to several unrelated drugs. Its high overproduction in Pdr1p transcription factor mutants allows us to study the molecular mechanism of multidrug transport and substrate specificity. We have developed

Membrane porters of ATP-binding cassette transport systems are polyphyletic.

Science.gov (United States)

Wang, Bin; Dukarevich, Maxim; Sun, Eric I; Yen, Ming Ren; Saier, Milton H

2009-09-01

The ATP-binding cassette (ABC) superfamily consists of both importers and exporters. These transporters have, by tradition, been classified according to the ATP hydrolyzing constituents, which are monophyletic. The evolutionary origins of the transmembrane porter proteins/domains are not known. Using five distinct computer programs, we here provide convincing statistical data suggesting that the transmembrane domains of ABC exporters are polyphyletic, having arisen at least three times independently. ABC1 porters arose by intragenic triplication of a primordial two-transmembrane segment (TMS)-encoding genetic element, yielding six TMS proteins. ABC2 porters arose by intragenic duplication of a dissimilar primordial three-TMS-encoding genetic element, yielding a distinctive protein family, nonhomologous to the ABC1 proteins. ABC3 porters arose by duplication of a primordial four-TMS-encoding genetic element, yielding either eight- or 10-TMS proteins. We assign each of 48 of the 50 currently recognized families of ABC exporters to one of the three evolutionarily distinct ABC types. Currently available high-resolution structural data for ABC porters are fully consistent with our findings. These results provide guides for future structural and mechanistic studies of these important transport systems.

Functional Analysis of an ATP-Binding Cassette Transporter Gene in Botrytis cinerea by Gene Disruption

OpenAIRE

Masami, NAKAJIMA; Junko, SUZUKI; Takehiko, HOSAKA; Tadaaki, HIBI; Katsumi, AKUTSU; School of Agriculture, Ibaraki University; School of Agriculture, Ibaraki University; School of Agriculture, Ibaraki University; Department of Agriculture and Environmental Biology, The University of Tokyo; School of Agriculture, Ibaraki University

2001-01-01

The BMR1 gene encoding an ABC transporter was cloned from Botrytis cinerea. To examine the function of BMR1 in B.cinerea, we isolated BMR1-deficient mutants after gene disruption. Disruption vector pBcDF4 was constructed by replacing the BMR1-coding region with a hygromycin B phosphotransferase gene(hph)cassette. The BMR1 disruptants had an increased sensitivity to polyoxin and iprobenfos. Polyoxin and iprobenfos, structurally unrelated compounds, may therefore be substrates of BMR1.

Functional analysis of the ATP-binding cassette (ABC) transporter gene family of Tribolium castaneum.

Science.gov (United States)

Broehan, Gunnar; Kroeger, Tobias; Lorenzen, Marcé; Merzendorfer, Hans

2013-01-16

The ATP-binding cassette (ABC) transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. Most are integral membrane proteins that transport a broad spectrum of substrates across lipid membranes. In insects, ABC transporters are of special interest because of their role in insecticide resistance. We have identified 73 ABC transporter genes in the genome of T. castaneum, which group into eight subfamilies (ABCA-H). This coleopteran ABC family is significantly larger than those reported for insects in other taxonomic groups. Phylogenetic analysis revealed that this increase is due to gene expansion within a single clade of subfamily ABCC. We performed an RNA interference (RNAi) screen to study the function of ABC transporters during development. In ten cases, injection of double-stranded RNA (dsRNA) into larvae caused developmental phenotypes, which included growth arrest and localized melanization, eye pigmentation defects, abnormal cuticle formation, egg-laying and egg-hatching defects, and mortality due to abortive molting and desiccation. Some of the ABC transporters we studied in closer detail to examine their role in lipid, ecdysteroid and eye pigment transport. The results from our study provide new insights into the physiological function of ABC transporters in T. castaneum, and may help to establish new target sites for insect control.

Pharmacogenetic Aspects of the Interaction of AT1 Receptor Antagonists With ATP-Binding Cassette Transporter ABCG2

Directory of Open Access Journals (Sweden)

Anne Ripperger

2018-05-01

Full Text Available The ATP-binding cassette transporter ABCG2 (BCRP and MXR is involved in the absorption, distribution, and elimination of numerous drugs. Thus, drugs that are able to reduce the activity of ABCG2, e.g., antihypertensive AT1 receptor antagonists (ARBs, may cause drug-drug interactions and compromise drug safety and efficacy. In addition, genetic variability within the ABCG2 gene may influence the ability of the transporter to interact with ARBs. Thus, the aim of this study was to characterize the ARB-ABCG2 interaction in the light of naturally occurring variations (F489L, R482G or amino acid substitutions with in silico-predicted relevance for the ARB-ABCG2 interaction (Y469A; M483F; Y570A. For this purpose, ABCG2 variants were expressed in HEK293 cells and the impact of ARBs on ABCG2 activity was studied in vitro using the pheophorbide A (PhA efflux assay. First, we demonstrated that both the F489L and the Y469A substitution, respectively, reduced ABCG2 protein levels in these cells. Moreover, both substitutions enhanced the inhibitory effect of candesartan cilexetil, irbesartan, losartan, and telmisartan on ABCG2-mediated PhA efflux, whereas the R482G substitution blunted the inhibitory effect of candesartan cilexetil and telmisartan in this regard. In contrast, the ARB-ABCG2 interaction was not altered in cells expressing either the M483F or the Y570A variant, respectively. In conclusion, our data indicate that the third transmembrane helix and adjacent regions of ABCG2 may be of major importance for the interaction of ARBs with the ABC transporter. Moreover, we conclude from our data that individuals carrying the F489L polymorphism may be at increased risk of developing ABCG2-related drug-drug interactions in multi-drug regimens involving ARBs.

Novel Resource and Energy Management for 5G Integrated Backhaul/Fronthaul (5G-Crosshaul)

OpenAIRE

Xi, Li; Ferdous, Raihana; Chiasserini, Carla Fabiana; Casetti, CLAUDIO ETTORE; Moscatelli, Francesca; Landi, Giada; Casellas, Ramon; Sakaguchi, Kei; Chundrigar, Shahzoob Bilal; Vilalta, Ricard; Mangues Bafalluy, Josep; Garcia Saavedra, Andres; Costa Perez, Xavier; Goratti, Leonardo; Siracusa, Domenico

2017-01-01

The integration of both fronthaul and backhaul into a single transport network (namely, 5G-Crosshaul) is envisioned for the future 5G transport networks. This requires a fully integrated and unified management of the fronthaul and backhaul resources in a cost-efficient, scalable and flexible way through the deployment of an SDN/NFV control framework. This paper presents the designed 5G-Crosshaul architecture, two selected SDN/NFV applications targeting for cost-efficient resource and energy u...

Small substrate transport and mechanism of a molybdate ATP binding cassette transporter in a lipid environment.

Science.gov (United States)

Rice, Austin J; Harrison, Alistair; Alvarez, Frances J D; Davidson, Amy L; Pinkett, Heather W

2014-05-23

Embedded in the plasma membrane of all bacteria, ATP binding cassette (ABC) importers facilitate the uptake of several vital nutrients and cofactors. The ABC transporter, MolBC-A, imports molybdate by passing substrate from the binding protein MolA to a membrane-spanning translocation pathway of MolB. To understand the mechanism of transport in the biological membrane as a whole, the effects of the lipid bilayer on transport needed to be addressed. Continuous wave-electron paramagnetic resonance and in vivo molybdate uptake studies were used to test the impact of the lipid environment on the mechanism and function of MolBC-A. Working with the bacterium Haemophilus influenzae, we found that MolBC-A functions as a low affinity molybdate transporter in its native environment. In periods of high extracellular molybdate concentration, H. influenzae makes use of parallel molybdate transport systems (MolBC-A and ModBC-A) to take up a greater amount of molybdate than a strain with ModBC-A alone. In addition, the movement of the translocation pathway in response to nucleotide binding and hydrolysis in a lipid environment is conserved when compared with in-detergent analysis. However, electron paramagnetic resonance spectroscopy indicates that a lipid environment restricts the flexibility of the MolBC translocation pathway. By combining continuous wave-electron paramagnetic resonance spectroscopy and substrate uptake studies, we reveal details of molybdate transport and the logistics of uptake systems that employ multiple transporters for the same substrate, offering insight into the mechanisms of nutrient uptake in bacteria. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Film sheet cassette

International Nuclear Information System (INIS)

1981-01-01

A novel film sheet cassette is described for handling CAT photographic films under daylight conditions and facilitating their imaging. A detailed description of the design and operation of the cassette is given together with appropriate illustrations. The resulting cassette is a low-cost unit which is easily constructed and yet provides a sure light-tight seal for the interior contents of the cassette. The individual resilient fingers on the light-trap permit the ready removal of the slide plate for taking pictures. The stippled, non-electrostatic surface of the pressure plate ensures an air layer and free slidability of the film for removal and withdrawal of the film sheet. The advantage of the daylight system is that a darkroom need not be used for inserting and removing the film in and out of the cassette resulting in a considerable time saving. (U.K.)

Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites.

Science.gov (United States)

Rijpma, Sanna R; van der Velden, Maarten; González-Pons, Maria; Annoura, Takeshi; van Schaijk, Ben C L; van Gemert, Geert-Jan; van den Heuvel, Jeroen J M W; Ramesar, Jai; Chevalley-Maurel, Severine; Ploemen, Ivo H; Khan, Shahid M; Franetich, Jean-Francois; Mazier, Dominique; de Wilt, Johannes H W; Serrano, Adelfa E; Russel, Frans G M; Janse, Chris J; Sauerwein, Robert W; Koenderink, Jan B; Franke-Fayard, Blandine M

2016-03-01

Multidrug resistance-associated proteins (MRPs) belong to the C-family of ATP-binding cassette (ABC) transport proteins and are known to transport a variety of physiologically important compounds and to be involved in the extrusion of pharmaceuticals. Rodent malaria parasites encode a single ABC transporter subfamily C protein, whereas human parasites encode two: MRP1 and MRP2. Although associated with drug resistance, their biological function and substrates remain unknown. To elucidate the role of MRP throughout the parasite life cycle, Plasmodium berghei and Plasmodium falciparum mutants lacking MRP expression were generated. P. berghei mutants lacking expression of the single MRP as well as P. falciparum mutants lacking MRP1, MRP2 or both proteins have similar blood stage growth kinetics and drug-sensitivity profiles as wild type parasites. We show that MRP1-deficient parasites readily invade primary human hepatocytes and develop into mature liver stages. In contrast, both P. falciparum MRP2-deficient parasites and P. berghei mutants lacking MRP protein expression abort in mid to late liver stage development, failing to produce mature liver stages. The combined P. berghei and P. falciparum data are the first demonstration of a critical role of an ABC transporter during Plasmodium liver stage development. © 2015 John Wiley & Sons Ltd.

ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells

Science.gov (United States)

Lara, Flavio Alves; Pohl, Paula C.; Gandara, Ana Caroline; Ferreira, Jessica da Silva; Nascimento-Silva, Maria Clara; Bechara, Gervásio Henrique; Sorgine, Marcos H. F.; Almeida, Igor C.; Vaz, Itabajara da Silva; Oliveira, Pedro L.

2015-01-01

In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus) microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA), a well-known inhibitor of ATP binding cassette (ABC) transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may represent a new

ATP Binding Cassette Transporter Mediates Both Heme and Pesticide Detoxification in Tick Midgut Cells.

Directory of Open Access Journals (Sweden)

Flavio Alves Lara

Full Text Available In ticks, the digestion of blood occurs intracellularly and proteolytic digestion of hemoglobin takes place in a dedicated type of lysosome, the digest vesicle, followed by transfer of the heme moiety of hemoglobin to a specialized organelle that accumulates large heme aggregates, called hemosomes. In the present work, we studied the uptake of fluorescent metalloporphyrins, used as heme analogs, and amitraz, one of the most regularly used acaricides to control cattle tick infestations, by Rhipicephalus (Boophilus microplus midgut cells. Both compounds were taken up by midgut cells in vitro and accumulated inside the hemosomes. Transport of both molecules was sensitive to cyclosporine A (CsA, a well-known inhibitor of ATP binding cassette (ABC transporters. Rhodamine 123, a fluorescent probe that is also a recognized ABC substrate, was similarly directed to the hemosome in a CsA-sensitive manner. Using an antibody against conserved domain of PgP-1-type ABC transporter, we were able to immunolocalize PgP-1 in the digest vesicle membranes. Comparison between two R. microplus strains that were resistant and susceptible to amitraz revealed that the resistant strain detoxified both amitraz and Sn-Pp IX more efficiently than the susceptible strain, a process that was also sensitive to CsA. A transcript containing an ABC transporter signature exhibited 2.5-fold increased expression in the amitraz-resistant strain when compared with the susceptible strain. RNAi-induced down-regulation of this ABC transporter led to the accumulation of metalloporphyrin in the digestive vacuole, interrupting heme traffic to the hemosome. This evidence further confirms that this transcript codes for a heme transporter. This is the first report of heme transport in a blood-feeding organism. While the primary physiological function of the hemosome is to detoxify heme and attenuate its toxicity, we suggest that the use of this acaricide detoxification pathway by ticks may

Association of ATP-Binding Cassette Transporter A1 Gene Polymorphisms in Type 2 Diabetes Mellitus among Malaysians

OpenAIRE

Haghvirdizadeh, Polin; Ramachandran, Vasudevan; Etemad, Ali; Heidari, Farzad; Ghodsian, Nooshin; Bin Ismail, Norzian; Ismail, Patimah

2015-01-01

Background. Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs22308...

The role of ATP-binding cassette transporters in neuro-inflammation: relevance for bioactive lipids

Directory of Open Access Journals (Sweden)

Gijs eKooij

2012-04-01

Full Text Available ATP-binding cassette (ABC transporters are highly expressed by brain endothelial cells that form the blood-brain barrier (BBB. These efflux pumps play an important role in maintaining brain homeostasis as they actively hinder the entry of unwanted blood-derived compounds into the central nervous system (CNS. Consequently, their high activity at the BBB has been a major hurdle for the treatment of several brain diseases, as they prevent numerous drugs to reach their site of action within the brain. Importantly, recent data indicate that endogenous substrates for ABC transporters may include inflammatory mediators, such as prostaglandins, leukotrienes, cytokines, chemokines and bioactive lipids, suggesting a potential role for ABC transporters in immunological responses, and more specifically in inflammatory brain disorders, such as multiple sclerosis (MS. In this review, we will give a comprehensive overview of recent findings that illustrate this novel role for ABC transporters in neuro-inflammatory processes. Moreover, we will provide first insights into underlying mechanisms and focus on the importance for bioactive lipids, in particular platelet-activating factor (PAF, herein. A thorough understanding of these events may form the basis for the development for selective treatment modalities to dampen the neuro-inflammatory attack in MS and thereby reducing tissue damage.

Evaluation of the role of ATP-binding cassette transporters as a defence mechanism against temephos in populations of Aedes aegypti

Directory of Open Access Journals (Sweden)

Estelita Pereira Lima

2014-11-01

Full Text Available The role of ATP-binding cassette (ABC transporters in the efflux of the insecticide, temephos, was assessed in the larvae of Aedes aegypti. Bioassays were conducted using mosquito populations that were either susceptible or resistant to temephos by exposure to insecticide alone or in combination with sublethal doses of the ABC transporter inhibitor, verapamil (30, 35 and 40 μM. The best result in the series was obtained with the addition of verapamil (40 μM, which led to a 2x increase in the toxicity of temephos, suggesting that ABC transporters may be partially involved in conferring resistance to the populations evaluated.

Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs

Directory of Open Access Journals (Sweden)

Hwanhee Jang

2017-05-01

Full Text Available Objective Prostaglandins (PGs function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4 and solute carrier organic anion transporter family, member 2A1 (SLCO2A1 are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta. Methods Uterine endometrial tissues were obtained from gilts on day (D 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy. Results ABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. Estradiol-17β increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of interleukin-1β induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues. Conclusion These data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

Science.gov (United States)

Kegler-Ebo, D M; Docktor, C M; DiMaio, D

1994-05-11

We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequences for the restriction endonuclease Sapl, an enzyme that cleaves outside of its recognition sequence. The intermediate molecule containing the mutagenic cassette is then digested with Sapl, thereby removing most of the mutagenic cassette, leaving only a three base cohesive overhang that is ligated to generate the final insertion or substitution mutation. A general method for constructing blunt-end target molecules suitable for this approach is also described. Because the mutagenic cassette is excised during this procedure and alters the target only by introducing the desired mutation, the same cassette can be used to introduce a particular codon at all target sites. Each cassette can deposit two different codons, depending on the orientation in which it is inserted into the target molecule. Therefore, a series of eleven cassettes is sufficient to insert all possible amino acids at any constructed target site. Thus codon cassettes are 'off-the-shelf' reagents, and this methodology should be a particularly useful and inexpensive approach for subjecting multiple different positions in a protein sequence to saturation mutagenesis.

An ATP Binding Cassette Transporter Mediates the Uptake of α-(1,6)-Linked Dietary Oligosaccharides in Bifidobacterium and Correlates with Competitive Growth on These Substrates.

Science.gov (United States)

Ejby, Morten; Fredslund, Folmer; Andersen, Joakim Mark; Vujičić Žagar, Andreja; Henriksen, Jonas Rosager; Andersen, Thomas Lars; Svensson, Birte; Slotboom, Dirk Jan; Abou Hachem, Maher

2016-09-16

The molecular details and impact of oligosaccharide uptake by distinct human gut microbiota (HGM) are currently not well understood. Non-digestible dietary galacto- and gluco-α-(1,6)-oligosaccharides from legumes and starch, respectively, are preferentially fermented by mainly bifidobacteria and lactobacilli in the human gut. Here we show that the solute binding protein (BlG16BP) associated with an ATP binding cassette (ABC) transporter from the probiotic Bifidobacterium animalis subsp. lactis Bl-04 binds α-(1,6)-linked glucosides and galactosides of varying size, linkage, and monosaccharide composition with preference for the trisaccharides raffinose and panose. This preference is also reflected in the α-(1,6)-galactoside uptake profile of the bacterium. Structures of BlG16BP in complex with raffinose and panose revealed the basis for the remarkable ligand binding plasticity of BlG16BP, which recognizes the non-reducing α-(1,6)-diglycoside in its ligands. BlG16BP homologues occur predominantly in bifidobacteria and a few Firmicutes but lack in other HGMs. Among seven bifidobacterial taxa, only those possessing this transporter displayed growth on α-(1,6)-glycosides. Competition assays revealed that the dominant HGM commensal Bacteroides ovatus was out-competed by B. animalis subsp. lactis Bl-04 in mixed cultures growing on raffinose, the preferred ligand for the BlG16BP. By comparison, B. ovatus mono-cultures grew very efficiently on this trisaccharide. These findings suggest that the ABC-mediated uptake of raffinose provides an important competitive advantage, particularly against dominant Bacteroides that lack glycan-specific ABC-transporters. This novel insight highlights the role of glycan transport in defining the metabolic specialization of gut bacteria. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

NpPDR1, a pleiotropic drug resistance-type ATP-binding cassette transporter from Nicotiana plumbaginifolia, plays a major role in plant pathogen defense.

Science.gov (United States)

Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

2005-09-01

Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family.

Molecular cloning and expression profile of an ATP-binding cassette (ABC) transporter gene from the hemipteran insect Nilaparvata lugens.

Science.gov (United States)

Zha, W J; Li, S H; Zhou, L; Chen, Z J; Liu, K; Yang, G C; Hu, G; He, G C; You, A Q

2015-03-30

The ATP-binding cassette (ABC) transporters belong to a large superfamily of proteins that have important physiological functions in all living organisms. In insects, ABC transporters have important functions in the transport of molecules, and are also involved in insecticide resistance, metabolism, and development. In this study, the Nilaparvata lugens Stal (Hemiptera: Delphacidae) ABCG (NlABCG) gene was identified and characterized. The complete mRNA sequence of NlABCG was 2608-bp long, with an open reading frame of 2064 bp encoding a protein comprised of 687 amino acids. The conserved regions include three N-glycosylation and 34 phosphorylation sites, as well as seven transmembrane domains. The amino acid identity with the closely related species Acyrthosiphon pisum was 42.8%. Developmental expression analysis using quantitative real-time reverse transcriptase PCR suggested that the NlABCG transcript was expressed at all developmental stages of N. lugens. The lowest expression of NlABCG was in the 1st instar, and levels increased with larval growth. The transcript profiles of NlABCG were analyzed in various tissues from a 5th instar nymph, and the highest expression was observed in the midgut. These results suggest that the sequence, characteristics, and expression of NlABCG are highly conserved, and basic information is provided for its functional analysis.

Fabrication of divertor cassette for ITER

International Nuclear Information System (INIS)

Sanguinetti, G.P.

2008-01-01

The Divertor is the component located on the bottom of the ITER vacuum vessel, whose main function is to adsorb the high thermal flux generated by the plasma whilst keeping the plasma impurity at a reasonable low level. The divertor consist of 54 units, each comprising outer components, facing the plasma and a component supporting the plasma facing components (PFC) and providing coolant distribution to them (divertor cassette). The divertor cassette is a box structure, butt welded and machined, made from plates and forgins of austenitic stainless steels. The cassette fabrication, which is in detail described, includes manufacturing of the attachments of the PFC to the cassette, the coolant distribution channels, and the cassette to vacuum vessel locking system. The divertor cassette is a pressure component (the cooling water runs at 40 bar) and therefore divertor cassette design, fabrication and service shall comply with the European PED and the applicable French law for the ITER. (orig.)

A survey of the radiographic cassettes disinfection of university hospitals in seoul

International Nuclear Information System (INIS)

Kweon, Dae Cheol; Park, Peom; Kim, Moon Sun; Kim, Dong Sung

2001-01-01

The purpose of this study is to prevent nosocomial infection in patients through contact of radiographic cassettes. Data were collected from radiographers working in 29 university hospitals in Seoul in February and March 2001. Radiographic cassettes were disinfected daily in 5 hospitals, weekly in 4 hospitals, monthly in 5 hospitals, bimonthly in 1 hospital and once every three months in another hospital. 12 other hospitals do not practice regular disinfections of radiographic cassettes. Gauze soaked in disinfectant solution is used in 7 hospitals while 11 hospitals used cotton and cloth soaked in disinfectant solution to clean the radiographic cassettes. 26 hospitals used 99% alcohol based disinfectant solutions while 3 hospitals used 75% alcohol based disinfectant, 26 hospitals use of intercourse cassettes outpatients and in patients. In 26 hospitals, all patients shared the same set of radiographic cassettes used in the hospitals, or in 26 hospitals, separate sets of radiographic cassettes are used for outpatients and inpatients. Separate sets of cassettes are used for ICU and inpatients in 6 others hospitals. 23 hospitals used the same sets of radiographic cassettes for all their patients. radiographic cassettes are cleaned in wash area in the study room of the radiographic department in 17 hospitals. 12 other hospitals do not have designated cleaning areas for the cassettes. All radiographers practiced hands washing with soap. All 29 hospitals surveyed have infection control committee. However, only 9 out of the 29 hospitals surveyed provided Infection · disinfections control education to radiographers. Only 3 hospitals have radiographers sitting in the infection control committee. Infection management education is conducted in 63 hospitals annually, twice a year in 1 hospital and once every 3 months in 2 hospitals

NpPDR1, a Pleiotropic Drug Resistance-Type ATP-Binding Cassette Transporter from Nicotiana plumbaginifolia, Plays a Major Role in Plant Pathogen Defense1

Science.gov (United States)

Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

2005-01-01

Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family. PMID:16126865

Divertor cassette movers prototypes for ITER

International Nuclear Information System (INIS)

Bogusch, E.; Batz, R.; Bieber, O.; Gottfried, R.; Cerdan, G.

1998-01-01

Following competitive tendering, in October 1996 Siemens was contracted by the European Commission to design and supply an assembly of four Divertor Cassette Movers Prototypes including the control and command systems for the movers proper. The assembly consisting of one Cassette Toroidal Mover (CTM), one Radial Mover Tractor (TRC), one Second Cassette Carrier (SCC), and one Radial Cassette Carrier (RCC) represents key components of the Divertor Test Platform at Brasimone, one of the seven large R+D projects for ITER. By detailed design, high-precision manufacturing and testing of these devices, Siemens contributed to the verification of an important task within the European R and D program towards ITER construction. Replacement of the divertor cassettes is a scheduled maintenance operation throughout the life of ITER. The successful fabrication and testing of the Divertor Cassette Movers Prototypes is all important milestone to verify this delicate operation. (authors)

7-ketocholesteryl-9-carboxynonanoate enhances ATP binding cassette transporter A1 expression mediated by PPARγ in THP-1 macrophages.

Science.gov (United States)

Chi, Yan; Wang, Le; Liu, Yuanyuan; Ma, Yanhua; Wang, Renjun; Han, Xiaofei; Qiao, Hui; Lin, Jiabin; Matsuura, Eiji; Liu, Shuqian; Liu, Qingping

2014-06-01

ATP binding cassette transporter A1 (ABCA1) is a member of the ATP-binding cassette transporter family. It plays an essential role in mediating the efflux of excess cholesterol. It is known that peroxisome proliferator-activated receptor gamma (PPARγ) promoted ABCA1 expression. We previously found 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) upregulated ABCA1 partially through CD36 mediated signals. In the present study, we intended to test if PPARγ signally is involved in the upregulation mediated by oxLig-1. First, we docked oxLig-1 and the ligand-binding domain (LBD) of PPARγ by using AutoDock 3.05 and subsequently confirmed the binding by ELISA assay. Western blotting analyses showed that oxLig-1 induces liver X receptor alpha (LXRα), PPARγ and consequently ABCA1 expression. Furthermore, oxLig-1 significantly enhanced ApoA-I-mediated cholesterol efflux. Pretreatment with an inhibitor for PPARγ (GW9662) or/and LXRα (GGPP) attenuated oxLig-1-induced ABCA1 expression. Under PPARγ knockdown by using PPARγ-shRNA, oxLig-1-induced ABCA1 expression and cholesterol efflux in THP-1 macrophages was blocked by 62% and 25% respectively. These observations suggest that oxLig-1 is a novel PPARγ agonist, promoting ApoA-I-mediated cholesterol efflux from THP-1 macrophages by increasing ABCA1 expression via induction of PPARγ. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Genome-wide identification of whole ATP-binding cassette (ABC) transporters in the intertidal copepod Tigriopus japonicus.

Science.gov (United States)

Jeong, Chang-Bum; Kim, Bo-Mi; Lee, Jae-Seong; Rhee, Jae-Sung

2014-08-05

The ATP-binding cassette (ABC) transporter superfamily is one of the largest transporter gene families and is observed in all animal taxa. Although a large set of transcriptomic data was recently assembled for several species of crustaceans, identification and annotation of the large ABC transporter gene family have been very challenging. In the intertidal copepod Tigriopus japonicus, 46 putative ABC transporters were identified using in silico analysis, and their full-length cDNA sequences were characterized. Phylogenetic analysis revealed that the 46 T. japonicus ABC transporters are classified into eight subfamilies (A-H) that include all the members of all ABC subfamilies, consisting of five ABCA, five ABCB, 17 ABCC, three ABCD, one ABCE, three ABCF, seven ABCG, and five ABCH subfamilies. Of them, unique isotypic expansion of two clades of ABCC1 proteins was observed. Real-time RT-PCR-based heatmap analysis revealed that most T. japonicus ABC genes showed temporal transcriptional expression during copepod development. The overall transcriptional profile demonstrated that half of all T. japonicus ABC genes were strongly associated with at least one developmental stage. Of them, transcripts TJ-ABCH_88708 and TJ-ABCE1 were highly expressed during all developmental stages. The whole set of T. japonicus ABC genes and their phylogenetic relationships will provide a better understanding of the comparative evolution of essential gene family resources in arthropods, including the crustacean copepods.

Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells

DEFF Research Database (Denmark)

Robey, R W; Medina-Pérez, W Y; Nishiyama, K

2001-01-01

We sought to characterize the interactions of flavopiridol with members of the ATP-binding cassette (ABC) transporter family. Cells overexpressing multidrug resistance-1 (MDR-1) and multidrug resistance-associated protein (MRP) did not exhibit appreciable flavopiridol resistance, whereas cell lines...... overexpressing the ABC half-transporter, ABCG2 (MXR/BCRP/ABCP1), were found to be resistant to flavopiridol. Flavopiridol at a concentration of 10 microM was able to prevent MRP-mediated calcein efflux, whereas Pgp-mediated transport of rhodamine 123 was unaffected at flavopiridol concentrations of up to 100...... analysis revealed overexpression of the ABCG2 gene. Western blot confirmed overexpression of ABCG2; neither P-glycoprotein nor MRP overexpression was detected. These results suggest that ABCG2 plays a role in resistance to flavopiridol....

Codon cassette mutagenesis: a general method to insert or replace individual codons by using universal mutagenic cassettes.

OpenAIRE

Kegler-Ebo, D M; Docktor, C M; DiMaio, D

1994-01-01

We describe codon cassette mutagenesis, a simple method of mutagenesis that uses universal mutagenic cassettes to deposit single codons at specific sites in double-stranded DNA. A target molecule is first constructed that contains a blunt, double-strand break at the site targeted for mutagenesis. A double-stranded mutagenic codon cassette is then inserted at the target site. Each mutagenic codon cassette contains a three base pair direct terminal repeat and two head-to-head recognition sequen...

Polycistronic transcription of fused cassettes and identification of translation initiation signals in an unusual gene cassette array from Pseudomonas aeruginosa [version 3; referees: 2 approved

Directory of Open Access Journals (Sweden)

Érica L. Fonseca

2015-11-01

Full Text Available The gene cassettes found in class 1 integrons are generally promoterless units composed by an open reading frame (ORF, a short 5’ untranslated region (UTR and a 3’ recombination site (attC. Fused gene cassettes are generated by partial or total loss of the attC from the first cassette in an array, creating, in some cases, a fusion with the ORF from the next cassette. These structures are rare and little is known about their mechanisms of mobilization and expression. The aim of this study was to evaluate the dynamic of mobilization and transcription of the gcu14-blaGES-1/aacA4 gene cassette array, which harbours a fused gene cassette represented by blaGES-1/aacA4. The cassette array was analyzed by Northern blot and real-time reverse transcription-polymerase chain reaction (RT-PCR in order to assess the transcription mechanism of blaGES-1/aacA4 fused cassette. Also, inverse polymerase chain reactions (PCR were performed to detect the free circular forms of gcu14, blaGES-1 and aacA4. The Northern blot and real time RT-PCR revealed a polycistronic transcription, in which the fused cassette blaGES-1/aacA4 is transcribed as a unique gene, while gcu14 (with a canonical attC recombination site has a monocistronic transcription. The gcu14 cassette, closer to the weak configuration of cassette promoter (PcW, had a higher transcription level than blaGES-1/aacA4, indicating that the cassette position affects the transcript amounts. The presence of ORF-11 at attI1, immediately preceding gcu14, and of a Shine-Dalgarno sequence upstream blaGES-1/aacA4 composes a scenario for the occurrence of array translation. Inverse PCR generated amplicons corresponding to gcu14, gcu14-aacA4 and gcu14-blaGES-1/aacA4 free circular forms, but not to blaGES-1 and aacA4 alone, indicating that the GES-1 truncated attC is not substrate of integrase activity and that these genes are mobilized together as a unique cassette. This study was original in showing the transcription

G5 PAMAM dendrimer versus liposome: a comparison study on the in vitro transepithelial transport and in vivo oral absorption of simvastatin.

Science.gov (United States)

Qi, Rong; Zhang, Heran; Xu, Lu; Shen, Wenwen; Chen, Cong; Wang, Chao; Cao, Yini; Wang, Yunan; van Dongen, Mallory A; He, Bing; Wang, Siling; Liu, George; Banaszak Holl, Mark M; Zhang, Qiang

2015-07-01

This study compared formulation effects of a dendrimer and a liposome preparation on the water solubility, transepithelial transport, and oral bioavailability of simvastatin (SMV). Amine-terminated G5 PAMAM dendrimer (G5-NH2) was chosen to form SMV/G5-NH2 molecular complexes, and SMV-liposomes were prepared by using a thin film dispersion method. The effects of these preparations on the transepithelial transport were investigated in vitro using Caco-2 cell monolayers. Results indicated that the solubility and transepithelial transport of SMV were significantly improved by both formulations. Pharmacokinetic studies in rats also revealed that both the SMV/G5-NH2 molecular complexes and the SMV-liposomes significantly improved the oral bioavailability of SMV with the liposomes being more effective than the G5-NH2. The overall better oral absorption of SMV-liposomes as compared to SMV/G5-NH2 molecular complexes appeared to arise from better liposomal solubilization and encapsulation of SMV and more efficient intracellular SMV delivery. Various carrier systems have been designed to enhance drug delivery via the oral route. In this study, the authors compared G5 PAMAM dendrimers to liposome preparations in terms of solubility, transepithelial transport, and oral bioavailability of this poorly water-soluble drug. This understanding has improved our knowledge in the further development of drug carrier systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Endothelial ATP-binding cassette G1 in mouse endothelium protects against hemodynamic-induced atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Xue, Shanshan [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Pediatrics, Baodi District People’s Hospital of Tianjin City, Tianjin, 301800 (China); Wang, Jiaxing [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Zhang, Xu; Shi, Ying; Li, Bochuan; Bao, Qiankun [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Pang, Wei [Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); Ai, Ding [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Zhu, Yi [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China); Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, 100191 (China); He, Jinlong, E-mail: hejinlong@tmu.edu.cn [Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, 300070 (China)

2016-08-19

Activated vascular endothelium inflammation under persistent hyperlipidemia is the initial step of atherogenesis. ATP-binding cassette G1 (ABCG1) is a crucial factor maintaining sterol and lipid homeostasis by transporting cholesterol efflux to high-density lipoprotein. In this study, we investigated the protective effects of ABCG1 in endothelial inflammation activation during early-stage atherogenesis in mice and the underlying mechanisms. Endothelial cell (EC)-specific ABCG1 transgenic (EC-ABCG1-Tg) mice were generated and cross-bred with low-density lipoprotein receptor–deficient (Ldlr{sup −/−}) mice. After a 4-week Western-type diet, the mice were sacrificed for assessing atherosclerosis. Human umbilical vein ECs were treated with different flows, and ABCG1 was adenovirally overexpressed to investigate the mechanism in vitro. Compared with Ldlr{sup −/−} mouse aortas, EC-ABCG1-Tg/Ldlr{sup −/−} aortas showed decreased early-stage lesions. Furthermore, the lesion area in the EC-ABCG1-Tg/Ldlr{sup −/−} mouse aortic arch but not thoracic aorta was significantly reduced, which suggests a protective role of ABCG1 under atheroprone flow. In vitro, overexpression of ABCG1 attenuated EC activation caused by oscillatory shear stress. Overexpression of ABCG1 blunted cholesterol-activated ECs in vitro. In exploring the mechanisms of ABCG1 attenuating endothelial inflammation, we found that ABCG1 inhibited oscillatory flow-activated nuclear factor kappa B and NLRP3 inflammasome in ECs. ABCG1 may play a protective role in early-stage atherosclerosis by reducing endothelial activation induced by oscillatory shear stress via suppressing the inflammatory response. - Highlights: • EC-ABCG1-Tg mice in a Ldlr{sup −/−} background showed decreased atherosclerosis. • Overexpression of ABCG1 in ECs decreased OSS-induced EC activation. • NLRP3 and NF-κB might be an underlying mechanism of ABCG1 protective role.

Radiographic film cassette unloading apparatus

International Nuclear Information System (INIS)

Stievenart, E.F.; Plessers, H.S.; Neujens, G.J.

1980-01-01

Apparatus for unloading cassettes, containing exposed radiographic films, has means for unfastening the cassettes, an inclined pathway for gravity feeding and rotating feed members (rollers or belts) to propel the films into the processor. (UK)

Selective ATP-Binding Cassette Subfamily C Gene Expression and Proinflammatory Mediators Released by BEAS-2B after PM2.5, Budesonide, and Cotreated Exposures

Directory of Open Access Journals (Sweden)

Jarline Encarnación-Medina

2017-01-01

Full Text Available ATP-binding cassette subfamily C (ABCC genes code for phase III metabolism proteins that translocate xenobiotic (e.g., particulate matter 2.5 (PM2.5 and drug metabolites outside the cells. IL-6 secretion is related with the activation of the ABCC transporters. This study assesses ABCC1–4 gene expression changes and proinflammatory cytokine (IL-6, IL-8 release in human bronchial epithelial cells (BEAS-2B exposed to PM2.5 organic extract, budesonide (BUD, used to control inflammation in asthmatic patients, and a cotreatment (Co-T: PM2.5 and BUD. A real-time PCR assay shows that ABCC1 was upregulated in BEAS-2B exposed after 6 and 7 hr to PM2.5 extract or BUD but downregulated after 6 hr of the Co-T. ABCC3 was downregulated after 6 hr of BUD and upregulated after 6 hr of the Co-T exposures. ABCC4 was upregulated after 5 hr of PM2.5 extract, BUD, and the Co-T exposures. The cytokine assay revealed an increase in IL-6 release by BEAS-2B exposed after 5 hr to PM2.5 extract, BUD, and the Co-T. At 7 hr, the Co-T decreases IL-6 release and IL-8 at 6 hr. In conclusion, the cotreatment showed an opposite effect on exposed BEAS-2B as compared with BUD. The results suggest an interference of the BUD therapeutic potential by PM2.5.

Universal modular dosimetric cassette

International Nuclear Information System (INIS)

Plichta, J.; Singer, J.; Trousil, J.; Pohnetal, F.; Kreisinger, F.; Feik, K.; Vaclavek, Z.; Jansky, B.

1987-01-01

The personnel dosemeter cassette is made of plastic and consists of front and rear parts joined with projections and a lock. The inner part is provided with recesses for securing different filters in position by gluing. A connecting part allows to firmly and easily lock more cassettes for the purposes of simultaneous measurement using different dosemeters. (M.D.). 6 figs

Hop Resistance in the Beer Spoilage Bacterium Lactobacillus brevis Is Mediated by the ATP-Binding Cassette Multidrug Transporter HorA

OpenAIRE

Sakamoto, Kanta; Margolles, Abelardo; van Veen, Hendrik W.; Konings, Wil N.

2001-01-01

Lactobacillus brevis is a major contaminant of spoiled beer. The organism can grow in beer in spite of the presence of antibacterial hop compounds that give the beer a bitter taste. The hop resistance in L. brevis is, at least in part, dependent on the expression of the horA gene. The deduced amino acid sequence of HorA is 53% identical to that of LmrA, an ATP-binding cassette multidrug transporter in Lactococcus lactis. To study the role of HorA in hop resistance, HorA was functionally expre...

Efficient purification and reconstitution of ATP binding cassette transporter B6 (ABCB6) for functional and structural studies.

Science.gov (United States)

Chavan, Hemantkumar; Khan, Mohiuddin Md Taimur; Tegos, George; Krishnamurthy, Partha

2013-08-02

The mitochondrial ATP binding cassette transporter ABCB6 has been associated with a broad range of physiological functions, including growth and development, therapy-related drug resistance, and the new blood group system Langereis. ABCB6 has been proposed to regulate heme synthesis by shuttling coproporphyrinogen III from the cytoplasm into the mitochondria. However, direct functional information of the transport complex is not known. To understand the role of ABCB6 in mitochondrial transport, we developed an in vitro system with pure and active protein. ABCB6 overexpressed in HEK293 cells was solubilized from mitochondrial membranes and purified to homogeneity. Purified ABCB6 showed a high binding affinity for MgATP (Kd = 0.18 μM) and an ATPase activity with a Km of 0.99 mM. Reconstitution of ABCB6 into liposomes allowed biochemical characterization of the ATPase including (i) substrate-stimulated ATPase activity, (ii) transport kinetics of its proposed endogenous substrate coproporphyrinogen III, and (iii) transport kinetics of substrates identified using a high throughput screening assay. Mutagenesis of the conserved lysine to alanine (K629A) in the Walker A motif abolished ATP hydrolysis and substrate transport. These results suggest a direct interaction between mitochondrial ABCB6 and its transport substrates that is critical for the activity of the transporter. Furthermore, the simple immunoaffinity purification of ABCB6 to near homogeneity and efficient reconstitution of ABCB6 into liposomes might provide the basis for future studies on the structure/function of ABCB6.

Novel Mutation in the ATP-Binding Cassette Transporter A3 (ABCA3) Encoding Gene Causes Respiratory Distress Syndrome in A Term Newborn in Southwest Iran

Science.gov (United States)

Rezaei, Farideh; Shafiei, Mohammad; Shariati, Gholamreza; Dehdashtian, Ali; Mohebbi, Maryam; Galehdari, Hamid

2016-01-01

Introduction ABCA3 glycoprotein belongs to the ATP-binding cassette (ABC) superfamily of transporters, which utilize the energy derived from hydrolysis of ATP for the translocation of a wide variety of substrates across the plasma membrane. Mutations in the ABCA3 gene are knowingly causative for fatal surfactant deficiency, particularly respiratory distress syndrome (RDS) in term babies. Case Presentation In this study, Sanger sequencing of the whole ABCA3 gene (NCBI NM_001089) was performed in a neonatal boy with severe RDS. A homozygous mutation has been identified in the patient. Parents were heterozygous for the same missense mutation GGA > AGA at position 202 in exon 6 of the ABCA3 gene (c.604G > A; p.G202R). Furthermore, 70 normal individuals have been analyzed for the mentioned change with negative results. Conclusions Regarding Human Genome Mutation Database (HGMD) and other literature recherche, the detected change is a novel mutation and has not been reported before. Bioinformatics mutation predicting tools prefer it as pathogenic. PMID:27437095

The economic potential of a cassette-type-reactor-installed nuclear ice-breaking container ship

International Nuclear Information System (INIS)

Kondo, Koichi; Takamasa, Tomoji

1999-01-01

An improved cassette-type marine reactor MRX (Marine Reactor X) which is currently researched and developed by the Japan Atomic Energy Research Institute is designed to be easily removed and transferred to another ship. If the reactor in a nuclear-powered ship, which is the reason for its higher cost, were replaced by the cassette-type-MRX, the reusability of the MRX would reduce the cost difference between nuclear-powered and diesel ships. As an investigation of one aspect of a cassette-type MRX, we attempted in this study to do an economic review of an MRX-installed nuclear-powered ice-breaking container ship sailing via the Arctic Ocean. The transportation cost between the Far East and Europe to carry one TEU (twenty-foot-equivalent container unit) over the entire life of the ship for an MRX (which is used for a 20-year period)-installed container ship sailing via the Arctic Ocean is about 70% higher than the Suez Canal diesel ship, carrying 8,000 TEU and sailing at 25 knots, and about 10% higher than the Suez Canal diesel ship carrying 4,000 TEU and sailing at 34 knots. The cost for a cassette-type-MRX (which is used for a 40-year period, removed and transferred to a second ship after being used for 20 years in the first ship)-installed nuclear-powered container ship is about 7% lower than that for the one operated for 20 years. Considering any loss or reduction in sales opportunities through the extension of the transportation period, the nuclear-powered container ship via the Arctic Sea is a more suitable means of transportation than a diesel ship sailing at 25 knots via the Suez Canal when the value of the commodities carried exceeds 2,800 dollars per freight ton. (author)

Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by the ATP-binding cassette multidrug transporter HorA.

Science.gov (United States)

Sakamoto, K; Margolles, A; van Veen, H W; Konings, W N

2001-09-01

Lactobacillus brevis is a major contaminant of spoiled beer. The organism can grow in beer in spite of the presence of antibacterial hop compounds that give the beer a bitter taste. The hop resistance in L. brevis is, at least in part, dependent on the expression of the horA gene. The deduced amino acid sequence of HorA is 53% identical to that of LmrA, an ATP-binding cassette multidrug transporter in Lactococcus lactis. To study the role of HorA in hop resistance, HorA was functionally expressed in L. lactis as a hexa-histidine-tagged protein using the nisin-controlled gene expression system. HorA expression increased the resistance of L. lactis to hop compounds and cytotoxic drugs. Drug transport studies with L. lactis cells and membrane vesicles and with proteoliposomes containing purified HorA protein identified HorA as a new member of the ABC family of multidrug transporters.

The yeast plasma membrane ATP binding cassette (ABC) transporter Aus1: purification, characterization, and the effect of lipids on its activity.

Science.gov (United States)

Marek, Magdalena; Milles, Sigrid; Schreiber, Gabriele; Daleke, David L; Dittmar, Gunnar; Herrmann, Andreas; Müller, Peter; Pomorski, Thomas Günther

2011-06-17

The ATP binding cassette (ABC) transporter Aus1 is expressed under anaerobic growth conditions at the plasma membrane of the yeast Saccharomyces cerevisiae and is required for sterol uptake. These observations suggest that Aus1 promotes the translocation of sterols across membranes, but the precise transport mechanism has yet to be identified. In this study, an extraction and purification procedure was developed to characterize the Aus1 transporter. The detergent-solubilized protein was able to bind and hydrolyze ATP. Mutagenesis of the conserved lysine to methionine in the Walker A motif abolished ATP hydrolysis. Likewise, ATP hydrolysis was inhibited by classical inhibitors of ABC transporters. Upon reconstitution into proteoliposomes, the ATPase activity of Aus1 was specifically stimulated by phosphatidylserine (PS) in a stereoselective manner. We also found that Aus1-dependent sterol uptake, but not Aus1 expression and trafficking to the plasma membrane, was affected by changes in cellular PS levels. These results suggest a direct interaction between Aus1 and PS that is critical for the activity of the transporter.

AtMRP1 gene of Arabidopsis encodes a glutathione S-conjugate pump: isolation and functional definition of a plant ATP-binding cassette transporter gene.

Science.gov (United States)

Lu, Y P; Li, Z S; Rea, P A

1997-07-22

Because plants produce cytotoxic compounds to which they, themselves, are susceptible and are exposed to exogenous toxins (microbial products, allelochemicals, and agrochemicals), cell survival is contingent on mechanisms for detoxifying these agents. One detoxification mechanism is the glutathione S-transferase-catalyzed glutathionation of the toxin, or an activated derivative, and transport of the conjugate out of the cytosol. We show here that a transporter responsible for the removal of glutathione S-conjugates from the cytosol, a specific Mg2+-ATPase, is encoded by the AtMRP1 gene of Arabidopsis thaliana. The sequence of AtMRP1 and the transport capabilities of membranes prepared from yeast cells transformed with plasmid-borne AtMRP1 demonstrate that this gene encodes an ATP-binding cassette transporter competent in the transport of glutathione S-conjugates of xenobiotics and endogenous substances, including herbicides and anthocyanins.

The ITER Divertor Cassette Project meeting

International Nuclear Information System (INIS)

Akiba, M.; Tivey, R.

2000-01-01

The Divertor Cassette Project topical meeting took place on April 5-7, 2000 at the JAERI Naka site in Japan. The meeting focused on the progress made by the three parties under task agreements on the development of carbon-fibre composite and tungsten armored high flux plasma-facing components

Disinfection Effect of Film Cassettes by Ultraviolet Irradiation

International Nuclear Information System (INIS)

Kweon, Dae Cheol; Park, Peom

2001-01-01

A bacteria infection on film cassette contact surface was examined at the diagnostic radiology department. Studies have demonstrated a bactericidal effect of ultraviolet irradiation, and to assess the contamination level on film cassette contact surface as a predictor of patient prevent from nosocomial infection. The study showed that the laboratory result was identified non-pathologic and pathologic bacterial in the five different cassette size of the contact surface. Film cassettes were exposed to ultraviolet light for 1, 2 and 3 minutes. Ultraviolet light disinfection practices suitable for bacteria. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. In conclusion, ultraviolet irradiate on film cassette over the surface more than 2 minutes. Ultraviolet dose of 1565 μW · s/cm 2 Win in 30 second relative to ultraviolet dose in time

Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion.

Science.gov (United States)

Zhang, J R; Norris, S J

1998-08-01

The Lyme disease spirochete Borrelia burgdorferi possesses 15 silent vls cassettes and a vls expression site (vlsE) encoding a surface-exposed lipoprotein. Segments of the silent vls cassettes have been shown to recombine with the vlsE cassette region in the mammalian host, resulting in combinatorial antigenic variation. Despite promiscuous recombination within the vlsE cassette region, the 5' and 3' coding sequences of vlsE that flank the cassette region are not subject to sequence variation during these recombination events. The segments of the silent vls cassettes recombine in the vlsE cassette region through a unidirectional process such that the sequence and organization of the silent vls loci are not affected. As a result of recombination, the previously expressed segments are replaced by incoming segments and apparently degraded. These results provide evidence for a gene conversion mechanism in VlsE antigenic variation.

Disinfection Effect of Film Cassettes by Ultraviolet Irradiation

Energy Technology Data Exchange (ETDEWEB)

Kweon, Dae Cheol; Park, Peom [Ajou Univ., Suwon (Korea, Republic of)

2001-12-15

A bacteria infection on film cassette contact surface was examined at the diagnostic radiology department. Studies have demonstrated a bactericidal effect of ultraviolet irradiation, and to assess the contamination level on film cassette contact surface as a predictor of patient prevent from nosocomial infection. The study showed that the laboratory result was identified non-pathologic and pathologic bacterial in the five different cassette size of the contact surface. Film cassettes were exposed to ultraviolet light for 1, 2 and 3 minutes. Ultraviolet light disinfection practices suitable for bacteria. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. In conclusion, ultraviolet irradiate on film cassette over the surface more than 2 minutes. Ultraviolet dose of 1565 {mu}W {center_dot} s/cm{sup 2}Win in 30 second relative to ultraviolet dose in time.

The x-ray source application test cassette for radiation exposures at the OMEGA laser

Energy Technology Data Exchange (ETDEWEB)

Fournier, K. B.; Rekow, V.; Emig, J. [Lawrence Livermore National Laboratory, Livermore, California 94551 (United States); Fisher, J. H.; Newlander, C. D. [Fifth Gait Technologies, Inc., Huntsville, Alabama 35803 (United States); Horton, R. [Gray Research, Inc., Huntsville, Alabama 35806 (United States); Davis, J. [Defense Threat Reduction Agency, Fort Belvoir, Virginia 22060 (United States)

2012-10-15

We have designed a sample cassette that can be used to position up to six samples in the OMEGA laser chamber. The cassette accommodates round samples up to 38.1 mm (1.5{sup Double-Prime }) in diameter and square samples up to 27 mm on a side, any of which can be up to 12.7 mm thick. Smaller specimens are centered with spacers. The test cassette allows each sample to have a unique filter scheme, with multiple filter regions in front of each sample. This paper will present mechanical design considerations and operational aspects of the x-ray source application cassette.

CMOS cassette for digital upgrade of film-based mammography systems

Science.gov (United States)

Baysal, Mehmet A.; Toker, Emre

2006-03-01

While full-field digital mammography (FFDM) technology is gaining clinical acceptance, the overwhelming majority (96%) of the installed base of mammography systems are conventional film-screen (FSM) systems. A high performance, and economical digital cassette based product to conveniently upgrade FSM systems to FFDM would accelerate the adoption of FFDM, and make the clinical and technical advantages of FFDM available to a larger population of women. The planned FFDM cassette is based on our commercial Digital Radiography (DR) cassette for 10 cm x 10 cm field-of-view spot imaging and specimen radiography, utilizing a 150 micron columnar CsI(Tl) scintillator and 48 micron active-pixel CMOS sensor modules. Unlike a Computer Radiography (CR) cassette, which requires an external digitizer, our DR cassette transfers acquired images to a display workstation within approximately 5 seconds of exposure, greatly enhancing patient flow. We will present the physical performance of our prototype system against other FFDM systems in clinical use today, using established objective criteria such as the Modulation Transfer Function (MTF), Detective Quantum Efficiency (DQE), and subjective criteria, such as a contrast-detail (CD-MAM) observer performance study. Driven by the strong demand from the computer industry, CMOS technology is one of the lowest cost, and the most readily accessible technologies available for FFDM today. Recent popular use of CMOS imagers in high-end consumer cameras have also resulted in significant advances in the imaging performance of CMOS sensors against rivaling CCD sensors. This study promises to take advantage of these unique features to develop the first CMOS based FFDM upgrade cassette.

Disruption of lolCDE, Encoding an ATP-Binding Cassette Transporter, Is Lethal for Escherichia coli and Prevents Release of Lipoproteins from the Inner Membrane

OpenAIRE

Narita, Shin-ichiro; Tanaka, Kimie; Matsuyama, Shin-ichi; Tokuda, Hajime

2002-01-01

ATP-binding cassette transporter LolCDE was previously identified, by using reconstituted proteoliposomes, as an apparatus catalyzing the release of outer membrane-specific lipoproteins from the inner membrane of Escherichia coli. Mutations resulting in defective LolD were previously shown to be lethal for E. coli. The amino acid sequences of LolC and LolE are similar to each other, but the necessity of both proteins for lipoprotein release has not been proved. Moreover, previous reconstituti...

Design of SMART steam generator cassette

International Nuclear Information System (INIS)

Kim, Y. W.; Kim, J. I.; Jang, M. H.

2001-01-01

Basic design development for the steam generator to be installed in the integral reactor SMART has been performed. Optimization of the steam generator shape, determination of the basic dimension and confirmation of the structural strength have been carried out. Individual steam generator cassette can be replaced in the optimized design concept of steam generator. Shape design of the steam generator cassette has been done on the computer based on 3-D CAE strategy. The structural integrity of the developed steam generator was investigated by performing the dynamic analysis for the steam generator cassette, flow induced vibration analysis for the tube bundle, and the thermo-mechanical analysis for the module header and tube. As for the manufacturing of steam generator, the numerical and the experimental simulation have been carried to control the amount of spring back and to eliminate residual stress. SMART steam generator cassette was developed by a sequential research of the aforementioned activities

Retinal-specific ATP-binding cassette transporter (ABCR/ABCA4) is expressed at the choroid plexus in rat brain.

Science.gov (United States)

Bhongsatiern, Jiraganya; Ohtsuki, Sumio; Tachikawa, Masanori; Hori, Satoko; Terasaki, Tetsuya

2005-03-01

ATP-binding cassette (ABC) transporter A4 is a member of the ABC transporter subfamily A which has been reported to be exclusively expressed in the retina. In contrast, a previous report has suggested a possible relationship between ABCA4 and CNS function. The purpose of the present study was to investigate the localization of ABCA4 mRNA and protein in rat brain. In situ hybridization analysis revealed that ABCA4 mRNA was localized in the lateral ventricles. RT-PCR analysis detected ABCA4 mRNA in isolated rat choroid plexus and conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB). Furthermore, ABCA4 protein was also detected in the isolated rat choroid plexus at about 250 kDa by western blot analysis, and its apparent molecular size was reduced by N-glycosidase F treatment. These results suggest that glycosylated ABCA4 protein is expressed in rat choroid plexus epithelial cells. ABCA4 may play a role in the function of the blood-cerebrospinal fluid barrier and affect CSF conditions.

ROLE OF ATP BINDING CASSETTE SUB-FAMILY MEMBER 2 (ABCG2) IN MOUSE EMBRYONIC STEM CELL DEVELOPMENT.

Science.gov (United States)

ATP binding cassette sub-family member 2 (ABCG2), is a member of the ABC transporter superfamily and a principal xenobiotic transporter. ABCG2 is also highly expressed in certain stem cell populations where it is thought to be related to stem cell plasticity, although the role o...

Bilirubin Decreases Macrophage Cholesterol Efflux and ATP-Binding Cassette Transporter A1 Protein Expression.

Science.gov (United States)

Wang, Dongdong; Tosevska, Anela; Heiß, Elke H; Ladurner, Angela; Mölzer, Christine; Wallner, Marlies; Bulmer, Andrew; Wagner, Karl-Heinz; Dirsch, Verena M; Atanasov, Atanas G

2017-04-28

Mild but chronically elevated circulating unconjugated bilirubin is associated with reduced total and low-density lipoprotein cholesterol concentration, which is associated with reduced cardiovascular disease risk. We aimed to investigate whether unconjugated bilirubin influences macrophage cholesterol efflux, as a potential mechanism for the altered circulating lipoprotein concentrations observed in hyperbilirubinemic individuals. Cholesterol efflux from THP-1 macrophages was assessed using plasma obtained from normo- and hyperbilirubinemic (Gilbert syndrome) humans (n=60 per group) or (heterozygote/homozygote Gunn) rats (n=20 per group) as an acceptor. Hyperbilirubinemic plasma from patients with Gilbert syndrome and Gunn rats induced significantly reduced cholesterol efflux compared with normobilirubinemic plasma. Unconjugated bilirubin (3-17.1 μmol/L) exogenously added to plasma- or apolipoprotein A1-supplemented media also decreased macrophage cholesterol efflux in a concentration- and time-dependent manner. We also showed reduced protein expression of the ATP-binding cassette transporter A1 (ABCA1), a transmembrane cholesterol transporter involved in apolipoprotein A1-mediated cholesterol efflux, in THP-1 macrophages treated with unconjugated bilirubin and in peripheral blood mononuclear cells obtained from hyperbilirubinemic individuals. Furthermore, we demonstrated that bilirubin accelerates the degradation rate of the ABCA1 protein in THP-1 macrophages. Cholesterol efflux from THP-1 macrophages is decreased in the presence of plasma obtained from humans and rats with mild hyperbilirubinemia. A direct effect of unconjugated bilirubin on cholesterol efflux was demonstrated and is associated with decreased ABCA1 protein expression. These data improve our knowledge concerning bilirubin's impact on cholesterol transport and represent an important advancement in our understanding of bilirubin's role in cardiovascular disease. © 2017 The Authors. Published on

A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

Science.gov (United States)

Polireddy, Kishore; Khan, Mohiuddin Md Taimur; Chavan, Hemantkumar; Young, Susan; Ma, Xiaochao; Waller, Anna; Garcia, Matthew; Perez, Dominique; Chavez, Stephanie; Strouse, Jacob J; Haynes, Mark K; Bologa, Cristian G; Oprea, Tudor I; Tegos, George P; Sklar, Larry A; Krishnamurthy, Partha

2012-01-01

ABCB6 is a member of the adenosine triphosphate (ATP)-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS), can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

Cassette pontoon bridge of high mobility

Directory of Open Access Journals (Sweden)

Krzysztof KOSIUCZENKO

2011-01-01

Full Text Available Looking through the known and used buoyant systems, it can be remarked that the single buoyant segments are the stiff objects made of steel or plastic with variable dimensions and a complex construction. The ready to use buoyant segments, that assure the proper displacement, must have the factory leak-tightness. They take up a big transportation volume and need the assurance of the suitably abundant means of transport. Usually the heavy wheeled vehicles are needed because of high own mass of buoyant segment and large gauges. The exploitation of such constructions is very expensive. A cassette pontoon bridge, presented in this paper, is the proposition of the increase of the mobility of construction. The decrease of the single buoyant segment dimensions with the assurance of the capacity leads that more segments fit into in the same dimensions of the loading compartment of the vehicle and storage accommodation. The application of standardized joints assures the assembly efficiency with not numerous crew.

Cassette for handling banknotes or the like

Science.gov (United States)

Lundblad, Leif

1981-08-11

A cassette for banknotes and like valuable articles is provided with a displaceable lid (6) and locking means (10) for latching the lid of the cassette when the cassette is located outside a housing (25) in which it is intended to be placed. An operating means (8) is arranged to co-act with the locking means and with a latching element (15). The latching element is arranged to be released in dependence upon a pre-set program. A signal circuit is arranged to send a code signal to a detector circuit (23) when electrical contact elements on the cassette and the housing co-act with one another, which detector circuit, when the signal coincides with the signal program in the detector circuit, causes a signal to be sent for moving the latching means to a non-latching position.

Genetic Analysis of the Mode of Interplay between an ATPase Subunit and Membrane Subunits of the Lipoprotein-Releasing ATP-Binding Cassette Transporter LolCDE†

OpenAIRE

Ito, Yasuko; Matsuzawa, Hitomi; Matsuyama, Shin-ichi; Narita, Shin-ichiro; Tokuda, Hajime

2006-01-01

The LolCDE complex, an ATP-binding cassette (ABC) transporter, releases lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane of Escherichia coli. The LolCDE complex is composed of two copies of an ATPase subunit, LolD, and one copy each of integral membrane subunits LolC and LolE. LolD hydrolyzes ATP on the cytoplasmic side of the inner membrane, while LolC and/or LolE recognize and release lipoproteins anchored to the periplasmic leaflet of the i...

The ITER divertor cassette project meeting

International Nuclear Information System (INIS)

Merola, M.; Riccardi, B.; Tivey, R.

1999-01-01

The Divertor Cassette Project topical meeting was held on May 26-28, 1999 at the ENEA Brasimone Research Centre in Camugnano (Bologna), Italy. Specialists from all the four Parties and the JCT participated in the meeting. It was concluded that the Divertor Cassette Project has significantly contributed to solving a large part of the critical issues of the ITER divertor design

A novel flow cytometric HTS assay reveals functional modulators of ATP binding cassette transporter ABCB6.

Directory of Open Access Journals (Sweden)

Kishore Polireddy

Full Text Available ABCB6 is a member of the adenosine triphosphate (ATP-binding cassette family of transporter proteins that is increasingly recognized as a relevant physiological and therapeutic target. Evaluation of modulators of ABCB6 activity would pave the way toward a more complete understanding of the significance of this transport process in tumor cell growth, proliferation and therapy-related drug resistance. In addition, this effort would improve our understanding of the function of ABCB6 in normal physiology with respect to heme biosynthesis, and cellular adaptation to metabolic demand and stress responses. To search for modulators of ABCB6, we developed a novel cell-based approach that, in combination with flow cytometric high-throughput screening (HTS, can be used to identify functional modulators of ABCB6. Accumulation of protoporphyrin, a fluorescent molecule, in wild-type ABCB6 expressing K562 cells, forms the basis of the HTS assay. Screening the Prestwick Chemical Library employing the HTS assay identified four compounds, benzethonium chloride, verteporfin, tomatine hydrochloride and piperlongumine, that reduced ABCB6 mediated cellular porphyrin levels. Validation of the identified compounds employing the hemin-agarose affinity chromatography and mitochondrial transport assays demonstrated that three out of the four compounds were capable of inhibiting ABCB6 mediated hemin transport into isolated mitochondria. However, only verteporfin and tomatine hydrochloride inhibited ABCB6's ability to compete with hemin as an ABCB6 substrate. This assay is therefore sensitive, robust, and suitable for automation in a high-throughput environment as demonstrated by our identification of selective functional modulators of ABCB6. Application of this assay to other libraries of synthetic compounds and natural products is expected to identify novel modulators of ABCB6 activity.

The new deterministic 3-D radiation transport code Multitrans: C5G7 MOX fuel assembly benchmark

International Nuclear Information System (INIS)

Kotiluoto, P.

2003-01-01

The novel deterministic three-dimensional radiation transport code MultiTrans is based on combination of the advanced tree multigrid technique and the simplified P3 (SP3) radiation transport approximation. In the tree multigrid technique, an automatic mesh refinement is performed on material surfaces. The tree multigrid is generated directly from stereo-lithography (STL) files exported by computer-aided design (CAD) systems, thus allowing an easy interface for construction and upgrading of the geometry. The deterministic MultiTrans code allows fast solution of complicated three-dimensional transport problems in detail, offering a new tool for nuclear applications in reactor physics. In order to determine the feasibility of a new code, computational benchmarks need to be carried out. In this work, MultiTrans code is tested for a seven-group three-dimensional MOX fuel assembly transport benchmark without spatial homogenization (NEA C5G7 MOX). (author)

A study on contamination and disinfection of film cassette

International Nuclear Information System (INIS)

Kweon, Dae Cheol; Chung, Kyung Mo; Choi, Ji Won

2000-01-01

In July 2000, a bacteria infection on film cassette contact surface was examined at the diagnostic radiology department of the S. hospital. The objective of this study was to assess the contamination level on film cassette contact surface as a predictor of patient to prevent from nosocomial infection. The study showed that the laboratory result was identified non-pathologic bacterial in the four different cassette size of the contact surface. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. Also the education of nosocomial infection for radiographer will be required

A study on contamination and disinfection of film cassette

Energy Technology Data Exchange (ETDEWEB)

Kweon, Dae Cheol; Chung, Kyung Mo [Seoul National University Hospital, Seoul (Korea, Republic of); Choi, Ji Won [University of Sydney, Sydney (Australia)

2000-04-15

In July 2000, a bacteria infection on film cassette contact surface was examined at the diagnostic radiology department of the S. hospital. The objective of this study was to assess the contamination level on film cassette contact surface as a predictor of patient to prevent from nosocomial infection. The study showed that the laboratory result was identified non-pathologic bacterial in the four different cassette size of the contact surface. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. Also the education of nosocomial infection for radiographer will be required.

Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus

Directory of Open Access Journals (Sweden)

Yu Lan

2012-08-01

Full Text Available Abstract Background The otrC gene of Streptomyces rimosus was previously annotated as an oxytetracycline (OTC resistance protein. However, the amino acid sequence analysis of OtrC shows that it is a putative ATP-binding cassette (ABC transporter with multidrug resistance function. To our knowledge, none of the ABC transporters in S. rimosus have yet been characterized. In this study, we aimed to characterize the multidrug exporter function of OtrC and evaluate its relevancy to OTC production. Results In order to investigate OtrC’s function, otrC is cloned and expressed in E. coli The exporter function of OtrC was identified by ATPase activity determination and ethidium bromide efflux assays. Also, the susceptibilities of OtrC-overexpressing cells to several structurally unrelated drugs were compared with those of OtrC-non-expressing cells by minimal inhibitory concentration (MIC assays, indicating that OtrC functions as a drug exporter with a broad range of drug specificities. The OTC production was enhanced by 1.6-fold in M4018 (P = 0.000877 and 1.4-fold in SR16 (P = 0.00973 duplication mutants, while it decreased to 80% in disruption mutants (P = 0.0182 and 0.0124 in M4018 and SR16, respectively. Conclusions The results suggest that OtrC is an ABC transporter with multidrug resistance function, and plays an important role in self-protection by drug efflux mechanisms. This is the first report of such a protein in S. rimosus, and otrC could be a valuable target for genetic manipulation to improve the production of industrial antibiotics.

ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function

Directory of Open Access Journals (Sweden)

Wen-Jung Lu

2018-03-01

Full Text Available Vibrio cholerae ATP-binding cassette transporter VcaM (V. cholerae ABC multidrug resistance pump has previously been shown to confer resistance to a variety of medically important drugs. In this study, we set to analyse its properties both in vitro in detergent-solubilised state and in vivo to differentiate its dependency on auxiliary proteins for its function. We report the first detailed kinetic parameters of purified VcaM and the rate of phosphate (Pi production. To determine the possible functional dependencies of VcaM on the tripartite efflux pumps we then utilized different E. coli strains lacking the principal secondary transporter AcrB (Acriflavine resistance protein, as well as cells lacking the outer membrane factor (OMF TolC (Tolerance to colicins. Consistent with the ATPase function of VcaM we found it to be susceptible to sodium orthovanadate (NaOV, however, we also found a clear dependency of VcaM function on TolC. Inhibitors targeting secondary active transporters had no effects on either VcaM-conferred resistance or Hoechst 33342 accumulation, suggesting that VcaM might be capable of engaging with the TolC-channel without periplasmic mediation by additional transporters. Our findings are indicative of VcaM being capable of a one-step substrate translocation from cytosol to extracellular space utilising the TolC-channel, making it the only multidrug ABC-transporter outside of the MacB-family with demonstrable TolC-dependency.

Purification and biochemical characterization of NpABCG5/NpPDR5, a plant pleiotropic drug resistance transporter expressed in Nicotiana tabacum BY-2 suspension cells.

Science.gov (United States)

Toussaint, Frédéric; Pierman, Baptiste; Bertin, Aurélie; Lévy, Daniel; Boutry, Marc

2017-05-04

Pleiotropic drug resistance (PDR) transporters belong to the ABCG subfamily of ATP-binding cassette (ABC) transporters and are involved in the transport of various molecules across plasma membranes. During evolution, PDR genes appeared independently in fungi and in plants from a duplication of a half-size ABC gene. The enzymatic properties of purified PDR transporters from yeast have been characterized. This is not the case for any plant PDR transporter, or, incidentally, for any purified plant ABC transporter. Yet, plant PDR transporters play important roles in plant physiology such as hormone signaling or resistance to pathogens or herbivores. Here, we describe the expression, purification, enzymatic characterization and 2D analysis by electron microscopy of NpABCG5/NpPDR5 from Nicotiana plumbaginifolia , which has been shown to be involved in the plant defense against herbivores. We constitutively expressed NpABCG5/NpPDR5, provided with a His-tag in a homologous system: suspension cells from Nicotiana tabacum (Bright Yellow 2 line). NpABCG5/NpPDR5 was targeted to the plasma membrane and was solubilized by dodecyl maltoside and purified by Ni-affinity chromatography. The ATP-hydrolyzing specific activity (27 nmol min -1  mg -1 ) was stimulated seven-fold in the presence of 0.1% asolectin. Electron microscopy analysis indicated that NpABCG5/NpPDR5 is monomeric and with dimensions shorter than those of known ABC transporters. Enzymatic data (optimal pH and sensitivity to inhibitors) confirmed that plant and fungal PDR transporters have different properties. These data also show that N. tabacum suspension cells are a convenient host for the purification and biochemical characterization of ABC transporters. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Recovery and evolutionary analysis of complete integron gene cassette arrays from Vibrio

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Gillings Michael R

2006-01-01

Full Text Available Abstract Background Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be. Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains. Results The complete Vibrio sp. DAT722 integron cassette array was determined through the streamlined approach described here. To place it in an evolutionary context, we compare the DAT722 array to known vibrio arrays and performed phylogenetic analyses for all of its components (integrase, 59-be sites, gene cassette encoded genes. It differs extensively in terms of genomic context as well as gene cassette content and organization. The phylogenetic tree of the 59-be sites collectively found in the Vibrio gene cassette pool suggests frequent transfer of cassettes within and between Vibrio species, with slower transfer rates between more phylogenetically distant relatives. We also identify multiple cases where non-integron chromosomal genes seem to have been assembled into gene cassettes and others where cassettes have been inserted into chromosomal locations outside integrons. Conclusion Our systematic approach greatly facilitates the isolation and annotation of large integrons gene cassette arrays. Comparative analysis of the Vibrio sp. DAT722 integron obtained through this approach to those found in other vibrios confirms the role of this genetic element in promoting lateral gene transfer and suggests a high rate of gene

Temperature variations around medication cassette and carry bag in routine use of epoprostenol administration in healthy volunteers.

Directory of Open Access Journals (Sweden)

Yuichi Tamura

Full Text Available BACKGROUND: According to several treatment guidelines, epoprostenol is an important treatment option for pulmonary arterial hypertension. However, the pharmacokinetic characteristics and poor stability of epoprostenol at room temperature make its administration challenging. We therefore studied temperature fluctuations between the drug administration cassette and atmosphere to promote the safe use of epoprostenol. METHODS AND FINDINGS: Five healthy volunteers carried a portable intravenous infusion pump attached to a medication cassette containing saline in a bag during their ordinary activities over 16 days during which the mean atmospheric temperature was 29.6 ± 1.5°C. The temperature around the medication cassette was not less than 25°C on any occasion, and the mean period over 24 h during which the temperature around the cassette exceeded 35°C and 40°C was 96.9 ± 156.4 min and 24.4 ± 77.3 min, respectively. Significant correlations were observed between the temperatures outside the bag and around the cassette, as well as between temperatures around the cassette and of the saline solution in the cassette (r = 0.9258 and 0.8276, respectively. There were no differences in the temperatures outside the bag or around the cassette with respect to the bag material. CONCLUSIONS: Temperatures around a medication cassette and outside the bag containing the medication increase with sunlight exposure. The temperature around cassettes used for administering epoprostenol must therefore be kept low for as long as possible during hot summer conditions to maintain the drug stability.

Medium-chain triglycerides promote macrophage reverse cholesterol transport and improve atherosclerosis in ApoE-deficient mice fed a high-fat diet.

Science.gov (United States)

Zhang, Xinsheng; Zhang, Yong; Liu, Yinghua; Wang, Jin; Xu, Qing; Yu, Xiaoming; Yang, Xueyan; Liu, Zhao; Xue, Changyong

2016-09-01

We previously observed that medium-chain triglycerides (MCTs) could reduce body fat mass and improve the metabolism of cholesterol. We hypothesized that MCTs can improve atherosclerosis by promoting the reverse cholesterol transport (RCT) process. Therefore, the objective of this study was to investigate the roles of MCTs in macrophage RCT and the progression of atherosclerosis. To test this hypothesis, 30 4-week-old ApoE-deficient (ApoE(-/-)) mice were randomly divided into 2 groups and fed a diet of 2% MCTs or long-chain triglycerides (LCTs) for 16 weeks. Ten age- and sex-matched C57BL/6J mice were fed a diet of 2% LCTs as the control. Macrophage-to-feces RCT was assessed in vivo by intraperitoneal injection of RAW 264.7 macrophages containing (3)H-labeled cholesterol, and atherosclerotic plaques were measured. The mRNA and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. There was a greater decrease in body fat mass, atherosclerotic plaques, and an improvement in serum lipid profiles. In addition, the MCT mice group showed an increase in (3)H-tracer in the feces and a decrease in the liver. Significantly higher levels of mRNA and protein expression of hepatic ATP-binding cassette transporter A1, ATP-binding cassette transporter G5, cholesterol 7α-hydroxylase, and intestinal ATP-binding cassette transporter G8, as well as lower levels of expression of intestinal Niemann-Pick C1-like 1, were found in the MCT group. These results suggest that MCTs could obviously promote macrophage RCT and improve atherosclerosis in ApoE(-/-) mice, indicating that MCTs have the potential to prevent cardiovascular disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization and expression profiling of ATP-binding cassette transporter genes in the diamondback moth, Plutella xylostella (L.).

Science.gov (United States)

Qi, Weiping; Ma, Xiaoli; He, Weiyi; Chen, Wei; Zou, Mingmin; Gurr, Geoff M; Vasseur, Liette; You, Minsheng

2016-09-27

ATP-binding cassette (ABC) transporters are one of the major transmembrane protein families found in all organisms and play important roles in transporting a variety of compounds across intra and extra cellular membranes. In some species, ABC transporters may be involved in the detoxification of substances such as insecticides. The diamondback moth, Plutella xylostella (L.), a destructive pest of cruciferous crops worldwide, is an important species to study as it is resistant to many types of insecticides as well as biological control Bacillus thuringiensis toxins. A total of 82 ABC genes were identified from our published P. xylostella genome, and grouped into eight subfamilies (ABCA-H) based on phylogenetic analysis. Genes of subfamilies ABCA, ABCC and ABCH were found to be expanded in P. xylostella compared with those in Bombyx mori, Manduca sexta, Heliconius melpomene, Danaus plexippus, Drosophila melanogaster, Tetranychus urticae and Homo sapiens. Phylogenetic analysis indicated that many of the ABC transporters in P. xylostella are orthologous to the well-studied ABC transporter genes in the seven other species. Transcriptome- and qRT-PCR-based analysis elucidated physiological effects of ABC gene expressions of P. xylostella which were developmental stage- and tissue-specific as well as being affected by whether or not the insects were from an insecticide-resistant strain. Two ABCC and one ABCA genes were preferentially expressed in midgut of the 4th-instar larvae of a susceptible strain (Fuzhou-S) suggesting their potential roles in metabolizing plant defensive chemicals. Most of the highly expressed genes in insecticide-resistant strains were also predominantly expressed in the tissues of Malpighian tubules and midgut. This is the most comprehensive study on identification, characterization and expression profiling of ABC transporter genes in P. xylostella to date. The diversified features and expression patterns of this gene family may be associated with

Efficient Long-Range Hole Transport Through G-Quadruplexes.

Science.gov (United States)

Wu, Jingyuan; Meng, Zhenyu; Lu, Yunpeng; Shao, Fangwei

2017-10-09

DNA offers a means of long-range charge transport for biology and electric nanodevices. Here, a series of tetra-stranded G-quadruplexes were assembled within a dendritic DNA architecture to explore oxidative charge transport (hole transport) through the G-quadruplex. Efficient charge transport was achieved over 28 Å upon UV irradiation. Over a longer G-quadruplex bridge, hole transport was escalated to a higher efficiency, which resulted in a higher yield than that of the optimal duplex DNA for charge transport, that is, the adenine tract. Efficient long-range hole transport suggests tetra-stranded G-quadruplexes, instead of an oxidation hotspot, hold better potential as an electron conduit than duplex DNA. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of ATP-binding cassette and solute carrier transporters in erlotinib CNS penetration and intracellular accumulation.

Science.gov (United States)

Elmeliegy, Mohamed A; Carcaboso, Angel M; Tagen, Michael; Bai, Feng; Stewart, Clinton F

2011-01-01

To study the role of drug transporters in central nervous system (CNS) penetration and cellular accumulation of erlotinib and its metabolite, OSI-420. After oral erlotinib administration to wild-type and ATP-binding cassette (ABC) transporter-knockout mice (Mdr1a/b(-/-), Abcg2(-/-), Mdr1a/b(-/-)Abcg2(-/-), and Abcc4(-/-)), plasma was collected and brain extracellular fluid (ECF) was sampled using intracerebral microdialysis. A pharmacokinetic model was fit to erlotinib and OSI-420 concentration-time data, and brain penetration (P(Brain)) was estimated by the ratio of ECF-to-unbound plasma area under concentration-time curves. Intracellular accumulation of erlotinib was assessed in cells overexpressing human ABC transporters or SLC22A solute carriers. P(Brain) in wild-type mice was 0.27 ± 0.11 and 0.07 ± 0.02 (mean ± SD) for erlotinib and OSI-420, respectively. Erlotinib and OSI-420 P(Brain) in Abcg2(-/-) and Mdr1a/b(-/-)Abcg2(-/-) mice were significantly higher than in wild-type mice. Mdr1a/b(-/-) mice showed similar brain ECF penetration as wild-type mice (0.49 ± 0.37 and 0.04 ± 0.02 for erlotinib and OSI-420, respectively). In vitro, erlotinib and OSI-420 accumulation was significantly lower in cells overexpressing breast cancer resistance protein (BCRP) than in control cells. Only OSI-420, not erlotinib, showed lower accumulation in cells overexpressing P-glycoprotein (P-gp) than in control cells. The P-gp/BCRP inhibitor elacridar increased erlotinib and OSI-420 accumulation in BCRP-overexpressing cells. Erlotinib uptake was higher in OAT3- and OCT2-transfected cells than in empty vector control cells. Abcg2 is the main efflux transporter preventing erlotinib and OSI-420 penetration in mouse brain. Erlotinib and OSI-420 are substrates for SLC22A family members OAT3 and OCT2. Our findings provide a mechanistic basis for erlotinib CNS penetration, cellular uptake, and efflux mechanisms. ©2010 AACR.

X-ray film cassette and method of making

International Nuclear Information System (INIS)

1980-01-01

An x-ray film cassette which is capable of providing forces on the film that vary across the surface of the cassette is described. Methods of manufacture are discussed. The system is of particular use when large area films are used in conjunction with intensifying screens. (U.K.)

Genome-wide analysis of the ATP-binding cassette (ABC) transporter gene family in the silkworm, Bombyx mori.

Science.gov (United States)

Xie, Xiaodong; Cheng, Tingcai; Wang, Genhong; Duan, Jun; Niu, Weihuan; Xia, Qingyou

2012-07-01

The ATP-binding cassette (ABC) superfamily is a larger protein family with diverse physiological functions in all kingdoms of life. We identified 53 ABC transporters in the silkworm genome, and classified them into eight subfamilies (A-H). Comparative genome analysis revealed that the silkworm has an expanded ABCC subfamily with more members than Drosophila melanogaster, Caenorhabditis elegans, or Homo sapiens. Phylogenetic analysis showed that the ABCE and ABCF genes were highly conserved in the silkworm, indicating possible involvement in fundamental biological processes. Five multidrug resistance-related genes in the ABCB subfamily and two multidrug resistance-associated-related genes in the ABCC subfamily indicated involvement in biochemical defense. Genetic variation analysis revealed four ABC genes that might be evolving under positive selection. Moreover, the silkworm ABCC4 gene might be important for silkworm domestication. Microarray analysis showed that the silkworm ABC genes had distinct expression patterns in different tissues on day 3 of the fifth instar. These results might provide new insights for further functional studies on the ABC genes in the silkworm genome.

Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

Science.gov (United States)

Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

2014-01-01

Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

ACID: annotation of cassette and integron data

Directory of Open Access Journals (Sweden)

Stokes Harold W

2009-04-01

Full Text Available Abstract Background Although integrons and their associated gene cassettes are present in ~10% of bacteria and can represent up to 3% of the genome in which they are found, very few have been properly identified and annotated in public databases. These genetic elements have been overlooked in comparison to other vectors that facilitate lateral gene transfer between microorganisms. Description By automating the identification of integron integrase genes and of the non-coding cassette-associated attC recombination sites, we were able to assemble a database containing all publicly available sequence information regarding these genetic elements. Specialists manually curated the database and this information was used to improve the automated detection and annotation of integrons and their encoded gene cassettes. ACID (annotation of cassette and integron data can be searched using a range of queries and the data can be downloaded in a number of formats. Users can readily annotate their own data and integrate it into ACID using the tools provided. Conclusion ACID is a community resource providing easy access to annotations of integrons and making tools available to detect them in novel sequence data. ACID also hosts a forum to prompt integron-related discussion, which can hopefully lead to a more universal definition of this genetic element.

The naphthoquinones, vitamin K3 and its structural analogue plumbagin, are substrates of the multidrug resistance linked ATP binding cassette drug transporter ABCG2.

Science.gov (United States)

Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V

2007-12-01

Vitamin K3 (menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2, which are essential for blood clotting. The naturally occurring structural analogue of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We here report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette drug transporter, ABCG2. Vitamin K3 and plumbagin specifically inhibited the ABCG2-mediated efflux of mitoxantrone but did not have any effect on the ABCB1-mediated efflux of rhodamine 123. This inhibition of ABCG2 function was due to their interaction at the substrate-binding site(s). Vitamin K3 and plumbagin inhibited the binding of [(125)I]iodoarylazidoprazosin, a substrate of ABCG2, to this transporter in a concentration-dependent manner with IC(50) values of 7.3 and 22.6 micromol/L, respectively, but had no effect on the binding of the photoaffinity analogue to ABCB1. Both compounds stimulated ABCG2-mediated ATP hydrolysis and also inhibited the mitoxantrone-stimulated ATPase activity of the ABCG2 transporter, but did not have any significant effect on the ATPase activity of ABCB1. In a cytotoxicity assay, ABCG2-expressing HEK cells were 2.8- and 2.3-fold resistant to plumbagin and vitamin K3, respectively, compared with the control cells, suggesting that they are substrates of this transporter. Collectively, these data show for the first time that vitamin K3 is a substrate of the ABCG2 transporter. Thus, ABCG2 may have a role in the regulation of vitamin K3 levels in the body. In addition, vitamin K3 and its structural derivative, plumbagin, could potentially be used to modulate ABCG2 function.

Suppression of c-Myc is involved in multi-walled carbon nanotubes' down-regulation of ATP-binding cassette transporters in human colon adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhaojing [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Xu, Yonghong [Institute of Ophthalmological Research, Department of Ophthalmology, Renmin Hospital of Wuhan University, 430060 Wuhan (China); Meng, Xiangning [School of Materials and Metallurgy, Northeastern University, Shenyang 110819 (China); Watari, Fumio [Department of Biomedical, Dental Materials and Engineering, Graduate School of Dental Medicine, Hokkaido University, Sapporo 060-8586 (Japan); Liu, Hudan, E-mail: hudanliu@hust.edu.cn [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China); Chen, Xiao, E-mail: mornsmile@yahoo.com [Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan (China)

2015-01-01

Over-expression of ATP-binding cassette (ABC) transporters, a large family of integral membrane proteins that decrease cellular drug uptake and accumulation by active extrusion, is one of the major causes of cancer multi-drug resistance (MDR) that frequently leads to failure of chemotherapy. Carbon nanotubes (CNTs)-based drug delivery devices hold great promise in enhancing the efficacy of cancer chemotherapy. However, CNTs' effects on the ABC transporters remain under-investigated. In this study, we found that multiwalled carbon nanotubes (MWCNTs) reduced transport activity and expression of ABC transporters including ABCB1/Pgp and ABCC4/MRP4 in human colon adenocarcinoma Caco-2 cells. Proto-oncogene c-Myc, which directly regulates ABC gene expression, was concurrently decreased in MWCNT-treated cells and forced over-expression of c-Myc reversed MWCNTs' inhibitory effects on ABCB1 and ABCC4 expression. MWCNT-cell membrane interaction and cell membrane oxidative damage were observed. However, antioxidants such as vitamin C, β-mecaptoethanol and dimethylthiourea failed to antagonize MWCNTs' down-regulation of ABC transporters. These data suggest that MWCNTs may act on c-Myc, but not through oxidative stress, to down-regulate ABC transporter expression. Our findings thus shed light on CNTs' novel cellular effects that may be utilized to develop CNTs-based drug delivery devices to overcome ABC transporter-mediated cancer chemoresistance.

On design and development of additional End-Effectors for the Cassette Multifunctional Mover

Energy Technology Data Exchange (ETDEWEB)

Valkama, Peetu, E-mail: peetu.valkama@tut.fi [Department of Intelligent Hydraulics and Automation, Tampere University of Technology, P.O. Box 589, FI-33720 Tampere (Finland); Mattila, J.; Amjad, F.; Vaeyrynen, J.; Vilenius, M. [Department of Intelligent Hydraulics and Automation, Tampere University of Technology, P.O. Box 589, FI-33720 Tampere (Finland); Siuko, M. [VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere (Finland); Semeraro, L.; Esque, S. [F4E, Fusion for Energy, Torres Diagonal Litoral B3, Josep Pla 2, 08019 Barcelona (Spain)

2011-10-15

The divertor area of ITER Vacuum Vessel (VV) consists of 54 modular cassettes which must be replaced three times during the estimated 20 years of operation of the ITER. Cassette Multifunctional Mover (CMM) and Cassette Toroidal Mover (CTM) are used in the cassette remote handling (RH). In this paper we discuss the design and development process for the RH equipment to be used in the ITER environment. Design concepts for the Standard Cassette End-Effector and Central Cassette End-Effector are described and the conceptual design phase methodology is presented. The main improvements of the new End-Effector concept designs are more robust and reliable assembly process with reduced CMM mover assembly accuracy requirement. New Central Cassette locking system was developed to address the high forces and contact pressures emerging during the Central Cassette installation. The chosen design concepts are verified with virtual reality simulations and are fulfilling the requirements defined in the concept design phase, including structural, assembly sequence, safety and reliability.

PfMDR2 and PfMDR5 are dispensable for Plasmodium falciparum asexual parasite multiplication but change in vitro susceptibility to anti-malarial drugs

NARCIS (Netherlands)

Velden, M. van der; Rijpma, S.R.; Russel, F.G.M.; Sauerwein, R.W.; Koenderink, J.B.

2015-01-01

BACKGROUND: Membrane-associated ATP binding cassette (ABC) transport proteins hydrolyze ATP in order to translocate a broad spectrum of substrates, from single ions to macromolecules across membranes. In humans, members from this transport family have been linked to drug resistance phenotypes, e.g.,

Genome-Wide Identification, Characterization and Phylogenetic Analysis of ATP-Binding Cassette (ABC) Transporter Genes in Common Carp (Cyprinus carpio).

Science.gov (United States)

Liu, Xiang; Li, Shangqi; Peng, Wenzhu; Feng, Shuaisheng; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A; Xu, Peng

2016-01-01

The ATP-binding cassette (ABC) gene family is considered to be one of the largest gene families in all forms of prokaryotic and eukaryotic life. Although the ABC transporter genes have been annotated in some species, detailed information about the ABC superfamily and the evolutionary characterization of ABC genes in common carp (Cyprinus carpio) are still unclear. In this research, we identified 61 ABC transporter genes in the common carp genome. Phylogenetic analysis revealed that they could be classified into seven subfamilies, namely 11 ABCAs, six ABCBs, 19 ABCCs, eight ABCDs, two ABCEs, four ABCFs, and 11 ABCGs. Comparative analysis of the ABC genes in seven vertebrate species including common carp, showed that at least 10 common carp genes were retained from the third round of whole genome duplication, while 12 duplicated ABC genes may have come from the fourth round of whole genome duplication. Gene losses were also observed for 14 ABC genes. Expression profiles of the 61 ABC genes in six common carp tissues (brain, heart, spleen, kidney, intestine, and gill) revealed extensive functional divergence among the ABC genes. Different copies of some genes had tissue-specific expression patterns, which may indicate some gene function specialization. This study provides essential genomic resources for future studies in common carp.

Genome-Wide Identification, Characterization and Phylogenetic Analysis of ATP-Binding Cassette (ABC) Transporter Genes in Common Carp (Cyprinus carpio)

Science.gov (United States)

Peng, Wenzhu; Feng, Shuaisheng; Feng, Jianxin; Mahboob, Shahid; Al-Ghanim, Khalid A.

2016-01-01

The ATP-binding cassette (ABC) gene family is considered to be one of the largest gene families in all forms of prokaryotic and eukaryotic life. Although the ABC transporter genes have been annotated in some species, detailed information about the ABC superfamily and the evolutionary characterization of ABC genes in common carp (Cyprinus carpio) are still unclear. In this research, we identified 61 ABC transporter genes in the common carp genome. Phylogenetic analysis revealed that they could be classified into seven subfamilies, namely 11 ABCAs, six ABCBs, 19 ABCCs, eight ABCDs, two ABCEs, four ABCFs, and 11 ABCGs. Comparative analysis of the ABC genes in seven vertebrate species including common carp, showed that at least 10 common carp genes were retained from the third round of whole genome duplication, while 12 duplicated ABC genes may have come from the fourth round of whole genome duplication. Gene losses were also observed for 14 ABC genes. Expression profiles of the 61 ABC genes in six common carp tissues (brain, heart, spleen, kidney, intestine, and gill) revealed extensive functional divergence among the ABC genes. Different copies of some genes had tissue-specific expression patterns, which may indicate some gene function specialization. This study provides essential genomic resources for future studies in common carp. PMID:27058731

Genome-Wide Identification, Characterization and Phylogenetic Analysis of ATP-Binding Cassette (ABC Transporter Genes in Common Carp (Cyprinus carpio.

Directory of Open Access Journals (Sweden)

Xiang Liu

Full Text Available The ATP-binding cassette (ABC gene family is considered to be one of the largest gene families in all forms of prokaryotic and eukaryotic life. Although the ABC transporter genes have been annotated in some species, detailed information about the ABC superfamily and the evolutionary characterization of ABC genes in common carp (Cyprinus carpio are still unclear. In this research, we identified 61 ABC transporter genes in the common carp genome. Phylogenetic analysis revealed that they could be classified into seven subfamilies, namely 11 ABCAs, six ABCBs, 19 ABCCs, eight ABCDs, two ABCEs, four ABCFs, and 11 ABCGs. Comparative analysis of the ABC genes in seven vertebrate species including common carp, showed that at least 10 common carp genes were retained from the third round of whole genome duplication, while 12 duplicated ABC genes may have come from the fourth round of whole genome duplication. Gene losses were also observed for 14 ABC genes. Expression profiles of the 61 ABC genes in six common carp tissues (brain, heart, spleen, kidney, intestine, and gill revealed extensive functional divergence among the ABC genes. Different copies of some genes had tissue-specific expression patterns, which may indicate some gene function specialization. This study provides essential genomic resources for future studies in common carp.

Phosphorus Partitioning of Soybean Lines Containing Different Mutant Alleles of Two Soybean Seed-Specific Adenosine Triphosphate-Binding Cassette Phytic Acid Transporter Paralogs

Directory of Open Access Journals (Sweden)

Jason D. Gillman

2013-03-01

Full Text Available Seed phytate is a repository of P and minerals in soybean [ (L. Merr.] seeds that limits P and mineral bioavailability for monogastric animals (e.g., humans, swine [], and poultry [especially chicken, ] due to insufficient digestive tract phytase activity. We previously identified epistatic recessive mutations affecting two paralogous adenosine triphosphate-binding cassette phytic acid transporter genes (one a nonsense mutation in and the other a missense mutation in as the molecular genetic basis in the ethyl methanesulfonate (EMS-induced mutant low phytate soybean line M153. An additional mutant low phytate line, M766, contained one single nucleotide polymorphism within the ninth intron of the locus as well as a nonsense mutation in . The objectives of this research were to clarify the genetics underlying the low phytate phenotype in line M766 and to determine P partitioning in new combinations of mutant alleles from M766 and M153. Inheritance of nonsense alleles affecting both ( genes (one from M153 and one from M766 led to the production of viable seeds that contained transgressive reductions in total seed phytate and significantly higher levels of inorganic phosphate than has been reported for nontransgenic soybean material and will allow efficient molecular selection of soybeans with even greater reductions of phytate for improved quality soybean meal.

The cost-effectiveness of carbon-fibre cassettes in mobile chest radiography

International Nuclear Information System (INIS)

Brennan, P.C.; Hourihan, S.P.

1998-01-01

Employment of carbon fibre materials is an effective method of reducing radiation dose, yet the increased associated costs have led to a reluctance in implementation. This study investigates the level of dose reduction achievable, while maintaining image quality, in mobile chest radiography using carbon-fibre cassettes, compared with plastic cassettes, and balances this against increased expense of the cassettes. Dose measurements using thermoluminescent dosimeters were carried out on intensive therapy unit (ITU) patients undergoing an anteroposterior chest X-ray examination. Resultant image quality was assessed using objective Commission of European Communities (CEC) criteria. A retrospective audit recorded number of ITU patients currently having chest X-rays to determine total dose savings over the life of the cassettes. The results show significant reductions (p < 0.0001) of 32 % for entrance surface and effective dose with carbon-fibre cassettes. No deterioration in total image quality was noted. The added expense of ≤ 2260 per personSievert (calculated from the effective dose reduction) for employing carbon-fibre cassettes is minimal compared with the estimated cost of manSievert exposures reported by other workers. (orig.)

Cassette - Foro. Un sistema de comunicación participatoria

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Mario Kaplún

2015-05-01

Full Text Available El Cassette-Foro es un modelo de comunicación para la promoción y educación de adultos, puesto al servicio de organizaciones de desarrollo comunitario -rurales y urbanas-, centrales cooperativas, centros de educación pública, etc. El método es grupal y bidireccional. Mediante el intercambio de mensaJes grabados en cassettes, permite entablar a distancia un diálogo entre los miembros de base de la organización y el núcleo dirigente de la misma y/o entre los grupos de base entre sí. El modelo combina la comunicación colectiva con la interpersonal: mensajes colectivos grabados en cassettes, audición del mensaje por parte de cada grupo, discusión del mismo y respuesta del grupo grabada en la otra pista del cassette, que retorna al centro emisor-receptor.

Polymorphisms in ATP-binding cassette transporter genes and interaction with diet and life style factors in relation to colorectal cancer in a Danish prospective case-cohort study

DEFF Research Database (Denmark)

Kopp, Tine Iskov; Andersen, Vibeke; Tjonneland, Anne

2015-01-01

to assess whether polymorphisms in ABCB1, ABCC2 and ABCG2 were associated with risk of colorectal cancer (CRC) and to investigate gene-environment (dietary factors, smoking and use of non-steroidal anti-inflammatory drugs) and gene-gene interactions between previously studied polymorphisms in IL1B and IL10......The ATP-binding cassette (ABC) transporter family transports various molecules across the enterocytes in the gut protecting the intestine against potentially harmful substances. Moreover, ABC transporters are involved in mucosal immune defence through interaction with cytokines. The study aimed...... of the polymorphisms were associated with CRC, but ABCB1 and ABCG2 haplotypes were associated with risk of CRC. ABCB1/rs1045642 interacted with intake of cereals and fiber (p-Value for interaction (Pint) = 0.001 and 0.01, respectively). In a three-way analysis, both ABCB1/rs1045642 and ABCG2/rs2231137 in combination...

The gBL transport equations

International Nuclear Information System (INIS)

Mynick, H.E.

1989-05-01

The transport equations arising from the ''generalized Balescu- Lenard'' (gBL) collision operator are obtained, and some of their properties examined. The equations contain neoclassical and turbulent transport as two special cases, having the same structure. The resultant theory offers potential explanation for a number of results not well understood, including the anomalous pinch, observed ratios of Q/ΓT on TFTR, and numerical reproduction of ASDEX profiles by a model for turbulent transport invoked without derivation, but by analogy to neoclassical theory. The general equations are specialized to consideration of a number of particular transport mechanisms of interest. 10 refs

On wiping the interior walls of 37-mm closed-face cassettes: an OSHA perspective.

Science.gov (United States)

Hendricks, Warren; Stones, Fern; Lillquist, Dean

2009-12-01

As early as 1976, Occupational Safety and Health Administration (OSHA) methods for analyzing metal samples collected using 37-mm polystyrene closed-face cassettes specified that any loose dust be transferred from the cassette to the digestion vessel, that the cassette be rinsed, and that, if necessary, the cassette be wiped out to help ensure that all particles that enter the cassette are included along with the filter as part of the sample for analysis. OSHA analytical methods for metal analysis were recently revised to explicitly require cassette wiping for all metal samples. This change was based on policy that any material entering the collection device constitutes part of the sample and on OSHA Salt Lake Technical Center research showing that invisible residue on the cassette walls can significantly contribute to the total sample results reported. OSHA procedures are consistent with guidance given in the NIOSH Manual of Analytical Methods. This guidance concludes that internal deposits in sampling cassettes should be included in the analysis and that one way to accomplish this would be to wipe or wash the internal surfaces of the cassette and include the material along with the filter for analysis.

What is 5G? Emerging 5G Mobile Services and Network Requirements

Directory of Open Access Journals (Sweden)

Heejung Yu

2017-10-01

Full Text Available In this paper, emerging 5G mobile services are investigated and categorized from the perspective of not service providers, but end-users. The development of 5G mobile services is based on an intensive analysis of the global trends in mobile services. Additionally, several indispensable service requirements, essential for realizing service scenarios presented, are described. To illustrate the changes in societies and in daily life in the 5G era, five megatrends, including the explosion of mobile data traffic, the rapid increase in connected devices, everything on the cloud, hyper-realistic media for convergence services and knowledge as a service enabled by big-data analysis, are examined. Based on such trends, we classify the new 5G services into five categories in terms of the end-users’ experience as follows: immersive 5G services, intelligent 5G services, omnipresent 5G services, autonomous 5G services and public 5G services. Moreover, several 5G service scenarios in each service category are presented, and essential technical requirements for realizing the aforementioned 5G services are suggested, along with a competitiveness analysis on 5G services/devices/network industries and the current condition of 5G technologies.

Towards a unified fronthaul-backhaul data plane for 5G The 5G-Crosshaul project approach

OpenAIRE

Cavaliere, Fabio; Iovanna, Paola; Mangues-Bafalluy, Josep; Baranda, Jorge; Núñez-Martínez, José; Lin, Kun-Yi; Chang, Hsien-Wen; Chanclou, Philippe; Farkas, Peter; Gomes, Jessé; Cominardi, Luca; Mourad, Alain; De La Oliva, Antonio; Hernández, José Alberto; Larrabeiti, David

2017-01-01

The paper presents a study of key aspects in the design of a flexible unified data plane capable of integrating both fronthaul and backhaul transport in future 5G systems. In this study, we first review candidate access and multiplexing technologies from the state of the art and assess their capability to support legacy and new fronthaul and backhaul traffic. We then propose a new design framework for the targeted flexible unified data plane, featuring a primary packet-switching path supporte...

CRISPR-Mediated Integration of Large Gene Cassettes Using AAV Donor Vectors

Directory of Open Access Journals (Sweden)

Rasmus O. Bak

2017-07-01

Full Text Available The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV vectors to serve as donor template DNA during homologous recombination (HR. However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing. We use the methodology in primary human T cells and CD34+ hematopoietic stem and progenitor cells to site-specifically integrate an expression cassette that, as a single donor vector, would otherwise amount to a total of 6.5 kb. This approach now provides an efficient way to integrate large transgene cassettes into the genomes of primary human cells using HR-mediated genome editing with AAV vectors.

An investigation of infection control for x-ray cassettes in a diagnostic imaging department

International Nuclear Information System (INIS)

Fox, Matthew; Harvey, Jane M.

2008-01-01

Introduction: This research was conducted to investigate if X-ray cassettes could be a possible source of pathogens capable of causing nosocomial infections, and if they could be a possible vector for cross infection within the hospital environment. Method: The research involved the swabbing of X-ray cassettes in a Diagnostic Imaging Department of a large hospital in the east of England. Two areas of the Diagnostic Imaging Department were included in the study. Research concentrated on X-ray cassettes used for mobile radiography, accident and emergency and inpatient use. Forty cassettes were swabbed in total specifically for general levels of bacterial contamination, also for the presence or absence of methicillin-resistant Staphylococcus aureus (MRSA). A mapping exercise was completed following the location of an X-ray cassette typically used in mobile radiography. The exercise noted the level of direct contact with patient's skin and other possible routes of infection. Results: The results demonstrated that there were large levels of growth of samples taken from cassettes and developed in the Microbiology Department. Coagulase-negative Staphylococcus, Micrococci, Diptheroids and species of Bacillus were all identified. The mapping exercise in which the journey of a 35/43 cm cassette used for mobile radiography was tracked found that contact with patient's skin and potential pathogens or routes of cross infection was a common occurrence whilst undertaking mobile radiography. Conclusion: The research has identified the presence of bacterial contamination on cassettes. The research established that X-ray cassettes/imaging plates are often exposed to pathogens and possible routes of cross infection; also that patient's skin often comes directly in contact with the X-ray cassette/imaging plate. The research also shows that as cassettes/imaging plates are a potential source of cross infection, the Diagnostic Imaging Department may be partly responsible for adding to

Mutant Allele-Specific Uncoupling of PENETRATION3 Functions Reveals Engagement of the ATP-Binding Cassette Transporter in Distinct Tryptophan Metabolic Pathways1[OPEN

Science.gov (United States)

Lu, Xunli; Dittgen, Jan; Piślewska-Bednarek, Mariola; Molina, Antonio; Schneider, Bernd; Doubský, Jan; Schneeberger, Korbinian; Schulze-Lefert, Paul

2015-01-01

Arabidopsis (Arabidopsis thaliana) PENETRATION (PEN) genes quantitatively contribute to the execution of different forms of plant immunity upon challenge with diverse leaf pathogens. PEN3 encodes a plasma membrane-resident pleiotropic drug resistance-type ATP-binding cassette transporter and is thought to act in a pathogen-inducible and PEN2 myrosinase-dependent metabolic pathway in extracellular defense. This metabolic pathway directs the intracellular biosynthesis and activation of tryptophan-derived indole glucosinolates for subsequent PEN3-mediated efflux across the plasma membrane at pathogen contact sites. However, PEN3 also functions in abiotic stress responses to cadmium and indole-3-butyric acid (IBA)-mediated auxin homeostasis in roots, raising the possibility that PEN3 exports multiple functionally unrelated substrates. Here, we describe the isolation of a pen3 allele, designated pen3-5, that encodes a dysfunctional protein that accumulates in planta like wild-type PEN3. The specific mutation in pen3-5 uncouples PEN3 functions in IBA-stimulated root growth modulation, callose deposition induced with a conserved peptide epitope of bacterial flagellin (flg22), and pathogen-inducible salicylic acid accumulation from PEN3 activity in extracellular defense, indicating the engagement of multiple PEN3 substrates in different PEN3-dependent biological processes. We identified 4-O-β-d-glucosyl-indol-3-yl formamide (4OGlcI3F) as a pathogen-inducible, tryptophan-derived compound that overaccumulates in pen3 leaf tissue and has biosynthesis that is dependent on an intact PEN2 metabolic pathway. We propose that a precursor of 4OGlcI3F is the PEN3 substrate in extracellular pathogen defense. These precursors, the shared indole core present in IBA and 4OGlcI3F, and allele-specific uncoupling of a subset of PEN3 functions suggest that PEN3 transports distinct indole-type metabolites in distinct biological processes. PMID:26023163

5G CHAMPION - rolling out 5G in 2018

OpenAIRE

Mueck, M.; Strinati, E.C.; Kim, I.-G.; Clemente, A.; Dore, J.-B.; Domenico, A. de; Kim, T.; Choi, T.; Chung, H.K.; Destino, G.; Pärssinen, A.; Pouttu, A.; Latva-aho, M.; Chuberre, N.; Gineste, M.

2016-01-01

The 5G CHAMPION Consortium will provide the first fully integrated and operational 5G prototype in 2018 - this effort is a major leap ahead compared to existing punctual technology trials, such as, e.g., Proof-of-Concept platforms focusing on mm Wave communication in specific bands, etc. This paper describes the overall set-up including a synergetic combination of technologies such as beamforming based mm Wave & Satellite service provisioning, virtualized infrastructure, software reconfigurat...

Characterization of a lactose-responsive promoter of ATP-binding cassette (ABC) transporter gene from Lactobacillus acidophilus 05-172.

Science.gov (United States)

Zeng, Zhu; Zuo, Fanglei; Yu, Rui; Zhang, Bo; Ma, Huiqin; Chen, Shangwu

2017-09-01

A novel lactose-responsive promoter of the ATP-binding cassette (ABC) transporter gene Lba1680 of Lactobacillus acidophilus strain 05-172 isolated from a traditionally fermented dairy product koumiss was characterized. In L. acidophilus 05-172, expression of Lba1680 was induced by lactose, with lactose-induced transcription of Lba1680 being 6.1-fold higher than that induced by glucose. This is in contrast to L. acidophilus NCFM, a strain isolated from human feces, in which expression of Lba1680 and Lba1679 is induced by glucose. Both gene expression and enzyme activity assays in L. paracasei transformed with a vector containing the inducible Lba1680 promoter (PLba1680) of strain 05-172 and a heme-dependent catalase gene as reporter confirmed that PLba1680 is specifically induced by lactose. Its regulatory expression could not be repressed by glucose, and was independent of cAMP receptor protein. This lactose-responsive promoter might be used in the expression of functional genes in L. paracasei incorporated into a lactose-rich environment, such as dairy products. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Whole-transcriptome survey of the putative ATP-binding cassette (ABC) transporter family genes in the latex-producing laticifers of Hevea brasiliensis.

Science.gov (United States)

Zhiyi, Nie; Guijuan, Kang; Yu, Li; Longjun, Dai; Rizhong, Zeng

2015-01-01

The ATP-binding cassette (ABC) proteins or transporters constitute a large protein family in plants and are involved in many different cellular functions and processes, including solute transportation, channel regulation and molecular switches, etc. Through transcriptome sequencing, a transcriptome-wide survey and expression analysis of the ABC protein genes were carried out using the laticiferous latex from Hevea brasiliensis (rubber tree). A total of 46 putative ABC family proteins were identified in the H. brasiliensis latex. These consisted of 12 'full-size', 21 'half-size' and 13 other putative ABC proteins, and all of them showed strong conservation with their Arabidopsis thaliana counterparts. This study indicated that all eight plant ABC protein paralog subfamilies were identified in the H. brasiliensis latex, of which ABCB, ABCG and ABCI were the most abundant. Real-time quantitative reverse transcription-polymerase chain reaction assays demonstrated that gene expression of several latex ABC proteins was regulated by ethylene, jasmonic acid or bark tapping (a wound stress) stimulation, and that HbABCB15, HbABCB19, HbABCD1 and HbABCG21 responded most significantly of all to the abiotic stresses. The identification and expression analysis of the latex ABC family proteins could facilitate further investigation into their physiological involvement in latex metabolism and rubber biosynthesis by H. brasiliensis.

Development of a full-size divertor cassette prototype for ITER

Energy Technology Data Exchange (ETDEWEB)

Ulrickson, M.A. [Sandia National Labs., Albuquerque, NM (United States); Vieider, G.; Pacher, H.D. [Max-Planck-Institut fuer Plasmaphysik, Garching (Germany). NET Design Team] [and others

1996-10-01

Production of a full-size divertor cassette involves eight major components. All of the components are mounted on the cassette body. Inner divertor channel components for the vertical target design are being provided by the Japan Home Team. Outer divertor channel components for the vertical target design are being provided by the European and United States Home Teams. Gas box liners are being provided by the Russian Home Team. The full-size components manufactured by the four parties will be shipped to the US Home Team for assembly into a full size divertor cassette. The techniques for assembly and maintenance of the cassette will be demonstrated during this process. The assembled cassette will be tested for proper flow distribution and proof of the filling and draining procedures. The testing will include vacuum leak tightness at full temperature and pressure, cyclic heating to 150 {degrees}C, verification of dimensional accuracy of the assembled components, and application of thermal gradients to measure dimensional stability. The development of the divertor for the International Thermonuclear Experimental Reactor (ITER) depends on successful R&D efforts on materials, joining, and plasma materials interactions. Results of the development program are presented. The scale-up of the processes developed in the basic research and development tasks is accomplished by producing and high-heat-flux testing medium and full-scale mock- ups. The design of the mock-ups is discussed.

Brucella abortus mutants lacking ATP-binding cassette transporter proteins are highly attenuated in virulence and confer protective immunity against virulent B. abortus challenge in BALB/c mice.

Science.gov (United States)

Truong, Quang Lam; Cho, Youngjae; Park, Soyeon; Park, Bo-Kyoung; Hahn, Tae-Wook

2016-06-01

Brucella abortus RB51 is an attenuated vaccine strain that has been most frequently used for bovine brucellosis. Although it is known to provide good protection in cattle, it still has some drawbacks including resistance to rifampicin, residual virulence and pathogenicity in humans. Thus, there has been a continuous interest on new safe and effective bovine vaccine candidates. In the present study, we have constructed unmarked mutants by deleting singly cydD and cydC genes, which encode ATP-binding cassette transporter proteins, from the chromosome of the virulent Brucella abortus isolate from Korean cow (referred to as IVK15). Both IVK15ΔcydD and ΔcydC mutants showed increased sensitivity to metal ions, hydrogen peroxide and acidic pH, which are mimic to intracellular environment during host infection. Additionally, the mutants exhibited a significant growth defect in RAW264.7 cells and greatly attenuated in mice. Vaccination of mice with either IVK15ΔcydC or IVK15ΔcydD mutant could elicit an anti-Brucella specific immunoglobulin G (IgG) and IgG subclass responses as well as enhance the secretion of interferon-gamma, and provided better protection against challenge with B. abortus strain 2308 than with the commercial B. abortus strain RB51 vaccine. Collectively, these results suggest that both IVK15ΔcydC and IVK15ΔcydD mutants could be an attenuated vaccine candidate against B. abortus. Copyright © 2016 Elsevier Ltd. All rights reserved.

The ATP-binding cassette transporter A1 regulates phosphoantigen release and Vγ9Vδ2 T cell activation by dendritic cells

Science.gov (United States)

Castella, Barbara; Kopecka, Joanna; Sciancalepore, Patrizia; Mandili, Giorgia; Foglietta, Myriam; Mitro, Nico; Caruso, Donatella; Novelli, Francesco; Riganti, Chiara; Massaia, Massimo

2017-01-01

Vγ9Vδ2 T cells are activated by phosphoantigens, such as isopentenyl pyrophosphate (IPP), which is generated in the mevalonate pathway of antigen-presenting cells. IPP is released in the extracellular microenvironment via unknown mechanisms. Here we show that the ATP-binding cassette transporter A1 (ABCA1) mediates extracellular IPP release from dendritic cells (DC) in cooperation with apolipoprotein A-I (apoA-I) and butyrophilin-3A1. IPP concentrations in the supernatants are sufficient to induce Vγ9Vδ2 T cell proliferation after DC mevalonate pathway inhibition with zoledronic acid (ZA). ZA treatment increases ABCA1 and apoA-I expression via IPP-dependent LXRα nuclear translocation and PI3K/Akt/mTOR pathway inhibition. These results close the mechanistic gap in our understanding of extracellular IPP release from DC and provide a framework to fine-tune Vγ9Vδ2 T cell activation via mevalonate and PI3K/Akt/mTOR pathway modulation. PMID:28580927

An investigation of infection control for x-ray cassettes in a diagnostic imaging department

Energy Technology Data Exchange (ETDEWEB)

Fox, Matthew [School of Allied Health Professions and Science, Faculty of Health, Wellbeing and Science, University Campus Suffolk, Rope Walk, Ipswich, Suffolk, IP4 1LT (United Kingdom); Harvey, Jane M. [School of Allied Health Professions and Science, Faculty of Health, Wellbeing and Science, University Campus Suffolk, Rope Walk, Ipswich, Suffolk, IP4 1LT (United Kingdom)], E-mail: j.harvey@ucs.ac.uk

2008-11-15

Introduction: This research was conducted to investigate if X-ray cassettes could be a possible source of pathogens capable of causing nosocomial infections, and if they could be a possible vector for cross infection within the hospital environment. Method: The research involved the swabbing of X-ray cassettes in a Diagnostic Imaging Department of a large hospital in the east of England. Two areas of the Diagnostic Imaging Department were included in the study. Research concentrated on X-ray cassettes used for mobile radiography, accident and emergency and inpatient use. Forty cassettes were swabbed in total specifically for general levels of bacterial contamination, also for the presence or absence of methicillin-resistant Staphylococcus aureus (MRSA). A mapping exercise was completed following the location of an X-ray cassette typically used in mobile radiography. The exercise noted the level of direct contact with patient's skin and other possible routes of infection. Results: The results demonstrated that there were large levels of growth of samples taken from cassettes and developed in the Microbiology Department. Coagulase-negative Staphylococcus, Micrococci, Diptheroids and species of Bacillus were all identified. The mapping exercise in which the journey of a 35/43 cm cassette used for mobile radiography was tracked found that contact with patient's skin and potential pathogens or routes of cross infection was a common occurrence whilst undertaking mobile radiography. Conclusion: The research has identified the presence of bacterial contamination on cassettes. The research established that X-ray cassettes/imaging plates are often exposed to pathogens and possible routes of cross infection; also that patient's skin often comes directly in contact with the X-ray cassette/imaging plate. The research also shows that as cassettes/imaging plates are a potential source of cross infection, the Diagnostic Imaging Department may be partly responsible

The stability of cassette walls in compression

Science.gov (United States)

Voutay, Pierre-Arnaud

Much research into the behaviour of cold formed steel columns in the last decade has focused on channel sections undergoing local, distortional and overall buckling. Light gauge steel cassette sections are a particular form of channel section which offers an alternative form of load-bearing wall assembly for use in low-rise steel framed construction. Cassette wall sections possess wide and slender flanges so that, by including intermediate stiffeners in these wide flanges, a significant increase in the ultimate load capacity may be achieved. However, the introduction of intermediate stiffeners also increases the number of buckling modes (stiffener buckling) and, therefore complicates the behaviour and increases the risk of interactive buckling between these modes. The work undertaken in this thesis aims to clarify the behaviour of wide flanges in compression with and without intermediate stiffeners. In this research, the distortional mode of web and narrow flange buckling was inhibited by connecting the narrow flanges of the cassettes together at suitable intervals. "Generalised Beam Theory" (GBT), which allows the individual buckling modes to be considered individually and in predetermined combinations, provides a particularly good tool with which to analyse and understand the buckling behaviour of cassette sections with and without intermediate stiffeners. "Generalised Beam Theory" (GBT) is used throughout this work to determine the elastic buckling stress of the sections studied (simply supported stiffened plates, as well as cassette sections). Since the economic design of cold-formed steel sections requires the consideration of post- buckling behaviour, elastic buckling values are not directly comparable with design code values which are usually based on the concept of effective width. Therefore, finite element analysis with both material and geometric nonlinearity has also been carried out in order to obtain the ultimate strength in the critical mode or mode

The economic potential of a cassette-type-reactor-installed nuclear ice-breaking container ship

International Nuclear Information System (INIS)

Kondo, K.; Takamasa, T.

2000-01-01

The design concept of the cassette-type-reactor MRX (Marine Reactor X), being under development in Japan for the nuclear ice-breaker container ship is described. The MRX reactor is the monoblock water-cooled and moderated reactor with passive cooling system of natural circulation. It is shown that application of the reactor being under consideration gives an opportunity to decrease greatly the difference in prices for similar nuclear and diesel ships. Economic estimations for applicability of the nuclear ice-breaker container ship with the MRX reactor in Arctics for transportation of standard containers TEU from Europe to Far East as compared with transportation of the same containers by diesel ships via Suets Canal are made [ru

The ABCG5 ABCG8 sterol transporter and phytosterols: implications for cardiometabolic disease

Science.gov (United States)

Sabeva, Nadezhda S.; Liu, Jingjing; Graf, Gregory A.

2014-01-01

Purpose of review This review summarizes recent developments in the activity, regulation, and physiology of the ABCG5 ABCG8 (G5G8) transporter and the use of its xenobiotic substrates, phytosterols, as cholesterol lowering agents in the treatment of cardiovascular disease. Recent progress has significant implications for the role of G5G8 and its substrates in complications associated with features of the metabolic syndrome. Recent findings Recent reports expand the clinical presentation of sitosterolemia to include platelet and adrenal dysfunction. The G5G8 sterol transporter is critical to hepatobiliary excretion of cholesterol under nonpathological conditions and has been linked to the cholesterol gallstone susceptibility. Finally, the cardiovascular benefits of cholesterol lowering through the use of phytosterol supplements were offset by vascular dysfunction, suggesting that alternative strategies to reduced cholesterol absorption offer greater benefit. Summary Insulin resistance elevates G5G8 and increases susceptibility to cholesterol gallstones. However, this transporter is critical for the exclusion of phytosterols from the absorptive pathways in the intestine. Challenging the limits of this protective mechanism through phytosterol supplementation diminishes the cardioprotective benefits of cholesterol lowering in mouse models of cardiovascular disease. PMID:19306529

Energy transport, polar amplification, and ITCZ shifts in the GeoMIP G1 ensemble

Directory of Open Access Journals (Sweden)

R. D. Russotto

2018-02-01

Full Text Available The polar amplification of warming and the ability of the Intertropical Convergence Zone (ITCZ to shift to the north or south are two very important problems in climate science. Examining these behaviors in global climate models (GCMs running solar geoengineering experiments is helpful not only for predicting the effects of solar geoengineering but also for understanding how these processes work under increased carbon dioxide (CO2. Both polar amplification and ITCZ shifts are closely related to the meridional transport of moist static energy (MSE by the atmosphere. This study examines changes in MSE transport in 10 fully coupled GCMs in experiment G1 of the Geoengineering Model Intercomparison Project (GeoMIP, in which the solar constant is reduced to compensate for the radiative forcing from abruptly quadrupled CO2 concentrations. In G1, poleward MSE transport decreases relative to preindustrial conditions in all models, in contrast to the Coupled Model Intercomparison Project phase 5 (CMIP5 abrupt4xCO2 experiment, in which poleward MSE transport increases. We show that since poleward energy transport decreases rather than increases, and local feedbacks cannot change the sign of an initial temperature change, the residual polar amplification in the G1 experiment must be due to the net positive forcing in the polar regions and net negative forcing in the tropics, which arise from the different spatial patterns of the simultaneously imposed solar and CO2 forcings. However, the reduction in poleward energy transport likely plays a role in limiting the polar warming in G1. An attribution study with a moist energy balance model shows that cloud feedbacks are the largest source of uncertainty regarding changes in poleward energy transport in midlatitudes in G1, as well as for changes in cross-equatorial energy transport, which are anticorrelated with ITCZ shifts.

Evolutionary relationships of ATP-Binding Cassette (ABC) uptake porters.

Science.gov (United States)

Zheng, Wei Hao; Västermark, Åke; Shlykov, Maksim A; Reddy, Vamsee; Sun, Eric I; Saier, Milton H

2013-05-06

The ATP-Binding Cassette (ABC) functional superfamily includes integral transmembrane exporters that have evolved three times independently, forming three families termed ABC1, ABC2 and ABC3, upon which monophyletic ATPases have been superimposed for energy-coupling purposes [e.g., J Membr Biol 231(1):1-10, 2009]. The goal of the work reported in this communication was to understand how the integral membrane constituents of ABC uptake transporters with different numbers of predicted or established transmembrane segments (TMSs) evolved. In a few cases, high resolution 3-dimensional structures were available, and in these cases, their structures plus primary sequence analyses allowed us to predict evolutionary pathways of origin. All of the 35 currently recognized families of ABC uptake proteins except for one (family 21) were shown to be homologous using quantitative statistical methods. These methods involved using established programs that compare native protein sequences with each other, after having compared each sequence with thousands of its own shuffled sequences, to gain evidence for homology. Topological analyses suggested that these porters contain numbers of TMSs ranging from four or five to twenty. Intragenic duplication events occurred multiple times during the evolution of these porters. They originated from a simple primordial protein containing 3 TMSs which duplicated to 6 TMSs, and then produced porters of the various topologies via insertions, deletions and further duplications. Except for family 21 which proved to be related to ABC1 exporters, they are all related to members of the previously identified ABC2 exporter family. Duplications that occurred in addition to the primordial 3 → 6 duplication included 5 → 10, 6 → 12 and 10 → 20 TMSs. In one case, protein topologies were uncertain as different programs gave discrepant predictions. It could not be concluded with certainty whether a 4 TMS ancestral protein or a 5 TMS ancestral protein

Seminal Plasma Characteristics and Expression of ATP-binding Cassette Transporter A1 (ABCA1) in Canine Spermatozoa from Ejaculates with Good and Bad Freezability.

Science.gov (United States)

Schäfer-Somi, S; Palme, N

2016-04-01

The composition of seminal plasma and the localization of the ATP-binding cassette transporter A1 (ABCA1) in spermatozoa from good and bad freezers were compared to frozen-thawed spermatozoa from the same dog. Ejaculates were obtained from 31 stud dogs, and the sperm-rich fraction (SRF) was kept for analysis. One aliquot was used for the analysis of concentration, progressive motility (P; CASA), viability (V; CASA) and leucocyte count, and the analysis was performed by flow cytometry (FITC-PNA/PI), SCSA and HOST. In seminal plasma, concentration of albumin, cholesterol, calcium, inorganic phosphate, sodium, potassium, zinc and copper was measured. Semen smears were prepared and evaluated for the expression of ABCA1. The remainder of each ejaculate was frozen. After thawing, the quality assessment was repeated and further smears were prepared. According to post-thaw semen quality, dogs were assigned to good freezers (n = 20) or bad freezers (n = 11), the latter were defined as 40% morphologically abnormal sperm and/or < 50% viability. Bad freezers were older than good freezers (5.3 vs 3.4 years, p < 0.05). In bad freezers, the percentage of sperm with ABCA1 signal in the acrosome was lower (26.3% vs 35.7%, p < 0.01) and the percentage of sperm with complete loss of ABCA1 signal higher (46.7% vs 30%, p < 0.01); the percentage of dead spermatozoa was higher (36.1% vs 25.5%, p < 0.05), and the concentration of cholesterol and sodium in seminal plasma was lower than in good freezers (p < 0.05). We conclude that in thawed bad freezer sperm, an increase in acrosome damages coincided with an increased loss of cholesterol transporters and cell death, and a lower cholesterol concentration in seminal plasma. Follow-up studies revealed whether a relation exists between these findings. © 2016 Blackwell Verlag GmbH.

Development of a full-size divertor cassette prototype for ITER

International Nuclear Information System (INIS)

Ulrickson, M.A.; Vieider, G.; Pacher, H.D.

1996-01-01

Production of a full-size divertor cassette involves eight major components. All of the components are mounted on the cassette body. Inner divertor channel components for the vertical target design are being provided by the Japan Home Team. Outer divertor channel components for the vertical target design are being provided by the European and United States Home Teams. Gas box liners are being provided by the Russian Home Team. The full-size components manufactured by the four parties will be shipped to the US Home Team for assembly into a full size divertor cassette. The techniques for assembly and maintenance of the cassette will be demonstrated during this process. The assembled cassette will be tested for proper flow distribution and proof of the filling and draining procedures. The testing will include vacuum leak tightness at full temperature and pressure, cyclic heating to 150 degrees C, verification of dimensional accuracy of the assembled components, and application of thermal gradients to measure dimensional stability. The development of the divertor for the International Thermonuclear Experimental Reactor (ITER) depends on successful R ampersand D efforts on materials, joining, and plasma materials interactions. Results of the development program are presented. The scale-up of the processes developed in the basic research and development tasks is accomplished by producing and high-heat-flux testing medium and full-scale mock- ups. The design of the mock-ups is discussed

Heterologous expression of the yeast Tpo1p or Pdr5p membrane transporters in Arabidopsis confers plant xenobiotic tolerance.

Science.gov (United States)

Remy, Estelle; Niño-González, María; Godinho, Cláudia P; Cabrito, Tânia R; Teixeira, Miguel C; Sá-Correia, Isabel; Duque, Paula

2017-07-03

Soil contamination is a major hindrance for plant growth and development. The lack of effective strategies to remove chemicals released into the environment has raised the need to increase plant resilience to soil pollutants. Here, we investigated the ability of two Saccharomyces cerevisiae plasma-membrane transporters, the Major Facilitator Superfamily (MFS) member Tpo1p and the ATP-Binding Cassette (ABC) protein Pdr5p, to confer Multiple Drug Resistance (MDR) in Arabidopsis thaliana. Transgenic plants expressing either of the yeast transporters were undistinguishable from the wild type under control conditions, but displayed tolerance when challenged with the herbicides 2,4-D and barban. Plants expressing ScTPO1 were also more resistant to the herbicides alachlor and metolachlor as well as to the fungicide mancozeb and the Co 2+ , Cu 2+ , Ni 2+ , Al 3+ and Cd 2+ cations, while ScPDR5-expressing plants exhibited tolerance to cycloheximide. Yeast mutants lacking Tpo1p or Pdr5p showed increased sensitivity to most of the agents tested in plants. Our results demonstrate that the S. cerevisiae Tpo1p and Pdr5p transporters are able to mediate resistance to a broad range of compounds of agricultural interest in yeast as well as in Arabidopsis, underscoring their potential in future biotechnological applications.

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo.

Science.gov (United States)

Murray, Jayne; Valli, Emanuele; Yu, Denise M T; Truong, Alan M; Gifford, Andrew J; Eden, Georgina L; Gamble, Laura D; Hanssen, Kimberley M; Flemming, Claudia L; Tan, Alvin; Tivnan, Amanda; Allan, Sophie; Saletta, Federica; Cheung, Leanna; Ruhle, Michelle; Schuetz, John D; Henderson, Michelle J; Byrne, Jennifer A; Norris, Murray D; Haber, Michelle; Fletcher, Jamie I

2017-09-01

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

MicroRNA-20a/b regulates cholesterol efflux through post-transcriptional repression of ATP-binding cassette transporter A1.

Science.gov (United States)

Liang, Bin; Wang, Xin; Song, Xiaosu; Bai, Rui; Yang, Huiyu; Yang, Zhiming; Xiao, Chuanshi; Bian, Yunfei

2017-09-01

ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and exhibits anti-atherosclerosis effects. Some microRNAs (miRs) regulate ABCA1 expression, and recent studies have shown that miR-20a/b might play a critical role in atherosclerotic diseases. Here, we attempted to clarify the potential contribution of miR-20a/b in post-transcriptional regulation of ABCA1, cholesterol efflux, and atherosclerosis. We performed bioinformatics analysis and found that miR-20a/b was highly conserved and directly bound to ABCA1 mRNA with low binding free energy. Luciferase-reporter assay also confirmed that miR-20a/b significantly reduced luciferase activity associated with the ABCA1 3' untranslated region reporter construct. Additionally, miR-20a/b decreased ABCA1 expression, which, in turn, decreased cholesterol efflux and increased cholesterol content in THP-1 and RAW 264.7 macrophage-derived foam cells. In contrast, miR-20a/b inhibitors increased ABCA1 expression and cholesterol efflux, decreased cholesterol content, and inhibited foam-cell formation. Consistent with our in vitro results, miR-20a/b-treated ApoE -/- mice showed decreased ABCA1expression in the liver and reductions of reverse cholesterol transport in vivo. Furthermore, miR-20a/b regulated the formation of nascent high-density lipoprotein and promoted atherosclerotic development, whereas miR-20a/b knockdown attenuated atherosclerotic formation. miR-20 is a new miRNA capable of targeting ABCA1 and regulating ABCA1 expression. Therefore, miR-20 inhibition constitutes a new strategy for ABCA1-based treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Structural elucidation of transmembrane domain zero (TMD0) of EcdL: A multidrug resistance-associated protein (MRP) family of ATP-binding cassette transporter protein revealed by atomistic simulation.

Science.gov (United States)

Bera, Krishnendu; Rani, Priyanka; Kishor, Gaurav; Agarwal, Shikha; Kumar, Antresh; Singh, Durg Vijay

2017-09-20

ATP-Binding cassette (ABC) transporters play an extensive role in the translocation of diverse sets of biologically important molecules across membrane. EchnocandinB (antifungal) and EcdL protein of Aspergillus rugulosus are encoded by the same cluster of genes. Co-expression of EcdL and echinocandinB reflects tightly linked biological functions. EcdL belongs to Multidrug Resistance associated Protein (MRP) subfamily of ABC transporters with an extra transmembrane domain zero (TMD0). Complete structure of MRP subfamily comprising of TMD0 domain, at atomic resolution is not known. We hypothesized that the transportation of echonocandinB is mediated via EcdL protein. Henceforth, it is pertinent to know the topological arrangement of TMD0, with other domains of protein and its possible role in transportation of echinocandinB. Absence of effective template for TMD0 domain lead us to model by I-TASSER, further structure has been refined by multiple template modelling using homologous templates of remaining domains (TMD1, NBD1, TMD2, NBD2). The modelled structure has been validated for packing, folding and stereochemical properties. MD simulation for 0.1 μs has been carried out in the biphasic environment for refinement of modelled protein. Non-redundant structures have been excavated by clustering of MD trajectory. The structural alignment of modelled structure has shown Z-score -37.9; 31.6, 31.5 with RMSD; 2.4, 4.2, 4.8 with ABC transporters; PDB ID 4F4C, 4M1 M, 4M2T, respectively, reflecting the correctness of structure. EchinocandinB has been docked to the modelled as well as to the clustered structures, which reveals interaction of echinocandinB with TMD0 and other TM helices in the translocation path build of TMDs.

Disinfection efficacy of an ultraviolet light on film cassettes for preventive of the nosocomial infection

International Nuclear Information System (INIS)

Kweon, Dae Cheol; Jeon, Yong Woong; Cho, Am

2001-01-01

The bacterial infection on film cassette contact surface was examined at the diagnostic radiology department of the S. hospital. The objective of this study was to assess the contamination level on film cassette contact surface as a predictor of patient prevention from nosocomial infection and for improvement of the hospital environment. The laboratory result was identified non-pathologic bacterial in the five different cassette size of the contact surface. Film cassettes were exposed to ultraviolet light for 1, 2 and 3 minutes. Ultraviolet light disinfection is proven suitable for bacterial. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. In addition education of nosocomial infection for radiographers will be required. In conclusion, ultraviolet is considered effective to irradiate bacterial. Additionally, two minutes are required to sterilize film cassettes

Disinfection efficacy of an ultraviolet light on film cassettes for preventive of the nosocomial infection

Energy Technology Data Exchange (ETDEWEB)

Kweon, Dae Cheol [Seoul National Univ. Hospital, Seoul (Korea, Republic of); Jeon, Yong Woong; Cho, Am [Dongguk Univ., Seoul (Korea, Republic of)

2001-06-01

The bacterial infection on film cassette contact surface was examined at the diagnostic radiology department of the S. hospital. The objective of this study was to assess the contamination level on film cassette contact surface as a predictor of patient prevention from nosocomial infection and for improvement of the hospital environment. The laboratory result was identified non-pathologic bacterial in the five different cassette size of the contact surface. Film cassettes were exposed to ultraviolet light for 1, 2 and 3 minutes. Ultraviolet light disinfection is proven suitable for bacterial. The study concludes that presence of a bacterial infection will prevent a using antiseptic technique on film cassette contact surface. In addition education of nosocomial infection for radiographers will be required. In conclusion, ultraviolet is considered effective to irradiate bacterial. Additionally, two minutes are required to sterilize film cassettes.

Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice

NARCIS (Netherlands)

Plosch, Torsten; van der Veen, Jelske N.; Havinga, Rick; Huijkman, Nicolette C. A.; Bloks, Vincent W.; Kuipers, Folkert

The ATP-binding cassette (ABC) half-transporters ABCG5 and ABCG8 heterodimerize into a functional complex that mediates the secretion of plant sterols and cholesterol by hepatocytes into bile and their apical efflux from enterocytes. We addressed the putative rate-controlling role of Abcg5/Abcg8 in

Conservation of gene cassettes among diverse viruses of the human gut.

Directory of Open Access Journals (Sweden)

Samuel Minot

Full Text Available Viruses are a crucial component of the human microbiome, but large population sizes, high sequence diversity, and high frequencies of novel genes have hindered genomic analysis by high-throughput sequencing. Here we investigate approaches to metagenomic assembly to probe genome structure in a sample of 5.6 Gb of gut viral DNA sequence from six individuals. Tests showed that a new pipeline based on DeBruijn graph assembly yielded longer contigs that were able to recruit more reads than the equivalent non-optimized, single-pass approach. To characterize gene content, the database of viral RefSeq proteins was compared to the assembled viral contigs, generating a bipartite graph with functional cassettes linking together viral contigs, which revealed a high degree of connectivity between diverse genomes involving multiple genes of the same functional class. In a second step, open reading frames were grouped by their co-occurrence on contigs in a database-independent manner, revealing conserved cassettes of co-oriented ORFs. These methods reveal that free-living bacteriophages, while usually dissimilar at the nucleotide level, often have significant similarity at the level of encoded amino acid motifs, gene order, and gene orientation. These findings thus connect contemporary metagenomic analysis with classical studies of bacteriophage genomic cassettes. Software is available at https://sourceforge.net/projects/optitdba/.

Patterns of Availability and Use of Audiotape Cassettes in Special Libraries. Ph.D. Thesis

Science.gov (United States)

Hughes, J. M., II

1975-01-01

The availability and use of audiotape cassettes is studied in terms of user requirements. The following factors were examined: how special libraries utilize audiotape cassettes; who the users of the medium are; how the libraries acquire and maintain their collection; and opinions of librarians as to the value of the audiotape cassette as a medium for dissemination of information.

Radiation exposure reduction by use of Kevlar cassettes in the neonatal nursery

International Nuclear Information System (INIS)

Herman, M.W.; Mak, H.K.; Lachman, R.S.

1987-01-01

A study was performed to determine whether the use of Kevlar cassettes in the neonatal intensive care nursery would reduce radiation exposure to patients. The radiation dose to the neonates was measured by using thermoluminescent dosimeters. In addition, the attenuation of the Kevlar cassettes and the sensitivity of the film-screen combination were compared with the previously used system. The greatest radiation reduction using a mobile X-ray unit was 27%; based on sensitivity measurements, the theoretical reduction averaged 38%. The reduction in radiation exposure resulted from reduced attenuation by the Kevlar cassette

Fuel cell cassette with compliant seal

Science.gov (United States)

Karl, Haltiner, Jr. J.; Anthony, Derose J.; Klotzbach, Darasack C.; Schneider, Jonathan R.

2017-11-07

A fuel cell cassette for forming a fuel cell stack along a fuel cell axis includes a cell retainer, a plate positioned axially to the cell retainer and defining a space axially with the cell retainer, and a fuel cell having an anode layer and a cathode layer separated by an electrolyte layer. The outer perimeter of the fuel cell is positioned in the space between the plate and the cell retainer, thereby retaining the fuel cell and defining a cavity between the cell retainer, the fuel cell, and the plate. The fuel cell cassette also includes a seal disposed within the cavity for sealing the edge of the fuel cell. The seal is compliant at operational temperatures of the fuel cell, thereby allowing lateral expansion and contraction of the fuel cell within the cavity while maintaining sealing at the edge of the fuel cell.

Internal Gene Cassette from a Genotype S H9N2 Avian Influenza Virus Attenuates the Pathogenicity of H5 Viruses in Chickens and Mice

Directory of Open Access Journals (Sweden)

Xiaoli Hao

2017-10-01

Full Text Available H9N2 avian influenza virus (AIV of genotype S frequently donate internal genes to facilitate the generation of novel reassortants such as H7N9, H10N8, H5N2 and H5N6 AIVs, posing an enormous threat to both human health and poultry industry. However, the pathogenicity and transmission of reassortant H5 viruses with internal gene cassette of genotype S H9N2-origin in chickens and mice remain unknown. In this study, four H5 reassortants carrying the HA and NA genes from different clades of H5 viruses and the remaining internal genes from an H9N2 virus of the predominant genotype S were generated by reverse genetics. We found that all four H5 reassortant viruses showed attenuated virulence in both chickens and mice, thus leading to increased the mean death times compared to the corresponding parental viruses. Consistently, the polymerase activity and replication ability in mammalian and avian cells, and the cytokine responses in the lungs of chickens and mice were also decreased when compared to their respective parental viruses. Moreover, these reassortants transmitted from birds to birds by direct contact but not by an airborne route. Our data indicate that the internal genes as a whole cassette from genotype S H9N2 viruses play important roles in reducing the pathogenicity of the H5 recombinants in chickens and mice, and might contribute to the circulation in avian or mammalian hosts.

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

Science.gov (United States)

Shibui, Tatsuro; Hara, Hiroyoshi

2017-09-01

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.

Phytosterol Feeding Causes Toxicity in ABCG5/G8 Knockout Mice

Science.gov (United States)

McDaniel, Allison L.; Alger, Heather M.; Sawyer, Janet K.; Kelley, Kathryn L.; Kock, Nancy D.; Brown, J. Mark; Temel, Ryan E.; Rudel, Lawrence L.

2014-01-01

Plant sterols, or phytosterols, are very similar in structure to cholesterol and are abundant in typical diets. The reason for poor absorption of plant sterols by the body is still unknown. Mutations in the ABC transporters G5 and G8 are known to cause an accumulation of plant sterols in blood and tissues (sitosterolemia). To determine the significance of phytosterol exclusion from the body, we fed wild-type and ABCG5/G8 knockout mice a diet enriched with plant sterols. The high-phytosterol diet was extremely toxic to the ABCG5/G8 knockout mice but had no adverse effects on wild-type mice. ABCG5/G8 knockout mice died prematurely and developed a phenotype that included high levels of plant sterols in many tissues, liver abnormalities, and severe cardiac lesions. This study is the first to report such toxic effects of phytosterol accumulation in ABCG5/G8 knockout mice. We believe these new data support the conclusion that plant sterols are excluded from the body because they are toxic when present at high levels. PMID:23380580

Cassette blanket and vacuum building: key elements in fusion reactor maintenance

International Nuclear Information System (INIS)

Werner, R.W.

1977-01-01

The integration of two concepts important to fusion power reactors is discussed. The first concept is the vacuum building which improves upon the current fusion reactor designs. The second concept, the use of the cassette blanket within the vacuum building environment, introduces four major improvements in blanket design: cassette blanket module, zoning concept, rectangular blanket concept, and internal tritium recovery

Recombinogenic engineering of conjugative plasmids with fluorescent marker cassettes

DEFF Research Database (Denmark)

Reisner, A.; Molin, Søren; Zechner, E.L.

2002-01-01

An efficient approach for the insertion of fluorescent marker genes with sequence specificity into conjugative plasmids in Escherichia coli is described. For this purpose, homologous recombination of linear double-stranded targeting DNA was mediated by the bacteriophage lambda recombination...... resistance genes and fluorescent markers. The choice of 5' non-homologous extensions in primer pairs used for amplifying the marker cassettes determines the site specificity of the targeting DNA. This methodology is applicable to the modification of all plasmids that replicate in E coli and is not restricted...

Galectin-3 silencing inhibits epirubicin-induced ATP binding cassette transporters and activates the mitochondrial apoptosis pathway via β-catenin/GSK-3β modulation in colorectal carcinoma.

Directory of Open Access Journals (Sweden)

Yung-Kuo Lee

Full Text Available Multidrug resistance (MDR, an unfavorable factor compromising the treatment efficacy of anticancer drugs, involves the upregulation of ATP binding cassette (ABC transporters and induction of galectin-3 signaling. Galectin-3 plays an anti-apoptotic role in many cancer cells and regulates various pathways to activate MDR. Thus, the inhibition of galectin-3 has the potential to enhance the efficacy of the anticancer drug epirubicin. In this study, we examined the effects and mechanisms of silencing galectin-3 via RNA interference (RNAi on the β-catenin/GSK-3β pathway in human colon adenocarcinoma Caco-2 cells. Galectin-3 knockdown increased the intracellular accumulation of epirubicin in Caco-2 cells; suppressed the mRNA expression of galectin-3, β-catenin, cyclin D1, c-myc, P-glycoprotein (P-gp, MDR-associated protein (MRP 1, and MRP2; and downregulated the protein expression of P-gp, cyclin D1, galectin-3, β-catenin, c-Myc, and Bcl-2. Moreover, galectin-3 RNAi treatment significantly increased the mRNA level of GSK-3β, Bax, caspase-3, and caspase-9; remarkably increased the Bax-to-Bcl-2 ratio; and upregulated the GSK-3β and Bax protein expressions. Apoptosis was induced by galectin-3 RNAi and/or epirubicin as demonstrated by chromatin condensation, a higher sub-G1 phase proportion, and increased caspase-3 and caspase-9 activity, indicating an intrinsic/mitochondrial apoptosis pathway. Epirubicin-mediated resistance was effectively inhibited via galectin-3 RNAi treatment. However, these phenomena could be rescued after galectin-3 overexpression. We show for the first time that the silencing of galectin-3 sensitizes MDR cells to epirubicin by inhibiting ABC transporters and activating the mitochondrial pathway of apoptosis through modulation of the β-catenin/GSK-3β pathway in human colon cancer cells.

Association of ATP-Binding Cassette Transporter A1 Gene Polymorphisms in Type 2 Diabetes Mellitus among Malaysians

Directory of Open Access Journals (Sweden)

Polin Haghvirdizadeh

2015-01-01

Full Text Available Background. Type 2 diabetes mellitus (T2DM is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1 gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K, rs1800977 (C69T, and rs9282541 (R230C polymorphisms Malaysian subjects. Methods. A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis. Results. There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TG P<0.05. There was a significant association between HOM of R219K P=0.005, among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219K P=0.003. But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism. Conclusion. R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

What is 5G? Emerging 5G Mobile Services and Network Requirements

OpenAIRE

Heejung Yu; Howon Lee; Hongbeom Jeon

2017-01-01

In this paper, emerging 5G mobile services are investigated and categorized from the perspective of not service providers, but end-users. The development of 5G mobile services is based on an intensive analysis of the global trends in mobile services. Additionally, several indispensable service requirements, essential for realizing service scenarios presented, are described. To illustrate the changes in societies and in daily life in the 5G era, five megatrends, including the explosion of mobi...

5G Spectrum Sharing

OpenAIRE

Nekovee, Maziar; Rudd, Richard

2017-01-01

In this paper an overview is given of the current status of 5G industry standards, spectrum allocation and use cases, followed by initial investigations of new opportunities for spectrum sharing in 5G using cognitive radio techniques, considering both licensed and unlicensed scenarios. A particular attention is given to sharing millimeter-wave frequencies, which are of prominent importance for 5G.

Neratinib Reverses ATP-Binding Cassette B1-Mediated Chemotherapeutic Drug Resistance In Vitro, In Vivo, and Ex Vivo

OpenAIRE

Zhao, Xiao-qin; Xie, Jing-dun; Chen, Xing-gui; Sim, Hong May; Zhang, Xu; Liang, Yong-ju; Singh, Satyakam; Talele, Tanaji T.; Sun, Yueli; Ambudkar, Suresh V.; Chen, Zhe-Sheng; Fu, Li-wu

2012-01-01

Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human epidermal receptor 2, is in phase III clinical trials for patients with human epidermal receptor 2-positive, locally advanced or metastatic breast cancer. The objective of this study was to explore the ability of neratinib to reverse tumor multidrug resistance attributable to overexpression of ATP-binding cassette (ABC) transporters. Our results showed that neratinib remarkably enhanced the sensitivity of ABCB1...

Single liposome analysis of peptide translocation by the ABC transporter TAPL

NARCIS (Netherlands)

Zollmann, Tina; Moiset Coll, Gemma; Tumulka, Franz; Tampé, Robert; Poolman, Bert; Abele, Rupert

2015-01-01

ATP-binding cassette (ABC) transporters use ATP to drive solute transport across biological membranes. Members of this superfamily have crucial roles in cell physiology, and some of the transporters are linked to severe diseases. However, understanding of the transport mechanism, especially of human

Molecular characterization of ABC transporters in marine ciliate, Euplotes crassus: Identification and response to cadmium and benzo[a]pyrene.

Science.gov (United States)

Kim, Hokyun; Yim, Bora; Kim, Jisoo; Kim, Haeyeon; Lee, Young-Mi

2017-11-30

ATP-binding cassette (ABC) transporters participate in transporting various substances, including xenobiotics, in or out of cells. However, their genetic information and function in ciliates remain still unclear. In this study, we sequenced and characterized two ABC transporter genes (EcABCB and EcABCC), and investigated the effect of cadmium (Cd) and benzo[a]pyrene (B[a]P) on their function and gene expression, using efflux assay and real-time reverse transcription-polymerase chain reaction (qRT-PCR), respectively, in the marine ciliate, Euplotes crassus. Sequencing analysis and efflux assay showed that EcABCB and EcABCC are typical ABC transporters, possessing conserved function. Exposure to Cd (≥5mg/L) and B[a]P (≥50.5μg/L) enhanced accumulation of a substrate. A significant increase in the expression of EcABCB and EcABC mRNA was observed at lower concentration in response to Cd and B[a]P. Our findings indicate that Cd and B[a]P could inhibit the efflux function of ABC transporters, leading to cellular toxicity in the ciliate. Copyright © 2017 Elsevier Ltd. All rights reserved.

ATP-binding Cassette (ABC) Transport System Solute-binding Protein-guided Identification of Novel d-Altritol and Galactitol Catabolic Pathways in Agrobacterium tumefaciens C58*

Science.gov (United States)

Wichelecki, Daniel J.; Vetting, Matthew W.; Chou, Liyushang; Al-Obaidi, Nawar; Bouvier, Jason T.; Almo, Steven C.; Gerlt, John A.

2015-01-01

Innovations in the discovery of the functions of uncharacterized proteins/enzymes have become increasingly important as advances in sequencing technology flood protein databases with an exponentially growing number of open reading frames. This study documents one such innovation developed by the Enzyme Function Initiative (EFI; U54GM093342), the use of solute-binding proteins for transport systems to identify novel metabolic pathways. In a previous study, this strategy was applied to the tripartite ATP-independent periplasmic transporters. Here, we apply this strategy to the ATP-binding cassette transporters and report the discovery of novel catabolic pathways for d-altritol and galactitol in Agrobacterium tumefaciens C58. These efforts resulted in the description of three novel enzymatic reactions as follows: 1) oxidation of d-altritol to d-tagatose via a dehydrogenase in Pfam family PF00107, a previously unknown reaction; 2) phosphorylation of d-tagatose to d-tagatose 6-phosphate via a kinase in Pfam family PF00294, a previously orphan EC number; and 3) epimerization of d-tagatose 6-phosphate C-4 to d-fructose 6-phosphate via a member of Pfam family PF08013, another previously unknown reaction. The epimerization reaction catalyzed by a member of PF08013 is especially noteworthy, because the functions of members of PF08013 have been unknown. These discoveries were assisted by the following two synergistic bioinformatics web tools made available by the Enzyme Function Initiative: the EFI-Enzyme Similarity Tool and the EFI-Genome Neighborhood Tool. PMID:26472925

Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.

Science.gov (United States)

Aida, Tomomi; Nakade, Shota; Sakuma, Tetsushi; Izu, Yayoi; Oishi, Ayu; Mochida, Keiji; Ishikubo, Harumi; Usami, Takako; Aizawa, Hidenori; Yamamoto, Takashi; Tanaka, Kohichi

2016-11-28

Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining. Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved convenient one-step knock-in of gene cassettes and floxed allele both in human cells and mouse zygotes. Our results provide a technical platform for high-throughput knock-in.

Blanket maintenance by remote means using the cassette blanket approach

International Nuclear Information System (INIS)

Werner, R.W.

1978-01-01

Induced radioactivity in the blanket and other parts of a fusion reactor close to the plasma zone will dictate remote assembly, disassembly, and maintenance procedures. Time will be of the essence in these procedures. They must be practicable and certain. This paper discusses the reduction of a complicated Tokamak reactor to a simpler assembly via the use of a vacuum building in which to house the reactor and the introduction in this new model of cassette blanket modules. The cassettes significantly simplify remote handling

A Survey of the ATP-Binding Cassette (ABC) Gene Superfamily in the Salmon Louse (Lepeophtheirus salmonis).

Science.gov (United States)

Carmona-Antoñanzas, Greta; Carmichael, Stephen N; Heumann, Jan; Taggart, John B; Gharbi, Karim; Bron, James E; Bekaert, Michaël; Sturm, Armin

2015-01-01

Salmon lice, Lepeophtheirus salmonis (Krøyer, 1837), are fish ectoparasites causing significant economic damage in the mariculture of Atlantic salmon, Salmo salar Linnaeus, 1758. The control of L. salmonis at fish farms relies to a large extent on treatment with anti-parasitic drugs. A problem related to chemical control is the potential for development of resistance, which in L. salmonis is documented for a number of drug classes including organophosphates, pyrethroids and avermectins. The ATP-binding cassette (ABC) gene superfamily is found in all biota and includes a range of drug efflux transporters that can confer drug resistance to cancers and pathogens. Furthermore, some ABC transporters are recognised to be involved in conferral of insecticide resistance. While a number of studies have investigated ABC transporters in L. salmonis, no systematic analysis of the ABC gene family exists for this species. This study presents a genome-wide survey of ABC genes in L. salmonis for which, ABC superfamily members were identified through homology searching of the L. salmonis genome. In addition, ABC proteins were identified in a reference transcriptome of the parasite generated by high-throughput RNA sequencing (RNA-seq) of a multi-stage RNA library. Searches of both genome and transcriptome allowed the identification of a total of 33 genes / transcripts coding for ABC proteins, of which 3 were represented only in the genome and 4 only in the transcriptome. Eighteen sequences were assigned to ABC subfamilies known to contain drug transporters, i.e. subfamilies B (4 sequences), C (11) and G (2). The results suggest that the ABC gene family of L. salmonis possesses fewer members than recorded for other arthropods. The present survey of the L. salmonis ABC gene superfamily will provide the basis for further research into potential roles of ABC transporters in the toxicity of salmon delousing agents and as potential mechanisms of drug resistance.

Genome-wide analysis of the ATP-binding cassette (ABC) transporter gene family in sea lamprey and Japanese lamprey.

Science.gov (United States)

Ren, Jianfeng; Chung-Davidson, Yu-Wen; Yeh, Chu-Yin; Scott, Camille; Brown, Titus; Li, Weiming

2015-06-06

Lampreys are extant representatives of the jawless vertebrate lineage that diverged from jawed vertebrates around 500 million years ago. Lamprey genomes contain information crucial for understanding the evolution of gene families in vertebrates. The ATP-binding cassette (ABC) gene family is found from prokaryotes to eukaryotes. The recent availability of two lamprey draft genomes from sea lamprey Petromyzon marinus and Japanese lamprey Lethenteron japonicum presents an opportunity to infer early evolutionary events of ABC genes in vertebrates. We conducted a genome-wide survey of the ABC gene family in two lamprey draft genomes. A total of 37 ABC transporters were identified and classified into seven subfamilies; namely seven ABCA genes, 10 ABCB genes, 10 ABCC genes, three ABCD genes, one ABCE gene, three ABCF genes, and three ABCG genes. The ABCA subfamily has expanded from three genes in sea squirts, seven and nine in lampreys and zebrafish, to 13 and 16 in human and mouse. Conversely, the multiple copies of ABCB1-, ABCG1-, and ABCG2-like genes found in sea squirts have contracted in the other species examined. ABCB2 and ABCB3 seem to be new additions in gnathostomes (not in sea squirts or lampreys), which coincides with the emergence of the gnathostome-specific adaptive immune system. All the genes in the ABCD, ABCE and ABCF subfamilies were conserved and had undergone limited duplication and loss events. In the sea lamprey transcriptomes, the ABCE and ABCF gene subfamilies were ubiquitously and highly expressed in all tissues while the members in other gene subfamilies were differentially expressed. Thirteen more lamprey ABC transporter genes were identified in this study compared with a previous study. By concatenating the same gene sequences from the two lampreys, more full length sequences were obtained, which significantly improved both the assignment of gene names and the phylogenetic trees compared with a previous analysis using partial sequences. The ABC

A fluorescent cassette-based strategy for engineering multiple domain fusion proteins

Directory of Open Access Journals (Sweden)

Khorchid Ahmad

2003-07-01

Full Text Available Abstract Background The engineering of fusion proteins has become increasingly important and most recently has formed the basis of many biosensors, protein purification systems, and classes of new drugs. Currently, most fusion proteins consist of three or fewer domains, however, more sophisticated designs could easily involve three or more domains. Using traditional subcloning strategies, this requires micromanagement of restriction enzymes sites that results in complex workaround solutions, if any at all. Results Therefore, to aid in the efficient construction of fusion proteins involving multiple domains, we have created a new expression vector that allows us to rapidly generate a library of cassettes. Cassettes have a standard vector structure based on four specific restriction endonuclease sites and using a subtle property of blunt or compatible cohesive end restriction enzymes, they can be fused in any order and number of times. Furthermore, the insertion of PCR products into our expression vector or the recombination of cassettes can be dramatically simplified by screening for the presence or absence of fluorescence. Conclusions Finally, the utility of this new strategy was demonstrated by the creation of basic cassettes for protein targeting to subcellular organelles and for protein purification using multiple affinity tags.

49 CFR Appendix A to Part 533 - Example of Calculating Compliance Under § 533.5 Paragraph (g)

Science.gov (United States)

2010-10-01

... 49 Transportation 6 2010-10-01 2010-10-01 false Example of Calculating Compliance Under § 533.5 Paragraph (g) A Appendix A to Part 533 Transportation Other Regulations Relating to Transportation... ECONOMY STANDARDS Pt. 533, App. A Appendix A to Part 533—Example of Calculating Compliance Under § 533.5...

Lipid dependence of ABC transporter localization and function

NARCIS (Netherlands)

Klappe, Karin; Hummel, Ina; Hoekstra, Dick; Kok, Jan Willem

2009-01-01

Lipid rafts have been implicated in many cellular functions, including protein and lipid transport and signal transduction. ATP-binding cassette (ABC) transporters have also been localized in these membrane domains. In this review the evidence for this specific localization will be evaluated and

Analysis of the structural and functional roles of coupling helices in the ATP-binding cassette transporter MsbA through enzyme assays and molecular dynamics simulations.

Science.gov (United States)

Furuta, Tadaomi; Yamaguchi, Tomohiro; Kato, Hiroaki; Sakurai, Minoru

2014-07-08

ATP-binding cassette (ABC) transporters are constructed from some common structural units: the highly conserved nucleotide-binding domains (NBDs), which work as a nucleotide-dependent engine for driving substrate transport, the diverse transmembrane domains (TMDs), which create the translocation pathway, and the coupling helices (CHs), which are located at the NBD-TMD interface. Although the CHs are believed to be essential for NBD-TMD communication, their roles remain unclear. In this study, we performed enzyme assays and molecular dynamics (MD) simulations of the ABC transporter MsbA and two MsbA mutants in which the amino acid residues of one of the CHs were mutated to alanines: (i) wild type (Wt), (ii) CH1 mutant (Mt1), and (iii) CH2 mutant (Mt2). The experiments show that the CH2 mutation decreases the ATPase activity (kcat) compared with that of the Wt (a decrease of 32%), and a nearly equal degree of decrease in the ATP binding affinity (Km) was observed for both Mt1 and Mt2. The MD simulations successfully accounted for several structural and dynamical origins for these experimental observations. In addition, on the basis of collective motion and morphing analyses, we propose that the reverse-rotational motions and noddinglike motions between the NBDs and TMDs are indispensable for the conformational transition between the inward- and outward-facing conformations. In particular, CH2 is significantly important for the occurrence of the noddinglike motion. These findings provide important insights into the structure-function relationship of ABC transporters.

Genome-wide identification of ATP-binding cassette (ABC) transporters and their roles in response to polycyclic aromatic hydrocarbons (PAHs) in the copepod Paracyclopina nana.

Science.gov (United States)

Jeong, Chang-Bum; Kim, Duck-Hyun; Kang, Hye-Min; Lee, Young Hwan; Kim, Hui-Su; Kim, Il-Chan; Lee, Jae-Seong

2017-02-01

The ATP-binding cassette (ABC) protein superfamily is one of the largest gene families and is highly conserved in all domains. The ABC proteins play roles in several biological processes, including multi-xenobiotic resistance (MXR), by functioning as transporters in the cellular membrane. They also mediate the cellular efflux of a wide range of substrates against concentration gradients. In this study, 37 ABC genes belonging to eight distinct subfamilies were identified in the marine copepod Paracyclopina nana and annotated based on a phylogenetic analysis. Also, the functions of P-glycoproteins (P-gp) and multidrug resistance-associated proteins (MRPs), conferring MXR, were verified using fluorescent substrates and specific inhibitors. The activities of MXR-mediated ABC proteins and their transcriptional level were examined in response to polyaromatic hydrocarbons (PAHs), main components of the water-accommodated fraction. This study increases the understanding of the protective role of MXR in response to PAHs over the comparative evolution of ABC gene families. Copyright © 2016 Elsevier B.V. All rights reserved.

Ratiometric Matryoshka biosensors from a nested cassette of green- and orange-emitting fluorescent proteins.

Science.gov (United States)

Ast, Cindy; Foret, Jessica; Oltrogge, Luke M; De Michele, Roberto; Kleist, Thomas J; Ho, Cheng-Hsun; Frommer, Wolf B

2017-09-05

Sensitivity, dynamic and detection range as well as exclusion of expression and instrumental artifacts are critical for the quantitation of data obtained with fluorescent protein (FP)-based biosensors in vivo. Current biosensors designs are, in general, unable to simultaneously meet all these criteria. Here, we describe a generalizable platform to create dual-FP biosensors with large dynamic ranges by employing a single FP-cassette, named GO-(Green-Orange) Matryoshka. The cassette nests a stable reference FP (large Stokes shift LSSmOrange) within a reporter FP (circularly permuted green FP). GO- Matryoshka yields green and orange fluorescence upon blue excitation. As proof of concept, we converted existing, single-emission biosensors into a series of ratiometric calcium sensors (MatryoshCaMP6s) and ammonium transport activity sensors (AmTryoshka1;3). We additionally identified the internal acid-base equilibrium as a key determinant of the GCaMP dynamic range. Matryoshka technology promises flexibility in the design of a wide spectrum of ratiometric biosensors and expanded in vivo applications.Single fluorescent protein biosensors are susceptible to expression and instrumental artifacts. Here Ast et al. describe a dual fluorescent protein design whereby a reference fluorescent protein is nested within a reporter fluorescent protein to control for such artifacts while preserving sensitivity and dynamic range.

4 CFR 5.5 - Travel, transportation, and subsistence.

Science.gov (United States)

2010-01-01

... 4 Accounts 1 2010-01-01 2010-01-01 false Travel, transportation, and subsistence. 5.5 Section 5.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM COMPENSATION § 5.5 Travel, transportation, and subsistence. The provisions of chapter 57 of title 5, U.S. Code and the implementing regulations for the...

Genome-wide analysis of ATP-binding cassette (ABC) transporters in the sweetpotato whitefly, Bemisia tabaci.

Science.gov (United States)

Tian, Lixia; Song, Tianxue; He, Rongjun; Zeng, Yang; Xie, Wen; Wu, Qingjun; Wang, Shaoli; Zhou, Xuguo; Zhang, Youjun

2017-04-26

ABC transporter superfamily is one of the largest and ubiquitous groups of proteins. Because of their role in detoxification, insect ABC transporters have gained more attention in recent years. In this study, we annotated ABC transporters from a newly sequenced sweetpotato whitefly genome. Bemisia tabaci Q biotype is an emerging global invasive species that has caused extensive damages to field crops as well as ornamental plants. A total of 55 ABC transporters containing all eight described subfamilies (A to H) were identified in the B. tabaci Q genome, including 8 ABCAs, 3 ABCBs, 6 ABCCs, 2 ABCDs, 1 ABCE, 3 ABCFs, 23 ABCGs and 9 ABCHs. In comparison to other species, subfamilies G and H in both phloem- and blood-sucking arthropods are expanded. The temporal expression profiles of these 55 ABC transporters throughout B. tabaci developmental stages and their responses to imidacloprid, a neonicotinoid insecticide, were investigated using RNA-seq analysis. Furthermore, the mRNA expression of 24 ABC transporters (44% of the total) representing all eight subfamilies was confirmed by the quantitative real-time PCR (RT-qPCR). Furthermore, mRNA expression levels estimated by RT-qPCR and RNA-seq analyses were significantly correlated (r = 0.684, p analysis of the entire repertoire of ABC transporters in B. tabaci. The identification of these ABC transporters, their temporal expression profiles during B. tabaci development, and their response to a neonicotinoid insecticide lay the foundation for functional genomic understanding of their contribution to the invasiveness of B. tabaci.

Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

Science.gov (United States)

Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

2017-06-25

Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of pharmacokinetics of newly discovered aromatase inhibitors by a cassette microdosing approach in healthy Japanese subjects.

Science.gov (United States)

Kusuhara, Hiroyuki; Takashima, Tadayuki; Fujii, Hisako; Takashima, Tsutomu; Tanaka, Masaaki; Ishii, Akira; Tazawa, Shusaku; Takahashi, Kazuhiro; Takahashi, Kayo; Tokai, Hidekichi; Yano, Tsuneo; Kataoka, Makoto; Inano, Akihiro; Yoshida, Suguru; Hosoya, Takamitsu; Sugiyama, Yuichi; Yamashita, Shinji; Hojo, Taisuke; Watanabe, Yasuyoshi

2017-12-01

The aim of the present study is to investigate the pharmacokinetics of our newly developed aromatase inhibitors (cetrozole and TMD-322) in healthy subjects by a cassette microdose strategy. A cocktail of cetrozole and TMD-322 was administered intravenously or orally (1.98 μg for each drug) to six healthy volunteers in a crossover fashion. Anastrozole (1.98 μg) was also included in the oral cocktail. Total body clearance and bioavailability were 12.1 ± 7.1 mL/min/kg and 34.9 ± 32.3% for cetrozole, and 16.8 ± 3.5 mL/min/kg and 18.4 ± 12.2% for TMD-322, respectively. The area under the plasma concentration-time curves of cetrozole and TMD-322 after oral administration was markedly lower than that of anastrozole because of their high hepatic clearance. Two subjects out of six exhibited 4- and 17-fold larger exposure of cetrozole than the others following intravenous and oral administration, respectively. Such variation was not observed for TMD-322 and anastrozole. Extensive metabolism of cetrozole and TMD-322 was observed in the CYP2C19 expression system among the test CYP isoforms (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). We report the first clinical investigation of our aromatase inhibitors by a cassette microdose strategy in healthy Japanese subjects. This strategy offers an optional approach for candidate selection as a phase zero study in drug development. Copyright © 2017. Published by Elsevier Ltd.

Characteriz ation of integrons and associated gene cassettes in Acinetobacter baumannii strains isolated from intensive care unit in Tehran, Iran

Directory of Open Access Journals (Sweden)

Hossein Goudarzi

2016-09-01

Full Text Available Objective: To determine the antimicrobial susceptibility patterns, the frequency of integrons and associated gene cassettes in Acinetobacter baumannii (A. baumannii strains isolated from selected hospital intensive care units. Methods: During a ten-month period, 120 A. baumannii isolates were studied. The resistance rates to different classes of antimicrobial agents were determined. PCR was used to detect different types of integrons and associated gene cassettes. Results: The resistance rates to the majority of antibiotics tested were found to be between 39.3% and 99.1%. No isolate was observed to be resistant to colistin and polymyxin B. The rate of extensive drug-resistance among these clinical isolates was 62.5%. The prevalence of class 1 and 2 integrons was found to be 74.1% and 12.5%, respectively. Seven different gene cassettes (ampC, aacA4-catB8, ISAba1-blaOXA-23-GES-14, aadA2-cm1A6-GES-14-qacF, VIM-25-GES-24-qacF, dfrA5-ISAba1-blaOXA-51-blaOXA-40 and aadA2-GES-11-IMP-1 were observed in Class 1 integron-carrying strains. Three gene cassettes (IMP-4, VIM-2-VEB-aacA4 and dfrA2-sat-2-aadA4 were detected in class 2 integron-bearing A. baumannii strains. Conclusions: A high prevalence of integron was described among multidrug resistant A. baumannii in the hospital. The findings highlighted the need for continuous surveillance in order to prevent dissemination of multidrug resistance among A. baumannii strains in Iran.

5G in Finland

OpenAIRE

Leinonen, Jami

2017-01-01

The thesis describes about 5G and studies what new it brings and how it is better than the previous telecommunication generation. Firstly, explains when 5G research began presents main user cases and how the new services, xMMB, mMTC and uMTC, will respond to these cases. After that, new concepts such as DyRAN, LSCP, Spectrum toolbox, D2D communication, mmW/cmW and massive MIMO systems are addressed. These all are 5G specific, and they all will provide more flexible systems to bring mobile com...

Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays.

NARCIS (Netherlands)

Krumpochova, P; Sapthu, S.; Brouwers, J.F.H.M.; de Haas, M.; de Vos, R.; Borst, P.; van de Wetering, K.

2013-01-01

ABSTRACT The ATP-binding cassette (ABC) genes encode the largest family of transmembrane proteins. ABC transporters translocate a wide variety of substrates across membranes, but their physiological function is often incompletely understood. We describe a new method to study the substrate spectrum

Energy Coupling Factor-Type ABC Transporters for Vitamin Uptake in Prokaryotes

NARCIS (Netherlands)

Erkens, Guus B.; Dosz-Majsnerowska, Maria; ter Beek, Josy; Slotboom, Dirk Jan

2012-01-01

Energy coupling factor (ECF) transporters are a subgroup of ATP-binding cassette (ABC) transporters involved in the uptake of vitamins and micronutrients in prokaryotes. In contrast to classical ABC importers, ECF transporters do not make use of water-soluble substrate binding proteins or domains

Effect of praziquantel on the differential expression of mouse hepatic genes and parasite ATP binding cassette transporter gene family members during Schistosoma mansoni infection.

Directory of Open Access Journals (Sweden)

Melissa C Sanchez

2017-06-01

Full Text Available Schistosomiasis is a chronic parasitic disease caused by sexually dimorphic blood flukes of the genus Schistosoma. Praziquantel (PZQ is the only drug widely available to treat the disease but does not kill juvenile parasites. Here we report the use of next generation sequencing to study the transcriptional effect of PZQ on murine hepatic inflammatory, immune and fibrotic responses to Schistosoma mansoni worms and eggs. An initial T helper cell 1 (Th1 response is induced against schistosomes in mice treated with drug vehicle (Vh around the time egg laying begins, followed by a T helper cell 2 (Th2 response and the induction of genes whose action leads to granuloma formation and fibrosis. When PZQ is administered at this time, there is a significant reduction in egg burden yet the hepatic Th1, Th2 and fibrotic responses are still observed in the absence of granuloma formation suggesting some degree of gene regulation may be induced by antigens released from the dying adult worms. Quantitative real-time PCR was used to examine the relative expression of 16 juvenile and adult S. mansoni genes during infection and their response to Vh and PZQ treatment in vivo. While the response of stress genes in adult parasites suggests the worms were alive immediately following exposure to PZQ, they were unable to induce transcription of any of the 9 genes encoding ATP-binding cassette (ABC transporters tested. In contrast, juvenile schistosomes were able to significantly induce the activities of ABCB, C and G family members, underscoring the possibility that these efflux systems play a major role in drug resistance.

Novel environmental class 1 integrons and cassette arrays recovered from an on-farm bio-purification plant.

Science.gov (United States)

Martini, María Carla; Quiroga, María Paula; Pistorio, Mariano; Lagares, Antonio; Centrón, Daniela; Del Papa, María Florencia

2018-03-01

Rapid dissemination and emergence of novel antibiotic resistance genes among bacteria are rising problems worldwide. Since their discovery in clinical isolates in the late 1980s, class 1 integrons have been found in a wide range of bacterial genera and have been extensively studied as contributors to dissemination of antibiotic resistance. The present study aimed to investigate the presence and structure of class 1 integrons in plasmid-carrying bacterial isolates obtained from a biopurification system used for decontamination of pesticide-contaminated water as well as their possible role as reservoir of antimicrobial resistance gene cassettes. A total of 35 representative isolates were screened for the presence of class 1 integron integrase encoded by intI1. PCR and DNA sequencing revealed the presence of six class 1 integrons with four variable regions: 5΄CS-aadA1b-3΄CS, 5΄CS-aadA2-3΄CS, 5΄CS-aadA11cΔ-3΄CS and 5΄CS-dfrB3-aadA1di-catB2-aadA6k-3΄CS, the last two being unseen arrays of antimicrobial resistance gene cassettes associated with novel environmental alleles of intI1. These four class 1 integrons were identified as being present in four different genera, including Ochrobactrum, and Variovorax, where class 1 integrons have not been previously reported. The results provide evidence of the biopurification systems as a tank of class 1 integron carrying strains and novel environmental class 1 integron integrases associated with antimicrobial resistance gene cassette arrays. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Use of virtual steam generator cassette for tube spatial design and SGC assembling procedure

International Nuclear Information System (INIS)

Kim, Y. W.; Kim, J. I.; Ji, S. K.

2003-01-01

A method of determining spatial arrangement of tube connection and assembling procedure of once-through helical steam generator cassette utilizing three dimensional virtual steam generator cassette has been developed on the basis of recent 3-D modelling technology. One ends of the steam generator tubes are connected to the module feed water header and the other sides are connected to the module steam header. Due to the complex geometry of tube arrangement, it is very difficult to connect the tubes to the module headers without the help of a physical engineering mock up. A comparative study has been performed at each design step for the tube arrangement and heat transfer area. Heat transfer area computed from thermal sizing was 4% less than that of measured. Heat transfer area calculated from the virtual steam generator cassette mock up has only 0.2% difference with that of measured. Assembling procedure of the steam generator cassette also, can be developed in the design stage

sphingosine-1-phosphate transport and its role in immunology

NARCIS (Netherlands)

Reitsema, V.; Bouma, Hjalmar; Kok, Jan

2014-01-01

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite with many important functions in cellular and systemic physiology, including the immune system. As it cannot traverse the membrane, it is exported from cells by transporters. Several members of the ATP-binding cassette (ABC) transporter

5G: 2020 and Beyond

DEFF Research Database (Denmark)

Prasad, Ramjee

he future society would be ushered in a new communication era with the emergence of 5G. 5G would be significantly different, especially, in terms of architecture and operation in comparison with the previous communication generations (4G, 3G...). This book discusses the various aspects...

A two-cassette reporter system for assessing target gene translation and target gene product inclusion body formation

DEFF Research Database (Denmark)

2016-01-01

The present invention relates to a dual cassette reporter system capable of assessing target gene translation and target gene product folding. The present invention further relates to vectors and host cells comprising the dual cassette reporter system. In addition the invention relates to the use...... of the dual cassette reporter system for assessing target gene translation and target gene product folding....

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma.

Science.gov (United States)

Setia, Namrata; Abbas, Ossama; Sousa, Yessica; Garb, Jane L; Mahalingam, Meera

2012-08-01

Distinct ABCB5 forms and ABCF2, members of the ATP-binding cassette (ABC) superfamily of transporters, are normally expressed in various tissues and cells, and enhanced expression of both has been demonstrated in select cancers. In melanoma cell lines, gene expression profiling of ABC transporters has revealed enhanced expression of melanocyte-specific ABCB5 and ABCF2 proteins. Given this, our primary aim was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations, including nevi (n=30), in situ (n=31) and invasive (n=24) primary cutaneous melanomas to assess their role in the stepwise development of malignancy. In addition, their expression was compared with established melanoma prognosticators to ascertain their utility as independent prognosticators. A semiquantitative scoring system was utilized by deriving a cumulative score (based on percentage positivity cells and intensity of expression) and statistical analyses was carried out using analysis of variance with linear contrasts. Mean cumulative score in nevi, in situ and invasive melanoma were as follows: 3.8, 4.4 and 5.3 for ABCB5, respectively (P1, after controlling for the presence of ulceration and mitotic activity, the expression of both proteins did not significantly correlate with known melanoma prognosticators. The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. On the basis of our findings, a prospective study with follow-up data is required to ascertain the utility of ABCB5 as a therapeutic target.

G5..., G6..., G7..., G8..., G?

OpenAIRE

Monteiro, António

2001-01-01

O G8 tem as suas raízes no primitivo embrião do G5 quando, em 1973, o então Secretário de Estado do Tesouro americano, George Schultz, convocou os Ministros das Finanças da França, Japão, Reino Unido e República Federal da Alemanha para uma reunião. O objectivo era analisar como fazer face à primeira crise do petróleo da OPEC e subsequente recessão económica nos países mais industrializados, ao colapso do sistema monetário das taxas de câmbio de paridades fixas de Bretton-Woods e ao alargamen...

A clinical trial of a rare earth screen/film system in a periapical cassette

International Nuclear Information System (INIS)

Kogon, S.L.; Stephens, R.G.; Reid, J.A.; Lubus, N.J.

1984-01-01

In a clinical trial, a slow rare earth screen/film system (Siemens Titan 2D/Kodak XG) was used to obtain intraoral radiographs at conventional monitoring stages in endodontic treatment. The screen film image proved to be an effective substitute for the direct-exposure Ultraspeed periapical film. The intraoral cassettes, designed and fabricated for the study, were an adaptation of the flexible, vacuum-sealed cassettes used in mammography. It is believed that when a practicable periapical cassette is manufactured, many additional indications for the system are probable. Major reductions in patient exposure of at least 85% to 90% per periapical film would be effected

ATP-Binding Cassette Proteins: Towards a Computational View of Mechanism

Science.gov (United States)

Liao, Jielou

2004-03-01

Many large machine proteins can generate mechanical force and undergo large-scale conformational changes (LSCC) to perform varying biological tasks in living cells by utilizing ATP. Important examples include ATP-binding cassette (ABC) transporters. They are membrane proteins that couple ATP binding and hydrolysis to the translocation of substrates across membranes [1]. To interpret how the mechanical force generated by ATP binding and hydrolysis is propagated, a coarse-grained ATP-dependent harmonic network model (HNM) [2,3] is applied to the ABC protein, BtuCD. This protein machine transports vitamin B12 across membranes. The analysis shows that subunits of the protein move against each other in a concerted manner. The lowest-frequency modes of the BtuCD protein are found to link the functionally critical domains, and are suggested to be responsible for large-scale ATP-coupled conformational changes. [1] K. P. Locher, A. T. Lee and D. C. Rees. Science 296, 1091-1098 (2002). [2] Atilgan, A. R., S. R. Durell, R. L. Jernigan, M. C. Demirel, O. Keskin, and I. Bahar. Biophys. J. 80, 505-515(2002); M. M Tirion, Phys. Rev. Lett. 77, 1905-1908 (1996). [3] J. -L. Liao and D. N. Beratan, 2003, to be published.

Construction of heterologous gene expression cassettes for the development of recombinant Clostridium beijerinckii.

Science.gov (United States)

Oh, Young Hoon; Eom, Gyeong Tae; Kang, Kyoung Hee; Joo, Jeong Chan; Jang, Young-Ah; Choi, Jae Woo; Song, Bong Keun; Lee, Seung Hwan; Park, Si Jae

2016-04-01

Gene-expression cassettes for the construction of recombinant Clostridium beijerinckii were developed as potential tools for metabolic engineering of C. beijerinckii. Gene expression cassettes containing ColE1 origin and pAMB origin along with the erythromycin resistance gene were constructed, in which promoters from Escherichia coli, Lactococcus lactis, Ralstonia eutropha, C. acetobutylicum, and C. beijerinckii are examined as potential promoters in C. beijerinckii. Zymogram analysis of the cell extracts and comparison of lipase activities of the recombinant C. beijerinckii strains expressing Pseudomonas fluorescens tliA gene suggested that the tliA gene was functionally expressed by all the examined promoters with different expression level. Also, recombinant C. beijerinckii expressing C. beijerinckii secondary alcohol dehydrogenase by the constructed expression cassettes successfully produced 2-propanol from glucose. The best promoter for TliA expression was the R. eutropha phaP promoter while that for 2-propanol production was the putative C. beijerinckii pta promoter. Gene expression cassettes developed in this study may be useful tools for the construction of recombinant C. beijerinckii strains as host strains for the valuable chemicals and fuels from renewable resources.

Construction of New Campylobacter Cloning Vectors and a New Mutational Cat Cassette

Science.gov (United States)

1993-01-01

mutational cat cassette PE - 61102A PR - 3M161102 6. AUTHOR(S) TA - BS13AK Yao R, Aim RA, Trust TJ, Guerry P WU- 1291 7. PERFORMING ORGANIZATION NAME(S) AND...mutational cat cassette %~ccesion For (Site-specific mutagenesis; recombinant DNA; multiple cloning site; PCR; shuttle vectors) NTIS CRA&I OTIC TAB E...campylobacter portion of these vectors, only three CAT , Cm acetyllraaseriase; car, gene encoding CAT , Cm, restriction sites in the IacZ MCS remain unique

The capacity of Listeria monocytogenes mutants with in-frame deletions in putative ATP-binding cassette transporters to form biofilms and comparison with the wild type

Directory of Open Access Journals (Sweden)

Marina Ceruso

2014-02-01

Full Text Available Listeria monocytogenes (Lm is a food-borne pathogen responsible for human listeriosis, an invasive infection with high mortality rates. Lm has developed efficient strategies for survival under stress conditions such as starvation and wide variations in temperature, pH, and osmolarity. Therefore, Lm can survive in food under multiple stress conditions. Detailed studies to determine the mode of action of this pathogen for survival under stress conditions are important to control Lm in food. It has been shown that genes encoding for ATP-binding cassette (ABC transporters are induced in Lm in food, in particular under stress conditions. Previous studies showed that these genes are involved in sensitivity to nisin, acids, and salt. The aim of this study was to determine the involvement of some ABC transporters in biofilm formation. Therefore, deletion mutants of ABC transporter genes (LMOf2365_1875 and LMOf2365_1877 were created in Lm F2365, and then were compared to the wild type for their capacity to form biofilms. Lm strain F2365 was chosen as reference since the genome is fully sequenced and furthermore this strain is particularly involved in food-borne outbreaks of listeriosis. Our results showed that DLMOf2365_1875 had an increased capacity to form biofilms compared to the wild type, indicating that LMOf2365_1875 negatively regulates biofilm formation. A deeper knowledge on the ability to form biofilms in these mutants may help in the development of intervention strategies to control Lm in food and in the environment.

Selective cytotoxicity of PAMAM G5 core–PAMAM G2.5 shell tecto-dendrimers on melanoma cells

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Schilrreff P

2012-07-01

Full Text Available Priscila Schilrreff,1 Cecilia Mundiña-Weilenmann,2 Eder Lilia Romero,1 Maria Jose Morilla11Programa de Nanomedicinas, Universidad Nacional de Quilmes, Buenos Aires, Argentina; 2Centro de Investigaciones Cardiovasculares, Universidad Nacional de La Plata, La Plata, ArgentinaBackground: The controlled introduction of covalent linkages between dendrimer building blocks leads to polymers of higher architectural order known as tecto-dendrimers. Because of the few simple steps involved in their synthesis, tecto-dendrimers could expand the portfolio of structures beyond commercial dendrimers, due to the absence of synthetic drawbacks (large number of reaction steps, excessive monomer loading, and lengthy chromatographic separations and structural constraints of high-generation dendrimers (reduction of good monodispersity and ideal dendritic construction due to de Gennes dense-packing phenomenon. However, the biomedical uses of tecto-dendrimers remain unexplored. In this work, after synthesizing saturated shell core–shell tecto-dendrimers using amine-terminated polyamidoamine (PAMAM generation 5 (G5 as core and carboxyl-terminated PAMAM G2.5 as shell (G5G2.5 tecto-dendrimers, we surveyed for the first time the main features of their interaction with epithelial cells.Methods: Structural characterization of G5G2.5 was performed by polyacrylamide gel electrophoresis, matrix-assisted laser desorption time-of-flight mass spectrometry, and microscopic techniques; their hydrodynamic size and Z-potential was also determined. Cellular uptake by human epidermal keratinocytes, colon adenocarcinoma, and epidermal melanoma (SK-Mel-28 cells was determined by flow cytometry. Cytotoxicity was determined by mitochondrial activity, lactate dehydrogenase release, glutathione depletion, and apoptosis/necrosis measurement.Results: The resultant 60%–67% saturated shell, 87,000-dalton G5G2.5 (mean molecular weight interacted with cells in a significantly different

Corticotropin-Releasing Hormone (CRH Promotes Macrophage Foam Cell Formation via Reduced Expression of ATP Binding Cassette Transporter-1 (ABCA1.

Directory of Open Access Journals (Sweden)

Wonkyoung Cho

Full Text Available Atherosclerosis, the major pathology of cardiovascular disease, is caused by multiple factors involving psychological stress. Corticotropin-releasing hormone (CRH, which is released by neurosecretory cells in the hypothalamus, peripheral nerve terminals and epithelial cells, regulates various stress-related responses. Our current study aimed to verify the role of CRH in macrophage foam cell formation, the initial critical stage of atherosclerosis. Our quantitative real-time reverse transcriptase PCR (qRT-PCR, semi-quantitative reverse transcriptase PCR, and Western blot results indicate that CRH down-regulates ATP-binding cassette transporter-1 (ABCA1 and liver X receptor (LXR-α, a transcription factor for ABCA1, in murine peritoneal macrophages and human monocyte-derived macrophages. Oil-red O (ORO staining and intracellular cholesterol measurement of macrophages treated with or without oxidized LDL (oxLDL and with or without CRH (10 nM in the presence of apolipoprotein A1 (apoA1 revealed that CRH treatment promotes macrophage foam cell formation. The boron-dipyrromethene (BODIPY-conjugated cholesterol efflux assay showed that CRH treatment reduces macrophage cholesterol efflux. Western blot analysis showed that CRH-induced down-regulation of ABCA1 is dependent on phosphorylation of Akt (Ser473 induced by interaction between CRH and CRH receptor 1(CRHR1. We conclude that activation of this pathway by CRH accelerates macrophage foam cell formation and may promote stress-related atherosclerosis.

Functional analysis of ABC transporter genes from Botrytis cinerea identifies BcatrB as a transporter of eugenol

NARCIS (Netherlands)

Schoonbeek, H.; Nistelrooy, van J.G.M.; Waard, de M.A.

2003-01-01

The role of multiple ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporter genes from the plant pathogenic fungus Botrytis cinerea in protection against natural fungitoxic compounds was studied by expression analysis and phenotyping of gene-replacement mutants. The

Plasminogen activator inhibitor-1 5G/5G genotype is a protecting factor preventing posttransplant diabetes mellitus.

Science.gov (United States)

Chang, Horng-Rong; Yang, Shun-Fa; Tsai, Jen-Pi; Hsieh, Ming-Chia; Wu, Sheng-Wen; Tsai, Hui-Ching; Hung, Tung-Wei; Huang, Jun-Huang; Lian, Jong-Da

2011-01-30

Plasminogen activator inhibitor 1 (PAI-1) is thought to play a role in the pathogenesis of obesity and insulin resistance. A connection between gestational diabetes mellitus and the functional -675 PAI-1 genotype has been reported. Therefore, we examined the role of the PAI-1 gene polymorphism in kidney transplant recipients. A total of 376 kidney transplant recipients were prospectively screened for posttransplant diabetes mellitus (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295 patients were non-diabetic following kidney transplantation. DNA samples were isolated from the sera and analyzed for the functional -675 4G/5G promoter polymorphisms of the PAI-1 gene. Kidney transplant recipients with PTDM were significantly associated with tacrolimus use (p=0.03), older age (p=0.036), and higher body mass index (p=0.001). The genotype distribution was significantly different between the patients with PTDM (genotype 4G/4G:4G/5G:5G/5G=33.3%:60.5%:6.2%) and those without PTDM (genotype 4G/4G:4G/5G:5G/5G=36.9%:44.1%:19.0%) (p=0.018). Patients with homozygosity for 5G had a significantly lower rate of PTDM (aOR, 0.286, p=0.022) and higher cumulative event-free probability of time to PTDM (log rank test, p=0.0058). Homozygosity for the 5G allele of the PAI-1 gene constitutes a protecting factor for the development of PTDM. Our findings are similar to a previous study on gestational diabetes mellitus, and strongly support a possible genetic role of PAI-1 in the development of PTDM. Copyright © 2010 Elsevier B.V. All rights reserved.

Polymorphisms in ATP-binding cassette transporters associated with maternal methylmercury disposition and infant neurodevelopment in mother-infant pairs in the Seychelles Child Development Study.

Science.gov (United States)

Engström, Karin; Love, Tanzy M; Watson, Gene E; Zareba, Grazyna; Yeates, Alison; Wahlberg, Karin; Alhamdow, Ayman; Thurston, Sally W; Mulhern, Maria; McSorley, Emeir M; Strain, J J; Davidson, Philip W; Shamlaye, Conrad F; Myers, G J; Rand, Matthew D; van Wijngaarden, Edwin; Broberg, Karin

2016-09-01

ATP-binding cassette (ABC) transporters have been associated with methylmercury (MeHg) toxicity in experimental animal models. To evaluate the association of single nucleotide polymorphisms (SNPs) in maternal ABC transporter genes with 1) maternal hair MeHg concentrations during pregnancy and 2) child neurodevelopmental outcomes. Nutrition Cohort 2 (NC2) is an observational mother-child cohort recruited in the Republic of Seychelles from 2008-2011. Total mercury (Hg) was measured in maternal hair growing during pregnancy as a biomarker for prenatal MeHg exposure (N=1313) (mean 3.9ppm). Infants completed developmental assessments by Bayley Scales of Infant Development II (BSID-II) at 20months of age (N=1331). Genotyping for fifteen SNPs in ABCC1, ABCC2 and ABCB1 was performed for the mothers. Seven of fifteen ABC SNPs (ABCC1 rs11075290, rs212093, and rs215088; ABCC2 rs717620; ABCB1 rs10276499, rs1202169, and rs2032582) were associated with concentrations of maternal hair Hg (pmothers with rs11075290 CC genotype (mean hair Hg 3.6ppm) scored on average 2 points lower on the Mental Development Index (MDI) and 3 points lower on the Psychomotor Development Index (PDI) than children born to mothers with TT genotype (mean hair Hg 4.7ppm) while children with the CT genotype (mean hair Hg 4.0ppm) had intermediate BSID scores. Genetic variation in ABC transporter genes was associated with maternal hair Hg concentrations. The implications for MeHg dose in the developing child and neurodevelopmental outcomes need to be further investigated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Scavenger Receptor Class B Type I Mediates Biliary Cholesterol Secretion Independent of ATP-Binding Cassette Transporter g5/g8 in Mice

NARCIS (Netherlands)

Wiersma, Harmen; Gatti, Alberto; Nijstad, Niels; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Tietge, Uwe J. F.

2009-01-01

Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not dear, if this effect is direct or indirect. The aim of this study was to determine the impact

The METIS 5G System Concept

DEFF Research Database (Denmark)

Tullberg, Hugo; Popovski, Petar; Li, Zexian

2016-01-01

The authors describe the most important system-level 5G features, enabled by the concept, necessary to meet the very diverse 5G requirements. System-level evaluation results of the METIS 5G system concept are presented, and they conclude that the 5G requirements can be met with the proposed system...... concept....

Attila calculations for the 3-D C5G7 benchmark extension

International Nuclear Information System (INIS)

Wareing, T.A.; McGhee, J.M.; Barnett, D.A.; Failla, G.A.

2005-01-01

The performance of the Attila radiation transport software was evaluated for the 3-D C5G7 MOX benchmark extension, a follow-on study to the MOX benchmark developed by the 'OECD/NEA Expert Group on 3-D Radiation Transport Benchmarks'. These benchmarks were designed to test the ability of modern deterministic transport methods to model reactor problems without spatial homogenization. Attila is a general purpose radiation transport software package with an integrated graphical user interface (GUI) for analysis, set-up and postprocessing. Attila provides solutions to the discrete-ordinates form of the linear Boltzmann transport equation on a fully unstructured, tetrahedral mesh using linear discontinuous finite-element spatial differencing in conjunction with diffusion synthetic acceleration of inner iterations. The results obtained indicate that Attila can accurately solve the benchmark problem without spatial homogenization. (authors)

Pouring and running a protein gel by reusing commercial cassettes.

Science.gov (United States)

Hwang, Alexander C; Grey, Paris H; Cuddy, Katrina; Oppenheimer, David G

2012-02-12

The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (~$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.

The accessibility in the external part of the TM5 of the glutamate transporter EAAT1 is conformationally sensitive during the transport cycle.

Directory of Open Access Journals (Sweden)

Xiuping Zhang

Full Text Available BACKGROUND: Excitatory amino acid transporter 1 (EAAT1 is a glutamate transporter which is a key element in the termination of the synaptic actions of glutamate. It serves to keep the extracellular glutamate concentration below neurotoxic level. However the functional significance and the change of accessibility of residues in transmembrane domain (TM 5 of the EAAT1 are not clear yet. METHODOLOGY/PRINCIPAL FINDINGS: We used cysteine mutagenesis with treatments with membrane-impermeable sulfhydryl reagent MTSET [(2-trimethylammonium methanethiosulfonate] to investigate the change of accessibility of TM5. Cysteine mutants were introduced from position 291 to 300 of the cysteine-less version of EAAT1. We checked the activity and kinetic parameters of the mutants before and after treatments with MTSET, furthermore we analyzed the effect of the substrate and blocker on the inhibition of the cysteine mutants by MTSET. Inhibition of transport by MTSET was observed in the mutants L296C, I297C and G299C, while the activity of K300C got higher after exposure to MTSET. V(max of L296C and G299C got lower while that of K300C got higher after treated by MTSET. The L296C, G299C, K300C single cysteine mutants showed a conformationally sensitive reactivity pattern. The sensitivity of L296C to MTSET was potentiated by glutamate and TBOA,but the sensitivity of G299C to MTSET was potentiated only by TBOA. CONCLUSIONS/SIGNIFICANCE: All these facts suggest that the accessibility of some positions of the external part of the TM5 is conformationally sensitive during the transport cycle. Our results indicate that some residues of TM5 take part in the transport pathway during the transport cycle.

Long-range charge transport in single G-quadruplex DNA molecules

DEFF Research Database (Denmark)

Livshits, Gideon I.; Stern, Avigail; Rotem, Dvir

2014-01-01

DNA and DNA-based polymers are of interest in molecular electronics because of their versatile and programmable structures. However, transport measurements have produced a range of seemingly contradictory results due to differences in the measured molecules and experimental set-ups, and transport......DNA and DNA-based polymers are of interest in molecular electronics because of their versatile and programmable structures. However, transport measurements have produced a range of seemingly contradictory results due to differences in the measured molecules and experimental set......-ups, and transporting significant current through individual DNA-based molecules remains a considerable challenge. Here, we report reproducible charge transport in guanine-quadruplex (G4) DNA molecules adsorbed on a mica substrate. Currents ranging from tens of picoamperes to more than 100 pA were measured in the G4......-DNA over distances ranging from tens of nanometres to more than 100 nm. Our experimental results, combined with theoretical modelling, suggest that transport occurs via a thermally activated long-range hopping between multi-tetrad segments of DNA. These results could re-ignite interest in DNA...

The Real World French Cassette Program. Script Book.

Science.gov (United States)

Sternburg, Sheldon G.; Sammarco, Anthony M., Jr.

This dual cassette package, accompanied by a script book, is designed to give students listening practice in French, particularly for regional differences of pronunciation and for variety in idiomatic constructions. The program may be integrated with texts used in intermediate and advanced levels of instruction. The announcements, jingles, and…

The Real World Spanish Cassette Program. Script Book.

Science.gov (United States)

Sternburg, Sheldon G.

This dual cassette program, accompanied by a script book, is designed to give students listening practice in Spanish, particularly for regional differences of pronunciation and for variety in idiomatic construction. The program may be integrated with texts used in intermediate and advanced levels of instruction. The announcements, jingles, and…

Expression and regulation of transmembrane transporters in healthy intestine and gastrointestinal diseases

OpenAIRE

Hruz, Petr

2006-01-01

Transmembrane transporters mediate energy dependent or independent translocation of drugs, potentially toxic compounds, and of various endogenous substrates such as bile acids and bilirubin across membranes. In this thesis the focus is on two classes of transporters, the ATPbinding cassette (ABC) transporters, which mediate ATP dependent transport and the solute carriers (SLC) which use electrochemical gradients for their transport. The transporters are expressed on membranes o...

Impact of Transport Control Protocol on Full Duplex Performance in 5G Networks

DEFF Research Database (Denmark)

Gatnau, Marta; Berardinelli, Gilberto; Mahmood, Nurul Huda

2016-01-01

Full duplex (FD) communication has attracted the attention of the industry and the academia as an important feature in the design of the future 5th generation (5G) wireless communication system. Such technology allows a device to simultaneously transmit and receive in the same frequency band......, which comes at the price of increased delay and reduced system throughput. FD is expected to accelerate the TCP congestion control mechanism and hence mitigate such consequences. System level results show that FD can outperform HD and alleviate the TCP drawbacks when the inter-cell interference...

Evaluation of an Audio Cassette Tape Lecture Course

Science.gov (United States)

Blank, Jerome W.

1975-01-01

An audio-cassette continuing education course (Selected Topics in Pharmacology) from Extension Services in Pharmacy at the University of Wisconsin was offered to a selected test market of pharmacists and evaluated using a pre-, post-test design. Results showed significant increase in cognitive knowledge and strong approval of students. (JT)

Uusien 5G-teknologioiden energiatehokkuus

OpenAIRE

Jurvakainen, Tuukka

2016-01-01

Mobiiliverkkojen datamäärän kasvaessa räjähdysmäisesti tarvitaan uutta 5G-teknologiaa lisäämään langattomien verkkojen kapasiteettia. 5G-verkkoja kehitettäessä yksi tärkeä tutkimuskysymys on, kuinka saada niistä energiatehokkaita. Tässä tutkielmassa käydään läpi tieteellistä keskustelua aiheesta. Tieteellisestä keskustelusta keskeisimmiksi teknologioiksi 5G-verkkoihin nousevat muun muassa laitteistotekniikan kehittyminen, millimetriaallot, kognitiivinen radioverkko, massiivinen MIMO ja hetero...

Natural polyphenols: Influence on membrane transporters

Directory of Open Access Journals (Sweden)

Saad Abdulrahman Hussain

2016-03-01

Full Text Available Accumulated evidences have focused on the use of natural polyphenolic compounds as nutraceuticals, since they showed a wide range of bioactivities and exhibited protection against variety of age related disorders. Polyphenols have variable potencies to interact, and hence alter the activities of various transporter proteins, many of them classified as ATP-Binding Cassette transporters, like multidrug resistance protein (MDRP, and p-glycoprotein (P-gp. Some of the efflux transporters are generally linked with anticancer and antiviral drug resistance; in this context, polyphenols may be beneficial in modulating drug resistance by increasing the efficacy of anticancer and antiviral drugs. Additionally, these effects were implicated to explain the influence of dietary polyphenols on drug efficacy as result of food-drug interactions. However, limited data are available about the influence of these components on uptake transporters. Therefore, the objective of this article is to review the potential efficacies of polyphenols in modulating the functional integrity of uptake transporter proteins, including those terminated the effect of neurotransmitters, and their possible influence in neuropharmacology. [J Complement Med Res 2016; 5(1.000: 97-104

5G. Trendthema 41

OpenAIRE

Tiemann, Jens

2016-01-01

Technikexperten und Politiker sprechen unter dem Schlagwort 5G von einer kommenden Mobilfunkgeneration, die die Digitalisierung der Gesellschaft auf eine neue Stufe heben wird. So soll 5G etwa Industrie-Roboter miteinander vernetzen und mobilen Anwendungen der erweiterten Realität zum Durchbruch verhelfen. Für solche Anwendungen braucht es hohe Bandbreiten, eine Übertragung in Echtzeit und die Vernetzung einer großen Anzahl an smarten Dingen - alles natürlich drahtlos und sicher. All dies sol...

Utilizing ARC EMCS Seedling Cassettes as Highly Versatile Miniature Growth Chambers for Model Organism Experiments

Science.gov (United States)

Freeman, John L.; Steele, Marianne K.; Sun, Gwo-Shing; Heathcote, David; Reinsch, S.; DeSimone, Julia C.; Myers, Zachary A.

2014-01-01

The aim of our ground testing was to demonstrate the capability of safely putting specific model organisms into dehydrated stasis, and to later rehydrate and successfully grow them inside flight proven ARC EMCS seedling cassettes. The ARC EMCS seedling cassettes were originally developed to support seedling growth during space flight. The seeds are attached to a solid substrate, launched dry, and then rehydrated in a small volume of media on orbit to initiate the experiment. We hypothesized that the same seedling cassettes should be capable of acting as culture chambers for a wide range of organisms with minimal or no modification. The ability to safely preserve live organisms in a dehydrated state allows for on orbit experiments to be conducted at the best time for crew operations and more importantly provides a tightly controlled physiologically relevant growth experiment with specific environmental parameters. Thus, we performed a series of ground tests that involved growing the organisms, preparing them for dehydration on gridded Polyether Sulfone (PES) membranes, dry storage at ambient temperatures for varying periods of time, followed by rehydration. Inside the culture cassettes, the PES membranes were mounted above blotters containing dehydrated growth media. These were mounted on stainless steel bases and sealed with plastic covers that have permeable membrane covered ports for gas exchange. The results showed we were able to demonstrate acceptable normal growth of C.elegans (nematodes), E.coli (bacteria), S.cerevisiae (yeast), Polytrichum (moss) spores and protonemata, C.thalictroides (fern), D.discoideum (amoeba), and H.dujardini (tardigrades). All organisms showed acceptable growth and rehydration in both petri dishes and culture cassettes initially, and after various time lengths of dehydration. At the end of on orbit ISS European Modular Cultivation System experiments the cassettes could be frozen at ultra-low temperatures, refrigerated, or chemically

Beta, gamma contamination analysis of thermo luminescence dosimeter cassettes using Geiger Muller counting set up and gamma spectrometry techniques

International Nuclear Information System (INIS)

Prasad, S.K.; Sudheer, T.S.; Sahoo, L.; Vinayagam, Bhakti; Kamble, Mahesh; Khuspe, R.R.; Anilkumar, Rekha; Verma, K.K.

2009-01-01

Β-γ contamination cheek up of TLD cassettes were carried out and the isotopes found were 137 Cs, 106 Ru, 60 Co, 64 Cu, 144 Ce and 95 Nb with activity per square cm varying from 0.05-4.70 Bq/cm 2 with median value 1.3. The assessed dose in TLD was in the range of 2.10 mSv to 22.05 mSv for beta, 0.05 mSv to 5.25 mSv for gamma. The beta doses have median value of 6.19 mSv. This contamination may be due to active water contamination on TLD's of personnel working for irradiated fuel handling or work in fuel rod (under water) storage area. This gives a method to estimate skin exposure of personnel due to skin contamination during work. Chances of getting TLD's contaminated due to various reasons were studied. Contamination was found maximum inside the cassette box having area 16 cm 2 . In case of plastic pouch of TLD disc contamination was detected in three cases. Contamination level on TLD cassettes using GM counter was found in the range of 0.30-3.6 Bq/cm 2 for cassettes. By opening the window of the surveymeter contamination and field of these cassettes in closed condition were found to increase by 20% due to the measurement of beta dose. With the same condition contamination of TLD cassette in open condition was found five times more. This is due to the a-contamination which is five times more than a contamination, The most prominent isotope 137 Cs in common chemical forms are soluble in water and if inhaled or ingested are rapidly and completely absorbed in the lungs and across the gastrointestinal tract. Thus a skin contamination of most prominent isotope 137 Cs can lead to intake in addition to skin dose. Fading studies of contamination of TLD cassettes were carried out. It was found negligible after counting with GM counting set up after a period of 3 months. But one of the TLD cassettes was showing an 80% reduction of contamination after 3 months with GM counting set up, the contaminants being 141 Ce, 103 Ru and 95 Nb. The gamma peaks in the external exposure

Fundamentals of 5G mobile networks

CERN Document Server

Rodriguez, Jonathan

2015-01-01

Fundamentals of 5G Mobile Networks provides an overview of the key features of the 5th Generation (5G) mobile networks,  discussing the motivation for 5G and the main challenges in developing this new technology. This book provides an insight into the key areas of research that will define this new system technology paving the path towards future research and development.  The book is multi-disciplinary in nature, and aims to cover a whole host of intertwined subjects that will predominantly influence the 5G landscape, including the future Internet, cloud computing, small cells and self-organ

10 CFR 960.5-2-7 - Transportation.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Transportation. 960.5-2-7 Section 960.5-2-7 Energy... REPOSITORY Preclosure Guidelines Environment, Socioeconomics, and Transportation § 960.5-2-7 Transportation... using reasonably available technology; (iii) will not require transportation system components to meet...

Conceptual Design Studies of the KSTAR Bay-Nm Cassette and Thomson Scattering Optics

International Nuclear Information System (INIS)

Feder, R.; Ellis, R.; Johnson, D.; Park, H.; Lee, H.G.

2005-01-01

A Multi-Channel Thomson Scattering System viewing the edge and core of the KSTAR plasma will be installed at the mid-plane port Bay-N. An engineering design study was undertaken at PPPL in collaboration with the Korea Basic Science Institute (KBSI) to determine the optimal optics and cassette design. Design criteria included environmental, mechanical and optical factors. All of the optical design options have common design features; the Thomson Scattering laser, an in-vacuum shutter, a quartz heat shield and primary vacuum window, a set of optical elements and a fiber optic bundle. Neutron radiation damage was a major factor in the choice of competing lens-based and mirror-based optical designs. Both the mirror based design and the lens design are constrained by physical limits of the Bay-N cassette and interference with the Bay-N micro-wave launcher. The cassette will contain the optics and a rail system for maintenance of the optics

Community Based Networks and 5G

DEFF Research Database (Denmark)

Williams, Idongesit

2016-01-01

The deployment of previous wireless standards has provided more benefits for urban dwellers than rural dwellers. 5G deployment may not be different. This paper identifies that Community Based Networks as carriers that deserve recognition as potential 5G providers may change this. The argument....... The findings indicate that 5G connectivity can be extended to rural areas by these networks, via heterogenous networks. Hence the delivery of 5G data rates delivery via Wireless WAN in rural areas can be achieved by utilizing the causal factors of the identified models for Community Based Networks....

Conceptual design of divertor cassette handling by remote handling system of JT-60SA

International Nuclear Information System (INIS)

Hayashi, Takao; Sakurai, Shinji; Masaki, Kei; Tamai, Hiroshi; Yoshida, Kiyoshi; Matsukawa, Makoto

2008-01-01

The JT-60SA aims to contribute and supplement ITER toward demonstration fusion reactor based on tokamak concept. One of the features of JT-60SA is its high power long pulse heating, causing the large annual neutron fluence. Because the expected dose rate at the vacuum vessel (VV) may exceed 1 mSv/hr after 10 years operation and three month cooling, the human access inside the VV is restricted. Therefore a remote handling (RH) system is necessary for the maintenance and repair of in-vessel components. This paper described the RH system of JT-60SA, especially the expansion of the RH rail and exchange of the divertor cassettes. The RH rail is divided into nine and three-point mounting. The nine sections can cover 225 degrees in toroidal direction. A divertor cassette, which is 10 degrees wide in toroidal direction and weighs 500 kg itself due to the limitations of port width and handling weight, can be exchanged by heavy weight manipulator (HWM). The HWM brings the divertor cassette to the front of the other RH port, which is used for supporting the rail and/or carrying in and out equipments. Then another RH device receives and brings out the cassette by a pallet installed from outside the VV. (author)

Are lipid rafts involved in ABC transporter-mediated drug resistance of tumor cells?

NARCIS (Netherlands)

Kok, Jan Willem; Klappe, Karin; Hummel, Ina; Kroesen, Bart-Jan; Sietsma, Hannie; Meszaros, Peter

2008-01-01

Since their discovery, lipid rafts have been implicated in several cellular functions, including protein transport in polarized cells and signal transduction. Also in multidrug resistance lipid rafts may be important with regard to the localization of ATP-binding cassette (ABC) transporters in these

Ion specificity and ionic strength dependence of the osmoregulatory ABC transporter OpuA

NARCIS (Netherlands)

Mahmood, N. A. B. Nik; Biemans-Oldehinkel, Esther; Patzlaff, Jason S.; Schuurman-Wolters, Gea K.; Poolman, Bert

2006-01-01

The ATPase subunit of the osmoregulatory ATP- binding cassette transporterOpuAfrom Lactococcus lactis has a C- terminal extension, the tandem cystathionine beta- synthase ( CBS) domain, which constitutes the sensor that allows the transporter to sense and respond to osmotic stress ( Biemans-

Challenges to 5G standardization

DEFF Research Database (Denmark)

Mihovska, Albena D.; Prasad, Ramjee

2013-01-01

Interoperable, ubiquitous and dynamic are key objectives for fifth-generation (5G) communication systems and applications. These characteristics are also at the core of the main challenges that researchers, manufacturers, regulators and standardization bodies face when designing targeted strategies...... for the successful deployment of 5G enabling technologies....

Downregulation of eIF4G by microRNA-503 enhances drug sensitivity of MCF-7/ADR cells through suppressing the expression of ABC transport proteins.

Science.gov (United States)

Pan, Xia; Yang, Xiaoyan; Zang, Jinglei; Zhang, Si; Huang, Nan; Guan, Xinxin; Zhang, Jianhua; Wang, Zhihui; Li, Xi; Lei, Xiaoyong

2017-06-01

Overexpression of adenosine triphosphate-binding cassette (ABC) transport protein is emerging as a critical contributor to anticancer drug resistance. The eukaryotic translation initiation factor (eIF) 4F complex, the key modulator of mRNA translation, is regulated by the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway in anticancer drug-resistant tumors. The present study demonstrated the roles of ABC translation protein alterations in the acquisition of the Adriamycin (ADM)-resistant phenotype of MCF-7 human breast cells. Quantitative polymerase chain reaction and western blot analysis were applied to examine the differences in mRNA and protein levels, respectively. It was found that the expression of the ABC sub-family B member 1, ABC sub-family C member 1 and ABC sub-family G member 2 transport proteins were upregulated in MCF-7/ADR cells. An MTT assay was used to detect the cell viability, from the results MCF-7/ADR cells were less sensitive to ADM, tamoxifen (TAM) and taxol (TAX) treatment compared with MCF-7 cells. We predicted that the 3'-untranslated region of eukaryotic translation initiation factor 4-γ 1 (eIF4G) contains a potential miRNA binding site for microRNA (miR)-503 through using computational programs. These binding sites were confirmed by luciferase reporter assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it was demonstrated that eIF4G and ABC translation proteins were significantly downregulated in MCF-7/ADR cells after transfection with miR-503. It was found that miR-503 mimics could sensitize the cells to treatment with ADM, TAM and TAX. These findings demonstrated for the first time that eIF4G acted as a key factor in MCF-7/ADR cells, and may be an efficient agent for preventing and reversing multi-drug resistance in breast cancer.

Transport mechanisms of hepatic uptake and bile excretion in clinical hepatobiliary scintigraphy with 99mTc-N-pyridoxyl-5-methyltryptophan

International Nuclear Information System (INIS)

Kobayashi, Masato; Nakanishi, Takeo; Nishi, Kodai; Higaki, Yusuke; Okudaira, Hiroyuki; Ono, Masahiro; Tsujiuchi, Takafumi; Mizutani, Asuka; Nishii, Ryuichi; Tamai, Ikumi; Arano, Yasushi; Kawai, Keiichi

2014-01-01

Introduction: In clinical hepatobiliary scintigraphy, 99m Tc-N-pyridoxyl-5-methyltryptophan ( 99m Tc-PMT) is an effective radiotracer among the 99m Tc-pyridoxylaminates. However, the mechanisms of human hepatic uptake and bile excretion transport of 99m Tc-PMT have not been determined. We thus investigated the transport mechanisms of human hepatic uptake and bile excretion in hepatobiliary scintigraphy with 99m Tc-PMT. Methods: Four solute carrier (SLC) transporters involved in hepatic uptake were evaluated using human embryonic kidney (HEK) and HeLa cells with high expression of SLC transporters (organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporters (OAT)2 and organic cation transporters (OCT)1) after 5 min of 99m Tc-PMT incubation. Metabolic analysis of 99m Tc-PMT was performed using pooled human liver S9. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters for bile excretion were examined using hepatic ABC transporter vesicles human expressing multiple drug resistance 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein or bile salt export pump. 99m Tc-PMT was incubated for 1, 3 and 5 min with ATP or adenosine monophosphate and these vesicles. SPECT scans were performed in normal and Eisai hyperbilirubinemic (EHBR) model rats, deficient in Mrp2 transporters, without and with verapamil (rat Mdr1 and human MDR1 inhibitor) after intravenous injection of 99m Tc-PMT. Results: Uptake of 99m Tc-PMT in HEK293/OATP1B1 and HeLa/OATP1B3 was significantly higher than that in HEK293- and HeLa-mock cells. 99m Tc-PMT was not metabolized in the human liver S9. In vesicles with high expression of ABC transporters, uptake of MDR1 or MRP2 was significantly higher at all incubation times. Bile excretion of 99m Tc-PMT was also identified by comparison between normal and EHBR rats with and without verapamil on in-vivo imaging. Conclusions: Human hepatic uptake of 99m Tc-PMT was transferred

Effect of genomic location on horizontal transfer of a recombinant gene cassette between Pseudomonas strains in the rhizosphere and spermosphere of barley seedlings

DEFF Research Database (Denmark)

Sengelov, G.; Kristensen, K. J.; Sørensen, Anders Morten Hay

2001-01-01

, horizontal transfer of a recombinant gene cassette inserted into the chromosome of a Pseudomonas strutzeri strain, into a mobilizable plasmid (pAGM42), and into a conjugative plasmid (pKJK5) isolated from barley rhizosphere was investigated. Horizontal transfer efficiencies of the gene cassette inserted...... efficiencies were up to 4.36 x 10(-3) transconjugants/(donors x recipients)(1/2). Transfer of chromosomal encoded genes could not be detected in the microcosms by conjugation or transformation. However, transformation did occur by using the same bacterial strains under laboratory conditions. The rhizosphere...

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

NARCIS (Netherlands)

Bloks, VW; Bakker-van Waarde, WM; Verkade, HJ; Kema, IP; Wolters, H; Vink, E; Groen, AK; Kuipers, F

Aim/hypothesis., Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both

4G/5G polymorphism modulates PAI-1 circulating levels in obese women.

Science.gov (United States)

Fernandes, Karla S; Sandrim, Valéria C

2012-05-01

The increase in plasminogen activator inhibitor type 1 (PAI-1) has been described as a risk factor to thrombosis-related diseases. In addition, it has been demonstrated that the variant 4G of polymorphism 4G/5G located in promoter region of PAI-1 gene is associated with higher PAI-1 levels. We investigate the role of this polymorphism on circulating PAI-1 concentration in a population of 57 obese women (23%, 4G/4G; 49%, 4G/5G and 28%, 5G/5G genotypes). Our results demonstrate a genotype-specific modulation on PAI-1 levels in obese women, thus 5G/5G genotype presented significantly lower levels of plasma PAI-1 when compared to 4G/4G group (46 ± 19 ng/mL vs. 63 ± 13 ng/mL, respectively). Our findings indicate that obese carriers of 4G/4G genotype may have increased risk to develop thrombotic diseases.

Functional Diversity of Tandem Substrate-Binding Domains in ABC Transporters from Pathogenic Bacteria

NARCIS (Netherlands)

Fulyani, Faizah; Schuurman-Wolters, Gea K.; Vujicic - Zagar, Andreja; Guskov, Albert; Slotboom, Dirk-Jan; Poolman, Bert

2013-01-01

The ATP-binding cassette (ABC) transporter GInPQ is an essential uptake system for amino acids in gram-positive pathogens and related nonpathogenic bacteria. The transporter has tandem substrate-binding domains (SBDs) fused to each transmembrane domain, giving rise to four SBDs per functional

Isolation and molecular characterization of methicillin-resistant Staphylococcus aureus from public transport.

Science.gov (United States)

Iwao, Yasuhisa; Yabe, Shizuka; Takano, Tomomi; Higuchi, Wataru; Nishiyama, Akihito; Yamamoto, Tatsuo

2012-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) not only causes disease in hospitals, but also in the community. The characteristics of MRSA transmission in the environment remain uncertain. In this study, MRSA were isolated from public transport in Tokyo and Niigata, Japan. Of 349 trains examined, eight (2.3%) were positive for MRSA. The MRSA isolated belonged to sequence types (STs) 5, 8, 88, and 89, and included community infection-associated ST8 MRSA (with novel type IV staphylococcal cassette chromosome mec) and the ST5 New York/Japan hospital clone. The data indicate that public transport could contribute to the spread of community-acquired MRSA, and awareness of this mode of transmission is necessary. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

Concept design of DEMO divertor cassette remote handling: Simply supported beam approach

Energy Technology Data Exchange (ETDEWEB)

Mozzillo, Rocco [CREATE, University of Naples Federico II, DII, P.le Tecchio 80, 80125, Naples (Italy); Di Gironimo, Giuseppei, E-mail: peppe.digironimo@gmail.com [CREATE, University of Naples Federico II, DII, P.le Tecchio 80, 80125, Naples (Italy); Mäkinen, Harri [VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere (Finland); Miccichè, Gioacchino [ENEA – CR Brasimone, I-40032 Camugnano, BO (Italy); Määttä, Timo [VTT Technical Research Centre of Finland, P.O. Box 1300, FI-33101 Tampere (Finland)

2017-03-15

Highlights: • The present work focused on a new approach to the design of DEMO Divertor Cassette Remote Handling Equipment. • The work provides an alternative approach to the design based on the concept of a simply supported beam. • The approach proposed focuses a Divertor Cassette mover that performs the maintenance of the three cassettes at each port. • First rough dimensioning of the main components has been provided and demonstrating the feasibility of the design solutions. • The main idea of the work consisted on a design capable to use knowledge already adopted in industrial contexts. - Abstract: The present work focused on the development of a new approach to the concept design of DEMO Divertor Cassette (DC) Remote Handling Equipment (RHE). The approach is based on three main assumptions: the DC remote handling activities and the equipment shall be simplified as much as possible; technologies well known and consolidated in the industrial context can be adopted also in the nuclear fusion field; the design of the RHE should be based on a simply supported beam approach instead of cantilever approach. In detail, during the maintenance activities the barycentre of the DC is centred with respect to DC supports. This solution could simplify the design of RHE with a consequent reduction of the design and development costs. Moreover also the DC remote handling tasks shall be simplified in order to better manage the DC maintenance processes. For this reason the DC assembly and disassembly process has been simplified dividing the main sequences in basic movements. For each movement a dedicated tool has been conceived.

Personal cassette players ('Walkman'). Do they cause noise-induced hearing loss?

Science.gov (United States)

Turunen-Rise, I; Flottorp, G; Tvete, O

1991-01-01

Playing selected types of music on five different personal cassette players (PCPs) and using different gain (volume) settings, A-weighted maximum and equivalent sound pressure levels (SPLs) were measured on KEMAR (Knowles Electronics Manikin for Acoustic Research). The octave band SPLs were measured on KEMAR ear and transformed to field values in order to compare measured values with the Norwegian noise risk criteria. Temporary threshold shifts (TTS) measured in 6 subjects after listening to two different pop music cassettes on one PCP in two separate sessions, are presented. Based upon these studies we conclude that the risk of acquiring permanent noise-induced hearing loss (NIHL) from use of PCP is very small for what we found to be normal listening conditions.

Optimized paired-sgRNA/Cas9 cloning and expression cassette triggers high-efficiency multiplex genome editing in kiwifruit.

Science.gov (United States)

Wang, Zupeng; Wang, Shuaibin; Li, Dawei; Zhang, Qiong; Li, Li; Zhong, Caihong; Liu, Yifei; Huang, Hongwen

2018-01-13

Kiwifruit is an important fruit crop; however, technologies for its functional genomic and molecular improvement are limited. The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system has been successfully applied to genetic improvement in many crops, but its editing capability is variable depending on the different combinations of the synthetic guide RNA (sgRNA) and Cas9 protein expression devices. Optimizing conditions for its use within a particular species is therefore needed to achieve highly efficient genome editing. In this study, we developed a new cloning strategy for generating paired-sgRNA/Cas9 vectors containing four sgRNAs targeting the kiwifruit phytoene desaturase gene (AcPDS). Comparing to the previous method of paired-sgRNA cloning, our strategy only requires the synthesis of two gRNA-containing primers which largely reduces the cost. We further compared efficiencies of paired-sgRNA/Cas9 vectors containing different sgRNA expression devices, including both the polycistronic tRNA-sgRNA cassette (PTG) and the traditional CRISPR expression cassette. We found the mutagenesis frequency of the PTG/Cas9 system was 10-fold higher than that of the CRISPR/Cas9 system, coinciding with the relative expressions of sgRNAs in two different expression cassettes. In particular, we identified large chromosomal fragment deletions induced by the paired-sgRNAs of the PTG/Cas9 system. Finally, as expected, we found both systems can successfully induce the albino phenotype of kiwifruit plantlets regenerated from the G418-resistance callus lines. We conclude that the PTG/Cas9 system is a more powerful system than the traditional CRISPR/Cas9 system for kiwifruit genome editing, which provides valuable clues for optimizing CRISPR/Cas9 editing system in other plants. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons

Plant ABC transporters enable many unique aspects of a terrestrial plant's lifestyle

DEFF Research Database (Denmark)

Hwang, Jae-Ung; Song, Won-Yong; Hong, Daewoong

2016-01-01

Terrestrial plants have two to four times more ATP-binding cassette (ABC) transporter genes than other organisms, including their ancestral microalgae. Recent studies found that plants harboring mutations in these transporters exhibit dramatic phenotypes, many of which are related to developmental...... to propose that diverse ABC transporters enabled many unique and essential aspects of a terrestrial plant's lifestyle, by transporting various compounds across specific membranes of the plant....

FANTASTIC-5G

DEFF Research Database (Denmark)

Schaich, Frank; Sayrac, Berna; Elayoubi, Salaheddine

2016-01-01

-service support below 6 GHz will be too costly. FANTASTIC-5G will develop a new multi-service air interface through a modular design. To allow the system to adapt to the anticipated heterogeneity, some properties need to be pursued, like simplicity, flexibility, scalability, versatility, efficiency and future...

Functional importance of different patterns of correlation between adjacent cassette exons in human and mouse.

Science.gov (United States)

Peng, Tao; Xue, Chenghai; Bi, Jianning; Li, Tingting; Wang, Xiaowo; Zhang, Xuegong; Li, Yanda

2008-04-26

Alternative splicing expands transcriptome diversity and plays an important role in regulation of gene expression. Previous studies focus on the regulation of a single cassette exon, but recent experiments indicate that multiple cassette exons within a gene may interact with each other. This interaction can increase the potential to generate various transcripts and adds an extra layer of complexity to gene regulation. Several cases of exon interaction have been discovered. However, the extent to which the cassette exons coordinate with each other remains unknown. Based on EST data, we employed a metric of correlation coefficients to describe the interaction between two adjacent cassette exons and then categorized these exon pairs into three different groups by their interaction (correlation) patterns. Sequence analysis demonstrates that strongly-correlated groups are more conserved and contain a higher proportion of pairs with reading frame preservation in a combinatorial manner. Multiple genome comparison further indicates that different groups of correlated pairs have different evolutionary courses: (1) The vast majority of positively-correlated pairs are old, (2) most of the weakly-correlated pairs are relatively young, and (3) negatively-correlated pairs are a mixture of old and young events. We performed a large-scale analysis of interactions between adjacent cassette exons. Compared with weakly-correlated pairs, the strongly-correlated pairs, including both the positively and negatively correlated ones, show more evidence that they are under delicate splicing control and tend to be functionally important. Additionally, the positively-correlated pairs bear strong resemblance to constitutive exons, which suggests that they may evolve from ancient constitutive exons, while negatively and weakly correlated pairs are more likely to contain newly emerging exons.

Brain barriers and functional interfaces with sequential appearance of ABC efflux transporters during human development

DEFF Research Database (Denmark)

Møllgård, Kjeld; Dziegielewska, Katarzyna M.; Holst, Camilla B.

2017-01-01

Adult brain is protected from entry of drugs and toxins by specific mechanisms such as ABC (ATP-binding Cassette) efflux transporters. Little is known when these appear in human brain during development. Cellular distribution of three main ABC transporters (ABCC1, ABCG2, ABCB1) was determined...... at blood-brain barriers and interfaces in human embryos and fetuses in first half of gestation. Antibodies against claudin-5 and-11 and antibodies to α-fetoprotein were used to describe morphological and functional aspects of brain barriers. First exchange interfaces to be established, probably at 4...... three transporters. Results provide evidence for sequential establishment of brain exchange interfaces and spatial and temporal timetable for three main ABC transporters in early human brain....

Extending the Glucosyl Ceramide Cassette Approach: Application in the Total Synthesis of Ganglioside GalNAc-GM1b

Directory of Open Access Journals (Sweden)

Miku Konishi

2013-12-01

Full Text Available The development of a novel cyclic glucosyl ceramide cassette acceptor for efficient glycolipid syntheses was investigated. p-Methoxybenzyl (PMB groups were selected as protecting groups at C2 and C3 of the glucose residue with the aim of improving the functionality of the cassette acceptor. The choice of the PMB group resulted in a loss of β-selectivity, which was corrected by using an appropriate tether to control the spatial arrangement and the nitrile solvent effect. To investigate the effect of linker structure on the β-selectivity of intramolecular glycosylation, several linkers for tethering the glucose and ceramide moiety were designed and prepared, namely, succinyl, glutaryl, dimethylmalonyl, and phthaloyl esters. The succinyl ester linker was the best for accessing the cassette form. The newly designed glucosyl ceramide cassette acceptor was then applied in the total synthesis of ganglioside GalNAc-GM1b.

5G: rethink mobile communications for 2020+.

Science.gov (United States)

Chih-Lin, I; Han, Shuangfeng; Xu, Zhikun; Sun, Qi; Pan, Zhengang

2016-03-06

The 5G network is anticipated to meet the challenging requirements of mobile traffic in the 2020s, which are characterized by super high data rate, low latency, high mobility, high energy efficiency and high traffic density. This paper provides an overview of China Mobile's 5G vision and potential solutions. Three key characteristics of 5G are analysed, i.e. super fast, soft and green. The main 5G R&D themes are further elaborated, which include five fundamental rethinkings of the traditional design methodologies. The 5G network design considerations are also discussed, with cloud radio access network, ultra-dense network, software defined network and network function virtualization examined as key potential solutions towards a green and soft 5G network. The paradigm shift to user-centric network operation from the traditional cell-centric operation is also investigated, where the decoupled downlink and uplink, control and data, and adaptive multiple connections provide sufficient means to achieve a user-centric 5G network with 'no more cells'. The software defined air interface is investigated under a uniform framework and can adaptively adapt the parameters to well satisfy various requirements in different 5G scenarios. © 2016 The Author(s).

[PAL-1 5G/4G polymorphism in patients with systemic lupus erythematosus].

Science.gov (United States)

Savov, A; Andonova, S; Tanev, D; Robeva, R; Marincheva, Ts; Tomova, A; Kumanov, Ph; Rashkov, R; Kolarov, Zl

2014-01-01

Systemic lupus erythematosus (SLE) is a connective tissue disease affecting predominantly women that has been widely associated with obstetric complications. Inherited thrombophilias are significant risk factors for pregnancy loss, but their role in patients with SLE, and especially in those without concomitant secondary antiphospholipid syndrome (APS) has not been clarified. The aim of the present study was to study PAI-1 5G/4G polymorphism in women with lupus. A total of 103 SLE patients as well as 69 healthy volunteers were genotyped for PAI-1 5G/4G (rs1799889). No significant differences in the PAI-1 5G/4G genotype prevalence between patients and controls were found. After exclusion of the women with secondary APS, the frequency of pregnancies and spontaneous abortions, as well as the number of live births were similar in the studied patients with different PAI-1 genotype (p> 0.05). PAI-1 5G/4G polymorphism was not significantly related to any of the lupus ACR criteria or disease activity (p > 0.05), but it could influence the platelet number in the studied patients (263.52 ± 91.10 [5G/5G genotype] versus 210.12 ± 71.79 [4G/4G genotype], p = 0.023). In conclusion, our results showed that PAI-1 4G/5G polymorphism did not worsen the reproductive outcome in SLE women without secondary APS.

10 CFR 71.5 - Transportation of licensed material.

Science.gov (United States)

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Transportation of licensed material. 71.5 Section 71.5 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL General Provisions § 71.5 Transportation of licensed material. (a) Each licensee who transports licensed...

Choroid plexus transport: gene deletion studies

Directory of Open Access Journals (Sweden)

Keep Richard F

2011-11-01

Full Text Available Abstract This review examines the use of transporter knockout (KO animals to evaluate transporter function at the choroid plexus (the blood-CSF barrier; BCSFB. Compared to the blood-brain barrier, there have been few such studies on choroid plexus (CP function. These have primarily focused on Pept2 (an oligopeptide transporter, ATP-binding cassette (ABC transporters, Oat3 (an organic anion transporter, Svct2 (an ascorbic acid transporter, transthyretin, ion transporters, and ion and water channels. This review focuses on the knowledge gained from such studies, both with respect to specific transporters and in general to the role of the CP and its impact on brain parenchyma. It also discusses the pros and cons of using KO animals in such studies and the technical approaches that can be used.

Polycyclic Aromatic Hydrocarbons (PAHs) Mediate Transcriptional Activation of the ATP Binding Cassette Transporter ABCB6 Gene via the Aryl Hydrocarbon Receptor (AhR)*

Science.gov (United States)

Chavan, Hemantkumar; Krishnamurthy, Partha

2012-01-01

Liver is endowed with a mechanism to induce hepatic cytochromes P450 (CYP450s) in response to therapeutic drugs and environmental contaminants, leading to increased detoxification and elimination of the xenobiotics. Each CYP450 is composed of an apoprotein moiety and a heme prosthetic group, which is required for CYP450 activity. Thus, under conditions of CYP450 induction, there is a coordinate increase in heme biosynthesis to compensate for the increased expression of CYP450s. ABCB6, a mitochondrial ATP binding cassette transporter, which regulates coproporphyrinogen transport from the cytoplasm into the mitochondria to complete heme biosynthesis, represents a previously unrecognized rate-limiting step in heme biosynthesis. However, it is not known if exposure to drugs and environmental contaminants induces ABCB6 expression, to assure an adequate and apparently coordinated supply of heme for the generation of functional cytochrome holoprotein. In the present study, we demonstrate that polycyclic aromatic hydrocarbons (PAHs), the widely distributed environmental toxicants shown to induce porphyrin accumulation causing hepatic porphyria, up-regulate ABCB6 expression in both mice and humans. Using siRNA technology and Abcb6 knock-out mice, we demonstrate that PAH-mediated increase in hepatic porphyrins is compromised in the absence of ABCB6. Moreover, in vivo studies in aryl hydrocarbon receptor (AhR) knock-out mice demonstrate that PAH induction of ABCB6 is mediated by AhR. Promoter activation studies combined with electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrate direct interactions between the AhR binding sites in the ABCB6 promoter and the AhR receptor, implicating drug activation mechanisms for ABCB6 similar to those found in inducible cytochrome P450s. These studies are the first to describe direct transcriptional activation of both mouse and human ABCB6 by xenobiotics. PMID:22761424

Security for 5G Mobile Wireless Networks

OpenAIRE

Fang, Dongfeng; Qian, Yi; Qingyang Hu, Rose

2017-01-01

The advanced features of 5G mobile wireless network systems yield new security requirements and challenges. This paper presents a comprehensive survey on security of 5G wireless network systems compared to the traditional cellular networks. The paper starts with a review on 5G wireless networks particularities as well as on the new requirements and motivations of 5G wireless security. The potential attacks and security services with the consideration of new service requirements and new use ca...

Fully Automated Data Collection Using PAM and the Development of PAM/SPACE Reversible Cassettes

Science.gov (United States)

Hiraki, Masahiko; Watanabe, Shokei; Chavas, Leonard M. G.; Yamada, Yusuke; Matsugaki, Naohiro; Igarashi, Noriyuki; Wakatsuki, Soichi; Fujihashi, Masahiro; Miki, Kunio; Baba, Seiki; Ueno, Go; Yamamoto, Masaki; Suzuki, Mamoru; Nakagawa, Atsushi; Watanabe, Nobuhisa; Tanaka, Isao

2010-06-01

To remotely control and automatically collect data in high-throughput X-ray data collection experiments, the Structural Biology Research Center at the Photon Factory (PF) developed and installed sample exchange robots PAM (PF Automated Mounting system) at PF macromolecular crystallography beamlines; BL-5A, BL-17A, AR-NW12A and AR-NE3A. We developed and installed software that manages the flow of the automated X-ray experiments; sample exchanges, loop-centering and X-ray diffraction data collection. The fully automated data collection function has been available since February 2009. To identify sample cassettes, PAM employs a two-dimensional bar code reader. New beamlines, BL-1A at the Photon Factory and BL32XU at SPring-8, are currently under construction as part of Targeted Proteins Research Program (TPRP) by the Ministry of Education, Culture, Sports, Science and Technology of Japan. However, different robots, PAM and SPACE (SPring-8 Precise Automatic Cryo-sample Exchanger), will be installed at BL-1A and BL32XU, respectively. For the convenience of the users of both facilities, pins and cassettes for PAM and SPACE are developed as part of the TPRP.

Engineered XcmI cassette-containing vector for PCR-based ...

Indian Academy of Sciences (India)

Unknown

A simple and general method is described to construct a new vector bearing a synthetic XcmI cassette for direct cloning of PCR-amplified genes of interest. Cleavage of the vector with XcmI generates a linearized molecule with a single thymidine (T) overhang at the 3′ ends (T-vector) that facilitates TA cloning of PCR ...

Plasminogen activator inhibitor 1 4G/5G and -844G/A variants in idiopathic recurrent pregnancy loss.

Science.gov (United States)

Magdoud, Kalthoum; Herbepin, Viviana G; Touraine, Renaud; Almawi, Wassim Y; Mahjoub, Touhami

2013-09-01

Plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis, and the common promoter region variants -675G/A (4G/5G) and -844G/A are associated with increased thrombotic risk. Despite evidence linking altered fibrinolysis with adverse pregnancy events, including idiopathic recurrent pregnancy loss (RPL), the contribution of PAI-1 variants to RPL risk remains controversial. We investigated the association between the PAI-1 -844G/A and 4G/5G (-675G/A) variants with altered risk of RPL. This was a case-control study involving 304 women with confirmed RPL and 371 age- and ethnically matched control women. PAI-1 genotyping was performed by PCR single-specific primer -675 (G/A) and real-time PCR (-844G/A) analysis. Minor allele frequency (MAF) of 4G/5G (P 5G single-nucleotide polymorphism (SNP) was significantly associated with RPL under additive, dominant, and recessive genetic models; no association of -844G/A with RPL was seen irrespective of the genetic model tested. Taking common -844G/5G haplotype as reference (OR = 1.00), multivariate analysis confirmed the association of 4G-containing -844A/4G (P 5G, but not -844G/A, PAI-1 variant is associated with an increased risk of RPL. © 2013 John Wiley & Sons Ltd.

Plasminogen activator inhibitor I 4G/5G polymorphism in neonatal respiratory distress syndrome.

Science.gov (United States)

Armangil, Didem; Yurdakök, Murat; Okur, Hamza; Gürgey, Aytemiz

2011-08-01

Fibrin monomers inhibit surfactant function. 4G/5G insertion/deletion polymorphism plays an important role in the regulation of plasminogen activator inhibitor 1 (PAI-1) gene expression. To examine the genotype distribution of PAI-1 polymorphism in 60 infants with respiratory distress syndrome (RDS) and 53 controls, an allele-specific polymerase chain reaction (PCR) was used. The proportion of 4G/4G, 4G/5G, and 5G/5G genotypes did not differ statistically between the RDS and control groups (P > .05). Having PAI-1 4G/4G genotype polymorphism appears to increase the risk of RDS (odds ratio [OR] =1.5; 95% confidence interval [CI], 0.5-4.3), although it was not statistically significant. No relation was found between the PAI-1 4G/5G polymorphisms and RDS, but there was an increased risk associated with the 4G variant of the PAI-1 gene. We believe that our findings of increased 4G allele of the PAI-1 gene in infants with RDS would also help to clarify the pathogenesis of RDS.

Glycolysis inhibition inactivates ABC transporters to restore drug sensitivity in malignant cells.

Directory of Open Access Journals (Sweden)

Ayako Nakano

Full Text Available Cancer cells eventually acquire drug resistance largely via the aberrant expression of ATP-binding cassette (ABC transporters, ATP-dependent efflux pumps. Because cancer cells produce ATP mostly through glycolysis, in the present study we explored the effects of inhibiting glycolysis on the ABC transporter function and drug sensitivity of malignant cells. Inhibition of glycolysis by 3-bromopyruvate (3BrPA suppressed ATP production in malignant cells, and restored the retention of daunorubicin or mitoxantrone in ABC transporter-expressing, RPMI8226 (ABCG2, KG-1 (ABCB1 and HepG2 cells (ABCB1 and ABCG2. Interestingly, although side population (SP cells isolated from RPMI8226 cells exhibited higher levels of glycolysis with an increased expression of genes involved in the glycolytic pathway, 3BrPA abolished Hoechst 33342 exclusion in SP cells. 3BrPA also disrupted clonogenic capacity in malignant cell lines including RPMI8226, KG-1, and HepG2. Furthermore, 3BrPA restored cytotoxic effects of daunorubicin and doxorubicin on KG-1 and RPMI8226 cells, and markedly suppressed subcutaneous tumor growth in combination with doxorubicin in RPMI8226-implanted mice. These results collectively suggest that the inhibition of glycolysis is able to overcome drug resistance in ABC transporter-expressing malignant cells through the inactivation of ABC transporters and impairment of SP cells with enhanced glycolysis as well as clonogenic cells.

The ITER divertor cassette. Steady state characterisation and draining and drying transient hydraulic analyses

International Nuclear Information System (INIS)

Pietro Alessandro Di Maio; Valerio Tomarchio; Giuseppe Vella; Irene Zammuto; Giovanni Dell'Orco

2005-01-01

gas bubbles. Due to the complex flow scheme of the hydraulic circuit, a pure theoretical study does not appears sufficient to address all the above mentioned items and an experimental validation of the models is mandatory. In addition to that, the assembly of the PFCs onto the cassette body as well as their integration by welding the coolant connections of the PFCs, also represent a critical step to be investigated. In order to investigate the aforementioned critical issues a theoretical and experimental research activity has been launched by the ENEA-Brasimone labs, in cooperation with the Department of Nuclear Engineering of the University of Palermo, with the specific aim of investigating the thermal-hydraulic behaviour of the whole divertor cassette both in steady state and operational or accidental transient conditions. The theoretical study, based on a computational approach, has been carried out with the RELAP5 code and the results obtained are herewith presented and critically discussed. In particular, the paper presents steady state and transient theoretical analyses intended to characterise the steady state behaviour of the cassette, determining flow distribution, pressure drop and CHF margin for each cooling channels, and to investigate the cassette behaviour during the draining and drying procedure, respectively. (authors)

Distinct effects of struvite and biochar amendment on the class 1 integron antibiotic resistance gene cassettes in phyllosphere and rhizosphere.

Science.gov (United States)

An, Xin-Li; Chen, Qing-Lin; Zhu, Dong; Su, Jian-Qiang

2018-08-01

Struvite recovered from wastewater is promising for recycling phosphorus into soil as fertilizers. However, struvite application may prompt the proliferation of antibiotic resistance in soil and plant. This study examined the impacts of struvite application and biochar amendment on integrons abundance and gene cassette contexts in rhizosphere soil and phyllosphere using quantitative PCR and clone library analysis. Microcosm experiments revealed that class 1 integron was the most prevalent in all samples, with higher concentration and higher relative abundance in rhizosphere than those in phyllosphere. The majority of resistance gene cassettes were associated with genes encoding resistance to aminoglycosides, beta-lactams and chloramphenicols. Struvite application significantly increased the genetic diversity of antibiotic resistance gene cassettes in both rhizosphere and phyllosphere. However, biochar amendment attenuated the increasing effect of struvite application exerting on the class 1 integron antibiotic resistance gene cassette pool in phyllosphere. These findings highlighted human activities to be the source of integron gene cassette pool and raised the possibility of using biochar amendment as an alternative mean for mitigating antibiotic resistance in environments. Copyright © 2018 Elsevier B.V. All rights reserved.

14 CFR 221.5 - Unauthorized air transportation.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Unauthorized air transportation. 221.5... PROCEEDINGS) ECONOMIC REGULATIONS TARIFFS General § 221.5 Unauthorized air transportation. Tariff publications... Department's granting authority to perform the foreign air transportation covered by such tariff publications...

X-ray transport and radiation response assessment (XTRRA) experiments at the National Ignition Facility

Energy Technology Data Exchange (ETDEWEB)

Fournier, K. B., E-mail: fournier2@llnl.gov; Brown, C. G.; Yeoman, M. F.; Compton, S.; Holdener, F. R.; Kemp, G. E.; Blue, B. E. [Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94551 (United States); Fisher, J. H.; Newlander, C. D.; Gilliam, R. P.; Froula, N. [Fifth Gait Technologies, Inc., 14040 Camden Circle, Huntsville, Alabama 35803 (United States); Seiler, S. W.; Davis, J. F.; Lerch, MAJ. A. [Defense Threat Reduction Agency, 8725 John J. Kingman Road, Fort Belvoir, Virginia 22060-6201 (United States); Hinshelwood, D. [Naval Research Laboratory, 4555 Overlook Ave. SW, Washington, DC 20375 (United States); Lilly, M. [Dynasen, Inc., 20 Arnold Pl., Goleta, California 93117 (United States)

2016-11-15

Our team has developed an experimental platform to evaluate the x-ray-generated stress and impulse in materials. Experimental activities include x-ray source development, design of the sample mounting hardware and sensors interfaced to the National Ignition Facility’s diagnostics insertion system, and system integration into the facility. This paper focuses on the X-ray Transport and Radiation Response Assessment (XTRRA) test cassettes built for these experiments. The test cassette is designed to position six samples at three predetermined distances from the source, each known to within ±1% accuracy. Built-in calorimeters give in situ measurements of the x-ray environment along the sample lines of sight. The measured accuracy of sample responses as well as planned modifications to the XTRRA cassette is discussed.

A Study on the Measurement of the Pollution Level of Bacteria and Disinfection of Table and IP Cassette

International Nuclear Information System (INIS)

Bae, Seok Hwan; Lee, Moo Sik; Lim, Chang Seon; Kim, Gha Jung

2008-01-01

For the number of microbes and the pollution level of bacteriology of IP Cassette and Table by laboratories, after identifying the bacteria before and after using alcohol and tissue including disinfectant and statistically testing, this research was intended to provide the basic data for the prevention and the right disinfection guideline for infection management of hospitals in diagnostic radiology. The subject of this research was the general room of diagnostic radiology of a university hospital in Daejeon City. The research was conducted from Apr 5 to Apr 12, 2007. The number of microbes and the pollution level of bacteriology of IP Cassette and Table by laboratories were tested before and after using alcohol and tissue for disinfection including disinfectant. In order to collect specimens exactly, they were collected with the nurse who specialized in infection management of the hospital, and statistical processing was done with SPSS V13.0. To compare the results before and after using alcohol and tissue, T-test was implemented, and post-hoc test was conducted. Bacteria were detected in 19 cases of 24 subjects(79.2%), however, they were not detected in 5 cases(20.8%). 7 kinds of bacteria were detected as isolated bacteria, of which Methicillin Resistant coagulase-negative Staphylococci(MRCNS) were detected in 15 cases(62.5%), which was most, Methicillin Resistant Staphylococcus Aureus(MRSA) in 6 cases(16.7%), Enterococcus Faecium(EFM) in 5 cases(20.8%), Acinetobacter baumannii(ABA) in 2 cases(8.3%), and Bacillus sp, Coagulase-negative Staphylococci(CNS), and Enterococcus sp(ENT) in 1 case, respectively(4.2%). In all bacteria except ABA, Gram positive bacillia were detected in 30 cases(97%), and Gram negative bacilli were detected only in 1 case(3%). As for the kinds of bacteria and the number of groups before and after using 70% Alcohol by Groups, when the bacteria were identified after disinfecting IP Cassette and Table with 70% Alcohol, all the bacteria became

A Study on the Measurement of the Pollution Level of Bacteria and Disinfection of Table and IP Cassette

Energy Technology Data Exchange (ETDEWEB)

Bae, Seok Hwan; Lee, Moo Sik; Lim, Chang Seon; Kim, Gha Jung [Koyang University, Koyang (Korea, Republic of)

2008-09-15

For the number of microbes and the pollution level of bacteriology of IP Cassette and Table by laboratories, after identifying the bacteria before and after using alcohol and tissue including disinfectant and statistically testing, this research was intended to provide the basic data for the prevention and the right disinfection guideline for infection management of hospitals in diagnostic radiology. The subject of this research was the general room of diagnostic radiology of a university hospital in Daejeon City. The research was conducted from Apr 5 to Apr 12, 2007. The number of microbes and the pollution level of bacteriology of IP Cassette and Table by laboratories were tested before and after using alcohol and tissue for disinfection including disinfectant. In order to collect specimens exactly, they were collected with the nurse who specialized in infection management of the hospital, and statistical processing was done with SPSS V13.0. To compare the results before and after using alcohol and tissue, T-test was implemented, and post-hoc test was conducted. Bacteria were detected in 19 cases of 24 subjects(79.2%), however, they were not detected in 5 cases(20.8%). 7 kinds of bacteria were detected as isolated bacteria, of which Methicillin Resistant coagulase-negative Staphylococci(MRCNS) were detected in 15 cases(62.5%), which was most, Methicillin Resistant Staphylococcus Aureus(MRSA) in 6 cases(16.7%), Enterococcus Faecium(EFM) in 5 cases(20.8%), Acinetobacter baumannii(ABA) in 2 cases(8.3%), and Bacillus sp, Coagulase-negative Staphylococci(CNS), and Enterococcus sp(ENT) in 1 case, respectively(4.2%). In all bacteria except ABA, Gram positive bacillia were detected in 30 cases(97%), and Gram negative bacilli were detected only in 1 case(3%). As for the kinds of bacteria and the number of groups before and after using 70% Alcohol by Groups, when the bacteria were identified after disinfecting IP Cassette and Table with 70% Alcohol, all the bacteria became

The prevalence of PAI-1 4G/5G gene variant in Serbian population

Directory of Open Access Journals (Sweden)

Đorđević Valentina

2013-01-01

Full Text Available Introduction: Plasminogen activator inhibitor 1 (PAI-1 has a major role in inhibition of firinolysis and normal haemostasis. The presence of the PAI-1 4G/4G genotype leads to increased expression of PAI-1. High blood level of PAI-1 is associated with many diseases such as thrombosis, cerebral insult, myocardial infarction, pregnancy loss, preeclampsia, insulin resistance, type 2 diabetes, breast cancer and asthma. In this study, the prevalence of PAI-1 4G/5G gene variant was determined in healthy subjects from Serbian population. Methods: The study was carried out in a group of 210 healthy subjects (105 women and 105 men. The presence of PAI-1 4G/5G gene variant was detected by PCR-RFLP analysis. Results: The prevalence of PAI-1 4G/4G genotype was 34.76% and it was increased compared to PAI-1 5G/5G genotype (19.05%. The most frequent was PAI-1 4G/5G genotype (46.19%. Allelic frequency for 4G allele was higher (0.58 compared to 5G allele (0.42. Conclusions: The prevalence of PAI-1 4G/5G gene variant in Serbian population is similar to the neighboring populations. Results of this study represent the first data for Serbian population. This study could be useful for further research where the role of PAI-1 4G/5G gene variant will be assessed in the pathogenesis of many diseases.

Insulin-like Growth Factor 1 Regulates the Expression of ATP-Binding Cassette Transporter A1 in Pancreatic Beta Cells.

Science.gov (United States)

Lyu, J; Imachi, H; Iwama, H; Zhang, H; Murao, K

2016-05-01

ATP-binding cassette transporter A1 (ABCA1) in pancreatic beta cells influences insulin secretion and cholesterol homeostasis. The present study investigates whether insulin-like growth factor 1 (IGF-1), which mediates stimulation of ABCA1 gene expression, could also interfere with the phosphatidylinositol 3-kinase (PI3-K) cascade.ABCA1 expression was examined by real-time polymerase chain reaction (PCR), Western blot analysis, and a reporter gene assay in rat insulin-secreting INS-1 cells incubated with IGF-1. The binding of forkhead box O1 (FoxO1) protein to the ABCA1 promoter was assessed by a chromatin immunoprecipitation (ChIP) assay. ABCA1 protein levels increased in response to rising concentrations of IGF-1. Real-time PCR analysis showed a significant increase in ABCA1 mRNA expression. However, both effects were suppressed after silencing the IGF-1 receptor. In parallel with its effect on endogenous ABCA1 mRNA levels, IGF-1 induced the activity of a reporter construct containing the ABCA1 promoter, while it was abrogated by LY294002, a specific inhibitor of PI3-K. Constitutively active Akt stimulated activity of the ABCA1 promoter, and a dominant-negative mutant of Akt or mutagenesis of the FoxO1 response element in the ABCA1 promoter abolished the ability of IGF-1 to stimulate promoter activity. A ChIP assay showed that FoxO1 mediated its transcriptional activity by directly binding to the ABCA1 promoter region. The knockdown of FoxO1 disrupted the effect of IGF-1 on ABCA1 expression. Furthermore, IGF-1 promoted cholesterol efflux and reduced the pancreatic lipotoxicity. These results demonstrate that the PI3-K/Akt/FoxO1 pathway contributes to the regulation of ABCA1 expression in response to IGF-1 stimulation. © Georg Thieme Verlag KG Stuttgart · New York.

Transporter-mediated natural product–drug interactions for the treatment of cardiovascular diseases

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Weibin Zha

2018-04-01

Full Text Available The growing use of natural products in cardiovascular (CV patients has been greatly raising the concerns about potential natural product–CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product–CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product–drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins have been identified to be substrates and inhibitors of the solute carrier (SLC transporters and the ATP-binding cassette (ABC transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product–CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product–CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product–CV drug interactions and help public and physicians understand these type of interactions. Keywords: Cardiovascular drugs, Natural products, Drug transporters, Natural product–drug interaction, Pharmacokinetics

Structural variations in wheat HKT1;5 underpin differences in Na+ transport capacity

KAUST Repository

Xu, Bo

2017-11-27

An important trait associated with the salt tolerance of wheat is the exclusion of sodium ions (Na+) from the shoot. We have previously shown that the sodium transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na+-exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression, we show that the affinity (Km) for the Na+ transport of TmHKT1;5-A, at 2.66 mM, is higher than that of TaHKT1;5-D at 7.50 mM. Through 3D structural modelling, we identify residues D471/a gap and D474/G473 that contribute to this property. We identify four additional mutations in amino acid residues that inhibit the transport activity of TmHKT1;5-A, which are predicted to be the result of an occlusion of the pore. We propose that the underlying transport properties of TmHKT1;5-A and TaHKT1;5-D contribute to their unique ability to improve Na+ exclusion in wheat that leads to an improved salinity tolerance in the field.

Structural variations in wheat HKT1;5 underpin differences in Na+ transport capacity

KAUST Repository

Xu, Bo; Waters, Shane; Byrt, Caitlin S.; Plett, Darren; Tyerman, Stephen D.; Tester, Mark A.; Munns, Rana; Hrmova, Maria; Gilliham, Mathew

2017-01-01

An important trait associated with the salt tolerance of wheat is the exclusion of sodium ions (Na+) from the shoot. We have previously shown that the sodium transporters TmHKT1;5-A and TaHKT1;5-D, from Triticum monoccocum (Tm) and Triticum aestivum (Ta), are encoded by genes underlying the major shoot Na+-exclusion loci Nax1 and Kna1, respectively. Here, using heterologous expression, we show that the affinity (Km) for the Na+ transport of TmHKT1;5-A, at 2.66 mM, is higher than that of TaHKT1;5-D at 7.50 mM. Through 3D structural modelling, we identify residues D471/a gap and D474/G473 that contribute to this property. We identify four additional mutations in amino acid residues that inhibit the transport activity of TmHKT1;5-A, which are predicted to be the result of an occlusion of the pore. We propose that the underlying transport properties of TmHKT1;5-A and TaHKT1;5-D contribute to their unique ability to improve Na+ exclusion in wheat that leads to an improved salinity tolerance in the field.

IMB2026791, a Xanthone, Stimulates Cholesterol Efflux by Increasing the Binding of Apolipoprotein A-I to ATP-Binding Cassette Transporter A1

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Zijian Xie

2012-03-01

Full Text Available It is known that the ATP-binding cassette transporter A1 (ABCA1 plays a major role in cholesterol homeostasis and high density lipoprotein (HDL metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791 was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC50 of 25.23 μM.

2. 5 MV Van de Graaff accelerator (VdG) and associated experimental equipments

Energy Technology Data Exchange (ETDEWEB)

Hasai, Hiromi; Iwatani, Kazuo; Shizuma, Kiyoshi; Nishiyama, Fumitaka

1984-12-01

A 2.5 MV VdG accelerator was recently installed in Saijo new campus, Higashi-Hiroshima and started into operation. This paper reports specifications of the accelerator and associated experimental equipments. Available ion beams are hydrogen, helium, nitrogen and, in addition, electrons by means of quick-conversion kit. A switching magnet, a beam transport tube with two beam slits and a vacuum chamber are connected to the accelerator. This VdG accelerator will be used not only for nuclear physics but also for researches of atomic, solid-state physics and microanalysis of elements of enviromental samples. (author).

Integron types, gene cassettes and antimicrobial resistance profile of Acinetobacter baumannii isolated from BAL samples in Babol, north of Iran.

Science.gov (United States)

Akrami, Fariba; Shahandashti, Elaheh Ferdosi; Yahyapour, Yousef; Sadeghi, Mohsen; Khafri, Soraya; Pournajaf, Abazar; Rajabnia, Ramazan

2017-08-01

Multi-drug resistant isolates of Acinetobacter baumannii have created therapeutic problems worldwide. This current study was intended to determine the Integron types, gene cassettes and antimicrobial resistance profile of A. baumannii isolated from BAL samples in Babol, north of Iran. During a 15-month period, 35 A. baumannii isolates were studied. Different classes of antimicrobial agents were used to determine the resistance ratios. Multiplex-PCR was used to detect different types of integrons and associated gene cassettes. The resistance rates to GM, FEP, AK, TOB, CP, PIP, SAM, IPM, SXT, CTX, CAZ, CL, TIM, MEM, and TZP were 85.7%, 100%, 91.4%, 68.5%, 94.3%, 88.5%, 97.1%, 94.3%, 100%, 100%, 100%, 0.0%, 91.4%, 94.3% and 91.4%, respectively. The distribution analysis of int genes showed that 25.7%, 88.6% and 28.6% of isolates carried the intI, intII and intIII genes, respectively. The prevalence of aadB, dfrA1, bla-OXA 30 and aadA1 genes were 94.3%, 77.1%, 40% and 5.7%, respectively. The current study showed that a high level of A. baumannii isolates harbor integrons in our therapeutic center, which may lead to distribution of multiple antimicrobial resistance. The different types of gene cassette arrays in the present study highlight the important role of geographical features in MDR isolates dissemination which could be credited to different profiles of drug consumption in different areas. The findings emphasized that the need for continuous surveillance to prevent distribution of multidrug resistance among A. baumannii strains in Iran. Copyright © 2017. Published by Elsevier Ltd.

Heterocyclic cyclohexanone monocarbonyl analogs of curcumin can inhibit the activity of ATP-binding cassette transporters in cancer multidrug resistance.

Science.gov (United States)

Revalde, Jezrael L; Li, Yan; Hawkins, Bill C; Rosengren, Rhonda J; Paxton, James W

2015-02-01

Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins 1 and 5 (MRP1 and MRP5). The use of CUR in the clinic however, is complicated by its instability and poor pharmacokinetic profile. Monocarbonyl analogs of CUR (MACs) are compounds without CUR's unstable β-diketone moiety and were reported to have improved stability and in vivo disposition. Whether the MACs can be used as MDR reversal agents is less clear, as the absence of a β-diketone may negatively impact transporter inhibition. In this study, we investigated 23 heterocyclic cyclohexanone MACs for inhibitory effects against P-gp, BCRP, MRP1 and MRP5. Using flow cytometry and resistance reversal assays, we found that many of these compounds inhibited the transport activity of the ABC transporters investigated, often with much greater potency than CUR. Overall the analogs were most effective at inhibiting BCRP and we identified three compounds, A12 (2,6-bis((E)-2,5-dimethoxy-benzylidene)cyclohexanone), A13 (2,6-bis((E)-4-hydroxyl-3-methoxybenzylidene)-cyclohexanone) and B11 (3,5-bis((E)-2-fluoro-4,5-dimethoxybenzylidene)-1-methylpiperidin-4-one), as the most promising BCRP inhibitors. These compounds inhibited BCRP activity in a non-cell line, non-substrate-specific manner. Their inhibition occurred by direct transporter interaction rather than modulating protein or cell surface expression. From these results, we concluded that MACs, such as the heterocyclic cyclohexanone analogs in this study, also have potential as MDR reversal agents and may be superior alternatives to the unstable parent compound, CUR. Copyright © 2014 Elsevier Inc. All rights reserved.

p21-ras effector domain mutants constructed by "cassette" mutagenesis

DEFF Research Database (Denmark)

Stone, J C; Vass, W C; Willumsen, B M

1988-01-01

A series of mutations encoding single-amino-acid substitutions within the v-rasH effector domain were constructed, and the ability of the mutants to induce focal transformation of NIH 3T3 cells was studied. The mutations, which spanned codons 32 to 40, were made by a "cassette" mutagenesis...

Transporter-mediated natural product-drug interactions for the treatment of cardiovascular diseases.

Science.gov (United States)

Zha, Weibin

2018-04-01

The growing use of natural products in cardiovascular (CV) patients has been greatly raising the concerns about potential natural product-CV drug interactions. Some of these may lead to unexpected cardiovascular adverse effects and it is, therefore, essential to identify or predict potential natural product-CV drug interactions, and to understand the underlying mechanisms. Drug transporters are important determinants for the pharmacokinetics of drugs and alterations of drug transport has been recognized as one of the major causes of natural product-drug interactions. In last two decades, many CV drugs (e.g., angiotensin II receptor blockers, beta-blockers and statins) have been identified to be substrates and inhibitors of the solute carrier (SLC) transporters and the ATP-binding cassette (ABC) transporters, which are two major transporter superfamilies. Meanwhile, in vitro and in vivo studies indicate that a growing number of natural products showed cardioprotective effects (e.g., gingko biloba, danshen and their active ingredients) are also substrates and inhibitors of drug transporters. Thus, to understand transporter-mediated natural product-CV drug interactions is important and some transporter-mediated interactions have already shown to have clinical relevance. In this review, we review the current knowledge on the role of ABC and SLC transporters in CV therapy, as well as transporter modulation by natural products used in CV diseases and their induced natural product-CV drug interactions through alterations of drug transport. We hope our review will aid in a comprehensive summary of transporter-mediated natural product-CV drug interactions and help public and physicians understand these type of interactions. Copyright © 2017. Published by Elsevier B.V.

PAI-1 4G/5G polymorphism contributes to cancer susceptibility: evidence from meta-analysis.

Science.gov (United States)

Wang, Shangqian; Cao, Qiang; Wang, Xiaoxiang; Li, Bingjie; Tang, Min; Yuan, Wanqing; Fang, Jianzheng; Qian, Jian; Qin, Chao; Zhang, Wei

2013-01-01

The plasminogen activator inhibitor-1 (PAI-1) is expressed in many cancer cell types and allows the modulation of cancer growth, invasion and angiogenesis. To date, studies investigated the association between a functional polymorphism in PAI-1 (4G/5G) and risk of cancer have shown inclusive results. A meta-analysis based on 25 case-control studies was performed to address this issue. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with I(2) test. Overall, a significant increased risk of cancer was associated with the PAI-1 4G/4G polymorphism for the allele contrast (4G vs. 5G: OR = 1.10, CI = 1.03-1.18, I(2) = 49.5%), the additive genetic model (4G/4G vs. 5G/5G: OR = 1.21, CI = 1.06-1.39, I(2) = 51.9%), the recessive genetic model (4G/4G vs. 4G/5G+5G/5G: OR = 1.11, CI = 1.04-1.18, I(2) = 20.8%). In the subgroup analysis by ethnicity, the results indicated that individuals with 4G/4G genotype had a significantly higher cancer risk among Caucasians (4G/4G vs. 5G/5G: OR = 1.31, 95%CI = 1.09-1.59, I(2) = 59.6%; 4G/4G vs. 4G/5G: OR = 1.12, 95%CI = 1.04-1.21, I(2) = 3.6%; recessive model: OR = 1.12, 95%CI = 1.05-1.21, I(2) = 25.3%). The results of the present meta-analysis support an association between the PAI-1 4G/5G polymorphism and increasing cancer risk, especially among Caucasians, and those with 4G allele have a high risk to develop colorectal cancer and endometrial cancer.

Sequencing of IncX-plasmids suggests ubiquity of mobile forms of a biofilm-promoting gene cassette recruited from Klebsiella pneumoniae.

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Mette Burmølle

Full Text Available Plasmids are a highly effective means with which genetic traits that influence human health, such as virulence and antibiotic resistance, are disseminated through bacterial populations. The IncX-family is a hitherto sparsely populated group of plasmids that are able to thrive within Enterobacteriaceae. In this study, a replicon-centric screening method was used to locate strains from wastewater sludge containing plasmids belonging to the IncX-family. A transposon aided plasmid capture method was then employed to transport IncX-plasmids from their original hosts (and co-hosted plasmids into a laboratory strain (Escherichia coli Genehogs® for further study. The nucleotide sequences of the three newly isolated IncX-plasmids (pLN126_33, pMO17_54, pMO440_54 and the hitherto un-sequenced type-plasmid R485 revealed a remarkable occurrence of whole or partial gene cassettes that promote biofilm-formation in Klebsiella pneumonia or E. coli, in all four instances. Two of the plasmids (R485 and pLN126_33 were shown to directly induce biofilm formation in a crystal violet retention assay in E. coli. Sequence comparison revealed that all plasmid-borne forms of the type 3 fimbriae encoding gene cassette mrkABCDF were variations of a composite transposon Tn6011 first described in the E. coli IncX plasmid pOLA52. In conclusion, IncX-plasmids isolated from Enterobacteriaceae over almost 40 years and on three different continents have all been shown to carry a type 3 fimbriae gene cassette mrkABCDF stemming from pathogenic K. pneumoniae. Apart from contributing general knowledge about IncX-plasmids, this study also suggests an apparent ubiquity of a mobile form of an important virulence factor and is an illuminating example of the recruitment, evolution and dissemination of genetic traits through plasmid-mediated horizontal gene transfer.

Sequencing of IncX-plasmids suggests ubiquity of mobile forms of a biofilm-promoting gene cassette recruited from Klebsiella pneumoniae.

Science.gov (United States)

Burmølle, Mette; Norman, Anders; Sørensen, Søren J; Hansen, Lars Hestbjerg

2012-01-01

Plasmids are a highly effective means with which genetic traits that influence human health, such as virulence and antibiotic resistance, are disseminated through bacterial populations. The IncX-family is a hitherto sparsely populated group of plasmids that are able to thrive within Enterobacteriaceae. In this study, a replicon-centric screening method was used to locate strains from wastewater sludge containing plasmids belonging to the IncX-family. A transposon aided plasmid capture method was then employed to transport IncX-plasmids from their original hosts (and co-hosted plasmids) into a laboratory strain (Escherichia coli Genehogs®) for further study. The nucleotide sequences of the three newly isolated IncX-plasmids (pLN126_33, pMO17_54, pMO440_54) and the hitherto un-sequenced type-plasmid R485 revealed a remarkable occurrence of whole or partial gene cassettes that promote biofilm-formation in Klebsiella pneumonia or E. coli, in all four instances. Two of the plasmids (R485 and pLN126_33) were shown to directly induce biofilm formation in a crystal violet retention assay in E. coli. Sequence comparison revealed that all plasmid-borne forms of the type 3 fimbriae encoding gene cassette mrkABCDF were variations of a composite transposon Tn6011 first described in the E. coli IncX plasmid pOLA52. In conclusion, IncX-plasmids isolated from Enterobacteriaceae over almost 40 years and on three different continents have all been shown to carry a type 3 fimbriae gene cassette mrkABCDF stemming from pathogenic K. pneumoniae. Apart from contributing general knowledge about IncX-plasmids, this study also suggests an apparent ubiquity of a mobile form of an important virulence factor and is an illuminating example of the recruitment, evolution and dissemination of genetic traits through plasmid-mediated horizontal gene transfer.

ABC transporters from Botrytis cinerea in biotic and abiotic interactions

NARCIS (Netherlands)

Schoonbeek, H.

2004-01-01

Botrytis cinereais the causal agent of grey mould disease on a wide variety of crop plants. It is relatively insensitive to natural and synthetic fungitoxic compounds. This thesis describes how ABC (ATP-binding cassette) transporters contribute to protection by actively

Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model [v1; ref status: indexed, http://f1000r.es/41n

Directory of Open Access Journals (Sweden)

Sergi Vaquer

2014-08-01

Full Text Available Abstract Microgravity has been shown to influence the expression of ABC (ATP-Binding Cassette transporters in bacteria, fungi and mammals, but also to modify the activity of certain cellular components with structural and functional similarities to ABC transporters. Changes in activity of ABC transporters could lead to important metabolic disorders and undesired pharmacological effects during spaceflights. However, no current means exist to study the functionality of these transporters in microgravity. To this end, a Vesicular Transport Assay® (Solvo Biotechnology, Hungary was adapted to evaluate multi-drug resistance-associated protein 2 (MRP2 trans-membrane estradiol-17-β-glucuronide (E17βG transport activity, when activated by adenosine-tri-phosphate (ATP during parabolic flights. Simple diffusion, ATP-independent transport and benzbromarone inhibition were also evaluated. A high accuracy engineering system was designed to perform, monitor and synchronize all procedures. Samples were analysed using a validated high sensitivity drug detection protocol. Experiments were performed in microgravity during parabolic flights, and compared to 1g on ground results using identical equipment and procedures in all cases. Our results revealed that sufficient equipment accuracy and analytical sensitivity were reached to detect transport activity in both gravitational conditions. Additionally, transport activity levels of on ground samples were within commercial transport standards, proving the validity of the methods and equipment used. MRP2 net transport activity was significantly reduced in microgravity, so was signal detected in simple diffusion samples. Ultra-structural changes induced by gravitational stress upon vesicle membranes or transporters could explain the current results, although alternative explanations are possible. Further research is needed to provide a conclusive answer in this regard. Nevertheless, the present validated technology

The standardisation process of 5G

DEFF Research Database (Denmark)

Sørensen, Jannick Kirk; Tadayoni, Reza; Henten, Anders

2016-01-01

The aim of the paper is to gain a better understanding of the processes of standardization relating to 5G. This includes an understanding of how 5G can be conceptualized. It also includes knowledge on where the processes of standardization take place. The paper introduces two different analytical...... for conceptualizing the more confrontational aspects....

Evaluation of D-1 tape and cassette characteristics: Moisture content of Sony and Ampex D-1 tapes when delivered

Science.gov (United States)

Ashton, Gary

Commercial D-1 cassette tapes and their associated recorders were designed to operate in broadcast studios and record in accordance with the International Radio Consultative Committee (CCIR) 607 digital video standards. The D-1 recorder resulted in the Society of Motion Picture and Television Engineers (SMPTE) standards 224 to 228 and is the first digital video recorder to be standardized for the broadcast industry. The D-1 cassette and associated media are currently marketed for broadcast use. The recorder was redesigned for data applications and is in the early stages of being evaluated. The digital data formats used are specified in MIL-STD-2179 and the American National Standards Institute (ANSI) X3.175-190 standard. In early 1990, the National Media Laboratory (NML) was asked to study the effects of time, temperature, and relative humidity on commercial D-1 cassettes. The environmental range to be studied was the one selected for the Advanced Tactical Air Reconnaissance System (ATARS) program. Several discussions between NML personnel, ATARS representatives, recorder contractors, and other interested parties were held to decide upon the experimental plan to be implemented. Review meetings were held periodically during the course of the experiment. The experiments were designed to determine the dimensional stability of the media and cassette since this is one of the major limiting factors of helical recorders when the media or recorders are subjected to non-broadcasting environments. Measurements were also made to characterize each sample of cassettes to give preliminary information on which purchase specifications could be developed. The actual tests performed on the cassettes and media before and after aging fall into the general categories listed.

5G wireless technologies

CERN Document Server

Alexiou, Angeliki

2017-01-01

Mobile data traffic is expected to exceed traffic from wired devices in the next couple of years. This book presents a roadmap of 5G, from advanced radio technologies to innovative resource management approaches and novel network architectures and system concepts.

3-D extension C5G7 MOX benchmark calculation using threedant code

International Nuclear Information System (INIS)

Kim, H.Ch.; Han, Ch.Y.; Kim, J.K.; Na, B.Ch.

2005-01-01

It pursued the benchmark on deterministic 3-D MOX fuel assembly transport calculations without spatial homogenization (C5G7 MOX Benchmark Extension). The goal of this benchmark is to provide a more through test results for the abilities of current available 3-D methods to handle the spatial heterogeneities of reactor core. The benchmark requires solutions in the form of normalized pin powers as well as the eigenvalue for each of the control rod configurations; without rod, with A rods, and with B rods. In this work, the DANTSYS code package was applied to analyze the 3-D Extension C5G7 MOX Benchmark problems. The THREEDANT code within the DANTSYS code package, which solves the 3-D transport equation in x-y-z, and r-z-theta geometries, was employed to perform the benchmark calculations. To analyze the benchmark with the THREEDANT code, proper spatial and angular approximations were made. Several calculations were performed to investigate the effects of the different spatial approximations on the accuracy. The results from these sensitivity studies were analyzed and discussed. From the results, it is found that the 4*4 grid per pin cell is sufficiently refined so that very little benefit is obtained by increasing the mesh size. (authors)

Polymorphism in ABC transporter genes of Dirofilaria immitis

Directory of Open Access Journals (Sweden)

Thangadurai Mani

2017-08-01

Full Text Available Dirofilaria immitis, a filarial nematode, causes dirofilariasis in dogs, cats and occasionally in humans. Prevention of the disease has been mainly by monthly use of the macrocyclic lactone (ML endectocides during the mosquito transmission season. Recently, ML resistance has been confirmed in D. immitis and therefore, there is a need to find new classes of anthelmintics. One of the mechanisms associated with ML resistance in nematodes has been the possible role of ATP binding cassette (ABC transporters in reducing drug concentrations at receptor sites. ABC transporters, mainly from sub-families B, C and G, may contribute to multidrug resistance (MDR by active efflux of drugs out of the cell. Gene products of ABC transporters may thus serve as the targets for agents that may modulate susceptibility to drugs, by inhibiting drug transport. ABC transporters are believed to be involved in a variety of physiological functions critical to the parasite, such as sterol transport, and therefore may also serve as the target for drugs that can act as anthelmintics on their own. Knowledge of polymorphism in these ABC transporter genes in nematode parasites could provide useful information for the process of drug design. We have identified 15 ABC transporter genes from sub-families A, B, C and G, in D. immitis, by comparative genomic approaches and analyzed them for polymorphism. Whole genome sequencing data from four ML susceptible (SUS and four loss of efficacy (LOE pooled populations were used for single nucleotide polymorphism (SNP genotyping. Out of 231 SNPs identified in those 15 ABC transporter genes, 89 and 75 of them were specific to the SUS or LOE populations, respectively. A few of the SNPs identified may affect gene expression, protein function, substrate specificity or resistance development and may be useful for transporter inhibitor/anthelmintic drug design, or in order to anticipate resistance development. Keywords: Dirofilaria immitis

SALL4, a stem cell factor, affects the side population by regulation of the ATP-binding cassette drug transport genes.

Directory of Open Access Journals (Sweden)

Ha-Won Jeong

2011-04-01

Full Text Available Our previous work shows that the stem cell factor SALL4 plays a central role in embryonic and leukemic stem cells. In this study, we report that SALL4 expression was higher in drug resistant primary acute myeloid leukemic patients than those from drug-responsive cases. In addition, while overexpression of SALL4 led to drug resistance in cell lines, cells with decreased SALL4 expression were more sensitive to drug treatments than the parental cells. This led to our investigation of the implication of SALL4 in drug resistance and its role in side population (SP cancer stem cells. SALL4 expression was higher in SP cells compared to non-SP cells by 2-4 fold in various malignant hematopoietic cell lines. Knocking down of SALL4 in isolated SP cells resulted in a reduction of SP cells, indicating that SALL4 is required for their self-renewal. The SP phenotype is known to be mediated by members of the ATP-binding cassette (ABC drug transport protein family, such as ABCG2 and ABCA3. Using chromatin-immunoprecipitation (ChIP, quantitative reverse transcription polymerase chain reaction (qRT-PCR and electrophoretic mobility shift assay(EMSA, we demonstrated that SALL4 was able to bind to the promoter region of ABCA3 and activate its expression while regulating the expression of ABCG2 indirectly. Furthermore, SALL4 expression was positively correlated to those of ABCG2 and ABCA3 in primary leukemic patient samples. Taken together, our results suggest a novel role for SALL4 in drug sensitivity, at least in part through the maintenance of SP cells, and therefore may be responsible for drug-resistance in leukemia. We are the first to demonstrate a direct link between stem cell factor SALL4, SP and drug resistance in leukemia.

Practical experience in the determination of the tube voltage using the Ardran-Crooks cassette

International Nuclear Information System (INIS)

Ewen, K.; Roesner, W.

1984-01-01

Within the framework of quality control measures in X-ray diagnostics and therapy, it is desirable to employ for the determination of tube voltage (e.g. in diagnostic X-ray equipment) methods which are as economical as possible while saving time and being simple to apply in spite of the fact that they are as highly accurate as ever possible. The absorber method described here, represented by the Ardran-Crooks cassette, possesses the advantage of low price and easy application. However, if it is operated in such a way that time is saved (assessment by the eye), it is not so accurate, whereas in accurate operation (assessment via luxmeter) it does require a relatively large amount of time. After the film has been exposed, it is necessary to estimate or measure the agreement of blackenings on one and the same film in order to determine the tube voltage. This voltage is then read off by means of a calibration curve. The error in the determination of the tube voltage via the Ardran-Crooks cassette depends on the accuracy of the calibration curve, which, in turn, depends on the number of measurements performed when producing the curve, and on the correct voltage of the standard X-ray equipment used in producing the calibration curve. In addition, assessment by eye adds a total error of 2.3% to 8%, depending on the amount of tube voltage. If the luxmeter is used instead of the eye, this additional error is less than 1% in relation to the magnitude of the tube voltage. (orig./BWU) [de

Generation of a gene cassette for genetically engineered Salmonella Enteritidis in the specific region of the sipC gene

Directory of Open Access Journals (Sweden)

M Ghasemi

2017-05-01

Full Text Available Introduction: Salmonellosis is an infection caused by eating contaminated food with Salmonella, and it can occur in humans and other animals. Salmonella has acquired the ability to create the infection due to the presence of several virulence genes. One of the virulence genes of salmonella is sipC gene that coding the SipC protein. The aim of this study was creating the gene cassette to genetically engineered Salmonella enteritidis in the specific region of the sipC gene. Methods: In this study, after DNA extraction from Salmonella, the upstream and downstream regions of the sipC gene was amplified based on PCR method. The PCR products were cloned with T/A cloning method and they were inserted into the pGEM vector. In order to generate the final gene cassette, each of the upstream and downstream regions of the sipC gene was subcloned into the pET32 vector, and cloning accuracy was assessed by PCR and enzyme digestion methods. Results: Amplification of the 320 bp upstream and 206 bp downstream of sipC gene was successful by PCR method. T/A cloning of these fragments were caused the formation of two pGEM-up and pGEM-down recombinant vectors. Results that were confirmed the sub-cloning accuracy indicate the formation of the final pET32-up-down gene cassette. Conclusion: The generated gene cassette in this study was considered as a multi-purpose cassette that is able to specific gene manipulation of Salmonella sipC gene by homologous recombination matched. This gene cassette has the necessary potential for sipC gene deletion or insertion of any useful gene instead of sipC gene.

5GCHAMPION – Disruptive 5G Technologies for Roll‐Out in 2018

Directory of Open Access Journals (Sweden)

Emilio Calvanese Strinati

2018-02-01

Full Text Available The 5GCHAMPION Europe–Korea collaborative project provides the first fully‐integrated and operational 5G prototype in 2018, in conjunction with the 2018 PyeongChang Winter Olympic Games. The corresponding technological advances comprise both an evolution and optimization of existing technological solutions and disruptive new features, which substantially outpace previous generations of technology. In this article, we focus on a subset of three disruptive technological solutions developed and experimented on by 5GCHAMPION during the 2018 PyeongChang Olympic Games: high speed communications, direct satellite‐user equipment communications, and post‐sale evolution of wireless equipment through software reconfiguration. Evaluating effectiveness and performing trials for these key 5G features permit us to learn about the actual maturity of 5G technology prototyping and the potential of new 5G services for vertical markets and end user enhanced experience two years before the launch of large‐scale 5G services.

5G: The Convergence of Wireless Communications.

Science.gov (United States)

Chávez-Santiago, Raúl; Szydełko, Michał; Kliks, Adrian; Foukalas, Fotis; Haddad, Yoram; Nolan, Keith E; Kelly, Mark Y; Masonta, Moshe T; Balasingham, Ilangko

As the rollout of 4G mobile communication networks takes place, representatives of industry and academia have started to look into the technological developments toward the next generation (5G). Several research projects involving key international mobile network operators, infrastructure manufacturers, and academic institutions, have been launched recently to set the technological foundations of 5G. However, the architecture of future 5G systems, their performance, and mobile services to be provided have not been clearly defined. In this paper, we put forth the vision for 5G as the convergence of evolved versions of current cellular networks with other complementary radio access technologies. Therefore, 5G may not be a single radio access interface but rather a "network of networks". Evidently, the seamless integration of a variety of air interfaces, protocols, and frequency bands, requires paradigm shifts in the way networks cooperate and complement each other to deliver data rates of several Gigabits per second with end-to-end latency of a few milliseconds. We provide an overview of the key radio technologies that will play a key role in the realization of this vision for the next generation of mobile communication networks. We also introduce some of the research challenges that need to be addressed.

Audio Cassettes as a Means of Professional Continuing Education for Pharmacists.

Science.gov (United States)

De Muth, James E.

1979-01-01

Lectures on audiotape cassettes are used by the University of Wisconsin-Extension for continuing profesional education of pharmacists. Evaluation statements from over 700 pharmacists revealed that participants viewed these courses as convenient, time-saving, and valuable learning experiences. The model presented in this study could be adapted for…

Reduction of radiation dose by using digital luminescence radiography compared to conventional screen film system with grid cassette

International Nuclear Information System (INIS)

Heyne, J.P.; Merbold, H.; Neumann, R.; Freesmeyer, M.; Jonetz-Mentzel, L.; Kaiser, W.A.; Sehner, J.

1999-01-01

Purpose: How much can the radiation dose be reduced for skull radiography by using digital luminescence radiography (DLR) compared to a conventional screen film system with a grid cassette? Methods and Materials: A skull phantom (3M) was X-rayed in anterior-posterior orientation using both a conventional screen film system with grid cassette and DLR (ADC-70, Agfa). The tube current time product (mAs) was diminished gradually while keeping the voltage constant. The surface entrance dose was measured by a sensor of Dosimax (Wellhoefer). Five investigators evaluated the images by characteristic and critical features, spatial resolution and contrast. Results: The surface entrance dose at 73 kV/22 mAs was 0,432 mGy in conventional screen film system and 0,435 mGy in DLR. The images could be evaluated very well down to an average dose of 71% (0,308 mGy; SD 0,050); sufficient images were obtained down to an average dose of 31% (0,136 mGy; SD 0,065). The resolution of the line pairs were reduced down to a 2 levels depending on the investigator. Contrast was assessed as being very good to sufficient. The acceptance of the postprocessed images (MUSICA-software) was individually different and resultde in an improvement of the assessment of bone structures an contrast in higher dose ranges only. Conclusion: For the sufficient assessment of a possible fracture/of paranasal sinuses/of measurement the skull the dose can be reduced to at least 56% (31%; SD 14,9%)/40% (27%; SD 9,3%)/18% (14%; SD 4,4%). Digital radiography allows question-referred exposure parameters with clearly reduced dose, so e.g. for fracture exclusion 73 kV/12,5 mAs and to skull measurement 73 kV/4 mAs. (orig.) [de

A Nostoc punctiforme sugar transporter necessary to establish a Cyanobacterium-plant symbiosis.

Science.gov (United States)

Ekman, Martin; Picossi, Silvia; Campbell, Elsie L; Meeks, John C; Flores, Enrique

2013-04-01

In cyanobacteria-plant symbioses, the symbiotic nitrogen-fixing cyanobacterium has low photosynthetic activity and is supplemented by sugars provided by the plant partner. Which sugars and cyanobacterial sugar uptake mechanism(s) are involved in the symbiosis, however, is unknown. Mutants of the symbiotically competent, facultatively heterotrophic cyanobacterium Nostoc punctiforme were constructed bearing a neomycin resistance gene cassette replacing genes in a putative sugar transport gene cluster. Results of transport activity assays using (14)C-labeled fructose and glucose and tests of heterotrophic growth with these sugars enabled the identification of an ATP-binding cassette-type transporter for fructose (Frt), a major facilitator permease for glucose (GlcP), and a porin needed for the optimal uptake of both fructose and glucose. Analysis of green fluorescent protein fluorescence in strains of N. punctiforme bearing frt::gfp fusions showed high expression in vegetative cells and akinetes, variable expression in hormogonia, and no expression in heterocysts. The symbiotic efficiency of N. punctiforme sugar transport mutants was investigated by testing their ability to infect a nonvascular plant partner, the hornwort Anthoceros punctatus. Strains that were specifically unable to transport glucose did not infect the plant. These results imply a role for GlcP in establishing symbiosis under the conditions used in this work.

Metabolism and transport of tamoxifen in relation to its effectiveness

DEFF Research Database (Denmark)

Cronin-Fenton, Deirdre P; Damkier, Per; Lash, Timothy L

2014-01-01

Tamoxifen reduces the rate of breast cancer recurrence by approximately a half. Tamoxifen is metabolized to more active metabolites by enzymes encoded by polymorphic genes, including cytochrome P450 2D6 (CYP2D6). Tamoxifen is a substrate for ATP-binding cassette transporter proteins. We review ta...

The recovery of 5-HT transporter and 5-HT immunoreactivity in injured rat spinal cord.

Science.gov (United States)

Saruhashi, Yasuo; Matsusue, Yoshitaka; Fujimiya, Mineko

2009-09-01

Experimental spinal cord injury. To determine the role of serotonin (5-HT) and 5-HT transporter in recovery from spinal cord injury. We examined 5-HT and 5-HT transporter of spinal cord immunohistologically and assessed locomotor recovery after extradural compression at the thoracic (T8) spinal cord in 21 rats. Eighteen rats had laminectomy and spinal cord injury, while the remaining three rats received laminectomy only. All rats were evaluated every other day for 4 weeks, using a 0-14 point scale open field test. Extradural compression markedly reduced mean hindlimbs scores from 14 to 1.5 +/- 2.0 (mean +/- standard error of mean). The rats recovered apparently normal walking by 4 weeks. The animals were perfused with fixative 1-3 days, 1, 2 and 4 weeks (three rats in each) after a spinal cord injury. The 5-HT transporter immunohistological study revealed a marked reduction of 5-HT transporter-containing terminals by 1 day after injury. By 4 weeks after injury, 5-HT transporter immunoreactive terminals returned to the control level. The 5-HT immunohistological study revealed a reduction of 5-HT-containing terminals by 1 week after injury. By 4 weeks after injury, 5-HT immunoreactive fibers and terminals returned to the control level. We estimated the recovery of 5-HT transporter and 5-HT neural elements in lumbosacral ventral horn by ranking 5-HT transporter and 5-HT staining intensity and counting 5-HT and 5-HT transporter terminals. The return of 5-HT transporter and 5-HT immunoreactivity of the lumbosacral ventral horn correlated with locomotor recovery, while 5-HT transporter showed closer relationship with locomotor recovery than 5-HT. The presence of 5-HT transporter indicates that the 5-HT fibers certainly function. This study shows that return of the function of 5-HT fibers predict the time course and extent of locomotory recovery after thoracic spinal cord injury.

Multicarrier Modulation Techniques for 5G Communications

OpenAIRE

QIANYU JIN

2018-01-01

This thesis focuses on multicarrier modulation techniques for 5G wireless communications. We study different properties of current multicarrier modulation techniques and propose methodologies to improve them in order to meet the demands of 5G wireless, e.g., low out-of-band radiation, low latency, relaxed synchronization, and stable performance against phase noise with low complexity over a wireless channel.

Interference Coordination for 5G New Radio

DEFF Research Database (Denmark)

Alvarez, Beatriz Soret; De Domenico, Antonio; Bazzi, Samer

2018-01-01

The arrival of the 5G NR provides a unique opportunity for introducing new inter-cell interference coordination (ICIC) mechanisms. The objective is twofold: to better exploit the benefits of ICIC in coherence with the rest of radio resource management (RRM) principles in 5G, and to support new...... results quantify the performance benefits of the different techniques under heterogeneous key performance indicators (KPIs). We also discuss the standardization effort required for having each of these techniques included in the 5G NR specifications....

Interference Coordination for 5G New Radio

DEFF Research Database (Denmark)

Alvarez, Beatriz Soret; De Domenico, Antonio; Bazzi, Samer

2017-01-01

The arrival of the 5G NR provides a unique opportunity for introducing new inter-cell interference coordination (ICIC) mechanisms. The objective is twofold: to better exploit the benefits of ICIC in coherence with the rest of radio resource management (RRM) principles in 5G, and to support new se...... results quantify the performance benefits of the different techniques under heterogeneous key performance indicators (KPIs). We also discuss the standardization effort required for having each of these techniques included in the 5G NR specifications....

A putative ABC transporter is involved in negative regulation of biofilm formation by Listeria monocytogenes

DEFF Research Database (Denmark)

Zhu, Xinna; Long, Fei; Chen, Yonghui

2008-01-01

Listeria monocytogenes may persist for long periods in food processing environments. In some instances, this may be due to aggregation or biofilm formation. To investigate the mechanism controlling biofilm formation in the food-borne pathogen L. monocytogenes, we characterized LM-49, a mutant...... with enhanced ability of biofilm-formation generated via transposon Tn917 mutagenesis of L. monocytogenes 4b G. In this mutant, a Tn917 insertion has disrupted the coding region of the gene encoding a putative ATP binding cassette (ABC) transporter permease identical to Lmof2365_1771 (a putative ABC...... the same amount of biofilm biomass as the wild-type strain. Furthermore, transcription of the downstream lm.G_1770 was not influenced by the upstream Tn917 insertion, and the presence of Tn917 has no effect on biofilm formation. These results suggest that lm.G_1771 was solely responsible for the negative...

5G - boundary object or battlefield

DEFF Research Database (Denmark)

Sørensen, Jannick Kirk; Tadayoni, Reza; Henten, Anders

2016-01-01

The aim of the paper is to better understand of the processes of standardization relating to 5G. This includes an understanding of how 5G can be conceptualized. It also includes knowledge on where the processes of standardization take place. The paper introduces two different analytical approache...... processes, while theories that are part of the concept of standards wars will be applicable for conceptualizing the more confrontational aspects....

Quantification of the sources of long-range transport of PM2.5 pollution in the Ordos region, Inner Mongolia, China

International Nuclear Information System (INIS)

Khuzestani, Reza Bashiri; Schauer, James J.; Wei, Yongjie; Zhang, Lulu; Cai, Tianqi; Zhang, Yang; Zhang, Yuanxun

2017-01-01

The Ordos region of Inner Mongolia is rapidly developing and suffers from poor air quality and unhealthy levels of fine particulate matter. PM 2.5 concentrations in the Ordos region were found to exceed 75 μg/m 3 on average, annually, with peak pollution days in excess of 350 μg/m 3 , but local air pollution emissions from surrounding sources are not sufficient to drive pollution levels to these concentrations. The current study was designed to quantify sources of PM 2.5 and assess the local source contributions and effects of regional transport on local pollution. The results show that the Ordos region is primarily impacted by regional long-range transport of pollutants from anthropogenic sources located outside of the Inner Mongolia in Shanxi province areas but is also largely affected by regional dust transported from the deserts located in western Inner Mongolia. The analysis proved that approximately 77% of PM 2.5 mass is transported long-range from the sites exterior to the study area and contributes 59.32 μg/m 3 on average, annually, while the local sources contribute 17.41 μg/m 3 (23%) on annual average to the PM 2.5 mass in the study area. High spatial correlation coefficients (R 2  > 0.6) were observed for most of the factors pointing to the transport of external emissions into the area. Spatial correlation analysis, bivariate polar plots and hybrid trajectory models for industrial and secondary inorganic factors provide evidence for the impact of long-range transport from Shanxi province areas. In addition, the deserts in western Inner Mongolia were found to be the source regions for dust. Finally, our analysis shows that the source of oil combustion and mobile factors are impacted by local sources in the Ordos region; however, some regional impacts from other regions were also observed for mobile source in the area. - Dominance of the regional long-range transport of PM 2.5 sources in the Ordos region. Around 77% of PM 2.5 mass is transported

miR-758-3p: a blood-based biomarker that's influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome.

Science.gov (United States)

O'Neill, Sadhbh; Larsen, Mette Bohl; Gregersen, Søren; Hermansen, Kjeld; O'Driscoll, Lorraine

2018-02-06

Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells. Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p's predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression. miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome.

miR-758-3p: a blood-based biomarker that’s influence on the expression of CERP/ABCA1 may contribute to the progression of obesity to metabolic syndrome

Science.gov (United States)

O’Neill, Sadhbh; Larsen, Mette Bohl; Gregersen, Søren; Hermansen, Kjeld; O’Driscoll, Lorraine

2018-01-01

Due to increasing prevalence of obesity, a simple method or methods for the diagnosis of metabolic syndrome are urgently required to reduce the risk of associated cardiovascular disease, diabetes and cancer. This study aimed to identify a miRNA biomarker that may distinguish metabolic syndrome from obesity and to investigate if such a miRNA may have functional relevance for metabolic syndrome. 52 adults with clinical obesity (n=26) or metabolic syndrome (n=26) were recruited. Plasma specimens were procured from all and were randomly designated to discovery and validation cohorts. miRNA discovery profiling was performed, using array technology, on plasma RNA. Validation was performed by quantitative polymerase chain reaction. The functional effect of miR-758-3p on its predicted target, cholesterol efflux regulatory protein/ATP-binding cassette transporter, was investigated using HepG2 liver cells. Custom miRNA profiling of 25 miRNAs in the discovery cohort found miR-758-3p to be detected in the obese cohort but undetected in the metabolic syndrome cohort. miR-758-3p was subsequently validated as a potential biomarker for metabolic syndrome by quantitative polymerase chain reaction. Bioinformatics analysis identified cholesterol efflux regulatory protein/ATP-binding cassette transporter as miR-758-3p’s predicted target. Specifically, mimicking miR-758-3p in HepG2 cells suppressed cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression; conversely, inhibiting miR-758-3p increased cholesterol efflux regulatory protein/ATP-binding cassette transporter protein expression. miR-758-3p holds potential as a blood-based biomarker for distinguishing progression from obesity to metabolic syndrome and as a driver in controlling cholesterol efflux regulatory protein/ATP-binding cassette transporter expression, indicating it potential role in cholesterol control in metabolic syndrome. PMID:29507696

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul

Science.gov (United States)

Alavi, S. E.; Soltanian, M. R. K.; Amiri, I. S.; Khalily, M.; Supa'At, A. S. M.; Ahmad, H.

2016-01-01

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated.

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul.

Science.gov (United States)

Alavi, S E; Soltanian, M R K; Amiri, I S; Khalily, M; Supa'at, A S M; Ahmad, H

2016-01-27

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides generating of the mm-wave signal in the 60 GHz frequency band the radio over fiber (RoF) system for transmission of orthogonal frequency division multiplexing (OFDM) with 5 GHz bandwidth is presented. For the purpose of wireless transmission for 5G application the required antenna is designed and developed. The total system performance in one small cell was studied and the error vector magnitude (EVM) of the system was evaluated.

ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A>G and c.5461-10T>C cause Stargardt disease due to defective splicing.

Science.gov (United States)

Jonsson, Frida; Westin, Ida Maria; Österman, Lennart; Sandgren, Ola; Burstedt, Marie; Holmberg, Monica; Golovleva, Irina

2018-02-20

Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing. The splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE-19, using a minigene system containing variants c.4773+3A>G and c.5461-10T>C. We showed that both ABCA4 variants, c.4773+3A>G and c.5461-10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type. Two intronic variants c.4773+3A>G and c.5461-10T>C, both predicted to affect splicing, are indeed disease-causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Combination of MALDI-MSI and cassette dosing for evaluation of drug distribution in human skin explant

DEFF Research Database (Denmark)

Sørensen, Isabella S; Janfelt, Christian; Nielsen, Mette Marie B

2017-01-01

Study of skin penetration and distribution of the drug compounds in the skin is a major challenge in the development of topical drug products for treatment of skin diseases. It is crucial to have fast and efficacious screening methods which can provide information concerning the skin penetration ...... that combination of MALDI-MSI and cassette dosing can be used as a medium throughput screening tool at an early stage in the drug discovery/development process. Graphical abstract Investigation of drug distribution in human skin explant by MALDI-MSI after cassette dosing....

Development of remote pipe welding tool for divertor cassettes in JT-60SA

Energy Technology Data Exchange (ETDEWEB)

Hayashi, Takao, E-mail: hayashi.takao@jaea.go.jp [Fusion Research and Development Directorate, Japan Atomic Energy Agency, Naka (Japan); Sakurai, Shinji; Sakasai, Akira; Shibanuma, Kiyoshi [Fusion Research and Development Directorate, Japan Atomic Energy Agency, Naka (Japan); Kono, Wataru; Ohnawa, Toshio; Matsukage, Takeshi [Toshiba Corporation, Yokohama, Kanagawa (Japan)

2015-12-15

Highlights: • Remote pipe welding tool accessing from inside of the pipe has been newly developed. • Cooling pipe with a jut on the edge expands the acceptable welding gap up to 0.5 mm. • Positioning accuracy of the laser beam is realized to be less than ±0.1 mm. • We have achieved robust welding for an angular misalignment of 0.5°. - Abstract: Remote pipe welding tool accessing from inside of the pipe has been newly developed for JT-60SA. Remote handling (RH) system is necessary for the maintenance and repair of the divertor cassette in JT-60SA. Because the space around the cooling pipe connected with the divertor cassette is very limited, the cooling pipe is to be remotely cut and welded from inside for the maintenance. A laser welding method was employed to perform circumferential welding by rotating the focusing mirror inside the pipe. However, the grooves of connection pipes are not precisely aligned for welding. The most critical issue is therefore to develop a reliable welding tool for pipe connection without a defect such as undercut weld due to a gap caused by angular and axial misalignments of grooves. In addition, an angular misalignment between two pipes due to inclination of pipe has to be taken into account for the positioning of the laser beam during welding. In this paper, the followings are proposed to solve the above issues: (1) Cooling pipe connected with the divertor is machined to have a jut on the edge so as to expand the acceptable welding gap up to 0.5 mm by filling the gap with welded jut. (2) Positioning accuracy of the laser beam for reliable welding is realized to be less than ±0.1 mm along the circumferential target for welding by a position control mechanism provided in the tool even in the case of up to angular misalignment of 0.5° between connection pipes. Based on the above proposals, we have achieved robust welding for a large gap up to 0.5 mm as well as the maximum angular misalignment of 0.5° between connection pipes

Verification of the shift Monte Carlo code with the C5G7 reactor benchmark

International Nuclear Information System (INIS)

Sly, N. C.; Mervin, B. T.; Mosher, S. W.; Evans, T. M.; Wagner, J. C.; Maldonado, G. I.

2012-01-01

Shift is a new hybrid Monte Carlo/deterministic radiation transport code being developed at Oak Ridge National Laboratory. At its current stage of development, Shift includes a parallel Monte Carlo capability for simulating eigenvalue and fixed-source multigroup transport problems. This paper focuses on recent efforts to verify Shift's Monte Carlo component using the two-dimensional and three-dimensional C5G7 NEA benchmark problems. Comparisons were made between the benchmark eigenvalues and those output by the Shift code. In addition, mesh-based scalar flux tally results generated by Shift were compared to those obtained using MCNP5 on an identical model and tally grid. The Shift-generated eigenvalues were within three standard deviations of the benchmark and MCNP5-1.60 values in all cases. The flux tallies generated by Shift were found to be in very good agreement with those from MCNP. (authors)

Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

Directory of Open Access Journals (Sweden)

David A. Rhodes

2018-04-01

Full Text Available Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg, the microbial metabolite (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated

Regulation of Human γδ T Cells by BTN3A1 Protein Stability and ATP-Binding Cassette Transporters

Science.gov (United States)

Rhodes, David A.; Chen, Hung-Chang; Williamson, James C.; Hill, Alfred; Yuan, Jack; Smith, Sam; Rhodes, Harriet; Trowsdale, John; Lehner, Paul J.; Herrmann, Thomas; Eberl, Matthias

2018-01-01

Activation of human Vγ9/Vδ2 T cells by “phosphoantigens” (pAg), the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) and the endogenous isoprenoid intermediate isopentenyl pyrophosphate, requires expression of butyrophilin BTN3A molecules by presenting cells. However, the precise mechanism of activation of Vγ9/Vδ2 T cells by BTN3A molecules remains elusive. It is not clear what conformation of the three BTN3A isoforms transmits activation signals nor how externally delivered pAg accesses the cytosolic B30.2 domain of BTN3A1. To approach these problems, we studied two HLA haplo-identical HeLa cell lines, termed HeLa-L and HeLa-M, which showed marked differences in pAg-dependent stimulation of Vγ9/Vδ2 T cells. Levels of IFN-γ secretion by Vγ9/Vδ2 T cells were profoundly increased by pAg loading, or by binding of the pan-BTN3A specific agonist antibody CD277 20.1, in HeLa-M compared to HeLa-L cells. IL-2 production from a murine hybridoma T cell line expressing human Vγ9/Vδ2 T cell receptor (TCR) transgenes confirmed that the differential responsiveness to HeLa-L and HeLa-M was TCR dependent. By tissue typing, both HeLa lines were shown to be genetically identical and full-length transcripts of the three BTN3A isoforms were detected in equal abundance with no sequence variation. Expression of BTN3A and interacting molecules, such as periplakin or RhoB, did not account for the functional variation between HeLa-L and HeLa-M cells. Instead, the data implicate a checkpoint controlling BTN3A1 stability and protein trafficking, acting at an early time point in its maturation. In addition, plasma membrane profiling was used to identify proteins upregulated in HMB-PP-treated HeLa-M. ABCG2, a member of the ATP-binding cassette (ABC) transporter family was the most significant candidate, which crucially showed reduced expression in HeLa-L. Expression of a subset of ABC transporters, including ABCA1 and ABCG1, correlated with

Effect of common polymorphisms of the farnesoid X receptor and bile acid transporters on the pharmacokinetics of ursodeoxycholic acid.

Science.gov (United States)

Hu, Miao; Fok, Benny S P; Wo, Siu-Kwan; Lee, Vincent H L; Zuo, Zhong; Tomlinson, Brian

2016-01-01

Ursodeoxycholic acid (UDCA), a natural, dihydroxy bile acid, promotes gallstone dissolution and has been attributed with several other beneficial effects. The farnesoid X receptor (FXR) may influence the pharmacokinetics of UDCA by modulating the expression of bile acid transporters. This exploratory study examined whether common functional polymorphisms in FXR and in bile acid transporter genes affect the pharmacokinetics of exogenous UDCA. Polymorphisms in genes for transporters involved in bile acid transport, solute carrier organic anion 1B1 (SLCO1B1) 388A>G and 521T>C, solute carrier 10A1 (SLC10A1) 800 C>T and ATP-binding cassette B11 (ABCB11) 1331T>C, and the FXR -1G>T polymorphism were genotyped in 26 male Chinese subjects who ingested single oral 500-mg doses of UDCA. Plasma concentrations of UDCA and its major conjugate metabolite glycoursodeoxycholic acid (GUDCA) were determined. The mean systemic exposure of UDCA was higher in the five subjects with one copy of the FXR -1G>T variant allele than in those homozygous for the wild-type allele (n = 21) (AUC0-24 h : 38.5 ± 28.2 vs. 20.9 ± 8.0 μg h/mL, P = 0.021), but this difference appeared mainly due to one outlier with the -1GT genotype and elevated baseline and post-treatment UDCA concentrations. After excluding the outlier, body weight was the only factor associated with plasma concentrations of UDCA and there were no significant associations with the other polymorphisms examined. None of the polymorphisms affected the pharmacokinetics of GUDCA. This study showed that the common polymorphisms in bile acid transporters had no significant effect on the pharmacokinetics of exogenous UDCA but an effect of the FXR polymorphism cannot be excluded. © 2015 Wiley Publishing Asia Pty Ltd.

Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology

DEFF Research Database (Denmark)

Andersen, Vibeke; Svenningsen, Katrine; Almind Knudsen, Lina

2015-01-01

AIM: To evaluate ATP-binding cassette (ABC) transporters in colonic pathophysiology as they had recently been related to colorectal cancer (CRC) development. METHODS: Literature search was conducted on PubMed using combinations of the following terms: ABC transporters, ATP binding cassette...... with glucocorticoids. The evidence for the involvement of ABCC2 and ABCG2 in colonic pathophysiology was weak. CONCLUSION: ABCB1, diet, and gut microbes mutually interact in colonic inflammation, a well-known risk factor for CRC. Further insight may be translated into preventive and treatment strategies....... transporter proteins, inflammatory bowel disease, ulcerative, colitis, Crohns disease, colorectal cancer, colitis, intestinal inflammation, intestinal carcinogenesis, ABCB1/P-glycoprotein (P-gp/CD243/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP), Abcb1...

Role of the SRRz/Rz1 lambdoid lysis cassette in the pathoadaptive evolution of Shigella.

Science.gov (United States)

Leuzzi, Adriano; Grossi, Milena; Di Martino, Maria Letizia; Pasqua, Martina; Micheli, Gioacchino; Colonna, Bianca; Prosseda, Gianni

2017-06-01

Shigella, the etiological agent of bacillary dysentery (shigellosis), is a highly adapted human pathogen. It evolved from an innocuous ancestor resembling the Escherichia coli strain by gain and loss of genes and functions. While the gain process concerns the acquisition of the genetic determinants of virulence, the loss is related to the adaptation of the genome to the new pathogenic status and occurs by pathoadaptive mutation of antivirulence genes. In this study, we highlight that the SRRz/Rz 1 lambdoid lysis cassette, even though stably adopted in E. coli K12 by virtue of its beneficial effect on cell physiology, has undergone a significant decay in Shigella. Moreover, we show the antivirulence nature of the SRRz/Rz 1 lysis cassette in Shigella. In fact, by restoring the SRRz/Rz 1 expression in this pathogen, we observe an increased release of peptidoglycan fragments, causing an unbalance in the fine control exerted by Shigella on host innate immunity and a mitigation of its virulence. This strongly affects the virulence of Shigella and allows to consider the loss of SRRz/Rz 1 lysis cassette as another pathoadaptive event in the life of Shigella. Copyright © 2017 Elsevier GmbH. All rights reserved.

Community Based Networks and 5G Wi-Fi

DEFF Research Database (Denmark)

Williams, Idongesit

2018-01-01

This paper argues on why Community Based Networks should be recognized as potential 5G providers using 5G Wi-Fi. The argument is hinged on findings in a research to understand why Community Based Networks deploy telecom and Broadband infrastructure. The study was a qualitative study carried out...... inductively using Grounded Theory. Six cases were investigated. Two Community Based Network Mobilization Models were identified. The findings indicate that 5G Wi-Fi deployment by Community Based Networks is possible if policy initiatives and the 5G Wi-Fi standards are developed to facilitate the causal...

Technical evaluation of the G.E. Transportable Modular AZTECH Plant topical report

International Nuclear Information System (INIS)

Henscheid, J.W.; Stalker, A.E.

1985-12-01

This report summarizes EG and G Idaho's review of the General Electric Company's topical report on their Transportable Modular AZTECH Plant. The review evaluated compliance with pertinent codes, standards and regulations. The initial review was discussed with G.E. and all outstanding issues resolved before this final evaluation was made

FSO-Based Vertical Backhaul/Fronthaul Framework for 5G+ Wireless Networks

KAUST Repository

Alzenad, Mohamed

2018-01-12

The presence of a super high rate, but also cost-efficient, easy-to-deploy, and scalable, back-haul/fronthaul framework, is essential in the upcoming 5G wireless networks and beyond. Motivated by the mounting interest in unmanned flying platforms of various types, including UAVs, drones, balloons, and HAPs/MAPs/LAPs, which we refer to as networked flying platforms (NFPs), for providing communications services, and by the recent advances in free space optics (FSO), this article investigates the feasibility of a novel vertical backhaul/fronthaul framework where the NFPs transport the backhaul/fronthaul traffic between the access and core networks via point-to-point FSO links. The performance of the proposed innovative approach is investigated under different weather conditions and a broad range of system parameters. Simulation results demonstrate that the FSO-based vertical backhaul/fronthaul framework can offer data rates higher than the baseline alternatives, and thus can be considered a promising solution to the emerging backhaul/fronthaul requirements of the 5G+ wireless networks, particularly in the presence of ultra-dense heterogeneous small cells. This article also presents the challenges that accompany such a novel framework and provides some key ideas toward overcoming these challenges.

United States Geological Survey (USGS) FM cassette seismic-refraction recording system

International Nuclear Information System (INIS)

Murphy, J.M.

1988-01-01

In this two chapter report, instrumentation used to collect seismic data is described. This data acquisition system has two parts: (1) portable anolog seismic recorders and related ''hand-held-testers'' (HHT) and (2) portable digitizing units. During the anolog recording process, ground motion is sensed by a 2-Hz vertical-component seismometer. The voltage output from the seismometer is split without amplification and sent to three parallel amplifier circuit boards. Each circuit board amplifiers the seismic signal in three stages and then frequency modulates the signal. Amplification at the last two stages can be set by the user. An internal precision clock signal is also frequency modulated. The three data carrier frequencies, the clock carrier frequency, and a tape-speed compensation carrier frequency are summed and recorded on a recorded on a cassette tape. During the digitizing process, the cassette tapes are played back and the signals are demultiplexed and demodulated. An anolog-to-digital converter converts the signals to digital data which are stored on 8-inch floppy disks. 7 refs., 19 figs., 6 tabs

Plasminogen activator inhibitor-1 4G/5G polymorphism in infertile women with and without endometriosis.

Science.gov (United States)

Gonçalves-Filho, Rubens P; Brandes, Ariel; Christofolini, Denise M; Lerner, Tatiana G; Bianco, Bianca; Barbosa, Caio P

2011-05-01

To evaluate PAI-1 genotypes in a group of infertile women with or without endometriosis and control subjects. Case-control study. Human Reproduction Center of Medicina do ABC Faculty. One hundred and forty infertile women with endometriosis, 64 women with idiopathic infertility and 148 fertile women as control subjects. The PAI-1 4G/5G polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. Genotype distribution and allele frequency of the 4G/5G polymorphism of the PAI-1 gene. The frequencies of genotypes 4G/4G, 4G/5G and 5G/5G of the PAI-1 gene in the infertile women with endometriosis were 38.6, 37.1 and 24.3%, respectively, and in the control group 24.3, 33.8 and 41.9%, respectively (p=0.003). When the infertile women with endometriosis were divided according to their endometriosis stage, genotypes 4G/4G, 4G/5G and 5G/5G were identified, respectively, in 36.7, 32.9 and 30.4% of the patients with minimal/mild endometriosis (p=0.102) and in 41.0, 42.6 and 16.4% of the patients with moderate/severe endometriosis (p=0.001); in the women with idiopathic infertility, these genotypes were found at a frequency of 29.7, 34.3 and 36%, respectively (p=0.637). The data suggest that, in Brazilian women, the PAI-1 4G/5G polymorphism may be associated with a risk of endometriosis-associated infertility. © 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.

41 CFR 102-117.5 - What is transportation management?

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is transportation management? 102-117.5 Section 102-117.5 Public Contracts and Property Management Federal Property Management... General § 102-117.5 What is transportation management? Transportation management is agency oversight of...

Adaptive Antenna System for Both 4G LTE and 5G Cellular Systems

Science.gov (United States)

Henderson, Kendrick Q. T.

Given the steep increase in the use of mobile communication systems, the current 4G/LTE (Long Term Evolution), cellular system will not be able to handle the increase in data. It is estimated that by 2020 the bandwidth requirements will be 10 times greater than what LTE can sustain. A new 5th generation (5G) communication system has been proposed to meet this demand. The physical layer or the antenna is the most critical part of any wireless communication systems as it is the interface between the free space medium and an electrical circuit. It sets the margin for almost all design parameters in the system such as the system noise and bandwidth. Several interactions of antennas have been proposed over the years for cellular services. These antennas are of various geometries, bandwidths, and radiation patterns with almost all having linear polarization. This thesis attempts to solve the multiple LTE antenna problem by creating a simple antenna that covers most of the LTE bands (850-2700 MHz) as well as introducing an antenna system at the 28 GHz 5G band. This allows for a greater educated hypothesis into what 5G can offer at the physical layer. The proposed concept will provide a solution to the co-existence problem of upcoming 5G wireless systems to be interoperable with existing 4G/LTE system.

Towards 5G: A Photonic Based Millimeter Wave Signal Generation for Applying in 5G Access Fronthaul

OpenAIRE

Alavi, S. E.; Soltanian, M. R. K.; Amiri, I. S.; Khalily, M.; Supa?at, A. S. M.; Ahmad, H.

2016-01-01

5G communications require a multi Gb/s data transmission in its small cells. For this purpose millimeter wave (mm-wave) RF signals are the best solutions to be utilized for high speed data transmission. Generation of these high frequency RF signals is challenging in electrical domain therefore photonic generation of these signals is more studied. In this work, a photonic based simple and robust method for generating millimeter waves applicable in 5G access fronthaul is presented. Besides gene...

5G Visions of User Privacy

DEFF Research Database (Denmark)

Sørensen, Lene Tolstrup; Khajuria, Samant; Skouby, Knud Erik

2015-01-01

Currently, the discussions are going on the elements and definition of 5G networks. One of the elements in this discussion is how to provide for user controlled privacy for securing users' digital interaction. The purpose of this paper is to present elements of user controlled privacy needed...... for the future 5G networks. The paper concludes that an ecosystem consisting of Trusted Third Party between the end user and the service providers as a distributed system could be integrated to secure the perspective of user controlled privacy for future systems...

Angular momentum transport by heat-driven g-modes in slowly pulsating B stars

Science.gov (United States)

Townsend, R. H. D.; Goldstein, J.; Zweibel, E. G.

2018-03-01

Motivated by recent interest in the phenomenon of waves transport in massive stars, we examine whether the heat-driven gravity (g) modes excited in slowly pulsating B (SPB) stars can significantly modify the stars' internal rotation. We develop a formalism for the differential torque exerted by g modes, and implement this formalism using the GYRE oscillation code and the MESASTAR stellar evolution code. Focusing first on a 4.21M⊙ model, we simulate 1 000 yr of stellar evolution under the combined effects of the torque due to a single unstable prograde g mode (with an amplitude chosen on the basis of observational constraints), and diffusive angular momentum transport due to convection, overshooting, and rotational instabilities. We find that the g mode rapidly extracts angular momentum from the surface layers, depositing it deeper in the stellar interior. The angular momentum transport is so efficient that by the end of the simulation, the initially non-rotating surface layers are spun in the retrograde direction to ≈ 30 per cent of the critical rate. However, the additional inclusion of magnetic stresses in our simulations almost completely inhibits this spin-up. Expanding our simulations to cover the whole instability strip, we show that the same general behaviour is seen in all SPB stars. After providing some caveats to contextualize our results, we hypothesize that the observed slower surface rotation of SPB stars (as compared to other B-type stars) may be the direct consequence of the angular momentum transport that our simulations demonstrate.

Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia

Directory of Open Access Journals (Sweden)

Nancy D Merner

2015-10-01

Full Text Available Many encoded gene products responsible for neurodevelopmental disorders (NDs like autism spectrum disorders (ASD, schizophrenia (SCZ, intellectual disability (ID, and idiopathic generalized epilepsy (IGE converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5 Cl- transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS, functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD in human ASD (R952H and R1049C and SCZ (R952H previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs.

Ultra-Reliable Communication in 5G Wireless Systems

DEFF Research Database (Denmark)

Popovski, Petar

2014-01-01

—Wireless 5G systems will not only be “4G, but faster”. One of the novel features discussed in relation to 5G is Ultra-Reliable Communication (URC), an operation mode not present in today’s wireless systems. URC refers to provision of certain level of communication service almost 100 % of the time....... Example URC applications include reliable cloud connectivity, critical connections for industrial automation and reliable wireless coordination among vehicles. This paper puts forward a systematic view on URC in 5G wireless systems. It starts by analyzing the fundamental mechanisms that constitute......-term URC (URC-S). The second dimension is represented by the type of reliability impairment that can affect the communication reliability in a given scenario. The main objective of this paper is to create the context for defining and solving the new engineering problems posed by URC in 5G....

Cooperative localization in 5G networks: A survey

Directory of Open Access Journals (Sweden)

Ping Zhang

2017-03-01

Full Text Available In upcoming 5G networks, key prospects such as increased bandwidth, smaller cells, higher mobile terminal (MT densities, multiple radio access technologies, and the capability of device-to-device communication are beneficial for localization. Meanwhile, technologies suggested in 5G, such as massive multiple-in multiple-out, would also benefit from the accurate locations of MTs. Therefore, an opportunity to develop and integrate mobile localization technology in 5G networks has presented itself at this early stage. This paper reviews recent literature relating to localization in 5G networks, and emphasizes the prospect for implementing cooperative localization, which exploits the location information from additional measurements between MTs. To evaluate the accuracy of cooperative localization, a performance evaluation approach is also suggested.

Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population.

Science.gov (United States)

Shammaa, Dina M R; Sabbagh, Amira S; Taher, Ali T; Zaatari, Ghazi S; Mahfouz, Rami A R

2008-09-01

Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

Transporter-mediated biofuel secretion.

Science.gov (United States)

Doshi, Rupak; Nguyen, Tuan; Chang, Geoffrey

2013-05-07

Engineering microorganisms to produce biofuels is currently among the most promising strategies in renewable energy. However, harvesting these organisms for extracting biofuels is energy- and cost-intensive, limiting the commercial feasibility of large-scale production. Here, we demonstrate the use of a class of transport proteins of pharmacological interest to circumvent the need to harvest biomass during biofuel production. We show that membrane-embedded transporters, better known to efflux lipids and drugs, can be used to mediate the secretion of intracellularly synthesized model isoprenoid biofuel compounds to the extracellular milieu. Transporter-mediated biofuel secretion sustainably maintained an approximate three- to fivefold boost in biofuel production in our Escherichia coli test system. Because the transporters used in this study belong to the ubiquitous ATP-binding cassette protein family, we propose their use as "plug-and-play" biofuel-secreting systems in a variety of bacteria, cyanobacteria, diatoms, yeast, and algae used for biofuel production. This investigation showcases the potential of expressing desired membrane transport proteins in cell factories to achieve the export or import of substances of economic, environmental, or therapeutic importance.

GEOS-5 Chemistry Transport Model User's Guide

Science.gov (United States)

Kouatchou, J.; Molod, A.; Nielsen, J. E.; Auer, B.; Putman, W.; Clune, T.

2015-01-01

The Goddard Earth Observing System version 5 (GEOS-5) General Circulation Model (GCM) makes use of the Earth System Modeling Framework (ESMF) to enable model configurations with many functions. One of the options of the GEOS-5 GCM is the GEOS-5 Chemistry Transport Model (GEOS-5 CTM), which is an offline simulation of chemistry and constituent transport driven by a specified meteorology and other model output fields. This document describes the basic components of the GEOS-5 CTM, and is a user's guide on to how to obtain and run simulations on the NCCS Discover platform. In addition, we provide information on how to change the model configuration input files to meet users' needs.

A Nostoc punctiforme Sugar Transporter Necessary to Establish a Cyanobacterium-Plant Symbiosis1[C][W

Science.gov (United States)

Ekman, Martin; Picossi, Silvia; Campbell, Elsie L.; Meeks, John C.; Flores, Enrique

2013-01-01

In cyanobacteria-plant symbioses, the symbiotic nitrogen-fixing cyanobacterium has low photosynthetic activity and is supplemented by sugars provided by the plant partner. Which sugars and cyanobacterial sugar uptake mechanism(s) are involved in the symbiosis, however, is unknown. Mutants of the symbiotically competent, facultatively heterotrophic cyanobacterium Nostoc punctiforme were constructed bearing a neomycin resistance gene cassette replacing genes in a putative sugar transport gene cluster. Results of transport activity assays using 14C-labeled fructose and glucose and tests of heterotrophic growth with these sugars enabled the identification of an ATP-binding cassette-type transporter for fructose (Frt), a major facilitator permease for glucose (GlcP), and a porin needed for the optimal uptake of both fructose and glucose. Analysis of green fluorescent protein fluorescence in strains of N. punctiforme bearing frt::gfp fusions showed high expression in vegetative cells and akinetes, variable expression in hormogonia, and no expression in heterocysts. The symbiotic efficiency of N. punctiforme sugar transport mutants was investigated by testing their ability to infect a nonvascular plant partner, the hornwort Anthoceros punctatus. Strains that were specifically unable to transport glucose did not infect the plant. These results imply a role for GlcP in establishing symbiosis under the conditions used in this work. PMID:23463784

Mutation of the Arabidopsis NRT1.5 nitrate transporter causes defective root-to-shoot nitrate transport.

Science.gov (United States)

Lin, Shan-Hua; Kuo, Hui-Fen; Canivenc, Geneviève; Lin, Choun-Sea; Lepetit, Marc; Hsu, Po-Kai; Tillard, Pascal; Lin, Huey-Ling; Wang, Ya-Yun; Tsai, Chyn-Bey; Gojon, Alain; Tsay, Yi-Fang

2008-09-01

Little is known about the molecular and regulatory mechanisms of long-distance nitrate transport in higher plants. NRT1.5 is one of the 53 Arabidopsis thaliana nitrate transporter NRT1 (Peptide Transporter PTR) genes, of which two members, NRT1.1 (CHL1 for Chlorate resistant 1) and NRT1.2, have been shown to be involved in nitrate uptake. Functional analysis of cRNA-injected Xenopus laevis oocytes showed that NRT1.5 is a low-affinity, pH-dependent bidirectional nitrate transporter. Subcellular localization in plant protoplasts and in planta promoter-beta-glucuronidase analysis, as well as in situ hybridization, showed that NRT1.5 is located in the plasma membrane and is expressed in root pericycle cells close to the xylem. Knockdown or knockout mutations of NRT1.5 reduced the amount of nitrate transported from the root to the shoot, suggesting that NRT1.5 participates in root xylem loading of nitrate. However, root-to-shoot nitrate transport was not completely eliminated in the NRT1.5 knockout mutant, and reduction of NRT1.5 in the nrt1.1 background did not affect root-to-shoot nitrate transport. These data suggest that, in addition to that involving NRT1.5, another mechanism is responsible for xylem loading of nitrate. Further analyses of the nrt1.5 mutants revealed a regulatory loop between nitrate and potassium at the xylem transport step.

The naphthoquinones, vitamin K3 and its structural analog plumbagin, are substrates of the multidrug resistance-linked ABC drug transporter ABCG2

OpenAIRE

Shukla, Suneet; Wu, Chung-Pu; Nandigama, Krishnamachary; Ambudkar, Suresh V.

2007-01-01

Vitamin K3 (Menadione; 2-methyl-1,4-naphthoquinone) is a structural precursor of vitamins K1 and K2 which are essential for blood clotting. The naturally occurring structural analog of this vitamin, plumbagin (5-hydroxy-menadione), is known to modulate cellular proliferation, apoptosis, carcinogenesis, and radioresistance. We, here, report that both vitamin K3 and plumbagin are substrates of the multidrug resistance-linked ATP binding cassette (ABC) drug transporter, ABCG2. Vitamin K3 and plu...

Simulation of the coupling between nucleotide binding and transmembrane domains in the ABC transporter BtuCD

DEFF Research Database (Denmark)

Sonne, Jacob; Kandt, C.; Peters, Günther H.j.

2007-01-01

The nucleotide-induced structural rearrangements in ATP binding cassette (ABC) transporters, leading to substrate translocation, are largely unknown. We have modeled nucleotide binding and release in the vitamin B12 importer BtuCD using perturbed elastic network calculations and biased molecular...

First Analysis of the Association Between CYP3A4/5, ABCB1 Genetic Polymorphisms and Oxcarbazepine Metabolism and Transport in Chinese Epileptic Patients with Oxcarbazepine Monotherapy and Bitherapy.

Science.gov (United States)

Wang, Ping; Yin, Tao; Ma, Hong-ying; Liu, Dan-Qi; Sheng, Yangh-ao; Zhou, Bo-Ting

2015-01-01

Oxcarbazepine (OXC) is widely used in anti-epileptic treatment. Cytochrome P450 3A4 (CYP3A4), cytochrome P450 3A5(CYP3A5), and ATP-binding cassette sub-family B member 1 (ABCB1) are potential genes involved in OXC metabolisms and transport in vivo. This study aims to examine the genetic effects of CYP3A4, CYP3A5, and ABCB1 on OXC metabolism and transport in Chinese epileptic patients using OXC as monotherapy and bitherapy with lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). Sixty-six Chinese epileptic patients were recruited from Xiangya Hospital Central South University, of whom 40 patients were receiving OXC monotherapy, 11 patients were placed in the OXC bitherapy group combined with one enzyme-inducing anti-epileptic drugs (LTG or LEV), and 15 patients were placed in the OXC bitherapy group combined with VPA. Oxcarbazepine and its main metabolite 10-hydrocarbazepine (MHD) plasma concentrations were measured using high performance liquid chromatography (HPLC)-UV method. In addition, eight single nucleotide polymorphisms (SNPs) in CYP3A4, CYP3A5, ABCB1 gene were genotyped by polymerase chain reaction-improved multiple ligase detection reaction (PCR-iMLDR). In the OXC+VPA group, ABCB1 rs2032582 and rs2032582-rs10234411-rs1045642 TAG haplotype were associated with MHD and MHD+OXC plasma concentration before permutation test. In OXC monotherapy and OXC+ LTG/LEV groups, no significant association between genetic polymorphisms in CYP3A4/5, ABCB1 gene and OXC plasma concentration parameters were observed. CYP3A4/5 and ABCB1 genetic variants might not take part in the metabolism and transport of MHD and OXC among epileptic patients using OXC monotherapy and bitherapy in combination with LEV, LTG or VPA.

Hygromycin B and apramycin antibiotic resistance cassettes for use in Campylobacter jejuni.

Directory of Open Access Journals (Sweden)

Andrew Cameron

Full Text Available Campylobacter jejuni genetic manipulation is restricted by the limited number of antibiotic resistance cassettes available for use in this diarrheal pathogen. In this study, two antibiotic resistance cassettes were developed, encoding for hygromycin B and apramycin resistance, for use in mutagenesis or for selection of gene expression and complementation constructs in C. jejuni. First, the marker genes were successfully modified to allow for insertional mutagenesis or deletion of a gene-of-interest, and were bracketed with restriction sites for the facilitation of site-specific cloning. These hygromycin B and apramycin markers are encoded by plasmids pAC1H and pAC1A, respectively. We also modified an insertional gene-delivery vector to create pRRH and pRRA, containing the hygromycin B and apramycin resistance genes, and 3 unique restriction sites for the directional introduction of genes into the conserved multi-copy rRNA gene clusters of the C. jejuni chromosome. We determined the effective antibiotic concentrations required for selection, and established that no harmful effects or fitness costs were associated with carrying hygromycin B or apramycin resistance under standard C. jejuni laboratory conditions. Using these markers, the arylsulfatase reporter gene astA was deleted, and the ability to genetically complement the astA deletion using pRRH and pRRA for astA gene insertion was demonstrated. Furthermore, the relative levels of expression from the endogenous astA promoter were compared to that of polycistronic mRNA expression from the constitutive promoter upstream of the resistance gene. The development of additional antibiotic resistance cassettes for use in Campylobacter will enable multiple gene deletion and expression combinations as well as more in-depth study of multi-gene systems important for the survival and pathogenesis of this important bacterium.

PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis.

Science.gov (United States)

Xu, Xin; Xie, Yanqi; Lin, Yiwei; Xu, Xianglai; Zhu, Yi; Mao, Yeqing; Hu, Zhenghui; Wu, Jian; Chen, Hong; Zheng, Xiangyi; Qin, Jie; Xie, Liping

2012-12-01

Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; data were extracted and analyzed independently by two reviewers. Ultimately, 21 eligible case-control studies with a total of 8,415 cancer cases and 9,208 controls were included. The overall odds ratio (OR) with its 95% confidence interval (CI) showed a statistically significant association between the PAI-1 promoter 4G/5G polymorphism and cancer risk (4G/4G vs. 5G/5G: OR=1.25, 95% CI=1.07-1.47, P(heterogeneity)=0.001; 4G/4G vs. 4G/5G+5G/5G: OR=1.10, 95% CI=1.03-1.17, P(heterogeneity)=0.194; 4G/4G+4G/5G vs. 5G/5G: OR=1.17, 95% CI=1.01-1.35, P(heterogeneity)=0.041). In further subgroup analyses, the increased risk of cancer was observed in a subgroup of Caucasians with regards to endometrial cancer. Our meta-analysis suggests that the PAI-1 4G/5G polymorphism most likely contributes to susceptibility to cancer, particularly in Caucasians. Furthermore, the 4G allele may be associated with an increased risk of endometrial cancer.

Diverse gene cassettes in class 1 integrons of facultative oligotrophic bacteria of River Mahananda,West Bengal, India.

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Ranadhir Chakraborty

Full Text Available BACKGROUND: In this study a large random collection (n=2188 of facultative oligotrophic bacteria, from 90 water samples gathered in three consecutive years (2007-2009 from three different sampling sites of River Mahananda in Siliguri, West Bengal, India, were investigated for the presence of class 1 integrons and sequences of the amplification products. METHODOLOGY/PRINCIPAL FINDINGS: Replica plating method was employed for determining the antibiotic resistance profile of the randomly assorted facultative oligotrophic isolates. Genomic DNA from each isolate was analyzed by PCR for the presence of class 1 integron. Amplicons were cloned and sequenced. Numerical taxonomy and 16S rRNA gene sequence analyses were done to ascertain putative genera of the class 1 integron bearing isolates. Out of 2188 isolates, 1667 (76.19% were antibiotic-resistant comprising of both single-antibiotic resistance (SAR and multiple-antibiotic resistant (MAR, and 521 (23.81% were sensitive to all twelve different antibiotics used in this study. Ninety out of 2188 isolates produced amplicon(s of varying sizes from 0.15 to 3.45 KB. Chi-square (χ(2 test revealed that the possession of class 1 integron in sensitive, SAR and MAR is not equally probable at the 1% level of significance. Diverse antibiotic-resistance gene cassettes, aadA1, aadA2, aadA4, aadA5, dfrA1, dfrA5, dfrA7, dfrA12, dfrA16, dfrA17, dfrA28, dfrA30, dfr-IIe, blaIMP-9, aacA4, Ac-6'-Ib, oxa1, oxa10 and arr2 were detected in 64 isolates. The novel cassettes encoding proteins unrelated to any known antibiotic resistance gene function were identified in 26 isolates. Antibiotic-sensitive isolates have a greater propensity to carry gene cassettes unrelated to known antibiotic-resistance genes. The integron-positive isolates under the class Betaproteobacteria comprised of only two genera, Comamonas and Acidovorax of family Comamonadaceae, while isolates under class Gammaproteobacteria fell under the families

Integron gene cassettes and degradation of compounds associated with industrial waste: the case of the Sydney tar ponds.

Directory of Open Access Journals (Sweden)

Jeremy E Koenig

Full Text Available Integrons are genetic platforms that accelerate lateral gene transfer (LGT among bacteria. They were first detected on plasmids bearing single and multiple drug resistance determinants in human pathogens, and it is abundantly clear that integrons have played a major role in the evolution of this public health menace. Similar genetic elements can be found in nonpathogenic environmental bacteria and in metagenomic environmental DNA samples, and it is reasonable to suppose that integrons have facilitated microbial adaptation through LGT in niches outside infectious disease wards. Here we show that a heavily impacted estuary, exposed for almost a century to products of coal and steel industries, has developed a rich and unique cassette metagenome, containing genes likely to aid in the catabolism of compounds associated with industrial waste found there. In addition, we report that the most abundant cassette recovered in this study is one that encodes a putative LysR protein. This autoregulatory transcriptional regulator is known to activate transcription of linked target genes or unlinked regulons encoding diverse functions including chlorocatechol and dichlorophenol catabolism. Finally, only class 1 integrase genes were amplified in this study despite using different primer sets, and it may be that the cassettes present in the Tar Ponds will prove to be associated with class 1 integrase genes. Nevertheless, our cassette library provides a snapshot of a complex evolutionary process involving integron-meditated LGT likely to be important in natural bioremediation.

Identification of a novel streptococcal gene cassette mediating SOS mutagenesis in Streptococcus uberis

NARCIS (Netherlands)

Varhimo, Emilia; Savijoki, Kirsi; Jalava, Jari; Kuipers, Oscar P.; Varmanen, Pekka

Streptococci have been considered to lack the classical SOS response, defined by increased mutation after UV exposure and regulation by LexA. Here we report the identification of a potential self-regulated SOS mutagenesis gene cassette in the Streptococcaceae family. Exposure to UV light was found

Polycyclic aromatic hydrocarbons (PAHs) associated with PM2.5 within boundary layer: Cloud/fog and regional transport.

Science.gov (United States)

Yang, Minmin; Wang, Yan; Li, Hongli; Li, Tao; Nie, Xiaoling; Cao, Fangfang; Yang, Fengchun; Wang, Zhe; Wang, Tao; Qie, Guanghao; Jin, Tong; Du, Lili; Wang, Wenxing

2018-06-15

A study of PM 2.5 -associated PAHs analysis at Mount Lushan (1165m) was conducted to investigate the distributions of PAHs in PM 2.5 and influences of cloud/fog. The main purpose was to quantify the main emission sources of PAHs and estimate regional transport effects within the boundary layer. Mount Lushan is located between the boundary layer and troposphere, which is an ideal site for atmosphere transport investigation. The concentrations of PAHs in PM 2.5 were analyzed with GC-MS. The results showed that the volume concentration was 6.98ng/m 3 with a range from 1.47 to 25.17ng/m 3 and PAHs mass were 160.24μg/g (from 63.86 to 427.97μg/g) during the sampling time at Mount Lushan. The dominant compounds are BbF, Pyr and BP. In terms of aromatic-ring PAHs distributions, 4-6-ring PAHs are predominant, indicating that the high-ring PAHs tend to contribute more than low-ring PAHs in particulates. Due to frequent cloud/fog days at Mount Lushan, PAHs concentrations in the PM 2.5 were determined before and after cloud/fog weather. The results demonstrated that the cloud/fog and rain conditions cause lower PAHs levels. Regression analysis was used for studying the relationship of PAHs distributions with meteorological conditions like temperature, humidity and wind. The results showed that the temperature and wind speed were inversely related with PAHs concentration but humidity had no significant relationship. Furthermore, backward trajectories and PCA combined with DR (diagnostic ratio analysis) were employed to identify the influences of regional transport and main emission sources. The results revealed that PAHs in PM 2.5 were mainly affected by regional transport with the main emissions by mobile vehicle and steel industry, which contributed about 56.0% to the total PAHs in the area of Mount Lushan. In addition, backward trajectories revealed that the dominant air masses were from the northwest accounting for about one third of total PAHs. Copyright © 2018

5G, an approach towards future telemedicine

DEFF Research Database (Denmark)

Anwar, Sadia; Prasad, Ramjee; Kumar, Ambuj

for telemedicine application. Telemedicine’s applications and high data medical information generally require high definition visuals and lower latency connection, in addition mobility and reliability. The next generation of wireless communication standard, known as 5G, will provide data speed in (Gigabit per...... second) Gb/s with lower latency and higher reliability connection, and can be better approach for future telemedicine. In this paper we survey the current state of telemedicine along with examining the characteristics of 5G technology. We also present research challenges concerning 5G and telemedicine.......The use of smartphones has been increasing rapidly and it is expected that in future most people will have a smartphone capable of high speed Internet connection. The capability of smartphones with high definition display, computation power and multitude of sensors made it an excellent candidate...

Open-Source Based Testbed for Multioperator 4G/5G Infrastructure Sharing in Virtual Environments

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Ricardo Marco Alaez

2017-01-01

Full Text Available Fourth-Generation (4G mobile networks are based on Long-Term Evolution (LTE technologies and are being deployed worldwide, while research on further evolution towards the Fifth Generation (5G has been recently initiated. 5G will be featured with advanced network infrastructure sharing capabilities among different operators. Therefore, an open-source implementation of 4G/5G networks with this capability is crucial to enable early research in this area. The main contribution of this paper is the design and implementation of such a 4G/5G open-source testbed to investigate multioperator infrastructure sharing capabilities executed in virtual architectures. The proposed design and implementation enable the virtualization and sharing of some of the components of the LTE architecture. A testbed has been implemented and validated with intensive empirical experiments conducted to validate the suitability of virtualizing LTE components in virtual infrastructures (i.e., infrastructures with multitenancy sharing capabilities. The impact of the proposed technologies can lead to significant saving of both capital and operational costs for mobile telecommunication operators.

5G Innovations for New Business Opportunities

OpenAIRE

Bedo, Jean Sebastien; El Ayoubi, Salah Eddine; Filippou, Miltiadis; Gavras, Anastasius; Giustiniano, Domenico; Iovanna, Paola; Manzalini, Antonio; Queseth, Olav; Rokkas, Theodoros; Surridge, Michael; Tjelta, Terje

2017-01-01

International audience; 5G is the next generation mobile network that enables innovation and supports progressive change across all vertical industries and across our society . Through its Radio Access Network (RAN) design and its orchestrated end-to-end architecture, it has the potential to boost innovation and generate economic growth in the European economy. The 5G service models support agility and dynamicity, thereby impacting the granularity, duration and trustworthiness of business rel...

Signal processing for 5G algorithms and implementations

CERN Document Server

Luo, Fa-Long

2016-01-01

A comprehensive and invaluable guide to 5G technology, implementation and practice in one single volume. For all things 5G, this book is a must-read. Signal processing techniques have played the most important role in wireless communications since the second generation of cellular systems. It is anticipated that new techniques employed in 5G wireless networks will not only improve peak service rates significantly, but also enhance capacity, coverage, reliability , low-latency, efficiency, flexibility, compatibility and convergence to meet the increasing demands imposed by applications such as big data, cloud service, machine-to-machine (M2M) and mission-critical communications. This book is a comprehensive and detailed guide to all signal processing techniques employed in 5G wireless networks. Uniquely organized into four categories, New Modulation and &n sp;Coding, New Spatial Processing, New Spectrum Opportunities and New System-level Enabling Technologies, it covers everything from network architecture...

Identification of Residues in the Lipopolysaccharide ABC Transporter That Coordinate ATPase Activity with Extractor Function.

Science.gov (United States)

Simpson, Brent W; Owens, Tristan W; Orabella, Matthew J; Davis, Rebecca M; May, Janine M; Trauger, Sunia A; Kahne, Daniel; Ruiz, Natividad

2016-10-18

The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, Gram-negative bacteria must extract newly synthesized LPS from the inner membrane, transport it across the aqueous periplasm, and translocate it across the outer membrane. The LptA to -G proteins assemble into a transenvelope complex that transports LPS from the inner membrane to the cell surface. The Lpt system powers LPS transport from the inner membrane by using a poorly characterized ATP-binding cassette system composed of the ATPase LptB and the transmembrane domains LptFG. Here, we characterize a cluster of residues in the groove region of LptB that is important for controlling LPS transport. We also provide the first functional characterization of LptFG and identify their coupling helices that interact with the LptB groove. Substitutions at conserved residues in these coupling helices compromise both the assembly and function of the LptB 2 FG complex. Defects in LPS transport conferred by alterations in the LptFG coupling helices can be rescued by changing a residue in LptB that is adjacent to functionally important residues in the groove region. This suppression is achieved by increasing the ATPase activity of the LptB 2 FG complex. Taken together, these data identify a specific binding site in LptB for the coupling helices of LptFG that is responsible for coupling of ATP hydrolysis by LptB with LptFG function to achieve LPS extraction. Lipopolysaccharide (LPS) is synthesized at the cytoplasmic membrane of Gram-negative bacteria and transported across several compartments to the cell surface, where it forms a barrier that protects these organisms from antibiotics. The LptB 2 FG proteins form an ATP-binding cassette (ABC) transporter that uses energy from ATP hydrolysis in the cytoplasm to facilitate extraction of LPS from the outer face of the

Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis

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Zhang Tengyue

2013-01-01

Full Text Available Abstract Background Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1 is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Methods Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs with 95% confidence intervals (CIs were used to assess the strength of associations. Results Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52. In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77. When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00. We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57. Conclusions The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of

Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis.

Science.gov (United States)

Zhang, Tengyue; Pang, Chong; Li, Ningdong; Zhou, Elaine; Zhao, Kanxing

2013-01-02

Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene

The protein source in embryo culture media influences birthweight: a comparative study between G1 v5 and G1-PLUS v5.

Science.gov (United States)

Zhu, Jinliang; Li, Ming; Chen, Lixue; Liu, Ping; Qiao, Jie

2014-07-01

Does protein source or human serum albumin (HSA) in embryo culture media influence the subsequent birthweight? A significant difference was observed in gestational age- and gender-adjusted birthweight (Z scores) and the proportion of large-for-gestational age (LGA) babies between embryos cultured in G1 v5 and those cultured in G1-PLUS v5 media. It has been reported that the birthweights of singletons born from embryos cultured in Vitrolife are significantly higher than those cultured in the Cook group of media, and that G1-PLUS (Vitrolife, Gothenburg, Sweden) is associated with increased birth and placenta weights compared with Medicult ISMI. This study was a retrospective analysis of neonatal birthweights, and included 1097 singletons born from fresh embryo transfer cycles at the Center for Reproductive Medicine of Peking University Third Hospital between January 2011 and August 2012. The number of singletons born from G1 v5 culture media was 489, and the number of singletons born from G1-PLUS v5 media was 608. Patients media groups. The absolute birthweights for singletons resulting from G1-PLUS v5 were not different from singletons resulting from G1 v5 (3375.9 ± 479.6 g versus 3333.2 ± 491.6 g, respectively; P = 0.14). However the Z scores for singletons from embryos cultured in G1-PLUS v5 were significantly higher than for singletons cultured in G1 v5 (0.28 ± 1.12 versus 0.09 ± 1.15, respectively; P = 0.04), and more LGA babies were born from G1-PLUS v5 culture compared with G1 v5 (16.8 versus 12.1%, respectively; P = 0.03) culture. Finally, multiple linear regression analysis suggested that female weight (P = 0.00), male height (P = 0.04), gestational age at birth (P = 0.00), infant gender (P = 0.00) and culture media (P = 0.04) all had significant effects on the birthweights of singleton newborns. This study was limited by its retrospective design. Our study suggests that protein source/HSA has a significant effect on birthweights of singleton newborns

Survey of Promising Technologies for 5G Networks

Directory of Open Access Journals (Sweden)

Nam Tuan Le

2016-01-01

Full Text Available As an enhancement of cellular networks, the future-generation 5G network can be considered an ultra-high-speed technology. The proposed 5G network might include all types of advanced dominant technologies to provide remarkable services. Consequently, new architectures and service management schemes for different applications of the emerging technologies need to be recommended to solve issues related to data traffic capacity, high data rate, and reliability for ensuring QoS. Cloud computing, Internet of things (IoT, and software-defined networking (SDN have become some of the core technologies for the 5G network. Cloud-based services provide flexible and efficient solutions for information and communications technology by reducing the cost of investing in and managing information technology infrastructure. In terms of functionality, SDN is a promising architecture that decouples control planes and data planes to support programmability, adaptability, and flexibility in ever-changing network architectures. However, IoT combines cloud computing and SDN to achieve greater productivity for evolving technologies in 5G by facilitating interaction between the physical and human world. The major objective of this study provides a lawless vision on comprehensive works related to enabling technologies for the next generation of mobile systems and networks, mainly focusing on 5G mobile communications.

Structure and mechanism of ATP-dependent phospholipid transporters

DEFF Research Database (Denmark)

Lopez Marques, Rosa Laura; Poulsen, Lisbeth Rosager; Bailly, Aurélien

2015-01-01

Background ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other. Scope of review This review aims to identify common mechanistic features...... in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters. Major conclusions Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further......, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic...

Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced transplacental transport.

Science.gov (United States)

Stapleton, Nigel M; Armstrong-Fisher, Sylvia S; Andersen, Jan Terje; van der Schoot, C Ellen; Porter, Charlene; Page, Kenneth R; Falconer, Donald; de Haas, Masja; Williamson, Lorna M; Clark, Michael R; Vidarsson, Gestur; Armour, Kathryn L

2018-03-01

We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Innovative electron transport methods in EGS5

International Nuclear Information System (INIS)

Bielajew, A.F.; Wilderman, S.J.

2000-01-01

The initial formulation of a Monte Carlo scheme for the transport of high-energy (>≅ 100 keV) electrons was established by Berger in 1963. Calling his method the 'condensed history theory', Berger combined the theoretical results of the previous generation of research into developing approximate solutions of the Boltzmann transport equation with numerical algorithms for exploiting the power of computers to permit iterative, piece-wise solution of the transport equation in a computationally intensive but much less approximate fashion. The methods devised by Berger, with comparatively little modification, provide the foundation of all present day Monte Carlo electron transport simulation algorithms. Only in the last 15 years, beginning with the development and publication of the PRESTA algorithm, has there been a significant revisitation of the problem of simulating electron transport within the condensed history framework. Research in this area is ongoing, highly active, and far from complete. It presents an enormous challenge, demanding derivation of new analytical transport solutions based on underlying fundamental interaction mechanisms, intuitive insight in the development of computer algorithms, and state of the art computer science skills in order to permit deployment of these techniques in an efficient manner. The EGS5 project, a modern ground-up rewrite of the EGS4 code, is now in the design phase. EGS5 will take modern photon and electron transport algorithms and deploy them in an easy-to-maintain, modern computer language-ANSI-standard C ++. Moreover, the well-known difficulties of applying EGS4 to practical geometries (geometry code development, tally routine design) should be made easier and more intuitive through the use of a visual user interface being designed by Quantum Research, Inc., work that is presented elsewhere in this conference. This report commences with a historical review of electron transport models culminating with the proposal of a

The association between PAI-1 -675 4G/5G polymorphism and type 2 diabetes mellitus.

Science.gov (United States)

Chen, L; Li, S-Y; Liu, M

2017-08-15

In this study, we aimed to analyze the association between plasminogen activator inhibitor 1 (PAI-1) -675 4G/5G polymorphism and type 2 diabetes mellitus (T2DM) risk. We included in 187 T2DM patients and 186 heathy controls between 2014 and 2017 from Tianjin Gong An Hospital, China. All patients and controls were ethnically Chinese Han population. The primers and polymerase chain reaction (PCR) conditions were performed. Results from this case-control study suggested that PAI-1 -675 4G/5G polymorphism was not associated with T2DM risk in four genetic models. Additionally, PAI-1 -675 4G/5G polymorphism was not associated with clinical and laboratory characteristics, such as age, gender, body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, and HbA1c. In conclusion, this case-control study suggested that PAI-1 -675 4G/5G polymorphism was not associated with T2DM risk in this population.

Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

NARCIS (Netherlands)

Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

An architectural framework for 5G indoor communications

NARCIS (Netherlands)

Chandra, Kishor; Prasad, R. Venkatesha; Niemegeers, Ignas

2015-01-01

In this paper, we emphasize on indoor networks in 5G era. We explore the possible technologies and architectural solutions for 5G indoor communications. Owing to the fact that requirements for indoor and outdoor communications will be quite different in the next generation networks, we try to define

Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development

NARCIS (Netherlands)

Rijpma, S.R.; Velden, M. van der; Annoura, T.; Matz, J.M.; Kenthirapalan, S.; Kooij, T.W.; Matuschewski, K.; Gemert, G.J.A. van; Vegte-Bolmer, M.G. van de; Siebelink-Stoter, R.; Graumans, W.; Ramesar, J.; Klop, O.; Russel, F.G.; Sauerwein, R.W.; Janse, C.J.; Franke-Fayard, B.M.; Koenderink, J.B.

2016-01-01

Multidrug resistance (MDR) proteins belong to the B subfamily of the ATP Binding Cassette (ABC) transporters, which export a wide range of compounds including pharmaceuticals. In this study, we used reverse genetics to study the role of all seven Plasmodium MDR proteins during the life cycle of

The Plasminogen Activator Inhibitor 1 4G/5G Polymorphism and the Risk of Alzheimer's Disease.

Science.gov (United States)

Fekih-Mrissa, Najiba; Mansour, Malek; Sayeh, Aicha; Bedoui, Ines; Mrad, Meriem; Riahi, Anis; Mrissa, Ridha; Nsiri, Brahim

2017-09-01

The aim of this study was to determine whether plasminogen activator inhibitor 1 (PAI-1) is associated with the risk of Alzheimer's disease (AD) in Tunisian patients. We analyzed the genotype and allele frequency distribution of the PAI-1 polymorphism in 60 Tunisian patients with AD and 120 healthy controls. The results show a significantly increased risk of AD in carriers of the 4G/4G and 4G/5G genotypes versus the wild-type 5G/5G genotype (4G/4G: 28.33% in patients vs 10.0% in controls; P 5G: 55.0% in patients vs 38.33% in controls; OR = 4.45; P < 10 -3 ). The 4G allele was also more frequently found in patients compared with controls; P < 10 -3 ; OR = 3.07. For all participants and by gender, homozygotic carriers (4G/4G) were at an increased risk of AD over heterozygotes and women were at an increased risk over their male genotype counterparts. The odds ratio for AD among 4G/4G carriers for any group was approximately twice that of heterozygotes in the same group. Women homozygotes ranked highest for AD risk (OR = 20.8) and, in fact, women heterozygotes (OR = 9.03) ranked higher for risk than male homozygotes (OR = 6.12). These preliminary exploratory results should be confirmed in a larger study.

3-D extension C5G7 MOX benchmark results using PARTISN

Energy Technology Data Exchange (ETDEWEB)

Dahl, J.A. [Los Alamos National Laboratory, CCS-4 Transport Methods Group, Los Alamos, NM (United States)

2005-07-01

We have participated in the Expert Group of 3-D Radiation Transport Benchmarks' proposed 3-dimensional Extension C5G7 MOX problems using the discrete ordinate transport code PARTISN. The computational mesh was created using the FRAC-IN-THE-BOX code, which produces a volume fraction Cartesian mesh from combinatorial geometry descriptions. k{sub eff} eigenvalues, maximum pin powers, and average fuel assembly powers are reported and compared to a benchmark quality Monte Carlo solution. We also present a two dimensional mesh convergence study examining the affects of using volume fractions to approximate the water-pin cell interface. It appears that the control rod pin cell must be meshed twice as fine as a fuel pin cell in order to achieve the same spatial error when using the volume fraction method to define water channel-pin cell interfaces. It is noted that the previous PARTISN results provided to the OECD/NEA Expert Group on 3-dimensional Radiation Benchmarks contained a cross section error, and therefore should be disregarded.

3-D extension C5G7 MOX benchmark results using PARTISN

International Nuclear Information System (INIS)

Dahl, J.A.

2005-01-01

We have participated in the Expert Group of 3-D Radiation Transport Benchmarks' proposed 3-dimensional Extension C5G7 MOX problems using the discrete ordinate transport code PARTISN. The computational mesh was created using the FRAC-IN-THE-BOX code, which produces a volume fraction Cartesian mesh from combinatorial geometry descriptions. k eff eigenvalues, maximum pin powers, and average fuel assembly powers are reported and compared to a benchmark quality Monte Carlo solution. We also present a two dimensional mesh convergence study examining the affects of using volume fractions to approximate the water-pin cell interface. It appears that the control rod pin cell must be meshed twice as fine as a fuel pin cell in order to achieve the same spatial error when using the volume fraction method to define water channel-pin cell interfaces. It is noted that the previous PARTISN results provided to the OECD/NEA Expert Group on 3-dimensional Radiation Benchmarks contained a cross section error, and therefore should be disregarded

Drug transporters in breast cancer

DEFF Research Database (Denmark)

Kümler, Iben; Stenvang, Jan; Moreira, José

2015-01-01

Despite the advances that have taken place in the past decade, including the development of novel molecular targeted agents, cytotoxic chemotherapy remains the mainstay of cancer treatment. In breast cancer, anthracyclines and taxanes are the two main chemotherapeutic options used on a routine...... basis. Although effective, their usefulness is limited by the inevitable development of resistance, a lack of response to drug-induced cancer cell death. A large body of research has resulted in the characterization of a plethora of mechanisms involved in resistance; ATP-binding cassette transporter...

Inactivation of the Ecs ABC Transporter of Staphylococcus aureus Attenuates Virulence by Altering Composition and Function of Bacterial Wall

NARCIS (Netherlands)

Jonsson, Ing-Marie; Juuti, Jarmo T.; Francois, Patrice; AlMajidi, Rana; Pietiainen, Milla; Girard, Myriam; Lindholm, Catharina; Saller, Manfred J.; Driessen, Arnold J. M.; Kuusela, Pentti; Bokarewa, Maria; Schrenzel, Jacques; Kontinen, Vesa P.

2010-01-01

Background: Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic Gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s)

The characteristics of Fugi IP Cassette Type PII and application for radiation oncology quality assurance tests and portal imaging

International Nuclear Information System (INIS)

Soh, H.S.; Ung, N.M.; Ng, K.H.

2008-01-01

Full text: The advancement of digital imaging has prompted more medical institutions to go filmless. The computed radiography (CR) system is becoming an important tool not only in diagnostic imaging, but also in radiation oncology. A new CR system that was specially designed for the use in radiation oncology. Fuji IP cassette type PII has been introduced to the market in the middle of year 2006. This project aimed to study some basic physical characteristics of this new type of cassette and explore its application for performing quality assurance (QA) tests and portal imaging in radiotherapy. All the images were read by FCR 5000 Plus reader. The image was found to reach its saturation value of 1023 (due to the image was stored in 10 bits data) by depending on the sensitivity value being adjusted. The uniformity test gave the result of 0.12%. The cassette was used to perform the QA tests which were previously performed using film. All the results met the specification as stated in AAPM Task Group 40. The comparison for the portal images of Portal Vision contrast-detail phantom showed that the spatial resolution of the images obtained by CR system (Fujifilm Co.. Ltd.. Tokyo. Japan) were better than the EPID (Varian Medical Systems. Inc.. Palo Alto. USA) and film system (Eastman Kodak Co.. New York. USA). The IP cassette type PII was found to be suitable as an alternative QA test tool and portal imaging in radiotherapy.

Construction of brewing-wine Aspergillus oryzae pyrG- mutant by pyrG gene deletion and its application in homology transformation.

Science.gov (United States)

Du, Yu; Xie, Guizhen; Yang, Chunfa; Fang, Baishan; Chen, Hongwen

2014-06-01

pyrG(-) host cells are indispensable for pyrG(-) based transformation system. Isolations of pyrG(-) host cells by random mutations are limited by time-consuming, unclear genetic background and potential interferences of homogenous recombination. The purpose of this study was to construct brewing-wine Aspergillus oryzae pyrG(-) mutant by site-directed mutation of pyrG gene deletion which would be used as a host for further transformation. pMD-pyrGAB, a vector carrying pyrG deletion cassette, was used to construct pyrG(-) mutant of A. oryzae. Three stable pyrG deletion mutants of A. oryzae were isolated by resistant to 5-fluoroorotic acid and confirmed by polymerase chain reaction analysis, indicating that pyrG was completely excised. The ΔpyrG mutants were applied as pyrG(-) host cells to disrupt xdh gene encoding xylitol dehydrogenase, which involves in xylitol production of A. oryzae. The xdh disruption mutants were efficiently constructed by transforming a pMD-pyrG-xdh disruption plasmid carrying pyrG, and the produced xylitol concentration of the Δxdh mutant was three times as much as that of the ΔpyrG recipient. Site-directed pyrG gene deletion is thus an effective way for the isolation of pyrG(-) host cells, and the established host-vector system could be applied in further functional genomics analysis and molecular breeding of A. oryzae. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

PAI-1 expression and its regulation by promoter 4G/5G polymorphism in clear cell renal cell carcinoma.

Science.gov (United States)

Choi, Jung-Woo; Lee, Ju-Han; Park, Hong Seok; Kim, Young-Sik

2011-10-01

To characterise patients with high plasminogen activator inhibitor-1 (PAI-1) expression as oral PAI-1 antagonists are currently in preclinical trials, and to determine whether the PAI-1 promoter 4G/5G polymorphism regulates PAI-1 expression in clear cell renal cell carcinoma (CCRCC). PAI-1 expression was examined by immunohistochemistry in 69 CCRCC specimens. In addition, the promoter 4G/5G polymorphism was investigated by both allele-specific PCR and direct DNA sequencing. PAI-1 was overexpressed in 25/69 (36.2%) patients with CCRCC. PAI-1 staining was intense in tumour cells with a high Fuhrman nuclear grade and in spindle-shaped tumour cells. PAI-1 expression was significantly associated with older age at diagnosis (p=0.027), high nuclear grade (p5G and 31.9% (22/69) 5G/5G. The homozygous 4G/4G or 5G/5G group showed a tendency for a high nuclear grade (p=0.05) but the 4G/5G polymorphism was not related to other prognostic parameters. PAI-1 expression was poorly correlated with its promoter 4G/5G polymorphism (Spearman ρ=0.088). CCRCC with high PAI-1 expression is characterised by older age, high nuclear grade, advanced stage, distant metastasis and/or shortened disease-free survival. PAI-1 expression is not affected by the promoter 4G/5G polymorphism.

Denial of Service Prevention for 5G

DEFF Research Database (Denmark)

Li, Yao; Kaur, Bipjeet; Andersen, Birger

2011-01-01

5G wireless mobile communication is expected to include a large number of advanced technologies in order to further increase bandwidth, Quality of Service (QoS), improve usability and security, decrease delays and cost of service. Software Defined Radio (SDR) will be the platform for advanced...... terminals. Our focus is security and especially prevention of Denial of Service (DoS) attacks which we believe will become more common in commercial networks through increasing availability of easy programmable SDRs. We propose a secret version of Adaptive Frequency Hopping, as a possible 5G technology...

A mutation within the extended X loop abolished substrate-induced ATPase activity of the human liver ATP-binding cassette (ABC) transporter MDR3.

Science.gov (United States)

Kluth, Marianne; Stindt, Jan; Dröge, Carola; Linnemann, Doris; Kubitz, Ralf; Schmitt, Lutz

2015-02-20

The human multidrug resistance protein 3 (MDR3/ABCB4) belongs to the ubiquitous family of ATP-binding cassette (ABC) transporters and is located in the canalicular membrane of hepatocytes. There it flops the phospholipids of the phosphatidylcholine (PC) family from the inner to the outer leaflet. Here, we report the characterization of wild type MDR3 and the Q1174E mutant, which was identified previously in a patient with progressive familial intrahepatic cholestasis type 3 (PFIC-3). We expressed different variants of MDR3 in the yeast Pichia pastoris, purified the proteins via tandem affinity chromatography, and determined MDR3-specific ATPase activity in the presence or absence of phospholipids. The ATPase activity of wild type MDR3 was stimulated 2-fold by liver PC or 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine lipids. Furthermore, the cross-linking of MDR3 with a thiol-reactive fluorophore blocked ATP hydrolysis and exhibited no PC stimulation. Similarly, phosphatidylethanolamine, phosphatidylserine, and sphingomyelin lipids did not induce an increase of wild type MDR3 ATPase activity. The phosphate analogues beryllium fluoride and aluminum fluoride led to complete inhibition of ATPase activity, whereas orthovanadate inhibited exclusively the PC-stimulated ATPase activity of MDR3. The Q1174E mutation is located in the nucleotide-binding domain in direct proximity of the leucine of the ABC signature motif and extended the X loop, which is found in ABC exporters. Our data on the Q1174E mutant demonstrated basal ATPase activity, but PC lipids were incapable of stimulating ATPase activity highlighting the role of the extended X loop in the cross-talk of the nucleotide-binding domain and the transmembrane domain. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The -675 4G/5G polymorphism in the PAI-1 gene may not contribute to the risk of PCOS.

Science.gov (United States)

Zhang, T-T; Yuan, L; Yang, Y-M; Ren, Y

2014-08-01

The association between the -675 4G/5G polymorphism in PAI-1 gene and PCOS has been studied with inconclusive results. We sought to investigate this inconsistency by performing a comprehensive meta-analysis on the polymorphism. Searches were performed in the PubMed, Embase, CNKI and Wanfang databases, covering all papers. Statistical analysis was performed using Revman5.2 and STATA11.0 software. A total of 11 case-control studies were extracted on the polymorphism involving 1861 PCOS cases and 1187 controls. The results showed that, no significant increased/decreased risk were found for the polymorphism for PCOS: OR = 1.03, 95% CI = 0.77-1.66, p = 0.52 for 4G4G + 4G5G vs. 5G5G; OR = 0.99, 95% CI = 0.66-1.49, p = 0.96 for 4G4G vs. 5G5G + 4G5G; OR = 1.08, 95% CI = 0.66-1.79, p = 0.76 for 4G4G vs. 5G5G; OR = 1.11, 95% CI = 0.78-1.58, p = 0.56 for 4G5G vs. 5G5G; OR = 1.00, 95% CI = 0.71-1.41, p = 0.99 for 4G vs. 5G. In the further subgroup analysis by ethnicity, we did not find a significant association between the polymorphism for PCOS risk in either Asians or Europeans. Our findings demonstrated that -675 4G/5G polymorphism in the PAI-1 gene might not be a risk factor for the development of PCOS.

ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer

NARCIS (Netherlands)

Trumpi, K.; Emmink, B. L.; Prins, A. M.; van Oijen, M. G. H.; van Diest, P. J.; Punt, C. J. A.; Koopman, M.; Kranenburg, O.; Borel Rinkes, I. H. M.

2015-01-01

Background: Active efflux of irinotecan by ATP-binding cassette (ABC)-transporters, in particular ABCB1 and ABCG2, is a well-established drug resistance mechanism in vitro and in pre-clinical mouse models, but its relevance in colorectal cancer (CRC) patients is unknown. Therefore, we assessed the

Design Considerations for a 5G Network Architecture

OpenAIRE

Bergren, Steven

2017-01-01

The data rates of up to 10 GB/s will characterize 5G networks telecommunications standards that are envisioned to replace the current 4G/IMT standards. The number of network-connected devices is expected to be 7 trillion by the end of this year and the traffic is expected to rise by an order of magnitude in the next 8 years. It is expected that elements of 5G will be rolled out by early 2020s to meet business and consumer demands as well as requirements of the Internet of Things. China's Mini...

Purification and biochemical characterisation of the yeast ABC transporter Pdr11p

DEFF Research Database (Denmark)

Laub, Katrine Rude

Sterols constitute an essential lipid class in eukaryotic membranes where intracellular distributions are highly regulated. In the yeast Saccharomyces cerevisiae sterol uptake has been attributed to the two plasma membrane-localised ATP-binding cassette (ABC) transporters, Aus1p and Pdr11p...... of the yeast ABC transporter Pdr11p. This includes optimising its overexpression utilising the galactose induction system in S. cerevisiae, screening for the best detergent to extract the protein from the membrane, and establishing purification and reconstitution protocols. By providing a purification...

Analysis of ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}D{sub 2}){gamma}{sub 5g}, {gamma}{sub 3g} and ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}L{sub 6}){gamma}{sub 1g}, a{gamma}{sub 5g} two-photon absorption spectra of Cs{sub 2}NaYF{sub 6}:Eu{sup 3+}

Energy Technology Data Exchange (ETDEWEB)

Ning Lixin; Wang Dianyuan; Xia Shangda [Structure Research Laboratory, Academica Sinica, Department of Physics, University of Science and Technology of China, Heifei, Anhui (China); Thorne, Jonathan R.G. [Inorganic Chemistry Laboratory, Department of Chemistry, University of Oxford (United Kingdom); Tanner, Peter A. [Department of Biology and Chemistry, City University of Hong Kong, Kowloon (China)

2002-04-15

The direct calculation of transition line strengths and relative intensities is presented for two intraconfigurational two-photon absorption (TPA) transitions of Eu{sup 3+} in the cubic Cs{sub 2}NaYF{sub 6} host. Crystal field wavefunctions were utilized for the initial and final f{sup N}-electron states and various approaches were used in constructing all the 4f{sup N-1} 5d{sup 1} intermediate-state wavefunctions. The calculated relative intensities of the ({sup 7}F{sub 0}) {gamma}{sub 1g}{yields}({sup 5}D{sub 2}){gamma}{sub 5g}, {gamma}{sub 3g} TPA transitions are in reasonable agreement with experiment. The neglect of J-mixing in the initial state has only a small effect upon the calculation, whereas the neglect of spin-orbit couplings within the initial and terminal states drastically reduces the calculated transition linestrengths, but does not markedly change the intensity ratios. In the case of the ({sup 7}F{sub 0}){gamma}{sub 1g}{yields}({sup 5}L{sub 6}){gamma}{sub 1g}, a{gamma}{sub 5g} transitions, serious discrepancies between experiment and theory are found if the intermediate states are constructed from a 4f{sup 5} core comprising free ion states and the 5d{sup 1} crystal field states. Satisfactory agreement is, however, found when the 4f{sup 5} crystal field states are utilized in constructing the intermediate states. The contributions to the transition moment have been evaluated for various Hamiltonian terms and the results are discussed. (author)

4G/5G and A-844G Polymorphisms of Plasminogen Activator Inhibitor-1 Associated with Glioblastoma in Iran--a Case-Control Study.

Science.gov (United States)

Pooyan, Honari; Ahmad, Ebrahimi; Azadeh, Rakhshan

2015-01-01

Glioblastoma is a highly aggressive and malignant brain tumor. Risk factors are largely unknown however, although several biomarkers have been identified which may support development, angiogenesis and invasion of tumor cells. One of these biomarkers is PAI-1. 4G/5G and A-844G are two common polymorphisms in the gene promotor of PAI 1 that may be related to high transcription and expression of this gene. Studies have shown that the prevalence of the 4G and 844G allele is significantly higher in patients with some cancers and genetic disorders. We here assessed the association of 4G/5G and A-844G polymorphisms with glioblastoma cancer risk in Iranians in a case-control study. All 71 patients with clinically confirmed and 140 volunteers with no history and symptoms of glioblastoma as control group were screened for 4G/5G and A-844G polymorphisms of PAI-1, using ARMS-PCR. Genotype and allele frequencies of case and control groups were analyzed using the DeFinetti program. Our results showed significant associations between 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms of the PAI-1 gene with glioblastoma cancer risk in our Iranian population. The results of this study supporting an association of the PAI-1 4G/5G (p=0.01824) and A-844G (p=0.02012) polymorphisms with increasing glioblastoma cancer risk in Iranian patients.

ABC transporters affect the elimination and toxicity of CdTe quantum dots in liver and kidney cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Mingli; Yin, Huancai; Bai, Pengli [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); Miao, Peng [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Deng, Xudong [Department of Chemical Engineering, McMaster University, Hamilton, Ontario, L8S 4L7 (Canada); Xu, Yingxue [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Hu, Jun [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China); Yin, Jian, E-mail: yinj@sibet.ac.cn [CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163 (China)

2016-07-15

This paper aimed to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters on the efflux and the toxicity of nanoparticles in liver and kidney cells. In this study, we synthesized CdTe quantum dots (QDs) that were monodispersed and emitted green fluorescence (maximum peak at 530 nm). Such QDs tended to accumulate in human hepatocellular carcinoma cells (HepG2), human kidney cells 2 (HK-2), and Madin-Darby canine kidney (MDCK) cells, and cause significant toxicity in all the three cell lines. Using specific inhibitors and inducers of P-glycoprotein (Pgp) and multidrug resistance associated proteins (Mrps), the cellular accumulation and subsequent toxicity of QDs in HepG2 and HK-2 cells were significantly affected, while only slight changes appeared in MDCK cells, corresponding well with the functional expressions of ABC transporters in cells. Moreover, treatment of QDs caused concentration- and time- dependent induction of ABC transporters in HepG2 and HK-2 cells, but such phenomenon was barely found in MDCK cells. Furthermore, the effects of CdTe QDs on ABC transporters were found to be greater than those of CdCl{sub 2} at equivalent concentrations of cadmium, indicating that the effects of QDs should be a combination of free Cd{sup 2+} and specific properties of QDs. Overall, these results indicated a strong dependence between the functional expressions of ABC transporters and the efflux of QDs, which could be an important reason for the modulation of QDs toxicity by ABC transporters. - Highlights: • ABC transporters contributed actively to the cellular efflux of CdTe quantum dots. • ABC transporters affected the cellular toxicity of CdTe quantum dots. • Treatment of CdTe quantum dots induced the gene expression of ABC transporters. • Free Cd{sup 2+} should be partially involved in the effects of QDs on ABC transporters. • Cellular efflux of quantum dots could be an important modulator for its toxicity.

Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis.

Science.gov (United States)

Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik

2013-01-01

Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

Random Linear Network Coding for 5G Mobile Video Delivery

Directory of Open Access Journals (Sweden)

Dejan Vukobratovic

2018-03-01

Full Text Available An exponential increase in mobile video delivery will continue with the demand for higher resolution, multi-view and large-scale multicast video services. Novel fifth generation (5G 3GPP New Radio (NR standard will bring a number of new opportunities for optimizing video delivery across both 5G core and radio access networks. One of the promising approaches for video quality adaptation, throughput enhancement and erasure protection is the use of packet-level random linear network coding (RLNC. In this review paper, we discuss the integration of RLNC into the 5G NR standard, building upon the ideas and opportunities identified in 4G LTE. We explicitly identify and discuss in detail novel 5G NR features that provide support for RLNC-based video delivery in 5G, thus pointing out to the promising avenues for future research.

Associations between dru Types and SCCmec Cassettes

DEFF Research Database (Denmark)

Bartels, Mette D; Boye, Kit; Oliveira, Duarte C

2013-01-01

SCCmec types I to VI. The isolates represented a broad genetic background based on Staphylococcal protein A (spa) typing and multilocus sequence typing (MLST) and included 68 isolates (68 patients) from an outbreak with t024-ST8-IVa and 26 isolates from the same patient. Sequencing identified 53 dru......Molecular typing is an important tool in the investigation of methicillin resistant Staphylococcus aureus (MRSA) outbreaks and in following the evolution of MRSA. The staphylococcal cassette chromosome mec (SCCmec) contains a hypervariable region with a variable number of 40 bp repeats named direct...... repeat units (dru). The dru region has been suggested as a supplementary typing method for MRSA and an international nomenclature exists. The purpose of this study was to investigate the diversity and variability of the dru region in a diverse collection of MRSA. We studied 302 MRSA isolates harbouring...

Excision of the Staphylococcal Cassette Chromosome mec (SCCmec) and its crucial role in the horizontal transfer of methicillin resistance in staphylococci.

OpenAIRE

Stojanov, M.

2012-01-01

Staphylococcus aureus est un pathogène humain majeur ayant développé des résistances contre la quasi totalité des antibiotiques disponibles, incluant la très importante famille des β- lactamines. La résistance à cette classe d'antibiotiques est conférée par la « Staphylococcal Cassette Chromosome mec » (SCCmec), qui est un élément génétique mobile capable de s'insérer dans le chromosome bactérien et capable d'être transféré horizontalement chez d'autres staphylocoques. Le mécanisme moléculair...

Structural design of DEMO Divertor Cassette Body: provisional FEM analysis and introductive application of RCC-MRx design rules

Energy Technology Data Exchange (ETDEWEB)

Frosi, Paolo, E-mail: paolo.frosi@enea.it [Unità Tecnica Fusione-ENEA C.R. Frascati, Via E. Fermi 45, 00044 Frascati (Italy); Mazzone, Giuseppe [Unità Tecnica Fusione-ENEA C.R. Frascati, Via E. Fermi 45, 00044 Frascati (Italy); You, Jeong-Ha [Max Planck Institute of Plasma Physics, Boltzmann Str. 2, 85748 Garching (Germany)

2016-11-01

This paper deals with the early steps in developing a structural fem model of DEMO Divertor. The study is focused on the thermal and structural analysis of the Cassette Body: a new geometry has been developed for this component: it is foreseen that the plasma facing component (PFC) will be directly placed on the cassette but for the Dome no choice has been adopted yet. For now the model contains only a suitable schematization of the Cassette Body and its objective is to analyze the effect produced by the main loads (electromagnetic loads, coolant pressure, thermal neutron and convective loads) on itself: an available estimate of loads is that one derived from ITER: for a proper translation some assumptions have been made and they are described in the paper. Now it is not a primary purpose to obtain some definitive statements about stresses, displacements, temperatures and so on; the authors want to construct a set of FEM models that will help all the decisions of DEMO Divertor design in its future development. This set is conceived as a tool that shall be improved to account for all the main enhancements that will be found in geometry, in material properties data and in load evaluations. Moreover, the main design variables (loads, material properties, some geometric items, mesh element size) are defined as parameters. This work considers also an introductive approach for future structural verification of the Divertor Cassette Body: so a concern of the Design and Construction Rules for Mechanical Components of Nuclear Installation (RCC-MRx) has been implemented. The FEM code used is Ansys rel. 15.

A Benzothiazole Derivative (5g) Induces DNA Damage And Potent G2/M Arrest In Cancer Cells.

Science.gov (United States)

Hegde, Mahesh; Vartak, Supriya V; Kavitha, Chandagirikoppal V; Ananda, Hanumappa; Prasanna, Doddakunche S; Gopalakrishnan, Vidya; Choudhary, Bibha; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C

2017-05-31

Chemically synthesized small molecules play important role in anticancer therapy. Several chemical compounds have been reported to damage the DNA, either directly or indirectly slowing down the cancer cell progression by causing a cell cycle arrest. Direct or indirect reactive oxygen species formation causes DNA damage leading to cell cycle arrest and subsequent cell death. Therefore, identification of chemically synthesized compounds with anticancer potential is important. Here we investigate the effect of benzothiazole derivative (5g) for its ability to inhibit cell proliferation in different cancer models. Interestingly, 5g interfered with cell proliferation in both, cell lines and tumor cells leading to significant G2/M arrest. 5g treatment resulted in elevated levels of ROS and subsequently, DNA double-strand breaks (DSBs) explaining observed G2/M arrest. Consistently, we observed deregulation of many cell cycle associated proteins such as CDK1, BCL2 and their phosphorylated form, CyclinB1, CDC25c etc. Besides, 5g treatment led to decreased levels of mitochondrial membrane potential and activation of apoptosis. Interestingly, 5g administration inhibited tumor growth in mice without significant side effects. Thus, our study identifies 5g as a potent biochemical inhibitor to induce G2/M phase arrest of the cell cycle, and demonstrates its anticancer properties both ex vivo and in vivo.

Research and development of remote maintenance equipment for ITER divertor maintenance

International Nuclear Information System (INIS)

Takeda, Nobukazu; Kakudate, Satoshi; Nakahira, Masataka

2005-02-01

To facilitate easy remote maintainability, the ITER divertor is divided into 60 cassettes, which are transported in the toroidal and radial directions for replacement through maintenance ports located every 90 degrees using the divertor remote maintenance equipment such as in- and ex-vessel transporters. The cassette of 25 tons has to be transported and installed in the vacuum vessel with a positioning accuracy less than 2 mm in the limited space of the vacuum vessel and maintenance port under the intense gamma radiation field. Based on these requirements, the following design and tests were performed. (1) Link mechanism was studied to apply to the transportation of the heavy cassette in the restricted space. A compact mechanism with links for transportation of heavy cassette is designed through the optimization of the link angle taking account of space requirement and force efficiency. As a test result, the lifting capacity of 30 tons (larger than the cassette weight of 25 tons) using two link mechanisms has been demonstrated in the limited space. (2) Compact link mechanism was also studied to apply for locking of the cassette through the optimization of the link angle taking account of space requirement and force efficiency. As a test result, the final positioning accuracy of 0.03 mm for the 25 tons-cassette installation on the vacuum vessel from the initial positioning error of 5 mm has been demonstrated, so that the test result satisfies the requirement less than 2 mm using the link mechanisms in the limited space. (3) Sensor-based control using simple sensors such as optical fiber for divertor maintenance was tested using the full-scale mock-up divertor cassette and remote maintenance equipment. As a result, it is found that the positioning accuracy of 0.16 mm has been achieved by the optical fiber sensor and this value is sufficient for sensor-based control. In addition, the maintenance operation has been carried out through the human-machine interface

PAI-1 4G/5G polymorphism and plasma levels association in patients with coronary artery disease.

Science.gov (United States)

Lima, Luciana Moreira; Carvalho, Maria das Graças; Fonseca Neto, Cirilo Pereira; Garcia, José Carlos Faria; Sousa, Marinez Oliveira

2011-12-01

Type-1 plasminogen activator inhibitor (PAI-1) 4G/5G polymorphism may influence the PAI-1 expression. High plasma levels of PAI-1 are associated with coronary artery disease (CAD). This study investigated the influence of PAI-1 4G/5G polymorphism on plasma PAI-1 levels and its association with CAD assessed by coronary angiography. Blood sample of 35 individuals with angiographically normal coronary arteries, 31 individuals presenting mild/moderate atheromatosis, 57 individuals presenting severe atheromatosis and 38 healthy individuals (controls) were evaluated. In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. Plasma PAI-1 levels were quantified by ELISA assay (American Diagnostica). No difference was found between groups regarding age, gender and body mass index. Plasma PAI-1 levels and 4G/4G genotype frequency were significantly higher in the severe atheromatosis group compared to the other groups (p5G/5G genotype (r=0.02, p=0.4511). In addition, in a multiple logistic regression model, adjusted for all the other variables, PAI-1 was observed to be independently associated with CAD > 70% (p<0.001). The most important finding of this study was the association between 4G/4G genotype, high plasma PAI-1 levels and coronary stenosis higher than 70% in Brazilian individuals. Whether high plasma PAI-1 levels are a decisive factor for atherosclerosis worsening or it is a consequence remains to be established.

The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

Science.gov (United States)

Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

2015-02-27

ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

Towards high capacity and low latency backhauling in 5G : the 5G STEP-FWD vision

NARCIS (Netherlands)

Vardakas, John S.; Monroy, Idelfonso Tafur; Wosinska, Lena; Agapiou, George; Brenot, Romain; Pleros, Nikos; Verikoukis, Christos

2017-01-01

This paper presents the vision of the 5G STEP-FWD project, funded by the European Commission, with the objective to propose a novel optical-wireless networking solution for the provision of high speed connectivity to end users. The features of the new architecture, based on the utilization of

A rapid detection method for PAI-1 promoter insertion/deletion polymorphism (4G/5G

Directory of Open Access Journals (Sweden)

Annichino-Bizzacchi Joyce M.

1998-01-01

Full Text Available Plasminogen activator inhibitor-1 (PAI-1 is an important inhibitor of fibrinolysis, and increased levels of PAI-1 are associated with atheroma and myocardial infarction. A common 4G/5G insertion/deletion polymorphism located in the promoter region of PAI-1 gene has been described associated with PAI-1 activity in plasma levels. Genotyping of this polymorphism is commonly conducted with an allele-specific oligonucleotide melting technique. In the present study, we describe a quick, easy method for genotyping 4G/5G polymorphism in the promoter region of the PAI-1 gene.

Transportation energy conservation data book: edition I. 5

Energy Technology Data Exchange (ETDEWEB)

Shonka, D B; Loebl, A S; Ogle, M C; Johnson, M L; Howard, E B

1977-01-01

This document contains statistical information on the major transportation modes, their respective energy consumption patterns, and other pertinent factors influencing performance in the transportation sector. Data relating to past, present, and projected energy use and conservation in the transportation sector are presented under seven chapter headings. These focus on (1) modal transportation characteristics, (2) energy characteristics of the transportation sector, (3) energy conservation alternatives involving the transportation sector, (4) government impacts on the transportation sector, (5) the supply of energy to the transportation sector, (6) characteristics of transportation demand, and (7) miscellaneous reference materials such as energy conversion factors and geographical maps. References are included for each set of data presented, and a more general bibliography is included at the end of the book. In addition, a glossary of key terms and a subject index is provided for the user. A second edition of this document is scheduled for publication in September 1977.

Security for 4G and 5G Cellular Networks: A Survey of Existing Authentication and Privacy-preserving Schemes

OpenAIRE

Ferrag, Mohamed Amine; Maglaras, Leandros; Argyriou, Antonios; Kosmanos, Dimitrios; Janicke, Helge

2017-01-01

This paper presents a comprehensive survey of existing authentication and privacy-preserving schemes for 4G and 5G cellular networks. We start by providing an overview of existing surveys that deal with 4G and 5G communications, applications, standardization, and security. Then, we give a classification of threat models in 4G and 5G cellular networks in four categories, including, attacks against privacy, attacks against integrity, attacks against availability, and attacks against authenticat...

ATP-binding cassette B10 regulates early steps of heme synthesis.

Science.gov (United States)

Bayeva, Marina; Khechaduri, Arineh; Wu, Rongxue; Burke, Michael A; Wasserstrom, J Andrew; Singh, Neha; Liesa, Marc; Shirihai, Orian S; Langer, Nathaniel B; Paw, Barry H; Ardehali, Hossein

2013-07-19

Heme plays a critical role in gas exchange, mitochondrial energy production, and antioxidant defense in cardiovascular system. The mitochondrial transporter ATP-binding cassette (ABC) B10 has been suggested to export heme out of the mitochondria and is required for normal hemoglobinization of erythropoietic cells and protection against ischemia-reperfusion injury in the heart; however, its primary function has not been established. The aim of this study was to identify the function of ABCB10 in heme synthesis in cardiac cells. Knockdown of ABCB10 in cardiac myoblasts significantly reduced heme levels and the activities of heme-containing proteins, whereas supplementation with δ-aminolevulinic acid reversed these defects. Overexpression of mitochondrial δ-aminolevulinic acid synthase 2, the rate-limiting enzyme upstream of δ-aminolevulinic acid export, failed to restore heme levels in cells with ABCB10 downregulation. ABCB10 and heme levels were increased by hypoxia, and reversal of ABCB10 upregulation caused oxidative stress and cell death. Furthermore, ABCB10 knockdown in neonatal rat cardiomyocytes resulted in a significant delay of calcium removal from the cytoplasm, suggesting a relaxation defect. Finally, ABCB10 expression and heme levels were altered in failing human hearts and mice with ischemic cardiomyopathy. ABCB10 plays a critical role in heme synthesis pathway by facilitating δ-aminolevulinic acid production or export from the mitochondria. In contrast to previous reports, we show that ABCB10 is not a heme exporter and instead is required for the early mitochondrial steps of heme biosynthesis.

Differential contributions of five ABC transporters to mutidrug resistance, antioxidion and virulence of Beauveria bassiana, an entomopathogenic fungus.

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Ting-Ting Song

Full Text Available Multidrug resistance (MDR confers agrochemical compatibility to fungal cells-based mycoinsecticdes but mechanisms involved in MDR remain poorly understood for entomopathogenic fungi, which have been widely applied as biocontrol agents against arthropod pests. Here we characterized the functions of five ATP-binding cassette (ABC transporters, which were classified to the subfamilies ABC-B (Mdr1, ABC-C (Mrp1 and ABC-G (Pdr1, Pdr2 and Pdr5 and selected from 54 full-size ABC proteins of Beauveria bassiana based on their main domain architecture, membrane topology and transcriptional responses to three antifungal inducers. Disruption of each transporter gene resulted in significant reduction in resistance to four to six of eight fungicides or antifungal drugs tested due to their differences in structure and function. Compared with wild-type and complemented (control strains, disruption mutants of all the five transporter genes became significantly less tolerant to the oxidants menadione and H₂O₂ based on 22-41% and 10-31% reductions of their effective concentrations required for the suppression of 50% colony growth at 25°C. Under a standardized spray, the killing actions of ΔPdr5 and ΔMrp1 mutants against Spodoptera litura second-instar larvae were delayed by 59% and 33% respectively. However, no significant virulence change was observed in three other delta mutants. Taken together, the examined five ABC transporters contribute differentially to not only the fungal MDR but antioxidant capability, a phenotype rarely associated with ABC efflux pumps in previous reports; at least some of them are required for the full virulence of B. bassiana, thereby affecting the fungal biocontrol potential. Our results indicate that ABC pump-dependent MDR mechanisms exist in entomopathogenic fungi as do in yeasts and human and plant pathogenic fungi.

The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis

Science.gov (United States)

Živković, Maja; Starčević Čizmarević, Nada; Lovrečić, Luca; Klupka-Sarić, Inge; Stanković, Aleksandra; Gašparović, Iva; Dinčić, Evica; Stojković, Ljiljana; Rudolf, Gorazd; Šega Jazbec, Saša; Perković, Olivio; Sinanović, Osman; Sepčić, Juraj; Kapović, Miljenko; Peterlin, Borut

2014-01-01

Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, P = 0.037) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, P = 0.038). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, P = 0.017). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS. PMID:24825926

Recognition of the group G2(5 by the prime graph

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Parivash Nosratpour

2014-05-01

Full Text Available Let $G$ be a finite group‎. ‎The prime graph of $G$‎ ‎is a graph $\\Gamma(G$ with vertex set $\\pi(G$‎, ‎the set of all‎ ‎prime divisors of $|G|$‎, ‎and two distinct vertices $p$ and $q$ are‎ ‎adjacent by an edge if $G$ has an element of order $pq$‎. ‎In this‎ ‎paper we prove that if $\\Gamma(G=\\Gamma(G_2(5$‎, ‎then $G$ has a‎ ‎normal subgroup $N$ such that $\\pi(N\\subseteq\\{2,3,5\\}$ and‎ ‎$G/N\\cong G_2(5$‎.

Obstacles to Brain Tumor Therapy: Key ABC Transporters

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Juwina Wijaya

2017-11-01

Full Text Available The delivery of cancer chemotherapy to treat brain tumors remains a challenge, in part, because of the inherent biological barrier, the blood–brain barrier. While its presence and role as a protector of the normal brain parenchyma has been acknowledged for decades, it is only recently that the important transporter components, expressed in the tightly knit capillary endothelial cells, have been deciphered. These transporters are ATP-binding cassette (ABC transporters and, so far, the major clinically important ones that functionally contribute to the blood–brain barrier are ABCG2 and ABCB1. A further limitation to cancer therapy of brain tumors or brain metastases is the blood–tumor barrier, where tumors erect a barrier of transporters that further impede drug entry. The expression and regulation of these two transporters at these barriers, as well as tumor derived alteration in expression and/or mutation, are likely obstacles to effective therapy.

The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction

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Tajinder Kumar Parpugga

2015-01-01

Full Text Available Objective. Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism factors with coronary artery occlusion in patients with myocardial infarction. Materials and Methods. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. Results. We identified n=122 (32.4% 4G/4G, n=186 (49.5% 4G/5G, and n=68 (18.1% 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009–2.718, p=0.046. Conclusions. Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes.

The Effect of PAI-1 4G/5G Polymorphism and Clinical Factors on Coronary Artery Occlusion in Myocardial Infarction.

Science.gov (United States)

Parpugga, Tajinder Kumar; Tatarunas, Vacis; Skipskis, Vilius; Kupstyte, Nora; Zaliaduonyte-Peksiene, Diana; Lesauskaite, Vaiva

2015-01-01

Data on the impact of PAI-1-675 4G/5G genotype for fibrinolysis during myocardial infarction are inconsistent. The aim of our study was to evaluate the association of clinical and genetic (PAI-1-675 4G/5G polymorphism) factors with coronary artery occlusion in patients with myocardial infarction. PAI-1-675 4G/5G detection was achieved by using Sanger sequencing in a sample of patients hospitalized for stent implantation due to myocardial infarction. We categorized the patients into two groups: patients with coronary artery occlusion and patients without coronary artery occlusion according to angiographic evaluation. We identified n = 122 (32.4%) 4G/4G, n = 186 (49.5%) 4G/5G, and n = 68 (18.1%) 5G/5G PAI-1 genotype carriers. Univariate and multivariate analysis showed that only the 4G/5G genotype was associated with coronary artery occlusion (OR: 1.656 and 95% CI: 1.009-2.718, p = 0.046). Our results showed that carriers of PAI-1 4G/5G genotype with myocardial infarction have increased odds of coronary artery occlusion more than 1.6 times in comparison to the carriers of homozygous genotypes.

Experimental infection of calves with a gI, gE, US9 negative bovine herpesvirus type 5

NARCIS (Netherlands)

Hubner, S.O.; Oliveira, A.P.; Franco, A.C.; Rijsewijk, F.A.M.; Roehe, P.M.

2005-01-01

In this work, a role for the genes encoding glycoproteins I (gI) and E (gE) and the US9 protein of bovine herpesvirus type 5 (BHV-5) in neuropathogenicity and reactivation of latent infections was examined. Calves infected intranasally with a gI/gE/US9 deleted recombinant shed up to 102.85 TCID50/ml

Survey of Promising Technologies for 5G Networks

OpenAIRE

Le, Nam Tuan; Hossain, Mohammad Arif; Islam, Amirul; Kim, Do-yun; Choi, Young-June; Jang, Yeong Min

2016-01-01

As an enhancement of cellular networks, the future-generation 5G network can be considered an ultra-high-speed technology. The proposed 5G network might include all types of advanced dominant technologies to provide remarkable services. Consequently, new architectures and service management schemes for different applications of the emerging technologies need to be recommended to solve issues related to data traffic capacity, high data rate, and reliability for ensuring QoS. Cloud computing, I...

Microwave plasma generation and filtered transport of O{sub 2} (a {sup 1}{delta}{sub g})

Energy Technology Data Exchange (ETDEWEB)

Williams, Skip [Air Force Research Laboratory, Mail Stop PRAS, 1950 Fifth Street, WPAFB, OH 45433-7251 (United States); Popovic, Svetozar [Department of Physics, Old Dominion University, Norfolk, VA 23529 (United States); Gupta, Manish [Los Gatos Research, Incorporated 67 East Evelyn Ave, Suite 3, Mountain View, CA 94041 (United States)], E-mail: skip.williams@wpafb.af.mil

2009-08-01

Singlet oxygen, O{sub 2}(a {sup 1}{delta}{sub g}), is generated using a low pressure, low power continuous microwave discharge operating at 2.45 GHz with a flow of helium seeded with 1-10% molecular oxygen. The absolute concentration of O{sub 2}(a {sup 1}{delta}{sub g}) is measured using off-axis integrated cavity output spectroscopy to probe the Q-branch transition of the (1, 0) band of the b{sup 1}{sigma}{sub g}{sup +}-a{sup 1}{delta}{sub g} Noxon system. In order to remove other energetic species from the flow, the post-discharge flow is passed through a coarse fritted quartz filter. The use of the quartz frit takes advantage of the substantially lower surface sticking probability of O{sub 2}(a {sup 1}{delta}{sub g}) in comparison with other excited species on the flow. Up to 6% of the total oxygen passing through the filter remains in the a {sup 1}{delta}{sub g} state, and absolute densities of 2.5 x 10{sup 14} cm{sup -3} are obtained using this method. This preparation method and transport is important in developing sources of singlet oxygen for kinetic and spectroscopic studies.

Nicotiana plumbaginifolia plants silenced for the ATP-binding cassette transporter gene NpPDR1 show increased susceptibility to a group of fungal and oomycete pathogens.

Science.gov (United States)

Bultreys, Alain; Trombik, Tomasz; Drozak, Anna; Boutry, Marc

2009-09-01

SUMMARY The behaviour of Nicotiana plumbaginifolia plants silenced for the ATP-binding cassette transporter gene NpPDR1 was investigated in response to fungal and oomycete infections. The importance of NpPDR1 in plant defence was demonstrated for two organs in which NpPDR1 is constitutively expressed: the roots and the petal epidermis. The roots of the plantlets of two lines silenced for NpPDR1 expression were clearly more sensitive than those of controls to the fungal pathogens Botrytis cinerea, Fusarium oxysporum sp., F. oxysporum f. sp. nicotianae, F. oxysporum f. sp. melonis and Rhizoctonia solani, as well as to the oomycete pathogen Phytophthora nicotianae race 0. The Ph gene-linked resistance of N. plumbaginifolia to P. nicotianae race 0 was totally ineffective in NpPDR1-silenced lines. In addition, the petals of the NpPDR1-silenced lines were spotted 15%-20% more rapidly by B. cinerea than were the controls. The rapid induction (after 2-4 days) of NpPDR1 expression in N. plumbaginifolia and N. tabacum mature leaves in response to pathogen presence was demonstrated for the first time with fungi and one oomycete: R. solani, F. oxysporum and P. nicotianae. With B. cinerea, such rapid expression was not observed in healthy mature leaves. NpPDR1 expression was not observed during latent infections of B. cinerea in N. plumbaginifolia and N. tabacum, but was induced when conditions facilitated B. cinerea development in leaves, such as leaf ageing or an initial root infection. This work demonstrates the increased sensitivity of NpPDR1-silenced N. plumbaginifolia plants to all of the fungal and oomycete pathogens investigated.

Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

Science.gov (United States)

Luo, Yuezhong; Wang, Chao; Tu, Haitao

2014-03-01

The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

Plasminogen activator inhibitor-1 5G/5G genotype is associated with early spontaneous recanalization of the infarct-related artery in patients presenting with acute ST-elevation myocardial infarction.

Science.gov (United States)

Cagliyan, Caglar E; Yuregir, Ozge O; Balli, Mehmet; Tekin, Kamuran; Akilli, Rabia E; Bozdogan, Sevcan T; Turkmen, Serdar; Deniz, Ali; Baykan, Oytun A; Aslan, Huseyin; Cayli, Murat

2013-05-01

We aimed to examine the association between plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism and early spontaneous recanalization in patients presenting with acute ST-elevation myocardial infarction. Patients admitted to our emergency department with ST-elevation myocardial infarction in the first 6 h of symptom onset were included. An immediate primary percutaneous coronary intervention was performed. Patients were grouped according to the initial patency of the infarct-related artery (IRA) as follows: total occlusion (TO) group [Thrombolysis in Myocardial Infarction (TIMI) 0-1 flow in the IRA], partial recanalization group (TIMI 2 flow in the IRA), and complete recanalization (CR) group (TIMI 3 flow in the IRA). PAI-1 4G/5G polymorphism was detected using the real-time PCR method. There were 107 patients in the TO group, 30 patients in the partial recanalization group, and 45 patients in the CR group. When we evaluated degrees of patency according to the PAI-1 genotype, TO of the IRA was the highest in patients with the PAI 4G/4G genotype (PAI-1 4G/4G: 66.7%, PAI-1 4G/5G: 65.9%, PAI-1 5G/5G: 40.4%) and CR of the IRA was the highest in patients with the PAI 5G/5G genotype (PAI-1 5G/5G: 38.5%, PAI-1 4G/5G: 19.8%, PAI-1 4G/4G: 17.9%). The distribution of genotypes in different degrees of patency of IRA was statistically significant (P=0.029). In logistic regression analysis, the PAI-1 5G/5G genotype was associated independently with the spontaneous CR of the IRA (odds ratio: 2.875, 95% confidence interval [1.059-7.086], P=0.038). Patients with the PAI-1 5G/5G genotype seem to be luckier than others in terms of early spontaneous recanalization of the IRA. Further prospective studies with large patient populations are required for more precise results.

Echinococcus ortleppi (G5) and Echinococcus granulosus sensu stricto (G1) loads in cattle from Southern Brazil.

Science.gov (United States)

Balbinotti, Helier; Santos, Guilherme B; Badaraco, Jeferson; Arend, Ana C; Graichen, Daniel Ângelo S; Haag, Karen L; Zaha, Arnaldo

2012-09-10

Echinococcus granulosus sensu stricto (G1) and Echinococcus ortleppi (G5) are haplotypes of the parasite formerly known as Echinococcus granulosus sensu lato, which in its larval stage causes cystic hydatid disease, endemic in Southern Brazil. Epidemiological and molecular knowledge about the haplotypes occurring in a region is essential to control the spread of the disease. The aim of this work was to analyze the haplotype frequency and fertility of hydatid cysts in cattle from the state of Rio Grande do Sul. Cysts were collected and classified according to their fertility status. DNA was extracted from protoscoleces and germinal layers and then used as template for the amplification of the cytochrome c oxidase subunit 1 gene by PCR. Amplicons were purified and sequenced, and the sequences were analyzed for haplotype identification. A total of 638 fertile cysts collected in the last ten years were genotyped. On average, G1 (56.6%) was more frequent than G5 (43.4%). In lungs, the G5 haplotype exhibited a higher parasite load (52.8%), whereas in the liver, G1 was more frequent (90.4%). The analysis revealed an increase in the frequency of G5 haplotype cysts during the period of sampling, and an increase in the abundance of fertile cysts has also been observed in the last several years. Most infertile cysts were genotyped as G1. The possible factors involved in the increase in the proportion of E. ortleppi (G5) and the consequences of this increase are discussed. This study suggests that the proportion of E. ortleppi (G5) loads in cattle may be increasing overtime. Copyright © 2012 Elsevier B.V. All rights reserved.

Conservation of targeting but divergence in function and quality control of peroxisomal ABC transporters: an analysis using cross-kingdom expression

NARCIS (Netherlands)

Zhang, Xuebin; de Marcos Lousa, Carine; Schutte-Lensink, Nellie; Ofman, Rob; Wanders, Ronald J.; Baldwin, Stephen A.; Baker, Alison; Kemp, Stephan; Theodoulou, Frederica L.

2011-01-01

ABC (ATP-binding cassette) subfamily D transporters are found in all eukaryotic kingdoms and are known to play essential roles in mammals and plants; however, their number, organization and physiological contexts differ. Via cross-kingdom expression experiments, we have explored the conservation of

On-road PM2.5 pollution exposure in multiple transport microenvironments in Delhi

Science.gov (United States)

Goel, Rahul; Gani, Shahzad; Guttikunda, Sarath K.; Wilson, Daniel; Tiwari, Geetam

2015-12-01

PM2.5 pollution in Delhi averaged 150 μg/m3 from 2012 through 2014, which is 15 times higher than the World Health Organization's annual-average guideline. For this setting, we present on-road exposure of PM2.5 concentrations for 11 transport microenvironments along a fixed 8.3-km arterial route, during morning rush hour. The data collection was carried out using a portable TSI DustTrak DRX 8433 aerosol monitor, between January and May (2014). The monthly-average measured ambient concentrations varied from 130 μg/m3 to 250 μg/m3. The on-road PM2.5 concentrations exceeded the ambient measurements by an average of 40% for walking, 10% for cycle, 30% for motorised two wheeler (2W), 30% for open-windowed (OW) car, 30% for auto rickshaw, 20% for air-conditioned as well as for OW bus, 20% for bus stop, and 30% for underground metro station. On the other hand, concentrations were lower by 50% inside air-conditioned (AC) car and 20% inside the metro rail carriage. We find that the percent exceedance for open modes (cycle, auto rickshaw, 2W, OW car, and OW bus) reduces non-linearly with increasing ambient concentration. The reduction is steeper at concentrations lower than 150 μg/m3 than at higher concentrations. After accounting for air inhalation rate and speed of travel, PM2.5 mass uptake per kilometer during cycling is 9 times of AC car, the mode with the lowest exposure. At current level of concentrations, an hour of cycling in Delhi during morning rush-hour period results in PM2.5 dose which is 40% higher than an entire-day dose in cities like Tokyo, London, and New York, where ambient concentrations range from 10 to 20 μg/m3.

Molecular Characterization of Echinococcus granulosus Cysts in North Indian Patients: Identification of G1, G3, G5 and G6 Genotypes

Science.gov (United States)

Sharma, Monika; Sehgal, Rakesh; Fomda, Bashir Ahmad; Malhotra, Anil; Malla, Nancy

2013-01-01

Background Cystic echinococcosis (CE) caused by the Echinococcus granulosus, is a major public health problem worldwide, including India. The different genotypes of E. granulosus responsible for human hydatidosis have been reported from endemic areas throughout the world. However, the genetic characterization of E. granulosus infecting the human population in India is lacking. The aim of study was to ascertain the genotype(s) of the parasite responsible for human hydatidosis in North India. Methodology/Principal Findings To study the transmission patterns of E. granulosus, genotypic analysis was performed on hydatid cysts obtained from 32 cystic echinococcosis (CE) patients residing in 7 different states of North India. Mitochondrial cytochrome c oxidase subunit1 (cox1) sequencing was done for molecular identification of the isolates. Most of the CE patients (30/32) were found to be infected with hydatid cyst of either G3 (53.1%) or G1 (40.62%) genotype and one each of G5 (cattle strain) and G6 (camel strain) genotype. Conclusions/Significance These findings demonstrate the zoonotic potential of G1 (sheep strain) and G3 (buffalo strain) genotypes of E. granulosus as these emerged as predominant genotypes infecting the humans in India. In addition to this, the present study reports the first human CE case infected with G5 genotype (cattle strain) in an Asian country and presence of G6 genotype (camel strain) in India. The results may have important implications in the planning of control strategies for human hydatidosis. PMID:23785531

VLSI and system architecture-the new development of system 5G

Energy Technology Data Exchange (ETDEWEB)

Sakamura, K.; Sekino, A.; Kodaka, T.; Uehara, T.; Aiso, H.

1982-01-01

A research and development proposal is presented for VLSI CAD systems and for a hardware environment called system 5G on which the VLSI CAD systems run. The proposed CAD systems use a hierarchically organized design language to enable design of anything from basic architectures of VLSI to VLSI mask patterns in a uniform manner. The cad systems will eventually become intelligent cad systems that acquire design knowledge and perform automatic design of VLSI chips when the characteristic requirements of VLSI chip is given. System 5G will consist of superinference machines and the 5G communication network. The superinference machine will be built based on a functionally distributed architecture connecting inferommunication network. The superinference machine will be built based on a functionally distributed architecture connecting inference machines and relational data base machines via a high-speed local network. The transfer rate of the local network will be 100 mbps at the first stage of the project and will be improved to 1 gbps. Remote access to the superinference machine will be possible through the 5G communication network. Access to system 5G will use the 5G network architecture protocol. The users will access the system 5G using standardized 5G personal computers. 5G personal logic programming stations, very high intelligent terminals providing an instruction set that supports predicate logic and input/output facilities for audio and graphical information.

Complex study of transport AC loss in various 2G HTS racetrack coils

Energy Technology Data Exchange (ETDEWEB)

Chen, Yiran, E-mail: yc315@cam.ac.uk [University of Cambridge, 9 JJ Thomson Avenue, Cambridge CB3 0FA (United Kingdom); Zhang, Min; Chudy, Michal; Matsuda, Koichi; Coombs, Tim [University of Cambridge, 9 JJ Thomson Avenue, Cambridge CB3 0FA (United Kingdom)

2013-04-15

Highlights: ► Comparing transport AC losses of two types of 2G HTS racetrack coils. ► The magnetic substrate in the MAG RABITS coil is the main difference. ► Experimental data agree well with simulation results. ► The transport AC loss in the MAG RABITS coil is 36% higher than that in the IBAD coil. ► It is better to keep all the substrate non-magnetic. -- Abstract: HTS racetrack coils are becoming important elements of an emerging number of superconducting devices such as generators or motors. In these devices the issue of AC loss is crucial, as performance and cooling power are derived from this quantity. This paper presents a comparative study of transport AC loss in two different types of 2G HTS racetrack coils. In this study, both experimental measurements and computer simulation approaches were employed. All the experiments were performed using classical AC electrical method. The finite-element computer model was used to estimate electromagnetic properties and calculate transport AC loss. The main difference between the characterized coils is covered inside tape architectures. While one coil uses tape based on RABITS magnetic substrate, the second coil uses a non-magnetic tape. Ferromagnetic loss caused by a magnetic substrate is an important issue involved in the total AC loss. As a result, the coil with the magnetic substrate surprised with high AC loss and rather low performance.

An ATP Binding Cassette Transporter Mediates the Uptake of α-(1,6)-Linked Dietary Oligosaccharides in Bifidobacterium and Correlates with Competitive Growth on These Substrates

DEFF Research Database (Denmark)

Hansen, Morten Ejby; Fredslund, Folmer; Andersen, Joakim Mark

2016-01-01

that the dominant HGM commensal Bacteroides ovatus was out-competed by B. animalis subsp. lactis Bl-04 in mixed cultures growing on raffinose, the preferred ligand for the BlG16BP. By comparison, B. ovatus mono-cultures grew very efficiently on this trisaccharide. These findings suggest that the ABC-mediated uptake...... of raffinose provides an important competitive advantage, particularly against dominant Bacteroides that lack glycan-specific ABC-transporters. This novel insight highlights the role of glycan transport in defining the metabolic specialization of gut bacteria....

Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2