WorldWideScience

Sample records for carrier proteins

  1. Protein carriers of conjugate vaccines

    Science.gov (United States)

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  2. Food proteins as potential carriers for phenolics

    NARCIS (Netherlands)

    Bohin, M.C.

    2013-01-01

    The development of phenolic-rich functional foods is often limited by the off-tastes of phenolics that might be counteracted by sequestering these compounds using a carrier, thereby preventing them to interact with bitter taste receptors and salivary proteins. A range of common animal food proteins

  3. Characterization of the "Escherichia Coli" Acyl Carrier Protein Phosphodiesterase

    Science.gov (United States)

    Thomas, Jacob

    2009-01-01

    Acyl carrier protein (ACP) is a small essential protein that functions as a carrier of the acyl intermediates of fatty acid synthesis. ACP requires the posttranslational attachment of a 4'phosphopantetheine functional group, derived from CoA, in order to perform its metabolic function. A Mn[superscript 2+] dependent enzymatic activity that removes…

  4. Preclinical studies on new proteins as carrier for glycoconjugate vaccines.

    Science.gov (United States)

    Tontini, M; Romano, M R; Proietti, D; Balducci, E; Micoli, F; Balocchi, C; Santini, L; Masignani, V; Berti, F; Costantino, P

    2016-07-29

    Glycoconjugate vaccines are made of carbohydrate antigens covalently bound to a carrier protein to enhance their immunogenicity. Among the different carrier proteins tested in preclinical and clinical studies, five have been used so far for licensed vaccines: Diphtheria and Tetanus toxoids, the non-toxic mutant of diphtheria toxin CRM197, the outer membrane protein complex of Neisseria meningitidis serogroup B and the Protein D derived from non-typeable Haemophilus influenzae. Availability of novel carriers might help to overcome immune interference in multi-valent vaccines containing several polysaccharide-conjugate antigens, and also to develop vaccines which target both protein as well saccharide epitopes of the same pathogen. Accordingly we have conducted a study to identify new potential carrier proteins. Twenty-eight proteins, derived from different bacteria, were conjugated to the model polysaccharide Laminarin and tested in mice for their ability in inducing antibodies against the carbohydrate antigen and eight of them were subsequently tested as carrier for serogroup meningococcal C oligosaccharides. Four out of these eight were able to elicit in mice satisfactory anti meningococcal serogroup C titers. Based on immunological evaluation, the Streptococcus pneumoniae protein spr96/2021 was successfully evaluated as carrier for serogroups A, C, W, Y and X meningococcal capsular saccharides. Copyright © 2016. Published by Elsevier Ltd.

  5. Efficacy of Food Proteins as Carriers for Flavonoids

    NARCIS (Netherlands)

    Bohin, M.C.; Vincken, J.P.; Hijden, H.T.W.M.; Gruppen, H.

    2012-01-01

    Enrichment of flavonoids in food is often limited by their off-tastes, which might be counteracted by the use of food proteins as carriers of flavonoids. Various milk proteins, egg proteins, and gelatin hydrolysates were compared for their binding characteristics to two flavan-3-ols. Among the

  6. Biotin Carboxyl Carrier Protein in Barley Chloroplast Membranes

    DEFF Research Database (Denmark)

    Kannangara, C. G.; Jense, C J

    1975-01-01

    Biotin localized in barley chloroplast lamellae is covalently bound to a single protein with an approximate molecular weight of 21000. It contains one mole of biotin per mole of protein and functions as a carboxyl carrier in the acetyl-CoA carboxylase reaction. The protein was obtained...... by solubilization of the lamellae in phenol/acetic acid/8 M urea. Feeding barley seedlings with [14C]-biotin revealed that the vitamin is not degraded into respiratory substrates by the plant, but is specifically incorporated into biotin carboxyl carrier protein....

  7. Characterization of chicken riboflavin carrier protein gene structure ...

    Indian Academy of Sciences (India)

    The chicken riboflavin carrier protein (RCP) is an estrogen induced egg yolk and white protein. Eggs from hens which have a splice mutation in RCP gene fail to hatch, indicating an absolute requirement of RCP for the transport of riboflavin to the oocyte. In order to understand the mechanism of regulation of this gene by ...

  8. Characterization of chicken riboflavin carrier protein gene structure ...

    Indian Academy of Sciences (India)

    Unknown

    chicken RCP gene regulation, the structure and the 5′ flanking region of the gene have been characterized. 2. Methods. 2.1 Isolation of RCP genomic clones ..... The work was supported by the Department of Science and Tech- nology, New Delhi by a grant to PK. References. Adiga P R 1994 Riboflavin Carrier Protein in ...

  9. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    Science.gov (United States)

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

  10. Protein carriers of conjugate vaccines: Characteristics, development, and clinical trials

    OpenAIRE

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characterist...

  11. Protein C/S ratio, an accurate and simple tool to identify carriers of a protein C gene mutation

    NARCIS (Netherlands)

    Libourel, EJ; Meinardi, [No Value; de Kam, PJ; Ruiters, MHJ; van der Meer, J; van der Schaaf, W; Veenstra, R.

    Hereditary protein C deficiency is demonstrated by lowered protein C plasma levels in a patient and at least one first-degree relative. This approach is insufficient in some cases owing to overlapping protein C levels in carriers and non-carriers of a protein C gene mutation. The protein C/S ratio

  12. Biogenesis of mitochondrial carrier proteins: molecular mechanisms of import into mitochondria.

    Science.gov (United States)

    Ferramosca, Alessandra; Zara, Vincenzo

    2013-03-01

    Mitochondrial metabolite carriers are hydrophobic proteins which catalyze the flux of several charged or hydrophilic substrates across the inner membrane of mitochondria. These proteins, like most mitochondrial proteins, are nuclear encoded and after their synthesis in the cytosol are transported into the inner mitochondrial membrane. Most metabolite carriers, differently from other nuclear encoded mitochondrial proteins, are synthesized without a cleavable presequence and contain several, poorly characterized, internal targeting signals. However, an interesting aspect is the presence of a positively charged N-terminal presequence in a limited number of mitochondrial metabolite carriers. Over the last few years the molecular mechanisms of import of metabolite carrier proteins into mitochondria have been thoroughly investigated. This review summarizes the present knowledge and discusses recent advances on the import and sorting of mitochondrial metabolite carriers. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Detection of carriers and genetic counseling in duchenne muscular dystrophy by ribosomal protein synthesis.

    Science.gov (United States)

    Ionasescu, V; Zellweger, H; Burmeister, L

    1976-11-01

    The in vitro protein synthesis by polyribosomes extracted from biopsied muscle (vastus lateralis) was studied in 47 known carriers, 87 possible carriers and in 60 normal females. A significant increase in specific activity of monomeric ribosomes, total polyribosomes and collagen synthesis was found in 46 (97.8 per cent) known carriers and 47 (54 per cent) possible carriers of Duchenne muscular dytrophy. The latter showed an increase in ribosomal protein synthesis in 10 (52.6 per cent) of 19 mothers of isolated cases, 31 (53.3 per cent) of 58 sisters, and 6 (60 per cent) of other female relatives. Serum creatine phosphokinase was increased in 30 (63.8 per cent) of 47 known carriers.

  14. High-throughput bioscreening system utilizing high-performance affinity magnetic carriers exhibiting minimal non-specific protein binding

    International Nuclear Information System (INIS)

    Hanyu, Naohiro; Nishio, Kosuke; Hatakeyama, Mamoru; Yasuno, Hiroshi; Tanaka, Toshiyuki; Tada, Masaru; Nakagawa, Takashi; Sandhu, Adarsh; Abe, Masanori; Handa, Hiroshi

    2009-01-01

    For affinity purification of drug target protein we have developed magnetic carriers, narrow in size distribution (184±9 nm), which exhibit minimal non-specific binding of unwanted proteins. The carriers were highly dispersed in aqueous solutions and highly resistant to organic solvents, which enabled immobilization of various hydrophobic chemicals as probes on the carrier surfaces. Utilizing the carriers we have automated the process of separation and purification of the target proteins that had been done by manual operation previously.

  15. Calcium Sulfate with Stearic Acid as an Encouraging Carrier for Reindeer Bone Protein Extract

    Directory of Open Access Journals (Sweden)

    Pekka Jalovaara

    2011-07-01

    Full Text Available Various bone proteins and growth factors in specific concentrations are required for bone formation. If the body cannot produce sufficient quantities of these factors, bone trauma can be healed with an implant that includes the required factors in a carrier. This study was designed to evaluate various calcium salt candidates that can be used as carrier with reindeer bone protein extract to induce ectopic bone formation in the muscle pouch model of mouse. The bone protein extract was either impregnated into the disc form of carrier or mixed with carrier powder before implantation. The radiographic analysis indicated increased bone formation in all of the active groups containing the bone protein extract compared to the controls within 21 days follow-up. The highest bone formation was seen in the group with calcium sulfate with stearic acid where new bone and calcified cartilage were clearly visible. The greatest bone formation occurred in the groups that had bone protein extract readily available. This indicates that the bone forming factors in sufficient concentrations are required at the early stage of bone formation. The calcium sulfate with stearic acid was the most suitable and effective carrier for reindeer bone protein extract.

  16. Reprogramming Acyl Carrier Protein Interactions of an Acyl-CoA Promiscuous trans-Acyltransferase

    DEFF Research Database (Denmark)

    Ye, Zhixia; Musiol-Kroll, Ewa Maria; Weber, Tilmann

    2014-01-01

    Protein interactions between acyl carrier proteins (ACPs) and trans-acting acyltransferase domains (trans-ATs) are critical for regioselective extender unit installation by many polyketide synthases, yet little is known regarding the specificity of these interactions, particularly for trans...... and for engineering modular polyketide synthases to produce analogs....

  17. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Warangkana Lohcharoenkal

    2014-01-01

    Full Text Available Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy.

  18. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    Science.gov (United States)

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  19. Mitochondrial carrier protein biogenesis: role of the chaperones Hsc70 and Hsp90.

    Science.gov (United States)

    Zara, Vincenzo; Ferramosca, Alessandra; Robitaille-Foucher, Philippe; Palmieri, Ferdinando; Young, Jason C

    2009-04-15

    Metabolite carrier proteins of the mitochondrial inner membrane share homology in their transmembrane domains, which also carries their targeting information. In addition, some carriers have cleavable presequences which are not essential for targeting, but have some other function before import. The cytosolic chaperones Hsc70 (heat-shock cognate 70) and Hsp90 (heat-shock protein 90) complex with carrier precursors and interact specifically with the Tom (translocase of the mitochondrial outer membrane) 70 import receptor to promote import. We analysed how the presequences of the PiC (phosphate carrier) and CIC (citrate carrier) relate to the mechanisms of chaperone-mediated import. Deletion of the PiC presequence reduced the efficiency of import but, notably, not by causing aggregation. Instead, binding of the protein to Hsc70 was reduced, as well as the dependence on Hsc70 for import. Hsp90 binding and function in import was not greatly affected, but it could not entirely compensate for the lack of Hsc70 interaction. Deletion of the presequence from CIC was shown to cause its aggregation, but had little effect on the contribution to import of either Hsc70 or Hsp90. The presequence of PiC, but not that of CIC, conferred Hsc70 binding to dihydrofolate reductase fusion proteins. In comparison, OGC (oxoglutarate carrier) lacks a presequence and was more soluble, though it is still dependent on both Hsc70 and Hsp90. We propose that carrier presequences evolved to improve targeting competence by different mechanisms, depending on physical properties of the precursors in the cytosolic targeting environment.

  20. Development of a stealth carrier system for structural studies of membrane proteins in solution

    DEFF Research Database (Denmark)

    Maric, Selma

    Structural studies of membrane proteins remain a great experimental challenge. Functional reconstitution into artificial carriers that mimic the native bilayer environment allows for the handling of membrane proteins in solution and enables the use of small-angle scattering techniques for fast...... and reliable structural analysis. The difficulty with this approach is that the carrier discs contribute to the measured scattering intensity in a highly non-trivial fashion, making subsequent data analysis challenging. This thesis presents the development of a specifically deuterated, stealth nanodisc system...

  1. Subpollen particles: Carriers of allergenic proteins and oxidases

    Science.gov (United States)

    Bacsi, Attila; Choudhury, Barun K.; Dharajiya, Nilesh; Sur, Sanjiv; Boldogh, Istvan

    2011-01-01

    Background Pollen is known to induce allergic asthma in atopic individuals, although only a few inhaled pollen grains penetrate into the lower respiratory tract. Objective We sought to provide evidence that subpollen particles (SPPs) of respirable size, possessing both antigenic and redox properties, are released from weed pollen grains and to test their role in allergic airway inflammation. Methods The release of SPPs was analyzed by means of microscopic imaging and flow cytometry. The redox properties of SPPs and the SPP-mediated oxidative effect on epithelial cells were determined by using redox-sensitive probes and specific inhibitors. Western blotting and amino acid sequence analysis were used to examine the protein components of the SPP. The allergenic properties of the SPP were determined in a murine model of experimental asthma. Results Ragweed pollen grains released 0.5 to 4.5 μm of SPPs on hydration. These contained Amb a 1, along with other allergenic proteins of ragweed pollen, and possessed nicotinamide adenine dinucleotide (reduced) or nicotinamide adenine dinucleotide phosphate (reduced) [NAD(P)H] oxidase activity. The SPPs significantly increased the levels of reactive oxygen species (ROS) in cultured cells and induced allergic airway inflammation in the experimental animals. Pretreatment of the SPPs with NAD(P)H oxidase inhibitors attenuated their capacity to increase ROS levels in the airway epithelial cells and subsequent airway inflammation. Conclusions The allergenic potency of SPPs released from ragweed pollen grains is mediated in tandem by ROS generated by intrinsic NAD(P)H oxidases and antigenic proteins. Clinical implications Severe clinical symptoms associated with seasonal asthma might be explained by immune responses to inhaled SPPs carrying allergenic proteins and ROS-producing NAD(P)H oxidases. PMID:17030236

  2. Structural and bioinformatic characterization of an Acinetobacter baumannii type II carrier protein

    International Nuclear Information System (INIS)

    Allen, C. Leigh; Gulick, Andrew M.

    2014-01-01

    The high-resolution crystal structure of a free-standing carrier protein from Acinetobacter baumannii that belongs to a larger NRPS-containing operon, encoded by the ABBFA-003406–ABBFA-003399 genes of A. baumannii strain AB307-0294, that has been implicated in A. baumannii motility, quorum sensing and biofilm formation, is presented. Microorganisms produce a variety of natural products via secondary metabolic biosynthetic pathways. Two of these types of synthetic systems, the nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), use large modular enzymes containing multiple catalytic domains in a single protein. These multidomain enzymes use an integrated carrier protein domain to transport the growing, covalently bound natural product to the neighboring catalytic domains for each step in the synthesis. Interestingly, some PKS and NRPS clusters contain free-standing domains that interact intermolecularly with other proteins. Being expressed outside the architecture of a multi-domain protein, these so-called type II proteins present challenges to understand the precise role they play. Additional structures of individual and multi-domain components of the NRPS enzymes will therefore provide a better understanding of the features that govern the domain interactions in these interesting enzyme systems. The high-resolution crystal structure of a free-standing carrier protein from Acinetobacter baumannii that belongs to a larger NRPS-containing operon, encoded by the ABBFA-003406–ABBFA-003399 genes of A. baumannii strain AB307-0294, that has been implicated in A. baumannii motility, quorum sensing and biofilm formation, is presented here. Comparison with the closest structural homologs of other carrier proteins identifies the requirements for a conserved glycine residue and additional important sequence and structural requirements within the regions that interact with partner proteins

  3. Structural and bioinformatic characterization of an Acinetobacter baumannii type II carrier protein

    Energy Technology Data Exchange (ETDEWEB)

    Allen, C. Leigh; Gulick, Andrew M., E-mail: gulick@hwi.buffalo.edu [University at Buffalo, Buffalo, NY 14203 (United States)

    2014-06-01

    The high-resolution crystal structure of a free-standing carrier protein from Acinetobacter baumannii that belongs to a larger NRPS-containing operon, encoded by the ABBFA-003406–ABBFA-003399 genes of A. baumannii strain AB307-0294, that has been implicated in A. baumannii motility, quorum sensing and biofilm formation, is presented. Microorganisms produce a variety of natural products via secondary metabolic biosynthetic pathways. Two of these types of synthetic systems, the nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs), use large modular enzymes containing multiple catalytic domains in a single protein. These multidomain enzymes use an integrated carrier protein domain to transport the growing, covalently bound natural product to the neighboring catalytic domains for each step in the synthesis. Interestingly, some PKS and NRPS clusters contain free-standing domains that interact intermolecularly with other proteins. Being expressed outside the architecture of a multi-domain protein, these so-called type II proteins present challenges to understand the precise role they play. Additional structures of individual and multi-domain components of the NRPS enzymes will therefore provide a better understanding of the features that govern the domain interactions in these interesting enzyme systems. The high-resolution crystal structure of a free-standing carrier protein from Acinetobacter baumannii that belongs to a larger NRPS-containing operon, encoded by the ABBFA-003406–ABBFA-003399 genes of A. baumannii strain AB307-0294, that has been implicated in A. baumannii motility, quorum sensing and biofilm formation, is presented here. Comparison with the closest structural homologs of other carrier proteins identifies the requirements for a conserved glycine residue and additional important sequence and structural requirements within the regions that interact with partner proteins.

  4. Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines.

    Science.gov (United States)

    Tontini, M; Berti, F; Romano, M R; Proietti, D; Zambonelli, C; Bottomley, M J; De Gregorio, E; Del Giudice, G; Rappuoli, R; Costantino, P; Brogioni, G; Balocchi, C; Biancucci, M; Malito, E

    2013-10-01

    Glycoconjugate vaccines are among the most effective and safest vaccines ever developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been mostly used as protein carriers in licensed vaccines. We evaluated the immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides conjugated to CRM197, DT and TT in naïve mice. The three carriers were equally efficient in inducing an immune response against the carbohydrate moiety in immunologically naïve mice. The effect of previous exposure to different dosages of the carrier protein on the anti-carbohydrate response was studied using serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed a strong propensity to positively prime the anti-carbohydrate response elicited by its conjugates or those with the antigenically related carrier DT. Conversely in any of the tested conditions TT priming did not result in enhancement of the anti-carbohydrate response elicited by the corresponding conjugates. Repeated exposure of mice to TT or to CRM197 before immunization with the respective MenA conjugates resulted in a drastic suppression of the anti-carbohydrate response in the case of TT conjugate and only in a slight reduction in the case of CRM197. The effect of carrier priming on the anti-MenA response of DT-based conjugates varied depending on their carbohydrate to protein ratio. These data may have implications for human vaccination since conjugate vaccines are widely used in individuals previously immunized with DT and TT carrier proteins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Characterization of Sfp, a Bacillus subtilis phosphopantetheinyl transferase for peptidyl carrier protein domains in peptide synthetases.

    Science.gov (United States)

    Quadri, L E; Weinreb, P H; Lei, M; Nakano, M M; Zuber, P; Walsh, C T

    1998-02-10

    The Bacillus subtilis enzyme Sfp, required for production of the lipoheptapeptide antibiotic surfactin, posttranslationally phosphopantetheinylates a serine residue in each of the seven peptidyl carrier protein domains of the first three subunits (SrfABC) of surfactin synthetase to yield docking sites for amino acid loading and peptide bond formation. With recombinant Sfp and 16-17-kDa peptidyl carrier protein (PCP) domains excised from the SrfB1 and SrfB2 modules as apo substrates, kcat values of 56-104 min-1 and K(m) values of 1.3-1.8 microM were determined, indicating equivalent recognition of the adjacent PCP domains by Sfp. In contrast to other phosphopantetheinyl transferases (PPTases) previously examined, Sfp will modify the apo forms of heterologous recombinant proteins, including the PCP domain of Saccharomyces cerevisiae Lys2 (involved in lysine biosynthesis), the aryl carrier protein (ArCP) domain of Escherichia coli EntB (involved in enterobactin biosynthesis), and the E. coli acyl carrier protein (ACP) subunit, suggesting Sfp as a good candidate for heterologous coexpression with peptide and polyketide synthase genes to overproduce holo-synthase enzymes. Cosubstrate coenzyme A (CoA), the phosphopantetheinyl group donor, has a K(m) of 0.7 microM. Desulfo-CoA and homocysteamine-CoA are also substrates of Sfp, and benzoyl-CoA and phenylacetyl-CoA are also utilized by Sfp, resulting in direct transfer of acyl phosphopantetheinyl moieties into the carrier protein substrate. Mutagenesis in Sfp of five residues conserved across the PPTase family was assessed for in vivo effects on surfactin production and in vitro effects on PPTase activity.

  6. Transient isotachophoresis in carrier ampholyte-based capillary electrophoresis for protein analysis

    Czech Academy of Sciences Publication Activity Database

    Busnel, J. M.; Descroix, S.; Godfrin, D.; Hennion, M. C.; Kašička, Václav; Peltre, G.

    2006-01-01

    Roč. 27, č. 18 (2006), s. 3591-3598 ISSN 0173-0835 Institutional research plan: CEZ:AV0Z40550506 Keywords : carrier ampholyte-based capillary electrophoresis * transient isotachophoresis * proteins Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 4.101, year: 2006

  7. A Rational Approach to Identify Inhibitors of Mycobacterium tuberculosis Enoyl Acyl Carrier Protein Reductase

    Czech Academy of Sciences Publication Activity Database

    Chhabria, M. T.; Parmar, K. B.; Brahmkshatriya, Pathik

    2013-01-01

    Roč. 19, č. 21 (2013), s. 3878-3883 ISSN 1381-6128 Institutional support: RVO:61388963 Keywords : mycobacterium tuberculosis * enoyl acyl carrier protein reductase * pharmacophore modeling * molecular docking * binding interactions Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.288, year: 2013

  8. Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors

    NARCIS (Netherlands)

    Jayapaul, J.; Arns, S.; Lederle, W.; Lammers, Twan Gerardus Gertudis Maria; Comba, P.; Gätjens, J.; Kiessling, F.

    2012-01-01

    Abstract Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by

  9. Recognition of hybrid peptidyl carrier proteins/acyl carrier proteins in nonribosomal peptide synthetase modules by the 4'-phosphopantetheinyl transferases AcpS and Sfp.

    Science.gov (United States)

    Mofid, Mohammad Reza; Finking, Robert; Marahiel, Mohamed A

    2002-05-10

    The acyl carrier proteins (ACPs) of fatty acid synthase and polyketide synthase as well as peptidyl carrier proteins (PCPs) of nonribosomal peptide synthetases are modified by 4'-phosphopantetheinyl transferases from inactive apo-enzymes to their active holo forms by transferring the 4'-phosphopantetheinyl moiety of coenzyme A to a conserved serine residue of the carrier protein. 4'-Phosphopantetheinyl transferases have been classified into two types; the AcpS type accepts ACPs of fatty acid synthase and some ACPs of type II polyketide synthase as substrates, whereas the Sfp type exhibits an extraordinarily broad substrate specificity. Based on the previously published co-crystal structure of Bacillus subtilis AcpS and ACP that provided detailed information about the interacting residues of the two proteins, we designed a novel hybrid PCP by replacing the Bacillus brevis TycC3-PCP helix 2 with the corresponding helix of B. subtilis ACP that contains the interacting residues. This was performed for the PCP domain as a single protein as well as for the TycA-PCP domain within the nonribosomal peptide synthetase module TycA from B. brevis. Both resulting proteins, designated hybrid PCP (hPCP) and hybrid TycA (hTycA), were modified in vivo during heterologous expression in Escherichia coli (hPCP, 51%; hTycA, 75%) and in vitro with AcpS as well as Sfp to 100%. The designated hTycA module contains two other domains: an adenylation domain (activating phenylalanine to Phe-AMP and afterward transferring the Phe to the PCP domain) and an epimerization domain (converting the PCP-bound l-Phe to d-Phe). We show here that the modified PCP domain of hTycA communicates with the adenylation domain and that the co-factor of holo-hPCP is loaded with Phe. However, communication between the hybrid PCP and the epimerization domain seems to be disabled. Nevertheless, hTycA is recognized by the next proline-activating elongation module TycB1 in vitro, and the dipeptide is formed and

  10. Unveiling the in Vivo Protein Corona of Circulating Leukocyte-like Carriers.

    Science.gov (United States)

    Corbo, Claudia; Molinaro, Roberto; Taraballi, Francesca; Toledano Furman, Naama E; Hartman, Kelly A; Sherman, Michael B; De Rosa, Enrica; Kirui, Dickson K; Salvatore, Francesco; Tasciotti, Ennio

    2017-03-28

    Understanding interactions occurring at the interface between nanoparticles and biological components is an urgent challenge in nanomedicine due to their effect on the biological fate of nanoparticles. After the systemic injection of nanoparticles, a protein corona constructed by blood components surrounds the carrier's surface and modulates its pharmacokinetics and biodistribution. Biomimicry-based approaches in nanotechnology attempt to imitate what happens in nature in order to transfer specific natural functionalities to synthetic nanoparticles. Several biomimetic formulations have been developed, showing superior in vivo features as a result of their cell-like identity. We have recently designed biomimetic liposomes, called leukosomes, which recapitulate the ability of leukocytes to target inflamed endothelium and escape clearance by the immune system. To gain insight into the properties of leukosomes, we decided to investigate their protein corona in vivo. So far, most information about the protein corona has been obtained using in vitro experiments, which have been shown to minimally reproduce in vivo phenomena. Here we directly show a time-dependent quantitative and qualitative analysis of the protein corona adsorbed in vivo on leukosomes and control liposomes. We observed that leukosomes absorb fewer proteins than liposomes, and we identified a group of proteins specifically adsorbed on leukosomes. Moreover, we hypothesize that the presence of macrophage receptors on leukosomes' surface neutralizes their protein corona-meditated uptake by immune cells. This work unveils the protein corona of a biomimetic carrier and is one of the few studies on the corona performed in vivo.

  11. Induction of the lac carrier and an associated membrane protein in Escherichia coli

    International Nuclear Information System (INIS)

    Lagarias, D.M.

    1985-01-01

    Induction of the lac operon in wild type Escherichia coli strains results in synthesis of a 16 kilodalton inner membrane protein in addition to the known products of the lacZ, lacY and lacA genes. Cells carrying the lacY gene on a plasmid over produce this 16 kilodalton polypeptide as well as the Lac carrier, the membrane protein product of the lacY gene. However, [ 35 S]methionine labeling of minicells carrying the lacY plasmid shows that the 16 kDa protein is not synthesized from the plasmid DNA. The 16 kDa protein was purified and partially characterized. It is an acidic membrane protein of apparent molecular weight 15,800 whose amino terminal sequence (NH 2 -Met-Arg-Asn-Phe-Asp-Leu-) does not correspond to any nucleotide sequence known in lac operon DNA. Using antibody prepared to the purified 16 kDa protein, a quantitative analysis of conditions under which this protein is made was accomplished, and reveals that the amount of 16 kDa protein which appears in the membrane is proportional to lac operon expression. Hybridization of a synthetic oligonucleotide probe complementary to the 5' end of 16 kDa protein mRNA shows that its synthesis is regulated at the level of transcription. A description of attempts to clone this gene is given. Possible functional roles for the 16 kDa protein are discussed

  12. Plant protein-based hydrophobic fine and ultrafine carrier particles in drug delivery systems.

    Science.gov (United States)

    Malekzad, Hedieh; Mirshekari, Hamed; Sahandi Zangabad, Parham; Moosavi Basri, S M; Baniasadi, Fazel; Sharifi Aghdam, Maryam; Karimi, Mahdi; Hamblin, Michael R

    2018-02-01

    For thousands of years, plants and their products have been used as the mainstay of medicinal therapy. In recent years, besides attempts to isolate the active ingredients of medicinal plants, other new applications of plant products, such as their use to prepare drug delivery vehicles, have been discovered. Nanobiotechnology is a branch of pharmacology that can provide new approaches for drug delivery by the preparation of biocompatible carrier nanoparticles (NPs). In this article, we review recent studies with four important plant proteins that have been used as carriers for targeted delivery of drugs and genes. Zein is a water-insoluble protein from maize; Gliadin is a 70% alcohol-soluble protein from wheat and corn; legumin is a casein-like protein from leguminous seeds such as peas; lectins are glycoproteins naturally occurring in many plants that recognize specific carbohydrate residues. NPs formed from these proteins show good biocompatibility, possess the ability to enhance solubility, and provide sustained release of drugs and reduce their toxicity and side effects. The effects of preparation methods on the size and loading capacity of these NPs are also described in this review.

  13. Structure, High Affinity, and Negative Cooperativity of the Escherichia coli Holo-(Acyl Carrier Protein):Holo-(Acyl Carrier Protein) Synthase Complex

    Energy Technology Data Exchange (ETDEWEB)

    Marcella, Aaron M.; Culbertson, Sannie J.; Shogren-Knaak, Michael A.; Barb, Adam W.

    2017-11-01

    The Escherichia coli holo-(acyl carrier protein) synthase (ACPS) catalyzes the coenzyme A-dependent activation of apo-ACPP to generate holo-(acyl carrier protein) (holo-ACPP) in an early step of fatty acid biosynthesis. E. coli ACPS is sufficiently different from the human fatty acid synthase to justify the development of novel ACPS-targeting antibiotics. Models of E. coli ACPS in unliganded and holo-ACPP-bound forms solved by X-ray crystallography to 2.05 and 4.10 Å, respectively, revealed that ACPS bound three product holo-ACPP molecules to form a 3:3 hexamer. Solution NMR spectroscopy experiments validated the ACPS binding interface on holo-ACPP using chemical shift perturbations and by determining the relative orientation of holo-ACPP to ACPS by fitting residual dipolar couplings. The binding interface is organized to arrange contacts between positively charged ACPS residues and the holo-ACPP phosphopantetheine moiety, indicating product contains more stabilizing interactions than expected in the enzyme:substrate complex. Indeed, holo-ACPP bound the enzyme with greater affinity than the substrate, apo-ACPP, and with negative cooperativity. The first equivalent of holo-ACPP bound with a KD = 62 ± 13 nM, followed by the binding of two more equivalents of holo-ACPP with KD = 1.2 ± 0.2 μM. Cooperativity was not observed for apo-ACPP which bound with KD = 2.4 ± 0.1 μM. Strong product binding and high levels of holo-ACPP in the cell identify a potential regulatory role of ACPS in fatty acid biosynthesis.

  14. Participation of Low Molecular Weight Electron Carriers in Oxidative Protein Folding

    Directory of Open Access Journals (Sweden)

    József Mandl

    2009-03-01

    Full Text Available Oxidative protein folding is mediated by a proteinaceous electron relay system, in which the concerted action of protein disulfide isomerase and Ero1 delivers the electrons from thiol groups to the final acceptor. Oxygen appears to be the final oxidant in aerobic living organisms, although the existence of alternative electron acceptors, e.g. fumarate or nitrate, cannot be excluded. Whilst the protein components of the system are well-known, less attention has been turned to the role of low molecular weight electron carriers in the process. The function of ascorbate, tocopherol and vitamin K has been raised recently. In vitro and in vivo evidence suggests that these redox-active compounds can contribute to the functioning of oxidative folding. This review focuses on the participation of small molecular weight redox compounds in oxidative protein folding.

  15. Crystal structure of a PCP/Sfp complex reveals the structural basis for carrier protein posttranslational modification.

    Science.gov (United States)

    Tufar, Peter; Rahighi, Simin; Kraas, Femke I; Kirchner, Donata K; Löhr, Frank; Henrich, Erik; Köpke, Jürgen; Dikic, Ivan; Güntert, Peter; Marahiel, Mohamed A; Dötsch, Volker

    2014-04-24

    Phosphopantetheine transferases represent a class of enzymes found throughout all forms of life. From a structural point of view, they are subdivided into three groups, with transferases from group II being the most widespread. They are required for the posttranslational modification of carrier proteins involved in diverse metabolic pathways. We determined the crystal structure of the group II phosphopantetheine transferase Sfp from Bacillus in complex with a substrate carrier protein in the presence of coenzyme A and magnesium, and observed two protein-protein interaction sites. Mutational analysis showed that only the hydrophobic contacts between the carrier protein's second helix and the C-terminal domain of Sfp are essential for their productive interaction. Comparison with a similar structure of a complex of human proteins suggests that the mode of interaction is highly conserved in all domains of life. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Protein edible films with emulsified maize oil as paprika carrier to improve color and rancidity in beef Bologna

    OpenAIRE

    Erick C. Tellez-Rangel; Ignacio Garcia-Martinez; Eva Rodriguez-Huezo; Alfonso Totosaus

    2017-01-01

    Edible films are a way to improve meat products shelf life. If edible films are formulated with proteins, oil can be emulsified by proteins, changing edible film properties. In this research protein edible films elaborated with milk protein concentrate or functional plasma proteins with or without emulsified oil were employed as carrier for functional ingredient, paprika, as antioxidant and to improve color in beef Bologna during vacuum packing storage at 4 °C. Edible films with emulsified oi...

  17. Development of a stealth carrier system for structural studies of membrane proteins in solution

    DEFF Research Database (Denmark)

    Maric, Selma

    Structural studies of membrane proteins remain a great experimental challenge. Functional reconstitution into artificial carriers that mimic the native bilayer environment allows for the handling of membrane proteins in solution and enables the use of small-angle scattering techniques for fast...... which can be used for SANS structural analysis of membrane proteins in solution. In combination with the D2O/H2O-based contrast variation method it is demonstrated that it is possible to prepare specifically deuterated analogues of the nanodisc, which give minimal contribution to the neutron scattering...... data when used in 100% D2O. An important challenge in the project was obtaining selective partial deuteration of the nanodisc system necessary for the total matching at 100% D2O. This was achieved through an E. coli based biosynthesis for both deuterated phosphatidylcholines as well as membrane...

  18. Evaluation of the use of amphipathic peptide-based protein carrier for in vitro cancer research.

    Science.gov (United States)

    Lo, Seong Loong; Wang, Shu

    2012-03-09

    Intracellular delivery of proteins offers an alternative to genetic modification or siRNA transfection for functional studies of proteins in live cells, especially for studies in cancer cells for therapeutics development. However, lack of efficient and biocompatible delivery system has limited the use of protein for in vitro cancer research. In this study, we design and evaluate an amphipathic peptide RV24, composing of a hydrophobic domain for protein binding, a flexible linker, and a hydrophilic domain to facilitate cell penetration. When using β-galactosidase as a cargo protein for comparison with commercially available peptide- and lipid-based carriers, RV24 peptide provides up to 5-fold increase in quantity delivered into 3 different cancer cell lines. Green fluorescent protein could also be delivered rapidly within 4h and transduced up to 83% of tested cancer cell lines. Although having a cell penetrating domain, RV24 peptide did not compromise cell viability, morphology and granularity significantly. These findings suggest the feasibility of using biocompatible amphipathic peptide to efficiently deliver protein-based molecules intracellularly for in vitro cancer research. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Purification of nonspecific lipid transfer protein (sterol carrier protein 2) from human liver and its deficiency in livers from patients with cerebro-hepato-renal (Zellweger) syndrome

    NARCIS (Netherlands)

    Amerongen, A. van; Helms, J.B.; Krift, T.P. van der; Schutgens, R.B.H.; Wirtz, K.W.A.

    1987-01-01

    The nonspecific lipid transfer protein (i.e., sterol carrier protein 2) from human liver was purified to homogeneity using ammonium sulfate precipitation, CM-cellulose chromatography, molecular sieve chromatography and fast protein liquid chromatography. Its amino acid composition was determined and

  20. Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Halavaty, Andrei S. [Center for Structural Genomics of Infectious Diseases, (United States); Northwestern University, Chicago, IL 60611 (United States); Kim, Youngchang [Center for Structural Genomics of Infectious Diseases, (United States); Argonne National Laboratory, Argonne, IL 60439 (United States); University of Chicago, Chicago, IL 60637 (United States); Minasov, George; Shuvalova, Ludmilla; Dubrovska, Ievgeniia; Winsor, James [Center for Structural Genomics of Infectious Diseases, (United States); Northwestern University, Chicago, IL 60611 (United States); Zhou, Min [Center for Structural Genomics of Infectious Diseases, (United States); Argonne National Laboratory, Argonne, IL 60439 (United States); University of Chicago, Chicago, IL 60637 (United States); Onopriyenko, Olena; Skarina, Tatiana [Center for Structural Genomics of Infectious Diseases, (United States); University of Toronto, Toronto, Ontario M5G 1L6 (Canada); Papazisi, Leka; Kwon, Keehwan; Peterson, Scott N. [Center for Structural Genomics of Infectious Diseases, (United States); J. Craig Venter Institute, Rockville, MD 20850 (United States); Joachimiak, Andrzej [Center for Structural Genomics of Infectious Diseases, (United States); Argonne National Laboratory, Argonne, IL 60439 (United States); University of Chicago, Chicago, IL 60637 (United States); Savchenko, Alexei [Center for Structural Genomics of Infectious Diseases, (United States); University of Toronto, Toronto, Ontario M5G 1L6 (Canada); Anderson, Wayne F., E-mail: wf-anderson@northwestern.edu [Center for Structural Genomics of Infectious Diseases, (United States); Northwestern University, Chicago, IL 60611 (United States)

    2012-10-01

    The structural characterization of acyl-carrier-protein synthase (AcpS) from three different pathogenic microorganisms is reported. One interesting finding of the present work is a crystal artifact related to the activity of the enzyme, which fortuitously represents an opportunity for a strategy to design a potential inhibitor of a pathogenic AcpS. Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-protein synthase (AcpS) enzyme. Its holo form post-translationally modifies the apo form of an acyl carrier protein (ACP), which assures the constant delivery of thioester intermediates to the discrete enzymes of FAS II. At the Center for Structural Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus (AcpS{sub SA}), Vibrio cholerae (AcpS{sub VC}) and Bacillus anthracis (AcpS{sub BA}) have been structurally characterized in their apo, holo and product-bound forms, respectively. The structure of AcpS{sub BA} is emphasized because of the two 3′, 5′-adenosine diphosphate (3′, 5′-ADP) product molecules that are found in each of the three coenzyme A (CoA) binding sites of the trimeric protein. One 3′, 5′-ADP is bound as the 3′, 5′-ADP part of CoA in the known structures of the CoA–AcpS and 3′, 5′-ADP–AcpS binary complexes. The position of the second 3′, 5′-ADP has never been described before. It is in close proximity to the first 3′, 5′-ADP and the ACP-binding site. The coordination of two ADPs in AcpS{sub BA} may possibly be exploited for the design of AcpS inhibitors that can block binding of both CoA and ACP.

  1. Structural characterization and comparison of three acyl-carrier-protein synthases from pathogenic bacteria

    International Nuclear Information System (INIS)

    Halavaty, Andrei S.; Kim, Youngchang; Minasov, George; Shuvalova, Ludmilla; Dubrovska, Ievgeniia; Winsor, James; Zhou, Min; Onopriyenko, Olena; Skarina, Tatiana; Papazisi, Leka; Kwon, Keehwan; Peterson, Scott N.; Joachimiak, Andrzej; Savchenko, Alexei; Anderson, Wayne F.

    2012-01-01

    The structural characterization of acyl-carrier-protein synthase (AcpS) from three different pathogenic microorganisms is reported. One interesting finding of the present work is a crystal artifact related to the activity of the enzyme, which fortuitously represents an opportunity for a strategy to design a potential inhibitor of a pathogenic AcpS. Some bacterial type II fatty-acid synthesis (FAS II) enzymes have been shown to be important candidates for drug discovery. The scientific and medical quest for new FAS II protein targets continues to stimulate research in this field. One of the possible additional candidates is the acyl-carrier-protein synthase (AcpS) enzyme. Its holo form post-translationally modifies the apo form of an acyl carrier protein (ACP), which assures the constant delivery of thioester intermediates to the discrete enzymes of FAS II. At the Center for Structural Genomics of Infectious Diseases (CSGID), AcpSs from Staphylococcus aureus (AcpS SA ), Vibrio cholerae (AcpS VC ) and Bacillus anthracis (AcpS BA ) have been structurally characterized in their apo, holo and product-bound forms, respectively. The structure of AcpS BA is emphasized because of the two 3′, 5′-adenosine diphosphate (3′, 5′-ADP) product molecules that are found in each of the three coenzyme A (CoA) binding sites of the trimeric protein. One 3′, 5′-ADP is bound as the 3′, 5′-ADP part of CoA in the known structures of the CoA–AcpS and 3′, 5′-ADP–AcpS binary complexes. The position of the second 3′, 5′-ADP has never been described before. It is in close proximity to the first 3′, 5′-ADP and the ACP-binding site. The coordination of two ADPs in AcpS BA may possibly be exploited for the design of AcpS inhibitors that can block binding of both CoA and ACP

  2. Expression of a green fluorescence protein-carrier protein into mouse spermatozoa.

    Science.gov (United States)

    Mogas, Teresa; Fernández-Novell, Josep M; Palomo, Maria Jesús; Otaegui, Pedro J; Gomis, Roger R; Ballester, Joan; Izquierdo, Dolors; Guinovart, Joan J; Ferrer, Joan C; Rigau, Teresa; Rodríguez-Gil, Joan E

    2002-10-04

    Intra-testicular inoculation of an adenoviral vector carrying the fusion gene Aequorea victoria green fluorescence protein/rat-liver glycogen synthase (GFP/LGS) resulted in the presence of GFP/GLS in spermatozoa from 7days to, at least, 16days after inoculation. The GFP/LGS was detected in the sperm heads after an "in vitro" fertilization procedure, either before or after the oocyte penetration. Our results indicate that spermatozoa carrying GFP/LGS protein conserved their fertilizing ability and were also detectable after oocyte penetration. This technique will allow to develop an easy system to follow the fate of mature sperm proteins.

  3. Role of acyl carrier protein isoforms in plant lipid metabolism: Progress report

    Energy Technology Data Exchange (ETDEWEB)

    Ohlrogge, J.B.

    1989-01-01

    Previous research from my lab has revealed that several higher plant species have multiple isoforms of acyl carrier protein (ACP) and therefore this trait appears highly conserved among higher plants. This level of conservation suggests that the existence of ACP isoforms is not merely the results of neutral gene duplications. We have developed techniques to examine a wider range of species. Acyl carrier proteins can be labelled very specifically and to high specific activity using H-palmitate and the E. coli enzyme acyl-ACP synthetase. Isoforms were then resolved by western blotting and native PAGE of H-palmitate labelled ACP's. Multiple isoforms of ACP were observed the leaf tissue of the monocots Avena sativa and Hordeum vulgare and dicots including Arabidopsis thallina, Cuphea wrightii, and Brassica napus. Lower vascular plants including the cycad, Dioon edule, Ginkgo biloba, the gymnosperm Pinus, the fern Anernia phyllitidis and Psilotum nudum, the most primitive known extant vascular plant, were also found to have multiple ACP isoforms as were the nonvascular liverwort, Marchantia and moss, Polytrichum. Therefore, the development of ACP isoforms occurred early in evolution. However, the uniellular alge Chlamydomonas and Dunaliella and the photosynthetic cyanobacteria Synechocystis and Agmnellum have only a single elecrophotetic form of ACP. Thus, multiple forms of ACP do not occur in all photosynthetic organisms but may be associated with multicellular plants.

  4. Electrospun fish protein fibers as a biopolymer-based carrier – implications for oral protein delivery

    DEFF Research Database (Denmark)

    Boutrup Stephansen, Karen; García-Díaz, María; Jessen, Flemming

    2014-01-01

    Purpose: Protein-based electrospun fibers have emerged as novel nanostructured materials for tissue engineering and drug delivery due to their unique structural characteristics, biocompatibility and biodegradability. The aim of this study was to explore the use of electrospun fibers based on fish...... sarcoplasmic proteins as an oral delivery platform for biopharmaceuticals, using insulin as a model protein. Methods: Fish sarcoplasmic proteins (FSP) were isolated from fresh cod and electrospun into nanomicrofibers using insulin as a model payload. The morphology of FSP fibers was characterized using...... was significantly enhanced when administered encapsulated in FSP fibers. The TEER was decreased after 4 h incubation, and no negative effect on cell viability was observed at any time. Conclusion: In this work we present electrospun FSP fibers as a novel oral drug delivery system for biopharmaceuticals...

  5. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines.

    Science.gov (United States)

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara

    2015-03-10

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  6. Sunflower (Helianthus annuus) fatty acid synthase complex: β-hydroxyacyl-[acyl carrier protein] dehydratase genes.

    Science.gov (United States)

    González-Thuillier, Irene; Venegas-Calerón, Mónica; Sánchez, Rosario; Garcés, Rafael; von Wettstein-Knowles, Penny; Martínez-Force, Enrique

    2016-02-01

    Two sunflower hydroxyacyl-[acyl carrier protein] dehydratases evolved into two different isoenzymes showing distinctive expression levels and kinetics' efficiencies. β-Hydroxyacyl-[acyl carrier protein (ACP)]-dehydratase (HAD) is a component of the type II fatty acid synthase complex involved in 'de novo' fatty acid biosynthesis in plants. This complex, formed by four intraplastidial proteins, is responsible for the sequential condensation of two-carbon units, leading to 16- and 18-C acyl-ACP. HAD dehydrates 3-hydroxyacyl-ACP generating trans-2-enoyl-ACP. With the aim of a further understanding of fatty acid biosynthesis in sunflower (Helianthus annuus) seeds, two β-hydroxyacyl-[ACP] dehydratase genes have been cloned from developing seeds, HaHAD1 (GenBank HM044767) and HaHAD2 (GenBank GU595454). Genomic DNA gel blot analyses suggest that both are single copy genes. Differences in their expression patterns across plant tissues were detected. Higher levels of HaHAD2 in the initial stages of seed development inferred its key role in seed storage fatty acid synthesis. That HaHAD1 expression levels remained constant across most tissues suggest a housekeeping function. Heterologous expression of these genes in E. coli confirmed both proteins were functional and able to interact with the bacterial complex 'in vivo'. The large increase of saturated fatty acids in cells expressing HaHAD1 and HaHAD2 supports the idea that these HAD genes are closely related to the E. coli FabZ gene. The proposed three-dimensional models of HaHAD1 and HaHAD2 revealed differences at the entrance to the catalytic tunnel attributable to Phe166/Val1159, respectively. HaHAD1 F166V was generated to study the function of this residue. The 'in vitro' enzymatic characterization of the three HAD proteins demonstrated all were active, with the mutant having intermediate K m and V max values to the wild-type proteins.

  7. Experimental study of osteoinduction using a new material as a carrier for bone morphogenetic protein-2.

    Science.gov (United States)

    Koyama, Noriaki; Okubo, Yasunori; Nakao, Kazumasa; Osawa, Kenji; Bessho, Kazuhisa

    2011-06-01

    We evaluated the usefulness of artificial collagen as a new carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) by comparing it with that of atelopeptide collagen, which is derived from porcine skin, and which we have previously shown to be useful for the induction of bone. rhBMP-2 5μg with either atelopeptide collagen 3mg or artificial collagen 3mg was implanted into the calf muscle of 10-week-old Wistar rats (n=3 in each group). Three rats were given artificial collagen alone and acted as controls (n=3). Radiographic evaluation, histological analysis, and biochemical examinations were made on day 21 after implantation. Soft radiographs (wavelength 10-0.10nm) showed opaque shadows in both groups. Histological analysis showed that new bone had formed in both experimental groups. Endochondral ossification was found at the outermost edge of the implanted collagen in the atelopeptide group. However, there was less ossification in the implanted collagen in the artificial collagen group. On biochemical examination, alkaline phosphatase activity and calcium concentrations in both experimental groups were higher than in the control group, and were higher in the atelopeptide group than in the artificial collagen group. Our results suggest that artificial collagen is useful as a carrier for rhBMP-2 designed to promote the formation of new bone. Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. Genes of ACYL CARRIER PROTEIN Family Show Different Expression Profiles and Overexpression of ACYL CARRIER PROTEIN 5 Modulates Fatty Acid Composition and Enhances Salt Stress Tolerance in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Jiexue Huang

    2017-06-01

    Full Text Available Acyl carrier proteins (ACPs are a group of small acidic proteins functioning as important cofactors in the de novo synthesis of fatty acids. In Arabidopsis, ACPs are encoded by a small gene family comprising five plastid members, AtACP1 to AtACP5, and three mitochondrial members. The biological functions and the transcriptional responses to abiotic stresses of most AtACPs have yet to be elucidated. The present study extends previous findings and provides new knowledge on the function of ACPs by examining the responses of AtACP-encoding genes to several abiotic stresses and, in particular, the role of AtACP5 in the adaptation to salt stress. Phylogenetic analysis showed that AtACP1, AtACP2, AtACP3, and AtACP5 can be classified into one group and separated from a group comprising AtACP4 and ACP homologs from related species. Quantitative RT-PCR analysis revealed that the expression of AtACP1, AtACP2, and AtACP3 was induced by drought. Both iron deficiency and nitrogen starvation resulted in down-regulation of AtACP4. The most pronounced response was observed for AtACP5, the expression of which was dramatically decreased by salt stress. Knock-out of AtACP5 showed increased sensitivity to NaCl stress, whereas transgenic lines overexpressing AtACP5 displayed increased salt tolerance relative to the wild-type. Overexpression of AtACP5 further led to an altered composition of fatty acids, mainly a decrease of oleic acid (C18:1 and an increase of palmitic acid (C16:0, and to a lower Na+/K+ ratio when compared to the salt stressed wild-type. The comprehensive transcriptional information on the small plastid AtACP gene family in response to various abiotic stresses and the further investigation of the AtACP5 indicate that AtACP5 might be critical for salt tolerance through alterations of the composition of fatty acids and, subsequently, the Na+/K+ ratio.

  9. Genes of ACYL CARRIER PROTEIN Family Show Different Expression Profiles and Overexpression of ACYL CARRIER PROTEIN 5 Modulates Fatty Acid Composition and Enhances Salt Stress Tolerance in Arabidopsis.

    Science.gov (United States)

    Huang, Jiexue; Xue, Caiwen; Wang, Han; Wang, Lisai; Schmidt, Wolfgang; Shen, Renfang; Lan, Ping

    2017-01-01

    Acyl carrier proteins (ACPs) are a group of small acidic proteins functioning as important cofactors in the de novo synthesis of fatty acids. In Arabidopsis , ACPs are encoded by a small gene family comprising five plastid members, AtACP1 to AtACP5 , and three mitochondrial members. The biological functions and the transcriptional responses to abiotic stresses of most AtACPs have yet to be elucidated. The present study extends previous findings and provides new knowledge on the function of ACPs by examining the responses of AtACP-encoding genes to several abiotic stresses and, in particular, the role of AtACP5 in the adaptation to salt stress. Phylogenetic analysis showed that AtACP1, AtACP2, AtACP3, and AtACP5 can be classified into one group and separated from a group comprising AtACP4 and ACP homologs from related species. Quantitative RT-PCR analysis revealed that the expression of AtACP1, AtACP2 , and AtACP3 was induced by drought. Both iron deficiency and nitrogen starvation resulted in down-regulation of AtACP4 . The most pronounced response was observed for AtACP5 , the expression of which was dramatically decreased by salt stress. Knock-out of AtACP5 showed increased sensitivity to NaCl stress, whereas transgenic lines overexpressing AtACP5 displayed increased salt tolerance relative to the wild-type. Overexpression of AtACP5 further led to an altered composition of fatty acids, mainly a decrease of oleic acid (C18:1) and an increase of palmitic acid (C16:0), and to a lower Na + /K + ratio when compared to the salt stressed wild-type. The comprehensive transcriptional information on the small plastid AtACP gene family in response to various abiotic stresses and the further investigation of the AtACP5 indicate that AtACP5 might be critical for salt tolerance through alterations of the composition of fatty acids and, subsequently, the Na + /K + ratio.

  10. Characterization of the yellow fever mosquito sterol carrier protein-2 like 3 gene and ligand-bound protein structure

    Energy Technology Data Exchange (ETDEWEB)

    Dyer, David H.; Vyazunova, Irina; Lorch, Jeffery M.; Forest, Katrina T.; Lan, Que; (UW)

    2009-06-12

    The sterol carrier protein-2 like 3 gene (AeSCP-2L3), a new member of the SCP-2 protein family, is identified from the yellow fever mosquito, Aedes aegypti. The predicted molecular weight of AeSCP-2L3 is 13.4 kDa with a calculated pI of 4.98. AeSCP-2L3 transcription occurs in the larval feeding stages and the mRNA levels decrease in pupae and adults. The highest levels of AeSCP-2L3 gene expression are found in the body wall, and possibly originated in the fat body. This is the first report of a mosquito SCP-2-like protein with prominent expression in tissue other than the midgut. The X-ray protein crystal structure of AeSCP-2L3 reveals a bound C16 fatty acid whose acyl tail penetrates deeply into a hydrophobic cavity. Interestingly, the ligand-binding cavity is slightly larger than previously described for AeSCP-2 (Dyer et al. J Biol Chem 278:39085-39091, 2003) and AeSCP-2L2 (Dyer et al. J Lipid Res M700460-JLR200, 2007). There are also an additional 10 amino acids in SCP-2L3 that are not present in other characterized mosquito SCP-2s forming an extended loop between {beta}3 and {beta}4. Otherwise, the protein backbone is exceedingly similar to other SCP-2 and SCP-2-like proteins. In contrast to this observed high structural homology of members in the mosquito SCP2 family, the amino acid sequence identity between the members is less than 30%. The results from structural analysis imply that there have been evolutionary constraints that favor the SCP-2 C{alpha} backbone fold while the specificity of ligand binding can be altered.

  11. Binding of 7-dehydrocholesterol to sterol carrier protein and vitamin D3 effect

    International Nuclear Information System (INIS)

    Takase, Sachiko; Oizumi, Kumiko; Moriuchi, Sachiko; Hosoya, Norimasa

    1975-01-01

    It was confirmed that deltasup(5,7)-sterol delta 7 -reductase activity was suppressed by cholecalciferol (vitamin D 3 ) in the enzyme system consisted of microsomes and sterol carrier protein (SCP). The enzyme activity was significantly decreased in the combination with microsomes obtained from either vitamin D-deficient or vitamin D 3 -treated rat liver and with SCP obtained from vitamin D 3 -treated rat. It was also demonstrated by the binding assay of the dextran-charcoal technique that 7-dehydrocholesterol binding to SCP could be specifically displaced by vitamin D 3 . The inhibition of cholecalciferol on 7-dehydro-cholesterol binding to liver SCP was confirmed to be non-competitive inhibition. (auth.)

  12. Effect of increased CRM₁₉₇ carrier protein dose on meningococcal C bactericidal antibody response.

    Science.gov (United States)

    Lee, Lucia H; Blake, Milan S

    2012-04-01

    New multivalent CRM(197)-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM(197) coadministration with CRM(197)-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM(197) carrier protein dose of ∼50 μg and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of ≥ 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM(197) conjugate vaccine immunogenicity using alternative dosing schedules.

  13. Evaluation of Enoyl-Acyl Carrier Protein Reductase Inhibitors as Pseudomonas aeruginosa Quorum-Quenching Reagents

    Directory of Open Access Journals (Sweden)

    Søren Molin

    2010-02-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen which is responsible for a wide range of infections. Production of virulence factors and biofilm formation by P. aeruginosa are partly regulated by cell-to-cell communication quorum-sensing systems. Identification of quorum-quenching reagents which block the quorum-sensing process can facilitate development of novel treatment strategies for P. aeruginosa infections. We have used molecular dynamics simulation and experimental studies to elucidate the efficiencies of two potential quorum-quenching reagents, triclosan and green tea epigallocatechin gallate (EGCG, which both function as inhibitors of the enoyl-acyl carrier protein (ACP reductase (ENR from the bacterial type II fatty acid synthesis pathway. Our studies suggest that EGCG has a higher binding affinity towards ENR of P. aeruginosa and is an efficient quorum-quenching reagent. EGCG treatment was further shown to be able to attenuate the production of virulence factors and biofilm formation of P. aeruginosa.

  14. Lysine(63)-linked ubiquitylation of PIN2 auxin carrier protein governs hormonally controlled adaptation of Arabidopsis root growth

    Czech Academy of Sciences Publication Activity Database

    Leitner, J.; Petrášek, Jan; Tomanov, K.; Retzer, K.; Pařezová, Markéta; Korbei, B.; Bachmair, A.; Zažímalová, Eva; Luschnig, Ch.

    2012-01-01

    Roč. 109, č. 21 (2012), s. 8322-8327 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GAP305/11/2476 Institutional research plan: CEZ:AV0Z50380511 Keywords : PLASMA-MEMBRANE PROTEIN * EFFLUX CARRIER * INTRACELLULAR TRAFFICKING Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.737, year: 2012

  15. A Biphasic Calcium Sulphate/Hydroxyapatite Carrier Containing Bone Morphogenic Protein-2 and Zoledronic Acid Generates Bone

    DEFF Research Database (Denmark)

    Raina, Deepak Bushan; Isaksson, Hanna; Hettwer, Werner

    2016-01-01

    -the-shelf osteoinductive bone substitutes that can replace bone grafts are required. We tested the carrier properties of a biphasic, calcium sulphate and hydroxyapatite ceramic material, containing a combination of recombinant human bone morphogenic protein-2 (rhBMP-2) to induce bone, and zoledronic acid (ZA) to delay...

  16. Plasma protein corona modulates the vascular wall interaction of drug carriers in a material and donor specific manner.

    Directory of Open Access Journals (Sweden)

    Daniel J Sobczynski

    Full Text Available The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid (PLGA spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.

  17. Lysine and arginine biosyntheses mediated by a common carrier protein in Sulfolobus.

    Science.gov (United States)

    Ouchi, Takuya; Tomita, Takeo; Horie, Akira; Yoshida, Ayako; Takahashi, Kento; Nishida, Hiromi; Lassak, Kerstin; Taka, Hikari; Mineki, Reiko; Fujimura, Tsutomu; Kosono, Saori; Nishiyama, Chiharu; Masui, Ryoji; Kuramitsu, Seiki; Albers, Sonja-Verena; Kuzuyama, Tomohisa; Nishiyama, Makoto

    2013-04-01

    LysW has been identified as a carrier protein in the lysine biosynthetic pathway that is active through the conversion of α-aminoadipate (AAA) to lysine. In this study, we found that the hyperthermophilic archaeon, Sulfolobus acidocaldarius, not only biosynthesizes lysine through LysW-mediated protection of AAA but also uses LysW to protect the amino group of glutamate in arginine biosynthesis. In this archaeon, after LysW modification, AAA and glutamate are converted to lysine and ornithine, respectively, by a single set of enzymes with dual functions. The crystal structure of ArgX, the enzyme responsible for modification and protection of the amino moiety of glutamate with LysW, was determined in complex with LysW. Structural comparison and enzymatic characterization using Sulfolobus LysX, Sulfolobus ArgX and Thermus LysX identify the amino acid motif responsible for substrate discrimination between AAA and glutamate. Phylogenetic analysis reveals that gene duplication events at different stages of evolution led to ArgX and LysX.

  18. Characterization of a structurally and functionally diverged acyl-acyl carrier protein desaturase from milkweed seed.

    Science.gov (United States)

    Cahoon, E B; Coughlan, S J; Shanklin, J

    1997-04-01

    A cDNA for a structurally variant acyl-acyl carrier protein (ACP) desaturase was isolated from milkweed (Asclepias syriaca) seed, a tissue enriched in palmitoleic (16:1delta9)* and cis-vaccenic (18:1delta11) acids. Extracts of Escherichia coli that express the milkweed cDNA catalyzed delta9 desaturation of acyl-ACP substrates, and the recombinant enzyme exhibited seven- to ten-fold greater specificity for palmitoyl (16:0)-ACP and 30-fold greater specificity for myristoyl (14:0)-ACP than did known delta9-stearoyl (18:0)-ACP desaturases. Like other variant acyl-ACP desaturases reported to date, the milkweed enzyme contains fewer amino acids near its N-terminus compared to previously characterized delta9-18:0-ACP desaturases. Based on the activity of an N-terminal deletion mutant of a delta9-18:0-ACP desaturase, this structural feature likely does not account for differences in substrate specificities.

  19. Stearoyl-acyl carrier protein desaturases are associated with floral isolation in sexually deceptive orchids

    Energy Technology Data Exchange (ETDEWEB)

    Schluter, P.M.; Shanklin, J.; Xu, S.; Gagliardini, V.; Whittle, E.; Grossniklaus, U.; Schiestl, F. P.

    2011-04-05

    The orchids Ophrys sphegodes and O. exaltata are reproductively isolated from each other by the attraction of two different, highly specific pollinator species. For pollinator attraction, flowers chemically mimic the pollinators sex pheromones, the key components of which are alkenes with different double-bond positions. This study identifies genes likely involved in alkene biosynthesis, encoding stearoyl-acyl carrier protein (ACP) desaturase (SAD) homologs. The expression of two isoforms, SAD1 and SAD2, is flower-specific and broadly parallels alkene production during flower development. SAD2 shows a significant association with alkene production, and in vitro assays show that O. sphegodes SAD2 has activity both as an 18:0-ACP {Delta}{sup 9} and a 16:0-ACP {Delta}{sup 4} desaturase. Downstream metabolism of the SAD2 reaction products would give rise to alkenes with double-bonds at position 9 or position 12, matching double-bond positions observed in alkenes in the odor bouquet of O. sphegodes. SAD1 and SAD2 show evidence of purifying selection before, and positive or relaxed purifying selection after gene duplication. By contributing to the production of species-specific alkene bouquets, SAD2 is suggested to contribute to differential pollinator attraction and reproductive isolation among these species. Taken together, these data are consistent with the hypothesis that SAD2 is a florally expressed barrier gene of large phenotypic effect and, possibly, a genic target of pollinator-mediated selection.

  20. Controlled slow release of anticancer drugs from protein-hydrophilic vinyl polymer carriers

    International Nuclear Information System (INIS)

    Asano, Masaharu; Yoshida, Masaru; Kaetsu, Isao

    1982-01-01

    The release behavior has been studied for bleomycin hydrochloride (BLM), an anticancer drug, from carrier composities prepared from mixtures of proteins and hydrophilic vinyl monomers by combined procedures of radiation polymerization and thermal denaturation. The magnitude, Q/tsup(1/2), for BLM release was the smallest when albumin was denatured by thermal treatment after the polymerization of albumin-2-hydroxyethyl methacrylate (HEMA) by radiation at -78 0 C. This retardation was further enhanced by the use of cross-linked polymers. On the other hand, the digestion of the albumin-HEMA composite, during the release test carried out in the saline containing some proteases, was markedly suppressed with increasing the HEMA content in the composite. The digestion was lowered more than expected from the albumin content in the composite. In summary of the release tests and the scanning electron microscopic observations, it was concluded that the release of BLM and the digestion of albumin component contained in the composites can be markedly suppressed by the incorporation of the polymeric component. (author)

  1. An enhanced chemoenzymatic method for loading substrates onto carrier protein domains.

    Science.gov (United States)

    Kittilä, Tiia; Cryle, Max J

    2017-11-24

    Non-ribosomal peptide synthetase (NRPS) machineries produce many medically relevant peptides that cannot be easily accessed by chemical synthesis. Thus, understanding NRPS mechanism is of crucial importance to allow efficient redesign of these machineries to produce new compounds. During NRPS-mediated synthesis, substrates are covalently attached to peptidyl carrier proteins (PCPs), and studies of NRPSs are impeded by difficulties in producing PCPs loaded with substrates. Different approaches to load substrates onto PCP domains have been described, but all suffer from difficulties in either the complexity of chemical synthesis or low enzymatic efficiency. Here, we describe an enhanced chemoenzymatic loading method that combines 2 approaches into a single, highly efficient one-pot loading reaction. First, d-pantetheine and ATP are converted into dephospho-coenzyme A via the actions of 2 enzymes from coenzyme A (CoA) biosynthesis. Next, phosphoadenylates are dephosphorylated using alkaline phosphatase to allow linker attachment to PCP domain by Sfp mutant R4-4, which is inhibited by phosphoadenylates. This route does not depend on activity of the commonly problematic dephospho-CoA kinase and, therefore, offers an improved method for substrate loading onto PCP domains.

  2. Cyanobacterial Sfp-type phosphopantetheinyl transferases functionalize carrier proteins of diverse biosynthetic pathways.

    Science.gov (United States)

    Yang, Guang; Zhang, Yi; Lee, Nicholas K; Cozad, Monica A; Kearney, Sara E; Luesch, Hendrik; Ding, Yousong

    2017-09-19

    Cyanobacteria produce structurally and functionally diverse polyketides, nonribosomal peptides and their hybrids. Sfp-type phosphopantetheinyl transferases (PPTases) are essential to the production of these compounds via functionalizing carrier proteins (CPs) of biosynthetic megaenzymes. However, cyanobacterial Sfp-type PPTases remain poorly characterized, posing a significant barrier to the exploitation of cyanobacteria for biotechnological and biomedical applications. Herein, we describe the detailed characterization of multiple cyanobacterial Sfp-type PPTases that were rationally selected. Biochemical characterization of these enzymes along with the prototypic enzyme Sfp from Bacillus subtilis demonstrated their varying specificities toward 11 recombinant CPs of different types of biosynthetic pathways from cyanobacterial and Streptomyces strains. Kinetic analysis further indicated that PPTases possess the higher binding affinity and catalytic efficiency toward their cognate CPs in comparison with noncognate substrates. Moreover, when chromosomally replacing the native PPTase gene of Synechocystis sp. PCC6803, two selected cyanobacterial PPTases and Sfp supported the growth of resulted mutants. Cell lysates of the cyanobacterial mutants further functionalized recombinant CP substrates. Collectively, these studies reveal the versatile catalysis of selected cyanobacterial PPTases and provide new tools to synthesize cyanobacterial natural products using in vitro and in vivo synthetic biology approaches.

  3. Sunflower (Helianthus annuus) fatty acid synthase complex: enoyl-[acyl carrier protein]-reductase genes.

    Science.gov (United States)

    González-Thuillier, Irene; Venegas-Calerón, Mónica; Garcés, Rafael; von Wettstein-Knowles, Penny; Martínez-Force, Enrique

    2015-01-01

    Enoyl-[acyl carrier protein]-reductases from sunflower. A major factor contributing to the amount of fatty acids in plant oils are the first steps of their synthesis. The intraplastidic fatty acid biosynthetic pathway in plants is catalysed by type II fatty acid synthase (FAS). The last step in each elongation cycle is carried out by the enoyl-[ACP]-reductase, which reduces the dehydrated product of β-hydroxyacyl-[ACP] dehydrase using NADPH or NADH. To determine the mechanisms involved in the biosynthesis of fatty acids in sunflower (Helianthus annuus) seeds, two enoyl-[ACP]-reductase genes have been identified and cloned from developing seeds with 75 % identity: HaENR1 (GenBank HM021137) and HaENR2 (HM021138). The two genes belong to the ENRA and ENRB families in dicotyledons, respectively. The genetic duplication most likely originated after the separation of di- and monocotyledons. RT-qPCR revealed distinct tissue-specific expression patterns. Highest expression of HaENR1 was in roots, stems and developing cotyledons whereas that of H a ENR2 was in leaves and early stages of seed development. Genomic DNA gel blot analyses suggest that both are single-copy genes. In vivo activity of the ENR enzymes was tested by complementation experiments with the JP1111 fabI(ts) E. coli strain. Both enzymes were functional demonstrating that they interacted with the bacterial FAS components. That different fatty acid profiles resulted infers that the two Helianthus proteins have different structures, substrate specificities and/or reaction rates. The latter possibility was confirmed by in vitro analysis with affinity-purified heterologous-expressed enzymes that reduced the crotonyl-CoA substrate using NADH with different V max.

  4. Only Acyl Carrier Protein 1 (AcpP1 Functions in Pseudomonas aeruginosa Fatty Acid Synthesis

    Directory of Open Access Journals (Sweden)

    Jin-Cheng Ma

    2017-11-01

    Full Text Available The genome of Pseudomonas aeruginosa contains three open reading frames, PA2966, PA1869, and PA3334, which encode putative acyl carrier proteins, AcpP1, AcpP2, and AcpP3, respectively. In this study, we found that, although these apo-ACPs were successfully phosphopantetheinylated by P. aeruginosa phosphopantetheinyl transferase (PcpS and all holo-forms of these proteins could be acylated by Vibrio harveyi acyl-ACP synthetase (AasS, only AcpP1 could be used as a substrate for the synthesis of fatty acids, catalyzed by P. aeruginosa cell free extracts in vitro, and only acpP1 gene could restore growth in the Escherichia coliacpP mutant strain CY1877. And P. aeruginosaacpP1 could not be deleted, while disruption of acpP2 or acpP3 in the P. aeruginosa genome allowed mutant strains to grow as well as the wild type strain. These findings confirmed that only P. aeruginosa AcpP1 functions in fatty acid biosynthesis, and that acpP2 and acpP3 do not play roles in the fatty acid synthetic pathway. Moreover, disruption of acpP2 and acpP3 did not affect the ability of P. aeruginosa to produce N-acylhomoserine lactones (AHL, but replacement of P. aeruginosaacpP1 with E. coliacpP caused P. aeruginosa to reduce the production of AHL molecules, which indicated that neither P. aeruginosa AcpP2 nor AcpP3 can act as a substrate for synthesis of AHL molecules in vivo. Furthermore, replacement of acpP1 with E. coliacpP reduced the ability of P. aeruginosa to produce some exo-products and abolished swarming motility in P. aeruginosa.

  5. Immunization of mice by Hollow Mesoporous Silica Nanoparticles as carriers of Porcine Circovirus Type 2 ORF2 Protein

    Directory of Open Access Journals (Sweden)

    Guo Hui-Chen

    2012-06-01

    Full Text Available Abstract Backgroud Porcine circovirus type 2 (PCV2 is a primary etiological agent of post-weaning multi-systemic wasting syndrome (PMWS, which is a disease of increasing importance to the pig industry worldwide. Hollow mesoporous silica nanoparticles (HMSNs have gained increasing interest for use in vaccines. Methods To study the potential of HMSNs for use as a protein delivery system or vaccine carriers. HMSNs were synthesized by a sol–gel/emulsion(oil-in-water/ethanol method, purified PCV2 GST-ORF2-E protein was loaded into HMSNs, and the resulting HMSN/protein mixture was injected into mice. The uptake and release profiles of protein by HMSNs in vitro were investigated. PCV2 GST-ORF2-E specific antibodies and secretion of IFN-γ were detected by enzyme-linked immunosorbent assays, spleen lymphocyte proliferation was measured by the MTS method, and the percentage of CD4+ and CD8+ were determined by flow cytometry. Results HMSNs were found to yield better binding capacities and delivery profiles of proteins; the specific immune response induced by PCV2 GST-ORF2-E was maintained for a relatively long period of time after immunization with the HMSN/protein complex. Conclusion The findings suggest that HMSNs are good protein carriers and have high potential for use in future applications in therapeutic drug delivery.

  6. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers.

    Directory of Open Access Journals (Sweden)

    Tingting Yue

    Full Text Available The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer, owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.

  7. Development of amphiphilic gamma-PGA-nanoparticle based tumor vaccine: potential of the nanoparticulate cytosolic protein delivery carrier.

    Science.gov (United States)

    Yoshikawa, Tomoaki; Okada, Naoki; Oda, Atsushi; Matsuo, Kazuhiko; Matsuo, Keisuke; Mukai, Yohei; Yoshioka, Yasuo; Akagi, Takami; Akashi, Mitsuru; Nakagawa, Shinsaku

    2008-02-08

    Nanoscopic therapeutic systems that incorporate biomacromolecules, such as protein and peptides, are emerging as the next generation of nanomedicine aimed at improving the therapeutic efficacy of biomacromolecular drugs. In this study, we report that poly(gamma-glutamic acid)-based nanoparticles (gamma-PGA NPs) are excellent protein delivery carriers for tumor vaccines that delivered antigenic proteins to antigen-presenting cells and elicited potent immune responses. Importantly, gamma-PGA NPs efficiently delivered entrapped antigenic proteins through cytosolic translocation from the endosomes, which is a key process of gamma-PGA NP-mediated anti-tumor immune responses. Our findings suggest that the gamma-PGA NP system is suitable for the intracellular delivery of protein-based drugs as well as tumor vaccines.

  8. Loss of nuclear BRCA1 protein staining in normal tissue cells derived from BRCA1 and BRCA2 mutation carriers

    Energy Technology Data Exchange (ETDEWEB)

    Brakeleer, Sylvia de [Laboratory of Molecular Oncology (Department of Medical Oncology), UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels (Belgium); Bogdani, Marika [Department of Experimental Pathology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels (Belgium); Greve, Jacques de [Laboratory of Molecular Oncology (Department of Medical Oncology), UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels (Belgium); Familial Cancer Clinic, UZ Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium); Decock, Julie [Laboratory of Molecular Oncology (Department of Medical Oncology), UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels (Belgium); Sermijn, Erica [Familial Cancer Clinic, UZ Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium); Bonduelle, Maryse [Familial Cancer Clinic, UZ Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium); Goelen, Guido [Familial Cancer Clinic, UZ Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium); Teugels, Erik [Laboratory of Molecular Oncology (Department of Medical Oncology), UZ Brussel, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels (Belgium) and Familial Cancer Clinic, UZ Brussel, Laarbeeklaan 101, 1090 Brussels (Belgium)]. E-mail: eteugels@uzbrussel.be

    2007-06-01

    Enhanced genomic instability has been recently reported in normal cells derived from BRCA1/2 mutation carriers when placed in vitro in non-physiological stress conditions. We present here original data which help to explain the observed genomic instability. Leucocytes from BRCA1/2 mutation carriers, sporadic breast cancer patients and controls were prepared for BRCA1 immunocytochemistry. We show that BRCA1 containing nuclear dot like structures are detectable in about 80% of the leucocytes from controls and sporadic breast cancer patients, but are absent in the majority of normal cells from BRCA1 as well as BRCA2 mutation carriers (also in their normal breast cells). Our results thus indicate that the genomic instability observed in normal cells from BRCA1 and BRCA2 mutation carriers is associated with a down-regulation of nuclear BRCA1 protein accumulation in the dot like structures. These results suggest in addition that immunocytochemical or alternative molecular screening strategies might help to identify women with a high risk for breast (ovarian) cancer even when the underlying genetic defect remains undetectable.

  9. Physical Stability of Octenyl Succinate-Modified Polysaccharides and Whey Proteins for Potential Use as Bioactive Carriers in Food Systems.

    Science.gov (United States)

    Puerta-Gomez, Alex F; Castell-Perez, M Elena

    2015-06-01

    The high cost and potential toxicity of biodegradable polymers like poly(lactic-co-glycolic)acid (PLGA) has increased the interest in natural and modified biopolymers as bioactive carriers. This study characterized the physical stability (water sorption and state transition behavior) of selected starch and proteins: octenyl succinate-modified depolymerized waxy corn starch (DWxCn), waxy rice starch (DWxRc), phytoglycogen, whey protein concentrate (80%, WPC), whey protein isolate (WPI), and α-lactalbumin (α-L) to determine their potential as carriers of bioactive compounds under different environmental conditions. After enzyme modification and particle size characterization, glass transition temperature and moisture isotherms were used to characterize the systems. DWxCn and DWxRc had increased water sorption compared to native starch. The level of octenyl succinate anhydrate (OSA) modification (3% and 7%) did not reduce the water sorption of the DWxCn and phytoglycogen samples. The Guggenheim-Andersen-de Boer model indicated that native waxy corn had significantly (P whey proteins had higher glass transition temperature (Tg) values. On the other hand, depolymerized waxy starches at 7%-OSA modification had a "melted" appearance when exposed to environments with high relative humidity (above 70%) after 10 days at 23 °C. The use of depolymerized and OSA-modified polysaccharides blended with proteins created more stable blends of biopolymers. Hence, this biopolymer would be suitable for materials exposed to high humidity environments in food applications. © 2015 Institute of Food Technologists®

  10. A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.

    Science.gov (United States)

    Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

    2008-08-18

    CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.

  11. Stealth carriers for low-resolution structure determination of membrane proteins in solution

    DEFF Research Database (Denmark)

    Maric, Selma; Skar-Gislinge, Nicholas; Midtgaard, Søren

    2014-01-01

    techniques for fast and reliable structural analysis. The difficulty with this approach is that the carrier discs contribute to the measured scattering intensity in a highly nontrivial fashion, making subsequent data analysis challenging. Here, an elegant solution to circumvent the intrinsic complexity...

  12. NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

    NARCIS (Netherlands)

    Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

    In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

  13. Structure of 3-ketoacyl-(acyl-carrier-protein) reductase from Rickettsia prowazekii at 2.25 Å resolution

    International Nuclear Information System (INIS)

    Subramanian, Sandhya; Abendroth, Jan; Phan, Isabelle Q. H.; Olsen, Christian; Staker, Bart L.; Napuli, A.; Van Voorhis, Wesley C.; Stacy, Robin; Myler, Peter J.

    2011-01-01

    The R. prowazekii 3-ketoacyl-(acyl-carrier-protein) reductase is similar to those from other prokaryotic pathogens but differs significantly from the mammalian orthologue, strengthening its case as a potential drug target. Rickettsia prowazekii, a parasitic Gram-negative bacterium, is in the second-highest biodefense category of pathogens of the National Institute of Allergy and Infectious Diseases, but only a handful of structures have been deposited in the PDB for this bacterium; to date, all of these have been solved by the SSGCID. Owing to its small genome (about 800 protein-coding genes), it relies on the host for many basic biosynthetic processes, hindering the identification of potential antipathogenic drug targets. However, like many bacteria and plants, its metabolism does depend upon the type II fatty-acid synthesis (FAS) pathway for lipogenesis, whereas the predominant form of fatty-acid biosynthesis in humans is via the type I pathway. Here, the structure of the third enzyme in the FAS pathway, 3-ketoacyl-(acyl-carrier-protein) reductase, is reported at a resolution of 2.25 Å. Its fold is highly similar to those of the existing structures from some well characterized pathogens, such as Mycobacterium tuberculosis and Burkholderia pseudomallei, but differs significantly from the analogous mammalian structure. Hence, drugs known to target the enzymes of pathogenic bacteria may serve as potential leads against Rickettsia, which is responsible for spotted fever and typhus and is found throughout the world

  14. Structure-based mutational analysis of the 4'-phosphopantetheinyl transferases Sfp from Bacillus subtilis: carrier protein recognition and reaction mechanism.

    Science.gov (United States)

    Mofid, Mohammad Reza; Finking, Robert; Essen, Lars Oliver; Marahiel, Mohamed A

    2004-04-13

    The activation of apo-peptidyl carrier proteins (PCPs) of nonribosomal peptide synthetases (NRPSs), apo-acyl carrier proteins (ACPs) of polyketide synthases (PKSs), and fatty acid synthases (FASs) to their active holo form is accomplished with dedicated 4'-phosphopantetheinyl transferases (PPTases). They catalyze the transfer of the essential prosthetic group 4'-phosphopantetheine (4'-Ppant) from coenzyme A (CoA) to a highly conserved serine residue in all PCPs and ACPs. PPTases, based on sequence and substrate specifity, have been classified into three types: bacterial holo-acyl carrier protein synthase (AcpS), fatty acid synthase of eukaryotes (FAS2) and Sfp, a PPTase of secondary metabolism. The recently solved crystal structures of AcpS and Sfp-type PPTases with CoA revealed a common alpha + beta-fold with a beta(1)alpha(3)beta(2) motif and similarities in CoA binding and polymerization mode. However, it was not possible to discern neither the PCP binding region of Sfp nor the priming reaction mechanism from the Sfp-CoA cocrystal. In this work, we provide a model for the reaction mechanism based on mutational analysis of Sfp that suggests a reaction mechanism in which the highly conserved E151 deprotonates the hydroxyl group of the invariant serine of PCP. That, in turn, acts as a nucleophile to attack the beta-phosphate of CoA. The Sfp mutants K112, E117, and K120 further revealed that the loop region between beta4 and alpha5 (residues T111-S124) in Sfp is the PCP binding region. Also, residues T44, K75, S89, H90, D107, E109, E151, and K155 that have been shown in the Sfp-CoA cocrystal structure to coordinate CoA are now all confirmed by mutational and biochemical analysis.

  15. Crystal Structure of Malonyl CoA-Acyl Carrier Protein Transacylase from Xanthomanous oryzae pv. oryzae and Its Proposed Binding with ACP

    Science.gov (United States)

    Natarajan, Sampath; Kim, Jin-Kwang; Jung, Tae-Kyun; Doan, Thanh Thi Ngoc; Ngo, Ho-Phuong-Thuy; Hong, Myoung-Ki; Kim, Seunghwan; Tan, Viet Pham; Ahn, Seok Joon; Lee, Sang Hee; Han, Yesun; Ahn, Yeh-Jin; Kang, Lin-Woo

    2012-01-01

    Xanthomonas oryzae pv. oryzae (Xoo) is a plant bacterial pathogen that causes bacterial blight (BB) disease, resulting in serious production losses of rice. The crystal structure of malonyl CoA-acyl carrier protein transacylase (XoMCAT), encoded by the gene fabD (Xoo0880) from Xoo, was determined at 2.3 Å resolution in complex with N-cyclohexyl-2-aminoethansulfonic acid. Malonyl CoA-acyl carrier protein transacylase transfers malonyl group from malonyl CoA to acyl carrier protein (ACP). The transacylation step is essential in fatty acid synthesis. Based on the rationale, XoMCAT has been considered as a target for antibacterial agents against BB. Protein-protein interaction between XoMCAT and ACP was also extensively investigated using computational docking, and the proposed model revealed that ACP bound to the cleft between two XoMCAT subdomains. PMID:22134719

  16. Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach

    Energy Technology Data Exchange (ETDEWEB)

    Economou, Nicoleta J.; Zentner, Isaac J. [Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102 (United States); Lazo, Edwin; Jakoncic, Jean; Stojanoff, Vivian [Brookhaven National Laboratory, Upton, NY 11973 (United States); Weeks, Stephen D.; Grasty, Kimberly C.; Cocklin, Simon; Loll, Patrick J. [Drexel University College of Medicine, 245 North 15th Street, Philadelphia, PA 19102 (United States)

    2013-04-01

    Using a carrier-protein strategy, the structure of teicoplanin bound to its bacterial cell-wall target has been determined. The structure reveals the molecular determinants of target recognition, flexibility in the antibiotic backbone and intrinsic radiation sensitivity of teicoplanin. Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a d-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein–peptide–antibiotic complex. The 2.05 Å resolution MBP–peptide–teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance.

  17. Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach

    International Nuclear Information System (INIS)

    Economou, Nicoleta J.; Zentner, Isaac J.; Lazo, Edwin; Jakoncic, Jean; Stojanoff, Vivian; Weeks, Stephen D.; Grasty, Kimberly C.; Cocklin, Simon; Loll, Patrick J.

    2013-01-01

    Using a carrier-protein strategy, the structure of teicoplanin bound to its bacterial cell-wall target has been determined. The structure reveals the molecular determinants of target recognition, flexibility in the antibiotic backbone and intrinsic radiation sensitivity of teicoplanin. Multidrug-resistant bacterial infections are commonly treated with glycopeptide antibiotics such as teicoplanin. This drug inhibits bacterial cell-wall biosynthesis by binding and sequestering a cell-wall precursor: a d-alanine-containing peptide. A carrier-protein strategy was used to crystallize the complex of teicoplanin and its target peptide by fusing the cell-wall peptide to either MBP or ubiquitin via native chemical ligation and subsequently crystallizing the protein–peptide–antibiotic complex. The 2.05 Å resolution MBP–peptide–teicoplanin structure shows that teicoplanin recognizes its ligand through a combination of five hydrogen bonds and multiple van der Waals interactions. Comparison of this teicoplanin structure with that of unliganded teicoplanin reveals a flexibility in the antibiotic peptide backbone that has significant implications for ligand recognition. Diffraction experiments revealed an X-ray-induced dechlorination of the sixth amino acid of the antibiotic; it is shown that teicoplanin is significantly more radiation-sensitive than other similar antibiotics and that ligand binding increases radiosensitivity. Insights derived from this new teicoplanin structure may contribute to the development of next-generation antibacterials designed to overcome bacterial resistance

  18. Escherichia coli fusion carrier proteins act as solubilizing agents for recombinant uncoupling protein 1 through interactions with GroEL

    International Nuclear Information System (INIS)

    Douette, Pierre; Navet, Rachel; Gerkens, Pascal; Galleni, Moreno; Levy, Daniel; Sluse, Francis E.

    2005-01-01

    Fusing recombinant proteins to highly soluble partners is frequently used to prevent aggregation of recombinant proteins in Escherichia coli. Moreover, co-overexpression of prokaryotic chaperones can increase the amount of properly folded recombinant proteins. To understand the solubility enhancement of fusion proteins, we designed two recombinant proteins composed of uncoupling protein 1 (UCP1), a mitochondrial membrane protein, in fusion with MBP or NusA. We were able to express soluble forms of MBP-UCP1 and NusA-UCP1 despite the high hydrophobicity of UCP1. Furthermore, the yield of soluble fusion proteins depended on co-overexpression of GroEL that catalyzes folding of polypeptides. MBP-UCP1 was expressed in the form of a non-covalent complex with GroEL. MBP-UCP1/GroEL was purified and characterized by dynamic light scattering, gel filtration, and electron microscopy. Our findings suggest that MBP and NusA act as solubilizing agents by forcing the recombinant protein to pass through the bacterial chaperone pathway in the context of fusion protein

  19. Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells

    NARCIS (Netherlands)

    Cohen, S.; Coué, G.M.J.P.C.; Beno, D.; Korenstein, R.; Engbersen, Johannes F.J.

    2012-01-01

    An effective intracellular protein delivery system was developed based on linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Two differently functionalized PAAs were synthesized by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to

  20. Lactose carrier protein of Escherichia coli. Structure and expression of plasmids carrying the Y gene of the lac operon.

    Science.gov (United States)

    Teather, R M; Bramhall, J; Riede, I; Wright, J K; Fürst, M; Aichele, G; Wilhelm, U; Overath, P

    1980-01-01

    The previously described hybrid plasmid pC7 which carries lacI+O+delta(Z)Y+A+ on a 12.3 X 10(6)-Mr DNA fragment [Teather et al. (1978) Mol. Gen. Genet. 159, 239-248] was partially digested with the restriction endonuclease EcoRI under conditions reducing the recognition sequence to d(A-A-T-T) and ligated to the vector pB322. lac Y-carrying inserts of various sized (Mr 1.5-4.7 X 10(6)) were obtained. Hybrid plasmid pTE18 (2300-base-pair insert) carries part of the I (repressor) gene, the promotor-operator region, part of the Z (beta-galactosidase) gene, the Y (lactose carrier) gene and part of the A (transacetylase) gene. Upon induction of pTE18-harbouring strains the Y-gene product is expressed at a nearly constant rate for several generations and accumulates to a level of 12-16% of the total cytoplasmic membrane protein. Integration into the membrane leads to active carrier as judged by binding and transport measurements.

  1. Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates.

    Science.gov (United States)

    Bröker, Michael

    2016-03-03

    When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that the conjugate carriers TT and DT can induce a protective immune response against a lethal challenge by toxins in animals, while glycoconjugates based on CRM197 failed to induce a protective immune response. Opportunities for new applications of glycoconjugates are discussed.

  2. Hydroxyapatite nanorod-assembled porous hollow polyhedra as drug/protein carriers.

    Science.gov (United States)

    Yu, Ya-Dong; Zhu, Ying-Jie; Qi, Chao; Jiang, Ying-Ying; Li, Heng; Wu, Jin

    2017-06-15

    Hydroxyapatite (HAP) with a porous hollow structure is an ideal biomaterial owing to its excellent biocompatibility and unique architecture. In this study, HAP nanorod-assembled porous hollow polyhedra, consisting of nanorod building blocks, have been successfully prepared at room temperature or under hydrothermal circumstances using a self-sacrificing Ca(OH) 2 template strategy. The hydrothermal treatment (at 180°C for 1h) can promote the HAP nanorods to be arranged with their axial direction normal to the polyhedron surface. The HAP nanorod-assembled porous hollow polyhedra have been explored for the potential application in drug/protein delivery, using ibuprofen (IBU) as a model drug and hemoglobin (Hb) as a model protein. The experimental results indicate that the HAP nanorod-assembled porous hollow polyhedra have a relatively high drug loading capacity and protein adsorption ability, and sustained drug and protein release. The HAP nanorod-assembled porous hollow polyhedra have promising applications in various biomedical fields such as the drug and protein delivery. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD+ and triclosan

    International Nuclear Information System (INIS)

    Mehboob, Shahila; Truong, Kent; Santarsiero, Bernard D.; Johnson, Michael E.

    2010-01-01

    Structure of the ternary complex of F. tularensis enoyl-acyl carrier protein reductase reveals the structure of the substrate binding loop whose electron density was missing in an earlier structure, and demonstrates a shift in the position of the NAD + cofactor. Enoyl-acyl carrier protein reductase (FabI) catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antimicrobial drug target in Francisella tularensis. The development of new antibiotic therapies is important both to combat potential drug-resistant bioweapons and to address the broader societal problem of increasing antibiotic resistance among many pathogenic bacteria. The crystal structure of FabI from F. tularensis (FtuFabI) in complex with the inhibitor triclosan and the cofactor NAD + has been solved to a resolution of 2.1 Å. Triclosan is known to effectively inhibit FabI from different organisms. Precise characterization of the mode of triclosan binding is required to develop highly specific inhibitors. Comparison of our structure with the previously determined FtuFabI structure which is bound to only NAD + reveals the conformation of the substrate-binding loop, electron density for which was missing in the earlier structure, and demonstrates a shift in the conformation of the NAD + cofactor. This shift in the position of the phosphate groups allows more room in the active site for substrate or inhibitor to bind and be better accommodated. This information will be crucial for virtual screening studies to identify novel scaffolds for development into new active inhibitors

  4. Molecular cloning and characterization of two β-ketoacyl-acyl carrier protein synthase I genes from Jatropha curcas L.

    Science.gov (United States)

    Xiong, Wangdan; Wei, Qian; Wu, Pingzhi; Zhang, Sheng; Li, Jun; Chen, Yaping; Li, Meiru; Jiang, Huawu; Wu, Guojiang

    2017-07-01

    The β-ketoacyl-acyl carrier protein synthase I (KASI) is involved in de novo fatty acid biosynthesis in many organisms. Two putative KASI genes, JcKASI-1 and JcKASI-2, were isolated from Jatropha curcas. The deduced amino acid sequences of JcKASI-1 and JcKASI-2 exhibit around 83.8% and 72.5% sequence identities with AtKASI, respectively, and both contain conserved Cys-His-Lys-His-Phe catalytic active sites. Phylogenetic analysis indicated that JcKASI-2 belongs to a clade with several KASI proteins from dicotyledonous plants. Both JcKASI genes were expressed in multiple tissues, most strongly in filling stage seeds of J. curcas. Additionally, the JcKASI-1 and JcKASI-2 proteins were both localized to the plastids. Expressing JcKASI-1 in the Arabidopsis kasI mutant rescued the mutant's phenotype and restored the fatty acid composition and oil content in seeds to wild-type, but expressing JcKASI-2 in the Arabidopsis kasI mutant resulted in only partial rescue. This implies that JcKASI-1 and JcKASI-2 exhibit partial functional redundancy and KASI genes play a universal role in regulating fatty acid biosynthesis, growth, and development in plants. Copyright © 2017 Elsevier GmbH. All rights reserved.

  5. The Two Functional Enoyl-Acyl Carrier Protein Reductases of Enterococcus faecalis Do Not Mediate Triclosan Resistance

    Science.gov (United States)

    Zhu, Lei; Bi, Hongkai; Ma, Jincheng; Hu, Zhe; Zhang, Wenbin; Cronan, John E.; Wang, Haihong

    2013-01-01

    ABSTRACT Enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the last step of the elongation cycle in the synthesis of bacterial fatty acids. The Enterococcus faecalis genome contains two genes annotated as enoyl-ACP reductases, a FabI-type enoyl-ACP reductase and a FabK-type enoyl-ACP reductase. We report that expression of either of the two proteins restores growth of an Escherichia coli fabI temperature-sensitive mutant strain under nonpermissive conditions. In vitro assays demonstrated that both proteins support fatty acid synthesis and are active with substrates of all fatty acid chain lengths. Although expression of E. faecalis fabK confers to E. coli high levels of resistance to the antimicrobial triclosan, deletion of fabK from the E. faecalis genome showed that FabK does not play a detectable role in the inherent triclosan resistance of E. faecalis. Indeed, FabK seems to play only a minor role in modulating fatty acid composition. Strains carrying a deletion of fabK grow normally without fatty acid supplementation, whereas fabI deletion mutants make only traces of fatty acids and are unsaturated fatty acid auxotrophs. PMID:24085780

  6. Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT--relationship to newly identified mitochondrial pyruvate carrier proteins.

    Directory of Open Access Journals (Sweden)

    Jerry R Colca

    Full Text Available Thiazolidinedione (TZD insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of these molecules remained to be identified. Here we use a photo-catalyzable drug analog probe and mass spectrometry-based proteomics to identify a previously uncharacterized mitochondrial complex that specifically recognizes TZDs. These studies identify two well-conserved proteins previously known as brain protein 44 (BRP44 and BRP44 Like (BRP44L, which recently have been renamed Mpc2 and Mpc1 to signify their function as a mitochondrial pyruvate carrier complex. Knockdown of Mpc1 or Mpc2 in Drosophila melanogaster or pre-incubation with UK5099, an inhibitor of pyruvate transport, blocks the crosslinking of mitochondrial membranes by the TZD probe. Knockdown of these proteins in Drosophila also led to increased hemolymph glucose and blocked drug action. In isolated brown adipose tissue (BAT cells, MSDC-0602, a PPARγ-sparing TZD, altered the incorporation of (13C-labeled carbon from glucose into acetyl CoA. These results identify Mpc1 and Mpc2 as components of the mitochondrial target of TZDs (mTOT and suggest that understanding the modulation of this complex, which appears to regulate pyruvate entry into the mitochondria, may provide a viable target for insulin sensitizing pharmacology.

  7. Food protein aggregates as vitamin-matrix carriers: impact of processing conditions.

    Science.gov (United States)

    Relkin, Perla; Shukat, Rizwan

    2012-10-15

    We studied the ability of protein aggregates for loading and protection of α-tocopherol, a model of heat- and light-sensitive bioactive compounds. Aqueous dispersions of whey proteins (4.5 wt.%, pH 6.7) in the absence and presence of α-tocopherol (4 wt.%) were prepared using an ultradisperser (10,000 rpm for 10 min and 65 °C), and then submitted to further high-pressure homogenisation (HPH) at 300 or 1200 bar for 12 cycles. Relative to free-vitamin dispersions, increasing HPH conditions in the presence of vitamin led to higher protein denaturation, more tryptophan quenching and wavelength blue-shift (by 10nm), in parallel with increased zeta potential values (by -10 mV), particle sizes (by 50%), and newly formed protein dimers, trimers and high molecular weight aggregates. As a result, the degree of vitamin degradation under increasing HPH and long-term storage was shown to decrease from 66% (ultradisper) to 50%, or to 30% (subject to further treatments at 300 or 1200 bar, respectively). Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Male Sterile2 Encodes a Plastid-Localized Fatty Acyl Carrier Protein Reductase Required for Pollen Exine Development in Arabidopsis

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.; Shanklin, J.; Yu, X.-H.; Zhang, K.; Shi, J.; De Oliveira, S.; Schreiber, L.; Zhang, D.

    2011-10-01

    Male Sterile2 (MS2) is predicted to encode a fatty acid reductase required for pollen wall development in Arabidopsis (Arabidopsis thaliana). Transient expression of MS2 in tobacco (Nicotiana benthamiana) leaves resulted in the accumulation of significant levels of C16 and C18 fatty alcohols. Expression of MS2 fused with green fluorescent protein revealed that an amino-terminal transit peptide targets the MS2 to plastids. The plastidial localization of MS2 is biologically important because genetic complementation of MS2 in ms2 homozygous plants was dependent on the presence of its amino-terminal transit peptide or that of the Rubisco small subunit protein amino-terminal transit peptide. In addition, two domains, NAD(P)H-binding domain and sterile domain, conserved in MS2 and its homologs were also shown to be essential for MS2 function in pollen exine development by genetic complementation testing. Direct biochemical analysis revealed that purified recombinant MS2 enzyme is able to convert palmitoyl-Acyl Carrier Protein to the corresponding C16:0 alcohol with NAD(P)H as the preferred electron donor. Using optimized reaction conditions (i.e. at pH 6.0 and 30 C), MS2 exhibits a K{sub m} for 16:0-Acyl Carrier Protein of 23.3 {+-} 4.0 {mu}m, a V{sub max} of 38.3 {+-} 4.5 nmol mg{sup -1} min{sup -1}, and a catalytic efficiency/K{sub m} of 1,873 m{sup -1} s{sup -1}. Based on the high homology of MS2 to other characterized fatty acid reductases, it was surprising that MS2 showed no activity against palmitoyl- or other acyl-coenzyme A; however, this is consistent with its plastidial localization. In summary, genetic and biochemical evidence demonstrate an MS2-mediated conserved plastidial pathway for the production of fatty alcohols that are essential for pollen wall biosynthesis in Arabidopsis.

  9. Isolation of recombinant proteins from culture broth by co-precipitation with an amino acid carrier to form stable dry powders.

    Science.gov (United States)

    Moore, Barry D; Deere, Joseph; Edrada-Ebel, RuAngelie; Ingram, Andrew; van der Walle, Christopher F

    2010-08-01

    Protein-coated microcrystals can be generated by co-precipitation of protein and a water-soluble crystalline carrier by addition to excess water miscible organic solvent. We have investigated this novel process for its utility in the concentration and partial purification of a recombinant protein exported into the culture broth during expression by Pichia pastoris. Co-precipitation with a L-glutamine carrier selectively isolated the protein content of the culture broth, with a minimal number of steps, and simultaneously removed contaminants including a novel yeast metabolite. This pigment co-elutes during aqueous chromatography but its elucidation as a benzoylated glycosamine suggested a simple route of removal by partition during the co-precipitation process. Scale-up of the process was readily achieved through in-line mixing and subsequent reconstitution of the dried protein-coated microcrystals yielded natively folded, bioactive protein. Additional washing of the crystals with saturated L-glutamine facilitated further purification of the recombinant protein immobilized on the L-glutamine carrier. Thus, we present a novel method for the harvesting of recombinant protein from culture broth as a dry powder, which may be of general applicability to bioprocessing. (c) 2010 Wiley Periodicals, Inc.

  10. The Biological Activity of alpha-Mangostin, a Larvicidal Botanic Mosquito Sterol Carrier Protein-2 Inhibitor

    Science.gov (United States)

    2010-01-01

    consider- ingG.mangostana is a tropical evergreen that ismainly found in India , Myanmar, Sri Lanka, and Thailand (Jung et al. 2006). Almost a decade...unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 ferase ( GST ) activities (Bullangpoti et al...Thermo ScientiÞc, Rockford, IL). The esterase activity was expressed as mol/mg protein/min substrate hydrolyzed. GST Activity. GST activity samples

  11. Cancer therapy using viral- and bacterial proteins, as vectors for vaccines or as carriers of cytostatics

    OpenAIRE

    Eriksson, Mathilda

    2012-01-01

    New cancer therapies are urgently needed, since available treatment options today have negative side effects, and cure only about half of the patients with invasive cancer. One, relatively new, option is to vaccinate against cancer, by introducing an antigen that is present on the tumor cells into the patient to stimulate specific immunity against the tumor. For this purpose viral capsid proteins, which can self-assemble into so called virus-like particles (VLPs), can be e...

  12. Structural and dynamic characterization of a freestanding acyl carrier protein involved in the biosynthesis of cyclic lipopeptide antibiotics.

    Science.gov (United States)

    Paul, Subrata; Ishida, Hiroaki; Nguyen, Leonard T; Liu, Zhihong; Vogel, Hans J

    2017-05-01

    Friulimicin is a cyclic lipodecapeptide antibiotic that is produced by Actinoplanes friuliensis. Similar to the related lipopeptide drug daptomycin, the peptide skeleton of friulimicin is synthesized by a large multienzyme nonribosomal peptide synthetase (NRPS) system. The LipD protein plays a major role in the acylation reaction of friulimicin. The attachment of the fatty acid group promotes its antibiotic activity. Phylogenetic analysis reveals that LipD is most closely related to other freestanding acyl carrier proteins (ACPs), for which the genes are located near to NRPS gene clusters. Here, we report that the solution NMR structure of apo-LipD is very similar to other four-helix bundle forming ACPs from fatty acid synthase (FAS), polyketide synthase, and NRPS systems. By recording NMR dynamics data, we found that the backbone motions in holo-LipD are more restricted than in apo-LipD due to the attachment of phosphopantetheine moiety. This enhanced stability of holo-LipD was also observed in differential scanning calorimetry experiments. Furthermore, we demonstrate that, unlike several other ACPs, the folding of LipD does not depend on the presence of divalent cations, although the presence of Mg 2+ or Ca 2+ can increase the protein stability. We propose that small structural rearrangements in the tertiary structure of holo-LipD which lead to the enhanced stability are important for the cognate enzyme recognition for the acylation reaction. Our results also highlight the different surface charges of LipD and FAS-ACP from A. friuliensis that would allow the acyl-CoA ligase to interact preferentially with the LipD instead of binding to the FAS-ACP. © 2017 The Protein Society.

  13. Properties of the mitochondrial carrier of adenine-nucleotide after purification. Study of the transport protein under isolated form and reincorporated form in phospho-lipidic vesicles

    International Nuclear Information System (INIS)

    Brandolin, Gerard

    1983-01-01

    The first part of this research thesis addresses the reconstitution of the ADP/ATP transport by incorporation of the specific carrier, isolated in presence of detergent, in phospholipids vesicles. Fundamental properties of the reconstituted transport are identical to that of transport in mitochondria, notably as far as the exchange stoichiometry, the turn over and the transport Km are concerned, as well as the asymmetric orientation of the carrier in the membrane. The second part of this research addresses the study of interactions of specific ligands with the ADP/ATP transport protein in presence of detergent. The study of the variations of the intrinsic fluorescence of the isolated ADP/ATP carrier highlights conformational changes exclusively induced by the presence of transportable nucleotides which are modulated in a different manner by carboxy-atractyloside or bongkrekic acid. Moreover, by using the isolated protein, a detailed analysis of binding parameters of fluorescent analogues of ATP is reported [fr

  14. Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Chunhong [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Zhao, Jianhao, E-mail: jhzhao@jnu.edu.cn [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China); Tu, Mei; Zeng, Rong; Rong, Jianhua [Department of Materials Science and Engineering, College of Science and Engineering, Jinan University, Guangzhou 510632 (China); Engineering Research Center of Artificial Organs and Materials, Ministry of Education, Guangzhou 510632 (China)

    2014-03-01

    Hyaluronan (HA) microgels with different crosslink network, i.e. HGPs-1, HGPs-1.5, HGPs-3, HGPs-6 and HGPs-15, were synthesized using divinyl sulfone (DVS) as the crosslinker in an inverse microemulsion system for controlling the sustained delivery of bovine serum albumin (BSA). With increasing the crosslinker content, the average particle size slightly increased from 1.9 ± 0.3 μm to 3.6 ± 0.5 μm by dynamic laser scattering analysis. However, the crosslinker content had no significant effect on the morphology of HA microgels by scanning and transmission electron microscopes. Fourier transform infrared spectroscopy and elemental analysis proved more sulfur participated in the crosslink reaction when raising the crosslinker amount. The water swelling test confirmed the increasing crosslink density with the crosslinker content by calculating the average molecular weight between two crosslink points to be 8.25 ± 2.51 × 10{sup 5}, 1.26 ± 0.43 × 10{sup 5}, 0.96 ± 0.09 × 10{sup 5}, 0.64 ± 0.03 × 10{sup 5}, and 0.11 ± 0.01 × 10{sup 5} respectively. The degradation of HA microgels by hyaluronidase slowed down by enhancing the crosslink density, only about 5% of HGPs-15 was degraded as opposed to over 90% for HGPs-1. BSA loading had no obvious influence on the surface morphology of HA microgels but seemed to induce their aggregation. The increase of crosslink density decreased the BSA loading capacity but facilitated its long-term sustained delivery. When the molar ratio of DVS to repeating unit of HA reached 3 or higher, similar delivery profiles were obtained. Among all these HA microgels, HGPs-3 was the optimal carrier for BSA sustained delivery in this system because it possessed both high BSA loading capacity and long-term delivery profile simultaneously. - Highlights: • HA microgels with different crosslink densities were prepared. • The crosslinker content had little effect on the morphology and size of HA microgels. • The crosslink density

  15. Resistance Mechanisms and the Future of Bacterial Enoyl-Acyl Carrier Protein Reductase (FabI) Antibiotics.

    Science.gov (United States)

    Yao, Jiangwei; Rock, Charles O

    2016-03-01

    Missense mutations leading to clinical antibiotic resistance are a liability of single-target inhibitors. The enoyl-acyl carrier protein reductase (FabI) inhibitors have one intracellular protein target and drug resistance is increased by the acquisition of single-base-pair mutations that alter drug binding. The spectrum of resistance mechanisms to FabI inhibitors suggests criteria that should be considered during the development of single-target antibiotics that would minimize the impact of missense mutations on their clinical usefulness. These criteria include high-affinity, fast on/off kinetics, few drug contacts with residue side chains, and no toxicity. These stringent criteria are achievable by structure-guided design, but this approach will only yield pathogen-specific drugs. Single-step acquisition of resistance may limit the clinical application of broad-spectrum, single-target antibiotics, but appropriately designed pathogen-specific antibiotics have the potential to overcome this liability. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  16. Tetanus Toxoid carrier protein induced T-helper cell responses upon vaccination of middle-aged adults.

    Science.gov (United States)

    van der Heiden, Marieke; Duizendstra, Aafke; Berbers, Guy A M; Boots, Annemieke M H; Buisman, Anne-Marie

    2017-10-09

    Vaccines frequently induce suboptimal immune responses in the elderly, due to immunological ageing. Timely vaccination may be a strategy to overcome this problem, which classifies middle-aged adults asan interesting target group for future vaccine interventions. However, the immunological fitness of the middle-aged population is ill-defined. It is currently unknown whether effective T-cell help towards B-cells is initiated by conjugate-carrier vaccines at middle-age. We characterized systemic Tetanus Toxoid (TT) specific T-helper cell responses in the circulation of middle-aged adults (50-65years of age, n=31) having received the MenACWY-TT vaccination. Blood samples were taken pre- as well as 7days, 28days, and 1year post-vaccination. TT-specific T-cell responses were determined by IFNγ Elispot and by the secretion of IFNγ, IL13, IL10, IL17, and IL21 in cell culture supernatants. Circulating CD4+CXCR5+ICOS+IL21+ cells were analyzed by flow cytometry, and meningococcal and TT-specific IgG responses by bead-based immunoassays. The correlation between the T-cell help and humoral responses was evaluated. Vaccination with a TT-carrier protein induced a mixed TT-specific Th1 (IFNγ), Th2 (IL13, IL10), and Th17 (IL17) response in most participants. Additionally, circulating CD4+CXCR5+ICOS+IL21+ cells were significantly increased 7days post-vaccination. Pre-vaccination TT-specific cytokine production and post-vaccination Th2 responses correlated positively with the increase of CD4+CXCR5+ICOS+IL21+ cells. No correlation between T-cell help and antibody responses was found. The characteristics of the T-cell response upon a TT-carrier vaccination suggests effective T-cell help towards B-cells in response to meningococcal polysaccharides, although the absence of a correlation with the antibody responses warrants further clarification. However, the robust T-helper cell response in middle-aged adults, decades after previous TT vaccinations, strengthens the classification of

  17. Gag Protein Epitopes Recognized by CD4+ T-Helper Lymphocytes from Equine Infectious Anemia Virus-Infected Carrier Horses

    Science.gov (United States)

    Lonning, S. M.; Zhang, W.; McGuire, T. C.

    1999-01-01

    Antigen-specific T-helper (Th) lymphocytes are critical for the development of antiviral humoral responses and the expansion of cytotoxic T lymphocytes (CTL). Identification of relevant Th lymphocyte epitopes remains an important step in the development of an efficacious subunit peptide vaccine against equine infectious anemia virus (EIAV), a naturally occurring lentivirus of horses. This study describes Th lymphocyte reactivity in EIAV carrier horses to two proteins, p26 and p15, encoded by the relatively conserved EIAV gag gene. Using partially overlapping peptides, multideterminant and possibly promiscuous epitopes were identified within p26. One peptide was identified which reacted with peripheral blood mononuclear cells (PBMC) from all five EIAV-infected horses, and three other peptides were identified which reacted with PBMC from four of five EIAV-infected horses. Four additional peptides containing both CTL and Th lymphocyte epitopes were also identified. Multiple epitopes were recognized in a region corresponding to the major homology region of the human immunodeficiency virus, a region with significant sequence similarity to other lentiviruses including simian immunodeficiency virus, puma lentivirus, feline immunodeficiency virus, Jembrana disease virus, visna virus, and caprine arthritis encephalitis virus. PBMC reactivity to p15 peptides from EIAV carrier horses also occurred. Multiple p15 peptides were shown to be reactive, but not all infected horses had Th lymphocytes recognizing p15 epitopes. The identification of peptides reactive with PBMC from outbred horses, some of which encoded both CTL and Th lymphocyte epitopes, should contribute to the design of synthetic peptide or recombinant vector vaccines for EIAV. PMID:10196322

  18. Carbohydrate particles as protein carriers and scaffolds: physico-chemical characterization and collagen stability

    Energy Technology Data Exchange (ETDEWEB)

    Peres, Ivone; Rocha, Sandra; Loureiro, Joana A.; Carmo Pereira, Maria do [University of Porto, LEPAE, Chemical Engineering Department, Faculty of Engineering (Portugal); Ivanova, Galya [Universidade do Porto, REQUIMTE, Departamento de Quimica, Faculdade de Ciencias (Portugal); Coelho, Manuel, E-mail: mcoelho@fe.up.pt [University of Porto, LEPAE, Chemical Engineering Department, Faculty of Engineering (Portugal)

    2012-09-15

    The preservation of protein properties after entrapping into polymeric matrices and the effects of drying the emulsions still remains uncertain and controversial. Carbohydrate particles were designed and prepared by homogenization of gum arabic and maltodextrin mixture, with collagen hydrolysate (CH) followed by spray-drying. The encapsulation of CH in the carbohydrate matrix was achieved with an efficiency of 85 {+-} 2 %. The morphology and the size of the particles, before (40-400 nm) and after spray-drying (<20 {mu}m), were characterized by scanning electron microscopy and dynamic light scattering. Measurements of the nuclear relaxation times and application of diffusion ordered spectroscopy, obtained through pulsed field gradient NMR experiments, have been performed to determine the structure of the CH-polysaccharide conjugates and to clarify the mechanism of CH immobilization in the polysaccharide matrix. In vitro release profiles in ultrapure water and in cellular medium reveal that the diffusion rate of CH from the polymeric matrix to the dialysis solution decreases in average 30-50 % over time, compared to free CH molecules. In cellular medium at 37 Degree-Sign C, the complete release of CH from the particles is achieved only after 24 h, demonstrating a significant decrease in the CH mass transfer process when compared with free CH. The findings of this study outline the ability of gum arabic/maltodextrin matrices to entrap and preserve CH original properties after the spray-drying process and support the potential of the polymeric scaffold for protein delivery and tissue engineering.

  19. Correlation of acidic and basic carrier ampholyte and immobilized pH gradient two-dimensional gel electrophoresis patterns based on mass spectrometric protein identification

    DEFF Research Database (Denmark)

    Nawrocki, A; Larsen, Martin Røssel; Podtelejnikov, A V

    1998-01-01

    Separation of proteins on either carrier ampholyte-based or immobilized pH gradient-based two-dimensional (2-D) gels gives rise to electrophoretic patterns that are difficult to compare visually. In this paper we have used matrix-assisted laser desorption/ionization mass spectrometry (MALDI...

  20. Carrier Diagnosis

    Science.gov (United States)

    ... Inheritance of Hemophilia Definitions & Terminology Bleeding Symptoms Carrier Diagnosis When to Test for Carrier Status Family Planning and Pregnancy Conception Options Prenatal Diagnosis Fetal Sex ...

  1. Fatty acid-binding proteins (FABPs) are intracellular carriers for Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD).

    Science.gov (United States)

    Elmes, Matthew W; Kaczocha, Martin; Berger, William T; Leung, KwanNok; Ralph, Brian P; Wang, Liqun; Sweeney, Joseph M; Miyauchi, Jeremy T; Tsirka, Stella E; Ojima, Iwao; Deutsch, Dale G

    2015-04-03

    Δ(9)-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Fatty Acid-binding Proteins (FABPs) Are Intracellular Carriers for Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD)*

    Science.gov (United States)

    Elmes, Matthew W.; Kaczocha, Martin; Berger, William T.; Leung, KwanNok; Ralph, Brian P.; Wang, Liqun; Sweeney, Joseph M.; Miyauchi, Jeremy T.; Tsirka, Stella E.; Ojima, Iwao; Deutsch, Dale G.

    2015-01-01

    Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) occur naturally in marijuana (Cannabis) and may be formulated, individually or in combination in pharmaceuticals such as Marinol or Sativex. Although it is known that these hydrophobic compounds can be transported in blood by albumin or lipoproteins, the intracellular carrier has not been identified. Recent reports suggest that CBD and THC elevate the levels of the endocannabinoid anandamide (AEA) when administered to humans, suggesting that phytocannabinoids target cellular proteins involved in endocannabinoid clearance. Fatty acid-binding proteins (FABPs) are intracellular proteins that mediate AEA transport to its catabolic enzyme fatty acid amide hydrolase (FAAH). By computational analysis and ligand displacement assays, we show that at least three human FABPs bind THC and CBD and demonstrate that THC and CBD inhibit the cellular uptake and catabolism of AEA by targeting FABPs. Furthermore, we show that in contrast to rodent FAAH, CBD does not inhibit the enzymatic actions of human FAAH, and thus FAAH inhibition cannot account for the observed increase in circulating AEA in humans following CBD consumption. Using computational molecular docking and site-directed mutagenesis we identify key residues within the active site of FAAH that confer the species-specific sensitivity to inhibition by CBD. Competition for FABPs may in part or wholly explain the increased circulating levels of endocannabinoids reported after consumption of cannabinoids. These data shed light on the mechanism of action of CBD in modulating the endocannabinoid tone in vivo and may explain, in part, its reported efficacy toward epilepsy and other neurological disorders. PMID:25666611

  3. Interchangeability of meningococcal group C conjugate vaccines with different carrier proteins in the United Kingdom infant immunisation schedule.

    Science.gov (United States)

    Ladhani, Shamez N; Andrews, Nick J; Waight, Pauline; Hallis, Bassam; Matheson, Mary; England, Anna; Findlow, Helen; Bai, Xilian; Borrow, Ray; Burbidge, Polly; Pearce, Emma; Goldblatt, David; Miller, Elizabeth

    2015-01-29

    An open, non-randomised study was undertaken in England during 2011-12 to evaluate vaccine antibody responses in infants after completion of the routine primary infant immunisation schedule, which included two doses of meningococcal group C (MenC) conjugate (MCC) vaccine at 3 and 4 months. Any of the three licensed MCC vaccines could be used for either dose, depending on local availability. Healthy term infants registered at participating general practices (GPs) in Hertfordshire and Gloucestershire, UK, were recruited prospectively to provide a single blood sample four weeks after primary immunisation, which was administered by the GP surgery. Vaccination history was obtained at blood sampling. MenC serum bactericidal antibody (SBA) and IgG antibodies against Haemophilus influenzae b (Hib), pertussis toxin (PT), diphtheria toxoid (DT), tetanus toxoid (TT) and thirteen pneumococcal serotypes were analysed according to MCC vaccines received. MenC SBA responses differed significantly (Pvaccine schedule as follows: MenC SBA geometric mean titres (GMTs) were significantly lower in infants receiving a diphtheria cross-reacting material-conjugated MCC (MCC-CRM) vaccine followed by TT-conjugated MCC (MCC-TT) vaccine (82.0; 95% CI, 39-173; n=14) compared to those receiving two MCC-CRM (418; 95% CI, 325-537; n=82), two MCC-TT (277; 95% CI, 223-344; n=79) or MCC-TT followed by MCC-CRM (553; 95% CI, 322-949; n=18). The same group also had the lowest Hib geometric mean concentrations (0.60 μg/mL, 0.27-1.34) compared to 1.85 μg/mL (1.23-2.78), 2.86 μg/mL (2.02-4.05) and 4.26 μg/mL (1.94-9.36), respectively. Our results indicate that MCC vaccines with different carrier proteins are not interchangeable. When several MCC vaccines are available, children requiring more than one dose should receive MCC vaccines with the same carrier protein or, alternatively, receive MCC-TT first wherever possible. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Protein nanocoatings on synthetic polymeric nanofibrous membranes designed as carriers for skin cells.

    Science.gov (United States)

    Bacakova, Marketa; Pajorova, Julia; Stranska, Denisa; Hadraba, Daniel; Lopot, Frantisek; Riedel, Tomas; Brynda, Eduard; Zaloudkova, Margit; Bacakova, Lucie

    2017-01-01

    Protein-coated resorbable synthetic polymeric nanofibrous membranes are promising for the fabrication of advanced skin substitutes. We fabricated electrospun polylactic acid and poly(lactide- co -glycolic acid) nanofibrous membranes and coated them with fibrin or collagen I. Fibronectin was attached to a fibrin or collagen nanocoating, in order further to enhance the cell adhesion and spreading. Fibrin regularly formed a coating around individual nanofibers in the membranes, and also formed a thin noncontinuous nanofibrous mesh on top of the membranes. Collagen also coated most of the fibers of the membrane and randomly created a soft gel on the membrane surface. Fibronectin predominantly adsorbed onto a thin fibrin mesh or a collagen gel, and formed a thin nanofibrous structure. Fibrin nanocoating greatly improved the attachment, spreading, and proliferation of human dermal fibroblasts, whereas collagen nanocoating had a positive influence on the behavior of human HaCaT keratinocytes. In addition, fibrin stimulated the fibroblasts to synthesize fibronectin and to deposit it as an extracellular matrix. Fibrin coating also showed a tendency to improve the ultimate tensile strength of the nanofibrous membranes. Fibronectin attached to fibrin or to a collagen coating further enhanced the adhesion, spreading, and proliferation of both cell types.

  5. Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner.

    Directory of Open Access Journals (Sweden)

    Arjun Seth

    Full Text Available Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH, poly (D,L-lactic-co-glycolic acid (PLGA and poly caprolactone (PCL nanoparticles (nps to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing. In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties.

  6. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  7. Photoaffinity labeling of the dopamine reuptake carrier protein with 3-azido 3H GBR-12935

    International Nuclear Information System (INIS)

    Berger, S.P.; Martenson, R.E.; Laing, P.; Thurkauf, A.; Decosta, B.; Rice, K.C.; Paul, S.M.

    1991-01-01

    A high affinity tritiated azido-diphenylpiperazine derivative, 3-azido 3 H GBR-12935, was synthesized as a potential photoaffinity probe of the dopamine transporter. Initially, the reversible binding of 3-azido 3 H GBR-12935 to crude synaptosomal membranes from the rat striatum was characterized. Specific binding was sodium dependent and inhibited by a variety of drugs that are known to potently inhibit dopamine uptake. Other neurotransmitter uptake inhibitors, as well as cis-flupenthixol, a potent inhibitor of 3 H GBR-12935 binding to piperazine binding sites, failed to inhibit specific binding at concentrations of less than or equal to 10 microM. A good correlation was observed between the relative potencies of these drugs in inhibiting dopamine uptake into synaptosomes and in inhibiting specific 3-azido 3 H GBR-12935 binding to rat striatal membranes. These data suggest that 3-azido 3 H GBR-12935, like other diphenylpiperazines such as 3 H GBR-12935 and 3 H GBR-12909, binds primarily to the dopamine transporter under defined assay conditions. After UV photolysis of crude synaptosomal membranes preincubated with 3-azido 3 H GBR-12935 (1-2 nM), a single radiolabeled polypeptide with an apparent molecular mass of 80 kDa was observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Photoincorporation of 3-azido 3 H GBR-12935 into this polypeptide was inhibited selectively by compounds that inhibit the uptake of dopamine and was completely dependent on the presence of Na+. No photolabeled proteins were observed when cerebellar membranes were substituted for striatal membranes. Essentially complete adsorption of the radiolabeled 80-kDa polypeptide to wheat germ agglutinin and elution with N-acetyl-D-glucosamine strongly suggest that the dopamine transporter polypeptide photolabeled by 3-azido 3 H GBR-12935 is glycosylated

  8. Solute carrier protein family 11 member 1 (Slc11a1) activation efficiently inhibits Leishmania donovani survival in host macrophages.

    Science.gov (United States)

    Singh, Nisha; Gedda, Mallikarjuna Rao; Tiwari, Neeraj; Singh, Suya P; Bajpai, Surabhi; Singh, Rakesh K

    2017-09-01

    Visceral leishmaniasis (kala-azar), a life threatening disease caused by L. donovani , is a latent threat to more than 147 million people living in disease endemic South East Asia region of the Indian subcontinent. The therapeutic option to control leishmanial infections are very limited, and at present comprise only two drugs, an antifungal amphotericin B and an antitumor miltefosine, which are also highly vulnerable for parasitic resistance. Therefore, identification and development of alternate control measures is an exigent requirement to control leishmanial infections. In this study, we report that functionally induced expression of solute carrier protein family 11 member 1 ( Slc11a1), a transmembrane divalent cationic transporter recruited on the surface of phagolysosomes after phagocytosis of parasites, effectively inhibits Leishmania donovani growth in host macrophages. Further, the increased Slc11a1 functionality also resulted in increased production of NOx, TNF-α and IL-12 by activated macrophages. The findings of this study signify the importance of interplay between Slc11a1 expression and macrophages activation that can be effectively used to control of Leishmania growth and survival.

  9. Defective Pollen Wall is Required for Anther and Microspore Development in Rice and Encodes a Fatty Acyl Carrier Protein Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Shi, J.; Shanklin, J.; Tan, H.; Yu, X.-H.; Liu, Y.; Liang, W.; Ranathunge, K.; Franke, R. B.; Schreiber, L.; Wang, Y.; Kai, G.; Ma, H.; Zhang, D.

    2011-06-01

    Aliphatic alcohols naturally exist in many organisms as important cellular components; however, their roles in extracellular polymer biosynthesis are poorly defined. We report here the isolation and characterization of a rice (Oryza sativa) male-sterile mutant, defective pollen wall (dpw), which displays defective anther development and degenerated pollen grains with an irregular exine. Chemical analysis revealed that dpw anthers had a dramatic reduction in cutin monomers and an altered composition of cuticular wax, as well as soluble fatty acids and alcohols. Using map-based cloning, we identified the DPW gene, which is expressed in both tapetal cells and microspores during anther development. Biochemical analysis of the recombinant DPW enzyme shows that it is a novel fatty acid reductase that produces 1-hexadecanol and exhibits >270-fold higher specificity for palmiltoyl-acyl carrier protein than for C16:0 CoA substrates. DPW was predominantly targeted to plastids mediated by its N-terminal transit peptide. Moreover, we demonstrate that the monocot DPW from rice complements the dicot Arabidopsis thaliana male sterile2 (ms2) mutant and is the probable ortholog of MS2. These data suggest that DPWs participate in a conserved step in primary fatty alcohol synthesis for anther cuticle and pollen sporopollenin biosynthesis in monocots and dicots.

  10. Modification of Triclosan Scaffold in Search of Improved Inhibitors for Enoyl-Acyl Carrier Protein (ACP) Reductase in Toxoplasma gondii

    Science.gov (United States)

    Stec, Jozef; Fomovska, Alina; Afanador, Gustavo A.; Muench, Stephen P.; Zhou, Ying; Lai, Bo-Shiun; Bissati, Kamal El; Hickman, Mark R.; Lee, Patty J.; Leed, Susan E.; Auschwitz, Jennifer M.; Sommervile, Caroline; Woods, Stuart; Roberts, Craig W.; Rice, David; Prigge, Sean T.; McLeod, Rima; Kozikowski, Alan P.

    2013-01-01

    Through our focused effort to discover new and effective agents against toxoplasmosis, a structure-based drug design approach was utilized to develop a series of potent inhibitors of the enoyl-acyl carrier protein (ACP) reductase (ENR) enzyme in Toxoplasma gondii (TgENR). Modifications to positions 5 and 4′ of the well-known ENR inhibitor triclosan afforded a series of 29 new analogs. Among the resulting compounds, many showed high potency and improved physicochemical properties in comparison with the lead. The most potent compounds 16a and 16c have IC50 values of 250 nM against Toxoplasma gondii tachyzoites without apparent toxicity to the host cells. Their IC50 values against the recombinant TgENR were 43 and 26 nM, respectively. Additionally, 11 other analogs in this series had IC50 values ranging from 17 to 130 nM in the enzyme-based assay. With respect to their excellent in vitro activity as well as improved drug-like properties, the lead compounds 16a and 16c are deemed to be an excellent starting point for the development of new medicines to effectively treat Toxoplasma gondii infections. PMID:23776166

  11. Inhibition of the Staphylococcus aureus NADPH-dependent enoyl-acyl carrier protein reductase by triclosan and hexachlorophene.

    Science.gov (United States)

    Heath, R J; Li, J; Roland, G E; Rock, C O

    2000-02-18

    Enoyl-acyl carrier protein reductase (FabI) plays a determinant role in completing cycles of elongation in type II fatty acid synthase systems and is an important target for antibacterial drugs. The FabI component of Staphylococcus aureus (saFabI) was identified, and its properties were compared with Escherichia coli FabI (ecFabI). ecFabI and saFabI had similar specific activities, and saFabI expression complemented the E. coli fabI(Ts) mutant, illustrating that the Gram-positive FabI was interchangeable with the Gram-negative FabI enzyme. However, ecFabI was specific for NADH, whereas saFabI exhibited specific and positive cooperative binding of NADPH. Triclosan and hexachlorophene inhibited both ecFabI and saFabI. The triclosan-resistant ecFabI(G93V) protein was also refractory to hexachlorophene inhibition, illustrating that both drugs bind at the FabI active site. Both the introduction of a plasmid expressing the safabI gene or a missense mutation in the chromosomal safabI gene led to triclosan resistance in S. aureus; however, these strains did not exhibit cross-resistance to hexachlorophene. The replacement of the ether linkage in triclosan by a carbon bridge in hexachlorophene prevented the formation of a stable FabI-NAD(P)(+)-drug ternary complex. Thus, the formation of this ternary complex is a key determinant of the antibacterial activity of FabI inhibitors.

  12. Bioinformatic evidence for a widely distributed, ribosomally produced electron carrier precursor, its maturation proteins, and its nicotinoprotein redox partners

    Directory of Open Access Journals (Sweden)

    Haft Daniel H

    2011-01-01

    as N,N-dimethyl-4-nitrosoaniline (NDMA for the enzyme to cycle. Conclusions Taken together, these findings suggest that the mycofactocin precursor is modified by the Rv0693 family rSAM protein and other enzymes in its cluster. It becomes an electron carrier molecule that serves in vivo as NDMA and other artificial electron acceptors do in vitro. Subclasses from three different nicotinoprotein families show "only-if" relationships to mycofactocin because they require its presence. This framework suggests a segregated redox pool in which mycofactocin mediates communication among enzymes with non-exchangeable cofactors.

  13. Crystal Structure of Epiphyas Postvittana Takeout 1 With Bound Ubiquinone Supports a Role As Ligand Carriers for Takeout Proteins in Insects

    Energy Technology Data Exchange (ETDEWEB)

    Hamiaux, C.; Stanley, D.; Greenwood, D.R.; Baker, E.N.; Newcomb, R.D.

    2009-05-19

    Takeout (To) proteins are found exclusively in insects and have been proposed to have important roles in various aspects of their physiology and behavior. Limited sequence similarity with juvenile hormone-binding proteins (JHBPs), which specifically bind and transport juvenile hormones in Lepidoptera, suggested a role for To proteins in binding hydrophobic ligands. We present the first crystal structure of a To protein, EpTo1 from the light brown apple moth Epiphyas postvittana, solved in-house by the single-wavelength anomalous diffraction technique using sulfur anomalous dispersion, and refined to 1.3 {angstrom} resolution. EpTo1 adopts the unusual {alpha}/{beta}-wrap fold, seen only for JHBP and several mammalian lipid carrier proteins, a scaffold tailored for the binding and/or transport of hydrophobic ligands. EpTo1 has a 45 {angstrom} long, purely hydrophobic, internal tunnel that extends for the full length of the protein and accommodates a bound ligand. The latter was shown by mass spectrometry to be ubiquinone-8 and is probably derived from Escherichia coli. The structure provides the first direct experimental evidence that To proteins are ligand carriers; gives insights into the nature of endogenous ligand(s) of EpTo1; shows, by comparison with JHBP, a basis for different ligand specificities; and suggests a mechanism for the binding/release of ligands.

  14. Purification, crystallization and preliminary X-ray diffraction analysis of enoyl-acyl carrier protein reductase (FabK) from Streptococcus mutans strain UA159

    International Nuclear Information System (INIS)

    Kim, Tae-O; Im, Dong-Won; Jung, Ha Yun; Kwon, Seong Jung; Heo, Yong-Seok

    2012-01-01

    Enoyl-acyl carrier protein reductase (FabK) from S. mutans strain UA159 was cloned, overexpressed, purified and crystallized. X-ray diffraction data were collected to a resolution of 2.40 Å. A triclosan-resistant flavoprotein termed FabK is the sole enoyl-acyl carrier protein reductase in Streptococcus pneumoniae and Streptococcus mutans. In this study, FabK from S. mutans strain UA159 was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 2.40 Å resolution using a synchrotron-radiation source. The crystal belonged to space group P6 2 , with unit-cell parameters a = b = 105.79, c = 44.15 Å. The asymmetric unit contained one molecule, with a corresponding V M of 2.05 Å 3 Da −1 and a solvent content of 39.9%

  15. Stearoyl-Acyl Carrier Protein Desaturase Mutations Uncover an Impact of Stearic Acid in Leaf and Nodule Structure.

    Science.gov (United States)

    Lakhssassi, Naoufal; Colantonio, Vincent; Flowers, Nicholas D; Zhou, Zhou; Henry, Jason; Liu, Shiming; Meksem, Khalid

    2017-07-01

    Stearoyl-acyl carrier protein desaturase (SACPD-C) has been reported to control the accumulation of seed stearic acid; however, no study has previously reported its involvement in leaf stearic acid content and impact on leaf structure and morphology. A subset of an ethyl methanesulfonate mutagenized population of soybean ( Glycine max ) 'Forrest' was screened to identify mutants within the GmSACPD-C gene. Using a forward genetics approach, one nonsense and four missense Gmsacpd-c mutants were identified to have high levels of seed, nodule, and leaf stearic acid content. Homology modeling and in silico analysis of the GmSACPD-C enzyme revealed that most of these mutations were localized near or at conserved residues essential for diiron ion coordination. Soybeans carrying Gmsacpd-c mutations at conserved residues showed the highest stearic acid content, and these mutations were found to have deleterious effects on nodule development and function. Interestingly, mutations at nonconserved residues show an increase in stearic acid content yet retain healthy nodules. Thus, random mutagenesis and mutational analysis allows for the achievement of high seed stearic acid content with no associated negative agronomic characteristics. Additionally, expression analysis demonstrates that nodule leghemoglobin transcripts were significantly more abundant in soybeans with deleterious mutations at conserved residues of GmSACPD-C. Finally, we report that Gmsacpd-c mutations cause an increase in leaf stearic acid content and an alteration of leaf structure and morphology in addition to differences in nitrogen-fixing nodule structure. © 2017 American Society of Plant Biologists. All Rights Reserved.

  16. Functional characterization of triclosan-resistant enoyl-acyl-carrier protein reductase (FabV in Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Yong-Heng Huang

    2016-11-01

    Full Text Available Pseudomonas aeruginosa is extremely resistant to triclosan. Previous studies have shown that P. aeruginosa encodes a triclosan-resistant enoyl-acyl-carrier protein reductase (ENR, FabV, and that deletion of fabV causes P. aeruginosa to be extremely sensitive to triclosan. In this report, we complemented a P. aeruginosa fabV deletion strain with several triclosan-resistant ENR encoding genes, including Vibrio cholera fabV, Bacillus subtilis fabL and Enterococcus faecalis fabK. All complemented strains restored triclosan resistance to the level of the wild-type strain, which confirmed that triclosan-resistant ENR allows P. aeruginosa to be extremely resistant to triclosan. Moreover, fabV exhibits pleiotropic effects. Deletion of fabV led P. aeruginosa to show attenuated swarming motility, decreased rhamnolipid, pyoverdine and acylhomoserine lactones (AHLs production. Complementation of the fabV mutant with any one ENR encoding gene could restore these features to some extent, in comparison with the wild-type strain. Furthermore, we found that addition of exogenous AHLs could restore to the fabV mutant strain the ability to swarm on semisolid plates and to produce more virulence factors than the fabV mutant strain. These findings indicate that deletion of fabV reduced the activity of ENR in P. aeruginosa, decreased fatty acid synthesis, and subsequently depressed the production of AHLs and other virulence factors, which finally may led to a reduction in the pathogenicity of P. aeruginosa. Therefore, fabV should be an ideal target for the control of P. aeruginosa infectivity.

  17. Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents

    Energy Technology Data Exchange (ETDEWEB)

    Muench, Stephen P. [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom); Prigge, Sean T. [Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); McLeod, Rima [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Rafferty, John B. [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom); Kirisits, Michael J. [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Roberts, Craig W. [Department of Immunology, University of Strathclyde, Glasgow G4 0NR, Scotland (United Kingdom); Mui, Ernest J. [Department of Ophthalmology and Visual Sciences, Paediatrics (Infectious Diseases) and Pathology and the Committees on Molecular Medicine, Genetics, Immunology and The College, The University of Chicago, Chicago, IL 60637 (United States); Rice, David W., E-mail: d.rice@sheffield.ac.uk [The Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN (United Kingdom)

    2007-03-01

    The crystal structures of T. gondii and P. falciparum ENR in complex with NAD{sup +} and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD{sup +} and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR–triclosan complex reveals the folding of a hydrophilic insert common to the apicomplexan family that flanks the substrate-binding domain and is disordered in all other reported apicomplexan ENR structures. Structural comparison of the apicomplexan ENR structures with their bacterial and plant counterparts has revealed that although the active sites of the parasite enzymes are broadly similar to those of their bacterial counterparts, there are a number of important differences within the drug-binding pocket that reduce the packing interactions formed with several inhibitors in the apicomplexan ENR enzymes. Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials.

  18. Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents

    International Nuclear Information System (INIS)

    Muench, Stephen P.; Prigge, Sean T.; McLeod, Rima; Rafferty, John B.; Kirisits, Michael J.; Roberts, Craig W.; Mui, Ernest J.; Rice, David W.

    2007-01-01

    The crystal structures of T. gondii and P. falciparum ENR in complex with NAD + and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD + and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 Å, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR–triclosan complex reveals the folding of a hydrophilic insert common to the apicomplexan family that flanks the substrate-binding domain and is disordered in all other reported apicomplexan ENR structures. Structural comparison of the apicomplexan ENR structures with their bacterial and plant counterparts has revealed that although the active sites of the parasite enzymes are broadly similar to those of their bacterial counterparts, there are a number of important differences within the drug-binding pocket that reduce the packing interactions formed with several inhibitors in the apicomplexan ENR enzymes. Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials

  19. Characterization of a stearoyl-acyl carrier protein desaturase gene family from chocolate tree, Theobroma cacao L.

    Science.gov (United States)

    Zhang, Yufan; Maximova, Siela N; Guiltinan, Mark J

    2015-01-01

    In plants, the conversion of stearoyl-ACP to oleoyol-ACP is catalyzed by a plastid-localized soluble stearoyl-acyl carrier protein (ACP) desaturase (SAD). The activity of SAD significantly impacts the ratio of saturated and unsaturated fatty acids, and is thus a major determinant of fatty acid composition. The cacao genome contains eight putative SAD isoforms with high amino acid sequence similarities and functional domain conservation with SAD genes from other species. Sequence variation in known functional domains between different SAD family members suggested that these eight SAD isoforms might have distinct functions in plant development, a hypothesis supported by their diverse expression patterns in various cacao tissues. Notably, TcSAD1 is universally expressed across all the tissues, and its expression pattern in seeds is highly correlated with the dramatic change in fatty acid composition during seed maturation. Interestingly, TcSAD3 and TcSAD4 appear to be exclusively and highly expressed in flowers, functions of which remain unknown. To test the function of TcSAD1 in vivo, transgenic complementation of the Arabidopsis ssi2 mutant was performed, demonstrating that TcSAD1 successfully rescued all AtSSI2 related phenotypes further supporting the functional orthology between these two genes. The identification of the major SAD gene responsible for cocoa butter biosynthesis provides new strategies for screening for novel genotypes with desirable fatty acid compositions, and for use in breeding programs to help pyramid genes for quality and other traits such as disease resistance.

  20. Characterization of a stearoyl-acyl carrier protein desaturase gene family from chocolate tree, Theobroma cacao L

    Science.gov (United States)

    Zhang, Yufan; Maximova, Siela N.; Guiltinan, Mark J.

    2015-01-01

    In plants, the conversion of stearoyl-ACP to oleoyol-ACP is catalyzed by a plastid-localized soluble stearoyl-acyl carrier protein (ACP) desaturase (SAD). The activity of SAD significantly impacts the ratio of saturated and unsaturated fatty acids, and is thus a major determinant of fatty acid composition. The cacao genome contains eight putative SAD isoforms with high amino acid sequence similarities and functional domain conservation with SAD genes from other species. Sequence variation in known functional domains between different SAD family members suggested that these eight SAD isoforms might have distinct functions in plant development, a hypothesis supported by their diverse expression patterns in various cacao tissues. Notably, TcSAD1 is universally expressed across all the tissues, and its expression pattern in seeds is highly correlated with the dramatic change in fatty acid composition during seed maturation. Interestingly, TcSAD3 and TcSAD4 appear to be exclusively and highly expressed in flowers, functions of which remain unknown. To test the function of TcSAD1 in vivo, transgenic complementation of the Arabidopsis ssi2 mutant was performed, demonstrating that TcSAD1 successfully rescued all AtSSI2 related phenotypes further supporting the functional orthology between these two genes. The identification of the major SAD gene responsible for cocoa butter biosynthesis provides new strategies for screening for novel genotypes with desirable fatty acid compositions, and for use in breeding programs to help pyramid genes for quality and other traits such as disease resistance. PMID:25926841

  1. Triclosan Resistance of Pseudomonas aeruginosa PAO1 Is Due to FabV, a Triclosan-Resistant Enoyl-Acyl Carrier Protein Reductase ▿

    OpenAIRE

    Zhu, Lei; Lin, Jinshui; Ma, Jincheng; Cronan, John E.; Wang, Haihong

    2009-01-01

    Triclosan, a very widely used biocide, specifically inhibits fatty acid synthesis by inhibition of enoyl-acyl carrier protein (ACP) reductase. Escherichia coli FabI is the prototypical triclosan-sensitive enoyl-ACP reductase, and E. coli is extremely sensitive to the biocide. However, other bacteria are resistant to triclosan, because they encode triclosan-resistant enoyl-ACP reductase isozymes. In contrast, the triclosan resistance of Pseudomonas aeruginosa PAO1 has been attributed to active...

  2. Dissecting the Structural Elements for the Activation of β-Ketoacyl-(Acyl Carrier Protein) Reductase from Vibrio cholerae.

    Science.gov (United States)

    Hou, Jing; Zheng, Heping; Chruszcz, Maksymilian; Zimmerman, Matthew D; Shumilin, Igor A; Osinski, Tomasz; Demas, Matt; Grimshaw, Sarah; Minor, Wladek

    2016-02-01

    β-Ketoacyl-(acyl carrier protein) reductase (FabG) catalyzes the key reductive reaction in the elongation cycle of fatty acid synthesis (FAS), which is a vital metabolic pathway in bacteria and a promising target for new antibiotic development. The activation of the enzyme is usually linked to the formation of a catalytic triad and cofactor binding, and crystal structures of FabG from different organisms have been captured in either the active or inactive conformation. However, the structural elements which enable activation of FabG require further exploration. Here we report the findings of structural, enzymatic, and binding studies of the FabG protein found in the causative agent of cholera, Vibrio cholerae (vcFabG). vcFabG exists predominantly as a dimer in solution and is able to self-associate to form tetramers, which is the state seen in the crystal structure. The formation of the tetramer may be promoted by the presence of the cofactor NADP(H). The transition between the dimeric and tetrameric states of vcFabG is related to changes in the conformations of the α4/α5 helices on the dimer-dimer interface. Two glycine residues adjacent to the dimer interface (G92 and G141) are identified to be the hinge for the conformational changes, while the catalytic tyrosine (Y155) and a glutamine residue that forms hydrogen bonds to both loop β4-α4 and loop β5-α5 (Q152) stabilize the active conformation. The functions of the aforementioned residues were confirmed by binding and enzymatic assays for the corresponding mutants. This paper describes the results of structural, enzymatic, and binding studies of FabG from Vibrio cholerae (vcFabG). In this work, we dissected the structural elements responsible for the activation of vcFabG. The structural information provided here is essential for the development of antibiotics specifically targeting bacterial FabG, especially for the multidrug-resistant strains of V. cholerae. Copyright © 2016, American Society for

  3. Radionuclide carriers

    International Nuclear Information System (INIS)

    Hartman, F.A.; Kretschmar, H.C.; Tofe, A.J.

    1977-01-01

    The invention provides physiologically acceptable particulate radionuclide carriers comprising a reducing agent bound to an anionic starch derivative, useful in the preparation of organ-specific diagnostic radiopharmaceuticals

  4. High-resolution structures of Thermus thermophilus enoyl-acyl carrier protein reductase in the apo form, in complex with NAD+ and in complex with NAD+ and triclosan

    International Nuclear Information System (INIS)

    Otero, José M.; Noël, Ann-Josée; Guardado-Calvo, Pablo; Llamas-Saiz, Antonio L.; Wende, Wolfgang; Schierling, Benno; Pingoud, Alfred; Raaij, Mark J. van

    2012-01-01

    T. thermophilus enoyl-acyl carrier protein reductase was crystallized in the apo form, with NAD + bound and with NAD + and the inhibitor triclosan bound. The structures were solved by molecular replacement and refined at 1.50, 1.86 and 1.90 Å resolution, respectively. The structures are described, analysed and compared with those of enoyl-acyl carrier protein reductases from other species. Enoyl-acyl carrier protein reductase (ENR; the product of the fabI gene) is an important enzyme that is involved in the type II fatty-acid-synthesis pathway of bacteria, plants, apicomplexan protozoa and mitochondria. Harmful pathogens such as Mycobacterium tuberculosis and Plasmodium falciparum use the type II fatty-acid-synthesis system, but not mammals or fungi, which contain a type I fatty-acid-synthesis pathway consisting of one or two multifunctional enzymes. For this reason, specific inhibitors of ENR are attractive antibiotic candidates. Triclosan, a broad-range antibacterial agent, binds to ENR, inhibiting fatty-acid synthesis. As humans do not have an ENR enzyme, they are not affected. Here, high-resolution structures of Thermus thermophilus (Tth) ENR in the apo form, bound to NAD + and bound to NAD + plus triclosan are reported. Differences from and similarities to other known ENR structures are reported; in general, the structures are very similar. The cofactor-binding site is also very similar to those of other ENRs and, as reported for other species, triclosan leads to greater ordering of the loop that covers the cofactor-binding site, which, together with the presence of triclosan itself, presumably provides tight binding of the dinucleotide, preventing cycling of the cofactor. Differences between the structures of Tth ENR and other ENRs are the presence of an additional β-sheet at the N-terminus and a larger number of salt bridges and side-chain hydrogen bonds. These features may be related to the high thermal stability of Tth ENR

  5. Radionuclide carriers

    International Nuclear Information System (INIS)

    Hartman, F.A.; Kretschmar, H.C.

    1976-01-01

    A new carrier for radionuclide technetium 99m has been prepared for scintiscanning purposes. The new preparate consists of physiologically acceptable water-insoluble Tcsup(99m)-carrier containing from 0.2 to 0.8 weight percent of stannic ion as reductor, bound to an anionic starch derivative with about 1-20% of phosphate substituents. (EG)

  6. Expression of Potato virus A (PVA) coat protein in Escherichia coli and possibility of its use as foreign antigen carrier

    Czech Academy of Sciences Publication Activity Database

    Čeřovská, Noemi; Moravec, Tomáš; Velemínský, Jiří

    2001-01-01

    Roč. 268, č. 1 (2001), s. 214 ISSN 0014-2956 R&D Projects: GA ČR GA522/01/1121; GA ČR GA310/00/0381 Institutional research plan: CEZ:AV0Z5038910 Keywords : Potato virus A ( PVA ) * Escherichia coli * antigen carrier Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.849, year: 2001

  7. Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway.

    Science.gov (United States)

    Gutiérrez-Martínez, Enric; Fernández-Ulibarri, Inés; Lázaro-Diéguez, Francisco; Johannes, Ludger; Pyne, Susan; Sarri, Elisabet; Egea, Gustavo

    2013-06-15

    The inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane.

  8. Poly(D,L-lactide-co-glycolide) Nanoparticle Agglomerates as Carriers in Dry Powder Aerosol Formulation of Proteins

    Science.gov (United States)

    Peek, Laura J.; Roberts, Lydia; Berkland, Cory

    2013-01-01

    A dry powder aerosol drug delivery system was designed with both nano- and microstructure to maximize the protein loading via surface adsorption and to facilitate delivery to the deep lung, respectively. Ovalbumin was employed as a model protein to adsorb to and controllably flocculate DOTAP-coated PLG nanoparticles into “nanoclusters” possessing low density microstructure. The mechanism of nanoparticle flocculation was probed by evaluating the effects of ionic strength, shear force, and protein concentration on the geometric and aerodynamic diameters of the nanoclusters as well as the protein adsorption efficiency. Salt ions were found to compete with ovalbumin adsorption to nanoparticles and facilitate flocculation; therefore, formulation of nanoclusters for inhaled drug delivery may require the lowest possible ionic strength to maximize protein adsorption. Additional factors, such as shear force and total protein–particle concentration can be altered to optimize nanocluster size, suggesting the possibility of regional lung delivery. Immediate release of ovalbumin was observed, and native protein structure upon release was confirmed by circular dichroism and fluorescence spectroscopy studies. Controlled flocculation of nanoparticles may provide a useful alternative to spray drying when formulating dry powders for pulmonary or nasal administration of protein therapeutics or antigens. PMID:18680321

  9. Solute carrier transporters: Pharmacogenomics research ...

    African Journals Online (AJOL)

    Aghogho

    2010-12-27

    -binding cassette) transporters, which include MDR1, a protein that pumps xenobiotics from cells, and the SLC (solute carrier) trans- porters, which take up neurotransmitters, nutrients, heavy metals, and other substrates into ...

  10. Aircraft Carriers

    DEFF Research Database (Denmark)

    Nødskov, Kim; Kværnø, Ole

    as their purchases of aircraft carrier systems, makes it more than likely that the country is preparing such an acquisition. China has territorial disputes in the South China Sea over the Spratly Islands and is also worried about the security of its sea lines of communications, by which China transports the majority...... of its foreign trade, as well as its oil imports, upon which the country is totally dependent. China therefore has good reasons for acquiring an aircraft carrier to enable it to protect its national interests. An aircraft carrier would also be a prominent symbol of China’s future status as a great power......, then the country will also acquire the capability to project military power into the region beyond Taiwan, which it does not possess today. In this way, China will have the military capability to permit a change of strategy from the mainly defensive, mainland, Taiwan-based strategy to a more assertive strategy...

  11. Crystallization and preliminary X-ray crystallographic studies of enoyl-acyl carrier protein reductase (FabI) from Psuedomonas aeruginosa

    International Nuclear Information System (INIS)

    Lee, Jeong Hye; Park, Ae Kyung; Chi, Young Min; Moon, Jin Ho; Lee, Ki Seog

    2011-01-01

    Enoyl-acyl carrier protein reductase (FabI) from P. aeruginosa was purified and crystallized. FabI was also cocrystallized with the inhibitor triclosan and the cofactor NADH. Crystals of native and complexed FabI diffracted to resolutions of 2.6 and 1.8 Å, respectively. During fatty-acid biosynthesis, enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the reduction of trans-2-enoyl-ACP to fully saturated acyl-ACP via the ubiquitous fatty-acid synthase system. NADH-dependent enoyl-ACP reductase (FabI) from Pseudomonas aeruginosa has been purified and crystallized as an apoenzyme and in a complex form with NADH and triclosan. Triclosan is an inhibitor of FabI and forms a stable ternary complex in the presence of NADH. The crystals of native and complexed FabI diffracted to resolutions of 2.6 and 1.8 Å, respectively. The crystals both belonged to space group P2 1 , with unit-cell parameters a = 117.32, b = 155.844, c = 129.448 Å, β = 111.061° for the native enzyme and a = 64.784, b = 107.573, c = 73.517 Å, β = 116.162° for the complex. Preliminary molecular replacement further confirmed the presence of four tetramers of native FabI and one tetramer of the complex in the asymmetric unit, corresponding to Matthews coefficients (V M ) of 2.46 and 2.05 Å 3 Da −1 and solvent contents of 50.1 and 40.1%, respectively

  12. Functional and in vitro gastric digestibility of the whey protein hydrogel loaded with nanostructured lipid carriers and gelled via citric acid-mediated crosslinking.

    Science.gov (United States)

    Hashemi, Behnaz; Madadlou, Ashkan; Salami, Maryam

    2017-12-15

    Nanostructured lipid carriers (NLCs) with mean size of 347nm were fabricated and added into a heat-denatured whey protein solution. The subsequent crosslinking of proteins by citric acid or CaCl 2 resulted in the formation of cold-set hydrogels. Fourier transform infrared spectroscopy (FTIR) proposed formation of more hydrogen bonds in gel due to NLC loading or citric acid-mediated gelation. It was also found based on FITR spectroscopy that citric acid crosslinking disordered whey proteins. Scanning electron microscopy (SEM) imaging showed a non-porous and finely meshed microstructure for the crosslinked gels compared to non-crosslinked counterparts. Crosslinking also increased the firmness and water-holding capacity of gels. In pepsin-free fluid, a strong correlation existed between reduction in gel swellability and digestibility over periods up to 60min due to NLC loading and citric acid gelation. However, in peptic fluid, NLC loading and citric acid crosslinking brought about much higher decrease in digestibility than swellability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. The role of ß-ketoacyl-acyl carrier protein synthase III in the condensation steps of fatty acid biosynthesis in sunflower

    DEFF Research Database (Denmark)

    González-Mellado, Damián; von Wettstein, Penny; Garcés, Rafael

    2010-01-01

    seeds, a cDNA coding for HaKAS III (EF514400) was isolated, cloned and sequenced. Its protein sequence is as much as 72% identical to other KAS III-like ones such as those from Perilla frutescens, Jatropha curcas, Ricinus communis or Cuphea hookeriana. Phylogenetic study of the HaKAS III homologous......The ß-ketoacyl-acyl carrier protein synthase III (KAS III; EC 2.3.1.180) is a condensing enzyme catalyzing the initial step of fatty acid biosynthesis using acetyl-CoA as primer. To determine the mechanisms involved in the biosynthesis of fatty acids in sunflower (Helianthus annuus L.) developing...... proteins infers its origin from cyanobacterial ancestors. A genomic DNA gel blot analysis revealed that HaKAS III is a single copy gene. Expression levels of this gene, examined by Q-PCR, revealed higher levels in developing seeds storing oil than in leaves, stems, roots or seedling cotyledons...

  14. Solution structure of the tandem acyl carrier protein domains from a polyunsaturated fatty acid synthase reveals beads-on-a-string configuration.

    Directory of Open Access Journals (Sweden)

    Uldaeliz Trujillo

    Full Text Available The polyunsaturated fatty acid (PUFA synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect and in structural stabilization of the multidomain protein (synergistic effect. While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of

  15. Solution Structure of the Tandem Acyl Carrier Protein Domains from a Polyunsaturated Fatty Acid Synthase Reveals Beads-on-a-String Configuration

    KAUST Repository

    Trujillo, Uldaeliz

    2013-02-28

    The polyunsaturated fatty acid (PUFA) synthases from deep-sea bacteria invariably contain multiple acyl carrier protein (ACP) domains in tandem. This conserved tandem arrangement has been implicated in both amplification of fatty acid production (additive effect) and in structural stabilization of the multidomain protein (synergistic effect). While the more accepted model is one in which domains act independently, recent reports suggest that ACP domains may form higher oligomers. Elucidating the three-dimensional structure of tandem arrangements may therefore give important insights into the functional relevance of these structures, and hence guide bioengineering strategies. In an effort to elucidate the three-dimensional structure of tandem repeats from deep-sea anaerobic bacteria, we have expressed and purified a fragment consisting of five tandem ACP domains from the PUFA synthase from Photobacterium profundum. Analysis of the tandem ACP fragment by analytical gel filtration chromatography showed a retention time suggestive of a multimeric protein. However, small angle X-ray scattering (SAXS) revealed that the multi-ACP fragment is an elongated monomer which does not form a globular unit. Stokes radii calculated from atomic monomeric SAXS models were comparable to those measured by analytical gel filtration chromatography, showing that in the gel filtration experiment, the molecular weight was overestimated due to the elongated protein shape. Thermal denaturation monitored by circular dichroism showed that unfolding of the tandem construct was not cooperative, and that the tandem arrangement did not stabilize the protein. Taken together, these data are consistent with an elongated beads-on-a-string arrangement of the tandem ACP domains in PUFA synthases, and speak against synergistic biocatalytic effects promoted by quaternary structuring. Thus, it is possible to envision bioengineering strategies which simply involve the artificial linking of multiple ACP

  16. Disposable Amperometric Immunosensor for the Determination of Human P53 Protein in Cell Lysates Using Magnetic Micro-Carriers

    Directory of Open Access Journals (Sweden)

    María Pedrero

    2016-11-01

    Full Text Available An amperometric magnetoimmunosensor for the determination of human p53 protein is described in this work using a sandwich configuration involving the covalent immobilization of a specific capture antibody onto activated carboxylic-modified magnetic beads (HOOC-MBs and incubation of the modified MBs with a mixture of the target protein and horseradish peroxidase-labeled antibody (HRP-anti-p53. The resulting modified MBs are captured by a magnet placed under the surface of a disposable carbon screen-printed electrode (SPCE and the amperometric responses are measured at −0.20 V (vs. an Ag pseudo-reference electrode, upon addition of hydroquinone (HQ as a redox mediator and H2O2 as the enzyme substrate. The magnetoimmunosensing platform was successfully applied for the detection of p53 protein in different cell lysates without any matrix effect after a simple sample dilution. The results correlated accurately with those provided by a commercial ELISA kit, thus confirming the immunosensor as an attractive alternative for rapid and simple determination of this protein using portable and affordable instrumentation.

  17. Non-viral bone morphogenetic protein 2 transfection of rat dental pulp stem cells using calcium phosphate nanoparticles as carriers.

    NARCIS (Netherlands)

    Yang, X.; Walboomers, X.F.; Dolder, J. van den; Yang, F.; Bian, Z.; Fan, M.; Jansen, J.A.

    2008-01-01

    Calcium phosphate nanoparticles have shown potential as non-viral vectors for gene delivery. The aim of this study was to induce bone morphogenetic protein (Bmp)2 transfection in rat dental pulp stem cells using calcium phosphate nanoparticles as a gene vector and then to evaluate the efficiency and

  18. Potentials and limitations of the low-molecular-weight protein lysozyme as a carrier for renal drug targeting

    NARCIS (Netherlands)

    Haverdings, RFG; Haas, M; Greupink, AR; de Vries, PAM; Moolenaar, F; de Zeeuw, D; Meijer, DKF

    2001-01-01

    Selective targeting of drugs to the kidney may enable an increased renal effectiveness combined with a reduction of extrarenal toxicity. Intrarenal delivery to the proximal tubular cell can be achieved using low-molecular-weight proteins, such as lysozyme. Administration of high dosages of lysozyme,

  19. Effect of dabigatran on a prothrombinase-based assay for detecting activated protein C resistance: an ex vivo and in vitro study in normal subjects and factor V Leiden carriers.

    Science.gov (United States)

    Gessoni, Gianluca; Valverde, Sara; Valle, Letizia; Caruso, Pierpaolo; Gessoni, Francesca; Valle, Roberto

    2017-10-01

    The aim of this study was to evaluate ex vivo and in vitro interference of a direct factor IIa inhibitor, dabigatran, on a prothrombinase-based assay to detect activated protein C resistance. An ex vivo study was performed in six heterozygous factor V Leiden carriers and 12 normal subjects without the factor V Leiden mutation who were treated with dabigatran. An in vitro study was also performed considering 12 plasma samples (six from normal subjects and six from heterozygous factor V Leiden carriers) spiked with dabigatran. The dabigatran concentration was evaluated using a diluted thrombin time assay, activated protein C resistance was evaluated using a prothrombinase-based assay. In both the ex vivo and in vitro studies dabigatran interfered significantly with activated protein C resistance ratios observed in normal subjects and in factor V Leiden heterozygous carriers. The results reported in this paper seem to confirm that dabigatran is able to interfere with the Penthafarm prothrombinase-based assay used to study activated protein C resistance, significantly increasing observed ratios. This effect appears to be present already at low concentrations of dabigatran (6 ng/mL) and affects both normal subjects and heterozygous carriers of factor V Leiden. In this group of patients, dabigatran, at concentrations in the therapeutic range (100-200 ng/mL), could markedly increase the activated protein C resistance ratio, bringing it up to within the reference range for normal subjects, thus potentially leading to misclassification of patients.

  20. Molecular engineering of proteins with predefined function. Part I: Design of a hemoglobin-based oxygen carrier.

    Science.gov (United States)

    Sivan, Sarit; Lotan, Noah

    2003-03-01

    Molecular engineering refers to a collection of complex, computer-based methods used to study molecular structures and properties. These methods include ones for determining properties as well as for accessing prior knowledge about them. Applying these methods, one can generate, manipulate and calculate the energy involved with the three-dimensional conformation of a given molecule. These computational tools were utilized in this study, to design cross-linking reagents for cell-free Hb, for the purpose of O(2)-carriers development. Hb, when removed from the red blood cell, misses some of its functional characteristics required. Yet, these characteristics can be rebuilt into the Hb molecule by appropriate chemical modifications. These modifications have been devised to prevent dimer formation, increase the retention time in circulation, and decrease the high oxygen affinity of free Hb. The reagent reported in this study, namely, oxidized-NAD (o-NAD), has been designed to fulfill both criteria of retention time and oxygen affinity, in a single package. Feasibility of the cross-linking reaction of o-NAD with Hb was assessed by studying the docking process of o-NAD within the 2,3-DPG pocket of Hb. In this study, we provide an insight into how the overall factors involved with the potential energy calculations contribute to the hydrogen bonding network, formed within the complex. Conformational search analysis has shown a high proximity, of functional moieties on the Hb molecule, to reactive groups on the o-NAD molecule suggested. This is an important step in the design and later synthesis of O(2)-carrying materials to be used as blood substitutes.

  1. Expression of scFv-Mel-Gal4 triple fusion protein as a targeted DNA-carrier in Escherichia Coli.

    Science.gov (United States)

    Wang, Weiyu; Luo, Jian; Xu, Lining; Zeng, Jianping; Cao, Limin; Dong, Jiahong; Cai, Shouwang

    2013-12-01

    Liver-directed gene therapy has become a promising treatment for many liver diseases. In this study, we constructed a multi-functional targeting molecule, which maintains targeting, endosome-escaping, and DNA-binding abilities for gene delivery. Two single oligonucleotide chains of Melittin (M) were synthesized. The full-length cDNA encoding anti-hepatic asialoglycoprotein receptor scFv C1 (C1) was purified from C1/pIT2. The GAL4 (G) gene was amplified from pSW50-Gal4 by polymerase chain reaction. M, C1 and G were inserted into plasmid pGC4C26H to product the recombinant plasmid pGC-C1MG. The fused gene C1MG was subsequently subcloned into plasmid pET32c to product the recombinant plasmid C1MG/pET32c and expressed in Escherichia coli BL21. The scFv-Mel-Gal4 triple fusion protein (C1MG) was purified with a Ni(2+) chelating HiTrap HP column. The fusion protein C1MG of roughly 64 kD was expressed in inclusion bodies; 4.5 mg/ml C1MG was prepared with Ni(2+) column purification. Western blot and immunohistochemistry showed the antigen-binding ability of C1MG to the cell surface of the liver-derived cell line and liver tissue slices. Hemolysis testing showed that C1MG maintained membrane-disrupting activity. DNA-binding capacity was substantiated by luciferase assay, suggesting that C1MG could deliver the DNA into cells efficiently on the basis of C1MG. Successful expression of C1MG was achieved in E. coli, and C1MG recombinant protein confers targeting, endosome-escaping and DNA-binding capacity, which makes it probable to further study its liver-specific DNA delivery efficacy in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

  2. Non-viral bone morphogenetic protein 2 transfection of rat dental pulp stem cells using calcium phosphate nanoparticles as carriers.

    Science.gov (United States)

    Yang, Xuechao; Walboomers, X Frank; van den Dolder, Juliette; Yang, Fang; Bian, Zhuan; Fan, Mingwen; Jansen, John A

    2008-01-01

    Calcium phosphate nanoparticles have shown potential as non-viral vectors for gene delivery. The aim of this study was to induce bone morphogenetic protein (Bmp)2 transfection in rat dental pulp stem cells using calcium phosphate nanoparticles as a gene vector and then to evaluate the efficiency and bioactivity of the transfection. We also intended to investigate the behavior of transfected cells when seeded on 3-dimensional titanium fiber mesh scaffolds. Nanoparticles of calcium phosphate encapsulating plasmid deoxyribonucleic acid (DNA) (plasmid enhanced green fluorescent protein-BMP2) were prepared. Then, STRO-1-selected rat dental pulp stem cells were transfected using these nanoparticles. Transfection and bioactivity of the secreted BMP2 were examined. Thereafter, the transfected cells were cultured on a fibrous titanium mesh. The cultures were investigated using scanning electron microscipy and evaluated for cell proliferation, alkaline phosphatase activity and calcium content. Finally, real-time polymerase chain reaction was performed for odontogenesis-related gene expression. The results showed that the size of the DNA-loaded particles was approximately 100 nm in diameter. Nanoparticles could protect the DNA encapsulated inside from external DNase and release the loaded DNA in a low-acid environment (pH 3.0). In vitro, nanoparticle transfection was shown to be effective and to accelerate or promote the odontogenic differentiation of rat dental pulp stem cells when cultured in the 3-dimensional scaffolds. Based on our results, plasmid DNA-loaded calcium phosphate nanoparticles appear to be an effective non-viral vector for gene delivery and functioned well for odontogenic differentiation through Bmp2 transfection.

  3. Characterization of SLCO5A1/OATP5A1, a solute carrier transport protein with non-classical function.

    Directory of Open Access Journals (Sweden)

    Katrin Sebastian

    Full Text Available Organic anion transporting polypeptides (OATP/SLCO have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20 and genes implicated in developmental processes (e.g. TGM2. A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration.

  4. Acyl carrier proteins from sunflower (Helianthus annuus L.) seeds and their influence on FatA and FatB acyl-ACP thioesterase activities.

    Science.gov (United States)

    Aznar-Moreno, Jose A; Venegas-Calerón, Mónica; Martínez-Force, Enrique; Garcés, Rafael; Salas, Joaquín J

    2016-08-01

    The kinetics of acyl-ACP thioesterases from sunflower importantly changed when endogenous ACPs were used. Sunflower FatB was much more specific towards saturated acyl-ACPs when assayed with them. Acyl carrier proteins (ACPs) are small (~9 kDa), soluble, acidic proteins involved in fatty acid synthesis in plants and bacteria. ACPs bind to fatty acids through a thioester bond, generating the acyl-ACP lipoproteins that are substrates for fatty acid synthase (FAS) complexes, and that are required for fatty acid chain elongation, acting as important intermediates in de novo fatty acid synthesis in plants. Plants, usually express several ACP isoforms with distinct functionalities. We report here the cloning of three ACPs from developing sunflower seeds: HaACP1, HaACP2, and HaACP3. These proteins were plastidial ACPs expressed strongly in seeds, and as such they are probably involved in the synthesis of sunflower oil. The recombinant sunflower ACPs were expressed in bacteria but they were lethal to the prokaryote host. Thus, they were finally produced using the GST gene fusion system, which allowed the apo-enzyme to be produced and later activated to the holo form. Radiolabelled acyl-ACPs from the newly cloned holo-ACP forms were also synthesized and used to characterize the activity of recombinant sunflower FatA and FatB thioesterases, important enzymes in plant fatty acids synthesis. The activity of these enzymes changed significantly when the endogenous ACPs were used. Thus, FatA importantly increased its activity levels, whereas FatB displayed a different specificity profile, with much high activity levels towards saturated acyl-CoA derivatives. All these data pointed to an important influence of the ACP moieties on the activity of enzymes involved in lipid synthesis.

  5. Perturbed rhythmic activation of signaling pathways in mice deficient for Sterol Carrier Protein 2-dependent diurnal lipid transport and metabolism.

    Science.gov (United States)

    Jouffe, Céline; Gobet, Cédric; Martin, Eva; Métairon, Sylviane; Morin-Rivron, Delphine; Masoodi, Mojgan; Gachon, Frédéric

    2016-04-21

    Through evolution, most of the living species have acquired a time keeping system to anticipate daily changes caused by the rotation of the Earth. In all of the systems this pacemaker is based on a molecular transcriptional/translational negative feedback loop able to generate rhythmic gene expression with a period close to 24 hours. Recent evidences suggest that post-transcriptional regulations activated mostly by systemic cues play a fundamental role in the process, fine tuning the time keeping system and linking it to animal physiology. Among these signals, we consider the role of lipid transport and metabolism regulated by SCP2. Mice harboring a deletion of the Scp2 locus present a modulated diurnal accumulation of lipids in the liver and a perturbed activation of several signaling pathways including PPARα, SREBP, LRH-1, TORC1 and its upstream regulators. This defect in signaling pathways activation feedbacks upon the clock by lengthening the circadian period of animals through post-translational regulation of core clock regulators, showing that rhythmic lipid transport is a major player in the establishment of rhythmic mRNA and protein expression landscape.

  6. Biomimetic coating of organic polymers with a protein-functionalized layer of calcium phosphate: the surface properties of the carrier influence neither the coating characteristics nor the incorporation mechanism or release kinetics of the protein.

    Science.gov (United States)

    Wu, Gang; Liu, Yuelian; Iizuka, Tateyuki; Hunziker, Ernst B

    2010-12-01

    Polymers that are used in clinical practice as bone-defect-filling materials possess many essential qualities, such as moldability, mechanical strength and biodegradability, but they are neither osteoconductive nor osteoinductive. Osteoconductivity can be conferred by coating the material with a layer of calcium phosphate, which can be rendered osteoinductive by functionalizing it with an osteogenic agent. We wished to ascertain whether the morphological and physicochemical characteristics of unfunctionalized and bovine-serum-albumin (BSA)-functionalized calcium-phosphate coatings were influenced by the surface properties of polymeric carriers. The release kinetics of the protein were also investigated. Two sponge-like materials (Helistat® and Polyactive®) and two fibrous ones (Ethisorb™ and poly[lactic-co-glycolic acid]) were tested. The coating characteristics were evaluated using state-of-the-art methodologies. The release kinetics of BSA were monitored spectrophotometrically. The characteristics of the amorphous and the crystalline phases of the coatings were not influenced by either the surface chemistry or the surface geometry of the underlying polymer. The mechanism whereby BSA was incorporated into the crystalline layer and the rate of release of the truly incorporated depot were likewise unaffected by the nature of the polymeric carrier. Our biomimetic coating technique could be applied to either spongy or fibrous bone-defect-filling organic polymers, with a view to rendering them osteoconductive and osteoinductive.

  7. Identification of a malonyl CoA-acyl carrier protein transacylase and its regulatory role in fatty acid biosynthesis in oleaginous microalga Nannochloropsis oceanica.

    Science.gov (United States)

    Chen, Jia-Wen; Liu, Wan-Jun; Hu, Dong-Xiong; Wang, Xiang; Balamurugan, Srinivasan; Alimujiang, Adili; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2017-09-01

    Oleaginous microalgae hold great promises for biofuel production. However, commercialization of microalgal biofuels remains impracticable due to the lack of suitable industrial strains with high growth rate and lipid productivity. Engineering of metabolic pathways is a potential strategy for the improvement of microalgal strains for the production of lipids and also value-added products in microalgae. Malonyl CoA-acyl carrier protein transacylase (MCAT) has been reported to be involved in fatty acid biosynthesis. Here, we identified a putative MCAT in the oleaginous marine microalga Nannochloropsis oceanica. NoMCAT overexpressing N. oceanica showed a higher growth rate and photosynthetic efficiency. The neutral lipid content of engineered lines showed a significant increase by up to 31% compared to wild type. Gas chromatography-mass spectrometry analysis revealed that NoMCAT overexpression significantly altered the fatty acid composition. The composition of eicosapentaenoic acid (C20:5), which is a polyunsaturated fatty acid necessary for animal nutrition, increased by 8%. These results demonstrate the role of MCAT in enhancing fatty acid biosynthesis and growth in microalgae, and also provide an insight into metabolic engineering of microalgae with high industrial potential. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

  8. X-ray structural analysis of Plasmodium falciparum enoyl acyl carrier protein reductase as a pathway toward the optimization of triclosan antimalarial efficacy.

    Science.gov (United States)

    Freundlich, Joel S; Wang, Feng; Tsai, Han-Chun; Kuo, Mack; Shieh, Hong-Ming; Anderson, John W; Nkrumah, Louis J; Valderramos, Juan-Carlos; Yu, Min; Kumar, T R Santha; Valderramos, Stephanie G; Jacobs, William R; Schiehser, Guy A; Jacobus, David P; Fidock, David A; Sacchettini, James C

    2007-08-31

    The x-ray crystal structures of five triclosan analogs, in addition to that of the isoniazid-NAD adduct, are described in relation to their integral role in the design of potent inhibitors of the malarial enzyme Plasmodium falciparum enoyl acyl carrier protein reductase (PfENR). Many of the novel 5-substituted analogs exhibit low micromolar potency against in vitro cultures of drug-resistant and drug-sensitive strains of the P. falciparum parasite and inhibit purified PfENR enzyme with IC50 values of <200 nM. This study has significantly expanded the knowledge base with regard to the structure-activity relationship of triclosan while affording gains against cultured parasites and purified PfENR enzyme. In contrast to a recent report in the literature, these results demonstrate the ability to improve the in vitro potency of triclosan significantly by replacing the suboptimal 5-chloro group with larger hydrophobic moieties. The biological and x-ray crystallographic data thus demonstrate the flexibility of the active site and point to future rounds of optimization to improve compound potency against purified enzyme and intracellular Plasmodium parasites.

  9. Discovery of vinylogous carbamates as a novel class of β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors.

    Science.gov (United States)

    Li, Huan-Qiu; Luo, Yin; Zhu, Hai-Liang

    2011-08-01

    β-ketoacyl-acyl carrier protein synthase III (FabH) catalyzes the initial step of fatty acid biosynthesis via a type II fatty acid synthase in most bacteria. The important role of this essential enzyme combined with its unique structural features and ubiquitous occurrence in bacteria has made it an attractive new target for the development of new FabH inhibitors. We first used a structure-based approach to develop 24 new vinylogous carbamates (4a-15a, 4b-15b) that target FabH for the development of new antibiotics in this paper. Potent FabH inhibitory and selective anti- Gram-negative bacteria activities were observed in most of these vinylogous carbamates. Especially, compound 6a and 7a showed the most potent FabH inhibitory activity with IC₅₀ of 2.6 and 3.3 μM, respectively. Docking simulation was performed to position compound 6a into the Escherichia coli FabH active site and the possible binding conformation of compounds has been proposed. The biological data and molecular docking indicated that compounds 6a and 7a were potent inhibitors of E. coli FabH as antibiotics deserving further research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD[superscript +] and triclosan

    Energy Technology Data Exchange (ETDEWEB)

    Mehboob, Shahila; Truong, Kent; Santarsiero, Bernard D.; Johnson, Michael E. (UIC)

    2010-11-19

    Enoyl-acyl carrier protein reductase (FabI) catalyzes the last rate-limiting step in the elongation cycle of the fatty-acid biosynthesis pathway and has been validated as a potential antimicrobial drug target in Francisella tularensis. The development of new antibiotic therapies is important both to combat potential drug-resistant bioweapons and to address the broader societal problem of increasing antibiotic resistance among many pathogenic bacteria. The crystal structure of FabI from F. tularensis (FtuFabI) in complex with the inhibitor triclosan and the cofactor NAD{sup +} has been solved to a resolution of 2.1 {angstrom}. Triclosan is known to effectively inhibit FabI from different organisms. Precise characterization of the mode of triclosan binding is required to develop highly specific inhibitors. Comparison of our structure with the previously determined FtuFabI structure (PDB code 2jjy) which is bound to only NAD{sup +} reveals the conformation of the substrate-binding loop, electron density for which was missing in the earlier structure, and demonstrates a shift in the conformation of the NAD{sup +} cofactor. This shift in the position of the phosphate groups allows more room in the active site for substrate or inhibitor to bind and be better accommodated. This information will be crucial for virtual screening studies to identify novel scaffolds for development into new active inhibitors.

  11. Core-Shell Soy Protein-Soy Polysaccharide Complex (Nano)particles as Carriers for Improved Stability and Sustained Release of Curcumin.

    Science.gov (United States)

    Chen, Fei-Ping; Ou, Shi-Yi; Tang, Chuan-He

    2016-06-22

    Using soy protein isolate (SPI) and soy-soluble polysaccharides (SSPS) as polymer matrixes, this study reported a novel process to fabricate unique core-shell complex (nano)particles to perform as carriers for curcumin (a typical poorly soluble bioactive). In the process, curcumin-SPI nanocomplexes were first formed at pH 7.0 and then coated by SSPS. At this pH, the core-shell complex was formed in a way the SPI nanoparticles might be incorporated into the interior of SSPS molecules without distinctly affecting the size and morphology of particles. The core-shell structure was distinctly changed by adjusting pH from 7.0 to 4.0. At pH 4.0, SSPS was strongly bound to the surface of highly aggregated SPI nanoparticles, and as a consequence, much larger complexes were formed. The bioaccessibility of curcumin in the SPI-curcumin complexes was unaffected by the SSPS coating. However, the core-shell complex formation greatly improved the thermal stability and controlled release properties of encapsulated curcumin. The improvement was much better at pH 4.0 than that at pH 7.0. All of the freeze-dried core-shell complex preparations exhibited good redispersion behavior. The findings provide a simple approach to fabricate food-grade delivery systems for improved water dispersion, heat stability, and even controlled release of poorly soluble bioactives.

  12. Low molecular weight polyethylenimine-grafted soybean protein gene carriers with low cytotoxicity and greatly improved transfection in vitro.

    Science.gov (United States)

    Yao, Weijing; Cheng, Xu; Fu, Shengxiang; Yan, Guoqing; Wang, Xin; Tang, Rupei

    2018-02-01

    A series of gene carriers (SP-PEI) have been synthesized by acylation reaction between soybean protein and branched polyethylenimine with low molecular weight of 600, 1200 and 1800 Da, and designed as SP-PEI600, SP-PEI1200 and SP-PEI1800, respectively. SP-PEI could effectively condense plasmid DNA into nanoscale polyplexes with size range of 100-200 nm, and exhibited much lower cytotoxicity against 293T and SH-SY5Y cells than that of branched polyethylenimine (25 kDa). In vitro gene transfection demonstrated that SP-PEI/DNA complex displayed increased transfection against 293T and SH-SY5Y cells with the increase of the weight ratio of SP-PEI/DNA complex with or without 10% serum. At weight ratio of 24, SP-PEI1800/DNA polyplexes showed the highest transfection on SH-SY5Y cells, which was almost three folds higher than PEI (25 kDa). Furthermore, these SP-PEIs/DNA polyplexes could effectively transfect 293T and SH-SY5Y cells with or without 10% serum, suggesting their excellent serum tolerance.

  13. THAP and ATF-2 regulated sterol carrier protein-2 promoter activities in the larval midgut of the yellow fever mosquito, Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Rong Peng

    Full Text Available Expression of sterol carrier protein-2 (SCP-2 in Aedes aegypti shows a distinct temporal/spatial pattern throughout the life cycle. In order to identify the transcription factors responsible for the larval temporal/spatial regulation of AeSCP-2 transcription, AeSCP-2 promoter activities were studied in vivo via transient transfection of promoter/reporter gene assays. Regulatory sequences upstream -1.3 kb of the transcription start site of AeSCP-2 were found to be critical for the in vivo temporal/spatial promoter activity. Interestingly, the -1.6 kb promoter sequence efficiently drove the larval midgut-specific siRNA expression, indicating that the -1.6 kb upstream sequence is sufficient for temporal/spatial AeSCP-2 transcriptional activity. Four transcription factors were identified in the midgut nuclear extract from feeding larvae via labeled -1.6/-1.3 kb DNA probe pull-down and proteomic analysis. Co-transfection of the promoter/reporter gene with inducible siRNA expression of each transcription factor was performed to confirm the regulatory function of individual transcription factor on AeSCP-2 transcriptional activities in the larval midgut. The results indicate that two of the identified transcription factors, Thanatos-associated protein (THAP and activating transcription factor-2 (ATF-2, antagonistically control AeSCP-2 transcriptional activity in the midgut of feeding larvae via the regulatory sequences between -1.6 to -1.3 kb 5' upstream of the transcription start site. In vivo expression knockdown of THAP and ATF-2 resulted in significant changes in developmental progression, which may be partially due to their effects on AeSCP-2 expression.

  14. Synthetic High-Density Lipoprotein-Like Nanocarrier Improved Cellular Transport of Lysosomal Cholesterol in Human Sterol Carrier Protein-Deficient Fibroblasts.

    Science.gov (United States)

    Nam, Da-Eun; Kim, Ok-Kyung; Park, Yoo Kyoung; Lee, Jeongmin

    2016-01-01

    Sterol carrier protein-2 (SCP-2), which is not found in tissues of people with Zellweger syndrome, facilitates the movement of cholesterol within cells, resulting in abnormal accumulation of cholesterol in SCP-2-deficient cells. This study investigated whether synthetic high-density lipoprotein-like nanocarrier (sHDL-NC) improves the cellular transport of lysosomal cholesterol to plasma membrane in SCP-2-deficient fibroblasts. Human SCP-2-deficient fibroblasts were incubated with [(3)H-cholesterol]LDL as a source of cholesterol and sHDL-NC. The cells were fractionated by centrifugation permit tracking of [(3)H]-cholesterol from lysosome into plasma membrane. Furthermore, cellular content of cholesteryl ester as a storage form and mRNA expression of low-density lipoprotein (LDL) receptor were measured to support the cholesterol transport to plasma membrane. Incubation with sHDL-NC for 8 h significantly increased uptake of [(3)H]-cholesterol to lysosome by 53% and further enhanced the transport of [(3)H]-cholesterol to plasma membrane by 32%. Treatment with sHDL-NC significantly reduced cellular content of cholesteryl ester and increased mRNA expression of LDL receptor (LDL-R). In conclusion, sHDL-NC enables increased transport of lysosomal cholesterol to plasma membrane. In addition, these data were indirectly supported by decreased cellular content of cholesteryl ester and increased gene expression of LDL-R. Therefore, sHDL-NC may be a useful vehicle for transporting cholesterol, which may help to prevent accumulation of cholesterol in SCP-2-deficient fibroblasts.

  15. Discrimination of potent inhibitor/span>s of Toxoplasma gondii enoyl-acyl carrier protein reductase by a thermal shift assay.

    Science.gov (United States)

    Afanador, Gustavo A; Muench, Stephen P; McPhillie, Martin; Fomovska, Alina; Schön, Arne; Zhou, Ying; Cheng, Gang; Stec, Jozef; Freundlich, Joel S; Shieh, Hong-Ming; Anderson, John W; Jacobus, David P; Fidock, David A; Kozikowski, Alan P; Fishwick, Colin W; Rice, David W; Freire, Ernesto; McLeod, Rima; Prigge, Sean T

    2013-12-23

    Many microbial pathogens rely on a type II fatty acid synthesis (FASII) pathway that is distinct from the type I pathway found in humans. Enoyl-acyl carrier protein reductase (ENR) is an essential FASII pathway enzyme and the target of a number of antimicrobial drug discovery efforts. The biocide triclosan is established as a potent inhibitor of ENR and has been the starting point for medicinal chemistry studies. We evaluated a series of triclosan analogues for their ability to inhibit the growth of Toxoplasma gondii, a pervasive human pathogen, and its ENR enzyme (TgENR). Several compounds that inhibited TgENR at low nanomolar concentrations were identified but could not be further differentiated because of the limited dynamic range of the TgENR activity assay. Thus, we adapted a thermal shift assay (TSA) to directly measure the dissociation constant (Kd) of the most potent inhibitor/span>s identified in this study as well as inhibitors from previous studies. Furthermore, the TSA allowed us to determine the mode of action of these compounds in the presence of the reduced nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide (NAD⁺) cofactor. We found that all of the inhibitors bind to a TgENR-NAD⁺ complex but that they differed in their dependence on NAD⁺ concentration. Ultimately, we were able to identify compounds that bind to the TgENR-NAD⁺ complex in the low femtomolar range. This shows how TSA data combined with enzyme inhibition, parasite growth inhibition data, and ADMET predictions allow for better discrimination between potent ENR inhibitors for the future development of medicine.

  16. Molecular Biology and Functions of Carrier Proteins. Annual Symposium (46th) of the Society of General Physiologists held in Woods Hole, Massachusetts on September 10-13, 1992. Volume 48

    Science.gov (United States)

    1993-09-13

    Biology and Function of Carrier Proteins Glucose-Galactose Malabsorption One approach to defining residues important for the function of membrane trans...hereditary disease of the transporter. In the case of the intestinal Na÷ /glucose cotransporter the disease is glucose-galactose malabsorption (GGM). Over...patients, there is a selective defect in glucose and galactose absorption by the Na+/glucose cotransporter (hSGLT1). The absorption of fructose via another

  17. Bacterial Carriers for Glioblastoma Therapy

    Directory of Open Access Journals (Sweden)

    Nalini Mehta

    2017-03-01

    Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

  18. Anomalous carrier life-time relaxation mediated by head group interaction in surface anchored MnSe quantum dots conjugated with albumin proteins

    Energy Technology Data Exchange (ETDEWEB)

    Sarma, Runjun; Mohanta, Dambarudhar, E-mail: best@tezu.ernet.in

    2017-02-01

    We report on the radiative emission decay dynamics of a less known, γ-phase manganese selenide quantum dot system (MnSe QDs) subjected to bio-functionalization. A short-ligand thioglycolic acid (TGA), and a long-chain sodium dodecyl sulfate (SDS) surfactants were used as surface anchors prior bioconjugation with albumin proteins (BSA). Time resolved photoluminescence (TR-PL) spectra of the QDs have revealed bi-exponential decay trends with the fast (τ{sub 1}) and slow (τ{sub 2}) decay parameters assigned to the core state recombination and surface trapped excitons; respectively. The average lifetime (τ{sub avg}) was found to get shortened from a value of ∼0.87 ns–0.72 ns in unconjugated and BSA conjugated MnSe-TGA QDs; respectively. Conversely, MnSe-SDS QDs with BSA conjugation exhibited nearly four-fold enhancement of τ{sub avg} with respect to its unconjugated counterpart. Moreover, a considerable amount of Förster resonance energy transfer (FRET) was found to occur from the TGA coated MnSe QDs to BSA and with an ensuing efficiency of ∼61%. The origin of anomalous carrier life-time relaxation features has also been encountered through a simplified model as regards head group interaction experienced by the MnSe QDs with different surfactant types. Exploiting luminescence decay characteristics of a magneto-fluorescent candidate could find immense scope in diverse biological applications including assays, labeling and imaging. - Highlights: • Surface anchored manganese selenide quantum dots (MnSe QDs) have been synthesized via a physico-chemical reduction route. • Time resolved luminescence spectra of the QDs have displayed bi-exponential decay trend. • Thioglycolic acid (TGA) coated QDs exhibited shorter lifetime as compared to sodium dodecyl sulfo-succinate (SDS) coated ones. • Upon BSA conjugation, the average life time is four-fold enhanced in MnSe-SDS QDs. • An efficient FRET process has been revealed in BSA conjugated TGA coated MnSe QDs.

  19. Toward production of jet fuel functionality in oilseeds: identification of FatB acyl-acyl carrier protein thioesterases and evaluation of combinatorial expression strategies in Camelina seeds

    Science.gov (United States)

    Kim, Hae Jin; Silva, Jillian E.; Vu, Hieu Sy; Mockaitis, Keithanne; Nam, Jeong-Won; Cahoon, Edgar B.

    2015-01-01

    Seeds of members of the genus Cuphea accumulate medium-chain fatty acids (MCFAs; 8:0–14:0). MCFA- and palmitic acid- (16:0) rich vegetable oils have received attention for jet fuel production, given their similarity in chain length to Jet A fuel hydrocarbons. Studies were conducted to test genes, including those from Cuphea, for their ability to confer jet fuel-type fatty acid accumulation in seed oil of the emerging biofuel crop Camelina sativa. Transcriptomes from Cuphea viscosissima and Cuphea pulcherrima developing seeds that accumulate >90% of C8 and C10 fatty acids revealed three FatB cDNAs (CpuFatB3, CvFatB1, and CpuFatB4) expressed predominantly in seeds and structurally divergent from typical FatB thioesterases that release 16:0 from acyl carrier protein (ACP). Expression of CpuFatB3 and CvFatB1 resulted in Camelina oil with capric acid (10:0), and CpuFatB4 expression conferred myristic acid (14:0) production and increased 16:0. Co-expression of combinations of previously characterized Cuphea and California bay FatBs produced Camelina oils with mixtures of C8–C16 fatty acids, but amounts of each fatty acid were less than obtained by expression of individual FatB cDNAs. Increases in lauric acid (12:0) and 14:0, but not 10:0, in Camelina oil and at the sn-2 position of triacylglycerols resulted from inclusion of a coconut lysophosphatidic acid acyltransferase specialized for MCFAs. RNA interference (RNAi) suppression of Camelina β-ketoacyl-ACP synthase II, however, reduced 12:0 in seeds expressing a 12:0-ACP-specific FatB. Camelina lines presented here provide platforms for additional metabolic engineering targeting fatty acid synthase and specialized acyltransferases for achieving oils with high levels of jet fuel-type fatty acids. PMID:25969557

  20. Cell plate-restricted association of Arabidopsis dynamin related proteins and PIN auxin efflux carriers is required for PIN endocytic trafficking during cytokinesis.

    NARCIS (Netherlands)

    Mravec, J.; Petrasek, J.; Li, N.; Boeren, J.A.; Karlova, R.B.; Kitakura, S.; Naramoto, S.; Nodzynski, T.; Dhonukshe, P.B.; Vries, de S.C.; Zazimalova, E.; Friml, J.

    2011-01-01

    The polarized transport of the phytohormone auxin [1], which is crucial for the regulation of different stages of plant development [ [2] and [3] ], depends on the asymmetric plasma membrane distribution of the PIN-FORMED (PIN) auxin efflux carriers [4 A. Vieten, M. Sauer, P.B. Brewer and J. Friml,

  1. Predicting carrier-mediated hepatic disposition of rosuvastatin in man by scaling from individual transfected cell-lines in vitro using absolute transporter protein quantification and PBPK modeling.

    NARCIS (Netherlands)

    Bosgra, S.; Steeg, E. van de; Vlaming, M.L.; Verhoeckx, K.C.; Huisman, M.T.; Verwei, M.; Wortelboer, H.M.

    2014-01-01

    In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter

  2. Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice

    Science.gov (United States)

    Pavliakova, Danka; Moncrief, J. Scott; Lyerly, David M.; Schiffman, Gerald; Bryla, Dolores A.; Robbins, John B.; Schneerson, Rachel

    2000-01-01

    Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile. PMID:10722615

  3. Highly immunogenic and fully synthetic peptide-carrier constructs targetting GnRH

    NARCIS (Netherlands)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Turkstra, J.A.; Meloen, R.H.

    1999-01-01

    To use peptides as synthetic vaccines, they have to be coupled to a carrier protein to make them more immunogenic. Coupling efficiency between a carrier protein and a peptide, however, is difficult to control with respect to loading density of the peptide. This makes these carrier proteins poorly

  4. Comparative immunogenicity of conjugates composed of the Staphylococcus aureus type 8 capsular polysaccharide bound to carrier proteins by adipic acid dihydrazide or N-succinimidyl-3-(2-pyridyldithio)propionate.

    Science.gov (United States)

    Fattom, A; Shiloach, J; Bryla, D; Fitzgerald, D; Pastan, I; Karakawa, W W; Robbins, J B; Schneerson, R

    1992-01-01

    Staphylococcus aureus type 8 capsular polysaccharide (CP) was conjugated either to diphtheria toxoid or to Pseudomonas aeruginosa recombinant exoprotein A by using adipic acid dihydrazide (ADH) or N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as the joining reagent. The polysaccharide/protein ratios of these two pairs of conjugates were similar. The two synthetic schemes bound the linker to the carboxyls of the type 8 CP by carbodiimide-mediated condensation. ADH was bound to the carboxyls of the protein, whereas SPDP reacted with the amino groups of the protein. Intermolecular linking of the carrier protein, caused by the carbodiimide during the conjugation reaction with the type 8 CP derivative, probably accounts for the larger size of the conjugates formed with ADH compared with those formed with SPDP. Both conjugates synthesized with ADH elicited higher levels of CP antibodies, especially after the first immunization, than did those prepared with SPDP. Similar levels of exoprotein A antibodies were elicited by both conjugates. Higher levels of diphtheria toxoid antibodies were elicited by the conjugate prepared with SPDP than by the one prepared with ADH. The basis for the differences in the immunogenicities of these two pairs of S. aureus type 8 CP conjugates is discussed. PMID:1730492

  5. Cell-penetrating DNA-binding protein as a safe and efficient naked DNA delivery carrier in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Sung; Yang, Seung-Woo [Department of Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Hong, Dong-Ki; Kim, Woo-Taek [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Ho-Guen [Department of Pathology, Yonsei Medical School, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Department of Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2010-01-29

    Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 {mu}g of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.

  6. Cell-penetrating DNA-binding protein as a safe and efficient naked DNA delivery carrier in vitro and in vivo

    International Nuclear Information System (INIS)

    Kim, Eun-Sung; Yang, Seung-Woo; Hong, Dong-Ki; Kim, Woo-Taek; Kim, Ho-Guen; Lee, Sang-Kyou

    2010-01-01

    Non-viral gene delivery is a safe and suitable alternative to viral vector-mediated delivery to overcome the immunogenicity and tumorigenesis associated with viral vectors. Using the novel, human-origin Hph-1 protein transduction domain that can facilitate the transduction of protein into cells, we developed a new strategy to deliver naked DNA in vitro and in vivo. The new DNA delivery system contains Hph-1-GAL4 DNA-binding domain (DBD) fusion protein and enhanced green fluorescent protein (EGFP) reporter plasmid that includes the five repeats of GAL4 upstream activating sequence (UAS). Hph-1-GAL4-DBD protein formed complex with plasmid DNA through the specific interaction between GAL4-DBD and UAS, and delivered into the cells via the Hph-1-PTD. The pEGFP DNA was successfully delivered by the Hph-1-GAL4 system, and the EGFP was effectively expressed in mammalian cells such as HeLa and Jurkat, as well as in Bright Yellow-2 (BY-2) plant cells. When 10 μg of pEGFP DNA was intranasally administered to mice using Hph-1-GAL4 protein, a high level of EGFP expression was detected throughout the lung tissue for 7 days. These results suggest that an Hph-1-PTD-mediated DNA delivery strategy may be an useful non-viral DNA delivery system for gene therapy and DNA vaccines.

  7. Lack of rivaroxaban influence on a prothrombinase-based assay for the detection of activated C protein resistance: an Italian ex vivo and in vitro study in normal subjects and factor V Leiden carriers.

    Science.gov (United States)

    Gessoni, G; Valverde, S; Valle, L; Gessoni, F; Caruso, P; Valle, R

    2017-08-01

    Activated protein C resistance (APCr) leads to hypercoagulability and is due, often but not exclusively, to Factor V Leiden (FVL). The aim of this study was to assess the ex vivo and in vitro interference of the direct factor Xa inhibitor rivaroxaban (RIV) on a prothrombinase-based assay for APCr detection. An ex vivo study was performed on fresh plasma samples obtained from 44 subjects with FV wild-type and seven with FVL heterozygous, all treated with RIV. An in vitro study was performed on 15 plasma samples (six from normal subjects, six from heterozygous, and three from homozygous FVL carriers, all frozen specimens) spiked with RIV. RIV concentration was evaluated using a chromogenic assay, and APCr was evaluated by a prothrombinase-based assay. No significant interference of RIV on APCr results obtained by a prothrombinase-based assay was observed for drug concentrations up to 400 ng/mL in FV wild-type and FVL carriers (homozygous and heterozygous). These results were confirmed both ex vivo and in vitro. RIV did not significantly interfere with the prothrombinase-based assay used for the assessment of APCr, and this was observed to occur independently of FV status. However, only concentrations up to 400 ng/mL were tested and, therefore, what occurs in the presence of higher doses remains to be investigated. © 2017 John Wiley & Sons Ltd.

  8. Method for manufacturing carrier containing e.g. proteins for human during oral drug delivery operation for food and drug administration application in pharmaceutical industry, involves providing active ingredient to core layer

    DEFF Research Database (Denmark)

    2015-01-01

    or plastically deformable layer to increase stiction of the release layer. The method enables manufacturing the micro-container including an outer diameter of 200-500 pm and a height of 2-70 pm such that wall thickness is larger than 5 m to increase geometrical stability and reduce buckling. The method enables...... of the micro-containers containing an active ingredient or containing a core layer that is configured to accept the active ingredient such that the barrier layer partially encloses the core layer. The active ingredient is provided to the core layer when the core layer is configured to accept the active...... ingredient. USE - Method for manufacturing a multi-layered micro-container i.e. carrier, containing an active ingredient e.g. small organic molecules, proteins, peptides, vitamins, antibodies, antibody fragments, vaccines, RNA, DNA and antibiotics, for a patient e.g. human and animal, during an oral drug...

  9. Comparative study on the anticancer activities and binding properties of a hetero metal binuclear complex [Co(dipic)2Ni(OH2)5]·2H2O (dipic=dipicolinate) with two carrier proteins.

    Science.gov (United States)

    Shahraki, Somaye; Shiri, Fereshteh; Majd, Mostafa Heidari; Razmara, Zohreh

    2017-10-25

    Recognizing of binding mechanisms between drugs and carrier proteins is basic for us to understand the pharmacokinetics and pharmacodynamics of them. In this research, the anticancer activities of a binuclear complex [Co(dipic) 2 Ni(OH 2 ) 5 ]·2H 2 O (dipic=dipicolinate) against MDA-MB-231 cell lines were studied. Results of MTT assay and flow cytometry analysis revealed that above complex can induce the cytotoxicity and the apoptosis in breast cancer cell lines. So, this complex was selected to investigate its binding to human serum albumin (HSA) and bovine β-lactoglobulin (βLG) by spectroscopic methods (UV-visible, fluorescence and FT-IR) along with molecular docking technique. The fluorescence data showed Co-Ni complex quench the fluorescence of both proteins by a static quenching mechanism and HSA has stronger binding affinity toward Co-Ni complex than βLG. The binding constant (K b ), number of binding sites (n) and thermodynamic parameters were calculated and showed that the Co-Ni complex binds to protein (HSA and βLG) through hydrogen bonding and van der Waals forces with one binding site. The results of UV-visible measurements indicated that the binding of above complex to HSA and βLG may induce conformational and micro-environmental changes of studied proteins. Protein-ligand docking analysis confirmed that the Co-Ni complex binds to residues located in the subdomain IIA of HSA and site II of βLG. Copyright © 2017. Published by Elsevier B.V.

  10. Willis H Carrier

    Indian Academy of Sciences (India)

    New York State. His father was Duane Carrier who settled down to farming after trying his hand at various other occupations. His mother was Elizabeth Haviland, whose .... Specific Volume is the cubic meter of moist air per kg of dry air represented as m3/kg. .... Carrier converted data obtained from his tests into equations,.

  11. Air Carrier Traffic Statistics.

    Science.gov (United States)

    2013-11-01

    This report contains airline operating statistics for large certificated air carriers based on data reported to U.S. Department of Transportation (DOT) by carriers that hold a certificate issued under Section 401 of the Federal Aviation Act of 1958 a...

  12. Lactobacillus bulgaricus proteinase expressed in Lactococcus lactis is a powerful carrier for cell wall-associated and secreted bovine beta-lactoglobulin fusion proteins.

    Science.gov (United States)

    Bernasconi, Eric; Germond, Jacques-Edouard; Delley, Michèle; Fritsché, Rodolphe; Corthésy, Blaise

    2002-06-01

    Lactic acid bacteria have a good potential as agents for the delivery of heterologous proteins to the gastrointestinal mucosa and thus for the reequilibration of inappropriate immune responses to food antigens. Bovine beta-lactoglobulin (BLG) is considered a major allergen in cow's milk allergy. We have designed recombinant Lactococcus lactis expressing either full-length BLG or BLG-derived octapeptide T6 (IDALNENK) as fusions with Lactobacillus bulgaricus extracellular proteinase (PrtB). In addition to constructs encoding full-length PrtB for the targeting of heterologous proteins to the cell surface, we generated vectors aiming at the release into the medium of truncated PrtB derivatives lacking 100 (PrtB partial differential, PrtB partial differential-BLG, and PrtB partial differential-T6) or 807 (PrtBdelta) C-terminal amino acids. Expression of recombinant products was confirmed using either anti-PrtB, anti-BLG, or anti-peptide T6 antiserum. All forms of the full-length and truncated recombinant products were efficiently translocated, irrespective of the presence of eucaryotic BLG sequences in the fusion proteins. L. lactis expressing PrtB partial differential-BLG yielded up to 170 microg per 10(9) CFU in the culture supernatant and 9 microg per 10(9) CFU at the bacterial cell surface within 14 h. Therefore, protein fusions relying on the use of PrtB gene products are adequate for concomitant cell surface display and secretion by recombinant L. lactis and thus may ensure maximal bioavailability of the eucaryotic antigen in the gut-associated lymphoid tissue.

  13. Defined carriers for synthetic antigens: Hinge Peptides

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Jan; Niederhafner, Petr; Gut, Vladimír; Hulačová, Hana; Maloň, Petr

    2005-01-01

    Roč. 29, č. 1 (2005), s. 68 ISSN 0939-4451. [International Congress on Amino Acids and Proteins /9./. 08.08.2005-12.08.2005, Gert Lubec] R&D Projects: GA ČR(CZ) GA203/03/1362 Institutional research plan: CEZ:AV0Z40550506 Keywords : synthetic carrier * antigen * hinge peptide Subject RIV: CC - Organic Chemistry

  14. Protein nanoparticles for therapeutic protein delivery.

    Science.gov (United States)

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  15. Encapsulation of proteins in hydrogel carrier systems for controlled drug delivery: influence of network structure and drug size on release rate.

    Science.gov (United States)

    Bertz, Andreas; Wöhl-Bruhn, Stefanie; Miethe, Sebastian; Tiersch, Brigitte; Koetz, Joachim; Hust, Michael; Bunjes, Heike; Menzel, Henning

    2013-01-20

    Novel hydrogels based on hydroxyethyl starch modified with polyethylene glycol methacrylate (HES-P(EG)₆MA) were developed as delivery system for the controlled release of proteins. Since the drug release behavior is supposed to be related to the pore structure of the hydrogel network the pore sizes were determined by cryo-SEM, which is a mild technique for imaging on a nanometer scale. The results showed a decreasing pore size and an increase in pore homogeneity with increasing polymer concentration. Furthermore, the mesh sizes of the hydrogels were calculated based on swelling data. Pore and mesh size were significantly different which indicates that both structures are present in the hydrogel. The resulting structural model was correlated with release data for bulk hydrogel cylinders loaded with FITC-dextran and hydrogel microspheres loaded with FITC-IgG and FITC-dextran of different molecular size. The initial release depended much on the relation between hydrodynamic diameter and pore size while the long term release of the incorporated substances was predominantly controlled by degradation of the network of the much smaller meshes. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Monodisperse 130 kDa and 260 kDa Recombinant Human Hemoglobin Polymers as Scaffolds for Protein Engineering of Hemoglobin-Based Oxygen Carriers

    Directory of Open Access Journals (Sweden)

    Jacqueline F. Aitken

    2012-01-01

    Full Text Available A recombinant 130 kDa dihemoglobin which is made up of a single-chain tetra-α globin and four β globins has been expressed as a soluble protein in E. coli. The sequence of the single chain tetra-α is: αI-Gly-αII-(SerGlyGly5Ser-αIII-Gly-αIV. This dihemoglobin has been purified and characterized in vitro by size exclusion chromatography, electrospray mass spectroscopy, equilibrium oxygen binding, and analytical ultracentrifugation. The observed values of P50 and nmax for the dihemoglobin are slightly lower than those observed for the recombinant hemoglobin rHb1.1 (a “monohemoglobin” comprised of two β globins and an αI-Gly-αII diα-globin chain. Titration of the deoxy form of dihemoglobin with CO shows that all eight heme centers bind ligand. In vivo, dihemoglobin showed increased circulating halflife and a reduced pressor response in conscious rats when compared to rHb1.1. These observations suggest that dihemoglobin is an oxygen carrying molecule with desirable in vivo properties and provides a platform for an isooncotic hemoglobin solution derived solely from a recombinant source. A 260 kDa tetrahemoglobin has also been produced by chemical crosslinking of a dihemoglobin that contains a Lys16Cys mutation in the C-terminal α-globin subunit. Tetrahemoglobin also shows reduced vasoactivity in conscious rats that is comparable to that observed for dihemoglobin.

  17. The Effect of Turmeric (Curcuma longa Extract on the Functionality of the Solute Carrier Protein 22 A4 (SLC22A4 and Interleukin-10 (IL-10 Variants Associated with Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Mark J. McCann

    2014-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual’s capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152 and interleukin-10 (IL-10, rs1800896 associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F and increasing anti-inflammatory cytokine gene promoter activity (IL-10, −1082A. The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

  18. The effect of turmeric (Curcuma longa) extract on the functionality of the solute carrier protein 22 A4 (SLC22A4) and interleukin-10 (IL-10) variants associated with inflammatory bowel disease.

    Science.gov (United States)

    McCann, Mark J; Johnston, Sarah; Reilly, Kerri; Men, Xuejing; Burgess, Elaine J; Perry, Nigel B; Roy, Nicole C

    2014-10-13

    Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual's capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, -1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions.

  19. The Effect of Turmeric (Curcuma longa) Extract on the Functionality of the Solute Carrier Protein 22 A4 (SLC22A4) and Interleukin-10 (IL-10) Variants Associated with Inflammatory Bowel Disease

    Science.gov (United States)

    McCann, Mark J.; Johnston, Sarah; Reilly, Kerri; Men, Xuejing; Burgess, Elaine J.; Perry, Nigel B.; Roy, Nicole C.

    2014-01-01

    Inflammatory bowel disease (IBD) is a chronic relapsing disease. Genetic predisposition to the disease reduces an individual’s capacity to respond appropriately to environmental challenges in the intestine leading to inappropriate inflammation. IBD patients often modify their diet to mitigate or reduce the severity of inflammation. Turmeric (Curcuma longa L., Zingiberaceae) has historically been used in Chinese, Hindu, and Ayurvedic medicine over several centuries to treat inflammatory disorders. To understand how turmeric may influence the consequences of a genetic predisposition to inappropriate inflammation, we used HEK293 cells to examine the in vitro capacity of turmeric extract and fractions to affect the functionality of two gene variants, solute carrier protein 22 A4 (SLC22A4, rs1050152) and interleukin-10 (IL-10, rs1800896) associated with IBD. We found that a turmeric extract and several chromatographically separated fractions beneficially affected the variants of SLC22A4 and IL-10 associated with IBD, by reducing inappropriate epithelial cell transport (SLC22A4, 503F) and increasing anti-inflammatory cytokine gene promoter activity (IL-10, −1082A). The effect of turmeric on the IL-10 variant was strongly associated with the curcumin content of the extract and its fractions. PMID:25314644

  20. β-Hydroxyacyl-acyl Carrier Protein Dehydratase (FabZ) from Francisella tularensis and Yersinia pestis : Structure Determination, Enzymatic Characterization, and Cross-Inhibition Studies

    Energy Technology Data Exchange (ETDEWEB)

    McGillick, Brian E.; Kumaran, Desigan; Vieni, Casey; Swaminathan, Subramanyam

    2016-02-23

    The bacterial system for fatty acid biosynthesis (FAS) contains several enzymes whose sequence and structure are highly conserved across a vast array of pathogens. This, coupled with their low homology and difference in organization compared to the equivalent system in humans, makes the FAS pathway an excellent target for antimicrobial drug development. To this end, we have cloned, expressed, and purified the β-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from both Francisella tularensis (FtFabZ) and Yersinia pestis (YpFabZ). We also solved the crystal structures and performed an enzymatic characterization of both enzymes and several mutant forms of YpFabZ. Additionally, we have discovered two novel inhibitors of FabZ, mangostin and stictic acid, which show similar potencies against both YpFabZ and FtFabZ. Lastly, we selected several compounds from the literature that have been shown to be active against single homologues of FabZ and tested them against both YpFabZ and FtFabZ. These results have revealed clues as to which scaffolds are likely to lead to broad-spectrum antimicrobials targeted against FabZ as well as modifications to existing FabZ inhibitors that may improve potency.

  1. Solution Structure of 4′-Phosphopantetheine - GmACP3 from Geobacter metallireducens: A Specialized Acyl Carrier Protein with Atypical Structural Features and a Putative Role in Lipopolysaccharide Biosynthesis†

    Science.gov (United States)

    Ramelot, Theresa A.; Smola, Matthew J.; Lee, Hsiau-Wei; Ciccosanti, Colleen; Hamilton, Keith; Acton, Thomas B.; Xiao, Rong; Everett, John K.; Prestegard, James H.; Montelione, Gaetano T.; Kennedy, Michael A.

    2011-01-01

    GmACP3 from Geobacter metallireducens is a specialized acyl carrier protein (ACP) whose gene, gmet_2339, is located near genes encoding many proteins involved in lipopolysaccharide (LPS) biosynthesis, indicating a likely function for GmACP3 in LPS production. By overexpression in Escherichia coli, about 50% holo-GmACP3 and 50% apo-GmACP3 were obtained. Apo-GmACP3 exhibited slow precipitation and non-monomeric behavior by 15N NMR relaxation measurements. Addition of 4′-phosphopantetheine (4′-PP) via enzymatic conversion by E. coli holo-ACP synthase, resulted in stable >95% holo-GmACP3 that was characterized as monomeric by 15N relaxation measurements and had no indication of conformational exchange. We have determined a high-resolution solution structure of holo-GmACP3 by standard NMR methods, including refinement with two sets of NH residual dipolar couplings, allowing for a detailed structural analysis of the interactions between 4′-PP and GmACP3. Whereas the overall four helix bundle topology is similar to previously solved ACP structures, this structure has unique characteristics, including an ordered 4′-PP conformation that places the thiol at the entrance to a central hydrophobic cavity near a conserved hydrogen-bonded Trp-His pair. These residues are part of a conserved WDSLxH/N motif found in GmACP3 and it’s orthologs. The helix locations and the large hydrophobic cavity are more similar to medium- and long-chain acyl-ACPs than to other apo- and holo-ACP structures. Taken together, structural characterization along with bioinformatic analysis of nearby genes suggest that GmACP3 is involved in lipid A acylation, possibly by atypical long-chain hydroxy fatty acids, and potentially involved in synthesis of secondary metabolites. PMID:21235239

  2. Duchenne muscular dystrophy carriers

    International Nuclear Information System (INIS)

    Matsumura, K.; Nakano, I.

    1989-01-01

    By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated from the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. (orig.)

  3. Willis H Carrier

    Indian Academy of Sciences (India)

    Permanent link: http://www.ias.ac.in/article/fulltext/reso/017/02/0117-0138. Keywords. W H Carrier; rational psychrometric formulae; psychrometric chart; invention of centrifugal machine; law of dew-point depression. Author Affiliations. R V Simha1. Director Airtron Consulting Engineers Pvt Ltd, No. 502/A, Ist Main Jayanagar ...

  4. Asymmetric Carrier Random PWM

    DEFF Research Database (Denmark)

    Mathe, Laszlo; Lungeanu, Florin; Rasmussen, Peter Omand

    2010-01-01

    index. The flat motor current spectrum generates an acoustical noise close to the white noise, which may improve the acoustical performance of the drive. The new carrier wave is easy to implement digitally, without employing any external circuits. The modulation method can be used in open, as well...

  5. Willis H Carrier

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 17; Issue 2. Willis H. Carrier - Father of Air Conditioning. R V Simha. General Article Volume 17 Issue 2 February 2012 pp 117-138. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/017/02/0117-0138 ...

  6. Plasmid AZOBR_p1-borne fabG gene for putative 3-oxoacyl-[acyl-carrier protein] reductase is essential for proper assembly and work of the dual flagellar system in the alphaproteobacterium Azospirillum brasilense Sp245.

    Science.gov (United States)

    Filip'echeva, Yulia A; Shelud'ko, Andrei V; Prilipov, Alexei G; Burygin, Gennady L; Telesheva, Elizaveta M; Yevstigneyeva, Stella S; Chernyshova, Marina P; Petrova, Lilia P; Katsy, Elena I

    2018-02-01

    Azospirillum brasilense can swim and swarm owing to the activity of a constitutive polar flagellum (Fla) and inducible lateral flagella (Laf), respectively. Experimental data on the regulation of the Fla and Laf assembly in azospirilla are scarce. Here, the coding sequence (CDS) AZOBR_p1160043 (fabG1) for a putative 3-oxoacyl-[acyl-carrier protein (ACP)] reductase was found essential for the construction of both types of flagella. In an immotile leaky Fla - Laf - fabG1::Omegon-Km mutant, Sp245.1610, defects in flagellation and motility were fully complemented by expressing the CDS AZOBR_p1160043 from plasmid pRK415. When pRK415 with the cloned CDS AZOBR_p1160045 (fliC) for a putative 65.2 kDa Sp245 Fla flagellin was transferred into the Sp245.1610 cells, the bacteria also became able to assemble a motile single flagellum. Some cells, however, had unusual swimming behavior, probably because of the side location of the organelle. Although the assembly of Laf was not restored in Sp245.1610 (pRK415-p1160045), this strain was somewhat capable of swarming motility. We propose that the putative 3-oxoacyl-[ACP] reductase encoded by the CDS AZOBR_p1160043 plays a role in correct flagellar location in the cell envelope and (or) in flagellar modification(s), which are also required for the inducible construction of Laf and for proper swimming and swarming motility of A. brasilense Sp245.

  7. OsPIN2, which encodes a member of the auxin efflux carrier proteins, is involved in root elongation growth and lateral root formation patterns via the regulation of auxin distribution in rice.

    Science.gov (United States)

    Inahashi, Hiroki; Shelley, Israt Jahan; Yamauchi, Takaki; Nishiuchi, Shunsaku; Takahashi-Nosaka, Misuzu; Matsunami, Maya; Ogawa, Atsushi; Noda, Yusaku; Inukai, Yoshiaki

    2018-02-15

    Auxin flow is important for different root developmental processes such as root formation, emergence, elongation and gravitropism. However, the detailed information about the mechanisms regulating the auxin flow is less well understood in rice. We characterized the auxin transport-related mutants, Ospin-formed2-1 (Ospin2-1) and Ospin2-2, which exhibited curly root phenotypes and altered lateral root-formation patterns in rice. The OsPIN2 gene encodes a member of the auxin-efflux carrier proteins that possibly regulates the basipetal auxin flow from the root tip towards the root-elongation zone. According to DR5-driven GUS expression, there is an asymmetric auxin distribution in the mutants that corresponded with the asymmetric cell elongation pattern in the mutant root tip. Auxin transport inhibitor, N-1-naphthylphthalamic acid (NPA), and Ospin2-1 Osiaa13 double mutant rescued the curly root phenotype indicating that this phenotype results from a defect in proper auxin distribution. The typical curly root phenotype was not observed when Ospin2-1 was grown in distilled water as an alternative to tap water, although higher auxin levels were found at the root tip region of the mutant than that of the wild type. Therefore, the lateral root formation zone in the mutant was shifted basipetally compared with the wild type. These results reflect that an altered auxin flow in the root tip region is responsible for root elongation growth and lateral root formation patterns in rice. This article is protected by copyright. All rights reserved.

  8. Two Fatty Acid Desaturases, STEAROYL-ACYL CARRIER PROTEIN Δ9-DESATURASE6 and FATTY ACID DESATURASE3, Are Involved in Drought and Hypoxia Stress Signaling in Arabidopsis Crown Galls1[W][OPEN

    Science.gov (United States)

    Klinkenberg, Joern; Faist, Hanna; Saupe, Stefanie; Lambertz, Sophie; Krischke, Markus; Stingl, Nadja; Fekete, Agnes; Mueller, Martin J.; Feussner, Ivo; Hedrich, Rainer; Deeken, Rosalia

    2014-01-01

    Agrobacterium tumefaciens-derived crown galls of Arabidopsis (Arabidopsis thaliana) contain elevated levels of unsaturated fatty acids and strongly express two fatty acid desaturase genes, ω3 FATTY ACID DESATURASE3 (FAD3) and STEAROYL-ACYL CARRIER PROTEIN Δ9-DESATURASE6 (SAD6). The fad3-2 mutant with impaired α-linolenic acid synthesis developed significantly smaller crown galls under normal, but not under high, relative humidity. This strongly suggests that FAD3 plays a role in increasing drought stress tolerance of crown galls. SAD6 is a member of the SAD family of as yet unknown function. Expression of the SAD6 gene is limited to hypoxia, a physiological condition found in crown galls. As no sad6 mutant exists and to link the function of SAD6 with fatty acid desaturation in crown galls, the lipid pattern was analyzed of plants with constitutive SAD6 overexpression (SAD6-OE). SAD6-OE plants contained lower stearic acid and higher oleic acid levels, which upon reduction of SAD6 overexpression by RNA interference (SAD6-OE-RNAi) regained wild-type-like levels. The development of crown galls was not affected either in SAD6-OE or SAD6-OE-RNAi or by RNA interference in crown galls. Since biochemical analysis of SAD6 in yeast (Saccharomyces cerevisiae) and Escherichia coli failed, SAD6 was ectopically expressed in the background of the well-known suppressor of salicylic acid-insensitive2 (ssi2-2) mutant to confirm the desaturase function of SAD6. All known ssi2-2 phenotypes were rescued, including the high stearic acid level. Thus, our findings suggest that SAD6 functions as a Δ9-desaturase, and together with FAD3 it increases the levels of unsaturated fatty acids in crown galls under hypoxia and drought stress conditions. PMID:24368335

  9. Yarn carrier with clutch

    Science.gov (United States)

    Doyne, Richard A. (Inventor); Benson, Rio H. (Inventor); El-Shiekh, Aly (Inventor)

    1994-01-01

    A yarn carrier apparatus particularly suited for use in braiding machinery or the like due to its capability of continuous yarn feeding and retraction of long lengths of yarn. The yarn carrier apparatus comprises a yarn supply spool which is rotatably mounted within the housing, a spring motor also mounted within the housing and operatively connected to the yarn supply spool through a mechanical transmission assembly which is adapted to multiply rotational movement between the first element of the gear assembly operatively connected to the spring motor and the final element of the gear assembly operatively connected to the yarn supply spool. The spring motor is adapted to tension the yarn during both feeding and retraction thereof, and it is further adapted to periodically rotatably slip within the housing and partially unwind so as to allow for continuous withdrawal of a long length of yarn without the spring motor becoming fully wound and preventing further yarn retraction.

  10. Carrier transport uphill. I. General

    DEFF Research Database (Denmark)

    Rosenberg, T; Wilbrandt, W

    1963-01-01

    A quantitative treatment of a carrier pump operating with two carrier forms C and Z is presented. Asymmetric metabolic reactions are assumed to transform Z into C on one and C into Z on the other side of the membrane, establishing a carrier cycle. The kinetical consequences of this mechanism...

  11. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...... membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption...

  12. Intestinal solute carriers

    DEFF Research Database (Denmark)

    Steffansen, Bente; Nielsen, Carsten Uhd; Brodin, Birger

    2004-01-01

    membrane transporters in the small intestine in order to increase oral bioavailabilities of drug or prodrug, the major influence on in vivo pharmacokinetics is suggested to be dose-dependent increase in bioavailability as well as prolonged blood circulation due to large capacity facilitated absorption......A large amount of absorptive intestinal membrane transporters play an important part in absorption and distribution of several nutrients, drugs and prodrugs. The present paper gives a general overview on intestinal solute carriers as well as on trends and strategies for targeting drugs and...

  13. Glycosylation of solute carriers

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Carlsson, Michael C; Pedersen, Stine Helene Falsig

    2016-01-01

    as their posttranslational regulation, but only relatively little is known about the role of SLC glycosylation. Glycosylation is one of the most abundant posttranslational modifications of animal proteins and through recent advances in our understanding of protein-glycan interactions, the functional roles of SLC...

  14. Carrier priming or suppression: understanding carrier priming enhancement of anti-polysaccharide antibody response to conjugate vaccines.

    Science.gov (United States)

    Pobre, Karl; Tashani, Mohamed; Ridda, Iman; Rashid, Harunor; Wong, Melanie; Booy, Robert

    2014-03-14

    With the availability of newer conjugate vaccines, immunization schedules have become increasingly complex due to the potential for unpredictable immunologic interference such as 'carrier priming' and 'carrier induced epitopic suppression'. Carrier priming refers to an augmented antibody response to a carbohydrate portion of a glycoconjugate vaccine in an individual previously primed with the carrier protein. This review aims to provide a critical evaluation of the available data on carrier priming (and suppression) and conceptualize ways by which this phenomenon can be utilized to strengthen vaccination schedules. We conducted this literature review by searching well-known databases to date to identify relevant studies, then extracted and synthesized the data on carrier priming of widely used conjugate polysaccharide vaccines, such as, pneumococcal conjugate vaccine (PCV), meningococcal conjugate vaccine (MenCV) and Haemophilus influenzae type b conjugate vaccines (HibV). We found evidence of carrier priming with some conjugate vaccines, particularly HibV and PCV, in both animal and human models but controversy surrounds MenCV. This has implications for the immunogenicity of conjugate polysaccharide vaccines following the administration of tetanus-toxoid or diphtheria-toxoid containing vaccine (such as DTP). Available evidence supports a promising role for carrier priming in terms of maximizing the immunogenicity of conjugate vaccines and enhancing immunization schedule by making it more efficient and cost effective. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Autonomous component carrier selection

    DEFF Research Database (Denmark)

    Garcia, Luis Guilherme Uzeda; Pedersen, Klaus; Mogensen, Preben

    2009-01-01

    management and efficient system operation. Due to the expected large number of user-deployed cells, centralized network planning becomes unpractical and new scalable alternatives must be sought. In this article, we propose a fully distributed and scalable solution to the interference management problem......Low-power base stations such as e.g. Femto-cells are one of the candidates for high data rate provisioning in local areas, such as residences, apartment complexes, business offices and outdoor hotspot scenarios. Unfortunately, the benefits are not without new challenges in terms of interference...... in local areas, basing our study case on LTE-Advanced. We present extensive network simulation results to demonstrate that a simple and robust interference management scheme, called autonomous component carrier selection allows each cell to select the most attractive frequency configuration; improving...

  16. The energy carrier hydrogen

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    The potential of hydrogen to be used as a clean fuel for the production of heat and power, as well as for the propulsion of aeroplanes and vehicles, is described, in particular for Germany. First, attention is paid to the application of hydrogen as a basic material for the (petro)chemical industry, as an indirect energy source for (petro)chemical processes, and as a direct energy source for several purposes. Than the importance of hydrogen as an energy carrier in a large-scale application of renewable energy sources is discussed. Next an overview is given of new and old hydrogen production techniques from fossil fuels, biomass, or the electrolysis of water. Energetic applications of hydrogen in the transportation sector and the production of electric power and heat are mentioned. Brief descriptions are given of techniques to store hydrogen safely. Finally attention is paid to hydrogen research in Germany. Two hydrogen projects, in which Germany participates, are briefly dealt with: the Euro-Quebec project (production of hydrogen by means of hydropower), and the HYSOLAR project (hydrogen production by means of solar energy). 18 figs., 1 tab., 7 refs

  17. 7 CFR 35.4 - Carrier.

    Science.gov (United States)

    2010-01-01

    ... AND PLUMS Definitions § 35.4 Carrier. Carrier means any common or private carrier, including, but not being limited to, trucks, rail, airplanes, vessels, tramp or chartered steamers, whether carrying for...

  18. Basic Stand Alone Carrier Line Items PUF

    Data.gov (United States)

    U.S. Department of Health & Human Services — This release contains the Basic Stand Alone (BSA) Carrier Line Items Public Use Files (PUF) with information from Medicare Carrier claims. The CMS BSA Carrier Line...

  19. Impact of carriers in oral absorption

    DEFF Research Database (Denmark)

    Gram, Luise Kvisgaard; Rist, Gerda Marie; Lennernäs, Hans

    2009-01-01

    Carriers may mediate the permeation across enterocytes for drug substances being organic anions. Carrier mediated permeation for the organic anions estrone-3-sulfate (ES) and glipizide across Caco-2 cells were investigated kinetically, and interactions on involved carriers evaluated. Initial...

  20. Nanostructured Lipid Carriers: A potential drug carrier for cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Selvamuthukumar Subramanian

    2012-11-01

    Full Text Available Abstract Nanotechnology having developed exponentially, the aim has been on therapeutic undertaking, particularly for cancerous disease chemotherapy. Nanostructured lipid carriers have attracted expanding scientific and commercial vigilance in the last couple of years as alternate carriers for the pharmaceutical consignment, particularly anticancer pharmaceuticals. Shortcomings often came across with anticancer mixtures, such as poor solubility, normal tissue toxicity, poor specificity and steadiness, as well as the high incidence rate of pharmaceutical resistance and the rapid degradation, need of large-scale output procedures, a fast release of the pharmaceutical from its carrier scheme, steadiness troubles, the residues of the organic solvents utilized in the output method and the toxicity from the polymer with esteem to the carrier scheme are anticipated to be overcome through use of the Nanostructured Lipid Carrier. In this review the benefits, types, drug release modulations, steadiness and output techniques of NLCs are discussed. In supplement, the function of NLC in cancer chemotherapy is presented and hotspots in research are emphasized. It is foreseen that, in the beside future, nanostructured lipid carriers will be further advanced to consign cytotoxic anticancer compounds in a more efficient, exact and protected manner.

  1. When is a carrier not a membrane carrier? The cytoplasmic transport of amphipathic molecules.

    Science.gov (United States)

    Weisiger, R A

    1996-11-01

    After entering the cell, small molecules must penetrate the cytoplasm before they are metabolized, excreted, or can convey information to the cell nucleus. Without efficient cytoplasmic transport, most such molecules would efflux back out of the cell before they could reach their targets. Cytoplasmic movement of amphipathic molecules (e.g., long-chain fatty acids, bilirubin, bile acids) is greatly slowed by their tendency to bind intracellular structures. Soluble cytoplasmic binding proteins reduce this binding by increasing the aqueous solubility of their ligands. These soluble carriers catalyze the transport of hydrophobic molecules across hydrophilic water layers, just as membrane carriers catalyze the transport of hydrophilic molecules across the hydrophobic membrane core. They even display the kinetic features of carrier-mediated transport, including saturation, mutual competition between similar molecules, and countertransport. Recent data suggest that amphipathic molecules cross the cytoplasm very slowly, with apparent diffusion constants 10(2) to 10(4) times smaller than in water. By modulating the rate of cytoplasmic transport, cytosolic binding proteins may regulate transport and metabolism of amphipathic molecules. Storage diseases may cause hepatocellular dysfunction by disrupting normal cytoplasmic transport.

  2. Stable wafer-carrier system

    Energy Technology Data Exchange (ETDEWEB)

    Rozenzon, Yan; Trujillo, Robert T; Beese, Steven C

    2013-10-22

    One embodiment of the present invention provides a wafer-carrier system used in a deposition chamber for carrying wafers. The wafer-carrier system includes a base susceptor and a top susceptor nested inside the base susceptor with its wafer-mounting side facing the base susceptor's wafer-mounting side, thereby forming a substantially enclosed narrow channel. The base susceptor provides an upward support to the top susceptor.

  3. Carrier peptide-mediated transepithelial permeation of biopharmaceuticals

    DEFF Research Database (Denmark)

    Kristensen, Mie; Nielsen, Hanne Mørck

    2015-01-01

    Oral delivery of therapeutic peptides and proteins is hampered by their poor enzymatic stability and large molecular size, thus limiting their permeation across the intestinal epithelium. A promising approach to overcome the latter is by co-administration with carrier-peptides, such as the cell...

  4. Serum levels of pancreatic stone protein (PSP)/reg1A as an indicator of beta-cell apoptosis suggest an increased apoptosis rate in hepatocyte nuclear factor 1 alpha (HNF1A-MODY) carriers from the third decade of life onward

    LENUS (Irish Health Repository)

    Bacon, Siobhan

    2012-07-18

    AbstractBackgroundMutations in the transcription factor hepatocyte nuclear factor-1-alpha (HNF1A) result in the commonest type of maturity onset diabetes of the young (MODY). HNF1A-MODY carriers have reduced pancreatic beta cell mass, partially due to an increased rate of apoptosis. To date, it has not been possible to determine when apoptosis is occurring in HNF1A-MODY.We have recently demonstrated that beta cell apoptosis stimulates the expression of the pancreatic stone protein\\/regenerating (PSP\\/reg) gene in surviving neighbour cells, and that PSP\\/reg1A protein is subsequently secreted from these cells. The objective of this study was to determine whether serum levels of PSP\\/reg1A are elevated during disease progression in HNF1A-MODY carriers, and whether it may provide information regarding the onset of beta-cell apoptosis.MethodsWe analysed serum PSP\\/reg1A levels and correlated with clinical and biochemical parameters in subjects with HNF1A-MODY, glucokinase (GCK-MODY), and type 1 diabetes mellitus. A control group of normoglycaemic subjects was also analysed.ResultsPSP\\/reg1A serum levels were significantly elevated in HNF1A-MODY (n = 37) subjects compared to controls (n = 60) (median = 12.50 ng\\/ml, IQR = 10.61-17.87 ng\\/ml versus median = 10.72 ng\\/ml, IQR = 8.94-12.54 ng\\/ml, p = 0.0008). PSP\\/reg1A correlated negatively with insulin levels during OGTT, (rho = −0.40, p = 0.02). Interestingly we noted a significant positive correlation of PSP\\/reg1A with age of the HNF1A-MODY carriers (rho = 0.40 p = 0.02) with an age of 25 years separating carriers with low and high PSP\\/reg1A levels. Patients with type 1 diabetes mellitus also had elevated serum levels of PSP\\/reg1A compared to controls, however this was independent of the duration of diabetes.ConclusionOur data suggest that beta cell apoptosis contributes increasingly to the pathophysiology of HNF1A-MODY in patients 25 years and

  5. Association of polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) and fatty acid-binding protein-3 and fatty acid-binding protein-4 (FABP3 and FABP4) with fatty acid composition of bovine milk.

    Science.gov (United States)

    Nafikov, R A; Schoonmaker, J P; Korn, K T; Noack, K; Garrick, D J; Koehler, K J; Minick-Bormann, J; Reecy, J M; Spurlock, D E; Beitz, D C

    2013-09-01

    The main goal of this study was to develop tools for genetic selection of animals producing milk with a lower concentration of saturated fatty acids (SFA) and a higher concentration of unsaturated fatty acids (UFA). The reasons for changing milk fatty acid (FA) composition were to improve milk technological properties, such as for production of more spreadable butter, and milk nutritional value with respect to the potentially adverse effects of SFA on human health. We hypothesized that genetic polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) fatty acid transport protein gene and fatty acid binding protein (FABP)-3 and FABP-4 (FABP3 and FABP4) would affect the selectivity of FA uptake into, and FA redistribution inside, mammary epithelial cells, resulting in altered FA composition of bovine milk. The objectives of our study were to discover genetic polymorphisms in SLC27A6, FABP3, and FABP4, and to test those polymorphisms for associations with milk FA composition. The results showed that after pairwise comparisons between SLC27A6 haplotypes for significantly associated traits, haplotype H3 was significantly associated with 1.37 weight percentage (wt%) lower SFA concentration, 0.091 lower SFA:UFA ratio, and 0.17 wt% lower lauric acid (12:0) concentration, but 1.37 wt% higher UFA and 1.24 wt% higher monounsaturated fatty acid (MUFA) concentrations compared with haplotype H1 during the first 3 mo of lactation. Pairwise comparisons between FABP4 haplotypes for significantly associated traits showed that haplotype H3 was significantly associated with 1.04 wt% lower SFA concentration, 0.079 lower SFA:UFA ratio, 0.15 wt% lower lauric acid (12:0), and 0.27 wt% lower myristic acid (14:0) concentrations, but 1.04 wt% higher UFA and 0.91 wt% higher MUFA concentrations compared with haplotype H1 during the first 3 mo of lactation. Percentages of genetic variance explained by H3 versus H1 haplotype substitutions for SLC27A6 and FABP4 ranged from 2.50 to 4.86% and

  6. 29 CFR 1201.1 - Carrier.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Carrier. 1201.1 Section 1201.1 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD DEFINITIONS § 1201.1 Carrier. The term carrier includes any express company, sleeping car company, carrier by railroad, subject to the Interstate Commerce Act...

  7. Carbon: Hydrogen Carrier or Disappearing Skeleton?

    NARCIS (Netherlands)

    Jong, K.P. de; Wechem, H.M.H. van

    1994-01-01

    The use of liquid hydrocarbons as energy carriers implies the use of carbon as a carrier for hydrogen to facilitate hydrogen transport and storage. The current trend for liquid energy carriers used in the transport sector is to maximize the load of hydrogen on the carbon carrier. The recently

  8. Straddle carrier radiation portal monitoring

    Science.gov (United States)

    Andersen, Eric S.; Samuel, Todd J.; Mullen, O. Dennis

    2005-05-01

    U.S. Customs and Border Protection (CBP) is the primary enforcement agency protecting the nation"s ports of entry. CBP is enhancing its capability to interdict the illicit import of nuclear and radiological materials and devices that may be used by terrorists. Pacific Northwest National Laboratory (PNNL) is providing scientific and technical support to CBP in their goal to enable rapid deployment of nuclear and radiation detection systems at U. S. ports of entry to monitor 100% of the incoming international traffic and cargo while not adversely impacting the operations or throughput of the ports. The U.S. ports of entry include the following vectors: land border crossings, seaports, airports, rail crossings, and mail and express consignment courier facilities. U.S. Customs and Border Protection (CBP) determined that a screening solution was needed for Seaport cargo containers being transported by Straddle Carriers (straddle carriers). A stationary Radiation Portal Monitor (RPM) for Straddle Carriers (SCRPM) is needed so that cargo containers can be scanned while in transit under a Straddle Carrier. The Straddle Carrier Portal operational impacts were minimized by conducting a time-motion study at the Port, and adaptation of a Remotely Operated RPM (RO-RPM) booth concept that uses logical lighting schemes for traffic control, cameras, Optical Character Recognition, and wireless technology.

  9. Water-structuring technology with the molecular chaperone proteins: indicated application of the α-crystallin domains and imidazole-containing peptidomimetics in cosmetic skin care systems or dermatological therapeutic drug carrier formulations.

    Science.gov (United States)

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2011-01-01

    Changes in structural proteins and hydration during aging are responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, and apparent dryness. Impairment in protein hydration may add to the ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin. At Innovative Vision Products, Inc., we have pioneered a molecular chaperone protein-activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology-related or skin aging and skin disease-related pathways. This cutting-edge technology has changed the hydration of proteins in photoaged skin which so that they are more compact and interact with water to limited degree. The mechanisms of skin diseases, aging, and cellular and signaling pathways mediated by targeting with molecular chaperone protein(s) are considered. Skin lesions that are growing, spreading, or pigmented, and those that occur on exposed areas of skin are likely to be treated by these emerging pharmacological chaperones that could have cosmetic or dermatological benefits. Examples of such chaperones are anti-/trans-glycation-imidazole-containing peptidomimetic(s) (natural L-carnosine derivatives and mimetics) combined with the molecular chaperone protein α-crystallin derived from a natural source, brine shrimp (Artemia franciscana) cysts, or with recombinant human αA-crystallin. This patented biotechnology represents an efficient tool with which to mitigate the consequences of free radical-induced skin damage. The article is organized to provide in one place all of the relevant technical information, such as high-performance nuclear magnetic resonance and electron spin resonance application tools, and to describe the entire process from sample preparation to data analysis, which is moving from biological studies to biotechnology batches of the product. The proposed biotechnology results in

  10. Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or β-galactosidase as a carrier of immunogenic epitopes

    International Nuclear Information System (INIS)

    Li Guangjin; Chen Weizao; Yan Weiyao; Zhao Kai; Liu Mingqiu; Zhang Jun; Fei Liang; Xu Quanxing; Sheng Zutian; Lu Yonggan; Zheng Zhaoxin

    2004-01-01

    Previously, we demonstrated that a fusion protein (Gal-FMDV) consisting of β-galactosidase and an immunogenic peptide, amino acids (141-160)-(21-40)-(141-160), of foot-and-mouth disease virus (FMDV) VP1 protein induced protective immune responses in guinea pigs and swine. We now designed a new potential recombinant protein vaccine against FMDV in swine. The immunogenic peptide, amino acids (141-160)-(21-40)-(141-160) from the VP1 protein of serotype O FMDV, was fused to the carboxy terminus of a swine immunoglobulin G single heavy chain constant region and expressed in Escherichia coli. The expressed fusion protein (IgG-FMDV) was purified and emulsified with oil adjuvant. Vaccination twice at an interval of 3 weeks with the emulsified IgG-FMDV fusion protein induced an FMDV-specific spleen proliferative T-cell response in guinea pigs and elicited high levels of neutralizing antibody in guinea pigs and swine. All of the immunized animals were efficiently protected against FMDV challenge. There was no significant difference between IgG-FMDV and Gal-FMDV in eliciting immunity after vaccination twice in swine. However, when evaluating the efficacy of a single inoculation of the fusion proteins, we found that IgG-FMDV could elicit a protective immune response in swine, while Gal-FMDV only elicited a weak neutralizing activity and could not protect the swine against FMDV challenge. Our results suggest that the IgG-FMDV fusion protein is a promising vaccine candidate for FMD in swine

  11. 78 FR 66801 - Motor Carrier Safety Advisory Committee; Charter Renewal

    Science.gov (United States)

    2013-11-06

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee; Charter Renewal AGENCY: Federal Motor Carrier Safety... and recommendations on motor carrier safety programs and motor carrier safety regulations through a...

  12. Hot carrier degradation in semiconductor devices

    CERN Document Server

    2015-01-01

    This book provides readers with a variety of tools to address the challenges posed by hot carrier degradation, one of today’s most complicated reliability issues in semiconductor devices.  Coverage includes an explanation of carrier transport within devices and book-keeping of how they acquire energy (“become hot”), interaction of an ensemble of colder and hotter carriers with defect precursors, which eventually leads to the creation of a defect, and a description of how these defects interact with the device, degrading its performance. • Describes the intricacies of hot carrier degradation in modern semiconductor technologies; • Covers the entire hot carrier degradation phenomenon, including topics such as characterization, carrier transport, carrier-defect interaction, technological impact, circuit impact, etc.; • Enables detailed understanding of carrier transport, interaction of the carrier ensemble with the defect precursors, and an accurate assessment of how the newly created defects imp...

  13. Solute carrier transporters: Pharmacogenomics research ...

    African Journals Online (AJOL)

    This paper reviews the solute carrier transporters and highlights the fact that there is much to be learnt from characterizing human genomic variation in South Africa and sub-Saharan Africa, especially with regards to health applications. Genomic diversity in this region is indeed relatively under-studied despite being home to ...

  14. Carrier multiplication in germanium nanocrystals

    NARCIS (Netherlands)

    Saeed, S.; de Weerd, C.; Stallinga, P.; Spoor, F.C.M.; Houtepen, A.J.; Siebbeles, L.D.A.; Gregorkiewicz, T.

    2015-01-01

    Carrier multiplication is demonstrated in a solid-state dispersion of germanium nanocrystals in a silicon-dioxide matrix. This is performed by comparing ultrafast photo-induced absorption transients at different pump photon energies below and above the threshold energy for this process. The average

  15. Experimental verification of carrier multiplication in graphene.

    Science.gov (United States)

    Plötzing, T; Winzer, T; Malic, E; Neumaier, D; Knorr, A; Kurz, H

    2014-09-10

    We report on the first direct experimental observation of carrier multiplication in graphene reaching a multiplication factor of up to 2 and persisting on a picoseconds time scale. Exploiting multicolor pump-probe measurement techniques, the excited nonequilibrium carrier distribution is retrieved on an ultrafast time scale. This provides access to the temporal evolution of the optically excited carrier density and thus allows quantitative conclusions on possible carrier multiplication. Microscopic time- and momentum-resolved calculations on the ultrafast relaxation dynamics of optically excited carriers confirm the observation of carrier multiplication under corresponding experimental conditions, suggesting graphene as a promising material for novel high-efficiency photodetection devices.

  16. Induced pluripotent stem cells (iPSCs) derived from a symptomatic carrier of a S305I mutation in the microtubule-associated protein tau (MAPT)-gene causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Nimsanor, Natakarn; Jørring, Ida; Rasmussen, Mikkel A.

    2016-01-01

    Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the gene coding the microtubule-associated protein tau (MAPT) can cause FTDP-17 but the underlying mechanisms of the disease are still unknown. Induced...

  17. Induced pluripotent stem cells (iPSCs) derived from af pre-symptomatic carrier of a R406W mutation in microtubule-associated protein tau (MAPT) causing frontotemporal dementia

    DEFF Research Database (Denmark)

    Rasmussen, Mikkel A.; Hjermind, Lena Elisabeth; Hasholt, Lis Frydenreich

    2016-01-01

    Skin fibroblasts were obtained from a 28-year-old pre-symptomatic woman carrying a R406W mutation in microtubule-associated protein tau (MAPT), known to cause frontotemporal dementia. Induced pluripotent stem cell (iPSCs) were established by electroporation with episomal plasmids containing hOCT4...

  18. Solute carrier transporters: potential targets for digestive system neoplasms

    Directory of Open Access Journals (Sweden)

    Xie J

    2018-01-01

    Full Text Available Jing Xie,1,2 Xiao Yan Zhu,1,2 Lu Ming Liu,1,2 Zhi Qiang Meng1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China Abstract: Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible

  19. Bioactive albumin-based carriers for tumour chemotherapy.

    Science.gov (United States)

    Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

    2014-01-01

    Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

  20. Efficiency of some spectrochemical carriers

    International Nuclear Information System (INIS)

    Gomes, R.P.

    1978-01-01

    A comparative study of the efficiency of some spectrochemical carriers for the quantitative spectrographic analysis of Ag, Al, B, Bi, Cd, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Pb, Si, Sn, V and Zn in uranium-base materials is presented. The volatility behavior of the eighteen elements is verified by means of the moving plate technique and each of the mentioned carriers. The best results are obtained with 4% In 2 O 3 , 6% AgCl and 5% NaF in a U 3 O 8 matrix. The sensitivities for some elements were extended to fractions of p.p.m. The precision, accuracy and acceptability of the method are calculated for all elements. The total error values as approximately in the range of 16-45% [pt

  1. At What Cost a Carrier?

    Science.gov (United States)

    2013-03-01

    unmanned aircra" – generally described as UCAVs , for “unmanned combat aerial vehicles” – as well as submarines in combination with long- range precision...means of operational e!ectiveness in the future. The Way Forward All these factors indicate that a turn toward UCAVs is long overdue. #e advent of...18 in accelerating the development and production of a UCAV that could operate both from large carriers and from smaller, less expensive, light

  2. 14 CFR 221.2 - Carrier's duty.

    Science.gov (United States)

    2010-01-01

    ... foreign air carrier from liability for violations of the statute, nor shall the filing of a tariff, or... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Carrier's duty. 221.2 Section 221.2... REGULATIONS TARIFFS General § 221.2 Carrier's duty. (a) Must file tariffs. (1) Except as provided in paragraph...

  3. 14 CFR 254.4 - Carrier liability.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Carrier liability. 254.4 Section 254.4... REGULATIONS DOMESTIC BAGGAGE LIABILITY § 254.4 Carrier liability. On any flight segment using large aircraft... large aircraft, an air carrier shall not limit its liability for provable direct or consequential...

  4. 14 CFR Section 04 - Air Carrier Groupings

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Air Carrier Groupings Section 04 Section 04 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS Section 04 Air Carrier Groupings (a) All large...

  5. 49 CFR 376.22 - Exemption for private carrier leasing and leasing between authorized carriers.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Exemption for private carrier leasing and leasing... MOTOR CARRIER SAFETY REGULATIONS LEASE AND INTERCHANGE OF VEHICLES Exemptions for the Leasing Regulations § 376.22 Exemption for private carrier leasing and leasing between authorized carriers. Regardless...

  6. Insulin Treatment May Alter Fatty Acid Carriers in Placentas from Gestational Diabetes Subjects.

    Science.gov (United States)

    Ruiz-Palacios, Maria; Prieto-Sánchez, Maria Teresa; Ruiz-Alcaraz, Antonio José; Blanco-Carnero, José Eliseo; Sanchez-Campillo, Maria; Parrilla, Juan José; Larqué, Elvira

    2017-06-06

    There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM.

  7. 76 FR 32390 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2011-06-06

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee (MCSAC) Meeting. SUMMARY...

  8. 77 FR 46555 - Motor Carrier Safety Advisory Committee: Public Meeting

    Science.gov (United States)

    2012-08-03

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee: Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of meeting of Motor Carrier Safety Advisory Committee (MCSAC...

  9. 75 FR 2923 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-01-19

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee Meeting. SUMMARY: FMCSA...

  10. 75 FR 29384 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-05-25

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2010-0143] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee meeting. SUMMARY: FMCSA...

  11. 75 FR 72863 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-11-26

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration, DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee Meeting. SUMMARY: FMCSA announces...

  12. 75 FR 50797 - Motor Carrier Safety Advisory Committee Public Meeting

    Science.gov (United States)

    2010-08-17

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2010-0143] Motor Carrier Safety Advisory Committee Public Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Motor Carrier Safety Advisory Committee Meeting. SUMMARY: FMCSA...

  13. Wuestite - a solar energy carrier

    Energy Technology Data Exchange (ETDEWEB)

    Weidenkaff, A.; Nueesch, P.; Wokaun, A. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Reller, A. [Hamburg Univ., Hamburg (Germany)

    1997-06-01

    Hydrogen is produced when Wuestite (Fe{sub 1-y}O) is oxidised by water. This reaction is part of a two-step thermochemical metal oxide cycle for the storage of solar energy in the form of chemical energy carriers, characterised by a high chemical potential. The reaction was studied in a tubular furnace with on-line gas analysis and further characterised in detail by DTA und high-temperature X-ray powder diffraction. The influence of non-stoichiometry, morphology and temperature on the mechanism and kinetics of the water-splitting reaction was determined. (author) 3 figs., tabs., 3 refs.

  14. Biocheese: A Food Probiotic Carrier

    Science.gov (United States)

    Castro, J. M.; Tornadijo, M. E.; Fresno, J. M.; Sandoval, H.

    2015-01-01

    This review describes some aspects related to the technological barriers encountered in the development and stability of probiotic cheeses. Aspects concerning the viability of probiotic cultures in this matrix are discussed and the potential of cheese as a biofunctional food carrier is analyzed, outlying some points related to health and safety. In general, the manufacture of probiotic cheese should have little change when compared with the elaboration of cheese in the traditional way. The physicochemical and technological parameters influencing the quality of these products have also to be measured so as to obtain a process optimization. PMID:25802862

  15. Solid phase carrier for radioimmuno analyses, as well as its manufacture and use

    International Nuclear Information System (INIS)

    Meriadec, B.; Roubertie, P.

    1979-01-01

    The solid phase carrier is in the form of a tablet containing freeze-dried protein-bonded gel, dicalcium phosphate and magnesium stearate. It is able to absorb 0.400 microlitre of an a solution containing antigen-antibody. When contacted with the solution, the tablet swells up and adapts to the shape of the column. The carrier is suitable for the TSH RIA test. (DG) [de

  16. Solute carrier transporters: potential targets for digestive system neoplasms.

    Science.gov (United States)

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

  17. Low-complexity Joint Sub-carrier Phase Noise Compensation for Digital Multi-carrier Systems

    DEFF Research Database (Denmark)

    Yankov, Metodi Plamenov; Barletta, Luca; Zibar, Darko

    2017-01-01

    Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM.......Joint sub-carrier phase noise processing is proposed which recovers the SNR penalty related to decreased sub-carrier baudrate w.r.t. single carrier systems. The method enables digital sub-banding to be safely employed for nonlinear mitigation for modulation formats of up to 256-QAM....

  18. Inert carriers for column extraction chromatography

    International Nuclear Information System (INIS)

    Katykhin, G.S.

    1978-01-01

    Inert carriers used in column extraction chromatography are reviewed. Such carriers are devided into two large groups: hydrophilic carriers which possess high surface energy and are well wetted only with strongly polar liquids (kieselguhrs, silica gels, glasses, cellulose, Al 2 O 3 ) and water-repellent carriers which possess low surface energy and are well wetted with various organic solvents (polyethylene, polytetrafluorethylene polytrifluorochlorethylene). Properties of various carriers are presented: structure, chemical and radiation stability, adsorption properties, extracting agent capacity. The effect of structure and sizes of particles on the efficiency of chromatography columns is considered. Ways of immovable phase deposition on the carrier and the latter's regeneration. Peculiarities of column packing for preparative and continuous chromatography are discussed

  19. Global Telecommunications Services: Strategies of Major Carriers

    OpenAIRE

    Jerry Mccreary; William R. Boulton; Chetan Sankar

    1993-01-01

    The globalization of telecommunications markets is of primary concern for today’s large telecommunications carriers. International business telecommunications is growing at a rate twice that of domestic traffic. Multi-national customers with offices around the world are demanding integrated solutions to their telecommunications needs. As telecommunication carriers respond to these customers’ needs, the carriers are beginning to expand outside their national boundaries. This paper identifi...

  20. Both Hemophilia Health Care Providers and Hemophilia A Carriers Report that Carriers have Excessive Bleeding

    Science.gov (United States)

    Paroskie, Allison; Oso, Olatunde; DeBaun, Michael R.; Sidonio, Robert F

    2014-01-01

    Introduction Hemophilia A, the result of reduced factor VIII (FVIII) activity, is an X-linked recessive bleeding disorder. Previous reports of Hemophilia A carriers suggest an increased bleeding tendency. Our objective was to determine the attitudes and understanding of the Hemophilia A carrier bleeding phenotype, and opinions regarding timing of carrier testing from the perspective of both medical providers and affected patients. Data from this survey was used as preliminary data for an ongoing prospective study. Material and Methods An electronic survey was distributed to physicians and nurses employed at Hemophilia Treatment Centers (HTC), and Hemophilia A carriers who were members of Hemophilia Federation of America. Questions focused on the clinical understanding of bleeding symptoms and management of Hemophilia A carriers, and the timing and intensity of carrier testing. Results Our survey indicates that 51% (36/51) of providers compared to 78% (36/46) of carriers believe that Hemophilia A carriers with normal FVIII activity have an increased bleeding tendency (pHemophilia A carriers report a high frequency of bleeding symptoms. Regarding carrier testing, 72% (50/69) of medical providers recommend testing after 14 years of age, conversely 65% (29/45) of Hemophilia A carriers prefer testing to be done prior to this age (pHemophilia A carriers self-report a higher frequency of bleeding than previously acknowledged, and have a preference for earlier testing to confirm carrier status. PMID:24309601

  1. Accesion number Protein name ENOA_MOUSE Alpha-enolase ...

    Indian Academy of Sciences (India)

    Sandra Feijoo Bandin

    Mitochondrial inner membrane protein. CMC1_MOUSE. Calcium-binding mitochondrial carrier protein Aralar1. CMC2_MOUSE. Calcium-binding mitochondrial carrier protein Aralar2. Biological process. Metabolic process. Glycolysis. Lipid metabolism. Respiratory electron transport chain. Others. Calcium ion homeostasis.

  2. Cyclodextrins in drug carrier systems.

    Science.gov (United States)

    Uekama, K; Otagiri, M

    1987-01-01

    One of the important characteristics of cyclodextrins is the formation of an inclusion complex with a variety of drug molecules in solution and in the solid state. As a consequence of intensive basic research, exhaustive toxic studies, and realization of industrial production during the past decade, there seem to be no more barriers for the practical application of natural cyclodextrins in the biomedical field. Recently, a number of cyclodextrin derivatives and cyclodextrin polymers have been prepared to obtain better inclusion abilities than parent cyclodextrins. The natural cyclodextrins and their synthetic derivatives have been successfully utilized to improve various drug properties, such as solubility, dissolution and release rates, stability, or bioavailability. In addition, the enhancement of drug activity, selective transfer, or the reduction of side effects has been achieved by means of inclusion complexation. The drug-cyclodextrin complex is generally formed outside of the body and, after administration, it dissociates, releasing the drug into the organism in a fast and nearly uniform manner. In the biomedical application of cyclodextrins, therefore, particular attention should be directed to the magnitude of the stability constant of the inclusion complex. In the case of parenteral application, a rather limited amount of work has been done because the cyclodextrins in the drug carrier systems have to be more effectively designed to compete with various biological components in the circulatory system. However, the works published thus far apparently indicate that the inclusion phenomena of cyclodextrin analogs may allow the rational design of drug formulation and that the combination of molecular encapsulation with other carrier systems will become a very effective and valuable method for the development of a new drug delivery system in the near future.

  3. Hydroxyapatite Nanoparticles as a Novel Gene Carrier

    Science.gov (United States)

    Zhu, S. H.; Huang, B. Y.; Zhou, K. C.; Huang, S. P.; Liu, F.; Li, Y. M.; Xue, Z. G.; Long, Z. G.

    2004-06-01

    Hydroxyapatite crystalline nanoparticles were created by a precipitation hydrothermal technique and the majority of crystal particles were in the size range of 40-60nm and exhibited a colloidal feature when suspended in water. The gastric cancer SGC-7901 cell line cells were cultivated in the presence of10-100 μg ml-1 hydroxyapatite nanoparticle suspension and verified by MTT evaluation for their biocompatibility in vitro. The agarose gel electrophoresis analysis demonstrated that the HA nanoparticles potentially adsorb the green fluorescence protein EGFP-N1 plasmid DNA at pH 2 and 7, but not at pH 12. The DNA-nanoparticle complexes transfected EGFP-N1 pDNA into SGC-7901 cells in vitro with the efficiency about 80% as referenced with Lipofectmine TM 2000. In vivo animal experiment revealed no acute toxic adverse effect 2weeks after tail vein injection into mice, and TEM examination demonstrated their biodistribution and expression within the cytoplasm and also a little in the nuclei of the liver, kidney and brain tissue cells. These results suggest that the HA nanoparticle is a promising material that can be used as gene carrier, vectors.

  4. Accesion number Protein name ENOA_MOUSE Alpha-enolase ...

    Indian Academy of Sciences (India)

    Sandra Feijoo Bandin

    binding mitochondrial carrier protein Aralar2. Biological process. Metabolic process. Glycolysis. Lipid metabolism. Respiratory electron transport chain. Others. Calcium ion homeostasis. Muscle contraction. Cellular component organization.

  5. Carrier-carrier relaxation kinetics in quantum well semiconductor structures with nonparabolic energy bands

    DEFF Research Database (Denmark)

    Dery, H.; Tromborg, Bjarne; Eisenstein, G.

    2003-01-01

    We describe carrier-carrier scattering dynamics in an inverted quantum well structure including the nonparabolic nature of the valance band. A solution of the semiconductor Bloch equations yields strong evidence to a large change in the temporal evolution of the carrier distributions compared...

  6. Providing resilience for carrier ethernet multicast traffic

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Wessing, Henrik; Zhang, Jiang

    2009-01-01

    This paper presents an overview of the Carrier Ethernet technology with specific focus on resilience. In particular, we detail how multicast traffic, which is essential for e.g. IPTV can be protected. We present Carrier Ethernet resilience methods for linear and ring networks and show by simulation...... that the availability of a multicast connection can be significantly increased by applying relevant resilience techniques....

  7. Driver citation/carrier data relationship project

    Science.gov (United States)

    1996-09-01

    The Driver/Carrier Relationship Project was commissioned to address three issues. The first was to determine if drivers of commercial motor vehicles get tickets at a different rate, depending on the carrier that they are working for. The second issue...

  8. Carrier multiplication in graphene under Landau quantization.

    Science.gov (United States)

    Wendler, Florian; Knorr, Andreas; Malic, Ermin

    2014-04-16

    Carrier multiplication is a many-particle process giving rise to the generation of multiple electron-hole pairs. This process holds the potential to increase the power conversion efficiency of photovoltaic devices. In graphene, carrier multiplication has been theoretically predicted and recently experimentally observed. However, due to the absence of a bandgap and competing phonon-induced electron-hole recombination, the extraction of charge carriers remains a substantial challenge. Here we present a new strategy to benefit from the gained charge carriers by introducing a Landau quantization that offers a tunable bandgap. Based on microscopic calculations within the framework of the density matrix formalism, we report a significant carrier multiplication in graphene under Landau quantization. Our calculations reveal a high tunability of the effect via externally accessible pump fluence, temperature and the strength of the magnetic field.

  9. Differential Analysis of the Nasal Microbiome of Pig Carriers or Non-Carriers of Staphylococcus aureus

    DEFF Research Database (Denmark)

    Espinosa-Gongora, Carmen; Larsen, Niels; Schonning, Kristian

    2016-01-01

    system. Carriers and non-carriers were selected on the basis of quantitative longitudinal data on S. aureus carriage in 600 pigs sampled at 20 Danish herds included in two previous studies in Denmark. Raw sequences were analysed with the BION meta package and the resulting abundance matrix was analysed...... using the DESeq2 package in R to identify operational taxonomic units (OTUs) with differential abundance between S. aureus carriers and non-carriers. Twenty OTUs were significantly associated to non-carriers, including species with known probiotic potential and antimicrobial effect such as lactic acid...

  10. 47 CFR 64.1140 - Carrier liability for slamming.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Carrier liability for slamming. 64.1140 Section... Providers § 64.1140 Carrier liability for slamming. (a) Carrier Liability for Charges. Any submitting... unauthorized carrier, the subscriber is absolved of liability for charges imposed by the unauthorized carrier...

  11. Rabies virus glycoprotein as a carrier for anthrax protective antigen

    International Nuclear Information System (INIS)

    Live viral vectors expressing foreign antigens have shown great promise as vaccines against viral diseases. However, safety concerns remain a major problem regarding the use of even highly attenuated viral vectors. Using the rabies virus (RV) envelope protein as a carrier molecule, we show here that inactivated RV particles can be utilized to present Bacillus anthracis protective antigen (PA) domain-4 in the viral membrane. In addition to the RV glycoprotein (G) transmembrane and cytoplasmic domains, a portion of the RV G ectodomain was required to express the chimeric RV G anthrax PA on the cell surface. The novel antigen was also efficiently incorporated into RV virions. Mice immunized with the inactivated recombinant RV virions exhibited seroconversion against both RV G and anthrax PA, and a second inoculation greatly increased these responses. These data demonstrate that a viral envelope protein can carry a bacterial protein and that a viral carrier can display whole polypeptides compared to the limited epitope presentation of previous viral systems

  12. Methanol as an energy carrier

    Energy Technology Data Exchange (ETDEWEB)

    Biedermann, P.; Grube, T.; Hoehlein, B. (eds.)

    2006-07-01

    For the future, a strongly growing energy demand is expected in the transport sector worldwide. Economically efficient oil production will run through a maximum in the next decade. Higher fuel prices and an environmentally desirable reduction of emissions will increase the pressure for reducing fuel consumption and emissions in road traffic. These criteria show the urgent necessity of structural changes in the fuel market. Due to its advantages concerning industrial-scale production, storage and global availability, methanol has the short- to medium-term potential for gaining increased significance as a substitution product in the energy market. Methanol can be produced both from fossil energy sources and from biomass or waste materials through the process steps of synthesis gas generation with subsequent methanol synthesis. Methanol has the potential to be used in an environmentally friendly manner in gasoline/methanol mixtures for flexible fuel vehicles with internal combustion engines and in diesel engines with pure methanol. Furthermore, it can be used in fuel cell vehicles with on-board hydrogen production in direct methanol fuel cell drives, and in stationary systems for electricity and heat generation as well as for hydrogen production. Finally, in portable applications it serves as an energy carrier for electric power generation. In this book, the processes for the production and use of methanol are presented and evaluated, markets and future options are discussed and issues of safety and environmental impacts are addressed by a team of well-known authors. (orig.)

  13. Hydrogen: the future energy carrier.

    Science.gov (United States)

    Züttel, Andreas; Remhof, Arndt; Borgschulte, Andreas; Friedrichs, Oliver

    2010-07-28

    Since the beginning of the twenty-first century the limitations of the fossil age with regard to the continuing growth of energy demand, the peaking mining rate of oil, the growing impact of CO2 emissions on the environment and the dependency of the economy in the industrialized world on the availability of fossil fuels became very obvious. A major change in the energy economy from fossil energy carriers to renewable energy fluxes is necessary. The main challenge is to efficiently convert renewable energy into electricity and the storage of electricity or the production of a synthetic fuel. Hydrogen is produced from water by electricity through an electrolyser. The storage of hydrogen in its molecular or atomic form is a materials challenge. Some hydrides are known to exhibit a hydrogen density comparable to oil; however, these hydrides require a sophisticated storage system. The system energy density is significantly smaller than the energy density of fossil fuels. An interesting alternative to the direct storage of hydrogen are synthetic hydrocarbons produced from hydrogen and CO2 extracted from the atmosphere. They are CO2 neutral and stored like fossil fuels. Conventional combustion engines and turbines can be used in order to convert the stored energy into work and heat.

  14. Optimal carrier frequency assignments for a two-carrier-level SCPS system

    Science.gov (United States)

    Vuong, X. T.; Forsey, R. J.

    A two-carrier-level SCPC system may occur in a star network where one master station (hub) with large G/T communicates with many remote stations with small G/T via one satellite transponder. By properly assigning the frequencies of carriers passing through the transponder, one can reduce and balance the relative intermodulation power levels falling into the SCPC channels. Through computer simulation, optimal carrier frequency assignments are found for four different criteria of optimality. The optimal assignments vary with respect to the difference in the two levels of carrier output power. All four criteria provide the conclusion that when the difference is around 3 dB, the assignment with small carriers stacked in the middle is best; and, when the difference is large (greater than 6 dB) the assignment with large carriers and small carriers alternated is best.

  15. Characterization of chicken riboflavin carrier protein gene structure ...

    Indian Academy of Sciences (India)

    Unknown

    described by Church and Gilbert (1984) and they were exposed to ... 3′ sequences of RCP cDNA were hybridized to these fragments to identify their relative orientation with respect to each other. The 7 kb fragment was found to contain the. 5′ region of .... berger and Deeley 1980; Wolffe and Tata 1983) and the apo very ...

  16. Nanodiamonds as Carriers for Address Delivery of Biologically Active Substances

    Directory of Open Access Journals (Sweden)

    Petunin AI

    2010-01-01

    Full Text Available Abstract Surface of detonation nanodiamonds was functionalized for the covalent attachment of immunoglobulin, and simultaneously bovine serum albumin and Rabbit Anti-Mouse Antibody. The nanodiamond-IgGI125 and RAM-nanodiamond-BSAI125 complexes are stable in blood serum and the immobilized proteins retain their biological activity. It was shown that the RAM-nanodiamond-BSAI125 complex is able to bind to the target antigen immobilized on the Sepharose 6B matrix through antibody–antigen interaction. The idea can be extended to use nanodiamonds as carriers for delivery of bioactive substances (i.e., drugs to various targets in vivo.

  17. Aptamers as Both Drugs and Drug-Carriers

    Directory of Open Access Journals (Sweden)

    Md. Ashrafuzzaman

    2014-01-01

    Full Text Available Aptamers are short nucleic acid oligos. They may serve as both drugs and drug-carriers. Their use as diagnostic tools is also evident. They can be generated using various experimental, theoretical, and computational techniques. The systematic evolution of ligands by exponential enrichment which uses iterative screening of nucleic acid libraries is a popular experimental technique. Theory inspired methodology entropy-based seed-and-grow strategy that designs aptamer templates to bind specifically to targets is another one. Aptamers are predicted to be highly useful in producing general drugs and theranostic drugs occasionally for certain diseases like cancer, Alzheimer’s disease, and so on. They bind to various targets like lipids, nucleic acids, proteins, small organic compounds, and even entire organisms. Aptamers may also serve as drug-carriers or nanoparticles helping drugs to get released in specific target regions. Due to better target specific physical binding properties aptamers cause less off-target toxicity effects. Therefore, search for aptamer based drugs, drug-carriers, and even diagnostic tools is expanding fast. The biophysical properties in relation to the target specific binding phenomena of aptamers, energetics behind the aptamer transport of drugs, and the consequent biological implications will be discussed. This review will open up avenues leading to novel drug discovery and drug delivery.

  18. Structures of Pseudomonas aeruginosa β-ketoacyl-(acyl-carrier-protein) synthase II (FabF) and a C164Q mutant provide templates for antibacterial drug discovery and identify a buried potassium ion and a ligand-binding site that is an artefact of the crystal form

    Energy Technology Data Exchange (ETDEWEB)

    Baum, Bernhard [Johannes Gutenberg-Universität, Staudinger Weg 5, 55128 Mainz (Germany); Lecker, Laura S. M.; Zoltner, Martin [University of Dundee, Dundee DD1 4EH, Scotland (United Kingdom); Jaenicke, Elmar [Johannes Gutenberg-Universität, Jakob Welder Weg 26, 55128 Mainz (Germany); Schnell, Robert [Karolinska Institutet, 17 177 Stockholm (Sweden); Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk [University of Dundee, Dundee DD1 4EH, Scotland (United Kingdom); Brenk, Ruth, E-mail: w.n.hunter@dundee.ac.uk [Johannes Gutenberg-Universität, Staudinger Weg 5, 55128 Mainz (Germany)

    2015-07-28

    Three crystal structures of recombinant P. aeruginosa FabF are reported: the apoenzyme, an active-site mutant and a complex with a fragment of a natural product inhibitor. The characterization provides reagents and new information to support antibacterial drug discovery. Bacterial infections remain a serious health concern, in particular causing life-threatening infections of hospitalized and immunocompromised patients. The situation is exacerbated by the rise in antibacterial drug resistance, and new treatments are urgently sought. In this endeavour, accurate structures of molecular targets can support early-stage drug discovery. Here, crystal structures, in three distinct forms, of recombinant Pseudomonas aeruginosa β-ketoacyl-(acyl-carrier-protein) synthase II (FabF) are presented. This enzyme, which is involved in fatty-acid biosynthesis, has been validated by genetic and chemical means as an antibiotic target in Gram-positive bacteria and represents a potential target in Gram-negative bacteria. The structures of apo FabF, of a C164Q mutant in which the binding site is altered to resemble the substrate-bound state and of a complex with 3-(benzoylamino)-2-hydroxybenzoic acid are reported. This compound mimics aspects of a known natural product inhibitor, platensimycin, and surprisingly was observed binding outside the active site, interacting with a symmetry-related molecule. An unusual feature is a completely buried potassium-binding site that was identified in all three structures. Comparisons suggest that this may represent a conserved structural feature of FabF relevant to fold stability. The new structures provide templates for structure-based ligand design and, together with the protocols and reagents, may underpin a target-based drug-discovery project for urgently needed antibacterials.

  19. Carrier testing for autosomal-recessive disorders.

    Science.gov (United States)

    Vallance, Hilary; Ford, Jason

    2003-08-01

    The aim of carrier testing is to identify carrier couples at risk of having offspring with a serious genetic (autosomal recessive) disorder. Carrier couples are offered genetic consultation where their reproductive options, including prenatal diagnosis, are explained. The Ashkenazi Jewish population is at increased risk for several recessively inherited disorders (Tay-Sachs disease, Cystic fibrosis, Canavan disease, Gaucher disease, Familial Dysautonomia, Niemann-Pick disease, Fanconi anemia, and Bloom syndrome). Unlike Tay-Sachs disease, there is no simple biochemical or enzymatic test to detect carriers for these other disorders. However, with the rapid identification of disease-causing genes in recent years, DNA-based assays are increasingly available for carrier detection. Approximately 5% of the world's population carries a mutation affecting the globin chains of the hemoglobin molecule. Among the most common of these disorders are the thalassemias. The global birth rate of affected infants is at least 2 per 1000 (in unscreened populations), with the greatest incidence in Southeast Asian, Indian, Mediterranean, and Middle Eastern ethnic groups. Carriers are detected by evaluation of red cell indices and morphology, followed by more sophisticated hematological testing and molecular analyses. The following issues need to be considered in the development of a carrier screening program: (1) test selection based on disease severity and test accuracy; (2) funding for testing and genetic counselling; (3) definition of the target population to be screened; (4) development of a public and professional education program; (5) informed consent for screening; and (6) awareness of community needs.

  20. Cardiolipin dynamics and binding to conserved residues in the mitochondrial ADP/ATP carrier.

    Science.gov (United States)

    Duncan, Anna L; Ruprecht, Jonathan J; Kunji, Edmund R S; Robinson, Alan J

    2018-01-31

    Cardiolipin in eukaryotes is found in the mitochondrial inner membrane, where it interacts with membrane proteins and, although not essential, is necessary for the optimal activity of a number of proteins. One of them is the mitochondrial ADP/ATP carrier, which imports ADP into the mitochondrion and exports ATP. In the crystal structures, cardiolipin is bound to three equivalent sites of the ADP/ATP carrier, but its role is unresolved. Conservation of residues at these cardiolipin binding sites across other members of the mitochondrial carrier superfamily indicates cardiolipin binding is likely to be important for the function of all mitochondrial carriers. Multiscale simulations were performed in a cardiolipin-containing membrane to investigate the dynamics of cardiolipin around the yeast and bovine ADP/ATP carriers in a lipid bilayer and the properties of the cardiolipin-binding sites. In coarse-grain simulations, cardiolipin molecules bound to the carriers for longer periods of time than phosphatidylcholine and phosphatidylethanolamine lipids-with timescales in the tens of microseconds. Three long-lived cardiolipin binding sites overlapped with those in the crystal structures of the carriers. Other shorter-lived cardiolipin interaction sites were identified in both membrane leaflets. However, the timescales of the interactions were of the same order as phosphatidylcholine and phosphatidylethanolamine, suggesting that these sites are not specific for cardiolipin binding. The calculation of lipid binding times and the overlap of the cardiolipin binding sites between the structures and simulations demonstrate the potential of multiscale simulations to investigate the dynamics and behavior of lipids interacting with membrane proteins. Copyright © 2018. Published by Elsevier B.V.

  1. Antiphospholipid antibodies in Brazilian hepatitis C virus carriers

    Directory of Open Access Journals (Sweden)

    A.M. Atta

    2008-06-01

    Full Text Available Hepatitis C, a worldwide viral infection, is an important health problem in Brazil. The virus causes chronic infection, provoking B lymphocyte dysfunction, as represented by cryoglobulinemia, non-organ-specific autoantibody production, and non-Hodgkin's lymphoma. The aim of this research was to screen for the presence of antiphospholipid autoantibodies in 109 Brazilian hepatitis C virus carriers without clinical history of antiphospholipid syndrome. Forty healthy individuals were used as the control group. IgA, IgG, and IgM antibodies against cardiolipin and β2-glycoprotein I were measured with an enzyme-linked immunosorbent assay, using a cut-off point of either 20 UPL or 20 SBU. While 24 (22.0% hepatitis C carriers had moderate titers of IgM anticardiolipin antibodies (median, 22.5 MPL; 95%CI: 21.5-25.4 MPL, only three carriers (<3% had IgG anticardiolipin antibodies (median, 23 GPL; 95%CI: 20.5-25.5 GPL. Furthermore, IgA anticardiolipin antibodies were not detected in these individuals. Male gender and IgM anticardiolipin seropositivity were associated in the hepatitis C group (P = 0.0004. IgA anti-β2-glycoprotein-I antibodies were detected in 29 of 109 (27.0% hepatitis C carriers (median, 41 SAU; 95%CI: 52.7-103.9 SAU. Twenty patients (18.0% had IgM anti-β2-glycoprotein I antibodies (median, 27.6 SMU; 95%CI: 23.3-70.3 SMU, while two patients had IgG antibodies against this protein (titers, 33 and 78 SGU. Antiphospholipid antibodies were detected in only one healthy individual, who was seropositive for IgM anticardiolipin. We concluded that Brazilian individuals chronically infected with hepatitis C virus present a significant production of antiphospholipid antibodies, mainly IgA anti-β2-glycoprotein I antibodies, which are not associated with clinical manifestations of antiphospholipid syndrome.

  2. High capacity carrier ethernet transport networks

    DEFF Research Database (Denmark)

    Rasmussen, Anders; Zhang, Jiang; Yu, Hao

    2009-01-01

    technology, making the use of Ethernet as a convergence layer for Next Generation Networks a distinct possibility. Triple Play services, in particular IPTV, are expected to be a main drivers for carrier Ethernet, however, a number of challenges must be addressed including QoS enabled control plane, enhanced...... OAM functions, survivability and the increased bandwidth requirements of carrier class systems. This article provides an overview of PBB-TE and T-MPLS and demonstrates how IPTV services can be realized in the framework of Carrier Ethernet. In addition we provide a case study on performing bit error...

  3. Spectroscopy of carrier multiplication in nanocrystals.

    Science.gov (United States)

    Bruhn, Benjamin; Limpens, Rens; Chung, Nguyen Xuan; Schall, Peter; Gregorkiewicz, Tom

    2016-02-08

    Carrier multiplication in nanostructures promises great improvements in a number of widely used technologies, among others photodetectors and solar cells. The decade since its discovery was ridden with fierce discussions about its true existence, magnitude, and mechanism. Here, we introduce a novel, purely spectroscopic approach for investigation of carrier multiplication in nanocrystals. Applying this method to silicon nanocrystals in an oxide matrix, we obtain an unambiguous spectral signature of the carrier multiplication process and reveal details of its size-dependent characteristics-energy threshold and efficiency. The proposed method is generally applicable and suitable for both solid state and colloidal samples, as well as for a great variety of different materials.

  4. Tunable carrier multiplication and cooling in graphene.

    Science.gov (United States)

    Johannsen, Jens Christian; Ulstrup, Søren; Crepaldi, Alberto; Cilento, Federico; Zacchigna, Michele; Miwa, Jill A; Cacho, Cephise; Chapman, Richard T; Springate, Emma; Fromm, Felix; Raidel, Christian; Seyller, Thomas; King, Phil D C; Parmigiani, Fulvio; Grioni, Marco; Hofmann, Philip

    2015-01-14

    Time- and angle-resolved photoemission measurements on two doped graphene samples displaying different doping levels reveal remarkable differences in the ultrafast dynamics of the hot carriers in the Dirac cone. In the more strongly (n-)doped graphene, we observe larger carrier multiplication factors (>3) and a significantly faster phonon-mediated cooling of the carriers back to equilibrium compared to in the less (p-)doped graphene. These results suggest that a careful tuning of the doping level allows for an effective manipulation of graphene's dynamical response to a photoexcitation.

  5. Air Carrier Financial Statistics : second quarter.

    Science.gov (United States)

    2013-01-01

    This report presents airline financial statistics obtained from carrier reports to DOT on BTS Form 41 financial schedules. Effective with a rule (ER-1297) adopted July 1982, the filing frequency for income statement and balance sheet data was changed...

  6. Air Carrier Financial Statistics : first quarter.

    Science.gov (United States)

    2010-01-01

    This report presents airline financial statistics obtained from carrier reports to DOT on BTS Form 41 financial schedules. Effective with a rule (ER-1297) adopted July 1982, the filing frequency for income statement and balance sheet data was changed...

  7. Air Carrier Financial Statistics : third quarter.

    Science.gov (United States)

    2010-01-01

    This report presents airline financial statistics obtained from carrier reports to DOT on BTS Form 41 financial schedules. Effective with a rule (ER-1297) adopted July 1982, the filing frequency for income statement and balance sheet data was changed...

  8. Air Carrier Financial Statistics : fourth quarter.

    Science.gov (United States)

    2012-01-01

    This report presents airline financial statistics obtained from carrier reports to DOT on BTS Form 41 financial schedules. Effective with a rule (ER-1297) adopted July 1982, the filing frequency for income statement and balance sheet data was changed...

  9. Maryland motor carrier program performance enhancement.

    Science.gov (United States)

    2014-02-01

    Using the inspection summary data (24-1 reports) from SHA for years 2006 to 2010 and inspection and violation : files of Motor Carrier Management Information System (MCMIS) for the same years, the Maryland State Police : (MSP) and Maryland Transporta...

  10. Auto Carrier Transporter Loading and Unloading Improvement

    National Research Council Canada - National Science Library

    Miller, Brian

    2003-01-01

    .... Any reduction in time and energy will result in a significant savings of money. The intent of this research is to develop an algorithm to solve the Auto Carrier Transport Pickup and Delivery Problem...

  11. Multiple sclerosis in an adrenoleukodystrophy carrier

    Directory of Open Access Journals (Sweden)

    Thomas Jenkins

    2011-11-01

    Full Text Available X-linked adrenoleukodystrophy (X-ALD is a rare inherited metabolic disorder, in which accumulation of very long chain fatty acids (VLCFAs results in damage to the central nervous system. As the disease is X-linked, males are affected severely, but female carriers may also present with neurological symptoms. We report the case of a young adult female, who presented with episodic sensorimotor symptoms. Although she was a heterozygous female carrier of X-ALD, subsequent investigations confirmed a diagnosis of multiple sclerosis (MS. To the best of our knowledge, this is the first reported case of a female X-ALD carrier in which the clinical features were more consistent with co-existent MS than ALD-related pathology. The case serves as a reminder that alternative, more common diagnoses should also be considered in carriers of rare neurological syndromes.

  12. What It Means to be a Carrier

    Science.gov (United States)

    ... begins the process with medical tests for any infectious diseases, RH type, thyroid and general health screening, etc. The egg donors go through their own screening, which includes hormone levels, genetic screening usually including FMR1 screening, and other carrier ...

  13. The Kinetics of Carrier Transport Inhibition

    DEFF Research Database (Denmark)

    Rosenberg, T.; Wilbrandt, Robert Walter

    1962-01-01

    The kinetical treatment of enzymatic carrier transports as given in previous communications has been extended to conditions of inhibition. Various possible types of inhibitors have been considered differing in the site of attack (enzyme or carrier), in the mode of action (competing...... and polyphloretinephosphate. The results of the analysis for these inhibitors indicate a substrate competitive mode of action. The effect of reversing the transport direction by interchanging the substrate concentration has been treated for the case of a non-penetrating substrate competitive inhibitor in the external medium...... with the substrate for the enzyme or the carrier or for both, competing with the carrier for the enzyme, or non-competitive) and in the ability of penetrating the membrane. Experiments are reported on the inhibition of glucose and fructose transport across the human red cell membrane by phlorizine, phloretine...

  14. China’s Aircraft Carrier Dilemma

    Science.gov (United States)

    2006-01-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing...When it comes to obtaining a working carrier, China has several options, but each largely limits what the carrier could be used for. Buying a big -deck...nothing developed from them. Empresa Nacional Bazán, which merged with Astilleros Españoles S.A. (AESA) to form Navantia in 2000, reportedly attempted

  15. 29 CFR 1202.13 - Air carriers.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Air carriers. 1202.13 Section 1202.13 Labor Regulations Relating to Labor (Continued) NATIONAL MEDIATION BOARD RULES OF PROCEDURE § 1202.13 Air carriers. By the terms of title II of the Railway Labor Act, which was approved April 10, 1936, all of title I, except section 3, which relates to the National...

  16. Protection switching for carrier ethernet multicast

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Wessing, Henrik; Berger, Michael Stübert

    2010-01-01

    This paper addresses network survivability for IPTV multicast transport in Carrier Ethernet networks. The impact of link failures is investigated and suggestions for intelligent multicast resilience schemes are proposed. In particular, functions of the multicast tree are integrated with the Carrier...... recovery path length, recovery time, number of branch nodes and operational complexity. The integrated approach therefore shows significant potential to increase the QoE for IPTV users in case of network failures and recovery actions....

  17. Evaluating multicast resilience in carrier ethernet

    DEFF Research Database (Denmark)

    Ruepp, Sarah Renée; Wessing, Henrik; Zhang, Jiang

    2010-01-01

    This paper gives an overview of the Carrier Ethernet technology with specific focus on resilience. In particular, we show how multicast traffic, which is essential for IPTV can be protected. We detail the ackground for resilience mechanisms and their control and e present Carrier Ethernet...... resilience methods for linear nd ring networks. By simulation we show that the vailability of a multicast connection can be significantly increased by applying protection methods....

  18. Sequence anatomy of mitochondrial anion carriers

    Czech Academy of Sciences Publication Activity Database

    Ježek, Petr; Ježek, Jan

    2003-01-01

    Roč. 534, 1-3 (2003), s. 15-25 ISSN 0014-5793 R&D Projects: GA AV ČR IAA5011106; GA ČR GA301/02/1215; GA MŠk ME 389 Institutional research plan: CEZ:AV0Z5011922 Keywords : mitochondrial anion carriers * carrier genomics * bioinformatics Subject RIV: CE - Biochemistry Impact factor: 3.609, year: 2003

  19. Preparative divergent flow IEF without carrier ampholytes for separation of complex biological samples

    Czech Academy of Sciences Publication Activity Database

    Šťastná, Miroslava; Šlais, Karel

    2010-01-01

    Roč. 31, č. 3 (2010), s. 433-439 ISSN 0173-0835 R&D Projects: GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : carrier-free divergent flow IEF * proteins * yeast lysate Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 3.569, year: 2010

  20. Increased Oxidative Damage in Carriers of the Germline TP53 p.R337H Mutation

    Science.gov (United States)

    Macedo, Gabriel S.; Lisbôa da Motta, Leonardo; Giacomazzi, Juliana; Netto, Cristina B. O.; Manfredini, Vanusa; S.Vanzin, Camila; Vargas, Carmen Regla; Hainaut, Pierre; Klamt, Fábio; Ashton-Prolla, Patricia

    2012-01-01

    Germline mutations in TP53 are the underlying defect of Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders characterized by predisposition to multiple early onset cancers. In Brazil, a variant form of LFS/LFL is commonly detected because of the high prevalence of a founder mutation at codon 337 in TP53 (p.R337H). The p53 protein exerts multiple roles in the regulation of oxidative metabolism and cellular anti-oxidant defense systems. Herein, we analyzed the redox parameters in blood samples from p.R337H mutation carriers (C, n = 17) and non-carriers (NC, n = 17). We identified a significant increase in erythrocyte GPx activity and in plasma carbonyl content,an indicator of protein oxidative damage, in mutation carriers compared to non-carriers (P = 0.048 and P = 0.035, respectively). Mutation carriers also showed a four-fold increase in plasma malondialdehyde levels, indicating increased lipid peroxidation (NC = 40.20±0.71, C = 160.5±0.88, P<0.0001). Finally, carriers showed increased total antioxidant status but a decrease in plasma ascorbic acid content. The observed imbalance could be associated with deregulated cell bioenergetics and/or with increased inflammatory stress, two effects that may result from loss of wild-type p53 function. These findings provide the first evidence that oxidative damage occurs in carriers of a germline TP53 mutation, and these may have important implications regarding our understanding of the mechanisms responsible for germline TP53 p.R337H mutation-associated carcinogenesis. PMID:23056559

  1. Differential Analysis of the Nasal Microbiome of Pig Carriers or Non-Carriers of Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Carmen Espinosa-Gongora

    Full Text Available Staphylococcus aureus is presently regarded as an emerging zoonotic agent due to the spread of specific methicillin-resistant S. aureus (MRSA clones in pig farms. Studying the microbiota can be useful for the identification of bacteria that antagonize such opportunistic veterinary and zoonotic pathogen in animal carriers. The aim of this study was to determine whether the nasal microbiome of pig S. aureus carriers differs from that of non-carriers. The V3-V5 region of the 16S rRNA gene was sequenced from nasal swabs of 44 S. aureus carriers and 56 non-carriers using the 454 GS FLX titanium system. Carriers and non-carriers were selected on the basis of quantitative longitudinal data on S. aureus carriage in 600 pigs sampled at 20 Danish herds included in two previous studies in Denmark. Raw sequences were analysed with the BION meta package and the resulting abundance matrix was analysed using the DESeq2 package in R to identify operational taxonomic units (OTUs with differential abundance between S. aureus carriers and non-carriers. Twenty OTUs were significantly associated to non-carriers, including species with known probiotic potential and antimicrobial effect such as lactic acid-producing isolates described among Leuconostoc spp. and some members of the Lachnospiraceae family, which is known for butyrate production. Further 5 OTUs were significantly associated to carriage, including known pathogenic bacteria such as Pasteurella multocida and Klebsiella spp. Our results show that the nasal microbiome of pigs that are not colonized with S. aureus harbours several species/taxa that are significantly less abundant in pig carriers, suggesting that the nasal microbiota may play a role in the individual predisposition to S. aureus nasal carriage in pigs. Further research is warranted to isolate these bacteria and assess their possible antagonistic effect on S. aureus for the pursuit of new strategies to control MRSA in pig farming.

  2. Performance of Uplink Carrier Aggregation in LTE-Advanced Systems

    DEFF Research Database (Denmark)

    Wang, Hua; Rosa, Claudio; Pedersen, Klaus

    2010-01-01

    Carrier aggregation (CA) has been proposed to aggregate two or more component carriers (CCs) to support a much wider transmission bandwidth for LTE-Advanced systems. With carrier aggregation, it is possible to schedule a user equipment (UE) on multiple component carriers simultaneously. In this p...

  3. Extracting hot carriers from photoexcited semiconductor nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Xiaoyang

    2014-12-10

    This research program addresses a fundamental question related to the use of nanomaterials in solar energy -- namely, whether semiconductor nanocrystals (NCs) can help surpass the efficiency limits, the so-called “Shockley-Queisser” limit, in conventional solar cells. In these cells, absorption of photons with energies above the semiconductor bandgap generates “hot” charge carriers that quickly “cool” to the band edges before they can be utilized to do work; this sets the solar cell efficiency at a limit of ~31%. If instead, all of the energy of the hot carriers could be captured, solar-to-electric power conversion efficiencies could be increased, theoretically, to as high as 66%. A potential route to capture this energy is to utilize semiconductor nanocrystals. In these materials, the quasi-continuous conduction and valence bands of the bulk semiconductor become discretized due to confinement of the charge carriers. Consequently, the energy spacing between the electronic levels can be much larger than the highest phonon frequency of the lattice, creating a “phonon bottleneck” wherein hot-carrier relaxation is possible via slower multiphonon emission. For example, hot-electron lifetimes as long as ~1 ns have been observed in NCs grown by molecular beam epitaxy. In colloidal NCs, long lifetimes have been demonstrated through careful design of the nanocrystal interfaces. Due to their ability to slow electronic relaxation, semiconductor NCs can in principle enable extraction of hot carriers before they cool to the band edges, leading to more efficient solar cells.

  4. Carbon: Hydrogen carrier or disappearing skeleton?

    International Nuclear Information System (INIS)

    De Jong, K.P.; Van Wechem, H.M.H.

    1994-01-01

    The use of liquid hydrocarbons as energy carriers implies the use of carbon as a carrier for hydrogen to facilitate hydrogen transport and storage. The current trend for liquid energy carriers used in the transport sector is to maximize the load of hydrogen on the carbon carrier. The recently developed Shell Middle Distillate Hydrogenation process for the manufacture of high quality diesel from aromatic refinery streams fits this picture. In the future, the hydrogen required to raise the product H/C ratio will be increasingly produced via gasification of large amounts of heavy residues. In the light of the strong preference towards using liquid fuels in the transport sector, the Shell Middle Distillate Synthesis process to convert natural gas into diesel of very high quality is discussed. Finally, a few comments on the use of hydrogen without a carbon carrier are made. Long lead times and the likelihood of producing the 'first' hydrogen from fossil fuel are highlighted. 13 figs., 6 tabs., 5 refs

  5. Carrier transport in layered nanolaminated carbides

    Science.gov (United States)

    Konar, Aniruddha; Pandey, Rajan K.; Ethirajan, Tamilmani

    2017-10-01

    This paper summarizes the ab-initio electronic and phonon band structures and the temperature-dependent carrier transport in layered Ti2AlC. It is found that the cylindrical Fermi surface is the origin of the anisotropic carrier effective mass (infinite effective mass along the c axis), which leads to a strong anisotropic (insulator along the c axis and metallic along the layer) carrier transport in these films. Using electronic and phonon band structure calculations, we have developed an analytical model for the carrier-phonon interaction and the in-plane carrier conductivity originating from the strong inter-valley (s → d) scattering in Ti2AlC. The density functional theory is used to calculate the average deformation potential corresponding to the acoustic phonon vibrations. The calculated deformation potential is in good agreement with the extracted deformation potential from the transport data available in the literature. The extracted deformation potential will be useful for predicting the transport quantities of these metals at elevated temperatures.

  6. Estimating motor carrier management information system crash file underreporting from carrier records : research brief.

    Science.gov (United States)

    2017-08-01

    This study estimated a significant amount of underreporting to the MCMIS crash file by the States, for the carriers who cooperated in the study. For the study carriers, it appears that the MCMIS file contained about 66 percent of their reportable cra...

  7. Estimating Motor Carrier Management Information System Crash File Underreporting from Carrier Records.

    Science.gov (United States)

    2017-08-01

    This FMCSA-sponsored research investigated the claim that motor carriers have a substantial number of crashes in their own records that are not contained in the Motor Carrier Management Information System (MCMIS) crash file. Based on the results of t...

  8. Natural carriers in bioremediation: A review

    Directory of Open Access Journals (Sweden)

    Anna Dzionek

    2016-09-01

    Full Text Available Bioremediation of contaminated groundwater or soil is currently the cheapest and the least harmful method of removing xenobiotics from the environment. Immobilization of microorganisms capable of degrading specific contaminants significantly promotes bioremediation processes, reduces their costs, and also allows for the multiple use of biocatalysts. Among the developed methods of immobilization, adsorption on the surface is the most common method in bioremediation, due to the simplicity of the procedure and its non-toxicity. The choice of carrier is an essential element for successful bioremediation. It is also important to consider the type of process (in situ or ex situ, type of pollution, and properties of immobilized microorganisms. For these reasons, the article summarizes recent scientific reports about the use of natural carriers in bioremediation, including efficiency, the impact of the carrier on microorganisms and contamination, and the nature of the conducted research.

  9. Hiding secret data into a carrier image

    Directory of Open Access Journals (Sweden)

    Ovidiu COSMA

    2012-06-01

    Full Text Available The object of steganography is embedding hidden information in an appropriate multimedia carrier, e.g., image, audio, or video. There are several known methods of solving this problem, which operate either in the space domain or in the frequency domain, and are distinguished by the following characteristics: payload, robustness and strength. The payload is the amount of secret data that can be embedded in the carrier without inducing suspicious artefacts, robustness indicates the degree in which the secret data is affected by the normal processing of the carrier e.g., compression, and the strength indicate how easy the presence of hidden data can be detected by steganalysis techniques. This paper presents a new method of hiding secret data into a digital image compressed by a technique based on the Discrete Wavelet Transform (DWT [2] and the Set Partitioning In Hierarchical Trees (SPIHT subband coding algorithm [6]. The proposed method admits huge payloads and has considerable strength.

  10. Development of radioisotope labeled polymeric carriers

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Jeong, Jea Min; Hwang, Hyun Jeong [Ewha Womans University, Seoul (Korea)

    2000-04-01

    This research was performed with the aim of developing polymeric radioisotope or drug carriers for obtaining efficient diagnostic therapeutic efficacy. As polymers, polyethylene oxides, polylactides, polycaprolactone were chosen to prepare the devices including micelle system, microemulsion, nanospheres. In addition, anticancer drug loaded polylactide microparticulates were fabricated as a regional chemotherapeutics for the treatment of cancer. Technetium or radioactive iodine was labeled to the polymeric carriers via ligands such as DTPA and HPP, respectively. Labeling efficiency was above 90% and stable enough up to 24 hours. Moreover, injected polymer carriers demonstrated higher blood maintenance and bone uptake than Tin colloid, a control. These results suggested that radioisotope carrying polymeric particulate are promising tools for diagnosing blood vessels or bones. Besides, anticancer drug loaded particulates demonstrated appropriate maintenance of therapeutic concentration and localization. Therefore it was proposed that this therapeutic system may be potential as a cancer therapy modality. 20 refs., 24 figs.,5 tabs. (Author)

  11. The Mimivirus Genome Encodes a Mitochondrial Carrier That Transports dATP and dTTP▿

    Science.gov (United States)

    Monné, Magnus; Robinson, Alan J.; Boes, Christoph; Harbour, Michael E.; Fearnley, Ian M.; Kunji, Edmund R. S.

    2007-01-01

    Members of the mitochondrial carrier family have been reported in eukaryotes only, where they transport metabolites and cofactors across the mitochondrial inner membrane to link the metabolic pathways of the cytosol and the matrix. The genome of the giant virus Mimiviridae mimivirus encodes a member of the mitochondrial carrier family of transport proteins. This viral protein has been expressed in Lactococcus lactis and is shown to transport dATP and dTTP. As the 1.2-Mb double-stranded DNA mimivirus genome is rich in A and T residues, we speculate that the virus is using this protein to target the host mitochondria as a source of deoxynucleotides for its replication. PMID:17229695

  12. Hot-carrier effects in MOS devices

    CERN Document Server

    Takeda, Eiji; Miura-Hamada, Akemi

    1995-01-01

    The exploding number of uses for ultrafast, ultrasmall integrated circuits has increased the importance of hot-carrier effects in manufacturing as well as for other technological applications. They are rapidly movingout of the research lab and into the real world.This book is derived from Dr. Takedas book in Japanese, Hot-Carrier Effects, (published in 1987 by Nikkei Business Publishers). However, the new book is much more than a translation. Takedas original work was a starting point for developing this much more complete and fundamental text on this increasingly important topic. The new work

  13. Effective Charge Carrier Utilization in Photocatalytic Conversions.

    Science.gov (United States)

    Zhang, Peng; Wang, Tuo; Chang, Xiaoxia; Gong, Jinlong

    2016-05-17

    Continuous efforts have been devoted to searching for sustainable energy resources to alleviate the upcoming energy crises. Among various types of new energy resources, solar energy has been considered as one of the most promising choices, since it is clean, sustainable, and safe. Moreover, solar energy is the most abundant renewable energy, with a total power of 173 000 terawatts striking Earth continuously. Conversion of solar energy into chemical energy, which could potentially provide continuous and flexible energy supplies, has been investigated extensively. However, the conversion efficiency is still relatively low since complicated physical, electrical, and chemical processes are involved. Therefore, carefully designed photocatalysts with a wide absorption range of solar illumination, a high conductivity for charge carriers, a small number of recombination centers, and fast surface reaction kinetics are required to achieve a high activity. This Account describes our recent efforts to enhance the utilization of charge carriers for semiconductor photocatalysts toward efficient solar-to-chemical energy conversion. During photocatalytic reactions, photogenerated electrons and holes are involved in complex processes to convert solar energy into chemical energy. The initial step is the generation of charge carriers in semiconductor photocatalysts, which could be enhanced by extending the light absorption range. Integration of plasmonic materials and introduction of self-dopants have been proved to be effective methods to improve the light absorption ability of photocatalysts to produce larger amounts of photogenerated charge carriers. Subsequently, the photogenerated electrons and holes migrate to the surface. Therefore, acceleration of the transport process can result in enhanced solar energy conversion efficiency. Different strategies such as morphology control and conductivity improvement have been demonstrated to achieve this goal. Fine-tuning of the

  14. Viruses - from pathogens to vaccine carriers.

    Science.gov (United States)

    Small, Juliana C; Ertl, Hildegund C J

    2011-10-01

    Vaccination is mankind's greatest public health success story. By now vaccines to many of the viruses that once caused fatal childhood diseases are routinely used throughout the world. Traditional methods of vaccine development through inactivation or attenuation of viruses have failed for some of the most deadly human pathogens, necessitating new approaches. Genetic modification of viruses not only allows for their attenuation but also for incorporation of sequences from other viruses, turning one pathogen into a vaccine carrier for another. Recombinant viruses have pros and cons as vaccine carriers, as discussed below using vectors based on adenovirus, herpesvirus, flavivirus, and rhabdovirus as examples.

  15. Low overhead slipless carrier phase estimation scheme.

    Science.gov (United States)

    Cheng, Haiquan; Li, Yan; Kong, Deming; Zang, Jizhao; Wu, Jian; Lin, Jintong

    2014-08-25

    Two slipless schemes are compared with application to single carrier 30 Gbaud quadrature phase shift keying (QPSK) system. An equivalent linewidth model considering the phase noise induced by both the laser linewidth and fiber nonlinearity is applied in the performance analysis. The simulation results show that it is possible to mitigate cycle slip (CS) using only 0.39% pilot overhead for the proposed blind carrier phase recovery (CPR) + pilot-symbols-aided phase unwrapping (PAPU) scheme within 1 dB signal-to-noise ratio (SNR) penalty limit at the bit error ratio (BER) of 10(-3) with 4 MHz equivalent linewidth.

  16. BISMUTH PHOSPHATE CARRIER PROCESS FOR Pu RECOVERY

    Science.gov (United States)

    Finzel, T.G.

    1959-02-01

    An improvement in the bismuth phosphate carrier precipitation process for recovering plutonium is described. It has been found that a more granular and more easily filterable carrier precipitiite is formed if the addition of the bismuth and phosphate ions is effected by first adding 9/10 of the bismuth ions necessary, then slowly adding all of the source of the phosphate ions to be incorporated in the precipitate, while digesting at 75 C and afterwards incorporating the remainder of the total bismuth ions necessary

  17. Line broadening caused by Coulomb carrier-carrier correlations and dynamics of carrier capture and emission in quantum dots

    DEFF Research Database (Denmark)

    Uskov, Alexander V; Magnúsdóttir, Ingibjörg; Tromborg, Bjarne

    2001-01-01

    Mechanisms of pure dephasing in quantum dots due to Coulomb correlations and the dynamics of carrier capture and emission are suggested, and a phenomenological model for the dephasing is developed. It is shown that, if the rates of these capture and emission processes are sufficiently high, signi...

  18. Biomedical applications of gold nanorod-based multifunctional nano-carriers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xin; Shao, Mingqian; Zhang, Song; Liu, Xinli, E-mail: vip.lxl@163.com [QiLu University of Technology, Shandong Provincial Key Laboratory of Microbial Engineering (China)

    2013-09-15

    Due to the good biocompatibility, ease of modification and unique optical properties, gold nanorods (AuNRs) have attracted more and more attentions in biomedical fields. In particular, through surface functionalization, AuNRs can be used as nano-carriers for drugs, probes, nucleic acids, and proteins in cancer treatment. In this review, we summarize the latest progress in biomedical applications of AuNRs-based nano-carriers including those in detection, biocatalysis, imaging, drug, and gene delivery. We also discuss the bioeffects of AuNRs such as in vivo distribution, translocation, localization, metabolism, and toxicity. Finally, we highlight some challenges in future biomedical applications of AuNRs-based nano-carriers.

  19. Biomedical applications of gold nanorod-based multifunctional nano-carriers

    International Nuclear Information System (INIS)

    Wang, Xin; Shao, Mingqian; Zhang, Song; Liu, Xinli

    2013-01-01

    Due to the good biocompatibility, ease of modification and unique optical properties, gold nanorods (AuNRs) have attracted more and more attentions in biomedical fields. In particular, through surface functionalization, AuNRs can be used as nano-carriers for drugs, probes, nucleic acids, and proteins in cancer treatment. In this review, we summarize the latest progress in biomedical applications of AuNRs-based nano-carriers including those in detection, biocatalysis, imaging, drug, and gene delivery. We also discuss the bioeffects of AuNRs such as in vivo distribution, translocation, localization, metabolism, and toxicity. Finally, we highlight some challenges in future biomedical applications of AuNRs-based nano-carriers

  20. Biomedical applications of gold nanorod-based multifunctional nano-carriers

    Science.gov (United States)

    Wang, Xin; Shao, Mingqian; Zhang, Song; Liu, Xinli

    2013-09-01

    Due to the good biocompatibility, ease of modification and unique optical properties, gold nanorods (AuNRs) have attracted more and more attentions in biomedical fields. In particular, through surface functionalization, AuNRs can be used as nano-carriers for drugs, probes, nucleic acids, and proteins in cancer treatment. In this review, we summarize the latest progress in biomedical applications of AuNRs-based nano-carriers including those in detection, biocatalysis, imaging, drug, and gene delivery. We also discuss the bioeffects of AuNRs such as in vivo distribution, translocation, localization, metabolism, and toxicity. Finally, we highlight some challenges in future biomedical applications of AuNRs-based nano-carriers.

  1. Solid state cloaking for electrical charge carrier mobility control

    Science.gov (United States)

    Zebarjadi, Mona; Liao, Bolin; Esfarjani, Keivan; Chen, Gang

    2015-07-07

    An electrical mobility-controlled material includes a solid state host material having a controllable Fermi energy level and electrical charge carriers with a charge carrier mobility. At least one Fermi level energy at which a peak in charge carrier mobility is to occur is prespecified for the host material. A plurality of particles are distributed in the host material, with at least one particle disposed with an effective mass and a radius that minimize scattering of the electrical charge carriers for the at least one prespecified Fermi level energy of peak charge carrier mobility. The minimized scattering of electrical charge carriers produces the peak charge carrier mobility only at the at least one prespecified Fermi level energy, set by the particle effective mass and radius, the charge carrier mobility being less than the peak charge carrier mobility at Fermi level energies other than the at least one prespecified Fermi level energy.

  2. A NEW SYNTHETIC FUNCTIONALIZED ANTIGEN CARRIER

    NARCIS (Netherlands)

    DRIJFHOUT, JW; BLOEMHOFF, W

    A new synthetic functionalized antigen carrier is described. It consists of a core of seven branched lysine residues, of which each of the four N-terminal lysine residues contains two N-(S-acetylmercaptoacetyl)-glutamyl residues. After removal of the protecting S-acetyl groups affording eight thiol

  3. Nuclear Submarines and Aircraft Carriers | Radiation ...

    Science.gov (United States)

    2017-08-07

    Nuclear submarines and aircraft carriers are powered by onboard nuclear reactors. Heat from the nuclear reaction makes the steam needed to power the submarine. When a nuclear vessel is taken out of service, its radioactive parts are disposed of and monitored.

  4. Air Carrier Industry Scheduled Service Traffic Stats.

    Science.gov (United States)

    2009-07-01

    Effective October 2002, the U.S. Department of Transportation (DOT) modified the T-100/T-100(f) Traffic Reporting System to remove the distinction between large and small aircraft. All U.S. certificated and commuter air carriers and all foreign air c...

  5. Physicochemical properties of nanostructured lipid carriers as ...

    African Journals Online (AJOL)

    The melting point depression of NLC80 was 5.71°C below bulk lipid's melting point (61.56°C), while NLC20 exhibited two melting points at 54.80 and 59.10°C. ... Key words: Nanostructured lipid carriers, colloidal delivery system, polysorbate 80, polysorbate 20, highpressure homogenization, physicochemical properties.

  6. Polyamidoamines as Drug Carriers: Synthesis of Polymers ...

    African Journals Online (AJOL)

    NJD

    The versatile polymerization of bisacrylamides with mono- and difunctional amines, first investigated and greatly expanded in. Ferruti's laboratory,1–3 is utilized in the present project for the synthesis of macromolecular drug carriers. Specifically, we report on the preparation of linear polyamidoamines possessing primary ...

  7. European regulatory framework for person carrier robots

    NARCIS (Netherlands)

    Fosch Villaronga, E.; Roig, A.

    The aim of this paper is to establish the grounds for a future regulatory framework for Person Carrier Robots, which includes legal and ethical aspects. Current industrial standards focus on physical human–robot interaction, i.e. on the prevention of harm. Current robot technology nonetheless

  8. Probing ultrafast carrier dynamics, nonlinear absorption and ...

    Indian Academy of Sciences (India)

    We investigate the relaxation dynamics of photogenerated carriers in silicon nanowires consisting of a crystalline core and a surrounding amorphous shell, using femtosecond time resolved differential reflectivity and transmission spectroscopy at 3.15 eV and 1.57 eV photon energies. The complex behaviour of the ...

  9. A new lubricant carrier for metal forming

    DEFF Research Database (Denmark)

    Arentoft, Mogens; Bay, Niels; Tang, Peter Torben

    2009-01-01

    A lubricant carrier for metal forming processes is developed. Surfaces with pores of micrometer size for entrapping lubricant are generated by electrochemical deposition of an alloy, consisting of two immiscible metals, of which one metal subsequently is etched away leaving 5 mu m layers with a s...... extrusion at high reduction and excessive stroke comparing with conventionally lubrication using phosphate coating and soap....

  10. Towards 100 gigabit carrier ethernet transport networks

    DEFF Research Database (Denmark)

    Rasmussen, Anders; Zhang, Jiang; Yu, Hao

    2010-01-01

    Ethernet as a transport technology has, up to now, lacked the features such as network layer architecture, customer separation and manageability that carriers require for wide-scale deployment. However, with the advent of PBB-TE and TMPLS, it is now possible to use Ethernet as a transport technol...

  11. Different nanocrystal systems for carrier multiplication

    NARCIS (Netherlands)

    Nguyen, X.C.

    2017-01-01

    Carrier multiplication is an important process which can enhance the efficiency of photovoltaic and electronic devices. To investigate this process, diverse experimental setups can be used; the thesis considers some particular artifacts which negatively impact the accuracy of the measurements, and

  12. Spectroscopy of carrier multiplication in nanocrystals

    NARCIS (Netherlands)

    Bruhn, B.; Limpens, R.; Chung, N.X.; Schall, P.; Gregorkiewicz, T.

    2016-01-01

    Carrier multiplication in nanostructures promises great improvements in a number of widely used technologies, among others photodetectors and solar cells. The decade since its discovery was ridden with fierce discussions about its true existence, magnitude, and mechanism. Here, we introduce a novel,

  13. Probing ultrafast carrier dynamics, nonlinear absorption and ...

    Indian Academy of Sciences (India)

    physics pp. 471–481. Probing ultrafast carrier dynamics, nonlinear absorption and refraction in core–shell silicon nanowires. SUNIL KUMAR1,∗, M KHORASANINEJAD2, M M ADACHI2,. K S KARIM2, S S SAINI2 and A K SOOD1. 1Department of Physics and Centre for Ultrafast Laser Applications, Indian Institute of Science,.

  14. Smart Carriers and Nanohealers: A Nanomedical Insight on Natural Polymers

    Directory of Open Access Journals (Sweden)

    Sreejith Raveendran

    2017-08-01

    Full Text Available Biodegradable polymers are popularly being used in an increasing number of fields in the past few decades. The popularity and favorability of these materials are due to their remarkable properties, enabling a wide range of applications and market requirements to be met. Polymer biodegradable systems are a promising arena of research for targeted and site-specific controlled drug delivery, for developing artificial limbs, 3D porous scaffolds for cellular regeneration or tissue engineering and biosensing applications. Several natural polymers have been identified, blended, functionalized and applied for designing nanoscaffolds and drug carriers as a prerequisite for enumerable bionano technological applications. Apart from these, natural polymers have been well studied and are widely used in material science and industrial fields. The present review explains the prominent features of commonly used natural polymers (polysaccharides and proteins in various nanomedical applications and reveals the current status of the polymer research in bionanotechnology and science sectors.

  15. Agricultural Commodity and Utility Carriers Hours of Service Exemption Analysis.

    Science.gov (United States)

    2010-05-01

    The study was conducted in two phases. Phase 1 compares the safety performance of agricultural and non-agricultural carriers for the period 2005 through 2008, and also examines two additional industries: livestock and utility carriers, whose operatio...

  16. 76 FR 6688 - Land Border Carrier Initiative Program

    Science.gov (United States)

    2011-02-08

    ... 142 Administrative Practice and Procedure, Canada, Computer technology (Line release), Common carriers... industry partnership program under which participating land and rail commercial carriers would agree to... smuggled into the United States. Because CBP has developed a more comprehensive voluntary industry...

  17. A new technique for measurement of carrier thallium

    International Nuclear Information System (INIS)

    Study, K.T.

    1982-01-01

    Manufacturers of thallium-201 use the Rhodamine-B spot test for detection of ''carrier'' or elemental thallium. A more exacting and simpler quantitative technique for measuring carrier thallium is described and this spectrophotofluorometric technique takes advantage of thallium's fluorescence

  18. Filamentous phage as an immunogenic carrier to elicit focused antibody responses against a synthetic peptide

    Science.gov (United States)

    van Houten, N.E.; Zwick, M.B.; Menendez, A.; Scott, J.K.

    2007-01-01

    Filamentous bacteriophage are widely used as immunogenic carriers for “phage-displayed” recombinant peptides. Here we report that they are an effective immunogenic carrier for synthetic peptides. The f1.K phage was engineered to have an additional Lys residue near the N-terminus of the major coat protein, pVIII, so as to enhance access to chemical cross-linking agents. The dimeric synthetic peptide, B2.1, was conjugated to f1.K (f1.K/B2.1) in high copy number and compared as an immunogen to B2.1 conjugated to ovalbumin (OVA/B2.1) and to phage-displayed, recombinant B2.1 peptide. All immunogens were administered without adjuvant. The serum antibody titers were measured against: the peptide, the carrier, and, if appropriate, the cross-linker. All immunogens elicited anti-peptide antibody titers, with those elicited by OVA/B2.1 exceeding those by f1.K/B2.1; both titers were greater than that elicited by recombinant B2.1 phage. Comparison of the anti-peptide and anti-carrier antibody responses showed that f1.K/B2.1 elicited a more focused anti-peptide antibody response than OVA/B2.1. The anti-peptide antibody response against f1.K/B2.1 was optimized for the injection route, dose and adjuvant. Dose and adjuvant did not have a significant effect on anti-peptide antibody titers, but a change in injection route from intraperitoneal (IP) to subcutaneous (SC) enhanced anti-peptide antibody titers after seven immunizations. The optimized anti-peptide antibody response exceeded the anti-carrier one by 21-fold, compared to 0.07-fold elicited by OVA/B2.1. This indicates that phage as a carrier can focus the antibody response against the peptide. The results are discussed with respect to the advantages of phage as an alternative to traditional carrier proteins for synthetic peptides, carbohydrates and haptens, and to further improvements in phage as immunogenic carriers. PMID:16488517

  19. Advanced carrier systems in cosmetics and cosmeceuticals: a review.

    Science.gov (United States)

    Li, Danhui; Wu, Zimei; Martini, Nataly; Wen, Jingyuan

    2011-01-01

    Carrier systems refer to carrier vesicles such as liposomes, nano/microparticles, emulsions, etc., that are coupled with active agents and applied to products to achieve the promoted effects of the active ingredients. This article reviews the recent research on carrier systems, focusing on cosmetic and cosmeceutical applications; the pros and cons of each carrier system and products on the market utilizing the technologies are discussed.

  20. Superconductivity in carrier-doped silicon carbide

    Directory of Open Access Journals (Sweden)

    Takahiro Muranaka, Yoshitake Kikuchi, Taku Yoshizawa, Naoki Shirakawa and Jun Akimitsu

    2008-01-01

    Full Text Available We report growth and characterization of heavily boron-doped 3C-SiC and 6H-SiC and Al-doped 3C-SiC. Both 3C-SiC:B and 6H-SiC:B reveal type-I superconductivity with a critical temperature Tc=1.5 K. On the other hand, Al-doped 3C-SiC (3C-SiC:Al shows type-II superconductivity with Tc=1.4 K. Both SiC:Al and SiC:B exhibit zero resistivity and diamagnetic susceptibility below Tc with effective hole-carrier concentration n higher than 1020 cm−3. We interpret the different superconducting behavior in carrier-doped p-type semiconductors SiC:Al, SiC:B, Si:B and C:B in terms of the different ionization energies of their acceptors.

  1. Competitive position of energy carriers in trade

    Energy Technology Data Exchange (ETDEWEB)

    Suding, P.H.; Forsbach, H.H.

    Industrial consumers and public institutions, which are classed with the group of minor consumers, differ in their behaviour in energy consumption greatly from the structure of the whole group. Also the willingness to convert from fuel oil to natural gas in these trade groups is relatively high. Within the framework of 5 model enterprises, the profitability of energy carriers and economizing technology in trade is analysed. The model enterprises are a bakery, a meat purveyor, a restaurant, a laundry and a hospital. The basic data are compared with the data from 1985. The comparison shows that the competitive positions of energy carriers in business and public in the process heat sector here not changed dramatically. The competitiveness of natural gas has improved since 1985 through the changes in price. However, in the sectors in which it belongs to the group of economical alternatives (e.g. in the bakeries), electricity has not lost much ground. (BR)

  2. Carrier molecules for use in veterinary vaccines.

    Science.gov (United States)

    Gerdts, Volker; Mutwiri, George; Richards, James; van Drunen Littel-van den Hurk, Sylvia; Potter, Andrew A

    2013-01-11

    The practice of immunization of animals and humans has been carried out for centuries and is generally accepted as the most cost effective and sustainable method of infectious disease control. Over the past 20 years there have been significant changes in our ability to produce antigens by conventional extraction and purification, recombinant DNA and synthesis. However, many of these products need to be combined with carrier molecules to generate optimal immune responses. This review covers selected topics in the development of carrier technologies for use in the veterinary vaccine field, including glycoconjugate and peptide vaccines, microparticle and nanoparticle formulations, and finally virus-like particles. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  3. Recovery of carrier-free gold-195

    International Nuclear Information System (INIS)

    Iofa, B.Z.; Ivanova, N.A.

    1995-01-01

    It is known that gold(III) is readily extracted from nitric acid solutions with ethers. The authors have studied extraction of trace amounts of gold(III) from nitric acid solutions with diethyl and diisopropyl ethers in the presence of significant excess of Pt(IV). Distribution coefficients of gold(III) were measured radiometrically using carrier-free gold-195 or spectrophotometrically in the presence of platinum(IV). Very high coefficients of gold separation from platinum may be achieved. Preliminary experiments have shown that zinc-65 was not extracted with ethers from nitric acid solutions. As an extraction system, the authors have chosen the system 10 M HNO 3 -diisopropyl ether. After model experiments, the authors have performed recovery of carrier-free gold-195 from a real platinum target irradiated with protons in a cyclotron

  4. DETECTION OF COMPLEXES OLIGODEOXYNUCLEOTIDES WITH POLYMERIC CARRIERS

    Directory of Open Access Journals (Sweden)

    V. V. Vlizlo

    2013-10-01

    Full Text Available The new method for detection of cationic oligoelectrolytes conjugates with oligodeoxyonucleotides, based on free diffusion of these substances in 0.8% agarose gels is developed. It enables to simplify and reduce the cost of visual identification of the best carrier among various polymer compounds and to uncover the fact of complex formation between the interacting agents resulting in formation of a ring precipitation. The universality of the proposed methodological approach is confirmed by interaction of coligodeoxynucleotides with other cationic polymer of natural origin, namely chitosan. Comparative analysis of our approach applicationto turbidimetry data concerning coligodeoxynucleotides complexes and their electrophoresis showed some advantages, among them are the ability to screen simultaneously a large number of polymeric carriers and no need for using of more expensive equipment and materials. To conclude the complexing occurrence it is enough nanomol amounts of oligodeoxynucleotide.

  5. Experimental distribution of entanglement with separable carriers

    Science.gov (United States)

    Fedrizzi, Alessandro; Zuppardo, Margherita; Gillett, Geoff; Broome, Matthew; de Almeida, Marcelo; Paternostro, Mauro; White, Andrew; Paterek, Tomasz

    2014-03-01

    Quantum networks will allow us to overcome distance limitations in quantum communication, and to share quantum computing tasks between remote quantum processors. The key requirement for quantum networking is the distribution of entanglement between nodes. Surprisingly, entanglement can be generated across a network without directly being communicated between nodes. In contrast to information gain, which cannot exceed the communicated information, the entanglement gain is bounded by the communicated quantum discord, a more general measure of quantum correlation that includes but is not limited to entanglement. Here we report an experiment in which two communicating parties who share three initially separable photonic qubits are entangled by exchange of a carrier photon that is not entangled with either party at all times. We show that distributing entanglement with separable carriers is resilient to noise and in some cases becomes the only way of distributing entanglement over noisy environments.

  6. Formic Acid as a Hydrogen Energy Carrier

    KAUST Repository

    Eppinger, Jorg

    2016-12-15

    The high volumetric capacity (S3 g H-2/L) and its low toxicity and flammability under ambient conditions make formic acid a promising hydrogen energy carrier. Particularly, in the past decade, significant advancements have been achieved in catalyst development for selective hydrogen generation from formic acid. This Perspective highlights the advantages of this approach with discussions focused on potential applications in the transportation sector together with analysis of technical requirements, limitations, and costs.

  7. A Multi-Carrier Scheduling Algorithm for LTE-Advanced

    DEFF Research Database (Denmark)

    Vulpe, Alexander; Mihovska, Albena D.; Prasad, Ramjee

    2013-01-01

    LTE-Advanced aims to provide a transmission bandwidth of 100 MHz by using Carrier Aggregation to aggregate LTE Rel. 8 carriers. In order to increase the system capacity, resource allocation becomes a very good tool, and, in the context of the existence of multiple Component Carriers in LTE-Advanc...

  8. 49 CFR 1150.22 - Exemptions and common carrier status.

    Science.gov (United States)

    2010-10-01

    ... the line itself, it will be considered a common carrier. However, when a State acquires a rail line... 49 Transportation 8 2010-10-01 2010-10-01 false Exemptions and common carrier status. 1150.22... common carrier status. The acquisition by a State of a fully abandoned line is not subject to the...

  9. 14 CFR 158.69 - Recordkeeping and auditing: Collecting carriers.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Recordkeeping and auditing: Collecting carriers. 158.69 Section 158.69 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF....69 Recordkeeping and auditing: Collecting carriers. (a) Collecting carriers shall establish and...

  10. 27 CFR 20.201 - Liability and responsibility of carrier.

    Science.gov (United States)

    2010-04-01

    ... Losses § 20.201 Liability and responsibility of carrier. (a) A person or carrier transporting specially... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Liability and responsibility of carrier. 20.201 Section 20.201 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  11. 27 CFR 22.121 - Liability and responsibility of carriers.

    Science.gov (United States)

    2010-04-01

    ... § 22.121 Liability and responsibility of carriers. (a) A person or carrier transporting tax-free... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Liability and responsibility of carriers. 22.121 Section 22.121 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX...

  12. Terahertz carrier dynamics in graphene and graphene nanostructures

    DEFF Research Database (Denmark)

    Jensen, Søren A.; Turchinovich, Dmitry; Tielrooij, Klaas Jan

    2014-01-01

    Photoexcited charge carriers in 2D graphene and in 1D graphene nanostructures were studied with optical pump-THz probe spectroscopy. We find efficient hot-carrier multiplication in 2D graphene, and predominantly free carrier early time response in 1D nanostructures. © 2014 OSA....

  13. 49 CFR 373.101 - Motor carrier bills of lading.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Motor carrier bills of lading. 373.101 Section 373.101 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS RECEIPTS AND...

  14. 49 CFR 397.67 - Motor carrier responsibility for routing.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Motor carrier responsibility for routing. 397.67 Section 397.67 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS...

  15. Junction depth measurement using carrier illumination

    International Nuclear Information System (INIS)

    Borden, Peter

    2001-01-01

    Carrier Illumination [trade mark] (CI) is a new method recently developed to meet the need for a non-destructive, high throughput junction depth measurement on patterned wafers. A laser beam creates a quasi-static excess carrier profile in the semiconductor underlying the activated junction. The excess carrier profile is fairly constant below the junction, and drops rapidly in the junction, creating a steep index of refraction gradient at the junction edge. Interference with light reflected from this index gradient provides a signal that is analyzed to determine the junction depth. The paper summarizes evaluation of performance in full NMOS and PMOS process flows, on both bare and patterned wafers. The aims have been to validate (1) performance in the presence of underlying layers typically found at the source/drain (S/D) process steps and (2) measurement on patterned wafers. Correlation of CI measurements to SIMS and transistor drive current are shown. The data were obtained from NMOS structures using As S/D and LDD implants. Correlations to SRP, SIMS and sheet resistance are shown for PMOS structures using B 11 LDD implants. Gage capability measurements are also presented

  16. Acoustic manipulation: Bessel beams and active carriers

    Science.gov (United States)

    Rajabi, Majid; Mojahed, Alireza

    2017-10-01

    In this paper, we address the interaction of zero-order acoustic Bessel beams as an acoustic manipulation tool, with an active spherical shell, as a carrier in drug, agent, or material delivery systems, in order to investigate the controllability of exerted acoustic radiation force as the driver. The active body is comprised of a spherical elastic shell stimulated in its monopole mode of vibrations with the same frequency as the incident wave field via an internally bonded and spatially uniformly excited piezoelectric actuator. The main aim of this work is to examine the performance of a nondiffracting and self-reconstructing zero-order Bessel beam to obtain the full manipulability condition of active carriers in comparison with the case of a plane wave field. The results unveil some unique potentials of the Bessel beams in the company of active carriers, with emphasis on the consumed power of the actuation system. This paper will widen the path toward the single-beam robust acoustic manipulation techniques and may lead to the prospect of combined tweezers and fields, with applications in delivery systems, microswimmers, and trapper designs.

  17. Biofilm carrier migration model describes reactor performance.

    Science.gov (United States)

    Boltz, Joshua P; Johnson, Bruce R; Takács, Imre; Daigger, Glen T; Morgenroth, Eberhard; Brockmann, Doris; Kovács, Róbert; Calhoun, Jason M; Choubert, Jean-Marc; Derlon, Nicolas

    2017-06-01

    The accuracy of a biofilm reactor model depends on the extent to which physical system conditions (particularly bulk-liquid hydrodynamics and their influence on biofilm dynamics) deviate from the ideal conditions upon which the model is based. It follows that an improved capacity to model a biofilm reactor does not necessarily rely on an improved biofilm model, but does rely on an improved mathematical description of the biofilm reactor and its components. Existing biofilm reactor models typically include a one-dimensional biofilm model, a process (biokinetic and stoichiometric) model, and a continuous flow stirred tank reactor (CFSTR) mass balance that [when organizing CFSTRs in series] creates a pseudo two-dimensional (2-D) model of bulk-liquid hydrodynamics approaching plug flow. In such a biofilm reactor model, the user-defined biofilm area is specified for each CFSTR; thereby, X carrier does not exit the boundaries of the CFSTR to which they are assigned or exchange boundaries with other CFSTRs in the series. The error introduced by this pseudo 2-D biofilm reactor modeling approach may adversely affect model results and limit model-user capacity to accurately calibrate a model. This paper presents a new sub-model that describes the migration of X carrier and associated biofilms, and evaluates the impact that X carrier migration and axial dispersion has on simulated system performance. Relevance of the new biofilm reactor model to engineering situations is discussed by applying it to known biofilm reactor types and operational conditions.

  18. Carrier Dynamics in Narrow Gap Ferromagnetic Semiconductors

    Science.gov (United States)

    Saha, D.; Pan, X.; Sanders, G. D.; Stanton, C. J.; Bhowmick, M.; Merritt, T.; Khodaparast, G. A.; Feeser, C.; Wessels, B. W.; McGill, S.

    2012-02-01

    Narrow gap ferromagnetic semiconductors are promising materials for spin photonic and spin transport devices because of their small effective masses, small energy gap, and high carrier mobility. We use time resolved differential transmission (TRDT) experiments to study carrier dynamics in ferromagnetic InMnAs and InMnSb. Electronic structure for InMnAs and InMnSb is calculated using an 8-band Pidgeon-Brown model generalized to include the effects of an external magnetic field. Our model includes the effects of the ferromagnetic Mn ions and their coupling to electrons and holes with or without an external magnetic field. Optical transitions are calculated from Fermi's Golden rule and interband transitions at a given pump or probe laser energy are identified. This allows us to understand a sign change seen in the TRDT. Our results show that 1) Phase-Space Filling, 2) Band Gap Renormalization and 3) Free Carrier Absorption all contribute to the TRDT and that the relative importance of these effects depends on the laser probe energy.

  19. Joint Iterative Carrier Synchronization and Signal Detection for Dual Carrier 448 Gb/s PDM 16-QAM

    DEFF Research Database (Denmark)

    Zibar, Darko; Carvalho, Luis; Estaran Tolosa, Jose Manuel

    2013-01-01

    Soft decision driven joint carrier synchronization and signal detection, employing expectation maximization, is experimentally demonstrated. Employing soft decisions offers an improvement of 0.5 dB compared to hard decision digital PLL based carrier synchronization and demodulation....

  20. Literature review of the passenger airline business models : Full service carrier, low-cost carrier and charter airlines

    NARCIS (Netherlands)

    Carmona Benitez, R.B.; Lodewijks, G.

    2008-01-01

    The deregulation and liberalization of the air transportation industry have developed three main passenger business models: full service carriers, low-cost carriers, and charter airlines. Deregulation removed regulated fares and routes increasing competition and yields. Airlines business models main

  1. The interaction of standard oxime reactivators with hemicholinium-3 sensitive choline carriers.

    Science.gov (United States)

    Soukup, O; Kristofikova, Z; Jun, D; Tambor, V; Ripova, D; Kuca, K

    2012-08-03

    Organophosphorus poisoning manifests as a cholinergic syndrome due to an inhibition of acetylcholinesterase. It is treated symptomatically by anticholinergics and oxime reactivators are used as causal antidotes. Reactivators possess a complex mechanism of action and interact at various levels of the cholinergic transmission. The aim of this study was to investigate the effect of standard oxime reactivators (HI-6, obidoxime, trimedoxime, methoxime and pralidoxime) on the hemicholinium-3 sensitive carriers, which are involved in the high-affinity choline uptake (HACU) transport, a key regulatory step in the synthesis of acetylcholine. The activity of the carriers was estimated in vitro on hippocampal synaptosomes using the substrate (3H)-choline and the competitive inhibitor (3H)-hemicholinium-3. Furthermore, the effect of the reactivators on the fluidity of hippocampal membranes was assessed. All tested compounds, except methoxime, showed an acute inhibitory effect on the carriers, however, only at μM concentrations. Trimedoxime showed the highest potency to inhibit HACU among all tested compounds (I(max) 62%, IC(50)=3 μM). All compounds, except HI-6, influenced also a membrane fluidity in the region of the hydrophilic heads of phospholipid bilayer, nevertheless, only methoxime was able to penetrate more deeply into the hydrocarbon core. We suggest that the direct interaction of oxime reactivators with the carrier protein (HI-6 and trimedoxime) and/or the changes in carrier conformation mediated by alterations in membrane fluidity (trimedoxime, obidoxime and pralidoxime) could occur here. The influence of reactivators on the carriers could be unfavorable in the case of their prolonged administration in vivo. From this point of view, the application of methoxime appears to be the best. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Thermal generation and mobility of charge carriers in collective proton transport in hydrogen-bonded chains

    Energy Technology Data Exchange (ETDEWEB)

    Peyrard, M.; Boesch, R.; Kourakis, I. (Dijon Univ., 21 (France). Faculte des Sciences)

    1991-01-01

    The transport of protons in hydrogen-bonded systems is a long standing problem which has not yet obtained a satisfactorily theoretical description. Although this problem was examined first for ice, it is relevant in many systems and in particular in biology for the transport along proteins or for proton conductance across membranes, an essential process in cell life. The broad relevance makes the study of proton conduction very appealing. Since the original work of Bernal and Fowler on ice, the idea that the transport occurs through chains of hydrogen bonds has been well accepted. Such proton wires'' were invoked by Nagle and Morowitz for proton transport across membranes proteins and more recently across lipid bilayers. In this report, we assume the existence of such an hydrogen-bonded chain and discuss its consequences on the dynamics of the charge carriers. We show that this assumption leads naturally to the idea of soliton transport and we put a special emphasis on the role of the coupling between the protons and heavy ions motions. The model is presented. We show how the coupling affects strongly the dynamics of the charge carriers and we discuss the role it plays in the thermal generation of carriers. The work presented has been performed in 1986 and 87 with St. Pnevmatikos and N. Flyzanis and was then completed in collaboration with D. Hochstrasser and H. Buettner. Therefore the results presented in this part are not new but we think that they are appropriate in the context of this multidisciplinary workshop because they provide a rather complete example of the soliton picture for proton conduction. This paper discusses the thermal generation of the charge carriers when the coupling between the protons and heavy ions dynamics is taken into account. The results presented in this part are very recent and will deserve further analysis but they already show that the coupling can assist for the formation of the charge carriers.

  3. Mitochondrial glutamate carriers from Drosophila melanogaster: biochemical, evolutionary and modeling studies.

    Science.gov (United States)

    Lunetti, Paola; Cappello, Anna Rita; Marsano, René Massimiliano; Pierri, Ciro Leonardo; Carrisi, Chiara; Martello, Emanuela; Caggese, Corrado; Dolce, Vincenza; Capobianco, Loredana

    2013-10-01

    The mitochondrial carriers are members of a family of transport proteins that mediate solute transport across the inner mitochondrial membrane. Two isoforms of the glutamate carriers, GC1 and GC2 (encoded by the SLC25A22 and SLC25A18 genes, respectively), have been identified in humans. Two independent mutations in SLC25A22 are associated with severe epileptic encephalopathy. In the present study we show that two genes (CG18347 and CG12201) phylogenetically related to the human GC encoding genes are present in the D. melanogaster genome. We have functionally characterized the proteins encoded by CG18347 and CG12201, designated as DmGC1p and DmGC2p respectively, by overexpression in Escherichia coli and reconstitution into liposomes. Their transport properties demonstrate that DmGC1p and DmGC2p both catalyze the transport of glutamate across the inner mitochondrial membrane. Computational approaches have been used in order to highlight residues of DmGC1p and DmGC2p involved in substrate binding. Furthermore, gene expression analysis during development and in various adult tissues reveals that CG18347 is ubiquitously expressed in all examined D. melanogaster tissues, while the expression of CG12201 is strongly testis-biased. Finally, we identified mitochondrial glutamate carrier orthologs in 49 eukaryotic species in order to attempt the reconstruction of the evolutionary history of the glutamate carrier function. Comparison of the exon/intron structure and other key features of the analyzed orthologs suggests that eukaryotic glutamate carrier genes descend from an intron-rich ancestral gene already present in the common ancestor of lineages that diverged as early as bilateria and radiata. © 2013.

  4. Carrier dynamics in graphene. Ultrafast many-particle phenomena

    Energy Technology Data Exchange (ETDEWEB)

    Malic, E.; Brem, S.; Jago, R. [Department of Physics, Chalmers University of Technology, Goeteborg (Sweden); Winzer, T.; Wendler, F.; Knorr, A. [Institut fuer Theoretische Physik, Technische Universitaet Berlin (Germany); Mittendorff, M.; Koenig-Otto, J.C.; Schneider, H.; Helm, M.; Winnerl, S. [Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Ploetzing, T.; Neumaier, D. [Advanced Microelectronic Center Aachen, AMO GmbH, Aachen (Germany)

    2017-11-15

    Graphene is an ideal material to study fundamental Coulomb- and phonon-induced carrier scattering processes. Its remarkable gapless and linear band structure opens up new carrier relaxation channels. In particular, Auger scattering bridging the valence and the conduction band changes the number of charge carriers and gives rise to a significant carrier multiplication - an ultrafast many-particle phenomenon that is promising for the design of highly efficient photodetectors. Furthermore, the vanishing density of states at the Dirac point combined with ultrafast phonon-induced intraband scattering results in an accumulation of carriers and a population inversion suggesting the design of graphene-based terahertz lasers. Here, we review our work on the ultrafast carrier dynamics in graphene and Landau-quantized graphene is presented providing a microscopic view on the appearance of carrier multiplication and population inversion. (copyright 2017 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Composite Biomaterial as a Carrier for Bone-Active Substances for Metaphyseal Tibial Bone Defect Reconstruction in Rats

    DEFF Research Database (Denmark)

    Horstmann, Peter Frederik; Raina, Deepak Bushan; Isaksson, Hanna

    2017-01-01

    /hydroxyapatite biomaterial (GBM) could serve as a carrier for local delivery of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA) in a tibia defect model in rats. Empty and allograft-filled defects were used as controls. A 3 × 4-mm metaphyseal bone defect was created in the proximal tibia, and the rats were...

  6. A divergent ADP/ATP carrier in the hydrogenosomes of Trichomonas gallinae argues for an independent origin of these organelles.

    NARCIS (Netherlands)

    Tjaden, J.; Haferkamp, I.; Boxma, B.; Tielens, A.G.; Huynen, M.A.; Hackstein, J.H.P.

    2004-01-01

    The evolution of mitochondrial ADP and ATP exchanging proteins (AACs) highlights a key event in the evolution of the eukaryotic cell, as ATP exporting carriers were indispensable in establishing the role of mitochondria as ATP-generating cellular organelles. Hydrogenosomes, i.e. ATP- and

  7. Carrier Load Balancing and Packet Scheduling for Multi-Carrier Systems

    DEFF Research Database (Denmark)

    Wang, Yuanye; Pedersen, Klaus; Sørensen, Troels Bundgaard

    2010-01-01

    allocation fairness among users, as compared to independent scheduling per CC. The Long Term Evolution (LTE)-Advanced is selected for the case study of a multi-carrier system. In such a system, RR provides better performance than MH balancing, and the proposed simple scheduling algorithm is shown......Abstract-In this paper we focus on resource allocation for next generation wireless communication systems with aggregation of multiple Component Carriers (CCs), i.e., how to assign the CCs to each user, and how to multiplex multiple users in each CC. We first investigate two carrier load balancing...... methods for allocating the CCs to the users- Round Robin (RR) and Mobile Hashing (MH) balancing by means of a simple theoretical formulation, as well as system level simulations. At Layer-2 we propose a simple cross-CC packet scheduling algorithm that improves the coverage performance and the resource...

  8. 78 FR 5243 - Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting of Subcommittees

    Science.gov (United States)

    2013-01-24

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Meeting of Subcommittees AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of meeting of Motor Carrier Safety...

  9. 76 FR 5424 - Motor Carrier Safety Advisory Committee; Request for Nominations

    Science.gov (United States)

    2011-01-31

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee; Request for Nominations AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Request for Nominations to the Motor Carrier Safety Advisory...

  10. How Europe's Low-Cost Carriers Sidestepped Traditional Carriers' Competitive Advantages

    DEFF Research Database (Denmark)

    Hvass, Kristian Anders

    The initial appearance of U.S. low-cost carriers forced incumbents to create new forms of competitive advantage. These were successful hindrances for nearly two decades. Concurrently, incumbents in Europe implemented similar tools, although within a regulated market. However, Europe's low...... and sidestepped traditional carriers' competitive advantages.......-cost airlines were more successful and had a greater initial impact in their early years than their U.S. compatriots. This paper will attempt to highlight some of the differences between the two markets and explain why European low-cost airlines had more advantages following their market deregulation...

  11. Dedicated Carrier Deployment in Heterogeneous Networks with Inter-site Carrier Aggregation

    DEFF Research Database (Denmark)

    Wang, Hua; Rosa, Claudio; Pedersen, Klaus I.

    2013-01-01

    Heterogeneous networks (HetNets) have been extensively discussed in 3GPP to further enhance the system throughput of traditional well-planned macrocell deployment. In this paper, we consider a HetNet scenario consisting of macro eNBs and low-power nodes implemented as remote radio heads (RRHs......) or picos with dedicated carrier deployment. Collaborative inter-site carrier aggregation (CA) is proposed in scenarios with macro+RRH deployment to make an efficient use of the fragmented spectrum from multiple cells. While in scenarios with macro+pico deployment, UEs can only connect to either...

  12. Carrier-Multiplication-Induced Structural Change during Ultrafast Carrier Relaxation and Nonthermal Phase Transition in Semiconductors.

    Science.gov (United States)

    Bang, Junhyeok; Sun, Y Y; Liu, X-Q; Gao, F; Zhang, S B

    2016-09-16

    While being extensively studied as an important physical process to alter exciton population in nanostructures at the fs time scale, carrier multiplication has not been considered seriously as a major mechanism for phase transition. Real-time time-dependent density functional theory study of Ge_{2}Sb_{2}Te_{5} reveals that carrier multiplication can induce an ultrafast phase transition in the solid state despite that the lattice remains cold. The results also unify the experimental findings in other semiconductors for which the explanation remains to be the 30-year old phenomenological plasma annealing model.

  13. The underexposed role of food matrices in probiotic products: Reviewing the relationship between carrier matrices and product parameters.

    Science.gov (United States)

    Flach, Joost; van der Waal, Mark B; van den Nieuwboer, Maurits; Claassen, Eric; Larsen, Olaf F A

    2017-06-13

    Probiotic microorganisms are increasingly incorporated into food matrices in order to confer proposed health benefits on the consumer. It is important that the health benefits, sensory properties, shelf-life and probiotic gastrointestinal tract (GIT) survival of these products are carefully balanced as they determine functionality and drive consumer acceptance. The strain-specific effects of probiotic species are imperative in this process but carrier matrices may play a pivotal role as well. This study therefore recapitulates the wealth of knowledge on carrier matrices and their interaction with probiotic strains. The most substantiated carrier matrices, factors that influence probiotic functionality and matrix effects on shelf-life, GIT survival and clinical efficacy are reviewed. Results indicate that carrier matrices have a significant impact on the quality of probiotic products. Matrix components, such as proteins, carbohydrates and flavoring agents are shown to alter probiotic efficacy and viability. In vivo studies furthermore revealed strain-dependent matrix effects on the GIT survival of probiotic bacteria. However, only a limited number of studies have specifically addressed the effects of carrier matrices on the aforementioned product-parameters; most studies seem to focus solely on the strain-specific effects of probiotic microorganisms. This hampers the innovation of probiotic products. More human studies, comparing not only different probiotic strains but different carrier matrices as well, are needed to drive the innovation cycle.

  14. Drug delivery to the kidneys and the bladder with the low molecular weight protein lysozyme

    NARCIS (Netherlands)

    Kok, Robbert J.; Haas, Marijke; Moolenaar, Frits; de Zeeuw, Dick; Meijer, Dirk K.F.

    1998-01-01

    The low molecular weight protein (LMWP) lysozyme is a suitable drug carrier for renal drug targeting. When the tubular reabsorption of a can be prevented, the protein will be excreted in the urine. In this way, lysozyme (LZM) conjugates might also be used as carriers for targeting to the urinary

  15. Drug delivery to the kidneys and the bladder with the low molecular weight protein lysozyme

    NARCIS (Netherlands)

    Kok, RJ; Haas, M; Moolenaar, F; de Zeeuw, D; Meijer, DKF

    1998-01-01

    The low molecular weight protein (LMWP) lysozyme is a suitable drug carrier for renal drug targeting. When the tubular reabsorption of a LMWP can be prevented, the protein will be excreted in the urine. In this way lysozyme (LZM) conjugates might also be used as carriers for targeting to the urinary

  16. Hydrogen, an energy carrier with a future

    International Nuclear Information System (INIS)

    Zimmer, K.H.

    1975-01-01

    The inefficient use, associated with pollutants, of the fossil energy carriers coal, crude oil and natural gas, will deplete resources, if the energy demand increases exponentially, in the not-too-distant future. That is the reason why the hydrogen-energy concept gains in importance. This requires drastic changes in structure in a lot of technological fields. This task is only to be mastered if there is cooperation between all special fields, in order to facilitate the economical production, distribution and utilization of hydrogen. (orig.) [de

  17. Carrier concentration induced ferromagnetism in semiconductors

    International Nuclear Information System (INIS)

    Story, T.

    2007-01-01

    In semiconductor spintronics the key materials issue concerns ferromagnetic semiconductors that would, in particular, permit an integration (in a single multilayer heterostructure) of standard electronic functions of semiconductors with magnetic memory function. Although classical semiconductor materials, such as Si or GaAs, are nonmagnetic, upon substitutional incorporation of magnetic ions (typically of a few atomic percents of Mn 2+ ions) and very heavy doping with conducting carriers (at the level of 10 20 - 10 21 cm -3 ) a ferromagnetic transition can be induced in such diluted magnetic semiconductors (also known as semimagnetic semiconductors). In the lecture the spectacular experimental observations of carrier concentration induced ferromagnetism will be discussed for three model semiconductor crystals. p - Ga 1-x Mn x As currently the most actively studied and most perspective ferromagnetic semiconductor of III-V group, in which ferromagnetism appears due to Mn ions providing both local magnetic moments and acting as acceptor centers. p - Sn 1-x Mn x Te and p - Ge 1-x Mn x Te classical diluted magnetic semiconductors of IV-VI group, in which paramagnet-ferromagnet and ferromagnet-spin glass transitions are found for very high hole concentration. n - Eu 1-x Gd x Te mixed magnetic crystals, in which the substitution of Gd 3+ ions for Eu 2+ ions creates very high electron concentration and transforms antiferromagnetic EuTe (insulating compound) into ferromagnetic n-type semiconductor alloy. For each of these materials systems the key physical features will be discussed concerning: local magnetic moments formation, magnetic phase diagram as a function of magnetic ions and carrier concentration as well as Curie temperature and magnetic anisotropy engineering. Various theoretical models proposed to explain the effect of carrier concentration induced ferromagnetism in semiconductors will be briefly discussed involving mean field approaches based on Zener and RKKY

  18. Carrier mobilities in microcrystalline silicon films

    International Nuclear Information System (INIS)

    Bronger, T.; Carius, R.

    2007-01-01

    For a better understanding of electronic transport mechanisms in thin-film silicon solar cell quality films, we have investigated the Hall mobility for electrons in microcrystalline/amorphous silicon over a range of crystallinities and doping concentrations. We find that Hall mobility increases with increasing doping concentration in accordance with earlier measurements. With increasing amorphous fraction, the measured mobility decreases suggesting a negative influence of the additional disorder. The results suggest a differential mobility model in which mobility depends on the energy level of the carriers that contribute to the electrical current

  19. An improved microculture-hemolytic spot assay for the study of carrier-specific antibody responses.

    Science.gov (United States)

    Kotkes, P; Weisman, Z; Mozes, E; Bentwich, Z

    1984-11-30

    A microculture system based on limiting dilution and a hemolytic spot assay was adapted for study of the carrier-specific anti-hapten response in vitro. Spleen or lymph node cells from normal mice or mice immunized with NIP-ovalbumin (NIP-OVA) or NIP-human thyroglobulin (NIP-Tg) were cultured for 5 days by the microculture technique. The anti-hapten (anti-NIP) response was measured by assaying the supernatants of the microcultures in a hemolytic spot test with NIP coupled to sheep red blood cells. A micro-ELISA reader was adapted to read the degree of lysis in the spot assay which gives an objective quantitation of the degree of lysis and thus reduces the number of culture replicates. In vivo induced specific helper cells in mice immunized with the carrier protein, human thyroglobulin, as well as carrier-specific T cell factors, gave rise to carrier-specific anti-NIP responses. The microculture system may enhance the expression of T-cell helper function when suppressor cells or their precursors are present in the initial cell preparation.

  20. Carrier-carrier scattering in the gain dynamics of InxGa1-xAs/AlyGa1-yAs diode lasers

    DEFF Research Database (Denmark)

    Sanders, Gary D; Sun, C.-K.; Golubovic, B.

    1996-01-01

    for the carrier distributions using an adaptive Runge-Kutta routine. This procedure is less computationally intensive than a full Monte Carlo simulation. The results show that the inclusion of carrier-carrier scattering improves previous results where only carrier-phonon scattering was included and that carrier...

  1. Radionuclide carriers for targeting of cancer

    Directory of Open Access Journals (Sweden)

    Stavroula Sofou

    2008-06-01

    Full Text Available Stavroula SofouLaboratory for Drug Delivery Systems, Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic University, Brooklyn, NY, USAAbstract: This review describes strategies for the delivery of therapeutic radionuclides to tumor sites. Therapeutic approaches are summarized in terms of tumor location in the body, and tumor morphology. These determine the radionuclides of choice for suggested targeting ligands, and the type of delivery carriers. This review is not exhaustive in examples of radionuclide carriers for targeted cancer therapy. Our purpose is two-fold: to give an integrated picture of the general strategies and molecular constructs currently explored for the delivery of therapeutic radionuclides, and to identify challenges that need to be addressed. Internal radiotherapies for targeting of cancer are at a very exciting and creative stage. It is expected that the current emphasis on multidisciplinary approaches for exploring such therapeutic directions should enable internal radiotherapy to reach its full potential.Keywords: cancer radiotherapy, targeted radiotherapy, radiotherapy of micrometastases, radiotherapy of solid tumors, radiotherapy of tumor vasculature

  2. Pathways to hydrogen as an energy carrier.

    Science.gov (United States)

    Sigfusson, Thorsteinn I

    2007-04-15

    When hydrogen is used as an alternative energy carrier, it is very important to understand the pathway from the primary energy source to the final use of the carrier. This involves, for example, the understanding of greenhouse gas emissions associated with the production of hydrogen and throughout the lifecycle of a given utilization pathway as well as various energy or exergy efficiencies and aspects involved. This paper which is based on a talk given at the Royal Society in London assesses and reviews the various production pathways for hydrogen with emphasis on emissions, energy use and energy efficiency. The paper also views some aspects of the breaking of the water molecule and examines some new emerging physical evidence which could pave the way to a new and more feasible pathway. A special attention will be given to the use of the renewable energy pathway. As an example of a hydrogen society that could be based on renewable primary energy, the paper describes the hydrogen society experiments in Iceland as well as unconventional hydrogen obtained from geothermal gases. In the light of our experience, attempts will be made to shed light upon drivers as well as obstacles in the development of a hydrogen society.

  3. Efficient Carrier Multiplication in Colloidal Silicon Nanorods.

    Science.gov (United States)

    Stolle, Carl Jackson; Lu, Xiaotang; Yu, Yixuan; Schaller, Richard D; Korgel, Brian A

    2017-09-13

    Auger recombination lifetimes, absorption cross sections, and the quantum yields of carrier multiplication (CM), or multiexciton generation (MEG), were determined for solvent-dispersed silicon (Si) nanorods using transient absorption spectroscopy (TAS). Nanorods with an average diameter of 7.5 nm and aspect ratios of 6.1, 19.3, and 33.2 were examined. Colloidal Si nanocrystals of similar diameters were also studied for comparison. The nanocrystals and nanorods were passivated with organic ligands by hydrosilylation to prevent surface oxidation and limit the effects of surface trapping of photoexcited carriers. All samples used in the study exhibited relatively efficient photoluminescence. The Auger lifetimes increased with nanorod length, and the nanorods exhibited higher CM quantum yield and efficiency than the nanocrystals with a similar band gap energy E g . Beyond a critical length, the CM quantum yield decreases. Nanorods with the aspect ratio of 19.3 had the highest CM quantum yield of 1.6 ± 0.2 at 2.9E g , which corresponded to a multiexciton yield that was twice as high as observed for the spherical nanocrystals.

  4. Drug carrier in cancer therapy: A simulation study based on magnetic carrier substances

    Science.gov (United States)

    Adam, Tijjani; Dhahi, Th S.; Mohammed, Mohammed; Hashim, U.; Noriman, N. Z.; Dahham, Omar S.

    2017-09-01

    The principle of magnetic carrier is a medium for transferring information by sending the drug to the specific part to kill tumor cells. Generally, there are seven stages of cancer. Most of the patient with cancer can only be detected when reaches stage four. At that stage, the cancer is difficult to destroy or to cure. Comparing to the nearly stage, there are probability to destroy tumor cell completely by sending the drug through magnetic carrier directly to nerve. Another way to destroyed tumor completely is by using Deoxyribonucleic acid (DNA). This project is about the simulation study based on magnetic carrier substances. The COMSOL multiphysic software is used in this project. The simulation model represents a permanent magnet, blood vessel, surrounding tissues and air in 2D. Based on result obtained, the graph shown during sending the magnetic flux is high. However, as its carry information the magnetic flux reducess from the above, the move from 0m until 0.009 m it become the lowers and start increase the flux from this until maximum at 0.018m. This is due the fact that carrier start to increase after because the low information is gradually reduce until 0.018m.

  5. 14 CFR 399.82 - Passing off of carrier identity by affiliation between carriers.

    Science.gov (United States)

    2010-01-01

    ... of the other within the meaning of section 408 of the Act; (3) Has any of the interlocking relationships described in section 409 of the Act; (4) Is jointly controlled with the other carrier, directly or..., express, and cargo transportation; airport transportation and hotel accommodations; local advertising and...

  6. Features of charge carrier transport determined from carrier extraction current in .mu.c-Si:H

    Czech Academy of Sciences Publication Activity Database

    Juška, G.; Arlauskas, K.; Nekrašas, N.; Stuchlík, Jiří; Niquille, X.; Wyrsch, N.

    299-302, - (2002), s. 375-379 ISSN 0022-3093 Grant - others:VMSF(LT) 01SP-02 Institutional research plan: CEZ:AV0Z1010914 Keywords : mobility of majority carriers * photoconductivity transport Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.435, year: 2002

  7. A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

    Science.gov (United States)

    Triggs-Raine, B. L.; Mules, E. H.; Kaback, M. M.; Lim-Steele, J. S. T.; Dowling, C. E.; Akerman, B. R.; Natowicz, M. R.; Grebner, E. E.; Navon, R.; Welch, J. P.; Greenberg, C. R.; Thomas, G. H.; Gravel, R. A.

    1992-01-01

    Deficiency of β-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. We analyzed the HEXA gene of one pseudodeficient subject and identified both a C739-to-T substitution that changes Arg247→Trp on one allele and a previously identified Tay-Sachs disease mutation on the second allele. Six additional pseudodeficient subjects were found to have the C739-to-T mutation. This allele accounted for 32% (20/62) of non-Jewish enzyme-defined Tay-Sachs disease carriers but for none of 36 Jewish enzyme-defined carriers who did not have one of three known mutations common to this group. The C739-to-T allele, together with a “true” Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C739-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses. ImagesFigure 1Figure 2Figure 3 PMID:1384323

  8. BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast.

    Science.gov (United States)

    Sanchis, D; Fleury, C; Chomiki, N; Goubern, M; Huang, Q; Neverova, M; Grégoire, F; Easlick, J; Raimbault, S; Lévi-Meyrueis, C; Miroux, B; Collins, S; Seldin, M; Richard, D; Warden, C; Bouillaud, F; Ricquier, D

    1998-12-18

    We report here the cloning and functional analysis of a novel homologue of the mitochondrial carriers predominantly expressed in the central nervous system and referred to as BMCP1 (brain mitochondrial carrier protein-1). The predicted amino acid sequence of this novel mitochondrial carrier indicates a level of identity of 39, 31, or 30%, toward the mitochondrial oxoglutarate carrier, phosphate carrier, or adenine nucleotide translocator, respectively, and a level of identity of 34, 38, or 39% with the mitochondrial uncoupling proteins UCP1, UCP2, or UCP3, respectively. Northern analysis of mouse, rat, or human tissues demonstrated that mRNA of this novel gene is mainly expressed in brain, although it is 10-30-fold less expressed in other tissues. In situ hybridization analysis of brain showed it is particularly abundant in cortex, hippocampus, thalamus, amygdala, and hypothalamus. Chromosomal mapping indicates that BMCP1 is located on chromosome X of mice and at Xq24 in man. Expression of the protein in yeast strongly impaired growth rate. Analysis of respiration of total recombinant yeast or yeast spheroplasts and in particular of the relationship between respiratory rate and membrane potential of yeast spheroplasts revealed a marked uncoupling activity of respiration, suggesting that although BMCP1 sequence is more distant from the uncoupling proteins (UCPs), this protein could be a fourth member of the UCP family.

  9. Identification of immunogenic Salmonella enterica serotype Typhi antigens expressed in chronic biliary carriers of S. Typhi in Kathmandu, Nepal.

    Directory of Open Access Journals (Sweden)

    Richelle C Charles

    Full Text Available Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT, to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479, an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70% chronic carriers, 0 of 8 bile culture-negative controls (0%, 0 of 8 healthy Bangladeshis (0%, and 1 of 8 (12.5% Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic

  10. Protein Foods

    Science.gov (United States)

    ... Text Size: A A A Listen En Español Protein Foods Foods high in protein such as fish, ... for the vegetarian proteins, whether they have carbohydrate. Protein Choices Plant-Based Proteins Plant-based protein foods ...

  11. [Recent progress of dry powder inhalation of proteins and peptides].

    Science.gov (United States)

    Zhou, Jie-yu; Zhang, Lan; Mao, Shi-rui

    2015-07-01

    To provide theoretical and practical basis for the successful formulation design of physically-mixed inhalation dry powder of proteins and peptides, related references were collected, analyzed and summarized. In this review drug micronization technology and commonly used carriers for inhalation dry powder preparation were introduced. For proteins and peptides, supercritical fluid technology and spray-drying are more suitable because of their capabilities of keeping drug activity. Being approved by U. S. Food and Drug Administration, lactose has been extensively used as carriers in many inhalation products. Formulation and process factors influencing drug deposition in the lung, including carrier properties, drug-carrier ratio, blending order, mixing methods, mixing time and the interaction between drug and carrier, were elucidated. The size, shape and surface properties of carries all influence the interaction between drug and carrier. Besides, influence of micromeritic properties of the dry powder, such as particle size, shape, density, flowability, charge, dispersibility and hygroscopicity, on drug deposition in the lung was elaborated. Among these particle size plays the most crucial role in particle deposition in the lung. Moreover, based on the mechanisms of powder dispersity, some strategies to improve drug lung deposition were put forward, such as adding carrier fines, adding adhesive-controlling materials and reprocessing micronized drug. In order to design physically-mixed inhalation dry powder for proteins and peptides with high lung deposition, it is essential to study drug-carriers interactions systematically and illustrate the potential influence of formulation, process parameters and micromeritic properties of the powder.

  12. Hydrophobic nano-carrier for lysozyme adsorption

    Indian Academy of Sciences (India)

    phobic interaction chromatography' to describe the separation of proteins adsorbed onto hydrophobic medium by salts [19]. HIC is based on the interaction between hydrophobic ligand carrying support material and hydrophobic amino acids bear- ing non-polar regions of protein surface [20]. The main driv- ing force for this ...

  13. Carrier's Liability Insurance in the Function of Transportation Service Quality

    Directory of Open Access Journals (Sweden)

    Dragica Dalić

    2008-01-01

    Full Text Available The quality of transportation se1vices understands quickness,accuracy and safety at minimal costs for the carrier andthe service user. Possible emergency situations may bring substantialmaterial and business damage both to the service userand to the transportation service provider. Carrier's liability insurancegives the carrier security in case of evidenced full orpartial loss or damage of goods, as well as in case of delay in delivery.The insurance allows annulment of carrier's costs generatedby emergency situations which favourably affects the operationof transportation companies and allows maintenance ofthe quality of the carrier's se1vices. The work analyses the presenceof can·ier's liability insurance in the Republic of Croatia atfive insurance companies, through the analysis of the totalnumber of insurances and the number of insured vehicles, followingthe trend in this type of insurance and its influence onthe quality of the carrier services.

  14. Carrier tracking by smoothing filter improves symbol SNR

    Science.gov (United States)

    Pomalaza-Raez, Carlos A.; Hurd, William J.

    1986-01-01

    The potential benefit of using a smoothing filter to estimate carrier phase over use of phase locked loops (PLL) is determined. Numerical results are presented for the performance of three possible configurations of the deep space network advanced receiver. These are residual carrier PLL, sideband aided residual carrier PLL, and finally sideband aiding with a Kalman smoother. The average symbol signal to noise ratio (SNR) after losses due to carrier phase estimation error is computed for different total power SNRs, symbol rates and symbol SNRs. It is found that smoothing is most beneficial for low symbol SNRs and low symbol rates. Smoothing gains up to 0.4 dB over a sideband aided residual carrier PLL, and the combined benefit of smoothing and sideband aiding relative to a residual carrier loop is often in excess of 1 dB.

  15. Carrier tracking by smoothing filter can improve symbol SNR

    Science.gov (United States)

    Hurd, W. J.; Pomalaza-Raez, C. A.

    1985-01-01

    The potential benefit of using a smoothing filter to estimate carrier phase over use of phase locked loops (PLL) is determined. Numerical results are presented for the performance of three possible configurations of the deep space network advanced receiver. These are residual carrier PLL, sideband aided residual carrier PLL, and finally sideband aiding with a Kalman smoother. The average symbol signal to noise ratio (CNR) after losses due to carrier phase estimation error is computed for different total power SNRs, symbol rates and symbol SNRs. It is found that smoothing is most beneficial for low symbol SNRs and low symbol rates. Smoothing gains up to 0.4 dB over a sideband aided residual carrier PLL, and the combined benefit of smoothing and sideband aiding relative to a residual carrier loop is often in excess of 1 dB.

  16. Computer assisted analysis of hand radiographs in infantile hypophosphatasia carriers

    International Nuclear Information System (INIS)

    Chodirker, B.N.; Greenberg, C.R.; Manitoba Univ., Winnipeg, MB; Roy, D.; Cheang, M.; Evans, J.A.; Manitoba Univ., Winnipeg, MB; Manitoba Univ., Winnipeg, MB; Reed, M.H.; Manitoba Univ., Winnipeg, MB

    1991-01-01

    Hand radiographs of 49 carriers of infantile hypophosphatasia and 67 non-carriers were evaluated using two Apple IIe Computer Programs and Apple Graphics Tablet. CAMPS was used to determine the bone lengths and calculate the metacarpophalangeal profiles. A newly developed program (ADAM) was used to determine bone density based on percent cortical area of the second metacarpal. Carriers of infantile hypophosphatasia had significantly less dense bones. (orig.)

  17. Suspended biofilm carrier and activated sludge removal of acidic pharmaceuticals

    DEFF Research Database (Denmark)

    Falås, Per; Baillon-Dhumez, Aude; Andersen, Henrik Rasmus

    2012-01-01

    Removal of seven active pharmaceutical substances (ibuprofen, ketoprofen, naproxen, diclofenac, clofibric acid, mefenamic acid, and gemfibrozil) was assessed by batch experiments, with suspended biofilm carriers and activated sludge from several full-scale wastewater treatment plants. A distinct...... and attached solids for the carriers) of diclofenac, ketoprofen, gemfibrozil, clofibric acid and mefenamic acid compared to the sludges. Among the target pharmaceuticals, only ibuprofen and naproxen showed similar removal rates per unit biomass for the sludges and biofilm carriers. In contrast...

  18. Insight into carrier lifetime impact on band-modulation devices

    Science.gov (United States)

    Parihar, Mukta Singh; Lee, Kyung Hwa; Park, Hyung Jin; Lacord, Joris; Martinie, Sébastien; Barbé, Jean-Charles; Xu, Yue; El Dirani, Hassan; Taur, Yuan; Cristoloveanu, Sorin; Bawedin, Maryline

    2018-05-01

    A systematic study to model and characterize the band-modulation Z2-FET device is developed bringing light to the relevance of the carrier lifetime influence. This work provides guidelines to optimize the Z2-FETs for sharp switching, ESD protection, and 1T-DRAM applications. Lower carrier lifetime in the Z2-FET helps in attaining the sharp switch. We provide new insights into the correlation between generation/recombination, diffusion, electrostatic barriers and carrier lifetime.

  19. Carrier Statistics and Quantum Capacitance Models of Graphene Nanoscroll

    Directory of Open Access Journals (Sweden)

    M. Khaledian

    2014-01-01

    schematic perfect scroll-like Archimedes spiral. The DOS model was derived at first, while it was later applied to compute the carrier concentration and quantum capacitance model. Furthermore, the carrier concentration and quantum capacitance were modeled for both degenerate and nondegenerate regimes, along with examining the effect of structural parameters and chirality number on the density of state and carrier concentration. Latterly, the temperature effect on the quantum capacitance was studied too.

  20. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Juan P de Macêdo

    2015-05-01

    Full Text Available Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug

  1. 48 CFR 1615.470 - Carrier investment of FEHB funds.

    Science.gov (United States)

    2010-10-01

    ... FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Contract Pricing 1615.470 Carrier investment of FEHB funds. (a) Except for...

  2. Obstacle avoidance and path planning for carrier aircraft launching

    Directory of Open Access Journals (Sweden)

    Wu Yu

    2015-06-01

    Full Text Available Launching safety and efficiency are important indexes to measure the fighting capacity of carrier. The study on path planning for taxi of carrier aircraft launching under actual deck environment is of great significance. In actual deck scheduling, manual command is applied to taxi of carrier aircraft, which has negative effects on the safety of staff and carrier aircraft launching. In consideration of both the safety and efficiency of carrier aircraft launching, the key elements of the problem are abstracted based on the analysis of deck environment, carrier aircraft maneuver performance and task requirements. According to the problem description, the mathematical model is established including various constraints. The carrier aircraft and the obstacles are reasonably simplified as circle and polygons respectively. What’s more, the proposed collision detection model reduces the calculations. Aimed at the features of model, the theory of model predictive control (MPC is applied to the path search. Then a dynamic weight heuristic function is designed and a dynamic multistep optimization algorithm is proposed. Taking the Nimitz-class aircraft carrier as an example, the paths from parking place to catapult are planned, which indicate the rationality of the model and the effectiveness of the algorithm by comparing the planning results under different simulation environments. The main contribution of research is the establishment of obstacle avoidance and path planning model. In addition, it provides the solution of model and technological foundations for comprehensive command and real-time decision-making of the carrier aircraft.

  3. Block division carrier slot setting for satellite SCPC systems

    Science.gov (United States)

    Yashima, Hiroyuki; Sasase, Iwao; Mori, Shinsaku

    1991-01-01

    A carrier slot setting plan is proposed to reduce intermodulation (IM) effects for satellite single-channel-per-carrier (SCPC) systems. Carrier slots are divided into blocks and slight frequency gaps are set among blocks. This setting introduces frequency offset between the center frequencies of carrier slots and the center frequencies of the IM components. A method of deriving optimum division in order to derive the upper bound of improvement of the C/IM ratio in the worst channel is developed. The results show that the setting plan achieves significant improvement of IM effects at a cost of only slight bandwidth expansion, even in fully loaded SCPC systems.

  4. Carrier-mediated transport of peptides by the kidney

    International Nuclear Information System (INIS)

    Skopicki, H.A.

    1988-01-01

    Small peptide transport was characterized to determine if: (1) Multiple carriers are present in the luminal membrane of renal proximal tubular cells; (2) Carrier-mediated peptide transport is limited by size; and (3) Gentamicin inhibits carrier-mediated reabsorption of peptides. Uptake of glycyl-[ 3 H]proline (Gly-Pro) into renal brush border membrane vesicles demonstrated a dual affinity carrier system. Whether multiple carriers are present was further investigated by characterizing the uptake of [ 3 H]pyroglutamyl-histidine. To determine if carrier-mediated transport of peptides is limited by size of the molecule, uptake of the hydrolytically resistant tripeptide, [ 3 H]pryroglutamyl-histidyl-tryptophan (pGlu-His-Trp), and tetrapeptide, [ 3 H]pyroglutamyl-histidyl-tryptophyl-serine (pGlu-His-Trp-Ser) were assessed. These data indicate: multiple carriers exist on the luminal membrane of renal proximal tubular cells for the transport of dipeptides, and tripeptide pGlu-His-Trp and the tetrapeptide pGlu-His-Trp-Ser are not taken up by a carrier-mediated mechanism, suggesting that the carrier may be limited by the size of the substrate

  5. Nonlinear gain suppression in semiconductor lasers due to carrier heating

    International Nuclear Information System (INIS)

    Willatzen, M.; Uskov, A.; Moerk, J.; Olesen, H.; Tromborg, B.; Jauho, A.P.

    1991-01-01

    We present a simple model for carrier heating in semiconductor lasers, from which the temperature dynamics of the electron and hole distributions can be calculated. Analytical expressions for two new contributions to the nonlinear gain coefficient ε are derived, which reflect carrier heating due to stimulated emission and free carrier absorption. In typical cases, carrier heating and spectral holeburning are found to give comparable contributions to nonlinear gain suppression. The results are in good agreement with recent measurements on InGaAsP laser diodes. (orig.)

  6. Heteroduplex analysis of the dystrophin gene: Application to point mutation and carrier detection

    Energy Technology Data Exchange (ETDEWEB)

    Prior, T.W.; Papp, A.C.; Snyder, P.J.; Sedra, M.S.; Western, L.M.; Bartolo, C.; Mendell, J.R. [Ohio State Univ., Columbus, OH (United States); Moxley, R.T. [Univ. of Rochester Medical Center, NY (United States)

    1994-03-01

    Approximately one-third of Duchenne muscular dystrophy patients have undefined mutations in the dystrophin gene. For carrier and prenatal studies in families without detectable mutations, the indirect restriction fragment length polymorphism linkage approach is used. Using a multiplex amplification and heteroduplex analysis of dystrophin exons, the authors identified nonsense mutations in two DMD patients. Although the nonsense mutations are predicted to severely truncate the dystrophin protein, both patients presented with mild clinical courses of the disease. As a result of identifying the mutation in the affected boys, direct carrier studies by heteroduplex analysis were extended to other relatives. The authors conclude that the technique is not only ideal for mutation detection but is also useful for diagnostic testing. 29 refs., 4 figs.

  7. A new approach on Brewer's spent grains treatment and potential use as lignocellulosic yeast cells carriers.

    Science.gov (United States)

    Pires, Eduardo J; Ruiz, Héctor A; Teixeira, José A; Vicente, António A

    2012-06-13

    The major objective of this work is to improve the pretreatments of brewer's spent grains (BSG) aiming at their use as a source for lignocellulosic yeast carriers (LCYC) production. Therefore, several pretreatments of BSG have been designed aiming at obtaining various yeast carriers, differing on their physicochemical composition. Cellulose, hemicellulose, lignin, fat, protein, and ash content were determined for crude BSG and the LCYCs. The long chain fatty acids profile for the crude BSG was also analyzed. Chemical treatments successfully produced several different LCYC based on BSG. The highest cellulose content in LCYC was achieved upon application of caustic (NaOH) treatment during 40 min. Either caustic or combined acid-caustic treatments predominately generated hydrophobic, negatively charged LCYC. The feasibility of using BSG for LCYC production is strengthened by the fact that added-value byproduct can be extracted before the chemical treatments are applied.

  8. Marine tumor vaccine carriers: structure of the molluscan hemocyanins KLH and htH.

    Science.gov (United States)

    Markl, J; Lieb, B; Gebauer, W; Altenhein, B; Meissner, U; Harris, J R

    2001-10-01

    Keyhole limpet hemocyanin (KLH) is a well-established immune stimulant and hapten carrier, and Haliotis tuberculata hemocyanin (HtH) is a related product. Biologically, KLH and HtH are blue copper proteins which serve as oxygen carriers in the blood of the keyhole limpet Megathura crenulata and the abalone H. tuberculata, respectively, two marine gastropods. Both hemocyanins occur as two distinct isoforms, termed KLH1 KLH2, HtH1, and HtH2. Each of these molecules is based on a very large polypeptide chain, the subunit (molecular mass ca 400 kDa), which is folded into a series of eight globular functional units (molecular mass ca 50 kDa each). Twenty copies of this subunit form a cylindrical quaternary structure (molecular mass ca 8 MDa). This article reviews the recent data on the biosynthesis, quaternary structure, subunit architecture, amino acid sequence, gene structure, and recombinant production of KLH and HtH.

  9. Robust GPS carrier tracking under ionospheric scintillation

    Science.gov (United States)

    Susi, M.; Andreotti, M.; Aquino, M. H.; Dodson, A.

    2013-12-01

    Small scale irregularities present in the ionosphere can induce fast and unpredictable fluctuations of Radio Frequency (RF) signal phase and amplitude. This phenomenon, known as scintillation, can degrade the performance of a GPS receiver leading to cycle slips, increasing the tracking error and also producing a complete loss of lock. In the most severe scenarios, if the tracking of multiple satellites links is prevented, outages in the GPS service can also occur. In order to render a GPS receiver more robust under scintillation, particular attention should be dedicated to the design of the carrier tracking stage, that is the receiver's part most sensitive to these types of phenomenon. This paper exploits the reconfigurability and flexibility of a GPS software receiver to develop a tracking algorithm that is more robust under ionospheric scintillation. For this purpose, first of all, the scintillation level is monitored in real time. Indeed the carrier phase and the post correlation terms obtained by the PLL (Phase Locked Loop) are used to estimate phi60 and S4 [1], the scintillation indices traditionally used to quantify the level of phase and amplitude scintillations, as well as p and T, the spectral parameters of the fluctuations PSD. The effectiveness of the scintillation parameter computation is confirmed by comparing the values obtained by the software receiver and the ones provided by a commercial scintillation monitoring, i.e. the Septentrio PolarxS receiver [2]. Then the above scintillation parameters and the signal carrier to noise density are exploited to tune the carrier tracking algorithm. In case of very weak signals the FLL (Frequency Locked Loop) scheme is selected in order to maintain the signal lock. Otherwise an adaptive bandwidth Phase Locked Loop (PLL) scheme is adopted. The optimum bandwidth for the specific scintillation scenario is evaluated in real time by exploiting the Conker formula [1] for the tracking jitter estimation. The performance

  10. Modeling malware propagation using a carrier compartment

    Science.gov (United States)

    Hernández Guillén, J. D.; Martín del Rey, A.

    2018-03-01

    The great majority of mathematical models proposed to simulate malware spreading are based on systems of ordinary differential equations. These are compartmental models where the devices are classified according to some types: susceptible, exposed, infectious, recovered, etc. As far as we know, there is not any model considering the special class of carrier devices. This type is constituted by the devices whose operative systems is not targeted by the malware (for example, iOS devices for Android malware). In this work a novel mathematical model considering this new compartment is considered. Its qualitative study is presented and a detailed analysis of the efficient control measures is shown by studying the basic reproductive number.

  11. Microemulsions as Potential Carriers of Nisin

    DEFF Research Database (Denmark)

    Chatzidaki, Maria D; Papadimitriou, Konstantinos; Alexandraki, Voula

    2016-01-01

    in an increase in the micellar size due to the penetration of water into the hydrophilic core of the inverse swollen micelles (hydration-induced swelling behavior). The dynamic properties of the surfactant monolayer were also affected by the nature of the used vegetable oil, the ethanol content, and the presence......Water-in-oil (W/O) microemulsions based on either refined olive oil (ROO) or sunflower oil (SO), distilled monoglycerides (DMG), and ethanol were used as nisin carriers in order to ensure its effectiveness as a biopreservative. This work presents experimental evidence on the effects of ethanol....... Modeling of representative SAXS profiles was applied to gain further insight into the effects of ethanol and solubilized water content on the inverse swollen micelles' size and morphology. With increasing ethanol content, the overall size of the inverse micelles decreased, whereas hydration resulted...

  12. Carrier Induced Magnetism In Correlated Materials

    Science.gov (United States)

    Lee, Byounghak; Trivedi, Nandini; Zhang, Shiwei; Martin, Richard

    2003-03-01

    We study a two dimensional Hubbard model with magnetic impurities using a combination of single particle and quantum Monte Carlo techniques. Our aim is to determine the interaction between magnetic ions in both strongly interacting hosts, such as magnetic perovskites, and weakly interacting hosts, such as magnetic semiconductors. In the first step, the interactions are treated within an inhomogeneous Hartree-Fock approach and self-consistency is demanded at each site, providing a more accurate treatment of disorder effects compared with other mean-field treatments such as virtual crystal and coherent potential approximations. These are then augmented with determinantal quantum Monte Carlo techniques that treat the electron interactions more accurately. We calculate the exchange coupling as a function of the magnetic impurity concentration, the repulsive electron-electron interaction, carrier concentration, and temperature. We compare the calculated local density of states with STM measurements and also obtain the ferromagnetic transition temperature.

  13. Measurement of carrier mobility in silicon nanowires.

    Science.gov (United States)

    Gunawan, Oki; Sekaric, Lidija; Majumdar, Amlan; Rooks, Michael; Appenzeller, Joerg; Sleight, Jeffrey W; Guha, Supratik; Haensch, Wilfried

    2008-06-01

    We report the first direct capacitance measurements of silicon nanowires (SiNWs) and the consequent determination of field carrier mobilities in undoped-channel SiNW field-effect transistors (FETs) at room temperature. We employ a two-FET method for accurate extraction of the intrinsic channel resistance and intrinsic channel capacitance of the SiNWs. The devices used in this study were fabricated using a top-down method to create SiNW FETs with up to 1000 wires in parallel for increasing the raw capacitance while maintaining excellent control on device dimensions and series resistance. We found that, compared with the universal mobility curves for bulk silicon, the electron and hole mobilities in nanowires are comparable to those of the surface orientation that offers a lower mobility.

  14. Carrier illumination measurement of dopant lateral diffusion

    International Nuclear Information System (INIS)

    Budiarto, E.; Segovia, M.; Borden, P.; Felch, S.

    2005-01-01

    This paper describes the application of the carrier illumination technique to non-destructively measure the lateral diffusion of implanted dopants after annealing. Experiments to validate the feasibility of this method employed test structures with a constant line width of 300 nm and varying undoped spaces of 100-5000 nm. The test patterns were implanted with a p-type dopant and annealed in a 3 x 3 matrix. For each implant condition, the measured lateral diffusion was found to increase with annealing temperature, as expected. More interestingly, the lateral diffusion was not observed to relate to the vertical diffusion by a fixed proportionality factor, as is usually assumed. The ratio of lateral to vertical diffusion varies with annealing temperature, with a trend that depends on the implant condition

  15. Viscoelastic gravel-pack carrier fluid

    International Nuclear Information System (INIS)

    Nehmer, W.L.

    1988-01-01

    The ability of a fluid to flow adequately into the formation during gravel-pack treatments is critical to achieving a good pack. Recent studies have indicated ''fish-eyes'' and/or ''microgels'' present in many polymer gelled carrier fluids will plug pore throats, leading to impaired leakoff and causing formation damage. Intensive manipulation of the polymer gelled fluid using shear and filter devices will help remove the particles, but it adds to the cost of the treatment in terms of equipment and manpower. Excessive shear will degrade the polymer leading to poor gravel suspension, while too little shear will cause filtration problems. A gelled carried fluid using a viscoelastic surfactant system has been found to leak off very efficiently to the formation, and cause no formation damage, without the use of shear/filter devices. Viscoelastic surfactant-base gelled fluids develop viscosity because of the association of surfactant moloecules into large rod-shaped aggregates. There is no hydration of polymer involved, so fish-eyes and microgels will not be formed in the viscoelastic fluid. A surfactant-base system having a yield point allows the gravel carrying properties to be much better than fluids gelled with conventional polymer systems (hydroxyethylcellulose [HEC]). For example, a gravel carried fluid gelled with 80 lb HEC/1,000 gal has a viscosity of about 400 cp at 170 sec/sup -1/; a viscoelastic surfactant-base system having only one-half the viscosity still flows into cores about four times more efficiently than the HEC-base fluid. The rheology, leakoff, formation damage and mixing properties of a viscoelastic, surfactant-base, gravel-pack carrier fluid are discussed

  16. Channel-mediated and carrier-mediated uptake of K+ into cultured ovine oligodendrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hertz, L.; Soliven, B.; Hertz, E.; Szuchet, S.; Nelson, D.J. (Univ. of Saskatchewan, Saskatoon (Canada))

    1990-01-01

    Uptake of radioactive K+ by mature ovine oligodendrocytes (OLGs) maintained in primary culture was measured under steady-state conditions, i.e., in cells maintained in a normal tissue culture medium (5.4 mM K+), and in cells after depletion of intracellular K+ to less than 15% of its normal value by pre-incubation in K(+)-free medium. The latter value is dominated by an active, carrier-mediated uptake (although it may include some diffusional uptake), whereas the former, in addition to active uptake, also reflects passive K+ diffusion through ion selective channels and possible self-exchange between extracellular and intracellular K+, which may be carrier-mediated. The total uptake rate was 144 +/- 10 nmol/min/mg protein, and the uptake after K+ depletion was 60 +/- 2 nmol/min/mg protein, much lower rates than previously observed in astrocytes. The uptake into K(+)-depleted cells was inhibited by about 80% in the presence of ouabain (1 mM) and about 30% in the presence of furosemide (2 mM). Activators of protein kinase C (phorbol esters) and cAMP-dependent protein kinase (forskolin) have been shown to alter the myelinogenic metabolism as well as outward K+ current in cultured OLGs. The present study demonstrates that K+ homeostasis in OLGs is modulated through similar second messenger pathways. Active uptake was inhibited by about 60% in the presence of active phorbol esters (100 nM) but was not affected by forskolin (100 nM). Forskolin likewise had no effect on total uptake, whereas phorbol esters caused a much larger inhibition than expected from their effect on carrier-mediated uptake alone, suggesting that channel-mediated uptake was also reduced.

  17. Carbon nanotubes as cancer therapeutic carriers and mediators.

    Science.gov (United States)

    Son, Kuk Hui; Hong, Jeong Hee; Lee, Jin Woo

    Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug-CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy.

  18. Enhancement of microalgal growth by using perfluorocarbon as oxygen carrier.

    Science.gov (United States)

    Wasanasathian, A; Peng, C A

    2001-01-01

    The contribution of green microalgae has been recognized in the production of useful products such as chemicals, fatty acids, proteins, carotenoids, pigments, polysaccharides, and pharmaceuticals. One of the challenges to the development of profitable bioproduct markets is the design, development, modeling, and evaluation of cost-effective production systems. The photobioreactors for microalgae can be either open or closed systems in large-scale production. In various situations, it has been reported that closed photobioreactors offer many advantages over open systems. These advantages include lower contamination, higher biomass densities, and better process control. Nevertheless, for the scale-up of enclosed tubular photobioreactors, the accumulation of oxygen as a photosynthetic byproduct has been a major limitation because it severely inhibits growth of microalgae. In this study, we use the distinctive feature of liquid perfluorocarbons (PFCs) as a carrier that efficiently removes the accumulated oxygen from algal medium phase in the spinner culture flasks. The results show the growth kinetics of microalgae cultivated by this approach is significantly improved.

  19. Carbon nanotubes as cancer therapeutic carriers and mediators

    Science.gov (United States)

    Son, Kuk Hui; Hong, Jeong Hee; Lee, Jin Woo

    2016-01-01

    Carbon nanotubes (CNTs) have received increasing attention in biomedical fields because of their unique structures and properties, including high aspect ratios, large surface areas, rich surface chemical functionalities, and size stability on the nanoscale. Particularly, they are attractive as carriers and mediators for cancer therapy. Through appropriate functionalization, CNTs have been used as nanocarriers for anticancer drugs including doxorubicin, camptothecin, carboplatin, cisplatin, paclitaxel, Pt(II), and Pt(IV), and genes including plasmid DNA, small-interfering RNA, oligonucleotides, and RNA/DNA aptamers. CNTs can also deliver proteins and immunotherapy components. Using combinations of light energy, they have also been applied as mediators for photothermal therapy and photodynamic therapy to directly destroy cancer cells without severely damaging normal tissue. If limitations such as a long-term cytotoxicity in the body, lack of size uniformity during the synthetic process, loading deviations for drug–CNT complexes, and release controllability at the target point are overcome, CNTs will become one of the strongest tools that are available for various other biomedical fields as well as for cancer therapy. PMID:27785021

  20. Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside.

    Science.gov (United States)

    Palacios, Miriam; Tampe, Ricardo; Del Campo, Miguel; Zhong, Ta-Ying; López, Mercedes N; Salazar-Onfray, Flavio; Becker, María Inés

    2018-04-25

    Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Carrier dynamics in InAs/AlAs quantum dots: lack in carrier transfer from wetting layer to quantum dots.

    Science.gov (United States)

    Shamirzaev, T S; Abramkin, D S; Nenashev, A V; Zhuravlev, K S; Trojánek, F; Dzurnák, B; Malý, P

    2010-04-16

    Structures with self-assembled InAs quantum dots (QDs) embedded in an AlAs matrix have been studied by steady-state and transient photoluminescence. It has been shown that in contrast to InAs/GaAs QD systems carriers are mainly captured by quantum dots directly from the AlAs matrix, while transfer of carriers captured by the wetting layer far away from QDs to the QDs is suppressed. At low temperatures the carriers captured by the wetting layer are localized by potential fluctuations at the wetting layer interface, while at high temperatures the carriers are delocalized but captured by nonradiative centers located in the wetting layer.

  2. Carrier detection and prenatal diagnosis in families with haemophilia.

    Science.gov (United States)

    Shetty, S; Ghosh, K; Bhide, A; Mohanty, D

    2001-01-01

    Haemophilias are the commonest X-linked disorders affecting approximately 1 in 10,000 male births. Detection of carrier women in families with haemophilia and subsequent antenatal diagnosis of confirmed carriers are important services for these patients and their relatives. Over the last 6 years we performed carrier detection and antenatal diagnosis in families with patients of haemophilia A and B. During the last 6 years, 159 families with haemophilia A and B were analysed for carrier detection by DNA analysis, using various polymorphic markers of factors VIII and IX genes. The polymorphisms used were intron 18 Bcl I, intron 19 Hind III, intron 22 Xbal and DXS52/St14 of the factor VIII gene and intron I Ddel, intron 4 Taql, 3 Hhal and Residue 148 codon Mnll of the factor IX gene. There were 189 probable carriers (whose carrier status was not known) and 99 obligatory carriers (confirmed carriers by family pedigree analysis) from 102 families with haemophilia A. Of the 57 families with haemophilia B analysed, there were 98 probable and 52 obligatory carriers. All the analyses were carried out by polymerase chain reaction. For antenatal diagnosis, prior to polymorphism analysis, the sex of the foetus was detected by Y chromosome-specific amplification. One hundred and four females were diagnosed as carriers and 63 as non-carriers by the intragenic polymorphic markers in families with haemophilia A. Eighteen women were informative with only the extragenic marker of factor VIII gene. Four women were not informative with any of the markers used. In families with haemophilia B, 37 women were diagnosed as carriers and 34 as non-carriers by the intragenic markers and 34 were informative only with the extragenic markers. Seventeen women were not informative with any of the markers used. Of the 25 antenatal diagnoses performed (20 haemophilia A, 5 haemophilia B) using the same markers as those used in carrier detection, 14 were male foetuses and 11 female as detected by Y

  3. CARRIER PREPARATION BUILDING MATERIALS HANDLING SYSTEM DESCRIPTION DOCUMENT

    Energy Technology Data Exchange (ETDEWEB)

    E.F. Loros

    2000-06-28

    The Carrier Preparation Building Materials Handling System receives rail and truck shipping casks from the Carrier/Cask Transport System, and inspects and prepares the shipping casks for return to the Carrier/Cask Transport System. Carrier preparation operations for carriers/casks received at the surface repository include performing a radiation survey of the carrier and cask, removing/retracting the personnel barrier, measuring the cask temperature, removing/retracting the impact limiters, removing the cask tie-downs (if any), and installing the cask trunnions (if any). The shipping operations for carriers/casks leaving the surface repository include removing the cask trunnions (if any), installing the cask tie-downs (if any), installing the impact limiters, performing a radiation survey of the cask, and installing the personnel barrier. There are four parallel carrier/cask preparation lines installed in the Carrier Preparation Building with two preparation bays in each line, each of which can accommodate carrier/cask shipping and receiving. The lines are operated concurrently to handle the waste shipping throughputs and to allow system maintenance operations. One remotely operated overhead bridge crane and one remotely operated manipulator is provided for each pair of carrier/cask preparation lines servicing four preparation bays. Remotely operated support equipment includes a manipulator and tooling and fixtures for removing and installing personnel barriers, impact limiters, cask trunnions, and cask tie-downs. Remote handling equipment is designed to facilitate maintenance, dose reduction, and replacement of interchangeable components where appropriate. Semi-automatic, manual, and backup control methods support normal, abnormal, and recovery operations. Laydown areas and equipment are included as required for transportation system components (e.g., personnel barriers and impact limiters), fixtures, and tooling to support abnormal and recovery operations. The

  4. Tracking Ultrafast Carrier Dynamics in Single Semiconductor Nanowire Heterostructures

    Directory of Open Access Journals (Sweden)

    Taylor A.J.

    2013-03-01

    Full Text Available An understanding of non-equilibrium carrier dynamics in silicon (Si nanowires (NWs and NW heterostructures is very important due to their many nanophotonic and nanoelectronics applications. Here, we describe the first measurements of ultrafast carrier dynamics and diffusion in single heterostructured Si nanowires, obtained using ultrafast optical microscopy. By isolating individual nanowires, we avoid complications resulting from the broad size and alignment distribution in nanowire ensembles, allowing us to directly probe ultrafast carrier dynamics in these quasi-one-dimensional systems. Spatially-resolved pump-probe spectroscopy demonstrates the influence of surface-mediated mechanisms on carrier dynamics in a single NW, while polarization-resolved femtosecond pump-probe spectroscopy reveals a clear anisotropy in carrier lifetimes measured parallel and perpendicular to the NW axis, due to density-dependent Auger recombination. Furthermore, separating the pump and probe spots along the NW axis enabled us to track space and time dependent carrier diffusion in radial and axial NW heterostructures. These results enable us to reveal the influence of radial and axial interfaces on carrier dynamics and charge transport in these quasi-one-dimensional nanosystems, which can then be used to tailor carrier relaxation in a single nanowire heterostructure for a given application.

  5. Investigation of carrier oil stabilized iron oxide nanoparticles and its ...

    African Journals Online (AJOL)

    Iron oxide nanoparticles were synthesized by co-precipitation method. The polyunsaturated carrier oil (flaxseed oil) is used as a stabilizing agent for iron oxide nanoparticles. Kirby Bauer method was used to investigate the antibiotic sensitivity of carrier oil stabilized and uncoated SPIONs at 10 and 20 μg/L on Gram-positive ...

  6. 40 CFR 792.113 - Mixtures of substances with carriers.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Mixtures of substances with carriers... § 792.113 Mixtures of substances with carriers. (a) For each test, control, or reference substance that... the uniformity of the mixture and to determine, periodically, the concentration of the test, control...

  7. 40 CFR 160.113 - Mixtures of substances with carriers.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Mixtures of substances with carriers... Mixtures of substances with carriers. (a) For each test, control, or reference substance that is mixed with... uniformity of the mixture and to determine, periodically, the concentration of the test, control, or...

  8. Current Consumption Measurements with a Carrier Aggregation Smartphone

    DEFF Research Database (Denmark)

    Sanchez-Mejias, Rafael; Guo, Yu; Lauridsen, Mads

    2014-01-01

    Carrier Aggregation (CA) is introduced in LTE release 10 to improve data rates by allowing the User Equipment (UE) to receive data on more than one LTE carrier. The related increased complexity is expected to affect the UE current consumption, but yet no empirical evaluation has been published on...

  9. Importance of polaron effects for charge carrier mobility above and ...

    Indian Academy of Sciences (India)

    Orifjon Ganiev

    2017-05-30

    May 30, 2017 ... It is shown that the scattering of polaronic charge carriers and bosonic Cooper pairs at acoustic and optical phonons are responsible for the charge carrier mobility above and below the PG temperature. We show that the energy scales of the binding energies of large polarons and polaronic Cooper pairs.

  10. 19 CFR 192.4 - Liability of carriers.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Liability of carriers. 192.4 Section 192.4 Customs... Liability of carriers. Under the provisions of 19 U.S.C. 1436, the vessel master is charged with the... inaccurately described thereon, a liability for penalties may be incurred. ...

  11. 47 CFR 73.1545 - Carrier frequency departure tolerances.

    Science.gov (United States)

    2010-10-01

    ... departure tolerances. (a) AM stations. The departure of the carrier frequency for monophonic transmissions... authorized transmitter output power more than 10 watts may not exceed ±2000 Hz from the assigned frequency. (2) The departure of the carrier or center frequency of an FM station with an authorized transmitter...

  12. Proposal for tutorial: Resilience in carrier Ethernet transport

    DEFF Research Database (Denmark)

    Berger, Michael Stübert; Wessing, Henrik; Ruepp, Sarah Renée

    2009-01-01

    This tutorial addresses how Carrier Ethernet technologies can be used in the transport network to provide resilience to the packet layer. Carrier Ethernet networks based on PBB-TE and T-MPLS/MPLS-TP are strong candidates for reliable transport of triple-play services. These technologies offer...

  13. Heat to electricity conversion by cold carrier emissive energy harvesters

    Energy Technology Data Exchange (ETDEWEB)

    Strandberg, Rune [Department of Engineering Sciences, University of Agder, Jon Lilletuns vei 9, 4879 Grimstad (Norway)

    2015-12-07

    This paper suggests a method to convert heat to electricity by the use of devices called cold carrier emissive energy harvesters (cold carrier EEHs). The working principle of such converters is explained and theoretical power densities and efficiencies are calculated for ideal devices. Cold carrier EEHs are based on the same device structure as hot carrier solar cells, but works in an opposite way. Whereas a hot carrier solar cell receives net radiation from the sun and converts some of this radiative heat flow into electricity, a cold carrier EEH sustains a net outflux of radiation to the surroundings while converting some of the energy supplied to it into electricity. It is shown that the most basic type of cold carrier EEHs have the same theoretical efficiency as the ideal emissive energy harvesters described earlier by Byrnes et al. In the present work, it is also shown that if the emission from the cold carrier EEH originates from electron transitions across an energy gap where a difference in the chemical potential of the electrons above and below the energy gap is sustained, power densities slightly higher than those given by Byrnes et al. can be achieved.

  14. Carrier screening in the era of expanding genetic technology.

    Science.gov (United States)

    Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

    2016-12-01

    The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

  15. Importance of polaron effects for charge carrier mobility above and ...

    Indian Academy of Sciences (India)

    It is shown that the scattering of polaronic charge carriers and bosonic Cooper pairs at acoustic and optical phonons are responsible for the charge carrier mobility above and below the PG temperature. We show that the energy scales of the binding energies of large polarons and polaronic Cooper pairs can be identified by ...

  16. Screening in crystalline liquids protects energetic carriers in hybrid perovskites

    Science.gov (United States)

    Zhu, Haiming; Miyata, Kiyoshi; Fu, Yongping; Wang, Jue; Joshi, Prakriti; Niesner, Daniel; Williams, Kristopher; Jin, Song; Zhu, Xiaoyang

    Hybrid lead halide perovskites exhibit carrier properties that resemble those of pristine nonpolar semiconductors despite static and dynamic disorder, but how carriers are protected from efficient scattering with charged defects and optical phonons is unknown. Here, we reveal the carrier protection mechanism by comparing three single-crystal lead bromide perovskites: CH3NH3PbBr3, CH(NH2)2PbBr3, and CsPbBr3. We observed hot fluorescence emission from energetic carriers with 102 picosecond lifetimes in CH3NH3PbBr3 or CH(NH,SUB>2)2PbBr3, but not in CsPbBr3. The hot fluorescence is correlated with liquid-like molecular reorientational motions, suggesting that dynamic screening protects energetic carriers via solvation or large polaron formation on time scales competitive with that of ultrafast cooling. Similar protections likely exist for band-edge carriers. The long-lived energetic carriers may enable hot-carrier solar cells with efficiencies exceeding the Shockley-Queisser limit. This work was supported by U.S. Department of Energy Grant ER46980, National Science Foundation, Grant DMR 1420634 (MRSEC), and Department of Energy Award DE-FG02-09ER46664.

  17. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, E. M.; van der Wouw, P. A.; Wilde, A. A.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; de Visser, M.

    1999-01-01

    A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers

  18. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, EM; van der Wouw, PA; Wilde, AAM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; van Essen, AJ; Leschot, NJ; de Visser, Marianne

    A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers

  19. Carrier dynamics in femtosecond-laser-excited bismuth telluride

    Science.gov (United States)

    Wang, J. L.; Guo, L.; Ling, C.; Song, Y. M.; Xu, X. F.; Ni, Z. H.; Chen, Y. F.

    2016-04-01

    The carrier dynamics of B i2T e3 is studied using the femtosecond pump-probe technique. Three distinct processes, including free carrier absorption, band filling, and electron-hole recombination, are found to contribute to the reflectivity changes. The two-temperature model is used to describe the intraband energy relaxation process of carriers, and the Drude contribution well explains the intensity dependence of the peak values of the nonoscillatory component in the reflectivity signal. The combined effects of free carrier absorption and band filling result in a reflection minimum at about 2 ps after laser excitation. The nonzero background signal increases linearly with the pump fluence, which is attributed to the electron-hole recombination. Finally, our results provide an illustration of investigating the carrier dynamics in semiconductors from the ultrafast reflectivity spectra.

  20. Imaging ballistic carrier trajectories in graphene using scanning gate microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Morikawa, Sei; Masubuchi, Satoru [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan); Dou, Ziwei; Wang, Shu-Wei; Smith, Charles G.; Connolly, Malcolm R., E-mail: mrc61@cam.ac.uk [Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE (United Kingdom); Watanabe, Kenji; Taniguchi, Takashi [National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044 (Japan); Machida, Tomoki, E-mail: tmachida@iis.u-tokyo.ac.jp [Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan); Institute for Nano Quantum Information Electronics, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan)

    2015-12-14

    We use scanning gate microscopy to map out the trajectories of ballistic carriers in high-mobility graphene encapsulated by hexagonal boron nitride and subject to a weak magnetic field. We employ a magnetic focusing geometry to image carriers that emerge ballistically from an injector, follow a cyclotron path due to the Lorentz force from an applied magnetic field, and land on an adjacent collector probe. The local electric field generated by the scanning tip in the vicinity of the carriers deflects their trajectories, modifying the proportion of carriers focused into the collector. By measuring the voltage at the collector while scanning the tip, we are able to obtain images with arcs that are consistent with the expected cyclotron motion. We also demonstrate that the tip can be used to redirect misaligned carriers back to the collector.

  1. Clinical manifestations of intermediate allele carriers in Huntington disease

    DEFF Research Database (Denmark)

    Cubo, Esther; Ramos-Arroyo, María A; Martinez-Horta, Saul

    2016-01-01

    into IA carriers (27-35 CAG) and controls (IA carriers and controls were compared for sociodemographic, environmental, and outcome measures. We used regression analysis to estimate the association of age and CAG repeats on the UHDRS scores. RESULTS: Of 12......OBJECTIVE: There is controversy about the clinical consequences of intermediate alleles (IAs) in Huntington disease (HD). The main objective of this study was to establish the clinical manifestations of IA carriers for a prospective, international, European HD registry. METHODS: We assessed......,190 participants, 657 (5.38%) with IA carriers (11.56%) and 581 controls (88.44%). After correcting for multiple comparisons, at baseline, we found no significant differences between IA carriers and controls for total UHDRS motor, SF-36, behavioral, cognitive, or TFC scores...

  2. Anisotropic charged impurity-limited carrier mobility in monolayer phosphorene

    Energy Technology Data Exchange (ETDEWEB)

    Ong, Zhun-Yong; Zhang, Gang; Zhang, Yong Wei [Institute of High Performance Computing, A*STAR, Singapore 138632 (Singapore)

    2014-12-07

    The room temperature carrier mobility in atomically thin 2D materials is usually far below the intrinsic limit imposed by phonon scattering as a result of scattering by remote charged impurities in its environment. We simulate the charged impurity-limited carrier mobility μ in bare and encapsulated monolayer phosphorene. We find a significant temperature dependence in the carrier mobilities (μ ∝ T{sup −γ}) that results from the temperature variability of the charge screening and varies with the crystal orientation. The anisotropy in the effective mass leads to an anisotropic carrier mobility, with the mobility in the armchair direction about one order of magnitude larger than in the zigzag direction. In particular, this mobility anisotropy is enhanced at low temperatures and high carrier densities. Under encapsulation with a high-κ overlayer, the mobility increases by up to an order of magnitude although its temperature dependence and its anisotropy are reduced.

  3. [Attachment theory and baby slings/carriers: technological network formation].

    Science.gov (United States)

    Lu, Zxy-Yann Jane; Lin, Wan-Shiuan

    2011-12-01

    Healthcare providers recognize the important role played by attachment theory in explaining the close relationship between mental health and social behavior in mothers and their children. This paper uses attachment theory in a socio-cultural context to ascertain the mechanism by which baby slings/carriers, a new technology, produced and reproduced the scientific motherhood. It further applies a social history of technology perspective to understand how baby carriers and attachment theory are socially constructed and historically contingent on three major transformations. These transformations include the use of attachment theory-based baby carriers to further scientific motherhood; the use of baby slings/carriers to further the medicalization of breastfeeding and enhance mother-infant attachment; and the use of baby slings/carriers to transform woman's identities by integrating scientific motherhood, independence and fashion. Implications for nursing clinical policy are suggested.

  4. Anisotropic charged impurity-limited carrier mobility in monolayer phosphorene

    International Nuclear Information System (INIS)

    Ong, Zhun-Yong; Zhang, Gang; Zhang, Yong Wei

    2014-01-01

    The room temperature carrier mobility in atomically thin 2D materials is usually far below the intrinsic limit imposed by phonon scattering as a result of scattering by remote charged impurities in its environment. We simulate the charged impurity-limited carrier mobility μ in bare and encapsulated monolayer phosphorene. We find a significant temperature dependence in the carrier mobilities (μ ∝ T −γ ) that results from the temperature variability of the charge screening and varies with the crystal orientation. The anisotropy in the effective mass leads to an anisotropic carrier mobility, with the mobility in the armchair direction about one order of magnitude larger than in the zigzag direction. In particular, this mobility anisotropy is enhanced at low temperatures and high carrier densities. Under encapsulation with a high-κ overlayer, the mobility increases by up to an order of magnitude although its temperature dependence and its anisotropy are reduced

  5. Differential effects of coconut oil- and fish oil-enriched diets on tricarboxylate carrier in rat liver mitochondria.

    Science.gov (United States)

    Giudetti, Anna Maria; Sabetta, Simona; di Summa, Roberta; Leo, Monica; Damiano, Fabrizio; Siculella, Luisa; Gnoni, Gabriele V

    2003-11-01

    The mitochondrial tricarboxylate carrier (TCC) plays an important role in lipogenesis being TCC-responsible for the efflux from the mitochondria to the cytosol of acetyl-CoA, the primer for fatty acid synthesis. In this study, we investigated the effects of two high-fat diets with different fatty acid composition on the hepatic TCC activity. Rats were fed for 3 weeks on a basal diet supplemented with 15% of either coconut oil (CO), abundant in medium-chain saturated fatty acids, or fish oil (FO), rich in n-3 polyunsaturated fatty acids. Mitochondrial fatty acid composition was differently influenced by the dietary treatments, while no appreciable change in phospholipid composition and cholesterol level was observed. Compared with CO, the TCC activity was markedly decreased in liver mitochondria from FO-fed rats; kinetic analysis of the carrier revealed a decrease of the Vmax, with no change of the Km. No difference in the Arrhenius plot between the two groups was observed. Interestingly, the carrier protein level and the corresponding mRNA abundance decreased following FO treatment. These data indicate that FO administration markedly decreased the TCC activity as compared with CO. This effect is most likely due to a reduced gene expression of the carrier protein.

  6. Effect of irradiation on microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers

    International Nuclear Information System (INIS)

    Mal'tseva, E.L.; Goloshchapov, A.N.; Pal'mina, N.P.; Burlakova, E.B.

    1982-01-01

    Changes of microviscosity of the cellular nuclear membrane of tumor and liver of tumor-carriers with developing Ehrlich ascites tumor (EAT) at various terms after lethal irradiation (650 R) were studied by spin probe method. Two iminoxyl radicals localized mainly in lipid bilayer and near probein layers of membrane lipids were used. The character and the degree of microviscosity changes in different zones of nuclear membranes point to different responses towards effect of radiation of cells of tumor-carrier organ and tumor both in viscosity properties, and in change of lipid-protein relations. The significant contribution of near protein lipid layers into general change of nuclear membrane microviscosity is marked. Microviscosity of nuclear membrane causes different responses of cellular nuclear membranes of liver of tumor-carriers and healthy animals as well as considerable (3 times) dilution of nuclear membrane of EAT cells after irradiation. It is shown that temperature dependence of times of rotatory correlation of both probes is more expressed in EAT cells of irradiated tumor-carriers, than in liver

  7. Relaxation of a kinetic hole due to carrier-carrier scattering in multisubband single-quantum-well semiconductors

    DEFF Research Database (Denmark)

    Dery, H.; Tromborg, Bjarne; Eisenstein, G.

    2003-01-01

    We describe a theoretical model for carrier-carrier scattering in an inverted semiconductor quantum well structure using a multisubband diagram. The model includes all possible nonvanishing interaction terms within the static screening approximation, and it enables one to calculate accurately...

  8. Gestational carrier in assisted reproductive technology.

    Science.gov (United States)

    Murugappan, Gayathree; Farland, Leslie V; Missmer, Stacey A; Correia, Katharine F; Anchan, Raymond M; Ginsburg, Elizabeth S

    2018-03-01

    To compare clinical outcomes of in vitro fertilization (IVF) cycles with the use of gestational carriers (GCs) with non-GC IVF cycles. Retrospective cohort study of assisted reproductive technology (ART) cycles performed with (24,269) and without (1,313,452) the use of a GC. ART centers. Infertile patients seeking IVF with or without use of a GC. Autologous and donor oocyte cycles, fresh and cryopreserved embryo transfer cycles. Live birth rate (LBR), twin and high-order multiple birth rates. Approximately 2% of embryo transfers used a GC. Per embryo transfer, GCs had greater pregnancy rate and LBR across all IVF types compared with non-GC cycles in crude models and models adjusted a priori for potential confounders. For women with uterine-factor infertility, embryo transfer with the use of a GC resulted in a higher odds of live birth for autologous fresh embryos and for cryopreserved embryos compared with patients with non-uterine-factor infertility diagnoses. GC benefits LBRs for some patients seeking ART. The highest LBRs occurred when the indication for GC was uterine-factor infertility. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  10. Drug Carrier for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Tilahun Ayane Debele

    2015-09-01

    Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

  11. Theoretical Evaluation of Foam Proppant Carriers

    Science.gov (United States)

    von Holt, H.; Kam, S.; Williams, W. C.

    2017-12-01

    Hydraulic fracturing in oil wells results in a large amount of produced water which must be properly disposed of and is currently a key environmental issue preventing further development in US domestic oil and gas production. The primary function of this liquid is to carry particulates, a.k.a. Proppant, into the stress fractures in order to hold open a pathway in which petroleum can flow into the wellbore. A potential superior technique is to use foam instead of liquid; liquids rely on turbulence to suspend proppant while foams carry particulates on the surfaces. Therefore, foams can carry more proppant deeper into the fractures while typically using 50%-90% less liquid, depending on foam quality. This comparative analysis uses the vorticity equation for a liquid to approximate the base case of particle suspension. This is then compared to a multitude of foam transport models in order to demonstrate the efficacy of foams when used in hydraulic fracturing. This work serves as the basis for future laboratory and hopefully field scale studies of foam proppant carriers.

  12. Drug Carrier for Photodynamic Cancer Therapy

    Science.gov (United States)

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  13. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers......, are reported. The aim is to depict how the elucidation of the interplay of structures requires the interplay of methods....

  14. The evidence that the DNC (SLC25A19) is not the mitochondrial deoxyribonucleotide carrier.

    Science.gov (United States)

    Kang, Jonghoon; Samuels, David C

    2008-03-01

    We review the evidence that the function of the SLC25A19 gene product, previously identified as the mitochondrial deoxyribonucleotide carrier (DNC), is actually the transport of thiamine pyrophosphate. This evidence comes from enzyme kinetics, homologous yeast protein alignments, gene knockout studies, and clinical samples from Amish Microcephaly patients. This diverse body of evidence consistently points to the conclusion that SLC25A19 is not the true mitochondrial DNC gene. The identification of the correct mitochondrial DNC is important for research on the genetic diseases of mitochondrial DNA maintenance and the toxicity experienced by many HIV patients undergoing antiretroviral therapy involving nucleoside analogs.

  15. Biomimetics: From Bioinformatics to Rational Design of Dendrimers as Gene Carriers

    Science.gov (United States)

    Araya-Durán, Ingrid; Varas-Concha, Ignacio; Almonacid, Daniel Eduardo; González-Nilo, Fernando Danilo

    2015-01-01

    Biomimetics, or the use of principles of Nature for developing new materials, is a paradigm that could help Nanomedicine tremendously. One of the current challenges in Nanomedicine is the rational design of new efficient and safer gene carriers. Poly(amidoamine) (PAMAM) dendrimers are a well-known class of nanoparticles, extensively used as non-viral nucleic acid carriers, due to their positively charged end-groups. Yet, there are still several aspects that can be improved for their successful application in in vitro and in vivo systems, including their affinity for nucleic acids as well as lowering their cytotoxicity. In the search of new functional groups that could be used as new dendrimer-reactive groups, we followed a biomimetic approach to determine the amino acids with highest prevalence in protein-DNA interactions. Then we introduced them individually as terminal groups of dendrimers, generating a new class of nanoparticles. Molecular dynamics studies of two systems: PAMAM-Arg and PAMAM-Lys were also performed in order to describe the formation of complexes with DNA. Results confirmed that the introduction of amino acids as terminal groups in a dendrimer increases their affinity for DNA and the interactions in the complexes were characterized at atomic level. We end up by briefly discussing additional modifications that can be made to PAMAM dendrimers to turned them into promising new gene carriers. PMID:26382062

  16. Phenotypic characterization of nevus and tumor patterns in MITF E318K mutation carrier melanoma patients.

    Science.gov (United States)

    Sturm, Richard A; Fox, Carly; McClenahan, Phil; Jagirdar, Kasturee; Ibarrola-Villava, Maider; Banan, Parastoo; Abbott, Nicola C; Ribas, Gloria; Gabrielli, Brian; Duffy, David L; Peter Soyer, H

    2014-01-01

    A germline polymorphism of the microphthalmia transcription factor (MITF) gene encoding a SUMOylation-deficient E318K-mutated protein has recently been described as a medium-penetrance melanoma gene. In a clinical assessment of nevi from 301 volunteers taken from Queensland, we identified six individuals as MITF E318K mutation carriers. The phenotype for 5 of these individuals showed a commonality of fair skin, body freckling that varied over a wide range, and total nevus count between 46 and 430; in addition, all were multiple primary melanoma patients. The predominant dermoscopic signature pattern of nevi was reticular, and the frequency of globular nevi in carriers varied, which does not suggest that the MITF E318K mutation acts to force the continuous growth of nevi. Excised melanocytic lesions were available for four MITF E318K carrier patients and were compared with a matched range of wild-type (WT) melanocytic lesions. The MITF staining pattern showed a predominant nuclear signal in all sections, with no significant difference in the nuclear/cytoplasmic ratio between mutation-positive or -negative samples. A high incidence of amelanotic melanomas was found within the group, with three of the five melanomas from one patient suggesting a genetic interaction between the MITF E318K allele and an MC1R homozygous red hair color (RHC) variant genotype.

  17. Hybrid nanostructured drug carrier with tunable and controlled drug release

    International Nuclear Information System (INIS)

    Depan, D.; Misra, R.D.K.

    2012-01-01

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: ► The novel synthesis of a hybrid nanostructured drug carrier is described. ► The drug carrier exhibits high drug loading ability and is physically stable. ► The high drug release is ascribed to a cavitation-type process.

  18. Clinical findings in obligate carriers of type I Usher syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wagenaar, M.; Rahe, B. ter; Aarem, A. van; Huygen, P.; Admiraal, R. [University Hospital Nijmegen (Netherlands)] [and others

    1995-11-20

    Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal puretone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electrooculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities. 29 refs., 1 fig., 3 tabs.

  19. Utilization of Waste Materials for Microbial Carrier in Wastewater Treatment

    Directory of Open Access Journals (Sweden)

    H. T. Le

    2016-01-01

    Full Text Available This research focused on the ammonium-nitrogen (NH4-N removal from the domestic wastewater using the attached growth reactors. Two types of waste material of corncob (biodegradable material and concrete (nonbiodegradable material were used as the carrier for microorganisms’ attachment. During operation, both reactors achieved absolutely high performance of ammonium removal (up to 99% and total nitrogen removal (up to 95%. The significant advantage of corncob carrier was that the corncob was able to be a source of carbon for biological denitrification, leading to no external carbon requirement for operating the system. However, the corncob caused an increasing turbidity of the effluent. On the other hand, the concrete carrier required the minimal external carbon of 3.5 C/N ratio to reach the good performance. Moreover, a longer period for microorganisms’ adaptation was found in the concrete carrier rather than the corncob carrier. Further, the same physiological and biochemical characteristics of active bacteria were found at the two carriers, which were negative gram, cocci shape, and smooth and white-turbid colony. Due to the effluent quality, the concrete was more appropriate carrier than the corncob for wastewater treatment.

  20. Utilization of Waste Materials for Microbial Carrier in Wastewater Treatment.

    Science.gov (United States)

    Le, H T; Jantarat, N; Khanitchaidecha, W; Ratananikom, K; Nakaruk, A

    2016-01-01

    This research focused on the ammonium-nitrogen (NH4-N) removal from the domestic wastewater using the attached growth reactors. Two types of waste material of corncob (biodegradable material) and concrete (nonbiodegradable material) were used as the carrier for microorganisms' attachment. During operation, both reactors achieved absolutely high performance of ammonium removal (up to 99%) and total nitrogen removal (up to 95%). The significant advantage of corncob carrier was that the corncob was able to be a source of carbon for biological denitrification, leading to no external carbon requirement for operating the system. However, the corncob caused an increasing turbidity of the effluent. On the other hand, the concrete carrier required the minimal external carbon of 3.5 C/N ratio to reach the good performance. Moreover, a longer period for microorganisms' adaptation was found in the concrete carrier rather than the corncob carrier. Further, the same physiological and biochemical characteristics of active bacteria were found at the two carriers, which were negative gram, cocci shape, and smooth and white-turbid colony. Due to the effluent quality, the concrete was more appropriate carrier than the corncob for wastewater treatment.

  1. Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy.

    Science.gov (United States)

    Hoogerwaard, E M; van der Wouw, P A; Wilde, A A; Bakker, E; Ippel, P F; Oosterwijk, J C; Majoor-Krakauer, D F; van Essen, A J; Leschot, N J; de Visser, M

    1999-07-01

    A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers with dilated cardiomyopathy and (3) to assess possible associations between dilated cardiomyopathy and genotype. One hundred and twenty nine DMD and BMD carriers, aged 18-60 years, were traced through the files of the central register kept at the department of Human Genetics in Leiden. Investigations included full medical history, physical examination, ECG and two-dimensional and M-mode echocardiographic examination. Forty-seven percent had ECG changes. Thirty-six percent (DMD 41%, BMD 27%) had at least one abnormality as is usually found in the male patients. Echocardiographic examination was abnormal in 36% (DMD 38%, BMD 34%). Dilated cardiomyopathy was found in seven DMD carriers (8%), and in none of BMD carriers. In addition, 18% had left ventricle dilatation (DMD 19%, BMD 16%). Only 38% had a completely normal investigation of the heart. We found no association between genotype and cardiac manifestations. Our study underlines that cardiac involvement is part of the dystrophinopathies. Carriers should be told about the increased risk of this complication when asking genetic advice. It also implicates that a complete cardiological evaluation should be performed at least once in all carriers. If left ventricle dilatation or dilated cardiomyopathy is present a yearly follow up is needed, in order to start timely therapy.

  2. FMCSA safety program effectiveness measurement : carrier intervention effectiveness model, version 1.0 : [analysis brief].

    Science.gov (United States)

    2015-01-01

    The Carrier Intervention Effectiveness Model (CIEM) : provides the Federal Motor Carrier Safety : Administration (FMCSA) with a tool for measuring : the safety benefits of carrier interventions conducted : under the Compliance, Safety, Accountability...

  3. 76 FR 62496 - Motor Carrier Safety Advisory Committee Series of Public Subcommittee Meetings

    Science.gov (United States)

    2011-10-07

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee Series of Public Subcommittee Meetings AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of meeting. SUMMARY: The FMCSA's Motor...

  4. 77 FR 60507 - Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration [Docket No. FMCSA-2006-26367] Motor Carrier Safety Advisory Committee (MCSAC): Public Subcommittee Meeting AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of Meeting of Compliance, Safety...

  5. Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection

    Directory of Open Access Journals (Sweden)

    Mónica Alejandra Anaya-Segura

    2015-06-01

    Full Text Available Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD. This neuromuscular disorder affects male children, causing weakness and disability, whereas female relatives are at risk of being carriers of the disease. A biomarker with both high sensitivity and specificity for accurate prediction is preferred. Until now creatine kinase (CK levels have been used for DMD diagnosis but these fail to assess disease progression. Herein we examined the potential applicability of serum levels of matrix metalloproteinase 9 (MMP-9 and matrix metalloproteinase 2 (MMP-2, tissue inhibitor of metalloproteinases 1 (TIMP-1, myostatin (GDF-8 and follistatin (FSTN as non-invasive biomarkers to distinguish between DMD steroid naïve patients and healthy controls of similar age and also for carrier detection. Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05, to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD and Limb-girdle muscular dystrophy (LGMD patients. In DMD individuals under steroid treatment, GDF-8 levels increased as FSTN levels decreased, resembling the proportions of these proteins in healthy controls and also the baseline ratio of patients without steroids. GDF-8 and FSTN serum levels were also useful for carrier detection (p < 0.05. Longitudinal studies with larger cohorts are necessary to confirm that these molecules correlate with disease progression. The biomarkers presented herein could potentially outperform CK levels for carrier detection and also harbor potential for monitoring disease progression.

  6. Safety and environmental aspects in LNG carrier design

    International Nuclear Information System (INIS)

    Takashi Yoneyama

    1997-01-01

    'Safety and Reliability' has been and will continue to be a key phr ase in marine transportation of LNG. Mitsui Engineering and Shipbuilding Co.,Ltd. has utilized its all expertise and state of art technologies to realize this objective, resulting in exceptionally successful operations of LNG carrier built by the Co. In line with growing global concern about environmental issues, we need to pay more attention to the environmental aspects of the design and construction of LNG carriers. Accordingly, in this paper, we present some topics related safety and environmental concerns which need to be taken into consideration in LNG carriers design and construction. (Author). 7 figs

  7. Influence of charge carriers on corrugation of suspended graphene

    Science.gov (United States)

    Kirilenko, Demid A.; Gorodetsky, Andrei; Baidakova, Marina V.

    2018-02-01

    Electronic degrees of freedom are predicted to play a significant role in mechanics of two-dimensional crystalline membranes. Here we show that appearance of charge carriers may cause a considerable impact on suspended graphene corrugation, thus leading to additional mechanism resulting in charge carriers mobility variation with their density. This finding may account for some details of suspended graphene conductivity dependence on its doping level and suggests that proper modeling of suspended graphene-based device properties must include the influence of charge carriers on its surface corrugation.

  8. Wafer-scale characterization of carrier dynamics in graphene

    DEFF Research Database (Denmark)

    Buron, Jonas Christian Due; Petersen, Dirch Hjorth; Bøggild, Peter

    2015-01-01

    The electronic properties of single-layer graphene, such as surface conductance, carrier concentration, scattering time and mobility, can be characterized in a noncontact manner by THz time-domain spectroscopy. Standard spectroscopic imaging reveals the AC conductance over large areas with a few...... hundred μm resolution, and spectroscopic imaging on back-gated graphene allows for extraction of both the carrier concentration and the mobility. We find that spatial variations of the conductance of single-layer CVD-grown graphene are predominantly due to variations in mobility rather than in carrier...

  9. Protein nanomedicines for cancer diagnostics and therapy

    International Nuclear Information System (INIS)

    Nair, Shantikumar

    2012-01-01

    New results and applications of the work on anti-cancer therapy using nanomedicines at the Amrita Centre for Nanosciences are presented. Proteins have been selected as having good potential for clinical translation and are excellent carriers for drugs, provide good release kinetics and are also amenable for fluorescent tagging with multiple functionalities for diagnostic purposes. (author)

  10. Genetic and epigenetic alterations of the reduced folate carrier in untreated diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kastrup, Ingelise Bjerring; Worm, Jesper; Ralfkiaer, Elisabeth

    2007-01-01

    The reduced folate carrier (RFC) is a transmembrane protein that mediates cellular uptake of reduced folates and antifolate drugs, including methotrexate (MTX). Acquired alterations of the RFC gene have been associated with resistance to MTX in cancer cell lines and primary osteosarcomas. Here, w...... with adverse outcome. In DLBCL, genetic and epigenetic alterations of RFC were detected at diagnosis in the absence of a selective MTX pressure, suggesting that these alterations may possibly contribute to the development of lymphoma. Udgivelsesdato: 2008-Jan...

  11. The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers.

    Science.gov (United States)

    Van Duong, Tu; Van den Mooter, Guy

    2016-11-01

    As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity. Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs. Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

  12. Spatial pattern separation differences in older adult carriers and non-carriers for the apolipoprotein E epsilon 4 allele.

    Science.gov (United States)

    Sheppard, David P; Graves, Lisa V; Holden, Heather M; Delano-Wood, Lisa; Bondi, Mark W; Gilbert, Paul E

    2016-03-01

    We examined the performance of healthy young (n=57) and older adults (n=43) genotyped as apolipoprotein E-ε4 (APOE-ε4) carriers or APOE-ε4 non-carriers on a delayed match-to-sample task involving varying degrees of spatial interference hypothesized to assess spatial pattern separation. Older adult ε4 carriers were further divided into "impaired" and "unimpaired" groups based on their performance on a standardized test of verbal memory. We found that performance on the spatial pattern separation test increased as a function of decreased spatial interference across all groups. The older ε4 carriers in the impaired group performed significantly worse (ppattern separation may be less efficient in a subset of healthy older adults with subtle memory decline who are carriers of the ε4 allele. However, pattern separation performance may be comparable to that of young adults in a subset of older adult ε4 carriers and more broadly among non-carriers. Our findings offer additional evidence that pattern separation may vary in older adults, and they provide novel insight into pattern separation efficiency in ε4-positive older adults. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Effective carrier sweepout in a silicon waveguide by a metal-semiconductor-metal structure

    DEFF Research Database (Denmark)

    Ding, Yunhong; Hu, Hao; Ou, Haiyan

    2015-01-01

    We demonstrate effective carrier depletion by metal-semiconductor-metal junctions for a silicon waveguide. Photo-generated carriers are efficiently swept out by applying bias voltages, and a shortest carrier lifetime of only 55 ps is demonstrated.......We demonstrate effective carrier depletion by metal-semiconductor-metal junctions for a silicon waveguide. Photo-generated carriers are efficiently swept out by applying bias voltages, and a shortest carrier lifetime of only 55 ps is demonstrated....

  14. A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

    Energy Technology Data Exchange (ETDEWEB)

    Triggs-Raine, B.L.; Akerman, B.R.; Gravel, R.A. (McGill Univ.-Montreal Children' s Hospital Research Institute, Montreal, Quebec (Canada)); Mules, E.H.; Thomas, G.H.; Dowling, C.E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Kaback, M.M.; Lim-Steele, J.S.T. (Univ. of California, San Diego, CA (United States)); Natowicz, M.R. (Eunice Kennedy Shriver Center for Mental Retardation, Waltham, MA (United States)); Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Navon, R.R. (Tel-Aviv Univ., Kfar-Sava (Israel)); Welch, J.P. (Dalhousie Univ., Halifax, Nova, Scotia (Canada)); Greenberg, C.R. (Univ. of Manitoba, Winnipeg (Canada))

    1992-10-01

    Deficiency of [beta]-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. The authors analyzed the HEXA gene of one pseudodeficient subject and identified both a C[sub 739]-to-T substitution that changes Arg[sub 247][yields]Trp on one allele and a previously identified Tay-Sachs disease mutation of the second allele. Six additional pseudodeficient subjects were found to have the C[sub 739]-to-T but for none of 36 Jewish enzyme-defined carries who did not have one of three known mutations common to this group. The C[sub 739]-to-T allele, together with a [open quotes]true[close quotes] Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C[sub 739]-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses. 40 refs., 3 figs., 4 tabs.

  15. Tri-metallic ferrite oxygen carriers for chemical looping combustion

    Science.gov (United States)

    Siriwardane, Ranjani V.; Fan, Yueying

    2017-10-25

    The disclosure provides a tri-metallic ferrite oxygen carrier for the chemical looping combustion of carbonaceous fuels. The tri-metallic ferrite oxygen carrier comprises Cu.sub.xFe.sub.yMn.sub.zO.sub.4-.delta., where Cu.sub.xFe.sub.yMn.sub.zO.sub.4-.delta. is a chemical composition. Generally, 0.5.ltoreq.x.ltoreq.2.0, 0.2.ltoreq.y.ltoreq.2.5, and 0.2.ltoreq.z.ltoreq.2.5, and in some embodiments, 0.8.ltoreq.x.ltoreq.1.2, y.ltoreq.1.2, and z.gtoreq.0.8. The tri-metallic ferrite oxygen carrier may be used in various applications for the combustion of carbonaceous fuels, including as an oxygen carrier for chemical looping combustion.

  16. Educational and technical assistance to CMV drivers and motor carriers

    Science.gov (United States)

    1999-07-01

    The Peer Exchange is a process adopted by the Office of Motor Carrier and Highway Safety in which teams of professionals, representing state and federal government and private industry, identify effective commercial motor vehicle safety findings for ...

  17. GUI Application for ATCA-based LLRF Carrier Board Management

    CERN Document Server

    Wychowaniak, Jan; Predki, Pawel; Napieralski, Andrzej

    2011-01-01

    The Advanced Telecommunications Computing Architecture (ATCA) standard describes an efficient and powerful platform, implementation of which was adopted to be used as a base for control systems in high energy physics. The ATCA platform is considered to be applied for the X-ray Free Electron Laser (X-FEL), being built at Deutsches Electronen- Synchrotron (DESY) in Hamburg, Germany. The Low Level Radio Frequency (LLRF) control system is composed of a few ATCA Carrier Boards. Carrier Board hosts Intelligent Platform Management Controller (IPMC), which is developed in compliance with the PICMG specifications. IPMC is responsible for management and monitoring of sub-modules installed on Carrier Boards and pluggable Advanced Mezzanine Card (AMC) modules. The ATCA Shelf Manager is the main control unit of a single ATCA crate, responsible for all power and fan modules and Carrier Boards installed in ATCA shelf. The device provides a system administrator with a set of control and diagnostic capabilities regarding the ...

  18. Importance of polaron effects for charge carrier mobility above and ...

    Indian Academy of Sciences (India)

    HTSCs) have been investigated theoretically. The appropriate Boltzmann transport equations under relaxation time approximation were used to calculate the mobility of polaronic charge carriers and bosonic Cooper pairs above and below the ...

  19. Study of Charge Carrier Transport in GaN Sensors

    Science.gov (United States)

    Gaubas, Eugenijus; Ceponis, Tomas; Kuokstis, Edmundas; Meskauskaite, Dovile; Pavlov, Jevgenij; Reklaitis, Ignas

    2016-01-01

    Capacitor and Schottky diode sensors were fabricated on GaN material grown by hydride vapor phase epitaxy and metal-organic chemical vapor deposition techniques using plasma etching and metal deposition. The operational characteristics of these devices have been investigated by profiling current transients and by comparing the experimental regimes of the perpendicular and parallel injection of excess carrier domains. Profiling of the carrier injection location allows for the separation of the bipolar and the monopolar charge drift components. Carrier mobility values attributed to the hydride vapor phase epitaxy (HVPE) GaN material have been estimated as μe = 1000 ± 200 cm2/Vs for electrons, and μh = 400 ± 80 cm2/Vs for holes, respectively. Current transients under injection of the localized and bulk packets of excess carriers have been examined in order to determine the surface charge formation and polarization effects. PMID:28773418

  20. Extending the unambiguous velocity range using multiple carrier frequencies

    DEFF Research Database (Denmark)

    Zhang, Z.; Jakobsson, A.; Nikolov, Svetoslav

    2005-01-01

    Typically, velocity estimators based on the estimation of the Doppler shift will suffer from a limited unambiguous velocity range. Proposed are two novel multiple carrier based velocity estimators extending the velocity range above the Nyquist velocity limit. Numerical simulations indicate...

  1. Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy

    NARCIS (Netherlands)

    Hoogerwaard, Edo M.; Ginjaar, Ieke B.; Bakker, Egbert; de Visser, Marianne

    2005-01-01

    Associations between clinical phenotype (muscle weakness, dilated cardiomyopathy) and dystrophin abnormalities in muscle tissue among definite carriers of Duchenne (DMD) and Becker muscular dystrophy (BMD) were investigated. No associations between dystrophin abnormalities and clinical variables in

  2. Stacking dependence of carrier transport properties in multilayered black phosphorous.

    Science.gov (United States)

    Sengupta, A; Audiffred, M; Heine, T; Niehaus, T A

    2016-02-24

    We present the effect of different stacking orders on carrier transport properties of multi-layer black phosphorous. We consider three different stacking orders AAA, ABA and ACA, with increasing number of layers (from 2 to 6 layers). We employ a hierarchical approach in density functional theory (DFT), with structural simulations performed with generalized gradient approximation (GGA) and the bandstructure, carrier effective masses and optical properties evaluated with the meta-generalized gradient approximation (MGGA). The carrier transmission in the various black phosphorous sheets was carried out with the non-equilibrium green's function (NEGF) approach. The results show that ACA stacking has the highest electron and hole transmission probabilities. The results show tunability for a wide range of band-gaps, carrier effective masses and transmission with a great promise for lattice engineering (stacking order and layers) in black phosphorous.

  3. Effect of carrier particle shape on dry powder inhaler performance.

    Science.gov (United States)

    Kaialy, Waseem; Alhalaweh, Amjad; Velaga, Sitaram P; Nokhodchi, Ali

    2011-12-12

    The aim of this study was to characterise the aerosolisation properties of salbutamol sulphate (SS) from dry powder inhaler (DPI) formulations containing different carrier products. The difference in the elongation ratio (ER) of the different carriers was highlighted. Different set of carriers, namely commercial mannitol (CM), commercial lactose (CL), cooling crystallised mannitol (CCM), acetone crystallised mannitol (ACM) and ethanol crystallised mannitol (ECM) were used and inspected in terms of size, shape, density, crystal form, flowability, and in vitro aerosolisation performance using Multi Stage Liquid Impinger (MSLI) and Aerolizer inhaler device. Solid-state and morphological characterization showed that CM product was in pure β-form having particles with smaller ER (CM: ER=1.62 ± 0.04) whereas ACM and ECM mannitol particles were in pure α form with higher ER (ACM: ER=4.83 ± 0.18, ECM: ER=5.89 ± 0.19). CCM product crystallised as mixtures of β-form and δ-form and showed the largest variability in terms of particle shape, size, and DPI performance. Linear relationships were established showing that carrier products with higher ER have smaller bulk density (D(b)), smaller tap density (D(t)), higher porosity (P), and poorer flow properties. In vitro aerosolisation assessments showed that the higher the ER of the carrier particles the greater the amounts of SS delivered to lower airway regions indicating enhanced DPI performance. Yet, DPI performance enhancement by increasing carrier ER reached a "limit" as increasing carrier ER from 4.83±0.18 (ACM) to 5.89±0.19 (ECM) did not significantly alter fine particle fraction (FPF) of SS. Also, carrier particles with higher ER were disadvantageous in terms of higher amounts of SS remained in inhaler device (drug loss) and deposited on throat. Linear relationship was established (r(2)=0.87) showing that the higher the carrier ER the lower the drug emission (EM) upon inhalation. Moreover, poorer flowability for

  4. Aging in Fragile X Premutation Carriers.

    Science.gov (United States)

    Lozano, Reymundo; Saito, Naomi; Reed, Dallas; Eldeeb, Marwa; Schneider, Andrea; Hessl, David; Tassone, Flora; Beckett, Laurel; Hagerman, Randi

    2016-10-01

    It is now recognized that FMR1 premutation carriers (PC) are at risk to develop a range of neurological, psychiatric, and immune-mediated disorders during adulthood. There are conflicting findings regarding the incidence of hypertension, hypothyroidism, diabetes, and cancer in these patients that warrant further study. A retrospective controlled study was performed in a convenience sample of 248 controls (130 men, 118 women) and 397 FMR1 PC with and without fragile X-associated tremor ataxia syndrome (FXTAS) (176 men, 221 women); all participants were at least 45 years old (men: mean 62.4, SD 9.5; women: mean 62.8, SD 9.9; p = 0.63). Memory and cognitive assessments (Wechsler Adult Intelligence Scale (WAIS-III), Wechsler Memory Scale (WMS-III)) and molecular testing (CGG repeats and FMR1-mRNA levels) were performed. Additional data included body mass index (BMI), cholesterol levels, blood pressure, hemoglobin A1c (HbA1c) levels, and medical history. A higher percentage of PC subjects self-reported having a diagnosis of hypertension (50.0 vs. 35.0 %, p = 0.006) and thyroid problems (20.4 vs. 10.0 %, p = 0.012) than control subjects. When comparing controls versus PC with FXTAS, the association was higher for diabetes (p = 0.043); however, the effect was not significant after adjusting for demographic predictors. Blood pressure, blood glucose levels, HbA1c, and BMI values were not significantly different between the two groups. The PC with FXTAS group performed consistently lower in neuropsychological testing compared with the PC without FXTAS group, but the differences were very small for all but the WAIS full-scale IQ. Based on these findings, it appears that the risk for hypertension, thyroid problems, and diabetes may be more frequent in PC with FXTAS, which will require verification in future studies.

  5. Vector Magnetometer Application with Moving Carriers

    Directory of Open Access Journals (Sweden)

    Andrii Prystai

    2016-12-01

    Full Text Available In magnetic prospecting the aeromagnetic survey is a widespread method used for research in large territories or in the areas with difficult access (forests, swamps, shallow waters. At present, a new type of mobile carriers – remotely piloted vehicles or drones – is becoming very common. The drones supplied by magnetometer can be also used for underground utility location (for example, steel and concrete constructions, buried power cables, to name a few. For aeromagnetic survey, obtaining of 3-component magnetic field data gives higher processing precision, so the fluxgate magnetometers (FGM seem to be the most preferable by reason of low weight, noise, power consumption and costs. During movement of FGM fixed to a drone practically permanent attitude changes in the Earth’s magnetic field arises with corresponding changes of its projection at FGM axes. Also the electromagnetic interference from the drone motor and uncontrolled oscillations of drone and suspension are the factors which limit the magnetometer sensitivity level. Aroused because of this, signals significantly exceed the expected signals from a studied object and so should be removed by proper interference filtration and use of stabilized towed construction, as well as at data processing. To find the necessary resolution threshold of a drone-portable FGM, the modeling was made to estimate magnetic field value from a small sphere about 1 cm radius at the minimal altitude of drone flight and it was shown that such a small object can be reliably detected if the FGM noise level is less than 0.15 nT. Next requirement is the necessity to decrease as much as possible the FGM power consumption with retention of low noise level. Finally, because of drone movement, the broadening of a frequency range should be done. The LEMI-026 magnetometer was developed satisfying all requirements to the drone-mounted device. The field tests were successfully performed using two of LEMI-026

  6. Chitosan nanoparticles as drug delivery carriers for biomedical engineering

    International Nuclear Information System (INIS)

    Shi, L.E.S.; Chen, M.; XINF, L.Y.; Guo, X.F.; Zhao, L.M.

    2011-01-01

    Chitosan is a rather abundant material, which has been widely used in food industrial and bioengineering aspects, including in encapsulating active food ingredients, in enzyme immobilization, and as a carrier for drug delivery, due to its significant biological and chemical properties such as biodegradable, biocompatible, bioactive and polycationic. This review discussed preparation and applications of chitosan nanoparticles in the biomedical engineering field, namely as a drug delivery carrier for biopharmaceuticals. (author)

  7. Magnetic Generation due to Mass Difference between Charge Carriers

    OpenAIRE

    Chen, Shi; Dan, JiaKun; Chen, ZiYu; Li, JianFeng

    2013-01-01

    The possibility of spontaneous magnetization due to the "asymmetry in mass" of charge carriers in a system is investigated. Analysis shows that when the masses of positive and negative charge carriers are identical, no magnetization is predicted. However, if the masses of two species are different, spontaneous magnetic field would appear, either due to the equipartition of magnetic energy or due to fluctuations together with a feedback mechanism. The conditions for magnetization to occur are ...

  8. Effects of copper on the carrier dynamics in black silicon

    DEFF Research Database (Denmark)

    Porte, Henrik; Turchinovich, Dmitry; Persheyev, S.

    2011-01-01

    Black silicon is produced by laser annealing of a-Si:H films. We show that by adding a thin Cu film on top of the a-Si:H film before laser annealing, the carrier lifetime can be significantly reduced.......Black silicon is produced by laser annealing of a-Si:H films. We show that by adding a thin Cu film on top of the a-Si:H film before laser annealing, the carrier lifetime can be significantly reduced....

  9. Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers.

    Science.gov (United States)

    Quiroz, Yakeel T; Stern, Chantal E; Reiman, Eric M; Brickhouse, Michael; Ruiz, Adriana; Sperling, Reisa A; Lopera, Francisco; Dickerson, Bradford C

    2013-05-01

    Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI. To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset. 40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions. Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe. Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD.

  10. Preparation and application of functionalized nano drug carriers

    OpenAIRE

    Gong, Rudong; Chen, Gaimin

    2016-01-01

    Objective: Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Methods: Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. Results: After first review of 1260 retrieved literature, it...

  11. Carrier-phonon interaction in semiconductor quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Seebeck, Jan

    2009-03-10

    In recent years semiconductor quantum dots have been studied extensively due to their wide range of possible applications, predominantly for light sources. For successful applications, efficient carrier scattering processes as well as a detailed understanding of the optical properties are of central importance. The aims of this thesis are theoretical investigations of carrier scattering processes in InGaAs/GaAs quantum dots on a quantum-kinetic basis. A consistent treatment of quasi-particle renormalizations and carrier kinetics for non-equilibrium conditions is presented, using the framework of non-equilibrium Green's functions. The focus of our investigations is the interaction of carriers with LO phonons. Important for the understanding of the scattering mechanism are the corresponding quasi-particle properties. Starting from a detailed study of quantum-dot polarons, scattering and dephasing processes are discussed for different temperature regimes. The inclusion of polaron and memory effects turns out to be essential for the description of the carrier kinetics in quantum-dot systems. They give rise to efficient scattering channels and the obtained results are in agreement with recent experiments. Furthermore, a consistent treatment of the carrier-LO-phonon and the carrier-carrier interaction is presented for the optical response of semiconductor quantum dots, both giving rise to equally important contributions to the dephasing. Beside the conventional GaAs material system, currently GaN based light sources are of high topical interest due to their wide range of possible emission frequencies. In this material additionally intrinsic properties like piezoelectric fields and strong band-mixing effects have to be considered. For the description of the optical properties of InN/GaN quantum dots a procedure is presented, where the material properties obtained from an atomistic tight-binding approach are combined with a many-body theory for non

  12. Apparatus and method for nanoflow liquid jet and serial femtosecond x-ray protein crystallography

    Science.gov (United States)

    Bogan, Michael J.; Laksmono, Hartawan; Sierra, Raymond G.

    2016-03-01

    Techniques for nanoflow serial femtosecond x-ray protein crystallography include providing a sample fluid by mixing a plurality of a first target of interest with a carrier fluid and injecting the sample fluid into a vacuum chamber at a rate less than about 4 microliters per minute. In some embodiments, the carrier fluid has a viscosity greater than about 3 centipoise.

  13. Ultrafast carrier dynamics in Landau-quantized graphene

    Directory of Open Access Journals (Sweden)

    Wendler Florian

    2015-01-01

    Full Text Available In an external magnetic field, the energy of massless charge carriers in graphene is quantized into non-equidistant degenerate Landau levels including a zero-energy level. This extraordinary electronic dispersion gives rise to a fundamentally new dynamics of optically excited carriers. Here, we review the state of the art of the relaxation dynamics in Landau-quantized graphene focusing on microscopic insights into possible many-particle relaxation channels.We investigate optical excitation into a non equilibrium distribution followed by ultrafast carrier- carrier and carrier-phonon scattering processes. We reveal that surprisingly the Auger scattering dominates the relaxation dynamics in spite of the non-equidistant Landau quantization in graphene. Furthermore, we demonstrate how technologically relevant carrier multiplication can be achieved and discuss the possibility of optical gain in Landau-quantized graphene. The provided microscopic view on elementary many-particle processes can guide future experimental studies aiming at the design of novel graphene-based optoelectronic devices, such as highly efficient photodetectors, solar cells, and spectrally broad Landau level lasers.

  14. Nanostructured lipid carriers system: recent advances in drug delivery.

    Science.gov (United States)

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  15. Defensin carriers for better mucosal immunity in the digestive system.

    Science.gov (United States)

    Froy, Oren; Chapnik, Nava; Nussinovitch, Amos

    2010-06-30

    The innate immunity utilizes a battery of broad-spectrum antibacterial cationic polypeptides named defensins. In humans, defensins are the first line of defense against pathogens, and their expression has been implicated in several diseases. In addition to exerting direct antimicrobial effects, defensins facilitate and amplify innate and adaptive immune responses. HD-5 is a polypeptide that plays a pivotal role in combating bacteria in the digestive system. Our results show that HD-5 can be entrapped within alginate carriers and strengthen their structure without changing their brittleness. In addition, carrier-entrapped HD-5 is released when incubated in buffer and/or stomach-simulating solution and still retains its activity after the release. This incubation also led to a decrease in carrier strength as well as an increase in their brittleness. Nevertheless the carriers did not disintegrate and remained intact throughout the diffusion process. The release of the defensin exhibited a bimodal behavior, suggesting that it was found both in a cross-linked and non-cross-linked form within the carrier. These results indicate that defensins encapsulated within alginate carriers could possibly be used for better mucosal immunity in the digestive system. 2010 Elsevier B.V. All rights reserved.

  16. Implications of asymptomatic carriers for infectious disease transmission and control.

    Science.gov (United States)

    Chisholm, Rebecca H; Campbell, Patricia T; Wu, Yue; Tong, Steven Y C; McVernon, Jodie; Geard, Nicholas

    2018-02-01

    For infectious pathogens such as Staphylococcus aureus and Streptococcus pneumoniae , some hosts may carry the pathogen and transmit it to others, yet display no symptoms themselves. These asymptomatic carriers contribute to the spread of disease but go largely undetected and can therefore undermine efforts to control transmission. Understanding the natural history of carriage and its relationship to disease is important for the design of effective interventions to control transmission. Mathematical models of infectious diseases are frequently used to inform decisions about control and should therefore accurately capture the role played by asymptomatic carriers. In practice, incorporating asymptomatic carriers into models is challenging due to the sparsity of direct evidence. This absence of data leads to uncertainty in estimates of model parameters and, more fundamentally, in the selection of an appropriate model structure. To assess the implications of this uncertainty, we systematically reviewed published models of carriage and propose a new model of disease transmission with asymptomatic carriage. Analysis of our model shows how different assumptions about the role of asymptomatic carriers can lead to different conclusions about the transmission and control of disease. Critically, selecting an inappropriate model structure, even when parameters are correctly estimated, may lead to over- or under-estimates of intervention effectiveness. Our results provide a more complete understanding of the role of asymptomatic carriers in transmission and highlight the importance of accurately incorporating carriers into models used to make decisions about disease control.

  17. Genes regulation encoding ADP/ATP carrier in yeasts Saccharomyces cerevisiae and Candida parapsilosis

    International Nuclear Information System (INIS)

    Nebohacova, M.

    2000-01-01

    Genes encoding a mitochondrial ADP/ATP carrier (AAC) in yeast Saccharomyces cerevisiae and Candida parapsilosis were investigated. AAC2 is coding for the major AAC isoform in S. cerevisiae. We suggest that AAC2 is a member of a syn-expression group of genes encoding oxidative phosphorylation proteins. Within our previous studies on the regulation of the AAC2 transcription an UAS (-393/-268) was identified that is essential for the expression of this gene. Two functional regulatory cis-elements are located within this UAS -binding sites for an ABFl factor and for HAP2/3/4/5 heteromeric complex. We examined relative contributions and mutual interactions of the ABFl and HAP2/3/4/5 factors in the activation of transcription from the UAS of the AAC2 gene. The whole UAS was dissected into smaller sub-fragments and tested for (i) the ability to form DNA-protein complexes with cellular proteins in vitro, (ii) the ability to confer heterologous expression using AAC3 gene lacking its own promoter, and (iii) the expression of AAC3-lacZ fusion instead of intact AAC3 gene. The obtained results demonstrated that: a) The whole UAS as well as sub-fragment containing only ABF1-binding site are able to form DNA-protein complexes with cellular proteins in oxygen- and heme- dependent manner. The experiments with antibody against the ABF1 showed that the ABF1 factor is one of the proteins binding to AAC2 promoter. We have been unsuccessful to prove the binding of cellular proteins to the HAP2/3/4/5-binding site. However, the presence of HAP2/3/4/5-binding site is necessary to drive a binding of cellular proteins to the ABF1-binding site in carbon source-dependent manner. b) The presence of both ABF1- and HAP2/3/4/5-binding sites and original spacing between them is necessary to confer the growth of Aaac2 mutant strain on non- fermentable carbon source when put in front of AAC3 gene introduced on centromeric vector to Aaac2 mutant strain. c) For the activation of AAC3-lacZ expression on

  18. pH-dependent and carrier-mediated transport of salicylic acid across Caco-2 cells.

    Science.gov (United States)

    Takanaga, H; Tamai, I; Tsuji, A

    1994-07-01

    The transport of monocarboxylic acid drugs such as salicylic acid was examined in the human colon adenocarcinoma cell line, Caco-2 cells that possess intestinal epithelia-like properties. [14C]Salicylic acid transport was pH-dependent and appeared to follow the pH-partition hypothesis. However, 10 mM unlabelled salicylic acid significantly reduced the permeability coefficient of [14C]salicylic acid. Kinetic analysis of the concentration dependence of the permeation rate of salicylic acid across Caco-2 cells showed both saturable (Kt = 5.28 +/- 0.72 mM Jmax = 36.6 +/- 3.54 nmol min-1 (mg protein)-1) and nonsaturable (kd = 0.37 +/- 0.08 microL min-1 (mg protein)-1) processes. The permeation rate of [14C]salicylic acid was competitively inhibited by both acetic acid and benzoic acid, which were demonstrated in our previous studies to be transported in the carrier-mediated-transport mechanism which is responsible for monocarboxylic acids. Furthermore, certain monocarboxylic acids significantly inhibited [14C]salicylic acid transport, whereas salicylamide and dicarboxylic acids such as succinic acid did not. From these results, it was concluded that the transcellular transport of [14C]salicylic acid across Caco-2 cells is by the pH-dependent and carrier-mediated transport mechanism specific for monocarboxylic acids.

  19. Literature review of the passenger airline business models: Full service carrier, low-cost carrier and charter airlines

    OpenAIRE

    Carmona Benitez, R.B.; Lodewijks, G.

    2008-01-01

    The deregulation and liberalization of the air transportation industry have developed three main passenger business models: full service carriers, low-cost carriers, and charter airlines. Deregulation removed regulated fares and routes increasing competition and yields. Airlines business models main objectives are to minimize operation costs and fares, and to maximize profits based on cost leadership, differentiation and focus strategy. This paper presents a literature review about airline bu...

  20. Characterization and cytotoxicity of nanostructured lipid carriers formulated with olive oil, hydrogenated palm oil, and polysorbate 80.

    Science.gov (United States)

    How, Chee W; Rasedee, Abdullah; Abbasalipourkabir, Roghayeh

    2013-06-01

    Nanostructured lipid carriers (NLC) composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Before NLC can be used as drug carriers, the cytotoxicity of their components must be ascertained. The cytotoxicity of solid lipids (trilaurin, palmitin, docosanoid acid, and hydrogenated palm oil [HPO]) and surfactants (Polysorbate 20, 80, and 85) were determined on BALB/c 3T3 cells. The HPO and Polysorbate 80 were least cytotoxic and used with olive oil in the formulation of NLC. The particle size, polydispersity index, zeta potential, specific surface area, and crystallinity index of the NLC were 61.14 nm, 0.461, -25.4 mV, and 49.07 m(2) and 27.12% respectively, while the melting point was 4.3 °C lower than of HPO. Unlike in serum-free, NLC incubated in fetal bovine serum-supplemented medium did not show particle growth, suggesting that serum proteins in medium inhibit nanoparticles aggregation. The study also showed that NLC was less toxic to BALB/c 3T3 cells than Polysorbate 80. Thus, NLC with olive oil, HPO, and Polysorbate 80 as components are potentially good drug carriers with minimal cytotoxicity on normal cells.

  1. A mutation in the glutamate-rich region of RNA-binding motif protein 20 causes dilated cardiomyopathy through missplicing of titin and impaired Frank-Starling mechanism

    DEFF Research Database (Denmark)

    Beqqali, Abdelaziz; Bollen, I. A. E.; Rasmussen, T. B.

    2016-01-01

    -rich region of RBM20. Western blot analysis of endogenous RBM20 protein revealed strongly reduced protein levels in the heart of an RBM20(E913K/+) carrier. RNA deep-sequencing demonstrated massive inclusion of exons coding for the spring region of titin in the RBM20(E913K/+) carrier. Titin isoform analysis...

  2. Surface plasmon polariton-induced hot carrier generation for photocatalysis.

    Science.gov (United States)

    Ahn, Wonmi; Ratchford, Daniel C; Pehrsson, Pehr E; Simpkins, Blake S

    2017-03-02

    Non-radiative plasmon decay in noble metals generates highly energetic carriers under visible light irradiation, which opens new prospects in the fields of photocatalysis, photovoltaics, and photodetection. While localized surface plasmon-induced hot carrier generation occurs in diverse metal nanostructures, inhomogeneities typical of many metal-semiconductor plasmonic nanostructures hinder predictable control of photocarrier generation and therefore reproducible carrier-mediated photochemistry. Here, we generate traveling surface plasmon polaritons (SPPs) at the interface between a noble metal/titanium dioxide (TiO 2 ) heterostructure film and aqueous solution, enabling simultaneous optical and electrochemical interrogation of plasmon-mediated chemistry in a system whose resonance may be continuously tuned via the incident optical excitation angle. To the best of our knowledge, this is the first experimental demonstration of SPP-induced hot carrier generation for photocatalysis. We found electrochemical photovoltage and photocurrent responses as SPP-induced hot carriers drive both solution-based oxidation of methanol and the anodic half-reaction of photoelectrochemical water-splitting in sodium hydroxide solution. A strong excitation angle dependence and linear power dependence in the electrochemical photocurrent confirm that the photoelectrochemical reactions are SPP-driven. SPP-generated hot carrier chemistry was recorded on gold and silver and with two different excitation wavelengths, demonstrating potential for mapping resonant charge transfer processes with this technique. These results will provide the design criteria for a metal-semiconductor hybrid system with enhanced hot carrier generation and transport, which is important for the understanding and application of plasmon-induced photocatalysis.

  3. Study on temperature-dependent carrier transport for bilayer graphene

    Science.gov (United States)

    Liu, Yali; Li, Weilong; Qi, Mei; Li, Xiaojun; Zhou, Yixuan; Ren, Zhaoyu

    2015-05-01

    In order to investigate the temperature-dependent carrier transport property of the bilayer graphene, graphene films were synthesized on Cu foils by a home-built chemical vapor deposition (CVD) with C2H2. Samples regularity, transmittance (T) and layer number were analyzed by transmission electron microscope (TEM) images, transmittance spectra and Raman spectra. Van Der Pauw method was used for resistivity measurements and Hall measurements at different temperatures. The results indicated that the sheet resistance (Rs), carrier density (n), and mobility (μ) were 1096.20 Ω/sq, 0.75×1012 cm-2, and 7579.66 cm2 V-1 s-1 at room temperature, respectively. When the temperature increased from 0 °C to 240 °C, carrier density (n) increased from 0.66×1012 cm-2 to 1.55×1012 cm-2, sheet resistance (Rs) decreased from 1215.55 Ω/sq to 560.77 Ω/sq, and mobility (μ) oscillated around a constant value 7773.99 cm2 V-1 s-1. The decrease of the sheet resistance (Rs) indicated that the conductive capability of the bilayer graphene film increased with the temperature. The significant cause of the increase of carrier density (n) was the thermal activation of carriers from defects and unconscious doping states. Because the main influence on the carrier mobility (μ) was the lattice defect scattering and a small amount of impurity scattering, the carrier mobility (μ) was temperature-independent for the bilayer graphene.

  4. Clinical and genetic characterization of manifesting carriers of DMD mutations.

    Science.gov (United States)

    Soltanzadeh, Payam; Friez, Michael J; Dunn, Diane; von Niederhausern, Andrew; Gurvich, Olga L; Swoboda, Kathryn J; Sampson, Jacinda B; Pestronk, Alan; Connolly, Anne M; Florence, Julaine M; Finkel, Richard S; Bönnemann, Carsten G; Medne, Livija; Mendell, Jerry R; Mathews, Katherine D; Wong, Brenda L; Sussman, Michael D; Zonana, Jonathan; Kovak, Karen; Gospe, Sidney M; Gappmaier, Eduard; Taylor, Laura E; Howard, Michael T; Weiss, Robert B; Flanigan, Kevin M

    2010-08-01

    Manifesting carriers of DMD gene mutations may present diagnostic challenges, particularly in the absence of a family history of dystrophinopathy. We review the clinical and genetic features in 15 manifesting carriers identified among 860 subjects within the United Dystrophinopathy Project, a large clinical dystrophinopathy cohort whose members undergo comprehensive DMD mutation analysis. We defined manifesting carriers as females with significant weakness, excluding those with only myalgias/cramps. DNA extracted from peripheral blood was used to study X-chromosome inactivation patterns. Among these manifesting carriers, age at symptom onset ranged from 2 to 47 years. Seven had no family history and eight had male relatives with Duchenne muscular dystrophy (DMD). Clinical severity among the manifesting carriers varied from a DMD-like progression to a very mild Becker muscular dystrophy-like phenotype. Eight had exonic deletions or duplications and six had point mutations. One patient had two mutations (an exonic deletion and a splice site mutation), consistent with a heterozygous compound state. The X-chromosome inactivation pattern was skewed toward non-random in four out of seven informative deletions or duplications but was random in all cases with nonsense mutations. We present the results of DMD mutation analysis in this manifesting carrier cohort, including the first example of a presumably compound heterozygous DMD mutation. Our results demonstrate that improved molecular diagnostic methods facilitate the identification of DMD mutations in manifesting carriers, and confirm the heterogeneity of mutational mechanisms as well as the wide spectrum of phenotypes. 2010 Elsevier B.V. All rights reserved.

  5. Incorporating medical interventions into carrier probability estimation for genetic counseling

    Directory of Open Access Journals (Sweden)

    Katki Hormuzd A

    2007-03-01

    Full Text Available Abstract Background Mendelian models for predicting who may carry an inherited deleterious mutation of known disease genes based on family history are used in a variety of clinical and research activities. People presenting for genetic counseling are increasingly reporting risk-reducing medical interventions in their family histories because, recently, a slew of prophylactic interventions have become available for certain diseases. For example, oophorectomy reduces risk of breast and ovarian cancers, and is now increasingly being offered to women with family histories of breast and ovarian cancer. Mendelian models should account for medical interventions because interventions modify mutation penetrances and thus affect the carrier probability estimate. Methods We extend Mendelian models to account for medical interventions by accounting for post-intervention disease history through an extra factor that can be estimated from published studies of the effects of interventions. We apply our methods to incorporate oophorectomy into the BRCAPRO model, which predicts a woman's risk of carrying mutations in BRCA1 and BRCA2 based on her family history of breast and ovarian cancer. This new BRCAPRO is available for clinical use. Results We show that accounting for interventions undergone by family members can seriously affect the mutation carrier probability estimate, especially if the family member has lived many years post-intervention. We show that interventions have more impact on the carrier probability as the benefits of intervention differ more between carriers and non-carriers. Conclusion These findings imply that carrier probability estimates that do not account for medical interventions may be seriously misleading and could affect a clinician's recommendation about offering genetic testing. The BayesMendel software, which allows one to implement any Mendelian carrier probability model, has been extended to allow medical interventions, so future

  6. Eukaryotic LYR Proteins Interact with Mitochondrial Protein Complexes

    Directory of Open Access Journals (Sweden)

    Heike Angerer

    2015-02-01

    Full Text Available In eukaryotic cells, mitochondria host ancient essential bioenergetic and biosynthetic pathways. LYR (leucine/tyrosine/arginine motif proteins (LYRMs of the Complex1_LYR-like superfamily interact with protein complexes of bacterial origin. Many LYR proteins function as extra subunits (LYRM3 and LYRM6 or novel assembly factors (LYRM7, LYRM8, ACN9 and FMC1 of the oxidative phosphorylation (OXPHOS core complexes. Structural insights into complex I accessory subunits LYRM6 and LYRM3 have been provided by analyses of EM and X-ray structures of complex I from bovine and the yeast Yarrowia lipolytica, respectively. Combined structural and biochemical studies revealed that LYRM6 resides at the matrix arm close to the ubiquinone reduction site. For LYRM3, a position at the distal proton-pumping membrane arm facing the matrix space is suggested. Both LYRMs are supposed to anchor an acyl-carrier protein (ACPM independently to complex I. The function of this duplicated protein interaction of ACPM with respiratory complex I is still unknown. Analysis of protein-protein interaction screens, genetic analyses and predicted multi-domain LYRMs offer further clues on an interaction network and adaptor-like function of LYR proteins in mitochondria.

  7. 49 CFR 385.303 - How does a motor carrier register with the FMCSA?

    Science.gov (United States)

    2010-10-01

    ... Washington, DC headquarters by mail at, Federal Motor Carrier Safety Administration, 1200 New Jersey Ave., SE... 49 Transportation 5 2010-10-01 2010-10-01 false How does a motor carrier register with the FMCSA...) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY...

  8. Carrier dynamics analysis in metal-semiconductor-metal device for mid-IR silicon photonics

    DEFF Research Database (Denmark)

    Hui, Alvin Tak Lok; Ding, Yunhong; Hu, Hao

    2017-01-01

    A modelling platform for active carrier removal based on metal-semiconductor-metal structure is reported on analysis of carrier dynamics. The analysis reveals electric current hot spots exist in geometric singularities and curly trajectory of carriers should be considered when accurately estimati...... the effective carrier lifetime....

  9. THE USE OF PREVENTIVE HEALTH-CARE SERVICES - CARRIER TESTING FOR THE GENETIC DISORDER HEMOPHILIA

    NARCIS (Netherlands)

    VAREKAMP, [No Value; SUURMEIJER, TPBM; ROSENDAAL, FR; BROCKERVRIENDS, AHJT

    A retrospective study was performed to explore carrier testing among women who were possible or obligate carriers of the haemophilia gene. Knowledge of the possibility of carrier testing and use of carrier testing were studied separately. In our exploration we were guided by the diffusion theory and

  10. Golgi coiled-coil proteins contain multiple binding sites for Rab family G proteins

    NARCIS (Netherlands)

    Sinka, Rita; Gillingham, Alison K.; Kondylis, Vangelis; Munro, Sean

    2008-01-01

    Vesicles and other carriers destined for the Golgi apparatus must be guided to the correct cisternae. Golgins, long coiled-coil proteins that localize to particular Golgi subdomains via their C termini, are candidate regulators of vesicle sorting. In this study, we report that the GRIP domain

  11. QPSK Carrier Signal Detection Based on Double Duffing Oscillators

    Directory of Open Access Journals (Sweden)

    Yongfeng WU

    2014-02-01

    Full Text Available The paper proposed a new method for the detection of QPSK carrier signal that based on double duffing oscillator to solve the problems as high attenuation and strong noise interference in the QPSK carrier communication of low voltage power line. This method has making use of the different phase of QPSK carrier signal to stimulate the double duffing oscillators to enter different states and through the judgment of the state of the double duffing oscillators to detect the phase information that the QPSK carrier signal carries. At the same time, through the study of the system solutions of duffing oscillator, obtained the change rule of them, based on these rules, the paper proposed a discriminant algorithm that used the difference distribution, and this algorithm is characterized by small calculating amount and low error judgment rate. The numerical simulation and experimental test show that the double duffing oscillator method can detect the phase information of QPSK carrier signal in low voltage power line accurately with the low SNR environment.

  12. Strain engineering on transmission carriers of monolayer phosphorene

    Science.gov (United States)

    Zhang, Wei; Li, Feng; Hu, Junsong; Zhang, Ping; Yin, Jiuren; Tang, Xianqiong; Jiang, Yong; Wu, Bozhao; Ding, Yanhuai

    2017-11-01

    The effects of uniaxial strain on the structure, band gap and transmission carriers of monolayer phosphorene were investigated by first-principles calculations. The strain induced semiconductor-metal as well as direct–indirect transitions were studied in monolayer phosphorene. The position of CBM which belonged to indirect gap shifts along the direction of the applied strain. We have concluded the change rules of the carrier effective mass when plane strains are applied. In band structure, the sudden decrease of band gap or the new formation of CBM (VBM) causes the unexpected change in carrier effective mass. The effects of zigzag and armchair strain on the effective electron mass in phosphorene are different. The strain along zigzag direction has effects on the electrons effective mass along both zigzag and armchair direction. By contrast, armchair-direction strain seems to affect only on the free electron mass along zigzag direction. For the holes, the effective masses along zigzag direction are largely affected by plane strains while the effective mass along armchair direction exhibits independence in strain processing. The carrier density of monolayer phosphorene at 300 K is calculated about 1.25× {{10}6} cm‑2, which is greatly influenced by the temperature and strain. Strain engineering is an efficient method to improve the carrier density in phosphorene.

  13. Comparison of methods to detect Pasteurella multocida in carrier waterfowl

    Science.gov (United States)

    Samuel, M.D.; Shadduck, D.J.; Goldberg, Diana R.; Johnson, W.P.

    2003-01-01

    We conducted laboratory challenge trials using mallard ducks (Anas platyrhynchos) to compare methods for detecting carriers of Pasteurella multocida, the bacterium that causes avian cholera, in wild birds. Birds that survived the initial infection were euthanized at 2-4 wk intervals up to 14 wk post challenge. Isolates of P. multocida were obtained at necropsy from 23% of the birds that survived initial infection. We found that swab samples (oral, cloacal, nasal, eye, and leg joint) were most effective for detecting carrier birds up to 14 wk post infection. No detectable differences in isolation were observed for samples stored in either 10% dimethysulfoxide or brain heart infusion broth. The frequency of detecting carriers in our challenge trials appeared to be related to mortality rates observed during the trial, but was not related to a number of other factors including time after challenge, time delays in collecting tissues postmortem, and route of infection. In our trials, there was little association between antibody levels and carrier status. We concluded that swabs samples collected from recently dead birds, stored in liquid nitrogen, and processed using selective broth provide a feasible field method for detecting P. multocida carriers in wild waterfowl.

  14. Cell carriers for oncolytic viruses: current challenges and future directions

    Directory of Open Access Journals (Sweden)

    Roy DG

    2013-10-01

    Full Text Available Dominic G Roy,1,2 John C Bell1–31Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, 2Department of Biochemistry, Immunology and Microbiology, 3Department of Medicine, University of Ottawa, Ottawa, ON, CanadaAbstract: The optimal route for clinical delivery of oncolytic viruses is thought to be systemic intravenous injection; however, the immune system is armed with several highly efficient mechanisms to remove pathogens from the circulatory system. To overcome the challenges faced in trying to delivery oncolytic viruses specifically to tumors via the bloodstream, carrier cells have been investigated to determine their suitability as delivery vehicles for systemic administration of oncolytic viruses. Cell carriers protect viruses from neutralization, one of the most limiting aspects of oncolytic virus interaction with the immune system. Cell carriers can also possess inherent tumor tropism, thus directing the delivery of the virus more specifically to a tumor. With preclinical studies already demonstrating the success and feasibility of this approach with multiple oncolytic viruses, clinical evaluation of cell-mediated delivery of viruses is on the horizon. Meanwhile, ongoing preclinical studies are aimed at identifying new cellular vehicles for oncolytic viruses and improving current promising cell carrier platforms.Keywords: oncolytic virus, cell carrier, systemic delivery, tumor targeting, cancer

  15. [Carriers of Neisseria meningitidis among children from a primary school].

    Science.gov (United States)

    Martínez, Isabel; López, Omar; Sotolongo, Franklin; Mirabal, Mayelin; Bencomo, Antonio

    2003-01-01

    A cross-sectional and descriptive study was conducted among 318 children from the "Mártires del Corynthia" Primary School under the authorization of the Municipal Division of Education and the informed consent of their parents aimed at knowing the prevalence of meningoccoco carriers in school children, determining the epidemiological markers of the isolated strains and establishing the possible relation existing between the carrier and variables, such as age, sex, acute respiratory infection history, hacinamiento, amigdalectomy, inhibitory effect of of the accompanying flora and the secretory state of ABH antigens in saliva. All of them underwent nasopharyngeal exudate and a saliva sample was taken. In adition, the paents were surveyed about the risks factors to be investigated. 6.9 % of meningoccoco carriers were found and the NA:NT:P1:NST:L3,7,9 strains predominated. The risk factors with statistically significant results regarding the condition of carrier Neisseria meningitidis carrier were age, acute respiratory infection history, and the presence of Streptococcus pneumoniae and Neisseria lactamica of the accompanying bacterial flora in the nasopharynx of the children under study.

  16. Charge carrier velocity in graphene field-effect transistors

    Science.gov (United States)

    Bonmann, Marlene; Vorobiev, Andrei; Andersson, Michael A.; Stake, Jan

    2017-12-01

    To extend the frequency range of transistors into the terahertz domain, new transistor technologies, materials, and device concepts must be continuously developed. The quality of the interface between the involved materials is a highly critical factor. The presence of impurities can degrade device performance and reliability. In this paper, we present a method that allows the study of the charge carrier velocity in a field-effect transistor vs impurity levels. The charge carrier velocity is found using high-frequency scattering parameter measurements followed by delay time analysis. The limiting factors of the saturation velocity and the effect of impurities are then analysed by applying analytical models of the field-dependent and phonon-limited carrier velocity. As an example, this method is applied to a top-gated graphene field-effect transistor (GFET). We find that the extracted saturation velocity is ca. 1.4 ×107 cm/s and is mainly limited by silicon oxide substrate phonons. Within the considered range of residual charge carrier concentrations, charged impurities do not limit the saturation velocity directly by the phonon mechanism. Instead, the impurities act as traps that emit charge carriers at high fields, preventing the current from saturation and thus limiting power gain of the GFETs. The method described in this work helps to better understand the influence of impurities and clarifies methods of further transistor development. High quality interfaces are required to achieve current saturation via velocity saturation in GFETs.

  17. Interfacing materials science and biology for drug carrier design.

    Science.gov (United States)

    Such, Georgina K; Yan, Yan; Johnston, Angus P R; Gunawan, Sylvia T; Caruso, Frank

    2015-04-08

    Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis. Although much progress has been made in this field, the specificity of polymeric carriers is still limited when compared with their biological counterparts. To synthesize the next generation of carriers, it is important to consider the biological rationale for materials design. This requires a detailed understanding of the cellular microenvironments and how these can be harnessed for specific applications. In this review, several important physiological cues in the cellular microenvironments are outlined, with a focus on changes in pH, redox potential, and the types of enzymes present in specific regions. Furthermore, recent studies that use such biologically inspired triggers to design polymeric carriers are highlighted, focusing on applications in the field of therapeutic delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Towards an understanding of hot carrier cooling mechanisms in multiple quantum wells

    Science.gov (United States)

    Conibeer, Gavin; Zhang, Yi; Bremner, Stephen P.; Shrestha, Santosh

    2017-09-01

    Multiple quantum wells have been shown significantly reduced hot carrier cooling rates compared to bulk material and are thus a promising candidate for hot carrier solar cell absorbers. However, the mechanism(s) by which hot carrier cooling is restricted is not clear. A systematic study of carrier cooling rates in GaAs/AlAs multiple quantum wells (MQWs) with either varying barrier thickness or varying well thickness is presented in this paper. These allow an investigation as to whether the mechanisms of either a modification in hot carrier diffusion or a localisation of phonons emitted by hot carriers are primarily responsible for reduced carrier cooling rates. With the conclusion that for the structures investigated the situation is rather more complex with both carrier mobility to modify hot carrier diffusion, different diffusion rates for electrons and holes and reflection and localisation of phonons to enhance phonon bottleneck all playing their parts in modulating phonon reabsorption and hot carrier behaviour.

  19. Tentacle carrier for immobilization of potato phenoloxidase and its application for halogenophenols removal from aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Loncar, Nikola, E-mail: nloncar@chem.bg.ac.rs [Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade (Serbia); Vujcic, Zoran, E-mail: zvujcic@chem.bg.ac.rs [Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, Belgrade (Serbia)

    2011-11-30

    Highlights: Black-Right-Pointing-Pointer We synthesized novel immobilization carrier from reused DEAE-cellulose. Black-Right-Pointing-Pointer We used it for immobilization of PPO through coordinative bonding with copper ions. Black-Right-Pointing-Pointer Immobilized PPO showed better characteristics than soluble PPO. Black-Right-Pointing-Pointer TC-PPO removed over 90% of halogenophenols at concentration of 100 mg/L. - Abstract: Halogenated compounds represent one of the most dangerous environmental pollutants, due to their widespread usage as biocides, fungicides, disinfectants, solvent and other industrial chemicals. Immobilization of a protein through coordinate bonds formed with divalent metal ions is becoming an attractive method due to its reversible nature, since the protein may be easily removed from the support matrix through interruption of the protein-metal bond hence giving inherently cleaner and cheaper technology for wastewater treatment. We have synthesized novel 'tentacle' carrier (TC) and used it for immobilization of partially purified potato polyphenol oxidase (PPO). The obtained biocatalyst TC-PPO showed pH optimum at 7.0-8.0 and temperature optimum at 25 Degree-Sign C. Immobilized PPO shows almost 100% of activity at 0 Degree-Sign C. TC-PPO was more resistant to the denaturation induced by sodium dodecyl sulphate (SDS) detergent as compared to its soluble counterpart and was even slightly activated at SDS concentration of 1%. TC-PPO was tested in the batch reactor for 4-chlorophenol and 4-bromophenol removal. More than 90% removal was achieved for both halogenophenols at concentration of 100 mg/L from aqueous solution. For both halogenophenols TC-PPO works with over 90% removal during first three cycles which decrease to 60% removal efficiency after six cycles each of 8 h duration.

  20. [Bacterial outer membrane vesicles as nano carriers to study immunological activities].

    Science.gov (United States)

    Qi, Chen; Min, W U; Hongzhen, Bai; Zeling, Guo; Jun, Zhou; Qingqing, Wang; Guping, Tang

    2017-03-25

    Objective: To prepare a nano-carrier based on combining bacterial outer membrane vesicles (OMV) with three block polymer pluronic F127 (PEO 100 -PPO 65 -PEO 100 ) (OMV-F127) and to investigate its immunological activity. Methods: Attenuated salmonella (sal) was cultivated. OMV were separated by centrifugal ultrafiltration or ultrasonication, and OMV-F127 was prepared by mechanical extrudation method. The protein contents and compositions were tested with BCA and SDS-PAGE; the morphology of OMV, F127 and OMV-F127 were observed with FM and TEM; the particle sizes and their zeta potential were determined with DLS. Mouse macrophage RAW246.7 cells were treated with OMV-F127 (50 μg/mL, 100 μg/mL) in vitro, and the concentrations of IL-12, TNF-α and IFN-γ in culture supernatant were measured with ELISA kits. Results: The contents of protein in separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL and 2.7 mg/mL, respectively. SDS-PAGE showed the marker protein OmpF/C in OMV. Under the FM and TEM, ball-like structure of F127 and OMV-F127 was observed. Size analysis revealed that the diameters of OMV, F127 and OMV-F127 were 72±2 nm, 90±3 nm and 92±2 nm, respectively. ELISA tests revealed that OMV-F127 significantly stimulated the secretion of IL-12, TNF-α and IFN-γ in RAW246.7 cells. Conclusion: A nano-carrier based on bacterial outer membrane vesicles has been prepared, which can stimulate the secretion of cytokines and may have immunomodulatory effects.