Diphtheria toxin can simultaneously bind to its receptor and adenylyl-(3',5')-uridine 3'-monophosphate

International Nuclear Information System (INIS)

Barbieri, J.T.; Collins, C.M.; Collier, R.J.

1986-01-01

Diphtheria toxin (DT) that was bound to receptors on BS-C-1 cells was able to bind approximately 1 molar equiv of adenylyl-(3',5')-uridine 3'-monophosphate (ApUp). In contrast, receptor-bound CRM197, a mutant form of toxin with greatly diminished affinity for dinucleotides, did not bind ApUp. Affinity of the dinucleotide for receptor-bound toxin differed from that for free toxin by less than an order of magnitude. These results indicate that the receptor site and the ApUp site on the toxin do not significantly overlap. BS-C-1 cells were incubated with or without 125 I-DT or CRM 197. They were then incubated with [ 32 P]ApUp, and assayed

Plasma and memory B-cell kinetics in infants following a primary schedule of CRM 197-conjugated serogroup C meningococcal polysaccharide vaccine.

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Kelly, Dominic F; Snape, Matthew D; Perrett, Kirsten P; Clutterbuck, Elizabeth A; Lewis, Susan; Blanchard Rohner, Geraldine; Jones, Meryl; Yu, Ly-Mee; Pollard, Andrew J

2009-05-01

The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

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Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

Diphtheria toxin- and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-alpha.

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Morimoto, H; Bonavida, B

1992-09-15

We have reported that diphtheria toxin (DTX) mediates target cell lysis and intranucleosomal DNA fragmentation (apoptosis) and also synergizes with TNF-alpha. In this paper, we examined which step in the pathway of DTX-mediated inhibition of protein synthesis was important for induction of cytolytic activity and for synergy. Using a DTX-sensitive tumor cell line, we first examined the activity of the mutant CRM 197, which does not catalyze the ADP ribosylation of elongation factor-2 (EF-2). CRM 197 was not cytolytic for target cells and did not mediate intranucleosomal DNA fragmentation of viable cells. The failure of CRM 197 to mediate target cell lysis suggested that the catalytic activity of DTX is prerequisite for target cell lysis. This was corroborated by demonstrating that MeSAdo, which blocks the biosynthesis of diphthamide, inhibited DTX-mediated protein synthesis inhibition and also blocked target cell lysis. Furthermore, the addition of nicotinamide, which competes with NAD+ on the DTX action site of EF-2, also blocked DTX-mediated lysis. These findings suggest that ADP-ribosylation of EF-2 may be a necessary step in the pathway leading to target cell lysis. In contrast to the sensitive line, the SKOV-3 tumor cell line is sensitive to protein synthesis inhibition by DTX but is not susceptible to cytolysis and apoptosis by DTX. Thus, protein synthesis inhibition by DTX is not sufficient to mediate target cell lysis. The synergy in cytotoxicity obtained with the combination of DTX and TNF-alpha was examined in order to determine the pathway mediated by DTX in synergy. Like the direct lysis by DTX, synergy was significantly reduced by MeSAdo and by nicotinamide. Furthermore, synergy was not observed with combination of CRM 197 and TNF-alpha. These results demonstrate that, in synergy, DTX may utilize the same pathway required for its cytolytic activity. Pseudomonas aeruginosa exotoxin shared most the properties shown for DTX. Altogether, these findings

Assessment of immunogenicity and safety following primary and booster immunisation with a CRM197 -conjugated Haemophilus influenzae type B vaccine in healthy Chinese infants.

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Jun, L; Yuguo, C; Zhiguo, W; Jinfeng, L; Huawei, M; Xiuhua, L; Yonggui, Z; Yanhua, X; Kong, Y; Hongtao, L; Yuliang, Z

2013-10-01

Invasive meningitis and pneumonia caused by Haemophilus influenzae type b (Hib) is an important cause of childhood mortality in countries where Hib vaccination is not routine. We evaluated the non-inferiority of a licensed Hib vaccine, PRP-CRM(197) compared with a second licensed Hib vaccine, PRP-T, following the recommended Chinese immunisation schedule for infants between 6 months and 1 year of age. In the first study phase, 6-12 month-old infants received two primary doses of either PRP-CRM(197) (n = 335) or PRP-T (n = 335) vaccine administered 1 month apart. In the second study phase 8 months later, the same children received a single booster dose of vaccine identical to that use for priming (PRP-CRM(197), n = 327; PRP-T, n = 333). Serum levels of anti-polyribosylribitol phosphate (PRP) antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Non-inferiority of primary and booster doses was assessed in terms of percentages of subjects with anti-PRP antibody levels associated with providing short-term (≥ 0.15 μg/ml) and long-term (≥ 1.0 μg/ml) protection; the non-inferiority margin was set at -5%. PRP-CRM(197) was demonstrated to be non-inferior to PRP-T. Anti-PRP antibodies levels ≥ 0.15 μg/ml and ≥ 1.0 μg/ml were achieved by 97% of infants in the PRP-CRM(197) group and 98% of infants in the PRP-T group 1 month after primary immunisation, and by all subjects (100%) in both vaccine groups 1 month after booster administration. Safety profiles for both vaccines were similar; no serious adverse events, deaths or adverse events leading to withdrawal occurred during the study. PRP-CRM(197) was well-tolerated and immunologically non-inferior to a licensed comparator Hib vaccine in Chinese infants (Clinicaltrials.gov: NCT01044316 & NCT01226953). © 2013 John Wiley & Sons Ltd.

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

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Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

RanBP3 influences interactions between CRM1 and its nuclear protein export substrates

OpenAIRE

Englmeier, Ludwig; Fornerod, Maarten; Bischoff, F. Ralf; Petosa, Carlo; Mattaj, Iain W.; Kutay, Ulrike

2001-01-01

We investigated the role of RanBP3, a nuclear member of the Ran-binding protein 1 family, in CRM1-mediated protein export in higher eukaryotes. RanBP3 interacts directly with CRM1 and also forms a trimeric complex with CRM1 and RanGTP. However, RanBP3 does not bind to CRM1 like an export substrate. Instead, it can stabilize CRM1–export substrate interaction. Nuclear RanBP3 stimulates CRM1-dependent protein export in permeabilized cells. These data indicate that RanBP3 functions by a novel mec...

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

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Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials.

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Bhutta, Zulfiqar A; Capeding, Maria Rosario; Bavdekar, Ashish; Marchetti, Elisa; Ariff, Shabina; Soofi, Sajid B; Anemona, Alessandra; Habib, Muhammad A; Alberto, Edison; Juvekar, Sanjay; Khan, Rana M Qasim; Marhaba, Rachid; Ali, Noshad; Malubay, Nelia; Kawade, Anand; Saul, Allan; Martin, Laura B; Podda, Audino

2014-02-01

Typhoid vaccination is a public health priority in developing countries where young children are greatly affected by typhoid fever. Because present vaccines are not recommended for children younger than 2 years, the Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant immunisation. We aimed to assess the immunogenicity and safety of Vi-CRM197 in participants of various ages in endemic countries in south and southeast Asia. We did two randomised, observer-blind, age de-escalation, phase 2 trials at two sites in Pakistan and India (study A), and at one site in the Philippines (study B), between March 2, 2011, and Aug 9, 2012. Adults aged 18-45 years, children aged 24-59 months, older infants aged 9-12 months, and infants aged 6-8 weeks were randomly assigned (1:1) with a computer-generated randomisation list (block size of four) to receive either 5 μg Vi-CRM197 or 25 μg Vi-polysaccharide vaccine (or 13-valent pneumococcal conjugate vaccine in children younger than 2 years). Both infant populations received Vi-CRM197 concomitantly with vaccines of the Expanded Programme on Immunization (EPI), according to WHO schedule. With the exception of designated study site personnel responsible for vaccine preparation, study investigators, those assessing outcomes, and data analysts were masked to treatment allocation. We specified no a-priori null hypothesis for the immunogenicity or safety objectives and all analyses were descriptive. Analyses were by modified intention-to-treat. These studies are registered with ClinicalTrials.gov, numbers NCT01229176 and NCT01437267. 320 participants were enrolled and vaccinated in the two trials: 200 in study A (all age groups) and 120 in study B (children and infants only), of whom 317 (99%) were included in the modified intention-to-treat analysis. One dose of Vi-CRM197 significantly increased concentrations of anti-Vi antibody in adults (from 113 U/mL [95% CI 67-190] to 208 U/mL [117

Mathematical modeling of mutant transferrin-CRM107 molecular conjugates for cancer therapy.

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Yoon, Dennis J; Chen, Kevin Y; Lopes, André M; Pan, April A; Shiloach, Joseph; Mason, Anne B; Kamei, Daniel T

2017-03-07

The transferrin (Tf) trafficking pathway is a promising mechanism for use in targeted cancer therapy due to the overexpression of transferrin receptors (TfRs) on cancerous cells. We have previously developed a mathematical model of the Tf/TfR trafficking pathway to improve the efficiency of Tf as a drug carrier. By using diphtheria toxin (DT) as a model toxin, we found that mutating the Tf protein to change its iron release rate improves cellular association and efficacy of the drug. Though this is an improvement upon using wild-type Tf as the targeting ligand, conjugated toxins like DT are unfortunately still highly cytotoxic at off-target sites. In this work, we address this hurdle in cancer research by developing a mathematical model to predict the efficacy and selectivity of Tf conjugates that use an alternative toxin. For this purpose, we have chosen to study a mutant of DT, cross-reacting material 107 (CRM107). First, we developed a mathematical model of the Tf-DT trafficking pathway by extending our Tf/TfR model to include intracellular trafficking via DT and DT receptors. Using this mathematical model, we subsequently investigated the efficacy of several conjugates in cancer cells: DT and CRM107 conjugated to wild-type Tf, as well as to our engineered mutant Tf proteins (K206E/R632A Tf and K206E/R534A Tf). We also investigated the selectivity of mutant Tf-CRM107 against non-neoplastic cells. Through the use of our mathematical model, we predicted that (i) mutant Tf-CRM107 exhibits a greater cytotoxicity than wild-type Tf-CRM107 against cancerous cells, (ii) this improvement was more drastic with CRM107 conjugates than with DT conjugates, and (iii) mutant Tf-CRM107 conjugates were selective against non-neoplastic cells. These predictions were validated with in vitro cytotoxicity experiments, demonstrating that mutant Tf-CRM107 conjugates is indeed a more suitable therapeutic agent. Validation from in vitro experiments also confirmed that such whole

SIALIDASE (NEURAMINIDASE) OF CORYNEBACTERIUM DIPHTHERIAE.

Science.gov (United States)

WARREN, L; SPEARING, C W

1963-11-01

Warren, Leonard (National Institute of Arthritis and Metabolic Diseases, Bethesda, Md.) and C. W. Spearing. Sialidase (neuraminidase) of Corynebacterium diphtheriae. J. Bacteriol. 86:950-955. 1963.-The characteristics of a sialidase produced by Corynebacterium diphtheriae were studied. The enzyme was partially purified from preparations of diphtheria toxin on a column of Sephadex G-75. By this means the lethal factor of diphtheria toxin was separated, in part, from the sialidase activity. There appeared to be a close immunological relationship between the sialidases of C. diphtheriae and clostridia, since a preparation of diphtheria antitoxin was as effective an inhibitor of diphtheria sialidase as of the sialidase of three species of clostridia. Conversely, antitoxin to clostridia inhibited diphtheria sialidase. Diphtheria antitoxin was essentially inactive toward influenza virus sialidase, and was completely inactive against purified sialidase of Vibrio cholerae. Removal of sialic acid from the proteins in a preparation of diphtheria antitoxin did not alter the inhibitory activity of the antitoxin against diphtheria sialidase. The enzyme operated optimally at pH 5.5 and did not require calcium ions for activity. The substrate specificity of diphtheria sialidase appears to be the same as that of other previously described sialidases.

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family.

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Antonets, Denis V; Nepomnyashchikh, Tatyana S; Shchelkunov, Sergei N

2010-10-27

Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

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Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

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Shchelkunov Sergei N

2010-10-01

Full Text Available Abstract Background Variola virus (VARV the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein. Findings De novo modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins. Conclusions Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.

The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.

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Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

2016-07-25

Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

A CRM domain protein functions dually in group I and group II intron splicing in land plant chloroplasts.

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Asakura, Yukari; Barkan, Alice

2007-12-01

The CRM domain is a recently recognized RNA binding domain found in three group II intron splicing factors in chloroplasts, in a bacterial protein that associates with ribosome precursors, and in a family of uncharacterized proteins in plants. To elucidate the functional repertoire of proteins with CRM domains, we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is associated with the group I intron in pre-trnL-UAA and group II introns in the ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog condition a defective-seed phenotype (strong allele) or chlorophyll-deficient seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3-int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns and act in a nonredundant fashion to promote their splicing. With these findings, CRM domain proteins are implicated in the activities of three classes of catalytic RNA: group I introns, group II introns, and 23S rRNA.

Use of MenACWY-CRM in adolescents in the United States.

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Black, Steven; Block, Stan L

2013-03-01

Adolescents constitute a high-risk group for invasive meningococcal disease. MenACWY-CRM (Menveo, Novartis Vaccines, Cambridge, MA) is a quadrivalent meningococcal conjugate vaccine indicated to prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W-135, and Y. It has been approved for use in persons age 2-55 years. The tolerability and immunogenicity of MenACWY-CRM in adolescents have been ascertained in phase 2 and 3 trials against MPSV4 (Menomune, sanofi pasteur, Swiftwater, PA), an unconjugated quadrivalent meningococcal vaccine, and MenACWY-D (Menactra, sanofi pasteur), another conjugated quadrivalent meningococcal vaccine. Clinical trials also have demonstrated that MenACWY-CRM is well tolerated and immunogenic when administered to adolescents concomitantly with the combined tetanus, diphtheria, and acellular pertussis vaccine (Boostrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent human papillomavirus vaccine (Gardasil, Merck & Co., Inc., Whitehouse Station, NJ). Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A

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McGinniss, M.J.; Kazazian, H.H. Jr.; Bi, L.; Antonarakis, S.E. (John Hopkins Univ., Baltimore, MD (United States)); Hoyer, L.W. (American Red Cross Blood Services, Rockville, MD (United States)); Inaba, H. (Tokyo Medical College (Japan))

1993-02-01

Hemophilia A is due to the functional deficiency of factor VIII (FVIII, gene locus F8C). Although half the patients have no detectable FVIII protein in their plasma, the more rare patients ([approximately]5%) have normal levels of a dysfunctional FVIII and are termed cross-reacting material (CRM)-positive. More commonly ([approximately]45%), patients have plasma FVIII protein reduced to an extent roughly comparable to the level of FVIII activity and are designated CRM-reduced. We used denaturing gradient gel electrophoresis to screen for mutations within the F8C gene of 11 patients (6CRM-positive, 5 CRM-reduced) and identified 9 different mutations in 9 patients after analyses of all 26 exons, the promoter region, and the polyadenylation site. Six mutations have not been described previously. Five weree missense (Ser289Leu, Ser558Phe, Val634Ala, Val634Met, Asn1441Lys), and the sixth was a 3-bp deletion ([Delta]Phe652). A review of the literature and the assay of FVIII antigen in 5 hemophilia A patients with previously identified missense mutations from this laboratory yielded a total of 20 other unique CRM-reduced and CRM-positive mutations. Almost all CRM-positive/reduced mutations (24/26) were missense, and many (12/26) occurred at CpG dinucleotides. We examined 19 missense mutation for evolutionary conservation using the portions of the porcine and murine F8C sequences that are known, and 18/19 amino acid residue altered by mutation in these patients wer conserved. Almost 50% of mutations (11/26) clustered in the A2 domain, suggesting that this region is critical for the function of FVIII. The results indicate a nonrandom distribution of mutations and suggest that mutations in a limited number of FVIII regions may cause CRM-positive and CRM-reduced heomphilia A. 48 refs., 1 fig., 1 tab.

The CRM domain: an RNA binding module derived from an ancient ribosome-associated protein.

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Barkan, Alice; Klipcan, Larik; Ostersetzer, Oren; Kawamura, Tetsuya; Asakura, Yukari; Watkins, Kenneth P

2007-01-01

The CRS1-YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved "GxxG" loop, contributes to its RNA binding activity. These and other results suggest that the CRM domain evolved in the context of ribosome function prior to the divergence of Archaea and Bacteria, that this function has been maintained in extant prokaryotes, and that the domain was recruited to serve as an RNA binding module during the evolution of plant genomes.

Vaccination against group B streptococcus.

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Heath, Paul T; Feldman, Robert G

2005-04-01

Streptococcus agalactiae (Group B streptococcus) is an important cause of disease in infants, pregnant women, the elderly and in immunosuppressed adults. An effective vaccine is likely to prevent the majority of infant disease (both early and late onset), as well as Group B streptococcus-related stillbirths and prematurity, to avoid the current real and theoretical limitations of intrapartum antibiotic prophylaxis, and to be cost effective. The optimal time to administer such a vaccine would be in the third trimester of pregnancy. The main limitations on the production of a Group B streptococcus vaccine are not technical or scientific, but regulatory and legal. A number of candidates including capsular conjugate vaccines using traditional carrier proteins such as tetanus toxoid and mutant diphtheria toxin CRM197, as well as Group B streptococcus-specific proteins such as C5a peptidase, protein vaccines using one or more Group B streptococcus surface proteins and mucosal vaccines, have the potential to be successful vaccines. The capsular conjugate vaccines using tetanus and CRM197 carrier proteins are the most advanced candidates, having already completed Phase II human studies including use in the target population of pregnant women (tetanus toxoid conjugate), however, no definitive protein conjugates have yet been trialed. However, unless the regulatory environment is changed specifically to allow the development of a Group B streptococcus vaccine, it is unlikely that one will ever reach the market.

Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

Science.gov (United States)

Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

2010-05-21

NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

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Hasnain Seyed

2004-09-01

Full Text Available Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG, an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase

Corynebacterium ulcerans cutaneous diphtheria.

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Moore, Luke S P; Leslie, Asuka; Meltzer, Margie; Sandison, Ann; Efstratiou, Androulla; Sriskandan, Shiranee

2015-09-01

We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms of sepsis such as fever, tachycardia, and elevated C-reactive protein, after contact with domestic cats and dogs, and a fox. We summarise the epidemiology, clinical presentation, microbiology, diagnosis, therapy, and public health aspects of this disease, with emphasis on improving recognition. In many European countries, C ulcerans has become the organism commonly associated with cutaneous diphtheria, usually seen as an imported tropical disease or resulting from contact with domestic and agricultural animals. Diagnosis relies on bacterial culture and confirmation of toxin production, with management requiring appropriate antimicrobial therapy and prompt administration of antitoxin, if necessary. Early diagnosis is essential for implementation of control measures and clear guidelines are needed to assist clinicians in managing clinical diphtheria. This case was a catalyst to the redrafting of the 2014 national UK interim guidelines for the public health management of diphtheria, released as final guidelines in March, 2015. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sexually transmitted diphtheria.

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Berger, Anja; Lensing, Carmen; Konrad, Regina; Huber, Ingrid; Hogardt, Michael; Sing, Andreas

2013-03-01

Diphtheria is caused by diphtheria toxin-producing Corynebacterium species. While classical respiratory diphtheria is transmitted by droplets, cutaneous diphtheria often results from minor trauma. This report concerns the first case of sexually transmitted diphtheria in a patient with non-gonococcal urethritis after orogenital contact.

The BRO proteins of Bombyx mori nucleopolyhedrovirus are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

International Nuclear Information System (INIS)

Kang, Won Kyung; Kurihara, Masaaki; Matsumoto, Shogo

2006-01-01

The BRO proteins of Bombyx mori nucleopolyhedrovirus (BmNPV) display a biphasic pattern of intracellular localization during infection. At early times, they reside in the nucleus but then show both cytoplasmic and nuclear localization as the infection proceeds. Therefore, we examined the possibility of nuclear export. Using inhibitors, we reveal that BmNPV BRO proteins shuttle between the nucleus and cytoplasm. Mutations on the leucine-rich region of BRO proteins resulted in nuclear accumulation of transiently expressed proteins, suggesting that this region functions as a CRM1-dependent nuclear export signal (NES). On the contrary, mutant BRO-D with an altered NES did not show nuclear accumulation in infected cells, although protein production seemed to be reduced. RT-PCR analysis showed that the lower level of protein production was due to a reduction in RNA synthesis. Taken together, our results suggest that BRO proteins are nucleocytoplasmic shuttling proteins that utilize the CRM1-mediated nuclear export pathway

Diphtheria Complications

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... Search Form Controls Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

Identification of a human monoclonal antibody to replace equine diphtheria antitoxin for treatment of diphtheria intoxication.

Science.gov (United States)

Sevigny, Leila M; Booth, Brian J; Rowley, Kirk J; Leav, Brett A; Cheslock, Peter S; Garrity, Kerry A; Sloan, Susan E; Thomas, William; Babcock, Gregory J; Wang, Yang

2013-11-01

Diphtheria antitoxin (DAT) has been the cornerstone of the treatment of Corynebacterium diphtheriae infection for more than 100 years. Although the global incidence of diphtheria has declined steadily over the last quarter of the 20th century, the disease remains endemic in many parts of the world, and significant outbreaks still occur. DAT is an equine polyclonal antibody that is not commercially available in the United States and is in short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we obtained human monoclonal antibodies (hMAbs) directly from antibody-secreting cells in the circulation of immunized human volunteers. We isolated a panel of diverse hMAbs that recognized diphtheria toxoid, as well as a variety of recombinant protein fragments of diphtheria toxin. Forty-five unique hMAbs were tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays with a 50% effective concentration of 0.65 ng/ml for the lead candidate hMAb, 315C4. In addition, 25 μg of 315C4 completely protected guinea pigs from intoxication in an in vivo lethality model, yielding an estimated relative potency of 64 IU/mg. In comparison, 1.6 IU of DAT was necessary for full protection from morbidity and mortality in this model. We further established that our lead candidate hMAb binds to the receptor-binding domain of diphtheria toxin and physically blocks the toxin from binding to the putative receptor, heparin-binding epidermal growth factor-like growth factor. The discovery of a specific and potent human neutralizing antibody against diphtheria toxin holds promise as a potential therapeutic.

Diphtheria

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Diphtheria is a serious bacterial infection. You can catch it from a person who has the infection ... as a toy, that has bacteria on it. Diphtheria usually affects the nose and throat. Symptoms include ...

Two CRM protein subfamilies cooperate in the splicing of group IIB introns in chloroplasts.

Science.gov (United States)

Asakura, Yukari; Bayraktar, Omer Ali; Barkan, Alice

2008-11-01

Chloroplast genomes in angiosperms encode approximately 20 group II introns, approximately half of which are classified as subgroup IIB. The splicing of all but one of the subgroup IIB introns requires a heterodimer containing the peptidyl-tRNA hydrolase homolog CRS2 and one of two closely related proteins, CAF1 or CAF2, that harbor a recently recognized RNA binding domain called the CRM domain. Two CRS2/CAF-dependent introns require, in addition, a CRM domain protein called CFM2 that is only distantly related to CAF1 and CAF2. Here, we show that CFM3, a close relative of CFM2, associates in vivo with those CRS2/CAF-dependent introns that are not CFM2 ligands. Mutant phenotypes in rice and Arabidopsis support a role for CFM3 in the splicing of most of the introns with which it associates. These results show that either CAF1 or CAF2 and either CFM2 or CFM3 simultaneously bind most chloroplast subgroup IIB introns in vivo, and that the CAF and CFM subunits play nonredundant roles in splicing. These results suggest that the expansion of the CRM protein family in plants resulted in two subfamilies that play different roles in group II intron splicing, with further diversification within a subfamily to accommodate multiple intron ligands.

Diphtheria Disease Villain

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... we can shield ourselves with vaccines, fewer than 5 people get diphtheria each year. Diphtheria is a stubborn ... always foiled by the vaccine against it. Ninety-five percent of people with up-to-date diphtheria vaccine are protected. ...

From CRM to Social CRM and FRM

Directory of Open Access Journals (Sweden)

Maria Cristina ENACHE

2016-04-01

Full Text Available C-R-M stands for Customer Relationship Management. At its simplest, a CRM system allows businesses to manage business relationships and the data and information associated with them. While a CRM system may not elicit as much enthusiasm these days as social networking platforms like Facebook or Twitter, any CRM system is similarly built around people and relationships. And that’s exactly why it can be so valuable for a fast-growing business. FRM was developed from learning of success and failures on conventional CRM. FRM – Relationship Management is a unique way to build and love your fans, is a form a Social CRM. Traditional Customer Relationship Management focuses on collecting and managing static customer data, such as past purchase information, contact history and customer demographics. This information is often sourced from email and phone interactions, commonly limited to direct interactions between the company and the customer. Social CRM adds a deeper layer of information onto traditional CRM by adding data derived from social networks like Facebook, Twitter, LinkedIn or any other social network where a user publicly shares information. The key benefit of Social CRM is the ability for companies to interact with customers in a multichannel retailing environment (commonly referred to as omnichannel and talk to customers the way they talk to each other. Social CRM enables companies to track a customer's social influence and source data from conversations occurring outside of formal, direct communication. Social CRM also allows companies to keep a full audit history of all customer interactions, regardless of social channel they choose to use, available to all customer care employees. FRM delivers probability while ensuring client partner expectation in revenue generation and customer expectation.

African Heath Sciences Vol 7 No 4.p65

African Journals Online (AJOL)

FOMCS2

no evidence of significant associative interactions between Hib-CRM197 and MenC-CRM197 in saline-based buffers, pH 7.2. African ... aggregation of vaccine saccharide or protein components. 17, 18 ... chromatography and for analysis of the generated data. .... protein would be expected to elute after the main MenC-.

Differential diagnosis diphtheria adults

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Yu. I. Liashenko

2010-01-01

Full Text Available A total of 1,824 human cases of diphtheria, treated at the Clinical Infectious Diseases Hospital SP Botkin (St. Petersburg during 1993, as well as 19 deaths in 1994. It is known that early diagnosis of infectious diseases, especially diphtheria, contributes to the favorable outcome of the disease. The diagnosis of diphtheria at the prehospital stage is always difficult. Presented in detail the differential diagnosis of the disease, clinically similar to diphtheria: Lacunal angina, angina Simanovsky, infectious mononucleosis, angina Ludwig’s angina Dugue, syphilis, non-infectious with clinical «masks» of diphtheria and other. Diphtheria epidemic of 1993–1994 in Russia and, in particular, in St. Petersburg, showed that the late admission of patients with diphtheria infection in hospitals, usually associated with irregular differential diagnosis of this dangerous disease.

From CRM to Social CRM and FRM

OpenAIRE

Maria Cristina ENACHE; Cornelia NOVAC UDUDEC; Corina SBUGHEA

2016-01-01

C-R-M stands for Customer Relationship Management. At its simplest, a CRM system allows businesses to manage business relationships and the data and information associated with them. While a CRM system may not elicit as much enthusiasm these days as social networking platforms like Facebook or Twitter, any CRM system is similarly built around people and relationships. And that’s exactly why it can be so valuable for a fast-growing business. FRM was developed from learning of success and failu...

Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin

International Nuclear Information System (INIS)

Rolf, J.M.; Gaudin, H.M.; Tirrell, S.M.; MacDonald, A.B.; Eidels, L.

1989-01-01

An anti-idiotypic serum prepared against the combining site (idiotype) of specific anti-diphtheria toxoid antibodies was characterized with respect to its interaction with highly diphtheria toxin-sensitive Vero cells. Although the anti-idiotypic serum protected Vero cells against the cytotoxic action of diphtheria toxin, it did not prevent the binding of 125 I-labeled diphtheria toxin to the cells but did inhibit the internalization and degradation of 125 I-labeled toxin. This anti-idiotypic serum immunoprecipitated a cell-surface protein from radiolabeled Vero cells with an apparent Mr of approximately 15,000. These results are consistent with the hypothesis that the anti-idiotypic serum contains antibodies that carry an internal image of an internalization site on the toxin and that a cell-surface protein involved in toxin internalization possesses a complementary site recognized by both the toxin and the anti-idiotypic antibodies

Diphtheria Diagnosis and Treatment

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... Search The CDC Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

Channels Formed by Botulinum, Tetanus, and Diphtheria Toxins in Planar Lipid Bilayers: Relevance to Translocation of Proteins across Membranes

Science.gov (United States)

Hoch, David H.; Romero-Mira, Miryam; Ehrlich, Barbara E.; Finkelstein, Alan; Dasgupta, Bibhuti R.; Simpson, Lance L.

1985-03-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as ``tunnel proteins'' for translocation of active peptide fragments. These findings support the hypothesis that the active fragments of botulinum neurotoxin and tetanus toxin, like that of diphtheria toxin, are translocated across the membranes of acidic vesicles.

A nuclear-encoded chloroplast protein harboring a single CRM domain plays an important role in the Arabidopsis growth and stress response.

Science.gov (United States)

Lee, Kwanuk; Lee, Hwa Jung; Kim, Dong Hyun; Jeon, Young; Pai, Hyun-Sook; Kang, Hunseung

2014-04-16

Although several chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins have been characterized for intron splicing and rRNA processing during chloroplast gene expression, the functional role of a majority of CRM domain proteins in plant growth and development as well as chloroplast RNA metabolism remains largely unknown. Here, we characterized the developmental and stress response roles of a nuclear-encoded chloroplast protein harboring a single CRM domain (At4g39040), designated CFM4, in Arabidopsis thaliana. Analysis of CFM4-GFP fusion proteins revealed that CFM4 is localized to chloroplasts. The loss-of-function T-DNA insertion mutants for CFM4 (cfm4) displayed retarded growth and delayed senescence, suggesting that CFM4 plays a role in growth and development of plants under normal growth conditions. In addition, cfm4 mutants showed retarded seed germination and seedling growth under stress conditions. No alteration in the splicing patterns of intron-containing chloroplast genes was observed in the mutant plants, but the processing of 16S and 4.5S rRNAs was abnormal in the mutant plants. Importantly, CFM4 was determined to possess RNA chaperone activity. These results suggest that the chloroplast-targeted CFM4, one of two Arabidopsis genes encoding a single CRM domain-containing protein, harbors RNA chaperone activity and plays a role in the Arabidopsis growth and stress response by affecting rRNA processing in chloroplasts.

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

Directory of Open Access Journals (Sweden)

Laura Morelli

2014-10-01

Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.

Diphtheria: forgotten, but not gone.

Science.gov (United States)

Adler, N R; Mahony, A; Friedman, N D

2013-02-01

Diphtheria is an acute, highly infectious, vaccine-preventable and previously endemic disease whose etiologic agent is Corynebacterium diphtheriae. Diphtheria may manifest as an upper respiratory tract infection, a cutaneous infection or as an asymptomatic carrier state. The most common sites of infection are the pharynx and the tonsils, with common clinical manifestations that include sore throat, malaise, cervical lymphadenopathy and low-grade fever. Absorption and dissemination of C. diphtheriae from the respiratory tract can cause disseminated infection and may lead to cardiac or neurological toxicity. The cornerstone of treatment for diphtheria is diphtheria antitoxin. Early treatment is critical as the degree of protection is inversely proportional to the duration of the illness before its administration. Routine childhood vaccination virtually eliminated diphtheria in most industrialised countries. However, in the pre-vaccination era, diphtheria was the most common infectious cause of death in Australia. A case of diphtheria in Brisbane in April 2011 and two recent positive cultures in regional Victoria underscore the need for heightened awareness of C. diphtheriae as an important pathogen. In order to prevent the re-emergence of diphtheria in Australia, public health measures are required to increase immunity in early school leavers and the adult population, and to ensure that travellers to endemic regions are fully immunised. Health policy-makers and clinicians alike should not underestimate the importance of primary vaccination and booster vaccination against diphtheria among healthy adults and travellers. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Anti-idiotypic antibodies that protect cells against the action of diphtheria toxin

Energy Technology Data Exchange (ETDEWEB)

Rolf, J.M.; Gaudin, H.M.; Tirrell, S.M.; MacDonald, A.B.; Eidels, L.

1989-03-01

An anti-idiotypic serum prepared against the combining site (idiotype) of specific anti-diphtheria toxoid antibodies was characterized with respect to its interaction with highly diphtheria toxin-sensitive Vero cells. Although the anti-idiotypic serum protected Vero cells against the cytotoxic action of diphtheria toxin, it did not prevent the binding of /sup 125/I-labeled diphtheria toxin to the cells but did inhibit the internalization and degradation of /sup 125/I-labeled toxin. This anti-idiotypic serum immunoprecipitated a cell-surface protein from radiolabeled Vero cells with an apparent Mr of approximately 15,000. These results are consistent with the hypothesis that the anti-idiotypic serum contains antibodies that carry an internal image of an internalization site on the toxin and that a cell-surface protein involved in toxin internalization possesses a complementary site recognized by both the toxin and the anti-idiotypic antibodies.

Tetanus, Diphtheria (Td) Vaccine

Science.gov (United States)

Decavac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They ... United States today, but people who do become infected often have severe ...

Travelers' Health: Diphtheria

Science.gov (United States)

... membrane tissue. Diphtheria is a nationally notifiable disease. TREATMENT Patients with respiratory diphtheria require hospitalization to monitor ... Jan 20;81(3):24–32. Chapter 3 - Dengue Chapter 3 - Ebola Virus Disease & Marburg Virus Disease ...

crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

Science.gov (United States)

Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

2007-11-01

We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

Epidemiology of diphtheria in South Dakota.

Science.gov (United States)

Golaz, A; Lance-Parker, S; Welty, T; Schaefer, L; Volmer, L; LaFromboise, C; Dixon, J; Haase, T; Kim, C; Popovic, T; Bisgard, K; Strebel, P; Wharton, M

2000-07-01

Respiratory diphtheria was one of the most common causes of death among children in the pre-vaccine era. Since the introduction of diphtheria toxoid vaccine in 1920s, and its widespread use by the late 1940s, diphtheria became increasingly rare in the United States. However, through the 1970s diphtheria remained endemic in some states, with reported incidence rates > 1.0 per million population in six states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington). Starting in 1980, less than five cases have been reported each year in the United States. The majority of culture-confirmed cases have been associated with importation from other countries. Toxigenic Corynebacterium diphtheriae, the organism causing diphtheria, was thought to have become rare or even have disappeared from previously endemic areas such as South Dakota. However, during four months in 1996, 11 persons (one index case, six patients and four household contacts) in an American Indian community in South Dakota were found to be infected by C. diphtheriae; six of these isolates were toxigenic. The findings in this report indicate that despite 20 years without reported respiratory diphtheria cases, toxigenic C. diphtheriae is still present in South Dakota. The continuous circulation of toxigenic strains of C. diphtheriae emphasizes the need for health care providers throughout South Dakota to promote timely vaccination against diphtheria among persons of all ages and ethnic groups, to be aware of the clinical signs and symptoms of diphtheria so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease.

Determinants of Clinical Diphtheria After Sub National Diphtheria Immunization Days In 2012 At Bangkalan

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Feranita Utama

2014-01-01

Full Text Available ABSTRACT The government had held sub-national diphtheria immunization days in 2012 to combat an outbreak of diphtheria in East Java province. However, there werestill regencies or cities which had high incidence and Bangkalanregencywas the highest. The research aimed to analyze the determinants of diphtheria in Bangkalan after SNIDs. This research was case control study with 31 subjects as case and 124 as control spread in 25 case villages and 25 control villages. Bivariate analysis used chi-square and simple logistic regression. Multivariate analysis used logistic regression. Bivariate analysisresult showed that individual and household variables that had associate with incidence of diphtheria in the Bangkalan after SNIDs of diphtheria vaccine in 2012 were DPT immunization status, the status of SNIDs, age, and mother's education level. In this study, there were not associate between village variables with diphtheria in the Bangkalan after SNIDs. Multivariate analysis result showed that had associate with incidence of diphtheria in Bangkalan after SNIDs were no DPT immunization (p=0,012; OR=4,765, incomplete DPT immunization (p=0,001; OR=6,276, 3-7 years of age (p=0,014; OR=15,137, 7-15 years of age (p=0,001;OR=41,984, and no immunization in SNIDs (p=0,020; OR=3,553. Conclusion, the dominantfactors that affected diphtheriainBangkalanwere status of DPTimmunization, ageand the SNIDs of diphtheria. Recommendation, DPTimmunizationshould becomplete, boosterimmunization should be needed, monitoring theimplementation ofsubPIN should be strict, especially inschool, and thecoverage ofDPT3andsubPIN should be increased and its report should be improved. Keywords: diphtheria, sub-nationaldiphtheriaimmunization days, DPT                              immunization

Corynebacterium diphtheriae in a free-roaming red fox: case report and historical review on diphtheria in animals.

Science.gov (United States)

Sing, Andreas; Konrad, Regina; Meinel, Dominik M; Mauder, Norman; Schwabe, Ingo; Sting, Reinhard

2016-08-01

Corynebacterium diphtheriae, the classical causative agent of diphtheria, is considered to be nearly restricted to humans. Here we report the first finding of a non-toxigenic C. diphtheriae biovar belfanti strain in a free-roaming wild animal. The strain obtained from the subcutis and mammary gland of a dead red fox (Vulpes vulpes) was characterized by biochemical and molecular methods including MALDI-TOF and Multi Locus Sequence Typing. Since C. diphtheriae infections of animals, usually with close contact to humans, are reported only very rarely, an intense review comprising also scientific literature from the beginning of the 20th century was performed. Besides the present case, only 11 previously reported C. diphtheriae animal infections could be verified using current scientific criteria. Our report is the first on the isolation of C. diphtheriae from a wildlife animal without any previous human contact. In contrast, the very few unambiguous publications on C. diphtheriae in animals referred to livestock or pet animals with close human contact. C. diphtheriae carriage in animals has to be considered as an exceptionally rare event.

Enabling local production of biopharmaceuticals in South Africa

CSIR Research Space (South Africa)

Tsekoa, Tsepo L

2017-10-01

Full Text Available - based pharmaceuticals. 9 Case study 1: Rabivir, new-generation rabies post-exposure prophylaxis 10 Case study 2: Microbial production of biosimilar CRM197 carrier protein • Problem/Need: Accessible and cost-competitive paediatric vaccines... • Prohibitively expensive pricing of protein reagent (CRM197) used in manufacture of conjugate vaccines for children (e.g. multivalent pneumococcal vaccine) • Solution: Fermentation-based production in recombinant E. coli • Stage: Proof of concept complete...

Diphtheria in Mayotte, 2007-2015.

Science.gov (United States)

Belchior, Emmanuel; Henry, Sabine; Badell, Edgar; Collet, Louis; Benoit-Cattin, Thierry; de Montera, Anne-Marie; Guiso, Nicole; Patey, Olivier; Levy-Bruhl, Daniel; Filleul, Laurent; Chieze, Francois; Olivier, Sophie

2017-07-01

Epidemiology of diphtheria in the southwestern Indian Ocean is poorly documented. We analyzed 14 cases of infection with toxigenic Corynebacterium diphtheriae reported during 2007-2015 in Mayotte, a French department located in this region. Local control of diphtheria is needed to minimize the risk for importation of the bacterium into disease-free areas.

Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

Science.gov (United States)

Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

2014-01-01

Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

Development of C-reactive protein certified reference material NMIJ CRM 6201-b: optimization of a hydrolysis process to improve the accuracy of amino acid analysis.

Science.gov (United States)

Kato, Megumi; Kinumi, Tomoya; Yoshioka, Mariko; Goto, Mari; Fujii, Shin-Ichiro; Takatsu, Akiko

2015-04-01

To standardize C-reactive protein (CRP) assays, the National Metrology Institute of Japan (NMIJ) has developed a C-reactive protein solution certified reference material, CRM 6201-b, which is intended for use as a primary reference material to enable the SI-traceable measurement of CRP. This study describes the development process of CRM 6201-b. As a candidate material of the CRM, recombinant human CRP solution was selected because of its higher purity and homogeneity than the purified material from human serum. Gel filtration chromatography was used to examine the homogeneity and stability of the present CRM. The total protein concentration of CRP in the present CRM was determined by amino acid analysis coupled to isotope-dilution mass spectrometry (IDMS-AAA). To improve the accuracy of IDMS-AAA, we optimized the hydrolysis process by examining the effect of parameters such as the volume of protein samples taken for hydrolysis, the procedure of sample preparation prior to the hydrolysis, hydrolysis temperature, and hydrolysis time. Under optimized conditions, we conducted two independent approaches in which the following independent hydrolysis and liquid chromatography-isotope dilution mass spectrometry (LC-IDMS) were combined: one was vapor-phase acid hydrolysis (130 °C, 24 h) and hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) method, and the other was microwave-assisted liquid-phase acid hydrolysis (150 °C, 3 h) and pre-column derivatization liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The quantitative values of the two different amino acid analyses were in agreement within their uncertainties. The certified value was the weighted mean of the results of the two methods. Uncertainties from the value-assignment method, between-method variance, homogeneity, long-term stability, and short-term stability were taken into account in evaluating the uncertainty for a certified value. The certified value and the

Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

Science.gov (United States)

Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

Radioimmunodiffusion technique for determining diphtheria antitoxin

International Nuclear Information System (INIS)

Maniar, A.C.

1977-01-01

A radioimmunodiffusion technique for detecting low levels of diphtheria antitoxin was developed. Diphtheria toxoid was labelled with 125 I to facilitate detection of lines of precipitation by the use of X-ray film, the lower limit of detection being 0.001 unit per millilitre of diphtheria antitoxin. (author)

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

Science.gov (United States)

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

The Druggable Pocketome of Corynebacterium diphtheriae: A New Approach for in silico Putative Druggable Targets

Science.gov (United States)

Hassan, Syed S.; Jamal, Syed B.; Radusky, Leandro G.; Tiwari, Sandeep; Ullah, Asad; Ali, Javed; Behramand; de Carvalho, Paulo V. S. D.; Shams, Rida; Khan, Sabir; Figueiredo, Henrique C. P.; Barh, Debmalya; Ghosh, Preetam; Silva, Artur; Baumbach, Jan; Röttger, Richard; Turjanski, Adrián G.; Azevedo, Vasco A. C.

2018-01-01

Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the “pocketome druggability.” To this end, we first computed the “modelome” (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (∼9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines

CRM done right.

Science.gov (United States)

Rigby, Darrell K; Ledingham, Dianne

2004-11-01

Disappointed by the high costs and elusive benefits, early adopters of customer relationship management systems came, in the post dot-com era, to view the technology as just another overhyped IT investment whose initial promise would never be fulfilled. But this year, something unexpected is happening. System sales are rising, and executives are reporting satisfaction with their CRM investments. What's changed? A wide range of companies are successfully taking a pragmatic, disciplined approach to CRM. Rather than use it to transform entire businesses, they've directed their investments toward solving clearly defined problems within their customer relationship cycle. The authors have distilled the experiences of these CRM leaders into four questions that all companies should ask themselves as they launch their own CRM initiatives: Is the problem strategic? Is the system focused on the pain point? Do we need perfect data? What's the right way to expand an initial implementation? The questions reflect a new realism about when and how to deploy CRM to best advantage. Understanding that highly accurate and timely data are not required everywhere in their businesses, CRM leaders have tailored their real-time initiatives to those customer relationships that can be significantly enhanced by "perfect" information. Once they've succeeded with their first targeted CRM project, they can use it as a springboard for solving additional problems. CRM, in other words, is coming to resemble any other valuable management tool, and the keys to successful implementation are also becoming familiar: strong executive and business-unit leadership, careful strategic planning, clear performance measures, and a coordinated program that combines organizational and process changes with the application of new technology.

Further Thoughts on CRM

NARCIS (Netherlands)

P.C. Verhoef (Peter); F. Langerak (Fred)

2002-01-01

textabstractSkepticism and disappointment have replaced the initial enthusiasm about CRM. The disappointing results of CRM-projects are often related to difficulties that managers encounter in embedding CRM in their strategy and organization structure. In this article we present a classification

Diphtheria outbreak in Thailand, 2012; seroprevalence of diphtheria antibodies among Thai adults and its implications for immunization programs.

Science.gov (United States)

Wanlapakorn, Nasamon; Yoocharoen, Pornsak; Tharmaphornpilas, Piyanit; Theamboonlers, Apiradee; Poovorawan, Yong

2014-09-01

An age distribution shift in diphtheria cases during a 2012 outbreak in northeastern of Thailand suggests adults are increasingly at risk for infection in Thailand. Data regarding immunity against diphtheria among the adult Thai population is limited. We review a 2012 diphtheria outbreak in Thailand and conducted a nationwide seroepidemiological survey to determine the prevalence of diphtheria antibodies among Thai adults in order to inform immunization programs. A total of 41 confirmed cases, 6 probable cases and 101 carriers of diphtheria were reported from northeastern and upper southern Thailand. The diphtheria outbreak in northeastern Thailand occurred among adults aged > or =15 years; sporadic cases occurred among children from upper southern Thailand. We conducted a seroepidemiological survey of 890 Thai adults from 4 age groups (20-29, 30-39, 40-49 and 50-59 years) in 7 different geographical areas of Thailand (Chiang Mai, Ratchaburi, Chon Buri, Nakhon Si Thammarat, Phitsanulok, Khon Kaen and Songkhla). Diptheria toxin antibody levels were measured with a commercially available ELISA test. The seroprotection rate ranged from 83% to 99%, with the highest in eastern Thailand (Chon Buri, 99%) and the lowest in northern Thailand (Chiang Mai, 83%). Diphtheria antibodies declined with increasing age. We recommend one doseof diphtheria-tetanus toxoid (dT) vaccine once after 20 years of age in order to boost the antibody and revaccinations every 10 years to prevent future outbreaks.

Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication

Directory of Open Access Journals (Sweden)

Leonie Schnell

2016-07-01

Full Text Available Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenylsemicarbazone (EGA has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT. Here, we demonstrate that EGA also protects human cells from diphtheria toxin by inhibiting the pH-dependent translocation of DTA across cell membranes. The results suggest that EGA might serve for treatment and/or prevention of the severe disease diphtheria.

Diphtheria: It is still prevalent!!!

Science.gov (United States)

Jain, Avani; Samdani, Sunil; Meena, Vinod; Sharma, Man Prakash

2016-07-01

Diphtheria is a respiratory infectious disease of childhood. It is a fatal disease and may cause complications if not recognized early and treated properly. Despite availability of effective vaccination it continues to be reported from many parts of the world particularly developing countries. To assess the demographic and clinical characteristics of diphtheria patients, and the predictors of outcomes of respiratory diphtheria. A prospective analysis of 180 patients with a clinical diagnosis of respiratory diphtheria admitted from 2011 to 2014 at a tertiary referral hospital. They were evaluated with respect to demographic details, immunization status, clinical features, complications and outcomes. Most common age group affected was children less than 5 years of age (87 cases, 48.33%). The peak incidence of diphtheria was seen in the months of September and October (111 cases, 62%). Majority of the patients were unimmunized (54%), followed by partially immunized (21%). The most common complication was respiratory in 80 cases (44%), followed by cardiac complications in 54 cases (30%), and renal (16%) and neurological complications (10%). Cardiac complications were associated with the highest mortality rate (63%). The presence of bull neck and pseudomembrane score >2 was associated with a high mortality. Diphtheria is still a preventable public health problem in many developing countries. Improved vaccination coverage, including booster dosage, coupled with early detection and effective treatment, may all reduce incidence and mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An allele of the crm gene blocks cyanobacterial circadian rhythms.

Science.gov (United States)

Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

2013-08-20

The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

Implementation Research of CRM System

Institute of Scientific and Technical Information of China (English)

无

2002-01-01

This paper firstly discusses the importance of impl em enting CRM (Costumer Relationship Management) in the information era, studies th e elementary theory of CRM, and the relationship between CRM and ERP(Enterprise Resource Planning). Then the present situation of application of CRM system in C hina is analyzed in details. Based on the actuality and development object in th e future of ChangSha Zoomlion Heavy Industry and Technology Development CO., LTD ., the objective of CRM implementation and organizat...

CRM System Optimization

OpenAIRE

Fučík, Ivan

2015-01-01

This thesis is focused on CRM solutions in small and medium-sized organizations with respect to the quality of their customer relationship. The main goal of this work is to design an optimal CRM solution in the environment of real organization. To achieve this goal it is necessary to understand the theoretical basis of several topics, such as organizations and their relationship with customers, CRM systems, their features and trends. On the basis of these theoretical topics it is possible to ...

Effect of Tdap when administered before, with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial.

Science.gov (United States)

Tashani, M; Alfelali, M; Barasheed, O; Alqahtani, A S; Heron, L; Wong, M; Rashid, H; Booy, R

2016-11-21

Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3-4weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3-4weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18-64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse

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.

SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

Directory of Open Access Journals (Sweden)

Oliinyk O. S.

2014-02-01

Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

Diphtheria in the Republic of Georgia: Use of Molecular Typing Techniques for Characterization of Corynebacterium diphtheriae Strains

Science.gov (United States)

Sulakvelidze, Alexander; Kekelidze, Merab; Gomelauri, Tsaro; Deng, Yingkang; Khetsuriani, Nino; Kobaidze, Ketino; De Zoysa, Aruni; Efstratiou, Androulla; Morris, J. Glenn; Imnadze, Paata

1999-01-01

Sixty-six Corynebacterium diphtheriae strains (62 of the gravis biotype and 4 of the mitis biotype) isolated during the Georgian diphtheria epidemic of 1993 to 1998 and 13 non-Georgian C. diphtheriae strains (10 Russian and 3 reference isolates) were characterized by (i) biotyping, (ii) toxigenicity testing with the Elek assay and PCR, (iii) the randomly amplified polymorphic DNA (RAPD) technique, and (iv) pulsed-field gel electrophoresis (PFGE). Fifteen selected strains were ribotyped. Six RAPD types and 15 PFGE patterns were identified among all strains examined, and 12 ribotypes were found among the 15 strains that were ribotyped. The Georgian epidemic apparently was caused by one major clonal group of C. diphtheriae (PFGE type A, ribotype R1), which was identical to the predominant epidemic strain(s) isolated during the concurrent diphtheria epidemic in Russia. A dendrogram based on the PFGE patterns revealed profound differences between the minor (nonpredominant) epidemic strains found in Georgia and Russia. The methodologies for RAPD typing, ribotyping, and PFGE typing of C. diphtheriae strains were improved to enable rapid and convenient molecular typing of the strains. The RAPD technique was adequate for biotype differentiation; however, PFGE and ribotyping were better (and equal to each other) at discriminating between epidemiologically related and unrelated isolates. PMID:10488190

Mutant with diphtheria toxin receptor and acidification function but defective in entry of toxin

International Nuclear Information System (INIS)

Kohno, Kenji; Hayes, H.; Mekada, Eisuke; Uchida, Tsuyoshi

1987-01-01

A mutant of Chinese hamster ovary cells, GE1, that is highly resistant to diphtheria toxin was isolated. The mutant contains 50% ADP-ribosylatable elongation factor 2, but its protein synthesis was not inhibited by the toxin even at concentrations above 100 μg/ml. 125 I-labeled diphtheria toxin was associated with GE1 cells as well as with the parent cells but did not block protein synthesis of GE1 cells even when the cells were exposed to low pH in the presence or absence of NH 4 Cl. The infections of GE1 cells and the parent cells by vesicular stomatitis virus were similar. GE1 cells were cross-resistant to Pseudomonas aeruginosa exotoxin A and so were about 1,000 times more resistant to this toxin than the parent cells. Hybrids of GE1 cells and the parent cells or mutant cells lacking a functional receptor were more sensitive to diphtheria toxin than GE1 cells. These results suggest that entry of diphtheria toxin into cells requires a cellular factor(s) in addition to those involved in receptor function and acidification of endosomes and that GE1 cells do not express this cellular factor. This character is recessive in GE1 cells

Neurologic manifestations of diphtheria and pertussis.

Science.gov (United States)

Sanghi, Viraj

2014-01-01

Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

Science.gov (United States)

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

SAP crm integration testing

OpenAIRE

Černiavskaitė, Marija

2017-01-01

This Bachelor's thesis presents SAP CRM and integration systems testing analysis: investigation in SAP CRM and SAP PO systems, presentation of relationship between systems, introduction to third-party system (non-SAP) – Network Informational System (NIS) which has integration with SAP, presentation of best CRM testing practises, analysis and recommendation of integration testing. Practical integration testing is done in accordance to recommendations.

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

International Nuclear Information System (INIS)

Rocchi, P.; Ferreri, A.M.; Capucci, A.; Prodi, G.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency (less than 8 x 10(-6)). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTr) mutants up to 1000-fold. The maximum recovery of DTr mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages

Induction of diphtheria toxin-resistant mutants in human cells by ultraviolet light

International Nuclear Information System (INIS)

Rocchi, P.; Ferreri, A.M.; Capucci, A.; Prodi, G.

1981-01-01

Stable spontaneous mutants resistant to the protein synthesis inhibitor diphtheria toxin (DT) have been selected in human cell line EUE at a very low frequency ( -6 ). U.v.-induced mutation has been quantitatively measured: treatment of cells with u.v. light increased the frequencies of diphtheria toxin resistant (DTsup(r)) mutants up to 1000-fold. The maximum recovery of DTsup(r) mutants was observed after a short expression period, for all u.v. doses tested, and was followed by a decrease in mutation frequency on subsequent passages. (author)

A fraction of Crm1 locates at centrosomes by its CRIME domain and regulates the centrosomal localization of pericentrin

International Nuclear Information System (INIS)

Liu, Qinying; Jiang, Qing; Zhang, Chuanmao

2009-01-01

Crm1 plays a role in exporting proteins containing nuclear export signals (NESs) from the nucleus to the cytoplasm. Some proteins that are capable of interacting with Ran/Crm1 were reported to be localized at centrosomes and to function as centrosome checkpoints. But it remains unclear how Crm1 locates at centrosomes. In this study, we found that a fraction of Crm1 is located at centrosomes through its N-terminal CRM1, importin β etc. (CRIME) domain, which is responsible for interacting with RanGTP, suggesting that Crm1 might target to centrosomes through binding centrosomal RanGTP. Moreover, overexpression of the CRIME domain, which is free of NES binding domain, resulted in the dissociation of pericentrin and γ-tubulin complex from centrosomes and the disruption of microtubule nucleation. Deficiency of Crm1 provoked by RNAi also decreased the spindle poles localization of pericentrin and γ-tubulin complex, coupled with mitotic defects. Since pericentrin was sensitive to Crm1 specific inhibitor leptomycin B, we propose that the centrosomal Crm1 might interact with pericentrin and regulate the localization and function of pericentrin at centrosomes.

An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

Directory of Open Access Journals (Sweden)

Syed Babar Jamal

Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

Evaluation of 13-valent pneumococcal conjugate vaccine and concomitant meningococcal group C conjugate vaccine in healthy infants and toddlers in Spain.

Science.gov (United States)

Diez-Domingo, Javier; Gurtman, Alejandra; Bernaola, Enrique; Gimenez-Sanchez, Francisco; Martinon-Torres, Federico; Pineda-Solas, Valentin; Delgado, Alfonso; Infante-Marquez, Pilar; Liang, John Z; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

2013-11-04

Given the concurrent administration of multiple vaccines during routine pediatric immunizations, efforts to elucidate the potential interference of any vaccine on the immune response to the concomitantly administered antigens are fundamental to prelicensure clinical research. This phase 3 randomized controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) versus 7-valent PCV (PCV7) assessed immune responses of concomitantly administered meningococcal group C conjugated to diphtheria toxin cross-reactive material 197 (MnCCV-CRM197) in a 2-dose infant series and 15-month toddler dose. 619 subjects were randomized, 315 to PCV13 and 304 to PCV7. MnCCV-CRM197-induced immune responses were similar between the PCV13 and PCV7 groups, with >97% of the subjects achieving a ≥1:8 meningococcal serum bactericidal assay (SBA) titer after both dose 2 and the toddler dose. Geometric mean titers were lower in the PCV13 group 191.22 (167.72, 218.02) versus 266.19 (234.86, 301.71) following dose 2 and 432.28 (361.22, 517.31) versus 730.84 (642.05, 831.91) following the toddler dose. The geometric mean (GM) meningococcal SBA titer ratios (PCV13/PCV7) were 0.72 after dose 2 and 0.59 after the toddler dose. The criteria for MnCCV-CRM197 non-inferiority for GM titers were satisfied after dose 2. Percent responders was similar up to titers of 1:128. PCV13 elicited substantial antipneumococcal responses against all 13 serotypes, with ≥90% of the subjects achieving an antibody concentration ≥0.35μg/mL after dose 3 in the infant series. Safety and tolerability were similar between the vaccine groups. Immunogenicity results of MnCCV-CRM197 for PCV13 compared with PCV7 included lower GMTs, but the clinical significance of this is unknown as the proportion of infants achieving protective MenC antibody titers was comparable in the two groups. Percent responders were similar up to titers of 1:128. PCV13 has an acceptable safety profile in infants and toddlers, while providing

Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.

Science.gov (United States)

Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

2009-12-01

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.

The Randomized CRM: An Approach to Overcoming the Long-Memory Property of the CRM.

Science.gov (United States)

Koopmeiners, Joseph S; Wey, Andrew

2017-01-01

The primary object of a Phase I clinical trial is to determine the maximum tolerated dose (MTD). Typically, the MTD is identified using a dose-escalation study, where initial subjects are treated at the lowest dose level and subsequent subjects are treated at progressively higher dose levels until the MTD is identified. The continual reassessment method (CRM) is a popular model-based dose-escalation design, which utilizes a formal model for the relationship between dose and toxicity to guide dose finding. Recently, it was shown that the CRM has a tendency to get "stuck" on a dose level, with little escalation or de-escalation in the late stages of the trial, due to the long-memory property of the CRM. We propose the randomized CRM (rCRM), which introduces random escalation and de-escalation into the standard CRM dose-finding algorithm, as well as a hybrid approach that incorporates escalation and de-escalation only when certain criteria are met. Our simulation results show that both the rCRM and the hybrid approach reduce the trial-to-trial variability in the number of cohorts treated at the MTD but that the hybrid approach has a more favorable tradeoff with respect to the average number treated at the MTD.

Channels formed by botulinum, tetanus, and diphtheria toxins in planar lipid bilayers: relevance to translocation of proteins across membranes.

OpenAIRE

Hoch, D H; Romero-Mira, M; Ehrlich, B E; Finkelstein, A; DasGupta, B R; Simpson, L L

1985-01-01

The heavy chains of both botulinum neurotoxin type B and tetanus toxin form channels in planar bilayer membranes. These channels have pH-dependent and voltage-dependent properties that are remarkably similar to those previously described for diphtheria toxin. Selectivity experiments with anions and cations show that the channels formed by the heavy chains of all three toxins are large; thus, these channels could serve as "tunnel proteins" for translocation of active peptide fragments. These f...

Open Source CRM Systems for SMEs

OpenAIRE

Marco Tereso; Jorge Bernardino

2011-01-01

Customer Relationship Management (CRM) systems are very common in large companies. However, CRM systems are not very common in Small and Medium Enterprises (SMEs). Most SMEs do not implement CRM systems due to several reasons, such as lack of knowledge about CRM or lack of financial resources to implement CRM systems. SMEs have to start implementing Information Systems (IS) technology into their business operations in order to improve business values and gain more competitive advantage over r...

STUDY OF CARDIAC INVOLVEMENT IN DIPHTHERIA

Directory of Open Access Journals (Sweden)

Bala Raju Gundam

2016-07-01

Full Text Available BACKGROUND Diphtheria still endemic in many developing countries and is responsible for high case fatality. Myocardial involvement is a serious complication of diphtheria and diphtheria myocarditis frequently complicated by arrhythmias causes sudden death if not managed properly. So, early and adequate administration of Anti-Diphtheritic Serum (ADS and frequent monitoring particularly 24 hrs. ECG monitoring is helpful to detect any serious cardiac arrhythmias. METHODS A prospective study on patients who were culture positive diagnosed on the basis of WHO definition were treated and analysed in respect to homographic details, immunisation strategy, and clinical features with particular attention to myocarditis. RESULTS In the study, common age group affected by diphtheria was 5 to 10 years. Incidence of myocarditis more in same age group. Out of 64 patients with myocarditis, 23 patients died. CONCLUSION Incidence of diphtheria has increased in the recent years. Commonly effected age group is 5 to 10 years and most of them are presented with asymptomatic myocarditis. Symptomatic diphtheritic myocarditis has high mortality rate even with aggressive management. Patient who presented with either LBBB alone are with combination of other conduction of abnormalities has high mortality rate.

Diphtheria in the postepidemic period, Europe, 2000-2009.

Science.gov (United States)

Wagner, Karen S; White, Joanne M; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S; Neal, Shona; Efstratiou, Androulla

2012-02-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.

Mathematical modeling of diphtheria transmission in Thailand.

Science.gov (United States)

Sornbundit, Kan; Triampo, Wannapong; Modchang, Charin

2017-08-01

In this work, a mathematical model for describing diphtheria transmission in Thailand is proposed. Based on the course of diphtheria infection, the population is divided into 8 epidemiological classes, namely, susceptible, symptomatic infectious, asymptomatic infectious, carrier with full natural-acquired immunity, carrier with partial natural-acquired immunity, individual with full vaccine-induced immunity, and individual with partial vaccine-induced immunity. Parameter values in the model were either directly obtained from the literature, estimated from available data, or estimated by means of sensitivity analysis. Numerical solutions show that our model can correctly describe the decreasing trend of diphtheria cases in Thailand during the years 1977-2014. Furthermore, despite Thailand having high DTP vaccine coverage, our model predicts that there will be diphtheria outbreaks after the year 2014 due to waning immunity. Our model also suggests that providing booster doses to some susceptible individuals and those with partial immunity every 10 years is a potential way to inhibit future diphtheria outbreaks. Copyright © 2017 Elsevier Ltd. All rights reserved.

Diphtheria outbreak with high mortality in northeastern Nigeria.

Science.gov (United States)

Besa, N C; Coldiron, M E; Bakri, A; Raji, A; Nsuami, M J; Rousseau, C; Hurtado, N; Porten, K

2014-04-01

SUMMARY A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64.3%) of whom were children aged diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.

CRM and the Bottom Line

DEFF Research Database (Denmark)

Josiassen, Alexander; Assaf, A. George; Cvelbar, Ljubica Knezevic

2014-01-01

Successful firms often endeavour to assure competitive advantages through the relationships with their customers. Consequently, customer relationship management (CRM) has become of pivotal importance to many firms. This study investigates the effect of each CRM dimension on the performance...... of hotels. We found that in general hotels should aim to improve CRM capabilities because it has a positive effect on firm performance. Contrary to some previous assumptions, CRM investments did not result in positive performance. These findings are important as hotels strive to allocate resources...

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

Science.gov (United States)

Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

Features of Diphtheria in Children

Directory of Open Access Journals (Sweden)

O.K. Koloskova

2014-09-01

Full Text Available The lecture describes the etiology, epidemiology, classification and clinical features of diphtheria in children, taking into account various sites, covers the issues of diagnosis. Treatment for diphtheria in children is carried as per the order of Ministry of Healthcare of Ukraine № 354 dated July 9, 2004 in accordance with the form and severity of the disease.

Current and future trends in cloud CRM

OpenAIRE

Nemček, Sebastian

2011-01-01

The diploma thesis is committed to mapping CRM applications available in cloud and trends within. The goal is to describe what CRM is, how it evolved into Cloud CRM, analyze main differences between the two approaches and analyze trends that can be observed in CRM market and CRM applications. This is coupled with description of the most common CRM solutions and products available both on-premises as well as on-demand. In the first part, the thesis introduces theory behind Customer Relationshi...

Epidemiology of Diphtheria in India, 1996-2016: Implications for Prevention and Control.

Science.gov (United States)

Murhekar, Manoj

2017-08-01

Diphtheria is an acute disease caused by exotoxin-producing Corynebacterium diphtheriae . Globally, diphtheria has been showing a declining trend due to effective childhood vaccination programs. A substantial proportion of global burden of diphtheria is contributed by India. Hospital-based surveillance studies as well as diphtheria outbreaks published in last 20 years (1996-2016) indicate that diphtheria cases are frequent among school-going children and adolescents. In some Indian states, Muslim children are affected more. As per the national level health surveys, coverage of three doses of diphtheria vaccine was 80% during 2015-2016. Information about coverage of diphtheria boosters is not routinely collected through these surveys, but is expected to be low. Few studies also indicate low diphtheria immunity among school-going children and adults. The strategies for prevention of diphtheria need to focus on improving coverage of primary and booster doses of diphtheria vaccines administered as a part of Universal Immunization Program as well as introducing diphtheria vaccine for school-going children.

Moving to E-CRM in Arab world to increase profit, AqsaCRM a case study of Building an Arabic E-CRM

OpenAIRE

Amroush, Fadi; Alkhoder, A.Baderddeen; Yusef, Talal

2008-01-01

There is hundreds of software that implement CRM methodology, but there are no Arabic complete solutions till now except a few products for big companies like Microsoft, so it is a big challenge to Arab world to benefit form CRM concept and implement theirs software to benefit from it. This paper aimed to discuss the difference between traditional marketing 4Ps and the new generation of marketing 4Cs, and then to explain what does CRM mean, its definition, features, and how to imple...

Diphtheria - 'The strangling angel' of children.

Science.gov (United States)

Byard, Roger W

2013-02-01

Diphtheria, an acute infectious condition caused by Corynebacterium diphtheriae, was once a major killer of children. Although the mortality rates dropped dramatically in the mid-twentieth century, due to a combination of improved standards of living and immunization programs, outbreaks are still occurring. Two children, aged four and five years respectively, are reported to demonstrate characteristic features of lethal cases. Death in case 1 was due to an extensive upper airway pseudomembrane causing acute respiratory failure. The diagnosis of diphtheria was only made at postmortem. Death in case 2 was due to acute cardiac failure with heart block complicating diphtheria. Other mechanisms in fatal cases involve disseminated intravascular coagulation, renal and endocrine failure. Declining levels of immunity among adults has resulted in a change in the epidemiological pattern of the disease with an older age of victims in recent outbreaks. As a result of population shifts and failure to immunize children it is likely that forensic pathologists may see more cases of diphtheria in the future. Due to the rarity of cases in Western communities and atypical presentations, the diagnosis may only be established at autopsy. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

An isolated outbreak of diphtheria in South Africa, 2015.

Science.gov (United States)

Mahomed, S; Archary, M; Mutevedzi, P; Mahabeer, Y; Govender, P; Ntshoe, G; Kuhn, W; Thomas, J; Olowolagba, A; Blumberg, L; McCarthy, K; Mlisana, K; DU Plessis, M; VON Gottberg, A; Moodley, P

2017-07-01

An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

The changing epidemiology of diphtheria in Jordan*

OpenAIRE

Khuri-Bulos, N.; Hamzah, Y.; Sammerrai, S. M.; Shehabi, A.; Hamed, R.; Arnaout, M. A.; Turk, J.; Qubain, H.

1988-01-01

Outbreaks of diphtheria used to occur regularly in Jordan, the last such outbreak being in 1977-78. Since that time, a massive immunization programme targeted at pre-school-age children has been markedly successful. Hence, when an outbreak of diphtheria occurred in 1982-83, it was unexpected. Of the 35 patients who were treated at the Jordan University Hospital, two died and the remaining 33 recovered uneventfully. Contrary to our findings in previous diphtheria epidemics in Jordan, this outb...

[First confirmed case of laryngeal diphtheria in Djibouti].

Science.gov (United States)

Koeck, J L; Merle, C; Bimet, F; Kiredjian, M; Goullin, B; Teyssou, R

2000-01-01

The first bacteriologically confirmed case of laryngeal diphtheria in Djibouti was reported in 1998. It involved a three-year-old native-born infant who had been vaccinated during the first year of life with three doses of a combined vaccine against diphtheria, tetanus, poliomyelitis, and pertussis. A rapid clinical improvement was observed under erythromycin treatment. Other cases of laryngeal diphtheria have been observed. It is important to reverse decreasing vaccinal coverage in Djibouti and to warn incoming travelers of the need to be adequate immunized against diphtheria. Enhanced epidemiologic surveillance of this disease is also needed.

Atviro kodo CRM tyrimas

OpenAIRE

Bukelis, Donatas

2006-01-01

The study deals with the features open source CRMs have, the ways we can change the code and make our own open source CRM system. The research is oriented to Web based CRMs. One open source CRM system is modyfied and translated into the Lithuanian language. Installation files were created for people who do not know databases and Web services software in order to help them install this CRM system and configure database as well as other system requirements. The final result of our work is open ...

Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations

NARCIS (Netherlands)

Bissumbhar, B.; Rakhmanova, A.G.; Berbers, G.; Iakolev, A.; Nosikova, E.; Melnick, O.; Ovtcharenko, E.; Rümke, H. C.; Ruitenberg, E.J.

2004-01-01

Aims: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer ≥3.0 IU/ml was used. In addition,

CRM System Implementation in a Multinational Enterprise

Science.gov (United States)

Mishra, Alok; Mishra, Deepti

The concept of customer relationship management (CRM) resonates with managers in today's competitive economy. As more and more organizations realize the significance of becoming customer-centric in today's competitive era, they embrace CRM as a core business strategy. CRM an integration of information technology and relationship marketing provides the infrastructure that facilitates long-term relationship building with customers at an enterprise-wide level. Successful CRM implementation is a complex, expensive and rarely technical projects. This paper presents the successful implementation of CRM in a multinational organization. This study will facilitate in understanding transition, constraints and implementation of CRM in multinational enterprises.

Nástroje CRM v bankovnictví

OpenAIRE

Petrová, Barbora

2008-01-01

Annotation This thesis is concerned with CRM approach - Customer relationship management. CRM covered new marketing methods, that are focused on client's needs rather than on product push strategy. Thanks to sophisticated data analysis clients are addressed with offers, that come up to their current needs. Thesis explains basic terms connected to CRM strategy, different sorts and its components. CRM concept is apllied on the banking area using the example of czech commercial bank.

ERP and CRM Data Integration

Directory of Open Access Journals (Sweden)

Željko Tomić

2016-05-01

As a rule, the CRM and ERP systems contain separate databases even if they come from the same manufacturer. Such separately kept databases also lead to separate basic records (identifiers, which primarily relate to business partners, items and services. This may create problems with updating and maintaining consistency of the data within the information system of a company. The CRM and ERP systems usually overlap in certain segments of business processes (e.g., orders, order confirmations, quotations, etc., thus potentially creating redundant information and documents. More often than not, the CRM and ERP also differ in terms of technology, both by their vertical architectures and with regard to the DBMS and API support. The objective of this paper is to generate an ERP-CRM integration data model by way of optimising the relevant processes and costs, and to provide details about the processes of integration of the logical and physical data models. The structural integration of the ERP-CRM databases provide the integration services that ensure all the necessary functionalities in various interface logics and technologies with regard to software solutions and applications given, or used for local adaptations of the existing ERP and CRM applications.

The changing epidemiology of diphtheria in Jordan*

Science.gov (United States)

Khuri-Bulos, N.; Hamzah, Y.; Sammerrai, S. M.; Shehabi, A.; Hamed, R.; Arnaout, M. A.; Turk, J.; Qubain, H.

1988-01-01

Outbreaks of diphtheria used to occur regularly in Jordan, the last such outbreak being in 1977-78. Since that time, a massive immunization programme targeted at pre-school-age children has been markedly successful. Hence, when an outbreak of diphtheria occurred in 1982-83, it was unexpected. Of the 35 patients who were treated at the Jordan University Hospital, two died and the remaining 33 recovered uneventfully. Contrary to our findings in previous diphtheria epidemics in Jordan, this outbreak largely involved adolescents and young adults. PMID:3260143

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

Postbooster Antibodies from Humans as Source of Diphtheria Antitoxin.

Science.gov (United States)

Bermejo-Martin, Jesús F; Avila-Alonso, Ana; González-Rivera, Milagros; Tamayo, Eduardo; Eiros, Jose María; Almansa, Raquel

2016-07-01

Diphtheria antitoxin for therapeutic use is in limited supply. A potential source might be affinity-purified antibodies originally derived from plasma of adults who received a booster dose of a vaccine containing diphtheria toxoid. These antibodies might be useful for treating even severe cases of diphtheria.

Diphtheria in the Postepidemic Period, Europe, 2000–2009

Science.gov (United States)

White, Joanne M.; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S.; Neal, Shona; Efstratiou, Androulla

2012-01-01

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections. PMID:22304732

A proposed Framework for CRM On-Demand System Evaluation : Evaluation Salesforce.com CRM and Microsoft Dynamics Online

OpenAIRE

Özcanli, Can

2012-01-01

Customer Relationship Management has been an integral part of the enterprise since two decades. Today, enterprises that focus on customer satisfaction need to manage their relationships with their customers effectively. This demand has allowed software vendors to create CRM solutions. The technology and broadband advancement allowed the CRM vendors to enhance their product portfolio by developing web-based CRM systems, in addition to their CRM on-premise solutions. These vendors adopted the b...

Cardiac complications in diphtheria and predictors of outcomes.

Science.gov (United States)

Samdani, Sunil; Jain, Avani; Meena, Vinod; Meena, C B

2018-01-01

To study the cardiac complications in diphtheria patients and to study the predictors of outcomes. Single centre prospective analysis of cardiac complications in diphtheria patients. In this study, there were 60 patients diagnosed with diphtheria with ECG changes. The ECG changes seen were sinus tachycardia (68.3%), T wave inversion (20%), ST segment depression (13.3%), right bundle branch block (5%), multiple atrial ectopics (3.3%). The case fatality rate in our study was 25% (15 patients). High CPK-MB, myoglobulin and cardiac troponin levels were associated with cardiac mortality. In our study, cardiac troponin T had the highest sensitivity (80%) and CK-MB had the highest specificity (95.56%). Cardiac involvement is a common complication of infection with C. diphtheria and is associated with high mortality. As diphtheria can be prevented by adequate vaccination, efforts should be maximized for high vaccine coverage with booster doses. Copyright © 2017. Published by Elsevier B.V.

CRM - I Want It My Way!

Science.gov (United States)

Henwood, Bart

2007-01-01

This viewgraph presentation provides an overview of crew resource management (CRM). Topics include what makes a good participant in a team process, human perception and response of individual behavior, characteristics of a bad participant, factors that affect performance, CRM assumptions and techniques, and CRM and individuality.

Autoradiographic assay of mutants resistant to diphtheria toxin in mammalian cells in vitro

International Nuclear Information System (INIS)

Ronen, A.; Gingerich, J.D.; Duncan, A.M.V.; Heddle, J.A.

1984-01-01

Diptheria toxin kills mammalian cells by ribosylating elongation factor 2, a protein factor necessary for protein synthesis. The frequency of cells able to form colonies in the presence of the toxin can be used as an assay for mutation to diphtheria toxin resistance. Resistance to diphtheria toxin can also be detected autoradiographically in cells exposed to [ 3 H]leucine after treatment with the toxin. In cultures of Chinese hamster ovary cells, the frequency of such resistant cells is increased by exposure of the cells to γ-rays, ultraviolet light, ethylnitrosourea, mitomycin c, ethidium bromide, and 5-bromo-2'-deoxyuridine in a dose- and time-dependent manner. The resistant cells form discrete microcolonies if they are allowed to divide several times before intoxication which indicates that they are genuine mutants. The assay is potentially adaptable to any cell population that can be intoxicated with diphtheria toxin and labeled with [ 3 H]leucine, whether or not the cells can form colonies. It may be useful, therefore, for measuring mutation rates in slowly growing or nondividing cell populations such as breast, brain, and liver, as well as in cells that do divide but cannot be readily cloned, such as the colonic epithelium. 23 references, 6 figures

Sudden death of a child due to respiratory diphtheria.

Science.gov (United States)

Swain, Rajanikanta; Behera, Chittaranjan; Arava, Sudheer Kumar; Kundu, Naveen

2016-06-01

A four-year-old girl presented to the emergency department with respiratory distress. Death occurred despite attempted resuscitation. The illness was not clinically diagnosed. Her father revealed that she had a fever and sore throat for the last four days and was not immunised for diphtheria. Characteristic gross and microscopic pathology of respiratory diphtheria and microbiological findings were observed. The cause of death was acute respiratory failure consequent upon upper airway obstruction from diphtheria. Forensic pathologists should remember that the diphtheria cases can cause sudden death especially in developing countries. © The Author(s) 2016.

Quantitative estimation of diphtheria and tetanus toxoids. 4. Toxoids as international reference materials defining Lf-units for diphtheria and tetanus toxoids.

Science.gov (United States)

Lyng, J

1990-01-01

The Lf-unit, which is used in the control of diphtheria and tetanus toxoid production and in some countries also to follow immunization of horses for production of antitoxins, has hitherto been defined by means of antitoxin preparations. A diphtheria toxoid and a tetanus toxoid preparation, both freeze-dried, were examined in an international collaborative study for their suitability to serve as reference reagents in the flocculation tests and for defining the Lf-units. It was shown that flocculation tests using the reference toxoids are very reproducible and reliable and the WHO Expert Committee on Biological Standardization established: the toxoid called DIFT as the International Reference Reagent of Diphtheria Toxoid for Flocculation Test with a defined content of 900 Lf-units of diphtheria toxoid per ampoule; and the toxoid called TEFT as the International Reference Reagent of Tetanus Toxoid for Flocculation Test with a defined content of 1000 Lf-units of diphtheria toxoid per ampoule.

Diphtheria in Andhra Pradesh-a clinical-epidemiological study.

Science.gov (United States)

M, Meera; M, Rajarao

2014-02-01

Clinical diphtheria is on the increase worldwide, mainly affecting developing countries. We sought to understand its presentation among patients at Sir Ronald Ross Institute of Tropical and Communicable Diseases in Hyderabad, Andhra Pradesh, India. Diphtheria patients presented with fever, pharyngitis, and a patch in the throat. Data collected for each patient included age, clinical presentation, morbidity, mortality, bacteria isolated from culture, and immunization status. Of 61 950 admissions from January 2008 to December 2012, 2925 (4.7%) had clinical diphtheria; 1194 had been immunized and 1731 were non-immunized. Immunized patients had a milder disease. Culture-positive immunized patients were positive for Corynebacterium other than diphtheriae (COD; n=104) or Corynebacterium diphtheriae (CD; n=23); these patients suffered mild disease and recovered completely. In contrast, culture-positive non-immunized patients were positive for COD (n=11) or CD (n=412). Eighty-one patients (3%) died, 77 of whom were non-immunized; death was usually as a result of myocarditis. Seventy-three percent of deaths were in patients aged diphtheria and its severity and morbidity differ considerably in immunized and non-immunized patients. Disease caused by CD can be deadly, while disease due to COD is mild and responds to treatment. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Diphtheria outbreak in Lao People's Democratic Republic, 2012-2013.

Science.gov (United States)

Sein, Carolyn; Tiwari, Tejpratap; Macneil, Adam; Wannemuehler, Kathleen; Soulaphy, Chanthavy; Souliphone, Phouthone; Reyburn, Rita; Ramirez Gonzalez, Alejandro; Watkins, Margaret; Goodson, James L

2016-08-05

Diphtheria is a vaccine-preventable disease. When vaccination coverage and population immunity are low, outbreaks can occur. We investigated a diphtheria outbreak in Lao People's Democratic Republic that occurred during 2012-2013 and highlighted challenges in immunization services delivery to children in the country. We reviewed diphtheria surveillance data from April 1, 2012-May 31, 2013. A diphtheria case was defined as a respiratory illness consisting of pharyngitis, tonsillitis, or laryngitis, and an adherent tonsillar or nasopharyngeal pseudomembrane. To identify potential risk factors for diphtheria, we conducted a retrospective case-control study with two aged-matched neighborhood controls per case-patient in Houaphan Province, using bivariate analysis to calculate matched odds ratio (mOR) with 95% confidence intervals (CI). Reasons for non-vaccination among unvaccinated persons were assessed. Sixty-two clinical cases of diphtheria and 12 diphtheria-related deaths were reported in seven of 17 provinces. Among case-patients, 43 (69%) were diphtheria case-patients from Houaphan province and 79 matched-controls were enrolled. Five (12%) case-patients and 20 (25%) controls had received DTP3 (mOR=0.4, CI=0.1-1.7). No diphtheria toxoid-containing vaccine was received by 20 (48%) case-patients and 38 (46%) controls. Among case-patients and controls with no DTP dose, 43% of case-patients and 40% of controls lacked access to routine immunization services. Suboptimal DTP3 coverage likely caused the outbreak. To prevent continued outbreaks, access to routine immunization services should be strengthened, outreach visits need to be increased, and missed opportunities need to be minimized. In the short term, to rapidly increase population immunity, three rounds of DTP immunization campaign should be completed, targeting children aged 0-14years in affected provinces. Copyright © 2016 Elsevier Ltd. All rights reserved.

Avoid the four perils of CRM.

Science.gov (United States)

Rigby, Darrell K; Reichheld, Frederick F; Schefter, Phil

2002-02-01

Customer relationship management is one of the hottest management tools today. But more than half of all CRM initiatives fail to produce the anticipated results. Why? And what can companies do to reverse that negative trend? The authors--three senior Bain consultants--have spent the past ten years analyzing customer-loyalty initiatives, both successful and unsuccessful, at more than 200 companies in a wide range of industries. They've found that CRM backfires in part because executives don't understand what they are implementing, let alone how much it will cost or how long it will take. The authors' research unveiled four common pitfalls that managers stumble into when trying to implement CRM. Each pitfall is a consequence of a single flawed assumption--that CRM is software that will automatically manage customer relationships. It isn't. Rather, CRM is the creation of customer strategies and processes to build customer loyalty, which are then supported by the technology. This article looks at best practices in CRM at several companies, including the New York Times Company, Square D, GE Capital, Grand Expeditions, and BMC Software. It provides an intellectual framework for any company that wants to start a CRM program or turn around a failing one.

METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

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Isayenko Ye. Yu

2016-12-01

Full Text Available Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount

Rational Design of Adjuvant for Skin Delivery: Conjugation of Synthetic β-Glucan Dectin-1 Agonist to Protein Antigen.

Science.gov (United States)

Donadei, Agnese; Gallorini, Simona; Berti, Francesco; O'Hagan, Derek T; Adamo, Roberto; Baudner, Barbara C

2015-05-04

The potential benefits of skin delivery of vaccines derive from the presence of a densely connected network of antigen presenting cells in the skin layer, most significantly represented by Langerhans cells and dermal dendritic cells. Targeting these cells by adjuvant conjugated to an antigen should result in enhanced immunogenicity of a vaccine. Since one of the most widely used adjuvants is an insoluble salt of aluminum (aluminum hydroxide) that cannot be used for skin delivery due to reactogenicity, we focused our attention on agonists of receptors present on skin dendritic cells, including the Dectin-1 receptor. β-(1-3)-glucans, which are the most abundant components of the fungal surface, are known to activate the innate immune response by interaction with the C-type lectin-like Dectin-1 receptor. In this work we identified by rational design a well-defined synthetic β-(1-3)-glucan hexasaccharide as a Dectin-1 agonist and chemically conjugated it to the genetically detoxified diphtheria toxin (CRM197) protein antigen, as a means to increase the binding to Dectin-1 receptor and to target to skin dendritic cells. We demonstrated that the in vitro activation of the receptor was significantly impacted by the presentation of the glucan on the protein carrier. In vivo results in mice showed that the conjugation of the synthetic β-(1-3)-glucan when delivered intradermally resulted in higher antibody titers in comparison to intramuscular (i.m.) immunization and was not different from subcutaneous (s.c.) delivery. These findings suggest that weak receptor binders can be turned into more potent agonists by the multivalent presentation of many ligands covalently conjugated to the protein core. Moreover, this approach is particularly valuable to increase the immunogenicity of antigens administered via skin delivery.

Nullbasic, a potent anti-HIV tat mutant, induces CRM1-dependent disruption of HIV rev trafficking.

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Min-Hsuan Lin

Full Text Available Nullbasic, a mutant of the HIV-1 Tat protein, has anti-HIV-1 activity through mechanisms that include inhibition of Rev function and redistribution of the HIV-1 Rev protein from the nucleolus to the nucleoplasm and cytoplasm. Here we investigate the mechanism of this effect for the first time, establishing that redistribution of Rev by Nullbasic is not due to direct interaction between the two proteins. Rather, Nullbasic affects subcellular localization of cellular proteins that regulate Rev trafficking. In particular, Nullbasic induced redistribution of exportin 1 (CRM1, nucleophosmin (B23 and nucleolin (C23 from the nucleolus to the nucleus when Rev was coexpressed, but never in its absence. Inhibition of the Rev:CRM1 interaction by leptomycin B or a non-interacting RevM10 mutant completely blocked redistribution of Rev by Nullbasic. Finally, Nullbasic did not inhibit importin β- or transportin 1-mediated nuclear import, suggesting that cytoplasmic accumulation of Rev was due to increased export by CRM1. Overall, our data support the conclusion that CRM1-dependent subcellular redistribution of Rev from the nucleolus by Nullbasic is not through general perturbation of either nuclear import or export. Rather, Nullbasic appears to interact with and disrupt specific components of a Rev trafficking complex required for its nucleocytoplasmic shuttling and, in particular, its nucleolar accumulation.

Microsoft Dynamics CRM 2011 cookbook

CERN Document Server

Bhattacharya, Dipankar

2013-01-01

This is a Cookbook with recipes aimed at all levels with lots of practical walkthroughs for virtualization techniques.This book is great for Dynamics CRM 2011 professionals who have a beginner level understanding of the system and are looking to get a good grounding in how to deploy, maintain, configure, and customize a Dynamics CRM 2011 application efficiently. It's assumed that the reader has a basic level understanding of IT infrastructure topologies along with functional knowledge of Dynamics CRM 2011 Sales, Marketing, and Services modules.

[Cutaneous diphtheria after a minor injury in Sri Lanka].

Science.gov (United States)

Berg, L; Mechlin, A; Schultz, E S

2016-02-01

Cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in Germany. Following travel in Sri Lanka, a 60-year-old German presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. Corynebacterium diphtheriae was isolated from a swab of the lesion. There were no clinical signs of toxic diphtheria. The patient was treated with penicillin G and erythromycin, followed by a slow healing of the lesion. The isolated strain could be identified as toxigenic C. diphtheriae mitis. Due to increased travel activity, dermatologists should have uncommon infections like cutaneous diphtheria in mind.

Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

Science.gov (United States)

Nanthavong, Naphavanh; Black, Antony P; Nouanthong, Phonethipsavanh; Souvannaso, Chanthasone; Vilivong, Keooudomphone; Muller, Claude P; Goossens, Sylvie; Quet, Fabrice; Buisson, Yves

2015-01-01

During late 2012 and early 2013 several outbreaks of diphtheria were notified in the North of the Lao People's Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12-59 months. Serum samples, socio-demographic data, nutritional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4-28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74-85, 4], p = 0.01) and the lack of advice on vaccination given at birth (OR: 9.8 [95% CI: 1.5-63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008-0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical deficiencies in the methods of storage and distribution of vaccines as well as unreliability of vaccination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against

Customer Relationship Marketing (CRM) Practices in Danish Small BusinessesCustomer Relationship Marketing (CRM) Practices in Danish Small Businesses

DEFF Research Database (Denmark)

Kuada, John; Serles, Dorthe

2006-01-01

This paper examines the extent to which the adoption of CRM software packages is a pre-requisite of customer orientation strategies of small firms. This is done by conducting an empirical investigation into the internal determinants of CRM adoption behavior of 179 randomly selected small firms...... in the Northern Jutland region of Denmark. The results suggest that top managers in these firms endorse the strategic value of customer orientation to their businesses but do not consider CRM software packages as necessary for building strong relationships with their customers. This suggests that small firms may...... make their CRM adoption/rejection decisions on the basis of a trade-off between expected benefits from using the available CRM packages compared with alternative modes of achieving customer loyalty....

CLINICAL FEATURES OF CHILDREN WITH DIPHTHERIA ON SOETOMO HOSPITAL

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Dwiyanti Puspitasari

2017-04-01

Full Text Available Introduction: Diphtheria is an important disease in children that could lead to fatal disease. East Java Province was declared to have Diphtheria outbreak in 2011 with increasing morbidity and mortality, including on Soetomo Hospital. Our paper aimed to describe the profi le of diphtheria cases in children admitted at dr Sutomo Hospital. Method: This descriptive study reviewed all medical records of diphtheritic patients admitted to Dr. Soetomo Hospital, January 2004–December 2010, of concerns were clinical presentations, age, sex, immunizations status, complications, and outcomes. Result: From 148 diphtheria cases, 22.3% were bacteriologically proven; 53.4% were male with sex ratio 1.1:1. The age proportion of ≤ 5 years old, 5- ≤ 10 years old, and > 10 years old were 61.5%, 31.8%, and 6.7%. Fever occurred in 99% cases, sore throat, stridor and bullneck occurred respectively in 62.2%, 39.9%, and 29.7% cases. There were 56.8% severe and 41.9% moderate diphtheria. Subjects were immunized in 84%, but none of them have adequate immunization. Myocarditis, being one of the commonest complications occurred in 11.4% cases and tracheostomy was the second (4.0%. All of the death cases (7.9% were unvaccinated and in severe form. Discussion: The mostly prevalent clinical manifestations in diphtheria children were fever and sore throat. Half of the cases came with severe diphtheria and most cases were inadequately vaccinated. Death occurred in the unvaccinated and severe form.

mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis.

Science.gov (United States)

Zmudjak, Michal; Colas des Francs-Small, Catherine; Keren, Ido; Shaya, Felix; Belausov, Eduard; Small, Ian; Ostersetzer-Biran, Oren

2013-07-01

The coding regions of many mitochondrial genes in plants are interrupted by intervening sequences that are classified as group II introns. Their splicing is essential for the expression of the genes they interrupt and hence for respiratory function, and is facilitated by various protein cofactors. Despite the importance of these cofactors, only a few of them have been characterized. CRS1-YhbY domain (CRM) is a recently recognized RNA-binding domain that is present in several characterized splicing factors in plant chloroplasts. The Arabidopsis genome encodes 16 CRM proteins, but these are largely uncharacterized. Here, we analyzed the intracellular location of one of these hypothetical proteins in Arabidopsis, mitochondrial CAF-like splicing factor 1 (mCSF1; At4 g31010), and analyzed the growth phenotypes and organellar activities associated with mcsf1 mutants in plants. Our data indicated that mCSF1 resides within mitochondria and its functions are essential during embryogenesis. Mutant plants with reduced mCSF1 displayed inhibited germination and retarded growth phenotypes that were tightly associated with reduced complex I and IV activities. Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

ACTION OF DIPHTHERIA TOXIN IN THE GUINEA PIG

Science.gov (United States)

Baseman, Joel B.; Pappenheimer, A. M.; Gill, D. M.; Harper, Annabel A.

1970-01-01

The blood clearance and distribution in the tissues of 125I after intravenous injection of small doses (1.5–5 MLD or 0.08–0.25 µg) of 125I-labeled diphtheria toxin has been followed in guinea pigs and rabbits and compared with the fate of equivalent amounts of injected 125I-labeled toxoid and bovine serum albumin. Toxoid disappeared most rapidly from the blood stream and label accumulated and was retained in liver, spleen, and especially in kidney. Both toxin and BSA behaved differently. Label was found widely distributed among all the organs except the nervous system and its rate of disappearance from the tissues paralleled its disappearance from the circulation. There was no evidence for any particular affinity of toxin for muscle tissue or for a "target" organ. Previous reports by others that toxin causes specific and selective impairment of protein synthesis in muscle tissue were not confirmed. On the contrary, both in guinea pigs and rabbits, a reduced rate of protein synthesis was observed in all tissues that had taken up the toxin label. In tissues removed from intoxicated animals of both species there was an associated reduction in aminoacyl transferase 2 content. It is concluded that the primary action of diphtheria toxin in the living animal is to effect the inactivation of aminoacyl transferase 2. The resulting inhibition in rate of protein synthesis leads to morphologic damage in all tissues reached by the toxin and ultimately to death of the animal. PMID:5511567

Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components

Science.gov (United States)

Otto, Robert B.D.; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T.; Bolgiano, Barbara

2015-01-01

The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP–Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. PMID:26194164

The ontology model of FrontCRM framework

Science.gov (United States)

Budiardjo, Eko K.; Perdana, Wira; Franshisca, Felicia

2013-03-01

Adoption and implementation of Customer Relationship Management (CRM) is not merely a technological installation, but the emphasis is more on the application of customer-centric philosophy and culture as a whole. CRM must begin at the level of business strategy, the only level that thorough organizational changes are possible to be done. Changes agenda can be directed to each departmental plans, and supported by information technology. Work processes related to CRM concept include marketing, sales, and services. FrontCRM is developed as framework to guide in identifying business processes related to CRM in which based on the concept of strategic planning approach. This leads to processes and practices identification in every process area related to marketing, sales, and services. The Ontology model presented on this paper by means serves as tools to avoid framework misunderstanding, to define practices systematically within process area and to find CRM software features related to those practices.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

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Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kondoh, Yasumitsu; Osada, Hiroyuki [Chemical Biology Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori [Laboratory of Viral Genomics, Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Disease Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

2017-07-15

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development

International Nuclear Information System (INIS)

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

2017-01-01

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. - Highlights: •DP2392-E10 inhibits replication of a broad range of influenza A subtypes. •DP2392-E10 inhibits nuclear exports of NP and NEP via their NP-NES3 and NEP-NES2 domains, respectively. •DP2392-E10 is predicted to directly bind CRM1 in the region near the HEAT9 and HEAT10 repeats.

Evaluating the role of CRM1-mediated export for adenovirus gene expression

International Nuclear Information System (INIS)

Carter, Christoph C.; Izadpanah, Reza; Bridge, Eileen

2003-01-01

A complex of the Adenovirus (Ad) early region 1b 55-kDa (E1b-55kDa) and early region 4 ORF6 34-kDa (E4-34kDa) proteins promotes viral late gene expression. E1b-55kDa and E4-34kDa have leucine-rich nuclear export signals (NESs) similar to that of HIV Rev. It was proposed that E1b-55kDa and/or E4-34kDa might promote the export of Ad late mRNA via their Rev-like NESs, and the transport receptor CRM1. We treated infected cells with the cytotoxin leptomycin B to inhibit CRM1-mediated export; treatment initially delays the onset of late gene expression, but this activity completely recovers as the late phase progresses. We find that the E1b-55kDa NES is not required to promote late gene expression. Previous results showed that E4-34kDa-mediated late gene expression does not require an intact NES (J. Virol. 74 (2000), 6684-6688). Our results indicate that these Ad regulatory proteins promote late gene expression without intact NESs or active CRM1

Modelling CRM implementation services with SysML

OpenAIRE

Bibiano, Luis H.; Pastor Collado, Juan Antonio; Mayol Sarroca, Enric

2009-01-01

CRM information systems are valuable tools for enterprises. But CRM implementation projects are risky and present a high failure rate. In this paper we regard CRM implementation projects as services that could be greatly improved by addressing them in a methodological way that can be designed with the help of tools such as SysML. Here we introduce and comment on our first experience on the use of SysML language, not very well known, for modelling the elements involved in the CRM implementatio...

A research on CRM systems in the Czech Republic

Directory of Open Access Journals (Sweden)

František Dařena

2008-01-01

Full Text Available Customer Relationship Management (CRM is seen as a holistic framework for interaction of organizations with their customers. It is focused on gaining customers’ loyalty through providing the value positively perceived by the customers and usually incorporates information and communication technologies in the form of CRM systems. The paper discusses various aspects of CRM phi­lo­so­phy and utilization of information and communication technologies in relation to CRM. A survey that was conducted among three hundred organizations in the Czech Republic (among them some major companies, such as ČEZ, T-Mobile, Česká spořitelna and others. The objective of the survey was to discover the scope and level of using CRM systems, factors influencing decisions about CRM, understanding the CRM concept, evaluating CRM benefits, issues related to implementation and ot­hers. Organizations mostly perceive CRM as a profitable approach although they do not see it as a global philosophy but rather as a set of separated tools. The most relevant argument for CRM implementation include better contact management, better understanding the customers, higher number of retained customers, longer relationships with customers and higher customer satisfaction.

Inhibition of CRM1-mediated nuclear export of influenza A nucleoprotein and nuclear export protein as a novel target for antiviral drug development.

Science.gov (United States)

Chutiwitoonchai, Nopporn; Mano, Takafumi; Kakisaka, Michinori; Sato, Hirotaka; Kondoh, Yasumitsu; Osada, Hiroyuki; Kotani, Osamu; Yokoyama, Masaru; Sato, Hironori; Aida, Yoko

2017-07-01

An anti-influenza compound, DP2392-E10 based on inhibition of the nuclear export function of the viral nucleoprotein-nuclear export signal 3 (NP-NES3) domain was successfully identified by our previous high-throughput screening system. Here, we demonstrated that DP2392-E10 exerts its antiviral effect by inhibiting replication of a broad range of influenza A subtypes. In regard to the molecular mechanism, we revealed that DP2392-E10 inhibits nuclear export of both viral NP and nuclear export protein (NEP). More specifically, in vitro pull-down assays revealed that DP2392-E10 directly binds cellular CRM1, which mediates nuclear export of NP and NEP. In silico docking suggested that DP2392-E10 binds at a region close to the HEAT9 and HEAT10 domains of CRM1. Together, these results indicate that the CRM1-mediated nuclear export function of influenza virus represents a new potential target for antiviral drug development, and also provide a core structure for a novel class of inhibitors that target this function. Copyright © 2017 Elsevier Inc. All rights reserved.

IMPLEMENTATION OF E-CRM IN MACEDONIAN COMPANIES

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MARGARITA JANESKA

2016-08-01

Full Text Available Customer Relationship Management (CRM in the digital economy is a challenge for companies that operate in the new electronic environment. In fact, companies that use the internet as basic infrastructure for their operations must adapt and to be ready to respond to the growing challenges who are posed from more sophisticated consumers. CRM concept includes possibilities, methodology and technology that enable companies to operate through improving relations with consumers. CRM as a strategic set of activities begins with a detailed analysis of organizational strategy and ending with measurement of value for stakeholders. CRM owes its expansion to the emergence of the Internet. Digital economy enables more effective targeting and personalization. The basic motive for the research is the fact that e-CRM is a relatively new concept and in recent years has made significant strides in companies around the world aimed at customers. Namely, e-CRM is positioned high on the priority list of today's corporate agendas. The aim of this paper is to consider the importance and benefits of the implementation of e-CRM concept in Macedonia, and to determine the factors that contribute to its successful implementation. The research results should contribute to increasing the profitability and competitiveness of Macedonian companies.

Anti-diphtheria immunity in Nigerian mothers and their newborns.

Science.gov (United States)

Cummings, Henry; Sadoh, Ayebo Evawere; Oviawe, Osawaru; Sadoh, Wilson Ehidiamen

2014-05-30

Immunity to diphtheria has been noted to wane with age such that previous studies have shown that a significant proportion of females with characteristics comparable to those of Nigerian women of reproductive age have inadequate levels of immunity to diphtheria. Thus, it is envisaged that Nigerian newborns may inherit inadequate levels of immunity to diphtheria from their mothers. Cord blood and peripheral maternal blood samples were collected from 231 mother-infant pairs at delivery. Anti-diphtheria antibody titres were assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Recruited babies were those born at term with normal birth weight. As much as 29.9% of both mothers and their babies had no protection (antibody titrediphtheria. Ninety (39.0% CI 33%,45%) mothers and 107 (46.3% CI 40%,52%) babies were inadequately protected (antibody titrediphtheria. The difference in the geometric mean antibody titres of mothers and babies was statistically significant (pdiphtheria. Vaccination of parturient women with booster doses of diphtheria toxoid vaccine is recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

SOCIAL CRM FOR CUSTOMER KNOWLEDGE MANAGEMENT

Directory of Open Access Journals (Sweden)

Dorota Buchnowska

2014-12-01

Full Text Available The recent development and expansion of Web 2.0 technologies have created remarkable opportunities for Customer Knowledge Management (CKM. The goals of this paper are to analyze how organizations can apply Social CRM (social technologies integrated with traditional CRM systems systems for CKM and to investigate what benefits they may derive from the use of social technologies. To achieve these objectives, the article shows the concept of Social CRM, differences between CRM and SCRM, and a review of CKM models presented in the literature. Then, there are indicated the possibilities of using SCRM solutions in the processes of customer knowledge management, and there are presented examples of the use of different types of social media in the management of different types of customer knowledge.

Contribution to the study of Pt197 and Au197 excited states

International Nuclear Information System (INIS)

Alves, S.M.C.

1971-01-01

The gamma transitions of the Ir 197β- → Pt 197β- → Au 197 decay chain were investigated using three Ge(Li) detectors of high resolution and spectroscopy techniques with one, two and three via of analysis. For the Ir 197β- →Pt 197 decay, four new gamma transitions with energy of 877.6; 938.7; 1049.6 and 1341.8 Kev were observed, presupposing to be energy levels in 877.6; 938.7; 1049.6 and 1347.8 Kev in the Ir 197 population by β- decay of Ir 197 . By the first time, the 299.5 Kev transition was observed, in the Pt 197 m (80min) decay, interpreted as a direct desexcitation of the 299.5Kev level in Pt 197 . A new scheme of Ir 197 β- → Au 197 decay based on the obtained results, is proposed. (M.C.K.) [pt

Culture in the Cockpit-CRM in a Multicultural World

Science.gov (United States)

Engle, Michael

2000-01-01

Crew Resource Management (CRM) is fundamentally a method for enhancing personal interactions among crewmembers so that safety and efficiency are increased, and at its core involves issues of culture and social interaction. Since CRM is increasingly being adopted by foreign carriers, it is important to evaluate standard CRM techniques from a cultural standpoint, especially if some of these techniques may be enhanced by adapting them to particular cultures. The purpose of this paper is to propose a model for an ideal CRM culture, and to suggest ways that CRM may be adapted to suit particular cultures. The research method was a simple literature search to gather data on CRM techniques and multicultural crews. The results indicate that CRM can be tailored to specific cultures for maximum effectiveness.

Baseline immunity to diphtheria and immunologic response after booster vaccination with reduced diphtheria and tetanus toxoid vaccine in Thai health care workers.

Science.gov (United States)

Wiboonchutikul, Surasak; Manosuthi, Weerawat; Sangsajja, Chariya; Thientong, Varaporn; Likanonsakul, Sirirat; Srisopha, Somkid; Termvises, Patamavadee; Rujitip, Jitlada; Loiusirirotchanakul, Suda; Puthavathana, Pilaipan

2014-07-01

A prospective study to evaluate immune status against diphtheria and immunologic response after tetanus-diphtheria (Td) booster vaccination was conducted in 250 Thai health care workers (HCWs). A protective antibody was found in 89.2% of the HCWs (95% confidence interval [CI], 83.3%-91.5%) before receipt of the Td booster vaccination, compared with 97.2% (95% CI, 95.1%-99.3%) after receipt of the first dose of booster (P diphtheria increased from 0.39 IU/mL (95% CI, 0.35-0.44 IU/mL) before the Td booster vaccination to 1.20 IU/mL (95% CI, 1.12-1.29 IU/mL) after the vaccination (P diphtheria, which still circulates in Thailand. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Hospital CRM: unexplored frontier of revenue growth?

Science.gov (United States)

Young, Thomas

2007-10-01

Customer relationship management (CRM) has a less-than-stellar reputation, in large part because efforts to implement it have been piecemeal and not well funded. The technologies now exist to make CRM much more effective than it has been in the past. Many hospitals today are demonstrating a substantial ROI from implementing a comprehensive CRM program.

Tetanus, Diphtheria, and Pertussis Vaccines: MedlinePlus Health Topic

Science.gov (United States)

... Know (Centers for Disease Control and Prevention) - PDF Topic Image MedlinePlus Email Updates Get Tetanus, Diphtheria, and ... updates by email What's this? GO Related Health Topics Childhood Immunization Diphtheria Immunization Tetanus Whooping Cough National ...

AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.

Science.gov (United States)

Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

2014-01-01

Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1α and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1α nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1α target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

De weg naar een succesvolle CRM-implementatie! TNO CRM Clusterplan Handleiding CRM-implementatie

NARCIS (Netherlands)

Kardol, H.; Loon, J. van; Oerlemans, K.

2006-01-01

Natuurlijk proberen CRM leveranciers u als klant hierin zo goed mogelijk te ondersteunen maar dan nog is het lastig om voor de betrokken partijen een gezamenlijk referentiekader te creëren. Hierdoor komt het nog regelmatig voor dat de verwachtingen bij de afnemer niet waargemaakt worden waardoor de

Immunity to tetanus and diphtheria in the UK in 2009.

Science.gov (United States)

Wagner, Karen S; White, Joanne M; Andrews, Nick J; Borrow, Ray; Stanford, Elaine; Newton, Emma; Pebody, Richard G

2012-11-19

This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (pdiphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, pdiphtheria in 2009 were 29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule. Copyright © 2012 Elsevier Ltd. All rights reserved.

CUSTOMER RELATIONSHIP MANAGEMENT ( CRM IN HOTEL INDUSTRY : A FRAMEWORK PROPOSAL ON THE RELATIONSHIP AMONG CRM DIMENSIONS, MARKETING CAPABILITIES, AND HOTEL PERFORMANCE

Directory of Open Access Journals (Sweden)

Abdul Alem Mohammed

2012-01-01

Full Text Available Customer relationship management (CRM has a growing popularity and is becoming one of the hottest academic and practical topics in the business field. In fact, due to the competitive environment, CRM is crucial and has become a niche for firm performance. However, there is limited research that reveals the relationship between CRM dimensions and hotel performance. Therefore this study is an attempt to provide a value conceptual model that explains the theoretical linkages existing between CRM dimensions and hotel performance. This study serves not only to clarify the relationship between CRM dimensions and hotel performance, but also to explain the mediation role of marketing capabilities in this relationship.

Salesforce CRM the definitive admin handbook

CERN Document Server

Goodey, Paul

2013-01-01

A practical guide which will help to discover how to setup and configure the Salesforce CRM application. It offers solutions and practical examples on how to further improve and maintain its functionality with clear systematic instructions. Being highly organized and compact, this book contains detailed instructions with screenshots, diagrams, and tips that clearly describe how you can administer and configure complex Salesforce CRM functionality with absolute ease.This book is for administrators who want to develop and strengthen their Salesforce CRM skills in the areas of configuration and s

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.

Science.gov (United States)

Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

2010-11-01

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ≥8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y.

Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.

Science.gov (United States)

Otto, Robert B D; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T; Bolgiano, Barbara

2015-09-01

The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

International External Quality Assurance for Laboratory Diagnosis of Diphtheria ▿

Science.gov (United States)

Neal, S. E.; Efstratiou, A.

2009-01-01

The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Many laboratories reported problems obtaining Elek reagents or media. Only six centers produced acceptable results for all six specimens. Overall, 21% of identification and 13% of toxigenicity reports were unacceptable. Many centers could not isolate the target organism, and most found difficulties with the specimens that contained Corynebacterium striatum as a commensal contaminant. Nineteen centers generated either false-positive or negative toxigenic results, which may have caused inappropriate medical management. The discrepancies in this diphtheria diagnostics EQA alarmingly reflect the urgent need to improve laboratory performance in diphtheria diagnostics in Europe, standardize feasible and robust microbiological methods, and build awareness among public health authorities. Therefore, DIPNET recommends that regular workshops and EQA distributions for diphtheria diagnostics should be supported and maintained. PMID:19828749

CRM ADOPTION IN A HIGHER EDUCATION INSTITUTION

Directory of Open Access Journals (Sweden)

Guy-Emmanuel Rigo

2016-04-01

Full Text Available More and more organisations, from private to public sectors, are pursuing higher levels of customer satisfaction, loyalty and retention. With this intent, higher education institutions (HEI have adopted CRM – Customer Relationship Management. In order to analyse some of the interesting aspects of this phenomenon n, we conducted an action research in a European Institute. The main research question we answered is “how to adopt a CRM strategy in a Higher Education Institution?” Some of the main findings of this study are (1 even though HEI’s main customer is the student, there are others stakeholders that a CRM project must consider; (2 universities can use their internal resources to implement a CRM project successfully; and (3 using Agile software methodology is an effective way to define clearer, more objective and more assertive technical requirements which result in a CRM software that meet send user’s expectations and organizational strategic goals. These findings can help other HEIs

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.

Factors preceding CRM readiness in small- and medium-sized tourism enterprises

Directory of Open Access Journals (Sweden)

Dinesh Vallabh

2015-07-01

Full Text Available Orientation: Customer relationship management (CRM is important to organisations striving for competitive advantage through building relationships with their customers. Research purpose: This study identified the factors preceding CRM and assessed selected South African small- and medium-sized tourism enterprises’ (SMTEs readiness for CRM. Motivation: CRM is likely to enhance SMTEs’ competitiveness. However, successful adoption and implementation of CRM is unlikely unless the organisation is ready for it. Research design, approach and method: A quantitative research approach and survey questionnaire yielded primary data from 332 respondent organisations selected by systematic sampling. Exploratory factor analysis was used to identify the latent factors preceding CRM readiness. Organisational CRM readiness was assessed based on CRM maturity in terms of data collection, use and sharing throughout the organisation. Main findings: Respondent-organisations performed well on the four factors preceding CRM readiness − business strategy, customer strategy, touch points and competencies, skills and technology and also on data collections and use, but not on data sharing. Practical/Managerial implications: CRM practice is believed to assist organisations in tailoring products and services to customers’ needs, providing customer satisfaction, enhancing customer retention and ultimately improving the organisation’s competitiveness and profitability. CRM might fail if SMTEs do not have CRM-enabling conditions in place and a CRM readiness audit should therefore be performed. Contribution: The study contributes to a largely under-researched area concerning CRM in SMTEs by providing an improved understanding of the factors that will enable SMTEs to engage in CRM activities.

MS CRM 3.0 Dymamics SBS

OpenAIRE

Salmensuu, Jussi

2008-01-01

Tämä opinnäytetyö käsittelee kuinka Microsoftin Customer Relationship Management (CRM) 3.0 SBS toimisi Primanet Oy:lle, joka on pieni IT-ylläpitoa ja - palveluja tarjoava yritys. Opinnäytetyön tavoitteena oli luoda testiympäristö, joka kattaisi CRM - järjestelmän testaamisen seuraavin osa-aluein: toimeksiantojen käsittely, asiakastietokannan luominen ja ylläpitäminen, työjonojen hallinta ja niihin liittyvät toiminnot. Primanet Oy päätti lähteä kokeilemaan CRM -järjestelmän soveltuvuutta, kosk...

Discussion on CRM applications in irradiation processing enterprise

International Nuclear Information System (INIS)

Liu Zhiling; Tang Yuxin; Xiao Rong; Cao Qingsui

2006-01-01

The necessity of customer relationship management (CRM) in irradiation processing enterprises is discussed on the basis of the competition status of irradiation industry and the CRM framework. In the meantime, an idiographic method of how to create the CRM system is put forward aimed at the present situation of irradiation industry. (authors)

Diphtheria in the Dominican Republic: reduction of cases following a large outbreak.

Science.gov (United States)

Garib, Zacarías; Danovaro-Holliday, M Carolina; Tavarez, Yira; Leal, Irene; Pedreira, Cristina

2015-10-01

To describe the most recent outbreak of diphtheria in the Dominican Republic and the disease's occurrence and vaccination coverage in 2004-2013. Clinical data of diphtheria cases that occurred in 2004 and that met the study's case definition were reviewed along with socioeconomic and epidemiological information from the cases' families. Univariate and multivariate analyses were performed to assess risk factors for fatal diphtheria. Routine surveillance and vaccination coverage data are presented. From January 2004-April 2005, a total of 145 diphtheria cases were reported; 80 (66%) of the 122 cases reported in 2004 met the case definition; 26 were fatal (case-fatality rate: 32.5%). Incidence was highest in the group 1-4 years of age at 5.3 per 100 000; 62.5% were male. Of the 80 cases, 61 (76%) where hospitalized in Hospital A, 17 in Hospital B, and 2 in two other hospitals. Earlier onset (first half of 2004), birth order, and tracheotomy were associated with fatal diphtheria (P diphtheria incidence was 4.91 cases/1 million people in 2000-2003, climbed to 8.8 cases per million in 2004-2005, and dropped to 0.38 in 2006-2014; no diphtheria cases have been reported since 2011. DTP3 vaccination coverage ranged from 72%-81% in 2000-2004 and from 81%-89% in 2005-2013. The 2004-2005 diphtheria outbreak in the Dominican Republic resulted in important and avoidable morbidity and mortality. Annual cases declined and no cases have been reported in recent years. Maintaining high vaccination coverage and diligent surveillance are crucial to preventing diphtheria outbreaks and controlling the disease.

Data Analytics in CRM Processes: A Literature Review

Directory of Open Access Journals (Sweden)

Gončarovs Pāvels

2017-12-01

Full Text Available Nowadays, the data scarcity problem has been supplanted by the data deluge problem. Marketers and Customer Relationship Management (CRM specialists have access to rich data on consumer behaviour. The current challenge is effective utilisation of these data in CRM processes and selection of appropriate data analytics techniques. Data analytics techniques help find hidden patterns in data. The present paper explores the characteristics of data analytics as the integrated tool in CRM for sales managers. The paper aims at analysing some of the different analytics methods and tools which can be used for continuous improvement of CRM processes. A systematic literature has been conducted to achieve this goal. The results of the review highlight the most frequently considered CRM processes in the context of data analytics.

Microbe Profile: Corynebacterium diphtheriae - an old foe always ready to seize opportunity.

Science.gov (United States)

Hoskisson, Paul A

2018-02-21

Corynebacterium diphtheriae is a globally important Gram-positive aerobic Actinobacterium capable of causing the toxin-mediated disease, diphtheria. Diphtheria was a major cause of childhood mortality prior to the introduction of the toxoid vaccine, yet it is capable of rapid resurgence following the breakdown of healthcare provision, vaccination or displacement of people. The mechanism and treatment of toxin-mediated disease is well understood, however there are key gaps in our knowledge on the basic biology of C. diphtheriae particularly relating to host colonisation, the nature of asymptomatic carriage, population genomics and host adaptation.

CUSTOMER RELATIONSHIP MANAGEMENT (CRM SUCCESS FACTORS: AN EXPLORATORY STUDY

Directory of Open Access Journals (Sweden)

Mohammed ALAMGIR

2015-02-01

Full Text Available Customer relationship management (CRM can improve organization’s performance through applying customer knowledge and maintaining relationships with customers. Literature on CRM in an integrative fashion is sparse, rather issues are presented in isolation mostly focusing on technology ignoring other extra-organizational issues like social rapport and customer knowledge. Likewise, CRM success is poorly sketched and social rapport as a facilitator of knowledge generation has received little attention in the previous literature. Therefore, the main purpose of this research is to investigate the role of CRM, customer knowledge and social rapport on CRM success. The present study considers the Resource-based view in developing CRM success framework. A Qualitative research approach has been taken in this study where ten customer-service managers of different telecom operators of Bangladesh have been interviewed. To identify the factors along with their associated variables and also to further develop a research model a content analysis technique has been utilized. The results of the interviews identified three factors affecting CRM success. This paper also highlights the research and managerial implications of the model.  

Accessibility Changes within Diphtheria Toxin T Domain upon Membrane Penetration Probed by Hydrogen Exchange and Mass Spectrometry

Czech Academy of Sciences Publication Activity Database

Man, Petr; Montagner, C.; Vitrac, H.; Kavan, Daniel; Pichard, S.; Gillet, D.; Forest, E.; Forge, V.

2011-01-01

Roč. 414, č. 1 (2011), s. 123-134 ISSN 0022-2836 Institutional research plan: CEZ:AV0Z50200510 Keywords : diphtheria toxin * translocation domain * protein/membrane interactions Subject RIV: CE - Biochemistry Impact factor: 4.001, year: 2011

Cloud CRM: State-of-the-Art and Security Challenges

OpenAIRE

Amin Shaqrah

2016-01-01

Security undoubtedly play the main role of cloud CRM deployment, since the agile firms utilized cloud services in the providers infrastructures to perform acute CRM operations. In this paper researcher emphasis on the cloud CRM themes, security threads the most concern. Some aspects of security discussed concern on deployment the cloud CRM like: Access customers’ database and control; secure data transfer over the cloud; trust among the enterprise and cloud service provider; confidentiality, ...

A Case-control Study of Diphtheria in the High Incidence City of Hyderabad, India.

Science.gov (United States)

Allam, Ramesh Reddy; Uthappa, Chengappa Kechamada; Duerst, Rebecca; Sorley, Evan; Udaragudi, Prasada Rao; Kampa, Shankar; Dworkin, Mark S

2016-03-01

India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. We performed a 1:1 case-control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls : There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58-8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18-13.45) remained significantly associated with diphtheria on multivariate analysis. To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered.

Marketingová strategie firmy v oblasti CRM IS

OpenAIRE

Všetička, Martin

2008-01-01

Diplomová práce se zabývá problematikou návrhu marketingové strategie firmy Melzer, spol. s r.o. v oblasti CRM informačních systémů. Rozebírá moderní marketingové koncepce a poukazuje na nutnost zdatného řízení vztahů se zákazníky – CRM. Popisuje důležité faktory spojené s úspěšnou implementací CRM IS. Analyzuje jak tuzemský trh CRM IS, včetně informačního systému QI dodávaného společností Melzer, tak interní CRM klima firmy. V praktické části jsou vyhodnoceny analýzy a sestavena doporučení, ...

Diphtheria in the Dominican Republic: reduction of cases following a large outbreak

Directory of Open Access Journals (Sweden)

Zacarías Garib

Full Text Available OBJECTIVE: To describe the most recent outbreak of diphtheria in the Dominican Republic and the disease's occurrence and vaccination coverage in 2004-2013. METHODS: Clinical data of diphtheria cases that occurred in 2004 and that met the study's case definition were reviewed along with socioeconomic and epidemiological information from the cases' families. Univariate and multivariate analyses were performed to assess risk factors for fatal diphtheria. Routine surveillance and vaccination coverage data are presented. RESULTS: From January 2004-April 2005, a total of 145 diphtheria cases were reported; 80 (66% of the 122 cases reported in 2004 met the case definition; 26 were fatal (case-fatality rate: 32.5%. Incidence was highest in the group 1-4 years of age at 5.3 per 100 000; 62.5% were male. Of the 80 cases, 61 (76% where hospitalized in Hospital A, 17 in Hospital B, and 2 in two other hospitals. Earlier onset (first half of 2004, birth order, and tracheotomy were associated with fatal diphtheria (P < 0.05; cases in Hospital A were also more likely to be fatal (P = 0.066. The average annual diphtheria incidence was 4.91 cases/1 million people in 2000-2003, climbed to 8.8 cases per million in 2004-2005, and dropped to 0.38 in 2006-2014; no diphtheria cases have been reported since 2011. DTP3 vaccination coverage ranged from 72%-81% in 2000-2004 and from 81%-89% in 2005-2013. CONCLUSIONS: The 2004-2005 diphtheria outbreak in the Dominican Republic resulted in important and avoidable morbidity and mortality. Annual cases declined and no cases have been reported in recent years. Maintaining high vaccination coverage and diligent surveillance are crucial to preventing diphtheria outbreaks and controlling the disease.

Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

NARCIS (Netherlands)

Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

2007-01-01

OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

CRM training for nuclear power plant operator

International Nuclear Information System (INIS)

Ohsuga, Y.; Sudou, K.; Sugimura, Z.

2008-01-01

It is training which expects that as for feature of CRM training, trainees observe the image of their own simulator training and become aware of the state of their selves. With this training, it is important for training crew to understand the idea and the skill of the CRM training. The CRM training consists of the lecture in order to understand what it is, the observation of simulator training image and the de-briefing which trainees discuss after their simulator practices. (author)

14 CFR 121.406 - Credit for previous CRM/DRM training.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Credit for previous CRM/DRM training. 121... previous CRM/DRM training. (a) For flightcrew members, the Administrator may credit CRM training received before March 19, 1998 toward all or part of the initial ground CRM training required by § 121.419. (b...

Leukemia-Associated Mutations in Nucleophosmin Alter Recognition by CRM1: Molecular Basis of Aberrant Transport.

Directory of Open Access Journals (Sweden)

Igor Arregi

Full Text Available Nucleophosmin (NPM is a nucleocytoplasmic shuttling protein, normally enriched in nucleoli, that performs several activities related to cell growth. NPM mutations are characteristic of a subtype of acute myeloid leukemia (AML, where mutant NPM seems to play an oncogenic role. AML-associated NPM mutants exhibit altered subcellular traffic, being aberrantly located in the cytoplasm of leukoblasts. Exacerbated export of AML variants of NPM is mediated by the nuclear export receptor CRM1, and due, in part, to a mutationally acquired novel nuclear export signal (NES. To gain insight on the molecular basis of NPM transport in physiological and pathological conditions, we have evaluated the export efficiency of NPM in cells, and present new data indicating that, in normal conditions, wild type NPM is weakly exported by CRM1. On the other hand, we have found that AML-associated NPM mutants efficiently form complexes with CRM1HA (a mutant CRM1 with higher affinity for NESs, and we have quantitatively analyzed CRM1HA interaction with the NES motifs of these mutants, using fluorescence anisotropy and isothermal titration calorimetry. We have observed that the affinity of CRM1HA for these NESs is similar, which may help to explain the transport properties of the mutants. We also describe NPM recognition by the import machinery. Our combined cellular and biophysical studies shed further light on the determinants of NPM traffic, and how it is dramatically altered by AML-related mutations.

An empirical study into the foundations of CRM success

NARCIS (Netherlands)

Peelen, E.; Montfort, van K.; Beltman, R.; Klerkx, A.

2009-01-01

Customer Relationship Management (CRM) has attracted the attention of both marketing practitioners and researchers over the last decade. Significant progress has been made in identifying and researching the components of CRM individually and in the design of a strategic framework. The role of CRM

Diphtheria outbreak in Maranhão, Brazil: microbiological, clinical and epidemiological aspects.

Science.gov (United States)

Santos, L S; Sant'anna, L O; Ramos, J N; Ladeira, E M; Stavracakis-Peixoto, R; Borges, L L G; Santos, C S; Napoleão, F; Camello, T C F; Pereira, G A; Hirata, R; Vieira, V V; Cosme, L M S S; Sabbadini, P S; Mattos-Guaraldi, A L

2015-03-01

We describe microbiological, clinical and epidemiological aspects of a diphtheria outbreak that occurred in Maranhão, Brazil. The majority of the 27 confirmed cases occurred in partially (n = 16) or completely (n = 10) immunized children (n = 26). Clinical signs and characteristic symptoms of diphtheria such as cervical lymphadenopathy and pseudomembrane formation were absent in 48% and 7% of the cases, respectively. Complications such as paralysis of lower limbs were observed. Three cases resulted in death, two of them in completely immunized children. Microbiological analysis identified the isolates as Corynebacterium diphtheriae biovar intermedius with a predominant PFGE type. Most of them were toxigenic and some showed a decrease in penicillin G susceptibility. In conclusion, diphtheria remains endemic in Brazil. Health professionals need to be aware of the possibility of atypical cases of C. diphtheriae infection, including pharyngitis without pseudomembrane formation.

A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

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Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

2015-12-01

The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae. © 2015 John Wiley & Sons Ltd.

Construction and Development of CRM Technology and Industry Chain in China

Science.gov (United States)

Liu, Chunnian; Wang, Yonglong; Pan, Qin

CRM is any application or initiative designed to help an organization optimize interactions with customers, suppliers, or prospects via one or more touch points. CRM has been interpreted and used in different ways by researchers in the various disciplines and researchers have identified a variety of technologies related to CRM. This paper highlights the implementation from the technology level and contributes to some successful factors in CRM application. The development of CRM is not fully developed in China. There are many critical factors that determine the CRM market development. Construction and development of CRM industry chain in China is a valuable research field and the paper provided some suggestions and analyses on it. In future, it requires our joint efforts of many aspects from every walk of life to make sure that CRM industry chain can improve and maturate gradually.

Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.

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Zasada, Aleksandra A; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

2013-11-19

Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

MICROSOFT DYNAMICS CRM IN CISCO IP TELEFONIJA

OpenAIRE

Knez, Margareta

2011-01-01

Microsoft Dynamics CRM je le ena od mnogih rešitev CRM, ki se iz dneva v dan bolj izpopolnjuje in postaja prijaznejša za uporabnike. Na trgu je še mnogo drugih konkurenčnih rešitev programskega orodja CRM. Tako je tudi Ciscova IP-telefonija le ena od mnogih ponudnikov te tehnologije. IP-telefonija bo počasi spodrinila navadno telefonsko linijo, saj je veliko cenejša in ponuja še mnogo dodatnih funkcionalnosti. Le lepa beseda in dobra komunikacija sta potrebni, da stranko zadovoljimo in...

[THE EFFECTIVENESS OF VACCINATION AGAINST DIPHTHERIA IN THE VORONEZH REGION].

Science.gov (United States)

Mamchik, N P; Gabbasova, N V; Sitnik, T N; Borisova, L S

2015-01-01

The purpose of the study was the assessment of the effectiveness of vaccination against diphtheria in the Voronezh region over the epidemic period of 1993-1997 and epidemiological welfare during 2010-2014. of the study: data of the official statistical reporting--forms number 1, 6, the serum level of antitoxic antibodies to diphtheria in 19319 healthy individuals were analyzed with the aid of epidemiological (descriptive and evaluative), immunological and statistical methods. During the epidemic rise of diphtheria (1993-1997) 75% of cases were amounted to the adult population of the Voronezh region, half of them--were not immunized against diphtheria. In 1993 there was begun mass vaccination of adult population, immunization coverage by 1998 reached 95%. According to seromonitoring data the share of seronegatives to diphtheria among cases examined during the period of 1995-2000 accountedfrom 11.9 to 24.9%. During the period of sporadic morbidity (1998-2007 years) among patients the 80% of cases have been vaccinated with an interval from the last inoculation of 3-5 years, which casts doubt on the effectiveness of vaccines. Since 2008 the incidence of diphtheria in the Voronezh region was not recorded. Against the background of 98% coverage of vaccination of the total population, the share of seronegatives for the last 5 years have decreased by 2.5 times and in 2014 reached the required performance. Documented inoculation indices fail to reflect the level of the actual protection against infection. In the conditions of the absence of the morbidity only serological monitoring is an objective criterion of the protectability of the population from infection.

CRM1 and its ribosome export adaptor NMD3 localize to the nucleolus and affect rRNA synthesis.

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Bai, Baoyan; Moore, Henna M; Laiho, Marikki

2013-01-01

CRM1 is an export factor that together with its adaptor NMD3 transports numerous cargo molecules from the nucleus to cytoplasm through the nuclear pore. Previous studies have suggested that CRM1 and NMD3 are detected in the nucleolus. However, their localization with subnucleolar domains or participation in the activities of the nucleolus are unclear. We demonstrate here biochemically and using imaging analyses that CRM1 and NMD3 co-localize with nucleolar marker proteins in the nucleolus. In particular, their nucleolar localization is markedly increased by inhibition of RNA polymerase I (Pol I) transcription by actinomycin D or by silencing Pol I catalytic subunit, RPA194. We show that CRM1 nucleolar localization is dependent on its activity and the expression of NMD3, whereas NMD3 nucleolar localization is independent of CRM1. This suggests that NMD3 provides nucleolar tethering of CRM1. While inhibition of CRM1 by leptomycin B inhibited processing of 28S ribosomal (r) RNA, depletion of NMD3 did not, suggesting that their effects on 28S rRNA processing are distinct. Markedly, depletion of NMD3 and inhibition of CRM1 reduced the rate of pre-47S rRNA synthesis. However, their inactivation did not lead to nucleolar disintegration, a hallmark of Pol I transcription stress, suggesting that they do not directly regulate transcription. These results indicate that CRM1 and NMD3 have complex functions in pathways that couple rRNA synthetic and processing engines and that the rRNA synthesis rate may be adjusted according to proficiency in rRNA processing and export.

Immunochromatographic Strip Test for Rapid Detection of Diphtheria Toxin: Description and Multicenter Evaluation in Areas of Low and High Prevalence of Diphtheria

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Engler, K. H.; Efstratiou, A.; Norn, D.; Kozlov, R. S.; Selga, I.; Glushkevich, T. G.; Tam, M.; Melnikov, V. G.; Mazurova, I. K.; Kim, V. E.; Tseneva, G. Y.; Titov, L. P.; George, R. C.

2002-01-01

An immunochromatographic strip (ICS) test was developed for the detection of diphtheria toxin by using an equine polyclonal antibody as the capture antibody and colloidal gold-labeled monoclonal antibodies specific for fragment A of the diphtheria toxin molecule as the detection antibody. The ICS test has been fully optimized for the detection of toxin from bacterial cultures; the limit of detection was approximately 0.5 ng of diphtheria toxin per ml within 10 min. In a comparative study with 915 pure clinical isolates of Corynebacterium spp., the results of the ICS test were in complete agreement with those of the conventional Elek test. The ICS test was also evaluated for its ability to detect toxigenicity from clinical specimens (throat swabs) in two field studies conducted within areas of the former USSR where diphtheria is epidemic. Eight hundred fifty throat swabs were examined by conventional culture and by use of directly inoculated broth cultures for the ICS test. The results showed 99% concordance (848 of 850 specimens), and the sensitivity and specificity of the ICS test were 98% (95% confidence interval, 91 to 99%) and 99% (95% confidence interval, 99 to 100%), respectively. PMID:11773096

Seroprevalence study of anti diphtheria antibodies in two age-groups of Romanian adults.

Science.gov (United States)

Dragomirescu, Cristiana Cerasella; Coldea, Ileana-Luminiţa; Ilie, Anamaria; Stănescu, Aurora; Ungureanu, Vasilica; Popa, Mircea Ioan

2014-01-01

Diphtheria represents a serious infectious disease with high epidemic potential. It is a vaccine preventable disease (a minimum vaccine coverage of 95% for children of 1 year and 90% in adults could prevent the disease). Diphtheria vaccination is included in the National Immunization Program (NIP). Complete vaccination for children consists in DTaP (diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine) vaccine administration from the age of 2 months until 4 years and dT vaccine (tetanus toxoid and a reduced dose of diphtheria toxoid) at 14 years old. The aim of this paper was to highlight the protection against diphtheria of an age segment of the Romanian adult population (20 to 39 years old) using a seroprevalence study. The Romanian subjects were selected from two age groups: 20-29 years (n = 219) and 30-39 years (n = 229), representative for all counties of Romania. The commercial kit Anti-Diphtheria Toxoid ELISA (IgG) (EUROIMMUN) was used to detect the antibodies of IgG class against diphtheria toxoid in the sera obtained from our subjects. We detected a 56.6% rate of positive sera (> 0.1 IU/ml--protection level) for the 20-29 age group and 31.7% positivity for the 30-39 age group. These data show a low protection level against diphtheria of the Romanian adult population, which decreases with age. The serologic data on preventable vaccine diseases are useful in order to evaluate the success of the immunization programs.

Toxigenic cutaneous diphtheria in a returned traveller.

Science.gov (United States)

Abdul Rahim, Nur R; Koehler, Ann P; Shaw, Doug D; Graham, Caitlin R

2014-12-31

Diphtheria is rarely reported in Australia. A case of cutaneous diphtheria was reported to the South Australian Department for Health and Ageing in April 2013 in an Australian-born 18-year-old female following travel in India. The case presented with a skin ulcer on her toe. Toxigenic Corynebacterium diphtheriae was isolated from a swab of the lesion. The case was treated with antibiotics. The public health response included infection control advice, assessing the case and household contacts for organism carriage and providing antimicrobial chemoprophylaxis to contacts. Although cutaneous diphtheria is not included as part of the Australian communicable disease surveillance case definition, this may be an oversight as international evidence demonstrates that it is a source of organism transmission and can potentially result in outbreaks among susceptible populations. This formed the rationale for the public health response to this particular case. The protocol for the public health management of diphtheria in South Australia has since been revised to include cutaneous lesions caused by the toxigenic strain of the organism as part of the surveillance case definition. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent

CRM-ohjelmiston käyttöönotto tilitoimistossa

OpenAIRE

Kempas, Mervi

2013-01-01

Opinnäytetyössä selvitettiin, mitä Pretax Pohjois-Karjala Oy:n tulisi ottaa huomioon CRM-ohjelmiston käyttöönotossa. Asiakashallinta eli Customer Relationship Management on osa asiakaslähtöistä liiketoimintamallia. Yrityksen liiketoiminta saadaan asiakaslähtöiseksi CRM-ohjelmiston avulla. CRM-ohjelmisto tarjoaa paljon mahdollisuuksia hyödynnettäväksi liiketoiminnassa. Tutkimuskohteena käytettiin Pretax Jyväskylä Oy:tä, jossa CRM-ohjelmisto oli otettu alkuvuodesta 2013 käyttöön. Tutkimustu...

Diphtheria and the Vaccine (Shot) to Prevent It: Information for Parents

Science.gov (United States)

... PARENTS | DISEASES and the VACCINES THAT PREVENT THEM | Diphtheria and the Vaccine (Shot) to Prevent It Last ... April 2017 The best way to protect against diphtheria is by getting the diphther ia-tet anus- ...

Tdap Vaccine (Tetanus, Diphtheria and Pertussis): What You Need to Know

Science.gov (United States)

... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

Use of simplifier scenarios for CRM training

Science.gov (United States)

Weatherly, D.

1984-01-01

Cockpit resource management (CRM) at Metro Airlines is discussed. The process by which the program of CRM training was initiated is mentioned. Management aspects of various flying scenarios are considered. The transfer of training from the classroom to the field is assessed.

A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly

Energy Technology Data Exchange (ETDEWEB)

Kang, Hae Joo; Paterson, Neil G. [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Kim, Chae Un [Cornell University, Ithaca, NY 14853 (United States); Middleditch, Martin [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Chang, Chungyu; Ton-That, Hung [University of Texas–Houston Medical School, Houston, TX 77030 (United States); Baker, Edward N., E-mail: ted.baker@auckland.ac.nz [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand)

2014-05-01

Two crystal structures of the major pilin SpaD from C. diphtheriae have been determined at 1.87 and 2.5 Å resolution. The N-terminal domain is found to contain an isopeptide bond that forms slowly over time in the recombinant protein. Given its structural context, this provides insight into the relationship between internal isopeptide-bond formation and pilus assembly. The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specific sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys–Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys–Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.

Pengembangan Aplikasi E-Crm pada PT Trafoindo Prima Perkasa

Directory of Open Access Journals (Sweden)

Honni Honni

2008-10-01

Full Text Available Various surveys show that the key to corporate success lies not only on the product or service being offered but how far the company’s efforts to satisfy the needs of its customers. Companies have to provide products or services that match customer needs and wants, and then maintain close relations with customers. Customer loyalty will be the key to success, not only in the short term but sustainable competitive advantage. This is because customer loyalty has strategic value for the company. One way that proved effective and successful to meet and satisfy customer needs is through the CRM (Customer Relationship Management. CRM is not new in the business world. Customer Relationship has long been applied by traditional businessmen. Technology in the form of a web can be utilized as a catalyst in improving the quality of CRM. Combining Technology and CRM in a business called E-CRM. E-CRM application development web based on PT Trafoindo Prima Perkasa aims to analyze and design company and customer needs. The research method used in this writing is descriptive survey method primarily associated with the customer. The analysis tool used is the model porter five forces and industry analysis: CPM Matrix, the External Factor Evaluation Matrix (EFE, the Internal Factor Evaluation Matrix (IFE, SWOT Matrix, IE Matrix, SPACE Matrix, and Grand Strategy Matrix to identify alternative strategies can be applied. Alternative strategy is then measured with a Matrix QSP charm, coupled with the approach of Object Oriented Analysis and Design as the basis for the development of E-CRM application based on web. Conclusions obtained are E-CRM applications have produced work as expected.Keywords: development, application of E-CRM, Trafoindo Prima Perkasa

Level of Immunological Protection against Diphtheria in the Population of Dnipropetrovsk Region

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G.O. Revenko

2016-11-01

Full Text Available Background. Diphtheria — an infectious disease, the spread of which is limited by population post-vaccination immunity. In the system of epidemiological surveillance of diphtheria, for objective assessment and prediction of epidemic situation in low intensity of epidemic process of this infection, the serological control of immunity is crucial. The objective: prognosis of epidemic situation in terms of the risk of diphtheria outbreaks in Ukraine by the detection of population post-vaccination immunity against diphtheria in Dnipropetrovsk region and evaluation of the effectiveness of widespread vaccination. Materials and methods. 483 people aged 0 to 78 years were examined in total in 2015 (children — 234, adults — 249 persons. Evaluation of specific immunity against diphtheria was carried on with the following criteria: those with levels of antibodies 0.015–0.06 IU/mL should be considered as relatively protected; 0.1–0.5 IU/ml — with average level of protection; > 1.0 IU/ml — with high level of protection. Protective antibody titer should be considered the concentration of not less than 0.1 IU/ml. Results. It was established that the level of protective immunity against diphtheria was 69.5 %. Reliable level of immunological protection of children was 70.9 %, among adults — 68.3 %. None age group had sufficient threshold level of antitoxic immunity required to stop the transmission of diphtheria pathogen. Percentage of protected persons decreased with increasing age of people (both in children and adults. This situation may create conditions for outbreaks of diphtheria in Dnipropetrovsk region. Conclusions. The presented results indicate the importance of maintaining protective antibody levels through widespread immunization of children, as well as booster vaccination among adolescents and adults that will exclude the category of susceptible layer of the population.

Application of neural networks in CRM systems

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Bojanowska Agnieszka

2017-01-01

Full Text Available The central aim of this study is to investigate how to apply artificial neural networks in Customer Relationship Management (CRM. The paper presents several business applications of neural networks in software systems designed to aid CRM, e.g. in deciding on the profitability of building a relationship with a given customer. Furthermore, a framework for a neural-network based CRM software tool is developed. Building beneficial relationships with customers is generating considerable interest among various businesses, and is often mentioned as one of the crucial objectives of enterprises, next to their key aim: to bring satisfactory profit. There is a growing tendency among businesses to invest in CRM systems, which together with an organisational culture of a company aid managing customer relationships. It is the sheer amount of gathered data as well as the need for constant updating and analysis of this breadth of information that may imply the suitability of neural networks for the application in question. Neural networks exhibit considerably higher computational capabilities than sequential calculations because the solution to a problem is obtained without the need for developing a special algorithm. In the majority of presented CRM applications neural networks constitute and are presented as a managerial decision-taking optimisation tool.

Deletion of a 197-Amino-Acid Region in the N-Terminal Domain of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Piglets.

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Hou, Yixuan; Lin, Chun-Ming; Yokoyama, Masaru; Yount, Boyd L; Marthaler, Douglas; Douglas, Arianna L; Ghimire, Shristi; Qin, Yibin; Baric, Ralph S; Saif, Linda J; Wang, Qiuhong

2017-07-15

We previously isolated a porcine epidemic diarrhea virus (PEDV) strain, PC177, by blind serial passaging of the intestinal contents of a diarrheic piglet in Vero cell culture. Compared with the highly virulent U.S. PEDV strain PC21A, the tissue culture-adapted PC177 (TC-PC177) contains a 197-amino-acid (aa) deletion in the N-terminal domain of the spike (S) protein. We orally inoculated neonatal, conventional suckling piglets with TC-PC177 or PC21A to compare their pathogenicities. Within 7 days postinoculation, TC-PC177 caused mild diarrhea and lower fecal viral RNA shedding, with no mortality, whereas PC21A caused severe clinical signs and 55% mortality. To investigate whether infection with TC-PC177 can induce cross-protection against challenge with a highly virulent PEDV strain, all the surviving piglets were challenged with PC21A at 3 weeks postinoculation. Compared with 100% protection in piglets initially inoculated with PC21A, 88% and 100% TC-PC177- and mock-inoculated piglets had diarrhea following challenge, respectively, indicating incomplete cross-protection. To investigate whether this 197-aa deletion was the determinant for the attenuation of TC-PC177, we generated a mutant (icPC22A-S1Δ197) bearing the 197-aa deletion from an infectious cDNA clone of the highly virulent PEDV PC22A strain (infectious clone PC22A, icPC22A). In neonatal gnotobiotic pigs, the icPC22A-S1Δ197 virus caused mild to moderate diarrhea, lower titers of viral shedding, and no mortality, whereas the icPC22A virus caused severe diarrhea and 100% mortality. Our data indicate that deletion of this 197-aa fragment in the spike protein can attenuate a highly virulent PEDV, but the virus may lose important epitopes for inducing robust protective immunity. IMPORTANCE The emerging, highly virulent PEDV strains have caused substantial economic losses worldwide. However, the virulence determinants are not established. In this study, we found that a 197-aa deletion in the N-terminal region

Exploring the Importance of Knowledge Management for CRM Success

OpenAIRE

Aurora Garrido-Moreno; Antonio Padilla-Meléndez; Ana Rosa Del Águila-Obra

2010-01-01

After reporting a literature review on Customer Relationship Management (CRM) and knowledge management, some important issued arise, in particular related to the lack of success of CRM strategies implementation. The paper contributes to this proposing an integrated model of CRM success taking into account complementary factors such as organizational factors, technology, knowledge management and customer orientation.

A study into the foundations of CRM success

OpenAIRE

Peelen, E.; Beltman, R.; Montfort, van, K.; Klerkx, A.

2006-01-01

Customer Relationship Management has attracted the attention of both marketing practitioners and researchers over the last decade. Despite, or maybe due to, the attention drawn to the subject, a clear agreement on what CRM is and especially how CRM should be developed remains lacking. It is now commonly understood that CRM involves technology, drives Marketing, Sales and Customer Services and is often approached as a business strategy to create value for an organization through the creation o...

Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.

Science.gov (United States)

Ishola, David A; Andrews, Nick; Waight, Pauline; Yung, Chee-Fu; Southern, Jo; Bai, Xilian; Findlow, Helen; Matheson, Mary; England, Anna; Hallis, Bassam; Findlow, Jamie; Borrow, Ray; Miller, Elizabeth

2015-08-01

Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age. Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting. Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events. Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.

The Implementation of CRM at FISC Norfolk Detachment Philadelphia

Science.gov (United States)

2003-06-01

Customer Relationship Management system. [28] If FISC decides to implement a CRM system, the decision will impact the duties of the...distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Customer Relations Management ( CRM ) can be defined in many ways. In...Norfolk Philadelphia Mission Statement. 15. NUMBER OF PAGES 91 14. SUBJECT TERMS Customer Relations Management System, CRM ,

System Dynamics Modelling in CRM: Window Fashions Gallery

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F.T. Yuen

2010-09-01

Full Text Available The core research issue on which this study focuses is customer relationship management (CRM in a designated window fashions firm. A system dynamics-based CRM model is developed to help evaluate the effectiveness of CRM in the firm and examine factors affecting customer satisfaction. Different relationships and linkages between the firm, its employees, and its customers are identified to establish feedback loops that analyze the system over time. The analysis of the CRM model shows that employee satisfaction is the key leverage point affecting customer satisfaction, number of customers, and sales volume of the firm. Product attractiveness and service quality also play an important role in influencing the level of customer satisfaction. On the other hand, advertising and employee training have only minor effects on customer satisfaction.

The use of technology in customer relationship management (CRM

Directory of Open Access Journals (Sweden)

M. Viljoen

2005-12-01

Full Text Available Relationships have increased in importance in the field of business and marketing in the recent past. This importance can be linked to the changing nature of competition and technological developments. In this context, the question that has been posed is how these two factors affect the development of relationships. In the case of competition, relationships can serve as the basis for competitive advantage, while technology serves as the enabler of relationship building. The focus of this article is a theoretical discussion of the technological developments and their application in the CRM context in the implementation of CRM strategy. The article examines the nature of CRM and the components of the various technological CRM systems as well as the specific types of systems that can be used in relationship building, concluding with a discussion of specific technological tools in the CRM context.

Effect of complete rumen modifier (CRM and Calliandra calothyrus on productivity and enteric methane productions of PE dairy goat

Directory of Open Access Journals (Sweden)

Ni Made Suci Sukmawati

2011-10-01

Full Text Available Methanogenesis in the rumen is thought to represent 2-12% loss of energy intake. The energy loss as methane can decrease animal productivity and feed efficiency. In addition, methane is potentially involves in global warming that affects the atmosphere adversely. A research to improve PE dairy goat productivity and reduce enteric methane emission by supplementation of calliandra and complete rumen modifier (CRM was conducted for 6 months. In this experiment 20 PE dairy goats were divided into five blocks according to body weight. The experimental design used was a randomized block design that consisted of four treatments, A. Elephant grass 50% + concentrate 50% (control, B. Elephant grass 40% + concentrate 40% + calliandra 20%, C. Elephant grass 50% + concentrate 48% + CRM 2% and D. Elephant grass 40% + concentrate 38% + calliandra 20% + CRM 2%. Data were analyzed statistically using ANOVA and Duncan test. The result showed that calliandra and CRM did not affect nutrient consumption, except that protein consumption increased (P < 0.05 in calliandra treatments (B and D. Nutrient digestibility increased in CRM (C treatment, while other treatments did not differ from control. CRM also increased total bacteria (36.84%, milk production (67.21%, milk fat (25.0%, and reduced enteric methane production (65.71%. The improvement of milk production in CRM treatment (C was followed by better feed efficiency than other treatments. In conclusion, CRM was more effective than calliandra in improving milk production of PE dairy goats and reduced enteric methane emission, but its effectivity was reduced in combination with calliandra.

Resurgence of diphtheria in rural areas of North Karnataka, India.

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Parande, Mahantesh V; Roy, Subarna; Mantur, B G; Parande, Aisha M; Shinde, Rupali S

2017-01-01

A diphtheria outbreak was identified from Vijayapura (formerly Bijapur) district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP) in North Karnataka since then. A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Throat swabs from 432 suspected cases of diphtheria during 2012-2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB) was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Thirty-eight (8.79%) out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26%) were between 1 and 5 years of age, 14 (36.84%) were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched 'Mission Indradhanush' programme in strengthening Universal Immunisation Programme (UIP).

Structural perturbation of diphtheria toxoid upon adsorption to aluminium hydroxide adjuvant

NARCIS (Netherlands)

Regnier, M.; Metz, B.; Tilstra, W.; Hendriksen, C.; Jiskoot, W.; Norde, W.; Kersten, G.

2012-01-01

Aluminium-containing adjuvants are often used to enhance the potency of vaccines. In the present work we studied whether adsorption of diphtheria toxoid to colloidal aluminium hydroxide induces conformational changes of the antigen. Diphtheria toxoid has a high affinity for the aluminium hydroxide

Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

Science.gov (United States)

Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

2014-06-30

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

Science.gov (United States)

2011-05-13

... Factor-Diphtheria Toxoid Conjugate AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. [[Page... veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid conjugate by subcutaneous... provides for the veterinary prescription use of IMPROVEST (gonadotropin releasing factor-diphtheria toxoid...

Respiratory diphtheria in an asylum seeker from Afghanistan arriving to Finland via Sweden, December 2015.

Science.gov (United States)

Sane, Jussi; Sorvari, Tiina; Widerström, Micael; Kauma, Heikki; Kaukoniemi, Ulla; Tarkka, Eveliina; Puumalainen, Taneli; Kuusi, Markku; Salminen, Mika; Lyytikäinen, Outi

2016-01-01

In December 2015, an asylum seeker originating from Afghanistan was diagnosed with respiratory diphtheria in Finland. He arrived in Finland from Sweden where he had already been clinically suspected and tested for diphtheria. Corynebacterium diphtheriae was confirmed in Sweden and shown to be genotypically and phenotypically toxigenic. The event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheria antitoxin availability.

POTENSI GEN dtx DAN dtxR SEBAGAI MARKER UNTUK DETEKSI DAN PEMERIKSAAN TOKSIGENISITAS Corynebacterium diphtheriae

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Sunarno Sunarno

2013-05-01

Full Text Available Abstract.   Corynebacterium diphtheriae is the causative agent of diphtheria. The main virulence determinant of the bacteria is diphtheria toxin, the cause of the systemic complication seen with diphtheria. Production of diphtheria toxin by toxigenic strain encoded by dtx/tox gene and repressed by dtxR gene. Gold standard for bacterial toxigenicity test carried out by conventional methods (Elek test, Guinea pig and vero cell cytotoxicity. However, Elek test have variety result, time consume and problem of the reagent availability. On the other hand, the animal (Guinea pig testing was opposed by many animal lovers and the vero cell cytotoxicity test require high cost. The study purposed to evaluate the using of dtx and dtxR genes as a detection marker of C.diphtheriae and bacterial toxigenicity test simultaneusly by Multiplex PCR. The study examined 44 bacterial and fungal isolates, included 22 C.diphtheriae (4 reference strains and 18 clinical isolates, 5 other specieses of Corynebacterium  (reference strains and 17 non-Corynebacterium (10 reference strains and 7 stock cultures . All of sample were examined by Multiplex PCR for 2 primer pairs targeted dtx and dtxR genes. The study showed that the Multiplex PCR for dtx and dtxR as target genes able to detect all of sample correctly thus concluded that dtx and dtxR genes could be used as a marker for alternative detection and toxigenicity test of C.diphtheriae by Multiplex PCR rapidly and accuratelly. Key words: Corynebacterium diphtheriae, dtx, dan dtxR Abstrak. Corynebacterium diphtheriae merupakan agen penyebab penyakit difteri.. Faktor virulensi utama  C. diphtheriae adalah toksigenisitas (kemampuan memproduksi toksin bakteri toxin. Produksi toksin diatur seperangkat gen yang disebut gen tox/dtx dan diregulasi oleh gen dtxR. Gold standard untuk pemeriksaan toksigenisitas C.diphtheriae adalah dengan metode konvensional (Elek test, Guinea pig dan vero cell cytotoxigenicity,namun  Elek test

CRM Systems with Social Networking Capabilities: The Value of Incorporating a CRM 2.0 System in Sales/Marketing Education

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Wang, Xin; Dugan, Riley; Sojka, Jane

2013-01-01

Implementation of a customer relationship management (CRM) 2.0 system can provide both a valuable pedagogical tool and a needed skill set in a marketing and sales curriculum. A CRM 2.0 system incorporated in the sales and marketing curriculum can help manage relationships between students, practitioners, and faculty while teaching students a…

CRM Implementation in Nonprofits: An Analysis of the Success Factors

Science.gov (United States)

Grattan, Kelly E.

2012-01-01

Constituent Relationship Management ("CRM") is defined as an organization-wide strategy designed to enable the organization to better manage, track and steward its constituents. CRM has benefited for-profit enterprises for nearly three decades. In the nonprofit sector, the concept of CRM is fairly new. Despite the increase in CRM…

DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

Science.gov (United States)

... STATEMENT DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are ... www. immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by ...

Social CRM Adoption and its Impact on Performance Outcomes: a Literature Review

Directory of Open Access Journals (Sweden)

Marolt Marjeta

2015-12-01

Full Text Available Background and Purpose: Social customer relationship management (social CRM is an emerging concept that integrates traditional CRM and social media in order to provide benefits for organizations and customers. Despite the benefits that social CRM can bring, many organizations are still at the early stage of adoption. To move beyond social marketing and to exploit opportunities offered by sales and customer service, organizations need to be aware of factors that drive social CRM adoption and different implications of social CRM adoption for performance outcomes. This paper aims to provide a review of scholarly literature on social CRM adoption with the focus on factors and performance outcomes.

Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

Science.gov (United States)

... is taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): ... vis-statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: ...

The Usage of CRM-Systems in the Activities of Franchising Retail Trade Networks

OpenAIRE

Kochubei Dmytro V.; Grygorenko Tetyana M.

2017-01-01

The article considers the main aspects of the CRM-systems usage in the management of relationships in franchise retail trade networks (FRTN). The essence of concepts of «CRM-strategy» and «CRM-system» has been disclosed, their differences have been defined. The basic directions of implementing the CRM-strategy of management of interaction of franchisor and franchisees, and also components of information support of CRM-systems have been defined. A methodology of introduction of CRM-strategy in...

External quality assessments for microbiologic diagnosis of diphtheria in Europe.

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Both, Leonard; Neal, Shona; De Zoysa, Aruni; Mann, Ginder; Czumbel, Ida; Efstratiou, Androulla

2014-12-01

The European Diphtheria Surveillance Network (EDSN) ensures the reliable epidemiological and microbiologic assessment of disease prevalence in the European Union. Here, we describe a survey of current diagnostic techniques for diphtheria surveillance conducted across the European Union and report the results from three external quality assessment (EQA) schemes performed between 2010 and 2014. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children

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Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-01-01

Abstract Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children. Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule. Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection. Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies. The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The

Effectiveness of CRM in HAAGA-HELIA

OpenAIRE

Hirvonen, Hanna-Reetta; Ify, Kingsley John

2011-01-01

This was a project organized and supervised by HAAGA-HELIA University of Applied Sciences to enhance the international students’ employment rate through work pair model (an international student and Finnish student working together), and the project was done by two students from different majors. The thesis task was to revive, create and strengthen the use of customer relationship management (CRM) in HAAGA-HELIA. The main aim of the project was to examine the effectiveness of CRM in HAAGA-HEL...

Putting market-facing technology to work: Organizational drivers of CRM performance

NARCIS (Netherlands)

Saini, A.; Grewall, R.; Johnson, J.L.

2010-01-01

A large proportion of firms that adopt customer relationship management (CRM) technology find it challenging to integrate CRM technology into their core marketing processes and utilize CRM strategically to appreciably improve their performance. The authors conceptualize a model to understand the

Changes in proHB-EGF expression after functional activation of the immune system cells

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T. O. Chudina

2017-12-01

Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

International Nuclear Information System (INIS)

Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

2005-01-01

Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

The Cellular Distribution of RanGAP1 Is Regulated by CRM1-Mediated Nuclear Export in Mammalian Cells.

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Keith Cha

Full Text Available The Ran GTPase activating protein RanGAP1 plays an essential role in nuclear transport by stimulating RanGTP hydrolysis in the cytoplasmic compartment. In mammalian cells, unmodified RanGAP1 is predominantly cytoplasmic, whereas modification by small ubiquitin-related modifier protein (SUMO targets RanGAP1 to the cytoplasmic filaments of nuclear pore complex (NPC. Although RanGAP1 contains nine putative nuclear export signals and a nuclear localization signal, little is known if RanGAP1 shuttles between the nuclear and cytoplasmic compartments and how its primary localization in the cytoplasm and at the NPC is regulated. Here we show that inhibition of CRM1-mediated nuclear export using RNAi-knockdown of CRM1 and inactivation of CRM1 by leptomycin B (LMB results in nuclear accumulation of RanGAP1. LMB treatment induced a more robust redistribution of RanGAP1 from the cytoplasm to the nucleoplasm compared to CRM1 RNAi and also uniquely triggered a decrease or loss of RanGAP1 localization at the NPC, suggesting that LMB treatment is more effective in inhibiting CRM1-mediated nuclear export of RanGAP1. Our time-course analysis of LMB treatment reveals that the NPC-associated RanGAP1 is much more slowly redistributed to the nucleoplasm than the cytoplasmic RanGAP1. Furthermore, LMB-induced nuclear accumulation of RanGAP1 is positively correlated with an increase in levels of SUMO-modified RanGAP1, suggesting that SUMOylation of RanGAP1 may mainly take place in the nucleoplasm. Lastly, we demonstrate that the nuclear localization signal at the C-terminus of RanGAP1 is required for its nuclear accumulation in cells treated with LMB. Taken together, our results elucidate that RanGAP1 is actively transported between the nuclear and cytoplasmic compartments, and that the cytoplasmic and NPC localization of RanGAP1 is dependent on CRM1-mediated nuclear export.

A study on how CRM influences marketing planning in telecommunication industry

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Naser Azad

2013-08-01

Full Text Available Customer relationship management (CRM plays an important role on marketing planning. In this paper, we re-examine the effect of having efficient CRM on efficiency of a telecommunication company. The proposed study considers three hypotheses. The first hypothesis examines whether implementation of CRM could improve customer’s perception in terms of customer retention, satisfaction, loyalty and awareness. The second hypothesis examines whether implementation of CRM influences on market performance in terms of reduction on customer complaints, quality improvement, improving customer perception, access to services and increase in market share. Finally, the third hypothesis considers the effect of CRM on financial figures in terms of sales growth, profit growth, earnings per share and productivity. The results of our survey have confirmed the first hypothesis and rejected the third hypothesis. In other words, while CRM improves customer perception it does not influence financial figures in most cases (P<0.01.

Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

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Andrea Cerutti

Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS, but no nuclear export signal (NES has yet been identified.We show here that the aa(109-133 region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126 in the identified NES or in the sequence encoding the mature core aa(1-173 significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

Identification of a functional, CRM-1-dependent nuclear export signal in hepatitis C virus core protein.

Science.gov (United States)

Cerutti, Andrea; Maillard, Patrick; Minisini, Rosalba; Vidalain, Pierre-Olivier; Roohvand, Farzin; Pecheur, Eve-Isabelle; Pirisi, Mario; Budkowska, Agata

2011-01-01

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. HCV core protein is involved in nucleocapsid formation, but it also interacts with multiple cytoplasmic and nuclear molecules and plays a crucial role in the development of liver disease and hepatocarcinogenesis. The core protein is found mostly in the cytoplasm during HCV infection, but also in the nucleus in patients with hepatocarcinoma and in core-transgenic mice. HCV core contains nuclear localization signals (NLS), but no nuclear export signal (NES) has yet been identified.We show here that the aa(109-133) region directs the translocation of core from the nucleus to the cytoplasm by the CRM-1-mediated nuclear export pathway. Mutagenesis of the three hydrophobic residues (L119, I123 and L126) in the identified NES or in the sequence encoding the mature core aa(1-173) significantly enhanced the nuclear localisation of the corresponding proteins in transfected Huh7 cells. Both the NES and the adjacent hydrophobic sequence in domain II of core were required to maintain the core protein or its fragments in the cytoplasmic compartment. Electron microscopy studies of the JFH1 replication model demonstrated that core was translocated into the nucleus a few minutes after the virus entered the cell. The blockade of nucleocytoplasmic export by leptomycin B treatment early in infection led to the detection of core protein in the nucleus by confocal microscopy and coincided with a decrease in virus replication.Our data suggest that the functional NLS and NES direct HCV core protein shuttling between the cytoplasmic and nuclear compartments, with at least some core protein transported to the nucleus. These new properties of HCV core may be essential for virus multiplication and interaction with nuclear molecules, influence cell signaling and the pathogenesis of HCV infection.

[Diphtheria in the military forces: lessons and current status of prophylaxis, prospects of epidemiological control process].

Science.gov (United States)

Belov, A B; Ogarkov, P I

2014-01-01

We analyzed the epidemiological situation of diphtheria in the world and in Russia and experience of mass vaccination of military personnel and civil population with diphtheria toxoid for the last 50 years. Early diagnosis of diphtheria in military personnel has a prognostic value. Authors described the peculiarities of epidemiological process of diphtheria in military personnel in 80-90 years of 20th century and organizational aspects of mass vaccination with diphtheria toxoid. Authors analyzed current problems of epidemiology and prophylaxis of diphtheria in military personnel and civil population and possible developments. According to long-term prognosis authors mentioned the increase of morbidity and came to conclusion that it is necessary enhance the epidemiological surveillance. Authors presented prospect ways of improvement of vaccination and rational approaches to immunization of military personnel under positive long-term epidemiological situation.

Resurgence of diphtheria in rural areas of North Karnataka, India

Directory of Open Access Journals (Sweden)

Mahantesh V Parande

2017-01-01

Full Text Available Background: A diphtheria outbreak was identified from Vijayapura (formerly Bijapur district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP in North Karnataka since then. Objectives: A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Materials and Methods: Throat swabs from 432 suspected cases of diphtheria during 2012–2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Results: Thirty-eight (8.79% out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26% were between 1 and 5 years of age, 14 (36.84% were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. Conclusion and Discussion: Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched 'Mission Indradhanush' programme in strengthening Universal Immunisation Programme

NESDIS OSPO Data Access Policy and CRM

Science.gov (United States)

Seybold, M. G.; Donoho, N. A.; McNamara, D.; Paquette, J.; Renkevens, T.

2012-12-01

The Office of Satellite and Product Operations (OSPO) is the NESDIS office responsible for satellite operations, product generation, and product distribution. Access to and distribution of OSPO data was formally established in a Data Access Policy dated February, 2011. An extension of the data access policy is the OSPO Customer Relationship Management (CRM) Database, which has been in development since 2008 and is reaching a critical level of maturity. This presentation will provide a summary of the data access policy and standard operating procedure (SOP) for handling data access requests. The tangential CRM database will be highlighted including the incident tracking system, reporting and notification capabilities, and the first comprehensive portfolio of NESDIS satellites, instruments, servers, applications, products, user organizations, and user contacts. Select examples of CRM data exploitation will show how OSPO is utilizing the CRM database to more closely satisfy the user community's satellite data needs with new product promotions, as well as new data and imagery distribution methods in OSPO's Environmental Satellite Processing Center (ESPC). In addition, user services and outreach initiatives from the Satellite Products and Services Division will be highlighted.

Team training in the skies: does crew resource management (CRM) training work?

Science.gov (United States)

Salas, E; Burke, C S; Bowers, C A; Wilson, K A

2001-01-01

The aviation community has invested great amounts of money and effort into crew resource management (CRM) training. Using D. L. Kirkpatrick's (1976) framework for evaluating training, we reviewed 58 published accounts of CRM training to determine its effectiveness within aviation. Results indicated that CRM training generally produced positive reactions, enhanced learning, and promoted desired behavioral changes. However, we cannot ascertain whether CRM has an effect on an organization's bottom line (i.e., safety). We discuss the state of the literature with regard to evaluation of CRM training programs and, as a result, call for the need to conduct systematic, multilevel evaluation efforts that will show the true effectiveness of CRM training. As many evaluations do not collect data across levels (as suggested by D. L. Kirkpatrick, 1976, and by G. M. Alliger, S. I. Tannenbaum, W. Bennett, Jr., & H. Traver, 1997), the impact of CRM cannot be truly determined; thus more and better evaluations are needed and should be demanded.

crm_v3.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v4.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v8.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v9.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v10.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v5.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v7.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v2.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v1.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

crm_v6.grd

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — NGDC's 3 arc-second U.S. Coastal Relief Model (CRM) provides the first comprehensive view of the U.S. coastal zone, integrating offshore bathymetry with land...

The B-cell response to a primary and booster course of MenACWY-CRM₁₉₇ vaccine administered at 2, 4 and 12 months of age.

Science.gov (United States)

Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Clutterbuck, Elizabeth A; Ohene-Kena, Brigitte; Klinger, Chaam L; Odrljin, Tatjana; Pollard, Andrew J

2013-05-07

A quadrivalent meningococcal vaccine conjugated to CRM197 (MenACWY-CRM197) is immunogenic in young infants. We assessed the memory B-cell and antibody responses after a primary and booster course of MenACWY-CRM197 in children. At 5 months of age, following primary immunisation, serogroup-specific memory B-cells were detectable in fewer than 25% of children, although protective antibody titres (hSBA ≥ 4) were detectable in 69% of children against serogroup A and more than 95% against the other serogroups. At 12 months, before booster immunisation the percentages with hSBA ≥ 4 were 5% for serogroup A, and between 44 and 70% for the other serogroups. One month after booster immunisation with MenACWY-CRM197 over 50% of children had detectable memory B-cells, and 91% had hSBA ≥ 4 against serogroup A and more than 99% against the other serogroups. These data show that few antigen-specific anticapsular memory B-cells can be detected after two-doses priming with MenACWY-CRM197. For MenC and CRM197, the antigens with the highest number of B-cells at 5 months, there was a definite (p ≤0 .02) but weak correlation with antibody persistence at 12 months. Although previous studies suggest that measuring memory B-cell responses after priming immunisations in infancy can be used to predict antibody persistence and memory responses, this may not be suitable for all antigens in young children. Copyright © 2013 Elsevier Ltd. All rights reserved.

Seroepidemiology of diphtheria and tetanus among children and young adults in Tajikistan: nationwide population-based survey, 2010.

Science.gov (United States)

Khetsuriani, Nino; Zakikhany, Katherina; Jabirov, Shamsiddin; Saparova, Nargis; Ursu, Pavel; Wannemuehler, Kathleen; Wassilak, Steve; Efstratiou, Androulla; Martin, Rebecca

2013-10-01

Tajikistan had a major diphtheria outbreak (≈ 10,000 cases) in the 1990 s, which was controlled after nationwide immunization campaigns with diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases have been reported. However, in coverage surveys conducted in 2000 and 2005, diphtheria-tetanus-pertussis vaccine coverage was lower than administratively reported estimates raising concerns about potential immunity gaps. To further assess population immunity to diphtheria in Tajikistan, diphtheria antibody testing was included in a large-scale nationwide serosurvey for vaccine-preventable diseases conducted in connection with a poliomyelitis outbreak in 2010. In addition, the serosurvey provided an opportunity to assess population immunity to tetanus. Residents of all regions of Tajikistan aged 1-24 years were included in the serosurvey implemented during September-October 2010. Participants were selected through stratified cluster sampling. Specimens were tested for diphtheria antibodies using a Vero cell neutralization assay and for tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations ≥ 0.1 IU/mL were considered seropositive. Overall, 51.4% (95% CI, 47.1%-55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%-82.5%) were seropositive for tetanus. The lowest percentages of seropositivity for both diseases were observed among persons aged 10-19 years: diphtheria seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3% (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%). Population immunity for diphtheria in Tajikistan is low, particularly among 10-19 year-olds. Population immunity to tetanus is generally higher than for diphtheria, but is suboptimal among 10-19 year-olds. These findings highlight the need to improve routine immunization service delivery, and support a

Tetanus and diphtheria immunity in refugees in Europe in 2015.

Science.gov (United States)

Jablonka, Alexandra; Behrens, Georg M N; Stange, Marcus; Dopfer, Christian; Grote, Ulrike; Hansen, Gesine; Schmidt, Reinhold Ernst; Happle, Christine

2017-04-01

Current political crises in the Middle East and economic discrepancies led millions of people to leave their home countries and to flee to Western Europe. This development raises unexpected challenges for receiving health care systems. Although pan-European initiatives strive for updated and optimized vaccination strategies, little data on immunity against vaccine-preventable diseases in the current refugee population exist. We quantified serum IgG against tetanus and diphtheria (TD) in n = 678 refugees currently seeking shelter in six German refugee centers. Reflecting current migration statistics in Europe, the median age within the cohort was 26 years, with only 23.9 % of female subjects. Insufficient IgG levels without long-term protection against tetanus were found in 56.3 % of all refugees. 76.1 % of refugees had no long-term protection against diphtheria. 47.7 % of subjects needed immediate vaccination against tetanus, and 47.7 % against diphtheria. For both diseases, an age-dependent decline in protective immunity occurred. We observed a considerably low rate of tetanus-protected refugees, and the frequency of diphtheria-immune refugees was far from sufficient to provide herd immunity. These findings strongly support recent intentions to implement and enforce stringent guidelines for refugee vaccination in the current crisis.

Prerequisites and Effects of CRM Systems Use in Poland

Science.gov (United States)

Buchnowska, Dorota; Wrycza, Stanislaw

It has been demonstrated in numerous studies that CRM implementation is beneficial in terms of higher revenues and lower costs (Aberdeen Group 2004: Thompson 2004) However, many potential CRM users in Poland are discouraged by high implementation costs and a high proportion of abortive implementations. Managers complain about lack of best practices that might convince them about the advisability of their strategy. The high failure rate in CRM implementation (Hellweg 2002) is often the result of the fact that the firms responsible for implementation lack an adequate and proven methodology.

Implementing SaaS Solution for CRM

Directory of Open Access Journals (Sweden)

Adriana LIMBASAN

2011-01-01

Full Text Available Greatest innovations in virtualization and distributed computing have accelerated interest in cloud computing (IaaS, PaaS, SaaS, aso. This paper presents the SaaS prototype for Customer Relationship Management of a real estate company. Starting from several approaches of e-marketing and SaaS features and architectures, we adopted a model for a CRM solution using SaaS Level 2 architecture and distributed database. Based on the system objective, functionality, we developed a modular solution for solve CRM and e-marketing targets in real estate companies.

Crew Resource Management (CRM video storytelling project: a team-based learning activity

Directory of Open Access Journals (Sweden)

Ma, Maggie Jiao

2011-01-01

Full Text Available This Crew Resource Management (CRM video storytelling project asks students to work in a team (4-5 people per team to create (write and produce a video story. The story should demonstrate lacking and ill practices of CRM knowledge and skills, or positive skills used to create a successful scenario in aviation (e. g. , flight training, commercial aviation, airport management. The activity is composed of two parts: (1 creating a video story of CRM in aviation, and (2 delivering a group presentation. Each tem creates a 5-8 minute long video clip of its story. The story must be originally created by the team to educate pilot and/or aviation management students on good practices of CRM in aviation. Accidents and incidents can be used as a reference to inspire ideas. However, this project is not to re-create any previous CRM accidents/incidents. The video story needs to be self-contained and address two or more aspects of CRM specified in the Federal Aviation Administration’s Advisory Circular 120-51. The presentation must include the use of PowerPoint or similar software and additional multimedia visual aids. The presentation itself will last no more than 17 minutes in length; including the actual video story (each group has additional 3 minutes to set up prior to the presentation. During the presentation following the video each team will discuss the CRM problems (or invite audience to identify CRM problems and explain what CRM practices were performed, and should have been performed. This presentation also should describe how each team worked together in order to complete this project (i. e. , good and bad CRM practiced

Transverse expansion in 197 Au + 197 Au collisions at RHIC

International Nuclear Information System (INIS)

Cheng, Y.; Liu, F.; Liu, K.; Schweda, K.; Xu, N.

2003-01-01

Using the RQMD model, transverse momentum distributions and particle ratios are studied for 197 Au + 197 Au collisions at √s NN = 200 GeV. In particular, they present results on the mean transverse momentum of charged pions, charged kaons, protons and anti-protons and compare with experimental measurements. They discuss an approach to study early partonic collectivity in high energy nuclear collisions

Access to diphtheria antitoxin for therapy and diagnostics.

Science.gov (United States)

Both, L; White, J; Mandal, S; Efstratiou, A

2014-06-19

The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore--besides efforts to improve the current supply of DAT--accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.

Paths to continuous improvement of a CRM strategy

Directory of Open Access Journals (Sweden)

Lluís G. Renart

2008-07-01

Full Text Available The concept of relationship marketing has led to a paradigm change in marketing. Over the last few decades, numerous studies have analyzed the impact of customer relationship management (CRM programs on customer satisfaction and loyalty. Quite a few CRM programs have been found to have little or no impact. Having already published several articles and cases on the subject, in this paper we set out to answer the following question: assuming a company already has a reasonably successful CRM strategy in place, how can it continuously adapt and improve that strategy? Our recommendation is that such companies implement a continuous improvement process at four different but complementary levels: first, review and reinforce the company’s mission, culture and values; second, reconsider and, if necessary, redesign the CRM strategy; third, manage the various relationship-building activities more effectively; and lastly, review and, if necessary, improve the quality of material and human resources, program execution and process governance. A systematic review of these four levels or “paths” of improvement should help generate and maintain high quality relationships over time.

Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

Science.gov (United States)

Both, Leonard; Collins, Sarah; de Zoysa, Aruni; White, Joanne; Mandal, Sema

2014-01-01

Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required. PMID:25502525

Social CRM adoption and its impact on performance outcomes: a literature review:

OpenAIRE

Marolt, Marjeta; Pucihar, Andreja; Zimmermann, Hans Dieter

2015-01-01

Background and Purpose: Social customer relationship management (social CRM) is an emerging concept that integrates traditional CRM and social media in order to provide benefits for organizations and customers. Despite the benefits that social CRM can bring, many organizations are still at the early stage of adoption. To move beyond social marketing and to exploit opportunities offered by sales and customer service, organizations need to be aware of factors that drive social CRM adoption and ...

The dynamics of CRM attitude change: Attitude stability

Science.gov (United States)

Gregorich, Steven E.

1993-01-01

Special training seminars in cockpit resource management (CRM) are designed to enhance crew effectiveness in multicrew air-transport cockpits. In terms of CRM, crew effectiveness is defined by teamwork rather than technical proficiency. These seminars are designed to promote factual learning, alter aviator attitudes, and motivate aviators to make use of what they have learned. However, measures of attitude change resulting from CRM seminars have been the most common seminar evaluation technique. The current investigation explores a broader range of attitude change parameters with specific emphasis on the stability of change between recurrent visits to the training center. This allows for a comparison of training program strengths in terms of seminar ability to effect lasting change.

The Usage of CRM-Systems in the Activities of Franchising Retail Trade Networks

Directory of Open Access Journals (Sweden)

Kochubei Dmytro V.

2017-11-01

Full Text Available The article considers the main aspects of the CRM-systems usage in the management of relationships in franchise retail trade networks (FRTN. The essence of concepts of «CRM-strategy» and «CRM-system» has been disclosed, their differences have been defined. The basic directions of implementing the CRM-strategy of management of interaction of franchisor and franchisees, and also components of information support of CRM-systems have been defined. A methodology of introduction of CRM-strategy in activity of FRTN has been suggested; a model of management of FRTN on the basis of CRM-system has been developed; the main advantages and disadvantages of the CRM-systems usage in the activities of FRTN have been defined. The scientific and practical benefit of the suggested management model provides franchisor to carefully analyze all business processes, make managerial decisions in order to improve cooperation and support of franchisees, increase sales volumes, increase profitability, maintain franchisee loyalty, and create competitive advantages for the entire franchise network.

Genetic relationships of Corynebacterium diphtheriae strains isolated from a diphtheria case and carriers by restriction fragment length polymorphism of rRNA genes Relação genética de cepas de Corynebacterium diphtheriae isoladas de caso e seus contatos por RLFP de rRNA gene

Directory of Open Access Journals (Sweden)

Claudio Tavares Sacchi

1995-08-01

Full Text Available In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells. The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain, that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.No presente estudo, nós reportamos os resultados de uma análise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma criança de 9 anos com difteria e seus 5 contatos. Análise quantitativa por RFLP de rRNA foi usada para determinar a relação destas 7 cepas de C. diphtheriae fornecendo dados de interesse epidemiológico. Nós também testamos estas cepas para toxicidade in vitro usando método de difusão de Elek e in vivo usando método de cultura celular com células VERO. Os resultados de hibridização revelaram que as 5 cepas de C. diphtheriae isoladas dos contatos e uma isolada do caso (cepa isolada

A case of pharyngeal diphtheria in Germany, June 2015.

Science.gov (United States)

Berger, A; Meinel, D M; Schaffer, A; Ziegler, R; Pitteroff, J; Konrad, R; Sing, Andreas

2016-10-01

In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics. A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection. No secondary cases were found and the patient completely recovered.

ORIGINAL ARTICLE DIPHTHERIA MORTALITY IN NIGERIA: THE ...

African Journals Online (AJOL)

Dr Oboro VO

AFRICAN JOURNAL OF CLINICAL AND EXPERIMENTAL MICROBIOLOGY MAY 2011 ... RESULTS: Nine cases of diphtheria were seen and three mortalities were recorded giving a mortality rate ... tissue edema and airway obstruction by the.

Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

Science.gov (United States)

Smith, Heidi L; Cheslock, Peter; Leney, Mark; Barton, Bruce; Molrine, Deborah C

2016-08-17

Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

Dose-escalation designs in oncology: ADEPT and the CRM.

Science.gov (United States)

Shu, Jianfen; O'Quigley, John

2008-11-20

The ADEPT software package is not a statistical method in its own right as implied by Gerke and Siedentop (Statist. Med. 2008; DOI: 10.1002/sim.3037). ADEPT implements two-parameter CRM models as described in O'Quigley et al. (Biometrics 1990; 46(1):33-48). All of the basic ideas (use of a two-parameter logistic model, use of a two-dimensional prior for the unknown slope and intercept parameters, sequential estimation and subsequent patient allocation based on minimization of some loss function, flexibility to use cohorts instead of one by one inclusion) are strictly identical. The only, and quite trivial, difference arises in the setting of the prior. O'Quigley et al. (Biometrics 1990; 46(1):33-48) used priors having an analytic expression whereas Whitehead and Brunier (Statist. Med. 1995; 14:33-48) use pseudo-data to play the role of the prior. The question of interest is whether two-parameter CRM works as well, or better, than the one-parameter CRM recommended in O'Quigley et al. (Biometrics 1990; 46(1):33-48). Gerke and Siedentop argue that it does. The published literature suggests otherwise. The conclusions of Gerke and Siedentop stem from three highly particular, and somewhat contrived, situations. Unlike one-parameter CRM (Biometrika 1996; 83:395-405; J. Statist. Plann. Inference 2006; 136:1765-1780; Biometrika 2005; 92:863-873), no statistical properties appear to have been studied for two-parameter CRM. In particular, for two-parameter CRM, the parameter estimates are inconsistent. This ought to be a source of major concern to those proposing its use. Worse still, for finite samples the behavior of estimates can be quite wild despite having incorporated the kind of dampening priors discussed by Gerke and Siedentop. An example in which we illustrate this behavior describes a single patient included at level 1 of 6 levels and experiencing a dose limiting toxicity. The subsequent recommendation is to experiment at level 6! Such problematic behavior is not

CRISPR/Cas9 and active genetics-based trans-species replacement of the endogenous Drosophila kni-L2 CRM reveals unexpected complexity.

Science.gov (United States)

Xu, Xiang-Ru Shannon; Gantz, Valentino Matteo; Siomava, Natalia; Bier, Ethan

2017-12-23

The knirps ( kni ) locus encodes transcription factors required for induction of the L2 wing vein in Drosophila . Here, we employ diverse CRISPR/Cas9 genome editing tools to generate a series of targeted lesions within the endogenous cis-regulatory module (CRM) required for kni expression in the L2 vein primordium. Phenotypic analysis of these ' in locus ' mutations based on both expression of Kni protein and adult wing phenotypes, reveals novel unexpected features of L2-CRM function including evidence for a chromosome pairing-dependent process that promotes transcription. We also demonstrate that self-propagating active genetic elements (CopyCat elements) can efficiently delete and replace the L2-CRM with orthologous sequences from other divergent fly species. Wing vein phenotypes resulting from these trans-species enhancer replacements parallel features of the respective donor fly species. This highly sensitive phenotypic readout of enhancer function in a native genomic context reveals novel features of CRM function undetected by traditional reporter gene analysis. © 2017, Xu et al.

Zavedení filosofie CRM v konkrétním podniku

OpenAIRE

Musilová, Eva

2015-01-01

The theoretical part of the bachelor thesis is focused on defining CRM, history of CRM and developing the CRM strategy. Phases of the Customer Relationship management are described in this part along with benefits from implementation of this philosophy. The practical part informs about selected company and about the range of its business activities. It analyses the current state of CRM in the company together with the internal processes. Feedback is emphasized in the end of this part, and the...

Mobile Banking: a Customer Relationship Management (Crm) Channel

OpenAIRE

Budiardjo, Eko K; Aprillovi, Dewi

2009-01-01

Meningkatnya pengguna handphone mendorong bank meluncurkan produk-produk layanan perbankan melalui handphone yang dikenal dengan sebutan Mobile Banking (M-Banking). Dalam konteks Customer Relationship Management (CRM), kehadiran M-Banking juga memberikan kontribusi dalam meningkatkan dan mempertahankan kesetiaan pelanggan. Strategi sukses membangun CRM sangat dipengaruhi oleh kepandaian tim pemasaran dalam memahami perilaku dan kebutuhan pelanggan, yang dapat diterjemahkan kedalam kelompok tr...

CUSTOMER RELATIONSHIP MANAGEMENT (CRM) IN PHYSICAL FITNESS CLUBS

OpenAIRE

Mahmoud Goodarzi

2011-01-01

Although customer relationship management has been identified as an important businessapproach in enterprise institutes; there is no universally accepted definition of CRM. Swiftdefined it as an enterprise approach to understanding and influencing customer behavior throughmeaningful communications in order to improve customer knowledge recovery; customeracquisition; customer retention; customer loyalty; and finally customer profitability (2).Thompson (2002) knows CRM as a business strategy to...

Eesti CRM-lahenduste kasv edestab kasvu maailmas kordades / Martin Goroshko

Index Scriptorium Estoniae

Goroshko, Martin

2005-01-01

Kliendihaldus- ehk CRM-lahendused, mis aitavad ettevõtetel kliendisuhteid juhtida ja äriprotsesse efektiivsemaks muuta, on saamas populaarseks nii mujal maailmas kui ka Eestis. Diagramm: CRM-i pakkuvate firmade turuosad. Kommenteerib Indrek Saul

Binding of Diphtheria Toxin to Phospholipids in Liposomes

Science.gov (United States)

Alving, Carl R.; Iglewski, Barbara H.; Urban, Katharine A.; Moss, Joel; Richards, Roberta L.; Sadoff, Jerald C.

1980-04-01

Diphtheria toxin bound to the phosphate portion of some, but not all, phospholipids in liposomes. Liposomes consisting of dimyristoyl phosphatidylcholine and cholesterol did not bind toxin. Addition of 20 mol% (compared to dimyristoyl phosphatidylcholine) of dipalmitoyl phosphatidic acid, dicetyl phosphate, phosphatidylinositol phosphate, cardiolipin, or phosphatidylserine in the liposomes resulted in substantial binding of toxin. Inclusion of phosphatidylinositol in dimyristol phosphatidylcholine / cholesterol liposomes did not result in toxin binding. The calcium salt of dipalmitoyl phosphatidic acid was more effective than the sodium salt, and the highest level of binding occurred with liposomes consisting only of dipalmitoyl phosphatidic acid (calcium salt) and cholesterol. Binding of toxin to liposomes was dependent on pH, and the pattern of pH dependence varied with liposomes having different compositions. Incubation of diphtheria toxin with liposomes containing dicetyl phosphate resulted in maximal binding at pH 3.6, whereas binding to liposomes containing phosphatidylinositol phosphate was maximal above pH 7. Toxin did not bind to liposomes containing 20 mol% of a free fatty acid (palmitic acid) or a sulfated lipid (3-sulfogalactosylceramide). Toxin binding to dicetyl phosphate or phosphatidylinositol phosphate was inhibited by UTP, ATP, phosphocholine, or p-nitrophenyl phosphate, but not by uracil. We conclude that (a) diphtheria toxin binds specifically to the phosphate portion of certain phospholipids, (b) binding to phospholipids in liposomes is dependent on pH, but is not due only to electrostatic interaction, and (c) binding may be strongly influenced by the composition of adjacent phospholipids that do not bind toxin. We propose that a minor membrane phospholipid (such as phosphatidylinositol phosphate or phosphatidic acid), or that some other phosphorylated membrane molecule (such as a phosphoprotein) may be important in the initial binding of

THE CIDOC CRM GAME: A Serious Game Approach to Ontology Learning

Science.gov (United States)

Guillem, A.; Bruseker, G.

2017-08-01

Formal ontologies such as CIDOC CRM (Conceptual Reference Model) form part of the central strategy for the medium and longterm integration of cultural heritage data to allow for its greater valorization and dissemination. Despite this, uptake of CIDOC CRM at the ground level of Cultural Heriage (CH) practice is limited. Part of the reason behind this lack of uptake lies in the fact that ontologies are considered too complicated and abstract for application in real life scenarios. This paper presents the rationale behind and the design of a CIDOC CRM game, the intent of which is to provide a learning mechanism to allow learners of wide backgrounds and interests to approach CIDOC CRM in a hands-on and interactive fashion. The CIDOC CRM game consist of decks of cards and game boards that allow players to engage with the concepts of a formal ontology in relation to real data in an entertaining and informative way. It is argued that the CIDOC CRM Game can form an important part of introducing the basic elements of formal ontology and this standard to a wider audience in order to aid wider understanding and adoption of the same.

A Theoretical Review of CRM Effects on Customer Satisfaction and Loyalty

Directory of Open Access Journals (Sweden)

S. M. Kamrul Islam Shaon

2015-03-01

Full Text Available This paper has been devoted to theoretically examining the Customer Relationship Management (CRM agenda which has been dominating the business world in recent years. Customer relationship management is a new competitive weapon for organizations for serving internal and external customers. Today’s organizations are focusing on conquering the minds of customers, to make them satisfied and loyal with the help of sophisticated, well-organized CRM efforts. This paper is to explore the CRM agenda in organizational interfaces and its effectiveness with regards to customer satisfaction and customer loyalty. The related literature demonstrates that there is a significant association among effective CRM, customer satisfaction and customer loyalty.

46 CFR 197.550 - Respiratory protection.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Respiratory protection. 197.550 Section 197.550 Shipping... GENERAL PROVISIONS Benzene § 197.550 Respiratory protection. (a) General. When the use of respirators in... section that is appropriate for the exposure. Table 197.550(b)—Respiratory Protection for Benzene Airborne...

Antibody persistence 5 years after vaccination at 2 to 10 years of age with Quadrivalent MenACWY-CRM conjugate vaccine, and responses to a booster vaccination.

Science.gov (United States)

Block, Stan L; Christensen, Shane; Verma, Bikash; Xie, Fang; Keshavan, Pavitra; Dull, Peter M; Smolenov, Igor

2015-04-27

In a multi-center extension study, children 2-10 years of age, initially vaccinated with one or two doses (2-5 year-olds) or one dose (6-10 year-olds) of quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM), were assessed five years later for antibody persistence and booster response using serum bactericidal assay with human complement (hSBA). Children 7-10 and 11-15 years of age, who received MenACWY-CRM in the original study, and age-matched vaccine-naïve children, were enrolled in this extension study. After an initial blood draw, children received one dose of MenACWY-CRM as booster or primary dose, with a second blood draw 28 days later. hSBA titers decreased five years after primary vaccination, but were higher than in non-vaccinated controls against serogroups C, W and Y, with substantial proportions having titers ≥8: 7-22% for A, 32-57% for C, 74-83% for W, and 48-54% for Y. Previously-vaccinated children demonstrated booster responses to revaccination against all four serogroups. Responses to primary vaccination in vaccine-naïve controls were lower and similar to primary responses observed in the original study. All vaccinations were generally well tolerated, with no safety concern raised. Approximately half the children vaccinated as 2-10 year-olds maintained protective antibodies against serogroups C, W and Y five years later, but fewer did against serogroup A. Declining titers five years after vaccination and robust booster responses suggest that five years may be an appropriate interval to revaccinate children, subject to epidemiology and delivery considerations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lichen planus following tetanus-diphtheria-acellular pertussis vaccination: A case report and review of the literature.

Science.gov (United States)

Rosengard, Heather C; Wheat, Chikoti M; Tilson, Matthew P; Cuda, Jonathan D

2018-01-01

Lichen planus is an inflammatory dermatosis with a prevalence of approximately 1%. Recent meta-analyses show that patients with hepatitis C virus have a 2.5- to 4.5-fold increased risk of developing lichen planus. Lichen planus has also followed vaccinations and has specifically been attributed to the hepatitis B vaccine, the influenza vaccine, and the tetanus-diphtheria-acellular pertussis vaccine. We describe a case of lichen planus in a hepatitis C virus-infected African American male occurring in temporal association with the administration of the tetanus-diphtheria-acellular pertussis vaccine. The patient's presentation was clinically consistent with lichen planus and confirmed by biopsy. It is likely that many cases of vaccine-induced lichen planus have gone unpublished or unrecognized. In areas with high prevalence of hepatitis C virus infection, we may expect to see more cases of vaccine-induced lichen planus especially in light of the updated Centers for Disease Control and Prevention tetanus-diphtheria-acellular pertussis vaccination recommendations. This case serves to educate healthcare providers about vaccine-induced lichen planus and, in particular, the need to counsel hepatitis C virus-infected patients about a potential risk of developing lichen planus following vaccination. We also reflect on current theories suggesting the T-cell-mediated pathogenesis of lichen planus and the role that hepatitis C virus and toxoid or protein vaccines may play in initiating the disease.

Identification of the smallest structure capable of evoking opsonophagocytic antibodies against Streptococcus pneumoniae type 14

NARCIS (Netherlands)

Safari, D.; Dekker, H.A.T.; Joosten, J.A.; Michalik, D.; de Souza, A.C.; Adamo, R.; Lahmann, M.; Oscarson, S.; Kamerling, J.P.|info:eu-repo/dai/nl/070433941; Snippe, H.

2008-01-01

Synthetic overlapping oligosaccharide fragments of Streptococcus pneumoniae serotype 14 capsular polysaccharide (Pn14PS), {6)-[β-D-Galp-(14)-]β-D-GlcpNAc-(13)-β-D-Galp-(14)-β-D-Glcp-(1}n, were conjugated to CRM197 protein and injected into mice to determine the smallest immunogenic structure. The

Mobile Marketing as a strategy in CRM

OpenAIRE

Goossens, Peter

2011-01-01

Mobile marketing is a young and still developing strategy in marketing. It thanks its creation and rapid evolution to the growth of mobile devices, such as mobile phones and tablets. This paper's research question, "can mobile marketing be used as a strategy in CRM?" investigates the strength of mobile marketing, its application and use by marketers as their sole or part of their marketing campaign and as strategy in customer relationship management (CRM). The two main components of the resea...

Evaluasiterhadapperancangan Sistem Informasi Crm untuk IKM Studi Kasus di IKM Tas Yanri Bogor

OpenAIRE

Yan Andriariza

2010-01-01

CRM is a business process that gave priority to relations with customers. The presence of CRM-based information systems in /KM to help /KM to get closer to its customers. Through this research will be evaluated the importance of CRM. With the CRM-based Information System will provide marry benefits, among others, is an automated process, marketing the more spacious, and customers can more easily communicate with the /KM in these.

Evaluating multidisciplinary health care teams: taking the crisis out of CRM.

Science.gov (United States)

Sutton, Gigi

2009-08-01

High-reliability organisations are those, such as within the aviation industry, which operate in complex, hazardous environments and yet despite this are able to balance safety and effectiveness. Crew resource management (CRM) training is used to improve the non-technical skills of aviation crews and other high-reliability teams. To date, CRM within the health sector has been restricted to use with "crisis teams" and "crisis events". The purpose of this discussion paper is to examine the application of CRM to acute, ward-based multidisciplinary health care teams and more broadly to argue for the repositioning of health-based CRM to address effective everyday function, of which "crisis events" form just one part. It is argued that CRM methodology could be applied to evaluate ward-based health care teams and design non-technical skills training to increase their efficacy, promote better patient outcomes, and facilitate a range of positive personal and organisational level outcomes.

77 FR 20010 - Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM...

Science.gov (United States)

2012-04-03

... DEPARTMENT OF COMMERCE Minority Business Development Agency Proposed Information Collection; Comment Request; Online Customer Relationship Management (CRM)/Performance Databases, the Online Phoenix... of program goals via the Online CRM/Performance Databases. The data collected through the Online CRM...

Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae

International Nuclear Information System (INIS)

Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M.; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L.

2004-01-01

The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ( 99m Tc). The stannous chloride (SnCl 2 ) has a significant influence on the labeling and stability of 99m Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by 99m Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl 2 bactericidal effects. Cell filamentation was observed for concentrations of SnCl 2 > 110 μg/ml. Adherence levels of 99m Tc labelled 241strain to coverslips coated with 20 μg/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% ± 1.2). Therefore, bacterial 99m Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

Durability of Vaccine-Induced Immunity Against Tetanus and Diphtheria Toxins: A Cross-sectional Analysis

Science.gov (United States)

Hammarlund, Erika; Thomas, Archana; Poore, Elizabeth A.; Amanna, Ian J.; Rynko, Abby E.; Mori, Motomi; Chen, Zunqiu; Slifka, Mark K.

2016-01-01

Background. Many adult immunization schedules recommend that tetanus and diphtheria vaccination be performed every 10 years. In light of current epidemiological trends of disease incidence and rates of vaccine-associated adverse events, the 10-year revaccination schedule has come into question. Methods. We performed cross-sectional analysis of serum antibody titers in 546 adult subjects stratified by age or sex. All serological results were converted to international units after calibration with international serum standards. Results. Approximately 97% of the population was seropositive to tetanus and diphtheria as defined by a protective serum antibody titer of ≥0.01 IU/mL. Mean antibody titers were 3.6 and 0.35 IU/mL against tetanus and diphtheria, respectively. Antibody responses to tetanus declined with an estimated half-life of 14 years (95% confidence interval, 11–17 years), whereas antibody responses to diphtheria were more long-lived and declined with an estimated half-life of 27 years (18–51 years). Mathematical models combining antibody magnitude and duration predict that 95% of the population will remain protected against tetanus and diphtheria for ≥30 years without requiring further booster vaccination. Conclusions. These studies demonstrate that durable levels of protective antitoxin immunity exist in the majority of vaccinated individuals. Together, this suggests that it may no longer be necessary to administer booster vaccinations every 10 years and that the current adult vaccination schedule for tetanus and diphtheria should be revisited. PMID:27060790

Immunity to Diphtheria and Tetanus in Army Personnel and Adult Civilians in Mashhad, Iran.

Science.gov (United States)

Hosseini Shokouh, Seyyed Javad; Mohammadi, Babak; Rajabi, Jalil; Mohammadian Roshan, Ghasem

2017-03-24

This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18-34 years had at least basic protection against diphtheria (antitoxin level ≥0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols.

Impact of CRM on the competitiveness level of ICT services in Croatian service providers

Directory of Open Access Journals (Sweden)

Dražen Alerić

2007-07-01

Full Text Available This paper proves a higher competitiveness of ICT service providers who utilize CRM versus the providers who do not. The study of observed participating ICT service providers in Croatia proves that the value added of the services incorporating CRM is more competitive than the same services but without CRM. There is also stronger demand from clients for the services enriched with CRM. Increased service competitiveness generated by CRM utilization raises the company’s general competitiveness. A systematic application of CRM creates a long-lasting relationship between clients and providers and thus enables high-quality long-term term solutions to client demands. CRM represents the value added that raises the level of service competitiveness and makes the service provider unique and recognizable among numerous competitors. Consequently, the satisfaction of clients with the provider and their preference for the same provider result in higher client loyalty. A service company that incorporates CRM in its practices has a higher success rate in fulfilling its mission and attaining goals in accordance with the marketing philosophy.

Strategic entrepreneurship: an integrated innovative entrepreneurial process for CRM implementation at Indian SMEs

OpenAIRE

Mehta, Arpita

2011-01-01

The purpose of this theoretical framework is, to provide a better understanding of the prospects, process, problems, usage and issues related to Customer Relationship Management (CRM) in Indian SMEs so that it may help to implement, adopt and use CRM as an interactive entrepreneurial tool for strategic and successful customer relationship management at Indian SMEs. To reach this understanding this research can starts with three dimensions or group of respondents like CRM Vendor (CRM professio...

Theory underlying CRM training: Psychological issues in flight crew performance and crew coordination

Science.gov (United States)

Helmreich, Robert L.

1987-01-01

What psychological theory and research can reveal about training in Cockpit Resource Management (CRM) is summarized. A framework is provided for the critical analysis of current approaches to CRM training. Background factors and definitions critical to evaluating CRM are reviewed, followed by a discussion of issues directly related to CRM training effectiveness. Some of the things not known about the optimization of crew performance and the research needed to make these efforts as effective as possible are described.

Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

International Nuclear Information System (INIS)

Tomkins, D.J.; Wei, L.; Laurie, K.E.

1985-01-01

It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dip/sup r/) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis ( 3 H-thymidine, autoradiography) or protein synthesis ( 35 S-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test

Transverse velocity scaling in 197Au+197Au fragmentation

International Nuclear Information System (INIS)

Lukasik, J.; Hudan, S.; Lavaud, F.

2002-07-01

Invariant transverse-velocity spectra of intermediate-mass fragments were measured with the 4π multi-detector system INDRA for collisions of 197 Au on 197 Au at incident energies between 40 and 150 MeV per nucleon. Their scaling properties as a function of incident energy and atomic number Z are used to distinguish and characterize the emissions in (i) peripheral collisions at the projectile and target rapidities, and in (ii) central and (iii) peripheral collisions near mid-rapidity. The importance of dynamical effects is evident in all three cases and their origin is discussed. (orig.)

Nuclear data sheets update for A = 197

Energy Technology Data Exchange (ETDEWEB)

Chunmei, Zhou [Chinese Nuclear Data Center, Beijing, BJ (China)

1996-06-01

The Nuclear Data Sheet for A = 197 has been carried out on the basis of the nuclear reaction and decay experiments leading to all the nuclei with mass number A = 197 since cutoff date of the last evaluation, December 1989. Most evaluation data have been updated or revised. The nuclei of updated data mainly are {sup 197}Hg, {sup 197}Pb, {sup 197}Bi and {sup 197}Po. The adopted levels and adopted gamma radiations for all nuclei are shown in the tables.

CRM Meets the Campus

Science.gov (United States)

Villano, Matt

2007-01-01

In the corporate world, the notion of customer relationship management (CRM) is nothing new. That particular technology sector is now jam-packed with software that enables organizations to monitor and manage every interaction with a customer, from the very first experience on, throughout the lifecycle of the relationship. That relationship spans…

Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study.

Science.gov (United States)

Li, Xiaomei; Chen, Meng; Zhang, Tiegang; Li, Juan; Zeng, Yang; Lu, Li

2015-01-01

The aim of this study was to assess the level of humoral immunity against diphtheria and pertussis by measuring IgG to diphtheria toxoid (DT) and pertussis toxin (PT) in general population of Beijing. A total of 2147 subjects aged 0-74 y were selected with a random sample of resident population in Beijing. The information of socio-demographic characteristics, vaccination history, disease history of diphtheria and pertussis were collected for each subject by questionnaire. Serum samples were tested for IgG antibodies to DT and PT by using commercial ELISA kits. The overall positivity rate of anti-DT IgG was 66.28% with the mean concentration of 2.169 IU/ml. Age stratified data showed that the highest positivity rate of 97.63% was observed in 1-4 y and the rates decreased with age. The positivity rates were only around 50% or below since 25 y old. The positivity rate of anti-PT IgG was 12.34% with the mean concentration of 15.163 IU/ml. The highest level of positivity rate (22.23%) and antibody level (23.101 IU/ml) was seen in diphtheria was observed at 1 y and 6 y respectively, which was consistent with the current immunization schedule. But there was no significant increase of immunity to pertussis observed after booster immunization at 18-24 months, but the proportions of undetectable were lowest in diphtheria and all the age groups showed a low immunity to pertussis indicating the potential risk of transmission and outbreaks of the 2 diseases in Beijing.

The analysis of suitability of crm product for organizations for disabled

OpenAIRE

Jeras, David

2013-01-01

The purpose of the thesis is to investigate the customization possibilities of Microsof Dynamics CRM, especially the extent and ways of customization. Moreover the goal is also to determine whether Microsoft Dynamics CRM is suitable for usage in organizations with which deal with disabled people and how it needs to be adjusted in order to achieve the best possible functionality for disabled users. Firslty, we discuss the general properties of CRM systems. Afterwords we describe Microsof...

CRM-järjestelmän hyödyt ja haitat: Case ICT-alan yritys

OpenAIRE

Äikäs, Kasperi

2014-01-01

Tämän tutkimuksellisen opinnäytetyön aiheena on tutkia CRM-järjestelmän hyötyjä ja haittoja ICT- alan pienyrityksessä. Työn tarkoituksena on perehtyä suomalaisen ICT-alan yrityksen käyttämään CRM- eli asiakkuudenhallintajärjestelmään, ja erityisesti tutkia CRM-järjestelmän hyötyjä ja haittoja yrityksen liiketoiminnan toteuttamisen työkaluna. Lisäksi opinnäytetyössä tehdään katselmus kohdeyrityksen CRM-järjestelmään. CRM on liiketoiminnan asiakkuudenhal-linnan tietojärjestelmä. CRM nimitys tul...

Seroprevalence of antibody against diphtheria among the population in Khon Kaen province, Thailand.

Science.gov (United States)

Bansiddhi, Hataichanok; Vuthitanachot, Viboonsuk; Vuthitanachot, Chanpim; Prachayangprecha, Slinporn; Theamboonlers, Apiradee; Poovorawan, Yong

2015-03-01

To assess diphtheria immunity in the northeastern region of Thailand, a seroepidemiological survey was undertaken in 2011 from 516 healthy individuals (age range 2-87 years) in Khon Kaen province. Diphtheria antitoxin levels were measured by enzyme-linked immunosorbent assay and titers of ≥0.1 IU/mL were considered to be protective antitoxin levels. Among the studied population, 94.8% have fully protective levels. The younger population (age range 2-19 years) has higher diphtheria immunity with seroprotection rates of 96.8% to 97.9%, compared with the adult population. The proportion of protective diphtheria antitoxin levels declines to 88.3% to 91.9% in the middle-aged group (20-50 years), and appeared to be higher again in the older age-group (50-70 years). To avoid epidemic spreading, promoting immunization booster programs will be helpful, especially among the adult population (20-50 years). Finally, this study may serve as a valuable guide in deciding exactly which age-groups should be targeted by such an effort. © 2012 APJPH.

Design study of a plasma-loaded CRM using TPD-II machine

International Nuclear Information System (INIS)

Minami, Kazuo

2007-08-01

Design study of an experiment for plasma-loaded cyclotron resonance maser (CRM) utilizing TPD-II Machine at NIFS, Japan is described in some detail. The principle of gyrotrons has been believed the CRM instability. However, all the existing linear theories of CRM instability include unphysical modes unstable at infinite values of axial wavenumber that can never be observed experimentally. To overcome the difficulty, we derive and analyze numerically an exact linear dispersion relation of a large orbit electron beam for CRM, and removed the unphysical modes. However, the relation is found to include two principles of cyclotron emission with oscillation frequencies above and below the branch of fast electron cyclotron wave. The former is CRM instability, and the latter is named Chrenkov instability in the azimuthal direction (CIAD). It is noted that the CIAD we found remains only a proposal of a new mechanism for cyclotron emission until the physical existence is verified experimentally. To verify the CIAD, the design study of a plasma-loaded CRM has been carried out. The apparatus consists of two portions installed in the TPD-II: A pair of helical wiggler windings to create a mono-energetic beam with 15 keV and pitch factor V θ /V z ≥1, and microwave circuits including a cylindrical TE 011 mode cavity with resonant frequency 3.45 GHz. For high plasma density n≥1.5x10 11 cm -3 from TPD-II, the CRM instability may be suppressed and the CIAD will take turn. The present experimental study contributes to a deeper understanding and a widened future prospect in gyrotron physics. (author)

Enacting cultural boundaries in French and German diphtheria serum research.

Science.gov (United States)

Klöppel, Ulrike

2008-06-01

The experimental development of a therapeutic serum against diphtheria between 1891 and 1894 was characterized by a scientific competition that pitted Emil Behring from the Institute for Infectious Diseases in Berlin against Emile Roux and Elie Metschnikoff from the Pasteur Institute in Paris. In general, their competition can be regarded as an extension of the fundamental differences that separated the research schools of Robert Koch and Louis Pasteur. However, to characterize the competition for a diphtheria-serum as "national rivalry" fails to account adequately for the mutual adoption of experimental practices by the Berlin and Parisian protagonists, whose contributions to the development of a therapeutic serum were intertwined in complex ways. Nor can it be characterized as "cooperation," given their fierce public disputes over scientific concepts and the fact that these disputes also shaped the peculiarities of the experimental procedures in Berlin and Paris. A close analysis reveals a complex picture of the dynamic interaction between the conceptual and experimental activities of Behring, Roux, and Metschnikoff- interaction that defined as well as bridged the "French" and "Prussian" experimental systems of diphtheria-serum research.

Remedial training: Will CRM work for everyone

Science.gov (United States)

Johnston, A. N.

1987-01-01

The subject of those pilots who seem unresponsive to Cockpit Resource Management (CRM) training is addressed. Attention is directed to the need and opportunity for remedial action. Emphasis is given to the requirement for new perspectives and additional training resources. It is also argued that, contrary to conventional training wisdom, such individuals do not represent a hard core which is beyond assistance. Some evidence is offered that such a new perspective will lend itself to a wider appreciation of certain specific training needs. The role of appropriately trained specialists is briefly outlined, and a selected bibliography is attached. The combined experiences of several Pilot Advisory Groups (PAG's) within IFALPA member association form the basis for this discussion. It does not purport to desribe the activities of any one PAG. While much of the activities of PAG's have no relevance to CRM, there are clearly some very important points of intersection. The relevance of these points to diagnostic skills, and remedial training in the general domain of CRM is made obvious.

Recall Responses to Tetanus and Diphtheria Vaccination Are Frequently Insufficient in Elderly Persons

Science.gov (United States)

Weinberger, Birgit; Schirmer, Michael; Matteucci Gothe, Raffaella; Siebert, Uwe; Fuchs, Dietmar; Grubeck-Loebenstein, Beatrix

2013-01-01

Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological “non-responder type.” Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite

Customer Relationship Management (CRM dan Nilai Pelanggan terhadap Loyalitas Pelanggan

Directory of Open Access Journals (Sweden)

Budiman Budiman

2010-09-01

Full Text Available The tourism world today gains a lot of attention and spotlight is greatly increased in many countries and in different places in the world. It is proven by the increasing number of tourist resorts built, due to visitors using the facility. The purpose of this study is to determine whether there is influence of Customer Relationship Management (CRM on Customer Value at Hotel Crystal, to see if there is influence of CRM on Customer Loyalty at Hotel Kristal, and to find out whether there is influence of Customer Value on Customer Loyalty at Hotel Kristal. The research is descriptive, while the research method used is survey of 100 customers in Hotel Kristal, South Jakarta. Path analyze is used to determine the influence between variables. Result indicates that the CRM provides a positive and significant influence on the Customer Value at Hotel Kristal. Meanwhile, CRM and Customer Value provide a positive and significant influence at Hotel Kristal subsequently affecting Customer Loyalty Hotel Kristal.

Impact strength of sintered astaloy CrM powders

International Nuclear Information System (INIS)

Kazior, J.; Ploszczak, J.; Nykiel, M.; Pieczonka, T.

2003-01-01

In this paper results of a series of impact tests on sintered Astaloy CrM powders alloys modified by boron are presented and discussed. Boron in different forms, i.e. as elemental boron powder, boron carbide B 4 C powder or mixture of boron and carbon elemental powders, was used in different weight percentage to activate sintering of Astaloy CrM powder and to increase hardenability, with aim of increasing impact strength in view of structural applications. (author)

CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization

International Nuclear Information System (INIS)

Neyton, Sophie; Lespinasse, Francoise; Lahaye, Francois; Staccini, Pascal; Paquis-Flucklinger, Veronique; Santucci-Darmanin, Sabine

2007-01-01

MSH4 and MSH5 are members of the MutS homolog family, a conserved group of proteins involved in DNA mismatch correction and homologous recombination. Although several studies have provided compelling evidences suggesting that MSH4 and MSH5 could act together in early and late stages of meiotic recombination, their precise roles are poorly understood and recent findings suggest that the human MSH4 protein may also exert a cytoplasmic function. Here we show that MSH4 is present in the cytoplasm and the nucleus of both testicular cells and transfected somatic cells. Confocal studies on transfected cells provide the first evidence that the subcellular localization of MSH4 is regulated, at least in part, by an active nuclear export pathway dependent on the exportin CRM1. We used deletion mapping and mutagenesis to define two functional nuclear export sequences within the C-terminal part of hMSH4 that mediate nuclear export through the CRM1 pathway. Our results suggest that CRM1 is also involved in MSH5 nuclear export. In addition, we demonstrate that dimerization of MSH4 and MSH5 facilitates their nuclear localization suggesting that dimerization may regulate the intracellular trafficking of these proteins. Our findings suggest that nucleocytoplasmic traffic may constitute a regulatory mechanism for MSH4 and MSH5 functions

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children: A cross-sectional study.

Science.gov (United States)

Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-12-01

Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in

Trh CRM systémů a jeho vývoj

OpenAIRE

Dudek, Martin

2008-01-01

The main aim of this diploma thesis is to create an overview of analytic CRM systems which are offered in the Czech Republic with the emphasis on systems which can be used for marketing processes of the firms. The overview contains the reflection of new trends in CRM systems and marketing and the development to the future. In the last decade there is a huge development of CRM systems, which are generally known as sales force automation and less as an instrument for marketing management of the...

The Effectiveness Of The Intelligence E-CRM Application In Enhancing Positive Customer Relationships

Directory of Open Access Journals (Sweden)

Bashar Ahmed

2015-07-01

Full Text Available AbstractE-CRM electronic customer relationship management is a derivation from CRM techniques which influenced direct marketing technology and call Centre to promote massively created products and services to small sub-segments of market. When CRM techniques are incorporated in e-commerce environment it becomes E-CRM which involves building a strong and sustainable customer relationship by using Internet. It is a strategy which is purely based on Internet and software development it requires to create essential integrated software suite to deal with all kinds of customer related issues like customer services sales and marketing field support. The essential parts of E-CRM are to focus on building new customer base segmentation of high valued customers enhancing the profitability of existing customer and maximize the value and life of profitable customers.

Customer Relationship Management (Crm) Berbasis Web Untuk Meningkatkan Daya Saing Toko Online

OpenAIRE

Kholil, Ishak

2017-01-01

Customer Relationship Management (CRM) is a thorough business strategy of a company that enables the company to effectively manage relationships with customers. relationships with CRM information technology is very important because without good information technology capabilities in managing information within the organization, CRM will be paralyzed and has no meaning. Synergy of these two things are needed what today's technology era. To generate a reliable performance of the organization m...

Advanced CRM training for instructors and evaluators

Science.gov (United States)

Taggart, William R.

1991-01-01

It is seen that if the maximum operational benefit of crew resource management (CRM) is to be achieved, the evaluator group is the principal key and specialized training that is ongoing is necessary for this group. The training must be customized to fit the needs of a particular organization, and the training must address key topical issues that influence organizational dynamics. Attention is given to the use of video and full length scripted NASA research LOFTS, behavioral markers and debriefing skills, the importance of policy and written CRM standards, and line oriented simulations debriefing performance indicators.

Perancangan E-CRM pada PT Multi Superindo Manunggal

Directory of Open Access Journals (Sweden)

Brata Wibawa Djojo

2010-03-01

Full Text Available The key to the success of a company does not only lie in the product or service being offered, but in how far the company's efforts in satisfying the needs of its customers. Results of the system analysis, shows that problems faced by the company are caused by still not optimal customer services. The purpose of this study is to analyze the appropriate strategy for the company and design systems to support the implementation of the strategy. The analytical method used in analyzing the industry with Porter's Five Forces model, and formulation of strategies for using the method of analysis of external and internal environment with matrix IFE and EFE, followed by a SWOT matrix, and strategy decisions based on the matrix QSPM. Results from the formulation of strategy are market penetration strategy. E-CRM system is considered to be the most appropriate in implementation of this strategy and overcoming the problems faced by the company. Web-based e-CRM systems, focusing on the development and maintenance of long-term relationships with customers that can provide added value to both. E-CRM system is expected to make transactions easier for customers to order and get customer service, and also for prospective customers to access accurate company information. Design of E-CRM systems are conducted using 7C method.

46 CFR 197.326 - Oxygen safety.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Oxygen safety. 197.326 Section 197.326 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND HEALTH STANDARDS GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.326 Oxygen safety. (a) Equipment used with...

De cruciale rol van inkoopgedraag : CRM in business to business

NARCIS (Netherlands)

Santema, S.C.; Rijt, van de J.

2002-01-01

Oak b-to-b bedrijven gaan steeds meer relationeel in plaats van transactioneel denken. Complicerende factor voor CRM in business to business is alleen, dat bedrijven niet alleen met een verkoper maar ook met een koper te maken hebben. Hoe kan CRM in business to business het beste worden ingezet?

Managing Change: the people side of implementing CRM processes

OpenAIRE

Hann, David

2006-01-01

This report has been produced with the remit of analysing the people side of change management with regard to a Customer Relationship Management (CRM) process implementation at Jupiter Design (Jupiter). An increasing churn of clients and 12- years of growth has made Jupiter realise they must maximise revenues from existing clients. The adoption of a CRM approach has been suggested as a possible solution.

Role of Knowledge Management and Analytical CRM in Business: Data Mining Based Framework

Science.gov (United States)

Ranjan, Jayanthi; Bhatnagar, Vishal

2011-01-01

Purpose: The purpose of the paper is to provide a thorough analysis of the concepts of business intelligence (BI), knowledge management (KM) and analytical CRM (aCRM) and to establish a framework for integrating all the three to each other. The paper also seeks to establish a KM and aCRM based framework using data mining (DM) techniques, which…

Dot immunoassay for the simultaneous determination of postvaccination immunity against pertussis, diphtheria, and tetanus.

Science.gov (United States)

Khramtsov, Pavel; Bochkova, Maria; Timganova, Valeria; Zamorina, Svetlana; Rayev, Mikhail

2017-06-01

A dot immunoassay for simultaneous semiquantitative detection of IgG against tetanus toxoid (Ttx) and diphtheria toxoid (Dtx) and qualitative detection of anti-Bordetella pertussis IgGs in human blood serum using carbon nanoparticles functionalized with streptococcal protein G was developed. Inactivated B. pertussis cells in suspension form were used as an antigen in the immunoassay. Pertussis, tetanus, and diphtheria antigens were separately spotted onto nitrocellulose strips, and then the immunostrips were successively incubated with blood sera and a suspension of carbon nanoparticles. The immunostrips were then scanned with a flatbed scanner, and the images obtained were processed with ImageJ. One hundred fifty-five venous blood serum samples from children vaccinated with diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine were tested in comparison with a conventional ELISA and agglutination test. The total time required for analysis of 32 serum samples was less than 3 h. Comparison between the results of the dot immunoassay and the corresponding ELISA/agglutination test revealed a high level of agreement (Cohen's kappa between 0.765 and 0.813). The lower limit of quantification was 0.06 IU/ml for anti-Ttx and anti-Dtx. The intra-assay coefficients of variation were less than 15% for anti-Ttx and anti-Dtx and less than 10% for anti-pertussis. The diagnostic sensitivity of detection of the antibody protection level was 93.5% for anti-Ttx [95% confidence interval (CI) 83.5-97.9%], 92.4% for anti-Dtx (95% CI 80.9297.5%), and 90.2% for anti-pertussis (95% CI 75.9-96.8%). The diagnostic specificity was 90.9% for anti-Ttx (95% CI 57.1-99.5%), 85% for anti-Dtx (95% CI 61.1-96.0%), and 89.3% for anti-pertussis (95%CI 80.8-94.5%). The dot immunoassay developed does not require expensive reading equipment, and allows detection of antibodies against three antigens in a single analysis. The immunostrips can be stored for a long time without changes in the

Estudo da difteria na cidade do Recife. I. Nota sôbre levantamento de portadores de Corynebacterium diphtheriae no bairro dos Coelhos Survey on diphtheriae carriers in "Bairro dos Coelhos" Recife, Brazil

Directory of Open Access Journals (Sweden)

Dalva A. Mello

1969-06-01

Full Text Available De uma amostra probabilística do bairro dos Coelhos da cidade do Recife, 410 indivíduos foram examinados para verificação de portadores de difteria. Sòmente duas amostras de C. diphtheriae foram isoladas de duas crianças de 8 a 9 anos, as quais não apresentaram sintomatologia compatível com o quadro diftérico.From a limited population living around the University Hospital in Recife, Brazil a randomic sample was examined in order to identify diphtheria carriers. Swabs were made from 410 persons in a house-to-house survey. Two strains of Corynebacterium diphtheriae were isolated from healthy 8 and 9-year old children.

Excitation functions for 197Au (d, p)198Au, 197Au(d, 2n)197mHg, 197Au(d, 2n)197Hg and 197Au(d, p2n)196Au

International Nuclear Information System (INIS)

Long Xianguan; Peng Xiufeng; He Fuqing

1987-01-01

By using activation method and stack-foil technique, the excitation functions for d + 197 Au reaction in 6.6-13.1 MeV energy range are measured. The measured values are compared with previous results and theoretical calculations

The effects of Crew Resource Management (CRM) training on flight attendants' safety attitudes.

Science.gov (United States)

Ford, Jane; Henderson, Robert; O'Hare, David

2014-02-01

A number of well-known incidents and accidents had led the aviation industry to introduce Crew Resource Management (CRM) training designed specifically for flight attendants, and joint (pilot and flight attendant) CRM training as a way to improve teamwork and communication. The development of these new CRM training programs during the 1990s highlighted the growing need for programs to be evaluated using research tools that had been validated for the flight attendant population. The FSAQ (Flight Safety Attitudes Questionnaire-Flight Attendants) was designed specifically to obtain safety attitude data from flight attendants working for an Asia-Pacific airline. Flight attendants volunteered to participate in a study before receiving CRM training (N=563) and again (N=526) after CRM training. Almost half (13) of the items from the 36-item FSAQ showed highly significant changes following CRM training. Years of experience, crew position, seniority, leadership roles, flight attendant crew size, and length of route flown were all predictive of safety attitudes. CRM training for flight attendants is a valuable tool for increasing positive teamwork behaviors between the flight attendant and pilot sub-groups. Joint training sessions, where flight attendants and pilots work together to find solutions to in-flight emergency scenarios, provide a particularly useful strategy in breaking down communication barriers between the two sub-groups. Copyright © 2013 National Safety Council and Elsevier Ltd. All rights reserved.

A COLLABORATIVE PERSPECTIVE OF CRM

Directory of Open Access Journals (Sweden)

Nicolae Marginean

2009-05-01

Full Text Available Today, companies are becoming more customer focused, trying to adapt their business systems in order to be more responsive to the ever-changing needs of customers. CRM software gives a new face to the relationship with the customer, using the new technolo

Assessment of Serologic Immunity to Diphtheria-Tetanus-Pertussis After Treatment of Korean Pediatric Hematology and Oncology Patients

Science.gov (United States)

Kwon, Hyo Jin; Lee, Jae-Wook; Chung, Nak-Gyun; Cho, Bin; Kim, Hack-Ki

2012-01-01

The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination. PMID:22219618

An exact linear dispersion relation for CRM instability

International Nuclear Information System (INIS)

Choyal, Y; Minami, K

2011-01-01

An exact self-consistent linear dispersion relation of a large orbit electron beam including two principles of cyclotron emission with oscillation frequencies above and below the relativistic electron frequency is derived and analyzed numerically for the first time in the literature. The two principles are cyclotron resonance maser (CRM) instability and Cherenkov instability in the azimuthal direction. Self-consistency in the formulation and inclusion of proper boundary conditions have removed the unphysical instability existing for infinitely large k z observed in conventional dispersion relations of CRM instability.

Seroprevalence and placental transmission of maternal antibodies specific for Neisseria meningitidis Serogroups A, C, Y and W135 and influence of maternal antibodies on the immune response to a primary course of MenACWY-CRM vaccine in the United Kingdom.

Science.gov (United States)

Blanchard-Rohner, Geraldine; Snape, Matthew D; Kelly, Dominic F; O'Connor, Daniel; John, Tessa; Kibwana, Elizabeth; Parks, Hannah; Ford, Karen; Dull, Peter M; Pollard, Andrew J

2013-07-01

Maternal antibodies give neonates some protection against bacterial infection. We measured antibodies against Neisseria meningitidis serogroups A, C, Y and W135 in mothers and their 2-month-old infants at study enrollment. We also assessed the impact of maternal antibody present at 2 months of age on the immune response to a primary course of quadrivalent meningococcal conjugate vaccine (MenACWY-CRM197) given at 2 and 4 months of age. This was a single-center, open-label, randomized study undertaken in Oxford, United Kingdom. Two hundred sixteen healthy infants were enrolled in the study and vaccinated with MenACWY-CRM197 at 2 and 4 months of age. Blood was obtained from all mothers, in a subset of infants at 2 months and all infants at 5 months. Antibody and memory B-cell responses at 5 months were correlated with maternal antibodies. Mothers had low IgG antibodies against serogroups C, W135 and Y polysaccharides, but high serogroup A antibody, whereas 61-78% had protective human complement serum bactericidal activity (hSBA) (≥1:4) for serogroups C, W135 and Y but only 31% for serogroup A. Only 9%, 32%, 45% and 19% of 2-month-old infants had hSBA ≥1:4 for serogroups A, C, W135 and Y, respectively. Maternal antibody had little association on responses to MenACWY-CRM197, except a moderate negative association between MenC-specific bactericidal antibody at 2 and 5 months (r = -0.5, P = 0.006, n = 28) and between carrier-specific IgG antibody at 2 months and MenC-specific hSBA/IgG antibody at 5 months (r = -0.4, P = 0.02 and 0.04, n = 32 and 23). Nonetheless, 90% of infants achieved protective MenC-hSBA titers after vaccination at 2 and 4 months of age. The levels of serogroup-specific meningococcal antibodies were low in mothers and 2-month-old infants. Immunizing mothers before or during pregnancy with meningococcal conjugate vaccines might increase antibody levels in early infancy and provide protection against infection due to N. meningitidis.

When are CRM Systems Successful? The Perspective of the User and of the Organization

NARCIS (Netherlands)

G.H. van Bruggen (Gerrit); B. Wierenga (Berend)

2005-01-01

textabstractThe individual impact of CRM systems is strongly related to impact at the organizational level. Fit with the task of the user is key. CRM systems are successful in organizations that reward customer-centric behavior and that have an analytical decision style. Acceptance of a CRM system

Microsoft Dynamics CRM 2011 New Features The Real-world Tutorial

CERN Document Server

Wang, Jim

2011-01-01

This book is packed with practical steps and screenshots to make learning fun and addictive. You will learn to build a complete Airline Compensation Management system using Dynamics CRM 2011. If you want a focused book that gets you up-to-speed with the new features of Microsft Dynamics CRM 2011 then this is the perfect book for you.

A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

Science.gov (United States)

Rohde, K A; Cunningham, K C; Henriquez, K M; Nielsen, A R; Worzella, S L; Hayney, M S

2014-12-01

Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

COMPARISON OF CRM PROGRAMS BASING ON IMPROVING CUSTOMER PROFITABILITY: USING THE AHP METHOD

Directory of Open Access Journals (Sweden)

Dong-Fei Xue

2014-04-01

Full Text Available In this paper, we generalize the cause-related marketing (CRM methods that used by most current enterprises. And then, we probe into the difference of the effects of different types of CRM programs aiming at improving customer profitability by analytic hierarchy process (AHP. Consequently, we find out the sequencing results and provide some reference to the enterprises while performing CRM programs.

Crew Resource Management (CRM) video storytelling project: a team-based learning activity

OpenAIRE

Ma, Maggie Jiao; Denando, John

2011-01-01

This Crew Resource Management (CRM) video storytelling project asks students to work in a team (4-5 people per team) to create (write and produce) a video story. The story should demonstrate lacking and ill practices of CRM knowledge and skills, or positive skills used to create a successful scenario in aviation (e. g. , flight training, commercial aviation, airport management). The activity is composed of two parts: (1) creating a video story of CRM in aviation, and (2) delivering a group pr...

The production and certification of a plutonium equal-atom reference material: NBL CRM 128

International Nuclear Information System (INIS)

Crawford, D.W.

1990-07-01

This report describes the design, production, and certification of the New Brunswick Laboratory plutonium equal-atom certified reference material (CRM), NBL CRM 128. The primary use of this CRM is for the determination of bias corrections encountered in the operation of a mass spectrometer. This reference material is available to the US Department of Energy contractor-operated and government-operated laboratories, as well as to the international nuclear safeguards community. The absolute, or unbiased, certified value for the CRM's Pu-242/Pu-239 ratio is 1.00063 ± 0.00026 (95% confidence interval) as of October 1, 1984. This value was obtained through the quantitative blending of high-purity, chemically and isotopically characterized separated isotopes, as well as through intercomparisons of CRM samples with calibration mixtures using thermal ionization mass spectrometry. 32 tabs

Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

Science.gov (United States)

Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

2011-01-01

This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

CRM NAS ORGANIZAÇÕES

Directory of Open Access Journals (Sweden)

Leonardo Arruda Ribas

2005-06-01

Full Text Available Frente às forças impostas pela globalização, Internet e evolução tecnológica, aliadas a uma era de descontinuidade, tem-se como resultado um novo tipo de consumidor, mais questionador e exigente, que as organizações têm de conquistar, de forma a atingir sua fidelização. Várias são as empresas que trabalham para conhecer melhor os seus clientes, operando mudanças das culturais organizacionais, que passam a ter o foco nas necessidades do seu público. Nesse contexto, muitas organizações implementam o CRM (Customer relationship management, objetivando maior integração com os clientes, através da coleta de informações sobre as atividades e necessidades destes, para entender o seu comportamento, obter sua satisfação e, conseqüentemente, sua retenção. Este trabalho pretende esclarecer a experiência do CRM e de sua implantação no âmbito internacional e nacional. Verificou-se forte tendência não apenas mundial, mas também das organizações brasileiras, à implementação do CRM. Uma das exigências fundamentais para sua implementação de sucesso é o completo entendimento dessa filosofia de trabalho e sua absorção pela cultura da organização. Outro aspecto relevante é a contribuição do suporte eletrônico (softwares na integração entre as vendas, o marketing e as funções de apoio ao cliente.

Re-emergence of diphtheria and pertussis: implications for Nigeria.

Science.gov (United States)

Sadoh, A E; Oladokun, R E

2012-11-26

In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

Directory of Open Access Journals (Sweden)

Ahmed Al-Jazzar

2016-12-01

Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

Magnetization of the oceanic crust: TRM or CRM?

Science.gov (United States)

Raymond, C. A.; Labrecque, J. L.

1987-01-01

A model was proposed in which chemical remanent magnetization (CRM) acquired within the first 20 Ma of crustal evolution may account for 80% of the bulk natural remanent magnetization (NRM) of older basalts. The CRM of the crust is acquired as the original thermoremanent magnetization (TRM) is lost through low temperature alteration. The CRM intensity and direction are controlled by the post-emplacement polarity history. This model explains several independent observations concerning the magnetization of the oceanic crust. The model accounts for amplitude and skewness discrepancies observed in both the intermediate wavelength satellite field and the short wavelength sea surface magnetic anomaly pattern. It also explains the decay of magnetization away from the spreading axis, and the enhanced magnetization of the Cretaceous Quiet Zones while predicting other systematic variations with age in the bulk magnetization of the oceanic crust. The model also explains discrepancies in the anomaly skewness parameter observed for anomalies of Cretaceous age. Further studies indicate varying rates of TRM decay in very young crust which depicts the advance of low temperature alteration through the magnetized layer.

Adoption of CRM: cross-cultural impact, a literature review

OpenAIRE

Ali, M; Alshawi, S

2004-01-01

In a competitive world there is a need for companies to maximise all their resources. One of the resources that is often overlooked is that of existing customer base. Customer Relationship Management (CRM) is an area that is becoming increasingly popular as it provides a method of maximising existing customer resource as well as adding value from the customers’ perception. CRM systems are used in many multinational organizations mainly to achieve customer loyalty and retention, increase cros...

CRM as a support for knowledge management and customer

OpenAIRE

Toriani, Silvana; Angeloni, Maria Terezinha

2011-01-01

This paper aims to analyze the role of Customer Relationship Management (CRM) as a support for Knowledge Management (KM) and the Customer Relationship Strategy Definition in an Information Technology (IT) Company. This work is based on theories of KM, IT, and Relationship Marketing. Our survey uses a descriptive approach, in which data is gathered by means of content analysis of semi-structured interviews. The study results have shown us that the company implements an effective system for CRM...

The importance of implementing CRM concept in the banking sector

Directory of Open Access Journals (Sweden)

Marinković Vladimir

2015-01-01

Full Text Available In the past banks traditionally operated at the predominantly stable market. With the outbreak of the economic crisis and the increased number of competitors the situation has drastically changed. Today banks are facing aggressive competition, which requires additional efforts in order to ensure survival at the competitive and unpredictable market. Customers are the essence and basis of the banking sector's development. Banks cannot function without customers. This is why Customer Relationship Management (CRM is of strategic importance for the banking sector. CRM helps banks to achieve profit by establishing long-term relations. High-quality customer relationship management is only possible with the support of a sound IT system. The practice among companies has shown that investments in the CRM system and customer relations are usually intuitive and based on the management's experience, with no detailed investment plan as in the case of other investment fields. Banks have realized that customer relationship management is an extremely significant factor of their success. CRM is a strategy that may help them build long-term relations with their clients, thereby increasing their profit through an adequate management system and implementation of customer-oriented strategy.

Peran E-crm (Electronic Customer Relationship Management) Dalam Meningkatkan Kualitas Pelayanan (Studi Pada Harris Hotel & Conventions Malang)

OpenAIRE

Ramadhan, Almira Bintang; Kusumawati, Andriani; Dewantara, Rizki Yudhi

2016-01-01

E-CRM (Electronic Customer Relationship Management) is one of business concepts and technology that supported by information systems to integrate all of business proccess that customer interacted. The most common E-CRM implementation in hotel industry is website. This research is to know the role of E-CRM to improve service quality, describe the implementation of E-CRM, understand the guest service procedure in, and to know the service quality through E-CRM in Harris Hotel & Conventions M...

Evaluation of [O-methyl-11C]RS-15385-197 as a positron emission tomography radioligand for central α2-adrenoceptors

International Nuclear Information System (INIS)

Hume, S.P.; Hirani, E.; Opacka-Juffry, J.; Osman, S.; Myers, R.; Gunn, R.N.; McCarron, J.A.; Pike, V.W.; Clark, R.D.; Melichar, J.; Nutt, D.J.

2000-01-01

Carbon-11 labelled RS-15385-197 and its ethylsulphonyl analogue, RS-79948-197, were evaluated in rats as potential radioligands to image central α 2 -adrenoceptors in vivo. The biodistributions of both compounds were comparable with that obtained in an earlier study using tritiated RS-79948-197 and were consistent with the known localisation of α 2 -adrenoceptors. The maximal signals (total to non-specific binding) were, however, reduced, in the order [ 11 C]RS-79948-197 11 C]RS-15385-197 3 H]RS-79948-197, primarily due to the difference in radiolabel position (O-methyl for carbon-11 compared with S-ethyl for tritium). This resulted in the in-growth of radiolabelled metabolites in plasma, which, in turn, contributed to the non-specific component of brain radioactivity. Nonetheless, the signal ratio of ∝5 for a receptor-dense tissue compared with the receptor-sparse cerebellum, at 90-120 min after radioligand injection, encouraged the development of [O-methyl- 11 C]RS-15385-197 for human positron emission tomography (PET). Unfortunately, in two human PET scans (each of 90 min), brain extraction of the radioligand was minimal, with volumes of distribution more than an order of magnitude lower than that measured in rats. Following intravenous injection, radioactivity was retained in plasma and metabolism of the radiolabelled compound was very low. Retrospective measurements of in vitro plasma protein binding and in vivo brain uptake index (BUI) in rats demonstrated a higher protein binding of the radioligand in human compared with rat plasma and a lower BUI in the presence of human plasma. It is feasible that a higher affinity of RS-15385-197 for human plasma protein compared with receptor limited the transport of the radioligand. Although one of the PET scans showed a slight heterogeneity in biodistribution of radioactivity which was consistent with the known localisation of α 2 -adrenoceptors in human brain, it was concluded that [O-methyl- 11 C]RS-15385-197

Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae; Marcacao de Corynebacterium diphtheriae com Tecnecio-99m e avaliacao da capacidade de ligacao a fibronectina de plasma humano

Energy Technology Data Exchange (ETDEWEB)

Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas

2004-04-15

The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ({sup 99m}Tc). The stannous chloride (SnCl{sub 2}) has a significant influence on the labeling and stability of {sup 99m}Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by {sup 99m}Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl{sub 2} bactericidal effects. Cell filamentation was observed for concentrations of SnCl{sub 2} > 110 {mu}g/ml. Adherence levels of {sup 99m}Tc labelled 241strain to coverslips coated with 20 {mu}g/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% {+-} 1.2). Therefore, bacterial {sup 99m}Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

Public health action following an outbreak of toxigenic cutaneous diphtheria in an Auckland refugee resettlement centre.

Science.gov (United States)

Reynolds, Gary E; Saunders, Helen; Matson, Angela; O'Kane, Fiona; Roberts, Sally A; Singh, Salvin K; Voss, Lesley M; Kiedrzynski, Tomasz

2016-12-24

Global forced displacement has climbed to unprecedented levels due largely to regional conflict. Degraded public health services leave displaced people vulnerable to multiple environmental and infectious hazards including vaccine preventable disease. While diphtheria is rarely notified in New Zealand, a 2 person outbreak of cutaneous diphtheria occurred in refugees from Afghanistan in February 2015 at the refugee resettlement centre in Auckland. Both cases had uncertain immunisation status. The index case presented with a scalp lesion during routine health screen and toxigenic Corynebacterium diphtheriae was isolated. A secondary case of cutaneous diphtheria and an asymptomatic carrier were identified from skin and throat swabs. The 2 cases and 1 carrier were placed in consented restriction until antibiotic treatment and 2 clearance swabs were available. A total of 164 contacts were identified from within the same hostel accommodation as well as staff working in the refugee centre. All high risk contacts (n=101) were swabbed (throat, nasopharynx and open skin lesions) to assess C. diphtheriae carriage status. Chemoprophylaxis was administered (1 dose of intramuscular benzathine penicillin or 10 days of oral erythromycin) and diphtheria toxoid-containing vaccine offered regardless of immunisation status. Suspected cases were restricted on daily monitoring until swab clearance. A group of 49 low risk contacts were also offered vaccination. Results suggest a significant public health effort was required for a disease rarely seen in New Zealand. In light of increased worldwide forced displacement, similar outbreaks could occur and require a rigorous public health framework for management.

The certification of oxygen in copper CRM No 054R

International Nuclear Information System (INIS)

1989-01-01

A reference material for the determination of low oxygen contents in copper (CRM 054R) has been prepared to replace the exhausted CRM 054. The homogeneity of the material is demonstrated. The oxygen content has been determined by charged particle activation analysis and confirmed by fusion extraction techniques. The mass fraction of oxygen is certified as (0.47 ± 0.04) μ g/g. 10 refs

Modulation of integrin-linked kinase nucleo-cytoplasmic shuttling by ILKAP and CRM1.

Science.gov (United States)

Nakrieko, Kerry-Ann; Vespa, Alisa; Mason, David; Irvine, Timothy S; D'Souza, Sudhir J A; Dagnino, Lina

2008-07-15

Integrin-linked kinase (ILK) plays key roles in a variety of cell functions, including cell proliferation, adhesion and migration. Within the cell, ILK localizes to multiple sites, including the cytoplasm, focal adhesion complexes that mediate cell adhesion to extracellular substrates, as well as cell-cell junctions in epidermal keratinocytes. Central to understanding ILK function is the elucidation of the mechanisms that regulate its subcellular localization. We now demonstrate that ILK is imported into the nucleus through sequences in its N-terminus, via active transport mechanisms that involve nuclear pore complexes. In addition, nuclear ILK can be rapidly exported into the cytoplasm through a CRM1-dependent pathway, and its export is enhanced by the type 2C protein phosphatase ILKAP. Nuclear localization of ILK in epidermal keratinocytes is associated with increased DNA synthesis, which is sensitive to inhibition by ILKAP. Our studies demonstrate the importance for keratinocyte proliferation of ILK regulation through changes in its subcellular localization, and establish ILKAP and CRM1 as pivotal modulators of ILK subcellular distribution and activity in these cells.

rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

Science.gov (United States)

Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N

2007-05-15

The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

CIDOC-CRM extensions for conservation processes: A methodological approach

Science.gov (United States)

Vassilakaki, Evgenia; Zervos, Spiros; Giannakopoulos, Georgios

2015-02-01

This paper aims to report the steps taken to create the CIDOC Conceptual Reference Model (CIDOC-CRM) extensions and the relationships established to accommodate the depiction of conservation processes. In particular, the specific steps undertaken for developing and applying the CIDOC-CRM extensions for defining the conservation interventions performed on the cultural artifacts of the National Archaeological Museum of Athens, Greece are presented in detail. A report on the preliminary design of the DOC-CULTURE project (Development of an integrated information environment for assessment and documentation of conservation interventions to cultural works/objects with nondestructive testing techniques [NDTs], www.ndt-lab.gr/docculture), co-financed by the European Union NSRF THALES program, can be found in Kyriaki-Manessi, Zervos & Giannakopoulos (1) whereas the NDT&E methods and their output data through CIDOC-CRM extension of the DOC-CULTURE project approach to standardize the documentation of the conservation were further reported in Kouis et al. (2).

Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.

LENUS (Irish Health Repository)

Wagner, K S

2011-04-01

Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.

Evaluation of the induction of immune memory following infant immunisation with serogroup C Neisseria meningitidis conjugate vaccines--exploratory analyses within a randomised controlled trial.

Directory of Open Access Journals (Sweden)

Ameneh Khatami

Full Text Available We measured meningococcal serogroup C (MenC-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001 or 2-dose (p<0.0001 MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

46 CFR 197.340 - Breathing gas supply.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Breathing gas supply. 197.340 Section 197.340 Shipping... GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.340 Breathing gas supply. (a) A primary breathing gas supply for surface-supplied diving must be sufficient to support the following for the...

CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.

Science.gov (United States)

Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen

2016-08-01

Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor 1B (p27Kip1) is a cyclin‑dependent kinase inhibitor and in the present study, we found that p27Kip1 expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III-IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip1 (Ser10), one of the phosphorylated forms of p27Kip1, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance 1 (CRM-1; also referred to as exportin 1 or Xpo1), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-1 in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip1 and a decrease of nuclear p27Kip1. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G1 arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-1 knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-1 and p27Kip1 may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments.

Effect of diphtheria toxin T-domain on endosomal pH

Directory of Open Access Journals (Sweden)

A. J. Labyntsev

2015-08-01

Full Text Available A key step in the mode of cytotoxic action of diphtheria toxin (DT is the transfer of its catalytic domain (Cd from endosomes into the cytosol. The main activity in this process is performed by the transport domain (Td, but the molecular mechanism of its action remains unknown. We have previously shown that Td can have some influence on the endosomal transport of DT. The aim of this work was to study the effect of diphtheria toxin on the toxin compartmentalization in the intracellular transporting pathway and endosomal pH. We used recombinant fragments of DT, which differed only by the presence of Td in their structure, fused with fluorescent proteins. It was shown that the toxin fragment with Td moved slower by the pathway early-late endosomes-lysosomes, and had a slightly different pattern of colocalization with endosomal markers than DT fragment without Td. In addition, endosomes containing DT fragments with Td had a constant pH of about 6.5 from the 10th to 50th minute of observation, for the same time endosomes containing DT fragments without Td demons­trated a decrease in pH from 6.3 to 5.5. These results indicate that Td inhibits acidification of endosomal medium. One of possible explanations for this may be the effect of the ion channel formed by the T-domain on the process of the endosomal acidification. This property of Td may not only inhibit maturation of endosomes but also inhibit activation of endosomal pH-dependent proteases, and this promotes successful transport of Cd into the cell cytosol.

Kajian Penerimaan Pengguna Terhadap Sistem CRM di Perusahaan X Menggunakan Model TAM

Directory of Open Access Journals (Sweden)

Muhammad Malik Hakim

2018-03-01

Full Text Available Pelayanan kepada pelanggan adalah salah satu tujuan bisnis setiap perusahaan dalam upayanya memberikan kepuasan kepada para pelanggannya. Untuk mengintegrasikan seluruh kegiatan pelayanan kepada pelanggan dari semua divisi yang terkait baik langsung maupun tidak langsung, Perusahaan X sebagai perusahaan yang bergerak dalam bidang TI telah mengimplementasikan sistem CRM (Customer Relationship Management. Implementasi CRM tersebut bertujuan untuk mensinergikan kegiatan pelayanan kepada pelanggan agar tidak saling tumpang tindih dan dapat terkoordinasi dengan baik. Untuk mendukung kesuksesan dan keberlanjutan penggunaan sistem CRM, penelitian ini mengkaji penerimaan pengguna sistem CRM di antara semua karyawan dalam divisi terkait di dalam perusahaan yang berjumlah 141 orang, menggunakan Model TAM (Technology Acceptance Model yang dimodifikasi, yaitu tanpa melibatkan variabel eksternal. Penelitian ini mengkaji penerimaan pengguna berdasarkan empat variabel penyusun Model TAM, yaitu Perceived Ease Of Use (PEOU, Perceived Usefulness (PU, Behavioral Intention (BI, dan Actual Use (AU. Studi membuktikan bahwa diperoleh pengaruh yang positif dan signifikan antara variabel – variabel penyusunnya, yaitu PEOU terhadap PU dan BI, PU terhadap BI, serta BI terhadap AU dengan nilai pengaruh masing – masing adalah 0,43; 0,67; 0,58; dan 0,77. Penelitian ini membuktikan bahwa penerimaan pengguna CRM sangat dipengaruhi oleh faktor manfaat, kemudahan, serta perilaku karyawan dalam menggunakannya.

Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

Science.gov (United States)

... Safe Videos for Educators Search English Español Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth / For ... child outweigh the potential risks. Caring for Your Child After DTaP Immunization Your child may have a ...

12 CFR 19.7 - Good faith certification.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Good faith certification. 19.7 Section 19.7... PROCEDURE Uniform Rules of Practice and Procedure § 19.7 Good faith certification. (a) General requirement... warranted by existing law or a good faith argument for the extension, modification, or reversal of existing...

46 CFR 197.312 - Breathing supply hoses.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Breathing supply hoses. 197.312 Section 197.312 Shipping... GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.312 Breathing supply hoses. (a) Each breathing supply hose must— (1) Have a maximum working pressure that is equal to or exceeds— (i) The maximum...

Evaluation of moisture damage in asphalt concrete with CRM motorcycle tire waste passing #50 sieve size

Science.gov (United States)

Siswanto, Henri; Supriyanto, Bambang; Pranoto, Pranoto; Chandra, Pria Rizky; Hakim, Arief Rahman

2017-09-01

The objective of this experimental research is to evaluate moisture damage in Asphalt Concrete (AC) with Crumb Rubber Modified (CRM) motorcycle tire waste passing #50 and retaining #100 sieve size. Two gradations were used in this research, the first gradation is usual for asphalt concrete base (ACB) and the second gradation is for asphalt concrete wearing course (ACWC). Marshall testing apparatus was used for testing the Marshall specimens. Seven levels of CRM content were used, namely 0%, 0.5%, 1%, 1.5%, 3%, 4.5% and 6% by weight of mixtures. Retained stability represent the level of moisture damage of AC pavement. The result indicates that addition CRM to the AC mixture increases their the stability to a maximum value and subsequent addition decrease the stability. The addition CRM to AC decreases their moisture damage susceptibility. AC with 1% CRM is the best asphalt-CRM mix.

Td Vaccine (Tetanus and Diphtheria): What You Need to Know

Science.gov (United States)

VACCINE INFORMATION STATEMENT Td Vaccine (Tetanus and Diphtheria) What You Need to Know Many Vaccine Information Statements are available in Spanish and other languages. See www. immunize. org/ vis Hojas de ...

Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

Science.gov (United States)

Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

2016-01-01

Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

Directory of Open Access Journals (Sweden)

Francisco A. B. Speranza

2012-09-01

Full Text Available We assessed the IgG levels anti-diphtheria (D-Ab and T cell counts (CD4+ and CD8+ in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART. Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml than HAART-patients (geometric mean of 0.39 IU/ml. The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

Zákaznícky servis ako nástroj CRM

OpenAIRE

Smiková, Lenka

2009-01-01

The bachelor thesis analyzes and assesses the marketing mix of Prague City Apartments, s.r.o. It is focused on functioning of customer service as a part of the concept of Customer Relationship Management (CRM). The analysis is based on theoretical knowledge of marketing of services and CRM and on the importance of customer service in rendition of services, particularly in tourism and hotel industry. The thesis provides, via SWOT analysis, suggestions for improving quality of customer service ...

CRM AS A SUPPORT FOR KNOWLEDGE MANAGEMENT AND CUSTOMER RELATIONSHIP

OpenAIRE

Silvana Toriani; Maria Terezinha Angeloni

2011-01-01

This paper aims to analyze the role of Customer Relationship Management (CRM) as a support for Knowledge Management (KM) and the Customer Relationship Strategy Definition in an Information Technology (IT) Company. This work is based on theories of KM, IT, and Relationship Marketing. Our survey uses a descriptive approach, in which data is gathered by means of content analysis of semi-structured interviews. The study results have shown us that the company implements an effective system for CRM...

Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.

Science.gov (United States)

Csuka, Dorottya; Czirják, László; Hóbor, Renáta; Illes, Zsolt; Bánáti, Miklós; Rajczy, Katalin; Tordai, Attila; Füst, George

2013-07-01

Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population. Copyright © 2013 Elsevier Ltd. All rights reserved.

What Lies behind the Concept of Customer Relationship Management? Discussing the Essence of CRM through a Phenomenological Approach

Directory of Open Access Journals (Sweden)

Cristiane Drebes Pedron

2009-01-01

Full Text Available Several authors and consulting firms show statistics indicating that at least 50% of all CRM projects fail. Some of them attempt to point out a list of factors in order to guarantee successful CRM implementation and application. However, few people (either academics or practitioners attempt to discuss or consider the essence of the idea of CRM. The main goal of this exploratory research is to discuss the CRM essence through a phenomenological approach. This paper assumes that one of the main reasons for CRM failure is the lack of understanding about the true meaning and implication of practices for managing the relationship with customers. Therefore, we need to question the essence of CRM itself and discuss the very concept of relationship. We claim that the idea of CRM involves very serious issues about institutions, roles, power and ethical values that have to be considered. In this article, we attempt to analyze the essence of relationship, trying to go beyond the common meaning of CRM. As the main results of this paper, we offer a critical reflection related to the different faces and aspects of the CRM phenomenon, not only as a matter of IT applications, but also as a strategy and even as an organizational philosophy.

CRM-tietojärjestelmän käyttöopas osana yrityksen asiakkuudenhallintaa : case: Fysioline Oy

OpenAIRE

Ilonen, Mikko

2012-01-01

Tämän opinnäytetyön aiheena on CRM-tietojärjestelmän käyttöopas osana yrityksen asiakkuudenhallintaa. Opinnäytetyön teoriaosuus käsittelee asiakkuudenhallintaa, CRM-tietojärjestelmiä ja CRM:n käyttöönottoa. Työn empiriaosuus muodostuu CRM-tietojärjestelmän käyttöoppaasta. CRM-tietojärjestelmän käyttöopas tehdään kohdeyritys Fysioline Oy:lle. Opinnäytetyön teoriaosuudessa selvitetään vastausta tutkimusongelmaan, miksi yrityksen tulee kiinnittää huomiota asiakkuudenhallintaan ja mitä hyötyä...

La estrategia CRM, una visión 360º del cliente

Directory of Open Access Journals (Sweden)

Ma. Rosa Llamas Alonso

2005-01-01

Full Text Available CRM strategy (customer relationship management is a business philosophy, stemming from relationship marketing that joins strategy and technology, with the objective of creating value for both customers and the company. In this paper we conceptualise this strategy, stressing key issues as well as challenges faced when implementing a CRM system, from different perspectives: business processes, structure, organizational culture and analytical techniques

INFLUENCE OF CUSTOMER VALUES AND SELF-IMAGE CONGRUITY ON CUSTOMER BEHAVIOR-BASED CRM PERFORMANCE

Directory of Open Access Journals (Sweden)

Mandy Loh

2015-10-01

Full Text Available The purpose of this study is to investigate the influence of the key dimensions of customer value (functional value, emotional value, social value, and perceived sacrifice and self-image congruity on customer-behavior based CRM performance. The study also attempts to investigate on the effect of key dimensions of customer value and self-image congruity on customer satisfaction and brand loyalty. The research model for this study was adopts an integrated framework from a previous study, and adds new element into it. This study has chosen to examine the framework in the retail industry, specifically hypermarket in Malaysia, where the adoption of CRM tools is increasing incrementally. The study target on the Generation Y who believed will be the future driver of retail industry. The findings show that perceived sacrifice appears to be a critical customer perceived value in influencing the customer behavior-based CRM performance and customer satisfaction. This study show that brand loyalty would directly influence the customer behavior-based CRM performance. Perceived sacrifice and brand loyalty should be focused when trying to improve the performance of CRM.

Analysis of the intermediate stage in the heavy ion interactions of 208Pb+197Au and 197Au+197Au

International Nuclear Information System (INIS)

Nasir, Tabassum; Khan, E.U.; Baluch, J.J.; Qureshi, I.E.; Sajid, M.; Shahzad, M.I.

2008-01-01

Two different projectiles 208 Pb and 197 Au at the same energy (11.67MeV/u) have been bombarded on 197 Au target to study heavy ion interactions using mica as a passive detector. In this paper we present results on the study of energy damping and time scale of the existence of di-nuclear composite system in the intermediate reaction step. The plots of Q-values as well as reaction cross sections in various angular bins of scattering angles suggest that K.E. damping was complete and dynamic equilibrium was established between the first and second reaction steps. The time scale of this duration was also determined

Fatal diphtheria myocarditis in a 3-year-old girl-related to late availability and administration of antitoxin?

NARCIS (Netherlands)

Van Damme, Karlijn; Peeters, Natasja; Jorens, Philippe G; Boiy, Tine; Deplancke, Marjan; Audiens, Hilde; Wojciechowski, Marek; De Dooy, Jozef; Te Wierik, Margreet; Vlieghe, Erika

2017-01-01

Sporadic cases of diphtheria are very rare throughout Europe. A 3-year-old incompletely vaccinated girl was admitted with pharyngotonsillitis caused by diphtheria. On day 9 of her illness, renal and cardiac failure with a third-degree AV-block occurred. Unfortunately, she died within 36 h of

Selective Neoplasm Localization with Mercury-197 Neohydrin; Localisation Selective de Neoplasmes a l'aide de la Neohydrine Marquee avec {sup 197}hg; Obnaruzhenie opukholej s pomoshch'yu neogidrina, mechennogo rtut'yu-197; Localizacion Selectiva de Neoplasmas con Neohidrina - {sup 197}hg

Energy Technology Data Exchange (ETDEWEB)

Sodee, D. B. [Doctors Hospital and Renner Clinic Foundation, Cleveland Heights, OH (United States)

1964-10-15

Hg{sup 197} a low-energy X- and gamma- ray emitter (2.7-d half-life, 69-keV conversion X-rays, 77-keV gamma-rays) was tested as a scanning agent in a large series of patients. Five hundred patients suspected of neuro-surgical disease were scanned with Hg{sup 197}-Neohydrin. Utilizing photoscanning techniques that brought out vascular lesions as well as tumours, this procedure had a 96% correlation with the final diagnostic evaluation. This screening procedure was done before all other diagnostic tests. As an outgrowth of this brain-scanning procedure, we have found localization of Hg{sup 197}-Neohydrin in lymphomas as well as in carcinomas. There seems to be selective deposition of the radioactive substance intercellularly. Areas of increased uptake of radioactivity can easily be delineated with standard commercial scanners. Hg{sup 197}-Neohydrin was also found to be useful as a screening agent in thc differentiation of eye tumours in a series of 88 patients and recently this low-energy radiopharmaceutical was found to concentrate in naso- pharangeal tumours which could then be delineated by photoscanning. The diagnostic dose of Hg{sup 197}-Neohydrin for brain scanning delivers a radiation dose of 3 rad to the kidneys as compared to the 70 rad delivered to the kidneys by that of Hg{sup 203}-Neohydrin. The high counting efficiency and ease of collimation of Hg{sup 197} make this isotope far better for scanning purposes than all other standard diagnostic scanning agents. (author) [French] Le mercure-197, emetteur de rayons X et de rayons gamma de faible energie (periode de 65 h, rayons X de 69 keV, rayons gamma de 77 keV), a ete essaye comme agent d'exploration scintigraphique sur un grand nombre de patients. On a utilise la neohydrine marquee avec {sup 197}Hg pour la scintigraphie de 500 cas de neurochirurgie. Par des procedes de photoscintigraphie qui permettaient la visualisation des lesions vasculaires aussi bien que celle de tumeurs, on a obtenu des resultats

NES consensus redefined by structures of PKI-type and Rev-type nuclear export signals bound to CRM1.

Science.gov (United States)

Güttler, Thomas; Madl, Tobias; Neumann, Piotr; Deichsel, Danilo; Corsini, Lorenzo; Monecke, Thomas; Ficner, Ralf; Sattler, Michael; Görlich, Dirk

2010-11-01

Classic nuclear export signals (NESs) confer CRM1-dependent nuclear export. Here we present crystal structures of the RanGTP-CRM1 complex alone and bound to the prototypic PKI or HIV-1 Rev NESs. These NESs differ markedly in the spacing of their key hydrophobic (Φ) residues, yet CRM1 recognizes them with the same rigid set of five Φ pockets. The different Φ spacings are compensated for by different conformations of the bound NESs: in the case of PKI, an α-helical conformation, and in the case of Rev, an extended conformation with a critical proline docking into a Φ pocket. NMR analyses of CRM1-bound and CRM1-free PKI NES suggest that CRM1 selects NES conformers that pre-exist in solution. Our data lead to a new structure-based NES consensus, and explain why NESs differ in their affinities for CRM1 and why supraphysiological NESs bind the exportin so tightly.

Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

Science.gov (United States)

Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

2014-09-01

This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

APLIKASI e-CRM BERBASIS WEB PADA RUMAH SAKIT

Directory of Open Access Journals (Sweden)

Luthfie Hawari

2015-04-01

Full Text Available The purpose of this research is to design an e-CRM application that serves as an Internet-based services for customers or patients to provide information needed by the customer or patient without being limited by distance or time. With the increased competition and technological development is rapidly increasing, then every hospital strives to provide the best service to customers, or patients with a hope to get customers or new patients and retain old customers or patients. One solution that appears is electronic-Customer Relationship Management (e-CRM is applied by using the Internet and SMS technology. The method used is waterfall method which includes, analysis and systems engineering, requirements analysis, design, programming, testing and maintenance. This application was built using the programming language PHP and MySQL to design database.Hasil achieved from the writing of this research is the application of customer service or patient that provides information (schedule doctor's office, clinic services, patient medical records, consultation and sms notifications check-up, provide member features pages to provide personalized services to customers or patients. With the application of e-CRM customer service Internet-based hospital is expected to maintain good long-term relationship with its customers.

Diphtheria in a 7-year-old child in north-eastern Nigeria - management in a resource-poor setting.

Science.gov (United States)

Goni, Baba Waru; Gofama, Mustapha M; Lawan, Gana M; Haruna, Yusuph; Bukar, Bakki; Musa, Kida I

2014-01-01

We report a case of a 7-year-old unimmunized child who presented with a 2 week history of nasal quality speech, hoarseness of the voice, regurgitation of feeds, and unstable gait. He had a previous history of fever, severe sore throat and bloody nasal discharge. A throat swab was negative for Corynebacterium diphtheria; however, he had received antibiotics at a primary care clinic prior to presentation. A clinical diagnosis of diphtheria with neurologic complication was made and the child was started on oral erythromycin, nasogastric tube feeding and daily physiotherapy, following which he improved. We did not prescribe diphtheria anti-toxin because of its unavailability.

Exploring the e-CRM – e-customer- e-loyalty nexus: a Kenyan commercial bank case study

Directory of Open Access Journals (Sweden)

Oumar Timothy K.

2017-12-01

Full Text Available This article scaffolds on customer relationship management (CRM theory and explores the association between electronic CRM (e-CRM and electronic customer’s (e-customer electronic loyalty (e-loyalty in the banking sector. By using a survey design, data was collected from a convenience sample of customers of a major Kenyan commercial bank, and analysed using structural equation and multiple regression modelling. The findings reveal that there is a positive relationship between e-CRM and e-customers’ loyalty. The e-CRM features at all three stages of an electronic transaction cycle namely, pre-service, during-service and after-service, significantly influence the e-customers’ loyalty in the banking sector. Thus, to capitalize on the range of benefits that emanate from the use of e-CRM, continued review and enhancement of marketing strategies is needed, so as to achieve e-customers’ loyalty particularly, at the post-service stage. Kenyan commercial bank managers should focus on customer satisfaction specifically at post-service stage, to increase their ecustomers’ loyalty.

A Rationally Designed TNF-α Epitope-Scaffold Immunogen Induces Sustained Antibody Response and Alleviates Collagen-Induced Arthritis in Mice.

Directory of Open Access Journals (Sweden)

Li Zhang

Full Text Available The TNF-α biological inhibitors have significantly improved the clinical outcomes of many autoimmune diseases, in particular rheumatoid arthritis. However, the practical uses are limited due to high costs and the risk of anti-drug antibody responses. Attempts to develop anti-TNF-α vaccines have generated encouraging data in animal models, however, data from clinical trials have not met expectations. In present study, we designed a TNF-α epitope-scaffold immunogen DTNF7 using the transmembrane domain of diphtheria toxin, named DTT as a scaffold. Molecular dynamics simulation shows that the grafted TNF-α epitope is entirely surface-exposed and presented in a native-like conformation while the rigid helical structure of DTT is minimally perturbed, thereby rendering the immunogen highly stable. Immunization of mice with alum formulated DTNF7 induced humoral responses against native TNF-α, and the antibody titer was sustained for more than 6 months, which supports a role of the universal CD4 T cell epitopes of DTT in breaking self-immune tolerance. In a mouse model of rheumatoid arthritis, DTNF7-alum vaccination markedly delayed the onset of collagen-induced arthritis, and reduced incidence as well as clinical score. DTT is presumed safe as an epitope carrier because a catalytic inactive mutant of diphtheria toxin, CRM197 has good clinical safety records as an active vaccine component. Taken all together, we show that DTT-based epitope vaccine is a promising strategy for prevention and treatment of autoimmune diseases.

Immunity against diphtheria and tetanus in human immunodeficiency virus-infected Danish men born 1950-59

DEFF Research Database (Denmark)

Kurtzhals, J A; Kjeldsen, K; Heron, I

1992-01-01

To evaluate the possible need for vaccination against diphtheria and tetanus of patients infected with the human immunodeficiency virus (HIV), antibodies were measured in blood samples from 78 Danish HIV-infected men, born 1950-59, who could be expected to have received primary vaccination before...... they contracted the HIV infection. No patients (95% confidence interval: 0-4) had tetanus antibodies below the protective level, whereas 24 of the 78 patients (16-33) were unprotected against diphtheria. In the background population of the same age group and sex, 5% and 10% have been found unprotected against...... tetanus and diphtheria, respectively. No relationship between disease stages and antibody levels could be found. Neither was there any difference between patients with normal and reduced numbers of CD4+ lymphocytes. From 25 patients two blood samples were taken at an interval of at least one year. Anti...

Social CRM -kehitysprojekti

OpenAIRE

Pohjoismäki, Lauri

2017-01-01

Työn tavoitteena oli löytää ratkaisu digitaaliseen markkinointiin erikoistuneen yrityksen ongelmaan ajankäytöstä sosiaalisen median hallinnassa. Yrityksen nykyisellä asiakasmäärällä ei ole enää kannattavaa ajankäytännöllisesti hallita jokaista asiakasyrityksen sosiaalisen median tiliä erikseen, vaan niille on löydettävä keskitetty hallintaympäristö. Työssäni käsiteltiin erilaisia Social CRM -sovelluksia sekä pohdittiin niiden käyttöarvoa ja soveltuvuutta yrityksen käyttöön. Työ myös sivua...

Field test of coordinated ramp metering (CRM).

Science.gov (United States)

2017-03-15

This project has focused on field implementation and testing of a Coordinated Ramp Metering (CRM) algorithm at California State Route 99 : Northbound corridor in Sacramento between Calvine Road and the SR50 interchange after 12th Ave. It is a 9 mile ...

A case of respiratory toxigenic diphtheria: contact tracing results and considerations following a 30-year disease-free interval, Catalonia, Spain, 2015.

Science.gov (United States)

Jané, Mireia; Vidal, Maria José; Camps, Neus; Campins, Magda; Martínez, Ana; Balcells, Joan; Martin-Gomez, Maria Teresa; Bassets, Gloria; Herrera-León, Silvia; Foguet, Anton; Maresma, Mar; Follia, Nuria; Uriona, Sonia; Pumarola, Tomàs

2018-03-01

In May 2015, following a 30-year diphtheria-free interval in Catalonia, an unvaccinated 6-year-old child was diagnosed with diphtheria caused by toxigenic Corynebacterium diphtheriae . After a difficult search for equine-derived diphtheria antitoxin (DAT), the child received the DAT 4 days later but died at the end of June. Two hundred and seventeen contacts were identified in relation to the index case, and their vaccination statuses were analysed, updated and completed. Of these, 140 contacts underwent physical examination and throat swabs were taken from them for analysis. Results were positive for toxigenic C. diphtheriae in 10 contacts; nine were asymptomatic vaccinated children who had been in contact with the index case and one was a parent of one of the nine children. Active surveillance of the 217 contacts was initiated by healthcare workers from hospitals and primary healthcare centres, together with public health epidemiological support. Lack of availability of DAT was an issue in our case. Such lack could be circumvented by the implementation of an international fast-track procedure to obtain it in a timely manner. Maintaining primary vaccination coverage for children and increasing booster-dose immunisation against diphtheria in the adult population is of key importance.

Pengaruh Customer Relationship Management (CRM) Terhadap Customer Satisfaction Dan Customer Loyalty Pada Pelanggan Sushi Tei Surabaya

OpenAIRE

Chandra Dewi, Ayu Abriyanti

2015-01-01

Manajemen hubungan pelanggan (CRM) merupakan bagian dari strategi pemasaran untuk memuaskan, dan menjaga loyalitas pelanggan. CRM dapat menjadi stimulus terhadap kepuasan dan loyalitas konsumen, bahwa CRM yang tepat berdampak pada kepuasan dan selanjutnya akan mempengaruhi loyalitas pelanggan. Populasi penelitian adalah seluruh pelanggan Sushi Tei Surabaya, dan sampel sebanyak 86 pelanggan Sushi Tei yang dipilih dengan teknik purposive sampling, dan teknik analisis yang digunakan adalah Gener...

Collaborative study for establishment of the European Pharmacopoeia BRP batch 1 for diphtheria toxin.

Science.gov (United States)

Sesardic, D; Prior, C; Daas, A; Buchheit, K H

2003-07-01

A stable liquid candidate Biological Reference Preparation (BRP) for diphtheria toxin was prepared in peptone buffer (nominal content of diphtheria toxin: 1 Lf/ml, 0.4 micro g/ml), filled in ampoules (filling volume: 1 ml) and characterised in a collaborative study. The toxin is to be used in the test "Absence of toxin and irreversibility of toxoid" as described in the current European Pharmacopoeia (Ph. Eur.) monograph Diphtheria Vaccine (Adsorbed) (2002:0443). Eleven laboratories assessed the specific activity of the preparation by in vivo and in vitro assays. The material is assumed to have satisfactory stability with a calculated predicted loss of activity of LD( 50)/ml (lethal challenge) and >75 000 Lr/Lf (intradermal challenge). The candidate BRP was successfully used in nine laboratories and confirmed suitable for use in the Vero cell test for "Absence of toxin and irreversibility of toxoid" as described in the Ph. Eur. monograph 2002:0443; i.e., concentrations of 5 x 10( -5) Lf/ml and below caused cytotoxic effects in the Vero cell test. Due to its liquid nature, the stability of the material will be monitored at regular intervals and preparation of a stable freeze-dried formulation will be considered for long-term use. Additional studies will be performed to confirm suitability of this BRP for other applications. The candidate BRP was adopted as the Ph. Eur. reference material for Diphtheria Toxin Batch 1 by the Ph. Eur. Commission at its session in March 2003.

In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine.

Science.gov (United States)

Carlin, Gunnar; Viitanen, Eila

2005-05-25

We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid.

Handelsbankens användande av CRM -Är det lönsamt?

OpenAIRE

Salman Kanbar, Ahmad

2012-01-01

Frågeställning: På vilket sätt används CRM av Handelsbanken och hur påverkar det bankens lönsamhet? Syfte: Syftet med detta arbete är att kunna öka kunskapen om hur Handelsbanken tillämpar CRM och för att undersöka om användandet av CRM i bankens verksamhet är lönsamt eller inte. Metod: För att svara på studiens syfte blev en intervju utförd med Handelsbanken. Ännu en anledning till varför en intervju gjordes var på grund av att det var nödvändigt för att få det primärdata som behövdes och fö...

Developments and Trends in CRM

OpenAIRE

Niþu Claudiu Valentin; Tileagã Cosmin Virgil; .tefanica Virginia

2012-01-01

CRM is an essential business strategy that integrates internal processes and functions with external networks, to create and deliver customer value target, given the profit. It is based on high quality customer data and on information technology. (Buttle, 2006). This definition highlights the bivalent customer relationship management scope, respectively creating and delivering value to both customers in target segments and for the organization. Also, an advantage of the definition is that it ...

Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age.

Science.gov (United States)

Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor

2016-01-01

We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.

Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

Directory of Open Access Journals (Sweden)

M.H. Sonobe

2007-01-01

Full Text Available A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test. In this study, the serum titers (values between 1.0 and 19.5 IU measured by a modified TOBI test (Modi-TOBI test and toxin neutralization assays were correlated (P < 0.0001. Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001 and for diphtheria (r² = 0.93, P < 0.0001 between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality?

DEFF Research Database (Denmark)

Aaby, Peter; Ravn, Henrik; Fisker, Ane B

2016-01-01

BACKGROUND: Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review...

Implementing a CRM in a gear reducers manufacturing and assembling company

OpenAIRE

Subirà Masana, Gerard

2017-01-01

A Customer Relationship Management, known as CRM for its acronym in English, is not a new philosophy of organizational work, but the result of joining ancient techniques of small commercial establishments with information technology. The maximum goal of CRM is to have, at any time, all the information about any client, either to meet their needs or to obtain market researches which allow to obtain better commercial strategies. The purpose of this document is to collect all the steps undertake...

Dynamic changes of horse serum T-globulin immunization with snake venoms, tetanus and diphtheria toxoids.

Science.gov (United States)

Lee, H F; Lee, J D; Lee, Y C

1979-12-01

In course of immunizing horses with snake venoms, tetanus and diphtheria toxoids, a new serum component, T-globulin, was formed and migrated between the beta- and gamma-globulins. The T-globulin content was parallel with the antibody titre after the middle course of immunization. There were many components in snake antivenin and T-globulin was composed of most of those components. The components of diphtheria T-globulin were the same as those of crude antitoxin and tetanus T-globulin except one precipitin.

CRM system benefits : A case study of banking sector

OpenAIRE

Murrawat, Adnan; Nasershariati, Foroozan

2011-01-01

Seminar Date: 05-11-2011 Level: Master Thesis in Information Technology Management,   15ECTS Institution: School of Sustainable Development of Society and Technology, Malardalen University Authors: Adnan Murrawat Khan [amt1001]         Foroozan Nasershariati [fni10002]                                              Title: CRM system benefits, a case study of banking sector Supervisor: Dr Ole Liljefors Problem statement: Customer relationship management (CRM) systems have been adopted to have b...

THE INFLUENCE OF CUSTOMER RELATIONSHIP MANAGEMENT (CRM ON CUSTOMER LOYALTY IN JW MARRIOTT HOTEL SURABAYA

Directory of Open Access Journals (Sweden)

Fransisca Andreani

2012-01-01

Full Text Available Customer Relationship Management (CRM merupakan salah satu strategi untuk mempertahankan pelanggan. Dengan terjalinnya hubungan yang erat diharapkan pelanggan menjadi loyal pada perusahaan. Penelitian ini bertujuan untuk mengetahui pengaruh CRM terhadap loyalitas pelanggan di Hotel JW Marriott Surabaya dengan teknik analisis regresi linier berganda. Hasil penelitian menunjukkan bahwa CRM yang meliputi financial benefits, social benefits dan structural ties berpengaruh positif dan signifikan terhadap loyalitas pelanggan Hotel JW Marriott Surabaya. Faktor yang berpengaruh dominan terhadap loyalitas pelanggan Hotel JW Marriott Surabaya adalah structural ties.

Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study.

Science.gov (United States)

Swart, E M; van Gageldonk, P G M; de Melker, H E; van der Klis, F R; Berbers, G A M; Mollema, L

2016-01-01

To evaluate the National Immunisation Programme (NIP) a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC) areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier. In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS) and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml) was used as minimum protective level. In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (pdiphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11) of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations) without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups. The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community after introduction in the Netherlands has not disappeared, despite national long-term high vaccination coverage.

CRM AS A SUPPORT FOR KNOWLEDGE MANAGEMENT AND CUSTOMER RELATIONSHIP

Directory of Open Access Journals (Sweden)

Silvana Toriani

2011-05-01

Full Text Available This paper aims to analyze the role of Customer Relationship Management (CRM as a support for Knowledge Management (KM and the Customer Relationship Strategy Definition in an Information Technology (IT Company. This work is based on theories of KM, IT, and Relationship Marketing. Our survey uses a descriptive approach, in which data is gathered by means of content analysis of semi-structured interviews. The study results have shown us that the company implements an effective system for CRM, in which the system users transform data into information and knowledge in order to support decision-making and strategy definition.

Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

Science.gov (United States)

Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter

2012-01-01

In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.

Evaluation of cross sections for 197Au(n,3n) and 197Au(n,4n) reactions from threshold to 50 MeV

International Nuclear Information System (INIS)

Yu Baosheng; Shen Qingbiao; Cai Dunjiu

1994-01-01

The measured data of cross sections for 197 Au(n,3n) and 197 Au(n,4n) reactions were collected and analysed. The theoretical calculations of above mentioned reactions were carried out to predict the data in higher energy region. The sets of cross sections for 197 Au(n,3n) and 197 Au(n,4n) reactions from threshold to 50 MeV were recommended on the basis of the experimental and calculated data. (2 figs)

CRM DEVELOPMENT IN HOSPITALITY COMPANIES FOR THE PURPOSE OF INCREASING THE COMPETITIVENESS IN THE TOURIST MARKET

Directory of Open Access Journals (Sweden)

Slobodan Ivanovic

2011-06-01

Full Text Available CRM as a trend in business and business philosophy consists of a series of complex and diverse business resources such as: modern technological resources, information resources, human resources and all other procedural resources which serve to improve services to end user and customer.Tourism as a service industry which business is based on selling services, has found great benefits and advantages in using CRM. Different kinds of CRM applications and systems have become extremely popular in all sectors. Thus, in the tourism sector, CRM has become one of the most important strategy in attracting and increasing tourist arrivals, in filling the tourist facilities and in satisfying the needs of guests.The main goals of CRM are to attract tourists, to meet a maximum of tourists (a new guarantee of return and achieve the most efficient promotion, increase the number of tourists and achieve customer loyalty. It enables more efficient marketing and sales and it improves the overall tourism industry and services aimed at tourists and their preferences. Implementation of CRM systems is very demanding and requires commitment at all levels of the company. Very big problem is the integration of CRM systems with existing information systems in the enterprise. It is often impossible to implement without the use of qualified personnel and software that has the task of bridging the gulf between the CRM and existing information systems to create an integrated system. It is desirable that the companies have been devoting increased funding for implementation of new technologies and that systems, in a short period of time, can realize a return on investment and greatly improve the business performance of enterprises. CRM gives the expected results only if it is fully integrated strategically and operationally in the business and in the information system of tourist enterprise. The fact is that this process and business philosophy will become important in the future

Energy dependence of collective flow of neutrons and charged particles in 197Au+197Au collisions

International Nuclear Information System (INIS)

Blaich, T.; Freiesleben, H.; Holzmann, R.; Keller, J.G.; Prokopowicz, W.; Schuetter, C.; Wajda, E.; Zude, E.

1994-01-01

Our contribution focusses on one particular aspect of collective flow of nuclear matter: the so-called ''squeeze-out'', i.e. the preferential emission of mid-rapidity particles perpendicular to the reaction plane. The data were taken for the system 197 Au + 197 Au at 400, 600 and 800 MeV/u. We cover two topics, the comparison of neutrons and protons, and the bombarding energy dependence of the neutrons' squeeze-out. (orig.)

Effect of moisture and freeze-thaw on mechanical properties of CRM asphalt mixture

Energy Technology Data Exchange (ETDEWEB)

Kim, Nak-Seok; Cho, Kee-Ju [Kyonggi University, Suwon(Korea)

2000-06-30

This paper presents the experimental test results on moisture and freeze-thaw resistance of hot mix crumb rubber modified (CRM) asphalt concrete mixture. To compare the differences in mechanical properties of conventional and CRM asphalt concretes, various tests were conducted under different moisture conditions and freeze-thaw cycles. Marshall mix design was also performed to determine the optimum asphalt contents for the both asphalt concrete mixtures. Test results revealed that the moisture and freeze-thaw resistance of CRM asphalt mixture was superior to the conventional asphalt concrete. As a result, it is considered that the utilization of waste tires in asphalt pavements has the potential of minimizing the damage due to the moisture and freeze-thaw. (author). 9 refs., 4 tabs., 8 figs.

Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

Science.gov (United States)

Ang, L W; James, L; Goh, K T

2016-03-01

In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P < 0.0005). It may be of value to consider additional vaccination efforts to protect older adults at higher risk for exposure against diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

MODELING THE CORROSION OF HIGH-LEVEL WASTE CONTAINERS CAM-CRM INTERFACE

International Nuclear Information System (INIS)

JOSEPH C. FARMER, PETER J. BEDROSSIAN, R. DANIEL MCCRIGHT

1998-01-01

A key component of the Engineered Barrier System (EBS) being designed for containment of spent-fuel and high-level waste at the proposed geological repository at Yucca Mountain, Nevada is a two-layer canister. In this particular design, the inner barrier is made of a corrosion resistant material (CRM) such as Alloy 625 or C-22, while the outer barrier is made of a corrosion-allowance material (CAM) such as carbon steel or Monel400. Initially, the containers will be hot and dry due to the heat generated by radioactive decay. However, the temperature will eventually drop to levels where both humid air and aqueous phase corrosion will be possible. As the outer barrier is penetrated, uniform corrosion of the CRM will be possible in exfoliated areas. The possibility for crevice formation between the CAM and CRM will also exist. In the case of either Alloy 625 or C-22, a crevice will have to form before significant penetration of the CRM can occur. Crevice corrosion of the CRMs has been well documented. Lillard and Scully have induced crevice corrosion in Alloy 625 during exposure to artificial sea water. Jones and Wilde have prepared simulated crevice solutions of FeCl 2 , NiCl 2 and CrCl 3 , and measured substantial pH suppression. Asphahani measured the dissolution rates of Alloys 625 and C-22 in such artificial crevice solutions at various temperatures. Others have observed no significant localized attack in less severe environments

46 CFR 197.454 - First aid and treatment equipment.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false First aid and treatment equipment. 197.454 Section 197.454 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE OCCUPATIONAL SAFETY AND... Equipment § 197.454 First aid and treatment equipment. The diving supervisor shall ensure that medical kits...

Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils.

Science.gov (United States)

Araman, Can; Thompson, Robert E; Wang, Siyao; Hackl, Stefanie; Payne, Richard J; Becker, Christian F W

2017-09-01

The prion protein (PrP) is an N -glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP Sc ) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP C ) into PrP Sc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.

Pharmacological inhibition of heparin-binding EGF-like growth factor promotes peritoneal angiogenesis in a peritoneal dialysis rat model.

Science.gov (United States)

Li, Zhenyuan; Yan, Hao; Yuan, Jiangzi; Cao, Liou; Lin, Aiwu; Dai, Huili; Ni, Zhaohui; Qian, Jiaqi; Fang, Wei

2018-04-01

Molecular mechanisms of peritoneal dialysis (PD) ultrafiltration failure, peritoneal neo-angiogenesis, and fibrosis remain to be determined. We aimed to determine the role of heparin-binding EGF-like growth factor (HB-EGF) inhibition on angiogenesis of peritoneal membrane in a PD rat model. 32 male Wistar rats were assigned into (1) control group; (2) uremic non-PD group: subtotal nephrectomy-induced uremic rats without PD; (3) uremic rats subjected to PD: uremic rats that were dialyzed with Dianeal ® for 4 weeks; (4) CRM 197 group: dialyzed uremic rats were supplemented with CRM197, a specific HB-EGF inhibitor. Peritoneal transport function was examined by peritoneal equilibration test. Expression of HB-EGF and EGFR in peritoneal samples were examined by real-time PCR, immunohistochemical staining, and western blot. Progressive angiogenesis and fibrosis were observed in uremic PD rats, and there were associated with decreased net ultrafiltration (nUF), increased permeability of peritoneal membrane, and reduced expression of HB-EGF and EGFR protein and mRNA in uremic PD rats compared to uremic non-PD or control groups (both p CRM197 significantly induced peritoneal membrane permeability, decreased nUF, increased higher vessel density, and reduced pericyte count compared to that of uremic PD rats. The levels of HB-EGF and EGFR expression negatively correlated with vessel density in peritoneal membrane (both p < 0.001). PD therapy was associated with peritoneal angiogenesis, functional deterioration, and downregulation of HB-EGF/EGFR. Pharmacological inhibition of HB-EGF promoted PD-induced peritoneal angiogenesis and fibrosis and ultrafiltration decline, suggesting that HB-EGF downregulation contributes to peritoneal functional deterioration in the uremic PD rat model.

46 CFR 197.314 - First aid and treatment equipment.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false First aid and treatment equipment. 197.314 Section 197... HEALTH STANDARDS GENERAL PROVISIONS Commercial Diving Operations Equipment § 197.314 First aid and... consists of— (i) Basic first aid supplies; and (ii) Any additional supplies necessary to treat minor trauma...

Differences in serum thyroglobulin measurements by 3 commercial immunoradiometric assay kits and laboratory standardization using Certified Reference Material 457 (CRM-457).

Science.gov (United States)

Lee, Ji In; Kim, Ji Young; Choi, Joon Young; Kim, Hee Kyung; Jang, Hye Won; Hur, Kyu Yeon; Kim, Jae Hyeon; Kim, Kwang-Won; Chung, Jae Hoon; Kim, Sun Wook

2010-09-01

Serum thyroglobulin (Tg) is essential in the follow-up of patients with differentiated thyroid carcinoma (DTC). However, interchangeability and standardization between Tg assays have not yet been achieved, even with the development of an international Tg standard (Certified Reference Material 457 [CRM-457]). Serum Tg from 30 DTC patients and serially diluted CRM-457 were measured using 3 different immunoradiometric assays (IRMA-1, IRMA-2, IRMA-3). The intraclass correlation coefficient (ICC) method was used to describe the concordance of each IRMA to CRM-457. The serum Tg measured by 3 different IRMAs correlated well (r > .85, p CRM-457, showed the best ICC (p(1) = .98) for the CRM-457. Hospitals caring for patients with DTC should either set their own cutoffs for IRMAs for Tg based on their patient pools, or adopt IRMAs standardized to CRM-457 and calibrate their laboratory using CRM-457.

Laser memory (hologram) and coincident redundant multiplex memory (CRM-memory)

International Nuclear Information System (INIS)

Ostojic, Branko

1975-01-01

It is shown that besides the memory which remembers the object by memorising of the phases of the interferenting waves of the light (i.e. hologram) it is possible to construct the memory which remembers the object by memorising of the phases of the interferenting impulses (CFM-memory). It is given the mathematical description of the memory, based on the experimental model. Although in the paper only the technical aspect of CRM memory is given. It is mentioned the possibility that the human memory has the same principle and that the invention of CRM memory is due to cybernetical analysis of the system human eye-visual cortex

Preparation and provisional certification of NBL Spectrographic Impurity Standards, CRM 123 (1-7) and 124 (1-7)

International Nuclear Information System (INIS)

Santoliquido, P.M.

1983-09-01

This report describes the design, production, and provisional certification of two new certified reference materials (CRMs): CRM No. 123 (1-7), U 3 O 8 containing 18 trace elements, and CRM No. 124 (1-7), U 3 O 8 containing 24 trace elements. The elements to be included and concentrations to be used were decided on the basis of information gathered from users of a previous CRM of this type, CRM No. 98 (1-7). The new CRMs were prepared by the addition of trace elements to high purity U 3 O 8 . Provisional certification was accomplished by an interlaboratory program in which four different laboratories analyzed the materials by carrier distillation dc arc emission spectrography

Implantación CRM en la FAS (Fundació Autònoma Solidària)

OpenAIRE

Cuevas Mayo, Ricart

2015-01-01

El propósito de este documento es el de consignar detalladamente la implantación de un CRM (Customer Relationship Management) en la Fundación Autònoma Solidària (FAS). El CRM se ha llevado a cabo por el proyecto SinergiaCRM a partir de una iniciativa de la Asociación SinergiaTIC, entidad sin ánimo de lucro, cuya misión es favorecer el desarrollo colaborativo de herramientas tecnológicas adaptadas a las necesidades del Tercer Sector. En concreto mis funciones han sido las de unificar todos los...

A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

Science.gov (United States)

Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

2013-10-21

Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

46 CFR 197.456 - Breathing supply hoses.

Science.gov (United States)

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Breathing supply hoses. 197.456 Section 197.456 Shipping....456 Breathing supply hoses. (a) The diving supervisor shall insure that— (1) Each breathing supply....5 times its maximum working pressure; (2) Each breathing supply hose assembly, prior to being placed...

NUHOMS registered - MP197 transport cask

International Nuclear Information System (INIS)

Shih, P.; Sicard, D.; Michels, L.

2004-01-01

The NUHOMS registered -MP197 cask is an optimized transport design which can be loaded in the spent fuel pool (wet loading) or loaded the canister from the NUHOMS concrete modules at the ISFSI site. With impact limiters attached, the package can be transported within the states or world-wide. The NUHOMS registered -MP197 packaging can be used to transport either BWR or PWR canisters. The NUHOMS registered -MP197 cask is designed to the ASME B and PV Code and meets the requirements of Section III, Division 3 for Transport Packaging. The cask with impact limiters has undergone drop testing to verify the calculated g loadings during the 9m drops. The test showed good correlation with analytical results and demonstrate that the impact limiters stay in place and protect the package and fuel during the hypothetical accidents

Meeting the needs of customers with health CRM.

Science.gov (United States)

Phillips, Jon; Panchal, Samir

2002-01-01

Customer relationship management (CRM) is a business strategy, supported by applications and technologies, that can fundamentally transform how healthcare delivery organizations manage patient and physician interactions, reduce cost, improve customer-facing processes, drive market and revenue growth, and manage regulatory compliance processes.

Diphtheria toxin-induced channels in Vero cells selective for monovalent cations

International Nuclear Information System (INIS)

Sandvig, K.; Olsnes, S.

1988-01-01

Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of 45 Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+, K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed

Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department

Science.gov (United States)

Zibners, Lara

2017-02-01

Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted.

An investigation on relationship between CRM and organizational learning through knowledge management: A case study of Tehran travel agency

Directory of Open Access Journals (Sweden)

Mirza Hasan Hosseini

2013-03-01

Full Text Available Customer relationship management (CRM plays essential role on the success of many business units. CRM integrates necessary data from internal and external sources to assist managers and employees for business development. This paper attempts to analyze relationship between CRM, organizational learning, and knowledge management. Research population includes travel agencies in Tehran, Iran and their manager are considered for the purpose of this study. This research has four variables 1- Successful implementation of KM, 2- Organizational learning, 3- customer orientation, and 4- information share with customers. The preliminary results of this survey indicate that any development of CRM will significantly contribute relative efficiency of this travel agency. The results also indicate that there is a meaningful relationship among components of CRM including organizational learning, and knowledge management in this travel agency.

Appraisal of CRM implementation as business strategy option in times of recession: The role of perceived value and benefits

Directory of Open Access Journals (Sweden)

Chrysa

2018-02-01

Full Text Available The present work investigates Customer Relationship Management (CRM implementation and performance during the fiscal crisis in Greece based on an appropriate questionnaire. All acquired responses using the questionnaire are suitably analysed using advanced statistical techniques, and show that Greek companies employ CRM, harvesting many of its benefits. Specifically, survey results show that most companies are satisfied by the implementation of CRM strategy and seem to recognize the vital strategic role of CRM in business performance and competitive advantage, despite the fiscal crisis. The benefits identified and interrelated concern business processes, customer loyalty, cost reduction, organizational and HR alignment, customer service and customer e-service. Finally, this work proposes a model relating CRM implementation and performance in Greece with respect to the four perspectives of Balanced Scorecard (BSC.

Souvislost mezi řízením vztahů k zákazníkům (CRM a tržní orientací (MO a vliv velikosti podniku a typu trhu na CRM a MO

Directory of Open Access Journals (Sweden)

Daniela Frejková

2014-03-01

Full Text Available Purpose of the article: This paper is concerned with Market Orientation (MO and Customer Relationship Management (CRM. These two topics have been frequently explored in the field of corporate management and marketing. Nevertheless, these two concepts are still analyzed separately in the literature. This article explains why these concepts are interdependent and sets the degree of dependence of these concepts. It also finds out whether the level of MO and CRM is dependent on company size or the type of market. Methodology/methods: This article has been prepared based on the analysis of secondary and primary sources. The primary research was conducted on a sample of 29 completed questionnaires provided by firms from the aerospace field in the Czech Republic. The level of CRM and MO was determined for each company and a statistical verification was conducted. Scientific aim: One aim of this article is to reveal the interconnections between MO and CRM. Other aim is to determine whether CRM and MO are affected by the size of the company and whether they depend on the type of market (business-to-business, i.e. B2B or business-to-customer, i.e. B2C. Findings: Findings of this article are new information in this area. The data strongly support the proposition that MO is interconnected with CRM, while no dependence on the size of the company or the type of market has been confirmed. Conclusions: This research supports the opinion that MO and CRM are appropriate for each of the researched type of the company (under certain conditions. The findings must be considered within the limitations of this study. Conclusions for the whole business may be drawn after the comparison of experiences across business sectors from different countries.

EFFICIENCY OF RECOMBINANT TNF-BINDING PROTEIN FROM VARIOLA VIRUS IN A MODEL OF COLLAGEN-INDUCED ARTHRITIS

Directory of Open Access Journals (Sweden)

D. D. Tsyrendorzhiev

2013-01-01

Full Text Available Abstract. This paper presents the results of the research on the effectiveness of recombinant TNF-binding protein of variola virus (VARV-CrmB in a model of collagen-induced arthritis (CIA in mice (CBAxC57Bl6 F1. The introduction of VARV-CrmB and polyclonal antibody to recombinant mouse TNF (poly-AbMuTNF led to an improvement of clinical manifestations of CIA by reducing the swelling and increasing the mobility of mice limbs. The introduction of VARV-CrmB and poly-AbMuTNF reduced the number of neutrophilic granulocytes and granulocytic precursors. The introduction of VARV-CrmB and poly-AbMuTNF into mice decreased collagenolysis in the blood serum and the content of glycosaminoglycans at the early stages of experimentation. Treatment with VARV-CrmB and poly-AbMuTNF of mice with CIA significantly decreased the chemiluminescence response of blood leukocytes. VARV-CrmB exerted more pronounced inhibitory effect on the production of reactive oxygen metabolites by blood leukocytes of mice with CIA than poly-AbMuTNF. Improvement of clinical condition of the mice with CIA has a more prolonged effect following introduction of the VARV-CrmB than after injection of poly-AbMuTNF. The results suggest the recombinant viral protein VARVCrmB to be a new potential TNF-antagonist.

Implementation and Benefits of CRM in Hotel Industry : A comparative study ofClarion Collection hotel and Scandic hotel in Västerås

OpenAIRE

Mu, Bin; Xiao, Meng; Gebray, Yonas

2015-01-01

This thesis is to identify the main factors that influence CRM implementation in Scandic hotel and Clarion hotel. Moreover, benefits of both hotels that can be reaped from using CRM. The result shows that CRM plays an important role in creating a long term successful to the hotels. But this can be achieved through considering major factors that influencing CRM implementation. CRM benefits also realized in both operational and strategic.

Hoffmeister Series Ions Protect Diphtheria Toxoid from Structural Damages at Solvent/Water Interface

Directory of Open Access Journals (Sweden)

Pedro S. de Araujo

2009-07-01

Full Text Available During the W1/O phase (in the W1/O/W2 process of protein microencapsulation within poly-lactide-co-glycolide (PLGA, hydrophobic interfaces are expanded where interfacial adsorption occurs followed by protein unfolding and aggregation. Spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on Diphtheria toxoid (Dtxd stability during the W1/O phase. A correlation was established between salts used in aqueous solutions and the changes in Dtxd solubility and conformation. The Dtxd α-helical content was quite stable thus leading to the conclusion that encapsulation was followed by protein aggregation, with minor exposition of hydrophobic residues and a small change at the S-S dihedral angle. Dtxd aggregation is 95% avoided by the chaotropic SCN-. This was used to prepare a stable Dtxd and immunologically recognized/PLGA formulation in the presence of 30 mM SNC-. The recovery increased by 10.42% or 23.2% when microencapsulation was within the -COOMe or -COOH (12kDa PLGA, respectively. In conclusion, the aim of this work was achieved, which was to obtain the maximum of Dtxd stability after contact with CH2Cl2 to begin its PLGA microencapsulation within ideal conditions. This was a technological breakthrough because a simple solution like salt addition avoided heterologous proteins usage.

A comparison of the intoxication pathways of tumor necrosis factor and diphtheria toxin

International Nuclear Information System (INIS)

Chang, M.P.

1988-01-01

The mechanism by which tumor necrosis factor-alpha (TNF) initiates tumor cell destruction is unknown. We have approached this problem by comparing the biological properties of TNF with diphtheria toxin (DTx), a well-characterized cytotoxin. Initial studies with human U937 cells revealed that a transient exposure to low pH enhances the cytotoxic activity of TNF. Detailed studies on the interaction of TNF with pure lipid vesicles revealed that the acid-enhanced cytolytic activity of this cytokine is correlated with the acquisition of membrane binding and insertion properties. Significantly, an increase in target membrane stabilization was observed in the presence of TNF; hence, TNF is not directly lytic for membranes. In susceptible target cells, DTx induces the release of 51 Cr- and 75 Se-labeled proteins within 7 h. Although DTx-triggered cell death has generally been accepted as a straightforward effect of translation inhibition, little or no cell lysis was observed over a 20-30 h period when target cells were exposed to cycloheximide, amino acid deficient medium or metabolic poisons even though protein synthesis was inhibited to levels observed with DTx. The protein synthesis inhibition and cytolytic activities of DTx showed similar dose-dependencies, target cell specificities, and sensitivities to NH 4 Cl inhibition. DTx-induced DNA fragmentation preceded cells lysis and did not occur in cells that were treated with the other protein synthesis inhibitors

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine.

Science.gov (United States)

Tomovici, A; Barreto, L; Zickler, P; Meekison, W; Noya, F; Voloshen, T; Lavigne, P

2012-03-30

Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap. Copyright © 2012 Elsevier Ltd. All rights reserved.

An empirical study to identify and rank CSFs in customer relationship management (CRM: A case study of oil products distribution

Directory of Open Access Journals (Sweden)

Seyed Mehdi Tofighi

2011-10-01

Full Text Available Customer relationship management (CRM is founded based on the value exchange between organization and customers and focuses merely on the value created in this connection. In this paper, the critical success factors are identified for a proper and effective implementation of CRM for an oil distribution company. The proposed survey of this paper identifies some important factors affecting the CRM implementation and determines the most important ones using a survey. The results indicate that there are twelve factors playing the most important roles on the success of CRM. There are CRM strategy, knowledge management in customer relationship, CRM technology, effective strategic committee, management of customer contact channels, customer information management, customer-oriented change management, training programs, strategic communication with staff, staff commitment, integration, and sectional implementation. We categorize the factors into two levels based on the level of their importance. The first level consists of the most important ones include only four items and the other eight items are categorized in level 2.

CRM-järjestelmän hyödyntäminen liiketoiminnassa

OpenAIRE

Sillman, Laura

2011-01-01

Tässä opinnäytetyössä tutkitaan mitä CRM eli customer relationship management (suom. asiakkuudenhallinta, asiakashallinta) tarkoittaa ja mitä siihen sisältyy. Työn tavoitteena on selvittää miten järjestelmätoimittajan olisi mahdollista auttaa asiakasta tavoittamaan CRM-käyttöönottoprojektin tavoitteet sekä jatkokehittää asiakkuudenhallintajärjestelmää ja liiketoimintaprosesseja myös käyttöönottoproejktin jälkeen. Tutkimus perustuu asiakkuudenhallinnan ja IT-alan tietokirjallisuuteen, haastat...

Uvajanje CRM rešitev na primeru podjetja Aksel d.o.o.

OpenAIRE

Skaza, Gašper

2016-01-01

Z novejšimi tehnologijami prihaja potreba po tem, da se podjetja posvečajo prenovi zastarelih informacijskih sistemov, ki so v veliko primerih nekompatibilni z novejšo tehnologijo. Kratica CRM (angl. Customer Relationship Management) v slovenskem prevodu pomeni sisteme za upravljanje odnosov s strankami. CRM je rešitev, ki pomaga konkurenčnost podjetja dvigniti na višjo raven, saj je dandanes ključno, da se posvetimo stranki na sodobne načine. Ker je zadovoljstvo stranke ključno za zvestobo,...

Penerapan Cutomer Relationship Management (CRM Dengan Menggunakan Metode Analytic Network Process (ANP Pada Perusahaan Ritel

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Nofiyati Nofiyati

2016-01-01

Full Text Available Retail industry or retail business is a fast-growing business in the midst of global competition conditions. One strategy to attract more consumers are Customer Relationship Management (CRM. The successful implementation of CRM in the enterprise is influenced by several environmental perspectives, strategies, customers and products / services, processes, participants, infrastructure, and information technology are integrated in the framework of Work System (WS. This research was carried out by applying the method of Multiple Criteria Decision Making (MCDM that is able to accommodate the outer and inner linkage from multiple nodes / indicators are considered, namely the Analytical Network Process (ANP to rank the quality of implementation CRM in retail companies and strong influential node / indicator of the best retail among three alternative the consisting of Alfamart, Indomaret and Smesco mart. From the results of application ANP method, obtained the rank quality of implementation CRM in retail companies with first rank is Indomaret the value of 1.0000; and the second is Alfamart with a value 0.9575; and the third is Smesco mart with a value of 0.8034. While node / indicator strong influence on the the best retail is level of chaos, long and short term planning, customer service, system integration, appropriate skills, technical infrastructure, easily of use and accessibility of information.   Keywords: Ritel, Customer Relationship Management (CRM, Analytic Network Process (ANP, Kerangka Work System (WS.

Customer Relationship Management System (CRM) and Information Ethics in Call Centres - 'You are the Weakest Link. Goodbye!'

OpenAIRE

Helen Richardson; Kate Richardson

2002-01-01

This paper catalogues the rise and rise of call centres in the North West of England, UK and their use of CRM systems. CRM systems often imply new technologies and new ways of working. However, in this account we explore the historical development of the telegraph and work in early telephone exchanges and find the same old story. Our consideration of the ethics of CRM system use and some inherent contradictions are in terms of privacy, communication richness, management methods and compute...

Management of Customer Relationship Management (CRM) Technological Attributes in Brazil: A B2B Relationship in the Software-Media Development Sector

OpenAIRE

Flávio Régio Brambilla; Gustavo Dalmarco

2015-01-01

Customer Relationship Management (CRM) represents a technological application based on the philosophy of Relationship Marketing and it recommends the interaction with high value consumers. Relating CRM to new social technologies, CRM 2.0 or social CRM deals with the relationship between companies and customers using online platforms such as blogs, RSS, forums and social network sites, among other facilities. Through a comparative study based on qualitative indicators, this article draws a rel...

Characterization of NIES CRM No. 23 Tea Leaves II for the determination of multielements.

Science.gov (United States)

Mori, Ikuko; Ukachi, Miyuki; Nagano, Kimiyo; Ito, Hiroyasu; Yoshinaga, Jun; Nishikawa, Masataka

2010-05-01

A candidate environmental certified reference material (CRM) for the determination of multielements in tea leaves and materials of similar matrix, NIES CRM No. 23 Tea Leaves II, has been developed and characterized by the National Institute for Environmental Studies (NIES), Japan. The origin of the material was tea leaves, which were ground, sieved through a 106-microm mesh, homogenized, and then subdivided into amber glass bottles. The results of homogeneity and stability tests indicated that the material was sufficiently homogeneous and stable for use as a reference material. The property values of the material were statistically determined based on chemical analyses by a network of laboratories using a wide range of methods. Sixteen laboratories participated in the characterization, and nine certified values and five reference values were obtained. These property values of the candidate CRM, which are expressed as mass fractions, were close to the median and/or mean values of the mass fractions of elements in various tea products. The candidate CRM is appropriate for use in analytical quality control and in the evaluation of methods used in the analysis of tea and materials of similar matrix.

Evaluation of Fatigue Life of CRM-Reinforced SMA and Its Relationship to Dynamic Stiffness

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Nuha Salim Mashaan

2014-01-01

Full Text Available Fatigue cracking is an essential problem of asphalt concrete that contributes to pavement damage. Although stone matrix asphalt (SMA has significantly provided resistance to rutting failure, its resistance to fatigue failure is yet to be fully addressed. The aim of this study is to evaluate the effect of crumb rubber modifier (CRM on stiffness and fatigue properties of SMA mixtures at optimum binder content, using four different modification levels, namely, 6%, 8%, 10%, and 12% CRM by weight of the bitumen. The testing undertaken on the asphalt mix comprises the dynamic stiffness (indirect tensile test, dynamic creep (repeated load creep, and fatigue test (indirect tensile fatigue test at temperature of 25°C. The indirect tensile fatigue test was conducted at three different stress levels (200, 300, and 400 kPa. Experimental results indicate that CRM-reinforced SMA mixtures exhibit significantly higher fatigue life compared to the mixtures without CRM. Further, higher correlation coefficient was obtained between the fatigue life and resilient modulus as compared to permanent strain; thus resilient modulus might be a more reliable indicator in evaluating the fatigue life of asphalt mixture.

Evaluation of fatigue life of CRM-reinforced SMA and its relationship to dynamic stiffness.

Science.gov (United States)

Mashaan, Nuha Salim; Karim, Mohamed Rehan; Abdel Aziz, Mahrez; Ibrahim, Mohd Rasdan; Katman, Herda Yati; Koting, Suhana

2014-01-01

Fatigue cracking is an essential problem of asphalt concrete that contributes to pavement damage. Although stone matrix asphalt (SMA) has significantly provided resistance to rutting failure, its resistance to fatigue failure is yet to be fully addressed. The aim of this study is to evaluate the effect of crumb rubber modifier (CRM) on stiffness and fatigue properties of SMA mixtures at optimum binder content, using four different modification levels, namely, 6%, 8%, 10%, and 12% CRM by weight of the bitumen. The testing undertaken on the asphalt mix comprises the dynamic stiffness (indirect tensile test), dynamic creep (repeated load creep), and fatigue test (indirect tensile fatigue test) at temperature of 25°C. The indirect tensile fatigue test was conducted at three different stress levels (200, 300, and 400 kPa). Experimental results indicate that CRM-reinforced SMA mixtures exhibit significantly higher fatigue life compared to the mixtures without CRM. Further, higher correlation coefficient was obtained between the fatigue life and resilient modulus as compared to permanent strain; thus resilient modulus might be a more reliable indicator in evaluating the fatigue life of asphalt mixture.

Analysis of the intermediate stage in the heavy ion interactions of {sup 208}Pb+{sup 197}Au and {sup 197}Au+{sup 197}Au

Energy Technology Data Exchange (ETDEWEB)

Nasir, Tabassum [Department of Physics, Gomal University D.I. Khan (Pakistan); Khan, E.U. [Department of Physics, CIIT, Islamabad (Pakistan)], E-mail: ehsan@comsats.edu.pk; Baluch, J J [Department of Environmental Sciences, CIIT, Abbottabad (Pakistan); Qureshi, I E [Pakistan Atomic Energy Commission, P.O. Box 1114, Islamabad (Pakistan); Sajid, M; Shahzad, M I [Physics Division, PINSTECH, P.O. Nilore, Islamabad (Pakistan)

2008-08-15

Two different projectiles {sup 208}Pb and {sup 197}Au at the same energy (11.67MeV/u) have been bombarded on {sup 197}Au target to study heavy ion interactions using mica as a passive detector. In this paper we present results on the study of energy damping and time scale of the existence of di-nuclear composite system in the intermediate reaction step. The plots of Q-values as well as reaction cross sections in various angular bins of scattering angles suggest that K.E. damping was complete and dynamic equilibrium was established between the first and second reaction steps. The time scale of this duration was also determined.

CRM as a General Practice of Every Business Organization

Science.gov (United States)

Ahmed, TS Ezaz; Prabhakar, D.

2012-11-01

Every business unit emphasizes on spurting a long term relationship with customers to nurture its stability in todayís blooming market. Customerís expectations are now not only limited to get best products and services, they also need a face-to-face business in which they want to receive exactly what they demand and in a quick time. Customer Relationship Management is an upright concept or strategy to solidify relations with customers and at the same time reducing cost and enhancing productivity and profitability in business. An ideal CRM system is a centralized collection all data sources under an organization and provides an atomistic real time vision of customer information. A CRM system is vast and significant, but it be can implemented for small business, as well as large enterprises also as the main goal is to assist the customers efficiently.

The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export*

Science.gov (United States)

Port, Sarah A.; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H.

2016-01-01

Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A)+ RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A)+ RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. PMID:27613868

The Oncogenic Fusion Proteins SET-Nup214 and Sequestosome-1 (SQSTM1)-Nup214 Form Dynamic Nuclear Bodies and Differentially Affect Nuclear Protein and Poly(A)+ RNA Export.

Science.gov (United States)

Port, Sarah A; Mendes, Adélia; Valkova, Christina; Spillner, Christiane; Fahrenkrog, Birthe; Kaether, Christoph; Kehlenbach, Ralph H

2016-10-28

Genetic rearrangements are a hallmark of several forms of leukemia and can lead to oncogenic fusion proteins. One example of an affected chromosomal region is the gene coding for Nup214, a nucleoporin that localizes to the cytoplasmic side of the nuclear pore complex (NPC). We investigated two such fusion proteins, SET-Nup214 and SQSTM1 (sequestosome)-Nup214, both containing C-terminal portions of Nup214. SET-Nup214 nuclear bodies containing the nuclear export receptor CRM1 were observed in the leukemia cell lines LOUCY and MEGAL. Overexpression of SET-Nup214 in HeLa cells leads to the formation of similar nuclear bodies that recruit CRM1, export cargo proteins, and certain nucleoporins and concomitantly affect nuclear protein and poly(A) + RNA export. SQSTM1-Nup214, although mostly cytoplasmic, also forms nuclear bodies and inhibits nuclear protein but not poly(A) + RNA export. The interaction of the fusion proteins with CRM1 is RanGTP-dependent, as shown in co-immunoprecipitation experiments and binding assays. Further analysis revealed that the Nup214 parts mediate the inhibition of nuclear export, whereas the SET or SQSTM1 part determines the localization of the fusion protein and therefore the extent of the effect. SET-Nup214 nuclear bodies are highly mobile structures, which are in equilibrium with the nucleoplasm in interphase and disassemble during mitosis or upon treatment of cells with the CRM1-inhibitor leptomycin B. Strikingly, we found that nucleoporins can be released from nuclear bodies and reintegrated into existing NPC. Our results point to nuclear bodies as a means of preventing the formation of potentially insoluble and harmful protein aggregates that also may serve as storage compartments for nuclear transport factors. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Impact of CRM practices on service quality in the banking industry

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Sana Hafeez

2017-06-01

Full Text Available The present study investigates the impact of customer relationship management practices on the service quality in the banking sector. CRM practices have been found to greatly influence not only the customer satisfaction and loyalty but also the quality of services provided by organization. The study focuses on three CRM practices of Attitude towards clients, Efficiency of banking services and Knowledge ability and their impact on the service quality. As customers are more aware about the services so they ensure service quality. Employee’s knowledge ability helps customers to gain experience that actually leads towards service quality and efficiency in services provided by the banks also help in service quality. The study used survey design and the sample consisted of 230 respondents. These respondents were customers of different banks in the city of Rawalpindi, Pakistan. The results indicate that knowledge ability of employees and attitude towards clients is having significant influence on service quality. However, CRM practice of Efficiency of banking services was found to be insignificant. The study has managerial implications for the banking industry. The study also provides future directions.

Optimizing the marketing interventions mix in intermediate-term CRM

NARCIS (Netherlands)

R.T. Rust (Roland); P.C. Verhoef (Peter)

2005-01-01

textabstractWe provide a fully personalized model for optimizing multiple marketing interventions in intermediate-term customer relationship management (CRM). We derive theoretically based propositions on the moderating effects of past customer behavior and conduct a longitudinal validation test to

42 CFR 84.197 - Respirator containers; minimum requirements.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Respirator containers; minimum requirements. 84.197... Cartridge Respirators § 84.197 Respirator containers; minimum requirements. Respirators shall be equipped with a substantial, durable container bearing markings which show the applicant's name, the type and...

Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

Science.gov (United States)

Pourakbari, Babak; Moradi, Behnaz; Mirzaee, Farin; Mahmoudi, Shima; Teymuri, Mostafa; Mamishi, Setareh

2013-01-01

Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

The Impact of CRM System Use on Companies’ Customer Understanding: The Case of the Russian Ophthalmology Market

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Denis Klimanov

2015-06-01

Full Text Available As the customer relationship management process comes to play an increasingly important role in business success, a number of authors are attempting to evaluate the impact of various CRM process components on the quality of company interaction with customers and, ultimately, on company performance. This paper explores the impact of CRM systems on the quality of companies’ customer understanding. This understanding is measured in the context of an international pharmaceutical company in the Russian market. The field research is based on quantitative data from online questionnaires and telephone interviews. The sample consists of 64 company representatives and 217 ophthalmologists. The authors developed and tested a model of physician loyalty drivers and studied employees’ perceptions of the CRM system. The findings of this paper demonstrate that, despite the fact that a CRM system is actively used and perceived as a crucial part of the customer relationship management process within the company, understanding of key customer loyalty drivers needs to be significantly improved. The paper contributes to existing theory by evaluating the link between the use of CRM applications and customer relationship performance as well as by developing a physician prescription loyalty influencers framework in the context of the Russian pharmaceutical market. This research could be used by other pharmaceutical companies as well in order to understand the influence of their CRM applications on customer loyalty and also to identify the drivers of physicians’ prescriptions.

Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

Science.gov (United States)

Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

2015-07-31

Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Implementing SaaS Solution for CRM

OpenAIRE

Adriana LIMBÄ‚ÅžAN; Lucia RUSU

2011-01-01

Greatest innovations in virtualization and distributed computing have accelerated interest in cloud computing (IaaS, PaaS, SaaS, aso). This paper presents the SaaS prototype for Customer Relationship Management of a real estate company. Starting from several approaches of e-marketing and SaaS features and architectures, we adopted a model for a CRM solution using SaaS Level 2 architecture and distributed database. Based on the system objective, functionality, we developed a modular solution f...

PEMBUATAN MODEL CUSTOMER RELATIONSHIP MANAGEMENT (CRM DINAS KESEHATAN DIY MENGGUNAKAN METODE COBIT 4.1 DENGAN DOMAIN DELIVERY AND SUPPORT (DS

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Ali Tarmuji

2015-07-01

Full Text Available The development of health information systems at the Department of Health DIY basically already developed in earlier periods, including the presence of DGS (Digital Government Services, but the ministry has not been able to maximize sample information service on the website Department of Health DIY, it is still not fully known by many society, so the lack of public knowledge about the latest information related to health. stage in this research is the search data by observation, interview, and literature study, analysis of current conditions, SWOT analysis, data analysis includes operational CRM, analytical CRM, collaborative CRM, and the stages of modeling CRM such as the design of the development strategy of services and applications, manufacture of data architecture, application architecture, technology architecture and network infrastructure, and testing models of CRM use due diligence devoted to DIY Health Service and customer satisfaction to the test. Based on the analysis results generated CRM DHO DIY model framework that can provide ease in interacting with customers through the services available.

Optimizing the marketing interventions mix in intermediate-term CRM

NARCIS (Netherlands)

Rust, RT; Verhoef, PC

2005-01-01

W e provide a fully personalized model for optimizing multiple marketing interventions in intermediate-term customer relationship management (CRM). We derive theoretically based propositions on the moderating effects of past customer behavior and conduct a longitudinal validation test to compare the

Management of Customer Relationship Management (CRM Technological Attributes in Brazil: A B2B Relationship in the Software-Media Development Sector

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Flávio Régio Brambilla

2015-03-01

Full Text Available Customer Relationship Management (CRM represents a technological application based on the philosophy of Relationship Marketing and it recommends the interaction with high value consumers. Relating CRM to new social technologies, CRM 2.0 or social CRM deals with the relationship between companies and customers using online platforms such as blogs, RSS, forums and social network sites, among other facilities. Through a comparative study based on qualitative indicators, this article draws a relationship between CRM theory and practice. In two high technology organizations it was identified that, although the indicators are appropriate to the business practices, their usage and understanding are oriented by the nature of businesses and by the company characteristics. Empirical results show that technology structure, data collection and analysis tools and interactive sales tools favor CRM. In this paper, four variables are treated theoretically and empirically: Information Technology; Information tools, where the Database and the Storage of Debugged Data are included; Data Mining; and, the Sales Force Automation Facilities.

IMPLEMENTACIJA IN UPORABA INFORMACIJSKE REŠITVE CRM NA PRIMERU ZALOŽNIŠKEGA PODJETJA

OpenAIRE

Lešnik Potočnik, Suzana

2013-01-01

Zaradi hitrih sprememb v podjetniškem poslovnem okolju in vse ostrejše konkurence znotraj posameznih panog predstavlja prilagodljivost, inovativnost in usmerjenost na stranke ključno konkurenčno prednost podjetja. Učinkovito orodje za uresničitev navedene usmerjenosti predstavlja strateška usmeritev podjetja, imenovana tudi upravljanje odnosov s strankami in jo označujemo s kratico CRM. CRM zadeva celotno podjetje, omogoča optimizacijo dobička in zadovoljstva strank ter združuje vse poslovne ...

Appraisal of CRM implementation as business strategy option in times of recession: The role of perceived value and benefits

OpenAIRE

Chrysa; Sotirios; Dimitrios

2018-01-01

The present work investigates Customer Relationship Management (CRM) implementation and performance during the fiscal crisis in Greece based on an appropriate questionnaire. All acquired responses using the questionnaire are suitably analysed using advanced statistical techniques, and show that Greek companies employ CRM, harvesting many of its benefits. Specifically, survey results show that most companies are satisfied by the implementation of CRM strategy and seem to recognize the vital st...

Sensitivity of cancer cells to truncated diphtheria toxin.

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Yi Zhang

2010-05-01

Full Text Available Diphtheria toxin (DT has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines.In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC tumor growth, respectively.Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50 ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice.DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.

Morbillivirus nucleoprotein possesses a novel nuclear localization signal and a CRM1-independent nuclear export signal

International Nuclear Information System (INIS)

Sato, Hiroki; Masuda, Munemitsu; Miura, Ryuichi; Yoneda, Misako; Kai, Chieko

2006-01-01

Morbilliviruses, which belong to the Mononegavirales, replicate its RNA genome in the cytoplasm of the host cell. However, they also form characteristic intranuclear inclusion bodies, consisting of nucleoprotein (N), in infected cells. To analyze the mechanisms of nucleocytoplasmic transport of N protein, we characterized the nuclear localization (NLS) and nuclear export (NES) signals of canine distemper virus (CDV) N protein by deletion mutation and alanine substitution of the protein. The NLS has a novel leucine/isoleucine-rich motif (TGILISIL) at positions 70-77, whereas the NES is composed of a leucine-rich motif (LLRSLTLF) at positions 4-11. The NLS and NES of the N proteins of other morbilliviruses, that is, measles virus (MV) and rinderpest virus (RPV), were also analyzed. The NLS of CDV-N protein is conserved at the same position in MV-N protein, whereas the NES of MV-N protein is located in the C-terminal region. The NES of RPV-N protein is also located at the same position as CDV-N protein, whereas the NLS motif is present not only at the same locus as CDV-N protein but also at other sites. Interestingly, the nuclear export of all these N proteins appears to proceed via a CRM1-independent pathway

[siRNAs with high specificity to the target: a systematic design by CRM algorithm].

Science.gov (United States)

Alsheddi, T; Vasin, L; Meduri, R; Randhawa, M; Glazko, G; Baranova, A

2008-01-01

'Off-target' silencing effect hinders the development of siRNA-based therapeutic and research applications. Common solution to this problem is an employment of the BLAST that may miss significant alignments or an exhaustive Smith-Waterman algorithm that is very time-consuming. We have developed a Comprehensive Redundancy Minimizer (CRM) approach for mapping all unique sequences ("targets") 9-to-15 nt in size within large sets of sequences (e.g. transcriptomes). CRM outputs a list of potential siRNA candidates for every transcript of the particular species. These candidates could be further analyzed by traditional "set-of-rules" types of siRNA designing tools. For human, 91% of transcripts are covered by candidate siRNAs with kernel targets of N = 15. We tested our approach on the collection of previously described experimentally assessed siRNAs and found that the correlation between efficacy and presence in CRM-approved set is significant (r = 0.215, p-value = 0.0001). An interactive database that contains a precompiled set of all human siRNA candidates with minimized redundancy is available at http://129.174.194.243. Application of the CRM-based filtering minimizes potential "off-target" silencing effects and could improve routine siRNA applications.

Empirical testing of selected critical success factors in CRM implementation projects - A study of SMEs in the B2B sector

OpenAIRE

Röschmann, Kathrin; Ziyadullaeva, Muhayyo

2011-01-01

Purpose:The purpose of this thesis is to describe and analyze critical success factors of CRM implementation projects with a special focus on SME’s in the B2B sector.  Method: This study is based on quantitative research using survey method.  Target Audience: SMEs of B2B business, which are planning to implement a CRM system Academic audience, which is interested in CRM implementation with focus on SME.  Conclusion: There are various critical success factors in CRM implementation projects and...

Effect of CRM team leader training on team performance and leadership behavior in simulated cardiac arrest scenarios: a prospective, randomized, controlled study.

Science.gov (United States)

Fernandez Castelao, Ezequiel; Boos, Margarete; Ringer, Christiane; Eich, Christoph; Russo, Sebastian G

2015-07-24

Effective team leadership in cardiopulmonary resuscitation (CPR) is well recognized as a crucial factor influencing performance. Generally, leadership training focuses on task requirements for leading as well as non-leading team members. We provided crisis resource management (CRM) training only for designated team leaders of advanced life support (ALS) trained teams. This study assessed the impact of the CRM team leader training on CPR performance and team leader verbalization. Forty-five teams of four members each were randomly assigned to one of two study groups: CRM team leader training (CRM-TL) and additional ALS-training (ALS add-on). After an initial lecture and three ALS skill training tutorials (basic life support, airway management and rhythm recognition/defibrillation) of 90-min each, one member of each team was randomly assigned to act as the team leader in the upcoming CPR simulation. Team leaders of the CRM-TL groups attended a 90-min CRM-TL training. All other participants received an additional 90-min ALS skill training. A simulated CPR scenario was videotaped and analyzed regarding no-flow time (NFT) percentage, adherence to the European Resuscitation Council 2010 ALS algorithm (ADH), and type and rate of team leader verbalizations (TLV). CRM-TL teams showed shorter, albeit statistically insignificant, NFT rates compared to ALS-Add teams (mean difference 1.34 (95% CI -2.5, 5.2), p = 0.48). ADH scores in the CRM-TL group were significantly higher (difference -6.4 (95% CI -10.3, -2.4), p = 0.002). Significantly higher TLV proportions were found for the CRM-TL group: direct orders (difference -1.82 (95% CI -2.4, -1.2), p CRM improves performance of the entire team, in particular guideline adherence and team leader behavior. Emphasis on training of team leader behavior appears to be beneficial in resuscitation and emergency medical course performance.

43 CFR 19.7 - Private contributions and gifts.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Private contributions and gifts. 19.7... National Wilderness Preservation System § 19.7 Private contributions and gifts. (a) The Secretary is... contributions and gifts to be used to further the purposes of the act. The Secretary, under the authorization of...

Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

Directory of Open Access Journals (Sweden)

Saliou Pierre

2005-11-01

Full Text Available Abstract Background Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi, stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP vaccines. Methods In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+ every two weeks for seven months or no chemoprophylaxis (CH-. After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05. The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05 and 77% and 91% for tetanus toxoid (P > 0.05. In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05. While analysis for pertussis showed a 43% (CH+ and 67% (CH- response (P Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

Immunogenicity and safety of the new reduced-dose tetanus-diphtheria vaccine in healthy Korean adolescents: A comparative active control, double-blind, randomized, multicenter phase III study.

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Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Kim, Sang Yong; Kim, Jong-Hyun; Kim, Hyun-Hee; Lee, Kyung-Yil; Kim, Hwang Min; Choi, Young Youn; Ma, Sang Hyuk; Kim, Chun Soo; Kim, Dong Ho; Ahn, Dong Ho; Kang, Jin Han

2017-04-01

A new reduced-dose tetanus-diphtheria (Td) vaccine was developed in Korea, and phase I and II clinical trials were successfully undertaken. We conducted this double-blind, randomized, multicenter phase III clinical trial to assess the immunogenicity and safety of the new Td vaccine. Healthy adolescents 11-12 years of age were enrolled and randomized to receive the new Td vaccine (study group) or a commercially available Td vaccine (control group). Blood samples were collected prior to and 4 weeks after the vaccination. Between the study and control groups, seroprotection rate, booster response, and geometric mean titer of antibodies against diphtheria and tetanus toxoids were compared after the vaccination. All solicited and unsolicited adverse events and serious adverse events during the 6-week study period were monitored. A total of 164 adolescents received vaccination, and 156 of them were evaluated to assess immunogenicity. The seroprotection rate and geometric mean titer for antibodies against diphtheria were significantly higher in the study group, whereas those against tetanus were significantly higher in the control group. However, all seroprotection rates against diphtheria and tetanus in the study and control groups were high: 100% against diphtheria and tetanus in the study group, and 98.7% against diphtheria and 100% against tetanus in the control group. No significant differences in the frequency of solicited and unsolicited adverse events were observed between the two vaccine groups. The new Td vaccine is highly immunogenic and safe, and this new Td vaccine can be effectively used for preventing diphtheria and tetanus. Copyright © 2015. Published by Elsevier B.V.

Mutagenic Deimmunization of Diphtheria Toxin for Use in Biologic Drug Development

Directory of Open Access Journals (Sweden)

Joerg U. Schmohl

2015-10-01

Full Text Available Background: Targeted toxins require multiple treatments and therefore must be deimmunized. We report a method of protein deimmunization based on the point mutation of highly hydrophilic R, K, D, E, and Q amino acids on the molecular surface of truncated diphtheria-toxin (DT390. Methods: Based on their surface position derived from an X-ray-crystallographic model, residues were chosen for point mutation that were located in prominent positions on the molecular surface and away from the catalytic site. Mice were immunized with a targeted toxin containing either a mutated DT390 containing seven critical point mutations or the non-mutated parental toxin form. Results: Serum analysis revealed a significant 90% reduction in anti-toxin antibodies in mice immunized with the mutant, but not the parental drug form despite multiple immunizations. The experiment was repeated in a second strain of mice with a different MHC-haplotype to address whether point mutation removed T or B cell epitopes. Findings were identical indicating that B cell epitopes were eliminated from DT. The mutant drug form lost only minimal activity in vitro as well as in vivo. Conclusion: These findings indicate that this method may be effective for deimmunizing of other proteins and that discovery of a deimmunized form of DT may lead to the development of more effective targeted toxin.

Diphtheria, pertussis, and tetanus: evidence-based management of pediatric patients in the emergency department [digest].

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Zibners, Lara; Chaudhari, Pradip

2017-02-22

Diphtheria, pertussis, and tetanus are potentially deadly bacterial infections that are largely preventable through vaccination, though they remain in the population. This issue reviews the epidemiology, pathophysiology, diagnosis, and current recommended emergency management of these conditions. Disease-specific medications, as well as treatment of the secondary complications, are examined in light of the best current evidence. Resources include obtaining diphtheria antitoxin from the United States Centers for Disease Control and Prevention and best-practice recommendations with regard to testing, involvement of government health agencies, isolation of the patient, and identification and treatment of close contacts. Most importantly, issues regarding vaccination and prevention are highlighted. [Points & Pearls is a digest of Pediatric Emergency Medicine Practice].

Detailed characterization of a Comparative Reactivity Method (CRM) instrument for ambient OH reactivity measurements: experiments vs. modeling

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Michoud, Vincent; Locoge, Nadine; Dusanter, Sébastien

2015-04-01

The Hydroxyl radical (OH) is the main daytime oxidant in the troposphere, leading to the oxidation of Volatile Organic Compounds (VOCs) and the formation of harmful pollutants such as ozone (O3) and Secondary Organic Aerosols (SOA). While OH plays a key role in tropospheric chemistry, recent studies have highlighted that there are still uncertainties associated with the OH budget, i.e the identification of sources and sinks and the quantification of production and loss rates of this radical. It has been demonstrated that ambient measurements of the total OH loss rate (also called total OH reactivity) can be used to identify and reduce these uncertainties. In this context, the Comparative Reactivity Method (CRM), developed by Sinha et al. (ACP, 2008), is a promising technique to measure total OH reactivity in ambient air and has already been used during several field campaigns. This technique relies on monitoring competitive reactions of OH with ambient trace gases and a reference compound (pyrrole) in a sampling reactor to derive ambient OH reactivity. However, this technique requires a complex data processing chain that has yet to be carefully investigated in the laboratory. In this study, we present a detailed characterization of a CRM instrument developed at Mines Douai, France. Experiments have been performed to investigate the dependence of the CRM response on humidity, ambient NOx levels, and the pyrrole-to-OH ratio inside the sampling reactor. Box modelling of the chemistry occurring in the reactor has also been performed to assess our theoretical understanding of the CRM measurement. This work shows that the CRM response is sensitive to both humidity and NOx, which can be accounted for during data processing using parameterizations depending on the pyrrole-to-OH ratio. The agreement observed between laboratory studies and model results suggests a good understanding of the chemistry occurring in the sampling reactor and gives confidence in the CRM

Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

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Tanriover, Mine Durusu; Soyler, Canan; Ascioglu, Sibel; Cankurtaran, Mustafa; Unal, Serhat

2014-07-01

Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital. Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values. A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis. We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of "lifelong vaccination" should be implemented and every encounter with the patient should be regarded as a chance for catch-up. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Improved accuracy of supervised CRM discovery with interpolated Markov models and cross-species comparison.

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Kazemian, Majid; Zhu, Qiyun; Halfon, Marc S; Sinha, Saurabh

2011-12-01

Despite recent advances in experimental approaches for identifying transcriptional cis-regulatory modules (CRMs, 'enhancers'), direct empirical discovery of CRMs for all genes in all cell types and environmental conditions is likely to remain an elusive goal. Effective methods for computational CRM discovery are thus a critically needed complement to empirical approaches. However, existing computational methods that search for clusters of putative binding sites are ineffective if the relevant TFs and/or their binding specificities are unknown. Here, we provide a significantly improved method for 'motif-blind' CRM discovery that does not depend on knowledge or accurate prediction of TF-binding motifs and is effective when limited knowledge of functional CRMs is available to 'supervise' the search. We propose a new statistical method, based on 'Interpolated Markov Models', for motif-blind, genome-wide CRM discovery. It captures the statistical profile of variable length words in known CRMs of a regulatory network and finds candidate CRMs that match this profile. The method also uses orthologs of the known CRMs from closely related genomes. We perform in silico evaluation of predicted CRMs by assessing whether their neighboring genes are enriched for the expected expression patterns. This assessment uses a novel statistical test that extends the widely used Hypergeometric test of gene set enrichment to account for variability in intergenic lengths. We find that the new CRM prediction method is superior to existing methods. Finally, we experimentally validate 12 new CRM predictions by examining their regulatory activity in vivo in Drosophila; 10 of the tested CRMs were found to be functional, while 6 of the top 7 predictions showed the expected activity patterns. We make our program available as downloadable source code, and as a plugin for a genome browser installed on our servers. © The Author(s) 2011. Published by Oxford University Press.