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Sample records for donors specific requirements

  1. Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

    Science.gov (United States)

    Wiebe, Chris; Rush, David N; Nevins, Thomas E; Birk, Patricia E; Blydt-Hansen, Tom; Gibson, Ian W; Goldberg, Aviva; Ho, Julie; Karpinski, Martin; Pochinco, Denise; Sharma, Atul; Storsley, Leroy; Matas, Arthur J; Nickerson, Peter W

    2017-11-01

    Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II de novo donor-specific antibody ( dn DSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software. We analyzed the frequency of tacrolimus trough levels below a series of thresholds mismatch. HLA-DR/DQ eplet mismatch was a significant multivariate predictor of dn DSA development. Recipients treated with a cyclosporin regimen had a 2.7-fold higher incidence of dn DSA development than recipients on a tacrolimus regimen. Recipients treated with tacrolimus who developed HLA-DR/DQ dn DSA had a higher proportion of tacrolimus trough levels mismatch. Mean tacrolimus trough levels in the 6 months before dn DSA development were significantly lower than the levels >6 months before dn DSA development in the same patients. Recipients with a high-risk HLA eplet mismatch score were less likely to tolerate low tacrolimus levels without developing dn DSA. We conclude that HLA-DR/DQ eplet mismatch and tacrolimus trough levels are independent predictors of dn DSA development. Recipients with high HLA alloimmune risk should not target tacrolimus levels <5 ng/ml unless essential, and monitoring for dn DSA may be advisable in this setting. Copyright © 2017 by the American Society of Nephrology.

  2. Development of Organ-Specific Donor Risk Indices

    Science.gov (United States)

    Akkina, Sanjeev K.; Asrani, Sumeet K.; Peng, Yi; Stock, Peter; Kim, Ray; Israni, Ajay K.

    2012-01-01

    Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ-specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C-positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End-Stage Liver Disease scores Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor-recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. PMID:22287036

  3. TWRSview system requirements specification

    International Nuclear Information System (INIS)

    Caldwell, J.A.; Lee, A.K.

    1995-12-01

    This document provides the system requirements specification for the TWRSview software system. The TWRSview software system is being developed to integrate electronic data supporting the development of the TWRS technical baseline

  4. Donor-specific rejection: Clinical and scan correlation

    International Nuclear Information System (INIS)

    Wilson, M.A.; Mehta, R.C.; Perlman, S.B.; Servilla, K.; Sollinger, H.W.; Deierhoi, M.H.; Belzer, F.O.

    1986-01-01

    All 470 scans on 132 consecutive renal transplantation patients were reviewed. Scan patterns identified included acute tubular necrosis and conventional rejection. A new pattern, donor specific rejection (DSR), was identified in 24 of 42 patients on the living related donor specific transfusion (DST) protocol. This was characterized by good perfusion and extraction but significant renal stasis of tracer. This pattern was unique to the DST recipients and improved with antirejection therapy. The clinical features (incidence, temporal onset) and severity (duration, serum creatinines) are compared in these patient populations. DSR occurs more frequently than conventional rejection but is a milder process

  5. 21 CFR 1271.80 - What are the general requirements for donor testing?

    Science.gov (United States)

    2010-04-01

    ... ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Donor Eligibility § 1271.80 What are... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What are the general requirements for donor... donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to 7 days...

  6. An Algorithm Measuring Donor Cell-Free DNA in Plasma of Cellular and Solid Organ Transplant Recipients That Does Not Require Donor or Recipient Genotyping

    Directory of Open Access Journals (Sweden)

    Paul MK Gordon

    2016-09-01

    Full Text Available Cell-free DNA (cfDNA has significant potential in the diagnosis and monitoring of clinical conditions but accurately and easily distinguishing the relative proportion of DNA molecules in a mixture derived from two different sources (i.e. donor and recipient tissues after transplantation is challenging. In human cellular transplantation there is currently no useable method to detect in vivo engraftment and blood-based non-invasive tests for allograft rejection in solid organ transplantation are either non-specific (e.g. creatinine in kidney transplantation, liver enzymes in hepatic transplantation or absent (i.e. heart transplantation. Elevated levels of donor cfDNA have been shown to correlate with solid organ rejection but complex methodology limits implementation of this promising biomarker. We describe a cost-effective method to quantify donor cfDNA in recipient plasma using a panel of high-frequency single nucleotide polymorphisms, next-generation (semiconductor sequencing and a novel mixture model algorithm. In vitro, our method accurately and rapidly determined donor/recipient DNA admixture. For in vivo testing, donor cfDNA was serially quantified in an infant with a urea cycle disorder after receiving six daily infusions of donor liver cells. Donor cfDNA isolated from 1-2 ml of recipient plasma was detected as late as 24 weeks after infusion suggesting engraftment. The percentage of circulating donor cfDNA was also assessed in pediatric and adult heart transplant recipients undergoing routine endomyocardial biopsy with levels observed to be stable over time and generally measuring <1% in cases without moderate or severe cellular rejection. Unlike existing non-invasive methods used to define the proportion of donor cfDNA in solid organ transplant patients, our assay does not require sex mismatch, donor genotyping or whole-genome sequencing and potentially has broad application to detect cellular engraftment or allograft injury after

  7. Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis.

    Science.gov (United States)

    Kuo, P C; Johnson, L B

    2000-05-27

    A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. LDN increases the supply of living donor kidneys.

  8. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  9. Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

    1985-01-01

    The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators

  10. Decline of influenza-specific CD8+ T cell repertoire in healthy geriatric donors

    Directory of Open Access Journals (Sweden)

    Ramachandra Lakshmi

    2011-08-01

    Full Text Available Abstract Background While influenza vaccination results in protective antibodies against primary infections, clearance of infection is primarily mediated through CD8+ T cells. Studying the CD8+ T cell response to influenza epitopes is crucial in understanding the disease associated morbidity and mortality especially in at risk populations such as the elderly. We compared the CD8+ T cell response to immunodominant and subdominant influenza epitopes in HLA-A2+ control, adult donors, aged 21-42, and in geriatric donors, aged 65 and older. Results We used a novel artificial Antigen Presenting Cell (aAPC based stimulation assay to reveal responses that could not be detected by enzyme-linked immunosorbent spot (ELISpot. 14 younger control donors and 12 geriatric donors were enrolled in this study. The mean number of influenza-specific subdominant epitopes per control donor detected by ELISpot was only 1.4 while the mean detected by aAPC assay was 3.3 (p = 0.0096. Using the aAPC assay, 92% of the control donors responded to at least one subdominant epitopes, while 71% of control donors responded to more than one subdominant influenza-specific response. 66% of geriatric donors lacked a subdominant influenza-specific response and 33% of geriatric donors responded to only 1 subdominant epitope. The difference in subdominant response between age groups is statistically significant (p = 0.0003. Conclusion Geriatric donors lacked the broad, multi-specific response to subdominant epitopes seen in the control donors. Thus, we conclude that aging leads to a decrease in the subdominant influenza-specific CTL responses which may contribute to the increased morbidity and mortality in older individuals.

  11. Relevance of Regulatory T cell Promotion of Donor-specific Tolerance in Solid Organ Transplantation

    Directory of Open Access Journals (Sweden)

    Pervinder eSagoo

    2012-07-01

    Full Text Available Current clinical strategies to control the alloimmune response after transplantation do not fully prevent induction of the immunological processes which lead to acute and chronic immune-mediated graft rejection, and as such the survival of a solid organ allograft is limited. Experimental research on naturally occurring CD4+CD25highFoxP3+ Regulatory T cells (Tregs has indicated their potential to establish stable long-term graft acceptance, with the promise of providing a more effective therapy for transplant recipients. Current approaches for clinical use are based on the infusion of freshly isolated or ex vivo polyclonally expanded Tregs into graft recipients with an aim to redress the in vivo balance of T effector cells to Tregs. However mounting evidence suggests that regulation of donor-specific immunity may be central to achieving immunological tolerance. Therefore the next stages in optimising translation of Tregs to organ transplantation will be through the refinement and development of donor alloantigen-specific Treg therapy. The altering kinetics and intensity of alloantigen presentation pathways and alloimmune priming following transplantation may indeed influence the specificity of the Treg required and the timing or frequency at which it needs to be administered. Here we review and discuss the relevance of antigen-specific regulation of alloreactivity by Tregs in experimental and clinical studies of tolerance and explore the concept of delivering an optimal Treg for the induction and maintenance phases of achieving transplantation tolerance.

  12. Donor-specific anti-HLA Abs and graft failure in matched unrelated donor hematopoietic stem cell transplantation

    Science.gov (United States)

    Ciurea, Stefan O.; Thall, Peter F.; Wang, Xuemei; Wang, Sa A.; Hu, Ying; Cano, Pedro; Aung, Fleur; Rondon, Gabriela; Molldrem, Jeffrey J.; Korbling, Martin; Shpall, Elizabeth J.; de Lima, Marcos; Champlin, Richard E.

    2011-01-01

    Anti-HLA donor-specific Abs (DSAs) have been reported to be associated with graft failure in mismatched hematopoietic stem cell transplantation; however, their role in the development of graft failure in matched unrelated donor (MUD) transplantation remains unclear. We hypothesize that DSAs against a mismatched HLA-DPB1 locus is associated with graft failure in this setting. The presence of anti-HLA Abs before transplantation was determined prospectively in 592 MUD transplantation recipients using mixed-screen beads in a solid-phase fluorescent assay. DSA identification was performed using single-Ag beads containing the corresponding donor's HLA-mismatched Ags. Anti-HLA Abs were detected in 116 patients (19.6%), including 20 patients (3.4%) with anti-DPB1 Abs. Overall, graft failure occurred in 19 of 592 patients (3.2%), including 16 of 584 (2.7%) patients without anti-HLA Abs compared with 3 of 8 (37.5%) patients with DSA (P = .0014). In multivariate analysis, DSAs were the only factor highly associated with graft failure (P = .0001; odds ratio = 21.3). Anti-HLA allosensitization was higher overall in women than in men (30.8% vs 12.1%; P < .0001) and higher in women with 1 (P = .008) and 2 or more pregnancies (P = .0003) than in men. We conclude that the presence of anti-DPB1 DSAs is associated with graft failure in MUD hematopoietic stem cell transplantation. PMID:21967975

  13. Prostate Specific Antigen-Positive Deceased Organ Donor: A Pathologist Is Indispensable.

    Science.gov (United States)

    Pabisiak, K; Ostrowski, M; Kram, A; Safranow, K; Słojewski, M; Ciechanowski, K

    2016-09-01

    Due to demographic projections, and lack of an algorithm in the case of a prostate specific antigen (PSA)-positive donor, the loss of organ recovery may occur more frequently in the near future without approved procedures. In Poland in recent years it has been recommended to determine tumor markers in potential donors. In the first year of the recommendation 10% of potential deceased donors were disqualified in our transplantation center on the basis of the elevated PSA levels (high PSA >10 ng/mL). Histopathologic evaluation of prostate was implemented in a donor qualification procedure to prevent reduction of the actual organ donor pool. In the period of January 2010-January 2014 each donor reported to a coordination center (n = 52; median age, 54 years) and underwent the routine histological evaluation of the whole prostate, regardless of the PSA level. Pathologist revealed in the study group of 52 male donors, 6 cases of carcinoma of the prostate (CaP; 12%). There was no correlation between PSA level and CaP (-)/CaP(+) (median 7.0 vs 3.9 ng/mL, respectively; P = .51) nor high-grade prostate intraepithelial neoplasia (HGPIN) (+)/HGPIN (-) (median 5.9 vs 4.3 ng/mL; P = .14). All of the recovered organs (12 kidneys and 3 livers) from donors with CaP were transplanted, resulting in a 15% increase in the organ donor pool. There is no association between PSA values and CaP occurrence in deceased organ donors. Histological verification allowed for an increase in the organ pool with maintenance of safety standards. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. 21 CFR 1271.85 - What donor testing is required for different types of cells and tissues?

    Science.gov (United States)

    2010-04-01

    ... Eligibility § 1271.85 What donor testing is required for different types of cells and tissues? (a) All donors... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What donor testing is required for different types of cells and tissues? 1271.85 Section 1271.85 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT...

  15. How much donor financing for health is channelled to global versus country-specific aid functions?

    Science.gov (United States)

    Schäferhoff, Marco; Fewer, Sara; Kraus, Jessica; Richter, Emil; Summers, Lawrence H; Sundewall, Jesper; Yamey, Gavin; Jamison, Dean T

    2015-12-12

    The slow global response to the Ebola crisis in west Africa suggests that important gaps exist in donor financing for key global functions, such as support for health research and development for diseases of poverty and strengthening of outbreak preparedness. In this Health Policy, we use the International Development Statistics databases to quantify donor support for such functions. We classify donor funding for health into aid for global functions (provision of global public goods, management of cross-border externalities, and fostering of leadership and stewardship) versus country-specific aid. We use a new measure of donor funding that combines official development assistance (ODA) for health with additional donor spending on research and development (R&D) for diseases of poverty. Much R&D spending falls outside ODA--ie, the assistance that is conventionally reported through ODA databases of the Organisation for Economic Co-operation and Development. This expanded definition, which we term health ODA plus, provides a more comprehensive picture of donor support for health that could reshape how policy makers will approach their support for global health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

    2012-01-01

    Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

  17. Donor Tag Game

    Science.gov (United States)

    ... Donor Community > Games > Donor Tag Game Donor Tag Game This feature requires version 6 or later of ... of Needles LGBTQ+ Donors Blood Donor Community SleevesUp Games Facebook Avatars and Badges Banners eCards Make a ...

  18. SOFTWARE REQUIREMENTS SPECIFICATION SINAPRA BERBASIS SISTEM INFORMASI

    Directory of Open Access Journals (Sweden)

    Nur Hadi Waryanto

    2015-07-01

    Full Text Available Sistem Informasi Sarana dan Prasarana (SINAPRA merupakan bagian dari beberapa sistem informasi yang dipakai oleh Univeristas Negeri Yogyakarta. SINAPRA merupakan salah satu sistem yang akan dikembangkan dalam Sistem Informasi Terpadu (SIPADU. Software Requirements Specification SINAPRA merupakan acuan teknis developer dalam mengembangkan sistem untuk tahap selanjutnya. Software Requirements Specification SINAPRA dikembangkan menggunakan model WSU-TC CptS 322  dengan berbasis sistem informasi terpadu UNY Kata Kunci : Software Requirements Specification, WSU-TC CptS 322, SINAPRA

  19. Behaviour of non-donor specific antibodies during rapid re-synthesis of donor specific HLA antibodies after antibody incompatible renal transplantation.

    Directory of Open Access Journals (Sweden)

    Nithya S Krishnan

    Full Text Available HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation.55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i DSA levels and ii rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified.Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002, even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00.In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection.

  20. 21 CFR 1271.90 - Are there exceptions from the requirement of determining donor eligibility, and what labeling...

    Science.gov (United States)

    2010-04-01

    ... determining donor eligibility, and what labeling requirements apply? 1271.90 Section 1271.90 Food and Drugs... CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Donor Eligibility § 1271.90 Are there exceptions from the requirement of...

  1. Technical requirements specification for tank waste retrieval

    Energy Technology Data Exchange (ETDEWEB)

    Lamberd, D.L.

    1996-09-26

    This document provides the technical requirements specification for the retrieval of waste from the underground storage tanks at the Hanford Site. All activities covered by this scope are conducted in support of the Tank Waste Remediation System (TWRS) mission.

  2. Business System Planning Project System Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    NELSON, R.E.

    2000-09-08

    The purpose of the Business Systems Planning Project System Requirements Specification (SRS) is to provide the outline and contents of the requirements for the CH2M HILL Hanford Group, Inc. (CHG) integrated business and technical information systems. The SRS will translate proposed objectives into the statement of the functions that are to be performed and data and information flows that they require. The requirements gathering methodology will use (1) facilitated group requirement sessions; (2) individual interviews; (3) surveys; and (4) document reviews. The requirements will be verified and validated through coordination of the technical requirement team and CHG Managers. The SRS document used the content and format specified in Lockheed Martin Services, Inc. Organization Standard Software Practices in conjunction with the Institute of Electrical and Electronics Engineers Standard 8340-1984 for Systems Requirements Documents.

  3. Successful reduction of immunosuppression in older renal transplant recipients who exhibit donor-specific regulation

    Science.gov (United States)

    Jankowska-Gan, E.; Sollinger, H. W.; Pirsch, J. D.; Cai, J.; Pascual, J.; Haynes, L. D.; Munoz del Rio, A.; Burlingham, W. J.

    2009-01-01

    Background We hypothesized that T regulatory cells (TR) specific for donor alloantigens would protect a renal transplant during partial withdrawal of immunosuppression (IS). Methods To test this hypothesis, 32 renal transplant recipients >55 years old with excellent renal function were tested for donor-specific regulation (DSR) by trans-vivo delayed type hypersensitivity (TV-DTH) assay at time of enrollment (T=0) and 6 months later (T=6). Twenty-two patients had prednisone withdrawn over a 3 month period, while 10 controls were maintained on triple therapy (prednisone, cyclosporin, mycophenolate). Results Out of 22 patients in the steroid withdrawal group, 10 were DSR+, and 12 were DSR- at the time of enrollment (T=0). None of the DSR+ patient experienced acute rejection, nor did any have donor-specific HLA antibody (DSA) during or after withdrawal. Out of 12 DSR- patients, 3 developed acute rejection, which were reversed with bolus steroid treatment, and 4 were DSA + at T=0 or T=6. Two years later, 80% (8/10) of DSR+ patients in the withdrawal group remain steroid free while maintaining excellent renal function, as compared with only 58% (7/12) DSR- patients. Patient survival at 4 years was similar for DSR+ (9/10) and DSR- (11/12) patients in the withdrawal group. Patients maintained on triple therapy remained rejection-free during the 4 yr follow up regardless of initial DSR status, with patient survival rate of 70% (7/10). Conclusions DSR prior to steroid withdrawal may identify a subset of transplant patients who could benefit from IS reduction without elevated risk of rejection, or deteriorating renal function. PMID:19696637

  4. Comparative analysis of Luminex-based donor-specific antibody mean fluorescence intensity values with complement-dependent cytotoxicity & flow crossmatch results in live donor renal transplantation

    OpenAIRE

    Ajay Kumar Baranwal; Deepali Krishan Bhat; Sanjeev Goswami; Sanjay Kumar Agarwal; Gurvinder Kaur; Jasmeet Kaur; Narinder Mehra

    2017-01-01

    Background & objectives: Antibodies specific to donor human leucocyte antigen (HLA) play a critical role in graft rejection and graft loss. In recent years, techniques for their detection have evolved significantly providing an ever-increasing degree of sensitivity and specificity, from the conventional cell-based assays to the advanced solid-phase system based on the Luminex platform. Consensus is still evolving on the routine employment of all these methods, either stand alone or in combina...

  5. Clinical relevance of HLA donor-specific antibodies detected by single antigen assay in kidney transplantation.

    Science.gov (United States)

    Caro-Oleas, José Luis; González-Escribano, María Francisca; González-Roncero, Francisco Manuel; Acevedo-Calado, María José; Cabello-Chaves, Virginia; Gentil-Govantes, Miguel Ángel; Núñez-Roldán, Antonio

    2012-03-01

    Clinical relevance of donor-specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch in pre-transplant serum samples from patients with a negative cytotoxicity-dependent complement crossmatch is controversial. The aim of this study was to analyse the influence of a pre-transplant positive virtual crossmatch in the outcome of kidney transplantation. A total of 892 patients who received a graft from deceased donors after a negative cytotoxicity crossmatch were included. Presence of anti-human leucocyte antigen (HLA) antibodies was investigated using a Luminex screening assay and anti-HLA specificities were assigned performing a Luminex single antigen assay. Graft survival was significantly worse among patients with anti-HLA DSA compared to both patients with anti-HLA with no DSA (P = 0.001) and patients without HLA antibodies (P HLA with no DSA and no HLA antibodies patient groups were observed (P = 0.595). Influence of both anti-Class I and anti-Class II DSA was detected (P 1500 (global P > 0.05). The presence of preformed HLA DSA in transplanted patients with a negative cytotoxicity crossmatch is associated with a lower allograft survival. The detection of anti-HLA with no DSA has no influence in the graft outcome. Finally, there were no demonstrable effects of mean fluorescence intensity (MFI) values >1500 on graft survival.

  6. Predictive Role of Neutrophil Gelatinase-Associated Lipocaline in Donor-Specific Antibody-Positive and Donor-Specific Antibody-Negative Renal Transplant Patients.

    Science.gov (United States)

    Mamatov, E; Kocaay, A F; Koc, M A; Celebi, Z K; Sengül, S; Keven, K; Tutkak, H; Tuzuner, A

    2015-01-01

    Renal transplantation is the best choice for the treatment of dialysis patients with end-stage renal failure because it provides better quality of life and more life time. However, despite successful surgical techniques, immunological issues in kidney transplantation are not completely resolved. Thus, after transplantation, patients must be followed up closely. Although patient follow-up with the use of creatinine and renal biopsy are common, it is thought that biopsy is too invasive and that creatinine is unreliable. Hence, new parameters that correlate with the patient's immunological condition are needed in clinical monitoring. One of the biomarkers that has been studied recently is neutrophil gelatinase-associated lipocalin (NGAL). Its diagnostic value in cases of acute renal failure, delayed graft function, and IgA nephropathy is widely investigated. However, data are insufficient as to whether NGAL can be used for follow-up in the chronic process after renal transplantation. We aimed to investigate the predictive value of NGAL in terms of rejection in donor-specific antibody (DSA)-positive and DSA-negative renal transplant patients. Ninety patients were included. We found that rejection rates were higher in patients whose NGAL values were ≥ 50 and DSA-positive. Delayed graft function was seen more frequently in patients whose NGAL values were ≥ 50. An increase in NGAL level does not always indicate renal injury because NGAL is also an acute-phase reactant. NGAL cannot be used alone to diagnose rejection, but, if NGAL level is high, it is necessary to study DSA, and sub-clinical rejection must be researched. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Bioengineering Thymus Organoids to Restore Thymic Function and Induce Donor-Specific Immune Tolerance to Allografts

    Science.gov (United States)

    Fan, Yong; Tajima, Asako; Goh, Saik Kia; Geng, Xuehui; Gualtierotti, Giulio; Grupillo, Maria; Coppola, Antonina; Bertera, Suzanne; Rudert, William A; Banerjee, Ipsita; Bottino, Rita; Trucco, Massimo

    2015-01-01

    One of the major obstacles in organ transplantation is to establish immune tolerance of allografts. Although immunosuppressive drugs can prevent graft rejection to a certain degree, their efficacies are limited, transient, and associated with severe side effects. Induction of thymic central tolerance to allografts remains challenging, largely because of the difficulty of maintaining donor thymic epithelial cells in vitro to allow successful bioengineering. Here, the authors show that three-dimensional scaffolds generated from decellularized mouse thymus can support thymic epithelial cell survival in culture and maintain their unique molecular properties. When transplanted into athymic nude mice, the bioengineered thymus organoids effectively promoted homing of lymphocyte progenitors and supported thymopoiesis. Nude mice transplanted with thymus organoids promptly rejected skin allografts and were able to mount antigen-specific humoral responses against ovalbumin on immunization. Notably, tolerance to skin allografts was achieved by transplanting thymus organoids constructed with either thymic epithelial cells coexpressing both syngeneic and allogenic major histocompatibility complexes, or mixtures of donor and recipient thymic epithelial cells. Our results demonstrate the technical feasibility of restoring thymic function with bioengineered thymus organoids and highlight the clinical implications of this thymus reconstruction technique in organ transplantation and regenerative medicine. PMID:25903472

  8. A Requirement Specification Language for AADL

    Science.gov (United States)

    2016-06-01

    Group. OMG Systems Modeling Language . OMG. 2015. http://www.omgsysml.org [OSATE 2016] Open Source AADL Tool Environment (OSATE), Version 2. Computer ...A Requirement Specification Language for AADL Peter H. Feiler Julien Delange Lutz Wrage June 2016 TECHNICAL REPORT CMU/SEI-2016-TR-008...reproduced in its entirety, without modification, and freely distrib- uted in written or electronic form without requesting formal permission. Permission

  9. Norovirus-specific memory T cell responses in adult human donors

    Directory of Open Access Journals (Sweden)

    Maria Malm

    2016-10-01

    Full Text Available Norovirus (NoV is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV specific serum antibodies which block the binding of NoV virus-like particles (VLPs to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney, and GI.3, and IFN-g production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539 amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-g in response to the peptides and five subjects produced IFN-g in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151 was identified in two subjects, both having human leukocyte antigen (HLA-A*02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

  10. Refining System Requirements to Program Specifications

    DEFF Research Database (Denmark)

    Olderog, Ernst-Ruediger; Ravn, Anders P.; Skakkebæk, Jens Ulrik

    1996-01-01

    A coherent and mathematically well-founded approach to the design ofreal-time and hybrid systems is presented.It covers requirementsanalysis and specification, design of controlling automatasatisfying the requirements, and derivation ofoccam-like communicating programs from these automata.......The generalized railroad crossing due to Heitmeyer and Lynchillustrates the approach.Requirements are analyzed within aconventional dynamic systems model of a plant, where states arefunctions of the reals, representing time. The requirements arespecified in an assumption-commitment style using Duration Calculus...... to component descriptions in asystems design language that uses timed trace assertions over statetransition events to constrain control flow.Components can under certain conditions be transformed tooccam-like communicating programs....

  11. Specificities of transplantation of kidneys procured from donors with situs inversus totalis: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Petrović Milica

    2015-01-01

    Full Text Available Introduction. Situs inversus totalis (SIT represents a total vertical transposition of the thoracic and abdominal organs which are arranged in a mirror image reversal of the normal positioning 1. We presented a successful pre-dialysis kidney transplantation from a living sibling donor with SIT and the longest donor follow-up period, along with analysis of the reviewed literature. Case report. The pair for pre-dialysis kidney transplantation included a 68-year-old mother and 34-year-old daughter at low immunological risk. Comorbidities evidenced in kidney donors with previously diagnosed SIT, included moderate arterial hypertension and borderline blood glucose level. Explantation of the left donor kidney and its placement into the right iliac fossa of the recipient were performed in the course of the surgical procedure. A month after nephrectomy, second degree renal failure was noticed in the donor. A 20-month follow-up of the donor’s kidney and graft in the recipient proved that their functions were excellent. Conclusion. In donors with previously diagnosed SIT the multidisciplinary approach, preoperative evaluation of the patient and detection of possible vascular anomalies are required to provide maximum safety for the donor.

  12. The transfer of adaptive immunity to CMV during hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor.

    Science.gov (United States)

    Scheinberg, Phillip; Melenhorst, Jan J; Brenchley, Jason M; Hill, Brenna J; Hensel, Nancy F; Chattopadhyay, Pratip K; Roederer, Mario; Picker, Louis J; Price, David A; Barrett, A John; Douek, Daniel C

    2009-12-03

    The successful reconstitution of adaptive immunity to human cytomegalovirus (CMV) in hematopoietic stem cell transplantation (HSCT) recipients is central to the reduction of viral reactivation-related morbidity and mortality. Here, we characterized the magnitude, specificity, phenotype, function, and clonotypic composition of CMV-specific T-cell responses in 18 donor-recipient pairs both before and after HSCT. The principal findings were: (1) the specificity of CMV-specific T-cell responses in the recipient after HSCT mirrors that in the donor; (2) the maintenance of these targeting patterns reflects the transfer of epitope-specific T-cell clonotypes from donor to recipient; (3) less differentiated CD27(+)CD57(-) CMV-specific memory T cells are more likely to persist in the recipient after HSCT compared with more terminally differentiated CD27(-) CD57(+) CMV-specific memory T cells; (4) the presence of greater numbers of less differentiated CD8(+) CMV-specific T cells in the donor appears to confer protection against viral reactivation in the recipient after HSCT; and (5) CMV-specific T cells acquire a more differentiated phenotype and a restricted functional profile after HSCT. Overall, these findings define the immunologic factors that influence the successful adoptive transfer of antigen-specific T-cell immunity during HSCT, which enables the identification of recipients at particular risk of CMV reactivation after HSCT.

  13. 21 CFR 1271.60 - What quarantine and other requirements apply before the donor-eligibility determination is complete?

    Science.gov (United States)

    2010-04-01

    ... OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Donor Eligibility § 1271.60 What quarantine and other requirements apply before the... 21 Food and Drugs 8 2010-04-01 2010-04-01 false What quarantine and other requirements apply...

  14. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT.

    Science.gov (United States)

    Yoshihara, S; Maruya, E; Taniguchi, K; Kaida, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Ikegame, K; Okada, M; Soma, T; Hayashi, K; Fujii, N; Onuma, T; Kusunoki, Y; Saji, H; Ogawa, H

    2012-04-01

    A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSA-corresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P=0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.

  15. Technical Specification action statements requiring shutdown

    International Nuclear Information System (INIS)

    Mankamo, T.; Kim, I.S.; Samanta, P.K.

    1993-11-01

    When safety systems fail during power operation, the limiting conditions for operation (LCOs) and associated action statements of technical specifications typically require that the plant be shut down within the limits of allowed outage time (AOT). However, when a system needed to remove decay heat, such as the residual heat removal (RHR) system, is inoperable or degraded, shutting down the plant may not necessarily be preferable, from a risk perspective, to continuing power operation over a usual repair time, giving priority to the repairs. The risk impact of the basic operational alternatives, i.e., continued operation or shutdown, was evaluated for failures in the RHR and standby service water (SSW) systems of a boiling-water reactor (BWR) nuclear power plant. A complete or partial failure of the SSW system fails or degrades not only the RHR system but other front-line safety systems supported by the SSW system. This report presents the methodology to evaluate the risk impact of LCOs and associated AOT; the results of risk evaluation from its application to the RHR and SSW systems of a BWR; the findings from the risk-sensitivity analyses to identify alternative operational policies; and the major insights and recommendations to improve the technical specifications action statements

  16. Identified adjustability dimensions when generating a product specific requirements specification by requirements reuse

    DEFF Research Database (Denmark)

    Hauksdóttir, Dagný; Mortensen, Niels Henrik; Nielsen, Poul Erik

    2014-01-01

    set. In this paper the objective is not to present a specific method for requirements reuse but to introduce and discuss the possible dimensions of adjustability when generating a product requirement set by reusing requirements from a reusable set. Six adjustability dimensions have been identified....... This discussion should help practitioners to better understand the possible methods that can be implemented and to design a user friendly and sustainable approach. A case study, describing how the dimensions are incorporated in two requirements reuse approaches, for Danfoss Solar Inverters (SI) and Danfoss...

  17. Requirements and specifications for a particle database

    International Nuclear Information System (INIS)

    2015-01-01

    particle stored inside. In order to make access as simple as possible, the database will include unique names (or 'id's) for every particle that it stores. Reaction databases can then refer to a specific particle either by id. Where possible, particle ids should be made descriptive to assist human readers in understanding the contents of reaction and particle databases. The particle database is being primarily developed to store nuclei and nuclear states, but it must also be capable of storing some atomic and molecular properties. In particular the database must support atomic electron configurations since they can play an important role in nuclear reactions and decays. Excited nuclear states sometimes decay via internal conversion, 'kicking out' an electron from an inner shell and leaving the remaining electrons to de-excite (emitting x-rays) to fill the new vacancy. Excited atomic states can also be populated through photo-atomic reactions Adding electronic configurations to the database has the potential to drastically increase its size: if unique ids must be given not only to each nucleus and excited nuclear level but also to every possible electron configuration for each nucleus and level, the database will quickly grow to an unmaintainable size. In order to get around this problem and support atomic and molecular properties without drastically increasing the number of particles, the database will allow the use of 'qualifiers' that can be added to a particle to modify its properties. This document describes the requirements and specifications for a particle data hierarchy, including documentation, bibliography information, particle qualifiers as well as particle families and particle groups. This document uses the XML meta-language to illustrate examples of how particle data will be stored. However, like other tasks under SG38, it should be possible to store the particle database in other meta-languages (that is, languages that define a

  18. Influences of Pre-formed Donor-Specific Anti-Human Leukocyte Antigen Antibodies in Living-Donor Renal Transplantation: Results With Graft Immunocomplex Capture Fluorescence Analysis.

    Science.gov (United States)

    Nakamura, T; Ushigome, H; Watabe, K; Imanishi, Y; Masuda, K; Matsuyama, T; Harada, S; Koshino, K; Iida, T; Nobori, S; Yoshimura, N

    2017-06-01

    Advances in immunosuppressants enable organ transplantation for sensitized patients. However, influences of pre-formed donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have not been fully understood in renal transplantation (RT). On the other hand, immunocomplex capture fluorescence analysis (ICFA) is a reliable method to detect donor-specific anti-HLA antibodies and HLA antigen complexes. Graft ICFA can detect DSA in an allograft (g-DSA). To elucidate the consequences of pre-formed DSA, 198 patients who underwent living-donor RT were enrolled for this study (observation period: 57.8 ± 34.9 months); 187 patients in the DSA- group (excluding ABO-incompatible cases) and 11 patients in the DSA+ group. Before RT, all DSA+ patients had undergone rituximab administration and plasmapheresis. For a graft ICFA, the biopsy specimen (1 × 10 5 cells) was dissolved, and HLA antigens were captured by anti-HLA beads. Finally, DSA-HLA complexes were detected by means of PE-conjugated anti-human IgG antibodies and analyzed by use of a Luminex system. A ratio (sample/blank beads, mean of fluorescence intensity) was calculated: ≥1.0 was determined as positive g-DSA. There were no significant differences in 5-year graft survival (87.9%/100% in the DSA-/DSA+ groups, respectively). In terms of antibody-mediated rejection (AMR), within 1 month after RT, pathologically determined AMR occurred 3.2% and 63.4% in the DSA- and DSA+ groups, respectively (P < .0001). However, interestingly, more than half of them (57.1%) indicated only subclinical AMR, that is, no fluctuation of S-Cr. As representative of 2 cases of subclinical AMR, g-DSA deposition could be confirmed (1.15 ± 0.04) at 1 hour after reperfusion by graft ICFA. Furthermore, g-DSA shifted to 2.20 ± 0.98 at 3 weeks after transplantation, along with a decline in s-DSA mean of fluorescence intensity (1718-506.5). Although pathologically determined AMR occurred more frequently in pre-formed DSA+ recipients, it

  19. Protection of Mice from Acute Graft-versus-Host Disease Requires CD28 Co-stimulation on Donor CD4+ Foxp3+ Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Anna Uri

    2017-06-01

    Full Text Available Acute graft-versus-host disease (aGvHD is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell plus T cell transplantation (allo-HSCT. In this study, we investigated the requirement for CD28 co-stimulation of donor CD4+ conventional (CD4+CD25−Foxp3−, Tconv and regulatory (CD4+CD25+Foxp3+, Treg T cells in aGvHD using tamoxifen-inducible CD28 knockout (iCD28KO or wild-type (wt littermates as donors of CD4+ Tconv and Treg. In the highly inflammatory C57BL/6 into BALB/c allo-HSCT transplantation model, CD28 depletion on donor CD4+ Tconv reduced clinical signs of aGvHD, but did not significantly prolong survival of the recipient mice. Selective depletion of CD28 on donor Treg did not abrogate protection of recipient mice from aGvHD until about day 20 after allo-HSCT. Later, however, the pool of CD28-depleted Treg drastically declined as compared to wt Treg. Consequently, only wt, but not CD28-deficient, Treg were able to continuously suppress aGvHD and induce long-term survival of the recipient mice. To our knowledge, this is the first study that specifically evaluates the impact of CD28 expression on donor Treg in aGvHD. Moreover, the delayed kinetics of aGvHD lethality after transplantation of iCD28KO Treg provides a novel animal model for similar disease courses found in patients after allo-HSCT.

  20. 46 CFR 63.20-1 - Specific control system requirements.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Specific control system requirements. 63.20-1 Section 63... AUXILIARY BOILERS Additional Control System Requirements § 63.20-1 Specific control system requirements. In... following requirements apply for specific control systems: (a) Primary safety control system. Following...

  1. Light duty utility arm software requirements specification

    International Nuclear Information System (INIS)

    Kiebel, G.R.

    1995-01-01

    This document defines the software requirements for the integrated control and data acquisition system of the Light Duty Utility Arm (LDUA) System. It is intended to be used to guide the design of the application software, to be a basis for assessing the application software design, and to establish what is to be tested in the finished application software product

  2. Ontology for quality specification in requirements engineering

    NARCIS (Netherlands)

    Heidari, F.; Loucopoulos, P.; Brazier, F.M.

    2013-01-01

    The field of Requirements Engineering (RE) is arguably one of the most crucial areas in the development of systems in support of organisational structures and processes. Eliciting, negotiating, analysing and validating are RE processes that rely on appropriate abstraction mechanisms. This paper

  3. Donor hematopoiesis in mice following total lymphoid irradiation requires host T-regulatory cells for durable engraftment

    Science.gov (United States)

    Müller, Antonia M. S.; Poyser, Jessica; Küpper, Natascha J.; Burnett, Cassandra; Ko, Rose M.; Kohrt, Holbrook E.K.; Florek, Mareike; Zhang, Pei; Negrin, Robert S.

    2014-01-01

    Total lymphoid irradiation (TLI) with antithymocyte globulin (ATG) is a unique regimen that prepares recipients for allogeneic hematopoietic cell transplantation by targeting lymph nodes, while sparing large areas of the bone marrow. TLI is reported to increase the frequency of CD4+CD25+FoxP3+ T-regulatory cells (Treg) relative to conventional T cells. In this study, barriers to hematopoietic stem cell (HSC) engraftment following this nonmyeloablative conditioning were evaluated. TLI/ATG resulted in profound lymphoablation but endogenous host HSC remained. Initial donor HSC engraftment occurred only in radiation exposed marrow sites, but gradually distributed to bone marrow outside the radiation field. Sustained donor engraftment required host lymphoid cells insofar as lymphocyte deficient Rag2γc−/− recipients had unstable engraftment compared with wild-type. TLI/ATG treated wild-type recipients had increased proportions of Treg that were associated with increased HSC frequency and proliferation. In contrast, Rag2γc−/− recipients who lacked Treg did not. Adoptive transfer of Treg into Rag2γc−/− recipients resulted in increased cell cycling of endogenous HSC. Thus, we hypothesize that Treg influence donor engraftment post-TLI/ATG by increasing HSC cell cycling, thereby promoting the exit of host HSC from the marrow niche. Our study highlights the unique dynamics of donor hematopoiesis following TLI/ATG, and the effect of Treg on HSC activity. PMID:24591203

  4. Simulation Data Management - Requirements and Design Specification

    Energy Technology Data Exchange (ETDEWEB)

    Clay, Robert L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Friedman-Hill, Ernest J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gibson, Marcus J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoffman, Edward L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Olson, Kevin H. [Science Applications International Corporation (SAIC), Reston, VA (United States); Laney, Daniel [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-11-01

    Simulation Data Management (SDM), the ability to securely organize, archive, and share analysis models and the artifacts used to create them, is a fundamental requirement for modern engineering analysis based on computational simulation. We have worked separately to provide secure, network SDM services to engineers and scientists at our respective laboratories for over a decade. We propose to leverage our experience and lessons learned to help develop and deploy a next-generation SDM service as part of a multi-laboratory team. This service will be portable across multiple sites and platforms, and will be accessible via a range of command-line tools and well-documented APIs. In this document, we’ll review our high-level and low-level requirements for such a system, review one existing system, and briefly discuss our proposed implementation.

  5. LHCb electronics - requirements, specifications and implementation

    CERN Document Server

    Bibby, J

    2001-01-01

    This document is intended to serve as a requirements document, a design manual and an implementation reference for the RICH electronics systems. At the current time, the electronics design is under active consideration and this is reflected in this document which represents a working proposal as regards both the functional model and physical implementation. Comments on installation, commissioning, and maintenance are included. For convenience a description of the proposed RICH data formats is appended.

  6. FLECH PowerMax Service Requirement Specification

    OpenAIRE

    2014-01-01

    It is expected that in the future, ancillary services will be required at distribution level. This work describes how one of these ancillary services, the PowerMax service, must be spec ified within a market framework. The basis of this work is the Flexibility Clearing House (FLE CH) platform and the Distribution System Operator (DSO) services defined in [1]. The PowerMax service has been further discussed in [2], and this technical report seeks to clarify the implementation details first dis...

  7. Specific demographic factors could predict deceased potential cornea donors: A retrospective study from Beijing Tongren Hospital Eye Bank.

    Science.gov (United States)

    Liu, Yang; Zhang, Yingnan; Zhang, Jing; Yu, Jin; Liang, Qingfeng; Pan, Zhiqiang

    2017-12-01

    Compared with evident cornea donors (ECDs), deceased potential cornea donors (DPCDs) have no obvious donor identifications to reference, which causes many eligible cornea tissues to be wasted. The demographic characteristics of DPCDs might be different from those of ECDs owing to the following different features: donation consent provided by relatives and willingness to donate before death. Thus, the aim of this study is to reveal the demographic characteristics of DPCDs by comparing DPCDs and ECDs.The demographic factors of 138 donors (both DPCDs and ECDs) were collected from the Beijing Tongren Hospital Eye Bank database and analyzed. To differentiate DPCDs from ECDs using the above-mentioned features, we interviewed the relatives of the donors by telephone. The relatives' attitudes toward cornea donation and their suggestions for our donation service were also acquired during the interview. Two logistic regressions were performed to reveal the demographic factors influencing the 2 features and indicate DPCDs.The donors had certain demographic characteristics (elderly, secondary, or tertiary education level, central district resident), and the most frequent cause of death for the donors was a malignant tumor (n = 56, 43.1%). All the relatives had positive attitudes toward cornea donations, and they hoped to increase publicity efforts to encourage more people to donate and establish more convenient and efficient access for cornea donation. In univariate regressions, age (P = .004, >50 years: odds ratio [OR] = 6.89, 95% confidence interval [CI]: 1.82-26.05), marital status (P = .043, divorced: OR = 9.00,95% CI: 1.33-60.80) significantly influenced relative consent, whereas age (P = .001, >50 years: OR = 15.00, 95% CI: 3.00-74.98), and family address (P = .001, central district: OR = 1) were significant factors influencing the willingness to donate before death. In multivariate regression, age (P = .021, >50 years: OR = 8

  8. Donor Specific Anti-HLA Antibody and Risk of Graft Failure in Haploidentical Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Piyanuch Kongtim

    2016-01-01

    Full Text Available Outcomes of allogeneic hematopoietic stem cell transplantation (AHSCT using HLA-half matched related donors (haploidentical have recently improved due to better control of alloreactive reactions in both graft-versus-host and host-versus-graft directions. The recognition of the role of humoral rejection in the development of primary graft failure in this setting has broadened our understanding about causes of engraftment failure in these patients, helped us better select donors for patients in need of AHSCT, and developed rational therapeutic measures for HLA sensitized patients to prevent this unfortunate event, which is usually associated with a very high mortality rate. With these recent advances the rate of graft failure in haploidentical transplantation has decreased to less than 5%.

  9. Engineering Specifications derived from Science Requirements

    Science.gov (United States)

    Stahl, H. Philip; Arnold, William; Bevan, Ryan M.; Smith, W. Scott; Kirk, Charles S.; Postman, Marc

    2013-01-01

    Advanced Mirror Technology Development (AMTD) is a multi-year effort to systematically mature to TRL-6 the critical technologies needed to produce 4-m or larger flight-qualified UVOIR mirrors by 2018 so that a viable mission can be considered by the 2020 Decadal Review. This technology must enable missions capable of both general astrophysics & ultra-high contrast observations of exoplanets. To accomplish our objective, we use a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND result in a high-performance low-cost low-risk system.

  10. FLECH PowerMax Service Requirement Specification

    DEFF Research Database (Denmark)

    It is expected that in the future, ancillary services will be required at distribution level. This work describes how one of these ancillary services, the PowerMax service, must be spec ified within a market framework. The basis of this work is the Flexibility Clearing House (FLE CH) platform...... by establishing a maximum power that a cluster of consumer devices may draw from the syste m. The consumers will receive a payment for providing this service, and the DSO will be able to postpone grid reinfo rcement...

  11. Smart grid standards specifications, requirements, and technologies

    CERN Document Server

    Sato, Takuro; Duan, Bin; Macuha, Martin; Zhou, Zhenyu; Wu, Jun; Tariq, Muhammad; Asfaw, Solomon A

    2015-01-01

    With numerous existing Smart Grid standards, it is clear that governments and industrial organizations world-wide have understood and acknowledged the critical role they play. This timely book is a useful guide for Smart Grid professionals in easily classifying fundamental Smart Grid standards, and to quickly find the building blocks they need to analyse and implement a Smart Grid system. The standards are organized in a systematic manner that aids identification, according to grid requirements. It also covers broader Smart Grid areas including, but not limited to, the following: A fully c

  12. The effect of induction therapy on established CMV specific t-cell immunity in living donor kidney transplantation.

    Science.gov (United States)

    Stranavova, L; Hruba, P; Girmanova, E; Tycova, I; Slavcev, A; Fronek, J; Slatinska, J; Reinke, P; Volk, H-D; Viklicky, O

    2018-01-05

    Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

  13. 22 CFR 226.49 - USAID-Specific procurement requirements

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false USAID-Specific procurement requirements 226.49... TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Post-award Requirements Procurement Standards § 226.49 USAID-Specific procurement requirements Procurement requirements which are applicable to USAID because of statute...

  14. ARIES: Acquisition of Requirements and Incremental Evolution of Specifications

    Science.gov (United States)

    Roberts, Nancy A.

    1993-01-01

    This paper describes a requirements/specification environment specifically designed for large-scale software systems. This environment is called ARIES (Acquisition of Requirements and Incremental Evolution of Specifications). ARIES provides assistance to requirements analysts for developing operational specifications of systems. This development begins with the acquisition of informal system requirements. The requirements are then formalized and gradually elaborated (transformed) into formal and complete specifications. ARIES provides guidance to the user in validating formal requirements by translating them into natural language representations and graphical diagrams. ARIES also provides ways of analyzing the specification to ensure that it is correct, e.g., testing the specification against a running simulation of the system to be built. Another important ARIES feature, especially when developing large systems, is the sharing and reuse of requirements knowledge. This leads to much less duplication of effort. ARIES combines all of its features in a single environment that makes the process of capturing a formal specification quicker and easier.

  15. Risk factors for human immunodeficiency virus among blood donors in Cameroon: evidence for the design of an Africa-specific donor history questionnaire.

    Science.gov (United States)

    Tagny, Claude T; Nguefack-Tsague, Georges; Fopa, Diderot; Ashu, Celestin; Tante, Estel; Ngo Balogog, Pauline; Donfack, Olivier; Mbanya, Dora; Laperche, Syria; Murphy, Edward

    2017-08-01

    In sub-Saharan Africa improving the deferral of at-risk blood donors would be a cost-effective approach to reducing transfusion-transmitted human immunodeficiency virus (HIV) infections. We performed a pilot case-control study to identify the risk factors for HIV infection and to develop an adapted donor history questionnaire (DHQ) for sub-Saharan Africa. We recruited 137 HIV-positive donors (cases) and 256 HIV-negative donors (controls) and gathered risk factor data using audio computer-assisted self-interview. Variables with univariate associations were entered into a logistic regression model to assess independent associations. A scoring scheme to distinguish between HIV-positive and HIV-negative donors was developed using receiver operating characteristics curves. We identified 16 risk factors including sex with sex worker, past history or treatment for sexually transmitted infections, and having a partner who used injected or noninjected illegal drugs. Two novel risks were related to local behavior: polygamy (odds ratio [OR], 22.7; 95% confidence interval [CI], 5.9-86.7) and medical or grooming treatment on the street (OR, 1.8; 95% CI, 1.0-3.0). Using the 16 selected items the mean scores (>100) were 82.6 ± 6.7 (range, 53.2-95.1) and 85.1 ± 5.2 for HIV-negative donors versus 77.9 ± 6.8 for HIV-positive ones (p = 0.000). Donors who scored between 80 and 90 were more likely to be HIV negative than those who scored less (OR, 31.4; 95% CI, 3.1-313.9). We identified both typical and novel HIV risk factors among Cameroonian blood donors. An adapted DHQ and score that discriminate HIV-negative donors may be an inexpensive means of reducing transfusion-transmitted HIV through predonation screening. © 2017 AABB.

  16. Structuring Formal Requirements Specifications for Reuse and Product Families

    Science.gov (United States)

    Heimdahl, Mats P. E.

    2001-01-01

    In this project we have investigated how formal specifications should be structured to allow for requirements reuse, product family engineering, and ease of requirements change, The contributions of this work include (1) a requirements specification methodology specifically targeted for critical avionics applications, (2) guidelines for how to structure state-based specifications to facilitate ease of change and reuse, and (3) examples from the avionics domain demonstrating the proposed approach.

  17. Proteome-wide analysis of HIV-specific naive and memory CD4(+) T cells in unexposed blood donors.

    Science.gov (United States)

    Campion, Suzanne L; Brodie, Tess M; Fischer, William; Korber, Bette T; Rossetti, Astrea; Goonetilleke, Nilu; McMichael, Andrew J; Sallusto, Federica

    2014-06-30

    The preexisting HIV-1-specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4(+) T cell repertoire in healthy HIV-1-negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the library technique, we examined whether naive, central memory, and/or effector memory CD4(+) T cells specific for overlapping peptides spanning the entire HIV-1 proteome were detectable in 10 HLA diverse, HIV-1-unexposed, seronegative donors. HIV-1-specific cells were detected in all donors at a mean of 55 cells/million naive cells and 38.9 and 34.1 cells/million in central and effector memory subsets. Remarkably, peptide mapping showed most epitopes recognized by naive (88%) and memory (56%) CD4(+) T cells had been previously reported in natural HIV-1 infection. Furthermore, 83% of epitopes identified in preexisting memory subsets shared epitope length matches (8-12 amino acids) with human microbiome proteins, suggestive of a possible cross-reactive mechanism. These results underline the power of a proteome-wide analysis of peptide recognition by human T cells for the identification of dominant antigens and provide a baseline for optimizing HIV-1-specific helper cell responses by vaccination. © 2014 Campion et al.

  18. Introducing a game approach towards IS requirements specification

    DEFF Research Database (Denmark)

    Jensen, Mika Yasuoka; Kadoya, Kyoichi; Niwa, Takashi

    2014-01-01

    Devising a system requirements specification is a challenging task. Even after several decades of system development research, specifications for large-scale, widely-used systems remain difficult. In this paper, we suggest a first step toward a requirements specification through a stakeholder inv...... stakeholder involvement method with game elements can be effectively utilized as a first step towards requirement specification....... involvement approach with game elements. We report preliminary findings from a practice case in which our methods are applied to the requirement specification phase of a project management system. The analysis showed that our game approach fostered innovative idea generation and captured implicit user...

  19. The clinical and genomic significance of donor-specific antibody-positive/C4d-negative and donor-specific antibody-negative/C4d-negative transplant glomerulopathy.

    Science.gov (United States)

    Hayde, Nicole; Bao, Yi; Pullman, James; Ye, Bin; Calder, R Brent; Chung, Monica; Schwartz, Daniel; Lubetzky, Michelle; Ajaimy, Maria; de Boccardo, Graciela; Akalin, Enver

    2013-12-01

    This study investigated the mechanisms involved in development of donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP) by allograft gene expression profiles using microarrays. This cohort study was conducted in kidney transplant recipients. Patients were eligible for inclusion if they required a clinically indicated biopsy at any time point after their transplant. They were then classified according to their histopathology findings and DSA and C4d results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d- TGP, 25 DSA-/C4d- TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA) biopsy specimens were identified. In a subset of patients from the study population, biopsy specimens in each group and normal transplant kidney specimens were analyzed with Affymetrix Human Gene 1.0 ST Arrays. The mean sum score of glomerulitis and peritubular capillaritis increased from 0.28±0.78 in IFTA specimens to 0.75±0.85 in DSA-/C4d- TGP specimens, 1.71±1.49 in DSA+/C4d-/TGP specimens, and 2.11±1.74 in CAMR specimens (PTGP specimens (14.3%), and DSA-/C4d- TGP specimens (16%) (P=0.01). With use of microarrays, comparison of the gene expression profiles of DSA-/C4d- TGP specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell-associated transcripts (QCAT). However, both CAMR and DSA+/C4d- TGP specimens had higher expression of not only QCAT but also IFN-γ and rejection-induced, constitutive macrophage-associated, natural killer cell-associated, and DSA-selective transcripts. Endothelial cell-associated transcript expression was upregulated only in CAMR biopsy specimens. These results suggested that DSA+/C4d- TGP biopsy specimens may be classified as CAMR. In contrast, DSA-/C4d- TGP specimens showed increased cytotoxic T cell-associated transcripts, suggesting T cell activation as a mechanism of injury.

  20. The Clinical and Genomic Significance of Donor-Specific Antibody–Positive/C4d-Negative and Donor-Specific Antibody–Negative/C4d-Negative Transplant Glomerulopathy

    Science.gov (United States)

    Hayde, Nicole; Bao, Yi; Pullman, James; Ye, Bin; Calder, R. Brent; Chung, Monica; Schwartz, Daniel; Lubetzky, Michelle; Ajaimy, Maria; de Boccardo, Graciela

    2013-01-01

    Summary Background This study investigated the mechanisms involved in development of donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP) by allograft gene expression profiles using microarrays. Design, Setting, Participants, & Measurements This cohort study was conducted in kidney transplant recipients. Patients were eligible for inclusion if they required a clinically indicated biopsy at any time point after their transplant. They were then classified according to their histopathology findings and DSA and C4d results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d− TGP, 25 DSA−/C4d− TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA) biopsy specimens were identified. In a subset of patients from the study population, biopsy specimens in each group and normal transplant kidney specimens were analyzed with Affymetrix Human Gene 1.0 ST Arrays. Results The mean sum score of glomerulitis and peritubular capillaritis increased from 0.28±0.78 in IFTA specimens to 0.75±0.85 in DSA−/C4d− TGP specimens, 1.71±1.49 in DSA+/C4d−/TGP specimens, and 2.11±1.74 in CAMR specimens (PTGP specimens (14.3%), and DSA−/C4d− TGP specimens (16%) (P=0.01). With use of microarrays, comparison of the gene expression profiles of DSA−/C4d− TGP specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell–associated transcripts (QCAT). However, both CAMR and DSA+/C4d− TGP specimens had higher expression of not only QCAT but also IFN-γ and rejection-induced, constitutive macrophage-associated, natural killer cell–associated, and DSA-selective transcripts. Endothelial cell–associated transcript expression was upregulated only in CAMR biopsy specimens. Conclusions These results suggested that DSA+/C4d− TGP biopsy specimens may be classified as CAMR. In contrast, DSA−/C4d− TGP specimens showed

  1. Humoral and cellular CMV responses in healthy donors; identification of a frequent population of CMV-specific, CD4+ T cells in seronegative donors

    DEFF Research Database (Denmark)

    Loeth, Nina; Assing, Kristian; Madsen, Hans O

    2012-01-01

    CMV status is an important risk factor in immune compromised patients. In hematopoeitic cell transplantations (HCT), both donor and recipient are tested routinely for CMV status by serological assays; however, one might argue that it might also be of relevance to examine CMV status by cellular (i...

  2. High frequency of human cytomegalovirus (HCMV)-specific CD8+ T cells detected in a healthy CMV-seropositive donor.

    Science.gov (United States)

    Lang, K S; Moris, A; Gouttefangeas, C; Walter, S; Teichgräber, V; Miller, M; Wernet, D; Hamprecht, K; Rammensee, H G; Stevanovic, S

    2002-06-01

    Human cytomegalovirus (HCMV) persists after infection but is controlled by cellular immune responses, particularly by CD8+ T cells. If infected individuals are immunosuppressed, HCMV can be reactivated. Upon testing the blood of healthy donors with human lymphocyte antigen tetramers, we found one individual with about 50% of his CD8+ T cells being specific for the immunodominant pp65 epitope NLVPMVATV Over a period of 2 years the high level of HCMV-specific T cells was maintained, and no HCMV DNA could be detected. At one timepoint, however, HCMV-specific DNA was detected, while 65% of CD8+ T cells were specific for HCMV. When virus was detectable, a lower percentage of HCMV-specific CD8+ T cells showed interferon gamma (IFN-gamma) production after peptide stimulation in vitro. These data suggest that HCMV reactivation may also occur in immunocompetent persons, accompanied by the presence of HCMV-specific CD8+ T cells which are not producing IFNy, and therefore potentially anergic or in vivo exhausted.

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

    Directory of Open Access Journals (Sweden)

    Daniel J Sobczynski

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

  4. Characterization of specific antibodies against cytomegalovirus (CMV)-encoded interleukin 10 produced by 28 % of CMV-seropositive blood donors

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia Søndergaard; Pedersen, Bente Klarlund

    2011-01-01

    Cytomegalovirus (CMV) has evolved multiple immunological evasion strategies, including the encoding of viral interleukin (IL)-10 homologues (cmvIL-10). In this study, cmvIL-10 bound avidly to the same receptors on blood mononuclear cells and was as bio-potent as native human IL-10. Seventeen...... percent of plasma samples from 3200 Danish blood donors (corresponding to 28¿% of the anti-CMV IgG-positive donors) contained substantial levels of anti-cmvIL-10 IgG antibodies, as measured by a radioimmunoassay for human anti-cmvIL-10 antibodies. The antibodies neither cross-reacted with native human IL......-10 nor with Epstein-Barr virus-encoded IL-10. Anti-cmvIL-10 antibodies potently inhibited the binding of cmvIL-10 to cellular receptors, and they specifically inhibited cmvIL-10-induced JAK-STAT signalling. Ultimately, anti-cmvIL-10 antibodies blocked the inhibitory effect of cmvIL-10...

  5. Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational Studies

    Directory of Open Access Journals (Sweden)

    Israel Sánchez-Moreno

    2015-11-01

    Full Text Available Dihydroxyacetone (DHA kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this enzyme from ATP to inorganic polyphosphate (poly-P; a directed evolution program has been initiated. In the first cycle of evolution, the native enzyme was subjected to one round of error-prone PCR (EP-PCR followed directly (without selection by a round of DNA shuffling. Although the wild-type DHAK did not show activity with poly-P, after screening, sixteen mutant clones showed an activity with poly-phosphate as phosphoryl donor statistically significant. The most active mutant presented a single mutation (Glu526Lys located in a flexible loop near of the active center. Interestingly, our theoretical studies, based on molecular dynamics simulations and hybrid Quantum Mechanics/Molecular Mechanics (QM/MM optimizations, suggest that this mutation has an effect on the binding of the poly-P favoring a more adequate position in the active center for the reaction to take place.

  6. Tuning the Phosphoryl Donor Specificity of Dihydroxyacetone Kinase from ATP to Inorganic Polyphosphate. An Insight from Computational Studies.

    Science.gov (United States)

    Sánchez-Moreno, Israel; Bordes, Isabel; Castillo, Raquel; Ruiz-Pernía, José Javier; Moliner, Vicent; García-Junceda, Eduardo

    2015-11-24

    Dihydroxyacetone (DHA) kinase from Citrobacter freundii provides an easy entry for the preparation of DHA phosphate; a very important C3 building block in nature. To modify the phosphoryl donor specificity of this enzyme from ATP to inorganic polyphosphate (poly-P); a directed evolution program has been initiated. In the first cycle of evolution, the native enzyme was subjected to one round of error-prone PCR (EP-PCR) followed directly (without selection) by a round of DNA shuffling. Although the wild-type DHAK did not show activity with poly-P, after screening, sixteen mutant clones showed an activity with poly-phosphate as phosphoryl donor statistically significant. The most active mutant presented a single mutation (Glu526Lys) located in a flexible loop near of the active center. Interestingly, our theoretical studies, based on molecular dynamics simulations and hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) optimizations, suggest that this mutation has an effect on the binding of the poly-P favoring a more adequate position in the active center for the reaction to take place.

  7. Pre-transplant donor HLA-specific antibodies: characteristics causing detrimental effects on survival after lung transplantation.

    Science.gov (United States)

    Smith, John D; Ibrahim, Mohamed W; Newell, Helen; Danskine, Anna J; Soresi, Simona; Burke, Margaret M; Rose, Marlene L; Carby, Martin

    2014-10-01

    The impact of Luminex-detected HLA antibodies on outcomes after lung transplantation is unclear. Herein we have undertaken a retrospective study of pre-transplant sera from 425 lung transplants performed between 1991 and 2003. Pre-transplant sera, originally screened by complement-dependent cytotoxicity (CDC) assays, were retrospectively tested for the presence of HLA-specific antibodies using HLA-coated Luminex beads and C4d deposition on Luminex beads. The results were correlated with graft survival at 1 year. Twenty-seven patients were retrospectively identified as having been transplanted against donor-specific HLA antibodies (DSA) and 36 patients against non-donor-specific HLA antibodies (NDSA). DSA-positive patients had 1-year survival of 51.9% compared with 77.8% for NDSA and 71.8% for antibody-negative patients (p = 0.029). One-year survival of patients with complement-fixing DSA was 12.5% compared with 62.5% for non-complement-fixing DSA, 75.8% for non-complement-fixing NDSA and 71.8% for antibody-negative patients (p 5,000 had 1-year survival of 33.3% compared with 71.4% for MFI 2,000 to 5000 and 62.5% for MFI 5,000 (p = 0.0001, HR = 5.512). Pre-formed DSA, particularly complement-fixing DSA, and high MFI are associated with poor survival within the first year after lung transplantation. Risk stratification according to complement fixation or MFI levels may allow for increased transplantation in sensitized patients. Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  8. Novel UDP-GalNAc Derivative Structures Provide Insight into the Donor Specificity of Human Blood Group Glycosyltransferase.

    Science.gov (United States)

    Wagner, Gerd K; Pesnot, Thomas; Palcic, Monica M; Jørgensen, Rene

    2015-12-25

    Two closely related glycosyltransferases are responsible for the final step of the biosynthesis of ABO(H) human blood group A and B antigens. The two enzymes differ by only four amino acid residues, which determine whether the enzymes transfer GalNAc from UDP-GalNAc or Gal from UDP-Gal to the H-antigen acceptor. The enzymes belong to the class of GT-A folded enzymes, grouped as GT6 in the CAZy database, and are characterized by a single domain with a metal dependent retaining reaction mechanism. However, the exact role of the four amino acid residues in the specificity of the enzymes is still unresolved. In this study, we report the first structural information of a dual specificity cis-AB blood group glycosyltransferase in complex with a synthetic UDP-GalNAc derivative. Interestingly, the GalNAc moiety adopts an unusual yet catalytically productive conformation in the binding pocket, which is different from the "tucked under" conformation previously observed for the UDP-Gal donor. In addition, we show that this UDP-GalNAc derivative in complex with the H-antigen acceptor provokes the same unusual binding pocket closure as seen for the corresponding UDP-Gal derivative. Despite this, the two derivatives show vastly different kinetic properties. Our results provide a important structural insight into the donor substrate specificity and utilization in blood group biosynthesis, which can very likely be exploited for the development of new glycosyltransferase inhibitors and probes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Chabot, J.; Pepino, P.; Reemtsma, K.; Hardy, M.A.

    1988-01-01

    Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts

  10. Probabilistic safety assessment improves surveillance requirements in technical specifications

    International Nuclear Information System (INIS)

    Cepin, M.; Mavko, B.

    1997-01-01

    Probabilistic Safety Assessment is widely becoming the standard method for assessing, maintaining, assuring and improving the nuclear power plant safety. To achieve one of its many potential benefits, the optimization approach of surveillance requirements in technical specifications was developed. Surveillance requirements in technical specifications define the surveillance test intervals for the equipment to be tested and the testing strategy. This optimization approach based mainly on probabilistic safety assessment results consists of three levels: component level, system level and plant level. The application of this optimization approach on system level has shown that the risk based surveillance requirements differ from existing ones in technical specifications

  11. Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation.

    Science.gov (United States)

    Sekine, Takuya; Marin, David; Cao, Kai; Li, Li; Mehta, Pramod; Shaim, Hila; Sobieski, Catherine; Jones, Roy; Oran, Betul; Hosing, Chitra; Rondon, Gabriela; Alsuliman, Abdullah; Paust, Silke; Andersson, Borje; Popat, Uday; Kebriaei, Partow; Muftuoglu, Muharrem; Basar, Rafet; Kondo, Kayo; Nieto, Yago; Shah, Nina; Olson, Amanda; Alousi, Amin; Liu, Enli; Sarvaria, Anushruti; Parmar, Simrit; Armstrong-James, Darius; Imahashi, Nobuhiko; Molldrem, Jeffrey; Champlin, Richard; Shpall, Elizabeth J; Rezvani, Katayoun

    2016-07-14

    The ability of cord blood transplantation (CBT) to prevent relapse depends partly on donor natural killer (NK) cell alloreactivity. NK effector function depends on specific killer-cell immunoglobulin-like receptors (KIR) and HLA interactions. Thus, it is important to identify optimal combinations of KIR-HLA genotypes in donors and recipients that could improve CBT outcome. We studied clinical data, KIR and HLA genotypes, and NK-cell reconstitution in CBT patients (n = 110). Results were validated in an independent cohort (n = 94). HLA-KIR genotyping of recipient germline and transplanted cord blood (CB) grafts predicted for large differences in outcome. Patients homozygous for HLA-C2 group alleles had higher 1-year relapse rate and worse survival after CBT than did HLA-C1/C1 or HLA-C1/C2 (HLA-C1/x) patients: 67.8% vs 26.0% and 15.0% vs 52.9%, respectively. This inferior outcome was associated with delayed posttransplant recovery of NK cells expressing the HLA-C2-specific KIR2DL1/S1 receptors. HLA-C1/x patients receiving a CB graft with the combined HLA-C1-KIR2DL2/L3/S2 genotype had lower 1-year relapse rate (6.7% vs 40.1%) and superior survival (74.2% vs 41.3%) compared with recipients of grafts lacking KIR2DS2 or HLA-C1 HLA-C2/C2 patients had lower relapse rate (44.7% vs 93.4%) and better survival (30.1% vs 0%) if they received a graft with the combined HLA-C2-KIR2DL1/S1 genotype. Relapsed/refractory disease at CBT, recipient HLA-C2/C2 genotype, and donor HLA-KIR genotype were independent predictors of outcome. Thus, we propose the inclusion of KIR genotyping in graft selection criteria for CBT. HLA-C1/x patients should receive an HLA-C1-KIR2DL2/L3/S2 CB graft, while HLA-C2/C2 patients may benefit from an HLA-C2-KIR2DL1/S1 graft. © 2016 by The American Society of Hematology.

  12. Solid Waste Information and Tracking System (SWITS) Software Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    MAY, D.L.

    2000-03-22

    This document is the primary document establishing requirements for the Solid Waste Information and Tracking System (SWITS) as it is converted to a client-server architecture. The purpose is to provide the customer and the performing organizations with the requirements for the SWITS in the new environment. This Software Requirement Specification (SRS) describes the system requirements for the SWITS Project, and follows the PHMC Engineering Requirements, HNF-PRO-1819, and Computer Software Qualify Assurance Requirements, HNF-PRO-309, policies. This SRS includes sections on general description, specific requirements, references, appendices, and index. The SWITS system defined in this document stores information about the solid waste inventory on the Hanford site. Waste is tracked as it is generated, analyzed, shipped, stored, and treated. In addition to inventory reports a number of reports for regulatory agencies are produced.

  13. Solid Waste Information and Tracking System (SWITS) Software Requirements Specification

    International Nuclear Information System (INIS)

    MAY, D.L.

    2000-01-01

    This document is the primary document establishing requirements for the Solid Waste Information and Tracking System (SWITS) as it is converted to a client-server architecture. The purpose is to provide the customer and the performing organizations with the requirements for the SWITS in the new environment. This Software Requirement Specification (SRS) describes the system requirements for the SWITS Project, and follows the PHMC Engineering Requirements, HNF-PRO-1819, and Computer Software Qualify Assurance Requirements, HNF-PRO-309, policies. This SRS includes sections on general description, specific requirements, references, appendices, and index. The SWITS system defined in this document stores information about the solid waste inventory on the Hanford site. Waste is tracked as it is generated, analyzed, shipped, stored, and treated. In addition to inventory reports a number of reports for regulatory agencies are produced

  14. Planning is not sufficient - Reliable computers need good requirements specifications

    International Nuclear Information System (INIS)

    Matras, J.R.

    1992-01-01

    Computer system reliability is the assurance that a computer system will perform its functions when required to do so. To ensure such reliability, it is important to plan the activities needed for computer system development. These development activities, in turn, require a Computer Quality Assurance Plan (CQAP) that provides the following: a Configuration Management Plan, a Verification and Validation (V and V) Plan, documentation requirements, a defined life cycle, review requirements, and organizational responsibilities. These items are necessary for system reliability; ultimately, however, they are not enough. Development of a reliable system is dependent on the requirements specification. This paper discusses how to use existing industry standards to develop a CQAP. In particular, the paper emphasizes the importance of the requirements specification and of methods for establishing reliability goals. The paper also describes how the revision of ANSI/IEE-ANS-7-4.3.2, Application Criteria for Digital Computer Systems of Nuclear Power Generating Stations, has addressed these issues

  15. Software Requirements Specification Verifiable Fuel Cycle Simulation (VISION) Model

    International Nuclear Information System (INIS)

    D. E. Shropshire; W. H. West

    2005-01-01

    The purpose of this Software Requirements Specification (SRS) is to define the top-level requirements for a Verifiable Fuel Cycle Simulation Model (VISION) of the Advanced Fuel Cycle (AFC). This simulation model is intended to serve a broad systems analysis and study tool applicable to work conducted as part of the AFCI (including costs estimates) and Generation IV reactor development studies

  16. High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors.

    Science.gov (United States)

    Walter, Steffen; Bioley, Gilles; Bühring, Hans-Jörg; Koch, Sven; Wernet, Dorothee; Zippelius, Alfred; Pawelec, Graham; Romero, Pedro; Stevanović, Stefan; Rammensee, Hans-Georg; Gouttefangeas, Cécile

    2005-10-01

    Combining cell surface phenotyping with functional analysis, human CD8+ T cells have been divided into several subsets which are being studied extensively in diverse physiological situations, such as viral infection, cancer and ageing. In particular, so-called terminally differentiated effector cells possess a CD45RA+ CCR7- CD27- CD28- phenotype, contain perforin and, in different models, have been shown to exert direct ex vivo killing and to release interleukins upon both antigen-nonspecific and -specific stimulation. Using HLA class I multimers, we have identified a high frequency of peripheral CD8+ T cells that recognize a peptide derived from the self protein cytokeratin 18 presented by the HLA-A*0201 molecule. These cells can be detected in approximately 15% of the HLA-A2-positive healthy donors tested. A detailed analysis revealed that they must have divided extensively in vivo, have an effector cell phenotype and express various natural killer cell-associated receptors. Interestingly, however, they remained unresponsive to antigen-specific stimulation in vitro in terms of cytotoxicity and cytokine secretion. Thus, cytokeratin 18-specific cells constitute a frequently encountered, new CD8+ T lymphocyte subpopulation without classical effector status and with so far unknown function.

  17. Human Platelet Antigen Alleles in 998 Taiwanese Blood Donors Determined by Sequence-Specific Primer Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Shun-Chung Pai

    2013-01-01

    Full Text Available Polymorphism of human platelet antigens (HPAs leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT, posttransfusion purpura (PTP, and platelet transfusion refractoriness (PTR. HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  18. Human platelet antigen alleles in 998 Taiwanese blood donors determined by sequence-specific primer polymerase chain reaction.

    Science.gov (United States)

    Pai, Shun-Chung; Burnouf, Thierry; Chen, Jen-Wei; Lin, Liang-In

    2013-01-01

    Polymorphism of human platelet antigens (HPAs) leads to alloimmunizations and immune-mediated platelet disorders including fetal-neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP), and platelet transfusion refractoriness (PTR). HPA typing and knowledge of antigen frequency in a population are important in particular for the provision of HPA-matched blood components for patients with PTR. We have performed allele genotyping for HPA-1 through -6 and -15 among 998 platelet donors from 6 blood centers in Taiwan using sequence-specific primer polymerase chain reaction. The HPA allele frequency was 99.55, and 0.45% for HPA-1a and -1b; 96.49, and 3.51% for HPA-2a and -2b; 55.81, and 44.19% for HPA-3a and -3b; 99.75, and 0.25% for HPA-4a and -4b; 98.50, and 1.50% for HPA-5a and -5b; 97.75 and 2.25% for HPA-6a and -6b; 53.71 and 46.29% for HPA-15a and -15b. HPA-15b and HPA-3a, may be considered the most important, followed by HPA-2, -6, -1, -5, and -4 systems, as a cause of FNAIT, PTP, and PTR based on allele frequency. HPA-4b and HPA-5b role cannot be excluded based on their immunogenicity. A larger-scale study will now be conducted to confirm these hypotheses and to establish an apheresis donor database for the procurement of HPA-matched apheresis platelets for patients with PTR.

  19. A Framework for RFID Survivability Requirement Analysis and Specification

    Science.gov (United States)

    Zuo, Yanjun; Pimple, Malvika; Lande, Suhas

    Many industries are becoming dependent on Radio Frequency Identification (RFID) technology for inventory management and asset tracking. The data collected about tagged objects though RFID is used in various high level business operations. The RFID system should hence be highly available, reliable, and dependable and secure. In addition, this system should be able to resist attacks and perform recovery in case of security incidents. Together these requirements give rise to the notion of a survivable RFID system. The main goal of this paper is to analyze and specify the requirements for an RFID system to become survivable. These requirements, if utilized, can assist the system in resisting against devastating attacks and recovering quickly from damages. This paper proposes the techniques and approaches for RFID survivability requirements analysis and specification. From the perspective of system acquisition and engineering, survivability requirement is the important first step in survivability specification, compliance formulation, and proof verification.

  20. Fulminant hepatitis linked to dapsone hypersensitivity syndrome requiring urgent living donor liver transplantation: a case report.

    Science.gov (United States)

    Garcia, Angelica; Yi, Nam-Joon; Lee, Kyoung Bun; Lee, Jeong-Moo; Choi, Young Rok; Suh, Suk-Won; You, Tae; Lee, Kwang-Woong; Park, June Dong; Kang, Hyoung Jin; Kim, Joon Gon; Kang, Eun Kyeong; Hong, Geun; Suh, Kyung-Suk

    2014-11-01

    Dapsone is a sulfone-type drug used widely for different infectious, immune, and hypersensitivity disorders as an antibacterial treatment alone or in combination for leprosy and sometimes for infected skin lesions. DHS is a severe idiosyncratic adverse reaction with multi-organ involvement. However, acute necrotic hepatitis requiring an emergent LT is rare. Herein, we report a case of 12-yr-old girl who suffered from fulminant hepatitis and multi-organ failure due to DHS for PPD. She was saved by emergent LDLT. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal but rare disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Validation of a Rapid and Reliable Test for Diagnosis of Chagas' Disease by Detection of Trypanosoma cruzi-Specific Antibodies in Blood of Donors and Patients in Central America

    Science.gov (United States)

    Ponce, Carlos; Ponce, Elisa; Vinelli, Elizabeth; Montoya, Alberto; de Aguilar, Vilma; Gonzalez, Antonio; Zingales, Bianca; Rangel-Aldao, Rafael; Levin, Mariano J.; Esfandiari, Javan; Umezawa, Eufrosina S.; Luquetti, Alejandro O.; da Silveira, José Franco

    2005-01-01

    In this study we compared the performance of the Chagas Stat-Pak rapid immunochromatographic test with a standard enzyme-linked immunosorbent assay (ELISA) in the serodiagnosis of Chagas' disease in Central America. Out of 3,400 blood donor samples, 156 (4.6%) were positive in both assays. Three sera out of 2,084 samples from reference laboratories were negative with the rapid test but positive with the ELISA (99.8% agreement). Agreement of 100% between the two tests was observed with 339 additional sera from patients with cardiopathies and 175 sera from potential blood donors in emergency surgical cases occurring on weekends or at night. In conclusion, Chagas Stat-Pak showed 99.6% and 99.9% sensitivity and specificity, respectively, when assayed with 5,998 serum samples. It is a sensitive and specific alternative to the ELISA, as required in medical emergencies and blood screenings in Central America. PMID:16207963

  2. Transforming Multidisciplinary Customer Requirements to Product Design Specifications

    Science.gov (United States)

    Ma, Xiao-Jie; Ding, Guo-Fu; Qin, Sheng-Feng; Li, Rong; Yan, Kai-Yin; Xiao, Shou-Ne; Yang, Guang-Wu

    2017-09-01

    With the increasing of complexity of complex mechatronic products, it is necessary to involve multidisciplinary design teams, thus, the traditional customer requirements modeling for a single discipline team becomes difficult to be applied in a multidisciplinary team and project since team members with various disciplinary backgrounds may have different interpretations of the customers' requirements. A new synthesized multidisciplinary customer requirements modeling method is provided for obtaining and describing the common understanding of customer requirements (CRs) and more importantly transferring them into a detailed and accurate product design specifications (PDS) to interact with different team members effectively. A case study of designing a high speed train verifies the rationality and feasibility of the proposed multidisciplinary requirement modeling method for complex mechatronic product development. This proposed research offersthe instruction to realize the customer-driven personalized customization of complex mechatronic product.

  3. Improving syphilis screening in deceased organ donors.

    Science.gov (United States)

    Theodoropoulos, Nicole; Jaramillo, Andrés; Penugonda, Sudhir; Wasik, Carol; Brooks, Katarzyna; Ladner, Daniela P; Jendrisak, Martin D; Ison, Michael G

    2015-02-01

    Current U.S. policy requires screening of all deceased organ donors for syphilis infection. To date, information on syphilis test performance in this population is limited. All donors with a positive rapid plasma reagin (RPR) and matched donors with negative RPR who were evaluated by one organ procurement organization from January 1, 2000, to September 30, 2012, were retrospectively tested, using retained, residual serum, with two alternate RPR tests and four treponemal-specific tests: A fluorescent treponemal antibody absorption test, a microhemagglutination test, a chemiluminescence immunoassay (CLIA), and a Treponema pallidum particle agglutination (TP-PA) test. Thirty-two of 3,555 (0.9%) potential deceased organ donors screened during the study period showed a positive RPR; 61 RPR-negative matched donor samples were studied as well. Thirteen (40.6%) of the RPR-positive donors were found to be false-positive based on confirmatory TP-PA. As compared to TP-PA, the sensitivity of the fluorescent treponemal antibody absorption, microhemagglutination, and CLIA was 87.5%, 91.7% and 100%, respectively. The CLIA and TP-PA results were 100% concordant. Only 17 (53.1%) of the RPR-positive donors had a total of 46 organs recovered for transplantation. Current screening of deceased organ donors by RPR yields a significant number of false-positive results. Use of alternative tests or the routine use of confirmatory tests may reduce the frequency of false-positive results in deceased organ donors.

  4. 18 CFR 12.35 - Specific inspection requirements.

    Science.gov (United States)

    2010-04-01

    ... COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND PROJECT WORKS Inspection by Independent Consultant § 12.35 Specific inspection requirements. (a) Scope of inspection. The inspection by the independent consultant shall include: (1) Due consideration of all relevant...

  5. Functional requirement specification in the packaging development chain

    NARCIS (Netherlands)

    Lutters, Diederick; ten Klooster, Roland

    2008-01-01

    As it is clear that the full packaging life cycle – at least partially – coincides with the product life cycle, both cycles are interwoven. Each has a network of functional requirements, with specific hierarchic propensities. These networks overlap, with prevailing hierarchies playing important

  6. 49 CFR 179.401-1 - Individual specification requirements.

    Science.gov (United States)

    2010-10-01

    .... Test pressure, psig (see § 179.400-16) 60 120. Safety vent bursting pressure, max. psig 60 120... control valve Start-to-vent, max. psig (see § 179.400-20(c)(4)) 17 Not required. Relief device discharge... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS...

  7. Understanding the technical content of requirements in specification document

    DEFF Research Database (Denmark)

    Sudin, Mohd Nizam Bin; Ahmed-Kristensen, Saeema

    2011-01-01

    in practice, 97 statements from 2 specification documents were analyzed in detail and the results are reported in this paper. These statements were analyzed quantitatively and qualitatively based on a pre-defined coding scheme. The results of the study show that the majority of requirements were related...

  8. Blockade of CD40-CD154 at the time of donor-specific blood transfusion does not lead to prolonged kidney allograft survival in nonhuman primates

    NARCIS (Netherlands)

    Ringers, J; Haanstra, KG; Kroczek, RA; Kliem, K; Kuhn, EM; Wubben, J; Ossevoort, MA; Volk, HD; Jonker, M

    2002-01-01

    Background. In rodents it has been demonstrated that blockade of the CD40-CD154 (CD40L) pathway at the time of donor-specific blood transfusion (DST) can result in indefinite graft survival. Because it has been reported in the past that DST in monkeys can have a favorable effect on graft outcome and

  9. Draft Geologic Disposal Requirements Basis for STAD Specification

    Energy Technology Data Exchange (ETDEWEB)

    Ilgen, Anastasia G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bryan, Charles R. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hardin, Ernest [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-03-25

    This document provides the basis for requirements in the current version of Performance Specification for Standardized Transportation, Aging, and Disposal Canister Systems, (FCRD-NFST-2014-0000579) that are driven by storage and geologic disposal considerations. Performance requirements for the Standardized Transportation, Aging, and Disposal (STAD) canister are given in Section 3.1 of that report. Here, the requirements are reviewed and the rationale for each provided. Note that, while FCRD-NFST-2014-0000579 provides performance specifications for other components of the STAD storage system (e.g. storage overpack, transfer and transportation casks, and others), these have no impact on the canister performance during disposal, and are not discussed here.

  10. Romanian regulatory requirements on nuclear field specific education needs

    International Nuclear Information System (INIS)

    Biro, L.; Velicu, O.

    2004-01-01

    This work is intended as a general presentation of the educational system and research field, with reference to nuclear sciences, and the legal system, with reference to requirements established by the regulatory body for the professional qualification and periodic training of personnel involved in different activities in the nuclear field. Thus, part 2 and 3 of the work present only public information regarding the education in nuclear sciences and nuclear research in Romania; in part 4 the CNCAN requirements for the personnel training, specific to nuclear activities are slightly detailed; part 5 consists of few words about the public information activities in Romania; and part 6 tries to draw a conclusion. (authors)

  11. ASSESSMENT OF REQUIREMENT OF THE POPULATION IN THE ORGAN TRANSPLANTATION, THE DONOR RESOURCE AND PLANNING OF THE EFFECTIVE NETWORK OF THE MEDICAL ORGANIZATIONS (THE CENTERS OF TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2013-01-01

    Full Text Available Aim. To estimate the requirement of the population of the Russian Federation for an organ transplantation and donor resource, to offer approach to planning of an effective network of the medical organizations (the centers of transplantation. Materials and methods. The analysis and comparison of statistical data on population, number of the patients receiving a dialysis, data about medical care on an organ transplantation in Russia and foreign countries is made. Results. On the basis of what the assessment of requirement of the population of the Russian Federation in an organ transplantation and donor resource is carried out, approach to planning of an effective network of the medical organizations (the centers of transplantation and scenarios of development of organ do- nation and transplantation in Russia is offered. Conclusion. To provide the population of the Russian Federation with medical care on an organ transplantation according to real requirement and donor resource, in each region of the Russian Federation have to be organized deceased organ donation and transplantation of a cadaveric kidney. But the transplantation of extrarenal organs is better to develop in the federal centers of hi-tech medical care with donor providing from territories of adjacent regions. 

  12. UVB pretreatment of rat bone marrow allografts. Prevention of GVHD and induction of allochimerism and donor-specific unresponsiveness

    International Nuclear Information System (INIS)

    Chabot, J.A.; Pepino, P.; Wasfie, T.; Stegall, M.D.; Marboe, C.; Hardy, M.A.

    1990-01-01

    Ultraviolet B irradiation has been used to pretreat blood and islets to prevent subsequent graft rejection. In this study the optimal dose of UVB irradiation of bone marrow was determined in syngeneic recipients and was subsequently applied to in-vitro treatment of bone marrow allografts. UVB pretreatment of donor bone marrow inoculum led to complete prevention of GVHD in allogeneic rat recipients without major marrow or other toxicity. Long-standing recipients of allogeneic UVB-BM became stable adult chimeras. The recipients of allogeneic BM were populated by donor-type peripheral blood lymphocytes and did not reject host or donor-type heart grafts. The BM allograft recipients were immunocompetent as measured by their ability to normally reject third-party cardiac allografts. We suggest that the prevention of GVHD and induction of stable chimerism in adult recipients of allogeneic UVB-BM may be mediated by suppressor mechanisms

  13. The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

    Science.gov (United States)

    O'Leary, Jacqueline G.; Samaniego, Millie; Barrio, Marta Crespo; Potena, Luciano; Zeevi, Adriana; Djamali, Arjang; Cozzi, Emanuele

    2016-01-01

    Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance. PMID:26680372

  14. Successful generation of primary virus-specific and anti-tumor T-cell responses from the naive donor T-cell repertoire is determined by the balance between antigen-specific precursor T cells and regulatory T cells.

    NARCIS (Netherlands)

    Jedema, I.; Meent, M. van de; Pots, J.M.; Kester, M.G.; Beek, M.T. van der; Falkenburg, J.H.F.

    2011-01-01

    BACKGROUND: One of the major challenges in allogeneic stem cell transplantation is to find a balance between the harmful induction of graft-versus-host disease and the beneficial graft-versus-leukemia and pathogen-specific immune responses. Adoptive transfer of in-vitro generated donor T cells with

  15. Memorizing innate instructions requires a sufficiently specific adaptive immune system.

    Science.gov (United States)

    Borghans, José A M; De Boer, Rob J

    2002-05-01

    During its primary encounter with a pathogen, the immune system has to decide which type of immune response is most appropriate. Based on signals from the innate immune system and the immunological context in which the pathogen is presented, responding lymphocytes will adopt a particular phenotype, e.g. secrete a particular profile of cytokines. Once stimulated, lymphocytes store the appropriate type of response by differentiating from a naive to a memory phenotype. This allows the appropriate type of immune reaction to be regenerated upon re-stimulation of those memory clones. We developed a computer simulation model in which cross-reacting effector/memory clones contribute to the immunological context of pathogens. If a pathogen is recognized by both naive clones and pre-existing effector/memory clones, the naive lymphocytes adopt the effector mechanism of the memory clone. The adaptive immune system thereby stores immunological decisions and somatically learns to induce the right type of immune response to pathogens sharing epitopes. The influence of effector/memory lymphocytes may be detrimental when they cross-react to new pathogens that require a different kind of immune response. Here, we show that the immune system needs to be sufficiently specific to avoid such mistakes and to profit from the information that is stored in effector/memory lymphocytes. Repertoire diversity is required to reconcile this specificity with reactivity against many pathogens.

  16. Independent donor ethical assessment: aiming to standardize donor advocacy.

    Science.gov (United States)

    Choudhury, Devasmita; Jotterand, Fabrice; Casenave, Gerald; Smith-Morris, Carolyn

    2014-06-01

    Living organ donation has become more common across the world. To ensure an informed consent process, given the complex issues involved with organ donation, independent donor advocacy is required. The choice of how donor advocacy is administered is left up to each transplant center. This article presents the experience and process of donor advocacy at University of Texas Southwestern Medical Center administered by a multidisciplinary team consisting of physicians, surgeons, psychologists, medical ethicists and anthropologists, lawyers, a chaplain, a living kidney donor, and a kidney transplant recipient. To ensure that advocacy remains fair and consistent for all donors being considered, the donor advocacy team at University of Texas Southwestern Medical Center developed the Independent Donor Ethical Assessment, a tool that may be useful to others in rendering donor advocacy. In addition, the tool may be modified as circumstances arise to improve donor advocacy and maintain uniformity in decision making.

  17. Software Requirements Specification for Lunar IceCube

    Science.gov (United States)

    Glaser-Garbrick, Michael R.

    Lunar IceCube is a 6U satellite that will orbit the moon to measure water volatiles as a function of position, altitude, and time, and measure in its various phases. Lunar IceCube, is a collaboration between Morehead State University, Vermont Technical University, Busek, and NASA. The Software Requirements Specification will serve as contract between the overall team and the developers of the flight software. It will provide a system's overview of the software that will be developed for Lunar IceCube, in that it will detail all of the interconnects and protocols for each subsystem's that Lunar IceCube will utilize. The flight software will be written in SPARK to the fullest extent, due to SPARK's unique ability to make software free of any errors. The LIC flight software does make use of a general purpose, reusable application framework called CubedOS. This framework imposes some structuring requirements on the architecture and design of the flight software, but it does not impose any high level requirements. It will also detail the tools that we will be using for Lunar IceCube, such as why we will be utilizing VxWorks.

  18. Required Equipment for Photo-Switchable Donor-Acceptor (D-A) Dyad Interfacial Self-Assembled Monolayers for Organic Photovoltaic Cells

    Science.gov (United States)

    2014-01-24

    Accessory, 6) a Jelight Co. UVO cleaner, and 7) a Laurell Technologies Spin Coater . These instruments were used to characterize a variety of...goniometer/tensiometer, UVO cleaner, spin coater U U U UU Luis Echegoyen (915) 747-7573 (HBCU) - Required Equipment for Photo-switchable Donor...are exposed to the spin coated photoactive layer over the ITO monolayer, the effectiveness of this monolayer will be difficult to study. We need

  19. A Novel Model on DST-Induced Transplantation Tolerance by the Transfer of Self-Specific Donor tTregs to a Haplotype-Matched Organ Recipient

    DEFF Research Database (Denmark)

    Gregoriussen, Angelica Maria Mohr; Bohr, Henrik Georg

    2017-01-01

    Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades...... during the course of tolerance induction. Based on the immunological status of the recipients, we suggest that one H2-haplotype-matched self-specific Tregs derived from the transfusion blood can be activated and multiply in the host by binding to antigen-presenting cells presenting allopeptides...

  20. In Silico Derivation of HLA-Specific Alloreactivity Potential from Whole Exome Sequencing of Stem Cell Transplant Donors and Recipients: Understanding the Quantitative Immunobiology of Allogeneic Transplantation

    Directory of Open Access Journals (Sweden)

    Max eJameson-Lee

    2014-11-01

    Full Text Available Donor T cell mediated graft versus host effects (GVH may result from the aggregate alloreactivity to minor histocompatibility antigens (mHA presented by the HLA molecules in each donor-recipient pair undergoing stem cell transplantation (SCT. Whole exome sequencing has previously demonstrated a large number of nonsynonymous single nucleotide polymorphisms (SNP present in HLA-matched recipients of SCT donors (GVH direction. The nucleotide sequence flanking each of these SNPs was obtained and the amino acid sequence determined. All the possible nonameric-peptides incorporating the variant amino acid resulting from these SNPs were interrogated in-silico for their likelihood to be presented by the HLA class I molecules using the Immune Epitope Database stabilized matrix method (SMM and NetMHCpan algorithms. The SMM algorithm predicted that a median of 18,396 peptides weakly bound HLA class I molecules in individual SCT recipients, and 2,254 peptides displayed strong binding. A similar library of presented peptides was identified when the data was interrogated using the NetMHCpan algorithm. The bioinformatic algorithm presented here demonstrates that there may be a high level of mHA variation in HLA-matched individuals, constituting an HLA-specific alloreactivity potential.

  1. Association of Local Intrapulmonary Production of Antibodies Specific to Donor Major Histocompatibility Complex Class I With the Progression of Chronic Rejection of Lung Allografts.

    Science.gov (United States)

    Miyamoto, Ei; Motoyama, Hideki; Sato, Masaaki; Aoyama, Akihiro; Menju, Toshi; Shikuma, Kei; Sowa, Terumasa; Yoshizawa, Akihiko; Saito, Masao; Takahagi, Akihiro; Tanaka, Satona; Takahashi, Mamoru; Ohata, Keiji; Kondo, Takeshi; Hijiya, Kyoko; Chen-Yoshikawa, Toyofumi F; Date, Hiroshi

    2017-05-01

    Antibody-mediated rejection may lead to chronic lung allograft dysfunction, but antibody-mediated rejection may develop in the absence of detectable donor-specific antibody (DSA) in recipient serum. This study investigated whether humoral immune responses develop not only systemically but locally within rejected lung allografts, resulting in local production of DSA. Lewis rats received orthotopic left lung transplantation from Lewis (syngeneic control) or Brown-Norway (major histocompatibility complex-mismatched allogeneic) donor rats. Rats that underwent allogeneic lung transplantation were subsequently administered cyclosporine until day 14 (short immunosuppression) or day 35 (long immunosuppression). The lung grafts and spleens of recipient animals were tissue cultured for 4 days, and the titer of antibody against donor major histocompatibility complex molecules was assayed by flow cytometry. Explanted lung grafts were also evaluated pathologically. By day 98, DSA titers in supernatants of lung graft (P = 0.0074) and spleen (P = 0.0167) cultures, but not serum, from the short immunosuppression group were significantly higher than titers in syngeneic controls. Cultures and sera from the long immunosuppression group showed no production of DSA. Microscopically, the lung grafts from the short immunosuppression group showed severe bronchiole obliteration and parenchymal fibrosis, along with lymphoid aggregates containing T and B cells, accompanying plasma cells. These findings suggestive of local humoral immune response were not observed by days 28 and 63. DSA can be locally produced in chronically rejected lung allografts, along with intragraft immunocompetent cells. Clinical testing of DSA in serum samples alone may underestimate lung allograft dysfunction.

  2. Surveillance Analysis Computer System (SACS) software requirements specification (SRS)

    International Nuclear Information System (INIS)

    Glasscock, J.A.; Flanagan, M.J.

    1995-09-01

    This document is the primary document establishing requirements for the Surveillance Analysis Computer System (SACS) Database, an Impact Level 3Q system. The purpose is to provide the customer and the performing organization with the requirements for the SACS Project

  3. Automated isolation of primary antigen-specific T cells from donor lymphocyte concentrates: results of a feasibility exercise.

    Science.gov (United States)

    Bunos, M; Hümmer, C; Wingenfeld, E; Sorg, N; Pfirrmann, V; Bader, P; Seifried, E; Bönig, H

    2015-11-01

    The safety and clinical efficacy of adoptive transfer of prospectively isolated antigen-specific T cells are well established. Several competing selection methods are available, one of which is based on immunomagnetic enrichment of T cells secreting IFNγ after incubation with the relevant antigen. The proprietary, GMP-conforming selection technology, called 'cytokine capture system' (CCS) is established in many laboratories for the CliniMACS Plus system. It is robust and efficient, but labour-intensive and incompatible with a single-shift working schedule. An automatic immunomagnetic cell processing system, CliniMACS Prodigy ('Prodigy'), including a protocol for fully automatic CCS execution was recently released. Feasibility of clinical-scale CMV-specific T-cell selection using Prodigy was evaluated using leukoapheresis products from five healthy CMV sero-positive volunteers. Clinical reagents and consumables were used throughout. The process required no operator input beyond set-up and QC-sample collection, that is, feasibility was given. An IFNγ-secreting target T-cell population was detectable after stimulation, and >2 log-scale relative depletion of not CMV-reactive T cells in the target population was achieved. Purity, that is the frequency of CMV-reactive T cells among all CD3(+) cells ranged between 64 and 93%. The CCS protocol on Prodigy is unrestrictedly functional. It runs fully automatically beyond set-up and thus markedly reduces labour. The quality of the products generated is similar to products generated with CliniMACS Plus. The automatic system is thus suitable for routine clinical application. © 2015 International Society of Blood Transfusion.

  4. A Method and Tool for Tracing Requirements into Specifications

    DEFF Research Database (Denmark)

    Hallerstede, Stefan; Jastram, Michael; Ladenberger, Lukas

    2014-01-01

    that the reasoning permits drawing conclusions about the system description. We describe an incremental approach to requirements modelling and validation that incorporates formal and informal reasoning. Our main contribution is an approach to requirements tracing that delivers the necessary connection that links...... the reasoning to the system description. Formal refinement is used in order to deal with large and complex system descriptions. We discuss tool support for our approach of requirements tracing that combines informal requirements modelling with formal modelling and verification while tracing requirements among......The creation of a consistent system description is a challenging problem of requirements engineering. Formal and informal reasoning can greatly contribute to meet this challenge. However, this demands that formal and informal reasoning and the system description are connected in such way...

  5. ARSENAL: Automatic Requirements Specification Extraction from Natural Language

    OpenAIRE

    Ghosh, Shalini; Elenius, Daniel; Li, Wenchao; Lincoln, Patrick; Shankar, Natarajan; Steiner, Wilfried

    2014-01-01

    Requirements are informal and semi-formal descriptions of the expected behavior of a complex system from the viewpoints of its stakeholders (customers, users, operators, designers, and engineers). However, for the purpose of design, testing, and verification for critical systems, we can transform requirements into formal models that can be analyzed automatically. ARSENAL is a framework and methodology for systematically transforming natural language (NL) requirements into analyzable formal mo...

  6. Specification for Visual Requirements of Work-Centered Software Systems

    Science.gov (United States)

    2006-10-01

    criteria listed in IEEE 830 and ISO 9126 , [10] gives the following listing: "* Correct each requirement is an accurate depiction of what the client...the requirements are stated, there are commonly used criteria that have been duly noted and propagated by IEEE and ISO . Taking a glance at some of these

  7. 49 CFR 178.35 - General requirements for specification cylinders.

    Science.gov (United States)

    2010-10-01

    ... of part 107 of this chapter; or (2) For DOT Specifications 3B, 3BN, 3E, 4B, 4BA, 4D (water capacity...) The word “spun” or “plug” must be placed near the DOT specification marking when an end closure in the... certifies that the processes of manufacture and heat treatment of cylinders were observed and found...

  8. Input data required for specific performance assessment codes

    International Nuclear Information System (INIS)

    Seitz, R.R.; Garcia, R.S.; Starmer, R.J.; Dicke, C.A.; Leonard, P.R.; Maheras, S.J.; Rood, A.S.; Smith, R.W.

    1992-02-01

    The Department of Energy's National Low-Level Waste Management Program at the Idaho National Engineering Laboratory generated this report on input data requirements for computer codes to assist States and compacts in their performance assessments. This report gives generators, developers, operators, and users some guidelines on what input data is required to satisfy 22 common performance assessment codes. Each of the codes is summarized and a matrix table is provided to allow comparison of the various input required by the codes. This report does not determine or recommend which codes are preferable

  9. Specification for Visual Requirements of Work-Centered Software Systems

    National Research Council Canada - National Science Library

    Knapp, James R

    2006-01-01

    ... aspects of the user interface design. Without the ability to specify such original requirements, the probability of creating an accurate and effective work-centered software system is significantly reduced...

  10. On the systematic transformation of requirements to specifications

    OpenAIRE

    Li, Zhi; Hall, Jon; Rapanotti, Lucia

    2014-01-01

    Formal approaches to development are widely acknowledged to have difficulty in the validation of realworld requirements; in contrast, non-formal approaches find it difficult to identify the formal structures in requirements that are useful in a solution. That the problems that computing treats are embedded in the real world with solutions being an essentially formal machine means this dichotomy will always exist, with some new approach to the development needed which can draw a boundary betwe...

  11. 40 CFR 35.3550 - Specific capitalization grant agreement requirements.

    Science.gov (United States)

    2010-07-01

    ... demonstrating that it has adequate personnel and resources to establish and manage the DWSRF program. (d) Accept... about its ability to comply with the binding commitment requirement, it must notify the RA and propose a... the capitalization grant to be used for projects into the Fund. (2) A State must agree to maintain...

  12. Risk-Based Confidentiality Requirements Specification for Outsourced IT Systems

    NARCIS (Netherlands)

    Morali, A.; Wieringa, Roelf J.

    Today, companies are required to be in control of their IT assets, and to provide proof of this in the form of independent IT audit reports. However, many companies have outsourced various parts of their IT systems to other companies, which potentially threatens the control they have of their IT

  13. 40 CFR 35.3135 - Specific capitalization grant agreement requirements.

    Science.gov (United States)

    2010-07-01

    ... received a capitalization grant and, if the deposit was expended, it was expended in accordance with title... after it receives the payment, the RA may withhold future quarterly grant payments, and require... procedures regarding the commitment or expenditure of revenues. (h) State accounting and auditing procedures...

  14. Automatic Requirements Specification Extraction from Natural Language (ARSENAL)

    Science.gov (United States)

    2014-10-01

    studies: the Time-Triggered Ethernet ( TTEthernet ) communication platform used in space, and FAA-Isolette infant incubators used in NICU. We...25 19 Synchronization FSM in TTEthernet ...We evaluated ARSENAL on complex requirements from two real- world case studies: the Time-Triggered Ethernet ( TTEthernet ) communication platform used

  15. 47 CFR 51.319 - Specific unbundling requirements.

    Science.gov (United States)

    2010-10-01

    ... (CONTINUED) INTERCONNECTION Additional Obligations of Incumbent Local Exchange Carriers § 51.319 Specific... uses to provide voice service, with the incumbent LEC using the low frequency portion of the loop and... frequency portion of the loop at the same rate that the incumbent LEC charged for such access prior to the...

  16. A Novel Model on DST-Induced Transplantation Tolerance by the Transfer of Self-Specific Donor tTregs to a Haplotype-Matched Organ Recipient.

    Science.gov (United States)

    Mohr Gregoriussen, Angelica Maria; Bohr, Henrik Georg

    2017-01-01

    Donor-specific blood transfusion (DST) can lead to significant prolongation of allograft survival in experimental animal models and sometimes human recipients of solid organs. The mechanisms responsible for the beneficial effect on graft survival have been a topic of research and debate for decades and are not yet fully elucidated. Once we discover how the details of the mechanisms involved are linked, we could be within reach of a procedure making it possible to establish donor-specific tolerance with minimal or no immunosuppressive medication. Today, it is well established that CD4+Foxp3+ regulatory T cells (Tregs) are indispensable for maintaining immunological self-tolerance. A large number of animal studies have also shown that Tregs are essential for establishing and maintaining transplantation tolerance. In this paper, we present a hypothesis of one H2-haplotype-matched DST-induced transplantation tolerance (in mice). The formulated hypothesis is based on a re-interpretation of data from an immunogenetic experiment published by Niimi and colleagues in 2000. It is of importance that the naïve recipient mice in this study were never immunosuppressed and were therefore fully immune competent during the course of tolerance induction. Based on the immunological status of the recipients, we suggest that one H2-haplotype-matched self-specific Tregs derived from the transfusion blood can be activated and multiply in the host by binding to antigen-presenting cells presenting allopeptides in their major histocompatibility complex (MHC) class II (MHC-II). We also suggest that the endothelial and epithelial cells within the solid organ allograft upregulate the expression of MHC-II and attract the expanded Treg population to suppress inflammation within the graft. We further suggest that this biological process, here termed MHC-II recruitment, is a vital survival mechanism for organs (or the organism in general) when attacked by an immune system.

  17. Losing Something In Translation: Turning Requirements Into Specifications

    Science.gov (United States)

    2016-06-01

    inspiring voice—except the quotation is in some unintelligible language. Another performer asks, “What does that mean in English ?” The translation is...process of progressing from high-level operational re- quirements to technical requirements to component speci- fications looks something like the...validate the trade-offs? As a development program progresses from analysis to pro- duction, many people have opportunities to apply the lessons

  18. Why Should Donors Care about Corruption?

    OpenAIRE

    Kolstad, Ivar

    2008-01-01

    Corruption is bad for donor business. Corruption reduces popular support for aid in donor countries. However, aid agencies should pay attention to corruption because it is the right thing to do, rather than just the smart thing to do. Donor anti-corruption policies require a strong grounding in ethics. Corruption produces bad development outcomes. This is the reasoning largely underlying donor anti-corruption efforts. The focus on consequences of corruption makes donor anticorruptioneffo...

  19. Kidney transplant outcomes from older deceased donors

    DEFF Research Database (Denmark)

    Pippias, Maria; Jager, Kitty J; Caskey, Fergus

    2018-01-01

    As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor ...... transplanted into differing donor-recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar-aged recipients....

  20. 77 FR 50726 - Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in...

    Science.gov (United States)

    2012-08-22

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Software Requirement Specifications for Digital Computer Software and Complex Electronics Used in Safety Systems of Nuclear Power Plants AGENCY: Nuclear...-1209, ``Software Requirement Specifications for Digital Computer Software and Complex Electronics used...

  1. PAMS photo image retrieval prototype system requirements specification

    Energy Technology Data Exchange (ETDEWEB)

    Conner, M.L.

    1996-04-30

    This project is part of the Photo Audiovisual Management System (PAMS). The project was initially identified in 1989 and has since been has been worked on under various names such as Image Retrieval and Viewing System, Photo Image Retrieval Subsystem and Image Processing and Compression System. This document builds upon the information collected and the analysis performed in the earlier phases of this project. The PAMS Photo Imaging subsystem will provide the means of capturing low resolution digital images from Photography`s negative files and associating the digital images with a record in the PAMS photo database. The digital images and key photo identification information will be accessible to HAN users to assist in locating and identifying specific photographs. After identifying desired photographs, users may request photo prints or high resolution digital images directly from Photography. The digital images captured by this project are for identification purposes only and are not intended to be of sufficient quality for subsequent use.

  2. Specification of advanced safety modeling requirements (Rev. 0).

    Energy Technology Data Exchange (ETDEWEB)

    Fanning, T. H.; Tautges, T. J.

    2008-06-30

    The U.S. Department of Energy's Global Nuclear Energy Partnership has lead to renewed interest in liquid-metal-cooled fast reactors for the purpose of closing the nuclear fuel cycle and making more efficient use of future repository capacity. However, the U.S. has not designed or constructed a fast reactor in nearly 30 years. Accurate, high-fidelity, whole-plant dynamics safety simulations will play a crucial role by providing confidence that component and system designs will satisfy established design limits and safety margins under a wide variety of operational, design basis, and beyond design basis transient conditions. Current modeling capabilities for fast reactor safety analyses have resulted from several hundred person-years of code development effort supported by experimental validation. The broad spectrum of mechanistic and phenomenological models that have been developed represent an enormous amount of institutional knowledge that needs to be maintained. Complicating this, the existing code architectures for safety modeling evolved from programming practices of the 1970s. This has lead to monolithic applications with interdependent data models which require significant knowledge of the complexities of the entire code in order for each component to be maintained. In order to develop an advanced fast reactor safety modeling capability, the limitations of the existing code architecture must be overcome while preserving the capabilities that already exist. To accomplish this, a set of advanced safety modeling requirements is defined, based on modern programming practices, that focuses on modular development within a flexible coupling framework. An approach for integrating the existing capabilities of the SAS4A/SASSYS-1 fast reactor safety analysis code into the SHARP framework is provided in order to preserve existing capabilities while providing a smooth transition to advanced modeling capabilities. In doing this, the advanced fast reactor safety models

  3. 75 FR 58400 - Donor Management Research: Improvements in Clinical Management of Deceased Organ Donors

    Science.gov (United States)

    2010-09-24

    ... generally focused on specific organ systems and not on donor management approaches with the goal of... donor management. A Donor Management Task Force was convened in August 2010 to address relevant issues... Management Research: Improvements in Clinical Management of Deceased Organ Donors AGENCY: Health Resources...

  4. C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch

    Directory of Open Access Journals (Sweden)

    José M. Arreola-Guerra

    2016-01-01

    Full Text Available The aim of the present study was to describe the association of positive flow cross match (FXM and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n=26, 52%. Ten patients (20.0% had DSA C1q+ Ab. Twenty-five (50% FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P=0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P=0.021 and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P=0.007. The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%. For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100 and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100. Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.

  5. Robust design requirements specification: a quantitative method for requirements development using quality loss functions

    DEFF Research Database (Denmark)

    Pedersen, Søren Nygaard; Christensen, Martin Ebro; Howard, Thomas J.

    2016-01-01

    Product requirements serve many purposes in the product development process. Most importantly, they are meant to capture and facilitate product goals and acceptance criteria, as defined by stakeholders. Accurately communicating stakeholder goals and acceptance criteria can be challenging and more...

  6. 40 CFR 166.32 - Reporting and recordkeeping requirements for specific, quarantine, and public health exemptions.

    Science.gov (United States)

    2010-07-01

    ... requirements for specific, quarantine, and public health exemptions. 166.32 Section 166.32 Protection of... AGENCIES FOR USE OF PESTICIDES UNDER EMERGENCY CONDITIONS Specific, Quarantine, and Public Health Exemptions § 166.32 Reporting and recordkeeping requirements for specific, quarantine, and public health...

  7. Functions and Requirements and Specifications for Replacement of the Computer Automated Surveillance System (CASS)

    International Nuclear Information System (INIS)

    SCAIEF, C.C.

    1999-01-01

    This functions, requirements and specifications document defines the baseline requirements and criteria for the design, purchase, fabrication, construction, installation, and operation of the system to replace the Computer Automated Surveillance System (CASS) alarm monitoring

  8. Dynamic mobility applications open source application development portal : Task 4 : system requirements specifications : final report.

    Science.gov (United States)

    2016-10-12

    This document describes the System Requirements Specifications (SyRS) of the Dynamic Mobility Applications (DMA) Open Source Application Development Portal (OSADP) system in details according to IEEE-Std. 1233-1998. The requirement statements discuss...

  9. 46 CFR 62.35-50 - Tabulated monitoring and safety control requirements for specific systems.

    Science.gov (United States)

    2010-10-01

    ... (CONTINUED) MARINE ENGINEERING VITAL SYSTEM AUTOMATION Requirements for Specific Types of Automated Vital... lubrication Pressure Low Main propulsion, controllable pitch propeller Hydraulic oil Pressure High, Low...

  10. Domestic and donor financing for tuberculosis care and control in low-income and middle-income countries: an analysis of trends, 2002-11, and requirements to meet 2015 targets.

    Science.gov (United States)

    Floyd, Katherine; Fitzpatrick, Christopher; Pantoja, Andrea; Raviglione, Mario

    2013-08-01

    Progress in tuberculosis control worldwide, including achievement of 2015 global targets, requires adequate financing sustained for many years. WHO began yearly monitoring of tuberculosis funding in 2002. We used data reported to WHO to analyse tuberculosis funding from governments and international donors (in real terms, constant 2011 US$) and associated progress in tuberculosis control in low-income and middle-income countries between 2002 and 2011. We then assessed funding needed to 2015 and how this funding could be mobilised. We included low-income and middle-income countries that reported data about financing for tuberculosis to WHO and had at least three observations between 2002 and 2011. When data were missing for specific country-year combinations, we imputed the missing data. We aggregated country-specific results for eight country groups defined according to income level, political and economic profile, geography, and tuberculosis burden. We compared absolute changes in total funding with those in the total number of patients successfully treated and did cross-country comparisons of cost per successfully treated patient relative to gross domestic product. We estimated funding needs for tuberculosis care and control for all low-income and middle-income countries to 2015, and compared these needs with domestic funding that could be mobilised. Total funding grew from $1·7 billion in 2002 to $4·4 billion in 2011. It was mostly spent on diagnosis and treatment of drug-susceptible tuberculosis. 43 million patients were successfully treated, usually for $100-500 per person in countries with high burdens of tuberculosis. Domestic funding rose from $1·5 billion to $3·9 billion per year, mostly in Brazil, Russia, India, China, and South Africa (BRICS), which collectively account for 45% of global cases, where national contributions accounted for more than 95% of yearly funding. Donor funding increased from $0·2 billion in 2002 to $0·5 billion in 2011, and

  11. Incidence, Characterization and Impact of Newly Detected Donor Specific Anti-HLA Antibody in the First Year after Pediatric Heart Transplantation: A Report From the CTOTC-04 Study.

    Science.gov (United States)

    Dipchand, A I; Webber, S; Mason, K; Feingold, B; Bentlejewski, C; Mahle, W T; Shaddy, R; Canter, C; Blume, E D; Lamour, J; Zuckerman, W; Diop, H; Morrison, Y; Armstrong, B; Ikle, D; Odim, J; Zeevi, A

    2018-02-14

    Data on the clinical importance of newly detected donor specific antibodies (ndDSA) following pediatric heart transplantation is lacking despite mounting evidence of the detrimental effect of de novo DSA in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSA in the first year post-transplant in order to determine their incidence, pattern and clinical impact. One third of patients developed ndDSA; when present, these were mostly detected within the first 6 weeks after transplant suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of pre-existing DSA, patients with ndDSA had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year post-transplant. Risk factors for ndDSA included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year following pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pre-transplant antibody screen. The impact on late graft and patient outcomes of first year ndDSA is being assessed in an extended cohort of patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Decreased donor-specific cytotoxic T cell precursor frequencies one year after clinical lung transplantation do not reflect transplantation tolerance : A comparison of lung transplant recipients with or without bronchiolitis obliterans syndrome

    NARCIS (Netherlands)

    de Haan, A; van der Gun, [No Value; Hepkema, BG; van der Bij, W; de Leij, LFMH; Prop, J

    2000-01-01

    Background. Decreased in vitro T cell alloreactivity, demonstrated by decreased frequencies of peripheral blood donor-specific T cell precursors, may reflect a tolerant state after transplantation and lower the risk for development of chronic graft dysfunction. It is unknown whether a decrease in

  13. Recruitment of feces donors among blood donors

    DEFF Research Database (Denmark)

    Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

    2018-01-01

    As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

  14. Screening Donors for Rare Antigen Constellations.

    Science.gov (United States)

    Wagner, Franz F

    2009-01-01

    SCREENING BLOOD DONORS FOR RARE ANTIGEN CONSTELLATIONS HAS BEEN IMPLEMENTED USING SIMPLE PCR METHODS: PCR with enzyme digestion has been used to type donor cohorts for Dombrock antigens, and PCR with sequence-specific priming to identify donors negative for antigens of high frequency. The advantages and disadvantages of the methods as well as their current state is discussed.

  15. 46 CFR 127.110 - Plans and specifications required for new construction.

    Science.gov (United States)

    2010-10-01

    ... level of crew associated with the engine department, the following plans must be submitted: (1) Plans... 46 Shipping 4 2010-10-01 2010-10-01 false Plans and specifications required for new construction... SUPPLY VESSELS CONSTRUCTION AND ARRANGEMENTS Plan Approval § 127.110 Plans and specifications required...

  16. A Hybrid Parallel Execution Model for Logic Based Requirement Specifications (Invited Paper

    Directory of Open Access Journals (Sweden)

    Jeffrey J. P. Tsai

    1999-05-01

    Full Text Available It is well known that undiscovered errors in a requirements specification is extremely expensive to be fixed when discovered in the software maintenance phase. Errors in the requirement phase can be reduced through the validation and verification of the requirements specification. Many logic-based requirements specification languages have been developed to achieve these goals. However, the execution and reasoning of a logic-based requirements specification can be very slow. An effective way to improve their performance is to execute and reason the logic-based requirements specification in parallel. In this paper, we present a hybrid model to facilitate the parallel execution of a logic-based requirements specification language. A logic-based specification is first applied by a data dependency analysis technique which can find all the mode combinations that exist within a specification clause. This mode information is used to support a novel hybrid parallel execution model, which combines both top-down and bottom-up evaluation strategies. This new execution model can find the failure in the deepest node of the search tree at the early stage of the evaluation, thus this new execution model can reduce the total number of nodes searched in the tree, the total processes needed to be generated, and the total communication channels needed in the search process. A simulator has been implemented to analyze the execution behavior of the new model. Experiments show significant improvement based on several criteria.

  17. 49 CFR 179.301 - Individual specification requirements for multi-unit tank car tanks.

    Science.gov (United States)

    2010-10-01

    ...-unit tank car tanks. 179.301 Section 179.301 Transportation Other Regulations Relating to... MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Multi-Unit Tank Car Tanks (Classes DOT-106A and 110AW) § 179.301 Individual specification requirements for multi-unit tank car tanks. (a) In...

  18. Effects of Using Requirements Catalogs on Effectiveness and Productivity of Requirements Specification in a Software Project Management Course

    Science.gov (United States)

    Fernández-Alemán, José Luis; Carrillo-de-Gea, Juan Manuel; Meca, Joaquín Vidal; Ros, Joaquín Nicolás; Toval, Ambrosio; Idri, Ali

    2016-01-01

    This paper presents the results of two educational experiments carried out to determine whether the process of specifying requirements (catalog-based reuse as opposed to conventional specification) has an impact on effectiveness and productivity in co-located and distributed software development environments. The participants in the experiments…

  19. Certification of packagings: compliance with DOT specification 7A packaging requirements

    International Nuclear Information System (INIS)

    Edling, D.A.

    1976-01-01

    A study was conducted to determine which of the packagings currently listed in CFR 49 Section 173.395 a.1-5, meet the Specification 7A requirements (CFR 49 Section 173.350). According to DOT HM-111 the present listing of various authorized DOT specifications in Section 173.394 and Section 173.395 (Type A containers) of ICC Tariff No. 27 would be deleted with complete reliance being placed on the use of DOT 7A, Type A general packaging specification. Each user of a Specification 7A package would be required to document and maintain on file for one year a written record of his determination of compliance with the DOT Specification 7A performance requirements. All the specification packagings listed in CFR 49 Section 173.395a.1-5 were tested and shown to meet the Specification 7A criteria; however, in many cases qualifications were placed on their use. Forty-nine specification packagings were tested and shown to meet the DOT Specification 7A performance requirements and since there were several styles of some specific packagings, this amounts to greater than 80 packagings. The extensive testing generally indicated a high degree of containment integrity in the packagings tested and the documentation discussed is a valuable tool for shippers of Type A quantities of radioactive materials

  20. Induction of Foxp3-expressing regulatory T-cells by donor blood transfusion is required for tolerance to rat liver allografts.

    Directory of Open Access Journals (Sweden)

    Yuta Abe

    Full Text Available BACKGROUND: Donor-specific blood transfusion (DST prior to solid organ transplantation has been shown to induce long-term allograft survival in the absence of immunosuppressive therapy. Although the mechanisms underlying DST-induced allograft tolerance are not well defined, there is evidence to suggest DST induces one or more populations of antigen-specific regulatory cells that suppress allograft rejection. However, neither the identity nor the regulatory properties of these tolerogenic lymphocytes have been reported. Therefore, the objective of this study was to define the kinetics, phenotype and suppressive function of the regulatory cells induced by DST alone or in combination with liver allograft transplantation (LTx. METHODOLOGY/PRINCIPAL FINDINGS: Tolerance to Dark Agouti (DA; RT1(a rat liver allografts was induced by injection (iv of 1 ml of heparinized DA blood to naïve Lewis (LEW; RT1(l rats once per week for 4 weeks prior to LTx. We found that preoperative DST alone generates CD4(+ T-cells that when transferred into naïve LEW recipients are capable of suppressing DA liver allograft rejection and promoting long-term survival of the graft and recipient. However, these DST-generated T-cells did not express the regulatory T-cell (Treg transcription factor Foxp3 nor did they suppress alloantigen (DA-induced activation of LEW T-cells in vitro suggesting that these lymphocytes are not fully functional regulatory Tregs. We did observe that DST+LTx (but not DST alone induced the time-dependent formation of CD4(+Foxp3(+ Tregs that potently suppressed alloantigen-induced activation of naïve LEW T-cells in vitro and liver allograft rejection in vivo. Finally, we present data demonstrating that virtually all of the Foxp3-expressing Tregs reside within the CD4(+CD45RC(- population whereas in which approximately 50% of these Tregs express CD25. CONCLUSIONS/SIGNIFICANCE: We conclude that preoperative DST, in the absence of liver allograft

  1. Antibody-dependent NK cell activation is associated with late kidney allograft dysfunction and the complement-independent alloreactive potential of donor-specific antibodies

    Directory of Open Access Journals (Sweden)

    Tristan Legris

    2016-08-01

    Full Text Available Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs. The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK cells as innate immune effectors of antibody-dependent cellular cytotoxicity, but few studies have investigated their alloreactive potential in the context of solid organ transplantation. Our study aimed to investigate the potential contribution of the antibody-dependent alloreactive function of NK cells to kidney graft dysfunction. We first conducted an observational study to investigate whether the cytotoxic function of NK cells is associated with chronic allograft dysfunction. The NK-Cellular Humoral Activation Test (NK-CHAT was designed to evaluate the recipient and antibody-dependent reactivity of NK cells against allogeneic target cells. The release of CD107a/Lamp1+ cytotoxic granules, resulting from the recognition of rituximab-coated B cells by NK cells, was analyzed in 148 kidney transplant recipients (KTRs, mean graft duration: 6.2 years. Enhanced ADCC responsiveness was associated with reduced graft function and identified as an independent risk factor predicting a decline in the estimated glomerular filtration rate (eGFR over a 1-year period (hazard ratio: 2.83. In a second approach, we used the NK-CHAT to reveal the cytotoxic potential of circulating alloantibodies in vitro. The level of CD16 engagement resulting from the in vitro recognition of serum-coated allogeneic B cells or splenic cells was further identified as a specific marker of DSA-induced ADCC. The NK-CHAT scoring of sera obtained from 40 patients at the time of transplant biopsy was associated with ABMR diagnosis. Our findings indicate that despite the administration

  2. Assessment of the best N3− donors in preparation of [M(N)(PNP)]-based (M = 99mTc-; 188Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ)

    International Nuclear Information System (INIS)

    Carta, Davide; Jentschel, Christian; Thieme, Stefan; Salvarese, Nicola; Morellato, Nicolò; Refosco, Fiorenzo; Ruzza, Paolo; Bergmann, Ralf; Pietzsch, Hans-Jurgen; Bolzati, Cristina

    2014-01-01

    Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO 2 C-PEG 600 -DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]‐complexes (M = 99m Tc and 188 Re). This study aims to compare the capability and the efficiency of these three N 3− group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M = 99m Tc, 188 Re; PNP = aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO 2 C-PEG 600 -DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys ∼)(PNP3)] 0/+ complexes (cys ∼ = cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(∼ cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N 3− donors and of the exchanging ligand, was determined. For 99m Tc, data clearly show that HDTCZ is the most efficient donor of N 3− ; however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [ 99m Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO 2 C-PEG 600 -DTCZ or HDTCZ are used in N 3− donation, high amounts of the exchanging ligand (10 −4 M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [ 188 Re(N)] preparation (0.050 mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [ 188 Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes

  3. Software requirements specification for the program analysis and control system risk management module

    International Nuclear Information System (INIS)

    SCHAEFER, J.C.

    1999-01-01

    TWR Program Analysis and Control System Risk Module is used to facilitate specific data processes surrounding the Risk Management program of the Tank Waste Retrieval environment. This document contains the Risk Management system requirements of the database system

  4. System requirement specifications for the Z-plant materials information tracking system (ZMITS)

    International Nuclear Information System (INIS)

    NEGIN, C.A.

    1999-01-01

    This is a system requirement specification for a database which will be developed to track classified information related to nuclear materials stored at PFP. The system will supplement existing databases to support both processing and disposition information needs

  5. Information technology -- Telecommunications and information exchange between systems -- Local and metropolitan area networks -- Specific requirements -- Part 11: Wireless LAN Medium Access Control (MAC) and Physical Layer (PHY) specifications

    CERN Document Server

    International Organization for Standardization. Geneva

    1997-01-01

    Information technology -- Telecommunications and information exchange between systems -- Local and metropolitan area networks -- Specific requirements -- Part 11: Wireless LAN Medium Access Control (MAC) and Physical Layer (PHY) specifications

  6. Treated effluent disposal system process control computer software requirements and specification

    International Nuclear Information System (INIS)

    Graf, F.A. Jr.

    1994-01-01

    The software requirements for the monitor and control system that will be associated with the effluent collection pipeline system known as the 200 Area Treated Effluent Disposal System is covered. The control logic for the two pump stations and specific requirements for the graphic displays are detailed

  7. 49 CFR 180.205 - General requirements for requalification of specification cylinders.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false General requirements for requalification of... Cylinders § 180.205 General requirements for requalification of specification cylinders. (a) General. Each... subchapter. (b) Persons performing requalification functions. No person may represent that a repair or...

  8. Treated effluent disposal system process control computer software requirements and specification

    Energy Technology Data Exchange (ETDEWEB)

    Graf, F.A. Jr.

    1994-06-03

    The software requirements for the monitor and control system that will be associated with the effluent collection pipeline system known as the 200 Area Treated Effluent Disposal System is covered. The control logic for the two pump stations and specific requirements for the graphic displays are detailed.

  9. 7 CFR 1724.54 - Requirements for RUS approval of plans and specifications.

    Science.gov (United States)

    2010-01-01

    ... paragraph (a) of this section. (d) Substations. (1)(i) Plans and specifications for all new substations must..., unless: (A) The substation design has been previously approved by RUS; and (B) No significant NESC... required by paragraph (a) of this section, plans and specifications for substation modifications and for...

  10. 46 CFR 91.55-5 - Plans and specifications required for new construction.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Plans and specifications required for new construction... new construction. (a) General. (1) Specifications. (2) General Arrangement Plan of decks, holds, inner... Watertight Decks. (11) *Details of Hinged Subdivision Watertight Doors and Operating Gear. (12) *Scuppers and...

  11. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

    Directory of Open Access Journals (Sweden)

    Chongsheng Qian

    2017-05-01

    Full Text Available Abstract Background Allogeneic hematopoietic stem cell transplantation (HSCT, the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB. Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9% or a third party haploidentical donor (57.1%. One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%. Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV

  12. Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with cyclosporine on rat cardiac allograft survival

    International Nuclear Information System (INIS)

    Oluwole, S.F.; Lau, H.T.; Reemtsma, K.; Hardy, M.A.

    1988-01-01

    We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI rats are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant cyclosporine (CsA) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The mean survival time (MST) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by CsA treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with CsA, graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant CsA, the MST was increased to 68.83 +/- 16.1 days as compared to an MST of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant CsA immunosuppression, the results were similar. However, when UV-DST was peritransplant CsA course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone (MST of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis rats, regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with CsA

  13. Getting the balance right between functional and non-functional requirements: the case of requirement specification in IT procurement

    Directory of Open Access Journals (Sweden)

    Björn Johansson

    2013-01-01

    Full Text Available IT procurement represents a business process of high importance, including the ability to articulate requirements that the procurement deals with. Furthermore, specifying requirements is of importance for both procurer and potential supplier, as it functions as central contractual element between the two. The purpose of this article is two-fold: (i to show how established terminology for requirement specification is represented in current call for bids for the procurement of IT; and (ii to introduce an organizing framework that may assist procurers in actively addressing functional requirements and business requirements. Ten “call for bids” were examined from a Swedish national procurement database. From the analysis of the bids, it can be concluded that: (i the call for bids displays a high degree of precision regarding hardware aspects, but less precision regarding software; (ii supplier experience and competence is stressed, but rarely elaborated on in detail; and (iii call for bids vagueness may be used as a lock-in opportunity for suppliers. From the discussion on this, a tentative procurement framework is suggested, aiming on increasing the logical transparency for the procurement of IT.

  14. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

    Directory of Open Access Journals (Sweden)

    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  15. Nyretransplantation med levende donor

    DEFF Research Database (Denmark)

    Kamper, A L; Løkkegaard, H; Rasmussen, F

    2000-01-01

    In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associated...

  16. Handbook of methods for risk-based analysis of Technical Specification requirements

    International Nuclear Information System (INIS)

    Samanta, P.K.; Vesely, W.E.

    1993-01-01

    Technical Specifications (TS) requirements for nuclear power plants define the Limiting Conditions for Operation (LCOs) and Surveillance Requirements (SRs) to assure safety during operation. In general, these requirements were based on deterministic analysis and engineering judgments. Experiences with plant operation indicate that some elements of the requirements are unnecessarily restrictive, while others may not be conducive to safety. Improvements in these requirements are facilitated by the availability of plant specific Probabilistic Safety Assessments (PSAs). The use of risk and reliability-based methods to improve TS requirements has gained wide interest because these methods can: quantitatively evaluate the risk impact and justify changes based on objective risk arguments. Provide a defensible basis for these requirements for regulatory applications. The United States Nuclear Regulatory Commission (USNRC) Office of Research is sponsoring research to develop systematic risk-based methods to improve various aspects of TS requirements. The handbook of methods, which is being prepared, summarizes such risk-based methods. The scope of the handbook includes reliability and risk-based methods for evaluating allowed outage times (AOTs), action statements requiring shutdown where shutdown risk may be substantial, surveillance test intervals (STIs), defenses against common-cause failures, managing plant configurations, and scheduling maintenances. For each topic, the handbook summarizes methods of analysis and data needs, outlines the insights to be gained, lists additional references, and presents examples of evaluations

  17. Handbook of methods for risk-based analysis of technical specification requirements

    International Nuclear Information System (INIS)

    Samanta, P.K.; Vesely, W.E.

    1994-01-01

    Technical Specifications (TS) requirements for nuclear power plants define the Limiting Conditions for Operation (LCOs) and Surveillance Requirements (SRs) to assure safety during operation. In general, these requirements were based on deterministic analysis and engineering judgments. Experiences with plant operation indicate that some elements of the requirements are unnecessarily restrictive, while others may not be conducive to safety. Improvements in these requirements are facilitated by the availability of plant specific Probabilistic Safety Assessments (PSAs). The use of risk and reliability-based methods to improve TS requirements has gained wide interest because these methods can: Quantitatively evaluate the risk and justify changes based on objective risk arguments; Provide a defensible basis for these requirements for regulatory applications. The US NRC Office of Research is sponsoring research to develop systematic risk-based methods to improve various aspects of TS requirements. The handbook of methods, which is being prepared, summarizes such risk-based methods. The scope of the handbook includes reliability and risk-based methods for evaluating allowed outage times (AOTs), action statements requiring shutdown where shutdown risk may be substantial, surveillance test intervals (STIs), defenses against common-cause failures, managing plant configurations, and scheduling maintenances. For each topic, the handbook summarizes methods of analysis and data needs, outlines the insights to be gained, lists additional references, and presents examples of evaluations

  18. A Methodology for Writing High Quality Requirement Specifications and for Evaluating Existing Ones

    Science.gov (United States)

    Rosenberg, Linda; Hammer, Theodore

    1999-01-01

    Requirements development and management have always been critical in the implementation of software systems-engineers are unable to build what analysts can not define. It is generally accepted that the earlier in the life cycle potential risks are identified the easier it is to eliminate or manage the conditions that introduce that risk. Problems that are not found until testing are approximately 14 times more costly to fix than if the problem was found in the requirement phase. The requirements specification, as the first tangible representation of the capability to be produced, establishes the basis for all of the project's engineering management and assurance functions. If the quality of the requirements specification is poor it can give rise to risks in all areas of the project. Recently, automated tools have become available to support requirements management. The use of these tools not only provides support in the definition and tracing of requirements, but it also opens the door to effective use of metrics in characterizing and assessing the quality of the requirement specifications.

  19. A Methodology for Writing High Quality Requirements Specification and Evaluating Existing Ones

    Science.gov (United States)

    Rosenberg, Linda; Hammer, Theodore

    1999-01-01

    Requirements development and management have always been critical in the implementation of software systems; engineers are unable to build what analysts can't define. It is generally accepted that the earlier in the life cycle potential risks are identified the easier it is to eliminate or manage the conditions that introduce that risk. Problems that are not found until testing are approximately 14 times more costly to fix than if the problem was found in the requirement phase. The requirements specification, as the first tangible representation of the capability to be produced, establishes the basis for all of the project's engineering management and assurance functions. If the quality of the requirements specification is poor it can give rise to risks in all areas of the project. Recently, automated tools have become available to support requirements management. The use of these tools not only provides support in the definition and tracing of requirements, but it also opens the door to effective use of metrics in characterizing and assessing the quality of the requirement specifications.

  20. A Methodology for Measuring the Risk Associated with A Software Requirements Specification

    Directory of Open Access Journals (Sweden)

    Trevor Moores

    1996-11-01

    Full Text Available This paper presents a six-step metrics-based methodology for assessing the risks associated with - and hence the resources required to implement - the requirements contained within a software requirements specification (SRS. The method seeks to eliminate the use of subjective probability assessments in models of risk exposure (RE and risk reduction leverage (RRL. Measurements are taken of the number of requirements and the class of risk, the number of change requests and their date of issue, and the cost of each requirement change. The class of requirements risk is tailored to a given organisation using the Delphi method. The information collected is stored as an historical database for use in the analysis of subsequent SRSs.

  1. The impact of technical specification surveillance requirements and allowable outage times on plant availability

    International Nuclear Information System (INIS)

    Webster, S.A.; Finnicum, D.J.

    1985-01-01

    Surveillances required to be conducted by a plant's Technical Specifications have resulted in plant shutdowns and lost availability. This paper looks at shutdowns which have occurred due to required surveillance testing and insufficient repair time allowed by Technical Specifications. A loss of plant availability of almost 3% per plant year was found for U.S. pressurized water reactors during the five year period, 1979 to 1984. This figure excludes major problems which required plant shutdown whether or not mandated by the Technical Specifications. In addition to their affect on availability, such shutdowns can add to the challenges to plant safety systems and can affect plant aging by increasing the thermal cycles on plant components

  2. Barriers to the use of a federal travel grant by living kidney donors.

    Science.gov (United States)

    Hays, Rebecca E; Thomas, Amy Elaine; Mathias, Erin; Mezrich, Joshua; Mandelbrot, Didier A

    2017-02-01

    Living organ donation involves significant out-of-pocket costs, which burden donor candidates and may be an obstacle to donation. There is a single US grant (the National Living Donor Assistance Center-NLDAC) to cover live donor travel costs. Although there may be center-specific variability in grant utilization, prospective donors-and their intended recipients-must also meet eligibility criteria. In fact, the NLDAC grant is used by 300% of the federal poverty level) (n=51; 82%). The remaining exclusions (n=11; 18%) included being a nondirected donor, not meeting residency requirements, and "other." Expanding NLDAC eligibility criteria-by broadening the recipient means test or by taking steps to eliminate it from the NLDAC charter-would reduce financial burdens associated with live donation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Specification of safety requirements for waste packages with respect to practicable quality control measures

    International Nuclear Information System (INIS)

    Gruendler, D.; Wurtinger, W.

    1987-01-01

    Waste packages for disposal in a repository in the Federal Republic of Germany have to meet safety requirements derived from site specific safety analyses. The examination of the waste packages with regard to compliance with these requirements is the main objective of quality control measures. With respect to quality control the requirements have to be specified in a way that practicable control measures can be applied. This is dealt with for the quality control of the activity inventory and the quality control of the waste form. The paper discusses the determination of the activity of hard-to-measure radionuclides and the specification of safety related requirements for the waste form and the packaging using typical examples

  4. Formal verification of functional properties of a SCR-style software requirements specification using PVS

    International Nuclear Information System (INIS)

    Kim, Taeho; Stringer-Calvert, David; Cha, Sungdeok

    2005-01-01

    Industrial software companies developing safety-critical systems are required to use rigorous safety analysis techniques to demonstrate compliance to regulatory bodies. In this paper, we describe an approach to formal verification of functional properties of requirements for an embedded real-time software written in software cost reduction (SCR)-style language using PVS specification and verification system. Key contributions of the paper include development of an automated method of translating SCR-style requirements into PVS input language as well as identification of property templates often needed in verification. Using specification for a nuclear power plant system, currently in operation, we demonstrate how safety demonstration on requirements can be accomplished while taking advantage of assurance provided by formal methods

  5. Evaluation procedure of software requirements specification for digital I and C of KNGR

    International Nuclear Information System (INIS)

    Lee, Jang Soo; Park, Jong Kyun; Lee, Ki Young; Kim, Jang Yeol; Cheon, Se Woo

    2001-06-01

    The accuracy of the specification of requirements of a digital system is of prime importance to the acceptance and success of the system. The development, use, and regulation of computer systems in nuclear reactor Instrumentation and Control (I and C) systems to enhance reliability and safety is a complex issue. This report is one of a series of reports from the Korean Next Generation Reactor (KNGR) Software Safety Verification and Validation (SSVV) Task, Korea Atomic Energy Research Institute, which investigates different aspects of computer software in reactor I and C systems, and describes the engineering procedures for developing such a software. The purpose of this guideline is to give the software safety evaluator the trail map between the code and standards layer and the design methodology and documents layer for the software important to safety in nuclear power plants. Recently, the requirements specification of safety-critical software systems and safety analysis of them are being recognized as one of the important issues in the software life cycle, and being developed new regulatory positions and standards by the regulatory and the standardization organizations such as IAEA, IEC, and IEEE. We presented the procedure for evaluating the software requirements specifications of the KNGR protection systems. We believe it can be useful for both licenser and licensee to conduct an evaluation of the safety in the requirements phase of developing the software. The guideline consists of the requirements engineering for software of KNGR protection systems in chapter 1, the evaluation checklist of software requirements specification in chapter2.3, and the safety evaluation procedure of KNGR software requirements specification in chapter 2.4

  6. Attitudes of Lay Stakeholders and Transplant Professionals About Disclosure to Living Kidney Donors in Exchanges and Chains.

    Science.gov (United States)

    Grubbs, Allison; Meadow, Jaqueline; Thistlethwaite, J Richard; Ross, Lainie F

    2016-12-01

    Current policies require very limited informational disclosure between living kidney donors and recipients regardless of the relationship type. No specific policies exist to suggest that exchange/chain donors and their recipients should be treated differently. We surveyed transplant professionals (surgeons and nephrologists) and members of the National Kidney Foundation (NKF) to determine their support for disclosing to donors the health, health behavior, and social information of their exchange/chain donors and exchange/chain recipients. Twenty questions regarding disclosing to donors information about both their exchange/chain donors and exchange/chain recipients were included in 2 larger surveys on disclosure about kidney transplantation. Survey A was sent electronically to NKF list-servs, and survey B was sent to transplant professionals both electronically and by postal mail. Survey A yielded 236 valid surveys from NKF donors and recipients (lay stakeholders). Survey B yielded 111 valid surveys from transplant professionals. Both sets of stakeholders support disclosing to donors some health and health behavior information of their exchange/chain donor and exchange/chain recipient, and mostly oppose disclosure of social information. Lay stakeholders favored disclosing significantly more information than transplant professionals. Among lay stakeholders, donor respondents were more supportive than recipient respondents in disclosing to donors health information about the exchange/chain recipient. Among transplant professionals, surgeons were more supportive than nephrologists in disclosing to donors information about the exchange/chain recipient that may impact graft survival. There is broad stakeholder support for disclosing some health and health behavior information to donors about their exchange/chain donors and recipients.

  7. Satellite-enabled educational services specification and requirements analysis based on user feedback

    OpenAIRE

    Tsekeridou, Sofia; Tiropanis, Thanassis; Rorris, Dimitris; Constantinos, Makropoulos; Serif, Tacha; Stergioulas, Lampros

    2008-01-01

    Advanced tele-education services provision in remote geographically dispersed user communities (such as agriculture and maritime), based on the specific needs and requirements of such communities, implies significant infrastructural and broadband connectivity requirements for rich media, timely and quality-assured content delivery and interactivity. The solution to broadband access anywhere is provided by satellite-enabled communication infrastructures. This paper aims to present such satelli...

  8. Surveillance Analysis Computer System (SACS): Software requirements specification (SRS). Revision 2

    International Nuclear Information System (INIS)

    Glasscock, J.A.

    1995-01-01

    This document is the primary document establishing requirements for the Surveillance Analysis Computer System (SACS) database, an Impact Level 3Q system. SACS stores information on tank temperatures, surface levels, and interstitial liquid levels. This information is retrieved by the customer through a PC-based interface and is then available to a number of other software tools. The software requirements specification (SRS) describes the system requirements for the SACS Project, and follows the Standard Engineering Practices (WHC-CM-6-1), Software Practices (WHC-CM-3-10) and Quality Assurance (WHC-CM-4-2, QR 19.0) policies

  9. Development Modules for Specification of Requirements for a System of Verification of Parallel Algorithms

    Directory of Open Access Journals (Sweden)

    Vasiliy Yu. Meltsov

    2012-05-01

    Full Text Available This paper presents the results of the development of one of the modules of the system verification of parallel algorithms that are used to verify the inference engine. This module is designed to build the specification requirements, the feasibility of which on the algorithm is necessary to prove (test.

  10. The impact of customer-specific requirements on supply chain management

    Directory of Open Access Journals (Sweden)

    Hubert I.P. Conceivious

    2010-11-01

    Full Text Available The complexities of being a supplier to motorcar manufacturers, also known as original equipment manufacturers (OEMs, provide an array of challenges to component manufacturers. Customer-specific requirements (CSRs add to the convolutions of a supplier’s quality management systems when producing components for the various motor manufacturers. The catalytic converter industry (CCI forms part of the component supply chain in the motor industry. The CCI consists of a plethora of suppliers to produce the catalytic converter. This paper focuses on three of the five main suppliers, namely the ‘monolith substrate manufacturers’, the ‘coaters’, and the ‘canners’. Most OEMs required that critical and strategic suppliers should be ISO/TS 16949:2009 certified. ISO/TS 16949:2009 refers to an internationally recognised specification, specifically adapted for the motor industry. The specification indicates the minimum requirements and also makes provision for additional requirements known as CSRs that can be specified by the OEM.

  11. 10 CFR 30.33 - General requirements for issuance of specific licenses.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false General requirements for issuance of specific licenses. 30.33 Section 30.33 Energy NUCLEAR REGULATORY COMMISSION RULES OF GENERAL APPLICABILITY TO DOMESTIC... other benefits against environmental costs and considering available alternatives, that the action...

  12. 41 CFR 301-2.5 - What travel arrangements require specific authorization or prior approval?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What travel arrangements require specific authorization or prior approval? 301-2.5 Section 301-2.5 Public Contracts and Property Management Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES INTRODUCTION 2-GENERAL...

  13. Shafting Alignment Computing Method of New Multibearing Rotor System under Specific Installation Requirement

    Directory of Open Access Journals (Sweden)

    Qian Chen

    2016-01-01

    Full Text Available The shafting of large steam turbine generator set is composed of several rotors which are connected by couplings. The computing method of shafting with different structure under specific installation requirement is studied in this paper. Based on three-moment equation, shafting alignment mathematical model is established. The computing method of bearing elevations and loads under corresponding installation requirements, where bending moment of each coupling is zero and there exist preset sag and gap in some couplings, is proposed, respectively. Bearing elevations and loads of shafting with different structure under specific installation requirement are calculated; calculation results are compared with installation data measured on site which verifies the validity and accuracy of the proposed shafting alignment computing method. The above work provides a reliable approach to analyze shafting alignment and could guide installation on site.

  14. Sharing data between mobile devices, connected vehicles, and infrastructure task 3: system requirements specifications (SyRS) final.

    Science.gov (United States)

    2016-07-14

    This report describes the system requirements specifications (SyRS) for the use of mobile devices in a connected vehicle environment. Specifically, it defines the different types of requirements (functional, interface, performance, security, data, an...

  15. A donor-specific QTL, exhibiting allelic variation for leaf sheath hairiness in a nested association mapping population, is located on barley chromosome 4H

    KAUST Repository

    Saade, Stephanie

    2017-12-07

    Leaf sheath hairiness is a morphological trait associated with various advantages, including tolerance to both abiotic and biotic stresses, thereby increasing yield. Understanding the genetic basis of this trait in barley can therefore improve the agronomic performance of this economically important crop. We scored leaf sheath hairiness in a two-year field trial in 1,420 BC1S3 lines from the wild barley nested association mapping (NAM) population HEB-25. Leaf sheath hairiness segregated in six out of 25 families with the reference parent Barke being glabrous. We detected the major hairy leaf sheath locus Hs (syn. Hsh) on chromosome 4H (111.3 cM) with high precision. The effects of the locus varied across the six different wild barley donors, with donor of HEB family 11 conferring the highest score of leaf sheath hairiness. Due to the high mapping resolution present in HEB-25, we were able to discuss physically linked pentatricopeptide repeat genes and subtilisin-like proteases as potential candidate genes underlying this locus. In this study, we proved that HEB-25 provides an appropriate tool to further understand the genetic control of leaf sheath hairiness in barley. Furthermore, our work represents a perfect starting position to clone the gene responsible for the 4H locus observed.

  16. A donor-specific QTL, exhibiting allelic variation for leaf sheath hairiness in a nested association mapping population, is located on barley chromosome 4H.

    Directory of Open Access Journals (Sweden)

    Stephanie Saade

    Full Text Available Leaf sheath hairiness is a morphological trait associated with various advantages, including tolerance to both abiotic and biotic stresses, thereby increasing yield. Understanding the genetic basis of this trait in barley can therefore improve the agronomic performance of this economically important crop. We scored leaf sheath hairiness in a two-year field trial in 1,420 BC1S3 lines from the wild barley nested association mapping (NAM population HEB-25. Leaf sheath hairiness segregated in six out of 25 families with the reference parent Barke being glabrous. We detected the major hairy leaf sheath locus Hs (syn. Hsh on chromosome 4H (111.3 cM with high precision. The effects of the locus varied across the six different wild barley donors, with donor of HEB family 11 conferring the highest score of leaf sheath hairiness. Due to the high mapping resolution present in HEB-25, we were able to discuss physically linked pentatricopeptide repeat genes and subtilisin-like proteases as potential candidate genes underlying this locus. In this study, we proved that HEB-25 provides an appropriate tool to further understand the genetic control of leaf sheath hairiness in barley. Furthermore, our work represents a perfect starting position to clone the gene responsible for the 4H locus observed.

  17. Differences in social representation of blood donation between donors and non-donors: an empirical study.

    Science.gov (United States)

    Guarnaccia, Cinzia; Giannone, Francesca; Falgares, Giorgio; Caligaris, Aldo Ozino; Sales-Wuillemin, Edith

    2015-11-04

    Both donors and non-donors have a positive image of blood donation, so donors and non-donors do not differ regarding their views on donation but do differ in converting their opinion into an active deed of donation. Several studies have identified altruism and empathy as the main factors underlying blood donation. However, a mixture of various motivational factors mould the complex behaviour of donation. This paper presents an exploratory study on differences of social representations of blood donation between blood donors and non-donors, in order to understand the reasons that bring someone to take the decision to become a blood donor. Participants filled in the Adapted Self-Report Altruism Scale, Toronto Empathy Questionnaire and answered a test of verbal association. Descriptive and correlation analyses were carried out on quantitative data, while a prototypic analysis was used for qualitative data. The study was carried out on a convenience sample of 786 individuals, 583 donors (mean age: 35.40 years, SD: 13.01 years; 39.3% female) and 203 non-donors (mean age: 35.10 years, SD: 13.30 years; 67.5% female). Social representations of donors seem to be more complex and articulated than those of non-donors. The terms that appear to be central were more specific in donors (life, needle, blood, help, altruism were the words most associated by non-donors; life, aid, altruism, solidarity, health, love, gift, generosity, voluntary, control, needed, useful, needle were the words most associated by donors). Furthermore, non-donors associated a larger number of terms referring to negative aspects of blood donation. Aspects related to training and the accuracy of any information on blood donation seem to be important in the decision to become a donor and stabilise the behaviour of donation over time, thus ensuring the highest levels of quality and safety in blood establishments.

  18. A PLC generic requirements and specification for safety-related applications in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jea Bok; Lee, C. K.; Lee, D. Y. [and others

    2001-12-01

    This report presents the requirements and specification to be applied to the generic qualification of programmable Logic Controller(PLC), which is being developed as part of the KNICS project, 'Development of the Digital Reactor Safety Systems' of which purpose is the application to safety-related instrumentation and control systems in nuclear power plants. This report defines the essential and critical characteristics that shall be included as part of a PLC design for safety-related application. The characteristics include performance, reliability, accuracy, the overall response time from an input to the PLC exceeding it trip condition to the resulting outputs, and the specification of processors and memories in digital controller. It also specifies the quality assurance process for software development, dealing with executive software, firmware, application software tools for developing the application software, and human machine interface(HMI). In addition, this report reviews the published standards and guidelines that are required for the PLC development and the quality assurance processes such as environment requirements, seismic withstand requirements, EMI/RFI withstand requirements, and isolation test.

  19. Host specific differences alter the requirement for certain Salmonella genes during swine colonization.

    Science.gov (United States)

    Bearson, Bradley L; Bearson, Shawn M D

    2011-06-02

    The pathogenic potential of Salmonella is determined during the complex interaction between pathogen and host, requiring optimal regulation of multiple bacterial genetic systems within variable in vivo environments. The mouse model of systemic disease has been an extremely productive model to investigate the pathogenesis of Salmonella enterica serovar Typhimurium (S. Typhimurium). Although the mouse model is a widely used paradigm for studying the pathogenesis of systemic disease caused by Salmonella, investigations concerning food safety interventions should employ natural hosts to examine gastrointestinal colonization by Salmonella. Recent research has demonstrated specific differences in the attenuation of certain S. Typhimurium mutants in mice compared to swine. This variation in pathogenesis between the mouse model and pigs for the S. Typhimurium mutants is presumably dependent upon either the requirements for specific gene products during systemic disease (mouse) versus gastrointestinal colonization (pig) or host specific differences. In addition, host specific diversity in Salmonella colonization of swine has also been described in comparison to other food-producing animals, including cattle and chickens. Differences in Salmonella colonization and pathogenesis across diverse animal species highlight the importance of species-specific studies of gastrointestinal colonization for the development of Salmonella interventions to enhance pork safety. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Being a Living Donor: Risks

    Science.gov (United States)

    ... to know FAQ Living donation What is living donation? Organs Types Being a living donor First steps Being ... are considering one of these types of living donation, please talk to your transplant center about the organ-specific risks. Psychological concerns You may also have ...

  1. Living related donor liver transplantation.

    Science.gov (United States)

    Chen, C L; Chen, Y S; Liu, P P; Chiang, Y C; Cheng, Y F; Huang, T L; Eng, H L

    1997-10-01

    Living related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra-operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra-operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n = 10) and glycogen storage disease (n = 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.

  2. Requirement for specific gravity and creatinine adjustments for urinary steroids and luteinizing hormone concentrations in adolescents.

    Science.gov (United States)

    Singh, Gurmeet K S; Balzer, Ben W R; Desai, Reena; Jimenez, Mark; Steinbeck, Katharine S; Handelsman, David J

    2015-11-01

    Urinary hormone concentrations are often adjusted to correct for hydration status. We aimed to determine whether first morning void urine hormones in growing adolescents require adjustments and, if so, whether urinary creatinine or specific gravity are better adjustments. The study population was adolescents aged 10.1 to 14.3 years initially who provided fasting morning blood samples at 0 and 12 months (n = 343) and first morning urine every three months (n = 644). Unadjusted, creatinine and specific gravity-adjusted hormonal concentrations were compared by Deming regression and Bland-Altman analysis and grouped according to self-rated Tanner stage or chronological age. F-ratios for self-rated Tanner stages and age groups were used to compare unadjusted and adjusted hormonal changes in growing young adolescents. Correlations of paired serum and urinary hormonal concentration of unadjusted and creatinine and specific gravity-adjusted were also compared. Fasting first morning void hormone concentrations correlated well and were unbiased between unadjusted or adjusted by either creatinine or specific gravity. Urine creatinine concentration increases with Tanner stages, age and male gender whereas urine specific gravity was not influenced by Tanner stage, age or gender. Adjustment by creatinine or specific gravity of urinary luteinizing hormone, estradiol, testosterone, dihydrotestosterone and dehydroepiandrosterone concentrations did not improve correlation with paired serum concentrations. Urine steroid and luteinizing hormone concentrations in first morning void samples of adolescents are not significantly influenced by hydration status and may not require adjustments; however, if desired, both creatinine and specific gravity adjustments are equally suitable. © The Author(s) 2015.

  3. Testing Requirements to Manage Data Exchange Specifications in Enterprise Integration - A Schema Design Quality Focus.

    Energy Technology Data Exchange (ETDEWEB)

    Kulvatunyou, Boonserm [ORNL; Ivezic, Nenad [ORNL; Buhwan, Jeong [POSTECH University, South Korea

    2004-07-01

    In this paper, we describe the requirements to test W3C XML Schema usage when defining message schemas for data exchange in any large and evolving enterprise integration project. We then decompose the XML Schema testing into four (4) aspects including the message schema conformance to the XML Schema specification grammar, the message schema conformance to the XML Schema specification semantics, the message schema conformance to design quality testing, and canonical semantics testing of the message schema. We describe these four testing aspects in some detail and point to other related efforts. We further focus to provide some technical details for the message schema design quality testing. As a future work, we describe the requirements for canonical semantics testing and potential solution approaches. Finally, we describe an implementation architecture for the message schema design quality testing.

  4. AMTD: Update of Engineering Specifications Derived from Science Requirements for Future UVOIR Space Telescopes

    Science.gov (United States)

    Stahl, H. Philip; Postman, Marc; Mosier, Gary; Smith, W. Scott; Blaurock, Carl; Ha, Kong; Stark, Christopher C.

    2014-01-01

    The Advance Mirror Technology Development (AMTD) project is in Phase 2 of a multiyear effort, initiated in FY12, to mature by at least a half TRL step six critical technologies required to enable 4 meter or larger UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND provide a high-performance low-cost low-risk system. To give the science community options, we are pursuing multiple technology paths. A key task is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints. A key finding of this effort is that the science requires an 8 meter or larger aperture telescope

  5. AMTD: update of engineering specifications derived from science requirements for future UVOIR space telescopes

    Science.gov (United States)

    Stahl, H. Philip; Postman, Marc; Mosier, Gary; Smith, W. Scott; Blaurock, Carl; Ha, Kong; Stark, Christopher C.

    2014-08-01

    The Advance Mirror Technology Development (AMTD) project is in Phase 2 of a multiyear effort, initiated in FY12, to mature by at least a half TRL step six critical technologies required to enable 4 meter or larger UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND provide a high-performance low-cost low-risk system. To give the science community options, we are pursuing multiple technology paths. A key task is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints. A key finding of this effort is that the science requires an 8 meter or larger aperture telescope.

  6. Requirements and Architecture Specification of the Joint Multi-Role (JMR) Joint Common Architecture (JCA) Demonstration System

    Science.gov (United States)

    2015-12-01

    layer above DCFM (see Section 3.5). In text-based requirement specifications, two rules are used to assess their quality:  traceability to...subsystem. They are reflected in the AADL as properties and in the ReqSpec notation as explicitly traceable decomposition of requirement specifications...ambiguously phrased, not verifiable, and in conflict with other goals and verifiable requirements .  provide traceability to requirements specification and

  7. The beneficial effect of donor-specific transfusions: a review of existing explanations and a new hypothesis based on a relatively unapplied theory of T cell immunoregulation. A regulatory hypothesis in progress...

    Science.gov (United States)

    Wendel, T D

    2000-06-01

    The mechanism by which donor specific transfusions protect a graft from the recipient's immune system is unknown. It is likely that this beneficial mechanism is a subset or distinct exhibition of the general rules governing the regulation of the immune system. This phenomenon provides a strong framework for investigation of immune regulation, considering its potential consanguinity to immune regulation, that it is a paradox representing a manifestation of regulatory rules, and that it provides a wealth of clinical experience and experimentation from which to make inferences. Vital in any exploration of immune regulation, is the promise held in reducing the immune system to its chief elemental regulatory mechanisms and interactions. Strangely, the majority of this consequential work may have already been accomplished by Gershon, Green and colleagues with their elegant demarcation of T cell regulation into suppressor and contrasuppressor pathways. The practical and theoretical implications of this discovery seem to be, for the most part, ignored by mainstream immunology. It is doubtful, based on the quality and quantity of their work, or confirming work by other laboratories that they were inaccurate in their findings. It remains a horrible waste that their discoveries are not in immunology's pantheon of hallowed discoveries and are little used. With all this kept in mind, a comprehensive hypothesis of regulation was put together based mainly on Gershon's portrait of the suppressor and contrasuppressor pathways' contributions to immune regulation and experimentation surrounding the unsolved paradox of donor specific transfusions.

  8. The NIMA Kinase Is Required To Execute Stage-Specific Mitotic Functions after Initiation of Mitosis

    Science.gov (United States)

    Govindaraghavan, Meera; Lad, Alisha A.

    2014-01-01

    The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events. PMID:24186954

  9. Disease specific stress of tumor patients at the beginning of radiotherapy. Effect on psychosocial support requirement

    International Nuclear Information System (INIS)

    Sehlen, S.; Hollenhorst, H.; Schymura, B.; Firsching, M.; Duehmke, E.; Herschbach, P.

    2001-01-01

    Purpose: Radiotherapy brings a tumor patient into a special life situation in which different variables play a role of often unknown importance. The goal of this study was to investigate disease specific stress of tumor patients at the beginning of radiotherapy with established psychodiagnostic questionnaires and to evaluate the effect on psychosocial support requirement in order to reduce stress and to improve quality of life and compliance during radiotherapeutical treatment. Patients and Methods: 732 patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion (refusals 21.0%, low Karnofsky performance status 6.6%, management problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%). Disease specific aspects of stress in the questionnaire (Fragebogen zur Belastung von Krebspatienten, FBK), life situation (LS) and self-defined care requirements (BB) were self-rated by patients with different tumor types before radiotherapy. Medical and sociodemographic data were also documented. We investigated 446 patients (262 male, 184 female; median age 60.0 years) with different diagnoses. Results: Stress was observed mainly due to reduction of efficiency, anxiety and pain on the subscales. Women had a significant higher stress on subscales of pain (p=0.016) and anxiety (p=0.009), patients younger than 45 years in the subscale information (p=0.002) and patients older than 45 and younger than 60 years in the subscale anxiety (p=0.002) and the total score (p=0.003). Patients with mamma carcinoma had the highest stress. The maximum percentages of patients under high stress were found for the subscales of efficiency (43%) and anxiety (40%). The support requirement was characterized by the need of more medical information and dialogue with the doctor. We saw a significant correlation of high stress and high care requirement. Conclusions: Psychosocial support should be founded on psychosocial stress diagnostic and self-defined care

  10. Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

    Science.gov (United States)

    Taniguchi, K; Yoshihara, S; Maruya, E; Ikegame, K; Kaida, K; Hayashi, K; Kato, R; Inoue, T; Fujioka, T; Tamaki, H; Okada, M; Onuma, T; Fujii, N; Kusunoki, Y; Soma, T; Saji, H; Ogawa, H

    2012-10-01

    Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

  11. Impact of donor-specific anti-HLA antibodies on graft failure and survival after reduced intensity conditioning-unrelated cord blood transplantation: a Eurocord, Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI) and Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) analysis.

    Science.gov (United States)

    Ruggeri, Annalisa; Rocha, Vanderson; Masson, Emeline; Labopin, Myriam; Cunha, Renato; Absi, Lena; Boudifa, Ali; Coeffic, Brigitte; Devys, Anne; De Matteis, Muriel; Dubois, Valérie; Hanau, Daniel; Hau, Françoise; Jollet, Isabelle; Masson, Dominique; Pedron, Beatrice; Perrier, Pascale; Picard, Christophe; Ramouneau-Pigot, Annie; Volt, Fernanda; Charron, Dominique; Gluckman, Eliane; Loiseau, Pascale

    2013-07-01

    Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. To analyze the effect of anti-HLA antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using Luminex™ platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Among 62 recipients (23%) who had anti-HLA antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA antibodies (DSA) (7 were donor-specific anti-HLA antibodies for single unrelated cord blood transplant and 7 for double unrelated cord blood transplant). Donor specific anti-HLA antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of Day-60 neutrophil engraftment was 76%: 44% for recipients with donor specific anti-HLA antibodies and 81% in those without donor specific anti-HLA antibodies (P=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor specific anti-HLA antibodies and 32% in those without antibodies (P=0.06). The presence of donor specific anti-HLA antibodies was associated with a trend for decreased survival rate (42% vs. 29%; P=0.07). Donor specific anti-HLA antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor specific anti-HLA antibodies before unrelated cord blood transplantation is recommended before choosing an HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit for which the patient has

  12. Hazard Analysis of Software Requirements Specification for Process Module of FPGA-based Controllers in NPP

    Energy Technology Data Exchange (ETDEWEB)

    Jung; Sejin; Kim, Eui-Sub; Yoo, Junbeom [Konkuk University, Seoul (Korea, Republic of); Keum, Jong Yong; Lee, Jang-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2016-10-15

    Software in PLC, FPGA which are used to develop I and C system also should be analyzed to hazards and risks before used. NUREG/CR-6430 proposes the method for performing software hazard analysis. It suggests analysis technique for software affected hazards and it reveals that software hazard analysis should be performed with the aspects of software life cycle such as requirements analysis, design, detailed design, implements. It also provides the guide phrases for applying software hazard analysis. HAZOP (Hazard and operability analysis) is one of the analysis technique which is introduced in NUREG/CR-6430 and it is useful technique to use guide phrases. HAZOP is sometimes used to analyze the safety of software. Analysis method of NUREG/CR-6430 had been used in Korea nuclear power plant software for PLC development. Appropriate guide phrases and analysis process are selected to apply efficiently and NUREG/CR-6430 provides applicable methods for software hazard analysis is identified in these researches. We perform software hazard analysis of FPGA software requirements specification with two approaches which are NUREG/CR-6430 and HAZOP with using general GW. We also perform the comparative analysis with them. NUREG/CR-6430 approach has several pros and cons comparing with the HAZOP with general guide words and approach. It is enough applicable to analyze the software requirements specification of FPGA.

  13. RET Functions as a Dual-Specificity Kinase that Requires Allosteric Inputs from Juxtamembrane Elements

    Directory of Open Access Journals (Sweden)

    Iván Plaza-Menacho

    2016-12-01

    Full Text Available Receptor tyrosine kinases exhibit a variety of activation mechanisms despite highly homologous catalytic domains. Such diversity arises through coupling of extracellular ligand-binding portions with highly variable intracellular sequences flanking the tyrosine kinase domain and specific patterns of autophosphorylation sites. Here, we show that the juxtamembrane (JM segment enhances RET catalytic domain activity through Y687. This phospho-site is also required by the JM region to rescue an otherwise catalytically deficient RET activation-loop mutant lacking tyrosines. Structure-function analyses identified interactions between the JM hinge, αC helix, and an unconventional activation-loop serine phosphorylation site that engages the HRD motif and promotes phospho-tyrosine conformational accessibility and regulatory spine assembly. We demonstrate that this phospho-S909 arises from an intrinsic RET dual-specificity kinase activity and show that an equivalent serine is required for RET signaling in Drosophila. Our findings reveal dual-specificity and allosteric components for the mechanism of RET activation and signaling with direct implications for drug discovery.

  14. Swedish sperm donors are driven by altruism, but shortage of sperm donors leads to reproductive travelling.

    Science.gov (United States)

    Ekerhovd, Erling; Faurskov, Anders; Werner, Charlotte

    2008-01-01

    Swedish legislation requires that sperm donors are identifiable to offspring. In Denmark sperm donors remain anonymous. The aim of this study was to examine sperm donation in Sweden by identifying socio-demographic backgrounds, motivations and attitudes among donors and to describe options and plans of sperm recipients. Furthermore, the willingness of Swedish health care providers to assist in treatment abroad, where sperm from an anonymous donor were to be used, was assessed. The extent of travelling to Denmark for reproductive purposes was also examined. Thirty Swedish sperm donors completed a questionnaire and were interviewed about their backgrounds, motivations and attitudes. Thirty couples where the infertility workup had shown azoospermia were interviewed about their options for achieving parenthood. The willingness to assist in fertility treatment abroad and the extent of reproductive cross border travelling were assessed by interviewing health care providers and by contacting Danish clinics. Almost all donors were Caucasian. The main motivation for sperm donors was to help others. Owing to shortage of sperm donors many Caucasian recipients intended to have treatment abroad. For most non-Caucasian recipients sperm from a donor of appropriate ethnicity were not available in Sweden. Whether the sperm donor was anonymous or identifiable was not of major importance to most sperm recipients. Health care providers expressed unanimous willingness to assist in treatment with sperm from an anonymous donor. Our inquiry indicated that more than 250 Swedish sperm recipients travel to Denmark annually. Identifiable sperm donors are driven by altruistic motives, but shortage of sperm donors leads to reproductive travelling. Recruitment strategies to increase the number of sperm donors in Sweden are therefore warranted.

  15. Nyretransplantation med levende donor

    DEFF Research Database (Denmark)

    Kamper, A L; Løkkegaard, H; Rasmussen, F

    2000-01-01

    In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associate...... in cadaver transplantation. The ethical and psychological aspects related to transplantation from a living donor are complex and need to be carefully evaluated when this treatment is offered to the patients.......In recent years transplantation from living donors has accounted for 25-30% of all kidney transplants in Denmark corresponding to 40-45 per year. Most of these living donors are parents or siblings, although internationally an increasing number are unrelated donors. Donor nephrectomy is associated...... with only few complications. The long-term outcome for kidney donors is good without increase in mortality or risk for development of hypertension and renal failure; proteinuria may be seen. Living kidney transplantation is the optimal treatment of end-stage renal disease with better graft survival than...

  16. High-Level software requirements specification for the TWRS controlled baseline database system

    International Nuclear Information System (INIS)

    Spencer, S.G.

    1998-01-01

    This Software Requirements Specification (SRS) is an as-built document that presents the Tank Waste Remediation System (TWRS) Controlled Baseline Database (TCBD) in its current state. It was originally known as the Performance Measurement Control System (PMCS). Conversion to the new system name has not occurred within the current production system. Therefore, for simplicity, all references to TCBD are equivalent to PMCS references. This SRS will reference the PMCS designator from this point forward to capture the as-built SRS. This SRS is written at a high-level and is intended to provide the design basis for the PMCS. The PMCS was first released as the electronic data repository for cost, schedule, and technical administrative baseline information for the TAAS Program. During its initial development, the PMCS was accepted by the customer, TARS Business Management, with no formal documentation to capture the initial requirements

  17. It is only fair: blood donors are more sensitive to violations of fairness norms than nondonors - converging psychometric and ultimatum game evidence.

    Science.gov (United States)

    Ferguson, E; Lawrence, C

    2018-04-01

    The design of effective donor recruitment campaigns requires an accurate understanding of donor motivations. This requires cross-validation of theoretically derived, psychometrically assessed motivations with behavioural preferences. Theoretical models suggest that blood donors should be more sensitive than nondonors to violations of fairness norms. Specifically, active blood donors, compared to nondonors, should endorse beliefs of reciprocal fairness, norms of both positive and negative reciprocity and reject more unfair offers in a behavioural economic game (the ultimatum game). This study is the first to test this hypothesis. Two studies are reported. One experimental psychometric study (N = 400) and one behavioural economic game using the ultimatum game (N = 60). Consistent with the predictions, active and lapsed donors, compared to nondonors, were more likely to endorse beliefs of reciprocal fairness and active donors to endorse norms of both positive and negative reciprocity and reject more unfair offers in the ultimatum game. This pattern of motivations was unique to blood donors and not observed for other health (i.e. being on the organ donor register) and nonhealth (e.g. volunteering) prosociality. Blood donors have a heightened sensitivity to unfairness violations. This indicates a very clear and specific line for the development of interventions that align fairness, self-interest and reciprocity, for example voluntary reciprocal altruism (VRA). We also highlight the importance of establishing intervention development within a clinical trials model and emphasize why experimental work of this type is vital. © 2018 International Society of Blood Transfusion.

  18. Technical specification action requirements for AFW system failures: Method development and application to four PWR plants

    International Nuclear Information System (INIS)

    Mankamo, T.; Kim, I.S.; Yang, Ji Wu; Samanta, P.K.

    1996-01-01

    Failures in the auxiliary feedwater (AFW) system of pressurized water reactors (PWRs) are considered to involve substantial risk whether a decision is made to either continue power operation while repair is being done, or to shut down the plant to undertake repairs. Technical specification action requirements usually require immediate plant shutdown in the case of multiple failures in the system (in some cases, immediate repair of one train is required when all AFW trains fail). This paper presents a probabilistic risk assessment-based method to quantitatively evaluate and compare both the risks of continued power operation and of shutting the plant down, given known failures in the system. The method is applied to the AFW system for four different PWRs. Results show that the risk of continued power operation and plant shutdown both are substantial, but the latter is larger than the former over the usual repair time. This was proven for four plants with different designs: two operating Westinghouse plants, one operating Asea-Brown Boveri Combustion Engineering Plant, and one of evolutionary design. The method can be used to analyze individual plant design and to improve AFW action requirements using risk-informed evaluations

  19. A study to develop the domestic functional requirements of the specific safety systems of CANDU

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Man Woong [Korea Institute of Nuclear Safety, Taejon (Korea, Republic of); Lee, Jae Young; Park, Kun Chul [Handong Global Univ., Pohang (Korea, Republic of)] (and others)

    2003-03-15

    The present research has been made to develop and review critically the functional requirements of the specific safety systems of CANDU such as SDS-1, SDS2, ECCS, and containment. Based on R documents for this, a systematic study was made to develop the domestic regulation statements. Also, the conventional laws are carefully reviewed to see the compatibility to CANDU. Also, the safety assessment method for CANDU was studied by reviewing C documents and recommendation of IAEA. Through the present works, the vague policy in the CANDU safety regulation is cleaning up in a systematic form and a new frame to measure the objective risk of nuclear power plants was developed.

  20. Statistical Study to Check the Conformity of Aggregate in Kirkuk City to Requirement of Iraqi Specification

    Directory of Open Access Journals (Sweden)

    Ammar Saleem Khazaal

    2018-01-01

    Full Text Available This research reviews a statistical study to check the conformity of aggregates (Coarse and Fine was used in Kirkuk city to the requirements of the Iraqi specifications. The data of sieve analysis (215 samples of aggregates being obtained from of National Central Construction Laboratory and Technical College Construction Laboratory in Kirkuk city have analyzed using the statistical program SAS. The results showed that 5%, 17%, and 18% of fine aggregate samples are passing sieve sizes 10 mm, 4.75 mm, and 2.36 mm, respectively, which were less than the minimum limit allowed by the Iraqi specifications for each sieve. The percentages passing sieve sizes 1.18mm, 600micrometers, and 300micrometers were more than the upper limit of specification by 5%, 20%, and 30% respectively. The samples were passing sieve sizes 1.18mm, and 600micrometers less than the minimum limit of specification by 17%, and 4%, respectively. The results showed that the deviation in a sieve size of 150 micrometers for the upper limit of the specification performs 2% of the total number of samples. For Coarse aggregate, the samples passing sieves size 37.5mm and 20mm were comforting the Iraqi specifications by 100% and 83% respectively, it has found that the samples were passing sieve sizes 10 mm was 5% was more than the higher limit of Iraqi specifications, and 27% of these samples were less than the minimum limit, whereas sample passing sieve size 5mm was 1% which is more than the upper limit of the Iraqi specification. As a result of statistical analysis of data for fine aggregate, it has found that the samples were passing sieve sizes 10 mm, 2.36 mm, 1.18 mm and 150micrometers conforming from statistical point of view the Iraqi specifications, whereas the samples were passing sieve sizes 4.75 mm, 600micrometers and 300 micrometers didn’t conform. Statistical analysis of the results of the coarse aggregates also showed that conforming to sieve sizes of 37.5 mm and 20 mm and

  1. 21 CFR 640.66 - Immunization of donors.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Immunization of donors. 640.66 Section 640.66 Food... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Source Plasma § 640.66 Immunization of donors. If specific immunization of a donor is to be performed, the selection and scheduling of the injection of the...

  2. Epitope analysis of the collagen type V-specific T cell response in lung transplantation reveals an HLA-DRB1*15 bias in both recipient and donor.

    Directory of Open Access Journals (Sweden)

    Melissa R Keller

    Full Text Available BACKGROUND: IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively. METHODOLOGY/PRINCIPAL FINDINGS: We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V. Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V low-responders (p=0.02. After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V responses most frequently (p=0.04 and 0.01 vs. controls, respectively. However, recipients of a lung from an HLA-DR15(+donor were at significantly elevated risk of developing anti-col(V responses (p=0.02 and BOS (p=0.03. To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the α1(V protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17 or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17 and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15. Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control for p799 (GIRGLKGTKGEKGED, and 193 for p1439 (LRGIPGPVGEQGLPG. These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1(+ and -DR15(+ col(V reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG was DR15-specific. Remarkably, a col(V-reactive HLA-DR1(+DR15(neg lung transplant patient, whose donor was HLA-DR15(+, responded not only to p799 and p1439, but also to p1049. CONCLUSIONS/SIGNIFICANCE: HLA-DR15 and IPF disease were independently associated with pre-transplant col(V autoimmunity. The increased risk of de

  3. Initial experience with purely laparoscopic living-donor right hepatectomy.

    Science.gov (United States)

    Hong, S K; Lee, K W; Choi, Y; Kim, H S; Ahn, S W; Yoon, K C; Kim, H; Yi, N J; Suh, K S

    2018-03-26

    There may be concerns about purely laparoscopic donor right hepatectomy (PLDRH) compared with open donor right hepatectomy, especially when performed by surgeons accustomed to open surgery. This study aimed to describe technical tips and pitfalls in PLDRH. Data from donors who underwent PLDRH at Seoul National University Hospital between December 2015 and July 2017 were analysed retrospectively. Endpoints analysed included intraoperative events and postoperative complications. All operations were performed by a single surgeon with considerable experience in open living donor hepatectomy. A total of 26 donors underwent purely laparoscopic right hepatectomy in the study interval. No donor required transfusion during surgery, whereas two underwent reoperation. In two donors, the dissection plane at the right upper deep portion of the midplane was not correct. One donor experienced portal vein injury during caudate lobe transection, and one developed remnant left hepatic duct stenosis. One donor experienced remnant portal vein angulation owing to a different approach angle, and one experienced arterial damage associated with the use of a laparoscopic energy device. One donor had postoperative bleeding due to masking of potential bleeding foci owing to intra-abdominal pressure during laparoscopy. Two donors experienced right liver surface damage caused by a xiphoid trocar. Purely laparoscopic donor hepatectomy differs from open donor hepatectomy in terms of angle and caudal view. Therefore, surgeons experienced in open donor hepatectomy must gain adequate experience in laparoscopic liver surgery and make adjustments when performing PLDRH. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

  4. Neurotransmitter Transporter-Like: a male germline-specific SLC6 transporter required for Drosophila spermiogenesis.

    Directory of Open Access Journals (Sweden)

    Nabanita Chatterjee

    2011-01-01

    Full Text Available The SLC6 class of membrane transporters, known primarily as neurotransmitter transporters, is increasingly appreciated for its roles in nutritional uptake of amino acids and other developmentally specific functions. A Drosophila SLC6 gene, Neurotransmitter transporter-like (Ntl, is expressed only in the male germline. Mobilization of a transposon inserted near the 3' end of the Ntl coding region yields male-sterile mutants defining a single complementation group. Germline transformation with Ntl cDNAs under control of male germline-specific control elements restores Ntl/Ntl homozygotes to normal fertility, indicating that Ntl is required only in the germ cells. In mutant males, sperm morphogenesis appears normal, with elongated, individualized and coiled spermiogenic cysts accumulating at the base of the testes. However, no sperm are transferred to the seminal vesicle. The level of polyglycylation of Ntl mutant sperm tubulin appears to be significantly lower than that of wild type controls. Glycine transporters are the most closely related SLC6 transporters to Ntl, suggesting that Ntl functions as a glycine transporter in developing sperm, where augmentation of the cytosolic pool of glycine may be required for the polyglycylation of the massive amounts of tubulin in the fly's giant sperm. The male-sterile phenotype of Ntl mutants may provide a powerful genetic system for studying the function of an SLC6 transporter family in a model organism.

  5. Donor Retention in Online Crowdfunding Communities: A Case Study of DonorsChoose.org.

    Science.gov (United States)

    Althoff, Tim; Leskovec, Jure

    2015-05-01

    Online crowdfunding platforms like DonorsChoose.org and Kick-starter allow specific projects to get funded by targeted contributions from a large number of people. Critical for the success of crowdfunding communities is recruitment and continued engagement of donors. With donor attrition rates above 70%, a significant challenge for online crowdfunding platforms as well as traditional offline non-profit organizations is the problem of donor retention. We present a large-scale study of millions of donors and donations on DonorsChoose.org, a crowdfunding platform for education projects. Studying an online crowdfunding platform allows for an unprecedented detailed view of how people direct their donations. We explore various factors impacting donor retention which allows us to identify different groups of donors and quantify their propensity to return for subsequent donations. We find that donors are more likely to return if they had a positive interaction with the receiver of the donation. We also show that this includes appropriate and timely recognition of their support as well as detailed communication of their impact. Finally, we discuss how our findings could inform steps to improve donor retention in crowdfunding communities and non-profit organizations.

  6. Choosing the order of deceased donor and living donor kidney transplantation in pediatric recipients: a Markov decision process model.

    Science.gov (United States)

    Van Arendonk, Kyle J; Chow, Eric K H; James, Nathan T; Orandi, Babak J; Ellison, Trevor A; Smith, Jodi M; Colombani, Paul M; Segev, And Dorry L

    2015-02-01

    Most pediatric kidney transplant recipients eventually require retransplantation, and the most advantageous timing strategy regarding deceased and living donor transplantation in candidates with only 1 living donor remains unclear. A patient-oriented Markov decision process model was designed to compare, for a given patient with 1 living donor, living-donor-first followed if necessary by deceased donor retransplantation versus deceased-donor-first followed if necessary by living donor (if still able to donate) or deceased donor (if not) retransplantation. Based on Scientific Registry of Transplant Recipients data, the model was designed to account for waitlist, graft, and patient survival, sensitization, increased risk of graft failure seen during late adolescence, and differential deceased donor waiting times based on pediatric priority allocation policies. Based on national cohort data, the model was also designed to account for aging or disease development, leading to ineligibility of the living donor over time. Given a set of candidate and living donor characteristics, the Markov model provides the expected patient survival over a time horizon of 20 years. For the most highly sensitized patients (panel reactive antibody > 80%), a deceased-donor-first strategy was advantageous, but for all other patients (panel reactive antibody Markov model illustrates how patients, families, and providers can be provided information and predictions regarding the most advantageous use of deceased donor versus living donor transplantation for pediatric recipients.

  7. Laparoscopic donor nephrectomy

    Directory of Open Access Journals (Sweden)

    Gupta Nitin

    2005-01-01

    Full Text Available Of the various options for patients with end stage renal disease, kidney transplantation is the treatment of choice for a suitable patient. The kidney for transplantation is retrieved from either a cadaver or a live donor. Living donor nephrectomy has been developed as a method to address the shortfall in cadaveric kidneys available for transplantation. Laparoscopic living donor nephrectomy (LLDN, by reducing postoperative pain, shortening convalescence, and improving the cosmetic outcome of the donor nephrectomy, has shown the potential to increase the number of living kidney donations further by removing some of the disincentives inherent to donation itself. The technique of LLDN has undergone evolution at different transplant centers and many modifications have been done to improve donor safety and recipient outcome. Virtually all donors eligible for an open surgical procedure may also undergo the laparoscopic operation. Various earlier contraindications to LDN, such as right donor kidney, multiple vessels, anomalous vasculature and obesity have been overcome with increasing experience. Laparoscopic live donor nephrectomy can be done transperitoneally or retroperitoneally on either side. The approach is most commonly transperitoneal, which allows adequate working space and easy dissection. A review of literature and our experience with regards to standard approach and the modifications is presented including a cost saving model for the developing countries. An assessment has been made, of the impact of LDN on the outcome of donor and the recipient.

  8. Krüppel-like is required for nonskeletogenic mesoderm specification in the sea urchin embryo.

    Science.gov (United States)

    Yamazaki, Atsuko; Kawabata, Rika; Shiomi, Kosuke; Tsuchimoto, Jun; Kiyomoto, Masato; Amemiya, Shonan; Yamaguchi, Masaaki

    2008-02-15

    The canonical Wnt pathway plays a central role in specifying vegetal cell fate in sea urchin embryos. SpKrl has been cloned as a direct target of nuclear beta-catenin. Using Hemicentrotus pulcherrimus embryos, here we show that HpKrl controls the specification of secondary mesenchyme cells (SMCs) through both cell-autonomous and non-autonomous means. Like SpKrl, HpKrl was activated in both micromere and macromere progenies. To examine the functions of HpKrl in each blastomere, we constructed chimeric embryos composed of blastomeres from control and morpholino-mediated HpKrl-knockdown embryos and analyzed the phenotypes of the chimeras. Micromere-swapping experiments showed that HpKrl is not involved in micromere specification, while micromere-deprivation assays indicated that macromeres require HpKrl for cell-autonomous specification. Transplantation of normal micromeres into a micromere-less host with morpholino revealed that macromeres are able to receive at least some micromere signals regardless of HpKrl function. From these observations, we propose that two distinct pathways of endomesoderm formation exist in macromeres, a Krl-dependent pathway and a Krl-independent pathway. The Krl-independent pathway may correspond to the Delta/Notch signaling pathway via GataE and Gcm. We suggest that Krl may be a downstream component of nuclear beta-catenin required by macromeres for formation of more vegetal tissues, not as a member of the Delta/Notch pathway, but as a parallel effector of the signaling (Krl-dependent pathway).

  9. Physician migration: donor country impact.

    Science.gov (United States)

    Aluwihare, A P R

    2005-01-01

    Physician migration from the developing to developed region of a country or the world occurs for reasons of financial, social, and job satisfaction. It is an old phenomenon that produces many disadvantages for the donor region or nation. The difficulties include inequities with the provision of health services, financial loss, loss of educated families, potential employers, and role models and diminished resources with which to conduct medical education. Staff for undergraduate and postgraduate education is depleted. The critical mass for research and development becomes difficult to achieve or maintain, and these disadvantages are not compensated for adequately by increased contacts, the introduction of new ideas, or financial inflow to the donor region or country. The political will of governments and international organizations regarding treaties about the ethics of physician recruitment is called into question by discrepancies between the text of agreements and the ground realities. Amelioration of this situation requires economic development and imaginative schemes by the donors and, ideally, ethical considerations from recipient governments. At the very least, adequate compensation should be made to the donor country for the gain obtained by the host country.

  10. Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis.

    Directory of Open Access Journals (Sweden)

    Michalis Barkoulas

    2016-09-01

    Full Text Available Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change-less than 30%-in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression.

  11. The Specific Direction Requirement for Aiding and Abetting: A Call for Revisiting Comparative Criminal Law

    DEFF Research Database (Denmark)

    Aksenova, Marina

    2015-01-01

    The ‘specific direction’ saga has been dominating the jurisprudence of the ICTY for nearly two years, and the end is yet to be seen. The story centers on the correct interpretation of liability for aiding and abetting, while, at the same time, exposing broader concerns of international criminal law...... a substantial effect on the crimes committed in the context of war - was insufficient to create individual criminal responsibility in these cases. The response to this new and heightened interpretation of aiding and abetting followed quickly, as the Šainović et al. appeal judgment rejected the novel requirement...... criminal law is essential to resolving the legal conundrum that this standard causes....

  12. A nodule-specific protein secretory pathway required for nitrogen-fixing symbiosis.

    Science.gov (United States)

    Wang, Dong; Griffitts, Joel; Starker, Colby; Fedorova, Elena; Limpens, Erik; Ivanov, Sergey; Bisseling, Ton; Long, Sharon

    2010-02-26

    The nitrogen-fixing symbiosis between Sinorhizobium meliloti and its leguminous host plant Medicago truncatula occurs in a specialized root organ called the nodule. Bacteria that are released into plant cells are surrounded by a unique plant membrane compartment termed a symbiosome. We found that in the symbiosis-defective dnf1 mutant of M. truncatula, bacteroid and symbiosome development are blocked. We identified the DNF1 gene as encoding a subunit of a signal peptidase complex that is highly expressed in nodules. By analyzing data from whole-genome expression analysis, we propose that correct symbiosome development in M. truncatula requires the orderly secretion of protein constituents through coordinated up-regulation of a nodule-specific pathway exemplified by DNF1.

  13. 49 CFR 173.427 - Transport requirements for low specific activity (LSA) Class 7 (radioactive) materials and...

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Transport requirements for low specific activity... SHIPMENTS AND PACKAGINGS Class 7 (Radioactive) Materials § 173.427 Transport requirements for low specific... must be transported in accordance with the following conditions: (1) The external dose rate may not...

  14. 33 CFR 154.1240 - Specific requirements for animal fats and vegetable oils facilities that could reasonably be...

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Specific requirements for animal... SECURITY (CONTINUED) POLLUTION FACILITIES TRANSFERRING OIL OR HAZARDOUS MATERIAL IN BULK Response Plans for Animal Fats and Vegetable Oils Facilities § 154.1240 Specific requirements for animal fats and vegetable...

  15. Regulation of IgE antibody production by serum molecules. II. Strain-specificity of the suppressive activity of serum from complete Freund's adjuvant-immune low responder mouse donors

    International Nuclear Information System (INIS)

    Katz, D.H.; Tung, A.S.

    1978-01-01

    IgE antibody production in mice of high and low IgE responder phenotypes, respectively, can be appreciably enhanced in magnitude after low-dose whole-body x irradiation. Such enhanced responses, as well as adoptive secondary IgE responses, can be markedly suppressed by passive transfer of CFA-immune serum in low responder strains, but not in high responder strains. The studies presented here demonstrate that the suppressive activity of CFA-immune serum on IgE antibody production is strain specific. This is true even in reciprocal combinations of low IgE responder SJL and C57BL/6 mice, in which it was shown that serum capable of suppressing mice of the isologous strain was ineffective in diminishing IgE antibody production in the other low responder strain. Absence of suppressive activity in CFA-immune sera obtained from H-2 haplotypes while sharing many similarities in the background genome and, conversely, effective suppressive activity of H-2 congenic donor sera when H-2-identities between donor and recipient mice existed, strongly suggested a role, at least in part, of H-2 genes in dictating the strain specificity of such suppressive activity. Additional experiments provided evidence for a possible role of macrophages in catabolism of the active molecules in CFA-immune sera. These observations, together with those presented in the preceding paper, may provide valuable insight toward successful development of appropriate manipulations that could ultimately convert high IgE responder individuals into low responders

  16. Environmental Molecular Sciences Laboratory Operations System: Version 4.0 - system requirements specification

    Energy Technology Data Exchange (ETDEWEB)

    Kashporenko, D.

    1996-07-01

    This document is intended to provide an operations standard for the Environmental Molecular Sciences Laboratory OPerations System (EMSL OPS). It is directed toward three primary audiences: (1) Environmental Molecular Sciences Laboratory (EMSL) facility and operations personnel; (2) laboratory line managers and staff; and (3) researchers, equipment operators, and laboratory users. It is also a statement of system requirements for software developers of EMSL OPS. The need for a finely tuned, superior research environment as provided by the US Department of Energy`s (DOE) Environmental Molecular Sciences Laboratory has never been greater. The abrupt end of the Cold War and the realignment of national priorities caused major US and competing overseas laboratories to reposition themselves in a highly competitive research marketplace. For a new laboratory such as the EMSL, this means coming into existence in a rapidly changing external environment. For any major laboratory, these changes create funding uncertainties and increasing global competition along with concomitant demands for higher standards of research product quality and innovation. While more laboratories are chasing fewer funding dollars, research ideas and proposals, especially for molecular-level research in the materials and biological sciences, are burgeoning. In such an economically constrained atmosphere, reduced costs, improved productivity, and strategic research project portfolio building become essential to establish and maintain any distinct competitive advantage. For EMSL, this environment and these demands require clear operational objectives, specific goals, and a well-crafted strategy. Specific goals will evolve and change with the evolution of the nature and definition of DOE`s environmental research needs. Hence, EMSL OPS is designed to facilitate migration of these changes with ease into every pertinent job function, creating a facile {open_quotes}learning organization.{close_quotes}

  17. Systems of donor transfer

    NARCIS (Netherlands)

    F.T. de Charro (Frank); J.E.M. Akveld (Hans); E. Hessing (Ellen)

    1993-01-01

    textabstractThe development of medical knowledge has resulted in a demand in society for donor organs, but the recruitment of donor organs for transplantation is difficult. This paper aims to provide some general insights into the complex interaction processes involved. A laissez-faire policy, in

  18. Dealing with Donor Anger.

    Science.gov (United States)

    McNamee, Mike

    1995-01-01

    Techniques that reduce donors' resistance to college fund-raising requests, either direct mail or telephone solicitations, are offered. These include: respecting the prospects' concerns about privacy; offering nonintrusive giving options; honesty and clarity of communication; reinforcing donor sense of control; connecting with prospects'…

  19. Structures of maltohexaose and maltoheptaose bound at the donor sites of cyclodextrin glycosyltransferase give insight into the mechanisms of transglycosylation activity and cyclodextrin size specificity

    NARCIS (Netherlands)

    Uitdehaag, JCM; van Alebeek, GJWM; Dijkhuizen, L; Dijkstra, BW; Alebeek, Gert-Jan W.M. van; Dijkstra, Bauke W.

    2000-01-01

    The enzymes from the cl-amylase family all share a similar alpha-retaining catalytic mechanism but can have different reaction and product specificities. One family member, cyclodextrin glycosyltransferase (CGTase), has an uncommonly high transglycosylation activity and is able to form

  20. Suppression of graft-versus-host reactivity by a single host-specific blood transfusion to prospective donors of hemopoietic cells

    NARCIS (Netherlands)

    Knulst, A.C.; Bril-Bazuin, C.; Savelkoul, H.F.J.; Benner, R.

    1991-01-01

    Delayed-type hypersensitivity responses against recipient's histocompatibility antigens can occur early in the course of a graft-versus-host reaction in lethally irradiated allogeneically reconstituted mice. This reactivity could be suppressed by a single host-specific blood transfusion to the

  1. Engineering Specification for Large-aperture UVO Space Telescopes Derived from Science Requirements

    Science.gov (United States)

    Stahl, H. Philip; Postman, Mark; Smith, W. Scott

    2013-01-01

    The Advance Mirror Technology Development (AMTD) project is a three year effort initiated in FY12 to mature by at least a half TRL step six critical technologies required to enable 4 to 8 meter UVOIR space telescope primary mirror assemblies for both general astrophysics and ultra-high contrast observations of exoplanets. AMTD uses a science-driven systems engineering approach. We mature technologies required to enable the highest priority science AND result in a high-performance low-cost low-risk system. To provide the science community with options, we are pursuing multiple technology paths. We have assembled an outstanding team from academia, industry, and government with extensive expertise in astrophysics and exoplanet characterization, and in the design/manufacture of monolithic and segmented space telescopes. A key accomplishment is deriving engineering specifications for advanced normal-incidence monolithic and segmented mirror systems needed to enable both general astrophysics and ultra-high contrast observations of exoplanets missions as a function of potential launch vehicles and their mass and volume constraints.

  2. Pseudouridine synthase 1: a site-specific synthase without strict sequence recognition requirements

    Science.gov (United States)

    Sibert, Bryan S.; Patton, Jeffrey R.

    2012-01-01

    Pseudouridine synthase 1 (Pus1p) is an unusual site-specific modification enzyme in that it can modify a number of positions in tRNAs and can recognize several other types of RNA. No consensus recognition sequence or structure has been identified for Pus1p. Human Pus1p was used to determine which structural or sequence elements of human tRNASer are necessary for pseudouridine (Ψ) formation at position 28 in the anticodon stem-loop (ASL). Some point mutations in the ASL stem of tRNASer had significant effects on the levels of modification and compensatory mutation, to reform the base pair, restored a wild-type level of Ψ formation. Deletion analysis showed that the tRNASer TΨC stem-loop was a determinant for modification in the ASL. A mini-substrate composed of the ASL and TΨC stem-loop exhibited significant Ψ formation at position 28 and a number of mutants were tested. Substantial base pairing in the ASL stem (3 out of 5 bp) is required, but the sequence of the TΨC loop is not required for modification. When all nucleotides in the ASL stem other than U28 were changed in a single mutant, but base pairing was retained, a near wild-type level of modification was observed. PMID:22102571

  3. Requirement for enhancer specificity in immunoglobulin heavy chain locus regulation1

    Science.gov (United States)

    Kuzin, Igor I.; Bagaeva, Ludmila; Young, Faith M.; Bottaro, Andrea

    2008-01-01

    The intronic Eμ enhancer has been implicated in immunoglobulin heavy chain (IgH) locus transcription, VDJ recombination, class switch recombination (CSR)2 and somatic hypermutation (SHM). How Eμ controls these diverse mechanisms is still largely unclear, but transcriptional enhancer activity is thought to play a central role. Here we compare the phenotype of mice lacking the Eμ element (ΔEμ) with that of mice in which Eμ was replaced with the ubiquitous SV40 transcriptional enhancer (SV40eR mutation), and show that SV40e cannot functionally complement Eμ loss in pro-B cells. Surprisingly, in fact, the SV40eR mutation yields a more profound defect than ΔEμ, with an almost complete block in μ0 germline transcription in pro-B cells. This active transcriptional suppression caused by enhancer replacement appears to be specific to the early stages of B cell development, as mature SV40eR B cells express μ0 transcripts at higher levels than ΔEμ mice, and undergo complete DNA demethylation at the IgH locus. These results indicate an unexpectedly stringent, developmentally-restricted requirement for enhancer specificity in regulating IgH function during the early phases of B cell differentiation, consistent with the view that coordination of multiple independent regulatory mechanisms and elements is essential for locus activation and VDJ recombination. PMID:18490744

  4. Recommendations for equipment requirements and specifications for digital and interventional radiology: Dosimetric aspects

    International Nuclear Information System (INIS)

    Suliman, I.I.; Zoetelief, J.

    2002-01-01

    The recognition of radiation induced injuries from fluoroscopically guided interventional procedures has resulted in the current demand for development of recommendations and standards to limit dose to both patients and staff. This paper outlines the recommendations drafted within the framework of European Project DIMOND III. The actual work involves survey and review of national and international documents as well as scientific publications in areas relevant to the digital and/or interventional radiology with an aim of developing recommendations for equipment requirements and specifications for digital and interventional radiology. A pilot study of experimental investigations in at least three hospitals will be conducted to test the requirements and the specifications, the result of which will be presented. The recommendations are expected to provide an effective means of dose reduction to both patients and staff while maintaining image quality adequate for the specific diagnosis or interventional procedure. Different components of x-ray systems that have direct impact on patient and staff doses have been considered. Where necessary a compromise between patient dose and image quality has been made. The dosimetric aspects of the recommendations propose detailed descriptions and limits to dosimetric information relevant to patient and staff doses. International recommendations on maximum patient entrance surface dose rate vary in the range from 25 to 65 mGy.min -1 for normal mode fluoroscopy. Maximum image intensifier or image receptor input dose rate around 0.1 Gy min -1 at a distance 30 cm from the image intensifier input surface has been generally recommended. Maximum fluoroscopic dose rate in air must not exceed 50 mGy.min -1 at a location depending on the configuration e.g. for undertable x-ray tube at 10 mm from the patient support on the patient side of the support. The use of pulsed fluoroscopy or low dose fluoroscopy is proposed as good options to minimize

  5. Donor policy rules and aid effectiveness

    DEFF Research Database (Denmark)

    Dalgaard, Carl-Johan Lars

    2008-01-01

    The present paper examines the macroeconomic impact of aid, by introducing endogenous aid allocations into a neoclassical growth framework. On this basis it is shown that donor policies can have important implications for the trajectory of recipients' GDP per capita. Depending on specific donor...... policy choices, aid disbursements may lead to faster transitional growth, stagnation or cyclical growth. Moreover, the analysis also suggests that donor policies may be part of the reason why foreign aid is not found to be uniformly effective in raising long-run productivity across recipients...

  6. Systems, methods and apparatus for implementation of formal specifications derived from informal requirements

    Science.gov (United States)

    Hinchey, Michael G. (Inventor); Rash, James L. (Inventor); Erickson, John D. (Inventor); Gracinin, Denis (Inventor); Rouff, Christopher A. (Inventor)

    2010-01-01

    Systems, methods and apparatus are provided through which in some embodiments an informal specification is translated without human intervention into a formal specification. In some embodiments the formal specification is a process-based specification. In some embodiments, the formal specification is translated into a high-level computer programming language which is further compiled into a set of executable computer instructions.

  7. Trophy hunting, size, rarity and willingness to pay: inter–specific analyses of trophy prices require reliable specific data

    Directory of Open Access Journals (Sweden)

    Sarasa, M.

    2013-12-01

    Full Text Available Awareness of the importance of the wildlife trade and human perception in animal conservation is growing. Recent studies carried out on a continental and world scale have analysed the associations between trophy score, rarity and prices. As a large range of ungulates are legally hunted throughout the world and numerous ungulate taxa are threatened, the relationship between rarity and trophy prices has been studied in several species. This article briefly reviews verifiable data on species and trophy prices and compares findings with data used in recent articles. The findings show that several elements of intra–specific data were inadequately addressed and that the trophy prices considered were not necessarily representative of real trophy prices. Furthermore, the body mass used for numerous taxa did not fit current knowledge of species, and several subspecies and rarity indexes that were considered disagreed with recognized subspecies or with the real conservation status of taxa. Thus, caution should be taken when considering some reported results. To improve our understanding of the associations between wildlife trade and wildlife conservation, further studies should take into account reliable specific data, such as that from government agencies, rather than publicity data.

  8. Niche-Specific Requirement for Hyphal Wall protein 1 in Virulence of Candida albicans

    Science.gov (United States)

    Staab, Janet F.; Datta, Kausik; Rhee, Peter

    2013-01-01

    Specialized Candida albicans cell surface proteins called adhesins mediate binding of the fungus to host cells. The mammalian transglutaminase (TG) substrate and adhesin, Hyphal wall protein 1 (Hwp1), is expressed on the hyphal form of C. albicans where it mediates fungal adhesion to epithelial cells. Hwp1 is also required for biofilm formation and mating thus the protein functions in both fungal-host and self-interactions. Hwp1 is required for full virulence of C. albicans in murine models of disseminated candidiasis and of esophageal candidiasis. Previous studies correlated TG activity on the surface of oral epithelial cells, produced by epithelial TG (TG1), with tight binding of C. albicans via Hwp1 to the host cell surfaces. However, the contribution of other Tgs, specifically tissue TG (TG2), to disseminated candidiasis mediated by Hwp1 was not known. A newly created hwp1 null strain in the wild type SC5314 background was as virulent as the parental strain in C57BL/6 mice, and virulence was retained in C57BL/6 mice deleted for Tgm2 (TG2). Further, the hwp1 null strains displayed modestly reduced virulence in BALB/c mice as did strain DD27-U1, an independently created hwp1Δ/Δ in CAI4 corrected for its ura3Δ defect at the URA3 locus. Hwp1 was still needed to produce wild type biofilms, and persist on murine tongues in an oral model of oropharyngeal candidiasis consistent with previous studies by us and others. Finally, lack of Hwp1 affected the translocation of C. albicans from the mouse intestine into the bloodstream of mice. Together, Hwp1 appears to have a minor role in disseminated candidiasis, independent of tissue TG, but a key function in host- and self-association to the surface of oral mucosa. PMID:24260489

  9. The rapidly evolving centromere-specific histone has stringent functional requirements in Arabidopsis thaliana.

    Science.gov (United States)

    Ravi, Maruthachalam; Kwong, Pak N; Menorca, Ron M G; Valencia, Joel T; Ramahi, Joseph S; Stewart, Jodi L; Tran, Robert K; Sundaresan, Venkatesan; Comai, Luca; Chan, Simon W-L

    2010-10-01

    Centromeres control chromosome inheritance in eukaryotes, yet their DNA structure and primary sequence are hypervariable. Most animals and plants have megabases of tandem repeats at their centromeres, unlike yeast with unique centromere sequences. Centromere function requires the centromere-specific histone CENH3 (CENP-A in human), which replaces histone H3 in centromeric nucleosomes. CENH3 evolves rapidly, particularly in its N-terminal tail domain. A portion of the CENH3 histone-fold domain, the CENP-A targeting domain (CATD), has been previously shown to confer kinetochore localization and centromere function when swapped into human H3. Furthermore, CENP-A in human cells can be functionally replaced by CENH3 from distantly related organisms including Saccharomyces cerevisiae. We have used cenh3-1 (a null mutant in Arabidopsis thaliana) to replace endogenous CENH3 with GFP-tagged variants. A H3.3 tail domain-CENH3 histone-fold domain chimera rescued viability of cenh3-1, but CENH3's lacking a tail domain were nonfunctional. In contrast to human results, H3 containing the A. thaliana CATD cannot complement cenh3-1. GFP-CENH3 from the sister species A. arenosa functionally replaces A. thaliana CENH3. GFP-CENH3 from the close relative Brassica rapa was targeted to centromeres, but did not complement cenh3-1, indicating that kinetochore localization and centromere function can be uncoupled. We conclude that CENH3 function in A. thaliana, an organism with large tandem repeat centromeres, has stringent requirements for functional complementation in mitosis.

  10. Marginal kidney donor

    Directory of Open Access Journals (Sweden)

    Ganesh Gopalakrishnan

    2007-01-01

    Full Text Available Renal transplantation is the treatment of choice for a medically eligible patient with end stage renal disease. The number of renal transplants has increased rapidly over the last two decades. However, the demand for organs has increased even more. This disparity between the availability of organs and waitlisted patients for transplants has forced many transplant centers across the world to use marginal kidneys and donors. We performed a Medline search to establish the current status of marginal kidney donors in the world. Transplant programs using marginal deceased renal grafts is well established. The focus is now on efforts to improve their results. Utilization of non-heart-beating donors is still in a plateau phase and comprises a minor percentage of deceased donations. The main concern is primary non-function of the renal graft apart from legal and ethical issues. Transplants with living donors outnumbered cadaveric transplants at many centers in the last decade. There has been an increased use of marginal living kidney donors with some acceptable medical risks. Our primary concern is the safety of the living donor. There is not enough scientific data available to quantify the risks involved for such donation. The definition of marginal living donor is still not clear and there are no uniform recommendations. The decision must be tailored to each donor who in turn should be actively involved at all levels of the decision-making process. In the current circumstances, our responsibility is very crucial in making decisions for either accepting or rejecting a marginal living donor.

  11. A symmetrical, planar SOFC design for NASA's high specific power density requirements

    Energy Technology Data Exchange (ETDEWEB)

    Cable, Thomas L. [University of Toledo, 21000 Brookpark Road, MS106-1, Cleveland, OH 44135 (United States); Sofie, Stephen W. [QSS at NASA Glenn Research Center, 21000 Brookpark Road, MS106-1, Cleveland, OH 44135 (United States)

    2007-11-22

    Solid oxide fuel cell (SOFC) systems for aircraft applications require an order of magnitude increase in specific power density (1.0 kW kg{sup -1}) and long life. While significant research is underway to develop anode supported cells which operate at temperatures in the range of 650-800 C, concerns about Cr-contamination from the metal interconnect may drive the operating temperature down further, to 750 C and lower. Higher temperatures, 850-1000 C, are more favorable in order to achieve specific power densities of 1.0 kW kg{sup -1}. Since metal interconnects are not practical at these high temperatures and can account for up to 75% of the weight of the stack, NASA is pursuing a design that uses a thin, LaCrO{sub 3}-based ceramic interconnect that incorporates gas channels into the electrodes. The bi-electrode supported cell (BSC) uses porous YSZ scaffolds, on either side of a 10-20 {mu}m electrolyte. The porous support regions are fabricated with graded porosity using the freeze-tape casting process which can be tailored for fuel and air flow. Removing gas channels from the interconnect simplifies the stack design and allows the ceramic interconnect to be kept thin, on the order of 50-100 {mu}m. The YSZ electrode scaffolds are infiltrated with active electrode materials following the high-temperature sintering step. The NASA-BSC is symmetrical and CTE matched, providing balanced stresses and favorable mechanical properties for vibration and thermal cycling. (author)

  12. Pax3 function is required specifically for inner ear structures with melanogenic fates.

    Science.gov (United States)

    Kim, Hongkyung; Ankamreddy, Harinarayana; Lee, Dong Jin; Kong, Kyoung-Ah; Ko, Hyuk Wan; Kim, Myoung Hee; Bok, Jinwoong

    2014-03-14

    Pax3 mutations result in malformed inner ears in Splotch mutant mice and hearing loss in humans with Waardenburg's syndrome type I. In the inner ear, Pax3 is thought to be involved mainly in the development of neural crest. However, recent studies have shown that Pax3-expressing cells contribute extensively to multiple inner ear structures, some of which were considered to be derived from the otic epithelium. To examine the specific functions of Pax3 during inner ear development, fate mapping of Pax3 lineage was performed in the presence or absence of functional Pax3 proteins using Pax3(Cre) knock-in mice bred to Rosa26 reporter (R26R) line. β-gal-positive cells were widely distributed in Pax3(Cre/+); R26R inner ears at embryonic day (E) 15.5, including the endolymphatic duct, common crus, cristae, maculae, cochleovestibular ganglion, and stria vascularis. In the absence of Pax3 in Pax3(Cre/Cre); R26R inner ears, β-gal-positive cells disappeared from regions with melanocytes such as the stria vascularis of the cochlea and dark cells in the vestibule. Consistently, the expression of Dct, a melanoblast marker, was also absent in the mutant inner ears. However, when examined at E11.5, β-gal positive cells were present in Pax3(Cre/Cre) mutant otocysts, whereas Dct expression was absent, suggesting that Pax3 lineage with a melanogenic fate migrated to the inner ear, yet failed to differentiate and survive without Pax3 function. Gross inner ear morphology was generally normal in Pax3(Cre/Cre) mutants, unless neural tube defects extended to the cranial region. Taken together, these results suggest that despite the extensive contribution of Pax3-expressing cells to multiple inner ear tissues, Pax3 function is required specifically for inner ear components with melanogenic fates. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Adenosine-uridine-rich element is one of the required cis-elements for epimastigote form stage-specific gene expression of the congolense epimastigote specific protein.

    Science.gov (United States)

    Suganuma, Keisuke; Mochabo, Kennedy Miyoro; Hakimi, Hassan; Yamasaki, Shino; Yamagishi, Junya; Asada, Masahito; Kawazu, Shin-Ichiro; Inoue, Noboru

    2013-09-01

    It is known that gene expression in kinetoplastida is regulated post-transcriptionally. Several previous studies have shown that stage-specific gene expression in trypanosomes is regulated by cis-elements located in the 3' untranslated region (UTR) of each mRNA and also by RNA binding proteins. Our previous study revealed that gene expression of congolense epimastigote specific protein (cesp) was regulated by cis-elements located in the 3'UTR. In the present study, we identified the adenosine and uridine rich region in the cesp 3'UTR. Using transgenic trypanosome cell lines with different egfp expression cassettes, we showed that this adenosine and uridine rich region is one of the regulatory elements for epimastigote form (EMF) stage-specific gene expression via the regulatory cis-element of the eukaryotic AU rich element (ARE). Therefore this required element within the cesp 3'UTR was designated as T. congolense ARE. This required cis-element might selectively stabilize mRNA in the EMF stage and destabilize mRNA in other stages. By RNA electro mobility shift assay, unknown stage-specific RNA binding proteins (RBPs) whose sequences specifically interacted with the required cis-element were found. These results indicate that EMF stage specific cis-element and RBP complexes might specifically stabilize cesp mRNA in EMF. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Propagation of Polycomb-repressed chromatin requires sequence-specific recruitment to DNA.

    Science.gov (United States)

    Laprell, Friederike; Finkl, Katja; Müller, Jürg

    2017-04-07

    Epigenetic inheritance models posit that during Polycomb repression, Polycomb repressive complex 2 (PRC2) propagates histone H3 lysine 27 trimethylation (H3K27me3) independently of DNA sequence. We show that insertion of Polycomb response element (PRE) DNA into the Drosophila genome creates extended domains of H3K27me3-modified nucleosomes in the flanking chromatin and causes repression of a linked reporter gene. After excision of PRE DNA, H3K27me3 nucleosomes become diluted with each round of DNA replication, and reporter gene repression is lost. After excision in replication-stalled cells, H3K27me3 levels stay high and repression persists. H3K27me3-marked nucleosomes therefore provide a memory of repression that is transmitted in a sequence-independent manner to daughter strand DNA during replication. In contrast, propagation of H3K27 trimethylation to newly incorporated nucleosomes requires sequence-specific targeting of PRC2 to PRE DNA. Copyright © 2017, American Association for the Advancement of Science.

  15. SB certification handout material requirements, test methods, responsibilities, and minimum classification levels for mixture-based specification for flexible base.

    Science.gov (United States)

    2012-10-01

    A handout with tables representing the material requirements, test methods, responsibilities, and minimum classification levels mixture-based specification for flexible base and details on aggregate and test methods employed, along with agency and co...

  16. Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

    Science.gov (United States)

    Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

    2012-01-01

    Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

  17. [Rare blood donors with irregular antibodies].

    Science.gov (United States)

    Milanović, Mirjana Krga; Bujandrić, Nevenka; Knezević, Natasa Milosavljević

    2013-01-01

    Blood groups are inherited biological characteristics that do not change throughout life in healthy people. Blood groups represent antigens found on the surface of red blood cells. Kell blood group system consists of 31 antigens. Kell antigen (K) is present in 0.2% of the population (the rare blood group). Cellano antigen is present in more than 99% (the high-frequency antigen). These antigens have a distinct ability to cause an immune response in the people after blood transfusion or pregnancy who, otherwise, did not have them before. This paper presents a blood donor with a rare blood group, who was found to have an irregular antibody against red blood cells by indirect antiglobulin test. Further testing determined the specificity of antibody to be anti-Cellano. The detected antibody was found in high titers (1024) with erythrocyte phenotype Kell-Cellano+. The blood donor was found to have a rare blood group KellKell. This donor was excluded from further blood donation. It is difficult to find compatible blood for a person who has developed an antibody to the high-frequency antigen. The donor's family members were tested and Cellano antigen was detected in her husband and child. A potential blood donor was not found among the family members. There was only one blood donor in the Register of blood donors who was compatible in the ABO and Kell blood group system. For the successful management of blood transfusion it is necessary to establish a unified national register of donors of rare blood groups and cooperate with the International Blood Group Reference Laboratory in Bristol with the database that registers donors of rare blood groups from around the world.

  18. Feasibility of liver graft procurement with donor gallbladder preservation in living donor liver transplantation.

    Science.gov (United States)

    Dong, Jia-Hong; Ye, Sheng; Duan, Wei-Dong; Ji, Wen-Bing; Liang, Yu-Rong

    2015-10-01

    Cholecystectomy is routinely performed at most transplant centers during living donor liver transplantation (LDLT). This study was performed to evaluate the feasibility of liver graft procurement with donor gallbladder preservation in LDLT. Eighty-nine LDLTs (from June 2006 to Dec 2012) were retrospectively analyzed at our hospital. The surgical approach for liver graft procurement with donor gallbladder preservation was assessed, and the anatomy of the cystic artery, the morphology and contractibility of the preserved gallbladder, postoperative symptoms, and vascular and biliary complications were compared among donors with or without gallbladder preservation. Twenty-eight donors (15 right and 13 left-liver grafts) successfully underwent liver graft procurement with gallbladder preservation. Among the 15 right lobectomy donors, for 12 cases (80.0 %) the cystic artery originated from right hepatic artery. From the left hepatic artery and proper hepatic artery accounted for 6.7 % (1/15), respectively. Postoperative symptoms among these 28 donors were slight, although donors with cholecystectomy often complained of fatty food aversion, dyspepsia, and diarrhea during an average follow-up of 58.6 (44-78) months. The morphology and contractibility of the preserved gallbladders were comparable with normal status; the rate of contraction was 53.8 and 76.7 %, respectively, 30 and 60 min after ingestion of a fatty meal. Biliary and vascular complications among donors and recipients, irrespective of gallbladder preservation, were not significantly different. These data suggest that for donors compliant with anatomical requirements, liver graft procurement with gallbladder preservation for the donor is feasible and safe. The preserved gallbladder was assessed as functioning well and postoperative symptoms as a result of cholecystectomy were significantly reduced during long-term follow-up.

  19. Gain of local structure in an amphipathic peptide does not require a specific tertiary framework.

    Science.gov (United States)

    Roman, Ernesto A; Rosi, Pablo; González Lebrero, Mariano C; Wuilloud, Rodolfo; González Flecha, F Luis; Delfino, José M; Santos, Javier

    2010-10-01

    In this work, we studied how an amphipathic peptide of the surface of the globular protein thioredoxin, TRX94-108, acquires a native-like structure when it becomes involved in an apolar interaction network. We designed peptide variants where the tendency to form alpha-helical conformation is modulated by replacing each of the leucine amino acid residues by an alanine. The induction of structure caused by sodium dodecyl sulfate (SDS) binding was studied by capillary zone electrophoresis, circular dichroism, DOSY-NMR, and molecular dynamics simulations (MDS). In addition, we analyzed the strength of the interaction between a C18 RP-HPLC matrix and the peptides. The results presented here reveal that (a) critical elements in the sequence of the wild-type peptide stabilize a SDS/peptide supramolecular cluster; (b) the hydrophobic nature of the interaction between SDS molecules and the peptide constrains the ensemble of conformations; (c) nonspecific apolar surfaces are sufficient to stabilize peptide secondary structure. Remarkably, MDS shed light on a contact network formed by a limited number of SDS molecules that serves as a structural scaffold preserving the helical conformation of this module. This mechanism might prevail when a peptide with low helical propensity is involved in structure consolidation. We suggest that folding of peptides sharing this feature does not require a preformed tightly-packed protein core. Thus, the formation of specific tertiary interactions would be the consequence of peptide folding and not its cause. In this scenario, folding might be thought of as a process that includes unspecific rounds of structure stabilization guiding the protein to the native state. 2010 Wiley-Liss, Inc.

  20. 49 CFR 179.201 - Individual specification requirements applicable to non-pressure tank car tanks.

    Science.gov (United States)

    2010-10-01

    ... to non-pressure tank car tanks. 179.201 Section 179.201 Transportation Other Regulations Relating to... MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes... car tanks. ...

  1. Requirements Analysis Study for Master Pump Shutdown System Project Development Specification [SEC 1 and 2

    International Nuclear Information System (INIS)

    BEVINS, R.R.

    2000-01-01

    This document has been updated during the definitive design portion of the first phase of the W-314 Project to capture additional software requirements and is planned to be updated during the second phase of the W-314 Project to cover the second phase of the Project's scope. The objective is to provide requirement traceability by recording the analysis/basis for the functional descriptions of the master pump shutdown system. This document identifies the sources of the requirements and/or how these were derived. Each requirement is validated either by quoting the source or an analysis process involving the required functionality, performance characteristics, operations input or engineering judgment

  2. Requirements Analysis Study for Master Pump Shutdown System Project Development Specification [SEC 1 and 2

    Energy Technology Data Exchange (ETDEWEB)

    BEVINS, R.R.

    2000-03-24

    This document has been updated during the definitive design portion of the first phase of the W-314 Project to capture additional software requirements and is planned to be updated during the second phase of the W-314 Project to cover the second phase of the Project's scope. The objective is to provide requirement traceability by recording the analysis/basis for the functional descriptions of the master pump shutdown system. This document identifies the sources of the requirements and/or how these were derived. Each requirement is validated either by quoting the source or an analysis process involving the required functionality, performance characteristics, operations input or engineering judgment.

  3. Requirements Analysis Study for Master Pump Shutdown System Project Development Specification

    International Nuclear Information System (INIS)

    BEVINS, R.R.

    2000-01-01

    This study is a requirements document that presents analysis for the functional description for the master pump shutdown system. This document identifies the sources of the requirements and/or how these were derived. Each requirement is validated either by quoting the source or an analysis process involving the required functionality, performance characteristics, operations input or engineering judgment. The requirements in this study apply to the first phase of the W314 Project. This document has been updated during the definitive design portion of the first phase of the W314 Project to capture additional software requirements and is planned to be updated during the second phase of the W314 Project to cover the second phase of the project's scope

  4. Requirements Analysis Study for Master Pump Shutdown System Project Development Specification [SEC 1 and 2

    Energy Technology Data Exchange (ETDEWEB)

    BEVINS, R.R.

    2000-09-20

    This study is a requirements document that presents analysis for the functional description for the master pump shutdown system. This document identifies the sources of the requirements and/or how these were derived. Each requirement is validated either by quoting the source or an analysis process involving the required functionality, performance characteristics, operations input or engineering judgment. The requirements in this study apply to the first phase of the W314 Project. This document has been updated during the definitive design portion of the first phase of the W314 Project to capture additional software requirements and is planned to be updated during the second phase of the W314 Project to cover the second phase of the project's scope.

  5. Deceased Donor Organ Transplantation Performed in the United States for Non- Citizens and Non-Residents.

    Science.gov (United States)

    Delmonico, Francis L; Gunderson, Susan; Iyer, Kishore R; Danovitch, Gabriel M; Pruett, Timothy L; Reyes, Jorge D; Ascher, Nancy L

    2018-01-11

    Since 2012, the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) has required transplant centers to record the citizenship and residency status of patients undergoing transplantation in the United States. This policy replaced the 5% threshold of the non-US citizen/non-U.S. residents (NC/NR) undergoing organ transplantation that could result in an audit of transplant center activity.We analyzed the frequency of NC/NR deceased donor organ transplants and wait list registrations at all US transplant centers using data provided by UNOS for that purpose to the UNOS Ad Hoc International Relations Committee. During the period of 2013 - 2016, 1,176 deceased donor transplants (of all organs) were performed in NC/NR candidates (1.2 % of the total number of transplants). There were 5 kidney and 7 liver transplant centers that performed > 5% of the deceased donor kidney and deceased donor liver transplants respectively in NC/NR during the years 2014-2016 with a total of 147 deceased donor kidney transplants and 120 deceased donor liver transplants in NC/NR.This report was prepared to fulfill the transparency policy of UNOS to assure a public trust in the distribution of organs. When viewed with a public awareness of deceased donor organ shortages, it suggests the need for a more comprehensive understanding of current NC/NR activity in the US. Patterns of organ specific NC/NR registrations and transplantations at high-volume centers should prompt a review of transplant center practices to determine whether the deceased donor and center resources may be compromised for their US patients.

  6. Mechanism of altruism approach to blood donor recruitment and retention: a review and future directions.

    Science.gov (United States)

    Ferguson, E

    2015-08-01

    Why do people donate blood? Altruism is the common answer. However, altruism is a complex construct and to answer this question requires a systematic analysis of the insights from the biology, economics and psychology of altruism. I term this the mechanism of altruism (MOA) approach and apply it here for understanding blood donor motivation. The answer also has enormous implications for the type of interventions we choose to adopt as a society. A MOA approach so far shows that blood donors are a mixture of (i) warm-glow givers (donation is emotionally rewarding) and (ii) reluctant altruists (cooperate rather than defect when free-riding is high). Donors also show 'saintly sinning' with the extra 'moral currency' form blood donation allowing them to be less generous in other contexts. The MOA approach suggests why financial incentives, in terms of gifts/lottery tickets, are effective and suggests a number of novel interventions for donor recruitment: 'voluntary reciprocal altruism' and 'charitable incentivisation'. The MOA approach also highlights the need for an intervention developed specifically for recipients to allow them to show their gratitude to donors and for society to celebrate blood donation. It is suggests a 'Monument to Blood Donors' will achieve this. The approach suggests a number of novel research questions into (i) donor self-selection effects, (ii) conditional cooperation and (iii) construct overlap with Theory of Planned Behaviour (e.g. affective attitudes and warm-glow). The MOA offers a powerful way to understand blood donor motivations around altruism and develop theoretically driven interventions. © 2015 British Blood Transfusion Society.

  7. Some Specific CASL Requirements for Advanced Multiphase Flow Simulation of Light Water Reactors

    Energy Technology Data Exchange (ETDEWEB)

    R. A. Berry

    2010-11-01

    Because of the diversity of physical phenomena occuring in boiling, flashing, and bubble collapse, and of the length and time scales of LWR systems, it is imperative that the models have the following features: • Both vapor and liquid phases (and noncondensible phases, if present) must be treated as compressible. • Models must be mathematically and numerically well-posed. • The models methodology must be multi-scale. A fundamental derivation of the multiphase governing equation system, that should be used as a basis for advanced multiphase modeling in LWR coolant systems, is given in the Appendix using the ensemble averaging method. The remainder of this work focuses specifically on the compressible, well-posed, and multi-scale requirements of advanced simulation methods for these LWR coolant systems, because without these are the most fundamental aspects, without which widespread advancement cannot be claimed. Because of the expense of developing multiple special-purpose codes and the inherent inability to couple information from the multiple, separate length- and time-scales, efforts within CASL should be focused toward development of a multi-scale approaches to solve those multiphase flow problems relevant to LWR design and safety analysis. Efforts should be aimed at developing well-designed unified physical/mathematical and high-resolution numerical models for compressible, all-speed multiphase flows spanning: (1) Well-posed general mixture level (true multiphase) models for fast transient situations and safety analysis, (2) DNS (Direct Numerical Simulation)-like models to resolve interface level phenmena like flashing and boiling flows, and critical heat flux determination (necessarily including conjugate heat transfer), and (3) Multi-scale methods to resolve both (1) and (2) automatically, depending upon specified mesh resolution, and to couple different flow models (single-phase, multiphase with several velocities and pressures, multiphase with single

  8. Donor milk: current perspectives

    Directory of Open Access Journals (Sweden)

    Giuliani F

    2014-07-01

    Full Text Available Francesca Giuliani,1 Ilaria Rovelli,1 Chiara Peila,1 Stefania Alfonsina Liguori,2 Enrico Bertino,1 Alessandra Coscia1 1SCDU Neonatologia, Dipartimento di Scienze Pediatriche e dell'Adolescenza, Università degli Studi di Torino, Torino, Italy; 2SC Neonatologia, Ospedale Maria Vittoria, Torino, Italy Abstract: Mother's own milk is widely recognized as the optimal feeding for term infants, but increasing evidence exists of its benefits also for sick and preterm infants in neonatal intensive care units. However, the nutritional needs for appropriate growth and neurodevelopmental outcomes of such a particular population of infants should be attentively evaluated, considering also the indication to an appropriate fortification of human milk. The target is to achieve growth potential for preterm newborns while ensuring good metabolic outcomes and normal neurological development. When mother's milk is unavailable or in short supply, donor human milk (DHM represents the second best choice and, although somewhat modified by the Holder pasteurization process, it preserves many benefits when compared to formula, as documented by more and more reports, randomized controlled trials, and meta-analyses published in the past few years. Evidence exists of the protection exerted by DHM from necrotizing enterocolitis, while further studies are required to look at possible beneficial effects regarding infections, bronchopulmonary dysplasia, long-term cardiovascular risk factors, feeding tolerance, neurological outcome, and allergy. Finally, the concern that the use of DHM might decrease preterm infant breastfeeding is being raised. Conversely, publications exist showing that the use of DHM in the neonatal unit increases breastfeeding rates at discharge for infants of very low birth weight. Keywords: human milk, preterm infant feeding, milk bank, breast milk, mother's own milk, pasteurized human milk, fortification

  9. Anonymous living liver donation: donor profiles and outcomes.

    Science.gov (United States)

    Reichman, T W; Fox, A; Adcock, L; Wright, L; Abbey, S E; Levy, G; Grant, D R

    2010-09-01

    There are no published series of the assessment process, profiles and outcomes of anonymous, directed or nondirected live liver donation. The outcomes of 29 consecutive potential anonymous liver donors at our center were assessed. We used our standard live liver assessment process, augmented with the following additional acceptance criteria: a logical rationale for donation, a history of social altruism, strong social supports and a willingness to maintain confidentiality of patient information. Seventeen potential donors were rejected and 12 donors were ultimately accepted (six male, six female). All donors were strongly motivated by a desire and sense of responsibility to help others. Four donations were directed toward recipients who undertook media appeals. The donor operations included five left lateral segmentectomies and seven right hepatectomies. The overall donor morbidity was 40% with one patient having a transient Clavien level 3 complication (a pneumothorax). All donors are currently well. None expressed regret about their decision to donate, and all volunteered the opinion that donation had improved their lives. The standard live liver donor assessment process plus our additional requirements appears to provide a robust assessment process for the selection of anonymous live liver donors. Acceptance of anonymous donors enlarges the donor liver pool. © 2010 The Authors Journal compilation © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

  10. 10 CFR 72.75 - Reporting requirements for specific events and conditions.

    Science.gov (United States)

    2010-01-01

    ... confinement system during use. (3) Any event requiring the transport of a radioactively contaminated person to... other worsening conditions, including those that require the declaration of any of the Emergency Classes... particular event: (i) The ISFSI or MRS operating conditions before the event; (ii) The status of structures...

  11. 46 CFR 164.009-3 - Noncombustible materials not requiring specific approval.

    Science.gov (United States)

    2010-10-01

    ...) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL MATERIALS Noncombustible Materials for... noncombustible materials may be used in merchant vessel construction though not specifically approved under this subpart: (a) Sheet glass, block glass, clay, ceramics, and uncoated fibers. (b) All metals, except...

  12. 49 CFR 179.101 - Individual specification requirements applicable to pressure tank car tanks.

    Science.gov (United States)

    2010-10-01

    ... to pressure tank car tanks. 179.101 Section 179.101 Transportation Other Regulations Relating to... MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Pressure Tank Car Tanks (Classes DOT... tank car tanks. Editorial Note: At 66 FR 45186, Aug. 28, 2001, an amendment published amending a table...

  13. Circuit architecture derivation starting from a formal requirements specification considering a DDS as example

    Science.gov (United States)

    Garbe, H.; Richter, R.; Jentschel, H.-J.

    2004-05-01

    Based on a formal specification of a direct digital synthesis (DDS) and assuming the availability of a set of possible circuit architectures we derive a customised system configuration. e calculate the design parameters that can be used for the specification to synthesise the circuit components. We show how the derived parameters and the selected IC technology influence the complexity of the circuit implementation.

  14. 49 CFR 180.407 - Requirements for test and inspection of specification cargo tanks.

    Science.gov (United States)

    2010-10-01

    ... leak into the heating system, and (ii) The specification plate heating system information is changed to... the material of construction indicated on the UIA form with no corrosion allowance. (10) For 400....413; or (ii) Be removed from hazardous materials service and the specification plate removed...

  15. 49 CFR 178.320 - General requirements applicable to all DOT specification cargo tank motor vehicles.

    Science.gov (United States)

    2010-10-01

    ... MATERIALS REGULATIONS SPECIFICATIONS FOR PACKAGINGS Specifications for Containers for Motor Vehicle... lading retention or containment function and provides no structural support to the cargo tank. Baffle.... Cargo tank means a bulk packaging that: (1) Is a tank intended primarily for the carriage of liquids...

  16. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets.

    Science.gov (United States)

    Chang, Ying-Jun; Zhao, Xiang-Yu; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Han, Wei; Chen, Huan; Wang, Feng-Rong; Mo, Xiao-Dong; Zhang, Yuan-Yuan; Huo, Ming-Rui; Zhao, Xiao-Su; Y, Kong; Liu, Kai-Yan; Huang, Xiao-Jun

    2015-07-10

    Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). A total of 342 patients (99.1%) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8-28 days) and 18 days (range, 6-330 days), respectively. The cumulative incidence of primary GF was 6.4 ± 1.3% and included GR (0.9 ± 0.5%) and PGF (5.5 ± .2%). Of the 345 cases tested, 39 (11.3%) were DSA positive. Multivariate models showed that DSAs (MFI ≥ 10,000) were correlated to primary GR (P < 0.001) and that DSAs (MFI ≥ 2000) were strongly associated with primary PGF (P = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 (n = 316), group B included cases with a 2000 ≤ MFI < 10,000 (n = 19), and group C included cases with a MFI ≥ 10,000 (n = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60%, for groups A, B, and C, respectively, P < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3%, for groups A, B, and C, respectively, P = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4%, for groups A, B, and C

  17. Rbfox proteins regulate tissue-specific alternative splicing of Mef2D required for muscle differentiation.

    Science.gov (United States)

    Runfola, Valeria; Sebastian, Soji; Dilworth, F Jeffrey; Gabellini, Davide

    2015-02-15

    Among the Mef2 family of transcription factors, Mef2D is unique in that it undergoes tissue-specific splicing to generate an isoform that is essential for muscle differentiation. However, the mechanisms mediating this muscle-specific processing of Mef2D remain unknown. Using bioinformatics, we identified Rbfox proteins as putative modulators of Mef2D muscle-specific splicing. Accordingly, we found direct and specific Rbfox1 and Rbfox2 binding to Mef2D pre-mRNA in vivo. Gain- and loss-of-function experiments demonstrated that Rbfox1 and Rbfox2 cooperate in promoting Mef2D splicing and subsequent myogenesis. Thus, our findings reveal a new role for Rbfox proteins in regulating myogenesis through activation of essential muscle-specific splicing events. © 2015. Published by The Company of Biologists Ltd.

  18. Experimental development based on mapping rule between requirements analysis model and web framework specific design model.

    Science.gov (United States)

    Okuda, Hirotaka; Ogata, Shinpei; Matsuura, Saeko

    2013-12-01

    Model Driven Development is a promising approach to develop high quality software systems. We have proposed a method of model-driven requirements analysis using Unified Modeling Language (UML). The main feature of our method is to automatically generate a Web user interface prototype from UML requirements analysis model so that we can confirm validity of input/output data for each page and page transition on the system by directly operating the prototype. We proposes a mapping rule in which design information independent of each web application framework implementation is defined based on the requirements analysis model, so as to improve the traceability to the final product from the valid requirements analysis model. This paper discusses the result of applying our method to the development of a Group Work Support System that is currently running in our department.

  19. Safety of Nuclear Power Plants: Design. Specific Safety Requirements (Chinese Edition)

    International Nuclear Information System (INIS)

    2016-01-01

    This publication establishes requirements applicable to the design of nuclear power plants and elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. It will be useful for organizations involved in design, manufacture, construction, modification, maintenance, operation and decommissioning of nuclear power plants, as well as for regulatory bodies. A review of Safety Requirements publications was commenced in 2011 following the accident in the Fukushima Daiichi nuclear power plant in Japan. The review revealed no significant areas of weakness and resulted in just a small set of amendments to strengthen the requirements and facilitate their implementation, which are contained in the present publication.

  20. Safety of Nuclear Power Plants: Design. Specific Safety Requirements (Arabic Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    This publication establishes requirements applicable to the design of nuclear power plants and elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. It will be useful for organizations involved in design, manufacture, construction, modification, maintenance, operation and decommissioning of nuclear power plants, as well as for regulatory bodies. A review of Safety Requirements publications was commenced in 2011 following the accident in the Fukushima Daiichi nuclear power plant in Japan. The review revealed no significant areas of weakness and resulted in just a small set of amendments to strengthen the requirements and facilitate their implementation, which are contained in the present publication.

  1. Waste Receiving and Processing Facility Module 1 Data Management System software requirements specification

    International Nuclear Information System (INIS)

    Rosnick, C.K.

    1996-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-0126). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  2. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    International Nuclear Information System (INIS)

    Brann, E.C. II.

    1994-01-01

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal

  3. An Optimization-Based Approach to Determine System Requirements Under Multiple-Domain Specific Uncertainties

    Science.gov (United States)

    2016-04-30

    prior efforts to develop a quantitative approach that identifies optimum design requirements of new, yet-to-be-designed systems that, when serving...requirements may have on fleet-level metrics of interest (e.g., choice of an aircraft may affect fleet-level productivity and fuel burn —quantities...between the same bases. Figure 1a shows the fluctuation in the number of pallets transported daily between a representative base pair in the Global Air

  4. Waste Receiving and Processing Facility Module 1 Data Management System Software Requirements Specification

    Energy Technology Data Exchange (ETDEWEB)

    Brann, E.C. II

    1994-09-09

    This document provides the software requirements for Waste Receiving and Processing (WRAP) Module 1 Data Management System (DMS). The DMS is one of the plant computer systems for the new WRAP 1 facility (Project W-026). The DMS will collect, store and report data required to certify the low level waste (LLW) and transuranic (TRU) waste items processed at WRAP 1 as acceptable for shipment, storage, or disposal.

  5. The Specific Direction Requirement for Aiding and Abetting: A Call for Revisiting Comparative Criminal Law

    DEFF Research Database (Denmark)

    Aksenova, Marina

    2015-01-01

    . After this judgment, the prosecution filed a motion to reconsider the acquittal in Perišić, which the Appeals Chamber denied. In sum, these developments diluted and mischaracterized the standard of aiding and abetting. Accordingly, this article has two purposes. First, it demonstrates......The ‘specific direction’ saga has been dominating the jurisprudence of the ICTY for nearly two years, and the end is yet to be seen. The story centers on the correct interpretation of liability for aiding and abetting, while, at the same time, exposing broader concerns of international criminal law....... The saga started with unexpected acquittals of Perišić, Stanišić, and Simatović due to a lack of specific direction in their aid and assistance towards specific offences. More specifically, the tribunal found that the traditional test - the provision of aid with the awareness that it would have...

  6. Mechanistic Resolution Required to Mediate Operant Learned Behaviors: Insights from Neuronal Ensemble-Specific Inactivation

    Directory of Open Access Journals (Sweden)

    Bruce T. Hope

    2017-04-01

    Full Text Available Many learned behaviors are directed by complex sets of highly specific stimuli or cues. The neural mechanisms mediating learned associations in these behaviors must be capable of storing complex cue information and distinguishing among different learned associations—we call this general concept “mechanistic resolution”. For many years, our understanding of the circuitry of these learned behaviors has been based primarily on inactivation of specific cell types or whole brain areas regardless of which neurons were activated during the cue-specific behaviors. However, activation of all cells or specific cell types in a brain area do not have enough mechanistic resolution to encode or distinguish high-resolution learned associations in these behaviors. Instead, these learned associations are likely encoded within specific patterns of sparsely distributed neurons called neuronal ensembles that are selectively activated by the cues. This review article focuses on studies of neuronal ensembles in operant learned responding to obtain food or drug rewards. These studies suggest that the circuitry of operant learned behaviors may need to be re-examined using ensemble-specific manipulations that have the requisite level of mechanistic resolution.

  7. Laparoscopic nephrectomy in live donor

    Directory of Open Access Journals (Sweden)

    Mitre Anuar I.

    2004-01-01

    Full Text Available OBJECTIVE: To present the initial experience of videolaparoscopic nephrectomy in live renal donor. MATERIALS AND METHODS: In the period from April 2000 to August 2003, 50 left nephrectomies in live donor were performed by videolaparoscopy for transplantation. Twenty-eight patients were male (56% and 22 female (44%. Mean age was 37.2 years, and the mean body mass index (BMI was 27.1 kg/m². RESULTS: Mean surgical time was 179.5 minutes, and warm ischemia time of the graft was 3.79 minutes. The mean estimated bleeding was 141 mL. There was no need of blood transfusion or conversion to open surgery. In 42 cases (84%, the vascular portion of the graft was considered good by the recipient's surgical team and in all cases, the ureter was considered of proper size, though in one of them (2% its vascularization was considered improper. The transplanted kidneys produced urine still in the surgical room in 46 of the 50 transplantations considered. In only 2 cases opioid was required for analgesia. In average, 3.1 doses of dipyrone were used for each patient during hospital stay, and hospital discharge occurred, in average, after 3.2 days post-operatively. Two patients required re-operations and one of them evolved to death. CONCLUSIONS: The laparoscopic nephrectomy in live donor for renal transplantation is an alternative to conventional open surgery. In relation to the graft, no alteration, either anatomic or functional, was detected. Though there is already a large documentation in the international literature regarding this procedure, in our setting a prospective randomized study with the usual surgical study is still necessary in order to prove the advantages and disadvantages of the method.

  8. Safety of Nuclear Power Plants: Commissioning and Operation. Specific Safety Requirements (Arabic Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    This publication is a revision of IAEA Safety Standards Series No. NS-R-2, Safety of Nuclear Power Plants: Operation, and has been extended to cover the commissioning stage. It describes the requirements to be met to ensure the safe commissioning, operation, and transition from operation to decommissioning of nuclear power plants. Over recent years there have been developments in areas such as long term operation of nuclear power plants, plant ageing, periodic safety review, probabilistic safety analysis review and risk informed decision making processes. It became necessary to revise the IAEA’s Safety Requirements in these areas and to correct and/or improve the publication on the basis of feedback from its application by both the IAEA and its Member States. In addition, the requirements are governed by, and must apply, the safety objective and safety principles that are established in the IAEA Safety Standards Series No. SF-1, Fundamental Safety Principles. A review of Safety Requirements publications, initiated in 2011 following the accident in the Fukushima Daiichi nuclear power plant in Japan, revealed no significant areas of weakness but resulted in a small set of amendments to strengthen the requirements and facilitate their implementation. These are contained in the present publication.

  9. A Formal Analysis of the Shlaer-Mellor method: towards a toolkit for formal and informal requirements specification techniques

    OpenAIRE

    Wieringa, Roelf J.; Saake, G.

    1996-01-01

    In this paper, we define a number of tools that we think belong to the core of any toolkit for requirements engineers. The tools are conceptual and hence, they need precise definitions that lay down as exactly as possible what their meaning and possible use is. We argue that this definition can best be achieved by a formal specification of the tool. This means that for each semi-formal requirements engineering tool we should provide a formal specification that precisely specifies its meaning....

  10. Assessment of donor heart viability during ex vivo heart perfusion.

    Science.gov (United States)

    White, Christopher W; Ambrose, Emma; Müller, Alison; Li, Yun; Le, Hoa; Hiebert, Brett; Arora, Rakesh; Lee, Trevor W; Dixon, Ian; Tian, Ganghong; Nagendran, Jayan; Hryshko, Larry; Freed, Darren

    2015-10-01

    Ex vivo heart perfusion (EVHP) may facilitate resuscitation of discarded donor hearts and expand the donor pool; however, a reliable means of demonstrating organ viability prior to transplantation is required. Therefore, we sought to identify metabolic and functional parameters that predict myocardial performance during EVHP. To evaluate the parameters over a broad spectrum of organ function, we obtained hearts from 9 normal pigs and 37 donation after circulatory death pigs and perfused them ex vivo. Functional parameters obtained from a left ventricular conductance catheter, oxygen consumption, coronary vascular resistance, and lactate concentration were measured, and linear regression analyses were performed to identify which parameters best correlated with myocardial performance (cardiac index: mL·min(-1)·g(-1)). Functional parameters exhibited excellent correlation with myocardial performance and demonstrated high sensitivity and specificity for identifying hearts at risk of poor post-transplant function (ejection fraction: R(2) = 0.80, sensitivity = 1.00, specificity = 0.85; stroke work: R(2) = 0.76, sensitivity = 1.00, specificity = 0.77; minimum dP/dt: R(2) = 0.74, sensitivity = 1.00, specificity = 0.54; tau: R(2) = 0.51, sensitivity = 1.00, specificity = 0.92), whereas metabolic parameters were limited in their ability to predict myocardial performance (oxygen consumption: R(2) = 0.28; coronary vascular resistance: R(2) = 0.20; lactate concentration: R(2) = 0.02). We concluded that evaluation of functional parameters provides the best assessment of myocardial performance during EVHP, which highlights the need for an EVHP device capable of assessing the donor heart in a physiologic working mode.

  11. TECHNICAL BASIS FOR VENTILATION REQUIREMENTS IN TANK FARMS OPERATING SPECIFICATIONS DOCUMENTS

    Energy Technology Data Exchange (ETDEWEB)

    BERGLIN, E J

    2003-06-23

    This report provides the technical basis for high efficiency particulate air filter (HEPA) for Hanford tank farm ventilation systems (sometimes known as heating, ventilation and air conditioning [HVAC]) to support limits defined in Process Engineering Operating Specification Documents (OSDs). This technical basis included a review of older technical basis and provides clarifications, as necessary, to technical basis limit revisions or justification. This document provides an updated technical basis for tank farm ventilation systems related to Operation Specification Documents (OSDs) for double-shell tanks (DSTs), single-shell tanks (SSTs), double-contained receiver tanks (DCRTs), catch tanks, and various other miscellaneous facilities.

  12. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2002-01-01

    Wednesday 13 November 2002 in restaurant nr 2, from 8.30 to 16.30 hrs will be held a blood donors campaign, organized by the Etablissement de Transfusion de Haute-Savoie If you already have a card giving your blood group, please bring this with you.

  13. BLOOD DONORS CAMPAIGN

    CERN Multimedia

    Medical Service

    2002-01-01

    Tuesday 19 March 2002 in restaurant nr 2, from 9.00 to 16.30 hrs A blood donors campaign, organized by the Centre de Transfusion sanguine of Geneva If you already have a card giving your blood group, please bring this with you.

  14. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion Sanguine of Geneva will be held at CERN on Tuesday 13 March 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  15. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2001-01-01

    A blood donors campaign, organized by the Centre de Transfusion d'Annemasse will be held at CERN on Tuesday 14 November 2001 in restaurant nr 2, from 9.00 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  16. BLOOD DONORS CAMPAIGN

    CERN Document Server

    2000-01-01

    A blood donors campaign, organized by the Établissement de Transfusion de Rhône-Alpes will be held at CERN on Tuesday 14 November 2000 in restaurant nr 2, from 8.30 to 16.30 hrs If you already have a card giving your blood group, please bring this with you.

  17. Specification of requirements for health social-network as Personal Health Record (PHR system

    Directory of Open Access Journals (Sweden)

    Mozhgan Tanhapour

    2015-09-01

    Conclusion: The proposed set of requirements are qualitatively compared with the other similar systems. Using the proposed health social network that provides PHR capabilities for its users will have an irrefutable impact on quality and efficiency of patient-centered care, and play an important role in improving the health of society.

  18. 10 CFR 73.23 - Protection of Safeguards Information-Modified Handling: Specific requirements.

    Science.gov (United States)

    2010-01-01

    ... transportation security measures, including physical security plans and procedures, immobilization devices, and... stored in a locked file drawer or cabinet. (3) A mobile device (such as a laptop computer) may also be... include non-public security-related requirements such as protective measures, interim compensatory...

  19. 40 CFR 270.17 - Specific part B information requirements for surface impoundments.

    Science.gov (United States)

    2010-07-01

    ... the leak detection system; (4) The construction quality assurance (CQA) plan if required under § 264... he will provide such a certification upon completion of construction in accordance with the plans and... under § 270.14(b)(7); (f) A description of how hazardous waste residues and contaminated materials will...

  20. 24 CFR 200.936 - Supplementary specific procedural requirements under HUD building products certification program...

    Science.gov (United States)

    2010-04-01

    ... requirements under HUD building products certification program for solid fuel type room heaters and fireplace... type room heaters and fireplace stoves. (a) Applicable standards. Solid fuel type room heaters and fireplace stoves certified under the HUD Building Products Certification Program shall be designed...

  1. The requirements and specific features related to power supply in telecommunications of Ukraine

    Energy Technology Data Exchange (ETDEWEB)

    Lubashenko, T. [Inst. Giprosvijaz, Kiev (Ukraine); Gordon, A. [ProElectro Ltd., Kiev (Ukraine)

    2000-07-01

    The article deals with the description of trends of power supplies in the telecommunication sector. The basic normative documents regarding the design of the power supplies are pointed out. The requirements concerning the design of the power supplies are outlined. The peculiarities of the power supplies in Ukrainian telecommunications are given. (orig.)

  2. 40 CFR 53.51 - Demonstration of compliance with design specifications and manufacturing and test requirements.

    Science.gov (United States)

    2010-07-01

    ... in an ISO 9001-registered facility under a quality system that meets ISO-9001 requirements for... quality system. (3) For the purposes of this section, the definitions of ISO 9001-registered facility and... as part of a designated PM2.5 or PM10−2.5 FRM or FEM will be manufactured in an ISO 9001-registered...

  3. Challenges in balancing the amount of solution information in requirement specifications for embedded products

    DEFF Research Database (Denmark)

    Savolainen, Juha; Hauksdóttir, Dagný; Mannion, Mike

    2013-01-01

    . In practice, on many industrial projects, separating the problem and solution domain entities can be difficult, and arguably there are benefits for not doing so. Many customers feel more confident describing their requirements, often as the difference between the existing products and their needs, some...

  4. Donor transplant programme

    International Nuclear Information System (INIS)

    Abu Bakar Sulaiman

    1999-01-01

    The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

  5. 49 CFR 180.509 - Requirements for inspection and test of specification tank cars.

    Science.gov (United States)

    2010-10-01

    ... cm (2 feet) of the bottom longitudinal center line by one or more of the following inspection and... specification tank cars. 180.509 Section 180.509 Transportation Other Regulations Relating to Transportation... REGULATIONS CONTINUING QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars...

  6. NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNF AIP3/A20

    NARCIS (Netherlands)

    Drennan, M.B. (Michael B.); Govindarajan, S. (Srinath); Verheugen, E. (Eveline); Coquet, J.M. (Jonathan M.); Staal, J. (Jens); McGuire, C. (Conor); T. Taghon (Tom); G. Leclercq (Georges); R. Beyaert (Rudi); G. van Loo (Geert); B.N.M. Lambrecht (Bart); Elewaut, D. (Dirk)

    2016-01-01

    textabstractNatural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the

  7. Interleukin-1 is required for cancer eradication mediated by tumor-specific Th1 cells.

    Science.gov (United States)

    Haabeth, Ole Audun Werner; Lorvik, Kristina Berg; Yagita, Hideo; Bogen, Bjarne; Corthay, Alexandre

    The role of inflammation in cancer is controversial as both tumor-promoting and tumor-suppressive aspects of inflammation have been reported. In particular, it has been shown that pro-inflammatory cytokines, like interleukin-1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor α (TNFα), may either promote or suppress cancer. However, the cellular and molecular basis underlying these opposing outcomes remains enigmatic. Using mouse models for myeloma and lymphoma, we have recently reported that inflammation driven by tumor-specific T helper 1 (Th1) cells conferred protection against B-cell cancer and that interferon-γ (IFN-γ) was essential for this process. Here, we have investigated the contribution of several inflammatory mediators. Myeloma eradication by Th1 cells was not affected by inhibition of TNF-α, TNF-related weak inducer of apoptosis (TWEAK), or TNF-related apoptosis-inducing ligand (TRAIL). In contrast, cancer elimination by tumor-specific Th1 cells was severely impaired by the in vivo neutralization of both IL-1α and IL-1β (collectively named IL-1) with IL-1 receptor antagonist (IL-1Ra). The antitumor functions of tumor-specific Th1 cells and tumor-infiltrating macrophages were both affected by IL-1 neutralization. Secretion of the Th1-derived cytokines IL-2 and IFN-γ at the incipient tumor site was severely reduced by IL-1 blockade. Moreover, IL-1 was shown to synergize with IFN-γ for induction of tumoricidal activity in tumor-infiltrating macrophages. This synergy between IL-1 and IFN-γ may explain how inflammation, when driven by tumor-specific Th1 cells, represses rather than promotes cancer. Collectively, the data reveal a central role of inflammation, and more specifically of the canonical pro-inflammatory cytokine IL-1, in enhancing Th1-mediated immunity against cancer.

  8. CRISP. Requirements Specifications of Intelligent ICT Simulation Tools for Power Applications

    International Nuclear Information System (INIS)

    Warmer, C.J.; Kester, J.C.P.; Kamphuis, I.G.; Carlsson, P; Fontela, M.; Gustavsson, R.

    2003-10-01

    This report, deliverable D2.1 in the CRISP project, serves as a preparation report for the development of simulation tools and prototype software which will be developed in forthcoming stages of the CRISP project. Application areas for these simulations are: fault detection and diagnosis, supply and demand matching and intelligent load shedding. The context in which these applications function is the power network with a high degree of distributed generation, including renewables. In order to control a so called distributed grid we can benefit from a high level of distributed control and intelligence. This requires, on top of the power system network, an information and communication network.. We argue that such a network should be seen as an enabler of distributed control and intelligence. The applications, through which control and intelligence is implemented, then form a third network layer, the service oriented network. Building upon this three-layered network model we derive in this report the requirements for a simulation tool and experiments which study new techniques for fault detection and diagnostics and for simulation tools and experiments implementing intelligent load shedding and supply and demand matching scenarios. We also look at future implementation of these services within the three-layered network model and the requirements that follow for the core information and communication network and for the service oriented network. These requirements, supported by the studies performed in the CRISP Workpackage 1, serve as a basis for development of the simulation tools in the tasks 2.2 to 2.4

  9. Screening of organ and tissue donors for West Nile virus by nucleic acid amplification--a three year experience in Alberta.

    Science.gov (United States)

    Tilley, Peter A G; Fox, Julie D; Lee, Bonita; Chui, Linda; Preiksaitis, Jutta

    2008-10-01

    West Nile Virus (WNV)-specific nucleic acid amplification testing (NAAT) of organ and tissue donors remains controversial. We report three years of WNV donor screening in Alberta Canada using NAAT. Between 2003 and 2005, 1549 initial specimens were received. A valid negative result was issued within the specified turnaround time on 1531 (98.8%). The initial NAAT was successful for 1393 samples (90%), while repeat testing using an alternate NAAT resolved a further 126 samples. For 12 of 14 donors, a second specimen provided a valid negative result. Failure to generate a valid negative result in time resulted in rescheduling of one living related organ transplant, and surgery proceeded in the absence of a final result in one multi-organ donation after risk assessment. For 11 tissue donors, tissues were discarded due to lack of a WNV result. Invalid results usually occurred on postmortem haemolyzed tissue donor samples due to inhibitory reactions. There were no confirmed positive donors, no false-positive results and no solid organs lost due to WNV testing. We conclude that WNV NAAT of organ and tissue donors can be implemented without compromising availability of donors but requires committed laboratory support.

  10. Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl

    Science.gov (United States)

    Zhu, Wei; Pao, Gerald M; Satoh, Akira; Cummings, Gillian; Monaghan, James R; Harkins, Timothy T; Bryant, Susan V; Voss, S Randal; Gardiner, David M; Hunter, Tony

    2013-01-01

    The capacity for tissue and organ regeneration in humans is dwarfed by comparison to that of salamanders. Emerging evidence suggests that mechanisms learned from the early phase of salamander limb regeneration – wound healing, cellular dedifferentiation and blastemal formation – will reveal therapeutic approaches for tissue regeneration in humans. Here we describe a unique transcriptional fingerprint of regenerating limb tissue in the Mexican axolotl (Ambystoma mexicanum) that is indicative of cellular reprogramming of differentiated cells to a germline-like state. Two genes that are required for self-renewal of germ cells in mice and flies, Piwi-like 1 (PL1) and Piwi-like 2 (PL2), are expressed in limb blastemal cells, the basal layer keratinocytes and the thickened apical epithelial cap in the wound epidermis in the regenerating limb. Depletion of PL1 and PL2 by morpholino oligonucleotides decreased cell proliferation and increased cell death in the blastema leading to a significant retardation of regeneration. Examination of key molecules that are known to be required for limb development or regeneration further revealed that FGF8 is transcriptionally downregulated in the presence of the morpholino oligos, indicating PL1 and PL2 might participate in FGF signaling during limb regeneration. Given the requirement for FGF signaling in limb development and regeneration, the results suggest that PL1 and PL2 function to establish a unique germline-like state that is associated with successful regeneration. PMID:22841627

  11. Specification and time required for the application of a lime-based render inside historic buildings

    Directory of Open Access Journals (Sweden)

    Vasco Peixoto de Freitas

    2008-01-01

    Full Text Available Intervention in ancient buildings with historical and architectural value requires traditional techniques, such as the use of lime mortars for internal and external wall renderings. In order to ensure the desired performance, these rendering mortars must be rigorously specified and quality controls have to be performed during application. The choice of mortar composition should take account of factors such as compatibility with the substrate, mechanical requirements and water behaviour. The construction schedule, which used to be considered a second order variable, nowadays plays a decisive role in the selection of the rendering technique, given its effects upon costs. How should lime-based mortars be specified? How much time is required for the application and curing of a lime-based render? This paper reflects upon the feasibility of using traditional lime mortars in three-layer renders inside churches and monasteries under adverse hygrothermal conditions and when time is critical. A case study is presented in which internal lime mortar renderings were applied in a church in Northern Portugal, where the very high relative humidity meant that several months were necessary before the drying process was complete.

  12. Lhx1 is required for specification of the renal progenitor cell field.

    Directory of Open Access Journals (Sweden)

    M Cecilia Cirio

    2011-04-01

    Full Text Available In the vertebrate embryo, the kidney is derived from the intermediate mesoderm. The LIM-class homeobox transcription factor lhx1 is expressed early in the intermediate mesoderm and is one of the first genes to be expressed in the nephric mesenchyme. In this study, we investigated the role of Lhx1 in specification of the kidney field by either overexpressing or depleting lhx1 in Xenopus embryos or depleting lhx1 in an explant culture system. By overexpressing a constitutively-active form of Lhx1, we established its capacity to expand the kidney field during the specification stage of kidney organogenesis. In addition, the ability of Lhx1 to expand the kidney field diminishes as kidney organogenesis transitions to the morphogenesis stage. In a complimentary set of experiments, we determined that embryos depleted of lhx1, show an almost complete loss of the kidney field. Using an explant culture system to induce kidney tissue, we confirmed that expression of genes from both proximal and distal kidney structures is affected by the absence of lhx1. Taken together our results demonstrate an essential role for Lhx1 in driving specification of the entire kidney field from the intermediate mesoderm.

  13. Nasopharyngeal infection by Streptococcus pyogenes requires superantigen-responsive Vβ-specific T cells

    Science.gov (United States)

    Zeppa, Joseph J.; Kasper, Katherine J.; Mohorovic, Ivor; Mazzuca, Delfina M.

    2017-01-01

    The globally prominent pathogen Streptococcus pyogenes secretes potent immunomodulatory proteins known as superantigens (SAgs), which engage lateral surfaces of major histocompatibility class II molecules and T-cell receptor (TCR) β-chain variable domains (Vβs). These interactions result in the activation of numerous Vβ-specific T cells, which is the defining activity of a SAg. Although streptococcal SAgs are known virulence factors in scarlet fever and toxic shock syndrome, mechanisms by how SAgs contribute to the life cycle of S. pyogenes remain poorly understood. Herein, we demonstrate that passive immunization against the Vβ8-targeting SAg streptococcal pyrogenic exotoxin A (SpeA), or active immunization with either wild-type or a nonfunctional SpeA mutant, protects mice from nasopharyngeal infection; however, only passive immunization, or vaccination with inactive SpeA, resulted in high-titer SpeA-specific antibodies in vivo. Mice vaccinated with wild-type SpeA rendered Vβ8+ T cells poorly responsive, which prevented infection. This phenotype was reproduced with staphylococcal enterotoxin B, a heterologous SAg that also targets Vβ8+ T cells, and rendered mice resistant to infection. Furthermore, antibody-mediated depletion of T cells prevented nasopharyngeal infection by S. pyogenes, but not by Streptococcus pneumoniae, a bacterium that does not produce SAgs. Remarkably, these observations suggest that S. pyogenes uses SAgs to manipulate Vβ-specific T cells to establish nasopharyngeal infection. PMID:28794279

  14. Structure-guided mutational analysis reveals the functional requirements for product specificity of DOT1 enzymes.

    Science.gov (United States)

    Dindar, Gülcin; Anger, Andreas M; Mehlhorn, Christine; Hake, Sandra B; Janzen, Christian J

    2014-11-12

    DOT1 enzymes are conserved methyltransferases that catalyse the methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, with different enzymatic activities. DOT1A mediates mono- and dimethylation of H3K76, the homologue of H3K79 in other organisms, whereas DOT1B additionally catalyses H3K76 trimethylation. However, it is unclear how these different enzymatic activities are achieved. Here we employ a trypanosomal nucleosome reconstitution system and structure-guided homology modelling to identify critical residues within and outside the catalytic centre that modulate product specificity. Exchange of these residues transfers the product specificity from one enzyme to the other, and reveals the existence of distinct regulatory domains adjacent to the catalytic centre. Our study provides the first evidence that a few crucial residues in DOT1 enzymes are sufficient to catalyse methyl-state-specific reactions. These results might also have far-reaching consequences for the functional understanding of homologous enzymes in higher eukaryotes.

  15. 33 CFR 154.1035 - Specific requirements for facilities that could reasonably be expected to cause significant and...

    Science.gov (United States)

    2010-07-01

    ... subsection of the plan must also separately list the resource providers and specific resources, including... required in this subpart. All resource providers and resources must be available by contract or other... product resource provider, location, and volume. Location data must include the stockpile's distance to...

  16. 40 CFR Table C-1 to Subpart C of... - Test Concentration Ranges, Number of Measurements Required, and Maximum Discrepancy Specification

    Science.gov (United States)

    2010-07-01

    ... Measurements Required, and Maximum Discrepancy Specification C Table C-1 to Subpart C of Part 53 Protection of... Reference Methods Pt. 53, Subpt. C, Table C-1 Table C-1 to Subpart C of Part 53—Test Concentration Ranges..., June 22, 2010, table C-1 to subpart C was revised, effective Aug. 23, 2010. For the convenience of the...

  17. Mini-donor nephrectomy: A viable and effective alternative

    Directory of Open Access Journals (Sweden)

    Sandeep Guleria

    2010-01-01

    Full Text Available Live kidney donation is an excellent way of increasing the donor pool. The introduction of the laparoscopic donor nephrectomy has resulted in an increase in live organ donation in the western hemisphere. There is no data on its impact on organ donation in India. However attractive as it may seem, the procedure is associated with a definite learning curve and does compromise donor safety. The procedure is also expensive in terms of the equipment required. The mini-donor nephrectomy is an excellent alternative, has no learning curve and is ideally suited for donors in India who have a low BMI. The procedure is also relatively inexpensive. We are in need of a donor registry rather than reports from single institutions to fully evaluate the risks and benefits of both procedures.

  18. Comparison of donor, and early and late recipient outcomes following hand assisted and laparoscopic donor nephrectomy.

    Science.gov (United States)

    Lucas, Steven M; Liaw, Aron; Mhapsekar, Rishi; Yelfimov, Daniel; Goggins, William C; Powelson, John A; Png, Keng Siang; Sundaram, Chandru P

    2013-02-01

    While laparoscopic donor nephrectomy has encouraged living kidney donation, debate exists about the safest laparoscopic technique. We compared purely laparoscopic and hand assisted laparoscopic donor nephrectomies in terms of donor outcome, early graft function and long-term graft outcome. We reviewed the records of consecutive laparoscopic and hand assisted laparoscopic donor nephrectomies performed by a single surgeon from 2002 to 2011. Donor operative time and perioperative morbidity were compared. Early graft function for kidneys procured by each technique was evaluated by rates of delayed graft function, need for dialysis and recipient discharge creatinine. Long-term outcomes were evaluated by graft function. A total of 152 laparoscopic donor nephrectomies were compared with 116 hand assisted laparoscopic donor nephrectomies. Hand assisted procedures were more often done for the right kidney (41.1% vs 17.1%, p recipient outcomes were also similar. Delayed function occurred after 0% hand assisted vs 0.9% purely laparoscopic nephrectomies, dialysis was required in 0.9% vs 1.7% and rejection episodes developed in 9.7% vs 18.4% (p >0.05). At last followup the organ was nonfunctioning in 6.1% of hand assisted and 7.7% of purely laparoscopic cases (p >0.05). The recipient glomerular filtration rate at discharge home was similar in the 2 groups. Hand assisted laparoscopic donor nephrectomy had shorter warm ischemia time but perioperative donor morbidity and graft outcome were comparable. The choice of technique should be based on patient and surgeon preference. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  19. The independent living donor advocate: a guidance document from the American Society of Transplantation's Living Donor Community of Practice (AST LDCOP).

    Science.gov (United States)

    Hays, R E; LaPointe Rudow, D; Dew, M A; Taler, S J; Spicer, H; Mandelbrot, D A

    2015-02-01

    The independent living donor advocate (ILDA) serves a mandated and supportive role in the care of the living organ donor, yet qualifications and role requirements are not clearly defined. Guidance comes from Centers for Medicare and Medicaid Services (CMS) Conditions for Transplant Center Participation and interpretive guidelines, Organ Procurement and Transplantation Network (OPTN) Policy and CMS and OPTN site surveys, yet interpretation of regulations varies. Herein, the AST Living Donor Community of Practice (LDCOP) offers seven recommendations to clarify and optimize the ILDA role: (a) the ILDA must have a certain skill set rather than a specific profession, (b) the ILDA must be educated and demonstrate competence in core knowledge components, (c) the ILDA's primary role is to assess components of informed consent, (d) centers must develop a transparent system to define ILDA independence, (e) the ILDA should have a reporting structure outside the transplant center, (f) the ILDA's role should be integrated throughout the donor care continuum, (g) the ILDA role should include a narrow "veto power." We address controversies in ILDA implementation, and offer pathways to maximize benefits and minimize limitations of approaches that may each meet regulatory requirements but confer different practice benefits. We propose a research agenda to explore the impact of the ILDA. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  20. [Survey of blood donors on the topic of "reimbursement for blood donors"].

    Science.gov (United States)

    Zeiler, T; Kretschmer, V

    1995-02-01

    Remuneration for blood donors, in the way as presently handled by governmental and communal blood transfusion services in Germany, is not generally accepted. It is feared that donors are recruited with increased risk to transmit infectious diseases, especially AIDS. Alternative incentives are discussed. After the so-called AIDS scandal in Germany, a change in the donor motivation was to be expected, associated with an increased willingness to renounce remuneration. Therefore, we performed the present survey, in which we evaluated the donor's willingness to renounce remuneration, possibilities of cashless remuneration and other alternative incentives. During March and April 1994, a total of 1,157 blood donors of the University Blood Bank Marburg were questioned anonymously by a questionnaire in the framework of whole-blood donations. Beside the above-mentioned aspects demoscopic data were included (age, sex, profession, journey). Cutting of remuneration without any other compensation was refused by 86.1% of the donors, 77% would not want to further donate blood in this case. Transfer of money to a bank account instead of cash payment was accepted by 78.6%, the use of non-negotiable cheques by 68.7%. Alternative compensation by tickets for theater, concert, cinema or coupons for restaurants met with the approval of only 27.3%; under these circumstances, 36.9% would be willing to continue blood donation. With increasing age and number of donations, but largely independent of social status, donors attached greater importance to retention of remuneration. Cutting of remuneration would result in a considerable reduction of the willingness to donate blood within the population of donors of the governmental and communal blood transfusion services. However, an increase of virus safety of the blood products would not be reached in this way, since especially the long-term donors would be driven away. Considerable bottlenecks, particularly in the specific blood supply of

  1. The Image Quality Translator – A Way to Support Specification of Imaging Requirements

    DEFF Research Database (Denmark)

    Kejser, Ulla Bøgvad; Bech, Mogens

    2015-01-01

    the process of specifying and controlling imaging requirements more efficient. The tool seeks to translate between the language used by collection managers and curators to express needs for image quality, and the more technical terms and metrics used by imaging experts and photographers to express......Archives, libraries, and museums run numerous imaging projects to digitize physical works and collections of cultural heritage. This study presents a tool called the 'Image Quality Translator' that is being designed at the Royal Library to support the planning of digitization projects and to make...

  2. Requirements for Value of Information (VoI) calculation over mission specifications

    Science.gov (United States)

    Michaelis, James R.

    2017-05-01

    Intelligence, Surveillance, and Reconnaissance (ISR) operations center on providing relevant situational understanding to military commanders and analysts to facilitate decision-making for execution of mission tasks. However, limitations exist in tactical-edge environments on the ability to disseminate digital materials to analysts and decision makers. This work investigates novel methods to calculate of Value of Information tied to digital materials (termed information objects) for consumer use, based on interpretation of mission specifications. Followed by a short survey of related VoI calculation efforts, discussion is provided on mission-centric VoI calculation for digital materials via adoption of the preexisting Missions and Means Framework model.

  3. Krüppel-like is required for nonskeletogenic mesoderm specification in the sea urchin embryo

    OpenAIRE

    Yamazaki, Atsuko; Kawabata, Rika; Shiomi, Kosuke; Tsuchimoto, Jun; Kiyomoto, Masato; Amemiya, Shonan; Yamaguchi, Masaaki

    2008-01-01

    The canonical Wnt pathway plays a central role in specifying vegetal cell fate in sea urchin embryos. SpKrl has been cloned as a direct target of nuclear β-catenin. Using Hemicentrotus pulcherrimus embryos, here we show that HpKrl controls the specification of secondary mesenchyme cells (SMCs) through both cell-autonomous and non-autonomous means. Like SpKrl, HpKrl was activated in both micromere and macromere progenies. To examine the functions of HpKrl in each blastomere, we constructed chi...

  4. Surgical PACS for the digital operating room. Systems engineering and specification of user requirements.

    Science.gov (United States)

    Korb, Werner; Bohn, Stefan; Burgert, Oliver; Dietz, Andreas; Jacobs, Stephan; Falk, Volkmar; Meixensberger, Jürgen; Strauss, Gero; Trantakis, Christos; Lemke, Heinz U

    2006-01-01

    For better integration of surgical assist systems into the operating room, a common communication and processing plattform that is based on the users needs is needed. The development of such a system, a Surgical Picture Aquisition and Communication System (S-PACS), according the systems engineering cycle is oulined in this paper. The first two steps (concept and specification) for the engineering of the S-PACS are discussed.A method for the systematic integration of the users needs', the Quality Function Deployment (QFD), is presented. The properties of QFD for the underlying problem and first results are discussed. Finally, this leads to a first definition of an S-PACS system.

  5. Comparison of energy consumption and specific energy requirements of different methods for drying mushroom slices

    International Nuclear Information System (INIS)

    Motevali, Ali; Minaei, Saeid; Khoshtaghaza, Mohammad Hadi; Amirnejat, Hamed

    2011-01-01

    Energy consumption for drying of mushroom slices was evaluated using various drying methods including hot air, microwave, vacuum, infrared, microwave-vacuum and hot air-infrared. Results of data analysis showed that the lowest and highest energy consumption levels in drying mushroom slices were associated with microwave and vacuum dryers, respectively. The use of vacuum in conjunction with microwave drying increased energy consumption relative to microwave drying alone. Energy consumption in the hot air dryer showed a downward trend with increasing temperature and an upward trend with increasing air velocity. In drying mushroom using infrared radiation, it was observed that increased air velocity increases drying time and consequently the amount of consumed energy. Using a combination of hot air and infrared drying decreased energy consumption relative to infrared drying alone and increased it relative to hot air drying. In the combined microwave-vacuum dryer, drying time and consequently energy consumption decreased in comparison to the vacuum dryer. Hot air-infrared drying of mushroom slices proved to have the lowest energy consumption. -- Highlights: ► In this study we comparing the amount of energy used and specific energy consumption in different drying methods. ► Six drying methods including Hot air, Infrared, Hot air-infrared, Microwave, Vacuum and microwave-vacuum were used. ► The maximum and minimum energy consumption was obtained in vacuum and microwave dryer, respectively. ► The best drying method in terms of energy consumption and specific energy consumption is the microwave dryer.

  6. NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20.

    Science.gov (United States)

    Drennan, Michael B; Govindarajan, Srinath; Verheugen, Eveline; Coquet, Jonathan M; Staal, Jens; McGuire, Conor; Taghon, Tom; Leclercq, Georges; Beyaert, Rudi; van Loo, Geert; Lambrecht, Bart N; Elewaut, Dirk

    2016-09-19

    Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells. © 2016 Drennan et al.

  7. Knowledge, Attitudes and Motivations Among Blood Donors in São Paulo, Brazil

    Science.gov (United States)

    Goncalez, Thelma T.; Sabino, Ester C.; Chen, Sanny; Salles, Nanci Alves; Chamone, Dalton A. F.; McFarland, Willi; Murphy, Edward L.

    2013-01-01

    Recruiting safe, volunteer blood donors requires understanding motivations for donating and knowledge and attitudes about HIV. We surveyed 1,600 persons presenting for blood donation at a large blood bank in São Paulo, Brazil using a self-administered, structured questionnaire, and classified motivations into three domains as well as categorizing persons by HIV test-seeking behavior. Motivations, in descending order, and their significant associations were: “altruism”: female gender, volunteer donor and repeat donor status; “direct appeal”: female gender, repeat donor status and age 21–50 years; “self-interest”: male gender, age under 20 years, first-time donor status and lower education. HIV test-seekers were more likely to give incorrect answers regarding HIV risk behavior and blood donation and the ability of antibody testing to detect recent HIV infections. Altruism is the main motivator for blood donation in Brazil; other motivators were associated with specific demographic subgroups. HIV test-seeking might be reduced by educational interventions. PMID:18389356

  8. Requirements and Specifications for a Simplified, Low Pressure Medium Sized PWR

    International Nuclear Information System (INIS)

    Nisan, S.; Raymond, P.; Gautier, G-M.; Pignatel, J-F.

    1998-01-01

    This paper summarises part of our on-going investigations on the possible introduction of nuclear energy in developing countries or countries with low capacity electrical grids. These investigations are principally concerned with future PWR developments and basically try to search for plausible and economic answers to the three difficult questions that each nuclear technology exporting country faces today: 1)- how to compensate the apparent loss of economic competitiveness, related to the scaling effect, of a small or medium sized reactor? 2)- how to reconcile the introduction of nuclear energy on the large scale with the two major preoccupations of nuclear safety and nuclear proliferation? 3)- how to demonstrate that the proposed concept(s) can effectively meet the safety objectives of the requirements for future reactors in Europe and in other countries?

  9. SELECTED REQUIREMENTS OF INTEGRATED MANAGEMENT SYSTEMS BASED ON PAS 99 SPECIFICATION

    Directory of Open Access Journals (Sweden)

    Paweł Nowicki

    2013-03-01

    Full Text Available The aim this research was to analyze the ways of integration of management systems in food sector. The study involved the documentation, audits, corrective and preventive actions and management's review phases described in the specification PAS 99, which is one of common elements of integrated management systems. Four organizations were selected for the study. The organizations had introduced and certified at least two standardized management systems. It was assumed that the investigated organizations should have implemented the HACCP system. Studies were conducted as a case study. The employees responsible for the functioning of management systems were interviewed in all four organizations. The study was conducted in the form of in-depth interviews based on pre-prepared script. The scenario was developed based on the PAS 99 guideline. The process of integration of management systems implemented in the studied companies reveals the full compliance of an integrated management system with PASS 99 in the policy area.

  10. Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

    Science.gov (United States)

    Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

    2013-04-01

    IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

  11. Eye bank procedures: donor selection criteria.

    Science.gov (United States)

    Sousa, Sidney Júlio de Faria E; Sousa, Stella Barretto de Faria E

    2018-01-01

    Eye banks use sterile procedures to manipulate the eye, antiseptic measures for ocular surface decontamination, and rigorous criteria for donor selection to minimize the possibility of disease transmission due to corneal grafting. Donor selection focuses on analysis of medical records and specific post-mortem serological tests. To guide and standardize procedures, eye bank associations and government agencies provide lists of absolute and relative contraindications for use of the tissue based on donor health history. These lists are guardians of the Hippocratic principle "primum non nocere." However, each transplantation carries risk of transmission of potentially harmful agents to the recipient. The aim of the procedures is not to eliminate risk, but limit it to a reasonable level. The balance between safety and corneal availability needs to be maintained by exercising prudence without disproportionate rigor.

  12. Serum-free media formulations are cell line-specific and require optimization for microcarrier culture.

    Science.gov (United States)

    Tan, Kah Yong; Teo, Kim Leng; Lim, Jessica F Y; Chen, Allen K L; Choolani, Mahesh; Reuveny, Shaul; Chan, Jerry; Oh, Steve Kw

    2015-08-01

    Mesenchymal stromal cells (MSCs) are being investigated as potential cell therapies for many different indications. Current methods of production rely on traditional monolayer culture on tissue-culture plastic, usually with the use of serum-supplemented growth media. However, the monolayer culturing system has scale-up limitations and may not meet the projected hundreds of billions to trillions batches of cells needed for therapy. Furthermore, serum-free medium offers several advantages over serum-supplemented medium, which may have supply and contaminant issues, leading to many serum-free medium formulations being developed. We cultured seven MSC lines in six different serum-free media and compared their growth between monolayer and microcarrier culture. We show that (i) expansion levels of MSCs in serum-free monolayer cultures may not correlate with expansion in serum-containing media; (ii) optimal culture conditions (serum-free media for monolayer or microcarrier culture) differ for each cell line; (iii) growth in static microcarrier culture does not correlate with growth in stirred spinner culture; (iv) and that early cell attachment and spreading onto microcarriers does not necessarily predict efficiency of cell expansion in agitated microcarrier culture. Current serum-free media developed for monolayer cultures of MSCs may not support MSC proliferation in microcarrier cultures. Further optimization in medium composition will be required for microcarrier suspension culture for each cell line. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  13. Infography use to requirements specification for the design of the building

    Science.gov (United States)

    Losev, Konstantin; Sinenko, Sergey

    2017-10-01

    The study contributes to a growing body of research Transport infrastructure in a construction object life cycle management and presents areas in which further investigation is needed. The object of study are Railway buildings and structures and the Employer’s information requirements (EIR) for design of individual residential building. The task of the study was to determine necessary and sufficient scope of parameters which contained in inforaphic form of EIR comparing with traditional text form of EIR. Also, the task was to determine what categories of the traditional EIR are transferred to an infographic representation form and what categories are ignored in case of a relatively low complexity building. Methods that have been used in the study were infographical representation of text and further expert evaluation. Conclusions of the study present the necessary and sufficient scope of parameters for inforaphic form of EIR, the relations between infographic parameters and categories of the EIR traditional form and subcategories of the traditional EIR that are ignored in case of a relatively low complexity building.

  14. The dynactin complex is required for cleavage plane specification in early Caenorhabditis elegans embryos

    Science.gov (United States)

    Skop, Ahna R.; White, John G.

    2013-01-01

    Background During metazoan development, cell diversity arises primarily from asymmetric cell divisions which are executed in two phases: segregation of cytoplasmic factors and positioning of the mitotic spindle – and hence the cleavage plane – relative to the axis of segregation. When polarized cells divide, spindle alignment probably occurs through the capture and subsequent shortening of astral microtubules by a site in the cortex. Results Here, we report that dynactin, the dynein-activator complex, is localized at cortical microtubule attachment sites and is necessary for mitotic spindle alignment in early Caenorhabditis elegans embryos. Using RNA interference techniques, we eliminated expression in early embryos of dnc-1 (the ortholog of the vertebrate gene for p150Glued) and dnc-2 (the ortholog of the vertebrate gene for p50/Dynamitin). In both cases, misalignment of mitotic spindles occurred, demonstrating that two components of the dynactin complex, DNC-1 and DNC-2, are necessary to align the spindle. Conclusions Dynactin complexes may serve as a tether for dynein at the cortex and allow dynein to produce forces on the astral microtubules required for mitotic spindle alignment. PMID:9778526

  15. Restricting calcium currents is required for correct fiber type specification in skeletal muscle.

    Science.gov (United States)

    Sultana, Nasreen; Dienes, Beatrix; Benedetti, Ariane; Tuluc, Petronel; Szentesi, Peter; Sztretye, Monika; Rainer, Johannes; Hess, Michael W; Schwarzer, Christoph; Obermair, Gerald J; Csernoch, Laszlo; Flucher, Bernhard E

    2016-05-01

    Skeletal muscle excitation-contraction (EC) coupling is independent of calcium influx. In fact, alternative splicing of the voltage-gated calcium channel CaV1.1 actively suppresses calcium currents in mature muscle. Whether this is necessary for normal development and function of muscle is not known. However, splicing defects that cause aberrant expression of the calcium-conducting developmental CaV1.1e splice variant correlate with muscle weakness in myotonic dystrophy. Here, we deleted CaV1.1 (Cacna1s) exon 29 in mice. These mice displayed normal overall motor performance, although grip force and voluntary running were reduced. Continued expression of the developmental CaV1.1e splice variant in adult mice caused increased calcium influx during EC coupling, altered calcium homeostasis, and spontaneous calcium sparklets in isolated muscle fibers. Contractile force was reduced and endurance enhanced. Key regulators of fiber type specification were dysregulated and the fiber type composition was shifted toward slower fibers. However, oxidative enzyme activity and mitochondrial content declined. These findings indicate that limiting calcium influx during skeletal muscle EC coupling is important for the secondary function of the calcium signal in the activity-dependent regulation of fiber type composition and to prevent muscle disease. © 2016. Published by The Company of Biologists Ltd.

  16. Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

    Science.gov (United States)

    Qian, Chen; Wong, Carol Wing Yan; Wu, Zhongluan; He, Qiuming; Xia, Huimin; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen; Lui, Vincent Chi Hang

    2017-01-01

    Platelet-derived growth factor receptor alpha (PDGFRα) is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures. To address the temporal requirement of Pdgfra in embryonic development. We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies. Current study showed that (i) conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5) resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii) the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives. Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a) the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b) if mutations / sequence variations of these regulatory elements cause these anomalies.

  17. A Clostridium difficile-Specific, Gel-Forming Protein Required for Optimal Spore Germination

    Directory of Open Access Journals (Sweden)

    M. Lauren Donnelly

    2017-01-01

    Full Text Available Clostridium difficile is a Gram-positive spore-forming obligate anaerobe that is a leading cause of antibiotic-associated diarrhea worldwide. In order for C. difficile to initiate infection, its aerotolerant spore form must germinate in the gut of mammalian hosts. While almost all spore-forming organisms use transmembrane germinant receptors to trigger germination, C. difficile uses the pseudoprotease CspC to sense bile salt germinants. CspC activates the related subtilisin-like protease CspB, which then proteolytically activates the cortex hydrolase SleC. Activated SleC degrades the protective spore cortex layer, a step that is essential for germination to proceed. Since CspC incorporation into spores also depends on CspA, a related pseudoprotease domain, Csp family proteins play a critical role in germination. However, how Csps are incorporated into spores remains unknown. In this study, we demonstrate that incorporation of the CspC, CspB, and CspA germination regulators into spores depends on CD0311 (renamed GerG, a previously uncharacterized hypothetical protein. The reduced levels of Csps in gerG spores correlate with reduced responsiveness to bile salt germinants and increased germination heterogeneity in single-spore germination assays. Interestingly, asparagine-rich repeat sequences in GerG’s central region facilitate spontaneous gel formation in vitro even though they are dispensable for GerG-mediated control of germination. Since GerG is found exclusively in C. difficile, our results suggest that exploiting GerG function could represent a promising avenue for developing C. difficile-specific anti-infective therapies.

  18. The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability.

    Directory of Open Access Journals (Sweden)

    Sabine S Lange

    2016-01-01

    Full Text Available DNA polymerase ζ (pol ζ is exceptionally important for maintaining genome stability. Inactivation of the Rev3l gene encoding the polymerase catalytic subunit causes a high frequency of chromosomal breaks, followed by lethality in mouse embryos and in primary cells. Yet it is not known whether the DNA polymerase activity of pol ζ is specifically essential, as the large REV3L protein also serves as a multiprotein scaffold for translesion DNA synthesis via multiple conserved structural domains. We report that Rev3l cDNA rescues the genomic instability and DNA damage sensitivity of Rev3l-null immortalized mouse fibroblast cell lines. A cDNA harboring mutations of conserved catalytic aspartate residues in the polymerase domain of REV3L could not rescue these phenotypes. To investigate the role of REV3L DNA polymerase activity in vivo, a Rev3l knock-in mouse was constructed with this polymerase-inactivating alteration. No homozygous mutant mice were produced, with lethality occurring during embryogenesis. Primary fibroblasts from mutant embryos showed growth defects, elevated DNA double-strand breaks and cisplatin sensitivity similar to Rev3l-null fibroblasts. We tested whether the severe Rev3l-/- phenotypes could be rescued by deletion of DNA polymerase η, as has been reported with chicken DT40 cells. However, Rev3l-/- Polh-/- mice were inviable, and derived primary fibroblasts were as sensitive to DNA damage as Rev3l-/- Polh+/+ fibroblasts. Therefore, the functions of REV3L in maintaining cell viability, embryonic viability and genomic stability are directly dependent on its polymerase activity, and cannot be ameliorated by an additional deletion of pol η. These results validate and encourage the approach of targeting the DNA polymerase activity of pol ζ to sensitize tumors to DNA damaging agents.

  19. The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability.

    Science.gov (United States)

    Lange, Sabine S; Tomida, Junya; Boulware, Karen S; Bhetawal, Sarita; Wood, Richard D

    2016-01-01

    DNA polymerase ζ (pol ζ) is exceptionally important for maintaining genome stability. Inactivation of the Rev3l gene encoding the polymerase catalytic subunit causes a high frequency of chromosomal breaks, followed by lethality in mouse embryos and in primary cells. Yet it is not known whether the DNA polymerase activity of pol ζ is specifically essential, as the large REV3L protein also serves as a multiprotein scaffold for translesion DNA synthesis via multiple conserved structural domains. We report that Rev3l cDNA rescues the genomic instability and DNA damage sensitivity of Rev3l-null immortalized mouse fibroblast cell lines. A cDNA harboring mutations of conserved catalytic aspartate residues in the polymerase domain of REV3L could not rescue these phenotypes. To investigate the role of REV3L DNA polymerase activity in vivo, a Rev3l knock-in mouse was constructed with this polymerase-inactivating alteration. No homozygous mutant mice were produced, with lethality occurring during embryogenesis. Primary fibroblasts from mutant embryos showed growth defects, elevated DNA double-strand breaks and cisplatin sensitivity similar to Rev3l-null fibroblasts. We tested whether the severe Rev3l-/- phenotypes could be rescued by deletion of DNA polymerase η, as has been reported with chicken DT40 cells. However, Rev3l-/- Polh-/- mice were inviable, and derived primary fibroblasts were as sensitive to DNA damage as Rev3l-/- Polh+/+ fibroblasts. Therefore, the functions of REV3L in maintaining cell viability, embryonic viability and genomic stability are directly dependent on its polymerase activity, and cannot be ameliorated by an additional deletion of pol η. These results validate and encourage the approach of targeting the DNA polymerase activity of pol ζ to sensitize tumors to DNA damaging agents.

  20. The influence of donor factors on corneal organ culture contamination.

    Science.gov (United States)

    Gruenert, Anja K; Rosenbaum, Katja; Geerling, Gerd; Fuchsluger, Thomas A

    2017-11-01

    To evaluate the contamination rate and the corresponding spectrum of microbes and to identify donor risk factors for corneal organ culture contaminations. A total of 3306 organ-cultured donor corneas were included in the study. We performed a retrospective database analysis to evaluate donor factors such as gender, age, death-to-explantation interval (DEI), procurement site and cause of death and to determine their influence on donor cornea contaminations. Odds ratios (ORs) were calculated for each factor. The overall contamination rate was 7.8% (n = 259). Younger donor age (OR: 2.2, p = 0.003, chi-squared test), a DEI of more than 24 hr (OR: 1.6, p donor gender did not have an effect on donor cornea contaminations. The most frequently isolated microbes were Enterococci (19%), Staphylococci (10.8%) and Candida (37.4%). This study helps to estimate the contamination risk of a cultured cornea based on specific donor factors. However, donors with risk factors should not be generally excluded from cornea donation. Further studies including antibiograms might clarify whether a change in the antibiotic composition of the culture medium would be useful to deal with the increasing number of multi-resistant microbes. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Lung Transplantation From Donors After Previous Cardiac Surgery: Ideal Graft in Marginal Donor?

    Science.gov (United States)

    Palleschi, A; Mendogni, P; Tosi, D; Montoli, M; Carrinola, R; Mariolo, A V; Briganti, F; Nosotti, M

    2017-05-01

    Lung transplantation is a limited by donor pool shortage. Despite the efforts to extend the graft acceptability with recurrent donor criteria reformulations, previous cardiothoracic surgery is still considered a contraindication. A donor who underwent cardiac surgery could potentially provide an ideal lung but high intraoperative risks and intrinsic technical challenges are expected during the graft harvesting. The purpose of this study is to present our dedicated protocol and four clinical cases of successful lung procurements from donors who had a previous major cardiac surgery. One donor had ascending aortic root (AAR) substitution, another had mitral valve substitution, and two had coronary artery bypass surgery. The others' eligibility criteria for organ allocation, such as ABO compatibility, PaO 2 /FiO 2 ratio, absence of aspiration, or sepsis were respected. In one of the cases with previous coronary bypass grafting, the donor had a veno-arterial extracorporeal membrane oxygenation support. Consequently, the grafts required an ex vivo lung perfusion evaluation. We report the technical details of procurement and postoperative courses of recipients. All procurements were uneventful, without lung damage or waste of abdominal organs related to catastrophic intraoperative events. All recipients had a successful clinical outcome. We believe that successful transplantation is achievable even in a complicated setting, such as cases involving donors with previous cardiac surgery frequently are. Facing lung donor shortage, we strongly support any effort to avoid the loss of possible acceptable lungs. In particular, previous major cardiac surgery does not strictly imply a poor quality of lungs as well as unsustainable graft procurement. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Oocyte cryopreservation for donor egg banking.

    Science.gov (United States)

    Cobo, Ana; Remohí, José; Chang, Ching-Chien; Nagy, Zsolt Peter

    2011-09-01

    Oocyte donation is an efficient alternative to using own oocytes in IVF treatment for different indications. Unfortunately, 'traditional' (fresh) egg donations are challenged with inefficiency, difficulties of synchronization, very long waiting periods and lack of quarantine measures. Given the recent improvements in the efficiency of oocyte cryopreservation, it is reasonable to examine if egg donation through oocyte cryopreservation has merits. The objective of the current manuscript is to review existing literature on this topic and to report on the most recent outcomes from two established donor cryobank centres. Reports on egg donation using slow freezing are scarce and though results are encouraging, outcomes are not yet comparable to a fresh egg donation treatment. Vitrification on the other hand appears to provide high survival rates (90%) of donor oocytes and comparable fertilization, embryo development, implantation and pregnancy rates to traditional (fresh) egg donation. Besides the excellent outcomes, the ease of use for both donors and recipients, higher efficiency, lower cost and avoiding the problem of synchronization are all features associated with the benefit of a donor egg cryobank and makes it likely that this approach becomes the future standard of care. Oocyte donation is one of the last resorts in IVF treatment for couples challenged with infertility problems. However, traditional (fresh) egg donation, as it is performed today, is not very efficient, as typically all eggs from one donor are given to only one recipient, it is arduous as it requires an excellent synchronization between the donor and recipient and there are months or years of waiting time. Because of the development of an efficient oocyte cryopreservation technique, it is now possible to cryo-store donor (as well as non-donor) eggs, maintaining their viability and allowing their use whenever there is demand. Therefore, creating a donor oocyte cryobank would carry many advantages

  3. Donor attention to reading materials.

    Science.gov (United States)

    O'Brien, S F; Osmond, L; Choquet, K; Yi, Q-L; Goldman, M

    2015-11-01

    Mandatory predonation reading materials inform donors about risk factors for transmissible disease, possible complications of donation and changes to the donation process. We aimed to assess the attention to predonation reading materials and factors which may affect attention. A national survey in 2008 of 18,108 blood donors asked about self-assessed attention to reading the materials. In face-to-face interviews, 441 donors completed additional questions about reading the materials and a literacy test. Qualitative interviews of 27 donors assessed their approach to reading. In the national survey, most of the first-time donors said they read all or most of the materials (90.9% first-time vs. 57.6% repeat donors, P reading them carefully (P read materials carefully, skimmed or did not read, most knew that donors are informed of positive transmissible disease test results (97.1%, 95.5, 98.0 P > 0.05), but fewer recalled seeing the definition of sex (77.2%, 56.9, 24.2 P read materials carefully, skimmed or did not read were compared (P > 0.05). Qualitative interviews showed that donors are reluctant to read any more than necessary and decide based on perceived importance or relevance. Attention to predonation reading materials tends to be better among first-time donors. The effectiveness is limited by low motivation to read, especially for repeat donors, as well as poor literacy. © 2015 International Society of Blood Transfusion.

  4. Compensatory Hypertrophy After Living Donor Nephrectomy.

    Science.gov (United States)

    Chen, K W; Wu, M W F; Chen, Z; Tai, B C; Goh, Y S B; Lata, R; Vathsala, A; Tiong, H Y

    2016-04-01

    Previous studies have shown that kidney volume enhances the estimation of glomerular filtration rate (eGFR) in kidney donors. This study aimed to describe the phenomenon of compensatory hypertrophy after donor nephrectomy as measured on computerized tomographic (CT) scans. An institutional Domain Specific Review Board (DSRB)-approved study involved approaching kidney donors to have a follow up CT scan from 6 months to 1 year after surgery; 29 patients participated; 55% were female. Clinical chart review was performed, and the patient's remaining kidney volume was measured before and after surgery based on CT scans. eGFR was determined with the use of the Modification of Diet in Renal Disease equation. Mean parenchymal volume of the remaining kidney for this population (mean age, 44.3 ± 8.5 y) was 204.7 ± 82.5 cc before surgery and 250.5 ± 113.3 cc after donor nephrectomy. Compensatory hypertrophy occurred in 79.3% of patients (n = 23). Mean increase in remaining kidney volume was 22.4 ± 23.2% after donor nephrectomy in healthy individuals. Over a median follow-up of 52.9 ± 19.8 months, mean eGFR was 68.9 ± 12.4 mL/min/1.73 m(2), with 24.1% of patients (n = 7) in chronic kidney disease grade 3. Absolute and relative change in kidney volume was not associated with sex, race, surgical approach, or background of hypertension (P = NS). There was a trend of decreased hypertrophy with increasing age (P = .5; Spearman correlation, -0.12). In healthy kidney donors, compensatory hypertrophy of the remaining kidney occurs in 79.3% of the patients, with an average increment of about 22.4%. Older patients may have a blunted compensatory hypertrophy response after surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Optogenetic determination of the myocardial requirements for extrasystoles by cell type-specific targeting of ChannelRhodopsin-2.

    Science.gov (United States)

    Zaglia, Tania; Pianca, Nicola; Borile, Giulia; Da Broi, Francesca; Richter, Claudia; Campione, Marina; Lehnart, Stephan E; Luther, Stefan; Corrado, Domenico; Miquerol, Lucile; Mongillo, Marco

    2015-08-11

    Extrasystoles lead to several consequences, ranging from uneventful palpitations to lethal ventricular arrhythmias, in the presence of pathologies, such as myocardial ischemia. The role of working versus conducting cardiomyocytes, as well as the tissue requirements (minimal cell number) for the generation of extrasystoles, and the properties leading ectopies to become arrhythmia triggers (topology), in the normal and diseased heart, have not been determined directly in vivo. Here, we used optogenetics in transgenic mice expressing ChannelRhodopsin-2 selectively in either cardiomyocytes or the conduction system to achieve cell type-specific, noninvasive control of heart activity with high spatial and temporal resolution. By combining measurement of optogenetic tissue activation in vivo and epicardial voltage mapping in Langendorff-perfused hearts, we demonstrated that focal ectopies require, in the normal mouse heart, the simultaneous depolarization of at least 1,300-1,800 working cardiomyocytes or 90-160 Purkinje fibers. The optogenetic assay identified specific areas in the heart that were highly susceptible to forming extrasystolic foci, and such properties were correlated to the local organization of the Purkinje fiber network, which was imaged in three dimensions using optical projection tomography. Interestingly, during the acute phase of myocardial ischemia, focal ectopies arising from this location, and including both Purkinje fibers and the surrounding working cardiomyocytes, have the highest propensity to trigger sustained arrhythmias. In conclusion, we used cell-specific optogenetics to determine with high spatial resolution and cell type specificity the requirements for the generation of extrasystoles and the factors causing ectopies to be arrhythmia triggers during myocardial ischemia.

  6. Donor Tracker: An Innovative Real-Time Tracking System for Blood ...

    African Journals Online (AJOL)

    User

    The problem is even worse if the blood group is rare. In this paper, we explore the possibility of using location-aware computing to track blood donors in Mauritius and locate the nearest donor in cases of emergencies and whenever fresh blood is required. A number of blood donor management systems exist but none of ...

  7. Keeping body and soul together: southern NGOs' strategic responses to donor constraints

    NARCIS (Netherlands)

    Elbers, W.; Arts, B.J.M.

    2011-01-01

    Most Southern Non-Governmental Organizations (SNGOs) depend on donor agencies for their survival. To qualify for donor funding, SNGOs typically have to meet a range of funding conditions. Critics argue that donor requirements may have undesirable consequences. Based on qualitative research involving

  8. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs.

    Science.gov (United States)

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-09-06

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.

  9. SHOCK VOLUME: A PATIENT-SPECIFIC INDEX THAT PREDICTS TRANSFUSION REQUIREMENTS AND ORGAN DYSFUNCTION IN MULTIPLY INJURED PATIENTS.

    Science.gov (United States)

    McKinley, Todd O; McCarroll, Tyler; Gaski, Greg E; Frantz, Travis L; Zarzaur, Ben L; Terry, Colin; Steenburg, Scott D

    2016-02-01

    Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt which causes organ dysfunction and can lead to death. We developed a noninvasive patient-specific index, Shock Volume (SV), to quantify the magnitude of hypoperfusion. SV integrates the magnitude and duration that incremental shock index values are elevated above known thresholds of hypoperfusion using serial individual vital sign data. SV can be monitored in real time to assess ongoing hypoperfusion. The goal of this study was to determine how SV corresponded to transfusion requirements and organ dysfunction in a retrospective cohort of 74 MIPs. We measured SV in 6-h increments for 48 h after injury in multiply injured adults (18-65; Injury Severity Score ≥18). Patients who had accumulated 40 units of SV within 6 h of injury and 100 units of SV within 12 h of injury were at high risk for requiring massive transfusion or multiple critical administration transfusions. SV measurements were equally sensitive and specific as compared with base deficit values in predicting transfusions. SV measurements at 6 h after injury stratified patients at risk for multiple organ failure determined by Denver scores. In addition, SV values corresponded to the magnitude of organ failure determined by Sequential Organ Failure Assessment scores. SV is a patient-specific index that can be quantified in real time in critically injured patients. It is a surrogate for cumulative hypoperfusion and it predicts high-volume transfusions and organ dysfunction.

  10. Biotrophy-specific downregulation of siderophore biosynthesis in Colletotrichum graminicola is required for modulation of immune responses of maize.

    Science.gov (United States)

    Albarouki, Emad; Schafferer, Lukas; Ye, Fanghua; von Wirén, Nicolaus; Haas, Hubertus; Deising, Holger B

    2014-04-01

    The hemibiotrophic maize pathogen Colletotrichum graminicola synthesizes one intracellular and three secreted siderophores. eGFP fusions with the key siderophore biosynthesis gene, SID1, encoding l-ornithine-N(5) -monooxygenase, suggested that siderophore biosynthesis is rigorously downregulated specifically during biotrophic development. In order to investigate the role of siderophores during vegetative development and pathogenesis, SID1, which is required for synthesis of all siderophores, and the non-ribosomal peptide synthetase gene NPS6, synthesizing secreted siderophores, were deleted. Mutant analyses revealed that siderophores are required for vegetative growth under iron-limiting conditions, conidiation, ROS tolerance, and cell wall integrity. Δsid1 and Δnps6 mutants were hampered in formation of melanized appressoria and impaired in virulence. In agreement with biotrophy-specific downregulation of siderophore biosynthesis, Δsid1 and Δnps6 strains were not affected in biotrophic development, but spread of necrotrophic hyphae was reduced. To address the question why siderophore biosynthesis is specifically downregulated in biotrophic hyphae, maize leaves were infiltrated with siderophores. Siderophore infiltration alone did not induce defence responses, but formation of biotrophic hyphae in siderophore-infiltrated leaves caused dramatically increased ROS formation and transcriptional activation of genes encoding defence-related peroxidases and PR proteins. These data suggest that fungal siderophores modulate the plant immune system. © 2014 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

  11. Q-FISH measurement of hepatocyte telomere lengths in donor liver and graft after pediatric living-donor liver transplantation: donor age affects telomere length sustainability.

    Directory of Open Access Journals (Sweden)

    Youichi Kawano

    Full Text Available Along with the increasing need for living-donor liver transplantation (LDLT, the issue of organ shortage has become a serious problem. Therefore, the use of organs from elderly donors has been increasing. While the short-term results of LDLT have greatly improved, problems affecting the long-term outcome of transplant patients remain unsolved. Furthermore, since contradictory data have been reported with regard to the relationship between donor age and LT/LDLT outcome, the question of whether the use of elderly donors influences the long-term outcome of a graft after LT/LDLT remains unsettled. To address whether hepatocyte telomere length reflects the outcome of LDLT, we analyzed the telomere lengths of hepatocytes in informative biopsy samples from 12 paired donors and recipients (grafts of pediatric LDLT more than 5 years after adult-to-child LDLT because of primary biliary atresia, using quantitative fluorescence in situ hybridization (Q-FISH. The telomere lengths in the paired samples showed a robust relationship between the donor and grafted hepatocytes (r = 0.765, p = 0.0038, demonstrating the feasibility of our Q-FISH method for cell-specific evaluation. While 8 pairs showed no significant difference between the telomere lengths for the donor and the recipient, the other 4 pairs showed significantly shorter telomeres in the recipient than in the donor. Multiple regression analysis revealed that the donors in the latter group were older than those in the former (p = 0.001. Despite the small number of subjects, this pilot study indicates that donor age is a crucial factor affecting telomere length sustainability in hepatocytes after pediatric LDLT, and that the telomeres in grafted livers may be elongated somewhat longer when the grafts are immunologically well controlled.

  12. Improving the action requirements of technical specifications: A risk-comparison of continued operation and plant shutdown

    International Nuclear Information System (INIS)

    Kim, I.S.; Samanta, P.K.

    1994-01-01

    When the systems needed to remove decay heat are inoperable or degraded, the risk of shutting down the plant may be comparable to, or even higher than, that of continuing power operation with the equipment inoperable while giving priority to repairs. This concern arises because the plant may not have sufficient capability for removing decay heat during the shutdown. However, Technical Specifications (TSs) often require ''immediate'' shutdown of the plant. In this paper, the authors present risk-based analyses of the various operational policy alternatives available in such situations, with an example application to the standby service water (SSW) system of a BWR. These analyses can be used to define risk-effective requirements for those standby safety systems under discussion

  13. Automata learning algorithms and processes for providing more complete systems requirements specification by scenario generation, CSP-based syntax-oriented model construction, and R2D2C system requirements transformation

    Science.gov (United States)

    Hinchey, Michael G. (Inventor); Margaria, Tiziana (Inventor); Rash, James L. (Inventor); Rouff, Christopher A. (Inventor); Steffen, Bernard (Inventor)

    2010-01-01

    Systems, methods and apparatus are provided through which in some embodiments, automata learning algorithms and techniques are implemented to generate a more complete set of scenarios for requirements based programming. More specifically, a CSP-based, syntax-oriented model construction, which requires the support of a theorem prover, is complemented by model extrapolation, via automata learning. This may support the systematic completion of the requirements, the nature of the requirement being partial, which provides focus on the most prominent scenarios. This may generalize requirement skeletons by extrapolation and may indicate by way of automatically generated traces where the requirement specification is too loose and additional information is required.

  14. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity

    Directory of Open Access Journals (Sweden)

    Marcela V Maus

    2016-01-01

    Full Text Available Chimeric antigen receptors (CARs are synthetic receptors that usually redirect T cells to surface antigens independent of human leukocyte antigen (HLA. Here, we investigated a T cell receptor-like CAR based on an antibody that recognizes HLA-A*0201 presenting a peptide epitope derived from the cancer-testis antigen NY-ESO-1. We hypothesized that this CAR would efficiently redirect transduced T cells in an HLA-restricted, antigen-specific manner. However, we found that despite the specificity of the soluble Fab, the same antibody in the form of a CAR caused moderate lysis of HLA-A2 expressing targets independent of antigen owing to T cell avidity. We hypothesized that lowering the affinity of the CAR for HLA-A2 would improve its specificity. We undertook a rational approach of mutating residues that, in the crystal structure, were predicted to stabilize binding to HLA-A2. We found that one mutation (DN lowered the affinity of the Fab to T cell receptor-range and restored the epitope specificity of the CAR. DN CAR T cells lysed native tumor targets in vitro, and, in a xenogeneic mouse model implanted with two human melanoma lines (A2+/NYESO+ and A2+/NYESO−, DN CAR T cells specifically migrated to, and delayed progression of, only the HLA-A2+/NY-ESO-1+ melanoma. Thus, although maintaining MHC-restricted antigen specificity required T cell receptor-like affinity that decreased potency, there is exciting potential for CARs to expand their repertoire to include a broad range of intracellular antigens.

  15. The specific radioimmunoassay in pharmacokinetics: potency, requirements and development for routine use as illustrated with an assay for Pirenzepin

    International Nuclear Information System (INIS)

    Bozler, G.

    1977-01-01

    Requirements for using RIA in pharmacokinetics are specified. An assay system developed for Pirenzepin was used as example to illustrate the general strategy striving mainly for specificity, sensitivity and reliability. The type of error in the final data is considered. It is a widespread assumption that weak crossreactions with metabolites result in a 'relative' error and, therefore, don't have relevance for the determination of the parent drug. In contrast, it was shown for biological samples that such weak crossreactivity gives rise to a concentration independent (absolute) error, which is analogous to that caused by a 'blank value' in chemical analysis. (orig.) [de

  16. Gia/Mthl5 is an aorta specific GPCR required for Drosophila heart tube morphology and normal pericardial cell positioning.

    Science.gov (United States)

    Patel, Meghna V; Zhu, Jun-Yi; Jiang, Zhiping; Richman, Adam; VanBerkum, Mark F A; Han, Zhe

    2016-06-01

    G-protein signaling is known to be required for cell-cell contacts during the development of the Drosophila dorsal vessel. However, the identity of the G protein-coupled receptor (GPCR) that regulates this signaling pathway activity is unknown. Here we describe the identification of a novel cardiac specific GPCR, called Gia, for "GPCR in aorta". Gia is the only heart-specific GPCR identified in Drosophila to date and it is specifically expressed in cardioblasts that fuse at the dorsal midline to become the aorta. Gia is the only Drosophila gene so far identified for which expression is entirely restricted to cells of the aorta. Deletion of Gia led to a broken-hearted phenotype, characterized by pericardial cells dissociated from cardioblasts and abnormal distribution of cell junction proteins. Both phenotypes were similar to those observed in mutants of the heterotrimeric cardiac G proteins. Lack of Gia also led to defects in the alignment and fusion of cardioblasts in the aorta. Gia forms a protein complex with G-αo47A, the alpha subunit of the heterotrimeric cardiac G proteins and interacts genetically with G-αo47A during cardiac morphogenesis. Our study identified Gia as an essential aorta-specific GPCR that functions upstream of cardiac heterotrimeric G proteins and is required for morphological integrity of the aorta during heart tube formation. These studies lead to a redefinition of the bro phenotype, to encompass morphological integrity of the heart tube as well as cardioblast-pericardial cell spatial interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Timing of Tissue-specific Cell Division Requires a Differential Onset of Zygotic Transcription during Metazoan Embryogenesis*

    Science.gov (United States)

    Wong, Ming-Kin; Guan, Daogang; Ng, Kaoru Hon Chun; Ho, Vincy Wing Sze; An, Xiaomeng; Li, Runsheng; Ren, Xiaoliang

    2016-01-01

    Metazoan development demands not only precise cell fate differentiation but also accurate timing of cell division to ensure proper development. How cell divisions are temporally coordinated during development is poorly understood. Caenorhabditis elegans embryogenesis provides an excellent opportunity to study this coordination due to its invariant development and widespread division asynchronies. One of the most pronounced asynchronies is a significant delay of cell division in two endoderm progenitor cells, Ea and Ep, hereafter referred to as E2, relative to its cousins that mainly develop into mesoderm organs and tissues. To unravel the genetic control over the endoderm-specific E2 division timing, a total of 822 essential and conserved genes were knocked down using RNAi followed by quantification of cell cycle lengths using in toto imaging of C. elegans embryogenesis and automated lineage. Intriguingly, knockdown of numerous genes encoding the components of general transcription pathway or its regulatory factors leads to a significant reduction in the E2 cell cycle length but an increase in cell cycle length of the remaining cells, indicating a differential requirement of transcription for division timing between the two. Analysis of lineage-specific RNA-seq data demonstrates an earlier onset of transcription in endoderm than in other germ layers, the timing of which coincides with the birth of E2, supporting the notion that the endoderm-specific delay in E2 division timing demands robust zygotic transcription. The reduction in E2 cell cycle length is frequently associated with cell migration defect and gastrulation failure. The results suggest that a tissue-specific transcriptional activation is required to coordinate fate differentiation, division timing, and cell migration to ensure proper development. PMID:27056332

  18. Frequency of Finding Family Donors: A Single Center Experience.

    Science.gov (United States)

    Kasar, Mutlu; Yeral, Mahmut; Solmaz, Soner; Büyükkurt, Nurhilal; Asma, Suheyl; Gereklioğlu, Çiğdem; Boğa, Can; Özdoğu, Hakan; Baştürk, Bilkay

    2018-03-01

    Allogeneic hematopoietic stem cell transplant is a curative treatment option for many hematologic diseases. The existence of a fully compatible donor for recipients is the first condition for minimized transplant-related mortality and morbidity. The best donor for hematopoietic stem cell transplant is an HLA-matched sibling donor. The possibility of finding an HLA-matched sibling is less than 30% worldwide. Hematopoietic stem cell transplant is needed for an increasing number of patients every year, but the ability to find a fully compatible donor has limited its use. From August 2012 to May 2017, we screened 412 adult patients who required AHSCT and their families for HLA tissue groups who were seen at our center (Baskent University Adana Dr. Turgut Noyan Research and Medical Center Hematology Unit). To screen tissue groups at our center, we perform lowresolution typing for HLA-A, -B, -C, -DRB1, and -DQB. If an HLA genotype cannot be identified, verification typing is done using highresolution testing. We found matched family donors in 227 (55%) of 412 patients screened at our center. The ratio of HLAmatched related donors was 83% for 279 patients who received allogeneic stem cell transplant. The likelihood of finding eligible unrelated donors has been gradually increasing, in part due to the development of the National Bone Marrow Bank. However, a careful screening for related donors is still important. Our findings indicate the importance of careful examination of family genealogy and of careful family screening in our region.

  19. Evaluation of the Medically Complex Living Kidney Donor

    Directory of Open Access Journals (Sweden)

    Yasar Caliskan

    2012-01-01

    Full Text Available Due to organ shortage and difficulties for availability of cadaveric donors, living donor transplantation is an important choice for having allograft. Live donor surgery is elective and easier to organize prior to starting dialysis thereby permitting preemptive transplantation as compared to cadaveric transplantation. Because of superior results with living kidney transplantation, efforts including the usage of “Medically complex living donors” are made to increase the availability of organs for donation. The term “Complex living donor” is probably preferred for all suboptimal donors where decision-making is a problem due to lack of sound medical data or consensus guidelines. Donors with advanced age, obesity, asymptomatic microhematuria, proteinuria, hypertension, renal stone disease, history of malignancy and with chronic viral infections consist of this complex living donors. This medical complex living donors requires careful evaluation for future renal risk. In this review we would like to present the major issues in the evaluation process of medically complex living kidney donor.

  20. International collaborative donor project.

    Science.gov (United States)

    Ríos Zambudio, Antonio

    2018-02-01

    The International Donor Collaborative Project (PCID) research group was created in 1996 in Spain with the aim of promoting research in the field of organ donation and transplantation, led by Spanish surgeons. During this period they have developed the questionnaires of the PCID, both the attitude towards cadaver and live donation, which are the most used questionnaires in publications in indexed journals. They have been the driving group of stratified studies representative of the populations under study, and of the performance of multivariate statistical analyzes in the field of psycho-social research in organ donation and transplantation. The main contributions of the group focus on the analysis of health center professionals and emerging migrant groups. In recent years, studies have been extended to the United States, Latin America (mainly Mexico) and Europe. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Lung procurement for transplantation: new criteria for lung donor selection.

    Science.gov (United States)

    Moretti, M P; Betto, C; Gambacorta, M; Vesconi, S; Scalamogna, M; Benazzi, E; Ravini, M

    2010-05-01

    In Italy, like everywhere in the world, the organ shortage for transplantation is a real problem. It is well known that lung donors (LD) are particularly difficult to procure and that management of the organ do not care during the diagnosis of cerebral death represents a difficult challenge. In this context, the salvage of the so-called "marginal donors" may increase the pool of donors, favoring organ retrieval. To increase lung procurement, the intensivist must recognize "marginal donors," optimizing organ selection and function. The aim of our study was to review LD procured in 2008, as identified by the unrestricted criteria, of the Nord Italian Transplant program Center (NITp). Particularly, the age and habits of donors and the presence of a parenchyma contusion were not sufficient per se to exclude donation. We revisited lung ventilation and monitoring modalities during cerebral death before retrieval. In 2008, the application of enlarged criteria for LD enabled us to collect 21 LD, namely 33% of all cerebral deaths, versus 13% in 2007. Seeking to maintain good gas exchange and lung function, we implemented a safe ventilation program avoided high peak pressures, and fluid therapy properly guided by the cardiac index and extravascular lung water index monitoring. Specific actions to improve LD procurement may help cope with the organ-donor shortage. Although our series was small, our results were encouraging; they underline the necessity to continuously review donor criteria and care, allowing good donor/recipient matching. Copyright (c) 2010. Published by Elsevier Inc.

  2. Combinatorial Modulation of Signaling Pathways Reveals Cell-Type-Specific Requirements for Highly Efficient and Synchronous iPSC Reprogramming

    Directory of Open Access Journals (Sweden)

    Simon E. Vidal

    2014-10-01

    Full Text Available The differentiated state of somatic cells provides barriers for the derivation of induced pluripotent stem cells (iPSCs. To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. Surprisingly, inhibition of transforming growth factor β (TGF-β together with activation of Wnt signaling in the presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after 1 week of reprogramming factor expression. In contrast, hepatic and blood progenitors predominantly required only TGF-β inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner, and we demonstrate that expression of specific chromatin-modifying enzymes and reduced TGF-β/mitogen-activated protein (MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Our observations define cell-type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

  3. A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition.

    Directory of Open Access Journals (Sweden)

    David Lutje Hulsik

    2013-03-01

    Full Text Available The membrane proximal external region (MPER of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH, 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10.

  4. Donor selection criteria and procurement

    International Nuclear Information System (INIS)

    Agcaoili, N.R.

    1999-01-01

    Donor selection is one of the most important aspects of tissue banking practice. Without a good donor selection criteria, the results of any effort of trying to preserve tissues will have disastrous outcome for the recipient of these tissues. While with a very good and strict donor selection the Tissue Bank can guarantee safe and effective tissue allografts. There are significant aspects in the history and physical examination of the donor that must be emphasized. A donor exclusion criteria has also been formulated together with a list of all the needed laboratory examinations to eliminate possible diseases that may be transferred from the donor. The methods of procurement of tissue allografts from living and cadaver donors will be described. The limitations and advantages of each will be taken.There are also special restrictions that are important in the practice of removing the tissues from the donors. All the necessary equipment should be ready and the potential risk on the personnel should be known to all doing Tissue Banking

  5. Determine The Factors Affecting The Blood Donors Of Selecting Blood Donor Program Me In Western Province Sri Lanka

    Directory of Open Access Journals (Sweden)

    Perera D. A. K.

    2015-08-01

    Full Text Available Abstract Blood and blood component transfusion is one of the major therapeutic practices throughout the world. National Blood Transfusion Service NBTS in Sri Lanka requires approximately 300000 blood units annually. After initiating mobile donor programme there have been two types of blood donation programs in Sri Lanka since 1980. Since second half of first decade of 21st century Sri Lanka shifted to 100 non-replacement blood transfusion policy. That means whole blood and blood component requirement of NBTS has to be collected through mobile blood donor program and voluntary In-house blood donor program. Therefore the objective of this study was to determine the factors affecting the blood donors of selecting blood donor program in Western province Sri Lanka. Methodology This was a cross sectional descriptive study. The study composed of two components. .First the factors that cause the blood donor to select a blood donor programme second the facility survey of blood banks In-house donation. An interviewer administered questionnaire was used to collect data from a sample of 410 Mobile blood donors. Facility survey was done using a checklist. The dependant variables were the attendance of the blood donors to Mobile blood donation and In-house blood donation. Independent variables included were the factors related to socio demography service quality accessibility availability and intrinsic extrinsic motivation. The analytical statistics applied for testing the association of factors with the blood donor programme was chi-square test. The study has shown some important findings. There was significant association between income level and donating blood. Only 3.3 of In-house blood donor population was female. Majority of In-house population belonged to 30-41 age group. A statistically significant association exists between age and repeat blood donation. The female blood donors tendency of becoming repeat donors was very low. Distance problem and non

  6. Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system.

    Science.gov (United States)

    Koudelka, Juraj; Horn, Jacqueline M; Vatanashevanopakorn, Chinnavuth; Minichiello, Liliana

    2014-09-26

    Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment.

  7. Heart transplantation from older donors

    Directory of Open Access Journals (Sweden)

    V. N. Poptsov

    2017-01-01

    Full Text Available In the current situation of the shortage of suitable donor organs, heart transplantation from older donors is one of the ways to increase the performance of more heart transplants, particularly, in patients with urgent need of transplantation. While planning a heart transplantation from older donor one should consider increased risk of early cardiac allograft dysfunction, preexisting coronary artery disease, accelerated transplant vasculopathy which may adversely affect early and long-term survival of recipients. Subject to careful selection of donor–recipient pairs, effective prevention and treatment of early cardiac allograft dysfunction, pre-existing atherosclerosis and transplant vasculopathy the early and long-term survival of heart transplant recipients from older donors is comparable to heart transplantation from young donors.

  8. Antibody levels correlate with detection of Trypanosoma cruzi DNA by sensitive PCR assays in seropositive blood donors and possible resolution of infection over time

    Science.gov (United States)

    Sabino, E.C.; Lee, T.H.; Montalvo, L.; Nguyen, M.L.; Leiby, D.A.; Carrick, D.M.; Otani, M.M.; Vinelli, E.; Wright, D.; Stramer, S.L.; Busch, M.

    2013-01-01

    Background The clinical significance of anti-T. cruzi low-level reactive samples is incompletely understood. PCR-positive rates and antibody levels among seropositive blood donors in three countries are described. Methods Follow-up whole blood and plasma samples were collected from T. cruzi-seropositive donors from 2008-2010 in the US (n=195) and Honduras (n=58). Also 143 samples from Brazil in 1996-2002, originally positive by three serological assays, were available and paired with contemporary follow-up samples from these donors. All samples were retested with the FDA-approved Ortho ELISA. PCR assays were performed on coded sample panels by two laboratories (BSRI and ARC) that amplified kinetoplast minicircle DNA sequences of T. cruzi. Results PCR testing at BSRI yielded slightly higher overall sensitivity and specificity (33% and 98%) compared with the ARC lab (28% and 94%). Among seropositive donors, PCR-positive rates varied by country (p<0.0001) for the BSRI laboratory: Brazil (57%), Honduras (32%) and the US (14%). ELISA signal/cutoff (S/CO) ratios were significantly higher for PCR-positive compared to PCR-negative donors (p<0.05 for all comparisons). Additionally, PCR-negative Brazilian donors exhibited greater frequencies of antibody decline over time versus PCR-positive donors (p=0.003). Conclusion For all three countries, persistent DNA positivity correlated with higher ELISA S/CO values, suggesting that high-level seroreactivity reflects chronic parasitemia. The higher rate of PCR positivity for Brazilian donors was likely attributable to required reactivity on three assays available a decade ago. Significant S/CO declines in 10% of the PCR-negative Brazilian donors may indicate seroreversion following parasite clearance in the absence of treatment. PMID:23002996

  9. High-field EPR spectroscopy of thermal donors in silicon

    DEFF Research Database (Denmark)

    Dirksen, R.; Rasmussen, F.B.; Gregorkiewicz, T.

    1997-01-01

    Thermal donors generated in p-type boron-doped Czochralski-grown silicon by a 450 degrees C heat treatment have been studied by high-field magnetic resonance spectroscopy. In the experiments conducted at a microwave frequency of 140 GHz and in a magnetic field of approximately 5 T four individual...... thermal donors species could be resolved. These were observed in their singly ionized TD+ charge state. For the first time in the four decades of thermal donor research the g tensor values for specific members of the Si-NL8 family are given. Also the symmetry of the observed species is discussed....

  10. The History and Challenges of Blood Donor Screening in China.

    Science.gov (United States)

    Li, Ling; Li, Ka Yi; Yan, Ke; Ou, Guojin; Li, Wenhui; Wang, Jue; Song, Ning; Tian, Li; Ji, Xin; Chen, Yongjun; Liang, Xiaohua; Liu, Zhong; Wu, Yanyun

    2017-04-01

    Since the establishment of People's Republic of China in 1949, the Chinese government has encountered several catastrophes related to transfusion transmitted diseases. The government's increasing attention to blood safety has prompted the initiation of a series of policies and measures that have enhanced the level of safety for the blood supply and met the basic clinical demands of blood for 1.3 billion people in the country. Blood donation screening strategies in China predominantly comprise donor screening and donor testing. Donor screening includes selection of low-risk blood donors by the use of a donor history questionnaire, predonation physical examination, and initial rapid donor testing. Donor testing includes direct pathogen detection and serology tests. The year 1998 marked the most transformative change in blood donor selection and screening policies in China. Before 1998, paid donation was the predominant mode of blood donation. Donor screening and donor testing were conducted before donation, and only those who were eligible were allowed to donate. To ensure the safety of blood, donor testing was performed again after donation. After the implementation of the Blood Donation Law in 1998, to promote voluntary and unpaid donation, predonation donor testing was eliminated to reduce the amount of waiting time and to provide a more convenient donation experience for blood donors. However, it is the national requirement that donated blood should undergo 2 rounds of testing using different equipment or reagents, conducted by different personnel. Donor selection has transitioned from paid donation and obligatory donation to voluntary donation with fixed volunteer groups, as the latter mode of donation provides the lowest risks. Donations are currently screened for syphilis, hepatitis C virus, HIV, and hepatitis B virus (HBV). Units, previously typed only for ABO, are now routinely tested for both ABO and Rh(D). Innovations in testing technologies and methods

  11. Mutual tolerance after liver and not after heart transplantation? Evaluation of patient-anti-donor and donor-anti-patient responses by mixed lymphocyte culture

    NARCIS (Netherlands)

    van der Mast, BJ; van Besouw, NM; Hepkema, BG; Weimar, W; van de Berg, AP; Slooff, MJH; Claas, FHJ

    The ultimate goal in organ transplantation is the induction of donor-specific transplantation tolerance. The fact that in some patients it is possible to withdraw immunosuppressive therapy completely, suggests that immunological adaptation or donor-specific nonresponsiveness can occur following

  12. Depletion of host CCR7(+) dendritic cells prevented donor T cell tissue tropism in anti-CD3-conditioned recipients.

    Science.gov (United States)

    He, Wei; Racine, Jeremy J; Johnston, Heather F; Li, Xiaofan; Li, Nainong; Cassady, Kaniel; Liu, Can; Deng, Ruishu; Martin, Paul; Forman, Stephen; Zeng, Defu

    2014-07-01

    We reported previously that anti-CD3 mAb treatment before hematopoietic cell transplantation (HCT) prevented graft-versus-host disease (GVHD) and preserved graft-versus-leukemia (GVL) effects in mice. These effects were associated with downregulated donor T cell expression of tissue-specific homing and chemokine receptors, marked reduction of donor T cell migration into GVHD target tissues, and deletion of CD103(+) dendritic cells (DCs) in mesenteric lymph nodes (MLN). MLN CD103(+) DCs and peripheral lymph node (PLN) DCs include CCR7(+) and CCR7(-) subsets, but the role of these DC subsets in regulating donor T cell expression of homing and chemokine receptors remain unclear. Here, we show that recipient CCR7(+), but not CCR7(-), DCs in MLN induced donor T cell expression of gut-specific homing and chemokine receptors in a retinoid acid-dependent manner. CCR7 regulated activated DC migration from tissue to draining lymph node, but it was not required for the ability of DCs to induce donor T cell expression of tissue-specific homing and chemokine receptors. Finally, anti-CD3 treatment depleted CCR7(+) but not CCR7(-) DCs by inducing sequential expansion and apoptosis of CCR7(+) DCs in MLN and PLN. Apoptosis of CCR7(+) DCs was associated with DC upregulation of Fas expression and natural killer cell but not T, B, or dendritic cell upregulation of FasL expression in the lymph nodes. These results suggest that depletion of CCR7(+) host-type DCs, with subsequent inhibition of donor T cell migration into GVHD target tissues, can be an effective approach in prevention of acute GVHD and preservation of GVL effects. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  13. Voluntary whole-blood donors, and compensated platelet donors and plasma donors: motivation to donate, altruism and aggression.

    Science.gov (United States)

    Trimmel, Michael; Lattacher, Helene; Janda, Monika

    2005-10-01

    To establish if voluntary whole-blood donors and compensated platelet donors and plasma donors may differ in their motivation to donate, altruism, aggression and autoaggression. Whole-blood (n=51), platelet (n=52) and plasma donors (n=48) completed a battery of validated questionnaires while waiting to donate. Bivariate and multivariate analyses of variance and t-tests were performed to detect differences between groups as noted. Altruism (mean=40.2) was slightly higher in whole-blood donors than in platelet (mean=38.3) and plasma donors (mean=39.1) (p=0.07). Blood donors (mean=2.8) scored lower in the spontaneous aggression measure than platelet (mean=4.1) and plasma donors (mean=4.4) (p=0.01). Plasma donors (mean=4.9) had higher auto-aggression than whole-blood donors and platelet donors (mean for both groups=3.4) (p=0.01). Differences between the three groups were mediated by sociodemographic variables (MANCOVA). Whole-blood donors donated to help others, platelet and plasma donors mostly to receive the compensation. However, those platelet and plasma donors, who would continue to donate without compensation were similar in altruism and aggression to whole-blood donors. While most platelet donors and plasma donors were motivated by the compensation, those who stated that they would continue to donate without compensation had altruism and aggression scores similar to voluntary whole-blood donors.

  14. Distinct requirements for cranial ectoderm and mesenchyme-derived wnts in specification and differentiation of osteoblast and dermal progenitors.

    Science.gov (United States)

    Goodnough, L Henry; Dinuoscio, Gregg J; Ferguson, James W; Williams, Trevor; Lang, Richard A; Atit, Radhika P

    2014-02-01

    The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation.

  15. Alloantigen-specific suppressor T cells are not inhibited by cyclosporin A, but do require IL 2 for activation

    International Nuclear Information System (INIS)

    Bucy, R.P.

    1986-01-01

    Alloantigen-specific suppressor T cells are activated from normal murine spleen cells in mixed lymphocyte reactions (MLR). These T cells are radioresistant and suppress the activation of cytotoxic T lymphocytes (CTL) in second primary MLR cultures. This report demonstrates that cyclosporin A (CsA) blocks the activation of these suppressor cells at a dose of 1 microgram/ml. However, reconstitution of CsA blocked cultures with IL 2 restores the activation of the suppressor T cells, but fails to significantly restore the activation of CTL in these same cultures. This differential activation requirement was used to establish T cell lines that demonstrate enriched suppressor cell activity but depletion of CTL activity. These findings are discussed in terms of the mechanism of action of CsA in these distinct T cell subsets and the relevance to models of allograft unresponsiveness

  16. Alloantigen-specific CD4(+) regulatory T cells induced in vivo by ultraviolet irradiation after alloantigen immunization require interleukin-10 for their induction and activation, and flexibly mediate bystander immunosuppression of allograft rejection.

    Science.gov (United States)

    Hori, Tomohide; Kuribayashi, Kagemasa; Saito, Kanako; Wang, Linan; Torii, Mie; Uemoto, Shinji; Kato, Takuma

    2015-06-01

    Ultraviolet (UV) irradiation prior to antigen immunization is employed to induce antigen-specific regulatory T cells (Tregs). UV-induced Tregs demonstrate unique bystander suppression, although antigen-specific activation is required initially. We previously reported the phenotype of alloantigen-specific transferable Tregs induced by UV-B irradiation after immunization was the same as T regulatory type 1-like CD4(+) T cells, with antigen-specific interleukin (IL)-10 production. Here, by using semi-allogeneic transplantation models in vivo, we investigated the role of IL-10 in the induction and activation of these Tregs, and the possibility of bystander suppression of third-party allograft rejection. Naïve mice (H-2(b)) were immunized with alloantigen (H-2(b/d)), and received UV-B irradiation (40 kJ/m(2)) 1 week later. Four weeks afterwards, splenic CD4(+) T cells were purified from the UV-irradiated immunized mice, and were transferred into naïve mice (H-2(b)). Allografts expressing the same alloantigen as T-cell donors were immunized against (H-2(b/d)) or an irrelevant alloantigen (H-2(b/k)) were transplanted to CD4(+) T-cell-transferred mice, and an alloantigen-specific prolongation of allograft survival observed. Experiments where IL-10 was neutralized by monoclonal antibody in the induction or effector phase revealed that IL-10 is critical, not only for induction but also for immunosuppressive function of CD4(+) Tregs induced by UV irradiation after alloantigen immunization. Third-party allografts (H-2(d/k)) were transplanted to CD4(+) T-cell-transferred mice, and graft survival was also prolonged. Even a graft only partially compatible with immunized alloantigen worked well in vivo to activate CD4(+) Tregs induced by UV irradiation after alloantigen immunization, which resulted in the bystander suppression of third-party allograft rejection. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Technical Specification action statements requiring shutdown. A risk perspective with application to the RHR/SSW systems of a BWR

    Energy Technology Data Exchange (ETDEWEB)

    Mankamo, T. [Avaplan Oy, Espoo (Finland); Kim, I.S.; Samanta, P.K. [Brookhaven National Lab., Upton, NY (United States)

    1993-11-01

    When safety systems fail during power operation, the limiting conditions for operation (LCOs) and associated action statements of technical specifications typically require that the plant be shut down within the limits of allowed outage time (AOT). However, when a system needed to remove decay heat, such as the residual heat removal (RHR) system, is inoperable or degraded, shutting down the plant may not necessarily be preferable, from a risk perspective, to continuing power operation over a usual repair time, giving priority to the repairs. The risk impact of the basic operational alternatives, i.e., continued operation or shutdown, was evaluated for failures in the RHR and standby service water (SSW) systems of a boiling-water reactor (BWR) nuclear power plant. A complete or partial failure of the SSW system fails or degrades not only the RHR system but other front-line safety systems supported by the SSW system. This report presents the methodology to evaluate the risk impact of LCOs and associated AOT; the results of risk evaluation from its application to the RHR and SSW systems of a BWR; the findings from the risk-sensitivity analyses to identify alternative operational policies; and the major insights and recommendations to improve the technical specifications action statements.

  18. ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons.

    Science.gov (United States)

    May, Melanie; Hwang, Kyu-Seok; Miles, Judith; Williams, Charlie; Niranjan, Tejasvi; Kahler, Stephen G; Chiurazzi, Pietro; Steindl, Katharina; Van Der Spek, Peter J; Swagemakers, Sigrid; Mueller, Jennifer; Stefl, Shannon; Alexov, Emil; Ryu, Jeong-Im; Choi, Jung-Hwa; Kim, Hyun-Taek; Tarpey, Patrick; Neri, Giovanni; Holloway, Lynda; Skinner, Cindy; Stevenson, Roger E; Dorsky, Richard I; Wang, Tao; Schwartz, Charles E; Kim, Cheol-Hee

    2015-09-01

    Miles-Carpenter syndrome (MCS) was described in 1991 as an XLID syndrome with fingertip arches and contractures and mapped to proximal Xq. Patients had microcephaly, short stature, mild spasticity, thoracic scoliosis, hyperextendable MCP joints, rocker-bottom feet, hyperextended elbows and knees. A mutation, p.L66H, in ZC4H2, was identified in a XLID re-sequencing project. Additional screening of linked families and next generation sequencing of XLID families identified three ZC4H2 mutations: p.R18K, p.R213W and p.V75in15aa. The families shared some relevant clinical features. In silico modeling of the mutant proteins indicated all alterations would destabilize the protein. Knockout mutations in zc4h2 were created in zebrafish and homozygous mutant larvae exhibited abnormal swimming, increased twitching, defective eye movement and pectoral fin contractures. Because several of the behavioral defects were consistent with hyperactivity, we examined the underlying neuronal defects and found that sensory neurons and motoneurons appeared normal. However, we observed a striking reduction in GABAergic interneurons. Analysis of cell-type-specific markers showed a specific loss of V2 interneurons in the brain and spinal cord, likely arising from mis-specification of neural progenitors. Injected human wt ZC4H2 rescued the mutant phenotype. Mutant zebrafish injected with human p.L66H or p.R213W mRNA failed to be rescued, while the p.R18K mRNA was able to rescue the interneuron defect. Our findings clearly support ZC4H2 as a novel XLID gene with a required function in interneuron development. Loss of function of ZC4H2 thus likely results in altered connectivity of many brain and spinal circuits. © The Author 2015. Published by Oxford University Press.

  19. South Korea as an emerging donor

    DEFF Research Database (Denmark)

    Chun, Hong-Min; Munyi, Elijah Nyaga; Lee, Heejin

    2010-01-01

    South Korea's official development assistance (ODA) has been increasing rapidly and will continue to do so. Korea is one of the few countries which have successfully transitioned from a recipient to a donor. It became a member of DAC (development assistance committee), OECD in November 2009. Korea......'s ODA policy, along with its growth in quantity, is at a crossroads for the enhancement of its quality. Discussions and debates are going on regarding the reforms in Korea's ODA activities, and this paper examines key issues raised. It first reviews the past and present of Korea's ODA, and identifies...... like the objective of ODA, positioning of Korea's ODA as an emerging donor and the nature of aid to North Korea. We also argue that a shift of ODA policy is required to promote reform, based on a thorough reflection on the role of ODA in the alleviation of poverty and promoting sustainable development...

  20. Transport Measurements on Si Nanostructures with Counted Sb Donors

    Science.gov (United States)

    Singh, Meenakshi; Bielejec, Edward; Garratt, Elias; Ten Eyck, Gregory; Bishop, Nathaniel; Wendt, Joel; Luhman, Dwight; Carroll, Malcolm; Lilly, Michael

    2014-03-01

    Donor based spin qubits are a promising platform for quantum computing. Single qubits using timed implant of donors have been demonstrated.1 Extending this to multiple qubits requires precise control over the placement and number of donors. Such control can be achieved by using a combination of low-energy heavy-ion implants (to reduce depth straggle), electron-beam lithography (to define position), focused ion beam (to localize implants to one lithographic site) and counting the number of implants with a single ion detector.2 We report transport measurements on MOS quantum dots implanted with 5, 10 and 20 Sb donors using the approach described above. A donor charge transition is identified by a charge offset in the transport characteristics. Correlation between the number of donors and the charge offsets is studied. These results are necessary first steps towards fabricating donor nanostructures for two qubit interactions. This work was performed, in part, at the Center for Integrated Nanotechnologies, a U.S. DOE Office of Basic Energy Sciences user facility. The work was supported by Sandia National Laboratories Directed Research and Development Program. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the U. S. Department of Energy under Contract No. DE-AC04-94AL85000. 1J. J. Pla et al., Nature 496, 334 (2013) 2J. A. Seamons et al., APL 93, 043124 (2008).

  1. The impact of accepting living kidney donors with mild hypertension or proteinuria on transplantation rates.

    Science.gov (United States)

    Karpinski, Martin; Knoll, Greg; Cohn, Adam; Yang, Robert; Garg, Amit; Storsley, Leroy

    2006-02-01

    As waiting times for kidney transplantation increase, individuals with hypertension or proteinuria may be considered as eligible living donors. We set out to determine how frequently donors are excluded because of hypertension or proteinuria and to what extent accepting such donors would increase transplantation rates. Wait lists from 4 Canadian transplantation centers were examined for causes of living kidney donor exclusion. Donors with hypertension (clinic blood pressure >140/90 mm Hg or requiring antihypertensive medication) or proteinuria historically have been excluded at these centers. We define potentially acceptable hypertension as a clinic blood pressure less than 150/100 mm Hg or less than 140/90 mm Hg if administered a single antihypertensive medication and define acceptable proteinuria as protein of 0.15 to 0.3 g/d. Only 35% (124 of 352 patients) of wait-listed patients had a living donor evaluated (n = 180 potential donors). Primary reasons for donor exclusion were immunologic: a positive cross-match (32%; n = 59) or blood group type incompatibility (22%; n = 40). Hypertension or proteinuria were less common (17%; n = 31). Of 31 donors excluded for hypertension or proteinuria, only 13 had results in the acceptable range. Acceptance of these donors would have resulted in transplantation of 3% (12 of 352 patients) of the wait-list population. Accepting living donors with mild hypertension and proteinuria will lead to a slight increase in transplantation rates. Efforts to improve living donor awareness and overcome immunologic barriers to transplantation may have a greater impact.

  2. Effects of donor proliferation in development aid for health on health program performance: A conceptual framework.

    Science.gov (United States)

    Pallas, Sarah Wood; Ruger, Jennifer Prah

    2017-02-01

    Development aid for health increased dramatically during the past two decades, raising concerns about inefficiency and lack of coherence among the growing number of global health donors. However, we lack a framework for how donor proliferation affects health program performance to inform theory-based evaluation of aid effectiveness policies. A review of academic and gray literature was conducted. Data were extracted from the literature sample on study design and evidence for hypothesized effects of donor proliferation on health program performance, which were iteratively grouped into categories and mapped into a new conceptual framework. In the framework, increases in the number of donors are hypothesized to increase inter-donor competition, transaction costs, donor poaching of recipient staff, recipient control over aid, and donor fragmentation, and to decrease donors' sense of accountability for overall development outcomes. There is mixed evidence on whether donor proliferation increases or decreases aid volume. These primary effects in turn affect donor innovation, information hoarding, and aid disbursement volatility, as well as recipient country health budget levels, human resource capacity, and corruption, and the determinants of health program performance. The net effect of donor proliferation on health will vary depending on the magnitude of the framework's competing effects in specific country settings. The conceptual framework provides a foundation for improving design of aid effectiveness practices to mitigate negative effects from donor proliferation while preserving its potential benefits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Donor deferral due to anemia: A tertiary care center-based study

    Directory of Open Access Journals (Sweden)

    Bahadur Shalini

    2011-01-01

    Full Text Available Background: The minimum hemoglobin cutoff for blood donation in India is 12.5 gm% for both male and female donors and the minimum donation interval is 3 months. Donation of one unit of blood results in decrease in hemoglobin by 1 gm% and loss of 200-250 mg of iron. Donor deferral due to anemia is one of the major reasons of temporary rejection of blood donors. In the absence of further workup or advise, it results in loss of valuable donor base. Aim and Objective: To provide baseline information regarding the prevalence and spectrum of anemia in prospective blood donors to help plan a future strategy for donor management. Materials and Methods: Hemoglobin testing of donors was performed using Hemocue and Copper sulfate specific gravity method. Ethylene diamine tetraacetic acid sample of all the donors who failed either or both the screening tests was tested on automated analyzer for evaluation of hemoglobin and red blood cell indices. Results: Of all the donors, 15.5% were deferred due to anemia. Prevalence of anemia in prospective blood donors was 1.8%. It was significantly higher in female donors compared with male donors (34.2% vs 1.2%. The most common type of anemia was normocytic normochromic.

  4. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

    Rigas, A S; Pedersen, O B; Magnussen, K

    2017-01-01

    and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark......, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels....

  5. Research Award: Donor Partnerships Division

    International Development Research Centre (IDRC) Digital Library (Canada)

    Corey Piccioni

    2013-08-07

    . The successful candidate must be willing to work as a member of the DPD team in its ongoing acvies, including providing research analysis and coordinang the producon and disseminaon of informaon related to donor.

  6. Shielding requirements for diagnostic and therapeutic X-ray apparatus in South Australia: regulatory requirements, specifications and assessment of X-ray rooms

    International Nuclear Information System (INIS)

    Bibbo, G.

    1988-01-01

    In South Australia the shielding requirements for diagnostic and therapeutic x-ray apparatus depend on the maximum power output of the equipment regardless of workload, usage or occupancy. The method of calculating the required shielding is discussed and the procedure for assessing the degree of radiation protection of the x-ray room once the apparatus has been installed is outlined

  7. Donor's understanding of the definition of sex as applied to predonation screening questions.

    Science.gov (United States)

    O'Brien, S F; Ram, S S; Yi, Q-L; Goldman, M

    2008-05-01

    Predonation screening questions about sexual risk factors should provide an extra layer of safety from recently acquired infections that may be too early to be detected by testing. Donors are required to read a definition of sex as it applies to predonation screening questions each time they come to donate, but how well donors apply such definitions has not been evaluated. We aimed to determine how donors define sex when answering screening questions. In total, 1297 whole blood donors were asked in a private interview to select from a list of sexual activities which ones they believed were being asked about in sexual background questions. Donors' definitions were coded as under-inclusive, correct or over-inclusive in relation to the blood services' definition. Qualitative interviews were carried out with 21 donors to understand reasoning behind definitions. Most donors had an over-inclusive definition (58.7%) or the correct definition (31.9%). Of the 9.4% of donors who had an under-inclusive definition, 95% included both vaginal and anal sex, but not oral sex. About 9% in each group were first-time donors (P > 0.05) who had never read the definition. The qualitative interviews indicated that donors reason their definition based on their own concept of transmissible disease risk. Donors apply a range of definitions of sex when answering questions about their sexual background. This may be due to different concepts of risk activities, and required reading of the definition has little impact.

  8. Bartonella spp. bacteremia in blood donors from Campinas, Brazil.

    Directory of Open Access Journals (Sweden)

    Luiza Helena Urso Pitassi

    2015-01-01

    Full Text Available Bartonella species are blood-borne, re-emerging organisms, capable of causing prolonged infection with diverse disease manifestations, from asymptomatic bacteremia to chronic debilitating disease and death. This pathogen can survive for over a month in stored blood. However, its prevalence among blood donors is unknown, and screening of blood supplies for this pathogen is not routinely performed. We investigated Bartonella spp. prevalence in 500 blood donors from Campinas, Brazil, based on a cross-sectional design. Blood samples were inoculated into an enrichment liquid growth medium and sub-inoculated onto blood agar. Liquid culture samples and Gram-negative isolates were tested using a genus specific ITS PCR with amplicons sequenced for species identification. Bartonella henselae and Bartonella quintana antibodies were assayed by indirect immunofluorescence. B. henselae was isolated from six donors (1.2%. Sixteen donors (3.2% were Bartonella-PCR positive after culture in liquid or on solid media, with 15 donors infected with B. henselae and one donor infected with Bartonella clarridgeiae. Antibodies against B. henselae or B. quintana were found in 16% and 32% of 500 blood donors, respectively. Serology was not associated with infection, with only three of 16 Bartonella-infected subjects seropositive for B. henselae or B. quintana. Bartonella DNA was present in the bloodstream of approximately one out of 30 donors from a major blood bank in South America. Negative serology does not rule out Bartonella spp. infection in healthy subjects. Using a combination of liquid and solid cultures, PCR, and DNA sequencing, this study documents for the first time that Bartonella spp. bacteremia occurs in asymptomatic blood donors. Our findings support further evaluation of Bartonella spp. transmission which can occur through blood transfusions.

  9. An adapted postdonation motivational interview enhances blood donor retention.

    Science.gov (United States)

    Sinclair, Kadian S; Campbell, Tavis S; Carey, Patricia M; Langevin, Eric; Bowser, Brent; France, Christopher R

    2010-08-01

    Blood donors may hold conflicting thoughts about future donation. While they may perceive the direct benefit to themselves and others, they often report compelling reasons not to give again. As a result the standard encouragements to return may not be sufficient to motivate some donors. This study examined the effects of a postdonation adapted motivational interview (AMI) on blood donor attitudes and repeat donation behavior. Donors (n = 215) were randomly assigned to either an AMI or a no-interview control group. Approximately 1 month after their index donation, donors in the AMI group completed a brief telephone interview to clarify individual-specific motivations and values concerning blood donation and address potential barriers. They were then asked to complete questionnaires regarding donation attitudes, anxiety, self-efficacy, and intention to donate. Donors in the control group were also contacted 1 month after donation and asked to complete the same series of questionnaires. Donors in the AMI group reported greater intention to provide a future donation (F = 8.13, p < 0.05), more positive donation attitudes (F = 4.59, p < 0.05), and greater confidence in their ability to avoid adverse reactions (F = 10.26, p < 0.01). Further, AMI was associated with higher rates of attempted donation at 12 months (odds ratio, 2.48; 95% confidence interval, 1.27-4.87). Application of an AMI may be an effective strategy to increase the donor pool by enhancing retention of existing donors. © 2010 American Association of Blood Banks.

  10. Organ transplantation from deceased donors with cancer: is it safe?

    Directory of Open Access Journals (Sweden)

    Nalesnik MA

    2011-08-01

    Full Text Available Michael A Nalesnik1, Michael G Ison21Division of Transplantation and Hepatic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburg, PA, USA; 2Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: The availability of donor organs continues to be insufficient to meet the needs of patients actively waiting for transplant. Consequently, there is continuing pressure to increase the donor organ pool while simultaneously assuring safety for the recipient population. The complication of donor malignancy transmission has been documented almost from the beginning of transplantation, and continues to be a concern today. The anecdotal nature of case reports and compiled series ensures that clinical decisions related to organ use from donors with malignancy will of necessity continue to be made on the basis of low-level evidence. Despite this limitation, the literature indicates that not all donor neoplasms have the same risk for transmission to the recipient, and it is necessary to consider the specific malignancy affecting the donor, as well as the condition of the recipient, before a decision is made to transplant or discard a given organ. Published cases suggest that certain forms of neoplasia, such as melanoma, choriocarcinoma, sarcoma, small cell carcinoma, or metastatic carcinomas serve as strong contraindications to organ donation. In contrast, considerable experience exists to suggest that certain tumors of the central nervous system, small subclinical prostate carcinomas, or small renal cell carcinomas resected prior to transplant, among other tumors, should not in themselves disqualify an individual from donating organs in the appropriate circumstance. This review presents the case for considering organ transplantation in the setting of certain donor malignancies and discusses factors to be weighed in such decisions. Additionally

  11. Conceptual waste package interim product specifications and data requirements for disposal of borosilicate glass defense high-level waste forms in salt geologic repositories

    Energy Technology Data Exchange (ETDEWEB)

    1983-06-01

    The conceptual waste package interim product specifications and data requirements presented are applicable specifically to the normal borosilicate glass product of the Defense Waste Processing Facility (DWPF). They provide preliminary numerical values for the defense high-level waste form parameters and properties identified in the waste form performance specification for geologic isolation in salt repositories. Subject areas treated include containment and isolation, operational period safety, criticality control, waste form/production canister identification, and waste package performance testing requirements. This document was generated for use in the development of conceptual waste package designs in salt. It will be revised as additional data, analyses, and regulatory requirements become available.

  12. Conceptual waste package interim product specifications and data requirements for disposal of borosilicate glass defense high-level waste forms in salt geologic repositories

    International Nuclear Information System (INIS)

    1983-06-01

    The conceptual waste package interim product specifications and data requirements presented are applicable specifically to the normal borosilicate glass product of the Defense Waste Processing Facility (DWPF). They provide preliminary numerical values for the defense high-level waste form parameters and properties identified in the waste form performance specification for geologic isolation in salt repositories. Subject areas treated include containment and isolation, operational period safety, criticality control, waste form/production canister identification, and waste package performance testing requirements. This document was generated for use in the development of conceptual waste package designs in salt. It will be revised as additional data, analyses, and regulatory requirements become available

  13. Socio-demographic characteristics of Danish blood donors

    DEFF Research Database (Denmark)

    Burgdorf, Kristoffer Sølvsten; Simonsen, Jacob; Sundby, Anna

    2017-01-01

    in Denmark in 2010. METHODS: The study population comprised all Danes in the age range eligible for blood donation (N = 3,236,753) at the end of 2010. From the Scandinavian Donations and Transfusions (SCANDAT) register, we identified 174,523 persons who donated blood in Danish blood banks at least once......BACKGROUND: Blood transfusion is an essential component of a modern healthcare system. Because knowledge about blood donor demography may inform the design of strategies for donor recruitment and retention, we used nationwide registers to characterize the entire population of blood donors...... in 2010. The association between sociodemographic characteristics and blood donor prevalence was examined using regression models. RESULTS: The overall prevalence of blood donation was 5.4% among both women and men. The age-specific prevalence of blood donation peaked at 25 years of age (6.8%) for women...

  14. Smed-dynA-1 is a planarian nervous system specific dynamin 1 homolog required for normal locomotion.

    Science.gov (United States)

    Talbot, Jared A; Currie, Ko W; Pearson, Bret J; Collins, Eva-Maria S

    2014-06-20

    Dynamins are GTPases that are required for separation of vesicles from the plasma membrane and thus are key regulators of endocytosis in eukaryotic cells. This role for dynamin proteins is especially crucial for the proper function of neurons, where they ensure that synaptic vesicles and their neurotransmitter cargo are recycled in the presynaptic cell. Here we have characterized the dynamin protein family in the freshwater planarian Schmidtea mediterranea and showed that it possesses six dynamins with tissue specific expression profiles. Of these six planarian homologs, two are necessary for normal tissue homeostasis, and the loss of another, Smed-dynA-1, leads to an abnormal behavioral phenotype, which we have quantified using automated center of mass tracking. Smed-dynA-1 is primarily expressed in the planarian nervous system and is a functional homolog of the mammalian Dynamin I. The distinct expression profiles of the six dynamin genes makes planarians an interesting new system to reveal novel dynamin functions, which may be determined by their differential tissue localization. The observed complexity of neurotransmitter regulation combined with the tools of quantitative behavioral assays as a functional readout for neuronal activity, renders planarians an ideal system for studying how the nervous system controls behavior. © 2014. Published by The Company of Biologists Ltd.

  15. Optimal functional levels of activation-induced deaminase specifically require the Hsp40 DnaJa1

    Science.gov (United States)

    Orthwein, Alexandre; Zahn, Astrid; Methot, Stephen P; Godin, David; Conticello, Silvestro G; Terada, Kazutoyo; Di Noia, Javier M

    2012-01-01

    The enzyme activation-induced deaminase (AID) deaminates deoxycytidine at the immunoglobulin genes, thereby initiating antibody affinity maturation and isotype class switching during immune responses. In contrast, off-target DNA damage caused by AID is oncogenic. Central to balancing immunity and cancer is AID regulation, including the mechanisms determining AID protein levels. We describe a specific functional interaction between AID and the Hsp40 DnaJa1, which provides insight into the function of both proteins. Although both major cytoplasmic type I Hsp40s, DnaJa1 and DnaJa2, are induced upon B-cell activation and interact with AID in vitro, only DnaJa1 overexpression increases AID levels and biological activity in cell lines. Conversely, DnaJa1, but not DnaJa2, depletion reduces AID levels, stability and isotype switching. In vivo, DnaJa1-deficient mice display compromised response to immunization, AID protein and isotype switching levels being reduced by half. Moreover, DnaJa1 farnesylation is required to maintain, and farnesyltransferase inhibition reduces, AID protein levels in B cells. Thus, DnaJa1 is a limiting factor that plays a non-redundant role in the functional stabilization of AID. PMID:22085931

  16. The Nanos3-3'UTR is required for germ cell specific NANOS3 expression in mouse embryos.

    Directory of Open Access Journals (Sweden)

    Hitomi Suzuki

    Full Text Available BACKGROUND: The regulation of gene expression via a 3' untranslated region (UTR plays essential roles in the discrimination of the germ cell lineage from somatic cells during embryogenesis. This is fundamental to the continuation of a species. Mouse NANOS3 is an essential protein required for the germ cell maintenance and is specifically expressed in these cells. However, the regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we show that differences in the stability of Nanos3 mRNA between germ cells and somatic cells is brought about in a 3'UTR-dependent manner in mouse embryos. Although Nanos3 is transcribed in both cell lineages, it is efficiently translated only in the germ lineage. We also find that the translational suppression of NANOS3 in somatic cells is caused by a 3'UTR-mediated mRNA destabilizing mechanism. Surprisingly, even when under the control of the CAG promoter which induces strong ubiquitous transcription in both germ cells and somatic cells, the addition of the Nanos3-3'UTR sequence to the coding region of exogenous gene was effective in restricting protein expression in germ cells. CONCLUSIONS/SIGNIFICANCE: Our current study thus suggests that Nanos3-3'UTR has an essential role in translational control in the mouse embryo.

  17. Smed-dynA-1 is a planarian nervous system specific dynamin 1 homolog required for normal locomotion

    Directory of Open Access Journals (Sweden)

    Jared A. Talbot

    2014-06-01

    Full Text Available Dynamins are GTPases that are required for separation of vesicles from the plasma membrane and thus are key regulators of endocytosis in eukaryotic cells. This role for dynamin proteins is especially crucial for the proper function of neurons, where they ensure that synaptic vesicles and their neurotransmitter cargo are recycled in the presynaptic cell. Here we have characterized the dynamin protein family in the freshwater planarian Schmidtea mediterranea and showed that it possesses six dynamins with tissue specific expression profiles. Of these six planarian homologs, two are necessary for normal tissue homeostasis, and the loss of another, Smed-dynA-1, leads to an abnormal behavioral phenotype, which we have quantified using automated center of mass tracking. Smed-dynA-1 is primarily expressed in the planarian nervous system and is a functional homolog of the mammalian Dynamin I. The distinct expression profiles of the six dynamin genes makes planarians an interesting new system to reveal novel dynamin functions, which may be determined by their differential tissue localization. The observed complexity of neurotransmitter regulation combined with the tools of quantitative behavioral assays as a functional readout for neuronal activity, renders planarians an ideal system for studying how the nervous system controls behavior.

  18. Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

    Directory of Open Access Journals (Sweden)

    Sung-Jun Park

    2017-04-01

    Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

  19. Adolescents with type 1 diabetes mellitus and attention-deficit/hyperactivity disorder require specific support from healthcare professionals.

    Science.gov (United States)

    Lindblad, Ida; Engström, Ann-Charlotte; Nylander, Charlotte; Fernell, Elisabeth

    2017-12-01

    Managing type 1 diabetes mellitus requires efficient cognitive and executive skills, and adolescents who have attention-deficit/hyperactivity disorder (ADHD) may face specific challenges. This study explored young people's experiences of diabetes treatment and care. In a population-based study, comprising 175 patients aged 5-16 years with type 1 diabetes mellitus in two Swedish counties, we found that eight also met criteria for ADHD. Six of these, aged 14.5-16 years, participated 2013-2014 in interviews that targeted aspects of their diabetes treatment. Conducted by two psychologists, these used the inductive qualitative, semi-structured interview format. The two boys and four girls all reported difficulties in creating routines for their diabetes treatment and that problems were aggravated during stress. They had been criticised by their parents and the diabetes team when their blood levels indicated inadequate diabetes control. They requested ongoing information, involvement of their friends, group meetings and easy access to the healthcare system during difficult times. Patients with type 1 diabetes mellitus and concomitant ADHD faced problems with their diabetes management, especially during stressful situations. Diabetes care provision should pay particular attention to patients with co-existing neuropsychiatric and neurodevelopmental disorders such as ADHD. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  20. Ubiquitin-specific protease 5 is required for the efficient repair of DNA double-strand breaks.

    Directory of Open Access Journals (Sweden)

    Satoshi Nakajima

    Full Text Available During the DNA damage response (DDR, ubiquitination plays an important role in the recruitment and regulation of repair proteins. However, little is known about elimination of the ubiquitination signal after repair is completed. Here we show that the ubiquitin-specific protease 5 (USP5, a deubiquitinating enzyme, is involved in the elimination of the ubiquitin signal from damaged sites and is required for efficient DNA double-strand break (DSB repair. Depletion of USP5 sensitizes cells to DNA damaging agents, produces DSBs, causes delayed disappearance of γH2AX foci after Bleocin treatment, and influences DSB repair efficiency in the homologous recombination pathway but not in the non-homologous end joining pathway. USP5 co-localizes to DSBs induced by laser micro-irradiation in a RAD18-dependent manner. Importantly, polyubiquitin chains at sites of DNA damage remained for longer periods in USP5-depleted cells. Our results show that disassembly of polyubiquitin chains by USP5 at sites of damage is important for efficient DSB repair.

  1. Uterus retrieval process from brain dead donors.

    Science.gov (United States)

    Gauthier, Tristan; Piver, Pascal; Pichon, Nicolas; Bibes, Romain; Guillaudeau, Angelique; Piccardo, Alessandro; Pesteil, Francis; Tricard, Jeremy; Gardet, Emmanuel; Laskar, Marc; Lalloué, Fabrice; Marquet, Pierre; Aubard, Yves

    2014-08-01

    To describe the feasibility of human uterus retrieval after donation after brain death. Single-center, prospective study. University hospital. Female brain dead donors. The families of female brain dead donors were informed about consent to uterus donation. A specific organ retrieval procedure was performed. At the end of the procedure the uterus was removed together with the hypogastric vessels, parametria, and vaginal fornix. The tolerance of the uterus to cold ischemia was evaluated with histology and TUNEL reaction up to 24 hours. Rate of uterus donation refusal. Between August 1, 2012 and July 31, 2013, seven uteri were retrieved from 14 female multiorgan donors. No refusal to uterus donation occurred. Our surgical protocol did not interfere with vital organ retrieval and was readily accepted by the other transplantation teams. The hypogastric vessels could be preserved in all cases but for one vein loss in the first retrieval. Histology studies did not find major morphologic changes after 24 hours of cold ischemia. Apoptosis was rare. Uterus retrieval could be part of a reproducible multiorgan procurement procedure. Uterus donation seems readily accepted. This preliminary study is a necessary step before any transplantation project. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  2. World marrow donor association crisis response, business continuity, and disaster recovery guidelines.

    Science.gov (United States)

    Pingel, Julia; Case, Cullen; Amer, Beth; Hornung, Raymond A; Schmidt, Alexander H

    2012-12-01

    Multiple institutions, such as donor registries, donor centers, transplantation centers, collection centers, and courier companies, are involved in the international exchange of hematopoietic stem cells. The ability to safely and efficiently ensure continued operation of a donor registry relies on an organization's resiliency in the face of an incident that could impede donor search, donor selection, stem cell collection, or transportation. The Quality Assurance Working Group of the World Marrow Donor Association has developed guidelines on how to establish an organizational resiliency program intended for donor registries initiating an emergency preparedness process. These guidelines cover the minimal requirements of preparedness in prevention and mitigation, crisis response, business continuity, and disaster recovery, and the need for continued maintenance and revision. Issues of international cooperation are addressed as well. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. The operational implications of donor behaviors following enrollment in STRIDE (Strategies to Reduce Iron Deficiency in blood donors).

    Science.gov (United States)

    Cable, Ritchard G; Birch, Rebecca J; Spencer, Bryan R; Wright, David J; Bialkowski, Walter; Kiss, Joseph E; Rios, Jorge; Bryant, Barbara J; Mast, Alan E

    2017-10-01

    Donor behaviors in STRIDE (Strategies to Reduce Iron Deficiency), a trial to reduce iron deficiency, were examined. Six hundred ninety-two frequent donors were randomized to receive either 19 or 38 mg iron for 60 days or an educational letter based on their predonation ferritin. Compliance with assigned pills, response to written recommendations, change in donation frequency, and future willingness to take iron supplements were examined. Donors who were randomized to receive iron pills had increased red blood cell donations and decreased hemoglobin deferrals compared with controls or with pre-STRIDE donations. Donors who were randomized to receive educational letters had fewer hemoglobin deferrals compared with controls. Of those who received a letter advising of low ferritin levels with recommendations to take iron supplements or delay future donations, 57% reported that they initiated iron supplementation, which was five times as many as those who received letters lacking a specific recommendation. The proportion reporting delayed donation was not statistically different (32% vs. 20%). Of donors who were assigned pills, 58% reported taking them "frequently," and forgetting was the primary reason for non-compliance. Approximately 80% of participants indicated that they would take iron supplements if provided by the center. Donors who were assigned iron pills had acceptable compliance, producing increased red blood cell donations and decreased low hemoglobin deferrals compared with controls or with pre-STRIDE rates. The majority of donors assigned to an educational letter took action after receiving a low ferritin result, with more donors choosing to take iron than delay donation. Providing donors with information on iron status with personalized recommendations was an effective alternative to directly providing iron supplements. © 2017 AABB.

  4. Donor KIR B Genotype Improves Progression-Free Survival of Non-Hodgkin Lymphoma Patients Receiving Unrelated Donor Transplantation.

    Science.gov (United States)

    Bachanova, Veronika; Weisdorf, Daniel J; Wang, Tao; Marsh, Steven G E; Trachtenberg, Elizabeth; Haagenson, Michael D; Spellman, Stephen R; Ladner, Martha; Guethlein, Lisbeth A; Parham, Peter; Miller, Jeffrey S; Cooley, Sarah A

    2016-09-01

    Donor killer immunoglobulin-like receptor (KIR) genotypes are associated with relapse protection and survival after allotransplantation for acute myelogenous leukemia. We examined the possibility of a similar effect in a cohort of 614 non-Hodgkin lymphoma (NHL) patients receiving unrelated donor (URD) T cell-replete marrow or peripheral blood grafts. Sixty-four percent (n = 396) of donor-recipient pairs were 10/10 allele HLA matched and 26% were 9/10 allele matched. Seventy percent of donors had KIR B/x genotype; the others had KIR A/A genotype. NHL patients receiving 10/10 HLA-matched URD grafts with KIR B/x donors experienced significantly lower relapse at 5 years (26%; 95% confidence interval [CI], 21% to 32% versus 37%; 95% CI, 27% to 46%; P = .05) compared with KIR A/A donors, resulting in improved 5-year progression-free survival (PFS) (35%; 95% CI, 26% to 44% versus 22%; 95% CI, 11% to 35%; P = .007). In multivariate analysis, use of KIR B/x donors was associated with significantly reduced relapse risk (relative risk [RR], .63, P = .02) and improved PFS (RR, .71, P = .008). The relapse protection afforded by KIR B/x donors was not observed in HLA-mismatched transplantations and was not specific to any particular KIR-B gene. Selecting 10/10 HLA-matched and KIR B/x donors should benefit patients with NHL receiving URD allogeneic transplantation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  5. Laparoscopy-Assisted Spleen-Preserving Distal Pancreatectomy for Living-Donor Pancreas Transplantation.

    Science.gov (United States)

    Date, S; Noguchi, H; Kaku, K; Kurihara, K; Miyasaka, Y; Okabe, Y; Nakamura, U; Ohtsuka, T; Nakamura, M

    2017-06-01

    Living pancreas transplantation plays an important role in the treatment of patients with severe type 1 diabetes. However, pancreatectomy is very invasive for the donor, and less-invasive surgical procedures are needed. Although some reports have described hand-assisted laparoscopic surgery for distal pancreatectomy in living-donor operations, less-invasive laparoscopy-assisted (LA) procedures are expected to increase the donor pool. We herein report the outcomes of four cases of LA spleen-preserving distal pancreatectomy (Warshaw technique [WT]) in living pancreas donors. Four living pancreas donors underwent LA-WT at our institution from September 2010 to January 2013. All donors fulfilled the donor criteria established by the Japan Society for Pancreas and Islet Transplantation. The median donor age was 54 years. Two donors underwent left nephrectomy in addition to LA-WT for simultaneous pancreas-kidney transplantation. The median donor operation time for pancreatectomy was 340.5 minutes. The median pancreas warm ischemic time was 3 minutes. The median donor blood loss was 246 g. All recipients immediately achieved insulin independence. One donor required reoperation because of obstructive ileus resulting from a port-site hernia. Another donor developed a pancreatic fistula (International Study Group of Pancreatic Fistula grade B), which was controlled with conservative management. After a maximum follow-up of 73 months, no clinically relevant adverse events had occurred. These results were comparable with those of previous studies concerning living-donor pancreas transplantation. The LA-WT is a safe and acceptable operation for living-donor pancreas transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Are there any alternatives for transfusion of AB plasma as universal donor in an emergency release setting?

    NARCIS (Netherlands)

    Balvers, Kirsten; Saleh, Sarah; Zeerleder, Sacha S.; Klinkspoor, J. Henriette; Goslings, J. Carel; Juffermans, Nicole P.

    2016-01-01

    AB plasma is used as the universal donor plasma product in patients requiring massive transfusion. However, currently it is a recommended policy to transfuse plasma derived from male donors only as transfusion of plasma from HLA antibody-positive female donors is associated with an increased risk

  7. Airborne Laser Remote Sensor for Oil Detection and Classification : Engineering Requirements and Technical Considerations Relevant to a Performance Specification

    Science.gov (United States)

    1975-08-01

    This report outlines the engineering requirements for an Airborne Laser Remote Sensor for Oil Detection and Classification System. Detailed engineering requirements are given for the major units of the system. Technical considerations pertinent to a ...

  8. The conjugation-specific Die5 protein is required for development of the somatic nucleus in both Paramecium and Tetrahymena.

    Science.gov (United States)

    Matsuda, Atsushi; Shieh, Annie Wan-Yi; Chalker, Douglas L; Forney, James D

    2010-07-01

    Development in ciliated protozoa involves extensive genome reorganization within differentiating macronuclei, which shapes the somatic genome of the next vegetative generation. Major events of macronuclear differentiation include excision of internal eliminated sequences (IESs), chromosome fragmentation, and genome amplification. Proteins required for these events include those with homology throughout eukaryotes as well as proteins apparently unique to ciliates. In this study, we identified the ciliate-specific Defective in IES Excision 5 (DIE5) genes of Paramecium tetraurelia (PtDIE5) and Tetrahymena thermophila (TtDIE5) as orthologs that encode nuclear proteins expressed exclusively during development. Abrogation of PtDie5 protein (PtDie5p) function by RNA interference (RNAi)-mediated silencing or TtDie5p by gene disruption resulted in the failure of developing macronuclei to differentiate into new somatic nuclei. Tetrahymena DeltaDIE5 cells arrested late in development and failed to complete genome amplification, whereas RNAi-treated Paramecium cells highly amplified new macronuclear DNA before the failure in differentiation, findings that highlight clear differences in the biology of these distantly related species. Nevertheless, IES excision and chromosome fragmentation failed to occur in either ciliate, which strongly supports that Die5p is a critical player in these processes. In Tetrahymena, loss of zygotic expression during development was sufficient to block nuclear differentiation. This observation, together with the finding that knockdown of Die5p in Paramecium still allows genome amplification, indicates that this protein acts late in macronuclear development. Even though DNA rearrangements in these two ciliates look to be quite distinct, analysis of DIE5 establishes the action of a conserved mechanism within the genome reorganization pathway.

  9. The Conjugation-Specific Die5 Protein Is Required for Development of the Somatic Nucleus in both Paramecium and Tetrahymena▿

    Science.gov (United States)

    Matsuda, Atsushi; Shieh, Annie Wan-Yi; Chalker, Douglas L.; Forney, James D.

    2010-01-01

    Development in ciliated protozoa involves extensive genome reorganization within differentiating macronuclei, which shapes the somatic genome of the next vegetative generation. Major events of macronuclear differentiation include excision of internal eliminated sequences (IESs), chromosome fragmentation, and genome amplification. Proteins required for these events include those with homology throughout eukaryotes as well as proteins apparently unique to ciliates. In this study, we identified the ciliate-specific Defective in IES Excision 5 (DIE5) genes of Paramecium tetraurelia (PtDIE5) and Tetrahymena thermophila (TtDIE5) as orthologs that encode nuclear proteins expressed exclusively during development. Abrogation of PtDie5 protein (PtDie5p) function by RNA interference (RNAi)-mediated silencing or TtDie5p by gene disruption resulted in the failure of developing macronuclei to differentiate into new somatic nuclei. Tetrahymena ΔDIE5 cells arrested late in development and failed to complete genome amplification, whereas RNAi-treated Paramecium cells highly amplified new macronuclear DNA before the failure in differentiation, findings that highlight clear differences in the biology of these distantly related species. Nevertheless, IES excision and chromosome fragmentation failed to occur in either ciliate, which strongly supports that Die5p is a critical player in these processes. In Tetrahymena, loss of zygotic expression during development was sufficient to block nuclear differentiation. This observation, together with the finding that knockdown of Die5p in Paramecium still allows genome amplification, indicates that this protein acts late in macronuclear development. Even though DNA rearrangements in these two ciliates look to be quite distinct, analysis of DIE5 establishes the action of a conserved mechanism within the genome reorganization pathway. PMID:20495055

  10. Donor Hemovigilance with Blood Donation

    Science.gov (United States)

    Diekamp, Ulrich; Gneißl, Johannes; Rabe, Angela; Kießig, Stephan T.

    2015-01-01

    Background Reports on unexpected events (UEs) during blood donation (BD) inadequately consider the role of technical UEs. Methods Defined local and systemic UEs were graded by severity; technical UEs were not graded. On January 1, 2008, E.B.P.S.-Logistics (EBPS) installed the UE module for plasma management software (PMS). Donor room physicians entered UEs daily into PMS. Medical directors reviewed entries quarterly. EBPS compiled data on donors, donations, and UEs from January 1, 2008 to June 30, 2011. Results 6,605 UEs were observed during 166,650 BDs from 57,622 donors for a corrected incidence of 4.30% (0.66% local, 1.59% systemic, 2.04% technical UEs). 2.96% of BDs were accompanied by one UE and 0.45% by >1 UE (2-4). 6.3% of donors donating blood for their first time, 3.5% of those giving blood for their second time, and 1.9% of donors giving their third or more BD experienced UEs. Most common UEs were: discontinued collections due to venous access problems, repeated venipuncture, and small hematomas. Severe circulatory UEs occurred at a rate of 16 per 100,000 BDs. Conclusions Technical UEs were common during BD. UEs accompanied first and second donations significantly more often than subsequent donations. PMID:26195932

  11. Negative peri-donation events among whole blood donors in a blood bank in Ibadan, Nigeria.

    Science.gov (United States)

    Fasola, Foluke A

    2017-12-31

    The existence and sustenance of the blood bank depends on blood donors. It is imperative that the donation experience is satisfactory for the donors. Therefore this study was carried out to determine the frequency of undesirable events experienced by the blood donor as part of donor haemovigilance. This was a retrospective descriptive study of the events that occurred amongst the blood donors of the blood bank of a tertiary institution. The blood donor incident book was reviewed for the period of six months. Negative undesirable events occurred in 2% of the donor populations, of which 45.8% could not complete the blood donation process while only 16.7% completed the blood donation process. Mild vasovagal attack occurred in 0.2% of the donor population. Undisclosed deferrable risk factors/ behaviours were identified by the phlebotomist in the bleeding room which made donors unfit for donation even though they had passed the donor screening criteria. This accounted for 20.8% of those with negative experience. Guidelines are required to identify donors that are not likely to complete donation to avoid wastage of time, blood, resources and reduce undesirable experiences.

  12. Matching donor to recipient in liver transplantation: Relevance in clinical practice

    OpenAIRE

    Reddy, Mettu Srinivas; Varghese, Joy; Venkataraman, Jayanthi; Rela, Mohamed

    2013-01-01

    Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as ...

  13. Requirements of Employers for Young Specialists and Issues of Their Training at the Educational Institutions: Regional Specificity of Moscow

    Directory of Open Access Journals (Sweden)

    Vyacheslav Nikolaevich Bobkov

    2016-12-01

    Full Text Available The subject-matter of the article is the study of the peculiarities of the youth labour market in such a specific region of Russia as the city of Moscow. The topic of the work is connected to the adaptation of young specialists training system to the regional requirements of the employers of Moscow. The main hypothesis of the research assumes that Moscow is the atypical region of Russia and it is inexpedient to apply criteria and methodological approaches, which are standard for our country, to its labour market. As a method of the research, a selective survey of key employers of Moscow and respondents aged from 14 till 30 years has been used. The data of the sociological survey conducted by the authors have allowed to establish the following features of the researched region: a respectively low level of youth unemployment compared with the whole Russia; focusing of employers on such features of personnel as a good communicative skills learning ability, professional knowledge and competences. Moscow employers don’t pay significant attention to such characteristics of young specialists as language and computer skills, computer knowledge and the diploma of a prestigious educational institution. The main difficulties in finding employment for young specialists in the city of Moscow are: overestimated salary expectations; the weak professional training level and unwillingness, in fact, to work. As a result of the survey, the practical offers have been formulated. There are two directions of their application: the offers focused on the behaviour of the youth at a stage of their training and those offers focused on the increase of a practical component of the activity of professional educational institutions. The authors came to conclusions about the need of a deep orientation of educational institutions to the applied training for specialists, of practical workers for teaching special disciplines, the development by future specialists their

  14. Maintenance-energy requirements and robustness of Saccharomyces cerevisiae at aerobic near-zero specific growth rates.

    Science.gov (United States)

    Vos, Tim; Hakkaart, Xavier D V; de Hulster, Erik A F; van Maris, Antonius J A; Pronk, Jack T; Daran-Lapujade, Pascale

    2016-06-17

    Saccharomyces cerevisiae is an established microbial platform for production of native and non-native compounds. When product pathways compete with growth for precursors and energy, uncoupling of growth and product formation could increase product yields and decrease formation of biomass as a by-product. Studying non-growing, metabolically active yeast cultures is a first step towards developing S. cerevisiae as a robust, non-growing cell factory. Microbial physiology at near-zero growth rates can be studied in retentostats, which are continuous-cultivation systems with full biomass retention. Hitherto, retentostat studies on S. cerevisiae have focused on anaerobic conditions, which bear limited relevance for aerobic industrial processes. The present study uses aerobic, glucose-limited retentostats to explore the physiology of non-dividing, respiring S. cerevisiae cultures, with a focus on industrially relevant features. Retentostat feeding regimes for smooth transition from exponential growth in glucose-limited chemostat cultures to near-zero growth rates were obtained by model-aided experimental design. During 20 days of retentostats cultivation, the specific growth rate gradually decreased from 0.025 h(-1) to below 0.001 h(-1), while culture viability remained above 80 %. The maintenance requirement for ATP (mATP) was estimated at 0.63 ± 0.04 mmol ATP (g biomass)(-1) h(-1), which is ca. 35 % lower than previously estimated for anaerobic retentostats. Concomitant with decreasing growth rate in aerobic retentostats, transcriptional down-regulation of genes involved in biosynthesis and up-regulation of stress-responsive genes resembled transcriptional regulation patterns observed for anaerobic retentostats. The heat-shock tolerance in aerobic retentostats far exceeded previously reported levels in stationary-phase batch cultures. While in situ metabolic fluxes in retentostats were intentionally low due to extreme caloric restriction, off-line measurements

  15. Specification of requirements for upgrades using digital instrument and control systems. Report prepared within the framework of the international working group on nuclear power plant control and instrumentation

    International Nuclear Information System (INIS)

    1999-01-01

    The need to develop good specifications of requirements for instrument and control (I and C) systems applies throughout the world and is becoming more and more important as more upgrades are planned. Better guidance on how to develop good requirements specifications would support safer, more effective and more economical refits and upgrades. The need for this was pointed out by the IAEA International Working Group on Nuclear Power Plant Control and Instrumentation (IWG-NPPCI). This report is the result of a series of advisory and consultants meetings held by the IAEA in 1997 and 1998 in Vienna. The scope of the activities described covers a methodology for the determination of requirements and the development of the necessary specifications and plans needed through the life-cycle of digital instrumentation and control systems. It is restricted to technical aspects and indicates subjects which should be included in specifications and plans at different phases

  16. Effective serological and molecular screening of deceased tissue donors.

    Science.gov (United States)

    Kitchen, A D; Newham, J A; Gillan, H L

    2013-12-01

    A comprehensive and effective screening programme is essential to support the banking of tissues from deceased donors. However, the overall quality of the samples obtained from deceased donors, quantity and condition, is often not ideal, and this may lead to problems in achieving accurate and reliable results. Additionally a significant percentage of referrals are still rejected upon receipt as unsuitable for screening. We are actively involved in improving the overall quality of deceased donor screening outcomes, and have specifically evaluated and validated both serological and molecular assays for this purpose, as well as developing a specific screening strategy to minimise the specificity issues associated with serological screening. Here we review the nature and effectiveness of the deceased donor screening programme implemented by National Health Service Blood and Transplant (NHSBT), the organisation with overall responsibility for the supply of tissue products within England. Deceased donor screening data, serological and molecular, from August 2007 until May 2012 have been collated and analysed. Of 10,225 samples referred for serology screening, 5.5 % were reported as reactive; of 2,862 samples referred for molecular screening, 0.1 % were reported as reactive/inhibitory. Overall 20 % of the serological and 100 % of the molecular screen reactivity was confirmed as reflecting true infection. The use of a sequential serology screening algorithm has resulted in a marked reduction of tissues lost unnecessarily due to non-specific screen reactivity. The approach taken by NHSBT has resulted in the development of an effective and specific approach to the screening of deceased tissue donors.

  17. Charged dopants in neutral supercells through substitutional donor (acceptor): nitrogen donor charging of the nitrogen-vacancy center in diamond

    Science.gov (United States)

    Löfgren, Robin; Pawar, Ravinder; Öberg, Sven; Larsson, J. Andreas

    2018-02-01

    Charged defects are traditionally computed by adding (subtracting) electrons for negative (positive) impurities. When using periodic boundary conditions this results in artificially charged supercells that also require a compensating background charge of the opposite sign, which makes slab supercells problematic because of an arbitrary dependence on the vacuum thickness. In this work, we test the method of using neutral supercells through the use of a substitutional electron donor (acceptor) to describe charged systems. We use density functional theory (DFT) to compare the effects of charging the well-studied NV-center in diamond by a substitutional donor nitrogen. We investigate the influence of the donor-N on the NV-center properties as a function of the distance between them, and find that they converge toward those obtained when adding an electron. We analyze the spin density and conclude that the donor-N has a zero magnetic moment, and thus, will not be seen in electron spin resonance. We validate our DFT energies through comparison to GW simulations. Charging the NV-center with a substitutional donor-N enables accurate calculations of slabs, without the ambiguity of using charged supercells. Implantation of donor-N atoms opens up the possibility to engineer NV-centers with the desired charge state for future ICT and sensor applications.

  18. 40 CFR 270.22 - Specific part B information requirements for boilers and industrial furnaces burning hazardous...

    Science.gov (United States)

    2010-07-01

    ... requirements for boilers and industrial furnaces burning hazardous waste. 270.22 Section 270.22 Protection of... requirements for boilers and industrial furnaces burning hazardous waste. When an owner or operator of a cement kiln, lightweight aggregate kiln, solid fuel boiler, liquid fuel boiler, or hydrochloric acid...

  19. Factors Influencing Donor Partnership Effectiveness

    International Development Research Centre (IDRC) Digital Library (Canada)

    (UN Global Compact Office, 2007); and “an alliance between organizations from two or more ... programs related to the environment, global health, and ..... partnering process and the factors of influence, drawing on an example of a flagship initiative with a bilateral donor for an environment-focused program. As in most joint ...

  20. Autotrophic denitrification of nitrate and nitrite using thiosulfate as an electron donor.

    Science.gov (United States)

    Chung, Jinwook; Amin, Khurram; Kim, Seungjin; Yoon, Seungjoon; Kwon, Kiwook; Bae, Wookeun

    2014-07-01

    This study was carried out to determine the possibility of autotrophic denitritation using thiosulfate as an electron donor, compare the kinetics of autotrophic denitrification and denitritation, and to study the effects of pH and sulfur/nitrogen (S/N) ratio on the denitrification rate of nitrite. Both nitrate and nitrite were removed by autotrophic denitrification using thiosulfate as an electron donor at concentrations up to 800 mg-N/L. Denitrification required a S/N ratio of 5.1 for complete denitrification, but denitritation was complete at a S/N ratio of 2.5, which indicated an electron donor cost savings of 50%. Also, pH during denitrification decreased but increased with nitrite, implying additional alkalinity savings. Finally, the highest specific substrate utilization rate of nitrite was slightly higher than that of nitrate reduction, and biomass yield for denitrification was relatively higher than that of denitritation, showing less sludge production and resulting in lower sludge handling costs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Seamless Requirements

    OpenAIRE

    Naumchev, Alexandr; Meyer, Bertrand

    2017-01-01

    Popular notations for functional requirements specifications frequently ignore developers' needs, target specific development models, or require translation of requirements into tests for verification; the results can give out-of-sync or downright incompatible artifacts. Seamless Requirements, a new approach to specifying functional requirements, contributes to developers' understanding of requirements and to software quality regardless of the process, while the process itself becomes lighter...

  2. Dissection of the beta-globin replication-initiation region reveals specific requirements for replicator elements during gene amplification.

    Directory of Open Access Journals (Sweden)

    Naoya Okada

    Full Text Available Gene amplification plays a pivotal role in malignant transformation of human cells. A plasmid with both a mammalian replication-initiation region (IR/origin/replicator and a nuclear matrix-attachment region (MAR is spontaneously amplified in transfected cells by a mechanism that involves amplification at the extrachromosomal site, followed by amplification at the chromosomal arm, ultimately generating a long homogeneously staining region (HSR. Several observations suggest that replication initiation from IR sequences might mediate amplification. To test this idea, we previously dissected c-myc and DHFR IRs to identify the minimum sequence required to support amplification. In this study, we applied an improved analysis that discriminates between two amplification steps to the ß-globin RepP IR, which contains separate elements already known to be essential for initiation on the chromosome arm. The IR sequence was required at least for the extrachromosomal amplification step. In addition to the vector-encoded MAR, amplification also required an AT-rich region and a MAR-like element, consistent with the results regarding replicator activity on the chromosome. However, amplification did not require the AG-rich tract necessary for replicator activity, but instead required a novel sequence containing another AG-rich tract. The differential sequence requirement might be a consequence of extrachromosomal replication.

  3. 49 CFR 173.304a - Additional requirements for shipment of liquefied compressed gases in specification cylinders.

    Science.gov (United States)

    2010-10-01

    ... in heavy burlap and bound by 12-gauge wire with the wire completely covered by friction tape...: Specification 3HT cylinders for aircraft use only, having a maximum service life of 24 years. Authorized only...

  4. Psychosocial counselling of identifiable sperm donors.

    Science.gov (United States)

    Visser, M; Mochtar, M H; de Melker, A A; van der Veen, F; Repping, S; Gerrits, T

    2016-05-01

    What do identifiable sperm donors feel about psychosocial counselling? Identifiable sperm donors found it important that psychosocial counselling focused on emotional consequences and on rules and regulations and they expected to have access to psychosocial counselling at the time that donor-offspring actually sought contact. Most studies on sperm donors are on anonymous donors and focus on recruitment, financial compensation, anonymity and motivations. There is limited knowledge on the value that identifiable sperm donors place on psychosocial counselling and what their needs are in this respect. We performed a qualitative study from March until June 2014 with 25 identifiable sperm donors, who were or had been a donor at the Centre for Reproductive Medicine of the Academic Medical Centre in Amsterdam any time between 1989 and 2014. We held semi-structured in-depth interviews with identifiable sperm donors with an average age of 44 years. The interviews were fully transcribed and analysed using the constant comparative method of grounded theory. Twelve out of 15 donors (former donors ITALIC! n = 8, active donors ITALIC! n = 7) who had received a counselling session during their intake procedure found it important that they had been able to talk about issues such as the emotional consequences of donation, disclosure to their own children, family and friends, future contact with donor-offspring and rules and regulations. Of the 10 former donors who had received no counselling session, 8 had regretted the lack of intensive counselling. In the years following their donation, most donors simply wanted to know how many offspring had been born using their sperm and had no need for further counselling. Nevertheless, they frequently mentioned that they were concerned about the well-being of 'their' offspring. In addition, they would value the availability of psychosocial counselling in the event that donor-offspring actually sought contact. A limitation of our study is its

  5. Engaging Living Kidney Donors in a New Paradigm of Postdonation Care.

    Science.gov (United States)

    Newell, K A; Formica, R N; Gill, J S

    2016-01-01

    Recent studies have highlighted the need for better understanding of the long-term health outcomes of living donors. Barriers to establishment of a dedicated long-term donor follow-up data system in the United States include infrastructure costs and donor retention. We propose providing all previous and future living donors with a lifelong health insurance benefit for the primary purpose of facilitating acquisition of health information after donation as an alternative to establishment of a dedicated donor follow-up data system. Donors would consent to allow collection and analysis of their medical data, and continuation of insurance coverage would require completion of regular health assessments. The extension of health insurance would be analogous to the established practice of paying people for participation in a research study and would provide a mechanism to engage donors in a new paradigm of postdonation care in which donors are actively involved in their own health maintenance. Rather than acting as an inducement for donation, providing donors with the ability to easily contribute information about their health status represents a practical strategy to acquire the long-term medical information necessary to better inform future generations of living kidney donors. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Risk factors for delayed healing at the free anterolateral thigh flap donor site

    Directory of Open Access Journals (Sweden)

    Yoshiro Abe

    2018-01-01

    Full Text Available Background The free anterolateral thigh (ALT flap has been widely used for various kinds of reconstructions. However, delayed healing at the donor site occasionally occurs due to wound dehiscence or the partial loss of grafted skin at the donor site. The aim of the present study was to identify reliable predictive factors for delayed healing at the donor site after the harvest of a free ALT flap. Methods This study included 52 patients who underwent reconstructive procedures using free ALT flaps. The delayed healing group included patients with wounds at the donor site that had not healed over 3 weeks after surgery, and the normal healing group included patients who showed wound healing within 3 weeks after surgery. Multivariate logistic regression models were created to identify the risk factors for delayed healing at the ALT flap donor site. Results Among the 52 patients, 24 (46.2% showed delayed healing at the donor site, and 6 patients required additional operative treatment. A high preoperative body mass index (BMI, smoking, and skin grafting were found to be significantly associated with delayed healing at the ALT donor site. Of the 37 patients who underwent skin grafting, 23 (62% experienced delayed healing at the donor site. Conclusions A high preoperative BMI, smoking, and skin grafting were risk factors for delayed healing at the free ALT donor site. Skin grafting at the ALT donor site should be avoided in patients with a high BMI or a habit of smoking.

  7. Pharmacists' guide to the management of organ donors after brain death.

    Science.gov (United States)

    Korte, Catherine; Garber, Jennifer L; Descourouez, Jillian L; Richards, Katelyn R; Hardinger, Karen

    2016-11-15

    This article reviews organ donor pathophysiology as it relates to medication use with the goal of maximizing the successful procurement and transplantation of donor organs. The number of patients requiring organ transplantation continues to grow, yet organ donation rates remain flat, making it critical to appropriately manage each organ donor in order to ensure viability of all transplantable organs. The care given to one organ donor is tantamount to the care of several transplant recipients. Aggressive donor management ensures that the largest number of organs can be successfully procured and improves the organs' overall quality. Hospital pharmacists are responsible for processing orders and preparing the medications outlined in donor management algorithms developed by their respective medical systems. It is important that pharmacists understand the details of the medications used in these protocols in order to critically evaluate each medication order and appropriately manage the donor. Typical medications used in organ donors after brain death include medications for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions. It is essential to provide optimal pharmacotherapy for each organ donor to ensure organ recovery and donation. Typical medications used in organ donors include agents for blood pressure management and fluid resuscitation, medications necessary for electrolyte management, blood products, vasopressors, hormone replacement therapy, antiinfectives, anticoagulants, paralytics, and organ preservation solutions. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  8. The Johnson Space Center Management Information Systems (JSCMIS). 1: Requirements Definition and Design Specifications for Versions 2.1 and 2.1.1. 2: Documented Test Scenario Environments. 3: Security Design and Specifications

    Science.gov (United States)

    1986-01-01

    The Johnson Space Center Management Information System (JSCMIS) is an interface to computer data bases at NASA Johnson which allows an authorized user to browse and retrieve information from a variety of sources with minimum effort. This issue gives requirements definition and design specifications for versions 2.1 and 2.1.1, along with documented test scenario environments, and security object design and specifications.

  9. IgE production after antigen-specific and cognate activation of HLA-DPw4-restricted T-cell clones, by 78% of randomly selected B-cell donors

    NARCIS (Netherlands)

    Baselmans, PJ; Pollabauer, EM; van Reijsen, FC; Heystek, HC; Hren, A; Stumptner, P; Tilanus, MGJ; Vooijs, WC; Mudde, GC

    The frequency of expression of the MHC class II antigen, HLA-DPw4, in the caucasoid population is approximately 78%, and is unmatched by phenotypic frequencies of other HLA class II molecules. Here we describe three human Der-P1-specific T-cell clones (TCC), restricted by the HLA-DPw4-variant

  10. Pax9 is required for filiform papilla development and suppresses skin-specific differentiation of the mammalian tongue epithelium.

    Science.gov (United States)

    Jonker, Leon; Kist, Ralf; Aw, Andrew; Wappler, Ilka; Peters, Heiko

    2004-11-01

    The epidermis is a derivative of the surface ectoderm. It forms a protective barrier and specific appendages including hair, nails, and different eccrine glands. The surface ectoderm also forms the epithelium of the oral cavity and tongue, which develop a slightly different barrier and form different appendages such as teeth, filiform papillae, taste papillae, and salivary glands. How this region-specific differentiation is genetically controlled is largely unknown. We show here that Pax9, which is expressed in the epithelium of the tongue but not in skin, regulates several aspects of tongue-specific epithelial differentiation. In Pax9-deficient mice filiform papillae lack the anterior-posterior polarity, a defect that is associated with temporal-spatial changes in Hoxc13 expression. Barrier formation is disturbed in the mutant tongue and genome-wide expression profiling revealed that the expression of specific keratins (Krt), keratin-associated proteins, and members of the epidermal differentiation complex is significantly down-regulated. In situ hybridization demonstrated that several 'hard' keratins, Krt1-5, Krt1-24, and Krt2-16, are not expressed in the absence of Pax9. Notably, specific 'soft' keratins, Krt2-1 and Krt2-17, normally weakly expressed in the tongue but present at high levels in skin and in orthokeratinized oral dysplasia are up-regulated in the mutant tongue epithelium. This result indicates a partial trans-differentiation to an epithelium with skin-specific characteristics. Together, our findings show that Pax9 regulates appendage formation in the mammalian tongue and identify Pax9 as an important factor for the region-specific differentiation of the surface ectoderm.

  11. Psychosocial counselling of identifiable sperm donors

    NARCIS (Netherlands)

    Visser, M.; Mochtar, M.H.; de Melker, A.A.; van der Veen, F.; Repping, S.; Gerrits, T.

    2016-01-01

    STUDY QUESTION: What do identifiable sperm donors feel about psychosocial counselling? SUMMARY ANSWER: Identifiable sperm donors found it important that psychosocial counselling focused on emotional consequences and on rules and regulations and they expected to have access to psychosocial

  12. Psychosocial counselling of identifiable sperm donors

    NARCIS (Netherlands)

    Visser, M. [=Marja; Mochtar, M. H.; de Melker, A. A.; van der Veen, F.; Repping, S.; Gerrits, T.

    2016-01-01

    What do identifiable sperm donors feel about psychosocial counselling? Identifiable sperm donors found it important that psychosocial counselling focused on emotional consequences and on rules and regulations and they expected to have access to psychosocial counselling at the time that

  13. Donor research and matching system based on data mining in organ transplantation.

    Science.gov (United States)

    Koyuncugil, Ali Serhan; Ozgulbas, Nermin

    2010-06-01

    It is very important to identify the appropriate donor in organ transplantation under the time constraint. Clearly, adequate time must be spent in appropriate donor research in that kind of vital operation. On the other hand, time is very important to search for other alternatives in case of inappropriate donor. However, the possibility for determining the most probable donors as fast as possible has an great importance in using time efficiently. From this point view, the main objective of this paper is developing a system which provides probabilistic prior information in donor transplantation via data mining. While the sytem development process, the basic element is the data of successful organ transplantations. Then, the hidden information and patterns will be discovered from this data. Therefore, this process requires the data mining methods from its definition. In this study, an appropriate donor detection system design based on data mining is suggested.

  14. Better innovate than compromise: a novel hepatic outflow reconstruction technique in pediatric living donor liver transplantation.

    Science.gov (United States)

    Cherian, P Thomas; Mishra, Ashish K; Bangaari, Ashish; Kota, Venugopal; Sathyanarayanan, Mohan; Raya, Ravichandra; Rela, Mohamed

    2015-05-01

    Pediatric LDLT using donors with unfavorable vascular anatomy is challenging in terms of donor safety, and complexity of reconstruction in the recipient. We describe an innovative technique of hepatic venous outflow reconstruction involving the recipient RHV, in the presence of a rudimentary RHV in the donor. The postoperative course of the donor and recipient was uneventful with satisfactory venous outflow in both. This technique avoided the use of prosthetic material, an important consideration given the recipient age and requirement for growth. This shows that donors previously considered unsuitable for donation can be utilized safely as long as principles of vascular anastomosis are adhered to. Moreover, it highlights that innovation is sometimes necessary to avoid compromise in donor safety. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Study on Effects of Electron Donors on Phosphine Production from Anaerobic Activated Sludge

    Directory of Open Access Journals (Sweden)

    Jianping Cao

    2017-07-01

    Full Text Available The effects of different types and concentrations of electron donors (glucose, starch, methanol and sodium acetate on the formation of phosphine from anaerobic activated sludge that has been domesticated for a prolonged period were studied in small batch experiments. The results show that types and concentrations of electron donor have significant effects on the production of phosphine from anaerobic activated sludge. Among them, glucose was the most favourable electron donor, whereas sodium acetate was the least favourable electron donor for the removal of phosphorus and the production of phosphine. Higher concentrations of electron donors were more favourable for the reduction of phosphate into phosphine, and supplying more than nine times the amount of electron donor as theoretically required for the reduction of phosphate into phosphine was favourable for the production of phosphine.

  16. Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host

    Directory of Open Access Journals (Sweden)

    Anna Schurich

    2016-08-01

    Full Text Available T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1hi T cell response against hepatitis B virus (HBV had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1hi HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.

  17. [Nursing management of a refractory cardiac death donor].

    Science.gov (United States)

    Kaufmann, Marion

    2016-09-01

    The nursing management of a refractory circulatory death donor is a new procedure which forms an integral part of patient care. It comprises technical and organisational aspects, and requires a conceptual, ethical and deontological effort. Copyright © 2016. Published by Elsevier Masson SAS.

  18. Distribution of potential eye and tissue donors within an Australian teaching hospital.

    Science.gov (United States)

    Dutch, Martin J; Denahy, Anthony F

    2017-12-11

    Eye and Tissue donation has the capacity to transform lives, yet the vast majority of potential in-hospital donors are not recognised. Studies which describe the relative importance of specific units or wards in determining the size of the donor pool are limited. The aim of this study was to map the distribution of potential Eye and Tissue donors within the study hospital. A 12-month retrospective analysis of all patient deaths at the study hospital was undertaken. The ability to donate corneal, heart valve, bone and skin tissue was investigated. Patients were classified as potential donors if they met specific age criteria and had an absence of contraindications based on electronic database search. There were 985 deaths during the study period. Deaths occurred under the care of 26 separate clinical units, and within 28 unique wards and treatment spaces. Four hundred and forty nine (45.6%) patients were identified as potential eye or tissue donors. The majority of potential donors occurred in ICU, Emergency and palliative care units. Of the subset of 328 deaths ≤ 70 years, the frequency of potential tissue donors was 55% (n = 181). ED and ICU had significantly higher frequencies of potential donor than other wards (86 and 77%, p Donors within our hospital. These will provide an important focus for future interventions to improve the rate of eye and tissue donation.

  19. 42 CFR 482.102 - Condition of participation: Patient and living donor rights.

    Science.gov (United States)

    2010-10-01

    ...-specific outcomes for living donors, as data are available; (7) The possibility that future health problems... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Patient and living... participation: Patient and living donor rights. In addition to meeting the condition of participation “Patients...

  20. Helical CT angiography : A single imaging modality to evaluate a live renal donor

    Directory of Open Access Journals (Sweden)

    Waheed Zaman

    2002-01-01

    Conclusions: Helical CT angiography, which is highly specific for arterial and venous anatomy as well as other anatomical and functional details, can become the single imaging modality for preoperative assessment of poten-tial donors in place of conventional angiography and IVU. CTA, being minimally invasive and cost effective, is well accepted by a normal healthy donor

  1. Risk Factors and Screening for Trypanosoma cruzi Infection of Dutch Blood Donors

    NARCIS (Netherlands)

    Slot, Ed; Hogema, Boris M.; Molier, Michel; Bart, Aldert; Zaaijer, Hans L.

    2016-01-01

    Blood donors unaware of Trypanosoma cruzi infection may donate infectious blood. Risk factors and the presence of T. cruzi antibodies in at-risk Dutch blood donors were studied to assess whether specific blood safety measures are warranted in the Netherlands. Birth in a country endemic for Chagas

  2. Plant-Specific Preprotein and Amino Acid Transporter Proteins Are Required for tRNA Import into Mitochondria1[OPEN

    Science.gov (United States)

    Kubiszewski-Jakubiak, Szymon; Teixeira, Pedro F.; Narsai, Reena; Ivanova, Aneta; Megel, Cyrille; Schock, Annette; Kraus, Sabrina; Glaser, Elzbieta; Philippar, Katrin; Maréchal-Drouard, Laurence; Soll, Jürgen

    2016-01-01

    A variety of eukaryotes, in particular plants, do not contain the required number of tRNAs to support the translation of mitochondria-encoded genes and thus need to import tRNAs from the cytosol. This study identified two Arabidopsis (Arabidopsis thaliana) proteins, Tric1 and Tric2 (for tRNA import component), which on simultaneous inactivation by T-DNA insertion lines displayed a severely delayed and chlorotic growth phenotype and significantly reduced tRNA import capacity into isolated mitochondria. The predicted tRNA-binding domain of Tric1 and Tric2, a sterile-α-motif at the C-terminal end of the protein, was required to restore tRNA uptake ability in mitochondria of complemented plants. The purified predicted tRNA-binding domain binds the T-arm of the tRNA for alanine with conserved lysine residues required for binding. T-DNA inactivation of both Tric proteins further resulted in an increase in the in vitro rate of in organello protein synthesis, which was mediated by a reorganization of the nuclear transcriptome, in particular of genes encoding a variety of proteins required for mitochondrial gene expression at both the transcriptional and translational levels. The characterization of Tric1/2 provides mechanistic insight into the process of tRNA import into mitochondria and supports the theory that the tRNA import pathway resulted from the repurposing of a preexisting protein import apparatus. PMID:27789739

  3. Cellular adhesion responses to the heparin-binding (HepII) domain of fibronectin require heparan sulfate with specific properties

    DEFF Research Database (Denmark)

    Mahalingam, Yashithra; Gallagher, John T; Couchman, John R

    2006-01-01

    Cell surface heparan sulfate (HS) proteoglycans are required in development and postnatal repair. Important classes of ligands for HS include growth factors and extracellular matrix macromolecules. For example, the focal adhesion component syndecan-4 interacts with the III(12-14) region of fibron......Cell surface heparan sulfate (HS) proteoglycans are required in development and postnatal repair. Important classes of ligands for HS include growth factors and extracellular matrix macromolecules. For example, the focal adhesion component syndecan-4 interacts with the III(12-14) region...... required for optimal inhibition. The presence of N-sulfated glucosamine in the HS was essential, whereas 2-O-sulfation of uronic acid or 6-O-sulfation of glucosamine had marginal effects. In the more complex response of focal adhesion formation through syndecan-4, N-sulfates were again required and also...... glucosamine 6-O-sulfate. The significance of polymer N-sulfation and sulfated domains in HS was confirmed by studies with mutant Chinese hamster ovary cells where heparan sulfation was compromised. Finally, focal adhesion formation was absent in fibroblasts synthesizing short HS chains resulting from a gene...

  4. 21 CFR 201.80 - Specific requirements on content and format of labeling for human prescription drug and...

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) DRUGS: GENERAL LABELING Labeling Requirements for Over-the-Counter Drugs § 201.80..., pathways of biotransformation, percentage of dose as unchanged drug and metabolites, rate or half-time of... account the importance of the drug to the mother.” If the drug is not associated with serious adverse...

  5. A Formal Analysis of the Shlaer-Mellor method: towards a toolkit for formal and informal requirements specification techniques

    NARCIS (Netherlands)

    Wieringa, Roelf J.; Saake, G.

    1996-01-01

    In this paper, we define a number of tools that we think belong to the core of any toolkit for requirements engineers. The tools are conceptual and hence, they need precise definitions that lay down as exactly as possible what their meaning and possible use is. We argue that this definition can best

  6. 40 CFR 152.95 - Citation of all studies in the Agency's files pertinent to a specific data requirement.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Citation of all studies in the Agency... PROCEDURES Procedures To Ensure Protection of Data Submitters' Rights § 152.95 Citation of all studies in the... for a data requirement by citation of all studies in the Agency's files pertinent of that data...

  7. Predictors of hemoglobin in Danish blood donors

    DEFF Research Database (Denmark)

    Kotze, Sebastian Ranzi; Pedersen, Ole B; Petersen, Mikkel S

    2015-01-01

    BACKGROUND: It is well known that blood donors are at increased risk of iron deficiency and subsequent development of iron deficiency anemia. We aimed to investigate the effect of factors influencing hemoglobin (Hb) levels. STUDY DESIGN AND METHODS: Initiated in 2010, the Danish Blood Donor Study...... measurement as a method of risk assessment among blood donors....

  8. The homeodomain factor Gbx1 is required for locomotion and cell specification in the dorsal spinal cord

    Directory of Open Access Journals (Sweden)

    Hamid Meziane

    2013-08-01

    Full Text Available Dorsal horn neurons in the spinal cord integrate and relay sensory information to higher brain centers. These neurons are organized in specific laminae and different transcription factors are involved in their specification. The murine homeodomain Gbx1 protein is expressed in the mantle zone of the spinal cord at E12.5-13.5, correlating with the appearance of a discernable dorsal horn around E14 and eventually defining a narrow layer in the dorsal horn around perinatal stages. At postnatal stages, Gbx1 identifies a specific subpopulation of GABAergic neurons in the dorsal spinal cord. We have generated a loss of function mutation for Gbx1 and analyzed its consequences during spinal cord development. Gbx1−/− mice are viable and can reproduce as homozygous null mutants. However, the adult mutant mice display an altered gait during forward movement that specifically affects the hindlimbs. This abnormal gait was evaluated by a series of behavioral tests, indicating that locomotion is impaired, but not muscle strength or motor coordination. Molecular analysis showed that the development of the dorsal horn is not profoundly affected in Gbx1−/− mutant mice. However, analysis of terminal neuronal differentiation revealed that the proportion of GABAergic inhibitory interneurons in the superficial dorsal horn is diminished. Our study unveiled a role for Gbx1 in specifying a subset of GABAergic neurons in the dorsal horn of the spinal cord involved in the control of posterior limb movement.

  9. Donor conversion rates depend on the assessment tools used in the evaluation of potential organ donors

    NARCIS (Netherlands)

    Y.J. de Groot (Yorick); E.F.M. Wijdicks (Eelco); M. van der Jagt (Mathieu); J. Bakker (Jan); B. Roozenbeek (Bob); J.N.M. IJzermans (Jan); E.J.O. Kompanje (Erwin)

    2011-01-01

    textabstractPurpose: It is desirable to identify a potential organ donor (POD) as early as possible to achieve a donor conversion rate (DCR) as high as possible which is defined as the actual number of organ donors divided by the number of patients who are regarded as a potential organ donor. The

  10. Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kállay, Krisztián; Kassa, Csaba; Réti, Marienn; Karászi, Éva; Sinkó, János; Goda, Vera; Stréhn, Anita; Csordás, Katalin; Horváth, Orsolya; Szederjesi, Attila; Tasnády, Szabolcs; Hardi, Apor; Kriván, Gergely

    2018-04-01

    Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

  11. Hypophosphatemia after Right Hepatectomy for Living Donor Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Kelly W Burak

    2004-01-01

    Full Text Available Hypophosphatemia has been described in patients undergoing right hepatectomy for liver cancer and in living donors for liver transplantation who also received total parenteral nutrition. At the study centre, significant hypophosphatemia (0.36 mmol/L or less requiring intravenous replacement was seen in two of the first nine living donors for adult-to-adult liver transplantation. To determine the frequency of hypophosphatemia in living donors, the authors obtained phosphate levels on stored serum samples from postoperative days 0, 1, 3 and 7 in all nine patients, none of whom were on total parenteral nutrition. Within the first week, hypophosphatemia developed in 55.6% of patients and phosphate levels returned to normal by day 7 in all nine patients. One patient had normal phosphate levels during the first week, but had profound hypophosphatemia (0.32 mmol/L on day 14 when he presented with a Staphylococcus aureus infection of a bile collection and significant hypoxemia. The extent of hepatectomy and the rate of liver regeneration, estimated by baseline and postoperative day 7 volumetric computed tomography scans, did not correlate with the development of hypophosphatemia. In conclusion, hypophosphatemia is common in living donors undergoing right hepatectomy and may be associated with complications. All living donors should be monitored for the development of hypophosphatemia during the first two postoperative weeks.

  12. Hyperbilirubinemia in normal healthy donors

    Directory of Open Access Journals (Sweden)

    Arora Veena

    2009-01-01

    Full Text Available The present study was carried out in B.A.R.C. Hospital Blood Bank over a span of five years, and includes 2734 donors. All the bags were screened for HIV, HBsAg, HCV and VDRL and the plasma in the pilot tubes of the blood bags was observed to detect any abnormality in color. In 27 cases plasma was found to be icteric and liver function tests were carried out on these samples. Two donors showed higher SGPT level, and were excluded. No significant increases in liver enzymes were recorded in the others. Causes of icteric plasma in these apparently healthy donors are discussed. Differential diagnosis includes Gilbert′s disease, hemolytic anemia, drug-induced anemia and other hepatic causes of hyperbilirubinemia, of which Gilbert′s disease is most probable cause with a prevalence of 0.91% in our population. As there are no studies to document the safety of the recipients receiving such abnormal colored plasma as well as to document the hazards in its transfusion, the question arises whether to transfuse such units or not. This study highlights this dilemma. A reassessment of existing policies and regulations is merited.

  13. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

    OpenAIRE

    Avijit Dutta; Ching-Tai Huang; Chun-Yen Lin; Tse-Ching Chen; Yung-Chang Lin; Chia-Shiang Chang; Yueh-Chia He

    2016-01-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus i...

  14. Algorithm for recall of HIV reactive Indian blood donors by sequential immunoassays enables selective donor referral for counseling

    Directory of Open Access Journals (Sweden)

    Thakral B

    2006-01-01

    Full Text Available Background: HIV/AIDS pandemic brought into focus the importance of safe blood donor pool. Aims: To analyze true seroprevalence of HIV infection in our blood donors and devise an algorithm for donor recall avoiding unnecessary referrals to voluntary counseling and testing centre (VCTC. Materials and Methods: 39,784 blood units were screened for anti-HIV 1/2 using ELISA immunoassay (IA-1. Samples which were repeat reactive on IA-1 were further tested using two different immunoassays (IA-2 and IA-3 and Western blot (WB. Based on results of these sequential IAs and WB, an algorithm for recall of true HIV seroreactive blood donors is suggested for countries like India where nucleic acid testing or p24 antigen assays are not mandatory and given the limited resources may not be feasible. Results: The anti-HIV seroreactivity by repeat IA-1, IA-2, IA-3 and WB were 0.16%, 0.11%, 0.098% and 0.07% respectively. Of the 44 IA-1 reactive samples, 95.2% (20/21 of the seroreactive samples by both IA-2 and IA-3 were also WB positive and 100% (6/6 of the non-reactive samples by these IAs were WB negative. IA signal/cutoff ratio was significantly low in biological false reactive donors. WB indeterminate results were largely due to non-specific reactivity to gag protein (p55. Conclusions: HIV seroreactivity by sequential immunoassays (IA-1, IA-2 and IA-3; comparable to WHO Strategy-III prior to donor recall results in decreased referral to VCTC as compared to single IA (WHO Strategy-I being followed currently in India. Moreover, this strategy will repose donor confidence in our blood transfusion services and strengthen voluntary blood donation program.

  15. Newborns as potential organ donors: a new perspective?

    Directory of Open Access Journals (Sweden)

    Ilias Chatziioannidis

    2015-02-01

    Full Text Available Demand for organ donation is increasing over the years in all age groups leading search for alternative sources. Donation pool expansion in newborns necessitates new approaches specifically for brain and circulatory death definition. The “dead donor rule” (the donor must be dead before organ removal starts remains the cornerstone for organ procurement. Brain death definition and time determination of circulatory death need to be uniformly accepted by the scientific community. Technical advances, uniform protocols for death determination and new proceedings in surgical field can maximize donation pool along with establishment of end-of-life care standard procedures and persistent support of the family. Newborns can serve as multivisceral donors in the near future to meet the increasing demand for organs in this age group.

  16. Patient experiences in advertising for an egg donor.

    Science.gov (United States)

    Nowoweiski, Sarah; Matic, Hayley; Foster, Penelope

    2011-06-01

    Advertising is a commonly used means of recruiting an egg donor within Australia. The aim of this study was to explore the experiences and outcomes of people's attempts to recruit an egg donor through advertising in a printed publication, Melbourne's Child. Individuals and couples who placed a new advertisement between July 2007 and December 2008 were invited to participate (n = 84), and those who expressed interest were mailed a questionnaire specifically designed for the purposes of this study. Thirty-one advertisers (37%) agreed to be sent the questionnaire and 28 were completed and returned (33%). Results showed that over half (56%) of respondents successfully recruited an egg donor through their advertisement in Melbourne's Child, 75% received at least one genuine reply and most people received a response within 2 weeks (50%) or 1-2 months (32%) after publication. At the time of completing the questionnaire, 48% had undergone a treatment cycle using donor eggs. Advertising was recalled as a stressful experience and 79% of respondents felt that more information about the success of advertising would have been helpful prior to embarking on this process. Results will be used to inform current clinical practice in assisting patients to recruit an egg donor. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  17. The dead donor rule, voluntary active euthanasia, and capital punishment.

    Science.gov (United States)

    Coons, Christian; Levin, Noah

    2011-06-01

    We argue that the dead donor rule, which states that multiple vital organs should only be taken from dead patients, is justified neither in principle nor in practice. We use a thought experiment and a guiding assumption in the literature about the justification of moral principles to undermine the theoretical justification for the rule. We then offer two real world analogues to this thought experiment, voluntary active euthanasia and capital punishment, and argue that the moral permissibility of terminating any patient through the removal of vital organs cannot turn on whether or not the practice violates the dead donor rule. Next, we consider practical justifications for the dead donor rule. Specifically, we consider whether there are compelling reasons to promulgate the rule even though its corresponding moral principle is not theoretically justified. We argue that there are no such reasons. In fact, we argue that promulgating the rule may actually decrease public trust in organ procurement procedures and medical institutions generally - even in states that do not permit capital punishment or voluntary active euthanasia. Finally, we examine our case against the dead donor rule in the light of common arguments for it. We find that these arguments are often misplaced - they do not support the dead donor rule. Instead, they support the quite different rule that patients should not be killed for their vital organs.

  18. Independent organ donor facilities: The future of organ donation?

    Science.gov (United States)

    Bruzzone, Paolo

    2014-01-01

    Since 2001 independent Organ Donor Facilities(OFOs) have been proposed within Organ Procurement Organizations (OPOs) with the aim of reducing organ procurement costs 1, cold ischemia time of donor organs and the flight-related risk 2 for donor surgeons, perfusionists and coordinators. An independent OFO has been established in 2001 in St. Louis 3, half away between the 2 Transplant Centers (TCs) (Washington University School of Medicine and St. Louis University) and now includes a two-bed intensive care facility, a complete laboratory, a cardiac catheterization facility, a Computed Tomography (CT) scanner and an operating room. All brain-dead (BD) patients within OPO (Mid-America Transplant Services), after family's informed consent, are transferred, if necessary by an OPO owned and operated airplane, to this facility, where undergo multiorgan harvesting. By doing so the organ acquisition charges (OACs) apparently decreased, as well as delay in recovery, which can affect organ viability and move families to withdraw consent; also risks and tiring of transplant surgeons were reduced. This independent OFO successfully procured in 2001 not only livers, but also pancreas, kidneys, hearts and lungs 4-6. Cold ischemia time was reduced and there was no Primary Non Function (PNF) of harvested organs, but only kidney delayed graft function (DGF). In the past, heart donors were moved to the recipient's hospital. With the development of multiorgan harvesting, usually donor surgeons are sent by the TCs in order to evaluate liver, pancreas, heart and lungs, while the only local surgeons is the "nephrectomist", that in local hospital is not a transplant surgeon. To move a donor, although hemodinamically stable, is always a risk. Finally, the decrease of OAC must balance the extra expenses to create and operate independent OFOs. In all the papers published by the members of this OFO, the control group of the retrospective analysis consisted of less selected BD donors, requiring

  19. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor.

    Science.gov (United States)

    Grigoleit, Gotz Ulrich; Kapp, Markus; Hebart, Holger; Fick, Kerstin; Beck, Robert; Jahn, Gerhard; Einsele, Hermann

    2007-09-01

    Vaccination with peptide-loaded dendritic cells (DCs) has been shown to be potent immunostimulatory therapy for the management of serious infections. After allogeneic stem cell transplant (SCT), a prolonged and severe immune deficiency often leads to infectious complications. Human cytomegalovirus (HCMV) infection is one such life-threatening complication after allogeneic SCT. A phase 1/2 study including 24 allogeneic SCT recipients at high risk for HCMV disease was performed to analyze the feasibility and efficacy of vaccination with HCMV peptide-loaded DCs. No acute adverse effects were observed, and a significant clinical benefit could be demonstrated in comparison to our historical control group. An induction or expansion of HCMV-specific cytotoxic T lymphocytes was observed in 5 patients after DC vaccination.

  20. Conceptual waste package interim product specifications and data requirements for disposal of glass commercial high-level waste forms in salt geologic repositories

    International Nuclear Information System (INIS)

    1983-10-01

    The conceptual waste package interim product specifications and data requirements presented are applicable to the reference glass composition described in PNL-3838 and carbon steel canister described in ONWI-438. They provide preliminary numerical values for the commercial high-level waste form parameters and properties identified in the waste form performance specification for geologic isolation in salt repositories. Subject areas treated include containment and isolation, operational period safety, criticality control, waste form/production canister identification, and waste package performance testing requirements. This document was generated for use in the development of conceptual waste package designs in salt. It will be revised as additional data, analyses and regulatory requirements become available. 13 references, 1 figure

  1. 'No daddy', 'A kind of daddy': words used by donor conceived children and (aspiring) parents to refer to the sperm donor.

    Science.gov (United States)

    Provoost, Veerle; Bernaerdt, Jodie; Van Parys, Hanna; Buysse, Ann; De Sutter, Petra; Pennings, Guido

    2018-04-01

    Research has shown that the recipients of donor sperm can experience difficulties finding appropriate language to refer to the donor. Based on two qualitative analysis techniques, namely word count and empirical discourse analysis, we studied the words used to refer to the donor in heterosexual and lesbian (aspiring) parents and in donor conceived children. Findings show that the words used in these households are highly diverse and have at least four different interlinked functions: (1) to position the donor in relation to the nuclear family; (2) to safeguard the role of the social parent; (3) to clarify family structure; and (4) to present a positive picture of the donor. Both parents and children consciously reflect on what words to use to refer to the donor. Although parents try to keep words like 'father' and 'daddy' out of the family narrative, children use these words. These findings show that it is important for healthcare personnel and policy makers to reflect on the careful use of terminology when they address questions around sperm donation because the terminology invokes specific meanings that have an effect on how the recipients and their children perceive the role of the donor.

  2. Mind bomb-1 in dendritic cells is specifically required for Notch-mediated T helper type 2 differentiation.

    Directory of Open Access Journals (Sweden)

    Hyun-Woo Jeong

    Full Text Available In dendritic cell (DC-CD4(+ T cell interaction, Notch signaling has been implicated in the CD4(+ T cell activation, proliferation, and subset differentiation. However, there has been a lot of debate on the exact role of Notch signaling. Here, we observed that expression of Mind bomb-1 (Mib1, a critical regulator of Notch ligands for the activation of Notch signaling, increases gradually as precursor cells differentiate into DCs in mice. To clarify the role of Mib1 in DC-CD4(+ T cell interactions, we generated Mib1-null bone marrow-derived DCs. These cells readily expressed Notch ligands but failed to initiate Notch activation in the adjacent cells. Nevertheless, Mib1-null DCs were able to prime the activation and proliferation of CD4(+ T cells, suggesting that Notch activation in CD4(+ T cells is not required for these processes. Intriguingly, stimulation of CD4(+ T cells with Mib1-null DCs resulted in dramatically diminished Th2 cell populations, while preserving Th1 cell populations, both in vitro and in vivo. Our results demonstrate that Mib1 in DCs is critical for the activation of Notch signaling in CD4(+ T cells, and Notch signaling reinforces Th2 differentiation, but is not required for the activation or proliferation of the CD4(+ T cells.

  3. A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response

    Directory of Open Access Journals (Sweden)

    Alison Iroz

    2017-10-01

    Full Text Available While the physiological benefits of the fibroblast growth factor 21 (FGF21 hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα, a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp−/− mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp−/− mice. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE in hepatocytes lacking PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21.

  4. Simulation shows that HLA-matched stem cell donors can remain unidentified in donor searches

    Science.gov (United States)

    Sauter, Jürgen; Solloch, Ute V.; Giani, Anette S.; Hofmann, Jan A.; Schmidt, Alexander H.

    2016-02-01

    The heterogeneous nature of HLA information in real-life stem cell donor registries may hamper unrelated donor searches. It is even possible that fully HLA-matched donors with incomplete HLA information are not identified. In our simulation study, we estimated the probability of these unnecessarily failed donor searches. For that purpose, we carried out donor searches in several virtual donor registries. The registries differed by size, composition with respect to HLA typing levels, and genetic diversity. When up to three virtual HLA typing requests were allowed within donor searches, the share of unnecessarily failed donor searches ranged from 1.19% to 4.13%, thus indicating that non-identification of completely HLA-matched stem cell donors is a problem of practical relevance. The following donor registry characteristics were positively correlated with the share of unnecessarily failed donor searches: large registry size, high genetic diversity, and, most strongly correlated, large fraction of registered donors with incomplete HLA typing. Increasing the number of virtual HLA typing requests within donor searches up to ten had a smaller effect. It follows that the problem of donor non-identification can be substantially reduced by complete high-resolution HLA typing of potential donors.

  5. Enzymatic activity of free-prostate-specific antigen (f-PSA) is not required for some of its physiological activities.

    Science.gov (United States)

    Chadha, Kailash C; Nair, Bindukumar B; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L; Aalinkeel, Ravikumar; Schwartz, Stanley A; Smith, Gary J

    2011-11-01

    Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+ . Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity. Copyright © 2011 Wiley-Liss, Inc.

  6. Enzymatic Activity of Free-Prostate-Specific Antigen (f-PSA) Is Not Required for Some of its Physiological Activities

    Science.gov (United States)

    Chadha, Kailash C.; Nair, Bindukumar B.; Chakravarthi, Srikant; Zhou, Rita; Godoy, Alejandro; Mohler, James L.; Aalinkeel, Ravikumar; Schwartz, Stanley A.; Smith, Gary J.

    2015-01-01

    BACKGROUND Prostate specific antigen (PSA) is a well known biomarker for early diagnosis and management of prostate cancer. Furthermore, PSA has been documented to have anti-angiogenic and anti-tumorigenic activities in both in vitro and in vivo studies. However, little is known about the molecular mechanism(s) involved in regulation of these processes, in particular the role of the serine-protease enzymatic activity of PSA. METHODS Enzymatic activity of PSA isolated directly from seminal plasma was inhibited specifically (>95%) by incubation with zinc2+. Human umbilical vein endothelial cells (HUVEC) were utilized to compare/contrast the physiological effects of enzymatically active versus inactive PSA. RESULTS Equimolar concentrations of enzymatically active PSA and PSA enzymatically inactivated by incubation with Zn2+ had similar physiological effects on HUVEC, including inhibiting the gene expression of pro-angiogenic growth factors, like VEGF and bFGF, and up-regulation of expression of the anti-angiogenic growth factor IFN-γ; suppression of mRNA expression for markers of blood vessel development, like FAK, FLT, KDR, TWIST-1; P-38; inhibition of endothelial tube formation in the in vitro Matrigel Tube Formation Assay; and inhibition of endothelial cell invasion and migration properties. DISCUSSION Our data provides compelling evidence that the transcriptional regulatory and the anti-angiogenic activities of human PSA are independent of the innate enzymatic activity PMID:21446007

  7. Issues in potential organ donor management.

    Science.gov (United States)

    Razek, T; Olthoff, K; Reilly, P M

    2000-06-01

    The shortage of organ donors has become a serious problem in modern medicine. Room for improvement exists in our ability to convert potential donors to actual donors based on the available numbers and a significant amount of recent research. A significant percentage of the potential donors represent head-injured patients, so a significant amount of responsibility falls on surgeons to optimize the opportunity for donation. There are clear steps along the pathway from potential to actual donor where physicians can have a significant effect on the rate of successful donation: 1. Identify all potential donors and institute a review system to verify that all potential donors are being identified in your area. 2. Establish an acceptable method to rapidly and accurately determine brain death in potential donors using the local available services. 3. Approach all potential donor families for consent, decouple death notification and consent request, use a member of the hospital team and an OPO representative to approach the family, and make the request in a private setting. 4. Use an aggressive, proactive approach to the medical management of the potential donor using the techniques described to limit the number of medical failures and maximize the number of organs donated per donor. Institute a review process to evaluate any medical failures that occur. Given the difference between the numbers of potential versus actual donors, the authors' significant contact with potential donors, and the clear opportunities for improvement in their approach, the surgical community must address these issues surrounding the optimal management of potential donors and their families.

  8. Donor Selection for Allogenic Hemopoietic Stem Cell Transplantation: Clinical and Ethical Considerations

    Directory of Open Access Journals (Sweden)

    Irene Riezzo

    2017-01-01

    Full Text Available Allogenic hematopoietic progenitor cell transplantation (allo-HSCT is an established treatment for many diseases. Stem cells may be obtained from different sources: mobilized peripheral blood stem cells, bone marrow, and umbilical cord blood. The progress in transplantation procedures, the establishment of experienced transplant centres, and the creation of unrelated adult donor registries and cord blood banks gave those without an human leucocyte antigen- (HLA- identical sibling donor the opportunity to find a donor and cord blood units worldwide. HSCT imposes operative cautions so that the entire donation/transplantation procedure is safe for both donors and recipients; it carries with it significant clinical, moral, and ethical concerns, mostly when donors are minors. The following points have been stressed: the donation should be excluded when excessive risks for the donor are reasonable, donors must receive an accurate information regarding eventual adverse events and health burden for the donors themselves, a valid consent is required, and the recipient’s risks must be outweighed by the expected benefits. The issue of conflict of interest, when the same physician has the responsibility for both donor selection and recipient care, is highlighted as well as the need of an adequate insurance protection for all the parties involved.

  9. Adult living donor liver transplantation: perspectives from 100 liver transplant surgeons.

    Science.gov (United States)

    Cotler, Scott J; Cotler, Sheldon; Gambera, Michele; Benedetti, Enrico; Jensen, Donald M; Testa, Giuliano

    2003-06-01

    The involvement of healthy living donors and the degree of technical difficulty make adult living donor liver transplantation (LDLT) different from any other surgical procedure. We surveyed 100 liver transplant surgeons to assess their views on the complex issues raised by LDLT. Data were collected at meetings on LDLT and by electronic mail. The study instrument was divided into general, donor, surgeon, recipient, and donor and recipient issues. Subjects provided the projected 1-year survival threshold that they would require for the recipient before they would perform LDLT. They listed the three topics that they thought were most critical for transplant fellows to know about LDLT. A majority agreed that transplant programs have a duty to their patients to offer LDLT, that the increasing success of the procedure will expand indications for liver transplantation, and that the risk to the donor causes them a moral dilemma. There was more divergence of opinion regarding who should have the final say about a potential donor's candidacy, whether it is difficult for donors to comprehend the risks of the procedure, and whether repeat cadaveric transplantations should be offered for failed LDLT performed for extended indications. Surgeons' median recipient survival threshold was a conservative 79%. Priorities for educating trainees focused on understanding complications and risks, technical factors, and ethical concerns such as putting the donor first. In conclusion, the findings of this survey indicate that transplant surgeons are working to balance their moral imperative to provide life-saving therapy for transplantation candidates with the risks posed to living donors.

  10. High Specificity in Circulating Tumor Cell Identification Is Required for Accurate Evaluation of Programmed Death-Ligand 1.

    Directory of Open Access Journals (Sweden)

    Jennifer L Schehr

    Full Text Available Expression of programmed-death ligand 1 (PD-L1 in non-small cell lung cancer (NSCLC is typically evaluated through invasive biopsies; however, recent advances in the identification of circulating tumor cells (CTCs may be a less invasive method to assay tumor cells for these purposes. These liquid biopsies rely on accurate identification of CTCs from the diverse populations in the blood, where some tumor cells share characteristics with normal blood cells. While many blood cells can be excluded by their high expression of CD45, neutrophils and other immature myeloid subsets have low to absent expression of CD45 and also express PD-L1. Furthermore, cytokeratin is typically used to identify CTCs, but neutrophils may stain non-specifically for intracellular antibodies, including cytokeratin, thus preventing accurate evaluation of PD-L1 expression on tumor cells. This holds even greater significance when evaluating PD-L1 in epithelial cell adhesion molecule (EpCAM positive and EpCAM negative CTCs (as in epithelial-mesenchymal transition (EMT.To evaluate the impact of CTC misidentification on PD-L1 evaluation, we utilized CD11b to identify myeloid cells. CTCs were isolated from patients with metastatic NSCLC using EpCAM, MUC1 or Vimentin capture antibodies and exclusion-based sample preparation (ESP technology.Large populations of CD11b+CD45lo cells were identified in buffy coats and stained non-specifically for intracellular antibodies including cytokeratin. The amount of CD11b+ cells misidentified as CTCs varied among patients; accounting for 33-100% of traditionally identified CTCs. Cells captured with vimentin had a higher frequency of CD11b+ cells at 41%, compared to 20% and 18% with MUC1 or EpCAM, respectively. Cells misidentified as CTCs ultimately skewed PD-L1 expression to varying degrees across patient samples.Interfering myeloid populations can be differentiated from true CTCs with additional staining criteria, thus improving the

  11. Temporal control of glial cell migration in the Drosophila eye requires gilgamesh, hedgehog, and eye specification genes.

    Science.gov (United States)

    Hummel, Thomas; Attix, Suzanne; Gunning, Dorian; Zipursky, S Lawrence

    2002-01-17

    In the Drosophila visual system, photoreceptor neurons (R cells) extend axons towards glial cells located at the posterior edge of the eye disc. In gilgamesh (gish) mutants, glial cells invade anterior regions of the eye disc prior to R cell differentiation and R cell axons extend anteriorly along these cells. gish encodes casein kinase Igamma. gish, sine oculis, eyeless, and hedgehog (hh) act in the posterior region of the eye disc to prevent precocious glial cell migration. Targeted expression of Hh in this region rescues the gish phenotype, though the glial cells do not require the canonical Hh signaling pathway to respond. We propose that the spatiotemporal control of glial cell migration plays a critical role in determining the directionality of R cell axon outgrowth.

  12. Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules.

    Science.gov (United States)

    Hanson, M Gartz; Landmesser, Lynn T

    2004-09-02

    Rhythmic spontaneous electrical activity occurs in many parts of the developing nervous system, where it plays essential roles in the refinement of neural connections. By blocking or slowing this bursting activity, via in ovo drug applications at precise developmental periods, we show that such activity is also required at much earlier stages for spinal motoneurons to accurately execute their first major dorsal-ventral pathfinding decision. Blockade or slowing of rhythmic bursting activity also prevents the normal expression patterns of EphA4 and polysialic acid on NCAM, which may contribute to the pathfinding errors observed. More prolonged (E2-5) blockade resulted in a downregulation of LIM homeodomain transcription factors, but since this occurred only after the pathfinding errors and alterations in guidance molecules, it cannot have contributed to them.

  13. Radiological source tracking in oil/gas, medical and other industries: requirements and specifications for passive RFID technology

    Energy Technology Data Exchange (ETDEWEB)

    Dowla, Farid U. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-01-01

    Subsurface sensors that employ radioisotopes, such 241Am-Be and 137Cs, for reservoir characterization must be tracked for safety and security reasons. Other radiological sources are also widely used in medicine. The radiological source containers, in both applications, are small, mobile and used widely worldwide. The nuclear sources pose radiological dispersal device (RDD) security risks. Security concerns with the industrial use of radionuclide sources is in fact quite high as it is estimated that each year hundreds of sealed sources go missing, either lost or stolen. Risk mitigation efforts include enhanced regulations, source-use guidelines, research and development on electronic tracking of sources. This report summarizes the major elements of the requirements and operational concepts of nuclear sources with the goal of developing automated electronic tagging and locating systems.

  14. Seropositivity of TTIs among blood donors in Hail, Saudi Arabia, from 2014 to 2015

    Directory of Open Access Journals (Sweden)

    Yousef Abd El Galil Ahmed Sarah

    2016-02-01

    Full Text Available Objective: To detect the seropositivity of transfusion transmitted infections among healthy blood donors in Hail Region, Saudi Arabia. Methods: In the study, about 361 blood donors from different nationalities and ages were tested. Serum samples were collected and tested by ELISA for detection of HIV, HTLV-I/II, hepatitis B virus, syphilis and hepatitis C virus (HCV. Results: Out of 361 donors, 26 were found to be positive for HCV in a percentage of 7.2% while 17 (4.7% of them were infected with HIV. There were eight donors infected with HTLV-I/II, and three donors infected with syphilis. Hepatitis B surface antigen was detected in 10% of donors while hepatitis B surface antibody and hepatitis B core antibody were positive in thirty-one blood donors. Conclusions: The obtained data revealed that the seropositivity of hepatitis B virus, HCV, syphilis, HTLV-I/II, and HIV in Hail Region during the period under study were 8.6%, 7.2%, 4.7%, 2.2% and 0.8%, respectively. It is recommended to continue screening blood donors with highly specific and sensitive tests, to counsel donors who are positive to transfusion transmitted infections.

  15. An Adapted Post-Donation Motivational Interview Enhances Blood Donor Retention

    Science.gov (United States)

    Sinclair, Kadian S.; Campbell, Tavis S.; Carey, Patricia M.; Langevin, Eric; Bowser, Brent; France, Christopher R.

    2010-01-01

    Background Blood donors may hold conflicting thoughts about future donation. While they may perceive the direct benefit to themselves and others, they often report compelling reasons not to give again. As a result the standard encouragements to return may not be sufficient to motivate some donors. The present study examined the effects of a post-donation adapted motivational interview on blood donor attitudes and repeat donation behavior. Study Design and Methods Donors (n=215) were randomly assigned to either an adapted motivational interview (AMI) or a no-interview control group. Approximately one month after their index donation, donors in the AMI group completed a brief telephone interview to clarify individual-specific motivations and values concerning blood donation and address potential barriers. They were then asked to complete questionnaires regarding donation attitudes, anxiety, self-efficacy and intention to donate. Donors in the control group were also contacted one month post-donation and asked to complete the same series of questionnaires. Results Donors in the AMI group reported greater intention to provide a future donation, F = 8.13, p motivational interview may be an effective strategy to increase the donor pool by enhancing retention of existing donors. PMID:20456674

  16. A Novel Testis-Specific Gene, Ccdc136, Is Required for Acrosome Formation and Fertilization in Mice.

    Science.gov (United States)

    Geng, Qiang; Ni, Liwei; Ouyang, Bin; Hu, Yanhua; Zhao, Yu; Guo, Jun

    2016-10-01

    Testis-specific genes are essential for the spermatogenesis in mammalian male reproduction. In this study, we have identified a novel testis-specific gene, Ccdc136 (coiled-coil domain containing 136), from the results of high-throughput gene expression profiling in the developmental stage of mouse testes. Ccdc136 was conserved across species in evolution. Quantitative real-time polymerase chain reaction and Western blot analyses showed that Ccdc136 messenger RNA and protein were extraordinarily expressed in mouse testes, which was first presented at postnatal 3 week and increased in an age-dependent manner before adulthood. Immunofluorescence staining revealed that CCDC136 protein was most abundantly located in the acrosome of round spermatids and elongating spermatids within seminiferous tubules of the adult mouse testes. To investigate the function of Ccdc136 in mouse testes, we generated the Ccdc136-knockout mice using Cas9/RNA-mediated gene targeting technology. Interestingly, we found Ccdc136(-/-) males were infertile, due to severe defect of disrupting acrosome formation. The expression levels of proteins (SPACA1 and PICK1) involved in acrosome formation were significantly downregulated in the testes of Ccdc136(-/-) mice than wide-type mice. Moreover, in vitro fertilization assay revealed that anti-CCDC136 antibody could remarkably inhibit fertilization, suggesting CCDC136 also plays an important role in fertilization. All of these demonstrated the essential role of CCDC136-mediated acrosome formation in spermatogenesis and fertilization, which might also provide new insight into the genetic causes of human infertility. © The Author(s) 2016.

  17. 21 CFR 864.9320 - Copper sulfate solution for specific gravity determinations.

    Science.gov (United States)

    2010-04-01

    ... determinations. 864.9320 Section 864.9320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... determinations. (a) Identification. A copper sulfate solution for specific gravity determinations is a device used to determine whether the hemoglobin content of a potential donor's blood meets the required level...

  18. Specific binding sites for an antifungal plant defensin from Dahlia (Dahlia merckii) on fungal cells are required for antifungal activity.

    Science.gov (United States)

    Thevissen, K; Osborn, R W; Acland, D P; Broekaert, W F

    2000-01-01

    Dm-AMP1, an antifungal plant defensin from seeds of dahlia (Dahlia merckii), was radioactively labeled with t-butoxycarbonyl-[35S]-L-methionine N-hydroxy-succinimi-dylester. This procedure yielded a 35S-labeled peptide with unaltered antifungal activity. [35S]Dm-AMP1 was used to assess binding on living cells of the filamentous fungus Neurospora crassa and the unicellular fungus Saccharomyces cerevisiae. Binding of [35S]Dm-AMP1 to fungal cells was saturable and could be competed for by preincubation with excess, unlabeled Dm-AMP1 as well as with Ah-AMP1 and Ct-AMP1, two plant defensins that are highly homologous to Dm-AMP1. In contrast, binding could not be competed for by more distantly related plant defensins or structurally unrelated antimicrobial peptides. Binding of [35S]Dm-AMP1 to either N. crassa or S. cerevisiae cells was apparently irreversible. In addition, whole cells and microsomal membrane fractions from two independently obtained S. cerevisiae mutants selected for resistance to Dm-AMP1 exhibited severely reduced binding affinity for [35S]Dm-AMP1, compared with wild-type yeast. This finding suggests that binding of Dm-AMP1 to S. cerevisiae plasma membranes is required for antifungal activity of this protein.

  19. Distributing and storing required data efficiently by means of specifically tailored data formats in the ATLAS collaboration

    CERN Document Server

    Koeneke, K; The ATLAS collaboration

    2011-01-01

    With the start of the LHC physics program, the ATLAS experiment started to record vast amounts of data. This data has to be distributed and stored on the world-wide computing grid in a smart way in order to enable an effective and efficient analysis by physicists. There are in principle two classes of analysis that are required. In the commissioning phase of the ATLAS experiment, low-level Event Summary Data (ESD), the result of the event reconstruction, has to be analyzed to evaluate the performance of the individual subdetectors, the performance of the reconstruction and particle identification algorithms, and to obtain calibration coefficients. For later physics analysis, it is usually sufficient to use the less detailed Analysis Object Data (AOD), which is a less-detailed version of the ESD. In the grid model of distributed analysis, these data must be transferred to Tier-2 sites before they can be analyzed. However, the large size of ESD (~1 MByte/event) constrains the amount of detailed data that can be...

  20. Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors

    Science.gov (United States)

    Lodge, Emily J.; Panousopoulos, Leonidas; Haston, Scott; Gonzalez-Meljem, Jose Mario; Hahn, Heidi; Martinez-Barbera, Juan Pedro

    2017-01-01

    Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead a crucial role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos. First, we show that conditional deletion of Shh in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of Lhx3/Lhx4 expression in RP epithelium at 9.0 days post coitum (dpc) and total loss of pituitary tissue by 12.5 dpc. Conversely, overactivation of the SHH pathway by conditional deletion of Ptch1 in RP progenitors leads to severe hyperplasia and enlargement of the Sox2+ stem cell compartment by the end of gestation. PMID:28807898

  1. Stage-Specific Changes in Plasmodium Metabolism Required for Differentiation and Adaptation to Different Host and Vector Environments.

    Directory of Open Access Journals (Sweden)

    Anubhav Srivastava

    2016-12-01

    Full Text Available Malaria parasites (Plasmodium spp. encounter markedly different (nutritional environments during their complex life cycles in the mosquito and human hosts. Adaptation to these different host niches is associated with a dramatic rewiring of metabolism, from a highly glycolytic metabolism in the asexual blood stages to increased dependence on tricarboxylic acid (TCA metabolism in mosquito stages. Here we have used stable isotope labelling, targeted metabolomics and reverse genetics to map stage-specific changes in Plasmodium berghei carbon metabolism and determine the functional significance of these changes on parasite survival in the blood and mosquito stages. We show that glutamine serves as the predominant input into TCA metabolism in both asexual and sexual blood stages and is important for complete male gametogenesis. Glutamine catabolism, as well as key reactions in intermediary metabolism and CoA synthesis are also essential for ookinete to oocyst transition in the mosquito. These data extend our knowledge of Plasmodium metabolism and point towards possible targets for transmission-blocking intervention strategies. Furthermore, they highlight significant metabolic differences between Plasmodium species which are not easily anticipated based on genomics or transcriptomics studies and underline the importance of integration of metabolomics data with other platforms in order to better inform drug discovery and design.

  2. Specific defects in different transcription complexes compensate for the requirement of the negative cofactor 2 repressor in Saccharomyces cerevisiae.

    Science.gov (United States)

    Peiró-Chova, Lorena; Estruch, Francisco

    2007-05-01

    Negative cofactor 2 (NC2) has been described as an essential and evolutionarily conserved transcriptional repressor, although in vitro and in vivo experiments suggest that it can function as both a positive and a negative effector of transcription. NC2 operates by interacting with the core promoter and components of the basal transcription machinery, like the TATA-binding protein (TBP). In this work, we have isolated mutants that suppress the growth defect caused by the depletion of NC2. We have identified mutations affecting components of three different complexes involved in the control of basal transcription: the mediator, TFIIH, and RNA pol II itself. Mutations in RNA pol II include both overexpression of truncated forms of the two largest subunits (Rpb1 and Rpb2) and reduced levels of these proteins. Suppression of NC2 depletion was also observed by reducing the amounts of the mediator essential components Nut2 and Med7, as well as by deleting any of the nonessential mediator components, except Med2, Med3, and Gal11 subunits. Interestingly, the Med2/Med3/Gal11 triad forms a submodule within the mediator tail. Our results support the existence of different components within the basic transcription complexes that antagonistically interact with the NC2 repressor and suggest that the correct balance between the activities of specific positive and negative components is essential for cell growth.

  3. Zygotic LvBMP5-8 is required for skeletal patterning and for left-right but not dorsal-ventral specification in the sea urchin embryo.

    Science.gov (United States)

    Piacentino, Michael L; Chung, Oliver; Ramachandran, Janani; Zuch, Daniel T; Yu, Jia; Conaway, Evan A; Reyna, Arlene E; Bradham, Cynthia A

    2016-04-01

    Skeletal patterning in the sea urchin embryo requires coordinated signaling between the pattern-dictating ectoderm and the skeletogenic primary mesenchyme cells (PMCs); recent studies have begun to uncover the molecular basis for this process. Using an unbiased RNA-Seq-based screen, we have previously identified the TGF-ß superfamily ligand, LvBMP5-8, as a skeletal patterning gene in Lytechinus variegatus embryos. This result is surprising, since both BMP5-8 and BMP2/4 ligands have been implicated in sea urchin dorsal-ventral (DV) and left-right (LR) axis specification. Here, we demonstrate that zygotic LvBMP5-8 is required for normal skeletal patterning on the left side, as well as for normal PMC positioning during gastrulation. Zygotic LvBMP5-8 is required for expression of the left-side marker soxE, suggesting that LvBMP5-8 is required for left-side specification. Interestingly, we also find that LvBMP5-8 knockdown suppresses serotonergic neurogenesis on the left side. While LvBMP5-8 overexpression is sufficient to dorsalize embryos, we find that zygotic LvBMP5-8 is not required for normal DV specification or development. In addition, ectopic LvBMP5-8 does not dorsalize LvBMP2/4 morphant embryos, indicating that, in the absence of BMP2/4, BMP5-8 is insufficient to specify dorsal. Taken together, our data demonstrate that zygotic LvBMP5-8 signaling is essential for left-side specification, and for normal left-side skeletal and neural patterning, but not for DV specification. Thus, while both BMP2/4 and BMP5-8 regulate LR axis specification, BMP2/4 but not zygotic BMP5-8 regulates DV axis specification in sea urchin embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from Legionella pneumophila: substrate specificity and requirement for virulence.

    Science.gov (United States)

    Sansom, Fiona M; Riedmaier, Patrice; Newton, Hayley J; Dunstone, Michelle A; Müller, Christa E; Stephan, Holger; Byres, Emma; Beddoe, Travis; Rossjohn, Jamie; Cowan, Peter J; d'Apice, Anthony J F; Robson, Simon C; Hartland, Elizabeth L

    2008-05-09

    Legionella pneumophila is the predominant cause of Legionnaires disease, a severe and potentially fatal form of pneumonia. Recently, we identified an ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila, termed Lpg1905, which enhances intracellular replication of L. pneumophila in eukaryotic cells. Lpg1905 is the first prokaryotic member of the CD39/NTPDase1 family of enzymes, which are characterized by the presence of five apyrase conserved regions and the ability to hydrolyze nucleoside tri- and diphosphates. Here we examined the substrate specificity of Lpg1905 and showed that apart from ATP and ADP, the enzyme catalyzed the hydrolysis of GTP and GDP but had limited activity against CTP, CDP, UTP, and UDP. Based on amino acid residues conserved in the apyrase conserved regions of eukaryotic NTPDases, we generated five site-directed mutants, Lpg1905E159A, R122A, N168A, Q193A, and W384A. Although the mutations E159A, R122A, Q193A, and W384A abrogated activity completely, N168A resulted in decreased activity caused by reduced affinity for nucleotides. When introduced into the lpg1905 mutant strain of L. pneumophila, only N168A partially restored the ability of L. pneumophila to replicate in THP-1 macrophages. Following intratracheal inoculation of A/J mice, none of the Lpg1905 mutants was able to restore virulence to an lpg1905 mutant during lung infection, thereby demonstrating the importance of NTPDase activity to L. pneumophila infection. Overall, the kinetic studies undertaken here demonstrated important differences to mammalian NTPDases and different sensitivities to NTPDase inhibitors that may reflect underlying structural variations.

  5. DoMINO: Donor milk for improved neurodevelopmental outcomes.

    Science.gov (United States)

    Unger, Sharon; Gibbins, Sharyn; Zupancic, John; O'Connor, Deborah L

    2014-05-13

    Provision of mother's own milk is the optimal way to feed infants, including very low birth weight infants (VLBW, pasteurized donor milk compared to preterm formula as a supplement to mother's own milk for 90 days or until hospital discharge, whichever comes first, will have an improved cognitive outcome as measured at 18 months corrected age on the Bayley Scales of Infant Development, 3(rd) ed. Secondary hypotheses are that the use of pasteurized donor milk will: (1) reduce a composite of death and serious morbidity; (2) support growth; and (3) improve language and motor development. Exploratory research questions include: Will use of pasteurized donor milk: (1) influence feeding tolerance and nutrient intake (2) have an acceptable cost effectiveness from a comprehensive societal perspective? DoMINO is a multi-centre, intent-to-treat, double blinded, randomized control trial. VLBW infants (n = 363) were randomized within four days of birth to either (1) pasteurized donor milk or (2) preterm formula whenever mother's own milk was unavailable. Study recruitment began in October 2010 and was completed in December 2012. The 90 day feeding intervention is complete and long-term follow-up is underway. Preterm birth and its complications are a leading cause long-term morbidity among Canadian children. Strategies to mitigate this risk are urgently required. As mother's own milk has been shown to improve neurodevelopment, it is essential to ascertain whether pasteurized donor milk will confer the same advantage over formula without undue risks and at acceptable costs. Knowledge translation from this trial will be pivotal in setting donor milk policy in Canada and beyond. ISRCTN35317141; Registered 10 August 2010.

  6. Outcomes of Organ Transplantation from Donors with a Cancer History

    Science.gov (United States)

    Huang, Shanzhou; Tang, Yunhua; Zhu, Zebin; Yang, Jie; Zhang, Zhiheng; Wang, Linhe; Sun, Chengjun; Zhang, Yixi; Zhao, Qiang; Chen, Maogen; Wu, Linwei; Wang, Dongping

    2018-01-01

    Background The inherent challenges of selecting an acceptable donor for the increasing number and acuity of recipients has forced programs to take increased risks, including accepting donors with a cancer history (DWCH). Outcomes of organ transplantation using organs from DWCH must be clarified. We assessed transplant outcomes of recipients of organs from DWCH. Material/Methods Retrospective analysis of the Scientific Registry of Transplant Recipients data from January 1, 2000 to December 31, 2014 identified 8385 cases of transplants from DWCH. A Cox-proportional hazard regression model and log-rank test were used to compare patient survival and hazard levels of various cancer types. Results DWCH was an independent risk factor of 5-year patient survival (HR=1.089, 95% CI: 1.009–1.176, P=0.03) and graft survival (HR=1.129, 95% CI: 1.056–1.208, Ptransplantation (patient survival: HR=1.112, 95% CI: 1.057–1.170, Ptransplantation. Donors with genitourinary and gastrointestinal cancers were associated with inferior outcomes in kidney transplantation. Transplantation from donors with central nervous system cancer resulted in poorer survival in liver transplant recipients. Recipients of organs from donors with hematologic malignancy and otorhinolaryngologic cancer had poorer survival following heart transplantation. Conclusions Under the current donor selection criteria, recipients of organs from DWCH had inferior outcomes in liver and heart transplantation, whereas organs from DWCH were safely applied in kidney and lung transplantation. Specific cancer types should be cautiously evaluated before performing certain types of organ transplantation. PMID:29455213

  7. Survey of U.S. Organ Procurement Organizations Regarding Pediatric Organ Donor Management.

    Science.gov (United States)

    Ream, Robert S; Armbrecht, Eric S

    2016-10-01

    To describe the current practice of pediatric organ donor management in the United States for donors declared dead based upon neurologic criteria. The study directs particular attention to how pediatric donors are defined, the use of donor management guidelines, the use of donor management goals, and the involvement of pediatric critical care or transplantation expertise. Cross-sectional observational study using a web-based survey and follow-up telephone interview with respondents from U.S. organ procurement organizations. The study also incorporated organ procurement organization-specific data on organ yield for the 4-year period (2010-2013) preceding the study. The 58 U.S. organ procurement organizations. Respondents chosen by each organ procurement organization. None. All 58 U.S. organ procurement organizations participated in the study. Fifty-two respondents (90%) indicated that their organ procurement organization distinguished pediatric from adult donors resulting in 28 unique pediatric definitions. Thirty-nine organ procurement organizations utilized some form of written pediatric management guidelines, and 27 (47%) maintained pediatric donor management goals; compliance was infrequently monitored for both guidelines (28%) and goals (33%). A pediatric intensivist was always or usually involved in pediatric donor management at 47 organ procurement organizations (81%); transplant/organ recovery surgeons were always or usually involved at 12 organ procurement organizations (21%). There was an increase in the number of organs transplanted per donor among donors 11-17 years old for organ procurement organizations that used donor management goals for the duration of the period studied (p organs transplanted among donors of 0-10 years old for organ procurement organizations that always or usually consulted a transplant/organ recovery surgeon (p = 0.02) although this did not reach our threshold for statistical significance.. There is little consensus among organ

  8. Use of computed tomography assessed kidney length to predict split renal GFR in living kidney donors

    International Nuclear Information System (INIS)

    Gaillard, Francois; Fournier, Catherine; Leon, Carine; Legendre, Christophe; Pavlov, Patrik; Tissier, Anne-Marie; Correas, Jean-Michel; Harache, Benoit; Hignette, Chantal; Weinmann, Pierre; Eladari, Dominique; Timsit, Marc-Olivier; Mejean, Arnaud; Friedlander, Gerard; Courbebaisse, Marie; Houillier, Pascal

    2017-01-01

    Screening of living kidney donors may require scintigraphy to split glomerular filtration rate (GFR). To determine the usefulness of computed tomography (CT) to split GFR, we compared scintigraphy-split GFR to CT-split GFR. We evaluated CT-split GFR as a screening test to detect scintigraphy-split GFR lower than 40 mL/min/1.73 m 2 /kidney. This was a monocentric retrospective study on 346 potential living donors who had GFR measurement, renal scintigraphy, and CT. We predicted GFR for each kidney by splitting GFR using the following formula: Volume-split GFR for a given kidney = measured GFR*[volume of this kidney/(volume of this kidney + volume of the opposite kidney)]. The same formula was used for length-split GFR. We compared length- and volume-split GFR to scintigraphy-split GFR at donation and with a 4-year follow-up. A better correlation was observed between length-split GFR and scintigraphy-split GFR (r = 0.92) than between volume-split GFR and scintigraphy-split GFR (r = 0.89). A length-split GFR threshold of 45 mL/min/1.73 m 2 /kidney had a sensitivity of 100 % and a specificity of 75 % to detect scintigraphy-split GFR less than 40 mL/min/1.73 m 2 /kidney. Both techniques with their respective thresholds detected living donors with similar eGFR evolution during follow-up. Length-split GFR can be used to detect patients requiring scintigraphy. (orig.)

  9. Use of computed tomography assessed kidney length to predict split renal GFR in living kidney donors

    Energy Technology Data Exchange (ETDEWEB)

    Gaillard, Francois; Fournier, Catherine; Leon, Carine; Legendre, Christophe [Paris Descartes University, AP-HP, Hopital Necker-Enfants Malades, Renal Transplantation Department, Paris (France); Pavlov, Patrik [Linkoeping University, Linkoeping (Sweden); Tissier, Anne-Marie; Correas, Jean-Michel [Paris Descartes University, AP-HP, Hopital Necker-Enfants Malades, Radiology Department, Paris (France); Harache, Benoit; Hignette, Chantal; Weinmann, Pierre [Paris Descartes University, AP-HP, Hopital Europeen Georges Pompidou, Nuclear Medicine Department, Paris (France); Eladari, Dominique [Paris Descartes University, and INSERM, Unit 970, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France); Timsit, Marc-Olivier; Mejean, Arnaud [Paris Descartes University, AP-HP, Hopital Europeen Georges Pompidou, Urology Department, Paris (France); Friedlander, Gerard; Courbebaisse, Marie [Paris Descartes University, and INSERM, Unit 1151, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France); Houillier, Pascal [Paris Descartes University, INSERM, Unit umrs1138, and CNRS Unit erl8228, AP-HP, Hopital Europeen Georges Pompidou, Physiology Department, Paris (France)

    2017-02-15

    Screening of living kidney donors may require scintigraphy to split glomerular filtration rate (GFR). To determine the usefulness of computed tomography (CT) to split GFR, we compared scintigraphy-split GFR to CT-split GFR. We evaluated CT-split GFR as a screening test to detect scintigraphy-split GFR lower than 40 mL/min/1.73 m{sup 2}/kidney. This was a monocentric retrospective study on 346 potential living donors who had GFR measurement, renal scintigraphy, and CT. We predicted GFR for each kidney by splitting GFR using the following formula: Volume-split GFR for a given kidney = measured GFR*[volume of this kidney/(volume of this kidney + volume of the opposite kidney)]. The same formula was used for length-split GFR. We compared length- and volume-split GFR to scintigraphy-split GFR at donation and with a 4-year follow-up. A better correlation was observed between length-split GFR and scintigraphy-split GFR (r = 0.92) than between volume-split GFR and scintigraphy-split GFR (r = 0.89). A length-split GFR threshold of 45 mL/min/1.73 m{sup 2}/kidney had a sensitivity of 100 % and a specificity of 75 % to detect scintigraphy-split GFR less than 40 mL/min/1.73 m{sup 2}/kidney. Both techniques with their respective thresholds detected living donors with similar eGFR evolution during follow-up. Length-split GFR can be used to detect patients requiring scintigraphy. (orig.)

  10. Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell Infusion: The importance of durable chimerism.

    Science.gov (United States)

    Leventhal, Joseph R; Ildstad, Suzanne T

    2018-03-01

    Successful solid organ transplantation currently requires the life-long use of medications to suppress the immune system in order to prevent transplant rejection. Drug-based immunosuppression significantly increases the risk of infection and cancer, as well as being very costly. Development of new therapies to minimize or eliminate entirely the need for anti-rejection drugs is of great interest to the transplant community. Therapeutic cell transfer for the control of the human immune system represents a compelling approach to reduce or eliminate the need for anti-rejection drugs. Establishment of durable hematopoietic chimerism through hematopoietic stem cell transplantation (HSCT) has been shown in preclinical models and patients to lead to donor specific tolerance. However, the application HSCT is limited by the potential toxicity of conditioning regimens, the risk of graft versus host disease (GVHD) and the challenge of HLA mismatching. In this review we describe the clinical outcomes and science behind a CD8 + /TCR - facilitating cell-based hematopoietic stem cell transplant approach (termed FCRx) to induce tolerance to mismatched renal allografts while minimizing the risk of graft-versus-host GVHD and achieving avoidance of long-term immunosuppressant drugs in living donor kidney transplant recipients. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  11. Attitudes of sperm, egg and embryo donors and recipients towards genetic information and screening of donors.

    Science.gov (United States)

    Amor, David J; Kerr, Annabelle; Somanathan, Nandini; McEwen, Alison; Tome, Marianne; Hodgson, Jan; Lewis, Sharon

    2018-02-09

    Gamete and embryo donors undergo genetic screening procedures in order to maximise the health of donor-conceived offspring. In the era of genomic medicine, expanded genetic screening may be offered to donors for the purpose of avoiding transmission of harmful genetic mutations. The objective of this study was to explore the attitudes of donors and recipients toward the expanded genetic screening of donors. Qualitative interview study with thematic analysis, undertaken in a tertiary fertility centre. Semi-structured in-depth qualitative interviews were conducted with eleven recipients and nine donors from three different cohorts (sperm, egg and embryo donors/recipients). Donors and recipients acknowledged the importance of genetic information and were comfortable with the existing level of genetic screening of donors. Recipients recognised some potential benefits of expanded genetic screening of donors; however both recipients and donors were apprehensive about extended genomic technologies, with concerns about how this information would be used and the ethics of genetic selectivity. Participants in donor programs support some level of genetic screening of donors, but are wary of expanding genetic screening beyond current levels.

  12. Donor risk factors for graft failure in the cornea donor study.

    Science.gov (United States)

    Sugar, Joel; Montoya, Monty; Dontchev, Mariya; Tanner, Jean Paul; Beck, Roy; Gal, Robin; Gallagher, Shawn; Gaster, Ronald; Heck, Ellen; Holland, Edward J; Kollman, Craig; Malling, Jackie; Mannis, Mark J; Woody, Jason

    2009-10-01

    The purpose of this study was to assess the relationship between donor factors and 5-year corneal graft survival in the Cornea Donor Study. Donor corneas met criteria established by the Eye Bank Association of America, had an endothelial cell density of 2300 to 3300/mm, and were determined to be of good to excellent quality by the eye banks. Donor corneas were assigned using a random approach and surgeons were masked to information about the donor cornea including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines and subjects were followed for 5 years. Donor and donor cornea factors were evaluated for their association with graft failure, which was defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. Graft failure was not significantly associated with the type of tissue retrieval (enucleation versus in situ), processing factors, timing of use of the cornea, or characteristics of the donor or the donor cornea. Adjusting for donor age did not affect the results. Donor and donor cornea characteristics do not impact graft survival rates for corneas comparable in quality to those used in this study.

  13. Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors.

    Science.gov (United States)

    Heim, Albert

    2016-05-01

    The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. ID-NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc-positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors.

  14. Should living donor liver transplantation be an option when deceased donation is not?

    Science.gov (United States)

    Lieber, Sarah R; Schiano, Thomas D; Rhodes, Rosamond

    2018-05-01

    When a liver transplantation candidate is declined for listing to receive a deceased organ, sometimes a loved one comes forward and offers to be a living donor. This raises the ethical question of whether a patient who is not eligible for deceased donor liver transplantation should be eligible for living donor liver transplantation. We compare living organ donation in kidney and liver transplantation and explore key ethical concepts of justice, fairness, and societal trust. Ultimately, because there is no alternative life-preserving therapy in end-stage liver disease, and because transplantation with a living donor organ does not involve removing a resource from the common pool of transplant organs, we argue that a standard of "slightly less benefit" than that required for deceased transplantation should be used to determine the acceptability of living donor liver transplantation. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  15. Prisoners as Living Donors: A Vulnerabilities Analysis.

    Science.gov (United States)

    Ross, Lainie Friedman; Thistlethwaite, J Richard

    2018-01-01

    Although national guidelines exist for evaluating the eligibility of potential living donors and for procuring their informed consent, no special protections or considerations exist for potential living donors who are incarcerated. Human research subject protections in the United States are codified in the Federal Regulations, 45 CFR 46, and special protections are given to prisoners. Living donor transplantation has parallels with human subject research in that both activities are performed with the primary goal of benefiting third parties. In this article, we describe what special considerations should be provided to prisoners as potential living donors using a vulnerabilities approach adapted from the human research subject protection literature.

  16. Transperitoneal laparoscopic live donor nephrectomy: Current status

    Directory of Open Access Journals (Sweden)

    A Srivastava

    2007-01-01

    Full Text Available Renal transplantation is the treatment of choice for a suitable patient with end stage renal disease. Unfortunately, the supply of donor organs is greatly exceeded by demand. In many countries the use of kidneys from living donors has been widely adopted as a partial solution. Traditionally donor nephrectomy has been performed via a open flank incision however with some morbidity like pain and a loin scar. Currently, the donor nephrectomy is increasingly being performed laparoscopically with the objective of reducing the morbidity. It is also hoped that this will lead to increasing acceptance of living donation. The first minimally invasive living donor nephrectomy was carried out in 1995 at the Johns Hopkins Medical Center and since then many centers have undertaken laparoscopic living donor nephrectomy. The laparoscopic approach substantially reduces the donor morbidity and wound related problems associated with open nephrectomy. The laparoscopic techniques thus have the potential to increase the number of living kidney donors. The present article attempts to review the safety and efficacy of transperitoneal laparoscopic donor nephrectomy.

  17. Alternative Donor Transplantation for Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nelli Bejanyan

    2015-06-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT is a potentially curative therapy for adult patients with acute myeloid leukemia (AML, but its use for consolidation therapy after first remission with induction chemotherapy used to be limited to younger patients and those with suitable donors. The median age of AML diagnosis is in the late 60s. With the introduction of reduced-intensity conditioning (RIC, many older adults are now eligible to receive allo-HCT, including those who are medically less fit to receive myeloablative conditioning. Furthermore, AML patients commonly have no human leukocyte antigen (HLA-identical or medically suitable sibling donor available to proceed with allo-HCT. Technical advances in donor matching, suppression of alloreactivity, and supportive care have made it possible to use alternative donors, such as unrelated umbilical cord blood (UCB and partially HLA-matched related (haploidentical donors. Outcomes after alternative donor allo-HCT are now approaching the outcomes observed for conventional allo-HCT with matched related and unrelated donors. Thus, with both UCB and haploidentical donors available, lack of donor should rarely be a limiting factor in offering an allo-HCT to adults with AML.

  18. The Stem Cell Club: a model for unrelated stem cell donor recruitment.

    Science.gov (United States)

    Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

    2017-12-01

    Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

  19. Prevalence of irregular red blood cell antibodies among healthy blood donors in Delhi population.

    Science.gov (United States)

    Garg, Neeraj; Sharma, Tanya; Singh, Bharat

    2014-06-01

    To evaluate the prevalence of the anti-red blood cell antibodies among healthy blood donors. Antibody screening of all voluntary blood donor serum was performed as routine immunohematological procedure. Positive sera were further investigated to identify the specificity of irregular erythrocyte antibody by commercially available red cell panel (ID-Dia Panel, Diamed-ID Microtyping System). A total of 47,450 donors were screened for the presence of irregular erythrocyte antibodies. A total of forty-six donors showed presence of alloantibodies in their serum (46/47,450%, 0.09%), yielding a prevalence of 0.09%. Most frequent alloantibodies identified were of MNS blood group system. The results showed statistically a higher prevalence of RBC alloantibodies in females than in males. Screening for presence of alloantibodies in donor blood is important to provide compatible blood products and to avoid transfusion reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Augmentation of Recipient Adaptive Alloimmunity by Donor Passenger Lymphocytes within the Transplant

    Directory of Open Access Journals (Sweden)

    Ines G. Harper

    2016-05-01

    Full Text Available Chronic rejection of solid organ allografts remains the major cause of transplant failure. Donor-derived tissue-resident lymphocytes are transferred to the recipient during transplantation, but their impact on alloimmunity is unknown. Using mouse cardiac transplant models, we show that graft-versus-host recognition by passenger donor CD4 T cells markedly augments recipient cellular and humoral alloimmunity, resulting in more severe allograft vasculopathy and early graft failure. This augmentation is enhanced when donors were pre-sensitized to the recipient, is dependent upon avoidance of host NK cell recognition, and is partly due to provision of cognate help for allo-specific B cells from donor CD4 T cells recognizing B cell MHC class II in a peptide-degenerate manner. Passenger donor lymphocytes may therefore influence recipient alloimmune responses and represent a therapeutic target in solid organ transplantation.

  1. The 40 donors per million population plan: an action plan for improvement of organ donation and transplantation in Spain.

    Science.gov (United States)

    Matesanz, R; Marazuela, R; Domínguez-Gil, B; Coll, E; Mahillo, B; de la Rosa, G

    2009-10-01

    Spain has been showing the highest rate of deceased donor organ recovery in the world for a whole country, namely, 33-35 donors per million population (pmp) during the last years. This activity is attributed to the so-called Spanish Model of organ donation, an integrated approach to improve organ donation since the start of the Organización Nacional de Trasplantes (ONT) in 1989. However, in 2007 there were 7/17 regions with >40 donors pmp and a marked regional variability. Thus, ONT has set a large-scale, comprehensive strategy to achieve a substantial improvement in donation and transplantation in Spain in the coming years: The 40 Donors pmp Plan. The overall objective is to increase the average rate of deceased donors to 40 pmp between 2008 and 2010. The areas of improvement, specific objectives, and actions have come from deep reflection on the data and the material generated from multidisciplinary discussions and open consultation with the donation and transplantation community. Detection and management of brain-dead donors, with 4 specific subareas: access to intensive care units, new forms of hospital management, foreigners and ethnic minorities, and evaluation/maintenance of thoracic organ donors. Expanded criteria donors, with 3 subareas: aging, donors with positive tests to certain viral serologies, and donors with rare diseases. Special surgical techniques. Donation after cardiac death.

  2. Survey of Living Organ Donors' Experience and Directions for Process Improvement.

    Science.gov (United States)

    Li, Timmy; Dokus, M Katherine; Kelly, Kristin N; Ugoeke, Nene; Rogers, James R; Asham, George; Sharma, Venkatesh Abhishek; Cirillo, Dominic J; Robinson, Mary K; Venniro, Erika K; Taylor, Jeremy G; Orloff, Mark S; McIntosh, Scott; Kashyap, Randeep

    2017-09-01

    Understanding living organ donors' experience with donation and challenges faced during the process is necessary to guide the development of effective strategies to maximize donor benefit and increase the number of living donors. An anonymous self-administered survey, specifically designed for this population based on key informant interviews, was mailed to 426 individuals who donated a kidney or liver at our institution. Quantitative and qualitative methods including open and axial coding were used to analyze donor responses. Of the 141 survey respondents, 94% would encourage others to become donors; however, nearly half (44%) thought the donation process could be improved and offered numerous suggestions. Five major themes arose: (1) desire for greater convenience in testing and scheduling; (2) involvement of previous donors throughout the process; (3) education and promotion of donation through social media; (4) unanticipated difficulties, specifically pain; and (5) financial concerns. Donor feedback has been translated into performance improvements at our hospital, many of which are applicable to other institutions. Population-specific survey development helps to identify vital patient concerns and provides valuable feedback to enhance the delivery of care.

  3. Effective Priming of Herpes Simplex Virus-Specific CD8+T CellsIn VivoDoes Not Require Infected Dendritic Cells.

    Science.gov (United States)

    Whitney, Paul G; Makhlouf, Christina; MacLeod, Beth; Ma, Joel Z; Gressier, Elise; Greyer, Marie; Hochheiser, Katharina; Bachem, Annabell; Zaid, Ali; Voehringer, David; Heath, William R; Wagle, Mayura V; Parish, Ian; Russell, Tiffany A; Smith, Stewart A; Tscharke, David C; Gebhardt, Thomas; Bedoui, Sammy

    2018-02-01

    Resolution of virus infections depends on the priming of virus-specific CD8 + T cells by dendritic cells (DC). While this process requires major histocompatibility complex (MHC) class I-restricted antigen presentation by DC, the relative contribution to CD8 + T cell priming by infected DC is less clear. We have addressed this question in the context of a peripheral infection with herpes simplex virus 1 (HSV). Assessing the endogenous, polyclonal HSV-specific CD8 + T cell response, we found that effective in vivo T cell priming depended on the presence of DC subsets specialized in cross-presentation, while Langerhans cells and plasmacytoid DC were dispensable. Utilizing a novel mouse model that allows for the in vivo elimination of infected DC, we also demonstrated in vivo that this requirement for cross-presenting DC was not related to their infection but instead reflected their capacity to cross-present HSV-derived antigen. Taking the results together, this study shows that infected DC are not required for effective CD8 + T cell priming during a peripheral virus infection. IMPORTANCE The ability of some DC to present viral antigen to CD8 + T cells without being infected is thought to enable the host to induce killer T cells even when viruses evade or kill infected DC. However, direct experimental in vivo proof for this notion has remained elusive. The work described in this study characterizes the role that different DC play in the induction of virus-specific killer T cell responses and, critically, introduces a novel mouse model that allows for the selective elimination of infected DC in vivo Our finding that HSV-specific CD8 + T cells can be fully primed in the absence of DC infection shows that cross-presentation by DC is indeed sufficient for effective CD8 + T cell priming during a peripheral virus infection. Copyright © 2018 American Society for Microbiology.

  4. Accelerating Quinoline Biodegradation and Oxidation with Endogenous Electron Donors.

    Science.gov (United States)

    Bai, Qi; Yang, Lihui; Li, Rongjie; Chen, Bin; Zhang, Lili; Zhang, Yongming; Rittmann, Bruce E

    2015-10-06

    Quinoline, a recalcitrant heterocyclic compound, is biodegraded by a series of reactions that begin with mono-oxygenations, which require an intracellular electron donor. Photolysis of quinoline can generate readily biodegradable products, such as oxalate, whose bio-oxidation can generate endogenous electron donors that ought to accelerate quinoline biodegradation and, ultimately, mineralization. To test this hypothesis, we compared three protocols for the biodegradation of quinoline: direct biodegradation (B), biodegradation after photolysis of 1 h (P1h+B) or 2 h (P2h+B), and biodegradation by adding oxalate commensurate to the amount generated from photolysis of 1 h (O1+B) or 2 h (O2+B). The experimental results show that P1h+B and P2h+B accelerated quinoline biodegradation by 19% and 50%, respectively, compared to B. Protocols O1+B and O2+B also gave 19% and 50% increases, respectively. During quinoline biodegradation, its first intermediate, 2-hydroxyquinoline, accumulated gradually in parallel to quinoline loss but declined once quinoline was depleted. Mono-oxygenation of 2-hydroxyquinoline competed with mono-oxygenation of quinoline, but the inhibition was relieved when extra electrons donors were added from oxalate, whether formed by UV photolysis or added exogenously. Rapid oxalate oxidation stimulated both mono-oxygenations, which accelerated the overall quinoline oxidation that provided the bulk of the electron donor.

  5. Telementoring facilitates independent hand-assisted laparoscopic living donor nephrectomy.

    Science.gov (United States)

    Challacombe, B; Kandaswamy, R; Dasgupta, P; Mamode, N

    2005-03-01

    Laparoscopic living donor nephrectomy is a major advance but a challenging procedure to learn even after laparoscopic training. It requires significant previous training in both laparoscopic and transplant surgery. Telementoring has been shown to reduce the laparoscopic learning curve in other fields. Of six cases of hand-assisted laparoscopic (HAL) living donor nephrectomy at our institution, an on-site mentor supervised the initial two. We present the subsequent four cases as the first documented examples of telementored HAL live donor nephrectomy. Telelink was established with a Comstation (Zydacron, UK) incorporating a Z360 telementoring codec and four ISDN lines (512 kb/s) with time delay of 500 ms for both audio and video. The remote surgeon in Minnesota (USA) could change independently between the laparoscopic and external views. The operating surgeons were able to look at the mentor and converse with him throughout. There were no adverse events in recipients and graft function was excellent. With regards to the telementored group the mean operative time was 240 minutes, the mean warm ischemic time 189 seconds, the mean estimated blood loss 171 mL, and the mean length of hospital stay 3 days. Telementoring for laparoscopic donor nephrectomy is feasible, effective, and likely to aid independent practice by providing continued supervision and reducing the learning period.

  6. Matching donor to recipient in liver transplantation: Relevance in clinical practice.

    Science.gov (United States)

    Reddy, Mettu Srinivas; Varghese, Joy; Venkataraman, Jayanthi; Rela, Mohamed

    2013-11-27

    Achieving optimum outcomes after liver transplantation requires an understanding of the interaction between donor, graft and recipient factors. Within the cohort of patients waiting for a transplant, better matching of the donor organ to the recipient will improve transplant outcomes and benefit the overall waiting list by minimizing graft failure and need for re-transplantation. A PubMed search was conducted to identify published literature investigating the effects of donor factors such as age, gender, ethnicity, viral serology; graft factors such as size and quality, recipient factors such as age, size, gender and transplant factors such as major or minor blood group incompatibility and immunological factors. We also report technical and therapeutic modifications that can be used to manage donor-recipient mismatch identified from literature and the authors' clinical experience. Multiple donor and recipient factors impact graft survival after liver transplantation. Appropriate matching based on donor-organ-recipient variables, modification of surgical technique and innovative peri-transplant strategies can increase the donor pool by utilizing grafts from marginal donors that are traditionally turned down.

  7. Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

    Science.gov (United States)

    Sharon, Eilon; Shi, Hao; Kharbanda, Sandhya; Koh, Winston; Martin, Lance R; Khush, Kiran K; Valantine, Hannah; Pritchard, Jonathan K; De Vlaminck, Iwijn

    2017-08-01

    Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

  8. Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

    Directory of Open Access Journals (Sweden)

    Eilon Sharon

    2017-08-01

    Full Text Available Quantification of cell-free DNA (cfDNA in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD quantifies donor-derived cfDNA (dd-cfDNA by taking advantage of single-nucleotide polymorphisms (SNPs distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM of identity-by-descent (IBD states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD. These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

  9. Flow cytometry PRA using lymphocyte pools from random donors.

    Science.gov (United States)

    Won, Dong Il; Jung, Hee Du; Jung, Ok-Ju; Huh, Seung; Suh, Jang Soo

    2007-07-01

    Pools of lymphocytes from carefully chosen donors have been used for flow cytometry (FC) panel reactive antibody (PRA) assays. We intended to devise an FC PRA assay using mixed lymphocyte pools from a large number of randomly selected donors (RD FC PRA) to accurately predict the likelihood of a positive HLA crossmatch. Lymphocyte pools were prepared from randomly selected donors (N = 120). %PRA was calculated based on the anti-IgG FITC histogram of the T cells. The proposed RD FC PRA assay was assessed in comparison with the bead FC PRA, antiglobulin-augmented CDC (AHG-CDC) PRA assay, and the expected %PRA calculated by summing up the antigen frequencies of the known specificities. In 29 FC crossmatch positive sera, the positivity rate for the bead FC, RD FC, and AHG-CDC PRA was 100, 100, and 79%, and the mean %PRA was 77% +/- 0.205). In 19 sensitized patients with a negative FC crossmatch, the positivity rate was 21% using the RD FC PRA and 16% using the bead FC PRA, which suggested that both assays had similar abilities to detect low levels of HLA antibodies. The RD FC PRA assay allows easy panel preparation, reduces cost, and naturally reflects the probabilities of a positive crossmatch in the population to which the cadaveric donor belongs. Therefore, this new assay is expected to be useful as another approach to determine the % PRA. Copyright 2007 Clinical Cytometry Society.

  10. Specification of requirements to get a license for an Independent Spent Fuel Dry Storage Installation (ISFSI) at the site of the NPP-LV

    International Nuclear Information System (INIS)

    Serrano R, M. L.

    2015-09-01

    This article describes some of the work done in the Comision Nacional de Seguridad Nuclear y Salvaguardias (CNSNS) to define specifically the requirements that the Federal Electricity Commission (CFE) shall meet to submit for consideration of CNSNS an operation request of an Independent Spent Fuel Dry Storage Installation (ISFSI). The project of a facility of this type arose from the need to provide storage capacity for spent nuclear fuel in the nuclear power plant of Laguna Verde (NPP-LV) and to continue the operation at the same facility in a safe manner. The licensing of these facilities in the United States of America has two modes: specific license or general license. The characteristics of these licenses are described in this article. However, in Mexico the existing national legislation is not designed for such license types, in fact there is a lack of standards or regulations in this regard. The regulatory law of Article 27 of the Constitution in the nuclear matter, only generally establishes that this type of facility requires an authorization from the Ministry of Energy. For this reason and because there is not a national legislation, was necessary to use the legislation that provides the Nuclear Regulatory Commission of USA, the US NRC. However, it cannot be applied as is established, so was necessary that the CNSNS analyze one by one the requirements of both types of license and determine what would be required to NPP-LV to submit its operating license of ISFSI. The American regulatory applicable to an ISFSI, the 10-Cfr-72 of the US NRC, establishes the requirements for both types of licenses. Chapter 10-Cfr was analyzed in all its clauses and coupled to the laws, regulations and standards as well as to the requirements established by CNSNS, all associated with a store spent fuel on site; the respective certification of containers for spent fuel dry storage was not included in this article, even though the CNSNS also performed that activity under the

  11. BLOODR: blood donor and requester mobile application.

    Science.gov (United States)

    Tatikonda, Vamsi Krishna; El-Ocla, Hosam

    2017-01-01

    With rapid increase in the usage of social networks sites across the world, there is also a steady increase in blood donation requests as being noticed in the number of posts on these sites such as Facebook and twitter seeking blood donors. Finding blood donor is a challenging issue in almost every country. There are some blood donor finder applications in the market such as Blood app by Red Cross and Blood Donor Finder application by Neologix. However, more reliable applications that meet the needs of users are prompted. Several software technologies including languages and framework are used to develop our blood-donor web application known as BLOODR application. These technologies comprise Ruby programming language (simply known as Ruby) along with JavaScript and PostgreSQL for database are used. Ruby on Rails (simply known as Rails) is an open source Web framework that makes it possible to quickly and easily create data-based web applications. We show screenshots for the BLOODR application for different types of users including requester, donor, and administrator. Various features of the application are described and their needs of use are analyzed. If a patient needs a blood at a clinic, blood donors in vicinity can be contacted through using a clinic management service provided in this application. Registered donors will get notification for the blood requests only if their blood group is compatible with the requested blood type and in the same city/region. Then matching blood donors can go to the requesting clinic and donate. BLOODR application provides a reliable platform to connect local blood donors with patients. BLOODR creates a communication channel through authenticated clinics whenever a patient needs blood donation. It is a useful tool to find compatible blood donors who can receive blood request posts in their local area. Clinics can use this web application to maintain the blood donation activity. Future improvement of the BLOODR is explained.

  12. Exchange living-donor kidney transplantation: diminution of donor organ shortage.

    Science.gov (United States)

    Park, K; Lee, J H; Huh, K H; Kim, S I; Kim, Y S

    2004-12-01

    To alleviate the organ shortage, the use of more living donors is strongly recommended world wide. A living donor exchange (swap) program was launched in Korea. After the success of a direct swap program between two families, we have developed the swap-around program to expand the donor pool by enrolling many kinds of unrelated donors. Herein, we report our results of a living donor exchange program. This retrospectively review of 978 recipients of kidney transplants from living donors, included analysis of donor-recipient relationships, mode of donor recruitment, episodes of acute rejection, and 5-year patient/graft survivals. Transplantation was performed in 101 patients (10.3%) by way of the swap program. The proportion of swap patients among the number of unrelated donor renal transplants has been increasing from 4.2% to 46.6%. The incidence of acute rejection and 5-year patient/graft survival rates were comparable between the groups. We have achieved some success in reducing the organ shortage with a swap program in addition to our current unrelated living donor programs without jeopardizing graft survival. Potentially exchangeable donors should undergo strict medical evaluation by physicians and social evaluation by social workers and coordinators as a pre-requisite for kidney transplantation. Expanding the swap around program to a regional or national pool could be an option to reduce the organ donor shortage in the future.

  13. Dedicated donor unit transfusions reduces donor exposure in pediatric surgery patients

    Directory of Open Access Journals (Sweden)

    Satyam Arora

    2017-01-01

    Full Text Available Background: Many strategies have been explored to reduce multiple donor exposures in neonates such as use of restrictive transfusion protocols, limiting iatrogenic blood loss, use of recombinant erythropoietin and single donor programs. Method: In our study we assessed the feasibility of dedicating single donor units with reserving all the components from the same donor for the specified neonates/ infants undergoing surgery and estimating reduction of donor exposure. Fifty neonates undergoing surgery were included in the prospective study group and the transfusion details were compared with 50 retrospective cases with same inclusion criteria. Results: An intra-operative blood loss of >13 ml/Kg was significantly associated with transfusion (P<0.05 which was most frequently administered in the intra-operative period. Donor exposure rate of overall transfusion was 1.15 in the study group as compared to 4.03 in the retrospective control group. In study group Donor Exposure Rate (DER: Transfusion Rate (TR ratio was 1:1.5 and Transfusion per Donor Unit (TPDU of 1.5, means that one donor unit contributed to 1.5 transfusions in each patient and contributed to 50% reduction in donor exposure in each patient as compared to retrospective control group. Conclusion: Our study showed that by practicing dedicated donor unit transfusion policy, for neonates undergoing surgery we could significantly reduce the donor exposure.

  14. Dedicated donor unit transfusions reduces donor exposure in pediatric surgery patients

    Science.gov (United States)

    Arora, Satyam; Marwaha, Neelam; Dhawan, Hari Krishan; Rao, K. L. N.

    2017-01-01

    BACKGROUND: Many strategies have been explored to reduce multiple donor exposures in neonates such as use of restrictive transfusion protocols, limiting iatrogenic blood loss, use of recombinant erythropoietin and single donor programs. METHOD: In our study we assessed the feasibility of dedicating single donor units with reserving all the components from the same donor for the specified neonates/infants undergoing surgery and estimating reduction of donor exposure. Fifty neonates undergoing surgery were included in the prospective study group and the transfusion details were compared with 50 retrospective cases with same inclusion criteria. RESULTS: An intra-operative blood loss of >13 ml/Kg was significantly associated with transfusion (P <0.05) which was most frequently administered in the intra-operative period. Donor exposure rate of overall transfusion was 1.15 in the study group as compared to 4.03 in the retrospective control group. In study group Donor Exposure Rate (DER): Transfusion Rate (TR) ratio was 1:1.5 and Transfusion per Donor Unit (TPDU) of 1.5, means that one donor unit contributed to 1.5 transfusions in each patient and contributed to 50% reduction in donor exposure in each patient as compared to retrospective control group. CONCLUSION: Our study showed that by practicing dedicated donor unit transfusion policy, for neonates undergoing surgery we could significantly reduce the donor exposure. PMID:28970679

  15. prevalence trend among blood donors in jimma university ...

    African Journals Online (AJOL)

    User

    The age specific prevalence was highest in the age group 30-39 years (2.2%) followed by 40. – 49 (1.4%). HIV sero-prevalence was ... tissue donors in the United States, the incidence of. HIV infection was estimated to be 40,000 ..... single and homeless; they could be at high risk to practice unsafe sex. On the other hand, ...

  16. Negotiating boundaries: Accessing donor gametes in India.

    Science.gov (United States)

    Widge, A; Cleland, J

    2011-01-01

    This paper documents how couples and providers access donor materials for conception in the Indian context and perceptions about using them. The objective is to facilitate understanding of critical issues and relevant concerns. A postal survey was conducted with a sample of 6000 gynaecologists and in-depth interviews were -conducted with 39 gynaecologists in four cities. Donor gametes are relatively more acceptable than a few years ago, especially if confidentiality can be -maintained, though lack of availability of donor materials is sometimes an impediment to infertility treatment. Donor sperms are usually accessed from in-house or commercial sperm banks, pathology laboratories, IVF centres, -professional donors, relatives or friends. There is scepticism about screening procedures of sperm banks. Donor eggs are usually accessed from voluntary donors, friends, relatives, egg sharing programmes, donation from other patients, advertising and commercial donors. There are several concerns regarding informed consent for using donated gametes, using -relatives and friends gametes, the unregulated use of gametes and embryos, record keeping and documentation, -unethical and corrupt practices and commercialisation. These issues need to be addressed by patients, providers and regulatory authorities by providing -information, counselling, ensuring informed consent, addressing exploitation and commercialisation, ensuring -monitoring, proper documentation and transparency.

  17. Normothermic machine perfusion for donor liver preservation

    NARCIS (Netherlands)

    Tolboom, H.

    2012-01-01

    Currently, liver transplantation is the only treatment for end-stage liver failure. Unfortunately, a sever shortage of donor organs causes significant mortality amongst patients awaiting transplantation. The donor organ shortage could be alleviated by using organs that are normally not accepted for

  18. and Tetradentate N,O-donor Ligands

    African Journals Online (AJOL)

    NICO

    )], derived from the oxidation reactions (by O2) of trans-[ReCl3(MeCN)(PPh3)2] with the tridentate N2O-donor chelate 2-[((2-pyridinylmethyl)amino)methyl]phenol (Hham) and the N2O2-donor N,N-bis(2-hydroxybenzyl)-aminomethyl- pyridine ...

  19. Posttransplantation Disseminated Coccidioidomycosis Acquired from Donor Lungs

    OpenAIRE

    Miller, Melissa B.; Hendren, Ryan; Gilligan, Peter H.

    2004-01-01

    A North Carolinian developed fatal coccidioidomycosis immediately after bilateral lung transplantation. The donor had previously traveled to Mexico, and the recipient had no travel history to an area where Coccidioides immitis is endemic. Immunosuppresive therapy of the transplant recipient likely reactivated latent Coccidioides infection in the donor lungs, leading to posttransplant coccidioidomycosis.

  20. Research Award: Donor Partnership Division | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2016-09-07

    Sep 7, 2016 ... IDRC's Donor Partnerships division (DPD) initiates, builds, and maintains relationships with donors, international organizations, and research funders ... We are particularly interested in research related to public-private partnerships for development, bilateral investments in research, trends in private ...