Sample records for early antigen ea

  1. Human T cell activation. III. Induction of an early activation antigen, EA 1 by TPA, mitogens and antigens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hara, T.; Jung, L.K.L.; FU, S.M.

    1986-03-01

    With human T cells activated for 12 hours by 12-o-tetradecanoyl phorbol-13-acetate (TPA) as immunogen, an IgG/sub 2a/ monoclonal antibody, mAb Ea 1, has been generated to a 60KD phosphorylated protein with 32KD and 28KD subunits. The antigen, Ea 1, is readily detected on 60% of isolated thymocytes by indirect immunofluorescence. A low level of Ea 1 expression is detectable on 2-6% of blood lymphocytes. Isolated T cells have been induced to express Ea 1 by TPA, mitogens and anitgens. TPA activated T cells express Ea 1 as early as 1 hour after activation. By 4 hours, greater than 95% ofmore » the T cells stain with mAb Ea 1. About 50% of the PHA or Con A activated T cells express Ea 1 with a similar kinetics. Ea 1 expression proceeds that of IL-2 receptor in these activation processes. T cells activated by soluble antigens (tetanus toxoid and PPD) and alloantigens in MLR also express Ea 1 after a long incubation. About 20% of the T cells stain for Ea 1 at day 6. Ea 1 expression is not limited to activated T cells. B cells activated by TPA or anti-IgM Ab plus B cell growth factor express Ea 1. The kinetics of Ea 1 expression is slower and the staining is less intense. Repeated attempts to detect Ea 1 on resting and activated monocytes and granulocytes have not been successful. Ea 1 expression is due to de novo synthesis for its induction is blocked by cycloheximide and actinomycin D. Ea 1 is the earliest activation antigen detectable to-date.« less

  2. Humoral immune response in infectious mononucleosis. Late emergence of anti-EA(R) and the effects of corticosteroid therapy.

    PubMed

    Fleisher, G R; Collins, M; Fager, S

    1985-11-01

    The antibody response to Epstein-Barr virus (EBV) antigens in patients with infectious mononucleosis (IM) was studied to assess antibody appearance to the restricted (R) component of the early antigen (EA) complex and to determine the effect of corticosteroids on all aspects of the humoral immune response. Sixty college students with heterophil-positive clinical IM, confirmed by EBV-specific serology, were followed for a period of 4-26 weeks, Half received prednisone for six days, and the remainder received no corticosteroid therapy. Regardless of therapy, 48% of the patients developed anti-EA(R) antibodies. The response to other antigens was similar in both groups with the exception that antibodies to the EB-associated nuclear antigen (EBNA) developed later during convalescence and at lower titers in the corticosteroid-treated group. We conclude that 1) anti-EA(R) antibodies develop with considerable frequency following IM and are not a marker, as previously proposed, of unusually severe disease, and 2) corticosteroid therapy may retard the formation of anti-EBNA antibodies but it does not otherwise influence the humoral immune response to EBV.

  3. Antigen-inducing ability of herpesvirus papio in human and baboon lymphoma lines, compared to Epstein-Barr virus.

    PubMed

    Klein, G; Falk, L; Falk, K

    1978-01-01

    Herpesvirus papio(HVP)-carrying baboon lymphoblastoid lines do not express a nuclear antigen like the Epstein-Barr virus(EBV)-determined nuclear antigen (EBNA), as judged by in situ anticomplement fluorescence staining, although the carry multiple viral genomes and, in the case of producerlines, early antigen (EA) and viral capsid antigen (VCA) that cross-react with the corresponding human EBV-determined antigens. To test whether the lack of in situ nuclear antigen expression is a property innate to the baboon virus or the baboon cell, nonproducer HVP-carrying baboon lymphoid cells of the 26 CB-1 line were superinfected with two human EBV strains. B95-8-derived EBV induced brilliant EBNA staining, proving that the baboon lymphoid cell was competent to synthesize EBNA. In the mirror experiment, HVP derived from the 9B or the 18C baboon line was added to the EBV-carrying Raji line, the EBV-negative Ramos and BJAB lines and the HVP-carrying nonproducer 26 CB-1 line, respectively. HVP induced EA and VCA in Raji, and EA in BJAB and 26 CB-1. EBNA was not induced in any of the three EBNA-negative lines, BJAB, Ramos and 26 CB-1. It is concluded that the lack of in situ nuclear staining in HVP-carrying baboon lines is a HVP-associated property and is not due to any innate inability of the baboon lymphoid cell to synthesize an antigen of the EBNA type.

  4. Increased antibody responses to Herpes virus papio (HVP) antigens in pre-lymphomatous baboons (Papio hamadryas) of the Sukhumi high lymphoma stock.

    PubMed

    Voevodin, A F; Yakovleva, L A; Lapin, B A; Ponomarjeva, T I

    1983-11-15

    Antibody responses to Herpes virus papio (HVP) antigens were studied in 21 pre-lymphoma baboons (which subsequently died of malignant lymphoma), 21 paired controls, i.e. age-, sex- and population-matched healthy baboons, and 185 randomly selected healthy baboons of the same population. The sera were all collected at the same time and were tested blind in the fixed-cell indirect immunofluorescence test against HVP viral capsid antigen (VCA)-positive, early antigen (EA)-positive cell targets before and after absorption with HVP. Eleven of the pre-lymphoma sera were anti-EA-positive whereas none of the paired controls contained anti-EA. Anti-VCA titers of pre-lymphoma sera were higher than those of paired controls in thirteen cases. Only in four cases were anti-VCA titers of pre-lymphoma sera lower than those of paired controls. Qualitatively, the same results were obtained when anti-VCA and anti-EA titers of pre-lymphoma sera were compared with respective mean population values. The differences between pre-lymphoma group and control groups, especially in the case of anti-EA, were statistically highly significant. Thus, elevated anti-HVP titers in healthy baboons of the Sukhumi lymphoma-prone stock can be considered as a marker of high risk for development of malignant lymphoma.

  5. Sequential detection of different antigens induced by Epstein-Barr virus and herpes simplex virus in the same Western blot by using dual antibody probes.

    PubMed

    Lin, J C; Pagano, J S

    1986-08-01

    A dual antibody probing technique that permitted a color-coded identification of polypeptides representing different classes of Epstein-Barr virus (EBV) antigens as well as differentiation of the polypeptides induced by different herpesviruses in the same Western blot was developed. When the nitrocellulose sheet was probed first with monoclonal antibody against EBV early antigen diffuse component (EA-D) and then stained with 4-chloro-1-naphthol, four polypeptides specific for EA-D were identified by purple bands. Subsequently, the same nitrocellulose sheet was reprobed with human serum containing antibodies against EBV early antigen, viral capsid antigen, and nuclear antigen and stained with 3,3'-diaminobenzidine. Several brown bands corresponding to early, viral capsid, and nuclear antigen polypeptides were detected. The dual antibody probing technique was used in an analysis to differentiate polypeptides resulting from either EBV or herpes simplex virus infection, either in cells infected by individual virus or in a cell line dually infected by both viruses. On the basis of different colored bands in different lanes of the same gel, 20 polypeptides with molecular weights ranging from 31,000 to 165,000 were identified as herpes simplex virus-specific proteins. These results suggested that the dual antibody probing technique may be applicable in clinical diagnosis for detecting antigens and antibodies derived from different pathogens.

  6. Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

    PubMed

    Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

    2007-05-01

    Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in

  7. Comparison of absolute intensity between EAS with gamma-families and general EAS at Mount Norikura

    NASA Technical Reports Server (NTRS)

    Mitsumune, T.; Nakatsuka, T.; Nishikawa, K.; Saito, T.; Sakata, M.; Shima, M.; Yamamoto, Y.; Dake, S.; Kawamoto, M.; Kusumose, M.

    1985-01-01

    Gamma-families with total energy greater than 10 TeV, found in the EX chamber which was cooperated with the EAS array were combined with EAS triggered by big bursts. The absolute intensity of the size spectrum of these combined EAS was compared with that of general EAS obtained by AS trigger. The EAS with sizes greater than 2x1 million were always accompanied by gamma-families with sigma E sub gamma H 10 TeV, n sub gamma, H 2 and Emin=3 TeV, although the rate of EAS accompaning such gamma-families decreases rapidly as their sizes decrease.

  8. Performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches in VQ codebook generation for image compression

    NASA Astrophysics Data System (ADS)

    Tsai, Jinn-Tsong; Chou, Ping-Yi; Chou, Jyh-Horng

    2015-11-01

    The aim of this study is to generate vector quantisation (VQ) codebooks by integrating principle component analysis (PCA) algorithm, Linde-Buzo-Gray (LBG) algorithm, and evolutionary algorithms (EAs). The EAs include genetic algorithm (GA), particle swarm optimisation (PSO), honey bee mating optimisation (HBMO), and firefly algorithm (FF). The study is to provide performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches. The PCA-EA-LBG approaches contain PCA-GA-LBG, PCA-PSO-LBG, PCA-HBMO-LBG, and PCA-FF-LBG, while the PCA-LBG-EA approaches contain PCA-LBG, PCA-LBG-GA, PCA-LBG-PSO, PCA-LBG-HBMO, and PCA-LBG-FF. All training vectors of test images are grouped according to PCA. The PCA-EA-LBG used the vectors grouped by PCA as initial individuals, and the best solution gained by the EAs was given for LBG to discover a codebook. The PCA-LBG approach is to use the PCA to select vectors as initial individuals for LBG to find a codebook. The PCA-LBG-EA used the final result of PCA-LBG as an initial individual for EAs to find a codebook. The search schemes in PCA-EA-LBG first used global search and then applied local search skill, while in PCA-LBG-EA first used local search and then employed global search skill. The results verify that the PCA-EA-LBG indeed gain superior results compared to the PCA-LBG-EA, because the PCA-EA-LBG explores a global area to find a solution, and then exploits a better one from the local area of the solution. Furthermore the proposed PCA-EA-LBG approaches in designing VQ codebooks outperform existing approaches shown in the literature.

  9. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Encoder. 11.32 Section 11.32....32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described... must additionally provide the following minimum specifications: (1) Encoder programming. Access to...

  10. Genetic and antigenic characterisation of serotype A FMD viruses from East Africa to select new vaccine strains

    PubMed Central

    Bari, Fufa D.; Parida, Satya; Tekleghiorghis, Tesfaalem; Dekker, Aldo; Sangula, Abraham; Reeve, Richard; Haydon, Daniel T.; Paton, David J.; Mahapatra, Mana

    2014-01-01

    Vaccine strain selection for emerging foot-and-mouth disease virus (FMDV) outbreaks in enzootic countries can be addressed through antigenic and genetic characterisation of recently circulating viruses. A total of 56 serotype A FMDVs isolated between 1998 and 2012, from Central, East and North African countries were characterised antigenically by virus neutralisation test using antisera to three existing and four candidate vaccine strains and, genetically by characterising the full capsid sequence data. A Bayesian analysis of the capsid sequence data revealed the viruses to be of either African or Asian topotypes with subdivision of the African topotype viruses into four genotypes (Genotypes I, II, IV and VII). The existing vaccine strains were found to be least cross-reactive (good matches observed for only 5.4–46.4% of the sampled viruses). Three bovine antisera, raised against A-EA-2007, A-EA-1981 and A-EA-1984 viruses, exhibited broad cross-neutralisation, towards more than 85% of the circulating viruses. Of the three vaccines, A-EA-2007 was the best showing more than 90% in-vitro cross-protection, as well as being the most recent amongst the vaccine strains used in this study. It therefore appears antigenically suitable as a vaccine strain to be used in the region in FMD control programmes. PMID:25171846

  11. Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker.

    PubMed

    Dellavedova, T

    2016-01-01

    Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate-specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer.

  12. Serum Hsp70 Antigen: Early Diagnosis Marker in Perinatal Asphyxia.

    PubMed

    Boskabadi, Hassan; Omidian, Masoud; Tavallai, Shima; Mohammadi, Shabnam; Parizadeh, Mostafa; Ghayour Mobarhan, Majid; Ferns, Gordon Aa

    2015-04-01

    Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve. A significant difference between the serum concentrations

  13. Serum Hsp70 Antigen: Early Diagnosis Marker in Perinatal Asphyxia

    PubMed Central

    Boskabadi, Hassan; Omidian, Masoud; Tavallai, Shima; Mohammadi, Shabnam; Parizadeh, Mostafa; Ghayour Mobarhan, Majid; Ferns, Gordon AA

    2015-01-01

    Background: Perinatal asphyxia is an important cause of mortality and permanent neurological and developmental deficit. Early and accurate diagnosis would help to establish the likely prognosis and may also help in determining the most appropriate treatment. Studies in experimental animal models suggest that a protein called Hsp70 may be a good and potentially useful marker of cellular stress that may be clinically useful in determining the presence of neonatal asphyxia. Objectives: Regarding the importance of early and accurate diagnosis of asphyxia, we conducted this study, which is the first investigation of the comparison of the serum Hsp70 antigen level between asphyxiated and healthy infants. Patients and Methods: In this observational study, the serum concentrations of Hsp70 antigen were compared between neonates suffering from perinatal asphyxia (n = 50) and normal neonates (n = 51). The inclusion criteria for the cases were neonates who had reached term and had at least two clinical criteria of asphyxia. Exclusion criteria were babies with gestational age < 37 weeks, infants with congenital abnormalities or positive blood culture. Exclusion criteria in this group were the requirement to hospital stay during first week of the life or babies whose mothers had difficulties during pregnancy or delivery. Term neonates without major anomalies who had asphyxia during delivery were enrolled in the first six hours after delivery, and control group consisted of healthy term neonates without problems and normal delivery process in the first week of life. The cord blood was taken during labor to measure Hsp70 antigen level by using an in-house ELISA (The enzyme-linked immunosorbent assay). Results: The median values of serum anti Hsp70 titers were significantly higher in asphyxiated neonates compared with non-asphyxiated neonates (0.36 [0.04 - 1.14] vs 0.24 [0.01 - 0.63]). At cutoff point = 0.3125 ng/mL, sensitivity was 58% and specificity 76% based on ROC curve

  14. View of EAS as it moves away from the ISS during Expedition 15

    NASA Image and Video Library

    2007-07-23

    ISS015-E-18967 (23 July 2007) --- An Early Ammonia Servicer (EAS) moves away from the International Space Station after it was jettisoned by astronaut Clay Anderson (out of frame), Expedition 15 flight engineer, during today's session of extravehicular activity (EVA). The EAS was installed on the P6 truss during STS-105 in August 2001, as an ammonia reservoir if a leak had occurred. It was never used, and was no longer needed after the permanent cooling system was activated last December.

  15. View of Anderson removing the EAS during a session of EVA on Expedition 15

    NASA Image and Video Library

    2007-07-23

    ISS015-E-19140 (23 July 2007) --- Anchored to the Canadarm2 foot restraint, astronaut Clay Anderson, Expedition 15 flight engineer, removes the Early Ammonia Servicer (EAS) from its place on the International Space Station during a session of extravehicular activity (EVA). Anderson later jettisoned the EAS by shoving it opposite of the station's direction of travel. The EAS was installed on the P6 truss during STS-105 in August 2001, as an ammonia reservoir if a leak had occurred. It was never used, and was no longer needed after the permanent cooling system was activated last December. The blackness of space and Earth's horizon provide the backdrop for the scene.

  16. View of Anderson removing the EAS during a session of EVA on Expedition 15

    NASA Image and Video Library

    2007-07-23

    ISS015-E-19135 (23 July 2007) --- Anchored to the Canadarm2 foot restraint, astronaut Clay Anderson, Expedition 15 flight engineer, removes the Early Ammonia Servicer (EAS) from its place on the International Space Station during a session of extravehicular activity (EVA). Anderson later jettisoned the EAS by shoving it opposite of the station's direction of travel. The EAS was installed on the P6 truss during STS-105 in August 2001, as an ammonia reservoir if a leak had occurred. It was never used, and was no longer needed after the permanent cooling system was activated last December. The blackness of space and Earth's horizon provide the backdrop for the scene.

  17. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is a... as specified in its EAS Local Area Plan. If it is unable to carry out this function, other LP sources... broadcast stations in the Local Area. (c) State Primary (SP) is a source of EAS State messages. These...

  18. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is a... as specified in its EAS Local Area Plan. If it is unable to carry out this function, other LP sources... broadcast stations in the Local Area. (c) State Primary (SP) is a source of EAS State messages. These...

  19. Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.

    PubMed

    Sakuma, Shinji; Yu, James Y H; Quang, Timothy; Hiwatari, Ken-Ichiro; Kumagai, Hironori; Kao, Stephanie; Holt, Alex; Erskind, Jalysa; McClure, Richard; Siuta, Michael; Kitamura, Tokio; Tobita, Etsuo; Koike, Seiji; Wilson, Kevin; Richards-Kortum, Rebecca; Liu, Eric; Washington, Kay; Omary, Reed; Gore, John C; Pham, Wellington

    2015-03-01

    Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level. © 2014 UICC.

  20. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.761 EA and Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in... 47 Telecommunication 5 2010-10-01 2010-10-01 false EA and Regional licenses. 90.761 Section 90.761...

  1. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.761 EA and Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in... 47 Telecommunication 5 2011-10-01 2011-10-01 false EA and Regional licenses. 90.761 Section 90.761...

  2. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and comparison of impacts should provide sufficient analysis to reach a conclusion regarding the... ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.34 EA components. EAs should be...

  3. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... and comparison of impacts should provide sufficient analysis to reach a conclusion regarding the... ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.34 EA components. EAs should be...

  4. Relative value of race, family history and prostate specific antigen as indications for early initiation of prostate cancer screening.

    PubMed

    Vertosick, Emily A; Poon, Bing Ying; Vickers, Andrew J

    2014-09-01

    Many guidelines suggest earlier screening for prostate cancer in men at high risk, with risk defined in terms of race and family history. Recent evidence suggests that baseline prostate specific antigen is strongly predictive of the long-term risk of aggressive prostate cancer. We compared the usefulness of risk stratifying early screening by race, family history and prostate specific antigen at age 45 years. Using estimates from the literature we calculated the proportion of men targeted for early screening using family history, black race or prostate specific antigen as the criterion for high risk. We calculated the proportion of prostate cancer deaths that would occur in those men by age 75 years. Screening based on family history involved 10% of men, accounting for 14% of prostate cancer deaths. Using black race as a risk criterion involved 13% of men, accounting for 28% of deaths. In contrast, 44% of prostate cancer deaths occurred in the 10% of men with the highest prostate specific antigen at age 45 years. In no sensitivity analysis for race and family history did the ratio of risk group size to number of prostate cancer deaths in that risk group approach that of prostate specific antigen. Basing decisions for early screening on prostate specific antigen at age 45 years provided the best ratio between men screened and potential cancer deaths avoided. Given the lack of evidence that race or family history affects the relationship between prostate specific antigen and risk, prostate specific antigen based risk stratification would likely include any black men or men with a family history who are destined to experience aggressive disease. Differential screening based on risk should be informed by baseline prostate specific antigen. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  5. Identification of early diagnostic antigens from major excretory-secretory proteins of Trichinella spiralis muscle larvae using immunoproteomics.

    PubMed

    Wang, Li; Cui, Jing; Hu, Dan Dan; Liu, Ruo Dan; Wang, Zhong Quan

    2014-01-22

    The excretory-secretory (ES) proteins of Trichinella spiralis muscle larvae (ML) come mainly from the excretory granules of the stichosome and the cuticles (membrane proteins), are directly exposed to the host's immune system, and are the main target antigens, which induce the immune responses. Although the ES proteins are the most commonly used diagnostic antigens for trichinellosis, their main disadvantage are the false negative results during the early stage of infection. The aim of this study was to identify early specific diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. Two-dimensional electrophoresis (2-DE) combined with Western blot were used to screen the early diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. The protein spots recognized by the sera from BALB/c mice infected with T. spiralis at 18 days post-infection (dpi) were identified by MALDI-TOF/TOF-MS and putatively annotated using GO terms obtained from the InterPro databases. The ES proteins were analyzed by 2-DE, and more than 33 protein spots were detected with molecular weight varying from 40 to 60 kDa and isoelectric point (pI) from 4 to 7. When probed with the sera from infected mice at 18 dpi, 21 protein spots were recognized and then identified, and they were characterized to correlate with five different proteins of T. spiralis, including two serine proteases, one deoxyribonuclease (DNase) II, and two kinds of trypsin. The five proteins were functionally categorized into molecular function and biological process according to GO hierarchy. 2-DE and Western blot combined with MALDI-TOF/TOF-MS were used to screen the diagnostic antigens from the main components of T. spiralis muscle larval ES proteins. The five proteins of T. spiralis identified (two serine proteases, DNase II and two kinds of trypsin) might be the early specific diagnostic antigens of trichinellosis.

  6. Reduced response to Epstein–Barr virus antigens by T-cells in systemic lupus erythematosus patients

    PubMed Central

    Draborg, Anette Holck; Jacobsen, Søren; Westergaard, Marie; Mortensen, Shila; Larsen, Janni Lisander; Houen, Gunnar; Duus, Karen

    2014-01-01

    Objective Epstein–Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. Methods T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay. Results SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients. Conclusions These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed. PMID:25396062

  7. 47 CFR 11.56 - EAS Participants receive CAP-formatted alerts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS Participants receive CAP-formatted alerts... SYSTEM (EAS) Emergency Operations § 11.56 EAS Participants receive CAP-formatted alerts. Notwithstanding anything herein to the contrary, all EAS Participants must be able to receive CAP-formatted EAS alerts no...

  8. 7 CFR 1794.23 - Proposals normally requiring an EA.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Proposals normally requiring an EA. 1794.23 Section... § 1794.23 Proposals normally requiring an EA. RUS will normally prepare an EA for all proposed actions... require an EA and shall be subject to the requirements of §§ 1794.40 through 1794.44. (a) General...

  9. 7 CFR 1794.23 - Proposals normally requiring an EA.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Proposals normally requiring an EA. 1794.23 Section... § 1794.23 Proposals normally requiring an EA. RUS will normally prepare an EA for all proposed actions... require an EA and shall be subject to the requirements of §§ 1794.40 through 1794.44. (a) General...

  10. 7 CFR 1794.23 - Proposals normally requiring an EA.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Proposals normally requiring an EA. 1794.23 Section... § 1794.23 Proposals normally requiring an EA. RUS will normally prepare an EA for all proposed actions... require an EA and shall be subject to the requirements of §§ 1794.40 through 1794.44. (a) General...

  11. Early appendectomy shortens antibiotic course and hospital stay in children with early perforated appendicitis.

    PubMed

    Tsai, Hsin-Yu; Chao, Hsun-Chin; Yu, Wan-Ju

    2017-10-01

    The optimal management of perforated appendicitis in the pediatric population has been controversial. This study aimed to compare the therapeutic efficacy between conservative treatment (CS) and early appendectomy (EA) in pediatric perforated appendicitis, and to determine whether surgical intervention is an optimal treatment modality for early perforated appendicitis in children. Patients treated between January 2012 and April 2014, aged 0-18 years, with an imaging-based diagnosis of perforated appendicitis were retrospectively reviewed. Patients were classified into nonabscess and abscess groups by image findings, and were further categorized into CS and EA groups by treatment modality. Early perforated appendicitis was defined as having duration of symptoms≤7 days, C-reactive protein level≤200 mg/L, maximum abscess diameter≤5 cm, and absence of general peritonitis, and unstable vital signs. The clinical features and therapeutic outcomes were compared between CS and EA in each group. A total of 326 patients had confirmed appendicitis, including 116 patients with an image diagnosis of perforation. The CS group had a significantly longer duration of symptoms, larger abscesses, and higher serum C-reactive protein levels at presentation (all p<0.05). Patients in the EA group had a shorter antibiotic course and length of hospitalization, and a lower rate of antibiotic escalation than those in the CS group (p<0.001, p<0.001, and p<0.05, respectively). In patients with early perforated appendicitis, the CS and EA groups showed no difference in baseline disease severity. Patients in the EA group also had a shorter antibiotic course and length of hospitalization than those in the CS group (p<0.001 and p<0.001, respectively). Compared with CS, EA shortens the antibiotic course and hospital stay in pediatric early perforated appendicitis, even in the presence of small abscesses. Copyright © 2017. Published by Elsevier B.V.

  12. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Preparation of an EA. 1010.11 Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11... prepare or require an EA at any time to assist planning and decision-making. (b) Content and format. An EA...

  13. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Preparation of an EA. 1010.11 Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11... prepare or require an EA at any time to assist planning and decision-making. (b) Content and format. An EA...

  14. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Preparation of an EA. 1010.11 Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11... prepare or require an EA at any time to assist planning and decision-making. (b) Content and format. An EA...

  15. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Preparation of an EA. 1010.11 Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11... prepare or require an EA at any time to assist planning and decision-making. (b) Content and format. An EA...

  16. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a rate of 520.83 bits per second to transmit the codes. Mark frequency is 2083.3 Hz and space frequency... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11...

  17. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a rate of 520.83 bits per second to transmit the codes. Mark frequency is 2083.3 Hz and space frequency... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11...

  18. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a rate of 520.83 bits per second to transmit the codes. Mark frequency is 2083.3 Hz and space frequency... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11...

  19. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a rate of 520.83 bits per second to transmit the codes. Mark frequency is 2083.3 Hz and space frequency... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11...

  20. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a rate of 520.83 bits per second to transmit the codes. Mark frequency is 2083.3 Hz and space frequency... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11...

  1. 47 CFR 11.61 - Tests of EAS procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... receipt, as specified in § 11.35(a) and 11.54(a)(3). (iii) The EAS weekly test is not required during the... message when transmitting the required weekly test. (3) National tests. (i) All EAS Participants shall... Management Agency (FEMA). Such tests will consist of the delivery by FEMA to PEP/NP stations of a coded EAS...

  2. 47 CFR 11.61 - Tests of EAS procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... receipt, as specified in § 11.35(a) and 11.54(a)(3). (iii) The EAS weekly test is not required during the... message when transmitting the required weekly test. (3) National tests. (i) All EAS Participants shall... Management Agency (FEMA). Such tests will consist of the delivery by FEMA to PEP/NP stations of a coded EAS...

  3. 47 CFR 11.61 - Tests of EAS procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... receipt, as specified in § 11.35(a) and 11.54(a)(3). (iii) The EAS weekly test is not required during the... message when transmitting the required weekly test. (3) National tests. (i) All EAS Participants shall... Management Agency (FEMA). Such tests will consist of the delivery by FEMA to PEP/NP stations of a coded EAS...

  4. Protective Efficacy of Coccidial Common Antigen Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) against Challenge with Three Eimeria Species

    PubMed Central

    Tian, Lu; Li, Wenyu; Huang, Xinmei; Tian, Di; Liu, Jianhua; Yang, Xinchao; Liu, Lianrui; Yan, Ruofeng; Xu, Lixin; Li, Xiangrui; Song, Xiaokai

    2017-01-01

    Coccidiosis is an intestinal disorder of poultry and often caused by simultaneous infections of several Eimeria species. GAPDH is one of the immunogenic common antigens among Eimeria tenella, E. acervulina, and E. maxima identified in our previous study. The present study was performed to further evaluate its immunogenicity and protective efficacy. The genes of GAPDH cloned from E. acervulina and E. maxima were named as EaGAPDH and EmGAPDH, respectively. The immunogenicity of recombinant proteins of EaGAPDH and EmGAPDH were analyzed by Western blot. The transcription and expression of pVAX-EaGAPDH and pVAX-EmGAPDH in the injected muscles were detected by reverse transcription PCR (RT-PCR) and Western blot, respectively. GAPDH-induced changes of T lymphocytes subpopulation, cytokines production, and antibody were determined using flow cytometry, quantitative real-time PCR (qPCR), and ELISA, respectively. Finally, the protective efficacies of pVAX-EaGAPDH and pVAX-EmGAPDH were evaluated by vaccination and challenge experiments. The results revealed that the recombinant GAPDH proteins reacted with the corresponding chicken antisera. The EaGAPDH genes were successfully transcribed and expressed in the injected muscles. Vaccination with pVAX-EaGAPDH and pVAX-EmGAPDH significantly increased the proportion of CD4+ and CD8+ T lymphocytes, the cytokines productions of IFN-γ, IL-2, IL-4 et al., and IgG antibody levels compared to controls. The vaccination increased the weight gains, decreased the oocyst outputs, alleviate the enteric lesions compared to controls, and induced moderate anti-coccidial index (ACI). In conclusion, the coccidial common antigen of GAPDH induced significant humoral and cellular immune response and effective protection against E. tenella, E. acervulina, E. maxima, and mixed infection of the three Eimeria species. PMID:28769877

  5. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS code and Attention Signal Transmission... SYSTEM (EAS) Emergency Operations § 11.51 EAS code and Attention Signal Transmission requirements. (a... programming before EAS message transmission should not cause television receivers to mute EAS audio messages...

  6. Reconceptualizing public participation in environmental assessment as EA civics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sinclair, A. John, E-mail: jsincla@umanitoba.ca; Diduck, Alan P., E-mail: a.diduck@uwinnipeg.ca

    Notwithstanding the considerable attention placed on creating meaningful opportunities for public participation in environmental assessment (EA), many participants and those who have reviewed participation processes often find practice sorely wanting. This reality stands in stark juxtaposition to future environmental governance needs, which will require increased openness, deliberation and transdisciplinary knowledge in order to deal with environmental change that is ever more uncertain, complex and conflictual. In this paper, our purpose was to consider how to meet those needs through reconceptualizing public participation as EA civics, founded on an active citizen base, deliberative in nature and orientated toward learning. We domore » this through developing a new conceptual model of next generation participation processes that is relevant at multiple spatial scales and institutional levels, is applicable to the entire assessment cycle and spans temporal scales through feedback loops. Our EA civics model builds on the “civics approach” to environmental governance and “action civics” by extending their core ideas to participation in EA. We did this by conducting an integrative literature review (including numerous papers we have contributed over the years) and reflecting on our own experiences as EA participants. We apply current thinking on public participation design to our EA civics conceptualization and highlight important design features that have received scant attention. We conclude that EA civics holds promise for fairer and more robust participation processes if all aspects of the model are considered and the actions related to each are implemented. - Highlights: • Consideration of the ‘civics approach’ and ‘action civics’ in an EA context • Conceptualization of public participation as EA civics • Reflection on the EA civics as a model of participation suitable for next generation assessment.« less

  7. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose...

  8. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose...

  9. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose...

  10. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose...

  11. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose...

  12. Identification of new antigen candidates for the early diagnosis of Mycobacterium avium subsp. paratuberculosis infection in goats.

    PubMed

    Souriau, Armel; Freret, Sandrine; Foret, Benjamin; Willemsen, Peter T J; Bakker, Douwe; Guilloteau, Laurence A

    2017-12-01

    Currently Mycobacterium avium subsp. paratuberculosis (MAP) infection is diagnosed through indirect tests based on the immune response induced by the infection. The antigens commonly used in IFN-γ release assays (IGRA) are purified protein derivative tuberculins (PPD). However, PPDs, lack both specificity (Sp) and sensitivity (Se) in the early phase of infection. This study investigated the potential of 16 MAP recombinant proteins and five lipids to elicit the release of IFN-γ in goats from herds with or without a history of paratuberculosis. Ten recombinant proteins were selected as potential candidates for the detection of MAP infection in young goats. They were found to detect 25 to 75% of infected shedder (IS) and infected non-shedder (INS) kids younger than 10months of age. In comparison, PPD was shown to detect only 10% of INS and no IS kids. For seven antigens, Se (21-33%) and Sp (≥90%) of IGRA were shown to be comparable with PPD at 20months old. Only three antigens were suitable candidates to detect IS adult goats, although Se was lower than that obtained with PPD. In paratuberculosis-free herds, IGRA results were negative in 97% of indoor goats and 86% of outdoor goats using the 10 antigens. However, 22 to 44% of one-year-old outdoor goats were positive suggesting that they may be infected. In conclusion, this study showed that ten MAP recombinant proteins are potential candidates for early detection of MAP infected goats. Combining these antigens could form a possible set of MAP antigens to optimize the Se of caprine IGRA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Surface antigen in early differentiation.

    PubMed Central

    Kemler, R; Babinet, C; Eisen, H; Jacob, F

    1977-01-01

    Addition of Fab fragments from rabbit antiserum to surface antigen F9 to 2-cell stage mouse embryos in culture does not alter cleavage; however, the addition prevents culture does not alter cleavage; however, the addition prevents the formation of compact morulae and blastocysts. A similar effect is observed when Fab fragments are added to already compact 8-cell stage or even older morulae, but disappears at the beginning of blastocoel formation. This effect is reversible: uncompact 30-cell embryos washed free of Fab become compact in a few hours, produce blastocysts, and upon reimplantation into pseudopregnant mothers can produce mice. Development is not altered by divalent anti-F9 antibodies, by Fab fragments from sera directed against other embryo surface antigens, or by succinyl concanavalin A. Images PMID:270688

  14. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... through the use of a single set of EAS equipment at the hub station (or common studio or control point... as low earth orbiting satellites, that wish to participate in the EAS may contact the FCC's Public... 47 Telecommunication 1 2010-10-01 2010-10-01 false The Emergency Alert System (EAS). 11.11 Section...

  15. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... through the use of a single set of EAS equipment at the hub station (or common studio or control point... as low earth orbiting satellites, that wish to participate in the EAS may contact the FCC's Public... 47 Telecommunication 1 2011-10-01 2011-10-01 false The Emergency Alert System (EAS). 11.11 Section...

  16. On the determination of the depth of EAS development maximum using the lateral distribution of Cerenkov light at distances 150 m from EAS axis

    NASA Technical Reports Server (NTRS)

    Aliev, N.; Alimov, T.; Kakhkharov, M.; Makhmudov, B. M.; Rakhimova, N.; Tashpulatov, R.; Kalmykov, N. N.; Khristiansen, G. B.; Prosin, V. V.

    1985-01-01

    The Samarkand extensive air showers (EAS) array was used to measure the mean and individual lateral distribution functions (LDF) of EAS Cerenkov light. The analysis of the individual parameters b showed that the mean depth of EAS maximum and the variance of the depth distribution of maxima of EAS with energies of approx. 2x10 to the 15th power eV can properly be described in terms of Kaidalov-Martirosyan quark-gluon string model (QGSM).

  17. 47 CFR 11.61 - Tests of EAS procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... message when transmitting the required weekly test. (3) National tests. (i) All EAS Participants shall... Management Agency (FEMA). Such tests will consist of the delivery by FEMA to PEP/NP stations of a coded EAS...

  18. Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients

    PubMed Central

    Draborg, Anette Holck; Sandhu, Noreen; Larsen, Nanna; Lisander Larsen, Janni; Jacobsen, Søren; Houen, Gunnar

    2016-01-01

    We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1β, IFNγ, TNFα, TNFβ, TGFβ, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFβ, IL1β, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients. PMID:27110576

  19. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message... audio messages. No Attention Signal is required for EAS messages that do not contain audio programming... EAS messages in the main audio channel. All DAB stations shall also transmit EAS messages on all audio...

  20. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message... audio messages. No Attention Signal is required for EAS messages that do not contain audio programming... EAS messages in the main audio channel. All DAB stations shall also transmit EAS messages on all audio...

  1. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Message (EOM) codes using the EAS Protocol. The Attention Signal must precede any emergency audio message... audio messages. No Attention Signal is required for EAS messages that do not contain audio programming... EAS messages in the main audio channel. All DAB stations shall also transmit EAS messages on all audio...

  2. 47 CFR 11.52 - EAS code and Attention Signal Monitoring requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS code and Attention Signal Monitoring... SYSTEM (EAS) Emergency Operations § 11.52 EAS code and Attention Signal Monitoring requirements. (a) EAS Participants must be capable of receiving the Attention Signal required by § 11.32(a)(9) and emergency messages...

  3. 77 FR 1676 - EasTrans, LLC; Notice Granting Extension of Time

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-30-002] EasTrans, LLC; Notice Granting Extension of Time On December 16, 2011, EasTrans, LLC (EasTrans) filed a request to... 20, 2010). Upon consideration, notice is hereby given that an extension of time for EasTrans to file...

  4. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed in...

  5. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed in...

  6. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed in...

  7. 47 CFR 11.19 - EAS Non-participating National Authorization Letter.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS Non-participating National Authorization Letter. 11.19 Section 11.19 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT... level EAS. It states that the EAS Participant has agreed to go off the air or discontinue programming on...

  8. 47 CFR 11.19 - EAS Non-participating National Authorization Letter.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Non-participating National Authorization Letter. 11.19 Section 11.19 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT... level EAS. It states that the EAS Participant has agreed to go off the air or discontinue programming on...

  9. Theoretical study of EAS hadronic structure

    NASA Technical Reports Server (NTRS)

    Popova, L.

    1985-01-01

    The structure of extensive air showers (EAS) is determined mainly by the energetic hadrons. They are strongly collimated in the core of the shower and essential difficulties are encountered for resolution of individual hadrons. The properties for resolution are different from the variety of hadron detectors used in EAS experiments. This is the main difficulty in obtaining a general agreement between actually registered data with different detectors. The most plausible source for disagreement is the uncertainty in determination of the energy of individual hadrons. This research demonstrates that a better agreement can be obtained with the average tendency of hadronic measurements if one assumes a larger coefficient of inelasticity and stronger energy increase of the total inelastic cross section in high energy pion interactions. EAS data above 10 to the 5th power GeV are revealing a faster development of hadronic cascades in the air then can be expected by extrapolating the parameters of hadron interactions obtained in accelerator measurements.

  10. The recruitment of patients to trials in head and neck cancer: a qualitative study of the EaStER trial of treatments for early laryngeal cancer.

    PubMed

    Hamilton, D W; de Salis, I; Donovan, J L; Birchall, M

    2013-08-01

    We aimed to investigate the factors contributing to poor recruitment to the EaStER trial "Early Stage glottic cancer: Endoscopic excision or Radiotherapy" feasibility study. We performed a prospective qualitative assessment of the EaStER trial at three centres to investigate barriers to recruitment and implement changes. Methods used included semi-structured interviews, focus groups and audio-recordings of recruitment encounters. First, surgeons and recruiters did not all accept the primary outcome as the rationale for the trial. Surgeons did not always adhere to the trial eligibility criteria leading to variations between centres in the numbers of "eligible" patients. Second, as both treatments were considered equally successful, recruiters and patients focused on the pragmatics of the different trial arms, favouring surgery over radiotherapy. The lack of equipoise was reflected in the way recruiters presented trial information. Third, patient views, beliefs and preferences were not fully elicited or addressed by recruiters. Fourth, in some centres, logistical issues made trial participation difficult. This qualitative research identified several major issues that explained recruitment difficulties. While there was insufficient time to address these in the EaStER trial, several factors would need to be addressed to launch further RCTs in head and neck cancer. These include the need for clear ongoing agreement among recruiting clinicians regarding details in the study protocol; an understanding of the logistical issues hindering recruitment at individual centres; and training recruiters to enable them to explain the need for randomisation and the rationale for the RCT to patients.

  11. 47 CFR 90.763 - EA, Regional and nationwide system operations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Frequencies in the 220-222 MHz Band Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.763 EA, Regional and nationwide system operations. (a) A nationwide licensee... 47 Telecommunication 5 2011-10-01 2011-10-01 false EA, Regional and nationwide system operations...

  12. 47 CFR 11.51 - EAS code and Attention Signal Transmission requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... transmitting requirements contained in this section for the combined stations or systems with one EAS Encoder... the encoder. (2) Manual interrupt of programming and transmission of EAS messages may be used. EAS...

  13. 28 CFR 91.64 - Supplemental EA or EIS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Supplemental EA or EIS. 91.64 Section 91.64 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GRANTS FOR CORRECTIONAL FACILITIES... Supplemental EA or EIS. (a) OJP's duty to supplement. OJP shall prepare supplements to either completed...

  14. 47 CFR 90.359 - Field strength limits for EA-licensed LMS systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Field strength limits for EA-licensed LMS... § 90.359 Field strength limits for EA-licensed LMS systems. EA-licensed multilateration systems shall limit the field strength of signals transmitted from their base stations to 47 dBuV/m at their EA...

  15. 47 CFR 11.61 - Tests of EAS procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... EAS header codes, Attention Signal, Test Script and EOM code. (i) Tests in odd numbered months shall... substitute for a monthly test, activation must include transmission of the EAS header codes, Attention Signal, emergency message and EOM code and comply with the visual message requirements in § 11.51. To substitute for...

  16. Purification and immunochemical characterization of type e polysaccharide antigen of Streptococcus mutans.

    PubMed

    Hamada, S; Slade, H D

    1976-07-01

    The type-specific antigen of Streptococcus mutans strain MT703, serotype e, has been chromatographically purified and characterized. Two chromatographic fractions were obtained from saline extracts which reacted with both anti-MT703 whole-cell serum and Lancefield group E serum. The major fraction (eI) was identified as a polysaccharide composed of 37% glucose, 56% rhamnose, 5% protein, and 0.3% phosphorus, whereas the minor fraction (eII) contained 66% protein in addition to 10% glucose and 17% rhamnose. The immunological specificity of these antigens was found to be the same by immunodiffusion in agar gel. Another fraction with a negative charge (eIII) reacted with polyglycerophosphate antisera from Streptococcus mutans and Streptococcus pyogenes. For comparison, the MT703 antigen in a hot trichloroacetic acid extract (eA) and the group E antigen from a saline extract of cells of strain K129 (EI) were similarly purified by anionic ion-exchange chromatography. Although the ratio of glucose and rhamnose in eA was 1:0.9 and in eI and eII approximately 1:1.5, reactions of identity were obtained in gel diffusion against specific anti-e serum. This difference in ratio is probably a result of the extraction procedures. Both the type e and group E antisera were reactive with both eI and EI antigens. The adsorption of group E antiserum with MT703 cells removed all E antibody, whereas type e-specific antibody remained after adsorption with K129 cells. These results suggest that eI antigen possesses both e and E specificities, whereas EI possesses E only. These findings were supported by the quantitative precipitin test and immunodiffusion and/or immunoelectrophoretic patterns in agar gel. Methyl-beta-D-glucopyranoside markedly inhibited the precipitin reaction in both type e and group E sera. However, a significantly stronger inhibition by cellobiose of type e serum than of group E serum indicates that a beta-linked glucose-glucose dimer is the predominant antigenic

  17. 47 CFR 90.691 - Emission mask requirements for EA-based systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Emission mask requirements for EA-based systems. 90.691 Section 90.691 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... of Ea-Based Smr Systems in the 809-824/851-869 Mhz Band § 90.691 Emission mask requirements for EA...

  18. Physical Properties and Evolutionary States of EA-type Eclipsing Binaries Observed by LAMOST

    NASA Astrophysics Data System (ADS)

    Qian, S.-B.; Zhang, J.; He, J.-J.; Zhu, L.-Y.; Zhao, E.-G.; Shi, X.-D.; Zhou, X.; Han, Z.-T.

    2018-03-01

    About 3196 EA-type binaries (EAs) were observed by LAMOST by 2017 June 16 and their spectral types were derived. Meanwhile, the stellar atmospheric parameters of 2020 EAs were determined. In this paper, those EAs are cataloged and their physical properties and evolutionary states are investigated. The period distribution of EAs suggests that the period limit of tidal locking for the close binaries is about 6 days. It is found that the metallicity of EAs is higher than that of EW-type binaries (EWs), indicating that EAs are generally younger than EWs and they are the progenitors of EWs. The metallicities of long-period EWs (0.4< P< 1 days) are the same as those of EAs with the same periods, while their values of Log (g) are usually smaller than those of EAs. These support the evolutionary process that EAs evolve into long-period EWs through the combination of angular momentum loss (AML) via magnetic braking and case A mass transfer. For short-period EWs, their metallicities are lower than those of EAs, while their gravitational accelerations are higher. These reveal that they may be formed from cool short-period EAs through AML via magnetic braking with little mass transfer. For some EWs with high metallicities, they may be contaminated by material from the evolution of unseen neutron stars and black holes or they have third bodies that may help them to form rapidly through a short timescale of pre-contact evolution. The present investigation suggests that the modern EW populations may have formed through a combination of these mechanisms.

  19. 36 CFR 1010.6 - Determination of requirement for EA or EIS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... for EA or EIS. 1010.6 Section 1010.6 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.6 Determination of requirement for EA or EIS. In deciding whether to require the preparation of an EA or an EIS, the NEPA Compliance Coordinator will determine whether the proposal is one...

  20. Observation of EAS using a large water tank

    NASA Technical Reports Server (NTRS)

    Inoue, K.; Sakuyama, H.; Suzuki, N.; Suzuki, T.

    1985-01-01

    Using a large water tank (30 m in diameter, 4.5 m in depth) transition of extensive air showers (EAS) was investigated at Taro (200 m above sea level). There are set 150,0.4 sq m proportional counters on the bottom of the water tank. A conventional EAS array of 25 plastic scintillation detectors was arranged within several tens meter from the water tank. A proportional counter (10x10x200 cc x2) is made of a square shaped pipe of iron. Tungsten wire (100 mu m phi) is stretched tight in the center of the counter. A gas mixture of 90% argon and 10% methane is used at 760 mmHg. About 3000 EAS were obtained through 1 m of water since 1984.

  1. 47 CFR 90.685 - Authorization, construction and implementation of EA licenses.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... into operation a sufficient number of base stations to provide coverage to at least one-third of the population of its EA-based service area. Further, each EA licensee must provide coverage to at least two-thirds of the population of the EA-based service area within five years of the grant of their initial...

  2. 47 CFR 90.685 - Authorization, construction and implementation of EA licenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... into operation a sufficient number of base stations to provide coverage to at least one-third of the population of its EA-based service area. Further, each EA licensee must provide coverage to at least two-thirds of the population of the EA-based service area within five years of the grant of their initial...

  3. 47 CFR 90.685 - Authorization, construction and implementation of EA licenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... into operation a sufficient number of base stations to provide coverage to at least one-third of the population of its EA-based service area. Further, each EA licensee must provide coverage to at least two-thirds of the population of the EA-based service area within five years of the grant of their initial...

  4. 47 CFR 90.685 - Authorization, construction and implementation of EA licenses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... into operation a sufficient number of base stations to provide coverage to at least one-third of the population of its EA-based service area. Further, each EA licensee must provide coverage to at least two-thirds of the population of the EA-based service area within five years of the grant of their initial...

  5. 47 CFR 90.685 - Authorization, construction and implementation of EA licenses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... into operation a sufficient number of base stations to provide coverage to at least one-third of the population of its EA-based service area. Further, each EA licensee must provide coverage to at least two-thirds of the population of the EA-based service area within five years of the grant of their initial...

  6. 7 CFR 1794.24 - Proposals normally requiring an EA with scoping.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 12 2014-01-01 2013-01-01 true Proposals normally requiring an EA with scoping. 1794... Classification of Proposals § 1794.24 Proposals normally requiring an EA with scoping. (a) General. Applications... development of the EA. These types of actions are subject to the requirements of §§ 1794.50 through 1794.54...

  7. 7 CFR 1794.24 - Proposals normally requiring an EA with scoping.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Proposals normally requiring an EA with scoping. 1794... Classification of Proposals § 1794.24 Proposals normally requiring an EA with scoping. (a) General. Applications... development of the EA. These types of actions are subject to the requirements of §§ 1794.50 through 1794.54...

  8. 7 CFR 1794.24 - Proposals normally requiring an EA with scoping.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Proposals normally requiring an EA with scoping. 1794... Classification of Proposals § 1794.24 Proposals normally requiring an EA with scoping. (a) General. Applications... development of the EA. These types of actions are subject to the requirements of §§ 1794.50 through 1794.54...

  9. 7 CFR 1794.24 - Proposals normally requiring an EA with scoping.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Proposals normally requiring an EA with scoping. 1794... Classification of Proposals § 1794.24 Proposals normally requiring an EA with scoping. (a) General. Applications... development of the EA. These types of actions are subject to the requirements of §§ 1794.50 through 1794.54...

  10. 7 CFR 1794.24 - Proposals normally requiring an EA with scoping.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Proposals normally requiring an EA with scoping. 1794... Classification of Proposals § 1794.24 Proposals normally requiring an EA with scoping. (a) General. Applications... development of the EA. These types of actions are subject to the requirements of §§ 1794.50 through 1794.54...

  11. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease

    PubMed Central

    Weiner, Zachary P.; Crew, Rebecca M.; Brandt, Kevin S.; Ullmann, Amy J.; Schriefer, Martin E.; Molins, Claudia R.

    2015-01-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. PMID:26376927

  12. Evaluation of Selected Borrelia burgdorferi lp54 Plasmid-Encoded Gene Products Expressed during Mammalian Infection as Antigens To Improve Serodiagnostic Testing for Early Lyme Disease.

    PubMed

    Weiner, Zachary P; Crew, Rebecca M; Brandt, Kevin S; Ullmann, Amy J; Schriefer, Martin E; Molins, Claudia R; Gilmore, Robert D

    2015-11-01

    Laboratory testing for the diagnosis of Lyme disease is performed primarily by serologic assays and is accurate for detection beyond the acute stage of the infection. Serodiagnostic assays to detect the early stages of infection, however, are limited in their sensitivity, and improvement is warranted. We analyzed a series of Borrelia burgdorferi proteins known to be induced within feeding ticks and/or during mammalian infection for their utility as serodiagnostic markers against a comprehensive panel of Lyme disease patient serum samples. The antigens were assayed for IgM and IgG reactivity in line immunoblots and separately by enzyme-linked immunosorbent assay (ELISA), with a focus on reactivity against early Lyme disease with erythema migrans (EM), early disseminated Lyme neuroborreliosis, and early Lyme carditis patient serum samples. By IgM immunoblotting, we found that recombinant proteins BBA65, BBA70, and BBA73 reacted with early Lyme EM samples at levels comparable to those of the OspC antigen used in the current IgM blotting criteria. Additionally, these proteins reacted with serum samples from patients with early neuroborreliosis and early carditis, suggesting value in detecting early stages of this disease progression. We also found serological reactivity against recombinant proteins BBA69 and BBA73 with early-Lyme-disease samples using IgG immunoblotting and ELISA. Significantly, some samples that had been scored negative by the Centers for Disease Control and Prevention-recommended 2-tiered testing algorithm demonstrated positive reactivity to one or more of the antigens by IgM/IgG immunoblot and ELISA. These results suggest that incorporating additional in vivo-expressed antigens into the current IgM/IgG immunoblotting tier in a recombinant protein platform assay may improve the performance of early-Lyme-disease serologic testing. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Early diagnosis of dengue in travelers: comparison of a novel real-time RT-PCR, NS1 antigen detection and serology.

    PubMed

    Huhtamo, Eili; Hasu, Essi; Uzcátegui, Nathalie Y; Erra, Elina; Nikkari, Simo; Kantele, Anu; Vapalahti, Olli; Piiparinen, Heli

    2010-01-01

    The increased traveling to dengue endemic regions and the numerous epidemics have led to a rise in imported dengue. The laboratory diagnosis of acute dengue requires several types of tests and often paired samples are needed for obtaining reliable results. Although several diagnostic methods are available, proper comparative data on their performance are lacking. To compare the performance of novel methods including a novel pan-DENV real-time RT-PCR and a commercially available NS1 capture-EIA in regard to IgM detection for optimizing the early diagnosis of DENV in travelers. A panel of 99 selected early phase serum samples of dengue patients was studied by real-time RT-PCR, NS1 antigen ELISA, IgM-EIA, IgG-IFA and cell culture virus isolation. The novel real-time RT-PCR was shown specific and sensitive for detection of DENV-1-4 RNA and suitable for diagnostic use. The diagnostic rate using combination of RNA and IgM detection was 99% and using NS1 and IgM detection 95.9%. The results of RNA and NS1 antigen detection disagreed in 15.5% of samples that had only RNA or NS1 antigen detected. The diagnostic rates of early samples are higher when either RNA or NS1 antigen detection is combined with IgM detection. Besides the differences in the RNA and NS1 detection assays, the observed discrepancy of results could suggest individual variation or differences in timing of these markers in patient serum. Copyright (c) 2009 Elsevier B.V. All rights reserved.

  14. EA Shuttle Document Retention Effort

    NASA Technical Reports Server (NTRS)

    Wagner, Howard A.

    2010-01-01

    This slide presentation reviews the effort of code EA at Johnson Space Center (JSC) to identify and acquire databases and documents from the space shuttle program that are adjudged important for retention after the retirement of the space shuttle.

  15. 47 CFR 90.763 - EA, Regional and nationwide system operations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... on a case-by-case basis upon submission by the EA or Regional licensee of: (A) A technical analysis... by a licensee or the Commission, an EA or regional licensee shall furnish the technical parameters...

  16. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection.

    PubMed

    Abo-Aziza, Faten A M; Hendawy, Seham H M; Namaky, Amira H El; Ashry, Heba M

    2017-06-01

    The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done concerning Th1/Th2 balance and cross-reactivity of S

  17. Th1/Th2 balance and humoral immune response to potential antigens as early diagnostic method of equine Strongylus nematode infection

    PubMed Central

    Abo-Aziza, Faten A. M.; Hendawy, Seham H. M.; Namaky, Amira H. El; Ashry, Heba M.

    2017-01-01

    Aim:: The aim of this study was to investigate the early diagnosis of strongyle infection based on early changes in Th1 and Th2 cytokines beside the diagnostic accuracy values and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting profiles using prepared strongyles antigens. Materials and Methods:: A total of 73 donkeys had a mean age of 4-32 years old were parasitologically examined for strongyle infection. The early changes in Th1 and Th2 cytokines were determined, and the diagnostic accuracy values and SDS-PAGE and western blotting profiles were performed using prepared strongyles antigens; crude somatic Strongylus vulgaris (CSS), excretory-secretory S. vulgaris (ESS), crude somatic Cyathostomins (CSC), and excretory-secretory Cyathostomins (ESC). Results:: The results revealed highest 437.04% and lowest 37.81% immunoglobulin G (IgG) in high and low egg shedder groups when using ESC and CSS antigens, respectively. Antibodies index for ESS and CSC were significantly higher in moderate egg shedder group while that for ESS and CSC, ESC was significantly higher in high egg shedder group. Tumor necrosis factor alpha (TNF-α)/interleukin-4 (IL-4) balance in S. vulgaris infected donkeys was approximately equal in apparently healthy, low and high egg shedder groups while TNF-α < IL-4 in moderate egg shedder. In Cyathostomins infected animals, TNF-α/IL-4 balance was approximately equal in apparently healthy group while it was low in moderate and high egg shedder groups. The diagnostic accuracy showed that the higher specificity (46.6%) and prevalence (95.40%) were recorded by CSS and ESC antigens, respectively. However, SDS-PAGE and western blotting profiling proved that the band at molecular weight 25 kDa is exhibited by CSS antigen. Conclusion:: Combination of detecting level of TNF-α/IL-4 balance, CSS antigen and IgG concentration is good tool for appropriate diagnosis of such infection. More advancement research must be done

  18. Effects of early childhood supplementation on the educational achievement of women.

    PubMed

    Li, Haojie; Barnhart, Huiman X; Stein, Aryeh D; Martorell, Reynaldo

    2003-11-01

    Malnutrition during early childhood has been suggested to cause functional disadvantages in adults, including reduced intelligence and lower educational achievement (EA). We assessed the effects of improved nutrition in early life on the EA of women in 4 rural Guatemalan villages. The study sample comprised 130 female singletons exposed to either Atole (53%, 91 kcal and 6.4 g protein/100 mL) or Fresco (47%, 33 kcal/100 mL, no protein) during the prenatal period and the first 2 years of life. EA was assessed at the ages of 22 to 29 years by knowledge, numeracy, and several reading tests. A summary measure of EA was computed based on 5 tests, and outcome variables were categorized into quintiles. Analysis was based on a proportional odds model. Generalized estimating equations were used to account for sibling clustering. Overall, 36.2% of women completed primary school. Women exposed to Atole had better EA than those exposed to Fresco (odds ratio [OR]: 2.8; 95% confidence interval [CI], 1.4, 5.4), with a significant treatment-by-schooling interaction. Atole was not associated with EA (OR: 1.5; 95% CI: 0.7, 3.2) among women who did not complete primary school, whereas among those who completed primary school, Atole was associated with improved EA (OR: 13.7; 95% CI: 3.7, 50.8). We conclude that better nutrition during early childhood improved adult EA, but only among children who completed primary school.

  19. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... through the use of a single set of EAS equipment at the hub station (or common studio or control point... the FCC in any agreements. (e) Other technologies and public service providers, such as low earth... 47 Telecommunication 1 2014-10-01 2014-10-01 false The Emergency Alert System (EAS). 11.11 Section...

  20. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... through the use of a single set of EAS equipment at the hub station (or common studio or control point... the FCC in any agreements. (e) Other technologies and public service providers, such as low earth... 47 Telecommunication 1 2013-10-01 2013-10-01 false The Emergency Alert System (EAS). 11.11 Section...

  1. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... through the use of a single set of EAS equipment at the hub station (or common studio or control point... the FCC in any agreements. (e) Other technologies and public service providers, such as low earth... 47 Telecommunication 1 2012-10-01 2012-10-01 false The Emergency Alert System (EAS). 11.11 Section...

  2. Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

    PubMed Central

    McConnell, Sean C.; Hernandez, Kyle M.; Wcisel, Dustin J.; Kettleborough, Ross N.; Stemple, Derek L.; Andrade, Jorge; de Jong, Jill L. O.

    2016-01-01

    Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e. We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC class I genes also retain ancient sequence lineages, indicating that alternative lineages may have been preserved throughout the entire MHC pathway since early diversification of the adaptive immune system ∼500 Mya. Furthermore, polymorphisms within the three MHC pathway steps (antigen cleavage, transport, and presentation) are each predicted to alter peptide specificity. Lastly, comparative analysis shows that antigen processing gene diversity is far more extensive than previously realized (with ancient coelacanth psmb8 lineages, shark psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune functions and conserved roles in shaping MHC pathway evolution throughout vertebrates. PMID:27493218

  3. 36 CFR § 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Preparation of an EA. § 1010.11 Section § 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010... Trust may prepare or require an EA at any time to assist planning and decision-making. (b) Content and...

  4. Performances of fourth generation HIV antigen/antibody assays on filter paper for detection of early HIV infections.

    PubMed

    Kania, Dramane; Truong, Tam Nguyen; Montoya, Ana; Nagot, Nicolas; Van de Perre, Philippe; Tuaillon, Edouard

    2015-01-01

    Point-of-care testing and diagnosis of HIV acute infections play important roles in preventing transmission, but HIV rapid diagnosis tests have poor capacity to detect early infections. Filter paper can be used for capillary blood collection and HIV testing using 4th generation immunoassays. Antigen/antibody combined immunoassays were evaluated for their capacity to identify early HIV infections using filter paper in comparison with rapid test. Thirty nine serum samples collected from HIV seroconverters were spotted onto filter paper and tested by the Roche Elecsys(®) HIV Combi PT test and the DiaSorin Liaison XL Murex HIV Ab/Ag assay. Fourth generation immunoassays identified 34 out of 39 HIV early infections using dried serum spot, whereas the Determine™ HIV-1/2 rapid test detected 24 out of 39 HIV positive serum (87.2% vs 61.5% respectively, p = 0.009). p24 antigen was detected by the Liaison XL in 19 dried serum samples (48.7%). In the group characterized by a negative western blot, 7 out of 8 (87.5%) and 6 out of 8 (75.0%) samples were found positive for HIV using the Elecsys and the Liaison XL, respectively. None of these eight samples classified in this group of early acute infections were found positive by the rapid test. Fourth generation Ag/Ab immunoassays performed on dried serum spot had good performance for HIV testing during the early phases of HIV infection. This method may be useful to detect HIV early infections in hard-to-reach populations and individuals living in remote areas before rapid tests become positive. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. EAS thermal neutron detection with the PRISMA-LHAASO-16 experiment

    NASA Astrophysics Data System (ADS)

    Li, B.-B.; Alekseenko, V. V.; Cui, S.-w.; Chen, T.-L.; Dangzengluobu; Feng, S.-H.; Gao, Q.; Liu, Y.; Huang, Q.-C.; He, Y.-Y.; Liu, M.-Y.; Ma, X.-H.; Pozdnyakov, E. I.; Shchegolev, O. B.; Shen, F.-Z.; Stenkin, Yu. V.; Stepanov, V. I.; Yanin, Ya. V.; Yao, J.-D.; Zhou, R.

    2017-12-01

    EAS (extensive air shower) thermal neutron measurement gives advantages to study energy and mass composition of primary cosmic rays especially in the knee region. After the success of the PRISMA-YBJ experiment, we build a new EAS thermal neutron detection array at Tibet University, Lhasa, China (3700 m a.s.l.) in March, 2017. This prototype array so called "PRISMA-LHAASO-16" consists of 16 EAS EN-detectors ("EN" is abbreviation for electron and neutron) measuring two main EAS components: hadronic and electromagnetic ones. Different from PRISMA-YBJ, these detectors use a thin layer of a novel type of ZnS(Ag) scintillator alloyed with natural boron compound for thermal neutron capture. PRISMA-LHAASO-16 will be moved to the LHAASO site in the near future. In this paper, we introduce principle of the detection technique, deployment of the array, and the test results of the array.

  6. Analysis of equi-intensity curves and NU distribution of EAS

    NASA Technical Reports Server (NTRS)

    Tanahashi, G.

    1985-01-01

    The distribution of the number of muons in extensive air showers (EAS) and the equi-intensity curves of EAS are analyzed on the basis of Monte Carlo simulation of various cosmic ray composition and the interaction models. Problems in the two best combined models are discussed.

  7. 47 CFR 11.54 - EAS operation during a National Level emergency.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... licensees and DBS providers may choose their two EAS sources, one of which must be a PEP station. (2... header codes for a national emergency. (3) After completing the above transmission procedures, key EAS...

  8. 47 CFR 11.54 - EAS operation during a National Level emergency.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... licensees and DBS providers may choose their two EAS sources, one of which must be a PEP station. (2... header codes for a national emergency. (3) After completing the above transmission procedures, key EAS...

  9. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Actions that normally require an EA. 1010.10 Section 1010.10 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL.... An EA assists the Trust in complying with NEPA when no EIS is necessary, and it facilitates the...

  10. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Actions that normally require an EA. 1010.10 Section 1010.10 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL.... An EA assists the Trust in complying with NEPA when no EIS is necessary, and it facilitates the...

  11. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Actions that normally require an EA. 1010.10 Section 1010.10 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL.... An EA assists the Trust in complying with NEPA when no EIS is necessary, and it facilitates the...

  12. 36 CFR 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Actions that normally require an EA. 1010.10 Section 1010.10 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL.... An EA assists the Trust in complying with NEPA when no EIS is necessary, and it facilitates the...

  13. 75 FR 33799 - EasTrans, LLC; Notice of Baseline Filing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-15

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-30-000] EasTrans, LLC; Notice of Baseline Filing June 8, 2010. Take notice that on June 4, 2010, EasTrans, LLC submitted a baseline filing of its Statement of Operating Conditions for services provided under section 311 of the...

  14. 47 CFR 11.54 - EAS operation during a National Level emergency.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... emergency, EAS Participants may transmit in lieu of the EAS audio feed an audio feed of the President's voice message from an alternative source, such as a broadcast network audio feed. [77 FR 16705, Mar. 22...

  15. 47 CFR 11.54 - EAS operation during a National Level emergency.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... emergency, EAS Participants may transmit in lieu of the EAS audio feed an audio feed of the President's voice message from an alternative source, such as a broadcast network audio feed. [77 FR 16705, Mar. 22...

  16. 47 CFR 11.54 - EAS operation during a National Level emergency.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... emergency, EAS Participants may transmit in lieu of the EAS audio feed an audio feed of the President's voice message from an alternative source, such as a broadcast network audio feed. [77 FR 16705, Mar. 22...

  17. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... day-to-day emergency situations posing a threat to life and property. Examples of natural emergencies... Participants providing foreign language programming should transmit all EAS announcements in the same language as the primary language of the EAS Participant. (5) Upon completion of the State or Local Area EAS...

  18. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... day-to-day emergency situations posing a threat to life and property. Examples of natural emergencies... Participants providing foreign language programming should transmit all EAS announcements in the same language as the primary language of the EAS Participant. (5) Upon completion of the State or Local Area EAS...

  19. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... day-to-day emergency situations posing a threat to life and property. Examples of natural emergencies... Participants providing foreign language programming should transmit all EAS announcements in the same language as the primary language of the EAS Participant. (5) Upon completion of the State or Local Area EAS...

  20. Evaluation of Mycobacterium tuberculosis Early Secreted Antigenic Target 6 Recombinant Protein as a Diagnostic Marker in Skin Test.

    PubMed

    Moradi, Jale; Mosavari, Nader; Ebrahimi, Mahmoud; Arefpajohi, Reza; Tebianian, Majid

    2015-02-01

    Tuberculosis (TB) is the leading infectious disease in the developing world. Delayed-type hypersensitivity skin test diagnoses TB using tuberculin purified protein derivative (PPD), but this test is incapable of distinguishing Mycobacterium tuberculosis (MTB) infection from bacillus Calmette-Guérin (BCG) vaccination or an infection caused by nontuberculous mycobacteria (NTM). This study was performed to evaluate the use of recombinant early secretory antigenic target 6 (rESAT-6), a secretory protein found only in MTB, Mycobacterium bovis, and few other mycobacterial species, as a skin marker for MTB in guinea pigs. We prepared recombinant MTB ESAT-6 and evaluated its use as a specific antigen for MTB in guinea pigs. Our results show that the purified MTB rESAT-6 antigen is capable of inducing a positive reaction only in guinea pigs sensitized to MTB. No such reaction was observed in the animals sensitized to M. bovis, BCG vaccination, or NTM (Mycobacterium avium). Our study results confirm that the ESAT-6 antigen is more specific to MTB infection than PPD and could be used in more specific skin tests for detection of MTB in large animals and in humans.

  1. Antigen Binding and Site-Directed Labeling of Biosilica-Immobilized Fusion Proteins Expressed in Diatoms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ford, Nicole R.; Hecht, Karen A.; Hu, Dehong

    2016-01-08

    The diatom Thalassiosira pseudonana was genetically modified to express biosilica-targeted fusion proteins incorporating a tetracysteine tag for site-directed labeling with biarsenical affinity probes and either EGFP or single chain antibody to test colocalization of probes with the EGFP-tagged recombinant protein or binding of biosilica-immobilized antibodies to large and small molecule antigens, respectively. Site-directed labeling with the biarsenical probes demonstrated colocalization with EGFP-encoded proteins in nascent and mature biosilica, supporting their use in studying biosilica maturation. Isolated biosilica transformed with a single chain antibody against either the Bacillus anthracis surface layer protein EA1 or small molecule explosive trinitrotoluene (TNT) effectively boundmore » the respective antigens. A marked increase in fluorescence lifetime of the TNT surrogate Alexa Fluor 555-trinitrobenzene reflected the high binding specificity of the transformed isolated biosilica. These results demonstrated the potential use of biosilica-immobilized single chain antibodies as binders for large and small molecule antigens in sensing and therapeutics.« less

  2. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... the State or Local Area EAS must discontinue normal programming and follow the procedures in the State...); and DBS providers must comply with § 11.54(b)(7). EAS Participants providing foreign language programming should comply with § 11.54(b)(8). (5) Upon completion of the State or Local Area EAS transmission...

  3. Specific destruction of islet transplants in NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation chimeras irrespective of allelic differences in beta-cell antigens.

    PubMed

    Leijon, K; Hillörn, V; Bergqvist, I; Holmberg, D

    1995-06-01

    We have tested the hypothesis that allelic differences in the antigens expressed by the beta-cells of the islets of Langerhans influence the development of insulitis in the non-obese diabetic (NOD) mouse. Islets of Langerhans from NOD, C57BL/6 and C3H/Tif mice were transplanted under the kidney capsule of NOD<-->C57BL/6 and NOD<-->C3H/Tif embryo aggregation (EA) chimeras and the infiltration was scored 5-7 weeks later. Mononuclear cell infiltration of pancreatic islets was observed in 60% of the NOD<-->C57BL/6 and in 55% of the NOD<-->C3H/Tif EA chimeras. All transplanted EA chimeras that developed insulitis also displayed mononuclear cell infiltrates in the transplants, irrespective of the origin of the transplanted islets. In contrast, no infiltration of transplants was detected in EA chimeras scoring negative for insulitis. These results demonstrate that the specific destruction of islet transplants does not require the expression of NOD specific antigens by the islets. Moreover, the beta-cell destruction appears not to be restricted to NOD-MHC. The correlation between insulitis and transplant beta-cell destruction suggests the possibility that the development of insulitis is a prerequisite for transplant specific destruction. MHC restricted destruction may, therefore, precede the beta-cell destruction of transplanted islets. The chimerism among the mononuclear cells infiltrating the islet transplants was found to correlate with the overall haematopoetic chimerism in each of the individual EA chimeras. This observation suggests that NOD bone marrow, as well as non-NOD bone marrow, generates cells contributing to the beta-cell destruction process.

  4. Expert Advisor (EA) Evaluation System Using Web-based ELECTRE Method in Foreign Exchange (Forex) Market

    NASA Astrophysics Data System (ADS)

    Satibi; Widodo, Catur Edi; Farikhin

    2018-02-01

    This research aims to optimize forex trading profit automatically using EA but its still keep considering accuracy and drawdown levels. The evaluation system will classify EA performance based on trading market sessions (Sydney, Tokyo, London and New York) to determine the right EA to be used in certain market sessions. This evaluation system is a web-based ELECTRE methods that interact in real-time with EA through web service and are able to present real-time charts performance dashboard using web socket protocol communications. Web applications are programmed using NodeJs. In the testing period, all EAs had been simulated 24 hours in all market sessions for three months, the best EA is valued by its profit, accuracy and drawdown criteria that calculated using web-based ELECTRE method. The ideas of this research are to compare the best EA on testing period with collaboration performances of each best classified EA by market sessions. This research uses three months historical data of EUR/USD as testing period and other 3 months as validation period. As a result, performance of collaboration four best EA classified by market sessions can increase profits percentage consistently in testing and validation periods and keep securing accuracy and drawdown levels.

  5. The specificity of heterophil antibodies in patients and healthy donors with no or minimal signs of infectious mononucleosis.

    PubMed

    Horwitz, C A; Henle, W; Henle, G; Polesky, H; Wexler, H; Ward, P

    1976-01-01

    Over several years sera were collected from 14 heterophil-positive students or patients who did not fulfill minimal hematologic criteria for infectious mononucleosis (I.M.) The specificity of these heterophil reactions for I.M. was investigated by determining antibodies to Epstein-Barr virus-determined antigens, i.e., to viral capsid antigens (VCA), early antigens (EA), and EBV-associated nuclear antigens (EBNA). On the basis of detectable anti-EA and/or the early absence and late emergence of anti-EBNA, four of these 14 individuals showed evidence of a current or very recent primary Epstein-Barr virus infection. The other ten patients showed antibody patterns indicative of Epstein-Barr virus infections in the past, and no firm conclusions could be drawn with regard to the specificity of their heterophil reactions. It was assumed, however, that some represented atypical clinical forms of EBV infection and that timing of specimen collection was a factor in explaining the paucity of Downey cells. In three patients, the absorbed heterophil-positive reactions persisted with little change in titer for at least 22 mo and thus might represent false-positive tests.

  6. Young stellar populations in early-type galaxies in the Sloan Digital Sky Survey

    NASA Astrophysics Data System (ADS)

    Nolan, Louisa A.; Raychaudhury, Somak; Kabán, Ata

    2007-02-01

    We use a purely data-driven rectified factor analysis to identify early-type galaxies with recent star formation in Data Release 4 of the Sloan Digital Sky Survey Spectroscopic Catalogue. We compare the spectra and environment of these galaxies with those of `normal' early-type galaxies, and a sample of independently selected E+A galaxies. We calculate the projected local galaxy surface density from the nearest five and 10 neighbours (Σ5 and Σ10) for each galaxy in our sample, and find that the dependence on projected local density, of the properties of E+A galaxies, is not significantly different from that of early-type galaxies with young stellar populations, dropping off rapidly towards denser environments, and flattening off at densities <~0.1-0.3 Mpc-2. The dearth of E+A galaxies in dense environments confirms that E+A galaxies are most likely the products of galaxy-galaxy merging or interactions, rather than star-forming galaxies whose star formation has been quenched by processes unique to dense environments, such as ram-pressure stripping or galaxy harassment. We see a tentative peak in the number of E+A galaxies at Σ10 ~ 0.1-0.3 Mpc-2, which may represent the local galaxy density at which the rate of galaxy-galaxy merging or interaction rate peaks. Analysis of the spectra of our early-type galaxies with young stellar populations suggests that they have a stellar component dominated by F stars, ~1-4 Gyr old, together with a mature, metal-rich population characteristic of `typical' early-type galaxies. The young stars represent >~10 per cent of the stellar mass in these galaxies. This, together with the similarity of the environments in which this `E+F' population and the E+A galaxy sample are found, suggests that E+F galaxies used to be E+A galaxies, but have evolved by a further ~ one to a few Gyr. Our rectified factor analysis is sensitive enough to identify this hidden population, which allows us to study the global and intrinsic properties of early

  7. 47 CFR 76.1711 - Emergency alert system (EAS) tests and activation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 4 2012-10-01 2012-10-01 false Emergency alert system (EAS) tests and activation. 76.1711 Section 76.1711 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Documents to be Maintained for Inspection § 76.1711 Emergency alert system (EAS)...

  8. 47 CFR 76.1711 - Emergency alert system (EAS) tests and activation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 4 2014-10-01 2014-10-01 false Emergency alert system (EAS) tests and activation. 76.1711 Section 76.1711 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Documents to be Maintained for Inspection § 76.1711 Emergency alert system (EAS)...

  9. Overexpression of EaDREB2 and pyramiding of EaDREB2 with the pea DNA helicase gene (PDH45) enhance drought and salinity tolerance in sugarcane (Saccharum spp. hybrid).

    PubMed

    Augustine, Sruthy Maria; Ashwin Narayan, J; Syamaladevi, Divya P; Appunu, C; Chakravarthi, M; Ravichandran, V; Tuteja, Narendra; Subramonian, N

    2015-02-01

    EaDREB2 overexpressed in sugarcane enhanced tolerance to drought and salinity. When co-transformed with plant DNA helicase gene, DREB2 showed greater level of salinity tolerance than in single-gene transgenics. Drought is one of the most challenging agricultural issues limiting sustainable sugarcane production and can potentially cause up to 50 % yield loss. DREB proteins play a vital regulatory role in abiotic stress tolerance in plants. We previously reported that expression of EaDREB2 is enhanced by drought stress in Erianthus arundinaceus. In this study, we have isolated the DREB2 gene from E. arundinaceus, transformed one of the most popular sugarcane variety Co 86032 in tropical India with EaDREB2 through Agrobacterium-mediated transformation, pyramided the EaDREB2 gene with the gene coding for PDH45 driven by Port Ubi 2.3 promoter through particle bombardment and evaluated the V1 transgenics for soil deficit moisture and salinity stresses. Soil moisture stress was imposed at the tillering phase by withholding irrigation. Physiological, molecular and morphological parameters were used to assess drought tolerance. Salinity tolerance was assessed through leaf disc senescence and bud sprout assays under salinity stress. Our results indicate that overexpression of EaDREB2 in sugarcane enhances drought and salinity tolerance to a greater extent than the untransformed control plants. This is the first report of the co-transformation of EaDREB2 and PDH45 which shows higher salinity tolerance but lower drought tolerance than EaDREB2 alone. The present study seems to suggest that, for combining drought and salinity tolerance together, co-transformation is a better approach.

  10. Screening for epitope specificity directly on culture supernatants in the early phase of monoclonal antibody production by an ELISA with biotin-labeled antigen.

    PubMed

    Andersen, Ditte C; Jensen, Charlotte H; Gregersen, Annemette; Brandt, Jette; Kliem, Anette; Skjødt, Karsten; Koch, Claus; Teisner, Børge

    2004-01-01

    This report describes an assay for comparison of epitope specificity in groups of monoclonal antibodies against a given antigen. The only prerequisite is the biotin-labeled antigen. One of the monoclonal antibodies is captured onto a plastic surface via a rabbit anti-mouse Ig, and the other preincubated with biotinylated antigen. When the two antibodies react with the same epitope subsequent binding of the biotin-labeled antigen is abolished (inhibition). In the cases where no inhibition was observed, the two antibodies were considered to react with distinct, independent epitopes. The obvious advantages using this assay, are that it can be performed directly on culture supernatants in the early phase of monoclonal antibody production, and also works for antigens with repetitive epitopes. Moreover, the bonus effect, i.e., a signal in excess of the reference signal when sets of monoclonal antibodies with different epitope specificity are compared, gives a relative measure of affinity.

  11. Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma.

    PubMed

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-Yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-04-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ≤ 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (≤55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner.

  12. Increased cardiogenesis in P19-GFP teratocarcinoma cells expressing the propeptide IGF-1Ea

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Poudel, Bhawana; Bilbao, Daniel; Sarathchandra, Padmini

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer In this study, we explored the function of IGF-1Ea propeptide in inducing cardiogenesis of stem cells. Black-Right-Pointing-Pointer IGF-1Ea promoted cardiac mesodermal induction in uncommitted cells. Black-Right-Pointing-Pointer Under differentiation condition, IGF-1Ea increased expression of cardiac differentiation markers. Black-Right-Pointing-Pointer Furthermore, it promoted formation of finely organized sarcomeric structure. Black-Right-Pointing-Pointer IGF-1Ea propeptide may be a good candidate to improve production of cardiomyocytes from pluripotent cells. -- Abstract: The mechanism implicated in differentiation of endogenous cardiac stem cells into cardiomyocytes to regenerate the heart tissue upon an insult remains elusive, limiting the therapeutical goals to exogenous cell injection and/or gene therapy. Wemore » have shown previously that cardiac specific overexpression of the insulin-like growth factor 1 propeptide IGF-1Ea induces beneficial myocardial repair after infarct. Although the mechanism is still under investigation, the possibility that this propeptide may be involved in promoting stem cell differentiation into the cardiac lineage has yet to be explored. To investigate whether IGF-1Ea promote cardiogenesis, we initially modified P19 embryonal carcinoma cells to express IGF-1Ea. Taking advantage of their cardiomyogenic nature, we analyzed whether overexpression of this propeptide affected cardiac differentiation program. The data herein presented showed for the first time that constitutively overexpressed IGF-1Ea increased cardiogenic differentiation program in both undifferentiated and DMSO-differentiated cells. In details, IGF-1Ea overexpression promoted localization of alpha-actinin in finely organized sarcomeric structure compared to control cells and upregulated the cardiac mesodermal marker NKX-2.5 and the ventricular structural protein MLC2v. Furthermore, activated IGF-1 signaling promoted cardiac

  13. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11... fundamental frequencies of 853 and 960 Hz and not vary over ±0.5 Hz. (ii) Harmonic Distortion. The total... the two tones for calibration of associated systems. (iv) Time Period for Transmission of Tones. The...

  14. Results of EAS characteristics calculations in the framework of the universal hadronic interaction model NEXUS

    NASA Astrophysics Data System (ADS)

    Kalmykov, N. N.; Ostapchenko, S. S.; Werner, K.

    An extensive air shower (EAS) calculation scheme based on cascade equations and some EAS characteristics for energies 1014 -1017 eV are presented. The universal hadronic interaction model NEXUS is employed to provide the necessary data concerning hadron-air collisions. The influence of model assumptions on the longitudinal EAS development is discussed in the framework of the NEXUS and QGSJET models. Applied to EAS simulations, perspectives of combined Monte Carlo and numerical methods are considered.

  15. 36 CFR § 1010.10 - Actions that normally require an EA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Actions that normally require an EA. § 1010.10 Section § 1010.10 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL.... An EA assists the Trust in complying with NEPA when no EIS is necessary, and it facilitates the...

  16. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... decoders manufactured after August 1, 2003 must provide a means to permit the selective display and logging... upgrade their decoders on an optional basis to include a selective display and logging capability for EAS... decoders after February 1, 2004 must install decoders that provide a means to permit the selective display...

  17. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... used for audio messages and at least one input port used for data messages. (3) Outputs. The encoder shall have at least one audio output port and at least one data output port. (4) Calibration. EAS... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  18. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... used for audio messages and at least one input port used for data messages. (3) Outputs. The encoder shall have at least one audio output port and at least one data output port. (4) Calibration. EAS... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  19. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... used for audio messages and at least one input port used for data messages. (3) Outputs. The encoder shall have at least one audio output port and at least one data output port. (4) Calibration. EAS... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  20. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION... assistance from professional experts and other HUD staff as needed. Additional information may also be...

  1. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION... assistance from professional experts and other HUD staff as needed. Additional information may also be...

  2. The Association of Low Parental Monitoring With Early Substance Use in European American and African American Adolescent Girls

    PubMed Central

    Blustein, Erica C.; Munn-Chernoff, Melissa A.; Grant, Julia D.; Sartor, Carolyn E.; Waldron, Mary; Bucholz, Kathleen K.; Madden, Pamela A. F.; Heath, Andrew C.

    2015-01-01

    Objective: Research indicates that low parental monitoring increases the risk for early substance use. Because low parental monitoring tends to co-occur with other familial and neighborhood factors, the specificity of the association is challenging to establish. Using logistic regression and propensity score analyses, we examined associations between low parental monitoring and early substance use in European American (EA) and African American (AA) girls, controlling for risk factors associated with low parental monitoring. Method: Participants were 3,133 EA and 523 AA girls from the Missouri Adolescent Female Twin Study with data on parental monitoring assessed via self-report questionnaire, and with ages at first use of alcohol, tobacco, and cannabis queried in at least one of three diagnostic interviews (median ages = 15, 22, and 24 years). Results: The rate of early alcohol use was greater in EA than AA girls, whereas the proportion of AA girls reporting low parental monitoring was higher than in EA girls. EA girls who experienced low parental monitoring were at elevated risk for early alcohol, tobacco, and cannabis use, findings supported in both logistic regression and propensity score analyses. Evidence regarding associations between low parental monitoring and risk for early substance use was less definitive forAA girls. Conclusions: Findings highlight the role of parental monitoring in modifying risk for early substance use in EA girls. However, we know little regarding the unique effects, if any, of low parental monitoring on the timing of first substance use in AA girls. PMID:26562593

  3. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...: (1) Inputs. Decoders must have the capability to receive at least two audio inputs from EAS... externally, at least two minutes of audio or text messages. A decoder manufactured without an internal means to record and store audio or text must be equipped with a means (such as an audio or digital jack...

  4. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...: (1) Inputs. Decoders must have the capability to receive at least two audio inputs from EAS... externally, at least two minutes of audio or text messages. A decoder manufactured without an internal means to record and store audio or text must be equipped with a means (such as an audio or digital jack...

  5. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...: (1) Inputs. Decoders must have the capability to receive at least two audio inputs from EAS... externally, at least two minutes of audio or text messages. A decoder manufactured without an internal means to record and store audio or text must be equipped with a means (such as an audio or digital jack...

  6. Characterization of a new ViI-like Erwinia amylovora bacteriophage phiEa2809.

    PubMed

    Lagonenko, Alexander L; Sadovskaya, Olga; Valentovich, Leonid N; Evtushenkov, Anatoly N

    2015-04-01

    Erwinia amylovora is a Gram-negative plant pathogenic bacteria causing fire blight disease in many Rosaceae species. A novel E. amylovora bacteriophage, phiEa2809, was isolated from symptomless apple leaf sample collected in Belarus. This phage was also able to infect Pantoea agglomerans strains. The genome of phiEa2809 is a double-stranded linear DNA 162,160 bp in length, including 145 ORFs and one tRNA gene. The phiEa2809 genomic sequence is similar to the genomes of the Serratia plymutica phage MAM1, Shigella phage AG-3, Dickeya phage vB DsoM LIMEstone1 and Salmonella phage ViI and lacks similarity to described E. amylovora phage genomes. Based on virion morphology (an icosahedral head, long contractile tail) and genome structure, phiEa2809 was classified as a member of Myoviridae, ViI-like bacteriophages group. PhiEa2809 is the firstly characterized ViI-like bacteriophage able to lyse E. amylovora. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. 47 CFR 90.767 - Construction and implementation of EA and Regional licenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Regional licenses. 90.767 Section 90.767 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... Use of Frequencies in the 220-222 MHz Band Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.767 Construction and implementation of EA and Regional licenses. (a...

  8. Analysing the Effect of Demand Uncertainty in Dynamic Pricing with EAs

    NASA Astrophysics Data System (ADS)

    Shakya, Siddhartha; Oliveira, Fernando; Owusu, Gilbert

    Dynamic pricing is a pricing strategy where a firm adjust the price for their products and services as a function of its perceived demand at different times. In this paper, we show how Evolutionary algorithms (EA) can be used to analyse the effect of demand uncertainty in dynamic pricing. The experiments are conducted in a range of dynamic pricing problems considering a number of different stochastic scenarios with a number of different EAs. The results are analysed, which suggest that higher demand fluctuation may not have adverse effect to the profit in comparison to the lower demand fluctuation, and that the reliability of EA for finding accurate policy could be higher when there is higher fluctuation then when there is lower fluctuation.

  9. 47 CFR 90.767 - Construction and implementation of EA and Regional licenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) An EA or Regional licensee must construct a sufficient number of base stations (i.e., base stations... all of their base stations or fixed stations. [69 FR 75172, Dec. 15, 2004] ... constructed stations. (d) EA and Regional licensees will not be permitted to count the resale of the services...

  10. Vaccination and the TAP-independent antigen processing pathways.

    PubMed

    López, Daniel; Lorente, Elena; Barriga, Alejandro; Johnstone, Carolina; Mir, Carmen

    2013-09-01

    The cytotoxic CD8(+) T lymphocyte-mediated cellular response is important for the elimination of virus-infected cells and requires the prior recognition of short viral peptide antigens previously translocated to the endoplasmic reticulum by the transporter associated with antigen processing (TAP). However, individuals with nonfunctional TAP complexes or infected cells with TAP molecules blocked by specific viral proteins, such as the cowpoxvirus, a component of the first source of early empirical vaccination against smallpox, are still able to present several HLA class I ligands generated by the TAP-independent antigen processing pathways to specific cytotoxic CD8(+) T lymphocytes. Currently, bioterrorism and emerging infectious diseases have renewed interest in poxviruses. Recent works that have identified HLA class I ligands and epitopes in virus-infected TAP-deficient cells have implications for the study of both the effectiveness of early empirical vaccination and the analysis of HLA class I antigen processing in TAP-deficient subjects.

  11. Productive infection of Epstein-Barr virus (EBV) in EBV-genome-positive epithelial cell lines (GT38 and GT39) derived from gastric tissues.

    PubMed

    Takasaka, N; Tajima, M; Okinaga, K; Satoh, Y; Hoshikawa, Y; Katsumoto, T; Kurata, T; Sairenji, T

    1998-08-01

    We characterized the expression of Epstein-Barr virus (EBV) on two epithelial cell lines, GT38 and GT39, derived from human gastric tissues. The EBV nuclear antigen (EBNA) was detected in all cells of both cell lines. The EBV immediate-early BZLF 1 protein (ZEBRA), the early antigen diffuse component (EA-D), and one of the EBV envelope proteins (gp350/220) were expressed spontaneously in small proportions in the cells. EBNA 1, EBNA2, latent membrane protein 1, ZEBRA, and EA-D molecules were then observed by Western blotting in the cells. The lytic cycle was enhanced with treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or n-butyrate. The virus particles were observed in the TPA treated GT38 cells by electron microscopy. Infectious EBV was detected with the transformation of cord blood lymphocytes and also with the induction of early antigen to Raji cells by the supernatants of both cells lines. A major single and minor multiple fused terminal fragments and a ladder of smaller fragments of the EBV genome were detected with a Xhol probe in both cell lines. These epithelial cells lines and viruses will be useful in studying their association with EBV in gastric epithelial cells.

  12. Transformation of lymphocytes by Herpesvirus papio.

    PubMed

    Falk, L A; Henle, G; Henle, W; Deinhardt, F; Schudel, A

    1977-08-15

    Cotton-topped (CT) or white-lipped (WL) marmoset lymphocytes were transformed in vitro with herpesvirus papio (HVP) into permanently growing lymphoblastoid cell lines (LCL). Five of 9 HVP-transformed CT cell lines contained cells with antigens reacting with antibodies to Epstein-Barr virus (EBV) capsid antigen (VCA) and/or to EBV-induced early antigens (EA). None of 12 WL LCL revealed such antigen-producing cells. Cells from both groups of cultures failed to react with antibodies to the EBV-specified nuclear antigen (EBNA). Exposure of baboon circulating lymphocytes to X-irradiated HVP or EBV-carring cells, or to suspensions of EBV resulted in establishment of LCL which all contained VCA and/or EA-positive, but no EBNA-positive cells. Nuclear antigens were undetectable also with anti-VCA-positive sera from baboons, chimpanzees, or other non-human primates. DNA-complementary RNA (cRNA) filter hybridization with EBV cRNA showed that with one exception transformed CT or WL marmoset cells contained at least 1-2 virus genome equivalents per cell, while at least 12-25 virus genome equivalents per cell were detected in transformed baboon cells. These data need confirmation by DNA-DNA reassociation kinetics.

  13. 47 CFR 90.767 - Construction and implementation of EA and Regional licenses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) An EA or Regional licensee must construct a sufficient number of base stations (i.e., base stations for land mobile and/or paging operations) to provide coverage to at least one-third of the population... the population of its EA or REAG within ten years of the issuance of its initial license. Licensees...

  14. 47 CFR 90.767 - Construction and implementation of EA and Regional licenses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) An EA or Regional licensee must construct a sufficient number of base stations (i.e., base stations for land mobile and/or paging operations) to provide coverage to at least one-third of the population... the population of its EA or REAG within ten years of the issuance of its initial license. Licensees...

  15. 47 CFR 90.767 - Construction and implementation of EA and Regional licenses.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) An EA or Regional licensee must construct a sufficient number of base stations (i.e., base stations for land mobile and/or paging operations) to provide coverage to at least one-third of the population... the population of its EA or REAG within ten years of the issuance of its initial license. Licensees...

  16. TRANSPORT PROPERTY MEASUREMENTS OF HFC-236EA

    EPA Science Inventory

    The report gives results of an evaluation of transport properties of 1,1,1,2,3,3,-hexafluoropropane (HFC-236ea), with liquid viscosity and thermal conductivity being the two main transport properties of interest. In addition, the specific heat and density of refrigerant/lubrican...

  17. 47 CFR 90.904 - Aggregation of EA licenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Service § 90.904 Aggregation of EA licenses. The Commission will license each Spectrum Block A through V in the 800 MHz band separately. Applicants may aggregate across spectrum blocks within the...

  18. 47 CFR 90.904 - Aggregation of EA licenses.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Service § 90.904 Aggregation of EA licenses. The Commission will license each Spectrum Block A through V in the 800 MHz band separately. Applicants may aggregate across spectrum blocks within the...

  19. 47 CFR 90.904 - Aggregation of EA licenses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Service § 90.904 Aggregation of EA licenses. The Commission will license each Spectrum Block A through V in the 800 MHz band separately. Applicants may aggregate across spectrum blocks within the...

  20. 47 CFR 90.904 - Aggregation of EA licenses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Service § 90.904 Aggregation of EA licenses. The Commission will license each Spectrum Block A through V in the 800 MHz band separately. Applicants may aggregate across spectrum blocks within the...

  1. 47 CFR 90.904 - Aggregation of EA licenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Service § 90.904 Aggregation of EA licenses. The Commission will license each Spectrum Block A through V in the 800 MHz band separately. Applicants may aggregate across spectrum blocks within the...

  2. Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans

    PubMed Central

    Tang, Weihong; Cushman, Mary; Green, David; Rich, Stephen S.; Lange, Leslie A.; Yang, Qiong; Tracy, Russell P.; Tofler, Geoffrey H.; Basu, Saonli; Wilson, James G.; Keating, Brendan J.; Weng, Lu-Chen; Taylor, Herman A.; Jacobs, David R.; Delaney, Joseph A.; Palmer, Cameron D.; Young, Taylor; Pankow, James S.; O'Donnell, Christopher J.; Smith, Nicholas L.; Reiner, Alexander P.; Folsom, Aaron R.

    2016-01-01

    Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 × 10−7 in EAs and P=3.88 × 10−3 in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 × 10−9 in EAs and P=2.98 × 10−2 in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 × 10−10), with VWF rs1800380 in AAs (P=5.62 × 10−11), and with MAT1A rs2236568 in AAs (P=1.69 × 10−6). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs. PMID:25779970

  3. Crystal Structure and Functional Characterization of an Esterase (EaEST) from Exiguobacterium antarcticum.

    PubMed

    Lee, Chang Woo; Kwon, Sena; Park, Sun-Ha; Kim, Boo-Young; Yoo, Wanki; Ryu, Bum Han; Kim, Han-Woo; Shin, Seung Chul; Kim, Sunghwan; Park, Hyun; Kim, T Doohun; Lee, Jun Hyuck

    2017-01-01

    A novel microbial esterase, EaEST, from a psychrophilic bacterium Exiguobacterium antarcticum B7, was identified and characterized. To our knowledge, this is the first report describing structural analysis and biochemical characterization of an esterase isolated from the genus Exiguobacterium. Crystal structure of EaEST, determined at a resolution of 1.9 Å, showed that the enzyme has a canonical α/β hydrolase fold with an α-helical cap domain and a catalytic triad consisting of Ser96, Asp220, and His248. Interestingly, the active site of the structure of EaEST is occupied by a peracetate molecule, which is the product of perhydrolysis of acetate. This result suggests that EaEST may have perhydrolase activity. The activity assay showed that EaEST has significant perhydrolase and esterase activity with respect to short-chain p-nitrophenyl esters (≤C8), naphthyl derivatives, phenyl acetate, and glyceryl tributyrate. However, the S96A single mutant had low esterase and perhydrolase activity. Moreover, the L27A mutant showed low levels of protein expression and solubility as well as preference for different substrates. On conducting an enantioselectivity analysis using R- and S-methyl-3-hydroxy-2-methylpropionate, a preference for R-enantiomers was observed. Surprisingly, immobilized EaEST was found to not only retain 200% of its initial activity after incubation for 1 h at 80°C, but also retained more than 60% of its initial activity after 20 cycles of reutilization. This research will serve as basis for future engineering of this esterase for biotechnological and industrial applications.

  4. 47 CFR 73.4097 - EBS (now EAS) attention signals on automated programing systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false EBS (now EAS) attention signals on automated programing systems. 73.4097 Section 73.4097 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... (now EAS) attention signals on automated programing systems. See Public Notice dated March 1, 1979. 72...

  5. Reliability and validity of the Euthanasia Attitude Scale (EAS) for Hong Kong medical doctors.

    PubMed

    Tang, Wai-Kiu; Mak, Kwok-Kei; Kam, Philip Ming-Ho; Ho, Joanna Wing-Kiu; Chan, Denise Che-Ying; Suen, To-Lam; Lau, Michael Chak-Kwan; Cheng, Adrian Ka-Chun; Wan, Yuen-Ting; Wan, Ho-Yan; Hussain, Assad

    2010-08-01

    This study aimed to examine the reliability and validity of the Euthanasia Attitude Scale (EAS) in Hong Kong medical doctors. A total of 107 medical doctors (61.7% men) participated in a survey at clinical settings in 2008. The 21-item EAS was used to assess their attitudes toward euthanasia. The mean (standard deviation) and median of the EAS were 63.60 (60.31) and 63.00. Total EAS scores correlated well with ''Ethical Considerations,'' ''Practical Considerations,'' and ''Treasuring Life'' (Spearman rho =.37-.96, P < .001) but not ''Naturalistic Beliefs.'' The construct validity of the 3-factor model was appropriate (Kaiser-Meyer-Olkin [KMO] value = 0.90) and showed high internal consistency (Cronbach alpha =.79-.92). Euthanasia Attitude Scale may be a reliable and valid measure for assessing the attitudes toward euthanasia in medical professionals.

  6. Mucosal Vaccination with Heterologous Viral Vectored Vaccine Targeting Subdominant SIV Accessory Antigens Strongly Inhibits Early Viral Replication.

    PubMed

    Xu, Huanbin; Andersson, Anne-Marie; Ragonnaud, Emeline; Boilesen, Ditte; Tolver, Anders; Jensen, Benjamin Anderschou Holbech; Blanchard, James L; Nicosia, Alfredo; Folgori, Antonella; Colloca, Stefano; Cortese, Riccardo; Thomsen, Allan Randrup; Christensen, Jan Pravsgaard; Veazey, Ronald S; Holst, Peter Johannes

    2017-04-01

    Conventional HIV T cell vaccine strategies have not been successful in containing acute peak viremia, nor in providing long-term control. We immunized rhesus macaques intramuscularly and rectally using a heterologous adenovirus vectored SIV vaccine regimen encoding normally weakly immunogenic tat, vif, rev and vpr antigens fused to the MHC class II associated invariant chain. Immunizations induced broad T cell responses in all vaccinees. Following up to 10 repeated low-dose intrarectal challenges, vaccinees suppressed early viral replication (P=0.01) and prevented the peak viremia in 5/6 animals. Despite consistently undetectable viremia in 2 out of 6 vaccinees, all animals showed evidence of infection induced immune responses indicating that infection had taken place. Vaccinees, with and without detectable viremia better preserved their rectal CD4+ T cell population and had reduced immune hyperactivation as measured by naïve T cell depletion, Ki-67 and PD-1 expression on T cells. These results indicate that vaccination towards SIV accessory antigens vaccine can provide a level of acute control of SIV replication with a suggestion of beneficial immunological consequences in infected animals of unknown long-term significance. In conclusion, our studies demonstrate that a vaccine encoding subdominant antigens not normally associated with virus control can exert a significant impact on acute peak viremia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Seroprevalence of human herpes simplex, hepatitis B and epstein-barr viruses in children with acute lymphoblastic leukemia in southern iran.

    PubMed

    Mahjour, Seyed Babak; Ghaffarpasand, Fariborz; Fattahi, Mohammad Javad; Ghaderi, Abbas; Fotouhi Ghiam, Alireza; Karimi, Mehran

    2010-12-01

    To investigate the seroprevalence of Herpes Simplex Viruses (HSV1 and HSV2), Ebstein-Barr Virus (EBV) and Hepatitis B Virus (HBV) in children with acute lymphoblastic leukemia (ALL) in southern Iran. 90 patients with ALL and 90 age-sex matched healthy participants were enrolled in this study. Antibodies (IgG) against HBsAg, HSV1, HSV2, EBV different antigens including Epstein-Barr nuclear antigen-1 (EBNA-1), viral capsid antigen (VCA) and early antigen (EA) were measured by enzyme-linked immunosorbent assay (ELISA). There were 54 (60%) male and 36 (40%) female in both study groups with mean age of 8.47 ± 3.61 and 8.61 ± 2.84 years in case and control group respectively (P = 0.812). The prevalence of antibodies against HBsAg (P = 0.002), HSV1 (P < 0.0001), VCA (P = 0.021) and EA (P < 0.0001) antigens of EBV were significantly higher in ALL patients. With the results of this study, we could not exclude a connection between these viral infections and later leukemogenesis in childhood ALL, although nor latent infection nor congenital infection cannot be excluded by this method.

  8. Isolation and characterization of new lignin streams derived from extractive-ammonia (EA) pretreatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    da Costa Sousa, Leonardo; Foston, Marcus; Bokade, Vijay

    One of the key challenges facing lignin conversion to fuels and chemicals is related to the level of carbohydrate and ash impurities found in extracted lignin. Structural modifications of lignin may also occur as a result of biomass pretreatment and harsh lignin extraction protocols. Extractive-Ammonia (EA) is a new pretreatment technology that uses liquid ammonia to cleave lignin–carbohydrate complexes, decrystallize cellulose, solubilize lignin, and selectively extract lignin from lignocellulosic biomass, enabling better utilization of both lignin and carbohydrate components in a biorefinery. The EA-based biorefinery produces two different lignin-rich streams, with different properties, that could potentially be upgraded to fuelsmore » and chemicals using green processes. Here, a water/ethanol-based fractionation method was developed to enrich the ammonia-soluble extractives, resulting in a major product stream containing 92% lignin. Detailed characterization of the various streams resulting from EA treatment, including compositional analysis, structural characterization by nuclear magnetic resonance (NMR) spectrometry, elemental analysis, molecular weight analysis, and thermo-gravimetric analysis provides a broad evaluation of the EA-derived lignin product stream structures and properties, assessing their potential for commercial applications. In conclusion, EA-derived lignins preserve much of lignin's functionality, including the sensitive β-aryl ether units. Furthermore, we observed nitrogen incorporation in the lignin-rich streams, notably due to the presence of hydroxycinnamoyl amides formed during ammonia pretreatment.« less

  9. The Stellar Kinematics of E+A Galaxies in SDSS IV-MaNGA

    NASA Astrophysics Data System (ADS)

    Johnson, Amalya; Dudley, Raymond; Edwards, Kay; Gonzalez, Andrea; Kerrison, Nicole; Marinelli, Mariarosa; Melchert, Nancy; Ojanen, Winonah; Liu, Charles; SDSS-IV MaNGA

    2018-01-01

    E+A galaxies, hypothesized to be “transition” galaxies between the blue cloud and the red sequence, are valuable sources for studying the evolution of galaxies. Using data from the Sloan Digital Sky Survey Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, a large scale integral field spectroscopic survey of nearby galaxies from 3600 to 10300 Å, we identifed galaxies that exhibitted E+A characteristics within their optical spectra. We analyzed the 2,812 galaxies thus far observed by MaNGA to identify those that showed evidence of a starburst about 1 billion years ago, followed by cessation of star formation and quenching of the galaxy. Through this process we identifed 39 E+A galaxies by directly looking at the optical spectra and ensuring they exhibited the necessary properties of an E+A spectra, including a strong break at the 4000 Å mark, little to no Hα emission and absorption through the Balmer series, and a blue slope of the continuum past ~5000 Å as the flux decreases. We analyzed the stellar kinematics of these galaxies to determine whether or not they were fast or slow rotators, a proposed indicator of a major merger in their recent past. Using Voronoi binned graphs from the MaNGA Marvin database, we measured their stellar rotation curves in order to more clearly show the range of velocities within the galaxies. Among our 39 E+A candidates, all but two exhibited significant, orderly rotation across the galaxy, and 29 out of 39 of our galaxies show rotation faster than 30 km/s. With the caveat that our selection process was biased toward galaxies with orderly rotation, this prevalence of rotation challenges the belief that all E+A galaxies are created from major mergers. This work was supported by grants AST-1460860 from the National Science Foundation and SDSS FAST/SSP-483 from the Alfred P. Sloan Foundation to the CUNY College of Staten Island.

  10. Comparison of three different serological techniques for primary diagnosis and monitoring of nasopharyngeal carcinoma in two age groups from Tunisia.

    PubMed

    Karray, H; Ayadi, W; Fki, L; Hammami, A; Daoud, J; Drira, M M; Frikha, M; Jlidi, R; Middeldorp, J M

    2005-04-01

    Nasopharyngeal carcinoma (NPC) in Tunisia is characterized by its bimodal age distribution involving juvenile patients of 10-24 years and adult patients of 40-60 years. Three serological techniques were compared for primary diagnosis (N = 117) and post-treatment monitoring (N = 21) of NPC patients separated in two age groups. Immunofluorescence assay (IFA) was used as the "gold standard" for detection of IgG and IgA antibodies reactive with Epstein-Barr virus (EBV) early (EA) and viral capsid (VCA) antigens. Results were compared with ELISA measuring IgG and IgA antibody reactivity to defined EBNA1, EA, and VCA antigens. Immunoblot was used to reveal the molecular diversity underlying the anti-EBV IgG and IgA antibody responses. The results indicate that young NPC patients have significantly more restricted anti-EBV IgG and IgA antibody responses with aberrant IgG VCA/EA levels in 78% compared to 91.7% in elder patients. IgA VCA/EA was detected in 50% of young patients versus 89.4% for the elder group (P < 0.001). Immunoblot revealed a reduced overall diversity of EBV antigen recognition for both IgG and IgA in young patients. A good concordance was observed between ELISA and IFA for primary NPC diagnosis with 81-91% overall agreement. Even better agreement (95-100%) was found for antibody changes during follow-up monitoring, showing declining reactivity in patients in remission and increasing reactivity in patients with persistent disease or relapse. ELISA for IgA anti-VCA-p18 and immunoblot proved most sensitive for predicting tumor relapse. VCA-p18 IgA ELISA seems suitable for routine diagnosis and early detection of NPC complication. (c) 2005 Wiley-Liss, Inc.

  11. Comparison of nonstructural protein-1 antigen detection by rapid and enzyme-linked immunosorbent assay test and its correlation with polymerase chain reaction for early diagnosis of dengue

    PubMed Central

    Gaikwad, Seema; Sawant, Sandhya S.; Shastri, Jayanthi S.

    2017-01-01

    INTRODUCTION: Early diagnosis of dengue is important for appropriate clinical management and vector control. Different serological tests based on the principle of immunochromatography and enzyme-linked immunosorbent assay (ELISA) are commonly used for detection of antigen and antibodies of dengue virus. The performance of these tests depends on the sensitivity and specificity. Hence, the study was undertaken to compare nonstructural protein-1 (NS1) antigen detection by rapid and ELISA with real-time polymerase chain reaction (RT-PCR) for diagnosis of dengue. MATERIALS AND METHODS: Prospective laboratory study was carried out on sera samples (n = 200) from clinically suspected cases of dengue. The sera samples were subjected for NS1 antigen detection test by rapid test, NS1 ELISA, and RT-PCR. The results of rapid and ELISA tests were compared with real Time PCR. RESULTS: The sensitivity, specificity, positive, and negative predictive value of rapid dengue NS1 antigen test were 81.5%, 66.7%, 78.2%, and 71.1%, respectively whereas that of NS1 ELISA were 89.9%, 100%, 100%, and 94%, respectively. Concordance of Rapid NS1 and NS1 ELISA with PCR was 75.5% and 94%. DISCUSSION AND CONCLUSION: NS1 antigen ELISA can be implemented in diagnostic laboratories for diagnosis of dengue in the acute phase of illness. The test also has great potential value for use in epidemic situations, as it could facilitate the early screening of patients and limit disease expansion. PMID:28706387

  12. Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

    PubMed

    Iwase, Y; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H; Kawaii, S; Yano, M; Mou, X Y; Takayasu, J; Tokuda, H; Nishino, H

    2000-06-01

    To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

  13. Probing the evolution of the EAS muon content in the atmosphere with KASCADE-Grande

    NASA Astrophysics Data System (ADS)

    Apel, W. D.; Arteaga-Velázquez, J. C.; Bekk, K.; Bertaina, M.; Blümer, J.; Bozdog, H.; Brancus, I. M.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Daumiller, K.; de Souza, V.; Di Pierro, F.; Doll, P.; Engel, R.; Fuhrmann, D.; Gherghel-Lascu, A.; Gils, H. J.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Huege, T.; Kampert, K.-H.; Kang, D.; Klages, H. O.; Link, K.; Łuczak, P.; Mathes, H. J.; Mayer, H. J.; Milke, J.; Mitrica, B.; Morello, C.; Oehlschläger, J.; Ostapchenko, S.; Pierog, T.; Rebel, H.; Roth, M.; Schieler, H.; Schoo, S.; Schröder, F. G.; Sima, O.; Toma, G.; Trinchero, G. C.; Ulrich, H.; Weindl, A.; Wochele, J.; Zabierowski, J.

    2017-10-01

    The evolution of the muon content of very high energy air showers (EAS) in the atmosphere is investigated with data of the KASCADE-Grande observatory. For this purpose, the muon attenuation length in the atmosphere is obtained to Λμ = 1256 ± 85-232+229 (syst) g/cm2 from the experimental data for shower energies between 1016.3 and 1017.0 eV. Comparison of this quantity with predictions of the high-energy hadronic interaction models QGSJET-II-02, SIBYLL 2.1, QGSJET-II-04 and EPOS-LHC reveals that the attenuation of the muon content of measured EAS in the atmosphere is lower than predicted. Deviations are, however, less significant with the post-LHC models. The presence of such deviations seems to be related to a difference between the simulated and the measured zenith angle evolutions of the lateral muon density distributions of EAS, which also causes a discrepancy between the measured absorption lengths of the density of shower muons and the predicted ones at large distances from the EAS core. The studied deficiencies show that all four considered hadronic interaction models fail to describe consistently the zenith angle evolution of the muon content of EAS in the aforesaid energy regime.

  14. Spectrophotometric Properties of E+A Galaxies in SDSS-IV MaNGA

    NASA Astrophysics Data System (ADS)

    Marinelli, Mariarosa; Dudley, Raymond; Edwards, Kay; Gonzalez, Andrea; Johnson, Amalya; Kerrison, Nicole; Melchert, Nancy; Ojanen, Winonah; Weaver, Olivia; Liu, Charles; SDSS-IV MaNGA

    2018-01-01

    Quenched post-starburst galaxies, or E+A galaxies, represent a unique and informative phase in the evolution of galaxies. We used a qualitative rubric-based methodology, informed by the literature, to manually select galaxies from the SDSS-IV IFU survey Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) using the single-fiber spectra from the Sloan Digital Sky Survey Data Release 8. Of the 2,812 galaxies observed so far in MaNGA, we found 39 galaxies meeting our criteria for E+A classification. Spectral energy distributions of these 39 galaxies from the far-UV to the mid-infrared demonstrate a heterogeneity in our sample emerging in the infrared, indicating many distinct paths to visually similar optical spectra. We used SDSS-IV MaNGA Pipe3D data products to analyze stellar population ages, and found that 34 galaxies exhibited stellar populations that were older at 1 effective radius than at the center of the galaxy. Given that our sample was manually chosen based on E+A markers in the single-fiber spectra aimed at the center of each galaxy, our E+A galaxies may have only experienced their significant starbursts in the central region, with a disk of quenched or quenching material further outward. This work was supported by grants AST-1460860 from the National Science Foundation and SDSS FAST/SSP-483 from the Alfred P. Sloan Foundation to the CUNY College of Staten Island.

  15. 47 CFR 1.1308 - Consideration of environmental assessments (EAs); findings of no significant impact.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 1969 § 1.1308 Consideration of environmental assessments (EAs); findings of no significant impact. (a) Applicants shall prepare EAs for actions that may have a significant environmental impact (see § 1.1307). An...), that the proposal will have a significant environmental impact upon the quality of the human...

  16. ComEA Is Essential for the Transfer of External DNA into the Periplasm in Naturally Transformable Vibrio cholerae Cells

    PubMed Central

    Seitz, Patrick; Pezeshgi Modarres, Hassan; Borgeaud, Sandrine; Bulushev, Roman D.; Steinbock, Lorenz J.; Radenovic, Aleksandra; Dal Peraro, Matteo; Blokesch, Melanie

    2014-01-01

    The DNA uptake of naturally competent bacteria has been attributed to the action of DNA uptake machineries resembling type IV pilus complexes. However, the protein(s) for pulling the DNA across the outer membrane of Gram-negative bacteria remain speculative. Here we show that the competence protein ComEA binds incoming DNA in the periplasm of naturally competent Vibrio cholerae cells thereby promoting DNA uptake, possibly through ratcheting and entropic forces associated with ComEA binding. Using comparative modeling and molecular simulations, we projected the 3D structure and DNA-binding site of ComEA. These in silico predictions, combined with in vivo and in vitro validations of wild-type and site-directed modified variants of ComEA, suggested that ComEA is not solely a DNA receptor protein but plays a direct role in the DNA uptake process. Furthermore, we uncovered that ComEA homologs of other bacteria (both Gram-positive and Gram-negative) efficiently compensated for the absence of ComEA in V. cholerae, suggesting that the contribution of ComEA in the DNA uptake process might be conserved among naturally competent bacteria. PMID:24391524

  17. Prognostic value of serum Epstein-Barr virus antibodies in patients with nasopharyngeal carcinoma and undetectable pretreatment Epstein-Barr virus DNA.

    PubMed

    Yao, Ji-Jin; Lin, Li; Jin, Ya-Nan; Wang, Si-Yang; Zhang, Wang-Jian; Zhang, Fan; Zhou, Guan-Qun; Cheng, Zhi-Bin; Qi, Zhen-Yu; Sun, Ying

    2017-08-01

    Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC). Serum IgA antibodies against early antigen (EA-IgA) and viral capsid antigen (VCA-IgA) are the most commonly used to screen for NPC in endemic areas. However, the prognostic value of serum EA-IgA and VCA-IgA in patients with NPC is less clear. We hypothesize that serum EA-IgA and VCA-IgA levels have prognostic impact for survival outcomes in NPC patients with undetectable pretreatment EBV (pEBV) DNA. In this series, 334 patients with non-metastatic NPC and undetectable pEBV DNA were included. Serum EA-IgA and VCA-IgA were determined by ELISA. After analysis, serum EA-IgA and VCA-IgA loads correlated positively with T, N, and overall stage (all P < 0.05). Serum EA-IgA was not associated with survival outcome in univariable analyses. But patients with serum VCA-IgA >1:120 had significantly inferior 5-year progression-free survival (80.4% vs 89.6%, P = 0.025), distant metastasis-free survival (88.4% vs 94.8%, P = 0.050), and locoregional relapse-free survival (88.4% vs 95.6%, P = 0.023; log-rank test). Multivariable analyses revealed that N stage was the only independent prognostic factor (all P < 0.05), but the VCA-IgA became insignificant. Further analyses revealed that serum VCA-IgA was not an independent prognostic factor in early N (N0-1) or advanced N (N2-3) stage NPC. In summary, although both EA-IgA and VCA-IgA correlate strongly with TNM stage, our analyses do not suggest that these antibodies are prognostic biomarkers in patients with NPC and undetectable pEBV DNA. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. A novel plasmid pEA68 of Erwinia amylovora and the description of a new family of plasmids.

    PubMed

    Ismail, Emadeldeen; Blom, Jochen; Bultreys, Alain; Ivanović, Milan; Obradović, Aleksa; van Doorn, Joop; Bergsma-Vlami, Maria; Maes, Martine; Willems, Anne; Duffy, Brion; Stockwell, Virginia O; Smits, Theo H M; Puławska, Joanna

    2014-12-01

    Recent genome analysis of Erwinia amylovora, the causal agent of fire blight disease on Rosaceae, has shown that the chromosome is highly conserved among strains and that plasmids are the principal source of genomic diversity. A new circular plasmid, pEA68, was found in E. amylovora strain 692 (LMG 28361), isolated in Poland from Sorbus (mountain ash) with fire blight symptoms. Annotation of the 68,763-bp IncFIIa-type plasmid revealed that it contains 79 predicted CDS, among which two operons (tra, pil) are associated with mobility. The plasmid is maintained stably in E. amylovora and does not possess genes associated with antibiotic resistance or known virulence genes. Curing E. amylovora strain 692 of pEA68 did not influence its virulence in apple shoots nor amylovoran synthesis. Of 488 strains of E. amylovora from seventeen countries, pEA68 was only found in two additional strains from Belgium. Although the spread of pEA68 is currently limited to Europe, pEA68 comprises, together with pEA72 and pEA78 both found in North America, a new plasmid family that spans two continents.

  19. Corticosteroid therapy in Epstein-Barr virus infection. Effect on lymphocyte class, subset, and response to early antigen.

    PubMed

    Brandfonbrener, A; Epstein, A; Wu, S; Phair, J

    1986-02-01

    Corticosteroid treatment of impending upper airway obstruction due to Epstein-Barr virus (EBV) infectious mononucleosis did not alter the pattern of lymphocyte changes induced by this viral infection during the first two weeks following administration of prednisone. By 12 weeks, 11 treated students had significantly fewer lymphocytes, including B, total T, helper, and T-suppressor cell numbers, than 11 untreated EBV-infected students, and values were closer to those noted in uninfected controls. Corticosteroid therapy did not alter the serologic response to early antigens of EBV. Fever and lymphadenopathy resolved somewhat more quickly in treated students.

  20. Independent prognostic impact of preoperative serum carcinoembryonic antigen and cancer antigen 15-3 levels for early breast cancer subtypes.

    PubMed

    Imamura, Michiko; Morimoto, Takashi; Nomura, Takashi; Michishita, Shintaro; Nishimukai, Arisa; Higuchi, Tomoko; Fujimoto, Yukie; Miyagawa, Yoshimasa; Kira, Ayako; Murase, Keiko; Araki, Kazuhiro; Takatsuka, Yuichi; Oh, Koshi; Masai, Yoshikazu; Akazawa, Kouhei; Miyoshi, Yasuo

    2018-02-12

    Although the prognosis for operable breast cancers is reportedly worse if serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) levels are above normal, the usefulness of this prognosis is limited due to the low sensitivity and specificity; in addition, the optimal cutoff levels remain unknown. A total of 1076 patients who were operated for breast cancers (test set = 608, validation set = 468) without evidence of metastasis were recruited, and their baseline and postoperative serum CEA and CA15-3 levels were analyzed. The optimal cutoff values of CEA and CA15-3 for disease-free survival (DFS) were 3.2 ng/mL and 13.3 U/mL, respectively, based on receiver operating characteristic curve and area under the curve analyses. The DFS of patients with high CEA levels (CEA-high: n = 191, 5-year DFS 70.6%) was significantly worse (p < 0.0001) than that of CEA-low patients (n = 885, 5-year DFS 87.2%). There was a significant difference in DFS (p < 0.0001) between CA15-3-high and CA15-3-low patients (n = 314 and n = 762, respectively; 5-year DFS 71.8 vs. 89.3%). Significant associations between DFS and CA15-3 levels were observed irrespective of the subtypes. Multivariable analysis indicated that tumor size, lymph node metastasis, tumor grade, and CEA (p = 0.0474) and CA15-3 (p < 0.0001) levels were independent prognostic factors (hazard ratio [HR] 1.520, 95% confidence interval [CI] 1.005-2.245 for CEA; HR 2.088, 95% CI 1.457-2.901 for CA15-3). These findings suggest that CEA and CA15-3 levels might be useful for predicting the prognosis of patients with operable early breast cancer irrespective of the subtype. Serum levels at baseline may reflect tumor characteristics for metastatic potential even when these levels are within the normal ranges.

  1. MISCIBILITY, SOLUBILITY, VISCOSITY, AND DENSITY MEASUREMENTS FOR R-236EA WITH FOUR DIFFERENT EXXON LUBRICANTS

    EPA Science Inventory

    The report discusses miscibility, solubility, viscosity, and density data for the refrigerant hydrofluorocarbon (HFC)-236ea (or R-236ea) and four lubricants supplied by Exxon Corporation. Such data are needed to determine the suitability of refrigerant/lubricant combinations for ...

  2. Evaluation of EA-934NA with 2.5 percent Cab-O-Sil

    NASA Technical Reports Server (NTRS)

    Caldwell, Gordon A.

    1990-01-01

    Currently, Hysol adhesive EA-934NA is used to bond the Field Joint Protection System on the Shuttle rocket motors at Kennedy Space Center. However, due to processing problems, an adhesive with a higher viscosity is needed to alleviate these difficulties. One possible solution is to add Cab-O-Sil to the current adhesive. The adhesive strength and bond strengths that can be obtained when 2.5 percent Cab-O-Sil is added to adhesive EA-934NA are examined and tested over a range of test temperatures from -20 to 300 F. Tensile adhesion button and lap shear specimens were bonded to D6AC steel and uniaxial tensile specimens (testing for strength, initial tangent modulus, elongation and Poisson's ratio) were prepared using Hysol adhesive EA-934NA with 2.5 percent Cab-O-Sil added. These specimens were tested at -20, 20, 75, 100, 125, 150, 200, 250, and 300 F, respectively. Additional tensile adhesion button specimens bonding Rust-Oleum primed and painted D6AC steel to itself and to cork using adhesive EA-934NA with 2.5 percent Cab-O-Sil added were tested at 20, 75, 125, 200, and 300 F, respectively. Results generally show decreasing strength values with increasing test temperatures. The bond strengths obtained using cork as a substrate were totally dependent on the cohesive strength of the cork.

  3. 78 FR 54635 - Notice of Intent To Prepare an Environmental Impact Statement for EA-18G Growler Airfield...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    ... the potential environmental effects associated with the introduction of two additional EA-18G Growler... CONTACT: EA-18G EIS Project Manager (Code EV21/ SS); Naval Facilities Engineering Command (NAVFAC... request should be submitted to: EA-18G EIS Project Manager (Code EV21/SS); Naval Facilities Engineering...

  4. [A sporadic case of episodic ataxia with nystagmus (EA-2)].

    PubMed

    Namekawa, M; Takiyama, Y; Ueno, N; Nishizawa, M

    1998-05-01

    A 39-year-old man with episodic ataxia with nystagmus (EA-2) was reported. He showed intermittent cerebellar dysfunction, i.e., ataxia, nystagmus, dysarthria and vertigo, since he was 10 years old. Although this attack lasted for several hours, he was normal with exception of interictal nystagmus. His parents and sister showed no episodic ataxia. We ruled out the diseases, which may cause episodic ataxia, such as multiple sclerosis, vascular disorders, metabolic disorders and congenital anomalies. He was released from the attack by treatment with acetazolamide. EA-2 has been associated with mutations in the alpha 1A-voltage dependent calcium channel gene (CACNL1A4), which is also affected in familial hemiplegic migraine (FMH) and spinocerebellar ataxia type 6 (SCA6). In EA-2, frame-shift mutation leading to premature stop and splice-site mutation leading to truncated, non-functional channel protein have been reported. However, our patient did not have the mutations in the CACNL1A4 gene that were previously reported. In addition, our patient did not have an expanded CAG allele in the CACNL1A4 gene which is responsible for SCA6. Further examination is required to address whether a new mutation exists in the CACNL1A4 gene in our patient.

  5. 76 FR 54525 - Notice of Availability of a Final Environmental Assessment (Final EA) and a Finding of No...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Environmental Assessment (Final EA) and a Finding of No Significant Impact (FONSI)/Record of Decision (ROD) for... Environmental Assessment (Final EA) and Finding of No Significant Impact (FONSI)/Record of Decision (ROD) for a...)/Record of Decision (ROD) based on the Final Environmental Assessment (Final EA) for a Proposed Airport...

  6. Primary EBV infection of human umbilical cord lymphocytes and EBV genome-negative lymphoblastoid cell lines (BJAB and Ramos).

    PubMed

    Takimoto, T; Sato, H; Ogura, H

    1986-01-01

    The appearance of Epstein-Barr virus (EBV)-associated nuclear antigen (EBNA) and induction of EBV-induced early antigen (EA) in human umbilical cord blood lymphocytes (HUCLs) and two EBV genome-negative Burkitt's lymphoma (BL) lines (BJAB and Ramos) were studied by infection with EBVs prepared from three different cell lines: marmoset cell line (B95-8) derived from infections mononucleosis, BL-derived cell line (P3HR-1) and human epithelial hybrid cell line (NPC-KT) derived from nasopharyngeal carcinoma. B95-8 virus can transform HUCLs but cannot superinfect Raji cells. P3HR-1 virus can transform HUCLs cells but cannot transform HUCLs. NPC-KT virus can transform HUCLs and can superinfect Raji cells. We have examined the time sequence of EBNA appearance and EA induction in HUCLs, BJAB cells and Ramos cells, in order to determine if three different strains of EBV differ in their abilities to infect their cells. We found that all three strains of EBV can induce EBNA in HUCLs, BJAB cells and Ramos cells. On the other hand, we found that P3HR-1 virus and NPC-KT virus can induce EA in BJAB cells and Ramos cells, but B95-8 virus cannot induce EA in their cells.

  7. Porritoxins, metabolites of Alternaria porri, as anti-tumor-promoting active compounds.

    PubMed

    Horiuchi, Masayuki; Tokuda, Harukuni; Ohnishi, Keiichiro; Yamashita, Masakazu; Nishino, Hoyoku; Maoka, Takashi

    2006-02-01

    To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of metabolites of Alternaria porri by examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The ethyl acetate extract of A. porri showed the inhibitory effect on EBV-EA activation. Three porritoxins (1-3) were obtained as inhibitory active compounds for EBV-EA from ethyl acetate extract. 6-(3',3'-Dimethylallyloxy)-4-methoxy-5-methylphthalide (2) showed the strongest activity among them. Inhibitory effect of porritoxin (1) and (2) was superior to that of beta-carotene, a well-known anti-tumor promoter. Furthermore, the structure-activity correlation of porritoxins and their related compounds were discussed.

  8. Business Architecture Development at Public Administration - Insights from Government EA Method Engineering Project in Finland

    NASA Astrophysics Data System (ADS)

    Valtonen, Katariina; Leppänen, Mauri

    Governments worldwide are concerned for efficient production of services to customers. To improve quality of services and to make service production more efficient, information and communication technology (ICT) is largely exploited in public administration (PA). Succeeding in this exploitation calls for large-scale planning which embraces issues from strategic to technological level. In this planning the notion of enterprise architecture (EA) is commonly applied. One of the sub-architectures of EA is business architecture (BA). BA planning is challenging in PA due to a large number of stakeholders, a wide set of customers, and solid and hierarchical structures of organizations. To support EA planning in Finland, a project to engineer a government EA (GEA) method was launched. In this chapter, we analyze the discussions and outputs of the project workshops and reflect emerged issues on current e-government literature. We bring forth insights into and suggestions for government BA and its development.

  9. Post-Starburst Galaxies At The End of The E+A Phase

    NASA Astrophysics Data System (ADS)

    Liu, Charles; Marinelli, Mariarosa; Chang, Madeleine; Lyczko, Camilla; Vega Orozco, Cecilia; SDSS-IV Collaboration

    2018-06-01

    Post-starburst galaxies, once thought to be rare curiosities, are now recognized to represent a key phase in the galaxy evolution. The post-starburst, or E+A phase, should however not be considered as a single, short-lived phenomenon; rather, it is an extended evolutionary process that occurs a galaxy transitions from an actively star-forming system into a quiescent one. We present a study of nearby galaxies at or near the end of the E+A phase, wherein all star formation has been quenched, the fossilized stellar population of the most recent starburst is highly localized, and the remainder of the galaxy's stellar population is old and quiescent. The luminosity and stellar age distribution of these "end-phase E+As" can provide insights into the evolution of galaxies onto and within the red sequence, from active to passive systems. This work is supported by National Science Foundation grants to CUNY College of Staten Island and the American Museum of Natural History; the College of Staten Island Office of Academic Affairs; the Sherman Fairchild Science Pathways Scholars Program (SP^2) at Barnard College; and the Alfred P. Sloan Foundation.

  10. 7 CFR 4280.190 - EA/REDA grant applications-content.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.190 EA/REDA...) Applicant's experience as follows: (i) If applying for a renewable energy development assistance grant, the applicant's experience in completing similar renewable energy development assistance activities, including...

  11. 7 CFR 4280.190 - EA/REDA grant applications-content.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.190 EA/REDA...) Applicant's experience as follows: (i) If applying for a renewable energy development assistance grant, the applicant's experience in completing similar renewable energy development assistance activities, including...

  12. 7 CFR 4280.190 - EA/REDA grant applications-content.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.190 EA/REDA...) Applicant's experience as follows: (i) If applying for a renewable energy development assistance grant, the applicant's experience in completing similar renewable energy development assistance activities, including...

  13. Viral Sequestration of Antigen Subverts Cross Presentation to CD8+ T Cells

    PubMed Central

    Tewalt, Eric F.; Grant, Jean M.; Granger, Erica L.; Palmer, Douglas C.; Heuss, Neal D.; Gregerson, Dale S.; Restifo, Nicholas P.; Norbury, Christopher C.

    2009-01-01

    Virus-specific CD8+ T cells (TCD8+) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector TCD8+. Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated TCD8+ response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the TCD8+ response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation must also be taken into

  14. Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.

    PubMed Central

    Laurence, J; Friedman, S M; Chartash, E K; Crow, M K; Posnett, D N

    1989-01-01

    HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS. PMID:2470786

  15. FluBreaks: early epidemic detection from Google flu trends.

    PubMed

    Pervaiz, Fahad; Pervaiz, Mansoor; Abdur Rehman, Nabeel; Saif, Umar

    2012-10-04

    The Google Flu Trends service was launched in 2008 to track changes in the volume of online search queries related to flu-like symptoms. Over the last few years, the trend data produced by this service has shown a consistent relationship with the actual number of flu reports collected by the US Centers for Disease Control and Prevention (CDC), often identifying increases in flu cases weeks in advance of CDC records. However, contrary to popular belief, Google Flu Trends is not an early epidemic detection system. Instead, it is designed as a baseline indicator of the trend, or changes, in the number of disease cases. To evaluate whether these trends can be used as a basis for an early warning system for epidemics. We present the first detailed algorithmic analysis of how Google Flu Trends can be used as a basis for building a fully automated system for early warning of epidemics in advance of methods used by the CDC. Based on our work, we present a novel early epidemic detection system, called FluBreaks (dritte.org/flubreaks), based on Google Flu Trends data. We compared the accuracy and practicality of three types of algorithms: normal distribution algorithms, Poisson distribution algorithms, and negative binomial distribution algorithms. We explored the relative merits of these methods, and related our findings to changes in Internet penetration and population size for the regions in Google Flu Trends providing data. Across our performance metrics of percentage true-positives (RTP), percentage false-positives (RFP), percentage overlap (OT), and percentage early alarms (EA), Poisson- and negative binomial-based algorithms performed better in all except RFP. Poisson-based algorithms had average values of 99%, 28%, 71%, and 76% for RTP, RFP, OT, and EA, respectively, whereas negative binomial-based algorithms had average values of 97.8%, 17.8%, 60%, and 55% for RTP, RFP, OT, and EA, respectively. Moreover, the EA was also affected by the region's population size

  16. 32 CFR 651.33 - Actions normally requiring an EA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

  17. 32 CFR 651.33 - Actions normally requiring an EA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

  18. 32 CFR 651.33 - Actions normally requiring an EA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... normally requiring an EA during the life cycle include, but are not limited to, testing, production... will use hazardous chemicals, drugs, or biological or radioactive materials. (p) An activity that affects a federally listed threatened or endangered plant or animal species, a federal candidate species...

  19. 47 CFR 90.683 - EA-based SMR system operations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... operate base stations using any of the base station frequencies identified in their spectrum block... use of frequencies identified in their spectrum block, including the provisions of § 90.619 relating... authorization for a previously authorized co-channel station within the EA licensee's spectrum block is...

  20. 47 CFR 90.683 - EA-based SMR system operations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... operate base stations using any of the base station frequencies identified in their spectrum block... use of frequencies identified in their spectrum block, including the provisions of § 90.619 relating... authorization for a previously authorized co-channel station within the EA licensee's spectrum block is...

  1. 47 CFR 90.683 - EA-based SMR system operations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... operate base stations using any of the base station frequencies identified in their spectrum block... use of frequencies identified in their spectrum block, including the provisions of § 90.619 relating... authorization for a previously authorized co-channel station within the EA licensee's spectrum block is...

  2. COMPACT E+A GALAXIES AS A PROGENITOR OF MASSIVE COMPACT QUIESCENT GALAXIES AT 0.2 < z < 0.8

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zahid, H. Jabran; Hochmuth, Nicholas Baeza; Geller, Margaret J.

    We search the Sloan Digital Sky Survey and the Baryon Oscillation Sky Survey to identify ∼5500 massive compact quiescent galaxy candidates at 0.2 < z < 0.8. We robustly classify a subsample of 438 E+A galaxies based on their spectral properties and make this catalog publicly available. We examine sizes, stellar population ages, and kinematics of galaxies in the sample and show that the physical properties of compact E+A galaxies suggest that they are a progenitor of massive compact quiescent galaxies. Thus, two classes of objects—compact E+A and compact quiescent galaxies—may be linked by a common formation scenario. The typicalmore » stellar population age of compact E+A galaxies is <1 Gyr. The existence of compact E+A galaxies with young stellar populations at 0.2 < z < 0.8 means that some compact quiescent galaxies first appear at intermediate redshifts. We derive a lower limit for the number density of compact E+A galaxies. Assuming passive evolution, we convert this number density into an appearance rate of new compact quiescent galaxies at 0.2 < z < 0.8. The lower limit number density of compact quiescent galaxies that may appear at z < 0.8 is comparable to the lower limit of the total number density of compact quiescent galaxies at these intermediate redshifts. Thus, a substantial fraction of the z < 0.8 massive compact quiescent galaxy population may descend from compact E+A galaxies at intermediate redshifts.« less

  3. MODELING AND DESIGN STUDY USING HFC-236EA AS AN ALTERNATIVE REFRIGERANT IN A CENTRIFUGAL COMPRESSOR

    EPA Science Inventory

    The report gives results of an investigation of the operation of a centrifugal compressor--part of a chlorofluorocarbon (CFC)-114 chiller installation--with the new refrigerant hydrofluorocarbon (HFC)-236ea, a proposed alternative to CFC-114. A large set of CFC-236ea operating da...

  4. AntigenMap 3D: an online antigenic cartography resource.

    PubMed

    Barnett, J Lamar; Yang, Jialiang; Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2012-05-01

    Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. http://sysbio.cvm.msstate.edu/AntigenMap3D

  5. The muon content of EAS as a function of primary energy

    NASA Technical Reports Server (NTRS)

    Blake, P. R.; Nash, W. F.; Saich, M. S.; Sephton, A. J.

    1985-01-01

    The muon content of extensive air showers (EAS) was measured over the wide primary energy range 10 to the 16th power to 10 to the 20th power eV. It is reported that the relative muon content of EAS decreases smoothly over the energy range 10 to the 17th power to 10 to the 19th power eV and concluded that the primary cosmic ray flux has a constant mass composition over this range. It is also reported that an apparent significant change in the power index occurs below 10 to the 17th power eV rho sub c (250 m) sup 0.78. Such a change indicates a significant change in primary mass composition in this range. The earlier conclusions concerning EAS of energy 10 to the 17th power eV are confirmed. Analysis of data in the 10 to the 16th power - 10 to the 17th power eV range revealed a previously overlooked selection bias in the data set. The full analysis of the complete data set in the energy range 10 to the 16th power - 10 to the 17th power ev with the selection bias eliminated is presented.

  6. 32 CFR 651.24 - Supplemental EAs and supplemental EISs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Supplemental EAs and supplemental EISs. 651.24 Section 651.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Records and Documents § 651.24...

  7. 7 CFR 1794.23 - Proposals normally requiring an EA.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... classification are: (1) Construction of fuel cell, combustion turbine, combined cycle, or diesel generating... be covered in the EA; (2) Construction of fuel cell, combustion turbine, combined cycle, or diesel... boundaries. (12) Installing a heat recovery steam generator and steam turbine with a rating of more than 200...

  8. Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.

    PubMed

    Singhal, Sunil; Bhojnagarwala, Pratik S; O'Brien, Shaun; Moon, Edmund K; Garfall, Alfred L; Rao, Abhishek S; Quatromoni, Jon G; Stephen, Tom Li; Litzky, Leslie; Deshpande, Charuhas; Feldman, Michael D; Hancock, Wayne W; Conejo-Garcia, Jose R; Albelda, Steven M; Eruslanov, Evgeniy B

    2016-07-11

    Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures.

    PubMed

    Michel, Fabrice; Franceschini, Bruno; Berger, Pierre; Arnal, Jean-Michel; Gainnier, Marc; Sainty, Jean-Marie; Papazian, Laurent

    2005-02-01

    To test whether routine quantitative cultures of endotracheal aspirates obtained before the onset of ventilator-associated pneumonia (VAP) could help to predict the causative microorganisms and to select early appropriate antimicrobial therapy before obtaining BAL culture results. Prospective observational study. French medical ICU. A total of 299 patients received mechanical ventilation for at least 48 h. Endotracheal aspiration (EA) was performed twice weekly in all mechanically ventilated patients. A diagnosis of VAP was made by BAL culture. Only the EA performed just before the suspicion of VAP (EA-pre) were evaluated. This strategy (ie, the EA-pre-based strategy) was compared with an antibiotic therapy that would have been prescribed if the recommendations of both the American Thoracic Society (ATS) and Trouillet et al (Am J Respir Crit Care Med 1998; 157:531-539) had been applied. VAP was diagnosed (by BAL culture) in 41 of the 75 patients in whom BAL was performed. Among the 41 BAL specimens that were positive for VAP, EA-pre had identified the same microorganisms (with the same antibiotic resistance patterns) in 34 cases (83%). In one case, EA-pre was not available at the time BAL was performed (a case of early-onset VAP), but the empiric antibiotic therapy was adequate. While EA-pre did not give the same results as the BAL culture, the antibiotic therapy based on the results of the EA-pre was adequate in four other cases. Finally, antibiotic therapy was delayed in only two cases. Antibiotic treatment was therefore adequate in 38 of the 40 assessable cases (95%). If the Trouillet-based strategy had been used, the antibiotic treatment would have been adequate in 34 of the 41 cases (83%; p = 0.15 [vs EA-pre strategy]). Based on the ATS classification, the antibiotic treatment would have been adequately prescribed in only 28 of the 41 cases (68%; p = 0.005 [vs EA-pre strategy]). Routine EA performed twice a week makes it possible to prescribe adequate

  10. 33 CFR 230.7 - Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Environmental Assessment (EA) but not necessarily an EIS. 230.7 Section 230.7 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.7 Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS. Actions...

  11. 33 CFR 230.7 - Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environmental Assessment (EA) but not necessarily an EIS. 230.7 Section 230.7 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.7 Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS. Actions...

  12. 33 CFR 230.7 - Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Environmental Assessment (EA) but not necessarily an EIS. 230.7 Section 230.7 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.7 Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS. Actions...

  13. 33 CFR 230.7 - Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Environmental Assessment (EA) but not necessarily an EIS. 230.7 Section 230.7 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.7 Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS. Actions...

  14. 33 CFR 230.7 - Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Environmental Assessment (EA) but not necessarily an EIS. 230.7 Section 230.7 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.7 Actions normally requiring an Environmental Assessment (EA) but not necessarily an EIS. Actions...

  15. Stress-induced reactivation of Epstein-Barr virus in astronauts

    NASA Technical Reports Server (NTRS)

    Stowe, R. P.; Pierson, D. L.; Feeback, D. L.; Barrett, A. D.

    2000-01-01

    Herpesviruses are leading causes of infectious blindness and death in immunocompromised individuals. Impaired cellular immunity, which is known to result in increased frequency and severity of herpesvirus infections, has been demonstrated both during and after spaceflight. Therefore, we examined whether Epstein-Barr virus (EBV), a well-characterized latent herpesvirus, undergoes reactivation in astronauts. Sera from Shuttle astronauts, taken before and after spaceflight, were examined for evidence of EBV reactivation. The geometric mean antibody titer to EBV viral capsid antigen (VCA) was significantly increased prior to flight compared to baseline (p = 0. 0001). After spaceflight, evidence of acute lytic replication was found in which 8- to 64-fold increases in EBV early antigen (EA) antibodies occurred without significant increases in antibodies to measles virus. Additionally, stress-induced shifts in circulating leukocytes and elevated levels of urinary cortisol and epinephrine were found. Overall, significant increases in EA or high VCA/EA antibody titers were found in 8 of 23 (35%) male astronauts and 3 of 5 (60%) female astronauts. These results indicate that stress reactivates EBV prior to flight and suggest that acute lytic replication of EBV occurs during spaceflight. Copyright 2000 S. Karger AG, Basel.

  16. 47 CFR 90.683 - EA-based SMR system operations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... operate base stations using any of the base station frequencies identified in their spectrum block... base stations at any location on the border of the EA service area in accordance with § 90.689; (4... with § 90.621(b), to all previously authorized co-channel stations that are not associated with another...

  17. Speed of sound and ideal-gas heat capacity of freon R-236ea

    NASA Astrophysics Data System (ADS)

    Komarov, S. G.; Gruzdev, V. A.; Stankus, S. V.

    2008-09-01

    Speed of sound in the gaseous freon R-236ea with the purity of 99.68 mol. % has been measured by the method of ultrasonic interferometer in the range from 263 to 423 K and at pressures from 17 kPA to 4.2 MPa. Errors of temperature, pressure, and speed of sound measurement were estimated to be within +/- 20 mK, ± 1.5 kPa, and ±(0.1+0.2) % respectively. Temperature dependence of ideal-gas heat capacity of R-236ea has been calculated on the basis of the obtained data.

  18. Spatially resolved medium resolution spectroscopy of an interacting E+A (post-starburst) system with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Goto, Tomotsugu; Yagi, Masafumi; Yamauchi, Chisato

    2008-12-01

    We have performed spatially resolved medium resolution long-slit spectroscopy of a nearby E+A (post-starburst) galaxy system, SDSSJ161330.18+510335.5, with the FOCAS spectrograph mounted on the Subaru Telescope. This E+A galaxy has an obvious companion galaxy 14kpc in front with the velocity difference of 61.8kms-1. Both galaxies have obviously disturbed morphology. Thus, this E+A system provides us with a perfect opportunity to investigate the relation between the post-starburst phenomena and galaxy-galaxy interaction. We have found that the Hδ equivalent width (EW) of the E+A galaxy is greater than 7Å galaxy wide (8.5kpc) with no significant spatial variation. The E+A galaxy has a weak [OIII] emission (EW ~ 1Å) offset by ~2.6kpc from the peak of the Balmer absorption lines. We detected a rotational velocity in the companion galaxy of >175kms-1. The progenitor of the companion may have been a rotationally supported, but yet passive S0 galaxy. We did not detect significant rotation on the E+A galaxy. A metallicity estimate based on the r - H colour suggests Z = 0.008 and 0.02, for the E+A and the companion galaxies, respectively. Assuming these metallicity estimates, the age of the E+A galaxy after quenching the star formation is estimated to be 100-500Myr, with its centre having a slightly younger stellar population. The companion galaxy is estimated to have an older stellar population of >2Gyr of age with no significant spatial variation. These findings are inconsistent with a simple picture where the dynamical interaction creates infall of the gas reservoir that causes the central starburst/post-starburst. Instead, our results present an important example where the galaxy-galaxy interaction can trigger a galaxy-wide post-starburst phenomenon. Based on data collected at the Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. E-mail: tomo@ifa.hawaii.edu ‡ Japan Society for the Promotion of Science (JSPS) SPD Fellow.

  19. Hot, humid air increases cellular influx during the late-phase response to nasal challenge with antigen.

    PubMed

    Assanasen, P; Baroody, F M; Naureckas, E; Naclerio, R M

    2001-12-01

    Inhalation of hot, humid air (HHA: 37 degrees C, > 95% relative humidity (RH)) partially inhibits the early response to nasal challenge with antigen. To investigate whether HHA inhibited the late-phase response to nasal challenge with antigen and increased hyper-responsiveness of the nasal mucosa to histamine. Twenty subjects with seasonal allergic rhinitis, outside of their allergy season, participated in a randomized, 2-way cross-over study. The subjects continuously breathed room air (25 degrees C, 30% RH) or HHA delivered via a face mask during the entire experiment. Subjects were challenged intranasally with antigen 1 h after beginning conditioning. The response was monitored by symptoms and nasal lavage at 2-h intervals after the last antigen challenge. Eight hours after antigen challenge, nasal challenge with histamine was performed. Exposure to HHA significantly increased nasal mucosal temperature from baseline without affecting nasal secretion osmolality. HHA significantly inhibited antigen-induced sneezes, congestion, pruritus, and human serum albumin levels during the early response to antigen challenge. HHA exposure, however, was associated with an 8-fold increase in the eosinophil influx and a 15-fold increase in the levels of eosinophil cationic protein during the late-phase response compared to room air. There were no significant differences in nasal hyper-responsiveness to histamine during either exposure. HHA partially decreases the early response to nasal challenge with antigen, but dramatically increases eosinophil influx. Increasing eosinophil number had no effects on the hyper-responsiveness to histamine. We speculate that the physical conditions of air differentially impact the stages of allergic inflammation.

  20. "Boys Should Have the Courage to Ask a Girl Out": Gender Norms in Early Adolescent Romantic Relationships.

    PubMed

    De Meyer, Sara; Kågesten, Anna; Mmari, Kristin; McEachran, Juliet; Chilet-Rosell, Elisa; Kabiru, Caroline W; Maina, Beatrice; Jerves, Elena M; Currie, Candace; Michielsen, Kristien

    2017-10-01

    The purpose of the study is to explore how gender norms emerge in romantic relationships among early adolescents (EAs) living in five poor urban areas. Data were collected as part of the Global Early Adolescent Study. The current research analyzed data from interviews with 30 EAs (aged 11-13 years) living in five poor urban sites: Baltimore, Cuenca, Edinburgh, Ghent, and Nairobi. All interviews were recorded, transcribed, and analyzed in English using Atlas.ti, focusing on how EAs experience and perceive gender norms in romantic relationships. Across the five sites, only a few respondents described having been in love, the majority of whom were boys. Findings indicate that stereotypical gender norms about romantic relationships prevail across these cultural settings, depicting boys as romantically/sexually active and dominant, and girls as innocent with less (romantic) agency. In spite of the similarities, Nairobi was unique in that respondents referred to how sexual behavior and violence can occur within EA relationships. In all countries, heterosexuality was perceived to be the norm. Nevertheless, there were examples of EAs accepting homosexuality and expressing supportive attitudes toward equality between the sexes. While EAs across five different cultural settings seem to endorse stereotypical gender norms in romantic relationships, a few stories also illustrate more gender-equal attitudes. As stereotypical gender norms have a demonstrated negative effect on adolescent sexual and reproductive health and well-being, additional research is needed to understand which factors-at the interpersonal and structural level-contribute to the construction of these norms among EAs. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  1. 7 CFR 520.6 - Preparation of an Environmental Assessment (EA).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Preparation of an Environmental Assessment (EA). 520.6 Section 520.6 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE PROCEDURES FOR IMPLEMENTING NATIONAL ENVIRONMENTAL POLICY ACT § 520.6...

  2. The website-based eaTracker® 'My Goals' feature: a qualitative evaluation.

    PubMed

    Lieffers, Jessica Rl; Haresign, Helen; Mehling, Christine; Arocha, Jose F; Hanning, Rhona M

    2017-04-01

    In 2011, Dietitians of Canada added 'My Goals' to its website-based nutrition/activity tracking program (eaTracker®, http://www.eaTracker.ca/); this feature allows users to choose 'ready-made' or 'write-your-own' goals and to self-report progress. The purpose of the present study was to document experiences and perceptions of goal setting and My Goals, and report users' feedback on what is needed in future website-based goal setting/tracking tools. One-on-one semi-structured interviews were conducted with (i) My Goals users and (ii) dietitians providing a public information support service, EatRight Ontario (ERO). My Goals users from Ontario and Alberta, Canada were recruited via an eaTracker website pop-up box; ERO dietitians working in Ontario, Canada were recruited via ERO. My Goals users (n 23; age 19-70 years; 91 % female; n 5 from Alberta/n 18 from Ontario) and ERO dietitians (n 5). Dietitians and users felt goal setting for nutrition (and activity) behaviour change was both a beneficial and a challenging process. Dietitians were concerned about users setting poor-quality goals and users felt it was difficult to stick to their goals. Both users and dietitians were enthusiastic about the My Goals concept, but felt the current feature had limitations that affected use. Dietitians and users provided suggestions to improve My Goals (e.g. more prominent presence of My Goals in eaTracker; assistance with goal setting; automated personalized feedback). Dietitians and users shared similar perspectives on the My Goals feature and both felt goal use was challenging. Several suggestions were provided to enhance My Goals that are relevant to website-based goal setting/tracking tool design in general.

  3. Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection.

    PubMed

    Fortner, Renée Turzanski; Damms-Machado, Antje; Kaaks, Rudolf

    2017-11-01

    Tumor-associated autoantibodies (AAbs), produced as an immune response to tumor-associated antigens (TAAs), are a novel pathway of early detection markers. We conducted a systematic review on AAbs and ovarian cancer to summarize the diagnostic performance of individual AAbs and AAb panels. A total of 29 studies including 85 AAbs were included; 27 of the studies were conducted in prevalent cases and cancer-free controls and 2 investigations included pre-diagnosis samples. The majority of studies were hypothesis-driven, evaluating AAbs to target TAAs; 10 studies used screening approaches such as serological expression cloning (SEREX) and nucleic acid-programmable protein arrays (NAPPA). The highest sensitivities for individual AAbs were reported for RhoGDI-AAbs (89.5%) and TUBA1C-AAbs (89%); however, specificity levels were relatively low (80% and 75%, respectively). High sensitivities at high specificities were reported for HOXA7-AAbs for detection of moderately differentiated ovarian tumors (66.7% sensitivity at 100% specificity) and IL8-AAbs in stage I-II ovarian cancer (65.5% sensitivity at 98% specificity). A panel of 11 AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) provided 45% sensitivity at 98% specificity for serous ovarian cancer, when at least 2 AAbs were above a threshold of 95% specificity. Twelve of the AAbs identified in this review were investigated in more than one study. Data on diagnostic discrimination by tumor histology and stage at diagnosis are sparse. Limited data suggest select AAb markers improve diagnostic discrimination when combined with markers such as CA125 and HE4. AAbs for ovarian cancer early detection is an emerging area, and large-scale, prospective investigations considering histology and stage are required for discovery and validation. However, data to date suggests panels of AAbs may eventually reach sufficient diagnostic discrimination to allow earlier detection of disease as a complement to

  4. East Atlantic (EA) and North Atlantic Oscillation (NAO) interplay over the Iberian Peninsula for the last two millennia

    NASA Astrophysics Data System (ADS)

    Hernandez, A.; Sánchez-López, G.; Pla-Rabes, S.; Trigo, R.; Toro, M.; Granados, I.; Sáez, A.; Masque, P.; Pueyo, J. J.; Rubio-Inglés, M. J.; Giralt, S.

    2016-12-01

    The multi-proxy approach from sediments of an Iberian alpine lake allowed us to establish the climatic conditions in the Iberian Central Range (ICR) over the last two millennia. The comparison with other Iberian reconstructions permitted to identify possible forcing climate mechanisms. Climatic conditions would be transmitted to the sediments via the frequency of intense run-off events, derived from rain-on-snow events, and the lake productivity, ruled by ice-cover duration. The early Roman Period (RP; 200 BC - 350 AD) in the ICR was characterized by oscillations of intense run-off events, as a consequence of an alternation between cold and warm periods. From the second half of the RP to the onset of the Early Middle Ages (EMA; 350 - 500 AD) an increase in the intense run-off events suggests warm conditions, although a noticeable decrease during the rest of the EMA (500 - 900 AD) evidences a shift to very cold temperatures in this region. In terms of humidity, both RP and EMA climatic periods displayed a transition from a dry to a wet scenario that led to a decrease in lake productivity. These climatic conditions have been registered by other reconstructions in the Iberian Peninsula (IP), and a North-South humidity gradient could be envisaged, although spatial climatic discrepancies were significant. Precipitation and temperature in the IP present a more homogeneous spatial pattern when the NAO and EA modes have the same sign than when they have the opposite sign. Hence, a predominance of periods with NAO - EA in opposite phases could explain the climatic spatial heterogeneity in the IP during these two periods. The Medieval Climate Anomaly (MCA; 900 - 1300 AD) in the ICR was characterized by warm and dry conditions represented by an increase in exceptional run-off episodes and lake productivity whereas the Little Ice Age (LIA; 1300 - 1850 AD) showed the opposite scenario. Similar climatic conditions were registered in all the IP, reflecting a spatial climatic

  5. Membrane topology and identification of key residues of EaDAcT, a plant MBOAT with unusual substrate specificity.

    PubMed

    Tran, Tam N T; Shelton, Jennifer; Brown, Susan; Durrett, Timothy P

    2017-10-01

    Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) catalyzes the transfer of an acetyl group from acetyl-CoA to the sn-3 position of diacylglycerol to form 3-acetyl-1,2-diacyl-sn-glycerol (acetyl-TAG). EaDAcT belongs to a small, plant-specific subfamily of the membrane bound O-acyltransferases (MBOAT) that acylate different lipid substrates. Sucrose gradient density centrifugation revealed that EaDAcT colocalizes to the same fractions as an endoplasmic reticulum (ER)-specific marker. By mapping the membrane topology of EaDAcT, we obtained an experimentally determined topology model for a plant MBOAT. The EaDAcT model contains four transmembrane domains (TMDs), with both the N- and C-termini orientated toward the lumen of the ER. In addition, there is a large cytoplasmic loop between the first and second TMDs, with the MBOAT signature region of the protein embedded in the third TMD close to the interface between the membrane and the cytoplasm. During topology mapping, we discovered two cysteine residues (C187 and C293) located on opposite sides of the membrane that are important for enzyme activity. In order to identify additional amino acid residues important for acetyltransferase activity, we isolated and characterized acetyltransferases from other acetyl-TAG-producing plants. Among them, the acetyltransferase from Euonymus fortunei possessed the highest activity in vivo and in vitro. Mutagenesis of conserved amino acids revealed that S253, H257, D258 and V263 are essential for EaDAcT activity. Alteration of residues unique to the acetyltransferases did not alter the unique acyl donor specificity of EaDAcT, suggesting that multiple amino acids are important for substrate recognition. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  6. SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).

    PubMed

    Soto, Timothy; Giserman Kiss, Ivy; Carter, Alice S

    2016-09-01

    Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. © 2016 Michigan Association for Infant Mental Health.

  7. 7 CFR 520.6 - Preparation of an Environmental Assessment (EA).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... commercial phase; (2) Field work having an impact on the local environment such as earth excavation... may have a significant environmental impact and thus warrant preparation of an EIS. The EA will... need for the project or other proposal, alternatives, environmental impacts of the proposed action and...

  8. NEW CHEMICAL ALTERNATIVE FOR OZONE-DEPLETING SUBSTANCES: HFC-236EA

    EPA Science Inventory

    The report gives results of a preliminary evaluation of a new hydrofluorocarbon (HFC-236ea or 1, 1, 1, 2, 3, 3-hexafluoropropane) as a possible alternative for chlorofluorocarbon (CFC)-114 (1, 2-dichloro-1, 1, 2, 2-tetrafluoroethane) refrigerant in chillers and high-temperature i...

  9. Thermophysical Properties and Spectral Characterization of EA 6043

    DTIC Science & Technology

    2014-10-01

    TGS) detector. The vapor-phase FTIR spectrum was measured using a Nicolet (Thermo Scientific Dionex ; Sunnyvale, CA) 6700 FTIR system equipped with a...3), 195 (1). A small feature near 267 m/z is probably associated with the parent ion . Figure 9. EI-MS of EA 6043. m/z 15 3.6 Nuclear...photometric detector with a phosphorus filter GC gas chromatography MCT mercury–cadmium telluride m/z mass-to-charge ratio NIR near infrared

  10. Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design

    PubMed Central

    Kong, Leopold; Sattentau, Quentin J

    2012-01-01

    Neutralizing antibodies can protect from infection by immunodeficiency viruses. However, the induction by active vaccination of antibodies that can potently neutralize a broad range of circulating virus strains is a goal not yet achieved, despite more than 2 decades of research. Here we review progress made in the field, from early empirical studies to today’s rational structure-based vaccine antigen design. We discuss the existence of broadly neutralizing antibodies, their implications for epitope discovery and recent progress made in antigen design. Finally, we consider the relationship between antigenicity and immunogenicity for B cell recognition and antibody production, a major hurdle for rational vaccine design to overcome. PMID:23227445

  11. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  12. Interdecadal change of the controlling mechanisms for East Asian early summer rainfall variation around the mid-1990s

    NASA Astrophysics Data System (ADS)

    Yim, So-Young; Wang, Bin; Kwon, MinHo

    2014-03-01

    East Asian (EA) summer monsoon shows considerable differences in the mean state and principal modes of interannual variation between early summer (May-June, MJ) and late summer (July-August, JA). The present study focuses on the early summer (MJ) precipitation variability. We find that the interannual variation of the MJ precipitation and the processes controlling the variation have been changed abruptly around the mid-1990s. The rainfall anomaly represented by the leading empirical orthogonal function has changed from a dipole-like pattern in pre-95 epoch (1979-1994) to a tripole-like pattern in post-95 epoch (1995-2010); the prevailing period of the corresponding principal component has also changed from 3-5 to 2-3 years. These changes are concurrent with the changes of the corresponding El Nino-Southern Oscillation (ENSO) evolutions. During the pre-95 epoch, the MJ EA rainfall anomaly is coupled to a slow decay of canonical ENSO events signified by an eastern Pacific warming, which induces a dipole rainfall feature over EA. On the other hand, during the post-95 epoch the anomalous MJ EA rainfall is significantly linked to a rapid decay of a central Pacific warming and a distinct tripolar sea surface temperature (SST) in North Atlantic. The central Pacific warming-induced Philippine Sea anticyclone induces an increased rainfall in southern China and decreased rainfall in central eastern China. The North Atlantic Oscillation-related tripolar North Atlantic SST anomaly induces a wave train that is responsible for the increase northern EA rainfall. Those two impacts form the tripole-like rainfall pattern over EA. Understanding such changes is important for improving seasonal to decadal predictions and long-term climate change in EA.

  13. After the Fall: The Dust and Gas in E+A Post-starburst Galaxies

    NASA Astrophysics Data System (ADS)

    Smercina, A.; Smith, J. D. T.; Dale, D. A.; French, K. D.; Croxall, K. V.; Zhukovska, S.; Togi, A.; Bell, E. F.; Crocker, A. F.; Draine, B. T.; Jarrett, T. H.; Tremonti, C.; Yang, Yujin; Zabludoff, A. I.

    2018-03-01

    The traditional picture of post-starburst galaxies as dust- and gas-poor merger remnants, rapidly transitioning to quiescence, has been recently challenged. Unexpected detections of a significant interstellar medium (ISM) in many post-starburst galaxies raise important questions. Are they truly quiescent, and if so, what mechanisms inhibit further star formation? What processes dominate their ISM energetics? We present an infrared spectroscopic and photometric survey of 33 E+A post-starbursts selected by the Sloan Digital Sky Survey, aimed at resolving these questions. We find compact, warm dust reservoirs with high PAH abundances and total gas and dust masses significantly higher than expected from stellar recycling alone. Both polycyclic aromatic hydrocarbon (PAH)/total infrared (TIR) and dust-to-burst stellar mass ratios are seen to decrease with post-burst age, indicative of the accumulating effects of dust destruction and an incipient transition to hot, early-type ISM properties. Their infrared spectral properties are unique, with dominant PAH emission, very weak nebular lines, unusually strong H2 rotational emission, and deep [C II] deficits. There is substantial scatter among star formation rate (SFR) indicators, and both PAH and TIR luminosities provide overestimates. Even as potential upper limits, all tracers show that the SFR has typically experienced a decline of more than two orders of magnitude since the starburst and that the SFR is considerably lower than expected given both their stellar masses and molecular gas densities. These results paint a coherent picture of systems in which star formation was, indeed, rapidly truncated, but in which the ISM was not completely expelled, and is instead supported against collapse by latent or continued injection of turbulent or mechanical heating. The resulting aging burst populations provide a “high-soft” radiation field that seemingly dominates the E+A galaxies’ unusual ISM energetics.

  14. Outcomes of Early Adolescent Donor Hearts in Adult Transplant Recipients.

    PubMed

    Madan, Shivank; Patel, Snehal R; Vlismas, Peter; Saeed, Omar; Murthy, Sandhya; Forest, Stephen; Jakobleff, William; Sims, Daniel; Lamour, Jacqueline M; Hsu, Daphne T; Shin, Julia; Goldstein, Daniel; Jorde, Ulrich P

    2017-12-01

    This study sought to determine outcomes of adult recipients of early adolescent (EA) (10 to 14 years) donor hearts. Despite a shortage of donor organs, EA donor hearts (not used for pediatric patients) are seldom used for adults because of theoretical concerns for lack of hormonal activation and changes in left ventricular mass. Nonetheless, the outcomes of adult transplantation using EA donor hearts are not clearly established. All adult (≥18 years of age) heart transplant recipients in the United Network for Organ Sharing database between April 1994 and September 2015 were eligible for this analysis. Recipients of EA donor hearts were compared with recipients of donor hearts from the usual adult age group (ages 18 to 55 years). Main outcomes were all-cause mortality and cardiac allograft vasculopathy up to 5 years, and primary graft failure up to 90 days post-transplant. Propensity score analysis was used to identify a cohort of recipients with similar baseline characteristics. Of the 35,054 eligible adult recipients, 1,123 received hearts from EA donors and 33,931 from usual-age adult donors. With the use of propensity score matching, 944 recipients of EA donor hearts were matched to 944 recipients of usual-age adult donor hearts. There was no difference in 30-day, 1-year, 3-year, and 5-year recipient survival or primary graft failure rates in the 2 groups using both Cox hazards ratio and Kaplan-Meier analysis. Of note, adult patients who received EA donor hearts had a trend toward less cardiac allograft vasculopathy (Cox hazard ratio, 0.80; 95% confidence interval: 0.62 to 1.01; p = 0.07). In this largest analysis to date, we found strong evidence that EA donor hearts, not used for pediatric patients, can be safely transplanted in appropriate adult patients and have good outcomes. This finding should help increase the use of EA donor hearts. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Identification of immunodominant Leishmania major antigenic markers of the early C57BL/6 and BALB/c mice infection stages.

    PubMed

    Sassi, Atfa; Kaak, Olfa; Elgaaied, Amel Benammar

    2015-08-24

    The C57BL/6 mouse strain is resistant to Leishmania (L.) major infection and, unlike susceptible BALB/c, develops small self healing cutaneous lesions. The specific antibody responses of C57BL/6 and BALB/c mice were previously characterized by the predominance of IgG2a ("resistant" isotype associated with Th1) and IgG1 ("pathogenic" isotype associated with Th2) antibodies, respectively. In this study, we looked for the presence of antigens able to elicit an exclusive or predominant IgG1 production during the early stages of C57BL/6 lesion development and checked whether they are recognized or not by BALB/c mice. We demonstrate first that IgG2a predominance in C57BL/6 sera occurs only late after infection whereas in BALB/c, IgG1 antibodies dominate mostly in the early stages. Interestingly, soon after inoculation of live amastigotes, C57BL/6 displayed an exclusive IgG1 reactivity against particular L. major antigens but with MWs different from those identified in BALB/c. Furthermore, mice immunized with killed amastigotes displayed striking differences in their immunodetection profiles, particularly for the IgG1 isotype. Taken together, the observed differences in the specific antibody repertoires between infected mice resulted, at least in part, from immunological events independent from those triggered by the replicating parasite, and bring new insights into the selection of future vaccine candidates. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0–5)

    PubMed Central

    SOTO, TIMOTHY; KISS, IVY GISERMAN; CARTER, ALICE S.

    2018-01-01

    Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0–5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. PMID:27556740

  17. Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance.

    PubMed

    McCallum, Fiona J; Persson, Kristina E M; Fowkes, Freya J I; Reiling, Linda; Mugyenyi, Cleopatra K; Richards, Jack S; Simpson, Julie A; Williams, Thomas N; Gilson, Paul R; Hodder, Anthony N; Sanders, Paul R; Anders, Robin F; Narum, David L; Chitnis, Chetan; Crabb, Brendan S; Marsh, Kevin; Beeson, James G

    2017-04-01

    Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance. © Society for Leukocyte Biology.

  18. Application of MPVR and TL-VR with 64-row MDCT in neonates with congenital EA and distal TEF.

    PubMed

    Wen, Yang; Peng, Yun; Zhai, Ren-You; Li, Ying-Zi

    2011-03-28

    To assess the application of multiple planar volume reconstruction (MPVR) and three-dimensional (3D) transparency lung volume rendering (TL-VR) with 64-row multidetector-row computed tomography (MDCT) in neonates with congenital esophageal atresia (EA) and distal tracheoesophageal fistula (TEF). Twenty neonates (17 boys, 3 girls) with EA and distal TEF at a mean age of 4.6 d (range 1-16 d) were enrolled in this study. A helical scan of 64-row MDCT was performed at the 64 mm × 0.625 mm collimation. EA and TEF were reconstructed with MPVR and TL-VR, respectively. Initial diagnosis of EA was made by chest radiography showing the inserted catheter in the proximal blind-ended esophageal pouch. Manifestations of MDCT images were compared with the findings at surgery. MDCT showed the proximal and distal esophageal pouches in 20 cases. No significant difference was observed in gaps between the proximal and distal esophageal pouches detected by MPVR and TL-VR. The lengths of gaps between the proximal and distal esophageal pouches detected by MPVR and TL-VR correlated well with the findings at surgery (R = 0.87, P < 0.001). The images of MPVR revealed the orifice of TEF in 13 cases, while TL-VR images showed the orifice of TEF in 4 cases. EA and distal TEF can be reconstructed using MPVR and TL-VR of 64-row MDCT, which is a noninvasive technique to demonstrate the distal esophageal pouches and inter-pouch distance in neonates with EA and distal TEF.

  19. Putative SF2 helicases of the early-branching eukaryote Giardia lamblia are involved in antigenic variation and parasite differentiation into cysts

    PubMed Central

    2012-01-01

    Background Regulation of surface antigenic variation in Giardia lamblia is controlled post-transcriptionally by an RNA-interference (RNAi) pathway that includes a Dicer-like bidentate RNase III (gDicer). This enzyme, however, lacks the RNA helicase domain present in Dicer enzymes from higher eukaryotes. The participation of several RNA helicases in practically all organisms in which RNAi was studied suggests that RNA helicases are potentially involved in antigenic variation, as well as during Giardia differentiation into cysts. Results An extensive in silico analysis of the Giardia genome identified 32 putative Super Family 2 RNA helicases that contain almost all the conserved RNA helicase motifs. Phylogenetic studies and sequence analysis separated them into 22 DEAD-box, 6 DEAH-box and 4 Ski2p-box RNA helicases, some of which are homologs of well-characterized helicases from higher organisms. No Giardia putative helicase was found to have significant homology to the RNA helicase domain of Dicer enzymes. Additionally a series of up- and down-regulated putative RNA helicases were found during encystation and antigenic variation by qPCR experiments. Finally, we were able to recognize 14 additional putative helicases from three different families (RecQ family, Swi2/Snf2 and Rad3 family) that could be considered DNA helicases. Conclusions This is the first comprehensive analysis of the Super Family 2 helicases from the human intestinal parasite G. lamblia. The relative and variable expression of particular RNA helicases during both antigenic variation and encystation agrees with the proposed participation of these enzymes during both adaptive processes. The putatives RNA and DNA helicases identified in this early-branching eukaryote provide initial information regarding the biological role of these enzymes in cell adaptation and differentiation. PMID:23190735

  20. Spectral Analysis, Synthesis, & Energy Distributions of Nearby E+A Galaxies Using SDSS-IV MaNGA

    NASA Astrophysics Data System (ADS)

    Weaver, Olivia A.; Anderson, Miguel Ricardo; Wally, Muhammad; James, Olivia; Falcone, Julia; Liu, Allen; Wallack, Nicole; Liu, Charles; SDSS Collaboration

    2017-01-01

    Utilizing data from the Mapping Nearby Galaxies at APO (MaNGA) Survey (MaNGA Product Launch-4, or MPL-4), of the latest generation of the Sloan Digital Sky Survey (SDSS-IV), we identified nine post-starburst (E+A) systems that lie within the Green Valley transition zone. We identify the E+A galaxies by their SDSS single fiber spectrum and u-r color, then confirmed their classification as post-starburst by coding/plotting methods and spectral synthesis codes (FIREFLY and PIPE3D), as well as with their Spectral Energy Distributions (SEDs) from 0.15 µm to 22 µm, using GALEX, SDSS, 2MASS, and WISE data. We produced maps of gaussian-fitted fluxes, equivalent widths, stellar velocities, metallicities and age. We also produced spectral line ratio diagrams to classify regions of stellar populations of the galaxies. We found that our sample of E+As retain their post-starburst properties across the entire galaxy, not just at their center. We detected matching a trend line in the ultraviolet and optical bands, consistent with the expected SEDs for an E+A galaxy, and also through the J, H and Ks bands, except for one object. We classified one of the nine galaxies as a luminous infrared galaxy, unusual for a post-starburst object. Our group seeks to further study stellar population properties, spectral energy distributions and quenching properties in E+A galaxies, and investigate their role in galaxy evolution as a whole. This work was supported by the Alfred P. Sloan Foundation via the SDSS-IV Faculty and Student Team (FAST) initiative, ARC Agreement #SSP483 to the CUNY College of Staten Island. This work was also supported by grants to The American Museum of Natural History, and the CUNY College of Staten Island through from National Science Foundation.

  1. Novel Treponema pallidum Recombinant Antigens for Syphilis Diagnostics: Current Status and Future Prospects

    PubMed Central

    Kubanov, Aleksey; Runina, Anastassia

    2017-01-01

    The recombinant protein technology considerably promoted the development of rapid and accurate treponema-specific laboratory diagnostics of syphilis infection. For the last ten years, the immunodominant recombinant inner membrane lipoproteins are proved to be sensitive and specific antigens for syphilis screening. However, the development of an enlarged T. pallidum antigen panel for diagnostics of early and late syphilis and differentiation of syphilis stages or cured syphilis remains as actual goal of multidisciplinary expertise. Current review revealed novel recombinant antigens: surface-exposed proteins, adhesins, and periplasmic and flagellar proteins, which are promising candidates for the improved syphilis serological diagnostics. The opportunities and limitations of diagnostic usage of these antigens are discussed and the criteria for selection of optimal antigens panel summarized. PMID:28523273

  2. Mini-review: Strategies for Variation and Evolution of Bacterial Antigens

    PubMed Central

    Foley, Janet

    2015-01-01

    Across the eubacteria, antigenic variation has emerged as a strategy to evade host immunity. However, phenotypic variation in some of these antigens also allows the bacteria to exploit variable host niches as well. The specific mechanisms are not shared-derived characters although there is considerable convergent evolution and numerous commonalities reflecting considerations of natural selection and biochemical restraints. Unlike in viruses, mechanisms of antigenic variation in most bacteria involve larger DNA movement such as gene conversion or DNA rearrangement, although some antigens vary due to point mutations or modified transcriptional regulation. The convergent evolution that promotes antigenic variation integrates various evolutionary forces: these include mutations underlying variant production; drift which could remove alleles especially early in infection or during life history phases in arthropod vectors (when the bacterial population size goes through a bottleneck); selection not only for any particular variant but also for the mechanism for the production of variants (i.e., selection for mutability); and overcoming negative selection against variant production. This review highlights the complexities of drivers of antigenic variation, in particular extending evaluation beyond the commonly cited theory of immune evasion. A deeper understanding of the diversity of purpose and mechanisms of antigenic variation in bacteria will contribute to greater insight into bacterial pathogenesis, ecology and coevolution with hosts. PMID:26288700

  3. Early postnatal exposure to cigarette smoke impairs the antigen-specific T-cell responses in the spleen.

    PubMed

    Singh, Shashi P; Razani-Boroujerdi, Seddigheh; Pena-Philippides, Juan C; Langley, Raymond J; Mishra, Neerad C; Sopori, Mohan L

    2006-12-15

    Annually, approximately two million babies are exposed to cigarette smoke in utero and postnatally through cigarette smoking of their mothers. Exposure to mainstream cigarette smoke is known to impair both innate and adaptive immunities, and it has been hypothesized that the effects of in utero exposure to cigarette smoke on children's health might primarily stem from the adverse effects of cigarette smoke on the immune system. To simulate the environment that babies from smoking mothers encounter, we examined the effects of prenatal mainstream and postnatal sidestream cigarette smoke on spleen cell responses. Results show that postnatal exposure of newborn Balb/c mouse pups to sidestream cigarette smoke through the first 6 weeks of life strongly suppresses the antibody response of spleen cells to the T-cell-dependent antigen, sheep red blood cells. The reduction in the antibody response seen within 6 weeks of postnatal smoke exposure is much quicker than the published data on the time 25 weeks) required to establish reproducible immunosuppression in adult rats and mice. Moreover, the immunosuppression is not associated with significant changes in T-cell numbers or subset distribution. While the postnatal exposure to cigarette smoke did not affect the mitogenic response of T and B cells, the exposure inhibited the T cell receptor-mediated rise in the intracellular calcium concentration. These results suggest that the early postnatal period is highly sensitive to the immunosuppressive effects of environmental tobacco smoke, and the effects are causally associated with impaired antigen-mediated signaling in T cells.

  4. 7 CFR 650.8 - When to prepare an environmental assessment (EA).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 6 2011-01-01 2011-01-01 false When to prepare an environmental assessment (EA). 650.8 Section 650.8 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES COMPLIANCE WITH NEPA Procedures...

  5. 7 CFR 650.8 - When to prepare an environmental assessment (EA).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false When to prepare an environmental assessment (EA). 650.8 Section 650.8 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES COMPLIANCE WITH NEPA Procedures...

  6. 7 CFR 650.8 - When to prepare an environmental assessment (EA).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 6 2012-01-01 2012-01-01 false When to prepare an environmental assessment (EA). 650.8 Section 650.8 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES COMPLIANCE WITH NEPA Procedures...

  7. 7 CFR 650.8 - When to prepare an environmental assessment (EA).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 6 2013-01-01 2013-01-01 false When to prepare an environmental assessment (EA). 650.8 Section 650.8 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES COMPLIANCE WITH NEPA Procedures...

  8. 7 CFR 650.8 - When to prepare an environmental assessment (EA).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 6 2014-01-01 2014-01-01 false When to prepare an environmental assessment (EA). 650.8 Section 650.8 Agriculture Regulations of the Department of Agriculture (Continued) NATURAL RESOURCES CONSERVATION SERVICE, DEPARTMENT OF AGRICULTURE SUPPORT ACTIVITIES COMPLIANCE WITH NEPA Procedures...

  9. 76 FR 24874 - Initiation of Scoping for an Environmental Assessment (EA)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ...) General Permit for Discharges from Construction Activities. The EA will evaluate the potential environmental impacts from the discharge of pollutants associated with stormwater runoff from construction... days of the date of the publication of the Proposed Construction General Permit in the Federal Register...

  10. Immunity to tumour antigens.

    PubMed

    Li, Geng; Ali, Selman A; McArdle, Stephanie E B; Mian, Shahid; Ahmad, Murrium; Miles, Amanda; Rees, Robert C

    2005-01-01

    During the last decade, a large number of human tumour antigens have been identified. These antigens are classified as tumour-specific shared antigens, tissue-specific differentiation antigens, overexpressed antigens, tumour antigens resulting from mutations, viral antigens and fusion proteins. Antigens recognised by effectors of immune system are potential targets for antigen-specific cancer immunotherapy. However, most tumour antigens are self-proteins and are generally of low immunogenicity and the immune response elicited towards these tumour antigens is not always effective. Strategies to induce and enhance the tumour antigen-specific response are needed. This review will summarise the approaches to discovery of tumour antigens, the current status of tumour antigens, and their potential application to cancer treatment.

  11. Identification of sero-reactive antigens for the early diagnosis of Johne’s disease in cattle

    PubMed Central

    Randall, Arlo; Grohn, Yrjo T.; Katani, Robab; Schilling, Megan; Radzio-Basu, Jessica

    2017-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease (JD), a chronic intestinal inflammatory disease of cattle and other ruminants. JD has a high herd prevalence and causes serious animal health problems and significant economic loss in domesticated ruminants throughout the world. Since serological detection of MAP infected animals during the early stages of infection remains challenging due to the low sensitivity of extant assays, we screened 180 well-characterized serum samples using a whole proteome microarray from Mycobacterium tuberculosis (MTB), a close relative of MAP. Based on extensive testing of serum and milk samples, fecal culture and qPCR for direct detection of MAP, the samples were previously assigned to one of 4 groups: negative low exposure (n = 30, NL); negative high exposure (n = 30, NH); fecal positive, ELISA negative (n = 60, F+E-); and fecal positive, ELISA positive (n = 60, F+E+). Of the 740 reactive proteins, several antigens were serologically recognized early but not late in infection, suggesting a complex and dynamic evolution of the MAP humoral immune response during disease progression. Ordinal logistic regression models identified a subset of 47 candidate proteins with significantly different normalized intensity values (p<0.05), including 12 in the NH and 23 in F+E- groups, suggesting potential utility for the early detection of MAP infected animals. Next, the diagnostic utility of four MAP orthologs (MAP1569, MAP2942c, MAP2609, and MAP1272c) was assessed and reveal moderate to high diagnostic sensitivities (range 48.3% to 76.7%) and specificity (range 96.7% to 100%), with a combined 88.3% sensitivity and 96.7% specificity. Taken together, the results of our analyses have identified several candidate MAP proteins of potential utility for the early detection of MAP infection, as well individual MAP proteins that may serve as the foundation for the next generation of well-defined serological

  12. Management of Pediatric Perforated Appendicitis: Comparing Outcomes Using Early Appendectomy Versus Solely Medical Management.

    PubMed

    Bonadio, William; Rebillot, Katie; Ukwuoma, Onyinyechi; Saracino, Christine; Iskhakov, Arthur

    2017-10-01

    There is controversy regarding whether children with perforated appendicitis should receive early appendectomy (EA) versus medical management (MM) with antibiotics and delayed interval appendectomy. The objective of this study was to compare outcomes of children with perforated appendicitis who receive EA versus MM. Case review of consecutive children <18 years of age with perforated appendicitis who received either EA or MM during an 8-year period. Criteria for hospital discharge included patient being afebrile for at least 24 hours, pain-free and able to tolerate oral intake. Of 203 patients diagnosed with perforated appendicitis, 122 received EA and 81 received MM. All received parenteral antibiotic therapy initiated in the emergency department and continued during hospitalization. There were no significant differences between groups in mean patient age, mean complete blood count total white blood cells count, gender distribution, rates of emergency department fever or rates of intra-abdominal infection (abscess or phlegmon) identified on admission. Compared with patients receiving MM, those receiving EA experienced significantly fewer (1) days of hospitalization, parenteral antibiotic therapy and in-hospital fever; (2) radiographic studies, percutaneous drainage procedures and placement of central venous catheters performed; (3) post admission intra-abdominal complications and (4) unscheduled repeat hospitalizations after hospital discharge. Only 1 EA-managed patient developed a postoperative wound infection. Children with perforated appendicitis who receive EA experience significantly less morbidity and complications versus those receiving MM. The theoretical concern for enhanced morbidity associated with EA management of perforated appendicitis is not supported by our analysis.

  13. Effects of Asian Dust Particles on the Early-Stage Antigen-Induced Immune Response of Asthma in NC/Nga Mice.

    PubMed

    Kurai, Jun; Watanabe, Masanari; Sano, Hiroyuki; Hantan, Degejirihu; Tohda, Yuji; Shimizu, Eiji

    2016-11-16

    Asian dust (AD) can aggravate airway inflammation in asthma, but the association between AD and the development of asthma remains unclear. This study aimed to investigate the effects of AD on the early stage of antigen sensitization using a mouse model of asthma, as well as the role of leukotrienes (LTs) in antigen-induced airway inflammation potentiated by AD particles. NC/Nga mice were co-sensitized by intranasal instillation of AD particles and/or Dermatophagoides farinae (Df) for five consecutive days. Df-sensitized mice were stimulated with an intranasal Df challenge at seven days. Mice were treated with the type 1 cysteinyl LT (CysLT₁) receptor antagonist orally 4 h before and 1 h after the allergen challenge. At 24 h post-challenge, the differential leukocyte count, inflammatory cytokines, and LTs in bronchoalveolar lavage fluid were assessed, and airway inflammation was evaluated histopathologically. AD augmented neutrophilic and eosinophilic airway inflammation with increased CysLTs and dihydroxy-LT in a mouse model of asthma. The CysLT₁ receptor antagonist was shown to attenuate both neutrophilic and eosinophilic airway inflammation augmented by AD. Therefore, exposure to AD may be associated with the development of asthma and LTs may play important roles in airway inflammation augmented by AD.

  14. The Early Innate Response of Chickens to Salmonella enterica Is Dependent on the Presence of O-Antigen but Not on Serovar Classification

    PubMed Central

    Varmuzova, Karolina; Matulova, Marta Elsheimer; Sebkova, Alena; Sekelova, Zuzana; Havlickova, Hana; Sisak, Frantisek; Babak, Vladimir; Rychlik, Ivan

    2014-01-01

    Salmonella vaccines used in poultry in the EU are based on attenuated strains of either Salmonella serovar Enteritidis or Typhimurium which results in a decrease in S. Enteritidis and S. Typhimurium but may allow other Salmonella serovars to fill an empty ecological niche. In this study we were therefore interested in the early interactions of chicken immune system with S. Infantis compared to S. Enteritidis and S. Typhimurium, and a role of O-antigen in these interactions. To reach this aim, we orally infected newly hatched chickens with 7 wild type strains of Salmonella serovars Enteritidis, Typhimurium and Infantis as well as with their rfaL mutants and characterized the early Salmonella-chicken interactions. Inflammation was characterized in the cecum 4 days post-infection by measuring expression of 43 different genes. All wild type strains stimulated a greater inflammatory response than any of the rfaL mutants. However, there were large differences in chicken responses to different wild type strains not reflecting their serovar classification. The initial interaction between newly-hatched chickens and Salmonella was found to be dependent on the presence of O-antigen but not on its structure, i.e. not on serovar classification. In addition, we observed that the expression of calbindin or aquaporin 8 in the cecum did not change if inflammatory gene expression remained within a 10 fold fluctuation, indicating the buffering capacity of the cecum, preserving normal gut functions even in the presence of minor inflammatory stimuli. PMID:24763249

  15. Mouse models expressing human carcinoembryonic antigen (CEA) as a transgene: Evaluation of CEA-based cancer vaccines

    PubMed Central

    Hance, Kenneth W.; Zeytin, Hasan E.; Greiner, John W.

    2010-01-01

    In recent years, investigators have carried out several studies designed to evaluate whether human tumor-associated antigens might be exploited as targets for active specific immunotherapy, specifically human cancer vaccines. Not too long ago such an approach would have been met with considerable skepticism because the immune system was believed to be a rigid discriminator between self and non-self which, in turn, protected the host from a variety of pathogens. That viewpoint has been challenged in recent years by a series of studies indicating that antigenic determinants of self have not induced absolute host immune tolerance. Moreover, under specific conditions that evoke danger signals, peptides from self-antigen can be processed by the antigen-presenting cellular machinery, loaded onto the major histocompatibility antigen groove to serve as targets for immune intervention. Those findings provide the rationale to investigate a wide range of tumor-associated antigens, including differentiation antigens, oncogenes, and tumor suppressor genes as possible immune-based targets. One of those tumor-associated antigens is the carcinoembryonic antigen (CEA). Described almost 40 years ago, CEA is a Mr 180–200,000 oncofetal antigen that is one of the more widely studied human tumor-associated antigens. This review will provide: (i) a brief overview of the CEA gene family, (ii) a summary of early preclinical findings on overcoming immune tolerance to CEA, and (iii) the rationale to develop mouse models which spontaneously develop gastrointestinal tumors and express the CEA transgene. Those models have been used extensively in the study of overcoming host immune tolerance to CEA, a self, tumor-associated antigen, and the experimental findings have served as the rationale for the design of early clinical trials to evaluate CEA-based cancer vaccines. PMID:15888344

  16. Town of Chino Valley Municipal Water System Improvement Project FONSI and EA

    EPA Pesticide Factsheets

    EPA Region 9 has prepared an Environmental Assessment (EA) describing the potential environmental impacts associated with, and the alternatives to, the proposed Water System Improvement Project in the town of China Valley, Arizona. This Finding of No Signi

  17. Towards Preserving the Immunogenicity of Protein Antigens Carried by Nanoparticles While Avoiding the Cold Chain

    PubMed Central

    Sloat, Brian R.; Sandoval, Michael A.; Cui, Zhengrong

    2010-01-01

    Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37°C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration. PMID:20416366

  18. Evaluation of RSDL, M291 SDK, 0.5% Bleach, 1% Soapy Water and SERPACWA. Part 12: Challenge with EA1212 (GF, cyclosarin)

    DTIC Science & Technology

    2016-01-01

    products in the haired guinea pig model following exposure to GF (EA1212). 15. SUBJECT TERMS decontamination, delayed decontamination, Reactive Skin...the four listed decontamination products in the haired guinea pig model following exposure to GF (EA1212). In all experiments, guinea pigs were close...the four listed decontamination products and SERPACWA in the haired guinea pig model following exposure to GF [cyclosarin, EA1212, Cyclohexyl

  19. Assessment of cancer and virus antigens for cross-reactivity in human tissues.

    PubMed

    Jaravine, Victor; Raffegerst, Silke; Schendel, Dolores J; Frishman, Dmitrij

    2017-01-01

    Cross-reactivity (CR) or invocation of autoimmune side effects in various tissues has important safety implications in adoptive immunotherapy directed against selected antigens. The ability to predict CR (on-target and off-target toxicities) may help in the early selection of safer therapeutically relevant target antigens. We developed a methodology for the calculation of quantitative CR for any defined peptide epitope. Using this approach, we performed assessment of 4 groups of 283 currently known human MHC-class-I epitopes including differentiation antigens, overexpressed proteins, cancer-testis antigens and mutations displayed by tumor cells. In addition, 89 epitopes originating from viral sources were investigated. The natural occurrence of these epitopes in human tissues was assessed based on proteomics abundance data, while the probability of their presentation by MHC-class-I molecules was modelled by the method of Keşmir et al. which combines proteasomal cleavage, TAP affinity and MHC-binding predictions. The results of these analyses for many previously defined peptides are presented as CR indices and tissue profiles. The methodology thus allows for quantitative comparisons of epitopes and is suggested to be suited for the assessment of epitopes of candidate antigens in an early stage of development of adoptive immunotherapy. Our method is implemented as a Java program, with curated datasets stored in a MySQL database. It predicts all naturally possible self-antigens for a given sequence of a therapeutic antigen (or epitope) and after filtering for predicted immunogenicity outputs results as an index and profile of CR to the self-antigens in 22 human tissues. The program is implemented as part of the iCrossR webserver, which is publicly available at http://webclu.bio.wzw.tum.de/icrossr/ CONTACT: d.frishman@wzw.tum.deSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press

  20. MISCIBILITY, SOLUBILITY, AND VISCOSITY MEASUREMENTS FOR R-236EA WITH POTENTIAL LUBRICANTS

    EPA Science Inventory

    The report gives results of miscibility, solubility, and viscosity measurements of refrigerant R-236ea with three potential lubricants. (NOTE: The data were needed to determine the suitability of refrigerant/lubricant combinations for use in refrigeration systems.) The lubricants...

  1. Ovarian tumor antigens.

    PubMed

    Bhattacharya, M; Barlow, J J

    1978-09-01

    Evidence has been reported for at least two common tumor-associated antigens, or antigenic determinants, in human cystadenocarcinomas of the ovary that are apparently absent in tissues of normal reproductive organs. These antigenic determinants are immunologically distinct from carcinoembryonic antigen, alpha-fetoprotein, ferritins and histocompatibility antigens. One of these two ovarian cystadenocarcinoma-associated antigens (OCAA) is not detectable in any ovarian carcinomas except serous or mucinous types, other gynecologic or nongynecologic malignancies thus far tested, while the second antigen is present in about 90% of all gynecologic tumors and occasionally in breast and colon tumors. OCAA has been purified and partially characterized. It is a high molecular weight glycoprotein which carries the unique ovarian tumor-specific antigenic determinant along with some normal cross-reacting determinants. High levels of this glycoprotein antigen have been detected in the sera of ovarian cancer patients with advanced disease by the radioimmunoassay inhibition technique. The serial determination of circulating OCAA appeared to correlate with tumor volume as well as the clinical status of the patients.

  2. Changes of serum IgG antibody reactivity to protein antigens of Treponema pallidum in syphilis patients after treatment.

    PubMed

    Kim, D K; Lee, M G; Lee, J B

    1989-06-01

    The changes of serum IgG antibody reactivity to protein antigens of Treponema pallidum after treatment of syphilis were observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. Until 9 to 12 months after treatment, it was seen that there was a loss of several antibodies and some diminution in their reactivity in primary, secondary and early latent syphilis, but no changes occurred in late latent and reinfected syphilis. In primary syphilis, there was a significant loss of two IgG antibodies to the treponemal antigens of molecular weights 68,500 and 47,000 at 11 months after treatment. According to our previous study, the treponemal antigen of molecular weight 68,500 was T. pallidum specific and appeared only in primary syphilis, and that of molecular weight 47,000 was one of the major antigens of T. pallidum. The reaction between serum IgG antibodies of 14 patients who had been treated for secondary, early latent and late latent syphilis 2 to 14 years ago and major antigens of T. pallidum was observed and any loss or decrease in reactivity was not discovered. From the results obtained, it was concluded that the observation of serum IgG antibody reactivity to protein antigens of T. pallidum is not helpful in evaluating the efficacy of treatment in secondary, early latent, late latent and reinfected syphilis. However, serum IgG antibodies to treponemal antigens of molecular weights 68,500 and 47,000 could possibly be useful in the assessment of the efficacy of treatment in primary syphilis.

  3. Changes of serum IgG antibody reactivity to protein antigens of Treponema pallidum in syphilis patients after treatment.

    PubMed Central

    Kim, D. K.; Lee, M. G.; Lee, J. B.

    1989-01-01

    The changes of serum IgG antibody reactivity to protein antigens of Treponema pallidum after treatment of syphilis were observed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. Until 9 to 12 months after treatment, it was seen that there was a loss of several antibodies and some diminution in their reactivity in primary, secondary and early latent syphilis, but no changes occurred in late latent and reinfected syphilis. In primary syphilis, there was a significant loss of two IgG antibodies to the treponemal antigens of molecular weights 68,500 and 47,000 at 11 months after treatment. According to our previous study, the treponemal antigen of molecular weight 68,500 was T. pallidum specific and appeared only in primary syphilis, and that of molecular weight 47,000 was one of the major antigens of T. pallidum. The reaction between serum IgG antibodies of 14 patients who had been treated for secondary, early latent and late latent syphilis 2 to 14 years ago and major antigens of T. pallidum was observed and any loss or decrease in reactivity was not discovered. From the results obtained, it was concluded that the observation of serum IgG antibody reactivity to protein antigens of T. pallidum is not helpful in evaluating the efficacy of treatment in secondary, early latent, late latent and reinfected syphilis. However, serum IgG antibodies to treponemal antigens of molecular weights 68,500 and 47,000 could possibly be useful in the assessment of the efficacy of treatment in primary syphilis. PMID:2688687

  4. Antigenic profile and localization of Clonorchis sinensis proteins in the course of infection

    PubMed Central

    Kim, Tae Yun; Song, Kye-Yong; Sohn, Woon-Mok; Kang, Shin-Yong

    2001-01-01

    In the course of Clonorchis sinensis infection, antigens presented to the hosts may be in a close relation to growth of the fluke. The antigenic proteins stimulating IgG antibody production were chronologically identified by immunoblot and localized by immunohistochemical staining. In the early stage of infection until 12 weeks post-infection (PI), antigens were proteins with molecular mass larger than 34 kDa which were derived from the tegument, testes and intrauterine eggs. After 20 weeks PI, antigens recognized were 29, 27 and 26 kDa proteins from the intestine, excretory bladder and reproductive organs. It is suggested that the tegumental proteins are the most potent antigens and the excretory-secretory proteins with middle molecular mass of 26-45 kDa contribute to the high level production of antibodies after 20 weeks of the C. sinensis infection. PMID:11775331

  5. Immunodiagnosis of fascioliasis using sandwich enzyme-linked immunosorbent assay for detection of Fasciola gigantica paramyosin antigen

    PubMed Central

    Abou-Elhakam, Hany Mohamed Adel; Bauomy, Ibraheem Rabia; El Deeb, Somaya Osman; El Amir, Azza Mohamed

    2013-01-01

    Background: Many immunological techniques have been developed over years using the different Fasciola antigens for diagnosis of parasitic infection and to replace the parasitological techniques, which are time consuming and usually lack sensitivity and reproducibility. Materials and Methods: In this study, Fasciola gigantica paramyosin (Pmy) antigen was early detected in cattle sera using sandwich enzyme-linked immunosorbent assay (ELISA), to evaluate the Pmy antigen performance in diagnosis. This work was conducted on 135 cattle blood samples, which were classified according to parasitological investigation into, healthy control (30), fascioliasis (75), and other parasites (30) groups. Results: The sensitivity of Sandwich ELISA was 97.33%, and the specificity was 95%, in comparison with parasitological examination, which recorded 66.66% sensitivity and 100% specificity, respectively. Conclusions: It was clear that the native F. gigantica Pmy is considered as a powerful antigen in early immunodiagnosis of fascioliasis, using a highly sensitive and specific sandwich ELISA technique. PMID:23961441

  6. The Doctrine of Original Antigenic Sin: Separating Good From Evil.

    PubMed

    Monto, Arnold S; Malosh, Ryan E; Petrie, Joshua G; Martin, Emily T

    2017-06-15

    The term "original antigenic sin" was coined approximately 60 years ago to describe the imprinting by the initial first influenza A virus infection on the antibody response to subsequent vaccination. These studies did not suggest a reduction in the response to current antigens but instead suggested anamnestic recall of antibody to earlier influenza virus strains. Then, approximately 40 years ago, it was observed that sequential influenza vaccination might lead to reduced vaccine effectiveness (VE). This conclusion was largely dismissed after an experimental study involving sequential administration of then-standard influenza vaccines. Recent observations have provided convincing evidence that reduced VE after sequential influenza vaccination is a real phenomenon. We propose that such reduction in VE be termed "negative antigenic interaction," given that there is no age cohort effect. In contrast, the potentially positive protective effect of early influenza virus infection later in life continues to be observed. It is essential that we understand better the immunologic factors underlying both original antigenic sin and negative antigenic interaction, to support development of improved influenza vaccines and vaccination strategies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  7. Global Inhibition of DC Priming Capacity in the Spleen of Self-Antigen Vaccinated Mice Requires IL-10.

    PubMed

    Marvel, Douglas M; Finn, Olivera J

    2014-01-01

    Dendritic cells (DC) in the spleen are highly activated following intravenous vaccination with a foreign-antigen, promoting expansion of effector T cells, but remain phenotypically and functionally immature after vaccination with a self-antigen. Up-regulation or suppression of expression of a cohort of pancreatic enzymes 24-72 h post-vaccination can be used as a biomarker of stimulatory versus tolerogenic DC, respectively. Here we show, using MUC1 transgenic mice and a vaccine based on the MUC1 peptide, which these mice perceive as a self-antigen, that the difference in enzyme expression that predicts whether DC will promote immune response or immune tolerance is seen as early as 4-8 h following vaccination. We also identify early production of IL-10 as a predominant factor that both correlates with this early-time point and controls DC function. Pre-treating mice with an antibody against the IL-10 receptor prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses. This study suggests that transient inhibition of IL-10 prior to vaccination could improve responses to cancer vaccines that utilize self-tumor antigens.

  8. Headspace solid phase microextraction--GC/C-IRMS for delta13CVPDB measurements of mono-aromatic hydrocarbons using EA-IRMS calibration.

    PubMed

    Ebongué, Véronique Woule; Geypens, Benny; Berglund, Michael; Taylor, Philip

    2009-03-01

    This work aims at comparing the delta(13)C(VPDB) of mono-aromatic hydrocarbons benzene, toluene, ethylbenzene and xylene isomers (BTEX) measured by elemental analyser (EA)-isotope ratio mass spectrometer (IRMS) with the delta(13)C(VPDB) measured on the same compounds by headspace solid phase microextraction - GC/C-IRMS (hSPME - GC/C-IRMS) with the final goal of using these compounds as internal standards on the latter system. The EA-IRMS measurements were done using calcium and lithium carbonate isotopic reference materials: NBS19 and L-SVEC for establishing the delta(13)C(VPDB) scale. The EA-IRMS measurements with helium dilution of a set of five reference materials (USGS40, USGS41, IAEA-CH-6, IAEA-CH-3 and IAEA-601) show systematic bias of 1 per thousand relative to their assigned values. This bias due to the dilution mechanism in the used ConfloII interface device could not be avoided. As the selected hydrocarbons: BTEX could not be analysed by EA-IRMS without helium dilution, their delta(13)C(VPDB) must be corrected from this observed bias using an external calibration. The CO(2) gas calibrated using EA-IRMS without helium dilution, was used as an in-house reference for the delta(13)C(VPDB) measurements of the BTEX by the hSPME - GC/C-IRMS system. The comparison made between the delta(13)C(VPDB) measured on the same BTEX compounds by EA-IRMS (with external calibration) and by hSPME - GC/C-IRMS techniques showed good agreement.

  9. 77 FR 33780 - Interim Staff Guidance JLD-ISG-2012-03; Compliance with Order EA-12-051, Order Modifying Licenses...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-07

    ... Fukushima Dai-ichi nuclear power plant in March 2011. Order EA-12-051 requires all licensees and... complying with Order EA-12-051. Following the events at the Fukushima Dai-ichi nuclear power plant, the NRC... agency should make additional improvements to these programs in light of the events at Fukushima Dai-ichi...

  10. cTnT can be a useful marker for early detection of anthracycline cardiotoxicity.

    PubMed

    Kilickap, S; Barista, I; Akgul, E; Aytemir, K; Aksoyek, S; Aksoy, S; Celik, I; Kes, S; Tekuzman, G

    2005-05-01

    The level of serum cardiac troponin-T (cTnT) increases with myocardial damage. We sought to assess whether cTnT level could be a useful marker for the early detection of anthracycline cardiotoxicity. Forty-one patients who had been scheduled to receive anthracycline-containing combination chemotherapy were included in the study. Serum cTnT levels were measured before (baseline) and after the first cycle of chemotherapy, and again, after the last cycle of chemotherapy. In all patients, the left ventricular ejection fraction (LVEF), fractional shortening (FS), early peak flow/atrial flow velocity (E/A) ratio, and the isovolemic relaxation time (IRT) were measured echocardiographically, both before and after the completion of chemotherapy. LVEF and FS did not change in any patients. In 21 patients (49%), the E/A ratio decreased after therapy as compared to the pre-treatment values. The decrease in E/A ratio was more prominent in patients who were older than the mean age of our study group, which was 44 years. The post-treatment IRT was prolonged compared with the pretreatment IRT (94.0 +/- 2.0 versus 85.6 +/- 10.5 ms, respectively). cTnT levels after completion of therapy were elevated in 14 (34%) patients, and exceeded the upper limit of the normal range (>0.1 ng/ml) in only one patient. cTnT levels measured after completion of therapy were significantly higher, compared with those measured at baseline and after the first cycle of therapy. In the younger age group (< or =44 years old), there was a two-fold decrease in the E/A ratio in those patients whose cTnT levels increased during the therapy, when compared with those whose cTnT levels did not change (21% versus 43%, respectively). Increased serum cTnT level can be detected in the early stages of anthracycline therapy and it is associated with diastolic dysfunction of the left ventricle. Therefore, serum cTnT level could be a useful measure for early detection of anthracycline-induced cardiotoxicity.

  11. Tumor-Derived Microvesicles Modulate Antigen Cross-Processing via Reactive Oxygen Species-Mediated Alkalinization of Phagosomal Compartment in Dendritic Cells.

    PubMed

    Battisti, Federico; Napoletano, Chiara; Rahimi Koshkaki, Hassan; Belleudi, Francesca; Zizzari, Ilaria Grazia; Ruscito, Ilary; Palchetti, Sara; Bellati, Filippo; Benedetti Panici, Pierluigi; Torrisi, Maria Rosaria; Caracciolo, Giulio; Altieri, Fabio; Nuti, Marianna; Rughetti, Aurelia

    2017-01-01

    Dendritic cells (DCs) are the only antigen-presenting cells able to prime naïve T cells and cross-prime antigen-specific CD8 + T cells. Their functionality is a requirement for the induction and maintenance of long-lasting cancer immunity. Albeit intensively investigated, the in vivo mechanisms underlying efficient antigen cross-processing and presentation are not fully understood. Several pieces of evidence indicate that antigen transfer to DCs mediated by microvesicles (MVs) enhances antigen immunogenicity. This mechanism is also relevant for cross-presentation of those tumor-associated glycoproteins such as MUC1 that are blocked in HLA class II compartment when internalized by DCs as soluble molecules. Here, we present pieces of evidence that the internalization of tumor-derived MVs modulates antigen-processing machinery of DCs. Employing MVs derived from ovarian cancer ascites fluid and established tumor cell lines, we show that MV uptake modifies DC phagosomal microenvironment, triggering reactive oxygen species (ROS) accumulation and early alkalinization. Indeed, tumor MVs carry radical species and the MV uptake by DCs counteracts the chemically mediated acidification of the phagosomal compartment. Further pieces of evidence suggest that efficacious antigen cross-priming of the MUC1 antigen carried by the tumor MVs results from the early signaling induced by MV internalization and the function of the antigen-processing machinery of DCs. These results strongly support the hypothesis that tumor-derived MVs impact antigen immunogenicity by tuning the antigen-processing machinery of DCs, besides being carrier of tumor antigens. Furthermore, these findings have important implications for the exploitation of MVs as antigenic cell-free immunogen for DC-based therapeutic strategies.

  12. 75 FR 45075 - Airworthiness Directives; Eclipse Aerospace, Inc. Model EA500 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-02

    ... Airworthiness Directives; Eclipse Aerospace, Inc. Model EA500 Airplanes AGENCY: Federal Aviation Administration... in the Federal Register on July 9, 2010 (75 FR 39472), and applies to certain Eclipse Aerospace, Inc... Federal holidays. For service information identified in this proposed AD, contact Eclipse Aerospace, Inc...

  13. The immunogenicity of Echinococcus granulosus antigen 5 is determined by its post-translational modifications.

    PubMed

    Lorenzo, C; Last, J A; González-Sapienza, G G

    2005-11-01

    Since its early introduction as a marker for the immunodiagnosis of hydatid disease, antigen 5 (Ag5) has been regarded as one of the more relevant antigens of Echinococcus granulosus, and it is still widely used in different confirmation techniques. In this work we prepared 2 recombinant forms of the antigen, namely, rAg5 (corresponding to the unprocessed polypeptide chain of the antigen) and rAg5-38s (corresponding to its 38 kDa subunit). Their antigenicities were compared to that of the native antigen using a human serum collection. There was a major drop in the reactivity of the sera, particularly against rAg5-38s, which was confirmed by analysis of the cross-reactivity of 2 panels of monoclonal antibodies specific for rAg5-38s and the native antigen. Using the chemically deglycosylated native antigen, we demonstrated that the reduced antigenicity of the recombinants is due to the loss of the sugar determinants, and not to their misfolding. Inhibition experiments using phosphorylcholine confirmed that this moiety also contributes to the reactivity of the antigen, but to a much lesser extent. The presence of immunodominant highly cross-reactive glycan moieties in the Ag5 molecule may involve a parasite evasion mechanism.

  14. Cancer chemopreventive agents, labdane diterpenoids from the stem bark of Thuja standishii (Gord.) Carr.

    PubMed

    Tanaka, R; Ohtsu, H; Iwamoto, M; Minami, T; Tokuda, H; Nishino, H; Matsunaga, S; Yoshitake, A

    2000-12-20

    Seven labdane-type diterpenoids from the stem bark of Thuja standishii (Gord.) Carr. (Cupressaceae) and their analogues showed strong inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among these compounds, 15,16-bisnor-13-oxolabda-8(17), 11E-dien-19-oic acid was revealed to have the strongest inhibitory effect on the EBV-EA activation, being stronger than that of beta-carotene which has been intensively studied in cancer prevention using animal models. 15,16-bisnor-13-Oxolabda-8(17), 11E-dien-19-oic acid was also found to exhibit the excellent anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

  15. Towards preserving the immunogenicity of protein antigens carried by nanoparticles while avoiding the cold chain.

    PubMed

    Sloat, Brian R; Sandoval, Michael A; Cui, Zhengrong

    2010-06-30

    Nanoparticles are an attractive vaccine carrier with potent adjuvant activity. Data from our previous studies showed that immunization of mice with lecithin/glyceryl monostearate-based nanoparticles with protein antigens conjugated onto their surface induced a strong, quick, and long-lasting antigen-specific immune response. In the present study, we evaluated the feasibility of preserving the immunogenicity of protein antigens carried by nanoparticles without refrigeration using these antigen-conjugated nanoparticles as a model. The nanoparticles were lyophilized, and the immunogenicity of the antigens was evaluated in a mouse model using bovine serum albumin or the Bacillus anthracis protective antigen protein as model antigens. With proper excipients, the nanoparticles can be lyophilized while maintaining the immunogenicity of the antigens. Moreover, the immunogenicity of the model antigen conjugated onto the nanoparticles was undamaged after a relatively extended period of storage at room temperature or under accelerated conditions (37 degrees C) when the nanoparticles were lyophilized with 5% mannitol plus 1% polyvinylpyrrolidone. To our knowledge, the present study represents an early attempt to preserve the immunogenicity of the protein antigens carried by nanoparticles without refrigeration. 2010 Elsevier B.V. All rights reserved.

  16. Galactofuranose antigens, a target for diagnosis of fungal infections in humans

    PubMed Central

    Marino, Carla; Rinflerch, Adriana; de Lederkremer, Rosa M

    2017-01-01

    The use of biomarkers for the detection of fungal infections is of interest to complement histopathological and culture methods. Since the production of antibodies in immunocompromised patients is scarce, detection of a specific antigen could be effective for early diagnosis. D-Galactofuranose (Galf) is the antigenic epitope in glycoconjugates of several pathogenic fungi. Since Galf is not biosynthesized by mammals, it is an attractive candidate for diagnosis of infection. A monoclonal antibody that recognizes Galf is commercialized for detection of aspergillosis. The linkage of Galf in the natural glycans and the chemical structures of the synthesized Galf-containing oligosaccharides are described in this paper. The oligosaccharides could be used for the synthesis of artificial carbohydrate-based antigens, not enough exploited for diagnosis. PMID:28883999

  17. Galactofuranose antigens, a target for diagnosis of fungal infections in humans.

    PubMed

    Marino, Carla; Rinflerch, Adriana; de Lederkremer, Rosa M

    2017-08-01

    The use of biomarkers for the detection of fungal infections is of interest to complement histopathological and culture methods. Since the production of antibodies in immunocompromised patients is scarce, detection of a specific antigen could be effective for early diagnosis. D-Galactofuranose (Gal f ) is the antigenic epitope in glycoconjugates of several pathogenic fungi. Since Gal f is not biosynthesized by mammals, it is an attractive candidate for diagnosis of infection. A monoclonal antibody that recognizes Gal f is commercialized for detection of aspergillosis. The linkage of Gal f in the natural glycans and the chemical structures of the synthesized Gal f -containing oligosaccharides are described in this paper. The oligosaccharides could be used for the synthesis of artificial carbohydrate-based antigens, not enough exploited for diagnosis.

  18. Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells.

    PubMed

    Chmielewski, Markus; Hombach, Andreas A; Abken, Hinrich

    2013-01-01

    Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a "tumor-associated antigen" and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer.

  19. Impacts of the EA and SCA patterns on the 20th century NAO-winter precipitation relationship in Europe

    NASA Astrophysics Data System (ADS)

    Comas-Bru, Laia; McDermott, Frank

    2013-04-01

    Much of the 20th century multi-decadal variability in the NAO-winter precipitation relationship over the N. Atlantic / European sector can be ascribed to the combined effects of the North Atlantic Oscillation (NAO) and either the East Atlantic pattern (EA) or the Scandinavian pattern (SCA). The NAO, EA and SCA indices employed here are defined as the three leading vectors of the cross-correlation matrix calculated from monthly sea-level pressure anomalies for 138 complete winters from the 20CRv2 dataset (Compo et al., 2011). Winter precipitation data over Europe for the entire 20th century is derived from the high resolution CRU-TS3.1 climate dataset (Mitchell and Jones, 2005). Here we document for the first time, that different NAO/EA and NAO/SCA combinations systematically influence winter precipitation conditions in Europe as a consequence of NAO dipole migrations. We find that the zero-correlated line of the NAO-winter precipitation relationship migrates southwards when the EA is in the opposite phase to the NAO. This can be related to a south-westwards migration of the NAO dipole under these conditions, as shown by teleconnectivity maps. Similarly, a clockwise movement of the NAO-winter climate correlated areas occurs when the phase of the SCA is opposite to that of the NAO, reflecting a clockwise movement of the NAO dipole under these conditions. An important implication of these migrations is that they influence the spatial and temporal stationarity of climate-NAO relationships. As a result, the link between winter precipitation patterns and the NAO is not straightforward in some regions such as the southern UK, Ireland and France. For instance, much of the inter-annual variability in the N-S winter precipitation gradient in the UK, originally attributed to inter-annual and inter-decadal variability of the NAO, reflects the migration of the NAO dipole, linked to linear combinations of the NAO and the EA. Our results indicate that when the N-S winter

  20. An SEM Assessment of the Internal Structure and Predictive Validity of the Abbreviated Early Adolescent HOME Inventory.

    PubMed

    Green, Samuel B; Pennar, Amy L; Bradley, Robert H

    2018-05-01

    The Home Observation for Measurement of the Environment (HOME) Inventory is designed to assess the quality and quantity of support, stimulation, and structure provided to children in the home environment. HOME has been widely used for research and applied purposes. We focused on an abbreviated version of the Early Adolescent HOME (EA-HOME-A) that was administered to 15-year-old adolescents and their parents ( N = 958) as part of the NICHD (National Institute of Child Health and Human Development) Study of Early Child Care and Youth Development. Our study had two objectives. First, we hypothesized and tested a bifactor model that specified a general factor in support of the use of the HOME total score and group factors for subsets of items in support of the content domain scores. Second, we applied structural equation modeling to relate the EA-HOME-A factors to outcome factors assessing maladaptive behaviors, autonomy, self-control, and cognitive-academic performance. The results supported the construct validity of the EA-HOME-A with respect to its internal structure as well as its correlates.

  1. Surface-water Interface Induces Conformational Changes Critical for Protein Adsorption: Implications for Monolayer Formation of EAS Hydrophobin.

    PubMed

    Ley, Kamron; Christofferson, Andrew; Penna, Matthew; Winkler, Dave; Maclaughlin, Shane; Yarovsky, Irene

    2015-01-01

    The class I hydrophobin EAS is part of a family of small, amphiphilic fungal proteins best known for their ability to self-assemble into stable monolayers that modify the hydrophobicity of a surface to facilitate further microbial growth. These proteins have attracted increasing attention for industrial and biomedical applications, with the aim of designing surfaces that have the potential to maintain their clean state by resisting non-specific protein binding. To gain a better understanding of this process, we have employed all-atom molecular dynamics to study initial stages of the spontaneous adsorption of monomeric EAS hydrophobin on fully hydroxylated silica, a commonly used industrial and biomedical substrate. Particular interest has been paid to the Cys3-Cys4 loop, which has been shown to exhibit disruptive behavior in solution, and the Cys7-Cys8 loop, which is believed to be involved in the aggregation of EAS hydrophobin at interfaces. Specific and water mediated interactions with the surface were also analyzed. We have identified two possible binding motifs, one which allows unfolding of the Cys7-Cys8 loop due to the surfactant-like behavior of the Cys3-Cys4 loop, and another which has limited unfolding due to the Cys3-Cys4 loop remaining disordered in solution. We have also identified intermittent interactions with water which mediate the protein adsorption to the surface, as well as longer lasting interactions which control the diffusion of water around the adsorption site. These results have shown that EAS behaves in a similar way at the air-water and surface-water interfaces, and have also highlighted the need for hydrophilic ligand functionalization of the silica surface in order to prevent the adsorption of EAS hydrophobin.

  2. Surface-water Interface Induces Conformational Changes Critical for Protein Adsorption: Implications for Monolayer Formation of EAS Hydrophobin

    PubMed Central

    Ley, Kamron; Christofferson, Andrew; Penna, Matthew; Winkler, Dave; Maclaughlin, Shane; Yarovsky, Irene

    2015-01-01

    The class I hydrophobin EAS is part of a family of small, amphiphilic fungal proteins best known for their ability to self-assemble into stable monolayers that modify the hydrophobicity of a surface to facilitate further microbial growth. These proteins have attracted increasing attention for industrial and biomedical applications, with the aim of designing surfaces that have the potential to maintain their clean state by resisting non-specific protein binding. To gain a better understanding of this process, we have employed all-atom molecular dynamics to study initial stages of the spontaneous adsorption of monomeric EAS hydrophobin on fully hydroxylated silica, a commonly used industrial and biomedical substrate. Particular interest has been paid to the Cys3-Cys4 loop, which has been shown to exhibit disruptive behavior in solution, and the Cys7-Cys8 loop, which is believed to be involved in the aggregation of EAS hydrophobin at interfaces. Specific and water mediated interactions with the surface were also analyzed. We have identified two possible binding motifs, one which allows unfolding of the Cys7-Cys8 loop due to the surfactant-like behavior of the Cys3-Cys4 loop, and another which has limited unfolding due to the Cys3-Cys4 loop remaining disordered in solution. We have also identified intermittent interactions with water which mediate the protein adsorption to the surface, as well as longer lasting interactions which control the diffusion of water around the adsorption site. These results have shown that EAS behaves in a similar way at the air-water and surface-water interfaces, and have also highlighted the need for hydrophilic ligand functionalization of the silica surface in order to prevent the adsorption of EAS hydrophobin. PMID:26636091

  3. ScreenPro FH: from the Czech MedPed to international collaboration. ScreenPro FH is a participating project of the EAS-FHCS.

    PubMed

    Ceska, R; Freiberger, T; Vaclova, M; Aleksicova, T; Votavova, L; Vrablik, M

    2017-04-05

    This article describes the evolution of our understanding of familial hypercholesterolemia (FH) in the Central, Eastern, and Southern Europe (CESE) region, and the dissemination of this understanding to other countries. Using the ScreenPro FH project as an example, we would like to illustrate the progression from national objectives, to regional networking and, finally, to international collaboration via the Familial Hypercholesterolemia Studies Collaboration (FHSC) project under the leadership of the European Atherosclerosis Society (EAS). It is essential to improve our ability to diagnose FH. In this regard, the EAS and its FHSC project must be commended for their educational and organizational activities which, above all, are dedicated to the creation of a global FH patient registry. In the CESE region, FH diagnostics and treatment situation are markedly different than in Western Europe or North America. Since the Czech MedPed project (Make Early Diagnoses to Prevent Early Deaths in Medical Pedigrees) has been so successful (with results not only comparable to, but, for some parameters, even surpassing the results of many Western countries) we decided to apply the Czech experience to the CESE region. Thus, the ScreenPro FH project was created. The aim of ScreenPro FH is to create a specialist network in the CESE region. The primary objective of the ScreenPro FH project was to dramatically reduce the number of premature deaths due to clinical complications of atherosclerosis in FH patients. At present, ScreenPro FH comprises 18 member countries with a total population of 500,000,000; which, in terms of the FH population, represents 1-2 million patients.

  4. A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer

    PubMed Central

    Lagisetty, Kiran H.; Tran, Eric; Zheng, Zhili; Gattinoni, Luca; Yu, Zhiya; Burns, William R.; Miermont, Anne M.; Teper, Yaroslav; Rudloff, Udo; Restifo, Nicholas P.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.

    2014-01-01

    Abstract Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity. PMID:24694017

  5. Hadronic interactions and EAS muon pseudorapidities investigated with the Muon Tracking Detector in KASCADE-Grande

    NASA Astrophysics Data System (ADS)

    Zabierowski, J.; Apel, W. D.; Arteaga, J. C.; Badea, F.; Bekk, K.; Bertaina, M.; Blümer, H.; Bozdog, H.; Brancus, I. M.; Brüggemann, M.; Buchholz, P.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Daumiller, K.; de Souza, V.; di Pierro, F.; Doll, P.; Engel, R.; Engler, J.; Finger, M.; Fuhrmann, D.; Ghia, P. L.; Gils, H. J.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Huege, T.; Isar, P. G.; Kampert, K.-H.; Kang, D.; Kickelbick, D.; Klages, H. O.; Kolotaev, Y.; Łuczak, P.; Mathes, H. J.; Mayer, H. J.; Milke, J.; Mitrica, B.; Morello, C.; Navarra, G.; Nehls, S.; Oehlschläger, J.; Ostapchenko, S.; Petcu, M.; Pierog, T.; Rebel, H.; Roth, M.; Schieler, H.; Schröder, F.; Sima, O.; Stümpert, M.; Toma, G.; Trinchero, G. C.; Ulrich, H.; van Buren, J.; Walkowiak, W.; Weindl, A.; Wochele, J.; Wommer, M.; KASCADE-Grande Collaboration

    2009-12-01

    The Muon Tracking Detector in the KASCADE-Grande EAS experiment allows the precise measurement of shower muon directions up to 700 m distance from the shower center. This directional information is used to study the pseudorapidity of muons in EAS, closely related to the pseudorapidity of their parent mesons. Moreover, the mean value of muon pseudorapidity in a registered shower reflects the longitudinal development of its hadronic component. All of this makes it a good tool for testing hadronic interaction models. The possibilities of such tests given by the KASCADE-Grande experimental setup are discussed and an example of the obtained muon pseudorapidity spectrum is shown.

  6. Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.

    PubMed

    Neubauer, R H; Rabin, H; Strnad, B C; Lapin, B A; Yakovleva, L A; Indzie, E

    1979-02-01

    An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses.

  7. Demonstration of human kidney differentiation antigens with monoclonal antibodies.

    PubMed

    Candelier, J J; Couillin, P; Bellon, G; Le Pendu, J; Eydoux, P; Boue, A

    1988-10-01

    Six human differentiation antigens (EE24.6, EG9.11, EG14.1, EI16.1, EK8.1, EK17.1) have been defined using monoclonal antibodies obtained from mice immunized with embryonic kidney cells. Their histologic distribution was determined on frozen sections of embryonic, fetal, and adult human kidneys by immunofluorescence assay. EE24.6, an ureteral bud marker, was detected only on the germ layer of mature kidney urothelium. EG9.11 and EG14.1 were detected on the S-shaped bodies and also on the adult proximal convoluted tubule for the former and the glomerular basement membrane for the latter. EI16.1, a marker of condensed mesenchyme, was detected only on epithelial cells of adult proximal convoluted tubule. EK8.1 was found in the mesangium, connective tissue, and with particularly dense labeling in the basement membranes. This labeling pattern was present throughout renal organogenesis. EK17.1 recognized both cell and plasma human fibronectins. Staining for all antibodies was nearly identical in mesonephros and metanephros. These results demonstate that some antigens follow their embryonic destiny. They indicate an antigenic similarity between the mesonephros and the metanephros and, therefore, a very early appearance of these antigens. During differentiation, these antigens concentrate on more defined structures, and staining became increased with an increased degree of differentiation.

  8. Characteristics of Ni-Cr-Fe laser clad layers on EA4T steel

    NASA Astrophysics Data System (ADS)

    Chen, Wenjing; Chen, Hui; Wang, Yongjing; Li, Congchen; Wang, Xiaoli

    2017-07-01

    The Ni-Cr-Fe metal powder was deposited on EA4T steel by laser cladding technology. The microstructure and chemical composition of the cladding layer were analyzed by optical microscopy (OM), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The bonding ability between the cladding layer and the matrix was measured. The results showed that the bonding between the cladding layer and the EA4T steel was metallurgical bonding. The microstructure of cladding layer was composed of planar crystals, columnar crystals and dendrite, which consisted of Cr2Ni3, γ phase, M23C6 and Ni3B phases. When the powder feeding speed reached 4 g/min, the upper bainite occurred in the heat affected zone (HAZ). Moreover, the tensile strength of the joint increased, while the yield strength and the ductility decreased.

  9. Miscibility, solubility, viscosity, and density measurements for R-236ea with four different Exxon lubricants. Final report, March 1995-March 1997

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kang, H.M.; Pate, M.B.

    1999-06-15

    The report discusses miscibility, solubility, viscosity, and density data for the refrigerant hydrofluorocarbon (HFC)-236ea (or R-236ea) and four lubricants supplied by Exxon Corporation. The miscibility tests were performed in a test facility consisting of a series of miniature test cells submerged in a constant temperature bath, precisely controlled over a range of {minus}50 to 90 C. Critical solution temperatures obtained from the miscibility data are presented for each refrigerant/lubricant combination. Data for the R-236ea in each of the test lubricants have been collected for refrigerant concentrations of 10--90%. The raw data have been presented, and the results have been summarized.more » Solubility, viscosity, and density data were also obtained for R-236ea mixed with the same four oils for a refrigerant concentration range of 0--40 wt% refrigerant over a temperature range of 30--100 C.« less

  10. Glioma antigen.

    PubMed

    Toda, Masahiro

    2012-01-01

    Because several antigenic peptides of human tumors that are recognized by T-lymphocytes have been identified, immune responses against cancer can now be artificially manipulated. Furthermore, since T-lymphocytes have been found to play an important role in the rejection of tumors by the host and also to have antigen-specific proliferative potentials and memory mechanisms, T-lymphocytes are thought to play a central role in cancer vaccination. Although multidisciplinary therapies have been attempted for the treatment of gliomas, the results remain unsatisfactory. For the development of new therapies against gliomas, it is required to identify tumor antigens as targets for specific immunotherapy. In this chapter, recent progress in research on glioma antigens is described.

  11. Global Inhibition of DC Priming Capacity in the Spleen of Self-Antigen Vaccinated Mice Requires IL-10

    PubMed Central

    Marvel, Douglas M.; Finn, Olivera J.

    2014-01-01

    Dendritic cells (DC) in the spleen are highly activated following intravenous vaccination with a foreign-antigen, promoting expansion of effector T cells, but remain phenotypically and functionally immature after vaccination with a self-antigen. Up-regulation or suppression of expression of a cohort of pancreatic enzymes 24–72 h post-vaccination can be used as a biomarker of stimulatory versus tolerogenic DC, respectively. Here we show, using MUC1 transgenic mice and a vaccine based on the MUC1 peptide, which these mice perceive as a self-antigen, that the difference in enzyme expression that predicts whether DC will promote immune response or immune tolerance is seen as early as 4–8 h following vaccination. We also identify early production of IL-10 as a predominant factor that both correlates with this early-time point and controls DC function. Pre-treating mice with an antibody against the IL-10 receptor prior to vaccination results in DC that up-regulate CD40, CD80, and CD86 and promote stronger IFNγ+ T cell responses. This study suggests that transient inhibition of IL-10 prior to vaccination could improve responses to cancer vaccines that utilize self-tumor antigens. PMID:24596571

  12. The maximum depth of shower with E sub 0 larger than 10(17) eV on average characteristics of EAS different components

    NASA Technical Reports Server (NTRS)

    Glushkov, A. V.; Efimov, N. N.; Makarov, I. T.; Pravdin, M. I.; Dedenko, L. G.

    1985-01-01

    The extensive air shower (EAS) development model independent method of the determination of a maximum depth of shower (X sub m) is considered. X sub m values obtained on various EAS parameters are in a good agreement.

  13. The genome of the Erwinia amylovora phage PhiEaH1 reveals greater diversity and broadens the applicability of phages for the treatment of fire blight.

    PubMed

    Meczker, Katalin; Dömötör, Dóra; Vass, János; Rákhely, Gábor; Schneider, György; Kovács, Tamás

    2014-01-01

    The enterobacterium Erwinia amylovora is the causal agent of fire blight. This study presents the analysis of the complete genome of phage PhiEaH1, isolated from the soil surrounding an E. amylovora-infected apple tree in Hungary. Its genome is 218 kb in size, containing 244 ORFs. PhiEaH1 is the second E. amylovora infecting phage from the Siphoviridae family whose complete genome sequence was determined. Beside PhiEaH2, PhiEaH1 is the other active component of Erwiphage, the first bacteriophage-based pesticide on the market against E. amylovora. Comparative genome analysis in this study has revealed that PhiEaH1 not only differs from the 10 formerly sequenced E. amylovora bacteriophages belonging to other phage families, but also from PhiEaH2. Sequencing of more Siphoviridae phage genomes might reveal further diversity, providing opportunities for the development of even more effective biological control agents, phage cocktails against Erwinia fire blight disease of commercial fruit crops.

  14. 47 CFR 90.359 - Field strength limits for EA-licensed LMS systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Field strength limits for EA-licensed LMS systems. 90.359 Section 90.359 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Intelligent Transportation Systems Radio Service § 90.359 Field strength limits for...

  15. [Recombinant OspC identification and antigenicity detection from Borrelia burgdorferi PD91 in China].

    PubMed

    Chen, Jian; Wan, Kang-Lin

    2003-10-01

    To recombine OspC gene from Borrelia burgdorferi PD91 of China and expressed it in E. coli for early diagnosis of Lyme disease. The OspC gene was amplified from the genome of Borrelia burgdorferi PD91 strain by polymerase chain reaction and recombined with plasmid PET-11D. The recombinant plasmid PET-11D-OspC was identified with PCR, restriction endonuclease analysis and sequencing. The antigenicity was verified with Western Blot. OspC gene was cloned correctly into vector PET-11D. The resultant sequence was definitely different from the published sequence. The recombinant OspC seemed to have had strong antigenicity. The findings laid basis for the studies on early diagnosis of Lyme disease.

  16. The Value of Workshops on Psychological Flexibility for Early Childhood Special Education Staff

    PubMed Central

    Biglan, Anthony; Layton, Georgia L.; Jones, Laura Backen; Hankins, Martin; Rusby, Julie C.

    2013-01-01

    High stress and burnout are common for early childhood special educators, contributing to high rates of attrition, diminished educational effectiveness, and high turnover. Acceptance and Commitment Therapy (ACT) is a promising approach for the prevention and treatment of a wide variety of problems. Using a randomized wait-list control design, this pilot study evaluated whether ACT workshops delivered to preschool teachers who serve children with developmental disabilities would improve stress-related problems of teachers (i.e., stress, depression, and burnout) and increase collegial support. At pretest, measures of experiential avoidance (EA) and mindful awareness (MA) showed significant relationships to reports of depression, stress, and burnout. The intervention reduced staff members' EA, increased teachers' MA and valued living (VL), and improved teachers' sense of efficacy. This suggests that ACT workshops can help influence factors affecting depression, stress, and burnout in an early childhood special education setting. PMID:24223451

  17. Lead-resistant Providencia alcalifaciens strain 2EA bioprecipitates Pb+2 as lead phosphate.

    PubMed

    Naik, M M; Khanolkar, D; Dubey, S K

    2013-02-01

    A lead-resistant bacteria isolated from soil contaminated with car battery waste were identified as Providencia alcalifaciens based on biochemical characteristics, FAME profile and 16S rRNA sequencing and designated as strain 2EA. It resists lead nitrate up to 0·0014 mol l(-1) by precipitating soluble lead as insoluble light brown solid. Scanning electron microscopy coupled with energy-dispersive X-ray spectrometric analysis (SEM-EDX) and X-ray diffraction spectroscopy (XRD) revealed extracellular light brown precipitate as lead orthophosphate mineral, that is, Pb(9) (PO(4))(6) catalysed by phosphatase enzyme. This lead-resistant bacterial strain also demonstrated tolerance to high levels of cadmium and mercury along with multiple antibiotic resistance. Providencia alcalifaciens strain 2EA could be used for bioremediation of lead-contaminated environmental sites, as it can efficiently precipitate lead as lead phosphate. © 2012 The Society for Applied Microbiology.

  18. Specific binding of antigen-antibody in physiological environments: Measurement, force characteristics and analysis

    NASA Astrophysics Data System (ADS)

    Gu, Xin; Zhou, Jun; Zhou, Lu; Xie, Shusen; Petti, Lucia; Wang, Shaomin; Wang, Fuyan

    2018-05-01

    The specific recognition of the antigen by the antibody is the crucial step in immunoassays. Measurement and analysis of the specific recognition, including the ways in which it is influenced by external factors are of paramount significance for the quality of the immunoassays. Using prostate-specific antigen (PSA)/anti-PSA antibody and α-fetoprotein (AFP) /anti-AFP antibody as examples, we have proposed a novel solution for measuring the binding forces between the antigens and their corresponding antibodies in different physiological environments by combining laminar flow control technology and optical tweezers technology. On the basis of the experimental results, the different binding forces of PSA/anti-PSA antibody and AFP/anti-AFP antibody in the same phosphate-buffered saline (PBS) environments are analysed by comparing the affinity constant of the two antibodies and the number of antigenic determinants of the two antigens. In different electrolyte environments, the changes of the binding force of antigens-antibodies are explained by the polyelectrolyte effect and hydrophobic interaction. Furthermore, in different pH environments, the changes of binding forces of antigens-antibodies are attributed to the role of the denaturation of protein. The study aims to recognise the antigen-antibody immune mechanism, thus ensuring further understanding of the biological functions of tumour markers, and it promises to be very useful for the clinical diagnosis of early-stage cancer.

  19. Type specificity of complement-fixing antibody against herpes simplex virus type 2 AG-4 early antigen in patients with asymptomatic infection.

    PubMed Central

    Sherlock, C H; Ashley, R L; Shurtleff, M L; Mack, K D; Corey, L

    1986-01-01

    We evaluated the type specificity of complement-fixing (CF) antibody against the AG-4 early antigen of herpes simplex virus (HSV) type 2 (HSV-2) by comparing a commercial AG-4 CF kit (Simplex-2; Gene Link Australia, Inc., Princeton, N.J.) with quantal microneutralization (MN) and absorption-Western blotting in testing sera from patients with and without a history of genital herpes. Sera characterized as HSV type 1 (HSV-1) or HSV-2 positive or negative by MN were selected and tested by CF, and those with discordant results were further analyzed for specific antibodies by absorption with HSV-1 or HSV-2 antigen and Western blotting with heterologous HSV proteins. A total of 34 of 42 (81%) sera HSV-2 positive by MN, 19 of 43 (44%) sera HSV-1 positive by MN, and 0 of 19 sera negative by MN were positive by CF. Absorption-Western blotting showed that 12 of 18 (67%) sera HSV-1 positive by MN but positive by CF had no HSV-2-specific antibody and that all 7 sera HSV-2 positive by MN but negative by CF had HSV-2-specific antibody. When MN and absorption-Western blotting data were combined to analyze patients with no history of genital herpes, 7 of 19 (37%) with no HSV-2-specific antibody were positive by CF, and 7 of 27 (26%) with HSV-2-specific antibody were negative by CF. The positive and negative predictive values for the CF test were 78 and 75%, respectively, in this group. The presence of antibody to the HSV AG-4 antigen does not discriminate sufficiently between HSV-1- and HSV-2-infected patients to be of value in predicting HSV-2 infection in the absence of symptomatic disease. Images PMID:3023439

  20. Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus-related oropharyngeal cancer.

    PubMed

    Dahlstrom, Kristina R; Anderson, Karen S; Field, Matthew S; Chowell, Diego; Ning, Jing; Li, Nan; Wei, Qingyi; Li, Guojun; Sturgis, Erich M

    2017-12-15

    Because of the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV-16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV-16 E antigens in screening for OPC. This case-control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non-OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV-16 E antibody levels in serum were identified with an enzyme-linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV-related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status. Of the 378 patients with OPC, 348 had p16-positive OPC. HPV-16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: 83% sensitivity and 99% specificity for p16-positive OPC). A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  1. Rods and cones contain antigenically distinctive S-antigens.

    PubMed

    Nork, T M; Mangini, N J; Millecchia, L L

    1993-09-01

    S-antigen (48 kDa protein or arrestin) is known to be present in rod photoreceptors. Its localization in cones is less clear with several conflicting reports among various species examined. This study employed three different anti-S-antigen antibodies (a48K, a polyclonal antiserum and two monoclonal antibodies, MAb A9-C6 and MAb 5c6.47) and examined their localization in rods and cones of human and cat retinas. To identify the respective cone types, an enzyme histochemical technique for carbonic anhydrase (CA) was employed to distinguish blue cones (CA-negative) from red or green cones (CA-positive). S-antigen localization was then examined by immunocytochemical staining of adjacent sections. In human retinas, a similar labeling pattern was seen with both a48K and MAb A9-C6, i.e., the rods and blue-sensitive cones were strongly positive, whereas the red- or green-sensitive cones showed little immunoreactivity. All human photoreceptors showed reactivity to MAb 5c6.47. In the cat retina, only CA-positive cones could be found. As in the human retina, both rods and cones of the cat were positive for MAb 5c6.47. A difference from the labeling pattern in human retina was noted for the other S-antigen antibodies; a48K labeled rods and all of the cones, whereas MAb A9-C6 reacted strongly with the rods but showed no cone staining. These results suggest that both rods and cones contain S-antigen but that they are antigenically distinctive.

  2. Genetic variants in one-carbon metabolism genes and breast cancer risk in European American (EA) and African American (AA) women

    PubMed Central

    Gong, Zhihong; Yao, Song; Zirpoli, Gary; Cheng, Ting-Yuan David; Roberts, Michelle; Khoury, Thaer; Ciupak, Gregory; Davis, Warren; Pawlish, Karen; Jandorf, Lina; Bovbjerg, Dana H.; Bandera, Elisa V.; Ambrosone, Christine B.

    2015-01-01

    Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair, and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We conducted a comprehensive analysis of SNPs in eleven genes involved in one-carbon metabolism and risk of breast cancer in 1,275 European-American (EA) and 1,299 African-American (AA) women who participated in the Women’s Circle of Health Study. Allele frequencies varied significantly between EA and AA populations. A number of these SNPs, specifically in genes including MTR, MTRR, SHMT1, TYMS, and SLC19A1, were associated with overall breast cancer risk, as well as risk by estrogen receptor (ER) status, in either EA or AA women. Associations appeared to be modified by dietary folate intake. Although single-SNP associations were not statistically significant after correcting for multiple comparisons, polygenetic score analyses revealed significant associations with breast cancer risk. Per unit increase of the risk score was associated with a modest 19% to 50% increase in risk of breast cancer overall, ER positive or ER negative cancer (all P<0.0005) in EAs or AAs. In summary, our data suggest that one-carbon metabolizing gene polymorphisms could play a role in breast cancer and that may differ between EA and AA women. PMID:25598430

  3. Simian virus 40-related antigens in three human meningiomas with defined chromosome loss.

    PubMed Central

    Weiss, A F; Portmann, R; Fischer, H; Simon, J; Zang, K D

    1975-01-01

    Two out of seven meningiomas tested in early cell cultures by indirect immunofluorescence staining showed simian virus 40 (SV40)-related tumor (T) antigen. In one tumor 90% of the cells were positive. An additional SV40-related antigen (U) was found in 10% of cells of a third tumor. These findings indicate that the meningioma cells showing a positive reaction are transformed by a papova virus that has at least partly the same antigenic properties as SV40 virus. SV40-related viral capsid (V) antigen was absent in all the meningiomas tested. No virus infectious for African green monkey kidney (AGMK) cells could be isolated. The tumors positive for T and U antigens showed the chromosome aberration typical for human meningiomas, i.e., the loss of one chromosome, G-22. The T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive tumors showed further hypodiploidization. Experiments to rescue virus from the T-antigen-positive meningioma cells were performed: fusion of cells pretreated with 8-azaguanine with cells premissive for SV40 led to a low percentage (0.01-0.05%) of V-antigen-positive nuclei in heterokaryon cultures. On the basis of these results, the possibility of a correlation between the meningioma, a relatively common intracranial tumor in man, and an SV40-related papova virus must be considered. It remains to be shown whether this virus is a causative agent for human meningiomas. Images PMID:164660

  4. [Antigens (CEA and CA 19-9) in diagnosis and prognosis colorectal cancer].

    PubMed

    Grotowski, Maciej

    2002-01-01

    carcinoembryonic antigen (CEA) was first described more than three decades ago, when its presence was demonstrated in fetal gut tissue and in tumors from gastrointestinal tract. Subsequently, CEA was detected in the circulation of patients and recognized as a serum marker for colorectal cancer. This tumor marker has not been advocated as a screening test for colorectal cancer, however a preoperative CEA serum level is useful for diagnosis and prognosis of recurrence and survival in colorectal cancer patients. The levels of CEA increased with increasing tumor stage. Expression of carbohydrate antigen (CA 19-9) has been described in various malignancies and also in colorectal cancer. This antigen also has not been advocated as a screening test for colorectal cancer. The levels of CA 19-9 increased in advanced stages of colorectal cancer. Despite its lower sensitivity than CEA in early stages of colorectal cancer, the combination of both antigens can provided more information than CEA alone for prognosis of recurrence and survival in those patients.

  5. O-antigen and Core Carbohydrate of Vibrio fischeri Lipopolysaccharide

    PubMed Central

    Post, Deborah M. B.; Yu, Liping; Krasity, Benjamin C.; Choudhury, Biswa; Mandel, Mark J.; Brennan, Caitlin A.; Ruby, Edward G.; McFall-Ngai, Margaret J.; Gibson, Bradford W.; Apicella, Michael A.

    2012-01-01

    Vibrio fischeri exists in a symbiotic relationship with the Hawaiian bobtail squid, Euprymna scolopes, where the squid provides a home for the bacteria, and the bacteria in turn provide camouflage that helps protect the squid from night-time predators. Like other Gram-negative organisms, V. fischeri expresses lipopolysaccharide (LPS) on its cell surface. The structure of the O-antigen and the core components of the LPS and their possible role in colonization of the squid have not previously been determined. In these studies, an O-antigen ligase mutant, waaL, was utilized to determine the structures of these LPS components and their roles in colonization of the squid. WaaL ligates the O-antigen to the core of the LPS; thus, LPS from waaL mutants lacks O-antigen. Our results show that the V. fischeri waaL mutant has a motility defect, is significantly delayed in colonization, and is unable to compete with the wild-type strain in co-colonization assays. Comparative analyses of the LPS from the wild-type and waaL strains showed that the V. fischeri LPS has a single O-antigen repeat composed of yersiniose, 8-epi-legionaminic acid, and N-acetylfucosamine. In addition, the LPS from the waaL strain showed that the core structure consists of l-glycero-d-manno-heptose, d-glycero-d-manno-heptose, glucose, 3-deoxy-d-manno-octulosonic acid, N-acetylgalactosamine, 8-epi-legionaminic acid, phosphate, and phosphoethanolamine. These studies indicate that the unusual V. fischeri O-antigen sugars play a role in the early phases of bacterial colonization of the squid. PMID:22247546

  6. Monoclonal antibodies against simian virus 40 T antigens: evidence for distinct sublcasses of large T antigen and for similarities among nonviral T antigens.

    PubMed Central

    Gurney, E G; Harrison, R O; Fenno, J

    1980-01-01

    We have isolated three clones of hybrid cells which synthesize antibodies specific for determinants on simian virus 40 (SV40) T antigens. Mouse myeloma NS1 cells were fused with spleen cells from mice that had been immunized with SV40-transformed mouse cells. Hybrid cells were selected in HAT medium and cloned in soft agar. We used an enzyme-linked immunosorbent assay for detection and quantification of mouse antibodies against SV40 T antigens. Monoclonal antibodies from 3 of the 24 clones that scored as positive in the enzyme-linked immunosorbent assay were verified by immunoprecipitation to be specific for SV40 T antigens. Two clones (7 and 412) produced antibodies that recognized denaturation-sensitive antigenic determinants unique to large T antigen. Antibodies from clone 7 appeared to have a low affinity for large T antigen. Antibodies from clone 412 had a higher affinity for large T antigen but did not recognize a subclass of large T antigen that was recognized by tumor serum. Antibodies of the third clone, clone 122, recognized a denaturation-stable antigenic determinant of the 53,000-dalton mouse nonviral T antigen in SV40-transformed cells. Antibodies from clone 122 also recognized similar (51,000- to 56,000-dalton) nonviral T antigens in SV40-transormed or lytically infected cells from five mammalian species and in four uninfected mouse lines. From these observations, we have concluded that (i) the 94,000-dalton SV40 large T antigen may exist as immunologically distinguishable subclasses, and (ii) the nonviral T antigens of five mammalian species share at least one antigenic determinant. Images PMID:6155477

  7. Special report. Update on EAS (electronic article surveillance) systems: protecting against patient wandering, infant abduction, property theft.

    PubMed

    1993-10-01

    Concern about wandering patients and infant abduction on the part of hospitals has sparked renewed interest in Electronic Article Surveillance (EAS) systems. Such systems had their origins in department stores and libraries where they are almost universally used. They also have applications in hospitals for preventing the theft of supplies and equipment. A number of companies provide EAS products for the health care field. How do you select the system that is best for your needs? "Talk to users. Pick out a number of profit and non-profit hospitals to get their views," advises Ted Algaier, vice president, marketing and sales, Innovative Control Systems, Inc., Waukesha, WI. "Examine the history of the company or vendor to determine if it understands the health care market and find out if the product really works." In this report, we'll review a number of EAS systems currently on the market, and present information on how they work, how effective they are, and costs involved. Also included are comments from users who have installed such systems.

  8. Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment.

    PubMed

    Gulley, James L; Madan, Ravi A; Pachynski, Russell; Mulders, Peter; Sheikh, Nadeem A; Trager, James; Drake, Charles G

    2017-04-01

    Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread). Immunotherapy-induced antigen spread has been shown in clinical studies. For example, in metastatic castration-resistant prostate cancer patients, sipuleucel-T induced early immune responses to the immunizing antigen (PA2024) and/or the target antigen (prostatic acid phosphatase). Thereafter, most patients developed increased antibody responses to numerous secondary proteins, several of which are expressed in prostate cancer with functional relevance in cancer. The ipilimumab-induced antibody profile in melanoma patients shows that antigen spread also occurs with immune checkpoint blockade. In contrast to chemotherapy, immunotherapy often does not result in short-term changes in conventional disease progression end points (eg, progression-free survival, tumor size), which may be explained, in part, by the time taken for antigen spread to occur. Thus, immune-related response criteria need to be identified to better monitor the effectiveness of immunotherapy. As immunotherapy antitumor effects take time to evolve, immunotherapy in patients with less advanced cancer may have greater clinical benefit vs those with more advanced disease. This concept is supported by prostate cancer clinical studies with sipuleucel-T, PSA-TRICOM, and ipilimumab. We discuss antigen spread with cancer immunotherapy and its implications for clinical outcomes. © The Author 2017. Published by Oxford University Press. All rights reserved. For

  9. Affinity of antigen encounter and other early B-cell signals determine B-cell fate

    PubMed Central

    Benson, Micah J; Erickson, Loren D; Gleeson, Michael W; Noelle, Randolph J

    2010-01-01

    Three possible effector fates await the naïve follicular B cell following antigen stimulation in thymus-dependent reactions. Short-lived plasma cells produce an initial burst of germline-encoded protective antibodies, and long-lived plasma cells and memory B cells arise from the germinal center and function to enhance and sustain the humoral immune response. The inherent B-cell receptor affinity of naïve follicular B cells and the contribution of other early B-cell signals pre-determines the pattern of transcription factor expression and the differentiation path taken by these cells. High initial B-cell receptor affinity shunts naïve follicular B-cell clones towards the short-lived plasma cell fate, whereas modest-affinity clones are skewed towards a plasma cell fate and low-affinity clones are recruited into the germinal center and are selected for both long-lived plasma cells and memory B cell pathways. In the germinal center reaction, increased levels of the transcription factor interferon regulatory factor-4 drive the molecular program that dictates differentiation into the long-lived plasma cell phenotype but has no impact on the memory B cell compartment. We hypothesize that graded interferon regulatory factor-4 levels driven by signals to B cells, including B-cell receptor signal strength, are responsible for this branch point in the B-cell terminal differentiation pathway. PMID:17433651

  10. Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

    PubMed

    Abugharib, Ahmed; Jackson, William C; Tumati, Vasu; Dess, Robert T; Lee, Jae Y; Zhao, Shuang G; Soliman, Moaaz; Zumsteg, Zachary S; Mehra, Rohit; Feng, Felix Y; Morgan, Todd M; Desai, Neil; Spratt, Daniel E

    2017-03-01

    Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy. We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013. Two comparisons were made to determine the optimal definition of early salvage radiotherapy, including 1) the time from radical prostatectomy to salvage radiotherapy (less than 9, 9 to 21, 22 to 47 or greater than 48 months) and 2) the level of detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 or greater than 0.5 ng/ml). Outcomes included freedom from salvage androgen deprivation therapy, and biochemical relapse-free, distant metastases-free and prostate cancer specific survival. Median followup was 9.8 years. Time from radical prostatectomy to salvage radiotherapy did not correlate with 10-year biochemical relapse-free survival rates (R 2 = 0.18). Increasing pre-salvage radiotherapy prostate specific antigen strongly correlated with biochemical relapse-free survival (R 2 = 0.91). Increasing detectable pre-salvage radiotherapy prostate specific antigen (0.01 to 0.2, greater than 0.2 to 0.5 and greater than 0.5 ng/ml) predicted worse 10-year biochemical relapse-free survival (62%, 44% and 27%), freedom from salvage androgen deprivation therapy (77%, 66% and 49%), distant metastases-free survival (86%, 79% and 66%, each p <0.001) and prostate cancer specific survival (93%, 89% and 80%, respectively, p = 0.001). On multivariable analysis early salvage radiotherapy (prostate specific antigen greater than 0.2 to 0.5 ng/ml) was associated with a twofold increase in biochemical failure, use of salvage androgen deprivation therapy and distant metastases compared to very early salvage radiotherapy (prostate specific antigen 0.01 to 0.2 ng/ml). The duration from radical prostatectomy to salvage

  11. Development and Validation of a High Throughput System for Discovery of Antigens for Autoantibody Detection

    PubMed Central

    Macdonald, Isabel K.; Allen, Jared; Murray, Andrea; Parsy-Kowalska, Celine B.; Healey, Graham F.; Chapman, Caroline J.; Sewell, Herbert F.; Robertson, John F. R.

    2012-01-01

    An assay employing a panel of tumor-associated antigens has been validated and is available commercially (EarlyCDT®-Lung) to aid the early detection of lung cancer by measurement of serum autoantibodies. The high throughput (HTP) strategy described herein was pursued to identify new antigens to add to the EarlyCDT-Lung panel and to assist in the development of new panels for other cancers. Two ligation-independent cloning vectors were designed and synthesized, producing fusion proteins suitable for the autoantibody ELISA. We developed an abridged HTP version of the validated autoantibody ELISA, determining that results reflected the performance of the EarlyCDT assay, by comparing results on both formats. Once validated this HTP ELISA was utilized to screen multiple fusion proteins prepared on small-scale, by a HTP expression screen. We determined whether the assay performance for these HTP protein batches was an accurate reflection of the performance of R&D or commercial batches. A HTP discovery platform for the identification and optimal production of tumor- associated antigens which detects autoantibodies has been developed and validated. The most favorable conditions for the exposure of immunogenic epitopes were assessed to produce discriminatory proteins for use in a commercial ELISA. This process is rapid and cost-effective compared to standard cloning and screening technologies and enables rapid advancement in the field of autoantibody assay discovery. This approach will significantly reduce timescale and costs for developing similar panels of autoantibody assays for the detection of other cancer types with the ultimate aim of improved overall survival due to early diagnosis and treatment. PMID:22815807

  12. Uniform cell-autonomous tumorigenesis of the choroid plexus by papovavirus large T antigens.

    PubMed Central

    Chen, J D; Van Dyke, T

    1991-01-01

    The simian virus 40 (SV40) large tumor antigen (T antigen) under its natural regulatory elements induces choroid plexus papillomas in transgenic mice. Because these tumors develop focally after several months, it has been suggested that secondary cellular alterations are required to induce a tumor in this tissue. In contrast to SV40, the related lymphotropic papovavirus early region induces rapid nonfocal choroid plexus neoplasia in transgenic mice. Here, using hybrid gene constructs, we showed that T antigen from either virus in in fact sufficient to induce these tumors. Their abilities to induce proliferative abnormalities in other tissues, such as kidney and thymus, were also indistinguishable. Differences in the rate of choroid plexus tumorigenesis reflected differences in the control regions of the two viruses, rather than differences in T antigen per se. Under SV40 regulation, expression was limited to a fraction of the choroid plexus cells prior to the formation of focal tumors. When SV40 T antigen was placed under lymphotropic papovavirus control, in contrast, expression was generally uniform in the choroid plexus and rapid expansion of the tissue ensued. We found a direct relationship between T-antigen expression, morphological transformation, and proliferation of the choroid plexus epithelial cells. Analysis of mosaic transgenic mice indicated further that T antigen exerts its mitogenic effect cell autonomously. These studies form the foundation for elucidating the role of various T-antigen subactivities in tumorigenesis. Images PMID:1658622

  13. Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.

    PubMed

    Koyama, Yoshiyuki; Ito, Tomoko; Hasegawa, Aya; Eriguchi, Masazumi; Inaba, Toshio; Ushigusa, Takahiro; Sugiura, Kikuya

    2016-11-01

    To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens. We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p < 0.05) evoked cellular immunity against both ESAT-6, and B16 tumor cells. Intra-tumoral injection of the exosomes significantly suppressed (p < 0.001) tumor growth in syngeneic B16 tumor-bearing mice, while the exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens. Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.

  14. Subcellular distribution and life cycle of Epstein-Barr virus in keratinocytes of oral hairy leukoplakia.

    PubMed Central

    Rabanus, J. P.; Greenspan, D.; Petersen, V.; Leser, U.; Wolf, H.; Greenspan, J. S.

    1991-01-01

    The authors investigated the life cycle of Epstein-Barr virus (EBV) in keratinocytes of oral hairy leukoplakia by combining immunohistochemistry. DNA in situ hybridization, and lectin histochemistry with electron microscopy. Diffuse-staining components of the EBV early antigen complex (EA-D), EBV 150-kd capsid antigen (VCA), EBV membrane antigen (gp350/220), and double-stranded DNA were labeled with monoclonal antibodies. An EBV-DNA probe was used to locate EBV DNA. Wheat-germ agglutinin (WGA) was employed to distinguish Golgi-associated compartments. The authors found EBV proteins and EBV DNA only in keratinocytes with apparent viral assembly. In situ hybridization showed EBV DNA in free corelike material and in electron-dense cores of mature nucleocapsids. Monoclonal antibodies to nonspecific double-stranded DNA attached to the same structures and to marginated chromatin. Components of EA-D were dispersed throughout the nuclei but accumulated near condensed chromatin and in 'punched-out' regions of the chromatin. Epstein-Barr virus 150-kd capsid antigen was found only in the nuclei, where it appeared preferentially on mature nucleocapsids. As yet unexplained arrays of intranuclear particles that remained unlabeled with all EBV-specific probes reacted intensely with an antiserum against common papillomavirus antigen. Gp350/220 was detectable in various cellular membrane compartments and was highly concentrated on EBV envelopes in peripheral Golgi-associated secretory vesicles. It was less abundant on the extracellular EBV, indicating that viral membrane antigen partly dissociates from the mature virus. Combined lectin-binding histochemistry and electron microscopy demonstrated for the first time that EBV is processed in the Golgi apparatus, which eventually releases the virus by fusion with the plasma membrane. These results provide insight into the biologic events that occur during complete EBV replication in vivo. Images Figure 1 Figure 2 Figure 3 Figure 4

  15. EMOTIONAL AVAILABILITY IN EARLY MOTHER–CHILD INTERACTIONS FOR CHILDREN WITH AUTISM SPECTRUM DISORDERS, OTHER PSYCHIATRIC DISORDERS, AND DEVELOPMENTAL DELAY

    PubMed Central

    GUL, HESNA; EROL, NESE; AKIN, DUYGU PAMIR; GULLU, BELGİN USTUN; AKCAKİN, MELDA; ALPAS, BAŞAK; ÖNER, ÖZGÜR

    2016-01-01

    Emotional availability (EA) is a method to assess early parent–child dyadic interactions for emotional awareness, perception, experience, and expression between child and parent that describe global relational quality (Z. Biringen & M. Easterbrooks, 2012). The current study aimed to examine the effects of an infant’s diagnosis of autism spectrum disorders (ASDs), other psychiatric disorders (OPD), and developmental delay (DD) on the maternal EA Scale (EAS; Z. Biringen & M. Easterbrooks, 2012; Z. Biringen, J.L. Robinson, & R.N. Emde, 2000) scores and the relative contributions of infant’s age, gender, diagnosis, developmental level, and maternal education on EAS scores in a clinical Turkish sample. Three hundred forty-five infant–mother dyads participated in this study. Results of the research indicated that EAS adult scores were associated with maternal education and infant’s diagnosis whereas child scores were associated with infant’s age, diagnosis, and developmental level. Infants’ involvement and responsiveness to the mother were lower in the group with ASD. Children with OPD, particularly when their mothers have lower education, might be at increased risk of having problems in parent–child interactions. Young ASD subjects with developmental delay are in greatest need of support to increase reactions toward their mother. These findings underscore the importance of using all of the EA dimensions rather than only one measure on children in high-risk populations. PMID:26891759

  16. Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

    PubMed Central

    BENNETT, CATHY; VAKIL, NIMISH; BERGMAN, JACQUES; HARRISON, REBECCA; ODZE, ROBERT; VIETH, MICHAEL; SANDERS, SCOTT; GAY, LAURA; PECH, OLIVER; LONGCROFT–WHEATON, GAIUS; ROMERO, YVONNE; INADOMI, JOHN; TACK, JAN; CORLEY, DOUGLAS A.; MANNER, HENDRIK; GREEN, SUSI; DULAIMI, DAVID AL; ALI, HAYTHEM; ALLUM, BILL; ANDERSON, MARK; CURTIS, HOWARD; FALK, GARY; FENNERTY, M. BRIAN; FULLARTON, GRANT; KRISHNADATH, KAUSILIA; MELTZER, STEPHEN J.; ARMSTRONG, DAVID; GANZ, ROBERT; CENGIA, GIANPAOLO; GOING, JAMES J.; GOLDBLUM, JOHN; GORDON, CHARLES; GRABSCH, HEIKE; HAIGH, CHRIS; HONGO, MICHIO; JOHNSTON, DAVID; FORBES–YOUNG, RICKY; KAY, ELAINE; KAYE, PHILIP; LERUT, TONI; LOVAT, LAURENCE B.; LUNDELL, LARS; MAIRS, PHILIP; SHIMODA, TADAKUZA; SPECHLER, STUART; SONTAG, STEPHEN; MALFERTHEINER, PETER; MURRAY, IAIN; NANJI, MANOJ; POLLER, DAVID; RAGUNATH, KRISH; REGULA, JAROSLAW; CESTARI, RENZO; SHEPHERD, NEIL; SINGH, RAJVINDER; STEIN, HUBERT J.; TALLEY, NICHOLAS J.; GALMICHE, JEAN–PAUL; THAM, TONY C. K.; WATSON, PETER; YERIAN, LISA; RUGGE, MASSIMO; RICE, THOMAS W.; HART, JOHN; GITTENS, STUART; HEWIN, DAVID; HOCHBERGER, JUERGEN; KAHRILAS, PETER; PRESTON, SEAN; SAMPLINER, RICHARD; SHARMA, PRATEEK; STUART, ROBERT; WANG, KENNETH; WAXMAN, IRVING; ABLEY, CHRIS; LOFT, DUNCAN; PENMAN, IAN; SHAHEEN, NICHOLAS J.; CHAK, AMITABH; DAVIES, GARETH; DUNN, LORNA; FALCK–YTTER, YNGVE; DECAESTECKER, JOHN; BHANDARI, PRADEEP; ELL, CHRISTIAN; GRIFFIN, S. MICHAEL; ATTWOOD, STEPHEN; BARR, HUGH; ALLEN, JOHN; FERGUSON, MARK K.; MOAYYEDI, PAUL; JANKOWSKI, JANUSZ A. Z.

    2017-01-01

    BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett’s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. PMID:22537613

  17. Measurement of the methyl cyanide E/A ratio in TMC-1

    NASA Technical Reports Server (NTRS)

    Minh, Y. C.; Irvine, W. M.; Ohishi, M.; Ishikawa, S.; Saito, S.; Kaifu, N.

    1993-01-01

    We have observed the methyl cyanide (CH3CN) J = 2-1 K = 0 and 1 transitions toward the cyanopolyyne peak of TMC-1 and have derived an E/A (ortho/para)abundance ratio N(E)/N(A) = 0.75 +/- 0.10. The total methyl cyanide column density is N(total) = 5 x 10 exp 12/sq cm toward TMC-1, in agreement with earlier results from the J = 1-0 lines.

  18. Antigen processing and remodeling of the endosomal pathway: requirements for antigen cross-presentation.

    PubMed

    Compeer, Ewoud Bernardus; Flinsenberg, Thijs Willem Hendrik; van der Grein, Susanna Geertje; Boes, Marianne

    2012-01-01

    Cross-presentation of endocytosed antigen as peptide/class I major histocompatibility complex complexes plays a central role in the elicitation of CD8(+) T cell clones that mediate anti-viral and anti-tumor immune responses. While it has been clear that there are specific subsets of professional antigen presenting cells capable of antigen cross-presentation, identification of mechanisms involved is still ongoing. Especially amongst dendritic cells (DC), there are specialized subsets that are highly proficient at antigen cross-presentation. We here present a focused survey on the cell biological processes in the endosomal pathway that support antigen cross-presentation. This review highlights DC-intrinsic mechanisms that facilitate the cross-presentation of endocytosed antigen, including receptor-mediated uptake, maturation-induced endosomal sorting of membrane proteins, dynamic remodeling of endosomal structures and cell surface-directed endosomal trafficking. We will conclude with the description of pathogen-induced deviation of endosomal processing, and discuss how immune evasion strategies pertaining endosomal trafficking may preclude antigen cross-presentation.

  19. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... leaks or liquid spills, widespread power failures, industrial explosions, and civil disorders. (1) DBS...); analog cable systems, digital cable systems, and wireless cable systems must comply with § 11.54(b)(6... programming should comply with § 11.54(b)(8). (5) Upon completion of the State or Local Area EAS transmission...

  20. Early transduction produces highly functional chimeric antigen receptor-modified virus-specific T-cells with central memory markers: a Production Assistant for Cell Therapy (PACT) translational application.

    PubMed

    Sun, Jiali; Huye, Leslie E; Lapteva, Natalia; Mamonkin, Maksim; Hiregange, Manasa; Ballard, Brandon; Dakhova, Olga; Raghavan, Darshana; Durett, April G; Perna, Serena K; Omer, Bilal; Rollins, Lisa A; Leen, Ann M; Vera, Juan F; Dotti, Gianpietro; Gee, Adrian P; Brenner, Malcolm K; Myers, Douglas G; Rooney, Cliona M

    2015-01-01

    Virus-specific T-cells (VSTs) proliferate exponentially after adoptive transfer into hematopoietic stem cell transplant (HSCT) recipients, eliminate virus infections, then persist and provide long-term protection from viral disease. If VSTs behaved similarly when modified with tumor-specific chimeric antigen receptors (CARs), they should have potent anti-tumor activity. This theory was evaluated by Cruz et al. in a previous clinical trial with CD19.CAR-modified VSTs, but there was little apparent expansion of these cells in patients. In that study, VSTs were gene-modified on day 19 of culture and we hypothesized that by this time, sufficient T-cell differentiation may have occurred to limit the subsequent proliferative capacity of the transduced T-cells. To facilitate the clinical testing of this hypothesis in a project supported by the NHLBI-PACT mechanism, we developed and optimized a good manufacturing practices (GMP) compliant method for the early transduction of VSTs directed to Epstein-Barr virus (EBV), Adenovirus (AdV) and cytomegalovirus (CMV) using a CAR directed to the tumor-associated antigen disialoganglioside (GD2). Ad-CMVpp65-transduced EBV-LCLs effectively stimulated VSTs directed to all three viruses (triVSTs). Transduction efficiency on day three was increased in the presence of cytokines and high-speed centrifugation of retroviral supernatant onto retronectin-coated plates, so that under optimal conditions up to 88% of tetramer-positive VSTs expressed the GD2.CAR. The average transduction efficiency of early-and late transduced VSTs was 55 ± 4% and 22 ± 5% respectively, and early-transduced VSTs maintained higher frequencies of T cells with central memory or intermediate memory phenotypes. Early-transduced VSTs also had higher proliferative capacity and produced higher levels of TH1 cytokines IL-2, TNF-α, IFN-γ, MIP-1α, MIP-1β and other cytokines in vitro. We developed a rapid and GMP compliant method for the early transduction of

  1. Early Ambulation Among Hospitalized Heart Failure Patients Is Associated With Reduced Length of Stay and 30-Day Readmissions.

    PubMed

    Fleming, Lisa M; Zhao, Xin; DeVore, Adam D; Heidenreich, Paul A; Yancy, Clyde W; Fonarow, Gregg C; Hernandez, Adrian F; Kociol, Robb D

    2018-04-01

    Early ambulation (EA) is associated with improved outcomes for mechanically ventilated and stroke patients. Whether the same association exists for patients hospitalized with acute heart failure is unknown. We sought to determine whether EA among patients hospitalized with heart failure is associated with length of stay, discharge disposition, 30-day post discharge readmissions, and mortality. The study population included 369 hospitals and 285 653 patients with heart failure enrolled in the Get With The Guidelines-Heart Failure registry. We used multivariate logistic regression with generalized estimating equations at the hospital level to identify predictors of EA and determine the association between EA and outcomes. Sixty-five percent of patients ambulated by day 2 of the hospital admission. Patient-level predictors of EA included younger age, male sex, and hospitalization outside of the Northeast ( P <0.01 for all). Hospital size and academic status were not predictive. Hospital-level analysis revealed that those hospitals with EA rates in the top 25% were less likely to have a long length of stay (defined as >4 days) compared with those in the bottom 25% (odds ratio, 0.83; confidence interval, 0.73-0.94; P =0.004). Among a subgroup of fee-for-service Medicare beneficiaries, we found that hospitals in the highest quartile of rates of EA demonstrated a statistically significant 24% lower 30-day readmission rates ( P <0.0001). Both end points demonstrated a dose-response association and statistically significant P for trend test. Multivariable-adjusted hospital-level analysis suggests an association between EA and both shorter length of stay and lower 30-day readmissions. Further prospective studies are needed to validate these findings. © 2018 American Heart Association, Inc.

  2. New installation for inclined EAS investigations

    NASA Astrophysics Data System (ADS)

    Zadeba, E. A.; Ampilogov, N. V.; Barbashina, N. S.; Bogdanov, A. G.; Borisov, A. A.; Chernov, D. V.; Dushkin, L. I.; Fakhrutdinov, R. M.; Kokoulin, R. P.; Kompaniets, K. G.; Kozhin, A. S.; Ovchinnikov, V. V.; Ovechkin, A. S.; Petrukhin, A. A.; Shutenko, V. V.; Volkov, N. S.; Vorobjev, V. S.; Yashin, I. I.

    2017-06-01

    The large-scale coordinate-tracking detector TREK for registration of inclined EAS is being developed in MEPhI. The detector is based on multiwire drift chambers from the neutrino experiment at the IHEP U-70 accelerator. Their key advantages are a large effective area (1.85 m2), a good coordinate and angular resolution with a small number of measuring channels. The detector will be operated as part of the experimental complex NEVOD, in particular, jointly with a Cherenkov water detector (CWD) with a volume of 2000 cubic meters and the coordinate detector DECOR. The first part of the detector named Coordinate-Tracking Unit based on the Drift Chambers (CTUDC), representing two coordinate planes of 8 drift chambers in each, has been developed and mounted on opposite sides of the CWD. It has the same principle of joint operation with the NEVOD-DECOR triggering system and the same drift chambers alignment, so the main features of the TREK detector will be examined. Results of the CTUDC development and a joint operation with NEVOD-DECOR complex are presented.

  3. COMPARISON OF CFC-114 AND HFC-236EA PERFORMANCE IN SHIPBOARD VAPOR COMPRESSION SYSTEMS

    EPA Science Inventory

    The report gives results of a comparison of the performance of two refrigerants - 1,1,1,2,3,3-hexafluoropropane (HFC-236ea) and 1,2-dichloro-tetrafluoroethane (CFC-114) - in shipboard vapor compression refrigeration systems. (NOTE: In compliance with the Montreal Protocol and Dep...

  4. HEAT TRANSFER EVALUATION OF HFC-236EA AND CFC-114 IN CONDENSATION AND EVAPORATION

    EPA Science Inventory

    The report gives results of a heat transfer evaluation of the refrigerants hexafluoropropane (HFC-236ea) and 1,1,2,2-dichloro-tetrafluoroethane (CFC-114). (NOTE: With the mandatory phase-out of chlorofluorocarbons (CFCs), as dictated by the Montreal Protocol and Clean Air Act Ame...

  5. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy

    PubMed Central

    Dai, Hanren; Wang, Yao; Lu, Xuechun

    2016-01-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

  6. Extracorporeal Shock Wave Therapy Suppresses the Early Proinflammatory Immune Response to a Severe Cutaneous Burn Injury

    DTIC Science & Technology

    2009-02-01

    Burn wound model Mice were anaesthetised using isoflurane inha- lation. After shaving the dorsum, the exposed skin was washed gently with room...Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn injury* Thomas A Davis, Alexander...S, Peoples GE, Tadaki D, Elster EA. Extracorporeal shock wave therapy suppresses the early proinflammatory immune response to a severe cutaneous burn

  7. Cancer vaccine--Antigenics.

    PubMed

    2002-01-01

    Antigenics is developing a therapeutic cancer vaccine based on heat-shock proteins (HSPs). The vaccine [HSPPC-96, Oncophage] is in a pivotal phase III clinical trial for renal cancer at 80 clinical sites worldwide. The trial is enrolling at least 500 patients who are randomised to receive surgical removal of the primary tumour followed by out-patient treatment with Oncophage((R)) or surgery only. This study was initiated on the basis of results from a pilot phase I/II study and preliminary results from a phase II study in patients with renal cell cancer. In October 2001, Oncophage was designated as a fast-track product by the Food and Drug Administration in the US for the treatment of renal cell carcinoma. Oncophage is in phase I/II trials in Italy for colorectal cancer (30 patients) and melanoma. The trials in Italy are being conducted at the Istituto dei Tumouri, Milan (in association with Sigma-Tau). Preliminary data from the phase II trial for melanoma was presented at the AACR-NCI-EORTC International Conference in Florida, USA, in October 2001. Oncophage is also in a phase I/II (42 patients) and a phase II trial (84 patients) in the US for renal cell cancer, a phase II trial in the US for non-Hodgkin's lymphoma (35 patients), a phase II trial in the US for sarcoma (20-35 patients), a phase I/II trial in the US for melanoma (36 patients), and phase I/II trials in Germany for gastric (30 patients) and pancreatic cancers. A pilot phase I trial in patients with pancreatic cancer began in the US in 1997 with 5 patients enrolled. In November 2000, Antigenics announced that this trial had been expanded to a phase I/II study which would now include survival as an endpoint and would enroll 5 additional patients. The US trials are being performed at Memorial Sloan-Kettering Cancer Center and the M.D. Anderson Cancer Center. The trials in Germany are being carried out at Johannes Gutenberg-University Hospital, Mainz. Oncophage is an autologous vaccine consisting of

  8. Presenting concerns of emerging adults seeking treatment at an early intervention outpatient mood and anxiety program.

    PubMed

    Arcaro, Justin; Summerhurst, Carolyn; Vingilis, Evelyn; Wammes, Michael; Osuch, Elizabeth

    2017-09-01

    This study examined presenting concerns and characteristics of emerging adults (EAs) seeking treatment at an early intervention program for mood and anxiety disorders to better understand presenting concerns when treatment is needed. During an intake assessment conducted by a social worker or clinical psychologist, participants (N = 548; 62% female, 38% male) reported their top three current life concerns, which were analyzed qualitatively using thematic analysis. Participants completed a battery of questionnaires assessing demographic information, symptomatology, and daily functioning. Females presented with significantly higher levels of anxiety, and both females and younger individuals (age 16-18) presented with significantly higher levels of depression compared to males and older individuals (age 19-26), respectively. The two most commonly reported presenting concerns were problems in interpersonal relationships and academics, and females were more likely to report academic concerns than males. The majority of participants reported seeking help for a wide range of problems commonly faced by EAs (83.7%), and participants rarely expressed concerns about particular symptoms of mood and/or anxiety disorders (16.3%). EAs and those supporting EAs may benefit from learning when psychosocial concerns are indicative of mental health challenges warranting professional attention.

  9. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

    DOE PAGES

    Hattori, Takamitsu; Lai, Darson; Dementieva, Irina S.; ...

    2016-02-09

    Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. Thismore » “antigen clasping” produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody–antigen recognition and suggests a strategy for developing extremely specific antibodies.« less

  10. Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hattori, Takamitsu; Lai, Darson; Dementieva, Irina S.

    Antibodies have a well-established modular architecture wherein the antigen-binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. Thismore » “antigen clasping” produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen-binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody–antigen recognition and suggests a strategy for developing extremely specific antibodies.« less

  11. 47 CFR 1.1311 - Environmental information to be included in the environmental assessment (EA).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... earth stations, a description of the facilities as well as supporting structures and appurtenances, and..., the applicant's analysis must utilize the best scientific and commercial data available, see 50 CFR...'s environmental impact, if any. The EA shall deal specifically with any feature of the site which...

  12. 47 CFR 1.1311 - Environmental information to be included in the environmental assessment (EA).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... earth stations, a description of the facilities as well as supporting structures and appurtenances, and..., the applicant's analysis must utilize the best scientific and commercial data available, see 50 CFR...'s environmental impact, if any. The EA shall deal specifically with any feature of the site which...

  13. 47 CFR 1.1311 - Environmental information to be included in the environmental assessment (EA).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... earth stations, a description of the facilities as well as supporting structures and appurtenances, and..., the applicant's analysis must utilize the best scientific and commercial data available, see 50 CFR...'s environmental impact, if any. The EA shall deal specifically with any feature of the site which...

  14. The role of childhood trauma, early maladaptive schemas, emotional schemas and experimental avoidance on depression: A structural equation modeling.

    PubMed

    Rezaei, Mehdi; Ghazanfari, Firoozeh; Rezaee, Fatemeh

    2016-12-30

    The present investigation was designed to examine disconnection and rejection (DR) schemas, negative emotional schemas (NESs) and experimental avoidance (EA) as mediating variables of the relationship between the childhood trauma (CT) and depression. Specifically we examined the mediating role of NESs and EA between DR schemas and depression. The study sample consist of 439 female college students (M age =22.47; SD=6.0), of whom 88 met the criteria for current major depressive disorder (MDD) and 351 who had history of MDD in the last 12 months. Subjects were assessed by Structured Clinical Interview for DSM-IV (SCID) and completed the Childhood Trauma Questionnaire (CTQ), the Early Maladaptive Schemas Questionnaire (SQ-SF), the Leahy Emotional Schemas Scale (LESS), the Acceptance and Action Questionnaire (AAQ-II), and the Beck Depression Inventory-II (BDI-II). The findings showed that DR schemas were mediator of the relationship CT and depression but CT through the NESs and EA did not predict depression. NESs were mediator of the relationship between DR schemas and depression and EA was mediator of the relationship between DR schemas and depression. In general, results suggest that intervention of depressed women may need to target the changing of DR schemas, NESs and reduction of EA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Prediction of early summer rainfall over South China by a physical-empirical model

    NASA Astrophysics Data System (ADS)

    Yim, So-Young; Wang, Bin; Xing, Wen

    2014-10-01

    In early summer (May-June, MJ) the strongest rainfall belt of the northern hemisphere occurs over the East Asian (EA) subtropical front. During this period the South China (SC) rainfall reaches its annual peak and represents the maximum rainfall variability over EA. Hence we establish an SC rainfall index, which is the MJ mean precipitation averaged over 72 stations over SC (south of 28°N and east of 110°E) and represents superbly the leading empirical orthogonal function mode of MJ precipitation variability over EA. In order to predict SC rainfall, we established a physical-empirical model. Analysis of 34-year observations (1979-2012) reveals three physically consequential predictors. A plentiful SC rainfall is preceded in the previous winter by (a) a dipole sea surface temperature (SST) tendency in the Indo-Pacific warm pool, (b) a tripolar SST tendency in North Atlantic Ocean, and (c) a warming tendency in northern Asia. These precursors foreshadow enhanced Philippine Sea subtropical High and Okhotsk High in early summer, which are controlling factors for enhanced subtropical frontal rainfall. The physical empirical model built on these predictors achieves a cross-validated forecast correlation skill of 0.75 for 1979-2012. Surprisingly, this skill is substantially higher than four-dynamical models' ensemble prediction for 1979-2010 period (0.15). The results here suggest that the low prediction skill of current dynamical models is largely due to models' deficiency and the dynamical prediction has large room to improve.

  16. E+A Galaxy Properties and Post-Starburst Galaxy Evolution Data through SDSS-IV MaNGA and Illustris: A Co-Analysis

    NASA Astrophysics Data System (ADS)

    Ojanen, Winonah; Dudley, Raymond; Edwards, Kay; Gonzalez, Andrea; Johnson, Amalya; Kerrison, Nicole; Marinelli, Mariarosa; Melchert, Nancy; Liu, Charles; Sloan Collaboration, SDSS-IV MaNGA

    2018-01-01

    E+A galaxies (Elliptical + A-type stars) are post-starburst galaxies that have experienced a sudden quenching phase. Using previous research methods, 39 candidates out of 2,812 galaxies observed, or 1.4%, were selected from the SDSS-IV MaNGA survey. We then identified morphological characteristics of the 39 galaxies including stellar kinematics, Gini coefficient, gas density and distribution and stellar ages. To study the origin of how E+A galaxies evolved to their present state, galaxy simulation data from the Illustris simulation was utilized to identify similar quenched post-starburst candidates. Seven post-starburst candidates were identified through star formation rate histories of Illustris simulated galaxies. The evolution of these galaxies is studied from 0 to 13.8 billion years ago to identify what caused the starburst and quenching of the Illustris candidates. Similar morphological characteristics of Illustris post-starburst candidates are pulled from before, during, and post-starburst and compared to the same morphological characteristics of the E+A galaxies from SDSS-IV MaNGA. The characteristics and properties of the Illustris galaxies are used to identify the possible evolutionary histories of the observed E+A galaxies. This work was supported by grants AST-1460860 from the National Science Foundation and SDSS FAST/SSP-483 from the Alfred P. Sloan Foundation to the CUNY College of Staten Island.

  17. Calcium-dependent antigen binding as a novel modality for antibody recycling by endosomal antigen dissociation

    PubMed Central

    Hironiwa, N; Ishii, S; Kadono, S; Iwayanagi, Y; Mimoto, F; Habu, K; Igawa, T; Hattori, K

    2016-01-01

    The pH-dependent antigen binding antibody, termed a recycling antibody, has recently been reported as an attractive type of second-generation engineered therapeutic antibody. A recycling antibody can dissociate antigen in the acidic endosome, and thus bind to its antigen multiple times. As a consequence, a recycling antibody can neutralize large amounts of antigen in plasma. Because this approach relies on histidine residues to achieve pH-dependent antigen binding, which could limit the epitopes that can be targeted and affect the rate of antigen dissociation in the endosome, we explored an alternative approach for generating recycling antibodies. Since calcium ion concentration is known to be lower in endosome than in plasma, we hypothesized that an antibody with antigen-binding properties that are calcium-dependent could be used as recycling antibody. Here, we report a novel anti-interleukin-6 receptor (IL-6R) antibody, identified from a phage library that binds to IL-6R only in the presence of a calcium ion. Thermal dynamics and a crystal structure study revealed that the calcium ion binds to the heavy chain CDR3 region (HCDR3), which changes and possibly stabilizes the structure of HCDR3 to make it bind to antigen calcium dependently (PDB 5AZE). In vitro and in vivo studies confirmed that this calcium-dependent antigen-binding antibody can dissociate its antigen in the endosome and accelerate antigen clearance from plasma, making it a novel approach for generating recycling antibody. PMID:26496237

  18. Lateral distribution on charged particles in EAS

    NASA Technical Reports Server (NTRS)

    Dedenko, L. G.; Kulikov, G. V.; Solovjeva, V. I.; Sulakov, V. F.

    1985-01-01

    Lateral distribution of charged particles which allow for the finiteness of energy gamma-quanta, the inhomogeneity of the atmosphere and the experimental selection of EAS are needed to interpret experimental data. The effects of finiteness of energy of gamma-quanta which produce the partial electron-photon cascades were considered by substituting K R sub m instead of R sub m in NKG approximation where K was found to be 0.56 from comparison with the experimental data. New results on the lateral distribution of electrons in the partial cascades from gamma-quanta were obtained. It is shown that the coefficient K can be regarded as a constant. The last approximation of K was found to be most adequate when compared with the experimental data. The inhomogeneity of the atmosphere, muons and experimental selection are considered. The calculation of Ne are extended from 100,000 to 10 million for sea level and for Akeno level.

  19. Chlorphenesin: an Antigen-Associated Immunosuppressant

    PubMed Central

    Whang, H. Y.; Neter, E.

    1970-01-01

    Chlorphenesin (3-p-chlorophenoxy-1,2-propanediol), when injected intravenously together with either of two common bacterial antigens, inhibits the antibody response of the rabbit. The antigens studied are those common to Enterobacteriaceae and to gram-positive bacteria. The immunosuppression is contingent upon incubation of chlorphenesin and antigen in vitro prior to administration, since separate injection of antigen and inhibitor or of mixtures without prior incubation yields undiminished antibody response. Chlorphenesin, as shown by hemagglutination-inhibition tests, does not alter the antigenic determinants, because antibody neutralization occurs in the presence or absence of the drug. The immunosuppressive effect is reversible, since precipitation of chlorphenesin at 4 C substantially restores immunogenicity. Animals immunized with antigen-drug mixtures, which fail to respond with significant antibody production, nonetheless are immunologically primed. It is concluded that chlorphenesin represents another example of antigen-associated immunosuppressants. PMID:16557800

  20. Chlorphenesin: an antigen-associated immunosuppressant.

    PubMed

    Whang, H Y; Neter, E

    1970-07-01

    Chlorphenesin (3-p-chlorophenoxy-1,2-propanediol), when injected intravenously together with either of two common bacterial antigens, inhibits the antibody response of the rabbit. The antigens studied are those common to Enterobacteriaceae and to gram-positive bacteria. The immunosuppression is contingent upon incubation of chlorphenesin and antigen in vitro prior to administration, since separate injection of antigen and inhibitor or of mixtures without prior incubation yields undiminished antibody response. Chlorphenesin, as shown by hemagglutination-inhibition tests, does not alter the antigenic determinants, because antibody neutralization occurs in the presence or absence of the drug. The immunosuppressive effect is reversible, since precipitation of chlorphenesin at 4 C substantially restores immunogenicity. Animals immunized with antigen-drug mixtures, which fail to respond with significant antibody production, nonetheless are immunologically primed. It is concluded that chlorphenesin represents another example of antigen-associated immunosuppressants.

  1. Chimeric antigen receptor T cells: power tools to wipe out leukemia and lymphoma.

    PubMed

    Riet, Tobias; Abken, Hinrich

    2015-08-01

    Adoptive cell therapy for malignant diseases is showing promise in recent early-phase trials in the treatment of B cell leukemia/lymphoma. Genetically engineered with a tumor-specific chimeric antigen receptor, patient's T cells produce lasting and complete leukemia regression. However, treatment is associated with some toxicity which needs our attention and the field still faces some hurdles at the scientific, technologic and clinical levels. Surmounting these obstacles will establish chimeric antigen receptor T cell therapy as a powerful approach to cure hematologic malignancies, paving the way for the treatment of other common types of cancer in the future.

  2. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

    PubMed

    Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

    2016-07-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. © The Author 2016. Published by Oxford University Press.

  3. Antibody Responses to Prostate-Associated Antigens in Patients with Prostatitis and Prostate Cancer

    PubMed Central

    Maricque, Brett B.; Eickhoff, Jens C.; McNeel, Douglas G.

    2010-01-01

    Background An important focus of tumor immunotherapy has been the identification of appropriate antigenic targets. Serum-based screening approaches have led to the discovery of hundreds of tumor-associated antigens recognized by IgG. Our efforts to identify immunologically recognized proteins in prostate cancer have yielded a multitude of antigens, however prioritizing these antigens as targets for evaluation in immunotherapies has been challenging. In this report, we set out to determine whether the evaluation of multiple antigenic targets would allow the identification of a subset of antigens that are common immunologic targets in patients with prostate cancer. Methods Using a phage immunoblot approach, we evaluated IgG responses in patients with prostate cancer (n=126), patients with chronic prostatitis (n=45), and men without prostate disease (n=53). Results We found that patients with prostate cancer or prostatitis have IgG specific for multiple common antigens. A subset of 23 proteins was identified to which IgG were detected in 38% of patients with prostate cancer and 33% patients with prostatitis versus 6% of controls (p<0.001 and p=0.003, respectively). Responses to multiple members were not higher in patients with advanced disease, suggesting antibody immune responses occur early in the natural history of cancer progression. Conclusions These findings suggest an association between inflammatory conditions of the prostate and prostate cancer, and suggest that IgG responses to a panel of commonly recognized prostate antigens could be potentially used in the identification of patients at risk for prostate cancer or as a tool to identify immune responses elicited to prostate tissue. PMID:20632317

  4. The effect of pH dependence of antibody-antigen interactions on subcellular trafficking dynamics.

    PubMed

    Devanaboyina, Siva Charan; Lynch, Sandra M; Ober, Raimund J; Ram, Sripad; Kim, Dongyoung; Puig-Canto, Alberto; Breen, Shannon; Kasturirangan, Srinath; Fowler, Susan; Peng, Li; Zhong, Haihong; Jermutus, Lutz; Wu, Herren; Webster, Carl; Ward, E Sally; Gao, Changshou

    2013-01-01

    A drawback of targeting soluble antigens such as cytokines or toxins with long-lived antibodies is that such antibodies can prolong the half-life of the target antigen by a "buffering" effect. This has motivated the design of antibodies that bind to target with higher affinity at near neutral pH relative to acidic endosomal pH (~pH 6.0). Such antibodies are expected to release antigen within endosomes following uptake into cells, whereas antibody will be recycled and exocytosed in FcRn-expressing cells. To understand how the pH dependence of antibody-antigen interactions affects intracellular trafficking, we generated three antibodies that bind IL-6 with different pH dependencies in the range pH 6.0-7.4. The behavior of antigen in the presence of these antibodies has been characterized using a combination of fixed and live cell fluorescence microscopy. As the affinity of the antibody:IL-6 interaction at pH 6.0 decreases, an increasing amount of antigen dissociates from FcRn-bound antibody in early and late endosomes, and then enters lysosomes. Segregation of antibody and FcRn from endosomes in tubulovesicular transport carriers (TCs) into the recycling pathway can also be observed in live cells, and the extent of IL-6 association with TCs correlates with increasing affinity of the antibody:IL-6 interaction at acidic pH. These analyses result in an understanding, in spatiotemporal terms, of the effect of pH dependence of antibody-antigen interactions on subcellular trafficking and inform the design of antibodies with optimized binding properties for antigen elimination.

  5. Effects of the foliar-applied protein "Harpin(Ea)" (messenger) on tomatoes infected with Phytophthora infestans.

    PubMed

    Fontanilla, M; Montes, M; De Prado, R

    2005-01-01

    The active ingredient in Messenger, is Harpin(Ea), a naturally occurring protein derived from Erwinia amylovora, a causal agent of fire blight. When Messenger is applied to a plant, the protein Harpin(Ea) binds foliar receptors to it. The receptors recognize the presence of Harpin(Ea), sending a signal that a pathogen is present, actually "tricking" the plant into thinking that it is under attack. This binding process triggers a cascade of responses affecting a global change of gene expressions, stimulating several distinct biochemical pathways within the plant responsible for growth and disease and insect resistance. The objective of this work is to characterize the development of an induced resistance against Phytophthora infestans. No effective treatment is currently available against this pathogenic agent, which causes the loss of complete harvests of different crops. Tomato plants with and without Messenger applications were inoculated with Phytophthora infestans in the same way. In addition, some plants with and without Messenger applications were not inoculated. Inoculated plants were symptomatologically checked for local and systemic symptoms. Evaluations of the number of tomatoes produced, with or without damage, and their growth, were also carried out. Based on the data obtained from the assays, significant changes were observed in the parameters measured due to Messenger treatment. The severe damage of this disease was reduced in the plants which received Messenger applications. These results open up new pathways in the control of diseases like Phytophthora infestans, in which effective means to combat them still do not exist, or these means are harmful to the environment.

  6. Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses.

    PubMed

    Tay, Szun Szun; Wong, Yik Chun; McDonald, David M; Wood, Nicole A W; Roediger, Ben; Sierro, Frederic; Mcguffog, Claire; Alexander, Ian E; Bishop, G Alex; Gamble, Jennifer R; Weninger, Wolfgang; McCaughan, Geoffrey W; Bertolino, Patrick; Bowen, David G

    2014-06-24

    CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.

  7. [Early diagnosis of streptococcal pharyngitis in paediatric practice: Validity of a rapid antigen detection test].

    PubMed

    Flores Mateo, Gemma; Conejero, Jaume; Grenzner Martinel, Elisabet; Baba, Zeki; Dicono, Susana; Echasabal, Mildrey; Gonzalo Santos, Concepción; Aliaga, Arantxa; Barredo, María; Ruiz, Luis; Carrau, Montserrat

    2010-07-01

    To determine the validity of the rapid antigen test for the diagnoses of acute pharyngitis caused by group A beta-haemolytic Streptococcus (GABHS) compared with culture. Observational study of a consecutive sample of paediatric patients. Two primary care centres (PCC) from the metropolitan area of Barcelona. Children aged 1-14 years with sore throat of no more than 5 days duration were chosen at PCC. Oropharyngeal samples were collected from tonsillar bed and posterior pharynx. A rapid diagnostic test was performed, as well as a throat culture. A total of 211 patients were studied. The overall prevalence of pharyngitis due to Streptococcus was 34.1%. Compared with the throat culture, the sensitivity of the rapid test was 90.3% (95% CI: 81.0-96.0), the specificity was 78.4% (95% CI: 70.6-84.9). The percentage of false negatives was 9.7% and the false positives was 21.6%. Spectrum bias was present, inasmuch as the rapid test sensitivity increased with Centor scores. The diagnostic value of a rapid antigen test for the diagnosis of streptococcal pharyngitis in paediatric patients at PCC is high. However, the percentage of false positives and negatives is too high, and also the sensitivity is too low in patients with fewer symptoms to support the use of rapid antigenic test without culture confirmation and bacterial sensitivity test. 2009 Elsevier España, S.L. All rights reserved.

  8. A Multi-Level Investigation into the Antecedents of Enterprise Architecture (EA) Assimilation in the U.S. Federal Government: A Longitudinal Mixed Methods Research Study

    ERIC Educational Resources Information Center

    Makiya, George K.

    2012-01-01

    This dissertation reports on a multi-dimensional longitudinal investigation of the factors that influence Enterprise Architecture (EA) diffusion and assimilation within the U.S. federal government. The study uses publicly available datasets of 123 U.S. federal departments and agencies, as well as interview data among CIOs and EA managers within…

  9. The molecular mechanism of the termination of insect diapause, part 1: A timer protein, TIME-EA4, in the diapause eggs of the silkworm Bombyx mori is a metallo-glycoprotein.

    PubMed

    Isobe, Minoru; Kai, Hidenori; Kurahashi, Takuya; Suwan, Sathorn; Pitchayawasin-Thapphasaraphong, Suthasinee; Franz, Thomas; Tani, Naoki; Higashi, Kenichiro; Nishida, Hideo

    2006-10-01

    TIME-EA4 is an ATPase that measures time intervals, functioning as a diapause duration clock in diapause eggs of the silkworm, Bombyx mori. Characterization of the primary and higher structures of the TIME-EA4 would be desirable to clarify the mechanism by which the protein measures the time intervals. In our current studies, the whole sequence of TIME-EA4 has been established as that of a metallo-glycoprotein by combinational means involving peptide sequence analysis, nano-HPLC-ESI-Q-TOF-MS and MS/MS, and cDNA dictation. The amino acid sequence of TIME-EA4 showed 46-55 % homology with the reported proteins of the Cu,Zn-SOD (superoxide dismutase) family; in particular, the SOD active site (core domain) includes metal-binding amino acid ligands and a disulfide bond, and these structures are completely identical in Bombyx SOD, bovine SOD, and TIME-EA4 proteins. We found, however, that TIME-EA4 contains one more copper ion than other SODs, as was proven under neutral nondenaturing conditions. ESI mass spectrometry revealed that the timer function was not in the SOD core domain. In addition, TIME-EA4 has an attached sugar chain, which is indispensable to its functioning as a timer protein.

  10. Ex vivo tetramer staining and cell surface phenotyping for early activation markers CD38 and HLA-DR to enumerate and characterize malaria antigen-specific CD8+ T-cells induced in human volunteers immunized with a Plasmodium falciparum adenovirus-vectored malaria vaccine expressing AMA1.

    PubMed

    Schwenk, Robert; Banania, Glenna; Epstein, Judy; Kim, Yohan; Peters, Bjoern; Belmonte, Maria; Ganeshan, Harini; Huang, Jun; Reyes, Sharina; Stryhn, Anette; Ockenhouse, Christian F; Buus, Soren; Richie, Thomas L; Sedegah, Martha

    2013-10-29

    Malaria is responsible for up to a 600,000 deaths per year; conveying an urgent need for the development of a malaria vaccine. Studies with whole sporozoite vaccines in mice and non-human primates have shown that sporozoite-induced CD8+ T cells targeting liver stage antigens can mediate sterile protection. There is a need for a direct method to identify and phenotype malaria vaccine-induced CD8+ T cells in humans. Fluorochrome-labelled tetramers consisting of appropriate MHC class I molecules in complex with predicted binding peptides derived from Plasmodium falciparum AMA-1 were used to label ex vivo AMA-1 epitope specific CD8+ T cells from research subjects responding strongly to immunization with the NMRC-M3V-Ad-PfCA (adenovirus-vectored) malaria vaccine. The identification of these CD8+ T cells on the basis of their expression of early activation markers was also investigated. Analyses by flow cytometry demonstrated that two of the six tetramers tested: TLDEMRHFY: HLA-A*01:01 and NEVVVKEEY: HLA-B*18:01, labelled tetramer-specific CD8+ T cells from two HLA-A*01:01 volunteers and one HLA-B*18:01 volunteer, respectively. By contrast, post-immune CD8+ T cells from all six of the immunized volunteers exhibited enhanced expression of the CD38 and HLA-DRhi early activation markers. For the three volunteers with positive tetramer staining, the early activation phenotype positive cells included essentially all of the tetramer positive, malaria epitope- specific CD8+ T cells suggesting that the early activation phenotype could identify all malaria vaccine-induced CD8+ T cells without prior knowledge of their exact epitope specificity. The results demonstrated that class I tetramers can identify ex vivo malaria vaccine antigen-specific CD8+ T cells and could therefore be used to determine their frequency, cell surface phenotype and transcription factor usage. The results also demonstrated that vaccine antigen-specific CD8+ T cells could be identified by activation markers

  11. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    PubMed

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

  12. Early Diagnosis of Scrub Typhus with a Rapid Flow Assay Using Recombinant Major Outer Membrane Protein Antigen (r56) of Orientia tsutsugamushi

    PubMed Central

    Ching, W.-M.; Rowland, D.; Zhang, Z.; Bourgeois, A. L.; Kelly, D.; Dasch, G. A.; Devine, P. L.

    2001-01-01

    The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the immunodominant antigen in human scrub typhus infections. We developed a rapid immunochromatographic flow assay (RFA) for the detection of immunoglobulin M (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated recombinant 56-kDa protein from the Karp strain as the antigen. The performance of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85 individuals suspected of scrub typhus) which were collected in the Pescadore Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp whole-cell antigen. In 29 cases specific responses were detected by the RFA earlier than by IFA, 44 cases had the same detection time, and 5 cases were detected earlier by IFA than by RFA. For IgG responses, 4 individuals were negative with both methods, 37 cases exhibited earlier detection by RFA than IFA, 42 cases were detected at the same time, and 2 cases were detected earlier by IFA than by RFA. The sensitivities of RFA detection of antibody in sera from confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG results were combined, the sensitivity was 89%. A panel of 78 individual sera collected from patients with no evidence of scrub typhus was used to evaluate the specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and were 78% when the results of IgM and IgG were combined. The RFA test was significantly better than the IFA test for the early detection of antibody to scrub typhus in primary infections, while both tests were equally sensitive with reinfected individuals. PMID:11238230

  13. Attenuation analysis of real GPR wavelets: The equivalent amplitude spectrum (EAS)

    NASA Astrophysics Data System (ADS)

    Economou, Nikos; Kritikakis, George

    2016-03-01

    Absorption of a Ground Penetrating Radar (GPR) pulse is a frequency dependent attenuation mechanism which causes a spectral shift on the dominant frequency of GPR data. Both energy variation of GPR amplitude spectrum and spectral shift were used for the estimation of Quality Factor (Q*) and subsequently the characterization of the subsurface material properties. The variation of the amplitude spectrum energy has been studied by Spectral Ratio (SR) method and the frequency shift by the estimation of the Frequency Centroid Shift (FCS) or the Frequency Peak Shift (FPS) methods. The FPS method is more automatic, less robust. This work aims to increase the robustness of the FPS method by fitting a part of the amplitude spectrum of GPR data with Ricker, Gaussian, Sigmoid-Gaussian or Ricker-Gaussian functions. These functions fit different parts of the spectrum of a GPR reference wavelet and the Equivalent Amplitude Spectrum (EAS) is selected, reproducing Q* values used in forward Q* modeling analysis. Then, only the peak frequencies and the time differences between the reference wavelet and the subsequent reflected wavelets are used to estimate Q*. As long as the EAS is estimated, it is used for Q* evaluation in all the GPR section, under the assumption that the selected reference wavelet is representative. De-phasing and constant phase shift, for obtaining symmetrical wavelets, proved useful in the sufficiency of the horizons picking. Synthetic, experimental and real GPR data were examined in order to demonstrate the effectiveness of the proposed methodology.

  14. Serological purification of polysaccharide antigens from Streptococcus mutans serotypes a and d: characterization of multiple antigenic determinants.

    PubMed

    Linzer, R; Mukasa, H; Slade, H D

    1975-10-01

    The polysaccharide antigen preparations from serotype a and serotype d strains of Streptococcus mutans contained both a serotype-specific antigenic determinant and a common a-d antigenic determinant, as demonstrated by agar gel diffusion studies and a quantitative cross-precipitin assay. The chromatographically purified antigens were isolated by a method which depended on their serological specificity to determine if these two antigenic determinants were located on the same molecule. The a and d polysaccharides were recovered from specific antigen-antibody complexes and characterized with respect to their immunological specificity and chemical composition. Agar gel diffusion tests demonstrated that, in both the a and d preparations, the serotype-specific antigenic determinant and the common a-d antigenic determinant were present in one molecule.

  15. Allergic aspergillosis and the antigens of Aspergillus fumigatus.

    PubMed

    Singh, Bharat; Singh, Seema; Asif, Abdul R; Oellerich, Michael; Sharma, Gainda L

    2014-01-01

    Incidence of fungal infections has increased alarmingly in past few decades. Of the fungal pathogens, the Aspergillus fumigatus has been a major cause of allergic bronchopulmonary aspergillosis (ABPA) which has five main stages--the acute, remission, exacerbation, glucocorticoid dependent and fibrotic stage. The diagnosis of ABPA remains difficult due to its overlapping clinical and radiological features with tuberculosis and cystic fibrosis. From past few decades, the crude fractions of A. fumigatus have been used for immunodiagnosis of ABPA. Most of the detection kits based on crude fractions of A. fumigatus are quite sensitive but have low specificity. Till date 21 known and 25 predicted allergens of A. fumigatus have been identified. Of these allergens, only five recombinants (rAsp f1-f4 and f6) are commercially used for diagnosis of allergic aspergillosis. Remaining allergens of A. fumigatus have been restricted for use in specific diagnosis of ABPA, due to sharing of common antigenic epitopes with other allergens. Complete sequencing of A. fumigatus genome identified 9926 genes and the reports on the proteome of A. fumigatus have shown the presence of large number of their corresponding proteins in the pathogen. The analysis of immunoproteomes developed from crude fractions of A. fumigatus by IgG/IgE reactivity with ABPA patients and animal sera have identified the panel of new antigens. A brief description on the current status of A. fumigatus antigens is provided in this review. The implementation of advance recombinant expression and peptidomic approaches on the A. fumigatus antigens may help in the selection of appropriate molecules for the development of tools for more specific early diagnosis of ABPA, and desensitization therapies for patients of allergic disorders.

  16. Oxygen isotope analysis of phosphate: improved precision using TC/EA CF-IRMS.

    PubMed

    LaPorte, D F; Holmden, C; Patterson, W P; Prokopiuk, T; Eglington, B M

    2009-06-01

    Oxygen isotope values of biogenic apatite have long demonstrated considerable promise for paleothermometry potential because of the abundance of material in the fossil record and greater resistance of apatite to diagenesis compared to carbonate. Unfortunately, this promise has not been fully realized because of relatively poor precision of isotopic measurements, and exceedingly small size of some substrates for analysis. Building on previous work, we demonstrate that it is possible to improve precision of delta18O(PO4) measurements using a 'reverse-plumbed' thermal conversion elemental analyzer (TC/EA) coupled to a continuous flow isotope ratio mass spectrometer (CF-IRMS) via a helium stream [Correction made here after initial online publication]. This modification to the flow of helium through the TC/EA, and careful location of the packing of glassy carbon fragments relative to the hot spot in the reactor, leads to narrower, more symmetrically distributed CO elution peaks with diminished tailing. In addition, we describe our apatite purification chemistry that uses nitric acid and cation exchange resin. Purification chemistry is optimized for processing small samples, minimizing isotopic fractionation of PO4(-3) and permitting Ca, Sr and Nd to be eluted and purified further for the measurement of delta44Ca and 87Sr/86Sr in modern biogenic apatite and 143Nd/144Nd in fossil apatite. Our methodology yields an external precision of +/- 0.15 per thousand (1sigma) for delta18O(PO4). The uncertainty is related to the preparation of the Ag3PO4 salt, conversion to CO gas in a reversed-plumbed TC/EA, analysis of oxygen isotopes using a CF-IRMS, and uncertainty in constructing calibration lines that convert raw delta18O data to the VSMOW scale. Matrix matching of samples and standards for the purpose of calibration to the VSMOW scale was determined to be unnecessary. Our method requires only slightly modified equipment that is widely available. This fact, and the

  17. Aggregation of recombinant human botulinum protein antigen serotype C in varying solution conditions: implications of conformational stability for aggregation kinetics.

    PubMed

    Bai, Shujun; Manning, Mark Cornell; Randolph, Theodore W; Carpenter, John F

    2011-03-01

    Solution conditions greatly affect the aggregation rate of a protein. Elucidating these influences provides insight into the critical factors governing aggregation. In this study, recombinant human botulinum protein antigen serotype C [rBoNTC (H(c))] was employed as a model protein. rBoNTC (H(c)) aggregated irreversibly during incubation at 42°C. The aggregation rate was studied as a function of solution conditions, including varying the pH from 3.5 to 8.0 and with or without 150 mM NaCl, 7.5% (w/v) trehalose, and 0.5 M urea. Some solution conditions retarded rBoNTC (H(c)) aggregation, whereas others accelerated aggregation, particularly acidic pH and addition of NaCl or urea. To better understand the mechanism by which these solution conditions influenced aggregation rates, the structure of rBoNTC (H(c)) was characterized using circular dichroism, fluorescence, and ultraviolet absorbance spectroscopies. Conformational stability was assessed from equilibrium urea-induced unfolding studies and by using differential scanning calorimetry (DSC). The activation energy of the aggregation reaction (E(a)) was estimated from an analysis of the heating-rate dependence of the thermal transition observed during DSC heating scans. Overall, for rBoNTC (H(c)), an inverse correlation was found between conformational stability and aggregation rate, as well as between the kinetic barrier to unfolding (i.e., E(a)) and aggregation rate. Copyright © 2010 Wiley-Liss, Inc.

  18. Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion.

    PubMed

    Kaartinen, Tanja; Luostarinen, Annu; Maliniemi, Pilvi; Keto, Joni; Arvas, Mikko; Belt, Heini; Koponen, Jonna; Loskog, Angelica; Mustjoki, Satu; Porkka, Kimmo; Ylä-Herttuala, Seppo; Korhonen, Matti

    2017-06-01

    Adoptive T-cell therapy offers new options for cancer treatment. Clinical results suggest that T-cell persistence, depending on T-cell memory, improves efficacy. The use of interleukin (IL)-2 for in vitro T-cell expansion is not straightforward because it drives effector T-cell differentiation but does not promote the formation of T-cell memory. We have developed a cost-effective expansion protocol for chimeric antigen receptor (CAR) T cells with an early memory phenotype. Lymphocytes were transduced with third-generation lentiviral vectors and expanded using CD3/CD28 microbeads. The effects of altering the IL-2 supplementation (0-300 IU/mL) and length of expansion (10-20 days) on the phenotype of the T-cell products were analyzed. High IL-2 levels led to a decrease in overall generation of early memory T cells by both decreasing central memory T cells and augmenting effectors. T memory stem cells (T SCM , CD95 + CD45RO - CD45RA + CD27 + ) were present variably during T-cell expansion. However, their presence was not IL-2 dependent but was linked to expansion kinetics. CD19-CAR T cells generated in these conditions displayed in vitro antileukemic activity. In summary, production of CAR T cells without any cytokine supplementation yielded the highest proportion of early memory T cells, provided a 10-fold cell expansion and the cells were functionally potent. The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost-effective T-cell manufacturing. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Antigenic evaluation of a recombinant baculovirus-expressed Sarcocystis neurona SAG1 antigen.

    PubMed

    Gupta, G D; Lakritz, J; Saville, W J; Livingston, R S; Dubey, J P; Middleton, J R; Marsh, A E

    2004-10-01

    Sarcocystis neurona is the primary parasite associated with equine protozoal myeloencephalitis (EPM). This is a commonly diagnosed neurological disorder in the Americas that infects the central nervous system of horses. Current serologic assays utilize culture-derived parasites as antigen. This method requires large numbers of parasites to be grown in culture, which is labor intensive and time consuming. Also, a culture-derived whole-parasite preparation contains conserved antigens that could cross-react with antibodies against other Sarcocystis species and members of Sarcocystidae such as Neospora spp., Hammondia spp., and Toxoplasma gondii. Therefore, there is a need to develop an improved method for the detection of S. neurona-specific antibodies. The sera of infected horses react strongly to surface antigen 1 (SnSAG1), an approximately 29-kDa protein, in immunoblot analysis, suggesting that it is an immunodominant antigen. The SnSAG1 gene of S. neurona was cloned, and recombinant S. neurona SAG1 protein (rSnSAG1-Bac) was expressed with the use of a baculovirus system. By immunoblot analysis, the rSnSAG1-Bac antigen detected antibodies to S. neurona from naturally infected and experimentally inoculated equids, cats, rabbit, mice, and skunk. This is the first report of a baculovirus-expressed recombinant S. neurona antigen being used to detect anti-S. neurona antibodies in a variety of host species.

  20. 36 CFR § 1010.7 - Actions that do not require an EA or EIS.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Actions that do not require an EA or EIS. § 1010.7 Section § 1010.7 Parks, Forests, and Public Property PRESIDIO TRUST... utility right-of-way; and (37) Experimental testing of no longer than 180 days of mass transit systems...

  1. Automatic and integrated micro-enzyme assay (AIμEA) platform for highly sensitive thrombin analysis via an engineered fluorescence protein-functionalized monolithic capillary column.

    PubMed

    Lin, Lihua; Liu, Shengquan; Nie, Zhou; Chen, Yingzhuang; Lei, Chunyang; Wang, Zhen; Yin, Chao; Hu, Huiping; Huang, Yan; Yao, Shouzhuo

    2015-04-21

    Nowadays, large-scale screening for enzyme discovery, engineering, and drug discovery processes require simple, fast, and sensitive enzyme activity assay platforms with high integration and potential for high-throughput detection. Herein, a novel automatic and integrated micro-enzyme assay (AIμEA) platform was proposed based on a unique microreaction system fabricated by a engineered green fluorescence protein (GFP)-functionalized monolithic capillary column, with thrombin as an example. The recombinant GFP probe was rationally engineered to possess a His-tag and a substrate sequence of thrombin, which enable it to be immobilized on the monolith via metal affinity binding, and to be released after thrombin digestion. Combined with capillary electrophoresis-laser-induced fluorescence (CE-LIF), all the procedures, including thrombin injection, online enzymatic digestion in the microreaction system, and label-free detection of the released GFP, were integrated in a single electrophoretic process. By taking advantage of the ultrahigh loading capacity of the AIμEA platform and the CE automatic programming setup, one microreaction column was sufficient for many times digestion without replacement. The novel microreaction system showed significantly enhanced catalytic efficiency, about 30 fold higher than that of the equivalent bulk reaction. Accordingly, the AIμEA platform was highly sensitive with a limit of detection down to 1 pM of thrombin. Moreover, the AIμEA platform was robust and reliable to detect thrombin in human serum samples and its inhibition by hirudin. Hence, this AIμEA platform exhibits great potential for high-throughput analysis in future biological application, disease diagnostics, and drug screening.

  2. In vitro antigen-induced, antigen-specific antibody production in man. Specific and polyclonal components, kinetics, and cellular requirements

    PubMed Central

    1981-01-01

    A highly specific and reproducible antigen-induced, antigen-specific culture and assay system for antibody production by human peripheral blood B lymphocytes has been developed. The system is clearly T cell and monocyte dependent and is independent of exogenous mitogens. The major factors in our ability to trigger specific antibody production with antigen alone have been the use of extremely low concentrations of antigen in vitro (doses several orders of magnitude below those inducing a peak blastogenic response), careful attention to in vitro cell density and culture vessel geometry, and appreciation of the kinetics of the circulating antigen-inducible B cell repertoire. A dichotomy and overlap between antigen-induced, antigen-specific and antigen-induced, polyclonal responses was observed in the study of doubly immunized individuals. Whereas antibody responses highly specific for the antigen in culture were observed under one set of culture conditions (flat-bottomed vessels, 1.5 x 10(6) cells), switching to another culture system (round-bottomed vessels, 5 x 10(5) cells) resulted in polyclonal responses to antigen. Despite these culture condition-related differences in the induction of antibody synthesis, the suppression of specific antibody production that occurred at high concentrations of antigen was specific only for the antigen in culture. The capability to easily and reproducibly look at truly antigen-induced, antigen specific antibody production should be a major tool in furthering the understanding of human B cell activation and immunoregulation. PMID:6169778

  3. Diagnostic Markers of Ovarian Cancer by High-Throughput Antigen Cloning and Detection on Arrays

    PubMed Central

    Chatterjee, Madhumita; Mohapatra, Saroj; Ionan, Alexei; Bawa, Gagandeep; Ali-Fehmi, Rouba; Wang, Xiaoju; Nowak, James; Ye, Bin; Nahhas, Fatimah A.; Lu, Karen; Witkin, Steven S.; Fishman, David; Munkarah, Adnan; Morris, Robert; Levin, Nancy K.; Shirley, Natalie N.; Tromp, Gerard; Abrams, Judith; Draghici, Sorin; Tainsky, Michael A.

    2008-01-01

    A noninvasive screening test would significantly facilitate early detection of epithelial ovarian cancer. This study used a combination of high-throughput selection and array-based serologic detection of many antigens indicative of the presence of cancer, thereby using the immune system as a biosensor. This high-throughput selection involved biopanning of an ovarian cancer phage display library using serum immunoglobulins from an ovarian cancer patient as bait. Protein macroarrays containing 480 of these selected antigen clones revealed 65 clones that interacted with immunoglobulins in sera from 32 ovarian cancer patients but not with sera from 25 healthy women or 14 patients having other benign or malignant gynecologic diseases. Sequence analysis data of these 65 clones revealed 62 different antigens. Among the markers, we identified some known antigens, including RCAS1, signal recognition protein-19, AHNAK-related sequence, nuclear autoantogenic sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gene product, eukaryotic initiation factor 5A, and casein kinase II, as well as many previously uncharacterized antigenic gene products. Using these 65 antigens on protein microarrays, we trained neural networks on two-color fluorescent detection of serum IgG binding and found an average sensitivity and specificity of 55% and 98%, respectively. In addition, the top 6 of the most specific clones resulted in an average sensitivity and specificity of 32% and 94%, respectively. This global approach to antigenic profiling, epitomics, has applications to cancer and autoimmune diseases for diagnostic and therapeutic studies. Further work with larger panels of antigens should provide a comprehensive set of markers with sufficient sensitivity and specificity suitable for clinical testing in high-risk populations. PMID:16424057

  4. The factor structure of the Buss and Plomin EAS Temperament Survey (parental ratings) in a Dutch sample of elementary school children.

    PubMed

    Boer, F; Westenberg, P M

    1994-06-01

    The psychometric properties of the Buss and Plomin (1984) EAS Temperament Survey for Children (Parental Ratings) were examined in a sample of Dutch children between 4 and 13 years of age. Ratings were obtained from 230 mothers and 172 fathers. The findings presented here provide the lacking cross-validation of the original analyses by Rowe and Plomin (1977): Emotionality, activity, and shyness were independent temperaments, regardless of age and gender. The factorial position of the yet experimental Sociability scale is more ambiguous: Sociability was significantly related to both shyness and activity but was more strongly associated with shyness in the youngest age cohort and most strongly with activity in the oldest cohort. This age trend, combined with a positive association with activity, supports the premise that sociability cannot be equated to nonshyness and justifies the inclusion of a separate Sociability scale in the EAS. All four EAS scales are reliable in terms of internal consistency and interrater agreement, but one modification of the Sociability scale is needed.

  5. The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

    PubMed Central

    Gabitzsch, Elizabeth S.; Tsang, Kwong Yok; Palena, Claudia; David, Justin M.; Fantini, Massimo; Kwilas, Anna; Rice, Adrian E.; Latchman, Yvette; Hodge, James W.; Gulley, James L.; Madan, Ravi A.; Heery, Christopher R.; Balint, Joseph P.

    2015-01-01

    Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies. PMID:26374823

  6. How effective are the ESC/EAS and 2013 ACC/AHA guidelines in treating dyslipidemia? Lessons from a lipid clinic.

    PubMed

    Barkas, Fotios; Milionis, Haralampos; Kostapanos, Michael S; Mikhailidis, Dimitri P; Elisaf, Moses; Liberopoulos, Evangelos

    2015-02-01

    There is a paucity of data regarding the attainment of lipid-lowering treatment goals according to the recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines. The aim of the present study was to assess how applicable these 2013 recommendations are in the setting of an Outpatient University Hospital Lipid Clinic. This was a retrospective (from 1999 to 2013) observational study including 1000 consecutive adults treated for hyperlipidemia and followed up for ≥3 years. Comparisons for the applicability of current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) and recent ACC/AHA guidelines were performed. Achievement rates of low density lipoprotein cholesterol (LDL-C) targets set by ESC/EAS were 21%, 44% and 62% among patients at very high, high and moderate cardiovascular risk, respectively, receiving statin monotherapy. Among individuals on high-intensity statins only 47% achieved the anticipated ≥50% LDL-C reduction, i.e. the ACC/AHA target. The corresponding rate was significantly greater among those on statin + ezetimibe (76%, p < 0.05). Likewise, higher rates of LDL-C target attainment according to ESC/EAS guidelines were observed in patients on statin + ezetimibe compared with statin monotherapy (37, 50 and 71% for the three risk groups, p < 0.05 for the very high risk group). The application of the ACC/AHA guidelines may be associated with undertreatment of high risk patients due to suboptimal LDL-C response to high-intensity statins in clinical practice. Adding ezetimibe substantially increases the rate of the ESC/EAS LDL-C target achievement together with the rate of LDL-C lowering response suggested by the ACC/AHA.

  7. Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

    PubMed

    Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

    2003-05-01

    Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

  8. Engineering antigen-specific immunological tolerance.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatorymore » responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.« less

  9. ANTIGENIC MODULATION

    PubMed Central

    Old, Lloyd J.; Stockert, Elisabeth; Boyse, Edward A.; Kim, Jae Ho

    1968-01-01

    Antigenic modulation (the loss of TL antigens from TL+ cells exposed to TL antibody in the absence of lytic complement) has been demonstrated in vitro. An ascites leukemia, phenotype TL.1,2,3, which modulates rapidly and completely when incubated with TL antiserum in vitro, was selected for further study of the phenomenon. Over a wide range of TL antibody concentrations modulation at 37°C was detectable within 10 min and was complete within approximately 1 hr. The cells were initially sensitized to C' by their contact with antibody, thereafter losing this sensitivity to C' lysis together with their sensitivity to TL antibody and C' in the cytotoxic test. The capacity of the cells to undergo modulation was abolished by actinomycin D and by iodoacetamide, and by reducing the temperature of incubation to 0°C. Thus modulation apparently is an active cellular process. Antigens TL. 1,2, and 3 are all modulated by anti-TL.1,3 serum and by anti-TL.3 serum. This modulation affects all three TL components together, even when antibody to one or two of them is lacking. aAnti-TL.2 serum does not induce modulation and in fact impairs modulation by the other TL antibodies. The influence of the TL phenotype of cells upon the demonstrable content of H-2 (D region) isoantigen, first shown in cells modulated in vivo, has been observed with cells modulated in vitro. Cells undergoing modulation show a progressive increase in H-2 (D region) antigen over a period of 4 hr, with no change in H-2 antigens of the K region. Restoration of the TL+ phenotype of modulated cells after removal of antibody is less rapid than TL+ → TL- modulation and may require several cell divisions. PMID:5636556

  10. The genetic origin of minor histocompatibility antigens.

    PubMed

    Roopenian, D C; Christianson, G J; Davis, A P; Zuberi, A R; Mobraaten, L E

    1993-01-01

    The purpose of this study was to elucidate the genetic origin of minor histocompatibility (H) antigens. Toward this end common inbred mouse strains, distinct subspecies, and species of the subgenus Mus were examined for expression of various minor H antigens. These antigens were encoded by the classical minor H loci H-3 and H-4 or by newly identified minor H antigens detected as a consequence of mutation. Both minor H antigens that stimulate MHC class I-restricted cytotoxic T cells (Tc) and antigens that stimulate MHC class II-restricted helper T cells (Th) were monitored. The results suggested that strains of distinct ancestry commonly express identical or cross-reactive antigens. Moreover, a correlation between the lack of expression of minor H antigens and ancestral heritage was observed. To address whether the antigens found on unrelated strains were allelic with the sensitizing minor H antigens or a consequence of antigen cross-reactivity, classical genetic segregation analysis was carried out. Even in distinct subspecies and species, the minor H antigens always mapped to the site of the appropriate minor H locus. Together the results suggest: 1) minor H antigen sequences are evolutionarily stable in that their pace of antigenic change is slow enough to predate subspeciation and speciation; 2) the minor H antigens originated in the inbred strains as a consequence of a rare polymorphism or loss mutation carried in a founder mouse stock that caused the mouse to perceive the wild-type protein as foreign; 3) there is a remarkable lack of antigenic cross-reactivity between the defined minor H antigens and other gene products.

  11. [Evaluation of Mascia Brunelli rapid antigen test in the diagnosis of group A streptococcal pharyngitis].

    PubMed

    Barış, Ayşe; Anlıaçık, Nur; Bulut, Mehmet Emin; Deniz, Rıdvan; Yücel, Elif; Aktaş, Elif

    2017-01-01

    Pharyngitis in most cases is due to viral microorganisms however drug therapy without the detection of etiological agent leads to unnecessary use of antibiotics. On the other hand, when the etiologic agent is group A beta-hemolytic streptococci (GAS) it is important to identify the etiologic agent rapidly which will guide the treatment with appropriate antibiotics. The use of highly sensitive rapid tests will contribute significantly to early diagnosis and appropriate therapy. The aim of this study is to evaluate the efficacy of Mascia Brunelli rapid antigen test for the detection of GAS in throat swab samples. A total of 833 throat swab samples submitted to our laboratory with pre-diagnosis of pharyngitis were assessed between June 2016 and August 2016. The samples were simultaneously cultured and tested by rapid Mascia Brunelli Strep-A Card (Mascia Brunelli S.p.a, Italy). For identification, bacitracin sensitivity, PYR test and latex agglutination test in addition to Bruker MALDI-TOF MS (Daltonics, Germany) system were used. The density of GAS growth in the culture was noted. The samples that were false negative with Mascia Brunelli test were re-tested with QuickVue + Strep A Test (Quidel Corporation, San Diego, USA) rapid antigen test. A total of 833 patients, 376 (45.2%) female and 457 (54.8%) male were included in the study. The age range was between 0-94 years with a mean value of 7.86 ± 6.72. 125 (15%) and 94 (11.28%) of the samples were positive with culture and rapid antigen test, respectively. Mascia Brunelli antigen test gave negative results for 31 culture positive samples. Of these 31 samples, 28 were found positive by QuickVue + Strep A antigen test. As a result, the sensitivity of the test was found to be independent of the inoculum effect. The culture positivity rate in patients between 5-15 years was 18.4%. The sensitivity, specificity, positive predictive value, negative predictive value and the accuracy of Mascia Brunelli antigen test, with

  12. A Qualitative Study to Explore How Parental Expectations and Rules Influence Beverage Choices in Early Adolescence

    ERIC Educational Resources Information Center

    Roth-Yousey, Lori; Chu, Yen Li; Reicks, Marla

    2012-01-01

    Objective: To understand parent beverage expectations for early adolescents (EAs) by eating occasion at home and in various settings. Methods: Descriptive study using focus group interviews and the constant comparative method for qualitative data analysis. Results: Six focus groups were completed, and 2 were conducted in Spanish. Participants (n =…

  13. Comparative study of radiation, chemical, and aging effects on viral transformation. Annual progress report, 1975

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Coggin, J.H. Jr.

    Progress is reported on the following research projects: evaluation of isotopic antiglobulin test (IAT) to detect tumor associated antigens using antisera induced by x-irradiated tumor cells; development of cytotoxic antibody for embryonic antigens (EA); acrylamide gel cell culture assay for transformation; and evaluation of 3-MCA induced sarcomas for TSTA and cross-reacting antigens. (HLW)

  14. Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

    PubMed Central

    Mirabelli, Peppino; Di Noto, Rosa; Lo Pardo, Catia; Morabito, Paolo; Abate, Giovanna; Gorrese, Marisa; Raia, Maddalena; Pascariello, Caterina; Scalia, Giulia; Gemei, Marica; Mariotti, Elisabetta; Del Vecchio, Luigi

    2008-01-01

    Background Aldehyde dehydrogenase (ALDH) is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007). The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i) multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii) fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii) detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively). As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a). Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA). Conclusion Our study, comparing surface antigen expression of ALDH+/CD34+, ALDH

  15. HEAT TRANSFER EVALUATION OF HFC-236EA WITH HIGH PERFORMANCE ENHANCED TUBES IN CONDENSATION AND EVAPORATION

    EPA Science Inventory

    The report gives results of an evaluation of the heat transfer performance of pure hydrofluorocarbon (HFC)-236ea for high performance enhanced tubes which had not been previously used in Navy shipboard chillers. Shell-side heat transfer coefficient data are presented for condensa...

  16. 76 FR 80366 - Availability of an Environmental Assessment (EA) and Finding of No Significant Impact (FONSI)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ...) General Permit for Discharges from Construction Activities (2012 Construction General Permit). The EA... runoff from construction activities greater than one acre, where EPA is the permitting authority. Based... significant environmental impacts are anticipated from the issuance of the 2012 Construction General Permit...

  17. Central Tolerance to Tissue-specific Antigens Mediated by Direct and Indirect Antigen Presentation

    PubMed Central

    Gallegos, Alena M.; Bevan, Michael J.

    2004-01-01

    Intrathymic expression of tissue-specific antigens (TSAs) by medullary thymic epithelial cells (Mtecs) leads to deletion of autoreactive T cells. However, because Mtecs are known to be poor antigen-presenting cells (APCs) for tolerance to ubiquitous antigens, and very few Mtecs express a given TSA, it was unclear if central tolerance to TSA was induced directly by Mtec antigen presentation or indirectly by thymic bone marrow (BM)-derived cells via cross-presentation. We show that professional BM-derived APCs acquire TSAs from Mtecs and delete autoreactive CD8 and CD4 T cells. Although direct antigen presentation by Mtecs did not delete the CD4 T cell population tested in this study, Mtec presentation efficiently deleted both monoclonal and polyclonal populations of CD8 T cells. For developing CD8 T cells, deletion by BM-derived APC and by Mtec presentation occurred abruptly at the transitional, CD4high CD8low TCRintermediate stage, presumably as the cells transit from the cortex to the medulla. These studies reveal a cooperative relationship between Mtecs and BM-derived cells in thymic elimination of autoreactive T cells. Although Mtecs synthesize TSAs and delete a subset of autoreactive T cells, BM-derived cells extend the range of clonal deletion by cross-presenting antigen captured from Mtecs. PMID:15492126

  18. Cellular Pathway(S) of Antigen Processing and Presentation in Fish APC: Endosomal Involvement and Cell-Free Antigen Presentation

    PubMed Central

    Vallejo, Abbe N.; Miller, Norman W.; Harvey, Nancy E.; Cuchens, Marvin A.; Warr, Gregory W.

    1992-01-01

    Studies were conducted to address further the role(s) of antigen processing and presentation in the induction of immune responses in a phylogenetically lower vertebrate, specifically a teleost, the channel catfish. In particular, studies were aimed at determining the subcellular compartments involved in antigen degradation by channel catfish antigen-presenting cells (APC) as well as ascertaining the reexpression of immunogenic peptides on the surfaces of APC. The results showed that exogenous protein antigens were actively endocytosed by APC as detected by flow cytometry. Use of radiolabeled antigen and subcellular fractionation protocols also showed that antigen localized in endosomes/lysosomes. Furthermore, there was an apparent redistribution of antigen between these organelles and the plasma membrane during the course of antigen pulsing. Functional assays for the induction of in vitro antigen-specific proliferation of immune catfish peripheral blood leukocytes (PBL) showed that membrane preparations from antigen-pulsed autologous APC were highly stimulatory. The magnitude of responses elicited with such membrane preparations was very similar to that of PBL cultures stimulated with native antigen-pulsed and fixed intact APC or prefixed intact APC incubated with a peptide fragment of the nominal antigen. Current data further corroborate our previous findings that steps akin to antigen processing and presentation are clearly important in the induction of immune responses in lower vertebrates like fish, in a manner similar to that seen in mammalian systems. Consequently, it would appear that many immune functions among the diverse taxa of vertebrates are remarkably conserved. PMID:1343103

  19. Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

    PubMed Central

    Balouz, Virginia; Cámara, María de los Milagros; Cánepa, Gaspar E.; Carmona, Santiago J.; Volcovich, Romina; Gonzalez, Nicolás; Altcheh, Jaime; Agüero, Fernán

    2015-01-01

    The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. PMID:25589551

  20. Antigen recognition in the islets changes with progression of autoimmune islet infiltration

    PubMed Central

    Lindsay, Robin S.; Corbin, Kaitlin; Mahne, Ashley; Levitt, Bonnie E.; Gebert, Matthew J.; Wigton, Eric J.; Bradley, Brenda J.; Haskins, Kathryn; Jacobelli, Jordan; Tang, Qizhi; Krummel, Matthew F.; Friedman, Rachel S.

    2014-01-01

    In type 1 diabetes, the pancreatic islets are an important site for therapeutic intervention since immune infiltration of the islets is well established at diagnosis. Therefore, understanding the events that underlie the continued progression of the autoimmune response and islet destruction is critical. Islet infiltration and destruction is an asynchronous process, making it important to analyze the disease process on a single islet basis. To understand how T cell stimulation evolves through the process of islet infiltration we analyzed the dynamics of T cell movement and interactions within individual islets of spontaneously autoimmune non-obese diabetic (NOD) mice. Using both intra-vital and explanted 2-photon islet imaging, we defined a correlation between increased islet infiltration and increased T cell motility. Early T cell arrest was antigen dependent and due, at least in part, to antigen recognition through sustained interactions with CD11c+ antigen presenting cells (APCs). As islet infiltration progressed, T cell motility became antigen-independent, with a loss of T cell arrest and sustained interactions with CD11c+ APCs. These studies suggest that the autoimmune T cell response in the islets may be temporarily dampened during the course of islet infiltration and disease progression. PMID:25505281

  1. Heterogeneous distribution of antigens on human platelets demonstrated by fluorescence flow cytometry.

    PubMed

    Dunstan, R A; Simpson, M B

    1985-12-01

    We have used fluorescence flow cytometry to analyse cell-to-cell variability in the density of platelet ABH, Ii, Lewis, P, P1A1, Bak,a and HLA class I antigens. Human IgG and IgM antibodies were used in a two-stage assay with goat FITC-conjugated antihuman IgG (H&L) antibody as the label, followed by single cell analysis of 10 000 platelets per sample using a 256-channel fluorescence flow cytometer (Becton-Dickinson FACS Analyser). Computer analysis of fluorescence intensity histograms for mean and peak channel and coefficient of variation shows that the degree of heterogeneity in platelet antigen density varies with each particular blood group. The broad fluorescence distribution curves with oligosaccharide antigens (CVs: A = 53, B = 40, I = 44, Lea = 40, P = 40) indicate that these antigens possess a greater variability in the number of sites per cell compared to the more homogeneous distribution of P1,A1 BaK,a and HLA (CVs: P1A1 = 24, HLA = 30). These findings may partly account for the mechanism by which transfusion of ABO-incompatible platelets results in a biphasic survival curve, with a period of early rapid removal of those platelets with a high density of antigen sites, followed by a relatively normal survival curve for those platelets that possess only a few or no antigen sites. In contrast, P1A1 and HLA sites are less variable in number from one platelet to another in a given donor, and immune-mediated removal would be more likely to approximate a single exponential curve.

  2. Evaluation of RSDL, M291 SDK, 0.5 Bleach, 1% Soapy Water and SERPACWA: Part 11: Challenge with EA4243 (VR, Russian VX)

    DTIC Science & Technology

    2016-01-01

    listed decontamination products in the haired guinea pig model following exposure to VR (Russian VX, EA4243). 15. SUBJECT TERMS decontamination...the efficacy of the barrier skin cream SERPACWA and the four listed decontamination products in the haired guinea pig model following exposure to VR...four listed decontamination products and SERPACWA in the haired guinea pig model following exposure to VR (Russian VX, EA4243, Soviet V-gas

  3. Antigen-Specific T-Cell Activation Independently of the MHC: Chimeric Antigen Receptor-Redirected T Cells

    PubMed Central

    Chmielewski, Markus; Hombach, Andreas A.; Abken, Hinrich

    2013-01-01

    Adoptive T-cell therapy has recently shown promise in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T-cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC) expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient’s T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR) which consists in the extracellular part of an antibody-derived domain for binding with a “tumor-associated antigen” and in the intracellular part of a T-cell receptor (TCR)-derived signaling moiety for T-cell activation. The specificity of CAR-mediated T-cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T-cell targeting by an engineered CAR in comparison to TCR modified T cells and the impact of the CAR activation threshold on redirected T-cell activation. Finally we review most significant progress recently made in early stage clinical trials to treat cancer. PMID:24273543

  4. Early results of immediate repair of obstetric third-degree tears: 65% are completely asymptomatic despite persistent sphincter defects in 61%.

    PubMed

    Hayes, J; Shatari, T; Toozs-Hobson, P; Busby, K; Pretlove, S; Radley, S; Keighley, M

    2007-05-01

    The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence.

  5. Radioimmunoassays of hidden viral antigens

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Neurath, A.R.; Strick, N.; Baker, L.

    1982-07-01

    Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis Bmore » virus DNA were detected. Antibody-bound adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.« less

  6. Quantitative analysis of antigen for the induction of tolerance in carcinoembryonic antigen transgenic mice.

    PubMed Central

    Hasegawa, T; Isobe, K; Nakashima, I; Shimokata, K

    1992-01-01

    In order to analyse the amounts of antigen in the thymus for the induction of tolerance, several carcinoembryonic antigen (CEA) transgenic lines were established which expressed human CEA antigen with different amounts. The chimeric KSN nude mice transplanted with the thymus of the B601 line (in which CEA mRNA and CEA protein could be detected in various tissues) to kidney capsule showed tolerance to human CEA. On the other hand, the chimeric KSN nude mice transplanted with the thymus of the B602 or BC60 line (in which neither CEA mRNA nor CEA protein could be detected by Northern blot analysis and flow cytometry analysis) or normal C57BL/6 (B6) did not develop the tolerance to human CEA. However, the chimeric KSN nude mice transplanted simultaneously with thymus of the B6 and spleen of the B601 line became tolerant to human CEA antigen. In the case of systemic immunization with cells which had CEA antigen, the B601 line was tolerant to human CEA. Surprisingly, the B602 and BC60 lines were also tolerant to CEA molecule. These results indicate that not only the antigen present in the thymus but also the antigen which flows from the peripheral organs to the thymus may be necessary for the induction of CEA tolerance. Images Figure 1 PMID:1493931

  7. Cytotoxicity of Tumor Antigen Specific Human T Cells Is Unimpaired by Arginine Depletion

    PubMed Central

    Knies, Diana; Medenhoff, Sergej; Wabnitz, Guido; Luckner-Minden, Claudia; Feldmeyer, Nadja; Voss, Ralf-Holger; Kropf, Pascale; Müller, Ingrid; Conradi, Roland; Samstag, Yvonne; Theobald, Matthias; Ho, Anthony D.; Goldschmidt, Hartmut; Hundemer, Michael

    2013-01-01

    Tumor-growth is often associated with the expansion of myeloid derived suppressor cells that lead to local or systemic arginine depletion via the enzyme arginase. It is generally assumed that this arginine deficiency induces a global shut-down of T cell activation with ensuing tumor immune escape. While the impact of arginine depletion on polyclonal T cell proliferation and cytokine secretion is well documented, its influence on chemotaxis, cytotoxicity and antigen specific activation of human T cells has not been demonstrated so far. We show here that chemotaxis and early calcium signaling of human T cells are unimpaired in the absence of arginine. We then analyzed CD8+ T cell activation in a tumor peptide as well as a viral peptide antigen specific system: (i) CD8+ T cells with specificity against the MART-1aa26–35*A27L tumor antigen expanded with in vitro generated dendritic cells, and (ii) clonal CMV pp65aa495–503 specific T cells and T cells retrovirally transduced with a CMV pp65aa495–503 specific T cell receptor were analyzed. Our data demonstrate that human CD8+ T cell antigen specific cytotoxicity and perforin secretion are completely preserved in the absence of arginine, while antigen specific proliferation as well as IFN-γ and granzyme B secretion are severely compromised. These novel results highlight the complexity of antigen specific T cell activation and demonstrate that human T cells can preserve important activation-induced effector functions in the context of arginine deficiency. PMID:23717444

  8. The Klebsiella pneumoniae O Antigen Contributes to Bacteremia and Lethality during Murine Pneumonia

    PubMed Central

    Shankar-Sinha, Sunita; Valencia, Gabriel A.; Janes, Brian K.; Rosenberg, Jessica K.; Whitfield, Chris; Bender, Robert A.; Standiford, Ted J.; Younger, John G.

    2004-01-01

    Bacterial surface carbohydrates are important pathogenic factors in gram-negative pneumonia infections. Among these factors, O antigen has been reported to protect pathogens against complement-mediated killing. To examine further the role of O antigen, we insertionally inactivated the gene encoding a galactosyltransferase necessary for serotype O1 O-antigen synthesis (wbbO) from Klebsiella pneumoniae 43816. Analysis of the mutant lipopolysaccharide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the absence of O antigen. In vitro, there were no detectable differences between wild-type K. pneumoniae and the O-antigen-deficient mutant in regard to avid binding by murine complement C3 or resistance to serum- or whole-blood-mediated killing. Nevertheless, the 72-h 50% lethal dose of the wild-type strain was 30-fold greater than that of the mutant (2 × 103 versus 6 × 104 CFU) after intratracheal injection in ICR strain mice. Despite being less lethal, the mutant organism exhibited comparable intrapulmonary proliferation at 24 h compared to the level of the wild type. Whole-lung chemokine expression (CCL3 and CXCL2) and bronchoalveolar inflammatory cell content were also similar between the two infections. However, whereas the wild-type organism produced bacteremia within 24 h of infection in every instance, bacteremia was not seen in mutant-infected mice. These results suggest that during murine pneumonia caused by K. pneumoniae, O antigen contributes to lethality by increasing the propensity for bacteremia and not by significantly changing the early course of intrapulmonary infection. PMID:14977947

  9. Definition of epitopes and antigens recognized by vaccinia specific immune responses: their conservation in variola virus sequences, and use as a model system to study complex pathogens.

    PubMed

    Sette, Alessandro; Grey, Howard; Oseroff, Carla; Peters, Bjoern; Moutaftsi, Magdalini; Crotty, Shane; Assarsson, Erika; Greenbaum, Jay; Kim, Yohan; Kolla, Ravi; Tscharke, David; Koelle, David; Johnson, R Paul; Blum, Janice; Head, Steven; Sidney, John

    2009-12-30

    In the last few years, a wealth of information has become available relating to the targets of vaccinia virus (VACV)-specific CD4(+) T cell, CD8(+) T cell and antibody responses. Due to the large size of its genome, encoding more than 200 different proteins, VACV represents a useful model system to study immunity to complex pathogens. Our data demonstrate that both cellular and humoral responses target a large number of antigens and epitopes. This broad spectrum of targets is detected in both mice and humans. CD4(+) T cell responses target late and structural antigens, while CD8(+) T cells preferentially recognize early antigens. While both CD4(+) and CD8(+) T cell responses target different types of antigens, the antigens recognized by T(H) cells are highly correlated with those recognized by antibody responses. We further show that protein abundance and antibody recognition can be used to predict antigens recognized by CD4(+) T cell responses, while early expression at the mRNA level predicts antigens targeted by CD8(+) T cells. Finally, we find that the vast majority of VACV epitopes are conserved in variola virus (VARV), thus suggesting that the epitopes defined herein also have relevance for the efficacy of VACV as a smallpox vaccine.

  10. Gene expression of cell surface antigens in the early phase of murine influenza pneumonia determined by a cDNA expression array technique.

    PubMed

    Sakai, Shinya; Mantani, Naoki; Kogure, Toshiaki; Ochiai, Hiroshi; Shimada, Yutaka; Terasawa, Katsutoshi

    2002-12-01

    Influenza virus is a worldwide health problem with significant economic consequences. To study the gene expression pattern induced by influenza virus infection, it is useful to reveal the pathogenesis of influenza virus infection; but this has not been well examined, especially in vivo study. To assess the influence of influenza virus infection on gene expression in mice, mRNA levels in the lung and tracheal tissue 48 h after infection were investigated by cDNA array analysis. Four-week-old outbred, specific pathogen free strain, ICR female mice were infected by intra-nasal inoculation of a virus solution under ether anesthesia. The mice were sacrificed 48 h after infection and the tracheas and lungs were removed. To determine gene expression, the membrane-based microtechnique with an Atlas cDNA expression array (mouse 1.2 array II) was performed in accordance with the manual provided. We focused on the expression of 46 mRNAs for cell surface antigens. Of these 46 mRNAs that we examined, four (CD1d2 antigen, CD39 antigen-like 1, CD39 antigen-like 3, CD68 antigen) were up-regulated and one (CD36 antigen) was down-regulated. Although further studies are required, these data suggest that these molecules play an important role in influenza virus infection, especially the phase before specific immunity.

  11. Characterization and storage of malaria antigens: Localization and chemical characterization of Plasmodium knowlesi schizont antigens

    PubMed Central

    Deans, J. A.; Cohen, S.

    1979-01-01

    The identification of malarial antigens that induce protective immunity could provide a rational basis for developing an effective antimalarial vaccine as well as specific serodiagnostic tests indicative of clinical immune status. Since protective immunity is probably induced by stage-dependent rather than stage-independent antigens, the antigenic composition of different stages of Plasmodium knowlesi has been compared, and a limited chemical characterization undertaken. This information should provide some insight into the types of preparative procedure appropriate for the purification of functionally important malarial antigens. PMID:120777

  12. Leukemia-associated antigens in man.

    PubMed

    Brown, G; Capellaro, D; Greaves, M

    1975-12-01

    Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

  13. Mapping antigenic motifs in the trypomastigote small surface antigen from Trypanosoma cruzi.

    PubMed

    Balouz, Virginia; Cámara, María de Los Milagros; Cánepa, Gaspar E; Carmona, Santiago J; Volcovich, Romina; Gonzalez, Nicolás; Altcheh, Jaime; Agüero, Fernán; Buscaglia, Carlos A

    2015-03-01

    The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide- and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acid-long peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Limited antigenic variation in the Trypanosoma cruzi candidate vaccine antigen TSA-1.

    PubMed

    Knight, J M; Zingales, B; Bottazzi, M E; Hotez, P; Zhan, B

    2014-12-01

    Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is one of the most important neglected tropical diseases in the Western Hemisphere. The toxicities and limited efficacies of current antitrypanosomal drugs have prompted a search for alternative technologies such as a therapeutic vaccine comprised of T. cruzi antigens, including a recombinant antigen encoding the N-terminal 65 kDa portion of Trypomastigote surface antigen-1 (TSA-1). With at least six known genetically distinct T. cruzi lineages, variability between the different lineages poses a unique challenge for the development of broadly effective therapeutic vaccine. The variability across the major lineages in the current vaccine candidate antigen TSA-1 has not previously been addressed. To assess the variation in TSA-1, we cloned and sequenced TSA-1 from several different T. cruzi strains representing three of the most clinically relevant lineages. Analysis of the different alleles showed limited variation in TSA-1 across the different strains and fit with the current theory for the evolution of the different lineages. Additionally, minimal variation in known antigenic epitopes for the HLA-A 02 allele suggests that interlineage variation in TSA-1 would not impair the range and efficacy of a vaccine containing TSA-1. © 2014 John Wiley & Sons Ltd.

  15. Production of a fusion protein consisting of the enterotoxigenic Escherichia coli heat-labile toxin B subunit and a tuberculosis antigen in Arabidopsis thaliana.

    PubMed

    Rigano, M M; Alvarez, M L; Pinkhasov, J; Jin, Y; Sala, F; Arntzen, C J; Walmsley, A M

    2004-02-01

    Transgenic plants are potentially safe and inexpensive vehicles to produce and mucosally deliver protective antigens. However, the application of this technology is limited by the poor response of the immune system to non-particulate, subunit vaccines. Co-delivery of therapeutic proteins with carrier proteins could increase the effectiveness of the antigen. This paper reports the ability of transgenic Arabidopsis thaliana plants to produce a fusion protein consisting of the B subunit of the Escherichia coli heat-labile enterotoxin and a 6 kDa tuberculosis antigen, the early secretory antigenic target ESAT-6. Both components of the fusion protein were detected using GM1-ganglioside-dependent enzyme-linked immunosorbant assay. This suggested the fusion protein retained both its native antigenicity and the ability to form pentamers.

  16. A Qualitative Evaluation of Contact Centre Dietitian Support and Electronic Motivational Messaging for eaTracker My Goals Users.

    PubMed

    Lieffers, Jessica R L; Haresign, Helen; Mehling, Christine; Arocha, Jose F; Hanning, Rhona M

    2018-06-01

    To conduct a qualitative evaluation of adjunct supports (brief motivational messaging regarding goals delivered by email/website, contact centre dietitian assistance) offered by EatRight Ontario (ERO) for users of a website-based nutrition/activity goal setting/tracking feature (eaTracker "My Goals"). One-on-one semi-structured interviews were conducted with My Goals users in Ontario (n = 18) and Alberta (n = 5) recruited via the eaTracker website and ERO contact centre dietitians (n = 5). Interview transcripts were analyzed using content analysis. Participants had mixed experiences and perspectives with ERO motivational messaging. Messages targeted towards specific goals (e.g., tips, recipes) were generally well-liked, and generic messages (e.g., eaTracker login reminders) were less useful. No interviewed users had contacted ERO dietitians regarding goals, and dietitians reported encountering few callers asking for assistance while using My Goals. Limited user knowledge was one explanation for this finding. Participants provided suggestions to enhance these supports. Electronic motivational messaging and contact centre dietitian assistance have the potential to support achievement of goals set with website-based features. When considering using electronic messaging, researchers and practitioners should consider message content and delivery tailoring. Marketing that focuses on how contact centre dietitians can assist website users with their goals is needed when services are used in naturalistic settings.

  17. Do FY antigens act as minor histocompatibility antigens in the graft-versus-host disease paradigm after human leukocyte antigen-identical sibling hematopoietic stem cell transplantation?

    PubMed

    Sellami, Mohamed Hichem; Chaabane, Manel; Kaabi, Houda; Torjemane, Lamia; Ladeb, Saloua; Ben Othmane, Tarek; Hmida, Slama

    2012-03-01

    FY antigens are candidate minor histocompatibility antigens relevant to renal allograft rejection, but no data have been reported about their role in graft-versus-host disease (GVHD) incidence after human leukocyte antigen (HLA)-identical siblings hematopoietic stem cell transplantation (HSCT). The aim of this study was to examine the effect of donor/recipient disparity at FY antigens on the incidence of GVHD in Tunisian patients receiving an HLA-identical HSCT. This work enrolled 105 Tunisian pairs of recipients and their HLA-identical sibling donors of HSCs. FY genotyping was performed with the polymerase chain reaction-sequence-specific primer method and donor/recipient disparity for these antigens was analyzed at two levels: incompatibility and nonidentity. The case-control analyses showed no significant correlation between FY disparity and the incidence of either acute or chronic GVHD. Sample size calculation showed that 572 cases and 1716 controls would be necessary to be able to detect a significant association with 80% power and two-sided type I error level of 5% (α=0.05). The lack of association in the studied cohort may be explained by the low immunogenicity of FY antigens in HSCT context, compared with other antigens such as HA-1 and CD31.

  18. ESAT-6 Targeting to DEC205+ Antigen Presenting Cells Induces Specific-T Cell Responses against ESAT-6 and Reduces Pulmonary Infection with Virulent Mycobacterium tuberculosis.

    PubMed

    Silva-Sánchez, Aarón; Meza-Pérez, Selene; Flores-Langarica, Adriana; Donis-Maturano, Luis; Estrada-García, Iris; Calderón-Amador, Juana; Hernández-Pando, Rogelio; Idoyaga, Juliana; Steinman, Ralph M; Flores-Romo, Leopoldo

    2015-01-01

    Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen's naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205+ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and pulmonary mycobacterial load). Treatment with α-DEC-ESAT alone induced ESAT-6-specific IFN-γ producing CD4+ T cells and prime-boost immunization prior to Mtb infection resulted in early influx (d14 post-infection) and increased IFN-γ+ production by specific T cells in the lungs, compared to scarce IFN-γ production in control mice. In vivo CTL killing was quantified in relevant tissues upon transferring target cells loaded with mycobacterial antigens. During infection, α-DEC-ESAT-treated mice showed increased target cell killing in the lungs, where histology revealed cellular infiltrate and considerably reduced bacterial burden. Targeting the mycobacterial antigen ESAT-6 to DEC205+ APCs before infection expands specific T cell clones responsible for early T cell responses (IFN-γ production and CTL activity) and substantially reduces lung bacterial burden. Delivering mycobacterial antigens directly to APCs provides a unique approach to study in vivo the role of APCs and specific T cell responses to assess their potential anti-mycobacterial functions.

  19. ESAT-6 Targeting to DEC205+ Antigen Presenting Cells Induces Specific-T Cell Responses against ESAT-6 and Reduces Pulmonary Infection with Virulent Mycobacterium tuberculosis

    PubMed Central

    Silva-Sánchez, Aarón; Meza-Pérez, Selene; Flores-Langarica, Adriana; Donis-Maturano, Luis; Estrada-García, Iris; Calderón-Amador, Juana; Hernández-Pando, Rogelio; Idoyaga, Juliana; Flores-Romo, Leopoldo

    2015-01-01

    Airways infection with Mycobacterium tuberculosis (Mtb) is contained mostly by T cell responses, however, Mtb has developed evasion mechanisms which affect antigen presenting cell (APC) maturation/recruitment delaying the onset of Ag-specific T cell responses. Hypothetically, bypassing the natural infection routes by delivering antigens directly to APCs may overcome the pathogen’s naturally evolved evasion mechanisms, thus facilitating the induction of protective immune responses. We generated a murine monoclonal fusion antibody (α-DEC-ESAT) to deliver Early Secretory Antigen Target (ESAT)-6 directly to DEC205+ APCs and to assess its in vivo effects on protection associated responses (IFN-γ production, in vivo CTL killing, and pulmonary mycobacterial load). Treatment with α-DEC-ESAT alone induced ESAT-6-specific IFN-γ producing CD4+ T cells and prime-boost immunization prior to Mtb infection resulted in early influx (d14 post-infection) and increased IFN-γ+ production by specific T cells in the lungs, compared to scarce IFN-γ production in control mice. In vivo CTL killing was quantified in relevant tissues upon transferring target cells loaded with mycobacterial antigens. During infection, α-DEC-ESAT-treated mice showed increased target cell killing in the lungs, where histology revealed cellular infiltrate and considerably reduced bacterial burden. Targeting the mycobacterial antigen ESAT-6 to DEC205+ APCs before infection expands specific T cell clones responsible for early T cell responses (IFN-γ production and CTL activity) and substantially reduces lung bacterial burden. Delivering mycobacterial antigens directly to APCs provides a unique approach to study in vivo the role of APCs and specific T cell responses to assess their potential anti-mycobacterial functions. PMID:25915045

  20. Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

    PubMed

    Iwase, Y; Takemura, Y; Ju-ichi, M; Kawaii, S; Yano, M; Okuda, Y; Mukainaka, T; Tsuruta, A; Okuda, M; Takayasu, J; Tokuda, H; Nishino, H

    1999-05-24

    To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

  1. Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L.

    PubMed

    Maoka, T; Mochida, K; Kozuka, M; Ito, Y; Fujiwara, Y; Hashimoto, K; Enjo, F; Ogata, M; Nobukuni, Y; Tokuda, H; Nishino, H

    2001-10-30

    Capsanthin and related carotenoids isolated from the fruits of red paprika Capsicum annuum L. showed potent in vitro anti-tumor-promoting activity with inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among them, capsanthin diester and capsorbin diester showed strong inhibitory effects. Furthermore, capsanthin , capsanthin 3'-ester and capsanthin 3,3'-diester , major carotenoids in paprika, exhibited potent anti-tumor-promoting activity in an in vivo mouse skin two-stage carcinogenesis assay using 7, 12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter.

  2. [Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space].

    PubMed

    Li, Y Q; Sheng, Y; Liang, L; Zhao, Y; Li, H Y; Bai, N; Wang, T; Yuan, L; Han, H B

    2018-04-18

    To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS). In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups. For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10 -4 mm 2 /s vs. (3.37±0.15)×10 -4 mm 2 /s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84

  3. Earthquake Analysis (EA) Software for The Earthquake Observatories

    NASA Astrophysics Data System (ADS)

    Yanik, K.; Tezel, T.

    2009-04-01

    -mail, data reading from anywhere that has ethernet connection and store the results in same centre. The Earthqukae Analysis (EA) program was developed considering above facilities. Microsoft Visual Basic 6.0 and Microsoft GDI tools were used as a basement for program development. EA program can image five different seismic formats (gcf, suds, seisan, sac, nanometrics-y) without any conversion and use all seismic process facilities that are filtering (band-pass, low-pass, high-pass), fast fourier transform, offset adjustment etc.

  4. [Pulse wave velocity as an early marker of diastolic heart failure in patients with hypertension].

    PubMed

    Moczulska, Beata; Kubiak, Monika; Bryczkowska, Anna; Malinowska, Ewa

    2017-04-21

    According to the WHO, hypertension is one of the major causes of death worldwide. It leads to a number of severe complications. Diastolic heart failure, that is heart failure with preserved ejection fraction (HFPEF), is especially common. New, but simple, indices for the early detection of patients who have not yet developed complications or are in their early developmental stages are still searched for. The aim of this study is to examine the correlation between pulse wave velocity (PWV) and markers of diastolic heart failure (DHF) assessed in echocardiography in patients with hypertension and no symptoms of heart failure. The study was comprised of 65 patients with treated hypertension. Patients with symptoms of heart failure, those with diabetes and smokers were excluded. Arterial stiffness was measured with the Mobil-O-Graph NG PWA. Pulse wave velocity (PWV) was estimated. The following markers of diastolic heart failure were assessed in the echocardiographic examination: E/A ratio - the ratio of the early (E) to late (A) ventricular filling velocities, DT - decceleration time, E/E' - the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity E' in tissue Doppler echocardiography. PWV was statistically significantly higher in the DHF group. In the group of patients with heart failure, the average E/A ratio was significantly lower as compared to the group with no heart failure. Oscillometric measurement of pulse wave velocity is non-invasive, lasts a few minutes and does not require the presence of a specialist. It allows for an early detection of patients at risk of diastolic heart failure even within the conditions of primary health care.

  5. Innate Immunity to Respiratory Infection in Early Life

    PubMed Central

    Lambert, Laura; Culley, Fiona J.

    2017-01-01

    Early life is a period of particular susceptibility to respiratory infections and symptoms are frequently more severe in infants than in adults. The neonatal immune system is generally held to be deficient in most compartments; responses to innate stimuli are weak, antigen-presenting cells have poor immunostimulatory activity and adaptive lymphocyte responses are limited, leading to poor immune memory and ineffective vaccine responses. For mucosal surfaces such as the lung, which is continuously exposed to airborne antigen and to potential pathogenic invasion, the ability to discriminate between harmless and potentially dangerous antigens is essential, to prevent inflammation that could lead to loss of gaseous exchange and damage to the developing lung tissue. We have only recently begun to define the differences in respiratory immunity in early life and its environmental and developmental influences. The innate immune system may be of relatively greater importance than the adaptive immune system in the neonatal and infant period than later in life, as it does not require specific antigenic experience. A better understanding of what constitutes protective innate immunity in the respiratory tract in this age group and the factors that influence its development should allow us to predict why certain infants are vulnerable to severe respiratory infections, design treatments to accelerate the development of protective immunity, and design age specific adjuvants to better boost immunity to infection in the lung. PMID:29184555

  6. Integrating influenza antigenic dynamics with molecular evolution

    PubMed Central

    Bedford, Trevor; Suchard, Marc A; Lemey, Philippe; Dudas, Gytis; Gregory, Victoria; Hay, Alan J; McCauley, John W; Russell, Colin A; Smith, Derek J; Rambaut, Andrew

    2014-01-01

    Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution. DOI: http://dx.doi.org/10.7554/eLife.01914.001 PMID:24497547

  7. [Limbic encephalitis with antibodies against intracellular antigens].

    PubMed

    Morita, Akihiko; Kamei, Satoshi

    2010-04-01

    Limbic encephalitis is a paraneoplastic syndrome that is often associated with small cell lung cancer (SCLC), breast cancer, testicular tumors, teratoma, Hodgkin's lymphoma and thymoma. The common clinical manifestations of limbic encephalitis are subacute onset, cognitive dysfunction, seizures and psychiatric symptoms. Paraneoplastic neurological disorders are considered to occur because of cytotoxic T cell responses and antibodies against target neuronal proteins that are usually expressed by an underlying tumor. The main intracellular antigens related to limbic encephalitis are Hu, Ma2, and less frequently CV2/CRMP5 and amphiphysin. The anti-Hu antibody, which is involved in cerebellar degeneration and extensive or multifocal encephalomyelitis such as limbic encephalitis is closely associated with a history of smoking and SCLC. The anti-Ma2 antibody is associated with encephalitis of the limbic system, hypothalamus and brain-stem. For this reason, some patients with limbic encephalitis have sleep disorders (including REM sleep abnormalities), severe hypokinesis and gaze palsy in addition to limbic dysfunction. In men aged less than 50 years, anti-Ma2 antibody encephalitis is almost always associated with testicular germ-cell tumors that are occasionally difficult to detect. In older men and women, the most common tumors are non-SCLC and breast cancer. Limbic encephalitis associated with cell-surface antigens (e.g., voltage-gated potassium channels, NMDA receptors) is mediated by antibodies and often improves after a reduction in the antibody titer and after tumor resection. Patients with antibodies against intracellular antigens, except for those with anti-Ma2 antibodies and testicular tumors, are less responsive. Early diagnosis and treatment with immunotherapy, tumor resection or both are important for improving or stabilizing the condition of limbic encephalitis.

  8. Chemotherapy Enhances Cross-Presentation of Nuclear Tumor Antigens

    PubMed Central

    Anyaegbu, Chidozie C.; Lake, Richard A.; Heel, Kathy; Robinson, Bruce W.; Fisher, Scott A.

    2014-01-01

    Cross-presentation of tumor antigen is essential for efficient priming of naïve CD8+ T lymphocytes and induction of effective anti-tumor immunity. We hypothesized that the subcellular location of a tumor antigen could affect the efficiency of cross-presentation, and hence the outcome of anti-tumor responses to that antigen. We compared cross-presentation of a nominal antigen expressed in the nuclear, secretory, or cytoplasmic compartments of B16 melanoma tumors. All tumors expressed similar levels of the antigen. The antigen was cross-presented from all compartments but when the concentration was low, nuclear antigen was less efficiently cross-presented than antigen from other cellular locations. The efficiency of cross-presentation of the nuclear antigen was improved following chemotherapy-induced tumor cell apoptosis and this correlated with an increase in the proportion of effector CTL. These data demonstrate that chemotherapy improves nuclear tumor antigen cross-presentation and could be important for anti-cancer immunotherapies that target nuclear antigens. PMID:25243472

  9. Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

    PubMed

    Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

    2018-01-01

    Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

  10. Antigen Binding and Site-Directed Labeling of Biosilica-Immobilized Fusion Proteins Expressed in Diatoms.

    PubMed

    Ford, Nicole R; Hecht, Karen A; Hu, DeHong; Orr, Galya; Xiong, Yijia; Squier, Thomas C; Rorrer, Gregory L; Roesijadi, Guritno

    2016-03-18

    The diatom Thalassiosira pseudonana was genetically modified to express biosilica-targeted fusion proteins comprising either enhanced green fluorescent protein (EGFP) or single chain antibodies engineered with a tetracysteine tagging sequence. Of interest were the site-specific binding of (1) the fluorescent biarsenical probe AsCy3 and AsCy3e to the tetracysteine tagged fusion proteins and (2) high and low molecular mass antigens, the Bacillus anthracis surface layer protein EA1 or small molecule explosive trinitrotoluene (TNT), to biosilica-immobilized single chain antibodies. Analysis of biarsenical probe binding using fluorescence and structured illumination microscopy indicated differential colocalization with EGFP in nascent and mature biosilica, supporting the use of either EGFP or bound AsCy3 and AsCy3e in studying biosilica maturation. Large increases in the lifetime of a fluorescent analogue of TNT upon binding single chain antibodies provided a robust signal capable of discriminating binding to immobilized antibodies in the transformed frustule from nonspecific binding to the biosilica matrix. In conclusion, our results demonstrate an ability to engineer diatoms to create antibody-functionalized mesoporous silica able to selectively bind chemical and biological agents for the development of sensing platforms.

  11. ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study.

    PubMed

    Mortensen, Martin Bødtker; Nordestgaard, Børge G; Afzal, Shoaib; Falk, Erling

    2017-02-21

    We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. We examined 44 889 individuals aged 40-75 recruited in 2003-09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (-35% for any ASCVD and -36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology

  12. ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study

    PubMed Central

    Mortensen, Martin Bødtker; Nordestgaard, Børge G.; Afzal, Shoaib; Falk, Erling

    2017-01-01

    Abstract Aim We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US Pooled Cohort Equations (US-PCE for any ASCVD) and European Systematic COronary Risk Evaluation system (European-SCORE for fatal ASCVD)] and different statin eligibility criteria. Methods and results We examined 44 889 individuals aged 40–75 recruited in 2003–09 in the Copenhagen General Population Study, all free of ASCVD, diabetes, and statin use at baseline. We detected 2217 any ASCVD events and 199 fatal ASCVD events through 2014. The predicted-to-observed event ratio was 1.2 using US-PCE for any ASCVD and 5.0 using European-SCORE for fatal ASCVD. The US-PCE, but not the European-SCORE, was well-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and +76% for fatal ASCVD) with a smaller loss in specificity (−35% for any ASCVD and −36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar to those of a European-SCORE risk of 1.4%, whereas a US-PCE risk of 7.5% was similar to a European-SCORE risk of 2.4%. Conclusions The ACC/AHA guidelines were superior to the ESC/EAS guidelines for primary prevention of ASCVD, that is, for accurately assigning statin therapy to those who would benefit. PMID:28363217

  13. Natural selection promotes antigenic evolvability.

    PubMed

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  14. Natural Selection Promotes Antigenic Evolvability

    PubMed Central

    Graves, Christopher J.; Ros, Vera I. D.; Stevenson, Brian; Sniegowski, Paul D.; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed ‘cassettes’ that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections

  15. Concepts and applications for influenza antigenic cartography

    PubMed Central

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  16. Atmospheric histories and global emissions of the anthropogenic hydrofluorocarbons HFC-365mfc, HFC-245fa, HFC-227ea, and HFC-236fa

    NASA Astrophysics Data System (ADS)

    Vollmer, Martin K.; Miller, Benjamin R.; Rigby, Matthew; Reimann, Stefan; Mühle, Jens; Krummel, Paul B.; O'Doherty, Simon; Kim, Jooil; Rhee, Tae Siek; Weiss, Ray F.; Fraser, Paul J.; Simmonds, Peter G.; Salameh, Peter K.; Harth, Christina M.; Wang, Ray H. J.; Steele, L. Paul; Young, Dickon; Lunder, Chris R.; Hermansen, Ove; Ivy, Diane; Arnold, Tim; Schmidbauer, Norbert; Kim, Kyung-Ryul; Greally, Brian R.; Hill, Matthias; Leist, Michael; Wenger, Angelina; Prinn, Ronald G.

    2011-04-01

    We report on ground-based atmospheric measurements and emission estimates of the four anthropogenic hydrofluorocarbons (HFCs) HFC-365mfc (CH3CF2CH2CF3, 1,1,1,3,3-pentafluorobutane), HFC-245fa (CHF2CH2CF3, 1,1,1,3,3-pentafluoropropane), HFC-227ea (CF3CHFCF3, 1,1,1,2,3,3,3-heptafluoropropane), and HFC-236fa (CF3CH2CF3, 1,1,1,3,3,3-hexafluoropropane). In situ measurements are from the global monitoring sites of the Advanced Global Atmospheric Gases Experiment (AGAGE), the System for Observations of Halogenated Greenhouse Gases in Europe (SOGE), and Gosan (South Korea). We include the first halocarbon flask sample measurements from the Antarctic research stations King Sejong and Troll. We also present measurements of archived air samples from both hemispheres back to the 1970s. We use a two-dimensional atmospheric transport model to simulate global atmospheric abundances and to estimate global emissions. HFC-365mfc and HFC-245fa first appeared in the atmosphere only ˜1 decade ago; they have grown rapidly to globally averaged dry air mole fractions of 0.53 ppt (in parts per trillion, 10-12) and 1.1 ppt, respectively, by the end of 2010. In contrast, HFC-227ea first appeared in the global atmosphere in the 1980s and has since grown to ˜0.58 ppt. We report the first measurements of HFC-236fa in the atmosphere. This long-lived compound was present in the atmosphere at only 0.074 ppt in 2010. All four substances exhibit yearly growth rates of >8% yr-1 at the end of 2010. We find rapidly increasing emissions for the foam-blowing compounds HFC-365mfc and HFC-245fa starting in ˜2002. After peaking in 2006 (HFC-365mfc: 3.2 kt yr-1, HFC-245fa: 6.5 kt yr-1), emissions began to decline. Our results for these two compounds suggest that recent estimates from long-term projections (to the late 21st century) have strongly overestimated emissions for the early years of the projections (˜2005-2010). Global HFC-227ea and HFC-236fa emissions have grown to average values of 2.4 kt yr-1

  17. Gastric Metastasis of Prostate Cancer as an Unusual Presentation Using 68Ga-Prostate-Specific Membrane Antigen PET/CT.

    PubMed

    Solis Lara, Hugo Enrique; Villarreal Del Bosque, Natalia; Sada Treviño, Miguel Antonio; Yamamoto Ramos, Masao; Argueta Ruiz, Rocío Del Carmen

    2018-05-01

    A 79-year-old man with prostate cancer underwent Ga prostate-specific membrane antigen (Ga-PSMA) dual-time-point PET/CT scan to evaluate tumor activity due to early satiety, unquantified weight loss, and elevation of prostate-specific antigen (PSA), demonstrating thickening of the gastric wall with intense tracer uptake. The immunohistochemistry of gastric biopsy showed CDX2 and CK20: negative; CK7, focal positive; PSA, positive, which confirmed metastatic disease. Metastatic disease was also found in bones, right lung, and retroperitoneal and pelvic lymphadenopathies.

  18. Development of a Multiantigen Panel for Improved Detection of Borrelia burgdorferi Infection in Early Lyme Disease

    PubMed Central

    Panas, Michael W.; Mao, Rong; Delanoy, Michelle; Flanagan, John J.; Binder, Steven R.; Rebman, Alison W.; Montoya, Jose G.; Soloski, Mark J.; Steere, Allen C.; Dattwyler, Raymond J.; Arnaboldi, Paul M.; Aucott, John N.

    2015-01-01

    The current standard for laboratory diagnosis of Lyme disease in the United States is serologic detection of antibodies against Borrelia burgdorferi. The Centers for Disease Control and Prevention recommends a two-tiered testing algorithm; however, this scheme has limited sensitivity for detecting early Lyme disease. Thus, there is a need to improve diagnostics for Lyme disease at the early stage, when antibiotic treatment is highly efficacious. We examined novel and established antigen markers to develop a multiplex panel that identifies early infection using the combined sensitivity of multiple markers while simultaneously maintaining high specificity by requiring positive results for two markers to designate a positive test. Ten markers were selected from our initial analysis of 62 B. burgdorferi surface proteins and synthetic peptides by assessing binding of IgG and IgM to each in a training set of Lyme disease patient samples and controls. In a validation set, this 10-antigen panel identified a higher proportion of early-Lyme-disease patients as positive at the baseline or posttreatment visit than two-tiered testing (87.5% and 67.5%, respectively; P < 0.05). Equivalent specificities of 100% were observed in 26 healthy controls. Upon further analysis, positivity on the novel 10-antigen panel was associated with longer illness duration and multiple erythema migrans. The improved sensitivity and comparable specificity of our 10-antigen panel compared to two-tiered testing in detecting early B. burgdorferi infection indicates that multiplex analysis, featuring the next generation of markers, could advance diagnostic technology to better aid clinicians in diagnosing and treating early Lyme disease. PMID:26447113

  19. Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

    PubMed

    Vordenbäumen, Stefan; Lueking, Angelika; Budde, Petra; Zucht, Hans-Dieter; Goehler, Heike; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Detert, Jacqueline; Langer, Hans-Eckhard; Sörgel, Anne; Burmester, Gerd-Rüdiger; Schulz-Knappe, Peter; Schneider, Matthias

    2016-10-12

    The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

  20. Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens.

    PubMed

    Zhang, S; Zhang, H S; Cordon-Cardo, C; Ragupathi, G; Livingston, P O

    1998-11-01

    The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.

  1. Antigen Cross-Priming of Cell-Associated Proteins is Enhanced by Macroautophagy within the Antigen Donor Cell

    PubMed Central

    Joubert, Pierre-Emmanuel; Albert, Matthew L.

    2012-01-01

    Phagocytosis of dying cells constitutes an important mechanism of antigen capture for the cross-priming of CD8+ T cells. This process has been shown to be critical for achieving tumor and viral immunity. While most studies have focused on the mechanisms inherent in the dendritic cell that account for exogenous antigen accessing MHC I, several recent reports have highlighted the important contribution made by the antigen donor cell. Specifically, the cell stress and cell death pathways that precede antigen transfer are now known to impact cross-presentation and cross-priming. Herein, we review the current literature regarding a role for macroautophagy within the antigen donor cell. Further examination of this point of immune regulation is warranted and may contribute to a better understanding of how to optimize immunotherapy for treatment of cancer and chronic infectious disease. PMID:22566942

  2. GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

    PubMed

    Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

    2016-12-01

    Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

  3. Core structure of EAS in 10(15) to 10(17) eV

    NASA Technical Reports Server (NTRS)

    Hara, T.; Hatano, Y.; Hayashida, N.; Kifune, T.; Nagano, M.; Tanahashi, G.

    1985-01-01

    With the use of Akeno calorimeter, the attenuation of particles in concrete is analyzed as the function of the shower size of 10 to the 5th power to 10 to the 7th power. The attenuation length does not depend much on the shower size but depends a little on the shower age. The average value is approx. 150 g/sq cm for s = 0.5 to 0.85 and approx. 40 g/sq cm for s = 0.85 to 1.15. These values and their fluctuations are consistent with the equi-intensity curves of extensive air showers (EAS).

  4. Early Lung Cancer Diagnosis by Biosensors

    PubMed Central

    Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

    2013-01-01

    Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

  5. Antigenic Distance Measurements for Seasonal Influenza Vaccine Selection

    PubMed Central

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza vaccination is one of the major options to counteract the effects of influenza diseases. Selection of an effective vaccine strain is the key to the success of an effective vaccination program since vaccine protection can only be achieved when the selected influenza vaccine strain matches the antigenic variants causing future outbreaks. Identification of an antigenic variant is the first step to determine whether vaccine strain needs to be updated. Antigenic distance derived from immunological assays, such as hemagglutination inhibition, is commonly used to measure the antigenic closeness between circulating strains and the current influenza vaccine strain. Thus, consensus on an explicit and robust antigenic distance measurement is critical in influenza surveillance. Based on the current seasonal influenza surveillance procedure, we propose and compare three antigenic distance measurements, including Average antigenic distance (A-distance), Mutual antigenic distance (M-distance), and Largest antigenic distance (L-distance). With the assistance of influenza antigenic cartography, our simulation results demonstrated that M-distance is a robust influenza antigenic distance measurement. Experimental results on both simulation and seasonal influenza surveillance data demonstrate that M-distance can be effectively utilized in influenza vaccine strain selection. PMID:22063385

  6. Antigen-specific T cell therapies for cancer

    PubMed Central

    Manzo, Teresa; Heslop, Helen E.; Rooney, Cliona M.

    2015-01-01

    Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusions of T cells targeting Epstein–Barr virus (EBV) antigens have shown encouraging response rates in patients with post-transplant lymphoproliferative disease as well as EBV-positive lymphomas and nasopharyngeal cancer, although a recent study also showed that human papilloma virus-reactive T cells can induce complete regression of metastatic cervical cancer. This strategy is also being evaluated to target non-viral tumor-associated antigens. Targeting these less immunogenic antigens is more challenging, as tumor antigens are generally weak, and high avidity T cells specific for self-antigens are deleted in the thymus, but tumor responses have been reported. Current research focusses on defining factors that promote in vivo persistence of transferred cells and ameliorate the immunosuppressive microenvironment. To this end, investigators are evaluating the effects of combining adoptive transfer of antigen-specific T cells with other immunotherapy moieties such as checkpoint inhibitors. Genetic modification of infused T cells may also be used to overcome tumor evasion mechanisms, and vaccines may be used to promote in vivo proliferation. PMID:26160910

  7. Presentation of lipid antigens to T cells.

    PubMed

    Mori, Lucia; De Libero, Gennaro

    2008-04-15

    T cells specific for lipid antigens participate in regulation of the immune response during infections, tumor immunosurveillance, allergy and autoimmune diseases. T cells recognize lipid antigens as complexes formed with CD1 antigen-presenting molecules, thus resembling recognition of MHC-peptide complexes. The biophysical properties of lipids impose unique mechanisms for their delivery, internalization into antigen-presenting cells, membrane trafficking, processing, and loading of CD1 molecules. Each of these steps is controlled at molecular and celular levels and determines lipid immunogenicity. Lipid antigens may derive from microbes and from the cellular metabolism, thus allowing the immune system to survey a large repertoire of immunogenic molecules. Recognition of lipid antigens facilitates the detection of infectious agents and the initiation of responses involved in immunoregulation and autoimmunity. This review focuses on the presentation mechanisms and specific recognition of self and bacterial lipid antigens and discusses the important open issues.

  8. 78 FR 70356 - Compliance With Order EA-13-109, Order Modifying Licenses With Regard to Reliable Hardened...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... industry guidance contained in Nuclear Energy Institute (NEI) 13-02, ``Industry Guidance for Compliance.... ML13295A225), and Nuclear Energy Institute by letter dated October 18, 2013 (ADAMS Accession No. ML13295A494... NUCLEAR REGULATORY COMMISSION [NRC-2013-0215] Compliance With Order EA-13-109, Order Modifying...

  9. EurEAs_Gplex--A new SNaPshot assay for continental population discrimination and gender identification.

    PubMed

    Daca-Roszak, P; Pfeifer, A; Żebracka-Gala, J; Jarząb, B; Witt, M; Ziętkiewicz, E

    2016-01-01

    Assays that allow analysis of the biogeographic origin of biological samples in a standard forensic laboratory have to target a small number of highly differentiating markers. Such markers should be easy to multiplex and the assay must perform well in the degraded and scarce biological material. SNPs localized in the genome regions, which in the past were subjected to differential selective pressure in various populations, are the most widely used markers in the studies of biogeographic affiliation. SNPs reflecting biogeographic differences not related to any phenotypic traits are not sufficiently explored. The goal of our study was to identify a small set of SNPs not related to any known pigmentation/phenotype-specific genes, which would allow efficient discrimination between populations of Europe and East Asia. The selection of SNPs was based on the comparative analysis of representative European and Chinese/Japanese samples (B-lymphocyte cell lines), genotyped using the Infinium HumanOmniExpressExome microarray (Illumina). The classifier, consisting of 24 unlinked SNPs (24-SNP classifier), was selected. The performance of a 14-SNP subset of this classifier (14-SNP subclassifier) was tested using genotype data from several populations. The 14-SNP subclassifier differentiated East Asians, Europeans and Africans with ∼100% accuracy; Palestinians, representative of the Middle East, clustered with Europeans, while Amerindians and Pakistani were placed between East Asian and European populations. Based on these results, we have developed a SNaPshot assay (EurEAs_Gplex) for genotyping SNPs from the 14-SNP subclassifier, combined with an additional marker for gender identification. Forensic utility of the EurEAs_Gplex was verified using degraded and low quantity DNA samples. The performance of the EurEAs_Gplex was satisfactory when using degraded DNA; tests using low quantity DNA samples revealed a previously not described source of genotyping errors, potentially

  10. Encryption of agonistic motifs for TLR4 into artificial antigens augmented the maturation of antigen-presenting cells.

    PubMed

    Ito, Masaki; Hayashi, Kazumi; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2017-01-01

    Adjuvants are indispensable for achieving a sufficient immune response from vaccinations. From a functional viewpoint, adjuvants are classified into two categories: "physical adjuvants" increase the efficacy of antigen presentation by antigen-presenting cells (APC) and "signal adjuvants" induce the maturation of APC. Our previous study has demonstrated that a physical adjuvant can be encrypted into proteinous antigens by creating artificial proteins from combinatorial assemblages of epitope peptides and those peptide sequences having propensities to form certain protein structures (motif programming). However, the artificial antigens still require a signal adjuvant to maturate the APC; for example, co-administration of the Toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) was required to induce an in vivo immunoreaction. In this study, we further modified the previous artificial antigens by appending the peptide motifs, which have been reported to have agonistic activity for TLR4, to create "adjuvant-free" antigens. The created antigens with triple TLR4 agonistic motifs in their C-terminus have activated NF-κB signaling pathways through TLR4. These proteins also induced the production of the inflammatory cytokine TNF-α, and the expression of the co-stimulatory molecule CD40 in APC, supporting the maturation of APC in vitro. Unexpectedly, these signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes (CTL) in vivo, while the parental proteins induced CTL. These results confirmed that the manifestation of a motif's function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens.

  11. Characterization of O-antigen delivered by Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against nontyphoidal Salmonella.

    PubMed

    De Benedetto, G; Alfini, R; Cescutti, P; Caboni, M; Lanzilao, L; Necchi, F; Saul, A; MacLennan, C A; Rondini, S; Micoli, F

    2017-01-11

    Invasive nontyphoidal Salmonella disease (iNTS) is a leading cause of death and morbidity in Africa. The most common pathogens are Salmonella enterica serovars Typhimurium and Enteritidis. The O-antigen portion of their lipopolysaccharide is a target of protective immunity and vaccines targeting O-antigen are currently in development. Here we investigate the use of Generalized Modules for Membrane Antigens (GMMA) as delivery system for S. Typhimurium and S. Enteritidis O-antigen. Gram-negative bacteria naturally shed outer membrane in a blebbing process. By deletion of the tolR gene, the level of shedding was greatly enhanced. Further genetic modifications were introduced into the GMMA-producing strains in order to reduce reactogenicity, by detoxifying the lipid A moiety of lipopolysaccharide. We found that genetic mutations can impact on expression of O-antigen chains. All S. Enteritidis GMMA characterized had an O-antigen to protein w/w ratio higher than 0.6, while the ratio was 0.7 for S. Typhimurium ΔtolR GMMA, but decreased to less than 0.1 when further mutations for lipid A detoxification were introduced. Changes were also observed in O-antigen chain length and level and/or position of O-acetylation. When tested in mice, the GMMA induced high levels of anti-O-antigen-specific IgG functional antibodies, despite variation in density and O-antigen structural modifications. In conclusion, simplicity of manufacturing process and low costs of production, coupled with encouraging immunogenicity data, make GMMA an attractive strategy to further investigate for the development of a vaccine against iNTS. Copyright © 2016. Published by Elsevier Ltd.

  12. Mapping replication dynamics in Trypanosoma brucei reveals a link with telomere transcription and antigenic variation

    PubMed Central

    Devlin, Rebecca; Marques, Catarina A; Paape, Daniel; Prorocic, Marko; Zurita-Leal, Andrea C; Campbell, Samantha J; Lapsley, Craig; Dickens, Nicholas; McCulloch, Richard

    2016-01-01

    Survival of Trypanosoma brucei depends upon switches in its protective Variant Surface Glycoprotein (VSG) coat by antigenic variation. VSG switching occurs by frequent homologous recombination, which is thought to require locus-specific initiation. Here, we show that a RecQ helicase, RECQ2, acts to repair DNA breaks, including in the telomeric site of VSG expression. Despite this, RECQ2 loss does not impair antigenic variation, but causes increased VSG switching by recombination, arguing against models for VSG switch initiation through direct generation of a DNA double strand break (DSB). Indeed, we show DSBs inefficiently direct recombination in the VSG expression site. By mapping genome replication dynamics, we reveal that the transcribed VSG expression site is the only telomeric site that is early replicating – a differential timing only seen in mammal-infective parasites. Specific association between VSG transcription and replication timing reveals a model for antigenic variation based on replication-derived DNA fragility. DOI: http://dx.doi.org/10.7554/eLife.12765.001 PMID:27228154

  13. Specific Antibodies Reacting with SV40 Large T Antigen Mimotopes in Serum Samples of Healthy Subjects

    PubMed Central

    Tognon, Mauro; Corallini, Alfredo; Manfrini, Marco; Taronna, Angelo; Butel, Janet S.; Pietrobon, Silvia; Trevisiol, Lorenzo; Bononi, Ilaria; Vaccher, Emanuela; Barbanti-Brodano, Giuseppe; Martini, Fernanda; Mazzoni, Elisa

    2016-01-01

    Simian Virus 40, experimentally assayed in vitro in different animal and human cells and in vivo in rodents, was classified as a small DNA tumor virus. In previous studies, many groups identified Simian Virus 40 sequences in healthy individuals and cancer patients using PCR techniques, whereas others failed to detect the viral sequences in human specimens. These conflicting results prompted us to develop a novel indirect ELISA with synthetic peptides, mimicking Simian Virus 40 capsid viral protein antigens, named mimotopes. This immunologic assay allowed us to investigate the presence of serum antibodies against Simian Virus 40 and to verify whether Simian Virus 40 is circulating in humans. In this investigation two mimotopes from Simian Virus 40 large T antigen, the viral replication protein and oncoprotein, were employed to analyze for specific reactions to human sera antibodies. This indirect ELISA with synthetic peptides from Simian Virus 40 large T antigen was used to assay a new collection of serum samples from healthy subjects. This novel assay revealed that serum antibodies against Simian Virus 40 large T antigen mimotopes are detectable, at low titer, in healthy subjects aged from 18–65 years old. The overall prevalence of reactivity with the two Simian Virus 40 large T antigen peptides was 20%. This new ELISA with two mimotopes of the early viral regions is able to detect in a specific manner Simian Virus 40 large T antigen-antibody responses. PMID:26731525

  14. Determination of O:4 antigen-antibody affinity level in O:5 antigen positive and negative variants of Salmonella enterica serovar Typhimurium.

    PubMed

    Nakai, Yuka; Ito, Akihisa; Ogawa, Yohsuke; Aribam, Swarmistha Devi; Elsheimer-Matulova, Marta; Shiraiwa, Kazumasa; Kisaka, Stevens M B; Hikono, Hirokazu; Nishikawa, Sayaka; Akiba, Masato; Kawahara, Kazuyoshi; Shimoji, Yoshihiro; Eguchi, Masahiro

    2017-04-01

    Salmonella enterica serovar Typhimurium (S. Typhimurium) has two serological variants: one that expresses the O:5 antigen (1,4,5,12:i:1,2) and one that lacks O:5 antigen (1,4,12:i:1,2). For serotyping, S. Typhimurium is agglutinated by diagnostic O:4 antigen serum. This study was carried out to compare the antigen-antibody affinity of O:4 antigen in S. Typhimurium χ3306 O:5-positive and S. Typhimurium χ3306 O:5-negative strains. The affinity of O:4 antigen with O:4 antigen serum was found to be stronger in the O:5-negative strains compared to O:5-positive strains. Next, we investigated the antigen-antibody affinity of O:4 antigen with O:4 antigen serum in field strains of S. Typhimurium, which showed the same tendency in affinity as seen with S. Typhimurium χ3306 O:5-positive and negative strains. This study suggests that the presence or absence of O:5 antigen causes differences in O:4 agglutination reactions with different field strains of S. Typhimurium. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Sailuotong Prevents Hydrogen Peroxide (H₂O₂)-Induced Injury in EA.hy926 Cells.

    PubMed

    Seto, Sai Wang; Chang, Dennis; Ko, Wai Man; Zhou, Xian; Kiat, Hosen; Bensoussan, Alan; Lee, Simon M Y; Hoi, Maggie P M; Steiner, Genevieve Z; Liu, Jianxun

    2017-01-05

    Sailuotong (SLT) is a standardised three-herb formulation consisting of Panax ginseng , Ginkgo biloba , and Crocus sativus designed for the management of vascular dementia. While the latest clinical trials have demonstrated beneficial effects of SLT in vascular dementia, the underlying cellular mechanisms have not been fully explored. The aim of this study was to assess the ability and mechanisms of SLT to act against hydrogen peroxide (H₂O₂)-induced oxidative damage in cultured human vascular endothelial cells (EAhy926). SLT (1-50 µg/mL) significantly suppressed the H₂O₂-induced cell death and abolished the H₂O₂-induced reactive oxygen species (ROS) generation in a concentration-dependent manner. Similarly, H₂O₂ (0.5 mM; 24 h) caused a ~2-fold increase in lactate dehydrogenase (LDH) release from the EA.hy926 cells which were significantly suppressed by SLT (1-50 µg/mL) in a concentration-dependent manner. Incubation of SLT (50 µg/mL) increased superoxide dismutase (SOD) activity and suppressed the H₂O₂-enhanced Bax/Bcl-2 ratio and cleaved caspase-3 expression. In conclusion, our results suggest that SLT protects EA.hy916 cells against H₂O₂-mediated injury via direct reduction of intracellular ROS generation and an increase in SOD activity. These protective effects are closely associated with the inhibition of the apoptotic death cascade via the suppression of caspase-3 activation and reduction of Bax/Bcl-2 ratio, thereby indicating a potential mechanism of action for the clinical effects observed.

  16. 9 CFR 113.407 - Pullorum antigen.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... shall be free from extraneous organisms as determined by Gram staining and microscopic examination. (b... standard for stained antigen K's and 50 ±10 times McFarland No. 1 standard for tube antigen. (c) Preservative requirements. (1) The formalin content of Pullorum Stained Antigen K shall be 1.0 ±0.2 percent as...

  17. 9 CFR 113.407 - Pullorum antigen.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... shall be free from extraneous organisms as determined by Gram staining and microscopic examination. (b... standard for stained antigen K's and 50 ±10 times McFarland No. 1 standard for tube antigen. (c) Preservative requirements. (1) The formalin content of Pullorum Stained Antigen K shall be 1.0 ±0.2 percent as...

  18. 9 CFR 113.407 - Pullorum antigen.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... shall be free from extraneous organisms as determined by Gram staining and microscopic examination. (b... standard for stained antigen K's and 50 ±10 times McFarland No. 1 standard for tube antigen. (c) Preservative requirements. (1) The formalin content of Pullorum Stained Antigen K shall be 1.0 ±0.2 percent as...

  19. 9 CFR 113.407 - Pullorum antigen.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... shall be free from extraneous organisms as determined by Gram staining and microscopic examination. (b... standard for stained antigen K's and 50 ±10 times McFarland No. 1 standard for tube antigen. (c) Preservative requirements. (1) The formalin content of Pullorum Stained Antigen K shall be 1.0 ±0.2 percent as...

  20. 9 CFR 113.407 - Pullorum antigen.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... shall be free from extraneous organisms as determined by Gram staining and microscopic examination. (b... standard for stained antigen K's and 50 ±10 times McFarland No. 1 standard for tube antigen. (c) Preservative requirements. (1) The formalin content of Pullorum Stained Antigen K shall be 1.0 ±0.2 percent as...

  1. Exotic geophysical phenomena observed in an environmental neutron flux study using EAS PRISMA detectors

    NASA Astrophysics Data System (ADS)

    Alekseenko, Victor; Bagrova, Anastasia; Cui, Shuwang; He, Yayun; Li, Bingbing; Ma, Xinhua; Pozdnyakov, Egor; Shchegolev, Oleg; Stenkin, Yuri; Stepanov, Vladimir

    2017-06-01

    Some exotic geophysical events are observed by a global net of electron-neutron detectors (en-detectors) developed in the framework of the PRISMA EAS project. Our en-detectors running both on the Earth's surface and underground are continuously measuring the environmental thermal neutron flux. Thermal neutrons are in equilibrium with media and are therefore sensitive to many geophysical phenomena, which are exotic for people studying ultra high-energy cosmic rays or carrying out low background experiments deep underground.

  2. Retardation of Antigen Release from DNA Hydrogel Using Cholesterol-Modified DNA for Increased Antigen-Specific Immune Response.

    PubMed

    Umeki, Yuka; Saito, Masaaki; Takahashi, Yuki; Takakura, Yoshinobu; Nishikawa, Makiya

    2017-10-01

    Our previous study indicates that cationization of an antigen is effective for sustained release of both immunostimulatory DNA containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides, or CpG DNA, and antigen from a DNA hydrogel. Another approach to sustained antigen release would increase the applicability and versatility of the system. In this study, a hydrophobic interaction-based sustained release system of ovalbumin (OVA), a model antigen, from immunostimulatory CpG DNA hydrogel is developed by the use of cholesterol-modified DNA and urea-denatured OVA (udOVA). Cholesterol-modified DNA forms a hydrogel, Dgel(chol), and induces IL-6 mRNA expression in mouse skin after intradermal injection, as DNA without cholesterol does. Cholesterol-modified DNA associated with OVA and denaturation of OVA using urea increases the interaction. The release of udOVA from Dgel(chol) is significantly slower than that from DNA hydrogel with no cholesterol, Dgel. Moreover, intratumoral injections of udOVA/Dgel(chol) significantly inhibit the growth of EG7-OVA tumors in mice. These results indicate that sustained release of antigen from Dgel can be achieved by the combination of urea denaturation and cholesterol modification, and retardation of antigen release is effective to induce antigen-specific cancer immunity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Improving dengue viral antigens detection in dengue patient serum specimens using a low pH glycine buffer treatment.

    PubMed

    Shen, Wen-Fan; Galula, Jedhan Ucat; Chang, Gwong-Jen J; Wu, Han-Chung; King, Chwan-Chuen; Chao, Day-Yu

    2017-04-01

    Early diagnosis of dengue virus (DENV) infection to monitor the potential progression to hemorrhagic fever can influence the timely management of dengue-associated severe illness. Nonstructural protein 1 (NS1) antigen detection in acute serum specimens has been widely accepted as an early diagnostic assay for dengue infection; however, lower sensitivity of the NS1 antigen-capture enzyme-linked immunosorbent assay (Ag-ELISA) in secondary dengue viral infection has been reported. In this study, we developed two forms of Ag-ELISA capable of detecting E-Ag containing virion and virus-like particles, and secreted NS1 (sNS1) antigens, respectively. The temporal kinetics of viral RNA, sNS1, and E-Ag were evaluated based on the in vitro infection experiment. Meanwhile, a panel of 62 DENV-2 infected patients' sera was tested. The sensitivity was 3.042 ng/mL and 3.840 ng/mL for sNS1 and E, respectively. The temporal kinetics of the appearance of viral RNA, E, NS1, and infectious virus in virus-infected tissue culture media suggested that viral RNAs and NS1 antigens could be detected earlier than E-Ag and infectious virus. Furthermore, a panel of 62 sera from patients infected by DENV Serotype 2 was tested. Treating clinical specimens with the dissociation buffer increased the detectable level of E from 13% to 92% and NS1 antigens from 40% to 85%. Inclusion of a low-pH glycine buffer treatment step in the commercially available Ag-ELISA is crucial for clinical diagnosis and E-containing viral particles could be a valuable target for acute DENV diagnosis, similar to NS1 detection. Copyright © 2015. Published by Elsevier B.V.

  4. Properties of 10 (18)-10 (19)eV EAS at far core distance

    NASA Technical Reports Server (NTRS)

    Teshima, M.; Nagano, M.; Hara, T.; Hatano, Y.; Hayashida, N.; He, C. X.; Honda, M.; Ishikawa, F.; Kamata, K.; Matsubara, Y.

    1985-01-01

    The properties of 10 to the 18th power - 10 to the 19th power eV EAS showers such as the electron lateral distribution, the muon lateral distribution ( 1Gev), the ratio of muon density to a electron density, the shower front structure and the transition effects in scintillator of 5cm thickness are investigated with the Akeno 4 sq km/20sq km array at far core distances between 500m and 3000m. The fluctuation of densities and arrival time increase rapidly at core distances greater than 2km.

  5. Encryption of agonistic motifs for TLR4 into artificial antigens augmented the maturation of antigen-presenting cells

    PubMed Central

    Hayashi, Kazumi; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2017-01-01

    Adjuvants are indispensable for achieving a sufficient immune response from vaccinations. From a functional viewpoint, adjuvants are classified into two categories: “physical adjuvants” increase the efficacy of antigen presentation by antigen-presenting cells (APC) and “signal adjuvants” induce the maturation of APC. Our previous study has demonstrated that a physical adjuvant can be encrypted into proteinous antigens by creating artificial proteins from combinatorial assemblages of epitope peptides and those peptide sequences having propensities to form certain protein structures (motif programming). However, the artificial antigens still require a signal adjuvant to maturate the APC; for example, co-administration of the Toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) was required to induce an in vivo immunoreaction. In this study, we further modified the previous artificial antigens by appending the peptide motifs, which have been reported to have agonistic activity for TLR4, to create “adjuvant-free” antigens. The created antigens with triple TLR4 agonistic motifs in their C-terminus have activated NF-κB signaling pathways through TLR4. These proteins also induced the production of the inflammatory cytokine TNF-α, and the expression of the co-stimulatory molecule CD40 in APC, supporting the maturation of APC in vitro. Unexpectedly, these signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes (CTL) in vivo, while the parental proteins induced CTL. These results confirmed that the manifestation of a motif’s function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens. PMID:29190754

  6. Extraction of Cell-Wall Polysaccharide Antigen from Streptococci

    PubMed Central

    Slade, Hutton D.

    1965-01-01

    Slade, Hutton D. (Northwestern University Medical School, Chicago, Ill., and Max-Planck Institut für Immunbiologie, Freiburg, Germany). Extraction of cell-wall polysaccharide antigen from streptococci. J. Bacteriol. 90:667–672. 1965.—The carbohydrate grouping antigens in the cell walls of streptococci belonging to groups A, E, G, L, and T were extracted with 5% trichloroacetic acid at 90 C. The antigens were removed also from dry whole cells by extraction with trichloroacetic acid followed by treatment with phenol-water. Details of the methods are presented. The antigens obtained by use of either of these procedures were suitable for studies on immunological specificity and chemical structure. Quantitative enzymatic and chemical analyses of two group E antigens and one group T preparation showed the presence of l-rhamnose (22 to 44%), d-glucose (7 to 22%), d-galactose (T antigen only, 26%), glucosamine (2 to 16%), and galactosamine (T antigen only, 3%). In addition, analyses of A and G antigen preparations are presented. The protein and phosphate content of the A and E antigens were about 1% each. Quantitative precipitin curves of these antigens are presented. PMID:16562065

  7. Inhibitory effects of thymus-independent type 2 antigens on MHC class II-restricted antigen presentation: comparative analysis of carbohydrate structures and the antigen presenting cell.

    PubMed

    González-Fernández, M; Carrasco-Marín, E; Alvarez-Domínguez, C; Outschoorn, I M; Leyva-Cobián, F

    1997-02-25

    The role of thymus-independent type 2 (TI-2) antigens (polysaccharides) on the MHC-II-restricted processing of protein antigens was studied in vitro. In general, antigen presentation is inhibited when both peritoneal and splenic macrophages (M phi) as well as Küpffer cells (KC) are preincubated with acidic polysaccharides or branched dextrans. However, the inhibitory effect of neutral polysaccharides was minimal when KC were used as antigen presenting cells (APC). Morphological evaluation of the uptake of fluoresceinated polysaccharides clearly correlates with this selective and differential interference. Polysaccharides do not block MHC-I-restricted antigen presentation. Some chemical characteristics shared by different saccharides seem to be specially related to their potential inhibitory abilities: (i) those where two anomeric carbon atoms of two interlinked sugars and (ii) those containing several sulfate groups per disaccharide repeating unit. No polysaccharide being inhibitory in M phi abrogated antigen processing in other APC: lipopolysaccharide-activated B cells, B lymphoma cells, or dendritic cells (DC). Using radiolabeled polysaccharides it was observed that DC and B cells incorporated less radioactivity as a function of time than M phi. Morphological evaluation of these different APC incubated for extended periods of time with inhibitory concentrations of polysaccharides revealed intense cytoplasmic vacuolization in M phi but not in B cells or DC. The large majority of M phi lysosomes containing polysaccharides fail to fuse with incoming endocytic vesicles and delivery of fluid-phase tracers was reduced, suggesting that indigestible carbohydrates reduced the fusion of these loaded lysosomes with endosomes containing recently internalized tracers. It is suggested that the main causes of this antigen presentation blockade are (i) the chemical characteristics of certain carbohydrates and whether the specific enzymatic machinery for their intracellular

  8. Recognition of Antigen-Specific B Cell Receptors From Chronic Lymphocytic Leukemia Patients By Synthetic Antigen Surrogates

    PubMed Central

    Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas

    2014-01-01

    In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe discovery of non-peptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used for discovery of other classes of antigen surrogates. PMID:25467125

  9. Recognition of antigen-specific B-cell receptors from chronic lymphocytic leukemia patients by synthetic antigen surrogates.

    PubMed

    Sarkar, Mohosin; Liu, Yun; Morimoto, Jumpei; Peng, Haiyong; Aquino, Claudio; Rader, Christoph; Chiorazzi, Nicholas; Kodadek, Thomas

    2014-12-18

    In patients with chronic lymphocytic leukemia (CLL), a single neoplastic antigen-specific B cell accumulates and overgrows other B cells, leading to immune deficiency. CLL is often treated with drugs that ablate all B cells, leading to further weakening of humoral immunity, and a more focused therapeutic strategy capable of targeting only the pathogenic B cells would represent a significant advance. One approach to this would be to develop synthetic surrogates of the CLL antigens allowing differentiation of the CLL cells and healthy B cells in a patient. Here, we describe nonpeptidic molecules capable of targeting antigen-specific B cell receptors with good affinity and selectivity using a combinatorial library screen. We demonstrate that our hit compounds act as synthetic antigen surrogates and recognize CLL cells and not healthy B cells. Additionally, we argue that the technology we developed can be used to identify other classes of antigen surrogates. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Antigenic change in feline calicivirus during persistent infection.

    PubMed Central

    Johnson, R P

    1992-01-01

    To determine if antigenic variation occurred during persistent infection of cats with feline caliciviruses (FCV), nine persistent (progeny) isolates from nine different carrier cats were compared antigenically to the original infecting parent strain, FCV 255, by two-way cross-neutralization tests with rabbit antisera. Five of the nine progeny viruses isolated 35 to 169 days after initial infection were antigenically different from the parent strain. These five isolates represented four distinct antigenic phenotypes. The emergence of four distinctly different antigenic variants from a single parent strain indicates that FCV, like many other RNA viruses, exhibits considerable antigenic heterogeneity during replication in its natural host, and supports the hypothesis that antigenic variation contributes to chronic FCV infection. PMID:1335833

  11. Covalent binding of C3b to tetanus toxin: influence on uptake/internalization of antigen by antigen-specific and non-specific B cells.

    PubMed Central

    Villiers, M B; Villiers, C L; Jacquier-Sarlin, M R; Gabert, F M; Journet, A M; Colomb, M G

    1996-01-01

    Antigen opsonization by the C3b fragment of complement is a significant event in the modulation of cell-mediated immune response, but its mechanism is still largely unknown. The structural characteristics of C3b allow it to act as a bifunctional ligand between antigen and cells via their membrane C3b receptors. It was thus of interest to study the influence of the covalent link between C3b and antigen on the fixation and internalization of this antigen by antigen-presenting cells. Tetanus toxin (TT) was used as antigen, either free or covalently linked to C3b (TT-C3b). The antigen-presenting cells were TT-specific (4.2) or non-specific (BL15) Epstein-Barr virus (EBV)-transformed B cells. C3b was found to play an important role in antigen fixation and internalization by both antigen-specific and antigen non-specific cells. Covalent binding of C3b on TT (1) permitted fixation and internalization of this antigen by non-specific cells via their complement receptors; (2) enhanced antigen fixation and resulted in cross-linking between membrane immunoglobulins and complement receptors on antigen-specific cells. The consequences of covalent C3b binding to TT were analysed using antigen-specific and antigen-nonspecific cells. In both cases, a net increase in antigen fixation was observed. At the intracellular level, covalent C3b binding to TT resulted in a large TT incorporation in endosomes of nonspecific cells, similar to that observed in antigen-specific cells. Thus, C3b covalently linked to antigen enlarges the array of B-cell types capable of presenting antigen, including non-specific cells. Images Figure 2 PMID:8958046

  12. The Leptospiral Antigen Lp49 is a Two-Domain Protein with Putative Protein Binding Function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oliveira Giuseppe,P.; Oliveira Neves, F.; Nascimento, A.

    2008-01-01

    Pathogenic Leptospira is the etiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. Currently available vaccines have limited effectiveness and therapeutic interventions are complicated by the difficulty in making an early diagnosis of leptospirosis. The genome of Leptospira interrogans was recently sequenced and comparative genomic analysis contributed to the identification of surface antigens, potential candidates for development of new vaccines and serodiagnosis. Lp49 is a membrane-associated protein recognized by antibodies present in sera from early and convalescent phases of leptospirosis patients. Its crystal structure was determined by single-wavelength anomalous diffraction using selenomethionine-labelled crystals and refined at 2.0 Angstromsmore » resolution. Lp49 is composed of two domains and belongs to the all-beta-proteins class. The N-terminal domain folds in an immunoglobulin-like beta-sandwich structure, whereas the C-terminal domain presents a seven-bladed beta-propeller fold. Structural analysis of Lp49 indicates putative protein-protein binding sites, suggesting a role in Leptospira-host interaction. This is the first crystal structure of a leptospiral antigen described to date.« less

  13. 75 FR 42819 - Notice of Availability of a Final Environmental Assessment (Final EA) and a Finding of No...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... the Proposed ORD Airport Surveillance Radar, Model 9, West Chicago, IL AGENCY: Federal Aviation... Surveillance Radar, Model 9, West Chicago, Illinois. SUMMARY: The Federal Aviation Administration (FAA) is... (Final EA) for the Proposed ORD Airport Surveillance Radar, Model 9 (ASR-9), in West Chicago, Illinois...

  14. 75 FR 20645 - Order Instituting Administrative Proceedings Pursuant to Section 15E(a)(2)(A)(ii) of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... nationally recognized statistical rating organization (``NRSRO'') pursuant to section 15E(a) of the... Exchange Act, and the rules thereunder, relating to making its books and records available for Commission examination, producing books and records to the Commission, and furnishing reports to the Commission...

  15. Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy

    PubMed Central

    Maus, Marcela V.; June, Carl H.

    2016-01-01

    Chimeric antigen receptors (CARs) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell. In early phase clinical trials, CAR T cells targeting CD19 have resulted in sustained complete responses within a population of otherwise refractory patients with B-cell malignancies and, more specifically, have shown complete response rates of ≈90% in patients with relapsed or refractory acute lymphoblastic leukemia. Given this clinical efficacy, preclinical development of CAR T-cell therapy for a number of cancer indications has been actively investigated, and the future of the CAR T-cell field is extensive and dynamic. Several approaches to increase the feasibility and safety of CAR T cells are currently being explored, including investigation into mechanisms regulating the persistence of CAR T cells. Additionally, numerous early-phase clinical trials are now investigating CAR T-cell therapy beyond targeting CD19, especially in solid tumors. Trials investigating combinations of CAR T cells with immune checkpoint blockade therapies are now beginning and results are eagerly awaited. This review evaluates several of the ongoing and future directions of CAR T-cell therapy. PMID:27084741

  16. Surface plasmon resonance measurements of plasma antibody avidity during primary and secondary responses to anthrax protective antigen

    PubMed Central

    Lynch, Heather E.; Stewart, Shelley M.; Kepler, Thomas B.; Sempowski, Gregory D.; Alam, S. Munir

    2014-01-01

    Establishment of humoral immunity against pathogens is dependent on events that occur in the germinal center and the subsequent induction of high-affinity neutralizing antibodies. Quantitative assays that allow monitoring of affinity maturation and duration of antibody responses can provide useful information regarding the efficacy of vaccines and adjuvants. Using an anthrax protective antigen (rPA) and alum model antigen/adjuvant system, we describe a methodology for monitoring antigen-specific serum antibody concentration and avidity by surface plasmon resonance during primary and secondary immune responses. Our analyses showed that following a priming dose in mice, rPA-specific antibody concentration and avidity increases over time and reaches a maximal response in about six weeks, but gradually declines in the absence of antigenic boost. Germinal center reactions were observed early with maximal development achieved during the primary response, which coincided with peak antibody avidity responses to primary immunization. Boosting with antigen resulted in a rapid increase in rPA-specific antibody concentration and five-fold increase in avidity, which was not dependent on sustained GC development. The described methodology couples surface plasmon resonance-based plasma avidity measurements with germinal center analysis and provides a novel way to monitor humoral responses that can play a role in facilitating vaccine and adjuvant development. PMID:24316020

  17. Soluble Antigen Fluorescent-Antibody Technique

    PubMed Central

    Toussaint, Andre J.; Anderson, Robert I.

    1965-01-01

    An indirect fluorescent-antibody (FA) procedure employing soluble antigen fixed onto an artificial matrix was developed, and a mechanical means for reading of test results was devised. The method employs two small cellulose acetate paper discs for each test. One disc contains soluble antigen diluted in 1% bovine serum albumin (BSA); the other contains only 1% BSA and serves as a control. After testing by the indirect FA procedure, the results of the tests are read on a fluorometer fitted with a paper chromatogram door. The instrument is set at zero with the control disc as a blank, and the specific fluorescence of the antigen disc is determined. Findings obtained with homologous and heterologous antisera indicated that the method yields excellent results. The soluble antigen fluorescent-antibody technique has definite advantages over the conventional indirect FA procedures. (i) The investigator may objectively select the antigen to be employed. (ii) It is possible to obtain objective mechanical reading of test results rather than the highly subjective readings required by conventional methods. (iii) The system compensates for any nonspecific fluorescence contributed either by the serum (e.g., drugs) or by free fluorescein in the conjugated antiserum. Images Fig. 1 PMID:14339261

  18. Engineered chimeric antigen receptor-expressing T cells for the treatment of pancreatic ductal adenocarcinoma

    PubMed Central

    Beatty, Gregory L

    2014-01-01

    Adoptive cell therapy with chimeric antigen receptor (CAR)-engineered T cells is under investigation as an approach to restore productive T cell immunosurveillance in patients with pancreatic ductal adenocarcinoma. Early findings demonstrate safety of this cell-based therapy and the capacity of CAR-expressing T cells to mediate anti-tumor activity as well as induce endogeneous antitumoral immune responses. PMID:25050204

  19. Prevalence of E/A wave fusion and A wave truncation in DDD pacemaker patients with complete AV block under nominal AV intervals.

    PubMed

    Poller, Wolfram C; Dreger, Henryk; Schwerg, Marius; Melzer, Christoph

    2015-01-01

    Optimization of the AV-interval (AVI) in DDD pacemakers improves cardiac hemodynamics and reduces pacemaker syndromes. Manual optimization is typically not performed in clinical routine. In the present study we analyze the prevalence of E/A wave fusion and A wave truncation under resting conditions in 160 patients with complete AV block (AVB) under the pre-programmed AVI. We manually optimized sub-optimal AVI. We analyzed 160 pacemaker patients with complete AVB, both in sinus rhythm (AV-sense; n = 129) and under atrial pacing (AV-pace; n = 31). Using Doppler analyses of the transmitral inflow we classified the nominal AVI as: a) normal, b) too long (E/A wave fusion) or c) too short (A wave truncation). In patients with a sub-optimal AVI, we performed manual optimization according to the recommendations of the American Society of Echocardiography. All AVB patients with atrial pacing exhibited a normal transmitral inflow under the nominal AV-pace intervals (100%). In contrast, 25 AVB patients in sinus rhythm showed E/A wave fusion under the pre-programmed AV-sense intervals (19.4%; 95% confidence interval (CI): 12.6-26.2%). A wave truncations were not observed in any patient. All patients with a complete E/A wave fusion achieved a normal transmitral inflow after AV-sense interval reduction (mean optimized AVI: 79.4 ± 13.6 ms). Given the rate of 19.4% (CI 12.6-26.2%) of patients with a too long nominal AV-sense interval, automatic algorithms may prove useful in improving cardiac hemodynamics, especially in the subgroup of atrially triggered pacemaker patients with AV node diseases.

  20. Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ.

    PubMed Central

    Deppert, W; Hanke, K; Henning, R

    1980-01-01

    Simian virus 40 (SV40)-transformed monolayer cells were analyzed in situ by indirect immunofluorescence microscopy for the postulated cell surface location of SV40 T-antigen-related molecules. With antisera prepared against purified, sodium dodecyl sulfate-denatured SV40 T-antigen, positive surface staining was obtained when the cells had been treated with formaldehyde before immunofluorescence analysis. In contrast, living SV40-transformed cells analyzed in monolayer were surface fluorescence negative. The fixation procedure developed in this study combined with a double staining immunofluorescence technique allowed the simultaneous analysis of the same cells for the expression of both SV40 T-antigen-related surface antigen and nuclear T-antigen. The localization of SV40 T-antigen-related surface antigen on the outer surface of the plasma membrane of formaldehyde-fixed SV40-transformed cells was demonstrated directly by the protein A-mediated binding of Staphylococcus aureus bacteria on formaldehyde-fixed SV40-transformed cells precoated with antiserum against sodium dodecyl sulfate-denatured T-antigen. Both cell surface staining and S. aureus binding were found to be highly specific for SV40 T-antigen-related binding sites. These results indicate that T-antigen-related molecules in a cryptic form are located on the surface of SV40-transformed monolayer cells and can be detected in situ after modification of the cell surface architecture. Images PMID:6255189

  1. Predictive value of different prostate-specific antigen-based markers in men with baseline total prostate-specific antigen <2.0 ng/mL.

    PubMed

    Fujizuka, Yuji; Ito, Kazuto; Oki, Ryo; Suzuki, Rie; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Suzuki, Kazuhiro

    2017-08-01

    To investigate the predictive value of various molecular forms of prostate-specific antigen in men with baseline prostate-specific antigen <2.0 ng/mL. The case cohort comprised 150 men with a baseline prostate-specific antigen level <2.0 ng/mL, and who developed prostate cancer within 10 years. The control cohort was 300 baseline prostate-specific antigen- and age-adjusted men who did not develop prostate cancer. Serum prostate-specific antigen, free prostate-specific antigen, and [-2] proenzyme prostate-specific antigen were measured at baseline and last screening visit. The predictive impact of baseline prostate-specific antigen- and [-2] proenzyme prostate-specific antigen-related indices on developing prostate cancer was investigated. The predictive impact of those indices at last screening visit and velocities from baseline to final screening on tumor aggressiveness were also investigated. The baseline free to total prostate-specific antigen ratio was a significant predictor of prostate cancer development. The odds ratio was 6.08 in the lowest quintile baseline free to total prostate-specific antigen ratio subgroup. No serum indices at diagnosis were associated with tumor aggressiveness. The Prostate Health Index velocity and [-2] proenzyme prostate-specific antigen/free prostate-specific antigen velocity significantly increased in patients with higher risk D'Amico risk groups and higher Gleason scores. Free to total prostate-specific antigen ratio in men with low baseline prostate-specific antigen levels seems to predict the risk of developing prostate cancer, and it could be useful for a more effective individualized screening system. Longitudinal changes in [-2] proenzyme prostate-specific antigen-related indices seem to correlate with tumor aggressiveness, and they could be used as prognostic tool before treatment and during active surveillance. © 2017 The Japanese Urological Association.

  2. Immunolocalization and immunodetection of the excretory/secretory (ES) antigens of Fasciola gigantica.

    PubMed

    Khan, M A Hannan; Ullah, Rizwan; Rehman, Abdur; Rehman, Lubna; P A, Ahammed Shareef; Abidi, S M A

    2017-01-01

    The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES) product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite of same habitat

  3. Immunolocalization and immunodetection of the excretory/secretory (ES) antigens of Fasciola gigantica

    PubMed Central

    Ullah, Rizwan; Rehman, Abdur; Rehman, Lubna; P. A., Ahammed Shareef; Abidi, S. M. A.

    2017-01-01

    The digenetic trematode Fasciola gigantica is a parasite of great agricultural and economic importance. Along with Fasciola hepatica, F. gigantica incurs huge economic losses to the agricultural sector. Because of unavailability of an effective and commercial vaccine, the earliest diagnosis of the disease is the only way to control the disease. The conventional coprological techniques are able to detect the disease only after the parasites get matured and starts releasing their eggs with the faeces of host, therefore prepatent infection remain undiagnosed. The alternative method is by serological tests that uses circulatory antigens. Despite high sensitivity, their reliability is quite low because of the common antigens shared between different helminth parasites. To overcome this, investigation was shifted to identify the copro-antigens which could be more sensitive and reliable. In the present study, we tried to identify some of the immunodominant proteins from the Excretory Secretory (ES) product of F. gigantica which can be further characterized and used for early detection of infection and also as drug and vaccine candidates. The ES products of F. gigantica were collected and used for raising the polyclonal antibody in rabbit. The polypeptide profile was generated as well as immunogenic polypeptides were identified. The Source of ES antigen was immunolocalized using confocal microscopy and dot blot assay was performed to diagnose field infection. The polypeptide profile of ES products revealed a total of 24 polypeptides out of which 12 immunogenic polypeptides were identified by western blotting. Confocal micrographs showed the immunolocalization of antigens in the intestinal caecae, vitalline glands, gonads as well as in the tegument of the worm. The dot blot assay confirmed the utility of ES products for the detection of field infection. Subsequently, cross reactivity was found negative with Gigantocotyle explanatum; an amphitome parasite of same habitat

  4. Mapping epitopes and antigenicity by site-directed masking

    NASA Astrophysics Data System (ADS)

    Paus, Didrik; Winter, Greg

    2006-06-01

    Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to -lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with -lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops. backbone flexibility | Freund's adjuvant | conformational epitope | antisera

  5. CELL SEPARATION ON ANTIGEN-COATED COLUMNS

    PubMed Central

    Wigzell, Hans; Andersson, Birger

    1969-01-01

    Glass and plastic bead columns coated with antigenic protein molecules were used as an immunological filter for cell populations containing immune cells of relevant specificity. A selective elimination of these immune cells from the passing cell suspension was regularly noted and it approached, in some experiments, complete abolition of the specific immune reactivity of the filtered cell population. This specific retention of immune cells by antigenic columns could be selectively blocked by the presence of free antigen molecules in the medium during filtration. The results obtained support the concept of a cell-associated antigen-specific receptor being present on the outer surface of immune cells, displaying the same antigen-binding specificity as the potential product of the cell, the humoral antibody. Using the present bead column system, results were obtained indicating that this receptor was an active product of the immune cells and not any passively adsorbed, cytophilic antibody. Antigenic bead columns may very well constitute a tool for the production in vitro of cell populations being specifically deprived of immune reactivity and allow detailed analysis of the characteristics of the cell-associated antibody of immune cells. PMID:5782770

  6. Transformation and radiosensitivity of human diploid skin fibroblasts transfected with activated ras oncogene and SV40 T-antigen.

    PubMed

    Su, L N; Little, J B

    1992-08-01

    Three normal human diploid cell strains were transfected with an activated Ha-ras oncogene (EJ ras) or SV40 T-antigen. Multiple clones were examined for morphological alterations, growth requirements, ability to grow under anchorage independent conditions, immortality and tumorigenicity in nude mice. Clones expressing SV40 T-antigen alone or in combination with ras protein p21 were significantly radioresistant as compared with their parent cells or clones transfected with the neo gene only. This radioresistant phenotype persisted in post-crisis, immortalized cell lines. Cells transfected with EJ ras alone showed no morphological alterations nor significant changes in radiosensitivity. Cell clones expressing ras and/or SV40 T-antigen showed a reduced requirement for serum supplements, an increase in aneuploidy and chromosomal aberrations, and enhanced growth in soft agar as an early cellular response to SV40 T-antigen expression. The sequential order of transfection with SV40 T-antigen and ras influenced radio-sensitivity but not the induction of morphological changes. These data suggest that expression of the SV40 T-antigen but not activated Ha-ras plays an important role in the radiosensitivity of human diploid cells. The radioresistant phenotype in SV40 T transfected cells was not related to the enhanced level of genetic instability seen in pre-crisis and newly immortalized cells, nor to the process of immortalization itself.

  7. Protamine-based nanoparticles as new antigen delivery systems.

    PubMed

    González-Aramundiz, José Vicente; Peleteiro Olmedo, Mercedes; González-Fernández, África; Alonso Fernández, María José; Csaba, Noemi Stefánia

    2015-11-01

    The use of biodegradable nanoparticles as antigen delivery vehicles is an attractive approach to overcome the problems associated with the use of Alum-based classical adjuvants. Herein we report, the design and development of protamine-based nanoparticles as novel antigen delivery systems, using recombinant hepatitis B surface antigen as a model viral antigen. The nanoparticles, composed of protamine and a polysaccharide (hyaluronic acid or alginate), were obtained using a mild ionic cross-linking technique. The size and surface charge of the nanoparticles could be modulated by adjusting the ratio of the components. Prototypes with optimal physicochemical characteristics and satisfactory colloidal stability were selected for the assessment of their antigen loading capacity, antigen stability during storage and in vitro and in vivo proof-of-concept studies. In vitro studies showed that antigen-loaded nanoparticles induced the secretion of cytokines by macrophages more efficiently than the antigen in solution, thus indicating a potential adjuvant effect of the nanoparticles. Finally, in vivo studies showed the capacity of these systems to trigger efficient immune responses against the hepatitis B antigen following intramuscular administration, suggesting the potential interest of protamine-polysaccharide nanoparticles as antigen delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 75 FR 42820 - Notice of Availability of a Final Environmental Assessment (Final EA) and a Finding of No...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... evaluated the construction and operation of a new 20,000-square-foot standard design Terminal Radar Approach Control Facility/Base Building conforming to the guidelines of the Terminal Facilities Design Standards... Airport Layout Plan. The Final EA has been prepared in accordance with the National Environmental Policy...

  9. Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort

    PubMed Central

    Adeola, Henry A.; Smith, Muneerah; Kaestner, Lisa; Blackburn, Jonathan M.; Zerbini, Luiz F.

    2016-01-01

    There is a growing need for high throughput diagnostic tools for early diagnosis and treatment monitoring of prostate cancer (PCa) in Africa. The role of cancer-testis antigens (CTAs) in PCa in men of African descent is poorly researched. Hence, we aimed to elucidate the role of 123 Tumour Associated Antigens (TAAs) using antigen microarray platform in blood samples (N = 67) from a South African PCa, Benign prostatic hyperplasia (BPH) and disease control (DC) cohort. Linear (fold-over-cutoff) and differential expression quantitation of autoantibody signal intensities were performed. Molecular signatures of candidate PCa antigen biomarkers were identified and analyzed for ethnic group variation. Potential cancer diagnostic and immunotherapeutic inferences were drawn. We identified a total of 41 potential diagnostic/therapeutic antigen biomarkers for PCa. By linear quantitation, four antigens, GAGE1, ROPN1, SPANXA1 and PRKCZ were found to have higher autoantibody titres in PCa serum as compared with BPH where MAGEB1 and PRKCZ were highly expressed. Also, p53 S15A and p53 S46A were found highly expressed in the disease control group. Statistical analysis by differential expression revealed twenty-four antigens as upregulated in PCa samples, while 11 were downregulated in comparison to BPH and DC (FDR = 0.01). FGFR2, COL6A1and CALM1 were verifiable biomarkers of PCa analysis using urinary shotgun proteomics. Functional pathway annotation of identified biomarkers revealed similar enrichment both at genomic and proteomic level and ethnic variations were observed. Cancer antigen arrays are emerging useful in potential diagnostic and immunotherapeutic antigen biomarker discovery. PMID:26885621

  10. Use of the Abbott Architect HIV antigen/antibody assay in a low incidence population.

    PubMed

    Dubravac, Terry; Gahan, Thomas F; Pentella, Michael A

    2013-12-01

    With the availability of 4th generation HIV diagnostic tests which are capable of detecting acute infection, Iowa evaluated the 3rd and 4th generation HIV test and compared the performance of these products in a low incidence population. This study was conducted to evaluate the performance of an HIV antigen/antibody combination (4th generation) assay compared to an EIA 3rd generation assay. Over a 4 month period, 2037 specimens submitted for HIV screening were tested by Bio-Rad GS HIV-1/HIV-2 Plus O EIA and the Abbott Architect i1000SR HIV Ag/Ab Combo. The performance characteristics of sensitivity, specificity, positive predictive value and negative predictive value were determined. Of the 2037 specimens tested, there were 13 (0.64%) true positives detected. None of the positive specimens were from patients in the acute phase of infection. The Abbott antigen/antibody combo assay had a sensitivity, specificity, positive-predictive value and negative predictive value of 100%, 99.85%, 81.25%, and 100% respectively. The Bio-Rad EIA assay had a sensitivity, specificity, positive-predictive value and negative predictive value of 100%, 99.80%, 76.47% and 100%, respectively. The EIA had four false positive results which tested negative by the antigen/antibody assay and western blot. In a low-incidence state where early infections are less commonly encountered, the EIA assay and the antigen/antibody assay performed with near equivalency. The antigen/antibody assay had one less false positive result. While no patients were detected in the acute stage of infection, the use of the antigen/antibody assay presents the opportunity to detect an infected patient sooner and prevent transmission to others. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Human heat shock protein 70 enhances tumor antigen presentation through complex formation and intracellular antigen delivery without innate immune signaling.

    PubMed

    Bendz, Henriette; Ruhland, Sibylle C; Pandya, Maya J; Hainzl, Otmar; Riegelsberger, Stefan; Braüchle, Christoph; Mayer, Matthias P; Buchner, Johannes; Issels, Rolf D; Noessner, Elfriede

    2007-10-26

    Heat shock proteins (HSPs) have shown promise for the optimization of protein-based vaccines because they can transfer exogenous antigens to dendritic cells and at the same time induce their maturation. Great care must be exercised in interpretating HSP-driven studies, as by-products linked to the recombinant generation of these proteins have been shown to mediate immunological effects. We generated highly purified human recombinant Hsp70 and demonstrated that it strongly enhances the cross-presentation of exogenous antigens resulting in better antigen-specific T cell stimulation. Augmentation of T cell stimulation was a direct function of the degree of complex formation between Hsp70 and peptides and correlated with improved antigen delivery to endosomal compartments. The Hsp70 activity was independent of TAP proteins and was not inhibited by exotoxin A or endosomal acidification. Consequently, Hsp70 enhanced cross-presentation of various antigenic sequences, even when they required different post-uptake processing and trafficking, as exemplified by the tumor antigens tyrosinase and Melan-A/MART-1. Furthermore, Hsp70 enhanced cross-presentation by different antigen-presenting cells (APCs), including dendritic cells and B cells. Importantly, enhanced cross-presentation and antigen-specific T cell activation were observed in the absence of innate signals transmitted by Hsp70. As Hsp70 supports the cross-presentation of different antigens and APCs and is inert to APC function, it may show efficacy in various settings of immune modulation, including induction of antigen-specific immunity or tolerance.

  12. Differentiation of lard, chicken fat, beef fat and mutton fat by GCMS and EA-IRMS techniques.

    PubMed

    Ahmad Nizar, Nina Naquiah; Nazrim Marikkar, Jalaldeen Mohamed; Hashim, Dzulkifly Mat

    2013-01-01

    A study was conducted to differentiate lard, chicken fat, beef fat and mutton fat using Gas Chromatography Mass Spectrometry (GC-MS) and Elemental Analyzer-Isotope Ratio Mass Spectrometry (EA-IRMS). The comparison of overall fatty acid data showed that lard and chicken fat share common characteristics by having palmitic, oleic and linoleic acid as major fatty acids while beef and mutton fats shared common characteristics by possessing palmitic, stearic and oleic acid as major fatty acids. The direct comparisons among the fatty acid data, therefore, may not be suitable for discrimination of different animal fats. When the fatty acid distributional data was subjected to Principle Component Analysis (PCA), it was demonstrated that stearic, oleic and linoleic acids as the most discriminating parameters in the clustering of animal fats into four subclasses. The bulk carbon analysis of animal fats using EA-IRMS showed that determination of the carbon isotope ratios (δ¹³C) would be a good indicator for discriminating lard, chicken fat, beef fat and mutton fat. This would lead to a faster and more efficient method to ascertain the source of origin of fats used in food products.

  13. Trichinella spiralis: strong antibody response to a 49 kDa newborn larva antigen in infected rats.

    PubMed

    Salinas-Tobon, Maria Del Rosario; Navarrete-Leon, Anaid; Mendez-Loredo, Blanca Esther; Esquivel-Aguirre, Dalia; Martínez-Abrajan, Dulce Maria; Hernandez-Sanchez, Javier

    2007-02-01

    In this work, we analyzed the kinetics of anti-Trichinella spiralis newborn larva (NBL) antibodies (Ab) and the antigenic recognition pattern of NBL proteins and its dose effects. Wistar rats were infected with 0, 700, 2000, 4000 and 8000 muscle larvae (ML) and bled at different time intervals up to day 31 post infection (p.i.). Ab production was higher with 2000 ML dose and decreased with 8000, 4000 and 700 ML. Abs were not detected until day 10, peaked on day 14 for the 2000 ML dose and on day 19 for the other doses and thereafter declined slowly from 19 to 31 days p.i. In contrast, Abs to ML increased from day 10, peaked on day 19 and remained high until the end of the study. Abs bound strongly at least to three NBL components of 188, 205 and 49 kDa. NBL antigen of 188 and 205 kDa were recognized 10-26 days p.i. and that of 49 kDa from day 10 to day 31 p.i. A weak recognition towards antigens of 52, 54, 62 and 83 kDa was also observed during the infection. An early recognition of 31, 43, 45, 55, 68 and 85 kDa ML antigens was observed whereas the response to those of 43, 45, 48, 60, 64 and 97 kDa (described previously as TSL-1 antigens) occurred late in the infection. A follow-up of antigen recognition up to day 61 with the optimal immunization dose (2000 ML) evidenced a decline of Ab production to the 49 kDa NBL antigen 42 days p.i., which suggested antigenic differences with the previously reported 43 kDa ML antigen strongly recognized late in the infection. To analyze the stage-specificity of the 49 kDa NBL antigen, polyclonal antibodies (PoAb) were obtained in rats immunized with 49 kDa NBL antigen. PoAb reacted strongly with the 49 kDa NBL component in NBL total soluble extract but no reactivity was observed with soluble antigen of the other T. spiralis stages. Albeit with less intensity, the 49 kDa component was also recognized by PoAb together with other antigens of 53, 97 and 107 kDa, in NBL excretory-secretory products (NBL-ESP). Thus, our results reveal

  14. Identification of specific antigenic epitope at N-terminal segment of enterovirus 71 (EV-71) VP1 protein and characterization of its use in recombinant form for early diagnosis of EV-71 infection.

    PubMed

    Zhang, Jianhua; Jiang, Bingfu; Xu, Mingjie; Dai, Xing; Purdy, Michael A; Meng, Jihong

    2014-08-30

    Human enterovirus 71 (EV-71) is the main etiologic agent of hand, foot and mouth disease (HFMD). We sought to identify EV-71 specific antigens and develop serologic assays for acute-phase EV-71 infection. A series of truncated proteins within the N-terminal 100 amino acids (aa) of EV-71 VP1 was expressed in Escherichia coli. Western blot (WB) analysis showed that positions around 11-21 aa contain EV-71-specific antigenic sites, whereas positions 1-5 and 51-100 contain epitopes shared with human coxsackievirus A16 (CV-A16) and human echovirus 6 (E-6). The N-terminal truncated protein of VP1, VP₁₆₋₄₃, exhibited good stability and was recognized by anti-EV-71 specific rabbit sera. Alignment analysis showed that VP₁₆₋₄₃ is highly conserved among EV-71 strains from different genotypes but was heterologous among other enteroviruses. When the GST-VP₁₆₋₄₃ fusion protein was incorporated as antibody-capture agent in a WB assay and an ELISA for detecting anti-EV-71 IgM in human sera, sensitivities of 91.7% and 77.8% were achieved, respectively, with 100% specificity for both. The characterized EV-71 VP1 protein truncated to positions 6-43 aa has potential as an antigen for detection of anti-EV-71 IgM for early diagnosis of EV-71 infection in a WB format. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Defective activity of Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes in children with chronic active EBV infection and in their parents.

    PubMed

    Fujieda, M; Wakiguchi, H; Hisakawa, H; Kubota, H; Kurashige, T

    1993-10-01

    Antibodies of Epstein-Barr virus (EBV), EBV-specific cytotoxic T lymphocyte (EBVCTL) activity and the lymphocyte subset of CTL were examined in 13 Japanese children with chronic active EBV infection (CAEBV) and their parents (eight fathers and 10 mothers). Anti-virus-capsid antigen (VCA)-IgG antibody titers ranged from 1:640 to 1:5120 in the patients with CAEBV and from 1:40 to 1:640 in the parents. While anti-VCA-IgM antibody was detected in three patients, anti-VCA-IgA antibody in five and anti-early-antigen (EA)-IgG antibody in 11, no antibody was detected in the parents except anti-EA antibody, which was positive in the mothers of cases 5 and 13 (1:10 and 1:40). Anti-EBV-associated nuclear antigen (EBNA) antibody was < or = 1:10 in six out of 13 patients with CAEBV and in 10 out of 18 parents tested. Epstein-Barr virus activity was significantly lower (P < 0.005) both in the children with CAEBV and in their parents than in seropositive age-matched controls. Proportions of a CTL subset (CD8+ CD11- lymphocytes) in the patients with CAEBV were significantly higher (P < 0.005) than in controls, while those in the parents were at the same level as in controls. Defective EBVCTL activity and anti-EBNA-antibody responses were frequently observed both in children with CAEBV and in their parents, which may suggest that the abnormal immune response to EBV may be based on a familial disorder, though no familial involvement has been reported in Japanese children with CAEBV.

  16. Chemoselective ligation and antigen vectorization.

    PubMed

    Gras-Masse, H

    2001-01-01

    The interest in cocktail-lipopeptide vaccines has now been confirmed by phase I clinical trials: highly diversified B-, T-helper or cytotoxic T-cell epitopes can be combined with a lipophilic vector for the induction of B- and T-cell responses of predetermined specificity. With the goal of producing an improved vaccine that should ideally induce a multispecific response in non-selected populations, increasing the diversity of the immunizing mixture represents one of the most obvious strategies.The selective delivery of antigens to professional antigen-presenting cells represents another promising approach for the improvement of vaccine efficacy. In this context, the mannose-receptor represents an attractive entry point for the targeting to dendritic cells of antigens linked to clustered glycosides or glycomimetics. In all cases, highly complex but fully characterized molecules must be produced. To develop a modular and flexible strategy which could be generally applicable to a large set of peptide antigens, we elected to explore the potentialities of chemoselective ligation methods. The hydrazone bond was found particularly reliable and fully compatible with sulphide ligation. Hydrazone/thioether orthogonal ligation systems could be developed to account for the nature of the antigens and the solubility of the vector systems. Copyright 2001 The International Association for Biologicals.

  17. Antibody-Antigen-Adjuvant Conjugates Enable Co-Delivery of Antigen and Adjuvant to Dendritic Cells in Cis but Only Have Partial Targeting Specificity

    PubMed Central

    Abuknesha, Ram; Uematsu, Satoshi; Akira, Shizuo; Nestle, Frank O.; Diebold, Sandra S.

    2012-01-01

    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC) that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (ODN). We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL) responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses. PMID:22808118

  18. Red Blood Cell Antigen Genotyping for Sickle Cell Disease, Thalassemia, and Other Transfusion Complications.

    PubMed

    Fasano, Ross M; Chou, Stella T

    2016-10-01

    Since the discovery of the ABO blood group in the early 20th century, more than 300 blood group antigens have been categorized among 35 blood group systems. The molecular basis for most blood group antigens has been determined and demonstrates tremendous genetic diversity, particularly in the ABO and Rh systems. Several blood group genotyping assays have been developed, and 1 platform has been approved by the Food and Drug Administration as a "test of record," such that no phenotype confirmation with antisera is required. DNA-based red blood cell (RBC) phenotyping can overcome certain limitations of hemagglutination assays and is beneficial in many transfusion settings. Genotyping can be used to determine RBC antigen phenotypes in patients recently transfused or with interfering allo- or autoantibodies, to resolve discrepant serologic typing, and/or when typing antisera are not readily available. Molecular RBC antigen typing can facilitate complex antibody evaluations and guide RBC selection for patients with sickle cell disease (SCD), thalassemia, and autoimmune hemolytic anemia. High-resolution RH genotyping can identify variant RHD and RHCE in patients with SCD, which have been associated with alloimmunization. In the future, broader access to cost-efficient, high-resolution RBC genotyping technology for both patient and donor populations may be transformative for the field of transfusion medicine. Copyright © 2016. Published by Elsevier Inc.

  19. Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors.

    PubMed

    Kochenderfer, James N; Rosenberg, Steven A

    2013-05-01

    Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19(+) B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.

  20. [Contribution of urinary pneumococcal antigen detection combined with the research of legionella antigen for diagnosis of pneumonia in hospitalized patients].

    PubMed

    Honoré, S; Trillard, M; Ould-Hocine, Z; Lesprit, P; Deforges, L; Legrand, P

    2004-10-01

    Bacteriological confirmation of pneumonia (PNM) in hospitalized patients is often erratic or belated. Because of importance of prognosis, early adaptation of treatment requires an empirical antimicrobial therapy (generally aminopenicillin and macrolide combination). The starting therapeutic strategy should profit by a fast and reliable test asserting a pneumococcal etiology. The Binax Now S. pneumoniae (BNP) test allows an urinary pneumococcal antigen (UPA) detection using an immunochromatographic membrane assay within 15 minutes. We first evaluated the BNP test for 28 patients with pneumococcal PNM proved by culture, and 118 negative control patients without PNM. The BNP test was then evaluated by testing urine from 158 hospitalized patients with a clinical picture of PNM (community-acquired: 90, nosocomial: 68) for whom a research of urinary Legionella antigen (Binax Now) was prescribed and was positive for only two cases. 57 patients (36.1%) were hospitalized in ICU. The sensitivity was 71.4% (85.7% for the 21 bacteriemic PNM), and the specificity was 98.3%; that is consistent with previous published data. Among the 158 patients with PNM, UPA was detected in 17 cases (10.8%): 15 within the community-acquired PNM (16.7%) and 2 (2.9%) within the nosocomial cases. The pneumococcal etiology was confirmed by bacteriological samples in 7/17 patients (6 by blood cultures). The 10 others showed clinical and radiological features in agreement with a pneumococcal PNM. Among the 141 patients with negative AUP, S. pneumoniae was isolated from 6 of them (2 in blood cultures). The Binax Now S. pneumoniae test allowed a fast and reliable etiological diagnosis in 10.8% of hospitalized PNM (16.7% of the community-acquired cases) having a research of urinary Legionella antigen (conceiving with severity factors). So it could conduce to an improved adjustment of the starting antimicrobial therapy of hospitalized adult patients with PNM.

  1. Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy.

    PubMed

    Fossati, Nicola; Karnes, R Jeffrey; Cozzarini, Cesare; Fiorino, Claudio; Gandaglia, Giorgio; Joniau, Steven; Boorjian, Stephen A; Goldner, Gregor; Hinkelbein, Wolfgang; Haustermans, Karin; Tombal, Bertrand; Shariat, Shahrokh; Karakiewicz, Pierre I; Montorsi, Francesco; Van Poppel, Hein; Wiegel, Thomas; Briganti, Alberto

    2016-04-01

    Early salvage radiation therapy (eSRT) represents a treatment option for patients who experience a prostate-specific antigen (PSA) rise after radical prostatectomy (RP); however, the optimal PSA level for eSRT administration is still unclear. To test the impact of PSA level on cancer control after eSRT according to pathologic tumour characteristics. The study included 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP. All patients received eSRT, defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml. Biochemical recurrence (BCR) after eSRT was defined as two consecutive PSA values ≥ 0.2 ng/ml. Multivariable Cox regression analysis tested the association between pre-eSRT PSA level and BCR after eSRT. Covariates consisted of pathologic stage (pT2 vs pT3a vs pT3b or higher), pathologic Gleason score (≤ 6, 7, or ≥ 8), and surgical margin status (negative vs positive). We tested an interaction with PSA level and baseline pathologic risk for the hypothesis that BCR-free survival differed by pre-eSRT PSA level. Three pathologic risk factors were identified: pathologic stage pT3b or higher, pathologic Gleason score ≥ 8, and negative surgical margins. Median follow-up among patients who did not experience BCR after eSRT was 57 mo (interquartile range: 27-105). At 5 yr after eSRT, BCR-free survival rate was 82% (95% confidence interval [CI], 78-85). At multivariable Cox regression analysis, pre-eSRT PSA level was significantly associated with BCR after eSRT (hazard ratio: 4.89; 95% CI, 1.40-22.9; p < 0.0001). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors showed an increased risk of 5-yr BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors. In this retrospective study, cancer control after eSRT greatly depended on

  2. Podocytes Are Nonhematopoietic Professional Antigen-Presenting Cells

    PubMed Central

    Burkard, Miriam; Ölke, Martha; Daniel, Christoph; Amann, Kerstin; Hugo, Christian; Kurts, Christian; Steinkasserer, Alexander; Gessner, André

    2013-01-01

    Podocytes are essential to the structure and function of the glomerular filtration barrier; however, they also exhibit increased expression of MHC class II molecules under inflammatory conditions, and they remove Ig and immune complexes from the glomerular basement membrane (GBM). This finding suggests that podocytes may act as antigen-presenting cells, taking up and processing antigens to initiate specific T cell responses, similar to professional hematopoietic cells such as dendritic cells or macrophages. Here, MHC–antigen complexes expressed exclusively on podocytes of transgenic mice were sufficient to activate CD8+ T cells in vivo. In addition, deleting MHC class II exclusively on podocytes prevented the induction of experimental anti-GBM nephritis. Podocytes ingested soluble and particulate antigens, activated CD4+ T cells, and crosspresented exogenous antigen on MHC class I molecules to CD8+ T cells. In conclusion, podocytes participate in the antigen-specific activation of adaptive immune responses, providing a potential target for immunotherapies of inflammatory kidney diseases and transplant rejection. PMID:23539760

  3. Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

    NASA Technical Reports Server (NTRS)

    O'Sullivan, Cathal E.; Peng, RongSheng; Cole, Kelly Stefano; Montelaro, Ronald C.; Sturgeon, Timothy; Jenson, Hal B.; Ling, Paul D.; Butel, J. S. (Principal Investigator)

    2002-01-01

    Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months. Copyright 2002 Wiley-Liss, Inc.

  4. Aberrant lymphoid antigen expression in acute myeloid leukemia in Saudi Arabia.

    PubMed

    El-Sissy, Azza H; El-Mashari, May A; Bassuni, Wafaa Y; El-Swaayed, Aziza F

    2006-09-01

    Immunophenotyping improves both accuracy and reproducibility of acute leukemia classification and is considered particularly useful for identifying aberrant lineage association of acute leukemia, biphenotypic and bilineal acute leukemia, as well as monitoring minimal residual disease. Some immunophenotypes correlate with cytogenetic abnormalities and prognosis. Is to determine aberrant lymphoid antigen expression in Saudi acute myeloid leukemia (AML), correlate them with FAB subtypes, evaluate early surface markers CD7 and CD56, and to investigate the role of cytoplasmic CD79a (a B cell marker that is assigned a high score of 2.0 in the WHO classification). Thirty four newly diagnosed AML cases were included in this study, 47% showed aberrant lymphoid antigen expression. CD9 was the most frequently expressed lymphoid antigen (29.4%) followed by CD7 & CD19 (11.8%), CD4 (8.8%) and CD22 (2.9%). CD9 was expressed in 3/6 (50%) of M3 cases, CD7 was expressed in 11.8% and was mostly confined to FAB M1 and M2 and associated with immature antigens CD34, HLA-DR and TdT. CD56 was expressed in 7/34 (20.6%) cases, three of these cases (42.9%) belonged to the monocytic group. CD56 was also detected in 2 cases with 11q23 rearrangement. CD56 was expressed in 2/7 (28.6%) M2 cases, and was associated with t (8;21) (q22;q22) together with CD19. Co-expression of CD56 and CD7 was detected in 2.9% of the cases. CD79a was expressed in one case together with CD19, diagnosed as acute biphenotypic leukemia, and was associated with t(8;21) (q22;q22). Minimal residual disease in AML is very difficult to trace, detection of aberrant expression of lymphoid antigens will make it easier. The high score given to CD79a by EGIL is questionable based on cytogenetic classification.

  5. Prostate-specific antigen velocity is not better than total prostate-specific antigen in predicting prostate biopsy diagnosis.

    PubMed

    Gorday, William; Sadrzadeh, Hossein; de Koning, Lawrence; Naugler, Christopher T

    2015-12-01

    1.) Identify whether prostate-specific antigen velocity improves the ability to predict prostate biopsy diagnosis. 2.) Test whether there is an increase in the predictive capability of models when Gleason 7 prostate cancers are separated into a 3+4 and a 4+3 group. Calgary Laboratory Services' Clinical Laboratory Information System was searched for prostate biopsies reported between January 1, 2009 and December 31, 2013. Total prostate-specific antigen tests were recorded for each patient from January 1, 2007 to the most recent test before their recorded prostate biopsy. The data set was divided into the following three groups for comparison; benign, all prostate cancer and Gleason 7-10. The Gleason grade 7-10 group was further divided into 4+3 and 3+4 Gleason 7 prostate cancers. Prostate-specific antigen velocity was calculated using four different methods found in the literature. Receiver operator curves were used to assess operational characteristics of the tests. 4622 men between the ages of 40-89 with a prostate biopsy were included for analysis. Combining prostate-specific antigen velocity with total prostate-specific antigen (AUC=0.570-0.712) resulted in small non-statistically significant changes to the area under the curve compared to the area under the curve of total prostate-specific antigen alone (AUC=0.572-0.699). There were marked increases in the area under curves when 3+4 and 4+3 Gleason 7 cancers were separated. Prostate-specific antigen velocity does not add predictive value for prostate biopsy diagnosis. The clinical significance of the prostate specific antigen test can be improved by separating Gleason 7 prostate cancers into a 3+4 and 4+3 group. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Confronting the EPOS-LHC model predictions on the charged particle and muon attenuation lengths of EAS with the measurements of the KASCADE-Grande observatory

    NASA Astrophysics Data System (ADS)

    Arteaga-Velázquez, J. C.; Apel, W. D.; Bekk, K.; Bertaina, M.; Blümer, J.; Bozdog, H.; Brancus, I. M.; Cantoni, E.; Chiavassa, A.; Cossavella, F.; Daumiller, K.; de Souza, V.; Di Pierro, F.; Doll, P.; Engel, R.; Engler, J.; Fuchs, B.; Fuhrmann, D.; Gherghel-Lascu, A.; Gils, H. J.; Glasstetter, R.; Grupen, C.; Haungs, A.; Heck, D.; Hörandel, J. R.; Huber, D.; Huege, T.; Kampert, K.-H.; Kang, D.; Klages, H. O.; Link, K.; Łuczak, P.; Mathes, H. J.; Mayer, H. J.; Milke, J.; Mitrica, B.; Morello, C.; Oehlschläger, J.; Ostapchenko, S.; Palmieri, N.; Petcu, M.; Pierog, T.; Rebel, H.; Roth, M.; Schieler, H.; Schoo, S.; Schröder, F. G.; Sima, O.; Toma, G.; Trinchero, G. C.; Ulrich, H.; Weindl, A.; Wochele, J.; Zabierowski, J.

    2015-08-01

    KASCADE-Grande was an air-shower experiment designed to study cosmic rays between 1016 and 1018 eV. The instrument was located at the site of the Karlsruhe Institute of Technology, Germany at an altitude of 110 m a.s.l. and covered an area of 0.5 km2. KASCADE-Grande consisted of several detector systems dedicated to measure different components of the EAS generated by the primary cosmic rays, i.e., the muon and the electron contents of the air-shower. With such a number of EAS observables and the precision of the measurements, the KASCADE-Grande data can be used to not only study in detail the properties of cosmic rays but also to test the predictions of hadronic-interaction models. In this work, in particular, the attenuation lengths of the muon number and the charged number of particles of EAS in the atmosphere were extracted from the KASCADE-Grande data and the results were compared with the predictions of the new EPOS-LHC hadronic-interaction model.

  7. [HL-A antigen distribution in duodenal ulcer patients].

    PubMed

    Ilieva, P; Minev, M; Etŭrska, M

    1980-01-01

    The incidence of HLA-antigens was studied in 405 patients with clinically, roentgenologically and gastroscopically confirmed ulcer of duodenum and in 1085 controls, healthy subjects. Increased incidence of both antigens from locus B was established among the patients: HLA-B17 and HLA-BW21. A reduction of HLA-A3 incidence was found from the antigens of locus A. In the determination of incidence of HLA antigenes, depending on blood grouping ABO both of patients and healthy subjects, it was established that antigen HLA-A3 is less frequent in the patients with blood group B, whereas antigen HLA-B12 is found more often among the patients with blood group A.

  8. Antigen-mediated regulation in monoclonal gammopathies and myeloma.

    PubMed

    Nair, Shiny; Sng, Joel; Boddupalli, Chandra Sekhar; Seckinger, Anja; Chesi, Marta; Fulciniti, Mariateresa; Zhang, Lin; Rauniyar, Navin; Lopez, Michael; Neparidze, Natalia; Parker, Terri; Munshi, Nikhil C; Sexton, Rachael; Barlogie, Bart; Orlowski, Robert; Bergsagel, Leif; Hose, Dirk; Flavell, Richard A; Mistry, Pramod K; Meffre, Eric; Dhodapkar, Madhav V

    2018-04-19

    A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies. Here, we show that recombinant Ig (rIg) cloned from sort-purified single tumor cells from lipid-reactive sporadic and GD-associated gammopathy specifically bound lysolipids. Liposome sedimentation and binding assays confirmed specific interaction of lipid-reactive monoclonal Ig with lysolipids. The clonal nature of lysolipid-binding Ig was validated by protein sequencing. Gene expression profiling and cytogenetic analyses from 2 patient cohorts showed enrichment of nonhyperdiploid tumors in lipid-reactive patients. In vivo antigen-mediated stimulation led to an increase in clonal Ig and plasma cells (PCs) in GD gammopathy and also reactivated previously suppressed antigenically related nonclonal PCs. These data support a model wherein antigenic stimulation mediates an initial polyclonal phase, followed by evolution of monoclonal tumors enriched in nonhyperdiploid genomes, responsive to underlying antigen. Targeting underlying antigens may therefore prevent clinical MM.

  9. 77 FR 14855 - Notice of Availability and Request for Comment on the Draft Environmental Assessment (EA) for the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... Reusable Suborbital Rockets at the Mojave Air and Space Port AGENCY: Federal Aviation Administration (FAA... of SpaceShipTwo Reusable Suborbital Rockets at the Mojave Air and Space Port. The Draft EA was... licenses to operate SpaceShipTwo Reusable Suborbital Rockets and WhiteKnightTwo carrier aircraft at the...

  10. Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

    PubMed Central

    Claudi, Beatrice; Mazé, Alain; Schemmer, Anne K.; Kirchhoff, Dennis; Schmidt, Alexander; Burton, Neil; Bumann, Dirk

    2012-01-01

    Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens. PMID:23093937

  11. Antigenic variation: Molecular and genetic mechanisms of relapsing disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cruse, J.M.; Lewis, R.E.

    1987-01-01

    This book contains 10 chapters. They are: Contemporary Concepts of Antigenic Variation; Antigenic Variation in the Influenza Viruses; Mechanisms of Escape of Visna Lentiviruses from Immunological Control; A Review of Antigenic Variation by the Equine Infectious Anemia Virus; Biologic and Molecular Variations in AIDS Retrovirus Isolates; Rabies Virus Infection: Genetic Mutations and the Impact on Viral Pathogenicity and Immunity; Immunobiology of Relapsing Fever; Antigenic Variation in African Trypanosomes; Antigenic Variation and Antigenic Diversity in Malaria; and Mechanisms of Immune Evasion in Schistosomiasis.

  12. Toxicities of chimeric antigen receptor T cells: recognition and management

    PubMed Central

    Brudno, Jennifer N.

    2016-01-01

    Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies. Yet the use of CAR T cells is limited by potentially severe toxicities. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy. PMID:27207799

  13. Detection of proliferating cell nuclear antigens and interleukin-2 beta receptor molecules on mitogen- and antigen-stimulated lymphocytes.

    PubMed Central

    Hesketh, J; Dobbelaere, D; Griffin, J F; Buchan, G

    1993-01-01

    The expression of interleukin-2 receptors (IL-2R) and proliferating cell nuclear antigens (PCNA) were compared for their usefulness as markers of lymphocyte activation. Heterologous polyclonal (anti-bovine IL-2R) and monoclonal (anti-human PCNA) antibodies were used to detect the expression of these molecules on activated deer lymphocytes. Both molecules were co-expressed on blast cells which had been activated with mitogen [concanavalin A (Con A)]. There was detectable up-regulation of IL-2R expression in response to antigen [Mycobacterium bovis-derived purified protein derivative (PPD)] stimulation while PCNA expression mimicked lymphocyte transformation (LT) reactivity. PCNA expression was found to more accurately reflect both antigen- and mitogen-activated lymphocyte activation, as estimated by LT activity. The expression of PCNA was used to identify antigen reactive cells from animals exposed to M. bovis. A very low percentage (1.1 +/- 0.4%) of peripheral blood lymphocytes from non-infected animals could be stimulated to express PCNA by in vitro culture with antigen (PPD). Within the infected group both diseased and healthy, 'in-contact', animals expressed significantly higher levels of PCNA upon antigen stimulation. PMID:8104884

  14. Antigen-mediated regulation in monoclonal gammopathies and myeloma

    PubMed Central

    Nair, Shiny; Sng, Joel; Boddupalli, Chandra Sekhar; Seckinger, Anja; Fulciniti, Mariateresa; Zhang, Lin; Rauniyar, Navin; Lopez, Michael; Neparidze, Natalia; Parker, Terri; Munshi, Nikhil C.; Sexton, Rachael; Barlogie, Bart; Orlowski, Robert; Bergsagel, Leif; Hose, Dirk; Mistry, Pramod K.; Meffre, Eric; Dhodapkar, Madhav V.

    2018-01-01

    A role for antigen-driven stimulation has been proposed in the pathogenesis of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) based largely on the binding properties of monoclonal Ig. However, insights into antigen binding to clonal B cell receptors and in vivo responsiveness of the malignant clone to antigen-mediated stimulation are needed to understand the role of antigenic stimulation in tumor growth. Lysolipid-reactive clonal Ig were detected in Gaucher disease (GD) and some sporadic gammopathies. Here, we show that recombinant Ig (rIg) cloned from sort-purified single tumor cells from lipid-reactive sporadic and GD-associated gammopathy specifically bound lysolipids. Liposome sedimentation and binding assays confirmed specific interaction of lipid-reactive monoclonal Ig with lysolipids. The clonal nature of lysolipid-binding Ig was validated by protein sequencing. Gene expression profiling and cytogenetic analyses from 2 patient cohorts showed enrichment of nonhyperdiploid tumors in lipid-reactive patients. In vivo antigen-mediated stimulation led to an increase in clonal Ig and plasma cells (PCs) in GD gammopathy and also reactivated previously suppressed antigenically related nonclonal PCs. These data support a model wherein antigenic stimulation mediates an initial polyclonal phase, followed by evolution of monoclonal tumors enriched in nonhyperdiploid genomes, responsive to underlying antigen. Targeting underlying antigens may therefore prevent clinical MM. PMID:29669929

  15. Antigen Masking During Fixation and Embedding, Dissected

    PubMed Central

    Scalia, Carla Rossana; Boi, Giovanna; Bolognesi, Maddalena Maria; Riva, Lorella; Manzoni, Marco; DeSmedt, Linde; Bosisio, Francesca Maria; Ronchi, Susanna; Leone, Biagio Eugenio; Cattoretti, Giorgio

    2016-01-01

    Antigen masking in routinely processed tissue is a poorly understood process caused by multiple factors. We sought to dissect the effect on antigenicity of each step of processing by using frozen sections as proxies of the whole tissue. An equivalent extent of antigen masking occurs across variable fixation times at room temperature. Most antigens benefit from longer fixation times (>24 hr) for optimal detection after antigen retrieval (AR; for example, Ki-67, bcl-2, ER). The transfer to a graded alcohol series results in an enhanced staining effect, reproduced by treating the sections with detergents, possibly because of a better access of the polymeric immunohistochemical detection system to tissue structures. A second round of masking occurs upon entering the clearing agent, mostly at the paraffin embedding step. This may depend on the non-freezable water removal. AR fully reverses the masking due both to the fixation time and the paraffin embedding. AR itself destroys some epitopes which do not survive routine processing. Processed frozen sections are a tool to investigate fixation and processing requirements for antigens in routine specimens. PMID:27798289

  16. Antigenic Competition Between and Endotoxic Adjuvant and a Protein Antigen

    PubMed Central

    Leong, Daniel L. Y.; Rudbach, Jon A.

    1971-01-01

    Antigenic competition between bovine gamma globulin (BGG) and endotoxin from a smooth strain (S-ET) and a rough (R-ET) heptoseless mutant strain of Salmonella minnesota was studied in mice. Both endotoxins acted as adjuvants for enhancing the antibody response to BGG. However, other work showed that the R-ET had minimal antigenicity, and it was used as a control for the competition studies. Antigenic competition between BGG and endotoxin as expressed by a suppression of the antibody response to BGG could not be demonstrated when varying adjuvant doses of S-ET or R-ET were injected simultaneously with a small constant dose of BGG into normal mice. However, mice presensitized with S-ET several weeks before immunization with the S-ET and BGG combination produced anti-BGG levels which were four to eightfold lower than in normal mice. Nearly complete suppression of the anti-BGG response could be obtained in presensitized mice by reducing the BGG dose 10-fold or by increasing the adjuvant dose of endotoxin. Mice pretreated with R-ET and challenged with BGG plus S-ET or R-ET showed no depression of the anti-BGG response. These and other experiments confirmed the immunological basis of the competitive effect. PMID:16557970

  17. JAL (RH48) blood group antigen: serologic observations

    PubMed Central

    Lomas-Francis, Christine; Alcantara, Denden; Westhoff, Connie; Uehlinger, Joan; Valvasori, Marilia; Castilho, Lillian; Reid, Marion E.

    2009-01-01

    BACKGROUND JAL (RH48) is a low-prevalence antigen in the Rh blood group system and anti-JAL has caused hemolytic disease of the newborn. JAL is associated with either a haplotype carrying depressed C and e antigens or one carrying depressed c and e antigens. Blood samples from JAL+ people were tested, published serologic findings were confirmed, serologic studies were extended to include expression of other Rh antigens, and the antibody specificities produced by three sensitized JAL+ probands are reported. STUDY DESIGN AND METHODS Red blood cell (RBC) samples from 17 (12 probands) JAL+ persons were tested by hemagglutination using standard methods. RESULTS RBCs from both the Caucasian JAL+ probands had the (C)(e) haplotype and weakened C, e, hrB, and hrS antigens. JAL+ samples from black persons had the (c)(e) haplotype and expressed weakened c, e, f, V, VS, hrB, and hrS antigens. Plasma from three sensitized c+e+ JAL+ probands contained alloanti-c, alloanti-e, or alloantibody of apparent anti-Rh17 specificity. This study shows that this alloanti-Rh17–like antibody recognizes the high-prevalence antigen antithetical to JAL that has been named CEST. CONCLUSIONS The presence of the JAL antigen has a quantitative (weakening) effect on the expression of C, e, hrB, and hrS antigens in Caucasian persons and of c, e, f, V, VS, hrB, and hrS antigens in people of black African ancestry. A qualitative effect also was demonstrated by the presence of alloanti-c or alloanti-e in the plasma of two transfused c+e+ patients and by an antibody (anti-CEST) that recognizes the high-prevalence antigen antithetical to JAL. PMID:19192256

  18. Telomere interactions may condition the programming of antigen expression in Trypanosoma brucei.

    PubMed Central

    Van der Werf, A; Van Assel, S; Aerts, D; Steinert, M; Pays, E

    1990-01-01

    The AnTat 1.1 antigen type typically occurs late in a chronic infection by the EATRO 1125 stock of Trypanosoma brucei. The AnTat 1.1 gene, which is located 24 kb from a chromosome end, seems exclusively expressed by acting as a donor in gene conversion events targeted to the telomeric expression site. We report that this gene is sufficiently provided with the homology blocks required for recombination with the expression site, and is not interrupted by stop codons up to the 3' block of homology. A possible reason for its low probability of activation is an inverse orientation with respect to the proximal chromosome end, since, if correctly positioned, it is readily expressed at an early stage of infection, following gene conversion. This suggests that interactions between chromosome ends may precede and favour the rearrangements leading to antigenic variation. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. PMID:2323332

  19. Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses.

    PubMed

    Lindh, Ingrid; Bråve, Andreas; Hallengärd, David; Hadad, Ronza; Kalbina, Irina; Strid, Åke; Andersson, Sören

    2014-04-25

    During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4(+) T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic A. thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses. Copyright © 2014. Published by Elsevier Ltd.

  20. Role of the Antigen Capture Pathway in the Induction of a Neutralizing Antibody Response to Anthrax Protective Antigen.

    PubMed

    Verma, Anita; Ngundi, Miriam M; Price, Gregory A; Takeda, Kazuyo; Yu, James; Burns, Drusilla L

    2018-02-27

    Toxin neutralizing antibodies represent the major mode of protective immunity against a number of toxin-mediated bacterial diseases, including anthrax; however, the cellular mechanisms that lead to optimal neutralizing antibody responses remain ill defined. Here we show that the cellular binding pathway of anthrax protective antigen (PA), the binding component of anthrax toxin, determines the toxin neutralizing antibody response to this antigen. PA, which binds cellular receptors and efficiently enters antigen-presenting cells by receptor-mediated endocytosis, was found to elicit robust anti-PA IgG and toxin neutralizing antibody responses. In contrast, a receptor binding-deficient mutant of PA, which does not bind receptors and only inefficiently enters antigen-presenting cells by macropinocytosis, elicited very poor antibody responses. A chimeric protein consisting of the receptor binding-deficient PA mutant tethered to the binding subunit of cholera toxin, which efficiently enters cells using the cholera toxin receptor rather than the PA receptor, elicited an anti-PA IgG antibody response similar to that elicited by wild-type PA; however, the chimeric protein elicited a poor toxin neutralizing antibody response. Taken together, our results demonstrate that the antigen capture pathway can dictate the magnitudes of the total IgG and toxin neutralizing antibody responses to PA as well as the ratio of the two responses. IMPORTANCE Neutralizing antibodies provide protection against a number of toxin-mediated bacterial diseases by inhibiting toxin action. Therefore, many bacterial vaccines are designed to induce a toxin neutralizing antibody response. We have used protective antigen (PA), the binding component of anthrax toxin, as a model antigen to investigate immune mechanisms important for the induction of robust toxin neutralizing antibody responses. We found that the pathway used by antigen-presenting cells to capture PA dictates the robustness of the

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