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Sample records for ctl line recognizes

  1. Broadly Immunogenic HLA Class I Supertype-Restricted Elite CTL Epitopes Recognized in a Diverse Population Infected with Different HIV-1 Subtypes

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    Pérez, Carina L; Larsen, Mette Voldby; Gustafsson, Rasmus

    2008-01-01

    The genetic variations of the HIV-1 virus and its human host constitute major obstacles for obtaining potent HIV-1-specific CTL responses in individuals of diverse ethnic backgrounds infected with different HIV-1 variants. In this study, we developed and used a novel algorithm to select 184......, not previously described in the HIV-1 immunology database. In addition, we identified 21 "elite" epitopes that induced CTL responses in at least 4 of the 31 patients. A majority (27 of 31) of the study population recognized one or more of these highly immunogenic epitopes. We also found a limited set of 9...

  2. Generation and characterization of peptide-specific, MHC-restricted cytotoxic T lymphocyte (CTL) and helper T cell lines from unprimed T cells under microculture conditions.

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    Sambhara, S R; Upadhya, A G; Miller, R G

    1990-06-12

    We describe a microculture system for the generation of CTL and T helper cells against peptides. Tryptic digest and cyanogen bromide fragments of chicken ovalbumin and synthetic peptides of ovalbumin (323-339) and influenza virus (NP 365-380) were used to generate CTL and T helper lines from unprimed T cells. These lines were both peptide-specific and MHC-restricted. The relative ease of generating peptide-specific, MHC-restricted CTL and helper T cell lines with as few as 10(6) unprimed lymphocytes can be an efficient method of detecting potential immunogenic determinants of an antigen.

  3. Antimelanoma CTL recognizes peptides derived from an ORF transcribed from the antisense strand of the 3′ untranslated region of TRIT1

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    Rolf K Swoboda

    2014-01-01

    Full Text Available Noncoding regions of the genome play an important role in tumorigenesis of cancer. Using expression cloning, we have identified a cytotoxic T lymphocyte (CTL–defined antigen that recognizes a protein sequence derived from an open reading frame transcribed from the reverse strand in the 3′ untranslated region of tRNA isopentenyltransferase 1 (TRIT1. A peptide derived from this open reading frame (ORF sequence and predicted to bind to HLA-B57, sensitized HLA-B57+ tumor cells to lysis by CTL793. The peptide also induced a CTL response in peripheral blood mononuclear cells (PBMC of patient 793 and in two other melanoma patients. The CTL lysed peptide-pulsed HLA-B57+ target cells and melanoma cells with endogenous antigen expression. The recognition of this antigen is not limited to HLA-B57-restricted CTLs. An HLA-A2 peptide derived from the ORF was able to induce CTLs in PBMC of 2 HLA-A2+ patients. This study describes for the first time a CTL-defined melanoma antigen that is derived from an ORF on the reverse strand of the putative tumor suppressor gene TRIT1. This antigen has potential use as a vaccine or its ability to induce CTLs in vitro could be used as a predictive biomarker.

  4. HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor

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    Tsukahara Tomohide

    2009-06-01

    Full Text Available Abstract Background To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2. Methods Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201+ patients with osteosarcoma using limiting dilution (LD/mixed lymphocyte peptide culture (MLPC followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by 51Cr release assay. Results Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 × 10-7 to 5 × 10-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2. Conclusion These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.

  5. Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

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    Jennifer Papuchon

    Full Text Available In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013 showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2 and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

  6. Kinetics of HIV-1 CTL epitopes recognized by HLA I alleles in HIV-infected individuals at times near primary infection: the Provir/Latitude45 study.

    Science.gov (United States)

    Papuchon, Jennifer; Pinson, Patricia; Guidicelli, Gwenda-Line; Bellecave, Pantxika; Thomas, Réjean; LeBlanc, Roger; Reigadas, Sandrine; Taupin, Jean-Luc; Baril, Jean Guy; Routy, Jean Pierre; Wainberg, Mark; Fleury, Hervé

    2014-01-01

    In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013) showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2) and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.

  7. Plasmodium falciparum CS protein - prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation

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    Denise L. Doolan

    1992-01-01

    Full Text Available Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by citotoxic T lymphocytes (CTL specific for epitopes within the circumsporozoite (CS protein. Humans, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans ralies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL. against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria.

  8. Anti-idiotypic antibodies against UV-induced tumor-specific CTL clones. Preparation in syngeneic combination

    International Nuclear Information System (INIS)

    Kuribayashi, K.; Tanaka, C.; Matsubayashi, Y.; Masuda, T.; Udono, H.; Abe, M.; Nakayama, E.; Shiku, H.

    1988-01-01

    In this study, we first established several CTL clones of (BALB/c x C57BL/6)F1 origin that were specific for either syngeneic UV female 1 or UV male 1 fibrosarcoma cell lines. All the CTL clones had Thy-1+ Lyt-2+ L3T4- phenotypes and showed Kd restriction when lysing the corresponding target cells. Sera obtained from syngeneic animals immunized with three CTL clones, 10B-5 for UV female 1, and CTL9 and CTL10 for UV male 1, showed specific inhibition of target cell lysis with the corresponding CTL clones. The inhibitory activities were found in sera of the majority of immunized animals. Because the inhibitory activity resides in protein A-binding fraction, mAb were produced by hybridizing spleen cells of hyperimmune animals. N1-56 was thus obtained from a mouse immunized with 10B-5 CTL clone reactive with UV female 1. N1-56 was clonotype specific, reacting with 10B-5 but not with other CTL lines or leukemia cell lines. No N1-56+ cells were detectable in thymocytes, lymph node cells, or spleen cells of either naive or UV female 1-immune CB6F1 mice. Immunoprecipitation showed that N1-56 reacts with 90,000 Mr molecules on 10B-5 CTL clone under nonreducing conditions and 45,000 Mr molecules under reducing conditions, indicating its reactivities with idiotypic determinants of TCR on the CTL clone. N1-56 inhibited lytic activity of 10B-5, but neither N1-56 nor alpha-10B-5 hyperimmune serum inhibited that of alpha-UV female 1 mixed lymphocyte tumor cell culture cells. N1-56 induced proliferation of 10B-5 without addition of Ag

  9. Figuring the Context of CTL under 2013 Curiculum

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    Chairina Nasir

    2017-06-01

    Full Text Available The 2013 curriculum states that the purpose of teaching English for junior high school is to develop students’ communicative competence. In line with this expectation, several learning characteristics have been defined i.e. learning from model, observing, questioning, gathering information, associating, and communicating. Therefore, the teaching approaches that are used by the teacher in teaching English must suit the criteria to promote students' communicative competence. Contextual Teaching and learning (CTL seems to be compatible as an approach since it has the the characteristics of constructivism, questioning, inquiry, learning community, modelling, reflection, and authentic assessment, which are similar to the learning characteristics mentioned above, which are similar to the learning characteristics mentioned above. , which are similar to the learning characteristics mentioned above. Therefore, a qualitative research concerning the issue was conducted to see how CTL approach is implemented under the 2013 curriculum in teaching reading comprehension. From the result of observation, questionnaire, and interview as the instruments, it was found that CTL was implemented properly from phase to phase and is applicable to be implemented under the curriculum. Also, it promotes active and enjoyable learning, facilitates the students to comprehend the material and helps them to implement the knowledge in real life. The. The teacher had implemented all of the procedures of CTL under the instruction of the 2013 curriculum. Thus, applying the CTL CTL approach in the process of teaching for the 2013 curriculum for the 2013 curriculum is recommended since it gives satisfactory benefits for students.

  10. Wnt signaling inhibits CTL memory programming.

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    Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

    2013-12-01

    Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

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    Tsujimura, Kunio; Takahashi, Toshitada; Morita, Akimichi; Hasegawa-Nishiwaki, Hitomi; Iwase, Shigeru; Obata, Yuichi

    1996-01-01

    To elucidate the function of the mouse TL antigen in the thymus, we have derived two TL transgenic mouse strains by introducing Tla a -3 of A strain origin with its own promoter onto a C3H background with no expression of TL in the thymus. These transgenic mouse strains, both of which express high levels of Tlaa-3-TL antigen in their thymus, were analyzed for their T cell function with emphasis on cytotoxic T lymphocyte (CTL) generation. A T cell response against TL was induced in Tg.Tlaa-3-1, Tg.Tlaa-3-2, and control C3H mice by skin grafts from H-2K b/T3 b transgenic mice, Tg.Con.3-1, expressing T3b-TL ubiquitously. Spleen cells from mice that had rejected the T3b-TL positive skin grafts were restimulated in vitro with Tg.Con.3-1 irradiated spleen cells. In mixed lymphocyte cultures (MLC), approximately 20% and 15% of Thy-1+ T cells derived from Tg.Tlaa-3-1 and Tg.Tlaa-3-2, respectively, expressed TCRγδ, whereas almost all those from C3H expressed TCRαβ. The MLC from Tg.Tlaa-3-2 and C3H demonstrated high CTL activity against TL, while those from Tg.Tlaa-3-1 had little or none. The generation of γδ CTL recognizing TL in Tg.Tlaa-3-2, but not C3H mice, was confirmed by the establishment of CTL clones. A total of 14 γδ CTL clones were established from Tg.Tlaa-3-2, whereas none were obtained from C3H. Of the 14 γδ CTL clones, 8 were CD8+ and 6 were CD4−CD8− double negative. The CTL activity of all these clones was TL specific and inhibited by anti-TL, but not by anti-H-2 antibodies, demonstrating that they recognize TL directly without antigen presentation by H-2. The CTL activity was blocked by antibodies to TCRγδ and CD3, and also by antibodies to CD8α and CD8β in CD8+ clones, showing that the activity was mediated by TCRγδ and coreceptors. The thymic origin of these γδ CTL clones was indicated by the expression of Thy-1 and Ly-1 (CD5), and also CD8αβ heterodimers in CD8+ clones on their surfaces and by the usage of TCR Vγ4 chains in 12 of

  12. CTL escape mediated by proteasomal destruction of an HIV-1 cryptic epitope.

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    Sylvain Cardinaud

    2011-05-01

    Full Text Available Cytotoxic CD8+ T cells (CTLs play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF. We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D and a majority encoding an asparagine (Q9VF/5N. We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes.

  13. Quantifying factors determining the rate of CTL escape and reversion during acute and chronic phases of HIV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ganusov, Vitaly V [Los Alamos National Laboratory; Korber, Bette M [Los Alamos National Laboratory; Perelson, Alan S [Los Alamos National Laboratory

    2009-01-01

    Human immunodeficiency virus (HIV) often evades cytotoxic T cell (CTL) responses by generating variants that are not recognized by CTLs. However, the importance and quantitative details of CTL escape in humans are poorly understood. In part, this is because most studies looking at escape of HIV from CTL responses are cross-sectional and are limited to early or chronic phases of the infection. We use a novel technique of single genome amplification (SGA) to identify longitudinal changes in the transmitted/founder virus from the establishment of infection to the viral set point at 1 year after the infection. We find that HIV escapes from virus-specific CTL responses as early as 30-50 days since the infection, and the rates of viral escapes during acute phase of the infection are much higher than was estimated in previous studies. However, even though with time virus acquires additional escape mutations, these late mutations accumulate at a slower rate. A poor correlation between the rate of CTL escape in a particular epitope and the magnitude of the epitope-specific CTL response suggests that the lower rate of late escapes is unlikely due to a low efficacy of the HIV-specific CTL responses in the chronic phase of the infection. Instead, our results suggest that late and slow escapes are likely to arise because of high fitness cost to the viral replication associated with such CTL escapes. Targeting epitopes in which virus escapes slowly or does not escape at all by CTL responses may, therefore, be a promising direction for the development of T cell based HIV vaccines.

  14. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL response.

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    Ryan M Troyer

    2009-04-01

    Full Text Available Human lymphocyte antigen (HLA-restricted CD8(+ cytotoxic T lymphocytes (CTL target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.

  15. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

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    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

  16. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells.

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    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach.

  17. Leukocyte function-associated antigen-1-dependent lysis of Fas+ (CD95+/Apo-1+) innocent bystanders by antigen-specific CD8+ CTL.

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    Kojima, H; Eshima, K; Takayama, H; Sitkovsky, M V

    1997-09-15

    Exquisite specificity toward Ag-bearing cells (cognate targets) is one of the most important properties of CD8+ CTL-mediated cytotoxicity. Using highly Ag-specific CD8+ CTL lines and clones, which spare noncognate, Ag-free targets, we found that in the presence of Ag-bearing targets the CTL acquire the ability to lyse noncognate target cells (bystanders). It is shown that the unexpectedly rapid and efficient lysis of bystanders by Ag-activated CTL is mediated by a Fas ligand (FasL)/Fas-based mechanism and does not depend on perforin. The CTL lysed Fas-expressing bystanders, but spared the Fas-negative or anti-Fas mAb-resistant bystander cells. Accordingly, the FasL-deficient gld/gld CTL did not kill bystanders, while perforin-deficient CTL did. Unlike anti-Fas mAb-induced cell death, the lysis of bystanders was not only FasL/Fas dependent but also required adhesion molecule LFA-1 on the surface of the activated CTL. Lysis of bystanders is viewed as acceptable "collateral" damage, but the persistent presence of activated CTL could result in immunopathologies involving functional Fas-expressing tissues.

  18. Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

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    Deng, Kai; Pertea, Mihaela; Rongvaux, Anthony; Wang, Leyao; Durand, Christine M.; Ghiaur, Gabriel; Lai, Jun; McHugh, Holly L.; Hao, Haiping; Zhang, Hao; Margolick, Joseph B.; Gurer, Cagan; Murphy, Andrew J.; Valenzuela, David M.; Yancopoulos, George D.; Deeks, Steven G.; Strowig, Till; Kumar, Priti; Siliciano, Janet D.; Salzberg, Steven L.; Flavell, Richard A.; Shan, Liang; Siliciano, Robert F.

    2015-01-01

    Despite antiretroviral therapy (ART), HIV-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6–8. A key remaining question is whether virus-specific immune mechanisms including cytolytic T lymphocytes (CTL) can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir. PMID:25561180

  19. Engineering a CTL-Tailored Replicon RNA Vaccine against PRRSV

    DEFF Research Database (Denmark)

    Welner, Simon; Werder, Simea; Nielsen, Morten

    The development of vaccines against porcine reproductive and respiratory syndrome virus (PRRSV) has been hampered by the high mutation rate and the multiple immunoevasive strategies of the virus. With the overall aim of designing a broad coverage vaccine that induces an effective CTL response aga...... will be available for IVIS. This study exemplifies how bioinformatics epitope prediction, recombinant SLA molecules and RNA virus replicon design can be used to engineer a replicating non-propagating vaccine tailored to deliver conserved and immunogenic CTL epitopes....... against PRRSV, we have used a bioinformatics approach to identify common PRRSV type 2 epitopes predicted to react broadly with predominant swine MHC (SLA) alleles. All possible 9- and 10-mer peptides derived from 104 wild-type strains were analyzed in silico for their predicted binding affinity to 3...... cloned into a classical swine fever virus (CSFV)-derived replicon vector. Virus replicon particles (VRP) were rescued by transfection of a complementing cell line with replicon RNA. Polyepitope expression and subsequent proteasomal degradation was confirmed indirectly by increased FLAG-tagged protein...

  20. Identification of novel HLA-A(*)0201-restricted CTL epitopes from Pokemon.

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    Yuan, Bangqing; Zhao, Lin; Xian, Ronghua; Zhao, Gang

    2012-01-01

    Pokemon is a member of the POK family of transcriptional repressors and aberrant overexpressed in various human cancers. Therefore, the related peptide epitopes derived from Pokemon is essential for the development of specific immunotherapy of malignant tumors. In this study, we predicted and identified HLA-A(*)0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from Pokemon with computer-based epitope prediction, peptide-binding assay and testing of the induced CTLs toward different kinds of carcinoma cells. The results demonstrated that effectors induced by peptides of Pokemon containing residues 32-40, 61-69, 87-95, and 319-327 could specifically secrete IFN-γ and lyse tumor cell lines of Pokemon-positive and HLA-A2-matched. The results suggest that Pokemon32, Pokemon61, Pokemon87, and Pokemon319 peptides are novel HLA-A(*)0201-restricted restricted CTL epitopes, and could be utilized in the cancer immunotherapy against a broad spectrum of tumors. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers.

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    Cho, S; Dong, S; Parent, K N; Chen, M

    2016-01-01

    Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers. We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs. Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells (DCs) and enhanced vaccine-induced CTL responses. A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines. It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.

  2. Cytotoxic T lymphocyte recognition of HLA-A/B antigens introduced into EL4 cells by cell-liposome fusion.

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    Engelhard, V H; Powers, G A; Moore, L C; Holterman, M J; Correa-Freire, M C

    1984-01-01

    HLA-A2 and -B7 antigens were introduced into EL4 (H-2b) cells by cell-liposome fusion and were used as targets or stimulators for cytotoxic T lymphocytes (CTL) generated in C57B1/6 (H-2b) mice. It was found that such EL4-HLA cells were not recognized by CTL that had been raised against either a human cell line bearing these HLA antigens or the purified HLA-A2 and -B7 antigens reconstituted into liposomes. In addition, EL4-HLA cells were not capable of inducing CTL that could recognize a human cell line bearing HLA-A2 and -B7 antigens. Instead, EL4-HLA cells induced CTL that specifically lysed EL4-HLA cells and not human cells expressing HLA-A2 and -B7. CTL recognition required the presence of HLA antigens on the EL4 cell surface and was inhibited by antibodies against either H-2b or HLA-A/B. Monoclonal antibody binding studies showed that the expected polymorphic determinants of the HLA-A2 and -B7 antigens were still present on EL4-HLA cells. However, the specificity of CTL or their precursors that are capable of recognizing HLA-A2 or -B7 was altered after these antigens became associated with the EL4 surface. Possible explanations for these results are discussed.

  3. Indirect coal liquefaction - the first commercial CTL project in the USA

    Energy Technology Data Exchange (ETDEWEB)

    Radtke, K.; Battensby, D.; Marsico, C.; Hooper, M.; Mather, C. [Uhde GmbH (Germany)

    2006-07-01

    The polygeneration of fuels, chemical and power offers an innovative and economically advantageous way to utilise disadvantaged fuels, such as lignite, waste coal and petroleum coke, in a coal-to-liquids (CTL) plant by means of integration of three main process blocks: gasification island to convert coal into clean synthesis gas; Fischer-Tropsch synthesis to convert synthesis gas into clean liquid fuels and chemicals; and combustion of synthesis gas to produce electric power and steam. This paper describes the process and technology side of this indirect coal liquefaction project with key plant data that has been elaborated for a commercial scale CTL project, which is expected to be the first CTL plant in the USA. The plant will use the Shell Coal Gasification process. 6 figs.

  4. CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from subtype A infected subjects in Kenya: Use of multiple peptide sets increases the detectable breadth of the CTL response

    Directory of Open Access Journals (Sweden)

    Birx Deborah L

    2006-04-01

    Full Text Available Abstract Background Subtype A is a major strain in the HIV-1 pandemic in eastern Europe, central Asia and in certain regions of east Africa, notably in rural Kenya. While considerable effort has been focused upon mapping and defining immunodominant CTL epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies have focused upon subtype A. Results We have used the IFN-γ ELIspot assay and overlapping peptide pools to show that the pattern of CTL recognition of the Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B and C. The p17 and p24 proteins of Gag and the central conserved region of Nef were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA associations commonly seen in subtype B and C infection were also observed in subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag 296–304; YL9 was observed, with 8/9 HLA-CW0304 subjects responding to this epitope. Screening the cohort with peptide sets representing subtypes A, C and D (the three most prevalent HIV-1 subtypes in east Africa, revealed that peptide sets based upon an homologous subtype (either isolate or consensus only marginally improved the capacity to detect CTL responses. While the different peptide sets detected a similar number of responses (particularly in the Gag protein, each set was capable of detecting unique responses not identified with the other peptide sets. Conclusion Hence, screening with multiple peptide sets representing different sequences, and by extension different epitope variants, can increase the detectable breadth of the HIV-1-specific CTL response. Interpreting the true extent of cross-reactivity may be hampered by the use of 15-mer peptides at a single concentration and a lack of knowledge of the sequence that primed any given CTL response. Therefore, reagent choice and knowledge of the exact sequences that prime CTL responses will be important factors in

  5. Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on antiviral treatment: toward a new concept of vaccine.

    Directory of Open Access Journals (Sweden)

    Jennifer Papuchon

    Full Text Available Eleven patients responding successfully to first-line antiretroviral therapy (ART were investigated for proviral drug resistance mutations (DRMs in RT by ultra-deep pyrosequencing (UDPS. After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA. For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.

  6. The Expression and Biological Significance of PD-L1 on Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Cheng CHEN

    2009-08-01

    Full Text Available Background and objective Tumor-associated PD-L1 expression was recently shown to promote T-cell apoptosis and proposed as a potential mechanism of immune evasion by tumors. On the basis of the ability of tumor-associated PD-L1 to mediate activated T-cell death, it is likely that manipulation of the PD-L1 pathway at defined time points during the development of the T-cell antitumor immune response can enhance the efficacy of T-cell-based immunotherapy. Here, the levels of expression of PD-L1 on lung cancer cell lines and its role in interaction of CTL and target cells was investigated. Methods Human PBMC derived DCs were loaded with apoptotic tumor cells and stimulated by CD40 mAb (5C11. Tumor specific CTL was generated in vitro by autologous T cells co-cultured with mature DCs. Expression of PD-L1 on lung cancer cell lines H1299 and A549 were analyzed by FCM. JAM assay was used to detect the cytolytic activity of CTL with or without blocking PD-L1 by PD-L1 mAb respectively. The concentrations of IFN-γ in supernatants from distinct groups were analyzed by ELISA. Results Tumor cells-loaded mature DCs could induce the generation of the tumor specific CTL. Expression of PD-L1 was low on A549 cell, but high on H1299 cell. Blockade of PD-L1 on A549 could not improve cytolytic effect of CTL on target cells and IFN-γ production, but fragmentation of H1299 cells and IFN-γ production were significantly enhanced by the combination of PD-L1 mAb and CTL. Conclusion Expression of PD-L1 on lung cancer cell line can decrease the cytolytic effect of CTL on target cells.

  7. TNF-Induced Target Cell Killing by CTL Activated through Cross-Presentation

    Directory of Open Access Journals (Sweden)

    Dirk Wohlleber

    2012-09-01

    Full Text Available Viruses can escape cytotoxic T cell (CTL immunity by avoiding presentation of viral components via endogenous MHC class I antigen presentation in infected cells. Cross-priming of viral antigens circumvents such immune escape by allowing noninfected dendritic cells to activate virus-specific CTLs, but they remain ineffective against infected cells in which immune escape is functional. Here, we show that cross-presentation of antigen released from adenovirus-infected hepatocytes by liver sinusoidal endothelial cells stimulated cross-primed effector CTLs to release tumor necrosis factor (TNF, which killed virus-infected hepatocytes through caspase activation. TNF receptor signaling specifically eliminated infected hepatocytes that showed impaired anti-apoptotic defense. Thus, CTL immune surveillance against infection relies on two similarly important but distinct effector functions that are both MHC restricted, requiring either direct antigen recognition on target cells and canonical CTL effector function or cross-presentation and a noncanonical effector function mediated by TNF.

  8. TNF-induced target cell killing by CTL activated through cross-presentation.

    Science.gov (United States)

    Wohlleber, Dirk; Kashkar, Hamid; Gärtner, Katja; Frings, Marianne K; Odenthal, Margarete; Hegenbarth, Silke; Börner, Carolin; Arnold, Bernd; Hämmerling, Günter; Nieswandt, Bernd; van Rooijen, Nico; Limmer, Andreas; Cederbrant, Karin; Heikenwalder, Mathias; Pasparakis, Manolis; Protzer, Ulrike; Dienes, Hans-Peter; Kurts, Christian; Krönke, Martin; Knolle, Percy A

    2012-09-27

    Viruses can escape cytotoxic T cell (CTL) immunity by avoiding presentation of viral components via endogenous MHC class I antigen presentation in infected cells. Cross-priming of viral antigens circumvents such immune escape by allowing noninfected dendritic cells to activate virus-specific CTLs, but they remain ineffective against infected cells in which immune escape is functional. Here, we show that cross-presentation of antigen released from adenovirus-infected hepatocytes by liver sinusoidal endothelial cells stimulated cross-primed effector CTLs to release tumor necrosis factor (TNF), which killed virus-infected hepatocytes through caspase activation. TNF receptor signaling specifically eliminated infected hepatocytes that showed impaired anti-apoptotic defense. Thus, CTL immune surveillance against infection relies on two similarly important but distinct effector functions that are both MHC restricted, requiring either direct antigen recognition on target cells and canonical CTL effector function or cross-presentation and a noncanonical effector function mediated by TNF. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  9. A new vesicle trafficking regulator CTL1 plays a crucial role in ion homeostasis.

    Science.gov (United States)

    Gao, Yi-Qun; Chen, Jiu-Geng; Chen, Zi-Ru; An, Dong; Lv, Qiao-Yan; Han, Mei-Ling; Wang, Ya-Ling; Salt, David E; Chao, Dai-Yin

    2017-12-01

    Ion homeostasis is essential for plant growth and environmental adaptation, and maintaining ion homeostasis requires the precise regulation of various ion transporters, as well as correct root patterning. However, the mechanisms underlying these processes remain largely elusive. Here, we reported that a choline transporter gene, CTL1, controls ionome homeostasis by regulating the secretory trafficking of proteins required for plasmodesmata (PD) development, as well as the transport of some ion transporters. Map-based cloning studies revealed that CTL1 mutations alter the ion profile of Arabidopsis thaliana. We found that the phenotypes associated with these mutations are caused by a combination of PD defects and ion transporter misregulation. We also established that CTL1 is involved in regulating vesicle trafficking and is thus required for the trafficking of proteins essential for ion transport and PD development. Characterizing choline transporter-like 1 (CTL1) as a new regulator of protein sorting may enable researchers to understand not only ion homeostasis in plants but also vesicle trafficking in general.

  10. Differential requirements of CD4(+) T-cell signals for effector cytotoxic T-lymphocyte (CTL) priming and functional memory CTL development at higher CD8(+) T-cell precursor frequency.

    Science.gov (United States)

    Umeshappa, Channakeshava S; Nanjundappa, Roopa H; Xie, Yufeng; Freywald, Andrew; Xu, Qingyong; Xiang, Jim

    2013-04-01

    Increased CD8(+) T-cell precursor frequency (PF) precludes the requirement of CD4(+) helper T (Th) cells for primary CD8(+) cytotoxic T-lymphocyte (CTL) responses. However, the key questions of whether unhelped CTLs generated at higher PF are functional effectors, and whether unhelped CTLs can differentiate into functional memory cells at higher PF are unclear. In this study, ovalbumin (OVA) -pulsed dendritic cells (DC(OVA)) derived from C57BL/6, CD40 knockout (CD40(-/-)) or CD40 ligand knockout (CD40L(-/-)) mice were used to immunize C57BL/6, Ia(b-/-), CD40(-/-) or CD40L(-/-) mice, whose PF was previously increased with transfer of 1 × 10(6) CD8(+) T cells derived from OVA-specific T-cell receptor (TCR) transgenic OTI, OTI(CD40(-/-)) or OTI(CD40L(-/-)) mice. All the immunized mice were then assessed for effector and memory CTL responses. Following DC immunization, relatively comparable CTL priming occurred without CD4(+) T-cell help and Th-provided CD40/CD40L signalling. In addition, the unhelped CTLs were functional effectors capable of inducing therapeutic immunity against established OVA-expressing tumours. In contrast, the functional memory development of CTLs was severely impaired in the absence of CD4(+) T-cell help and CD40/CD40L signalling. Finally, unhelped memory CTLs failed to protect mice against lethal tumour challenge. Taken together, these results demonstrate that CD4(+) T-cell help at higher PF, is not required for effector CTL priming, but is required for functional memory CTL development against cancer. Our data may impact the development of novel preventive and therapeutic approaches in cancer patients with compromised CD4(+) T-cell functions. © 2012 Blackwell Publishing Ltd.

  11. Direct Coal -to-Liquids (CTL) for Jet Fuel Using Biomass-Derived Solvents

    Energy Technology Data Exchange (ETDEWEB)

    Chauhan, Satya P. [Battelle Memorial Inst., Columbus, OH (United States); Garbark, Daniel B. [Battelle Memorial Inst., Columbus, OH (United States); Taha, Rachid [Battelle Memorial Inst., Columbus, OH (United States); Peterson, Rick [Battelle Memorial Inst., Columbus, OH (United States)

    2017-09-30

    Battelle has demonstrated a novel and potentially breakthrough technology for a direct coal-to-liquids (CTL) process for producing jet fuel using biomass-derived coal solvents (bio-solvents). The Battelle process offers a significant reduction in capital and operating costs and a substantial reduction in greenhouse gas (GHG) emissions, without requiring carbon capture and storage (CCS). The results of the project are the advancement of three steps of the hybrid coal/biomass-to-jet fuel process to the technology readiness level (TRL) of 5. The project objectives were achieved over two phases. In Phase 1, all three major process steps were explored and refined at bench-scale, including: (1) biomass conversion to high hydrogen-donor bio-solvent; (2) coal dissolution in biomass-derived bio-solvent, without requiring molecular H2, to produce a synthetic crude (syncrude); and (3) two-stage catalytic hydrotreating/hydrogenation of syncrude to jet fuel and other distillates. In Phase 2, all three subsystems of the CTL process were scaled up to a pre-pilot scale, and an economic analysis was carried out. A total of over 40 bio-solvents were identified and prepared. The most unique attribute of Battelle’s bio-solvents is their ability to provide much-needed hydrogen to liquefy coal and thus increase its hydrogen content so much that the resulting syncrude is liquid at room temperature. Based on the laboratory-scale testing with bituminous coals from Ohio and West Virginia, a total of 12 novel bio-solvent met the goal of greater than 80% coal solubility, with 8 bio-solvents being as good as or better than a well-known but expensive hydrogen-donor solvent, tetralin. The Battelle CTL process was then scaled up to 1 ton/day (1TPD) at a pre-pilot facility operated in Morgantown, WV. These tests were conducted, in part, to produce enough material for syncrude-upgrading testing. To convert the Battelle-CTL syncrude into a form suitable as a blending stock for jet

  12. PERBEDAAN JENIS PEMBELAJARAN MODEL CTL DAN DISCOVERY LEARNING DITINJAU DARI MOTIVASI BELAJAR IPS

    Directory of Open Access Journals (Sweden)

    Elpri Darta Putra

    2015-06-01

    Full Text Available Tujuan penelitian ini adalah menganalisis perbedaan motivasi belajar siswa melalui model pembelajaran Contextual Teaching And Learning, Discovery Learning dan pembelajaran ekspositori. Subjek penelitian ini adalah siswa kelas IV SDN Kuningan 01, SDN Kuningan 04, dan SDN Dadapsari Semarang tahun ajaran 2014/2015. Penelitian dilakukan empat kali pertemuan. Instrumen penelitian ini adalah angket yang berupa butir-butir pernyataan dan lembar wawancara guru. Penelitian ini dalam bentuk penelitian quasi-experimental atau eksperimen semu. Jumlah sampel dalam penelitian ini adalah 85 siswa. Hasil penelitian tentang motivasi belajar siswa di kelas empat menunjukkan bahwa melalui model pembelajaran CTL motivasi belajar siswa dengan nilai rata-rata pada kelas tersebut 81,92 melalui model pembelajaran Discovery Learning 77,66dan melalui pembelajaran ekspositori memiliki rata-rata 52.28. Berdasarkan hasil penelitian tersebut terdapat perbedaan antara motivasi belajar siswa yang menggunakan model pembelajaran CTL, Discovery Learning dan ekspositori, pembelajaran melalui model CTL lebih baik dari pembelajaran melalui model discovery learning dan ekspositrori. The purpose of this study was to analyze differences in student motivation through learning model Contextual Teaching And Learning, Discovery Learning and expository. Subjects in this study were fourth grade students of SDN 01 Brass, Brass SDN 04, and SDN Dadapsari Semarang academic year 2014/2015. The study was conducted four meetings. Data collection instruments in this study was a questionnaire in the form of grains statements and teacher questionnaires. The study is in the form of quasi-experimental or quasi-experimental, the number of samples in this study were 85 students .. The results of students' motivation in the fourth grade showed that through learning model CTL student motivation with the average value in the class 81, 92 through Discovery Learning learning model through expository 77.66 and

  13. C-type lectin B (SpCTL-B) regulates the expression of antimicrobial peptides and promotes phagocytosis in mud crab Scylla paramamosain.

    Science.gov (United States)

    Wei, Xiaoyuan; Wang, Limin; Sun, Wanwei; Zhang, Ming; Ma, Hongyu; Zhang, Yueling; Zhang, Xinxu; Li, Shengkang

    2018-07-01

    As pattern recognition receptors, C-type lectins (CTLs) play important roles in immune system of crustaceans through identifying and binding to the conservative pathogen-associated molecular patterns (PAMPs) on pathogen surfaces. In this study, a new CTL, SpCTL-B, was identified from the hemocytes of mud crab Scylla paramamosain. The full-length of SpCTL-B cDNA was 1278 bp with an open reading frame (ORF) of 348 bp. The predicted SpCTL-B protein contains a single carbohydrate-recognition domain (CRD). SpCTL-B transcripts were distributed in all examined tissues with the highest levels in hepatopancreas. After challenged with Vibrio parahaemolyticus, LPS, polyI:C and white spot syndrome virus (WSSV), the mRNA levels of SpCTL-B in hemocytes and hepatopancreas were up-regulated. The recombinant SpCTL-B (rSpCTL-B) purified by Ni-affinity chromatography showed stronger binding activities with Staphylococcus aureus, β-hemolytic Streptococcus, Escherichia coli, Aeromonas hydrophila, Vibrio alginolyticus than those with V. parahaemolyticus and Saccharomyces cerevisiae. rSpCTL-B exhibited a broad spectrum of microorganism-agglutination activities against Gram-positive bacteria (S. aureus, β-hemolytic Streptococcus) and Gram-negative bacteria (E. coli, V. parahaemolyticus, A. hydrophila, V. alginolyticus) in a Ca 2+ -dependent manner. The agglutination activities of rSpCTL-B could be inhibited by D-mannose and LPS, but not by d-fructose and galactose. The antimicrobial assay showed that rSpCTL-B exhibited the growth inhibition against all examined gram-positive bacteria and gram-negative bacteria. When SpCTL-B was silenced by RNAi, the bacterial clearance ability in mud crab was decreased and the transcript levels of five antimicrobial peptides (AMPs) (SpCrustin, SpHistin, SpALF4 (anti-lipopolysaccharide factor), SpALF5 and SpALF6) were significantly decreased in hemocytes. In our study, knockdown of SpCTL-B could down-regulate the expression of SpSTAT at m

  14. Effect of the CTL proliferation program on virus dynamics

    DEFF Research Database (Denmark)

    Wodarz, Dominik; Thomsen, Allan Randrup

    2005-01-01

    Experiments have established that CTLs do not require continuous antigenic stimulation for expansion. Instead, responses develop by a process of programmed proliferation which involves approximately 7-10 antigen-independent cell divisions, the generation of effector cells and the differentiation...... virus loads and thus acute symptoms. The reason is that the programmed divisions are independent from antigenic stimulation, and an increase in virus load does not speed up the rate of CTL expansion. We hypothesize that the 7-10 programmed divisions observed in vivo represent an optimal solution...... into memory cells. The effect of this program on the infection dynamics and the advantages gained by the program have, however, not been explored yet. We investigate this with mathematical models. We find that more programmed divisions can make virus clearance more efficient because CTL division continues...

  15. Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system.

    Science.gov (United States)

    Han, Seung-Soo; Lee, Jinjoo; Jung, Yideul; Kang, Myeong-Ho; Hong, Jung-Hyub; Cha, Min-Suk; Park, Yu-Jin; Lee, Ezra; Yoon, Cheol-Hee; Bae, Yong-Soo

    2015-09-11

    We developed a CTL vaccine vector by modification of the RPS-Vax system, a mucosal vaccine vector derived from a poliovirus Sabin 1 strain, and generated an oral CTL vaccine against HIV-1. A DNA fragment encoding a cytoplasmic transduction peptide (CTP) was integrated into the RPS-Vax system to generate RPS-CTP, a CTL vaccine vector. An HIV-1 p24 cDNA fragment was introduced into the RPS-CTP vector system and a recombinant poliovirus (rec-PV) named vRPS-CTP/p24 was produced. vRPS-CTP/p24 was genetically stable and efficiently induced Th1 immunity and p24-specific CTLs in immunized poliovirus receptor-transgenic (PVR-Tg) mice. In challenge experiments, PVR-Tg mice that were pre-immunized orally with vRPS-CTP/p24 were resistant to challenge with a lethal dose of p24-expressing recombinant vaccinia virus (rMVA-p24). These results suggested that the RPS-CTP vector system had potential for developing oral CTL vaccines against infectious diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals.

    Science.gov (United States)

    Mendiratta, Sanjay; Vajpayee, Madhu; Malhotra, Uma; Kaushik, Shweta; Dar, Lalit; Mojumdar, Kamalika; Chauhan, Neeraj Kumar; Sreenivas, Vishnubhatla

    2009-02-01

    Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.

  17. Chitinase-like (CTL) and cellulose synthase (CESA) gene expression in gelatinous-type cellulosic walls of flax (Linum usitatissimum L.) bast fibers.

    Science.gov (United States)

    Mokshina, Natalia; Gorshkova, Tatyana; Deyholos, Michael K

    2014-01-01

    Plant chitinases (EC 3.2.1.14) and chitinase-like (CTL) proteins have diverse functions including cell wall biosynthesis and disease resistance. We analyzed the expression of 34 chitinase and chitinase-like genes of flax (collectively referred to as LusCTLs), belonging to glycoside hydrolase family 19 (GH19). Analysis of the transcript expression patterns of LusCTLs in the stem and other tissues identified three transcripts (LusCTL19, LusCTL20, LusCTL21) that were highly enriched in developing bast fibers, which form cellulose-rich gelatinous-type cell walls. The same three genes had low relative expression in tissues with primary cell walls and in xylem, which forms a xylan type of secondary cell wall. Phylogenetic analysis of the LusCTLs identified a flax-specific sub-group that was not represented in any of other genomes queried. To provide further context for the gene expression analysis, we also conducted phylogenetic and expression analysis of the cellulose synthase (CESA) family genes of flax, and found that expression of secondary wall-type LusCESAs (LusCESA4, LusCESA7 and LusCESA8) was correlated with the expression of two LusCTLs (LusCTL1, LusCTL2) that were the most highly enriched in xylem. The expression of LusCTL19, LusCTL20, and LusCTL21 was not correlated with that of any CESA subgroup. These results defined a distinct type of CTLs that may have novel functions specific to the development of the gelatinous (G-type) cellulosic walls.

  18. Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine

    International Nuclear Information System (INIS)

    Xu Wei; Chu Yiwei; Zhang Ruihua; Xu Huanbin; Wang Ying; Xiong Sidong

    2005-01-01

    CD8 + T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc 18-27 , was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C 18-27 encoding gene. ERTS fusion significantly enhanced specific CD8 + T cell responses in terms of CTL cytolysis as well as IFN-γ secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine

  19. Seminar 'World CTL 2008'

    International Nuclear Information System (INIS)

    Chevalier, B.

    2008-01-01

    'Coal to liquid' (CTL) is a well known technic used since years especially by the Germans during the last world war and South Africa during the oil embargo. The combination of coal gasification and Fischer-Tropsch synthesis allows the production of synthetic diesel and gasoline. Nice alternative for those countries with large reserves of coal (China, South Africa, USA) which want to be more 'oil-free' in the long term, it faces however quite a lot of challenges: Very sophisticated technic, not yet proven for large scale of unit, high investment costs, necessity to add up CO 2 capture and storage (CCS) due to climate change constraints... In any cases this process seems more adequate and competitive to produce electricity and power than to focus on transportation fuels which are more easily manufactured from oil. (author)

  20. Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

    Science.gov (United States)

    Wang, Chuang-Wei; Yang, Lan-Yan; Chen, Chun-Bing; Ho, Hsin-Chun; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Chee-Jen; Su, Shih-Chi; Hui, Rosaline Chung-Yee; Chin, See-Wen; Huang, Li-Fang; Lin, Yang Yu-Wei; Chang, Wei-Yang; Fan, Wen-Lang; Yang, Chin-Yi; Ho, Ji-Chen; Chang, Ya-Ching; Lu, Chun-Wei; Chung, Wen-Hung

    2018-03-01

    Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. ClinicalTrials.gov NCT01276314. Ministry of Science and Technology of Taiwan.

  1. IMPLEMENTASI PENDEKATAN CONTEXTUAL TEACHING AND LEARNING (CTL BERBASIS WEB PADA PRAKTIKUM KIMIA

    Directory of Open Access Journals (Sweden)

    Anggun Zuhaida

    2016-11-01

    The learning process chemistry in SMA/MA still tends to be a conventional means are still teoritik out the lesson and had yet to develop the ability of students to the maximum. Practical learning can provide an opportunity to students to test and apply the theory by using the facilities of the laboratory and outside the laboratory. This research aims to know the influence of the use of web-based CTL approach towards learning outcomes subject matter the reaction rate. The population in this research is the grade XI IPA in MAN 2 Kudus. Sampling is done using cluster random sampling techniques, namely class XI IPA 4 as a class experiments who got the treatment by using web-based CTL approach and Class XI IPA 5 as a control class get conventional learning with media powerpoint. Method of data collection in this research is a method of documentation, tests, observation and question form. Test hypotheses using the coefficient of biserial correlation and coefficient of determination and acquired rb 0.65 with the amount of contributions 42,11%. The conclusion is the use of web-based CTL influential approach towards learning outcomes subject matter the rate of grade XI IPA MAN 2 Kudus with contributions 42,11%.

  2. A novel C-type lectin from the sea cucumber Apostichopus japonicus (AjCTL-2) with preferential binding of d-galactose.

    Science.gov (United States)

    Wang, Hui; Xue, Zhuang; Liu, Zhaoqun; Wang, Weilin; Wang, Feifei; Wang, Ying; Wang, Lingling; Song, Linsheng

    2018-05-15

    C-type lectins (CTLs) are Ca 2+ dependent carbohydrate-binding proteins that share structural homology in their carbohydrate-recognition domains (CRDs). In the present study, a novel CTL was identified from sea cucumber Apostichopus japonicus (named as AjCTL-2). The deduced amino acid sequence of AjCTL-2 was homologous to CTLs from other animals with the identities ranging from 33% to 40%. It contained a canonical signal peptide at the N-terminus, a low density lipoprotein receptor class A (LDLa), a C1r/C1s/Uegf/bone morphogenetic protein 1 (CUB), and a CRD with two motifs Glu-Pro-Asn (EPN) and Trp-Asn-Asp (WND) in Ca 2+ binding site 2. The mRNA transcripts of AjCTL-2 were extensively expressed in all the tested tissues including respiratory tree, muscle, gut, coelomocyte, tube-foot, body wall and gonad, and the highest expression level of AjCTL-2 in coelomocyte was about 4.2-fold (p sea cucumber. Copyright © 2018. Published by Elsevier Ltd.

  3. Local Model Checking of Weighted CTL with Upper-Bound Constraints

    DEFF Research Database (Denmark)

    Jensen, Jonas Finnemann; Larsen, Kim Guldstrand; Srba, Jiri

    2013-01-01

    We present a symbolic extension of dependency graphs by Liu and Smolka in order to model-check weighted Kripke structures against the logic CTL with upper-bound weight constraints. Our extension introduces a new type of edges into dependency graphs and lifts the computation of fixed-points from...

  4. Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara

    International Nuclear Information System (INIS)

    Sharpe, Sally; Hanke, Tomas; Tinsley-Bown, Anne; Dennis, Mike; Dowall, Stuart; McMichael, Andrew; Cranage, Martin

    2003-01-01

    Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 μm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01 + rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals

  5. Isolation of antigenic substances from HIV-1 envelope gp160 gene transfectants by mild acid elution and X-irradiation treatment. For the development of CTL-based immunotherapy

    International Nuclear Information System (INIS)

    Fujimoto, Chiaki; Nakagawa, Yohko; Shimizu, Masumi; Ohara, Kunitoshi; Takahashi, Hidemi

    2003-01-01

    Cytotoxic T lymphocytes (CTLs) play a central role in a broad spectrum of tumor immunity. Such CTLs generally recognize processed antigenic fragments in association with class I major histocompatibility complex (MHC) molecules. Thus, it is important to identify naturally processed antigens associated with class I MHC molecules to generate and activate antigen-specific CTLs. Those processed antigens fitted in the groove of class I MHC molecules are fixed by the β2-microglobulin. Mild acid elution is one method used to isolate antigenic fragments from class I MHC molecules on tumor cells by unfastening a clasp of β2-microglobulin, a critical component for stabilizing class I MHC molecules on the cell surface. Indeed, after the mild acid treatment, the expression of class I MHC molecules was temporarily down-modulated and a strong antigenic fraction for CTL recognition was obtained. To our surprise, such down-modulation of class I MHC molecule expression was also observed when the tumor cells were irradiated. Therefore, using human immunodeficiency virus type I (HIV-1) gp160 env gene transfectants, we examined the effect of X-irradiation on releasing the loaded antigenic fragments. Functional extracts were obtained from X-irradiated cell supernatants that sensitized syngeneic fibroblasts for specific CTL recognition, suggesting that X-irradiation extracts would also contain known antigenic epitopes. These results indicate that, in addition to the conventional mild acid elution treatment, X-irradiation method shown in this paper may provide a new approach for CTL-based vaccine development via isolating antigenic molecules from various tumors or virally infected cells. (author)

  6. Driving forces and barriers in the development and implementation of coal-to-liquids (CtL) technologies in Germany

    International Nuclear Information System (INIS)

    Vallentin, Daniel

    2008-01-01

    Because of a growing global energy demand and rising oil prices coal-abundant nations, such as China and the United States, are pursuing the application of technologies which could replace crude oil imports by converting coal to synthetic hydrocarbon fuels-so-called coal-to-liquids (CtL) technologies. The case of CtL is well suited to analyse techno-economic, resources-related, policy-driven and actor-related parameters, which are affecting the market prospects of a technology that eases energy security constraints but is hardly compatible with a progressive climate policy. This paper concentrates on Germany as an example-the European Union (EU)'s largest member state with considerable coal reserves. It shows that in Germany and the EU, CtL is facing rather unfavourable market conditions as high costs and ambitious climate targets offset its energy security advantage

  7. UPAYA MENGEMBANGKAN LEARNING COMMUNITY SISWA KELAS X SMA MELALUI PENERAPAN MODEL PEMBELAJARAN KOOPERATIF TIPE STAD BERBASIS CTL PADA PEMBELAJARAN FISIKA

    Directory of Open Access Journals (Sweden)

    Wahyudi -

    2012-04-01

    Full Text Available Penelitian ini bertujuan untuk mendeskripsikan penerapan model pembelajaran kooperatif tipe STAD berbasis CTL pada pembelajaran fisika dalam mengembangkan learning community dan meningkatkan hasil belajar siswa serta mengetahui dampak penerapannya terhadap learning community dan hasil belajar siswa kelas X-7 SMA N 1 Tahunan Jepara. Hasil penelitian menunjukkan meningkatnya hasil belajar serta berkembangnya learning community siswa kelas X-7 SMA N 1 Tahunan Jepara setelah penerapan model pembelajaran kooperatif tipe STAD berbasis CTL pada pokok bahasan listrik dinamis.This research is describe the implementation of cooperative learning model STAD CTL-based for Physics learning subject to develop learning community, improve students learning and also find out the outcome of its implementation  to the learning community and learning result of SMA N 1 Tahunan Jepara Students class of X-7. The research result shows that there is an improvement of students’ learning result and also a development of learning community of N 1 Tahunan Jepara Students class of X-7 after implementing cooperative learning model STAD CTL-based for Dynamic Electricity topic.

  8. Induction of systemic CTL responses in melanoma patients by dendritic cell vaccination: Cessation of CTL responses is associated with disease progression

    DEFF Research Database (Denmark)

    Andersen, M.H.; Keikavoussi, P.; Brocker, E.B.

    2001-01-01

    Two HLA-A2-positive patients with advanced stage IV melanoma were treated with monocyte-derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART-1 and MAGE- 3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease...... by Western blotting was decreased in PBL at this time. In summary, our data confirm that DC-based vaccinations induce peptide-specific T cells in the peripheral blood of advanced-stage melanoma patients. Although successful induction of systemic tumor antigen-specific CTL may not lead to objective clinical...

  9. CTL lysis: there is a hyperbolic relation of killing rate to exocytosable granzyme A for highly cytotoxic murine cytotoxic T lymphocytes.

    Science.gov (United States)

    Poe, M; Wu, J K; Talento, A; Koo, G C

    1996-06-10

    The lysis of susceptible targets by efficient cytotoxic T lymphocytes (CTL) increases both with time and with the ratio of CTL to target. Simple methods for calculating a killing rate constant from the time dependence of killing and for calculating the relation of the killing rate constant to the concentration of exocytosable granzyme A are given. Application of these methods to the killing of target cells by the highly efficient mouse CTL AR1 is presented. AR1 needed granzyme A for efficient killing. AR1 contained sufficient exocytosable granzyme A to kill at about 80% of the rate possible at infinite exocytosable granzyme A.

  10. Induction of cytotoxic T-cell responses by gene gun DNA vaccination with minigenes encoding influenza A virus HA and NP CTL-epitopes

    DEFF Research Database (Denmark)

    Fomsgaard, A; Nielsen, H V; Kirkby, N

    1999-01-01

    degree of controllability. We have examined the induction of murine CTL's by this approach using DNA plasmid minigene vaccines encoding known mouse K(k) minimal CTL epitopes (8 amino acids) from the influenza A virus hemagglutinin and nucleoprotein. We here report that such an approach is feasible...

  11. An Approach for a Synthetic CTL Vaccine Design against Zika Flavivirus Using Class I and Class II Epitopes Identified by Computer Modeling

    Directory of Open Access Journals (Sweden)

    Edecio Cunha-Neto

    2017-06-01

    Full Text Available The threat posed by severe congenital abnormalities related to Zika virus (ZKV infection during pregnancy has turned development of a ZKV vaccine into an emergency. Recent work suggests that the cytotoxic T lymphocyte (CTL response to infection is an important defense mechanism in response to ZKV. Here, we develop the rationale and strategy for a new approach to developing cytotoxic T lymphocyte (CTL vaccines for ZKV flavivirus infection. The proposed approach is based on recent studies using a protein structure computer model for HIV epitope selection designed to select epitopes for CTL attack optimized for viruses that exhibit antigenic drift. Because naturally processed and presented human ZKV T cell epitopes have not yet been described, we identified predicted class I peptide sequences on ZKV matching previously identified DNV (Dengue class I epitopes and by using a Major Histocompatibility Complex (MHC binding prediction tool. A subset of those met the criteria for optimal CD8+ attack based on physical chemistry parameters determined by analysis of the ZKV protein structure encoded in open source Protein Data File (PDB format files. We also identified candidate ZKV epitopes predicted to bind promiscuously to multiple HLA class II molecules that could provide help to the CTL responses. This work suggests that a CTL vaccine for ZKV may be possible even if ZKV exhibits significant antigenic drift. We have previously described a microsphere-based CTL vaccine platform capable of eliciting an immune response for class I epitopes in mice and are currently working toward in vivo testing of class I and class II epitope delivery directed against ZKV epitopes using the same microsphere-based vaccine.

  12. Generation of B-cell chronic lymphocytic leukemia (B-CLL)-reactive T-cell lines and clones from HLA class I-matched donors using modified B-CLL cells as stimulators: implications for adoptive immunotherapy.

    Science.gov (United States)

    Hoogendoorn, M; Wolbers, J Olde; Smit, W M; Schaafsma, M R; Barge, R M Y; Willemze, R; Falkenburg, J H F

    2004-07-01

    Allogeneic stem cell transplantation following reduced-intensity conditioning is being evaluated in patients with advanced B-cell chronic lymphocytic leukemia (B-CLL). The curative potential of this procedure is mediated by donor-derived alloreactive T cells, resulting in a graft-versus-leukemia effect. However, B-CLL may escape T-cell-mediated immune reactivity since these cells lack expression of costimulatory molecules. We examined the most optimal method to transform B-CLL cells into efficient antigen-presenting cells (APC) using activating cytokines, by triggering toll-like receptors (TLRs) using microbial pathogens and by CD40 stimulation with CD40L-transfected fibroblasts. CD40 activation in the presence of IL-4 induced strongest upregulation of costimulatory and adhesion molecules on B-CLL cells and induced the production of high amounts of IL-12 by the leukemic cells. In contrast to primary B-CLL cells as stimulator cells, these malignant APCs were capable of inducing the generation of B-CLL-reactive CD8(+) CTL lines and clones from HLA class I-matched donors. These CTL lines and clones recognized and killed primary B-CLL as well as patient-derived lymphoblasts, but not donor cells. These results show the feasibility of ex vivo generation of B-CLL-reactive CD8(+) CTLs. This opens new perspectives for adoptive immunotherapy, following allogeneic stem cell transplantation in patients with advanced B-CLL.

  13. Keefektifan Implementasi CTL berbantuan Komik Matematika dan Langkah Penyelesaian Krulik dan Rudnick untuk Meningkatkan Kemampuan Pemahaman dan Disposisi Matematis Siswa

    Directory of Open Access Journals (Sweden)

    Christina Widayanti

    2017-03-01

    Full Text Available This study aims to know the effectiveness of the CTL models aided by mathematical comics and Krulik and Rudnick’s steps in problem solving to improve the ability of student’s mathematical understanding and disposition. Population in this study were VIIIA grade students up to VIIIE of SMP Negeri 1 Pulokulon year 2015/2016 with a true experimental design types posttest­only control design and samples are chosen randomly. Data analysis that used in this study were an average of completeness test, the proportion test, the average difference test, and Mann­Whitney test. The results showed that (1 the ability of student’s mathematical understanding of the subject that have gained CTL models aided by mathematical comics and Krulik and Rudnick’s steps in problem solving have achieved the completeness in groups and classical; (2 the ability of student’s mathematical understanding of students who have gained CTL models aided by mathematical comics and Krulik and Rudnick’s steps in problem solving more than students with expository models aided by LKS, (3 the mathematical disposition of student’s who have gained CTL models aided by mathematical comics and Krulik and Rudnick’s steps in problem solving more than students with expository models aided by LKS.

  14. T-cell receptor (TCR) phenotype of nodal Epstein-Barr virus (EBV)-positive cytotoxic T-cell lymphoma (CTL): a clinicopathologic study of 39 cases.

    Science.gov (United States)

    Kato, Seiichi; Asano, Naoko; Miyata-Takata, Tomoko; Takata, Katsuyoshi; Elsayed, Ahmed Ali; Satou, Akira; Takahashi, Emiko; Kinoshita, Tomohiro; Nakamura, Shigeo

    2015-04-01

    Among Epstein-Barr virus (EBV)-positive cytotoxic T/NK-cell lymphoma, there are only a few reports on the clinicopathologic features of patients with primary nodal presentation (nodal EBV cytotoxic T-cell lymphoma [CTL]). Here, we compared the clinicopathologic profiles of 39 patients with nodal EBV CTL with those of 27 cases of "extranasal" NK/T-cell lymphoma of nasal type (ENKTL), especially addressing their T-cell receptor (TCR) phenotype. Histologically, 22 of 39 nodal EBV CTL cases (56%) were unique in having centroblastoid appearance, which was contrasted with the lower incidence of this feature in ENKTL (15%, P=0.001). In contrast, pleomorphic appearance was more frequently seen in ENKTL than in nodal EBV CTL (67% vs. 23%, P=0.001). Thirty-three of 39 nodal EBV CTL cases (85%) were of T-cell lineage on the basis of TCR expression and/or TCRγ gene rearrangement; in detail, 18 cases (46%) were TCRβ positive (αβ T), 5 (13%) were TCRγ and/or δ positive (γδ T), and 10 (26%) were TCR-silent type with clonal TCRγ gene rearrangement but no expression of TCRβ, γ, or δ. These results were clearly contrasted by a lower incidence of T-cell lineage in ENKTL (7 cases, 26%, P<0.001). Notably, the survival time of the 5 nodal lymphoma patients with γδ T-cell phenotype was within 3 months, which was inferior to those of αβ T and TCR-silent types (P=0.003), and 3 of those with available clinical information were all found to be associated with autoimmune diseases. These data suggest that nodal EBV CTL is distinct from ENKTL.

  15. A mathematical model for CTL effect on a latently infected cell inclusive HIV dynamics and treatment

    Science.gov (United States)

    Tarfulea, N. E.

    2017-10-01

    This paper investigates theoretically and numerically the effect of immune effectors, such as the cytotoxic lymphocyte (CTL), in modeling HIV pathogenesis (via a newly developed mathematical model); our results suggest the significant impact of the immune response on the control of the virus during primary infection. Qualitative aspects (including positivity, boundedness, stability, uncertainty, and sensitivity analysis) are addressed. Additionally, by introducing drug therapy, we analyze numerically the model to assess the effect of treatment consisting of a combination of several antiretroviral drugs. Our results show that the inclusion of the CTL compartment produces a higher rebound for an individual's healthy helper T-cell compartment than drug therapy alone. Furthermore, we quantitatively characterize successful drugs or drug combination scenarios.

  16. Policy drivers and barriers for coal-to-liquids (CtL) technologies in the United States

    International Nuclear Information System (INIS)

    Vallentin, Daniel

    2008-01-01

    Because of a growing dependence on oil imports, powerful industrial, political and societal stakeholders in the United States are trying to enhance national energy security through the conversion of domestic coal into synthetic hydrocarbon liquid fuels-so-called coal-to-liquids (CtL) processes. However, because of the technology's high costs and carbon intensity, its market deployment is strongly affected by the US energy, technology and climate policy setting. This paper analyses and discusses policy drivers and barriers for CtL technologies in the United States and reaches the conclusion that an increasing awareness of global warming among US policy-makers raises the requirements for the technology's environmental performance and, thus, limits its potential to regional niche markets in coal-producing states or strategic markets, such as the military, with specific security and fuel requirements

  17. HIV-1 Gag-specific exosome-targeted T cell-based vaccine stimulates effector CTL responses leading to therapeutic and long-term immunity against Gag/HLA-A2-expressing B16 melanoma in transgenic HLA-A2 mice

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2014-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1-specific dendritic cell (DC vaccines have been applied to clinical trials that show only induction of some degree of immune responses, warranting the search of other more efficient vaccine strategies. Since HIV-1-specific CD8+ cytotoxic T lymphocytes (CTLs have been found to recognize some HIV-1 structural protein Gag conserved and cross-strain epitopes, Gag has become one of the most attractive target candidates for HIV-1 vaccine development. In this study, we generated HIV-1 Gag-specific Gag-Texo vaccine by using ConA-stimulated polyclonal CD8+ T-cells with uptake of Gag-expressing adenoviral vector AdVGag-transfected DC (DCGag-released exosomes (EXOs, and assessed its stimulation of Gag-specific CD8+ CTL responses and antitumor immunity. We demonstrate that Gag-Texo and DCGag vaccines comparably stimulate Gag-specific effector CD8+ CTL responses. Gag-Texo-stimulated CTL responses result in protective immunity against Gag-expressing BL6-10Gag melanoma in 8/8 wild-type C57BL/6 mice. In addition, we show that Gag-Texo vaccine also induces CTL responses leading to protective and long-term immunity against Gag/HLA-A2-expressing BL6-10Gag/A2 melanoma in 8/8 and 2/8 transgenic HLA-A2 mice, respectively. The average number of lung tumor colonies in mice with 30-days post-immunization is only 23, which is significantly less than that (>300 in control ConA-T-immunized HLA-A2 mice. Furthermore, Gag-Texo vaccine also induces some degree of therapeutic immunity. The average number (50 and size (0.23 mm in diameter of lung tumor colonies in Gag-Texo-immunized HLA-A2 mice bearing 6-day-established lung BL6-10Gag/A2 melanoma metastasis are significantly less than the average number (>300 and size (1.02 mm in diameter in control ConA-T-immunized HLA-A2 mice. Taken together, HIV-1 Gag-Texo vaccine capable of stimulating Gag-specific CTL responses and therapeutic immunity may be useful as a new immunotherapeutic

  18. Generation of cytotoxic T lymphocytes in vitro. VII. Suppressive effect of irradiated MLC cells on CTL response

    International Nuclear Information System (INIS)

    Fitch, F.W.; Engers, H.D.; Cerottini, J.C.; Bruner, K.T.

    1976-01-01

    Irradiated cells obtained from MLC at the peak of the CTL response caused profound suppression of generation of CTL when added in small numbers at the initiation of primary MLC prepared with normal spleen cells. The inhibitory activity of the MLC cells was not affected by irradiation (1000 rads) but was abolished by treatment with anti-theta serum and complement. The suppression was immunologically specific. The response of A (H-2/sup a/) spleen cells toward C3H (H-2/sup k/) alloantigens was suppressed by irradiated MLC cells obtained from MLC prepared with A spleen cells and irradiated C3H-stimulating cells, whereas the response of A spleen cells toward DBA/2 (H-2/sup d/) alloantigens was affected relatively little. However, if irradiated C3H x DBA/2F1 hybrid spleen cells were used to stimulate A spleen cells in MLC, addition of irradiated MLC cells having cytotoxic activity toward C3H antigens abolished the response to both C3H and DBA/2 antigens. The response to DBA/2 antigens was much less affected when a mixture of irradiated C3H and DBA/2 spleen cells was used as stimulating cells. Thus, the presence of MLC cells having cytotoxic activity toward one alloantigen abolished the response to another non-cross-reacting antigen only when both antigens were present on the same F1 hybrid-stimulating cells. This suppression of generation of CTL by irradiated MLC cells apparently involves inactivation of alloantigen-bearing stimulating cells as a result of residual cytotoxic activity of the irradiated MLC cells. This mechanism may be active during the decline in CTL activity noted in the normal immune response in vivo and in vitro

  19. PENGARUH PENDEKATAN CONTEXTUAL TEACHING AND LEARNING (CTL BERBANTUAN MEDIA POWERPOINT TERHADAP PENINGKATAN HASIL BELAJAR IPA FISIKA

    Directory of Open Access Journals (Sweden)

    Suprianto Suprianto

    2016-12-01

    Full Text Available Berdasarkan hasil wawancara terbatas dengan sebagian guru IPA fisika MTs di kecamatan Camplong Kabupaten Sampang didapatkan informasi bahwa hasil belajar siswa masih rendah dibawah KKM yang sudah ditentukan pihak sekolah. Hal ini disebabkan karena kurangnya penggunaan media pembelajaran, proses pembelajaran masih bersifat teacher centered sehingga sebagian besar siswa tidak mampu menghubungkan antara apa yang mereka pelajari dengan bagaimana pemanfaatannya dalam kehidupan nyata. Adapun tujuan penelitian ini adalah untuk mengidentifikasi pengaruh pendekatan CTL berbantuan media powerpoint terhadap peningkatan hasil belajar IPA fisika siswa. Metode penelitian yang digunakan adalah metode Quasi Experimen dengan menggunakan Nonrandomized Control Group Pretest-Postest Design dan dibagi menjadi dua kelompok, yaitu kelompok eksperimen dan kelompok kontrol. Instrumen penelitian yang digunakan berupa tes objektif bentuk pilihan ganda. Tes ini terdiri dari empat pilihan (opsi dan hasilnya diuji melalui statistik uji “t”. Dari hasil perhitungan diperoleh nilai thitung sebesar 10,81 sedangkan ttabel sebesar 2,021 pada taraf signifikansi 0,05 atau dapat diketahui thitung > ttabel. Dari perhitungan N-gain, dapat dinyatakan bahwa peningkatan hasil belajar fisika yang diterapkan pendekatan CTL berbantuan media powerpoint lebih tinggi dari pada pembelajaran konvensional yaitu 0,71 > 0,52. Berdasarkan hasil analisis statistika dan deskriptif maka dapat di simpulkan bahwa terdapat pengaruh yang signifikan pendekatan CTL berbantuan media powerpoint terhadap peningkatan hasil belajar fisika siswa di kelas VIII MTs.

  20. Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape.

    Directory of Open Access Journals (Sweden)

    Jens Dinter

    2015-03-01

    Full Text Available Dendritic cells (DCs and macrophages (Møs internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8⁺ T cells (CTL. However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Møs. The cross-presentation of HIV proteins by both DCs and Møs led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mø cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation.

  1. The Effect of CTL Approach Based on NHT Learning Model toward Students’ motivation, Science Achievement, and Retention

    Directory of Open Access Journals (Sweden)

    Muhammad Mifta Fausan

    2017-07-01

    Full Text Available The learning is an interaction process between students and their environment in order to improve good behavior. The results of observation which has been done in grade V SDN No. 4 Tanjung Batu showed that the students’ motivation and science achievement were low. This was becaused by the learning process which was still product oriented (based on material content, consequently, this lead to limit the learning is merely on memorizing concept activities. One of the learning approach that can be used to solve this problem is the Contextual Teaching and Learning (CTL based on Numbered Head Together (NHT. This research aims to determine the effect of CTL based on NHT toward student’s motivation, science achievement, and retention. Subjects in this research were the students of grade V SDN No. 4 Tanjung Batu. This research is a quasi-experimental using post-test only control design. The data obtained were analyzed by using descriptive and inferential statistical analysis. The research instruments were observation sheets and written test. The results showed that there was significant effect of CTL based on NHT toward students’ motivation, science achievement, and retention. It can be seen from the independent sample t-test results which showed significant value less than 0.05.

  2. An integrative approach to CTL epitope prediction: A combined algorithm integrating MHC class I binding, TAP transport efficiency, and proteasomal cleavage predictions

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lundegaard, Claus; Lamberth, K

    2005-01-01

    Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have al.......The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php....

  3. Expression, refolding and preliminary X-ray crystallographic analysis of equine MHC class I molecule complexed with an EIAV-Env CTL epitope

    International Nuclear Information System (INIS)

    Yao, Shugang; Qi, Jianxun; Liu, Jun; Chen, Rong; Pan, Xiaocheng; Li, Xiaoying; Gao, Feng; Xia, Chun

    2011-01-01

    The equine MHC class I molecule was crystallized in complex with β 2 -microglobulin and a CTL epitope and X-ray diffraction data were collected to 2.3 Å resolution. In order to clarify the structure and the peptide-presentation characteristics of the equine major histocompatibility complex (MHC) class I molecule, a complex of equine MHC class I molecule (ELA-A1 haplotype, 7-6 allele) with mouse β 2 -microglobulin and the cytotoxic T lymphocyte (CTL) epitope Env-RW12 (RVEDVTNTAEYW) derived from equine infectious anaemia virus (EIAV) envelope protein (residues 195–206) was refolded and crystallized. The crystal, which belonged to space group P2 1 , diffracted to 2.3 Å resolution and had unit-cell parameters a = 82.5, b = 71.4, c = 99.8 Å, β = 102.9°. The crystal structure contained two molecules in the asymmetric unit. These results should help to determine the first equine MHC class I molecule structure presenting an EIAV CTL epitope

  4. The Addition of the BTK Inhibitor Ibrutinib to Anti-CD19 Chimeric Antigen Receptor T Cells (CART19) Improves Responses against Mantle Cell Lymphoma.

    Science.gov (United States)

    Ruella, Marco; Kenderian, Saad S; Shestova, Olga; Fraietta, Joseph A; Qayyum, Sohail; Zhang, Qian; Maus, Marcela V; Liu, Xiaobin; Nunez-Cruz, Selene; Klichinsky, Michael; Kawalekar, Omkar U; Milone, Michael; Lacey, Simon F; Mato, Anthony; Schuster, Stephen J; Kalos, Michael; June, Carl H; Gill, Saar; Wasik, Mariusz A

    2016-06-01

    Responses to therapy with chimeric antigen receptor T cells recognizing CD19 (CART19, CTL019) may vary by histology. Mantle cell lymphoma (MCL) represents a B-cell malignancy that remains incurable despite novel therapies such as the BTK inhibitor ibrutinib, and where data from CTL019 therapy are scant. Using MCL as a model, we sought to build upon the outcomes from CTL019 and from ibrutinib therapy by combining these in a rational manner. MCL cell lines and primary MCL samples were combined with autologous or normal donor-derived anti-CD19 CAR T cells along with ibrutinib. The effect of the combination was studied in vitro and in mouse xenograft models. MCL cells strongly activated multiple CTL019 effector functions, and MCL killing by CTL019 was further enhanced in the presence of ibrutinib. In a xenograft MCL model, we showed superior disease control in the CTL019- as compared with ibrutinib-treated mice (median survival not reached vs. 95 days, P ibrutinib to CTL019 and showed that 80% to 100% of mice in the CTL019 + ibrutinib arm and 0% to 20% of mice in the CTL019 arm, respectively, remained in long-term remission (P ibrutinib represents a rational way to incorporate two of the most recent therapies in MCL. Our findings pave the way to a two-pronged therapeutic strategy in patients with MCL and other types of B-cell lymphoma. Clin Cancer Res; 22(11); 2684-96. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Specialities of the differentiation conditions for the memory cells - either initial or enriched secondary cytotoxic T lymphocyte precursors (pCTL-2) specific to the MHC molecule class 1

    International Nuclear Information System (INIS)

    Brondz, B.D.; Osipova, T.V.; Aptikaeva, G.F.; Kronin, V.V.

    1989-01-01

    The in vivo induced pCTL-2 with phenotype L3T4 - Lyt2 + , specific to the H-2K b molecule, turn into effector CTLs during 4 days in the mixed lymphocyte culture (with heat-treated donor stimulators) much more efficiency when donor and recipient are different from one another not only in MHC class 1 (anti-BIO, MBR BIO.AKM) but in 1+2 (K b +1 b ) anti-C57BL/6 BIAD2(R1O1). The initial pCTL-2 differentiation in enhanced as a result of synergistic effect between the K b alloantigen and rIL2. The anti-K b pCTL-2, being separated from helper T cells by means of absorption onto the macrophage donor monolayer and elution from it, give rise to pronounced differentiation in simplified conditions, irrespective of the stimulator presence and without external rIL2. It is supposed that these phenomena are roused to secrection of the CTL differentiation factor by the eluted pCTL-2 themselves, and besides, rIL2 may promote for secretion of this factor additionally

  6. Eksprimentasi Pembelajaran Kooperatif Tipe Stad dan Tps dengan Pendekatan Ctl pada Materi Pokok Sistem Persamaan Linear Dua Variabel Ditinjau dari Gaya Belajar Siswa

    OpenAIRE

    Zamroni, Zamroni; Budiyono, Budiyono; Sujadi, Imam

    2013-01-01

    The objective of research was to find out: (1) which ones having better achievement, the students using TPS (Think Pair Share) learning with CTL approach or STAD (Students Teams Achievement Divisions) cooperative learning model with CTL approach or direct learning, (2) which ones having better learning achievement, the students with kinesthetic or visual or auditory learning style, (3) in each learning style, which ones having better achievement, the students using TPS (Think Pair Share) lear...

  7. Th cells promote CTL survival and memory via acquired pMHC-I and endogenous IL-2 and CD40L signaling and by modulating apoptosis-controlling pathways.

    Directory of Open Access Journals (Sweden)

    Channakeshava Sokke Umeshappa

    Full Text Available Involvement of CD4(+ helper T (Th cells is crucial for CD8(+ cytotoxic T lymphocyte (CTL-mediated immunity. However, CD4(+ Th's signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4(+ Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4(+ T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA-pulsed dendritic cell (DCova. CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2K(b/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I complex signaling, CD4(+ Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4(+ Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2 and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7 molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4(+ Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy.

  8. Th cells promote CTL survival and memory via acquired pMHC-I and endogenous IL-2 and CD40L signaling and by modulating apoptosis-controlling pathways.

    Science.gov (United States)

    Umeshappa, Channakeshava Sokke; Xie, Yufeng; Xu, Shulin; Nanjundappa, Roopa Hebbandi; Freywald, Andrew; Deng, Yulin; Ma, Hong; Xiang, Jim

    2013-01-01

    Involvement of CD4(+) helper T (Th) cells is crucial for CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity. However, CD4(+) Th's signals that govern CTL survival and functional memory are still not completely understood. In this study, we assessed the role of CD4(+) Th cells with acquired antigen-presenting machineries in determining CTL fates. We utilized an adoptive co-transfer into CD4(+) T cell-sufficient or -deficient mice of OTI CTLs and OTII Th cells or Th cells with various gene deficiencies pre-stimulated in vitro by ovalbumin (OVA)-pulsed dendritic cell (DCova). CTL survival was kinetically assessed in these mice using FITC-anti-CD8 and PE-H-2K(b)/OVA257-264 tetramer staining by flow cytometry. We show that by acting via endogenous CD40L and IL-2, and acquired peptide-MHC-I (pMHC-I) complex signaling, CD4(+) Th cells enhance survival of transferred effector CTLs and their differentiation into the functional memory CTLs capable of protecting against highly-metastasizing tumor challenge. Moreover, RT-PCR, flow cytometry and Western blot analysis demonstrate that increased survival of CD4(+) Th cell-helped CTLs is matched with enhanced Akt1/NF-κB activation, down-regulation of TRAIL, and altered expression profiles with up-regulation of prosurvival (Bcl-2) and down-regulation of proapoptotic (Bcl-10, Casp-3, Casp-4, Casp-7) molecules. Taken together, our results reveal a previously unexplored mechanistic role for CD4(+) Th cells in programming CTL survival and memory recall responses. This knowledge could also aid in the development of efficient adoptive CTL cancer therapy.

  9. Optimalisasi Pembelajaran IPS Pada Siswa Kelas VI Melalui Metode Contextual Teaching And Learning (CTL

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    Mahfud Mahfud

    2014-08-01

    Full Text Available Peranan guru dalam pembelajaran IPS mempunyai hubungan erat dengan dengan cara mengaktifkan siswa dalam belajar, terutama dalam proses pengembangan kemampuan dan keterampilan.Untuk mengurangi sifat verbalisme siswa dan membantah pemahaman konsep yang terdapat dalam materi IPS yang terdapat di SD, guru diharapkan memiliki kemampuan untuk mengembangkan model interaktif dalam pembelajaran IPS serta mengidentifikasi sumber-sumber pelajaran. Salah satu model interaktif yang bisa diterapkan guru salah satunya adalah model pembelajaran kontekstual atau Contextual Teaching and Learning (CTL. Pembelajarn kontekstual merupakan suatu proses yang bertujuan untuk membantu siswa memahami materi pelajaran yang sedang mereka pelajari dengan menghubungkan pokok materi pelajaran dengan penerapannya dalam kehidupan sehari-hari.Dari hasil kegiatan penelitian tindakan kelas yang telah dilakukan dalam dua siklus terhadap siswa kelas VIA di SDN Pinggir Papas 1 Kecamatan Kalianget Kabupaten Sumenep, dan berdasarkan seluruh pembahasan dari hasil analisis yang telah dilakukan, dapat disimpulkan bahwaOptimalisasi Pembelajaran IPS pada Siswa Kelas VIAmelalui Metode Contextual Teaching And Learning(CTL dapat meningkatkan kemampuan siswa memahami materi pembelajaran IPS, sehingga berpengaruh terhadap peningkatan prestasi belajar siswa, serta siswa menjadi aktif dan tertarik mengikuti proses pembelajaranyang dilaksanakan oleh guru di kelas.

  10. Viral CTL escape mutants are generated in lymph nodes and subsequently become fixed in plasma and rectal mucosa during acute SIV infection of macaques.

    Directory of Open Access Journals (Sweden)

    Thomas H Vanderford

    2011-05-01

    Full Text Available SIV(mac239 infection of rhesus macaques (RMs results in AIDS despite the generation of a strong antiviral cytotoxic T lymphocyte (CTL response, possibly due to the emergence of viral escape mutants that prevent recognition of infected cells by CTLs. To determine the anatomic origin of these SIV mutants, we longitudinally assessed the presence of CTL escape variants in two MamuA*01-restricted immunodominant epitopes (Tat-SL8 and Gag-CM9 in the plasma, PBMCs, lymph nodes (LN, and rectal biopsies (RB of fifteen SIV(mac239-infected RMs. As expected, Gag-CM9 did not exhibit signs of escape before day 84 post infection. In contrast, Tat-SL8 escape mutants were apparent in all tissues by day 14 post infection. Interestingly LNs and plasma exhibited the highest level of escape at day 14 and day 28 post infection, respectively, with the rate of escape in the RB remaining lower throughout the acute infection. The possibility that CTL escape occurs in LNs before RBs is confirmed by the observation that the specific mutants found at high frequency in LNs at day 14 post infection became dominant at day 28 post infection in plasma, PBMC, and RB. Finally, the frequency of escape mutants in plasma at day 28 post infection correlated strongly with the level Tat-SL8-specific CD8 T cells in the LN and PBMC at day 14 post infection. These results indicate that LNs represent the primary source of CTL escape mutants during the acute phase of SIV(mac239 infection, suggesting that LNs are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.

  11. Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity

    DEFF Research Database (Denmark)

    Harndahl, Mikkel Nors; Rasmussen, Michael; Nielsen, Morten

    2012-01-01

    Peptide-MHC class I stability is a stronger predictor of CTL immunogenicity than peptide affinity Mikkel Harndahla, Michael Rasmussena, Morten Nielsenb, Soren Buusa,∗ a Laboratory of Experimental Immunology, Faculty of Health Sciences, University of Copenhagen, Denmark b Center for Biological Seq...... al., 2007. J. Immunol. 178, 7890–7901. doi:10.1016/j.molimm.2012.02.025...

  12. Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.

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    Kiichiro Kaji

    Full Text Available Squamous cell carcinoma antigen recognized by T cells 3 (SART3, a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC.The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315 were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ enzyme-linked immunospot and cytotoxic T lymphocyte (CTL assays using peripheral blood mononuclear cells (PBMCs in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677.The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677.

  13. Response of ELA-A1 horses immunized with lipopeptide containing an equine infectious anemia virus ELA-A1-restricted CTL epitope to virus challenge.

    Science.gov (United States)

    Ridgely, Sherritta L; Zhang, Baoshan; McGuire, Travis C

    2003-01-17

    Lipopeptide containing an ELA-A1-restricted cytotoxic T lymphocyte (CTL) epitope from the envelope surface unit (SU) protein of the EIAV(WSU5) strain was used to immunize three horses having the ELA-A1 haplotype. Peptide-specific ELA-A1-restricted CTL were induced in all three horses, although these were present transiently in PBMC. These horses were further immunized with lipopeptide containing the corresponding CTL epitope from the EIAV(PV) strain. Then, the three immunized horses and three non-immunized horses were challenged by intravenous inoculation with 300 TCID(50) EIAV(PV). All horses developed cell free viremia, fever and thrombocytopenia. However, there was a statistically lower fever and thrombocytopenia severity score in the immunized group. Shorter duration of plasma viral load in two of the three immunized horses likely explains the less severe clinical disease in this group. Results indicate that lipopeptide immunization had a protective effect against development of clinical disease following virus challenge.

  14. Cytotoxic T-lymphocyte clones, established by stimulation with the HLA-A2 binding p5365-73 wild type peptide loaded on dendritic cells In vitro, specifically recognize and lyse HLA-A2 tumour cells overexpressing the p53 protein

    DEFF Research Database (Denmark)

    Barfoed, Annette Malene; Petersen, T R; Kirkin, A F

    2000-01-01

    of recognizing p53 derived wild type (self) peptides. Furthermore, the capacity of R9V specific T cell clones to exert HLA restricted cytotoxicity, argues that the R9V peptide is naturally presented on certain cancer cells. This supports the view that p53 derived wild type peptides might serve as candidate......Mutations in the tumour suppressor gene p53 are among the most frequent genetic alterations in human malignancies, often associated with an accumulation of the p53 protein in the cytoplasm. We have generated a number of cytotoxic T lymphocyte (CTL) clones that specifically recognize the HLA-A*0201...

  15. Characterization of CTL Recognized Epitopes on Human Breast Tumors

    Science.gov (United States)

    1996-09-01

    M., DePaoli-Roach, A. A., and Newton, A. C. (1994) 54. Klopman, G., Srivastava, S., Kolossvary, I., Epand, R. F., Ahmed , N., and J. Biol. Chem. 269...opacification requiring steroids or antibiotics antibiotics Dry eye Normal Reqi artificial - Requires enucleation teami Glaucoma No change Yes Nr

  16. Strategi Bisnis pada PT CTL Dengan Pendekatan Metode Tows

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    Tjia Fie Tjoe

    2010-11-01

    Full Text Available The purpose of this research is determining direction of the correct business strategy to be applied by PT CTL, a garment company producing cloth for men. Research method used by the author is descriptive analysis with a case study research method. Research is conducted by collecting data obtained through survey by interview and giving questionnaire to all staff and head and also observation by evaluating directly the research object and also through literature study. Data analysis is conducted through input phase by using IFAS and EFAS matrix, adaptation phase with TOWS diagram, TOWS matrix and Internal-External matrix, and also uses SPACE matrix and also BCG matrix to analyse company's finance situation. Based on the conducted analysist the recommended corporation level strategy to be used by the company is diversification strategy direct to growth and stability. 

  17. Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

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    Masanori Matsui

    2014-01-01

    Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

  18. Human dendritic cells sequentially matured with CD4(+) T cells as a secondary signal favor CTL and long-term T memory cell responses.

    Science.gov (United States)

    Simon, Thomas; Tanguy-Royer, Séverine; Royer, Pierre-Joseph; Boisgerault, Nicolas; Frikeche, Jihane; Fonteneau, Jean-François; Grégoire, Marc

    2012-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL) responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  19. ELISPOT Assay for Monitoring Cytotoxic T Lymphocytes (CTL Activity in Cancer Vaccine Clinical Trials

    Directory of Open Access Journals (Sweden)

    Thomas J. Sayers

    2012-05-01

    Full Text Available The profiling and monitoring of immune responses are key elements in the evaluation of the efficacy and development of new biotherapies, and a number of assays have been introduced for analyzing various immune parameters before, during, and after immunotherapy. The choice of immune assays for a given clinical trial depends on the known or suggested immunomodulating mechanisms associated with the tested therapeutic modality. Cell-mediated cytotoxicity represents a key mechanism in the immune response to various pathogens and tumors. Therefore, the selection of monitoring methods for the appropriate assessment of cell-mediated cytotoxicity is thought to be crucial. Assays that can detect both cytotoxic T lymphocytes (CTL frequency and function, such as the IFN-γ enzyme-linked immunospot assay (ELISPOT have gained increasing popularity for monitoring clinical trials and in basic research. Results from various clinical trials, including peptide and whole tumor cell vaccination and cytokine treatment, have shown the suitability of the IFN-γ ELISPOT assay for monitoring T cell responses. However, the Granzyme B ELISPOT assay and Perforin ELISPOT assay may represent a more direct analysis of cell-mediated cytotoxicity as compared to the IFN-γ ELISPOT, since Granzyme B and perforin are the key mediators of target cell death via the granule-mediated pathway. In this review we analyze our own data and the data reported by others with regard to the application of various modifications of ELISPOT assays for monitoring CTL activity in clinical vaccine trials.

  20. Development of a Luminex Bead Based Assay for Diagnosis of Toxocariasis Using Recombinant Antigens Tc-CTL-1 and Tc-TES-26.

    Directory of Open Access Journals (Sweden)

    John P Anderson

    Full Text Available The clinical spectrum of human disease caused by the roundworms Toxocara canis and Toxocara cati ranges from visceral and ocular larva migrans to covert toxocariasis. The parasite is not typically recovered in affected tissues, so detection of parasite-specific antibodies is usually necessary for establishing a diagnosis. The most reliable immunodiagnostic methods use the Toxocara excretory-secretory antigens (TES-Ag in ELISA formats to detect Toxocara-specific antibodies. To eliminate the need for native parasite materials, we identified and purified immunodiagnostic antigens using 2D gel electrophoresis followed by electrospray ionization mass spectrometry. Three predominant immunoreactive proteins were found in the TES; all three had been previously described in the literature: Tc-CTL-1, Tc-TES-26, and Tc-MUC-3. We generated Escherichia coli expressed recombinant proteins for evaluation in Luminex based immunoassays. We were unable to produce a functional assay with the Tc-MUC-3 recombinant protein. Tc-CTL-1 and Tc-TES-26 were successfully coupled and tested using defined serum batteries. The use of both proteins together generated better results than if the proteins were used individually. The sensitivity and specificity of the assay for detecting visceral larval migrans using Tc-CTL-1 plus Tc-TES-26 was 99% and 94%, respectively; the sensitivity for detecting ocular larval migrans was 64%. The combined performance of the new assay was superior to the currently available EIA and could potentially be employed to replace current assays that rely on native TES-Ag.

  1. Transgene IL-6 Enhances DC-Stimulated CTL Responses by Counteracting CD4+25+Foxp3+ Regulatory T Cell Suppression via IL-6-Induced Foxp3 Downregulation

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    Kalpana Kalyanasundaram Bhanumathy

    2014-03-01

    Full Text Available Dendritic cells (DCs, the most potent antigen-presenting cells have been extensively applied in clinical trials for evaluation of antitumor immunity. However, the efficacy of DC-mediated cancer vaccines is still limited as they are unable to sufficiently break the immune tolerance. In this study, we constructed a recombinant adenoviral vector (AdVIL-6 expressing IL-6, and generated IL-6 transgene-engineered DC vaccine (DCOVA/IL-6 by transfection of murine bone marrow-derived ovalbumin (OVA-pulsed DCs (DCOVA with AdVIL-6. We then assessed DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL responses and antitumor immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 vaccine up-regulates expression of DC maturation markers, secretes transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL responses and therapeutic immunity against OVA-expressing B16 melanoma BL6-10OVA in vivo than the control DCOVA/Null vaccine. Moreover, DCOVA/IL-6-stimulated CTL responses were relatively maintained in mice with transfer of CD4+25+Foxp3+ Tr-cells, but significantly reduced when treated with anti-IL-6 antibody. In addition, we demonstrate that IL-6 down-regulates Foxp3-expression of CD4+25+Foxp3+ Tr-cells in vitro. Taken together, our results demonstrate that AdV-mediated IL-6 transgene-engineered DC vaccine stimulates potent CTL responses and antitumor immunity by counteracting CD4+25+ Tr immunosuppression via IL-6-induced Foxp3 down-regulation. Thus, IL-6 may be a good candidate for engineering DCs for cancer immunotherapy.

  2. Choline transport via choline transporter-like protein 1 in conditionally immortalized rat syncytiotrophoblast cell lines TR-TBT.

    Science.gov (United States)

    Lee, N-Y; Choi, H-M; Kang, Y-S

    2009-04-01

    Choline is an essential nutrient for phospholipids and acetylcholine biosynthesis in normal development of fetus. In the present study, we investigated the functional characteristics of choline transport system and inhibitory effect of cationic drugs on choline transport in rat conditionally immortalized syncytiotrophoblast cell line (TR-TBT). Choline transport was weakly Na(+) dependent and significantly influenced by extracellular pH and by membrane depolarization. The transport process of choline is saturable with Michaelis-Menten constants (K(m)) of 68microM and 130microM in TR-TBT 18d-1 and TR-TBT 18d-2 respectively. Choline uptake in the cells was inhibited by unlabeled choline and hemicholinium-3 as well as various organic cations including guanidine, amiloride and acetylcholine. However, the prototypical organic cation tetraethylammonium and cimetidine showed very little inhibitory effect of choline uptake in TR-TBT cells. RT-PCR revealed that choline transporter-like protein 1 (CTL1) and organic cation transporter 2 (OCT2) are expressed in TR-TBT cells. The transport properties of choline in TR-TBT cells were similar or identical to that of CTL1 but not OCT2. CTL1 was also detected in human placenta. In addition, several cationic drugs such as diphenhydramine and verapamil competitively inhibited choline uptake in TR-TBT 18d-1 with K(i) of 115microM and 55microM, respectively. Our results suggest that choline transport system, which has intermediate affinity and weakly Na(+) dependent, in TR-TBT seems to occur through a CTL1 and this system may have relevance with the uptake of pharmacologically important organic cation drugs.

  3. Human dendritic cells sequentially matured with CD4+ T cells as a secondary signal favor CTL and long-term T memory cell responses

    Directory of Open Access Journals (Sweden)

    Thomas Simon

    2012-01-01

    Full Text Available Dendritic cells (DCs are professional antigen-presenting cells involved in the control and initiation of immune responses. In vivo, DCs exposed at the periphery to maturation stimuli migrate to lymph nodes, where they receive secondary signals from CD4+ T helper cells. These DCs become able to initiate CD8+ cytotoxic T lymphocyte (CTL responses. However, in vitro investigations concerning human monocyte-derived DCs have never focused on their functional properties after such sequential maturation. Here, we studied human DC phenotypes and functions according to this sequential exposure to maturation stimuli. As first signals, we used TNF-α/polyI:C mimicking inflammatory and pathogen stimuli and, as second signals, we compared activated CD4+ T helper cells to a combination of CD40-L/ IFN-γ. Our results show that a sequential activation with activated CD4+ T cells dramatically increased the maturation of DCs in terms of their phenotype and cytokine secretion compared to DCs activated with maturation stimuli delivered simultaneously. Furthermore, this sequential maturation led to the induction of CTL with a long-term effector and central memory phenotypes. Thus, sequential delivery of maturation stimuli, which includes CD4+ T cells, should be considered in the future to improve the induction of long-term CTL memory in DC-based immunotherapy.

  4. Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection.

    Directory of Open Access Journals (Sweden)

    Grégoire Chevalier

    2011-11-01

    Full Text Available Following infection of the central nervous system (CNS, the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL because they do not express major histocompatibility class I (MHC I molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV, in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and

  5. Dynamics of a viral infection model with delayed CTL response and immune circadian rhythm

    International Nuclear Information System (INIS)

    Bai Zhenguo; Zhou Yicang

    2012-01-01

    This paper studies the global dynamics of a viral infection model that takes into account circadian rhythm and time delay in the CTL response. It is shown that the basic reproduction numbers, R 0 and R 1 , determine the outcome of viral infection. Numerical simulations demonstrate that the changes in the amplitude of lytic component can generate a variety of dynamical patterns, ranging from simple daily oscillation to multi-day dynamics and eventually chaos, whereas time delay can alter the period of oscillation for the larger level of periodic forcing. These results can help to explain the viral oscillation behaviors, which were observed in chronic HBV and HCV infection patients.

  6. Novel CTL epitopes identified through a Y. pestis proteome-wide analysis in the search for vaccine candidates against plague.

    Science.gov (United States)

    Zvi, Anat; Rotem, Shahar; Zauberman, Ayelet; Elia, Uri; Aftalion, Moshe; Bar-Haim, Erez; Mamroud, Emanuelle; Cohen, Ofer

    2017-10-20

    The causative agent of Plague, Yersinia pestis, is a highly virulent pathogen and a potential bioweapon. Depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. The latter has a high fatality rate. In the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the F1 and LcrV antigens are currently under clinical trials. It is well known that a cellular immune response might have an essential additive value to immunity and protection against Y. pestis infection. Nevertheless, very few documented epitopes eliciting a protective T-cell response have been reported. Here, we present a combined high throughput computational and experimental effort towards identification of CD8 T-cell epitopes. All 4067 proteins of Y. pestis were analyzed with state-of-the-art recently developed prediction algorithms aimed at mapping potential MHC class I binders. A compilation of the results obtained from several prediction methods revealed a total of 238,000 peptide candidates, which necessitated downstream filtering criteria. Our previously established and proven approach for enrichment of true positive CTL epitopes, which relies on mapping clusters rich in tandem or overlapping predicted MHC binders ("hotspots"), was applied, as well as considerations of predicted binding affinity. A total of 1532 peptides were tested for their ability to elicit a specific T-cell response by following the production of IFNγ from splenocytes isolated from vaccinated mice. Altogether, the screen resulted in 178 positive responders (11.8%), all novel Y. pestis CTL epitopes. These epitopes span 113 Y. pestis proteins. Substantial enrichment of membrane-associated proteins was detected for epitopes selected from hotspots of predicted MHC binders. These results considerably expand the repertoire of known CTL epitopes in Y. pestis and pave the way to

  7. Exhaustion of CTL memory and recrudescence of viremia in lymphocytic choriomeningitis virus-infected MHC class II-deficient mice and B cell-deficient mice

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Johansen, J; Marker, O

    1996-01-01

    To study the contribution of CD4+ T cells and B cells to antiviral immunity and long term virus control, MHC class II-deficient and B cell-deficient mice were infected with lymphocytic choriomeningitis virus. In class II-deficient mice, which lack CD4+ T cells, the primary CTL response is virtually...... this phenomenon could reflect participation of B cells and/or Abs in long term virus control, similar experiments were performed with mice that do not have mature B cells because of a disrupted membrane exon of the mu chain gene. In these mice, the cell-mediated immune response was slightly delayed, but transient...... and that in their absence, the virus-specific CTL potential becomes exhausted. Together our results indicate that while CD8+ cells play a dominant role in acute virus control, all three major components of the immune system are required for long term virus control....

  8. A novel strategy for the identification of antigens that are recognised by bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology.

    Science.gov (United States)

    Graham, Simon P; Honda, Yoshikazu; Pellé, Roger; Mwangi, Duncan M; Glew, E Jane; de Villiers, Etienne P; Shah, Trushar; Bishop, Richard; van der Bruggen, Pierre; Nene, Vishvanath; Taracha, Evans L N

    2007-02-09

    Immunity against the bovine protozoan parasite Theileria parva has previously been shown to be mediated through lysis of parasite-infected cells by MHC class I restricted CD8+ cytotoxic T lymphocytes. It is hypothesized that identification of CTL target schizont antigens will aid the development of a sub-unit vaccine. We exploited the availability of the complete genome sequence data and bioinformatics tools to identify genes encoding secreted or membrane anchored proteins that may be processed and presented by the MHC class I molecules of infected cells to CTL. Of the 986 predicted open reading frames (ORFs) encoded by chromosome 1 of the T. parva genome, 55 were selected based on the presence of a signal peptide and/or a transmembrane helix domain. Thirty six selected ORFs were successfully cloned into a eukaryotic expression vector, transiently transfected into immortalized bovine skin fibroblasts and screened in vitro using T. parva-specific CTL. Recognition of gene products by CTL was assessed using an IFN-gamma ELISpot assay. A 525 base pair ORF encoding a 174 amino acid protein, designated Tp2, was identified by T. parva-specific CTL from 4 animals. These CTL recognized and lysed Tp2 transfected skin fibroblasts and recognized 4 distinct epitopes. Significantly, Tp2 specific CD8+ T cell responses were observed during the protective immune response against sporozoite challenge. The identification of an antigen containing multiple CTL epitopes and its apparent immunodominance during a protective anti-parasite response makes Tp2 an attractive candidate for evaluation of its vaccine potential.

  9. One-pot, mix-and-read peptide-MHC tetramers

    DEFF Research Database (Denmark)

    Leisner, Christian Valdemar Vinge; Loeth, Nina; Lamberth, Kasper

    2008-01-01

    BACKGROUND: Cytotoxic T Lymphocytes (CTL) recognize complexes of peptide ligands and Major Histocompatibility Complex (MHC) class I molecules presented at the surface of Antigen Presenting Cells (APC). Detection and isolation of CTL's are of importance for research on CTL immunity, and development...... molecules can be refolded in vitro, tetramerized with streptavidin, and used for specific T cell staining-all in a one-pot reaction without any intervening purification steps. CONCLUSIONS/SIGNIFICANCE: We have developed an efficient "one-pot, mix-and-read" strategy for peptide-MHC tetramer generation...

  10. Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

    Directory of Open Access Journals (Sweden)

    Paul Oykhman

    2010-01-01

    Full Text Available Cytotoxic T-lymphocytes (CTL are famous for their ability to kill tumor, allogeneic and virus-infected cells. However, an emerging literature has now demonstrated that CTL also possess the ability to directly recognize and kill bacteria, parasites, and fungi. Here, we review past and recent findings demonstrating the direct microbicidal activity of both CD4+ and CD8+ CTL against various microbial pathogens. Further, this review will outline what is known regarding the mechanisms of direct killing and their underlying signalling pathways.

  11. Amino acid similarity accounts for T cell cross-reactivity and for "holes" in the T cell repertoire

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; de Boer, Rob J.; Lund, Ole

    2008-01-01

    Background: Cytotoxic T cell (CTL) cross-reactivity is believed to play a pivotal role in generating immune responses but the extent and mechanisms of CTL cross-reactivity remain largely unknown. Several studies suggest that CTL clones can recognize highly diverse peptides, some sharing no obvious...... sequence identity. The emerging realization in the field is that T cell receptors (TcR) recognize multiple distinct ligands. Principal Findings: First, we analyzed peptide scans of the HIV epitope SLFNTVATL (SFL9) and found that TCR specificity is position dependent and that biochemically similar amino...... to demonstrate that seemingly distinct T cell epitopes, i.e., ones with low sequence identity, are in fact more biochemically similar than expected. Additionally, an analysis of HIV immunogenicity data with our model showed that CTLs have the tendency to respond mostly to peptides that do not resemble self...

  12. Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

    Science.gov (United States)

    Molinier-Frenkel, Valérie; Gahery-Segard, Hanne; Mehtali, Majid; Le Boulaire, Christophe; Ribault, Sébastien; Boulanger, Pierre; Tursz, Thomas; Guillet, Jean-Gérard; Farace, Françoise

    2000-01-01

    We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218–2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8+ CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses. PMID:10906225

  13. Epitopes recognized by CBV4 responding T cells: effect of type 1 diabetes and associated HLA-DR-DQ haplotypes

    International Nuclear Information System (INIS)

    Marttila, Jane; Hyoety, Heikki; Naentoe-Salonen, Kirsti; Simell, Olli; Ilonen, Jorma

    2004-01-01

    The present study aimed at characterizing the epitopes recognized by coxsackievirus B4 (CBV4)-specific T-cell lines established from 23 children with type 1 diabetes (T1D) and 29 healthy children with T1D risk-associated HLA genotypes. Responsiveness to VP1 region was dependent on the specific infection history as 55% of the T-cell lines from donors with neutralizing antibodies to CBV serotypes responded to VP1 peptides compared to none of the T-cell lines from other donors (P = 0.01). The pattern of recognized peptides was dependent of the HLA genotype. Forty-two percent of the T-cell lines from donors carrying the HLA-(DR4)-DQB1*0302 haplotype responded to VP1 peptides 71-80 compared to none of the T-cell lines from donors without this haplotype (P = 0.02). No evidence for the existence of diabetes-specific epitopes was found. Only few epitopes were exclusive recognized by T cells from diabetic children, and in each case only one or two T-cell lines were responding

  14. Regulation of CTL responses to MHC-restricted class I peptide of the gp70 tumour antigen by splenic parenchymal CD4+ T cells in mice failing immunotherapy with DISC-mGM-CSF.

    Science.gov (United States)

    Ahmad, Murrium; Rees, Robert C; McArdle, Stephanie E; Li, Geng; Mian, Shahid; Entwisle, Claire; Loudon, Peter; Ali, Selman A

    2005-07-20

    Direct intratumour injection of the disabled infectious single-cycle-herpes simplex virus-encoding murine granulocyte/macrophage colony-stimulating factor (DISC-HSV-mGM-CSF) into established colon carcinoma CT26 tumours induced complete tumour rejection in up to 70% of treated animals (regressors), while the remaining mice developed progressive tumours (progressors). This murine Balb/c model was used to dissect the cellular mechanisms involved in tumour regression or progression following immunotherapy. CTLs were generated by coculturing lymphocytes and parenchymal cells from the same spleens of individual regressor or progressor animals in the presence of the relevant AH-1 peptide derived from the gp70 tumour-associated antigens expressed by CT26 tumours. Tumour regression was correlated with potent CTL responses, spleen weight and cytokine (IFN-gamma) production. Conversely, progressor splenocytes exhibited weak to no CTL activity and poor IFN-gamma production, concomitant with the presence of a suppressor cell population in the progressor splenic parenchymal cell fraction. Further fractionation of this parenchymal subpopulation demonstrated that cells inhibitory to the activation of AH-1-specific CTLs, restimulated in vitro with peptide, were present in the nonadherent parenchymal fraction. In vitro depletion of progressor parenchymal CD3+/CD4+ T cells restored the CTL response of the cocultured splenocytes (regressor lymphocytes and progressor parenchymal cells) and decreased the production of IL-10, suggesting that CD3+CD4+ T lymphocytes present in the parenchymal fraction regulated the CTL response to AH-1. We examined the cellular responses associated with tumour rejection and progression, identifying regulatory pathways associated with failure to respond to immunotherapy. Copyright 2005 Wiley-Liss, Inc.

  15. Detection of choline transporter-like 1 protein CTL1 in neuroblastoma × glioma cells and in the CNS, and its role in choline uptake

    Czech Academy of Sciences Publication Activity Database

    Machová, Eva; O´Regan, S.; Newcombe, J.; Meunier, F. M.; Prentice, J.; Dove, R.; Lisá, Věra; Doležal, Vladimír

    2009-01-01

    Roč. 110, č. 4 (2009), s. 1297-1309 ISSN 0022-3042 R&D Projects: GA MŠk(CZ) LC554; GA AV ČR(CZ) IAA500110703 Institutional research plan: CEZ:AV0Z50110509 Keywords : CTL1 * choline * cell growth Subject RIV: ED - Physiology Impact factor: 3.999, year: 2009

  16. Recognition of HIV-1 peptides by host CTL is related to HIV-1 similarity to human proteins.

    Directory of Open Access Journals (Sweden)

    Morgane Rolland

    Full Text Available BACKGROUND: While human immunodeficiency virus type 1 (HIV-1-specific cytotoxic T lymphocytes preferentially target specific regions of the viral proteome, HIV-1 features that contribute to immune recognition are not well understood. One hypothesis is that similarities between HIV and human proteins influence the host immune response, i.e., resemblance between viral and host peptides could preclude reactivity against certain HIV epitopes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the extent of similarity between HIV-1 and the human proteome. Proteins from the HIV-1 B consensus sequence from 2001 were dissected into overlapping k-mers, which were then probed against a non-redundant database of the human proteome in order to identify segments of high similarity. We tested the relationship between HIV-1 similarity to host encoded peptides and immune recognition in HIV-infected individuals, and found that HIV immunogenicity could be partially modulated by the sequence similarity to the host proteome. ELISpot responses to peptides spanning the entire viral proteome evaluated in 314 individuals showed a trend indicating an inverse relationship between the similarity to the host proteome and the frequency of recognition. In addition, analysis of responses by a group of 30 HIV-infected individuals against 944 overlapping peptides representing a broad range of individual HIV-1B Nef variants, affirmed that the degree of similarity to the host was significantly lower for peptides with reactive epitopes than for those that were not recognized. CONCLUSIONS/SIGNIFICANCE: Our results suggest that antigenic motifs that are scarcely represented in human proteins might represent more immunogenic CTL targets not selected against in the host. This observation could provide guidance in the design of more effective HIV immunogens, as sequences devoid of host-like features might afford superior immune reactivity.

  17. Theileria parva antigens recognized by CD8+ T cells show varying degrees of diversity in buffalo-derived infected cell lines.

    Science.gov (United States)

    Sitt, Tatjana; Pelle, Roger; Chepkwony, Maurine; Morrison, W Ivan; Toye, Philip

    2018-05-06

    The extent of sequence diversity among the genes encoding 10 antigens (Tp1-10) known to be recognized by CD8+ T lymphocytes from cattle immune to Theileria parva was analysed. The sequences were derived from parasites in 23 buffalo-derived cell lines, three cattle-derived isolates and one cloned cell line obtained from a buffalo-derived stabilate. The results revealed substantial variation among the antigens through sequence diversity. The greatest nucleotide and amino acid diversity were observed in Tp1, Tp2 and Tp9. Tp5 and Tp7 showed the least amount of allelic diversity, and Tp5, Tp6 and Tp7 had the lowest levels of protein diversity. Tp6 was the most conserved protein; only a single non-synonymous substitution was found in all obtained sequences. The ratio of non-synonymous: synonymous substitutions varied from 0.84 (Tp1) to 0.04 (Tp6). Apart from Tp2 and Tp9, we observed no variation in the other defined CD8+ T cell epitopes (Tp4, 5, 7 and 8), indicating that epitope variation is not a universal feature of T. parva antigens. In addition to providing markers that can be used to examine the diversity in T. parva populations, the results highlight the potential for using conserved antigens to develop vaccines that provide broad protection against T. parva.

  18. A replicating cytomegalovirus-based vaccine encoding a single Ebola virus nucleoprotein CTL epitope confers protection against Ebola virus.

    Directory of Open Access Journals (Sweden)

    Yoshimi Tsuda

    2011-08-01

    Full Text Available Human outbreaks of Ebola virus (EBOV are a serious human health concern in Central Africa. Great apes (gorillas/chimpanzees are an important source of EBOV transmission to humans due to increased hunting of wildlife including the 'bush-meat' trade. Cytomegalovirus (CMV is an highly immunogenic virus that has shown recent utility as a vaccine platform. CMV-based vaccines also have the unique potential to re-infect and disseminate through target populations regardless of prior CMV immunity, which may be ideal for achieving high vaccine coverage in inaccessible populations such as great apes.We hypothesize that a vaccine strategy using CMV-based vectors expressing EBOV antigens may be ideally suited for use in inaccessible wildlife populations. To establish a 'proof-of-concept' for CMV-based vaccines against EBOV, we constructed a mouse CMV (MCMV vector expressing a CD8+ T cell epitope from the nucleoprotein (NP of Zaire ebolavirus (ZEBOV (MCMV/ZEBOV-NP(CTL. MCMV/ZEBOV-NP(CTL induced high levels of long-lasting (>8 months CD8+ T cells against ZEBOV NP in mice. Importantly, all vaccinated animals were protected against lethal ZEBOV challenge. Low levels of anti-ZEBOV antibodies were only sporadically detected in vaccinated animals prior to ZEBOV challenge suggesting a role, at least in part, for T cells in protection.This study demonstrates the ability of a CMV-based vaccine approach to protect against an highly virulent human pathogen, and supports the potential for 'disseminating' CMV-based EBOV vaccines to prevent EBOV transmission in wildlife populations.

  19. Identification of a C-type lectin with antiviral and antibacterial activity from pacific white shrimp Litopenaeus vannamei.

    Science.gov (United States)

    Li, Ming; Li, Chaozheng; Ma, Chunxia; Li, Haoyang; Zuo, Hongliang; Weng, Shaoping; Chen, Xiaohan; Zeng, Digang; He, Jianguo; Xu, Xiaopeng

    2014-10-01

    C-type lectins (CTLs) play crucial roles in innate immune responses in invertebrates by recognizing and eliminating microinvaders. In this study, a CTL from pacific white shrimp Litopenaeus vannamei (LvCTL3) was identified. LvCTL3 contains a single C-type lectin-like domain (CTLD), which shows similarities to those of other shrimp CTLs and has a mutated 'EPD' motif in Ca(2+)-binding site 2. LvCTL3 mRNA can be detected in all tested tissues and expression of LvCTL3 in gills was up-regulated after Lipopolysaccharides, poly (I:C), Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenges, suggesting activation responses of LvCTL3 to bacterial, virus and immune stimulant challenges. The 5'flanking regulatory region of LvCTL3 was cloned and we identified a NF-κB binding motif in the LvCTL3 promoter region. Dual-luciferase reporter assays indicated that over-expression of L. vannamei dorsal can dramatically up regulate the promoter activity of LvCTL3, suggesting that LvCTL3 expression could be regulated through NF-κB signaling pathway. As far as we know, this is the first report on signaling pathway involve in shrimp CTLs expression. The recombinant LvCTL3 protein was expressed in Escherichia coli and purified by Ni-affinity chromatography. The purified LvCTL3 can agglutinate Gram-negative microbe Vibrio alginolyticus and V. parahaemolyticus and Gram-positive bacteria Bacillus subtilis in the presence of calcium ions, but cannot agglutinate Gram-positive bacteria Streptococcus agalactiae. The agglutination activity of LvCTL3 was abolished when Ca(2+) was chelated with EDTA, suggesting the function of LvCTL3 is Ca(2+)-dependent. In vivo challenge experiments showed that the recombinant LvCTL3 protein can significantly reduce the mortalities of V. parahemolyticus and WSSV infection, indicating LvCTL3 might play significant roles in shrimp innate immunity defense against bacterial and viral infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Identification of naturally processed hepatitis C virus-derived major histocompatibility complex class I ligands.

    Directory of Open Access Journals (Sweden)

    Benno Wölk

    Full Text Available Fine mapping of human cytotoxic T lymphocyte (CTL responses against hepatitis C virus (HCV is based on external loading of target cells with synthetic peptides which are either derived from prediction algorithms or from overlapping peptide libraries. These strategies do not address putative host and viral mechanisms which may alter processing as well as presentation of CTL epitopes. Therefore, the aim of this proof-of-concept study was to identify naturally processed HCV-derived major histocompatibility complex (MHC class I ligands. To this end, continuous human cell lines were engineered to inducibly express HCV proteins and to constitutively express high levels of functional HLA-A2. These cell lines were recognized in an HLA-A2-restricted manner by HCV-specific CTLs. Ligands eluted from HLA-A2 molecules isolated from large-scale cultures of these cell lines were separated by high performance liquid chromatography and further analyzed by electrospray ionization quadrupole time of flight mass spectrometry (MS/tandem MS. These analyses allowed the identification of two HLA-A2-restricted epitopes derived from HCV nonstructural proteins (NS 3 and 5B (NS3₁₄₀₆₋₁₄₁₅ and NS5B₂₅₉₄₋₂₆₀₂. In conclusion, we describe a general strategy that may be useful to investigate HCV pathogenesis and may contribute to the development of preventive and therapeutic vaccines in the future.

  1. Recognizing Textual Entailment: Challenges in the Portuguese Language

    Directory of Open Access Journals (Sweden)

    Gil Rocha

    2018-03-01

    Full Text Available Recognizing textual entailment comprises the task of determining semantic entailment relations between text fragments. A text fragment entails another text fragment if, from the meaning of the former, one can infer the meaning of the latter. If such relation is bidirectional, then we are in the presence of a paraphrase. Automatically recognizing textual entailment relations captures major semantic inference needs in several natural language processing (NLP applications. As in many NLP tasks, textual entailment corpora for English abound, while the same is not true for more resource-scarce languages such as Portuguese. Exploiting what seems to be the only Portuguese corpus for textual entailment and paraphrases (the ASSIN corpus, in this paper, we address the task of automatically recognizing textual entailment (RTE and paraphrases from text written in the Portuguese language, by employing supervised machine learning techniques. We employ lexical, syntactic and semantic features, and analyze the impact of using semantic-based approaches in the performance of the system. We then try to take advantage of the bi-dialect nature of ASSIN to compensate its limited size. With the same aim, we explore modeling the task of recognizing textual entailment and paraphrases as a binary classification problem by considering the bidirectional nature of paraphrases as entailment relationships. Addressing the task as a multi-class classification problem, we achieve results in line with the winner of the ASSIN Challenge. In addition, we conclude that semantic-based approaches are promising in this task, and that combining data from European and Brazilian Portuguese is less straightforward than it may initially seem. The binary classification modeling of the problem does not seem to bring advantages to the original multi-class model, despite the outstanding results obtained by the binary classifier for recognizing textual entailments.

  2. IMPLEMENTASI CTL DALAM MATA KULIAH PRAKTIKUM METEOROLOGI- KLIMATOLOGI UNTUK MENINGKATKAN KOMPETENSI BEKERJA ILMIAH PADA MAHASISWA JURUSAN PENDIDIKAN GEOGRAFI UNNES

    Directory of Open Access Journals (Sweden)

    Sriyanto Sriyanto

    2014-12-01

    Full Text Available The results of self-evaluation Geography Unnes shows that theaverage duration of the study undergraduate Education Studies Geography is more than 4 years. The main causative factor lies in the preparation of the thesis that the time average of more than 12 months. Difficulty in writing his thesis student allegedly because they are not used to working scientific. The concept or practice of law that have been described in the classroom, it seems less able to develop the ability to work ilmiah.Penelitian is done in theDepartment of Geography at the subject of research students department of Geography. Types of research in the form of class action with some procedures or steps to be carried out. These stages are planning, action, observation / evaluation and ends with reflections. The results show the value than lab report results indicate that by using CTL there is an increasein student how scientific work. This is demonstrated by the increasing number of students who are able to work and make a map of rainfall at each cycle a cycle first, 56. 7 still confusion make maps of rainfall with nets Thiesen, only 43.3% were understand and be able to create a map of rainfall is in the second cycle, students are able to create and draw a map of rainfall with jarinng-nets models Thiesen increased to 83.3%. This result has met the completeness criteria that researchers set that is equal to 75% of the total sample / students. This shows that the models and approaches, students CTL capable and able to work scientifically in solving a particular problem in the lecture.

  3. THE EFFECTIVENESS OF CTL MODEL GUIDED INQUIRI-BASED IN THE TOPIC OF CHEMICALS IN DAILY LIFE TO IMPROVE STUDENTS’ LEARNING OUTCOMES AND ACTIVENESS

    OpenAIRE

    N. R. Fitriani; A. Widiyatmoko; M. Khusniati

    2016-01-01

    Science learning in school can be applied by connecting the material in the learning with real life. However in fact science learning process in SMP Negeri 10 Magelang has not emphasized students’ activity to relate science to real life. Learning science using CTL guided inquiry-based model implement the learning in where teacher provides initial questions related issues or events in everyday life, then students do experiments to prove concepts of science guided by teacher.The purpose of this...

  4. Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.

    Directory of Open Access Journals (Sweden)

    Jessica L Prince

    Full Text Available Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02. Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01, demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029 with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone.

  5. A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR.

    Directory of Open Access Journals (Sweden)

    Kelly Broen

    Full Text Available Nonmyeloablative allogeneic stem cell transplantation (SCT can induce remission in patients with renal cell carcinoma (RCC, but this graft-versus-tumor (GVT effect is often accompanied by graft-versus-host disease (GVHD. Here, we evaluated minor histocompatibility antigen (MiHA-specific T cell responses in two patients with metastatic RCC who were treated with reduced-intensity conditioning SCT followed by donor lymphocyte infusion (DLI. One patient had stable disease and emergence of SMCY.A2-specific CD8+ T cells was observed after DLI with the potential of targeting SMCY-expressing RCC tumor cells. The second patient experienced partial regression of lung metastases from whom we isolated a MiHA-specific CTL clone with the capability of targeting RCC cell lines. Whole genome association scanning revealed that this CTL recognizes a novel HLA-B7-restricted MiHA, designated ZAPHIR, resulting from a polymorphism in the splice donor site of the ZNF419 gene. Tetramer analysis showed that emergence of ZAPHIR-specific CD8+ T cells in peripheral blood occurred in the absence of GVHD. Furthermore, the expression of ZAPHIR in solid tumor cell lines indicates the involvement of ZAPHIR-specific CD8+ T cell responses in selective GVT immunity. These findings illustrate that the ZNF419-encoded MiHA ZAPHIR is an attractive target for specific immunotherapy after allogeneic SCT.

  6. A chicken influenza virus recognizes fucosylated α2,3 sialoglycan receptors on the epithelial cells lining upper respiratory tracts of chickens.

    Science.gov (United States)

    Hiono, Takahiro; Okamatsu, Masatoshi; Nishihara, Shoko; Takase-Yoden, Sayaka; Sakoda, Yoshihiro; Kida, Hiroshi

    2014-05-01

    Influenza viruses recognize sialoglycans as receptors. Although viruses isolated form chickens preferentially bind to sialic acid α2,3 galactose (SAα2,3Gal) glycans as do those of ducks, chickens were not experimentally infected with viruses isolated from ducks. A chicken influenza virus, A/chicken/Ibaraki/1/2005 (H5N2) (Ck/IBR) bound to fucose-branched SAα2,3Gal glycans, whereas the binding towards linear SAα2,3Gal glycans was weak. On the epithelial cells of the upper respiratory tracts of chickens, fucose-branched SAα2,3Gal glycans were detected, but not linear SAα2,3Gal glycans. The growth of Ck/IBR in MDCK-FUT cells, which were genetically prepared to express fucose-branched SAα2,3Gal glycans, was significantly higher than that in the parental MDCK cells. The present results indicate that fucose-branched SAα2,3Gal glycans existing on the epithelial cells lining the upper respiratory tracts of chickens are critical for recognition by Ck/IBR. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Model Pembelajaran CTL (Contextual Teaching and Learning dalam Meningkatkan Hasil Belajar Mahasiswa PGSD Pada MataKuliah Konsep IPS Dasar

    Directory of Open Access Journals (Sweden)

    Wahyu Susiloningsih

    2016-03-01

    Full Text Available Hasil belajar adalah suatu proses perubahan tingkah laku dalam pengetahuan, sikap, dan ketrampilan yang diperoleh dalam jangka waktu yang lama.Mata kuliah Konsep IPS Dasar merupakan mata kuliah yang memberikan pemahaman kepada mahasiswa PGSD tentang konsep dasar IPS sebagai landasan kajian yang bahannya bersumber dari kehidupan manusia di masyarakat, yang aspek-aspeknya meliputi social science (ilmu sosial, social studies (studi sosial, Ilmu Pengetahuan Sosial (IPS. IPS merupakan pembelajaran pada tingkat sekolah yang berperan mengfungsionalkan ilmu-ilmu sosial yang bersifat teoritik dalam kehidupan nyata dalam masyarakat. Model pembelajaran CTL adalah model pembelajaran yang menuntut kreatifitas guru dalam mengaitkan subject matter dengan kehidupan nyata mahasiswa guna membantu mahasiswa untuk lebih mudah memaknai materi tersebut.

  8. Presentation of human minor histocompatibility antigens by HLA-B35 and HLA-B38 molecules

    International Nuclear Information System (INIS)

    Yamamoto, Junji; Kariyone, Ai; Kano, Kyoichi; Takiguchi, Masafumi; Akiyama, Nobuo

    1990-01-01

    Cytotoxic T lymphocyte (CTL) clones specific for human minor histocompatibility antigens (hmHAs) were produced from a patient who had been grafted with the kidneys from his mother and two HLA-identical sisters. Of eight CTL clones generated, four recognized an hmHA (hmHA-1) expressed on cells from the mother and sister 3 (second donor); two recognized another antigen (hmHA-2) on cells from the father, sister (third donor), and sister 3; and the remaining two clones recognized still another antigen (hmHA-3) on cells from the father and sister 3. Panel studies revealed that CTL recognition of hmHA-1 was restricted by HLA-B35 and that of hmHA-2 and hmHA-3 was restricted by HLA-B38. The HLA-B35 restriction of the hmHA-1 -specific CTL clones was substantiated by the fact that they killed HLA-A null/HLA-B null Hmy2CIR targets transfected with HLA-B35 but not HLA-B51, -Bw52, or -Bw53 transfected Hmy2CIR targets. These data demonstrated that the five amino acids substitutions on the α 1 domain between HLA-B35 and -Bw53, which are associated with Bw4/Bw6 epitopes, play a critical role in the relationship of hmHA-1 to HLA-B35 molecules. The fact that the hmHA-1-specific CTLs failed to kill Hmy2CIR cells expressing HLA-B35/51 chimeric molecules composed of the α 1 domain of HLA-B35 and other domains of HLA-B51 indicated that eight residues on the α 2 domain also affect the interaction of hmHA-1 and the HLA-B35 molecules

  9. CISH is induced during DC development and regulates DC-mediated CTL activation.

    Science.gov (United States)

    Miah, Mohammad Alam; Yoon, Cheol-Hee; Kim, Joonoh; Jang, Jinah; Seong, Young-Rim; Bae, Yong-Soo

    2012-01-01

    The cytokine inducible SH2-domain protein (CISH) is a well-known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC-mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co-stimulatory molecules and pro-inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell-cycle activation and reduction of cell apoptosis. Down-regulation of cell proliferation at the later stage of DC development was found to be associated with CISH-mediated negative feedback regulation of STAT5 activation. In T-cell immunity, OT-1 T-cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT-2 T-cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC-based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Characterization of gastric adenocarcinoma cell lines established from CEA424/SV40 T antigen-transgenic mice with or without a human CEA transgene

    International Nuclear Information System (INIS)

    Nöckel, Jessica; Engel, Natasja K van den; Winter, Hauke; Hatz, Rudolf A; Zimmermann, Wolfgang; Kammerer, Robert

    2006-01-01

    Gastric carcinoma is one of the most frequent cancers worldwide. Patients with gastric cancer at an advanced disease stage have a poor prognosis, due to the limited efficacy of available therapies. Therefore, the development of new therapies, like immunotherapy for the treatment of gastric cancer is of utmost importance. Since the usability of existing preclinical models for the evaluation of immunotherapies for gastric adenocarcinomas is limited, the goal of the present study was to establish murine in vivo models which allow the stepwise improvement of immunotherapies for gastric cancer. Since no murine gastric adenocarcinoma cell lines are available we established four cell lines (424GC, mGC3, mGC5, mGC8) from spontaneously developing tumors of CEA424/SV40 T antigen (CEA424/Tag) mice and three cell lines derived from double-transgenic offsprings of CEA424/Tag mice mated with human carcinoembryonic antigen (CEA)-transgenic (CEA424/Tag-CEA) mice (mGC2 CEA , mGC4 CEA , mGC11 CEA ). CEA424/Tag is a transgenic C57BL/6 mouse strain harboring the Tag under the control of a -424/-8 bp CEA gene promoter which leads to the development of invasive adenocarcinoma in the glandular stomach. Tumor cell lines established from CEA424/Tag-CEA mice express the well defined tumor antigen CEA under the control of its natural regulatory elements. The epithelial origin of the tumor cells was proven by morphological criteria including the presence of mucin within the cells and the expression of the cell adhesion molecules EpCAM and CEACAM1. All cell lines consistently express the transgenes CEA and/or Tag and MHC class I molecules leading to their susceptibility to lysis by Tag-specific CTL in vitro. Despite the presentation of CTL-epitopes derived from the transgene products the tumor cell lines were tumorigenic when grafted into C57BL/6, CEA424/Tag or CEA424/Tag-CEA-transgenic hosts and no significant differences in tumor take and tumor growth were observed in the different hosts

  11. Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Tamai, Yotaro; Hasegawa, Atsuhiko; Takamori, Ayako; Sasada, Amane; Tanosaki, Ryuji; Choi, Ilseung; Utsunomiya, Atae; Maeda, Yasuhiro; Yamano, Yoshihisa; Eto, Tetsuya; Koh, Ki-Ryang; Nakamae, Hirohisa; Suehiro, Youko; Kato, Koji; Takemoto, Shigeki; Okamura, Jun; Uike, Naokuni; Kannagi, Mari

    2013-04-15

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We previously reported that Tax-specific CD8(+) cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4(+) T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4(+) as well as CD8(+) T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4(+) T cell responses, we identified a novel HLA-DRB1*0101-restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4(+) Th1-like cells, a major population of HTLV-1-specific CD4(+) T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8(+) T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101(+) patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4(+) T cells were present in all HTLV-1-infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4(+) T cells in HLA-DRB1*0101(+)-infected individuals and that Tax-specific CD4(+) T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8(+) T cell responses.

  12. Use of two predictive algorithms of the world wide web for the identification of tumor-reactive T-cell epitopes.

    Science.gov (United States)

    Lu, J; Celis, E

    2000-09-15

    Tumor cells can be effectively recognized and eliminated by CTLs. One approach for the development of CTL-based cancer immunotherapy for solid tumors requires the use of the appropriate immunogenic peptide epitopes that are derived from defined tumor-associated antigens. Because CTL peptide epitopes are restricted to specific MHC alleles, to design immune therapies for the general population it is necessary to identify epitopes for the most commonly found human MHC alleles. The identification of such epitopes has been based on MHC-peptide-binding assays that are costly and labor-intensive. We report here the use of two computer-based prediction algorithms, which are readily available in the public domain (Internet), to identify HL4-B7-restricted CTL epitopes for carcinoembryonic antigen (CEA). These algorithms identified three candidate peptides that we studied for their capacity to induce CTL responses in vitro using lymphocytes from HLA-B7+ normal blood donors. The results show that one of these peptides, CEA9(632) (IPQQHTQVL) was efficient in the induction of primary CTL responses when dendritic cells were used as antigen-presenting cells. These CTLs were efficient in killing tumor cells that express HLA-B7 and produce CEA. The identification of this HLA-B7-restricted CTL epitope will be useful for the design of ethnically unbiased, widely applicable immunotherapies for common solid epithelial tumors expressing CEA. Moreover, our strategy of identifying MHC class I-restricted CTL epitopes without the need of peptide/HLA-binding assays provides a convenient and cost-saving alternative approach to previous methods.

  13. Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T helper peptides in VacciMax®

    Directory of Open Access Journals (Sweden)

    Korets-Smith Ella

    2007-04-01

    Full Text Available Abstract Background Melanoma tumors are known to express antigens that usually induce weak immune responses of short duration. Expression of both tumor-associated antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously targeting more than one antigen in a therapeutic vaccine. In this report, we show that VacciMax® (VM, a novel liposome-based vaccine delivery platform, can increase the immunogenicity of melanoma associated antigens, resulting in tumor elimination. Methods C57BL/6 mice bearing B16-F10 melanoma tumors were vaccinated subcutaneously 6 days post tumor implantation with a mixture of synthetic peptides (modified p53: 232–240, TRP-2: 181–188 and PADRE and CpG. Tumor growth was monitored and antigen-specific splenocyte responses were assayed by ELISPOT. Results Vaccine formulated in VM increased the number of both TRP2- and p53-specific IFN-γ producing splenocytes following a single vaccination. Vaccine formulated without VM resulted only in enhanced IFN-γ producing splenocytes to one CTL epitopes (TRP2:180–188, suggesting that VM overcomes antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides formulated in VM successfully eradicated tumors in all mice. A control vaccine which contained all ingredients except liposomes resulted in eradication of tumors in no more than 20% of mice. Conclusion A single administration of VM is capable of inducing an effective CTL response to multiple tumor-associated antigens. The responses generated were able to reject 6-day old B16-F10 tumors.

  14. Protective immunization with B16 melanoma induces antibody response and not cytotoxic T cell response

    International Nuclear Information System (INIS)

    Sarzotti, M.; Sriyuktasuth, P.; Klimpel, G.R.; Cerny, J.

    1986-01-01

    C57BL/6 mice immunized with three intraperitoneal injections of syngeneic, irradiated B16 melanoma cells, became resistant to B16 tumor challenge. Immunized mice had high levels of serum antibody against a membrane antigen of B16 cells. The B16 antigen recognized by the anti-B16 sera formed a major band of 90 KD in gel electrophoresis. The anti-B16 antibody was partially protective when mixed with B16 cells and injected into normal recipient mice. Surprisingly, B16 resistance mice were incapable of generating cytotoxic T cells (CTL) specific for the B16 tumor. Both spleen and lymph node cell populations from immunized mice did not generate B16-specific CTL. Allogeneic mice (DBA/2 or C3H) were also unable to generate B16-specific CTL: however, alloreactive CTL produced in these strains of mice by immunization with C57BL/6 lymphocytes, did kill B16 target cells. Interestingly, spleen cells from syngeneic mice immunized with B16 tumor produced 6-fold more interleukin-2 (IL-2) than normal spleen cells, in vitro. These data suggest that immunization with B16 tumor activates a helper subset of T cells (for antibody and IL-2 production) but not the effector CTL response

  15. The effect of application of contextual teaching and learning (CTL model-based on lesson study with mind mapping media to assess student learning outcomes on chemistry on colloid systems

    Directory of Open Access Journals (Sweden)

    Annisa Fadillah

    2017-08-01

    Full Text Available The research was conducted to determine the effect of the application of CTL learning model based on lesson study with mind mapping media to the learning outcomes of students on colloid systems. The population of this research was all students of grade XI of SMA N 1 Sunggal. The sample was taken using on the purposive random sampling. The Experiment class was taught with Contextual Teaching and Learning (CTL model based on Lesson Study with Mind Mapping media and the control class taught with conventional learning model. The data was collected using an objective test was consisting of 20 questions which validity, reliability, level of difficulty and power of difference had been tested. T test results showed that tcalculate = 2.1 and ttable = 1.6697 thus tcalculate> ttable which means that Ha is accepted and Ho is rejected. The enhancement of the student learning outcomes showed that the results of experiment class are g = 72.88%, while the control class is 68.97%. From the percentage, it can be seen that learning outcomes of the experiment class are greater than the control class. The analysis of developing cognitive aspects pointed out that C1 = 70.02%, C2 = 73.58%, C3 = 68.63%, Thus the domain of cognitive level are on the cognitive aspects of C2. The result of Lesson Study Analysis showed the results of 71.09% at the first lesson and 88.28% at the second lesson. It means that there is increasing adherence to the indicators after two lessons. Based on the above results, it can be concluded that the result of studying chemistry of the students of class XI of SMA Negeri I Sunggal TA 2014/2015 taught by a CTL model based  on Lesson Study with Mind Mapping media was higher (72.88% than those taught by conventional learning models (68.97% in the subject matter of colloids System.

  16. Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Sørensen, Rikke Bæk; Ritter, Cathrin

    2011-01-01

    . Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition......, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion......, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors....

  17. Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors

    DEFF Research Database (Denmark)

    Andersen, Rikke Sick; Sørensen, Rikke Bæk; Ritter, Cathrin

    2011-01-01

    . Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-¿ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition......, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion......, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors....

  18. Evaluation of Drought Tolerance of Bread Wheat Recombinant Inbred Lines

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    N Zafar Naderi

    2014-10-01

    Full Text Available To evaluateresponse of bread wheat recombinant inbred lines to water deficit, a split plot experiment arranged in randomized complete block design (CRBD was conducted using eight recombinant inbred lines and their parental cultivars (Roshan and Super Head with three replications under three irrigation levels (80, 120 and 160 mm evaporation from class A pan at the Agriculture Research Station of Islamic Azad University, Tabriz Branch during 2009. The results of analysis of variance data collected revealed significant difference among lines and irrigation levels for grain yield. While line × irrigation level interaction was non significant for grain yield. Based on SSI and TOL, drought tolerance indices lines number 1, 7, 41 and Roshan cultivar under 120 mm evaporation, and lines number 7 and 19 under 160 mm evaporation were the tolerant lines. Under both stress conditions according to STI, MP and GMP indices, lines number 37, 38 and Roshan cultivar were recognized as the tolerant lines to water deficiet. Cluster analyses based on grain yield and drought tolerance indices recognized the lines number 1, 30, 32, 37, 38, 41 and Roshan cultivar under 120 mm and lines number 30, 37 and 38 and Roshan under 160 mm evaporation as the most drought tolerants and higher producers.

  19. MUC1-specific cytotoxic T lymphocytes eradicate tumors when adoptively transferred in vivo.

    Science.gov (United States)

    Mukherjee, P; Ginardi, A R; Tinder, T L; Sterner, C J; Gendler, S J

    2001-03-01

    We have reported previously that MUC1 transgenic mice with spontaneous tumors of the pancreas (designated MET) naturally develop MHC class I-restricted, MUC1-specific CTLs as tumors progress (P. Mukherjee et al., J. Immunol., 165: 3451-3460, 2000). From these MET mice, we have isolated, expanded, and cloned naturally occurring MUC1-specific CTLs in vitro. In this report, we show that the CTL line is predominantly CD8+ T cells and expresses T-cell receptor Vbeta chains 5.1/5.2, 11, 13, and 2 and Valpha chains 2, 8.3, 3.2, and 11.1/11.2. These CTLs recognize several epitopes on the MUC1 tandem repeat with highest affinity to APGSTAPPA. The CTL clone, on the other hand, is 100% CD8+ cells and expresses a single Vbeta chain of 5.1/5.2 and Valpha2. It recognizes only the H-2Db class I-restricted epitope of MUC1, APGSTAPPA. When adoptively transferred, the CTLs were effective in eradicating MUC1-expressing injected tumor cells including mammary gland cells (C57mg) and B16 melanomas. These results suggest that MUC1-specific CTLs are capable of possibly preventing, or at least substantially delaying, MUC1-expressing tumor formation. To our knowledge, this is the first evidence that demonstrates that the naturally occurring MUC1-specific CTLs isolated from one tumor model has antitumor effects on other MUC1-expressing tumors in vivo. Therefore, our data confirm that MUC1 is an important tumor rejection antigen and can serve as a target for immunotherapy.

  20. Association of serine protease with the rise of intracellular calcium in cytotoxic T lymphocytes.

    Science.gov (United States)

    Koo, G C; Luk, Y; Talento, A; Wu, J; Sirotina, A; Fischer, P A; Blake, J T; Nguyen, M P; Parsons, W; Poe, M

    1996-12-15

    The precise role of the granular enzyme A (granzyme A), a serine protease, in the lytic process of cytotoxic T lymphocytes (CTL) is not clear. We have recently constructed a CTL line transfected with the antisense gene of granzyme A (a-GrA). These a-GrA CTL had lower GrA activity as well as decreased lytic activities, as measured by 51Cr and by DNA degradation assays. Furthermore, at low effector:target ratio (1:8) in prolonged lytic assays, they could not lyse targets as rapidly as the control CTL. When we examined their ability to exocytose BLT (CBZ-L-lys-thiobenzyl)-esterase in the presence of anti-CD3 antibody, the a-GrA CTL exocytosed poorly compared to the parental CTL or control transfectant with a CAT gene. Most strikingly, a-GrA cells could not release intracellular stores of Ca2+ in response to anti-CD3 induction, although the Ca2+ flux was normal when they were stimulated with ionomycin. When the parental CTL was treated with a specific benzyllactam inhibitor of BLT-esterase or N-tosyl-L-phenylalanylchloromethyl ketone, the Ca2+ flux induced by anti-CD3 was also suppressed. We propose that granzyme A is involved in the signal transduction pathway that causes the rise of the intracellular calcium.

  1. Efficient algorithm for generating spectra using line-by-line methods

    International Nuclear Information System (INIS)

    Sonnad, V.; Iglesias, C.A.

    2011-01-01

    A method is presented for efficient generation of spectra using line-by-line approaches. The only approximation is replacing the line shape function with an interpolation procedure, which makes the method independent of the line profile functional form. The resulting computational savings for large number of lines is proportional to the number of frequency points in the spectral range. Therefore, for large-scale problems the method can provide speedups of two orders of magnitude or more. A method was presented to generate line-by-line spectra efficiently. The first step was to replace the explicit calculation of the profile by the Newton divided-differences interpolating polynomial. The second step is to accumulate the lines effectively reducing their number to the number of frequency points. The final step is recognizing the resulting expression as a convolution and amenable to FFT methods. The reduction in computational effort for a configuration-to-configuration transition array with large number of lines is proportional to the number of frequency points. The method involves no approximations except for replacing the explicit profile evaluation by interpolation. Specifically, the line accumulation and convolution are exact given the interpolation procedure. Furthermore, the interpolation makes the method independent of the line profile functional form contrary to other schemes using FFT methods to generate line-by-line spectra but relying on the analytic form of the profile Fourier transform. Finally, the method relies on a uniform frequency mesh. For non-uniform frequency meshes, however, the method can be applied by using a suitable temporary uniform mesh and the results interpolated onto the final mesh with little additional cost.

  2. Universal cytotoxic activity of a HTLV-1 Tax-specific T cell clone from an HLA-A*24:02⁺ patient with adult T-cell leukemia against a variety of HTLV-I-infected T-cells.

    Science.gov (United States)

    Tanaka, Yukie; Yamazaki, Rie; Terasako-Saito, Kiriko; Nakasone, Hideki; Akahoshi, Yu; Nakano, Hirofumi; Ugai, Tomotaka; Wada, Hidenori; Yamasaki, Ryoko; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Kimura, Shun-ichi; Kikuchi, Misato; Kako, Shinichi; Kanda, Junya; Tanihara, Aki; Nishida, Junji; Kanda, Yoshinobu

    2014-01-01

    Adult T cell leukemia/lymphoma (ATL) is an aggressive mature T cell malignancy that is causally associated with human T cell lymphotropic virus type 1 (HTLV-1) infection. The HTLV-1 regulatory protein Tax aggressively accelerates the proliferation of host cells and is also an important target antigen for CD8(+) cytotoxic T cells (CTLs). We previously reported that several predominant HLA-A*24:02-restricted HTLV-1 Tax301-309-specific CTL clones commonly expressed a particular amino acid sequence motif (P-D-R) in complementarity-determining region 3 of T-cell receptor (TCR)-β chain among unrelated ATL patients who underwent allogeneic stem cell transplantation (allo-HSCT). Furthermore, a PDR-motif(+) CTL clone persistently existed in a long-term survivor as a central CTL clone with strong CTL activities after HSCT. Although a larger analysis of the relationship between PDR-motif(+) CTLs and the clinical course is required, the expression of PDR-motif(+) TCR on CD8(+) T cells may play a critical role in the management of anti-HTLV-1 activities for HLA-A24:02(+) ATL patients. Therefore, in this study, we prepared an HTLV-1 Tax301-309 peptide-specific CTL clone (HT-9) expressing PDR-motif(+) TCR isolated from a long-term survivor after HSCT, and evaluated its CTL activity against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients. Before the assay of CTL function, we confirmed that HT-9 expressed less-differentiated effector-memory phenotypes (CD45RA(-)CCR7(-)CD27(+)CD28(+/-)CD57(+/-)) and T-cell exhaustion marker PD-1(+). In assays of CTL function, HT-9 recognized HTLV-1 Tax in an HLA-restricted fashion and demonstrated strong CTL activities against a variety of HTLV-1-infected T-cells from HLA-A*24:02(+) ATL patients regardless of whether the sources were autologous or allogeneic, but not normal cells. These data indicate that PDR-motif(+) TCR could be an important TCR candidate for TCR-gene immunotherapy for HLA-A24:02(+) ATL patients, provided

  3. Evaluation of the alert line of partogram in recognizing the need for neonatal resuscitation

    Directory of Open Access Journals (Sweden)

    Nahid Bolbol-Haghighi

    2015-01-01

    Conclusions: In mothers who had normal vaginal delivery, with normal fetal heart rate, and with no oxytocin administration or omniotomy, the alert line showed appropriate sensitivity, specificity, and negative prediction value. So, it can assist in predicting the necessity of action for neonatal resuscitation 20–30 s after delivery.

  4. The Duty to Recognize Culture

    DEFF Research Database (Denmark)

    Nielsen, Morten Ebbe Juul

    2012-01-01

    On Taylor and Honneth's theories of recognition and whether one can derive a "duty to recognize Culture" from these......On Taylor and Honneth's theories of recognition and whether one can derive a "duty to recognize Culture" from these...

  5. Activation of cellular immunity and marked inhibition of liver cancer in a mouse model following gene therapy and tumor expression of GM-SCF, IL-21, and Rae-1.

    Science.gov (United States)

    Cheng, Mingrong; Zhi, Kangkang; Gao, Xiaoyan; He, Bing; Li, Yingchun; Han, Jiang; Zhang, Zhiping; Wu, Yan

    2013-12-18

    Cancer is both a systemic and a genetic disease. The pathogenesis of cancer might be related to dampened immunity. Host immunity recognizes nascent malignant cells - a process referred to as immune surveillance. Augmenting immune surveillance and suppressing immune escape are crucial in tumor immunotherapy. A recombinant plasmid capable of co-expressing granulocyte-macrophage colony- stimulating factor (GM-SCF), interleukin-21 (IL-21), and retinoic acid early transcription factor-1 (Rae-1) was constructed, and its effects determined in a mouse model of subcutaneous liver cancer. Serum specimens were assayed for IL-2 and INF-γ by ELISA. Liver cancer specimens were isolated for Rae-1 expression by RT-PCR and Western blot, and splenocytes were analyzed by flow cytometry. The recombinant plasmid inhibited the growth of liver cancer and prolonged survival of tumor-loaded mice. Activation of host immunity might have contributed to this effect by promoting increased numbers and cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) following expression of GM-SCF, IL-21, and Rae-1. By contrast, the frequency of regulatory T cells was decreased, Consequently, activated CTL and NK cells enhanced their secretion of INF-γ, which promoted cytotoxicity of NK cells and CTL. Moreover, active CTL showed dramatic secretion of IL-2, which stimulates CTL. The recombinant expression plasmid also augmented Rae-1 expression by liver cancer cells. Rae-1 receptor expressing CTL and NK cells removed liver cancer. The recombinant expression plasmid inhibited liver cancer by a mechanism that involved activation of cell-mediated immunity and Rae-1 in liver cancer.

  6. Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: identification of indolent CD5+ diseases.

    Science.gov (United States)

    Yamashita, Daisuke; Shimada, Kazuyuki; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Kohno, Kei; Satou, Akira; Sakakibara, Ayako; Nakamura, Shigeo; Asano, Naoko; Kato, Seiichi

    2018-05-29

    Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV-negative CTL less frequently showed hepatic involvement (P = 0.007), B symptoms (P = 0.020), hemophagocytosis (P = 0.024), and detectable CD4 (P = 0.002) and CD5 (P = 0.009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age diseases: CD5 + TCRαβ (n = 13), and CD5 + NK-cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. PEMBELAJARAN PENJUMLAHAN BILANGAN PECAHAN DENGAN METODE CONTEXTUAL TEACHING AND LEARNING (CTL DI SD MUHAMMADIYAH PROGRAM KHUSUS, KOTA BARAT, SURAKARTA

    Directory of Open Access Journals (Sweden)

    Yulia Maftuhah Hidayati

    2015-07-01

    Full Text Available This study is aimed to describe the lesson plan, teaching learning process of sum of fractions based of Contextual Teaching and Learning (CTL, and the motivation of learners attend classes in learning. This study used a qualitative approach. The type of research is a case study. Validation of data is done through triangulation. Data were collected through interviews, observation, documentation, and testing. The technique of data analysis is descriptive, entrepretative. The results of this study indicate that (1 the development of lesson plan has been implemented routinely in every new school year, (2 the process of learning mathematics goes through three stages, namely preinstructional phase (preliminary / initial activity, instructional phase (core activities, and appraisal, (3 during the learning process, the students have a high motivation to participate in activities  because of the method used by teachers is fun and enjoyable

  8. PENERAPAN CTL (CONTEXTUAL TEACHING AND LEARNING MENGGUNAKAN MEDIA AJAR KLIPING UNTUK MENINGKATKAN PRESTASI BELAJAR, KOMPETENSI DASAR "MENEMUKAN PELUANG BARU DARI PELANGGAN" KELAS XI PEMASARAN SMK N 1 JAPARA KABUPATEN KUNINGAN

    Directory of Open Access Journals (Sweden)

    Marlina

    2012-05-01

    Full Text Available CTL adalah suatu konsep belajar di mana guru menghadirkan situasi dunia nyata dalam kelas dan mendorong siswa membuat hubungan antara pengetahuan yang dimiliki dengan penerapannya dalam kehidupan, sementara siswa memperoleh pengetahuan sedikit demi sedikit, dan dari proses mengkonstruksi sendiri, sebagai bekal memecahkan masalah dalam kehidupannya. Dari hasil observasi awal kelas XI Pemasaran SMK Negeri 1 Japara, diperoleh bahwa pada pelaksanaan pembelajaran kompetensi dasar Menemukan Peluang Baru dari pelanggan kurang berkembang, hal tersebut karena proses pembelajaran tersebut hanya terjadi satu arah atau hanya berfokus pada Guru yaitu menggunakan pembelajaran konvensional, sedangkan rata-rata nilai ujian tengah semester tahun pelajaran 2010 sebesar 60,32 dimana terdapat 14 siswa yang nilainya belum memenuhi Kriteria Ketuntasan Minimum (KKM. Permasalahan dalam penelitian ini adalah �Apakah Model pembelajaran CTL (Contextual Teaching Learning berbantuan media kliping dapat meningkatkan prestasi belajar siswa pada kompetensi dasar menemukan peluang baru dari pelanggan kelas XI Pemasaran SMK Negeri 1 Japara?�. Tujuan penelitian ini adalah untuk mengetahui efektifitas Media kliping dengan model pembelajaran CTL guna meningkatkan prestasi belajar siswa� Kompetensi dasar menemukan peluang baru dari pelanggan Kelas XI Pemasaran SMK Negeri 1 Japara Kabupaten Kuningan. Subyek penelitian ini adalah siswa SMK Negeri 1 Japara� yang terdiri dari 2 siswa laki-laki dan 29 siswa perempuan. Penelitian ditempuh dalam 2 siklus, yaitu siklus I dan siklus II, tiap siklus terdiri atas perencanaan, tindakan, pengamatan, dan refleksi. Indikator keberhasilan adalah tercapainya tujuan penelitian ini sesuai dengan alokasi waktu yang dirancang dalam penelitian untuk membahas materi yang ditunjukkan dengan terlampauinya nilai sesuai dengan KKM yang diterapkan Sekolah yaitu 7. Hasil penelitian ini dapat disimpulkan bahwa hasil tes siklus I menunjukkan rata

  9. How can we recognize continuous quality improvement?

    Science.gov (United States)

    Rubenstein, Lisa; Khodyakov, Dmitry; Hempel, Susanne; Danz, Margie; Salem-Schatz, Susanne; Foy, Robbie; O'Neill, Sean; Dalal, Siddhartha; Shekelle, Paul

    2014-02-01

    Continuous quality improvement (CQI) methods are foundational approaches to improving healthcare delivery. Publications using the term CQI, however, are methodologically heterogeneous, and labels other than CQI are used to signify relevant approaches. Standards for identifying the use of CQI based on its key methodological features could enable more effective learning across quality improvement (QI) efforts. The objective was to identify essential methodological features for recognizing CQI. Previous work with a 12-member international expert panel identified reliably abstracted CQI methodological features. We tested which features met rigorous a priori standards as essential features of CQI using a three-phase online modified-Delphi process. Primarily United States and Canada. 119 QI experts randomly assigned into four on-line panels. Participants rated CQI features and discussed their answers using online, anonymous and asynchronous discussion boards. We analyzed ratings quantitatively and discussion threads qualitatively. Main outcome measure(s) Panel consensus on definitional CQI features. /st> Seventy-nine (66%) panelists completed the process. Thirty-three completers self-identified as QI researchers, 18 as QI practitioners and 28 as both equally. The features 'systematic data guided activities,' 'designing with local conditions in mind' and 'iterative development and testing' met a priori standards as essential CQI features. Qualitative analyses showed cross-cutting themes focused on differences between QI and CQI. We found consensus among a broad group of CQI researchers and practitioners on three features as essential for identifying QI work more specifically as 'CQI.' All three features are needed as a minimum standard for recognizing CQI methods.

  10. The kinematics of cytotoxic lymphocytes influence their ability to kill target cells.

    Directory of Open Access Journals (Sweden)

    Purnima Bhat

    Full Text Available Cytotoxic lymphocytes (CTL have been reported to show a range of motility patterns from rapid long-range tracking to complete arrest, but how and whether these kinematics affect their ability to kill target cells is not known. Many in vitro killing assays utilize cell lines and tumour-derived cells as targets, which may be of limited relevance to the kinetics of CTL-mediated killing of somatic cells. Here, live-cell microscopy is used to examine the interactions of CTL and primary murine skin cells presenting antigens. We developed a qualitative and quantitative killing assay using extended-duration fluorescence time-lapse microscopy coupled with large-volume objective software-based data analysis to obtain population data of cell-to-cell interactions, motility and apoptosis. In vivo and ex vivo activated antigen-specific cytotoxic lymphocytes were added to primary keratinocyte targets in culture with fluorometric detection of caspase-3 activation in targets as an objective determinant of apoptosis. We found that activated CTL achieved contact-dependent apoptosis of non-tumour targets after a period of prolonged attachment - on average 21 hours - which was determined by target cell type, amount of antigen, and activation status of CTL. Activation of CTL even without engagement of the T cell receptor was sufficient to mobilise cells significantly above baseline, while the addition of cognate antigen further enhanced their motility. Highly activated CTL showed markedly increased vector displacement, and velocity, and lead to increased antigen-specific target cell death. These data show that the inherent kinematics of CTL correlate directly with their ability to kill non-tumour cells presenting cognate antigen.

  11. Spent Pot Lining Characterization Framework

    Science.gov (United States)

    Ospina, Gustavo; Hassan, Mohamed I.

    2017-09-01

    Spent pot lining (SPL) management represents a major concern for aluminum smelters. There are two key elements for spent pot lining management: recycling and safe storage. Spent pot lining waste can potentially have beneficial uses in co-firing in cement plants. Also, safe storage of SPL is of utmost importance. Gas generation of SPL reaction with water and ignition sensitivity must be studied. However, determining the feasibility of SPL co-firing and developing the required procedures for safe storage rely on determining experimentally all the necessary SPL properties along with the appropriate test methods, recognized by emissions standards and fire safety design codes. The applicable regulations and relevant SPL properties for this purpose are presented along with the corresponding test methods.

  12. Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.

    Science.gov (United States)

    Talento, A; Nguyen, M; Law, S; Wu, J K; Poe, M; Blake, J T; Patel, M; Wu, T J; Manyak, C L; Silberklang, M

    1992-12-15

    Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.

  13. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2003-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  14. Recognizing teen depression

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000648.htm Recognizing teen depression To use the sharing features on this page, ... life. Be Aware of the Risk for Teen Depression Your teen is more at risk for depression ...

  15. Double-stranded RNA promotes CTL-independent tumor cytolysis mediated by CD11b+Ly6G+ intratumor myeloid cells through the TICAM-1 signaling pathway

    Science.gov (United States)

    Shime, Hiroaki; Matsumoto, Misako; Seya, Tsukasa

    2017-01-01

    PolyI:C, a synthetic double-stranded RNA analog, acts as an immune-enhancing adjuvant that regresses tumors in cytotoxic T lymphocyte (CTL)-dependent and CTL-independent manner, the latter of which remains largely unknown. Tumors contain CD11b+Ly6G+ cells, known as granulocytic myeloid-derived suppressor cells (G-MDSCs) or tumor-associated neutrophils (TANs) that play a critical role in tumor progression and development. Here, we demonstrate that CD11b+Ly6G+ cells respond to polyI:C and exhibit tumoricidal activity in an EL4 tumor implant model. PolyI:C-induced inhibition of tumor growth was attributed to caspase-8/3 cascade activation in tumor cells that occurred independently of CD8α+/CD103+ dendritic cells (DCs) and CTLs. CD11b+Ly6G+ cells was essential for the antitumor effect because depletion of CD11b+Ly6G+ cells totally abrogated tumor regression and caspase activation after polyI:C treatment. CD11b+Ly6G+ cells that had been activated with polyI:C showed cytotoxicity and inhibited tumor growth through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS). These responses were abolished in either Toll/interleukin-1 receptor domain-containing adaptor molecule-1 (TICAM-1)−/− or interferon (IFN)-αβ receptor 1 (IFNAR1)−/− mice. Thus, our results suggest that polyI:C activates the TLR3/TICAM-1 and IFNAR signaling pathways in CD11b+Ly6G+ cells in tumors, thereby eliciting their antitumor activity, independent of those in CD8α+/CD103+ DCs that prime CTLs. PMID:27834952

  16. "RecognizeCane" : The new concept of a cane which recognizes the most common objects and safety clues.

    Science.gov (United States)

    Scherlen, Anne-Catherine; Dumas, Jean Claude; Guedj, Benjamin; Vignot, Alexandre

    2007-01-01

    This paper introduces the new concept of an electronic cane for blind people. While some systems inform the subject only of the presence of the object and its relative distance, RecognizeCane is also able to recognize most common objects and environment clues to increase the safety and confidence of the navigation process. The originality of RecognizeCane is the use of simple sensors, such as infrared, brilliance or water sensors to inform the subject of the presence, for example, of a stairway, a water puddle, a zebra crossing or a trash can. This cane does not use an embedded vision system. RecognizeCane is equipped with several sensors and microprocessors to collect sensor data and extract the desired information about the close environment by means of a dynamic analysis of output signals.

  17. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...... recognizing gp63 can take part in the host defence against L. major infections....

  18. Rejection of large HPV-16 expressing tumors in aged mice by a single immunization of VacciMax® encapsulated CTL/T helper peptides

    Directory of Open Access Journals (Sweden)

    MacDonald Lisa

    2007-06-01

    Full Text Available Abstract The incidence of cancer increases significantly in later life, yet few pre-clinical studies of cancer immunotherapy use mice of advanced age. A novel vaccine delivery platform (VacciMax®,VM is described that encapsulates antigens and adjuvants in multilamellar liposomes in a water-in-oil emulsion. The therapeutic potential of VM-based vaccines administered as a single dose was tested in HLA-A2 transgenic mice of advanced age (48–58 weeks old bearing large palpable TC1/A2 tumors. The VM-based vaccines contained one or more peptides having human CTL epitopes derived from HPV 16 E6 and E7. VM formulations contained a single peptide, a mixture of four peptides or the same four peptides linked together in a single long peptide. All VM formulations contained PADRE and CpG as adjuvants and ISA51 as the hydrophobic component of the water-in-oil emulsion. VM-formulated vaccines containing the four peptides as a mixture or linked together in one long peptide eradicated 19-day old established tumors within 21 days of immunization. Peptide-specific cytotoxic cellular responses were confirmed by ELISPOT and intracellular staining for IFN-γ producing CD8+ T cells. Mice rendered tumor-free by vaccination were re-challenged in the opposite flank with 10 million HLF-16 tumor cells, another HLA-A2/E6/E7 expressing tumor cell line. None of these mice developed tumors following the re-challenge. In summary, this report describes a VM-formulated therapeutic vaccine with the following unprecedented outcome: a eradication of large tumors (> 700 mm3 b in mice of advanced age c in less than three weeks post-immunization d following a single vaccination.

  19. The Differentiation and Protective Function of Cytolytic CD4 T Cells in Influenza Infection

    Directory of Open Access Journals (Sweden)

    Deborah M. Brown

    2016-03-01

    Full Text Available CD4 T cells that recognize peptide antigen in the context of Class II MHC can differentiate into various subsets that are characterized by their helper functions. However, increasing evidence indicates that CD4 cells with direct cytolytic activity (CD4 CTL play a role in chronic, as well as, acute infections such as influenza A virus (IAV infection. In the last couple of decades, techniques to measure the frequency and activity of these cytolytic cells has demonstrated their abundance in infections such as HIV, mouse pox, murine gamma herpes virus, CMV, EBV and influenza among others. We now appreciate a greater role for CD4 CTL as direct effectors in viral infections and anti-tumor immunity through their ability to acquire perforin mediated cytolytic activity and contribution to lysis of virally infected targets or tumors. As early as the 1980s, CD4 T cell clones with cytolytic potential were identified after influenza virus infection, yet much of this early work was dependent on in vitro culture and little was known about the physiological relevance of CD4 CTL. Here, we discuss the direct role CD4 CTL play in protection against lethal IAV infection and the factors that drive the generation of perforin mediated lytic activity in CD4 cells in vivo during IAV infection. While focusing on CD4 CTL generated during IAV infection, we pull comparisons from the literature in other anti-viral and anti-tumor systems. Further, we highlight what is currently known about CD4 CTL secondary and memory responses, as well as vaccination strategies to induce these potent killer cells that provide an extra layer of cell mediated immune protection against heterosubtypic IAV infection.

  20. Recognizing Bedside Events Using Thermal and Ultrasonic Readings

    Directory of Open Access Journals (Sweden)

    Danielsen Asbjørn

    2017-06-01

    Full Text Available Falls in homes of the elderly, in residential care facilities and in hospitals commonly occur in close proximity to the bed. Most approaches for recognizing falls use cameras, which challenge privacy, or sensor devices attached to the bed or the body to recognize bedside events and bedside falls. We use data collected from a ceiling mounted 80 × 60 thermal array combined with an ultrasonic sensor device. This approach makes it possible to monitor activity while preserving privacy in a non-intrusive manner. We evaluate three different approaches towards recognizing location and posture of an individual. Bedside events are recognized using a 10-second floating image rule/filter-based approach, recognizing bedside falls with 98.62% accuracy. Bed-entry and exit events are recognized with 98.66% and 96.73% accuracy, respectively.

  1. Cytotoxic T lymphocytes and CD4 epitope mutations in the pre-core/core region of hepatitis B virus in chronic hepatitis B carriers in Northeast Iran.

    Science.gov (United States)

    Zhand, Sareh; Tabarraei, Alijan; Nazari, Amineh; Moradi, Abdolvahab

    2017-07-01

    Hepatitis B virus (HBV) is vulnerable to many various mutations. Those within epitopes recognized by sensitized T cells may influence the re-emergence of the virus. This study was designed to investigate the mutation in immune epitope regions of HBV pre-core/core among chronic HBV patients of Golestan province, Northeast Iran. In 120 chronic HBV carriers, HBV DNA was extracted from blood plasma samples and PCR was done using specific primers. Direct sequencing and alignment of the pre-core/core region were applied using reference sequence from Gene Bank database (Accession Number AB033559). The study showed 27 inferred amino acid substitutions, 9 of which (33.3%) were in CD4 and 2 (7.4%) in cytotoxic T lymphocytes' (CTL) epitopes and 16 other mutations (59.2%) were observed in other regions. CTL escape mutations were not commonly observed in pre-core/core sequences of chronic HBV carriers in the locale of study. It can be concluded that most of the inferred amino acid substitutions occur in different immune epitopes other than CTL and CD4.

  2. FDA Recognized Consensus Standards

    Data.gov (United States)

    U.S. Department of Health & Human Services — This database consists of those national and international standards recognized by FDA which manufacturers can declare conformity to and is part of the information...

  3. THE DEVELOPMENT OF ELECTRONIC TEACHING MATERIALS BY FLIPBOOK ASSISTANCE BASED PROBLEM SOLVING SKILL WITH CTL APPROACH ON LEARNING MATHEMATICS CLASS V

    Directory of Open Access Journals (Sweden)

    RUSNILAWATI Eva Gustiana RUSNILAWATI

    2018-01-01

    Full Text Available The purpose of this research is to produce Flipbook-based Electronic Teaching Materials (BAE based on problem solving skills with CTL Approach on Vocational School Class V learning valid, practical, and effective. This type of research is development research (Development Research. This research developed Flipbook-assisted Electronic Teaching Materials (BAE on the mathematics learning of Class V Primary School by using the 4-D development model developed by Thiagarajan, Semmel, and Semmel. The validation results show that the developed Teaching Materials are worthy of use with a good minimum category. The results of the experiments show that Electronic Materials developed are practical and effective. Completed learning in the classical has reached the minimum criteria of 75% that is for problem-solving test reached 86%. Based on a questionnaire of attitudes toward mathematics, 88% of students showed an increase in attitude scores on mathematics, and 85% of students showed attitudes toward mathematics with a good minimum category.

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

    International Nuclear Information System (INIS)

    Bucy, R.P.

    1986-01-01

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

  5. 46 CFR 42.05-60 - Recognized classification society.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Recognized classification society. 42.05-60 Section 42... FOREIGN VOYAGES BY SEA Definition of Terms Used in This Subchapter § 42.05-60 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  6. 46 CFR 90.10-35 - Recognized classification society.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Recognized classification society. 90.10-35 Section 90... VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 90.10-35 Recognized classification society. The term recognized classification society means the American Bureau of Shipping or other...

  7. Experiment list: SRX367328 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available nology) || sirna transfection=siCTL http://dbarchive.bio...=HEK293T cell || cell line=Human Embryonic Kidney 293 cells || chip antibody=CDK9 || chip antibody details=2316S (Cell Signaling Tech

  8. MENINGKATKAN MINAT BELAJAR BIOLOGI MENGGUNAKAN PEMBELAJARAN CTL (Contextual Teaching and Learning PADA SISWA DI KELAS VII-B MTs NEGERI PURWOKERTO

    Directory of Open Access Journals (Sweden)

    Teguh Julianto

    2010-09-01

    Full Text Available Improving Student’s Interest in Biology lesson by using contextual teaching and learning (CLT methods is n action research study which had an aim to improve student’s interest in biology. The indicator of student’s interest covers the student’s diligence in learning process, active in following teaching and learning process, active in doing a task, the facility and the sources of learning. The result of this researched showed that there were an improvement of students learning interest. The percentage result in cycle I was 39.5%, in cycle 2 was 72.67% and in Cycle 3 was 80.92%. The improvement of students learning interests gave a positive effect toward the students achievement. The students learning achievement in cycle 1 I was 39%, in cycle II was 82% and in cycle III was 93%. In conclusion Contextual Teaching and Learning (CLT can improve the students learning interest in Biology at the Second Grade Students of MTs Negeri Purwokerto. Key words : Improving, Student’s learning interest, Contextual Teaching and Learning (CTL

  9. Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells.

    Science.gov (United States)

    Brown, Christine E; Starr, Renate; Aguilar, Brenda; Shami, Andrew F; Martinez, Catalina; D'Apuzzo, Massimo; Barish, Michael E; Forman, Stephen J; Jensen, Michael C

    2012-04-15

    To evaluate IL13Rα2 as an immunotherapeutic target for eliminating glioma stem-like cancer initiating cells (GSC) of high-grade gliomas, with particular focus on the potential of genetically engineered IL13Rα2-specific primary human CD8(+) CTLs (IL13-zetakine(+) CTL) to target this therapeutically resistant glioma subpopulation. A panel of low-passage GSC tumor sphere (TS) and serum-differentiated glioma lines were expanded from patient glioblastoma specimens. These glioblastoma lines were evaluated for expression of IL13Rα2 and for susceptibility to IL13-zetakine(+) CTL-mediated killing in vitro and in vivo. We observed that although glioma IL13Rα2 expression varies between patients, for IL13Rα2(pos) cases this antigen was detected on both GSCs and more differentiated tumor cell populations. IL13-zetakine(+) CTL were capable of efficient recognition and killing of both IL13Rα2(pos) GSCs and IL13Rα2(pos) differentiated cells in vitro, as well as eliminating glioma-initiating activity in an orthotopic mouse tumor model. Furthermore, intracranial administration of IL13-zetakine(+) CTL displayed robust antitumor activity against established IL13Rα2(pos) GSC TS-initiated orthotopic tumors in mice. Within IL13Rα2 expressing high-grade gliomas, this receptor is expressed by GSCs and differentiated tumor populations, rendering both targetable by IL13-zetakine(+) CTLs. Thus, our results support the potential usefullness of IL13Rα2-directed immunotherapeutic approaches for eradicating therapeutically resistant GSC populations. ©2012 AACR.

  10. Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

    Science.gov (United States)

    Chen, B P; Madrigal, A; Parham, P

    1990-09-01

    Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

  11. RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity

    Science.gov (United States)

    2013-01-01

    A substantial number of “retrogenes” that are derived from the mRNA of various intron-containing genes have been reported. A class of mammalian retroposons, long interspersed element-1 (LINE1, L1), has been shown to be involved in the reverse transcription of retrogenes (or processed pseudogenes) and non-autonomous short interspersed elements (SINEs). The 3′-end sequences of various SINEs originated from a corresponding LINE. As the 3′-untranslated regions of several LINEs are essential for retroposition, these LINEs presumably require “stringent” recognition of the 3′-end sequence of the RNA template. However, the 3′-ends of mammalian L1s do not exhibit any similarity to SINEs, except for the presence of 3′-poly(A) repeats. Since the 3′-poly(A) repeats of L1 and Alu SINE are critical for their retroposition, L1 probably recognizes the poly(A) repeats, thereby mobilizing not only Alu SINE but also cytosolic mRNA. Many flowering plants only harbor L1-clade LINEs and a significant number of SINEs with poly(A) repeats, but no homology to the LINEs. Moreover, processed pseudogenes have also been found in flowering plants. I propose that the ancestral L1-clade LINE in the common ancestor of green plants may have recognized a specific RNA template, with stringent recognition then becoming relaxed during the course of plant evolution. PMID:23984183

  12. 26 CFR 1.1374-2 - Net recognized built-in gain.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Net recognized built-in gain. 1.1374-2 Section 1...-in gain. (a) In general. An S corporation's net recognized built-in gain for any taxable year is the... considering only its recognized built-in gain, recognized built-in loss, and recognized built-in gain...

  13. PENINGKATAN HASIL BELAJAR MATA PELAJARAN EKONOMI DENGAN PENERAPAN MODEL PEMBELAJARAN CONTEXTUAL TEACHING AND LEARNING (CTL

    Directory of Open Access Journals (Sweden)

    Nur Alifah Fitriana

    2013-02-01

    Full Text Available Proses pembelajaran yang variatif akan membantu siswa dalam pemahaman materi pembelajaran yang diberikan oleh guru. Pada sekolah MA Yasis AT-Taqwa Pahesan, model pembelajaran yang digunakan masih menggunakan model pembelajaran yang konvensional. Disini siswa kurang berperan aktif dalam proses belajar mengajar dan siswa akan cenderung merasa bosan. Untuk menyelesaikan masalah tersebut peneliti mencoba menerapkan model pembelajaran Contextual Teaching and Learning (CTLsebagai upaya meningkatkan hasil belajar siswa. Rancangan penelitian ini merupakan penelitian tindakan kelas dengan dua siklus, setiap siklus meliputi perencanaan, pelaksanaan, pengamatan dan refleksi. Hasil penelitian diperoleh nilai rata-rata pada siklus I yaitu 64,58 dengan ketuntasan klasikal 54,16%, sedangkan untuk siklus II nilai rata-ratanya 79,79 dengan ketuntasan klasikal 79,16%. Pada siklus I aktivitas siswa 55,47% dan siklus II menjadi 76,54%. Sedangkan kinerja guru pada siklus I 51,42% dan meningkat disiklus II 91,42%. Abstract ___________________________________________________________________ The learning processwill help studentsvariedin understandinglearning materialsprovided bythe teacher. AtschoolMAYasisAT-Taqwa Pahesan, learning modelused is stillusingconventionallearning models. Here thestudents areactively involved inthe learning processand students willtend to feelbored. To solvethe problem, the researcher tried toapply thelearning modelContextual Teaching andLearning(CTL as an effort toimprove student learning outcomes. The design ofthis studyisaction researchwithtwocycles, each cycleincluding planning, implementation, observationand reflection. The result showedthe average valuein the first cycleis64.58withclassical completeness54.16%, while forthe second cycleaverage value79.79withclassical completeness79.16%. In the first cycleof student activityand55.47% to76.54% the second cycle. While theperformance of teachersin the first cycleincreased51

  14. Recognizing Banknote Fitness with a Visible Light One Dimensional Line Image Sensor

    Directory of Open Access Journals (Sweden)

    Tuyen Danh Pham

    2015-08-01

    Full Text Available In general, dirty banknotes that have creases or soiled surfaces should be replaced by new banknotes, whereas clean banknotes should be recirculated. Therefore, the accurate classification of banknote fitness when sorting paper currency is an important and challenging task. Most previous research has focused on sensors that used visible, infrared, and ultraviolet light. Furthermore, there was little previous research on the fitness classification for Indian paper currency. Therefore, we propose a new method for classifying the fitness of Indian banknotes, with a one-dimensional line image sensor that uses only visible light. The fitness of banknotes is usually determined by various factors such as soiling, creases, and tears, etc. although we just consider banknote soiling in our research. This research is novel in the following four ways: first, there has been little research conducted on fitness classification for the Indian Rupee using visible-light images. Second, the classification is conducted based on the features extracted from the regions of interest (ROIs, which contain little texture. Third, 1-level discrete wavelet transformation (DWT is used to extract the features for discriminating between fit and unfit banknotes. Fourth, the optimal DWT features that represent the fitness and unfitness of banknotes are selected based on linear regression analysis with ground-truth data measured by densitometer. In addition, the selected features are used as the inputs to a support vector machine (SVM for the final classification of banknote fitness. Experimental results showed that our method outperforms other methods.

  15. Recognizing Banknote Fitness with a Visible Light One Dimensional Line Image Sensor.

    Science.gov (United States)

    Pham, Tuyen Danh; Park, Young Ho; Kwon, Seung Yong; Nguyen, Dat Tien; Vokhidov, Husan; Park, Kang Ryoung; Jeong, Dae Sik; Yoon, Sungsoo

    2015-08-27

    In general, dirty banknotes that have creases or soiled surfaces should be replaced by new banknotes, whereas clean banknotes should be recirculated. Therefore, the accurate classification of banknote fitness when sorting paper currency is an important and challenging task. Most previous research has focused on sensors that used visible, infrared, and ultraviolet light. Furthermore, there was little previous research on the fitness classification for Indian paper currency. Therefore, we propose a new method for classifying the fitness of Indian banknotes, with a one-dimensional line image sensor that uses only visible light. The fitness of banknotes is usually determined by various factors such as soiling, creases, and tears, etc. although we just consider banknote soiling in our research. This research is novel in the following four ways: first, there has been little research conducted on fitness classification for the Indian Rupee using visible-light images. Second, the classification is conducted based on the features extracted from the regions of interest (ROIs), which contain little texture. Third, 1-level discrete wavelet transformation (DWT) is used to extract the features for discriminating between fit and unfit banknotes. Fourth, the optimal DWT features that represent the fitness and unfitness of banknotes are selected based on linear regression analysis with ground-truth data measured by densitometer. In addition, the selected features are used as the inputs to a support vector machine (SVM) for the final classification of banknote fitness. Experimental results showed that our method outperforms other methods.

  16. Antigen recognition by cloned cytotoxic T lymphocytes follows rules predicted by the altered-self hypothesis

    International Nuclear Information System (INIS)

    Huenig, T.R.; Bevan, M.J.

    1982-01-01

    Radiation chimeras prepared by injecting H-2 heterozygous F1 stem cells into lethally irradiated parental hosts show a marked, but not absolute, preference for host-type H-2 antigens in the H-2-restricted cytotoxic T lymphocyte (CTL) response to minor histocompatibility (minor H) antigens. We have selected for the anti-minor HCTL that are restricted to the parental H-2 type absent from the chimeric host and found that in two out of eight cases, such CTL lysed target cells of either parental H-2 type. From one of these CTL populations that lysed H-2d and H-2k target cells expressing BALB minor H antigens, clones were derived and further analyzed. The results showed that: (a) lysis of both H-2d and H-2k target cells was H-2 restricted; (b) H-2d restriction mapped to Dd, and H-2k restriction mapped to Kk; (c) testing against various H-2d and H-2k strains of different and partially overlapping minor H backgrounds as well as against the appropriate F1 crosses revealed that in Dd- and Kk-restricted killing, different minor H antigens were recognized. In a second system, a CTL population was selected from normal (H-2d x H-2k)F1 mice that was specific for H-2d plus minor H antigens and for H-2k plus trinitrophenylated bovine serum albumin. We interpret these findings in terms of the altered-self hypothesis: The association of one H-2 antigen with one conventional antigen X may be recognized by the same T cell receptor specific for the complex formed by a different H-2 antigen in association with a second conventional antigen Y. The implications of these observations for the influence of self H-2 on the generation of the T cell receptor repertoire are discussed

  17. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  18. Promiscuous prediction and conservancy analysis of CTL binding epitopes of HCV 3a viral proteome from Punjab Pakistan: an In Silico Approach

    Directory of Open Access Journals (Sweden)

    Idrees Muhammad

    2011-02-01

    Full Text Available Abstract Background HCV is a positive sense RNA virus affecting approximately 180 million people world wide and about 10 million Pakistani populations. HCV genotype 3a is the major cause of infection in Pakistani population. One of the major problems of HCV infection especially in the developing countries that limits the limits the antiviral therapy is the long term treatment, high dosage and side effects. Studies of antigenic epitopes of viral sequences of a specific origin can provide an effective way to overcome the mutation rate and to determine the promiscuous binders to be used for epitope based subunit vaccine design. An in silico approach was applied for the analysis of entire HCV proteome of Pakistani origin, aimed to identify the viral epitopes and their conservancy in HCV genotypes 1, 2 and 3 of diverse origin. Results Immunoinformatic tools were applied for the predictive analysis of HCV 3a antigenic epitopes of Pakistani origin. All the predicted epitopes were then subjected for their conservancy analysis in HCV genotypes 1, 2 and 3 of diverse origin (worldwide. Using freely available web servers, 150 MHC II epitopes were predicted as promiscuous binders against 51 subjected alleles. E2 protein represented the 20% of all the predicted MHC II epitopes. 75.33% of the predicted MHC II epitopes were (77-100% conserve in genotype 3; 47.33% and 40.66% in genotype 1 and 2 respectively. 69 MHC I epitopes were predicted as promiscuous binders against 47 subjected alleles. NS4b represented 26% of all the MHC I predicted epitopes. Significantly higher epitope conservancy was represented by genotype 3 i.e. 78.26% and 21.05% for genotype 1 and 2. Conclusions The study revealed comprehensive catalogue of potential HCV derived CTL epitopes from viral proteome of Pakistan origin. A considerable number of predicted epitopes were found to be conserved in different HCV genotype. However, the number of conserved epitopes in HCV genotype 3 was

  19. Power-line electrocution of birds (Electrocucion de Aves en Lineas Electricas en Mexico)

    Science.gov (United States)

    Patricia Manzano Fischer

    2006-01-01

    A result of rapid growth in human population and energy use, is proliferating power lines that electrocute birds, killing eagles and causing power outages. The United States was one of the first countries to recognize the significance of this problem. Suggested Practices for the Protection of Raptors on Power Lines, first published in the 1970s, has now been translated...

  20. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

    Science.gov (United States)

    Boissonnas, Alexandre; Fetler, Luc; Zeelenberg, Ingrid S; Hugues, Stéphanie; Amigorena, Sebastian

    2007-02-19

    Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8(+) cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.

  1. PERBANDINGAN HASIL BELAJAR IPA SEKOLAH DASAR MELALUI PENGGUNAAN PENDEKATAN GUIDED DISCOVERY DAN PENDEKATAN CTL (CONTEXTUAL TEACHING AND LEARNING

    Directory of Open Access Journals (Sweden)

    Fiky Ernawati

    2016-09-01

    Full Text Available Abstrak. Penelitian ini bertujuan untuk mengetahui perbandingan hasil belajar pada mata pelajaran IPA setelah menggunakan pendekatan pembelajaran Guided Discovery dengan pendekatan pembelajaran CTL (Contextual Teaching and Learning pada siswa  kelas  IV SD Negeri  3  Kramatwatu.  Metode  penelitian yang digunakan adalah metode kuasi ekpserimen, sedangkan desain penelitian yang digunakan adalah non equivalent control group design. Ada dua kelas dalam penelitian ini, yaitu kelompok eksperimen dan kelompok kontrol. Kelompok eksperimen yaitu siswa  kelas  IV-A  terdiri  dari  35  siswa  yang  diberikan  perlakuan  dengan pendekatan pembelajaran Guided Discovery dan kelas kontrol yaitu siswa kelas IV-B terdiri dari 33 siswa yang diberikan perlakuan pendekatan pembelajaran CTL (Contextual Teaching and Learning. Ada pun teknik pengumpulan data yang dilakukan meliputi tes hasil belajar berupa posttest serta nontes berupa dokumentasi.   Berdasarkan   hasil   penelitian   menunjukkan   bahwa   terdapat perbedaan hasil belajar siswa kelas eksperimen dan siswa kelas kontrol. Hasil belajar IPA siswa kelas eksperimen lebih tinggi daripada hasil belajar IPA siswa kelas kontrol. Rata-rata hasil belajar IPA kelas eksperimen yaitu 76,07 dan kelas kontrol memperoleh rata-rata 69,34. Kata Kunci : Hasil Belajar IPA, Guided Discovery, Contextual Teaching and Learning   Abstract. This research attempts to know the comparison of the results learning on subject’s science  class  after  using  learning  guided  discovery  approach  with  contextual teaching  and  learning  approach  to  their  student’s  grade  4  of  public  school Kramatwatu  7.  Research methodology used  is the method quasi  experiments, while design research used is non equivalent control group design.There are two classes  in  this  research,  namely  experiment  group  and  control  groups.  The experiment group that is a

  2. Cell surface antigens of radiation leukemia virus-induced BALB/c leukemias defined by syngeneic cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Kaneko, Yukio; Oettgen, H.F.; Obata, Yuichi; Nakayama, Eiichi.

    1989-01-01

    Two cell surface antigens of mouse leukemias were defined by BALB/c cytotoxic T lymphocytes (CTL) generated against syngeneic radiation leukemia virus (RadLV)-induced leukemia, BALBRV1 or BALBRVD. Hyperimmunization of BALB/c mice with irradiated leukemias followed by in vitro sensitization of primed spleen cells resulted in the generation of CTL with high killing activity. The specificity of CTL was examined by direct cytotoxicity assays and competitive inhibition assays. A shared cell surface antigen, designated as BALBRV1 antigen, was detected by BALB/c anti-BALBRV1 CTL. BALBRV1 antigen was expressed not only on RadLV-induced BALB/c leukemias except for BALBRVD, but also on spontaneous or X-ray-induced BALB/c leukemias, chemically-induced leukemias with the H-2 d haplotype and some chemically-induced BALB/c sarcomas. In contrast, a unique cell surface antigen, designated as BALBRVD antigen, was detected by BALB/c anti-BALBRVD CTL. BALBRVD antigen was expressed only on BALBRVD, but not on thirty-nine normal lymphoid or tumor cells. These two antigens could be distinguished from those previously defined on Friend, Moloney, Rauscher or Gross murine leukemia virus (MuLV) leukemias, or MuLV-related antigens. Both cytotoxic responses were blocked by antisera against H-2K d , but not H-2D d . The relationship of BALBRV1 antigen and BALBRVD antigen to endogenous MuLV is discussed with regard to the antigenic distribution on tumor cell lines. (author)

  3. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Directory of Open Access Journals (Sweden)

    Danushka K Wijesundara

    Full Text Available Qualitative characteristics of cytotoxic CD8+ T cells (CTLs are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV-HIV prime followed by a recombinant vaccinia virus (VV-HIV booster were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold, to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  4. Use of an in vivo FTA assay to assess the magnitude, functional avidity and epitope variant cross-reactivity of T cell responses following HIV-1 recombinant poxvirus vaccination.

    Science.gov (United States)

    Wijesundara, Danushka K; Ranasinghe, Charani; Jackson, Ronald J; Lidbury, Brett A; Parish, Christopher R; Quah, Benjamin J C

    2014-01-01

    Qualitative characteristics of cytotoxic CD8+ T cells (CTLs) are important in measuring the effectiveness of CTLs in controlling HIV-1 infections. Indeed, in recent studies patients who are naturally resistant to HIV-1 infections have been shown to possess CTLs that are of high functional avidity and have a high capacity to recognize HIV epitope variants, when compared to HIV-1 infection progressors. When developing efficacious vaccines, assays that can effectively measure CTL quality specifically in vivo are becoming increasingly important. Here we report the use of a recently developed high-throughput multi-parameter technique, known as the fluorescent target array (FTA) assay, to simultaneously measure CTL killing magnitude, functional avidity and epitope variant cross-reactivity in real time in vivo. In the current study we have applied the FTA assay as a screening tool to assess a large cohort of over 20 different HIV-1 poxvirus vaccination strategies in mice. This screen revealed that heterologous poxvirus prime-boost vaccination regimes (i.e., recombinant fowlpox (FPV)-HIV prime followed by a recombinant vaccinia virus (VV)-HIV booster) were the most effective in generating high quality CTL responses in vivo. In conclusion, we have demonstrated how the FTA assay can be utilized as a cost effective screening tool (by reducing the required number of animals by >100 fold), to evaluate a large range of HIV-1 vaccination strategies in terms of CTL avidity and variant cross-reactivity in an in vivo setting.

  5. Generation of murine tumor cell lines deficient in MHC molecule surface expression using the CRISPR/Cas9 system.

    Directory of Open Access Journals (Sweden)

    Krishna Das

    Full Text Available In this study, the CRISPR/Cas9 technology was used to establish murine tumor cell lines, devoid of MHC I or MHC II surface expression, respectively. The melanoma cell line B16F10 and the murine breast cancer cell line EO-771, the latter stably expressing the tumor antigen NY-BR-1 (EO-NY, were transfected with an expression plasmid encoding a β2m-specific single guide (sgRNA and Cas9. The resulting MHC I negative cells were sorted by flow cytometry to obtain single cell clones, and loss of susceptibility of peptide pulsed MHC I negative clones to peptide-specific CTL recognition was determined by IFNγ ELISpot assay. The β2m knockout (KO clones did not give rise to tumors in syngeneic mice (C57BL/6N, unless NK cells were depleted, suggesting that outgrowth of the β2m KO cell lines was controlled by NK cells. Using sgRNAs targeting the β-chain encoding locus of the IAb molecule we also generated several B16F10 MHC II KO clones. Peptide loaded B16F10 MHC II KO cells were insusceptible to recognition by OT-II cells and tumor growth was unaltered compared to parental B16F10 cells. Thus, in our hands the CRISPR/Cas9 system has proven to be an efficient straight forward strategy for the generation of MHC knockout cell lines. Such cell lines could serve as parental cells for co-transfection of compatible HLA alleles together with human tumor antigens of interest, thereby facilitating the generation of HLA matched transplantable tumor models, e.g. in HLAtg mouse strains of the newer generation, lacking cell surface expression of endogenous H2 molecules. In addition, our tumor cell lines established might offer a useful tool to investigate tumor reactive T cell responses that function independently from MHC molecule surface expression by the tumor.

  6. Recognizing, Confronting, and Eliminating Workplace Bullying.

    Science.gov (United States)

    Berry, Peggy Ann; Gillespie, Gordon L; Fisher, Bonnie S; Gormley, Denise K

    2016-07-01

    Workplace bullying (WPB) behaviors negatively affect nurse productivity, satisfaction, and retention, and hinder safe patient care. The purpose of this article is to define WPB, differentiate between incivility and WPB, and recommend actions to prevent WPB behaviors. Informed occupational and environmental health nurses and nurse leaders must recognize, confront, and eliminate WPB in their facilities and organizations. Recognizing, confronting, and eliminating WPB behaviors in health care is a crucial first step toward sustained improvements in patient care quality and the health and safety of health care employees. © 2016 The Author(s).

  7. Recognizing textual entailment models and applications

    CERN Document Server

    Dagan, Ido; Sammons, Mark

    2013-01-01

    In the last few years, a number of NLP researchers have developed and participated in the task of Recognizing Textual Entailment (RTE). This task encapsulates Natural Language Understanding capabilities within a very simple interface: recognizing when the meaning of a text snippet is contained in the meaning of a second piece of text. This simple abstraction of an exceedingly complex problem has broad appeal partly because it can be conceived also as a component in other NLP applications, from Machine Translation to Semantic Search to Information Extraction. It also avoids commitment to any sp

  8. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.

    Directory of Open Access Journals (Sweden)

    Caroline B Madsen

    Full Text Available Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr, STn (NeuAcα2-6GalNAc-Ser/Thr, T (Galβ1-3GalNAc-Ser/Thr, and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn. Glyco-engineering was performed by zinc finger nuclease (ZFN knockout (KO of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC and cytotoxic T lymphocyte (CTL-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.

  9. 76 FR 33419 - Nationally Recognized Statistical Rating Organizations

    Science.gov (United States)

    2011-06-08

    ... 232, 240, 249, et al. Nationally Recognized Statistical Rating Organizations; Proposed Rule #0;#0...-11] RIN 3235-AL15 Nationally Recognized Statistical Rating Organizations AGENCY: Securities and... rating organizations (``NRSROs''). In addition, in accordance with the Dodd-Frank Act, the Commission is...

  10. Recognizing Body Dysmorphic Disorder (Dysmorphophobia)

    Science.gov (United States)

    Varma, Anukriti; Rastogi, Rajesh

    2015-01-01

    Dysmorphophobia is a psychiatric condition which frequently presents in the clinics of dermatologists and plastic surgeons. This disorder (also called body dysmorphic disorder) is troublesome to the patient whilst being confusing for the doctor. This commonly undiagnosed condition can be detected by a few simple steps. Timely referral to a psychiatrist benefits most patients suffering from it. This article describes with a case vignette, how to recognize body dysmorphic disorder presenting in the dermatological or aesthetic surgery set up. Diagnostic criteria, eitiology, approach to patient, management strategy and when to refer are important learning points. The importance of recognizing this disorder timely and referring the patient to the psychiatrist for appropriate treatment is crucial. This article covers all aspects of body dysmorphic disorder relevant to dermatologists and plastic surgeons and hopes to be useful in a better understanding of this disorder. PMID:26644741

  11. 46 CFR 188.10-59 - Recognized classification society.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Recognized classification society. 188.10-59 Section 188... VESSELS GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 188.10-59 Recognized classification society. This term means the American Bureau of Shipping or other classification society...

  12. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

    International Nuclear Information System (INIS)

    Chu, G.; Chang, E.

    1990-01-01

    Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair

  13. Recognizing Facial Slivers.

    Science.gov (United States)

    Gilad-Gutnick, Sharon; Harmatz, Elia Samuel; Tsourides, Kleovoulos; Yovel, Galit; Sinha, Pawan

    2018-07-01

    We report here an unexpectedly robust ability of healthy human individuals ( n = 40) to recognize extremely distorted needle-like facial images, challenging the well-entrenched notion that veridical spatial configuration is necessary for extracting facial identity. In face identification tasks of parametrically compressed internal and external features, we found that the sum of performances on each cue falls significantly short of performance on full faces, despite the equal visual information available from both measures (with full faces essentially being a superposition of internal and external features). We hypothesize that this large deficit stems from the use of positional information about how the internal features are positioned relative to the external features. To test this, we systematically changed the relations between internal and external features and found preferential encoding of vertical but not horizontal spatial relationships in facial representations ( n = 20). Finally, we employ magnetoencephalography imaging ( n = 20) to demonstrate a close mapping between the behavioral psychometric curve and the amplitude of the M250 face familiarity, but not M170 face-sensitive evoked response field component, providing evidence that the M250 can be modulated by faces that are perceptually identifiable, irrespective of extreme distortions to the face's veridical configuration. We theorize that the tolerance to compressive distortions has evolved from the need to recognize faces across varying viewpoints. Our findings help clarify the important, but poorly defined, concept of facial configuration and also enable an association between behavioral performance and previously reported neural correlates of face perception.

  14. Dendritic cells loaded with HeLa-derived exosomes simulate an antitumor immune response.

    Science.gov (United States)

    Ren, Guoping; Wang, Yanhong; Yuan, Shexia; Wang, Baolian

    2018-05-01

    The aim of the present study was to investigate the effect of loading dendritic cells (DCs) with HeLa-derived exosomes on cytotoxic T-lymphocyte (CTL) responses, and the cytotoxic effects of CTL responses on the HeLa cell line. Ultrafiltration centrifugation combined with sucrose density gradient ultracentrifugation was applied to isolate exosomes (HeLa-exo) from the supernatant of HeLa cells. Morphological features of HeLa-exo were identified by transmission electron microscopy (TEM), and the expression of cluster of differentiation (CD)63 was detected by western blotting. Next, monocytes were isolated from peripheral blood and cultured with the removal of adherent cells to induce DC proliferation. DCs were then phenotypically characterized by flow cytometry. Finally, MTT assays were performed to analyze the effects of DCs loaded with HeLa-exo on T cell proliferation and cytotoxicity assays to evaluate the effect of CTL responses on HeLa cells. TEM revealed that HeLa-exo exhibit typical cup-shaped morphology with a diameter range of 30-100 nm. It was also identified that the CD63 surface antigen is expressed on HeLa-exo. Furthermore, monocyte-derived DCs were able to express CD1a, suggesting that DC induction was a success. DCs exhibited hair-like protrusions and other typical dendritic cell morphology. Furthermore, DCs loaded with HeLa-exo could enhance CTL proliferation and the cytotoxic activity of CTLs compared with DCs without HeLa-exo (PHeLa-exo may promote T cell proliferation and induce CTL responses to inhibit the growth of cervical cancer cells in vitro .

  15. Recognizing Multi-user Activities using Body Sensor Networks

    DEFF Research Database (Denmark)

    Gu, Tao; Wang, Liang; Chen, Hanhua

    2011-01-01

    The advances of wireless networking and sensor technology open up an interesting opportunity to infer human activities in a smart home environment. Existing work in this paradigm focuses mainly on recognizing activities of a single user. In this work, we address the fundamental problem...... activity classes of data—for building activity models and design a scalable, noise-resistant, Emerging Pattern based Multi-user Activity Recognizer (epMAR) to recognize both single- and multi-user activities. We develop a multi-modal, wireless body sensor network for collecting real-world traces in a smart...... home environment, and conduct comprehensive empirical studies to evaluate our system. Results show that epMAR outperforms existing schemes in terms of accuracy, scalability and robustness....

  16. Do You Recognize This Parent?

    Science.gov (United States)

    Wallace, Edna

    1997-01-01

    Suggests effective ways to work with parents who may be permissive, busy, detached, overprotective, or negative. Recommends that child care professionals be sensitive and understanding, recognize other demands on parents' time and communicate competitively with them, use terms parents understand, accept various levels of parental involvement, be…

  17. Autologous monoclonal antibodies recognize tumour-associated antigens in X-irradiated C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Artus, A; Guillemain, B; Legrand, E; Astier-Gin, T; Mamoun, R; Duplan, J -F

    1986-09-01

    X-irradiation of C57BL/6 mice induces thymic lymphosarcomas which sometimes contain retroviruses which upon injection into normal mice mimic the effect of the irradiation. We examined whether specific antigenicities, viral or cellular, were expressed by tumour cells that could be recognized by antibodies from the irradiated animals. We developed monoclonal antibodies (MAbs) using splenocytes of the diseased animal. The reactivity of such MAbs towards thymoma cell lines established in vitro was investigated by means of an ELISA. At least 10 antibody specificities were detected on the 13 tumours investigated, allowing separation of the MAbs into three classes: (i) those recognizing the autologous tumour, heterologous tumours as well as normal thymic tissue, (ii) those specific for the autologous tumour, and (iii) those specific for one tumour, but not ones of autologous origin. The last two classes corresponded to specific tumour-associated antigens. Our panel of MAbs defined each tumour by the particular pattern of antigens harboured. It is striking that most of the antigens were present in the normal thymus and that only two tumours had additional antigenicities. Additionally, quantitative variations were observed in the levels of expression of these antigens.

  18. Equipping African American Clergy to Recognize Depression.

    Science.gov (United States)

    Anthony, Jean Spann; Morris, Edith; Collins, Charles W; Watson, Albert; Williams, Jennifer E; Ferguson, Bʼnai; Ruhlman, Deborah L

    2016-01-01

    Many African Americans (AAs) use clergy as their primary source of help for depression, with few being referred to mental health providers. This study used face-to-face workshops to train AA clergy to recognize the symptoms and levels of severity of depression. A pretest/posttest format was used to test knowledge (N = 42) about depression symptoms. Results showed that the participation improved the clergy's ability to recognize depression symptoms. Faith community nurses can develop workshops for clergy to improve recognition and treatment of depression.

  19. Recognizing and Managing Interpersonal Conflict.

    Science.gov (United States)

    Deane, Nancy; Hovland, Michael

    1993-01-01

    Practical advice is offered, to managers and supervisors at any level, on recognizing and analyzing interpersonal conflicts, managing such conflicts and making them productive, and ensuring that performance reviews result in progress for both supervisor and employee. Conflict is seen as inevitable, an opportunity to take action, and manageable.…

  20. Recognizing Prefixes in Scientific Quantities

    Science.gov (United States)

    Sokolowski, Andrzej

    2015-01-01

    Although recognizing prefixes in physical quantities is inherent for practitioners, it might not be inherent for students, who do not use prefixes in their everyday life experiences. This deficiency surfaces in AP Physics exams. For example, readers of an AP Physics exam reported "a common mistake of incorrectly converting nanometers to…

  1. Gram-positive bacterial lipoglycans based on a glycosylated diacylglycerol lipid anchor are microbe-associated molecular patterns recognized by TLR2.

    Directory of Open Access Journals (Sweden)

    Landry Blanc

    Full Text Available Innate immune recognition is the first line of host defense against invading microorganisms. It is a based on the detection, by pattern recognition receptors (PRRs, of invariant molecular signatures that are unique to microorganisms. TLR2 is a PRR that plays a major role in the detection of Gram-positive bacteria by recognizing cell envelope lipid-linked polymers, also called macroamphiphiles, such as lipoproteins, lipoteichoic acids and mycobacterial lipoglycans. These microbe-associated molecular patterns (MAMPs display a structure based on a lipid anchor, being either an acylated cysteine, a glycosylated diacylglycerol or a mannosyl-phosphatidylinositol respectively, and having in common a diacylglyceryl moiety. A fourth class of macroamphiphile, namely lipoglycans, whose lipid anchor is made, as for lipoteichoic acids, of a glycosylated diacylglycerol unit rather than a mannosyl-phosphatidylinositol, is found in Gram-positive bacteria and produced by certain Actinobacteria, including Micrococcus luteus, Stomatococcus mucilaginosus and Corynebacterium glutamicum. We report here that these alternative lipoglycans are also recognized by TLR2 and that they stimulate TLR2-dependant cytokine production, including IL-8, TNF-α and IL-6, and cell surface co-stimulatory molecule CD40 expression by a human macrophage cell line. However, they differ by their co-receptor requirement and the magnitude of the innate immune response they elicit. M. luteus and S. mucilaginosus lipoglycans require TLR1 for recognition by TLR2 and induce stronger responses than C. glutamicum lipoglycan, sensing of which by TLR2 is dependent on TLR6. These results expand the repertoire of MAMPs recognized by TLR2 to lipoglycans based on a glycosylated diacylglycerol lipid anchor and reinforce the paradigm that macroamphiphiles based on such an anchor, including lipoteichoic acids and alternative lipoglycans, induce TLR2-dependant innate immune responses.

  2. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  3. Self-recognition specificity expressed by T cells from nude mice. Absence of detectable Ia-restricted T cells in nude mice that do exhibit self-K/D-restricted T cell responses

    International Nuclear Information System (INIS)

    Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.; Longo, D.L.

    1984-01-01

    The presence in athymic nude mice of precursor T cells with self-recognition specificity for either H-2 K/D or H-2 I region determinants was investigated. Chimeras were constructed of lethally irradiated parental mice receiving a mixture of F1 nude mouse (6-8 wk old) spleen and bone marrow cells. The donor inoculum was deliberately not subjected to any T cell depletion procedure, so that any potential major histocompatibility complex-committed precursor T cells were allowed to differentiate and expand in the normal parental recipients. 3 mo after reconstitution, the chimeras were immunized with several protein antigens in complete Freund's adjuvant in the footpads and their purified draining lymph node T cells tested 10 d later for ability to recognize antigen on antigen-presenting cells of either parental haplotype. Also, their spleen and lymph node cells were tested for ability to generate a cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified stimulator cells of either parental haplotype. It was demonstrated that T cell proliferative responses of these F1(nude)----parent chimeras were restricted solely to recognizing parental host I region determinants as self and expressed the Ir gene phenotype of the host. In contrast, CTL responses could be generated (in the presence of interleukin 2) to TNP-modified stimulator cells of either parental haplotype. Thus these results indicate that nude mice which do have CTL with self-specificity for K/D region determinants lack proliferating T cells with self-specificity for I region determinants. These results provide evidence for the concepts that development of the I region-restricted T cell repertoire is strictly an intrathymically determined event and that young nude mice lack the unique thymic elements responsible for education of I region-restricted T cells

  4. FEDIX on-line information service: Design, develop, test, and implement an on-line research and education information service. Annual status report, September 1992--August 1993

    Energy Technology Data Exchange (ETDEWEB)

    Rodman, J.A.

    1993-08-01

    Federal Information Exchange, Inc. (FIE) is a diversified information services company that is recognized as the major electronic link between the higher education community and the Federal government in the field of research administration. FIE provides a range of information related services to the government, academic and private sectors, including database management, software development and technical support. FEDIX is the on-line information service designed, developed and implemented by FIE to accomplish the following objectives: (1). Broaden the participation of the education community in Federal research and education programs by providing free and unrestricted on-line access to information from all participating Federal agencies; and (2). Provide the education community with on-line access to a single keyword-searchable system for research and educational funding opportunities at the participating Federal agencies.

  5. Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Aurélie Durgeau

    2018-01-01

    Full Text Available Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA-4 and programmed cell death (PD-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI. Cytotoxic T lymphocytes (CTL eliminate malignant cells through recognition by the T-cell receptor (TCR of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B. T-cell adhesion molecules and, in particular, lymphocyte-function-associated antigen-1 and CD103 integrins, and their cognate ligands, respectively, intercellular adhesion molecule 1 and E-cadherin, on target cells, are involved in strengthening the interaction between CTL and tumor cells. Tumor-specific CTL have been isolated from tumor-infiltrating lymphocytes and peripheral blood lymphocytes (PBL of patients with varied cancers. TCRβ-chain gene usage indicated that CTL identified in vitro selectively expanded in vivo at the tumor site compared to autologous PBL. Moreover, functional studies indicated that these CTL mediate human leukocyte antigen class I-restricted cytotoxic activity toward autologous tumor cells. Several of them recognize truly tumor-specific antigens encoded by mutated genes, also known as neoantigens, which likely play a key role in antitumor CD8 T-cell immunity. Accordingly, it has been shown that the presence of T lymphocytes directed toward tumor neoantigens is associated with patient response to immunotherapies, including ICI, adoptive cell transfer

  6. Ionizing radiation affects generation of MART-1-specific cytotoxic T cell responses by dendritic cells

    International Nuclear Information System (INIS)

    Liao, Y.P.; Wang, C.-C.; McBride, W.H.

    2003-01-01

    Full text: The human MART-1/Melan-A (MART-1) melanoma tumor antigen is known to be recognized by cytotoxic T lymphocytes (CTLs) and several groups are using this target for clinical immunotherapy. Most approaches use dendritic cells (DCs) that are potent antigen presentation cells for initiating CTL responses. In order for CTL recognition to occur, DCs must display 9-residue antigenic peptides on MHC class I molecules. These peptides are generated by proteasome degradation and then transported through the endoplasmic reticulum to the cell surface where they stabilize MHC class I expression. Our previous data showed that irradiation inhibits proteasome function and, therefore, we hypothesized that irradiation may inhibit antigen processing and CTL activation, as has been shown for proteasome inhibitors. To study the importance of irradiation effects on DCs, we studied the generation MART-1-specific CTL responses. Preliminary data showed that irradiation of murine bone marrow derived DCs did not affect expression of MHC class I, II, CD80, or CD86, as assessed by flow cytometric analyses 24-hour after irradiation. The effect of irradiation on MART-1 antigen processing by DCs was evaluated using DC transduced with adenovirus MART-1 (AdVMART1). C57BL/6 mice were immunized with AdVMART1 transduced DCs, with and without prior irradiation. IFN-γ production was measured by ELISPOT assays after 10-14 days of immunization. Prior radiation treatment resulted in a significant decrease in MART-1-specific T cell responses. The ability of irradiated and non-irradiated AdVMART1/DC vaccines to protect mice against growth of murine B16 tumors, which endogenously express murine MART-1, was also examined. AdVMART1/DC vaccination protected C57BL/6 mice against challenge with viable B16 melanoma cells while DCs irradiated (10 Gy) prior to AdVMART1 transduction abrogated protection. These results suggest that proteasome inhibition in DCs by irradiation may be a possible pathway in

  7. Focusing errors in radiography - how they can be recognized and avoided. 2. rev. ed.

    International Nuclear Information System (INIS)

    Zimmer, E.A.; Zimmer-Brossy, M.

    1979-01-01

    The importance of the problem of recognizing and judging focusing errors for the daily practice has caused the authors to give this systematic and abundantly pictured account of the most frequent focusing errors, for as yet no such book has been published either in Germany or abroad. To keep it as concise and handy as possible the authors have restricted themselves to the most important standard pictures and omitted to list errors such as: blurred pictures owing to breathing or movement as well as under and overexposed pictures, which are easy to recognize and avoid. By contrast, they describe in detail those characteristic points and lines of orientation that must be checked to verify the technical quality of an X-ray picture. Knowledge of the typical aspects in a correctly focused X-ray picture is a precondition for understanding incorrectly focused pictures which have some characteristic properties as well. Proper interpretation of an incorrectly focused picture then permits to detect also the cause of the focusing error, be it false centring or false positioning. Thus quick and aimed correction becomes possible. To avoid unnecessary repeat X-rays, which are self-prohibitive for reasons of radiation protection alone, each chapter contains at the end a remark starting in which cases the medical indication requires the repetition of an unserviceable X-ray. (orig./ORU) [de

  8. Burnout: Recognize and Reverse.

    Science.gov (United States)

    Anne, Samantha

    2014-07-01

    Physician burnout may be underrecognized and can cause significant detrimental effects on personal health and job satisfaction. Burnout has been associated with medical errors, alcohol and drug abuse, and neglect and abandonment of career goals. With self-awareness, development of coping mechanisms, and the adoption of a strong social and professional support network, burnout can be combated. This article focuses on recognizing characteristics of burnout and providing strategies to cope to avoid reaching a high degree of burnout. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

  9. A biased competition theory of cytotoxic T lymphocyte interaction with tumor nodules.

    Directory of Open Access Journals (Sweden)

    Claire Christophe

    Full Text Available The dynamics of the interaction between Cytotoxic T Lymphocytes (CTL and tumor cells has been addressed in depth, in particular using numerical simulations. However, stochastic mathematical models that take into account the competitive interaction between CTL and tumors undergoing immunoediting, a process of tumor cell escape from immunesurveillance, are presently missing. Here, we introduce a stochastic dynamical particle interaction model based on experimentally measured parameters that allows to describe CTL function during immunoediting. The model describes the competitive interaction between CTL and melanoma cell nodules and allows temporal and two-dimensional spatial progression. The model is designed to provide probabilistic estimates of tumor eradication through numerical simulations in which tunable parameters influencing CTL efficacy against a tumor nodule undergoing immunoediting are tested. Our model shows that the rate of CTL/tumor nodule productive collisions during the initial time of interaction determines the success of CTL in tumor eradication. It allows efficient cytotoxic function before the tumor cells acquire a substantial resistance to CTL attack, due to mutations stochastically occurring during cell division. Interestingly, a bias in CTL motility inducing a progressive attraction towards a few scout CTL, which have detected the nodule enhances early productive collisions and tumor eradication. Taken together, our results are compatible with a biased competition theory of CTL function in which CTL efficacy against a tumor nodule undergoing immunoediting is strongly dependent on guidance of CTL trajectories by scout siblings. They highlight unprecedented aspects of immune cell behavior that might inspire new CTL-based therapeutic strategies against tumors.

  10. Drawing and Recognizing Chinese Characters with Recurrent Neural Network.

    Science.gov (United States)

    Zhang, Xu-Yao; Yin, Fei; Zhang, Yan-Ming; Liu, Cheng-Lin; Bengio, Yoshua

    2018-04-01

    Recent deep learning based approaches have achieved great success on handwriting recognition. Chinese characters are among the most widely adopted writing systems in the world. Previous research has mainly focused on recognizing handwritten Chinese characters. However, recognition is only one aspect for understanding a language, another challenging and interesting task is to teach a machine to automatically write (pictographic) Chinese characters. In this paper, we propose a framework by using the recurrent neural network (RNN) as both a discriminative model for recognizing Chinese characters and a generative model for drawing (generating) Chinese characters. To recognize Chinese characters, previous methods usually adopt the convolutional neural network (CNN) models which require transforming the online handwriting trajectory into image-like representations. Instead, our RNN based approach is an end-to-end system which directly deals with the sequential structure and does not require any domain-specific knowledge. With the RNN system (combining an LSTM and GRU), state-of-the-art performance can be achieved on the ICDAR-2013 competition database. Furthermore, under the RNN framework, a conditional generative model with character embedding is proposed for automatically drawing recognizable Chinese characters. The generated characters (in vector format) are human-readable and also can be recognized by the discriminative RNN model with high accuracy. Experimental results verify the effectiveness of using RNNs as both generative and discriminative models for the tasks of drawing and recognizing Chinese characters.

  11. Recognizing Variable Environments The Theory of Cognitive Prism

    CERN Document Server

    Dong, Tiansi

    2012-01-01

    Normal adults do not have any difficulty in recognizing their homes. But can artificial systems do in the same way as humans? This book collects interdisciplinary evidences and presents an answer from the perspective of computing, namely, the theory of cognitive prism. To recognize an environment, an intelligent system only needs to classify objects, structures them based on the connection relation (not through measuring!), subjectively orders the objects, and compares with the target environment, whose knowledge is similarly structured. The intelligent system works, therefore, like a prism: when a beam of light (a scene) reaches (is perceived) to an optical prism (by an intelligent system), some light (objects) is reflected (are neglected), those passed through (the recognized objects) are distorted (are ordered differently). So comes the term 'cognitive prism'! Two fundamental propositions used in the theory can be informally stated as follow: an orientation relation is a kind of distance comparison relatio...

  12. Creation and evaluation of best cotton mutant lines

    International Nuclear Information System (INIS)

    Rastegari, S. J.; Hosseini, Z.

    2001-01-01

    During (1997-1999) a study was carried out to recognize the best mutant lines, which were already obtained from a mutation breeding project. A Triple Rectangular Latis Design (8 7) in form of randomized complete blocks (RCB) with fifty- six treatments and three replications, were used in Estahban, Kordkouy and Varamin, under different ecological conditions, rainfall (Kordkouy) desert (Varamin) hot and dry (Estahban). During growing season some important morphological characteristics were recorded. Some lines had specific characters, for example: line 3191 (Chirpan 150 gray) had a low leaf number per plant, line 3169 (Bakhtegan 200 gray) plants were clustered. The results of the data in Varamin station showed that Bakhtegan irradiated with 150 gray line 3485 and Tashkand with 300 gray line 3451 compared to check (Varamin with 4373 kg/ha) had highest yield with 4942 kg/ha, and 4871 kg/ha respectively. In view of boll weight line 3405 of Sahel irradiated with 200 gray had highest boll weight (6.5 g/boll). In Kordkouy station the best mutant line was Chirpan irradiated with 250 gray, line 3208, with 20% yield increase compared to Sahel and 30% yield increase compared to original Chirpan. In respect to irradiation effect on lint percentage and fiber quality, the results showed; there was a positive effect on lint percentage of all varieties, especially in Tashkant, Bakhtegan and Chirpan which are inherently weak in lint percentage. As a whole gamma radiation did not have any negative effect on fiber quality. Even in Estahban 1.6 to 2.4 mm fiber increase were observed in some Chirpan irradiated material (C150-3516) and (C200-3523)

  13. Kodune energiakulu kontrolli alla / Leo Backman, Heigo Ensling

    Index Scriptorium Estoniae

    Backman, Leo

    2012-01-01

    Energiakulumõõturite test: Axxel HH-549, Efergy e2 (juhtmevaba mõõtur), Electric EMT707CTL, Electronic PM 498, Electronic UPM DEM1379, Energy Meter LX-0805, Eco Line EM235, Energy Saving Meter HH-549, Art.35-617 (multifunktsionaalne mõõtur), EMT7110/EMR7370 (juhtmevaba mõõtur)

  14. Super-Memorizers Are Not Super-Recognizers

    NARCIS (Netherlands)

    Ramon, M.; Miellet, S.; Dzieciol, A.M.; Konrad, B.N; Dresler, M.; Caldara, R.

    2016-01-01

    Humans have a natural expertise in recognizing faces. However, the nature of the interaction between this critical visual biological skill and memory is yet unclear. Here, we had the unique opportunity to test two individuals who have had exceptional success in the World Memory Championships,

  15. Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.

    Science.gov (United States)

    Lorente, Elena; Barriga, Alejandro; García-Arriaza, Juan; Lemonnier, François A; Esteban, Mariano; López, Daniel

    2017-10-01

    The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized. By infection of HLA-A*0201-transgenic mice with a recombinant vaccinia virus that encodes the CHIKV structural polyprotein (rVACV-CHIKV), we identified the first human T cell epitopes from CHIKV. These three novel 6K transmembrane protein-derived epitopes are presented by the common HLA class I molecule, HLA-A*0201. One of these epitopes is processed and presented via a complex pathway that involves proteases from different subcellular locations. Specific chemical inhibitors blocked these events in rVACV-CHIKV-infected cells. Our data have implications not only for the identification of novel Alphavirus and Togaviridae antiviral CTL responses, but also for analyzing presentation of antigen from viruses of different families and orders that use host proteinases to generate their mature envelope proteins.

  16. The bacterial tubulin FtsZ requires its intrinsically disordered linker to direct robust cell wall construction.

    Science.gov (United States)

    Sundararajan, Kousik; Miguel, Amanda; Desmarais, Samantha M; Meier, Elizabeth L; Casey Huang, Kerwyn; Goley, Erin D

    2015-06-23

    The bacterial GTPase FtsZ forms a cytokinetic ring at midcell, recruits the division machinery and orchestrates membrane and peptidoglycan cell wall invagination. However, the mechanism for FtsZ regulation of peptidoglycan metabolism is unknown. The FtsZ GTPase domain is separated from its membrane-anchoring C-terminal conserved (CTC) peptide by a disordered C-terminal linker (CTL). Here we investigate CTL function in Caulobacter crescentus. Strikingly, production of FtsZ lacking the CTLCTL) is lethal: cells become filamentous, form envelope bulges and lyse, resembling treatment with β-lactam antibiotics. This phenotype is produced by FtsZ polymers bearing the CTC and a CTL shorter than 14 residues. Peptidoglycan synthesis still occurs downstream of ΔCTL; however, cells expressing ΔCTL exhibit reduced peptidoglycan crosslinking and longer glycan strands than wild type. Importantly, midcell proteins are still recruited to sites of ΔCTL assembly. We propose that FtsZ regulates peptidoglycan metabolism through a CTL-dependent mechanism that extends beyond simple protein recruitment.

  17. NuCoal CTL wood mountain project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-09-15

    The province of Saskatchewan experienced significant growth between 2005 and 2008. The growing economy included an abundance of different commodities and made Saskatchewan the newest hub for the latest technologies and investment. This report outlined the various opportunities in Saskatchewan for a coal to liquids plant and its technologies. The coal from southern Saskatchewan is generally lignite, which is found in the Ravenscrag Formation near the Big Muddy Badlands. The report discussed the Ravenscrag Formation as well as mining activity that was largely concentrated near Estevan and Bienfait in southeastern Saskatchewan, where Sherritt International operated two surface mines. The Coronach Poplar River Power Station, located 10 kilometres north of the Canada-United States border in southern Saskatchewan was also discussed. Population density, labour, land use, First Nations, and proximity to major centres were factors that were discussed. The programs that were identified included the Saskatchewan immigrant nominee program, an alternative program to the Canadian federal immigration program for those who want to come to Saskatchewan as a permanent resident of Canada; the Weyburn-Midale carbon dioxide project, the world's first carbon dioxide measuring, monitoring and verification initiative; and the Federated Co-op in Regina, a 100,000 barrel/day refinery located close to the Coronach area in Saskatchewan. Political climate, access to the electrical grid, access to water, access to major pipelines, access to rail lines, and access to highways were other topics that were presented. It was concluded that southern Saskatchewan had a broad range of opportunities for a coal to liquids plant. The area has numerous advantages including access to rail and pipelines. refs., tabs., figs., appendices.

  18. The roles of categorical and coordinate spatial relations in recognizing buildings.

    Science.gov (United States)

    Palermo, Liana; Piccardi, Laura; Nori, Raffaella; Giusberti, Fiorella; Guariglia, Cecilia

    2012-11-01

    Categorical spatial information is considered more useful for recognizing objects, and coordinate spatial information for guiding actions--for example, during navigation or grasping. In contrast with this assumption, we hypothesized that buildings, unlike other categories of objects, require both categorical and coordinate spatial information in order to be recognized. This hypothesis arose from evidence that right-brain-damaged patients have deficits in both coordinate judgments and recognition of buildings and from the fact that buildings are very useful for guiding navigation in urban environments. To test this hypothesis, we assessed 210 healthy college students while they performed four different tasks that required categorical and coordinate judgments and the recognition of common objects and buildings. Our results showed that both categorical and coordinate spatial representations are necessary to recognize a building, whereas only categorical representations are necessary to recognize an object. We discuss our data in view of a recent neural framework for visuospatial processing, suggesting that recognizing buildings may specifically activate the parieto-medial-temporal pathway.

  19. Induction of immunity to antigens expressed by recombinant adeno-associated virus depends on the route of administration.

    Science.gov (United States)

    Brockstedt, D G; Podsakoff, G M; Fong, L; Kurtzman, G; Mueller-Ruchholtz, W; Engleman, E G

    1999-07-01

    Recombinant adeno-associated virus (rAAV) is a replication-defective parvovirus which is being explored as a vector for gene therapy because of its broad host range, excellent safety profile, and durable transgene expression in infected hosts. rAAV has also been reported by several groups to induce little or no immune response to its encoded transgene products. In this study we examined the immunogenicity of rAAV by studying the immune response of C57BL/6 mice to a single dose of rAAV-encoding ovalbumin (AAV-Ova) administered by a variety of routes. Mice injected with AAV-Ova intraperitoneally (ip), intravenously, or subcutaneously developed potent ovalbumin-specific cytotoxic T lymphocytes (CTL) as well as anti-ovalbumin antibodies and antibodies to AAV. In contrast, mice injected with AAV-Ova intramuscularly developed a humoral response to the virus and the transgene but minimal ovalbumin-specific CTLs. The induced CTL response after ip administration of AAV-Ova protected mice against a subsequent tumor challenge with an ovalbumin-transfected B16 melanoma cell line. Studies of the mechanism by which AAV-Ova induces CTL confirmed that the virus delivers the transgene product into the classical MHC class I pathway of antigen processing. Mice that previously had been exposed to rAAV vectors failed to develop ovalbumin-specific CTL following administration of AAV-Ova. Analysis of these mice revealed the presence of circulating anti-AAV antibodies that blocked rAAV transduction in vitro and inhibited CTL induction in vivo. These results suggest a possible role for rAAV in the immunotherapy of malignancies and viral infections, although induced antibody responses to AAV may limit its ability to be administered for repeated vaccinations. Copyright 1999 Academic Press.

  20. Antarctic skuas recognize individual humans.

    Science.gov (United States)

    Lee, Won Young; Han, Yeong-Deok; Lee, Sang-Im; Jablonski, Piotr G; Jung, Jin-Woo; Kim, Jeong-Hoon

    2016-07-01

    Recent findings report that wild animals can recognize individual humans. To explain how the animals distinguish humans, two hypotheses are proposed. The high cognitive abilities hypothesis implies that pre-existing high intelligence enabled animals to acquire such abilities. The pre-exposure to stimuli hypothesis suggests that frequent encounters with humans promote the acquisition of discriminatory abilities in these species. Here, we examine individual human recognition abilities in a wild Antarctic species, the brown skua (Stercorarius antarcticus), which lives away from typical human settlements and was only recently exposed to humans due to activities at Antarctic stations. We found that, as nest visits were repeated, the skua parents responded at further distances and were more likely to attack the nest intruder. Also, we demonstrated that seven out of seven breeding pairs of skuas selectively responded to a human nest intruder with aggression and ignored a neutral human who had not previously approached the nest. The results indicate that Antarctic skuas, a species that typically inhabited in human-free areas, are able to recognize individual humans who disturbed their nests. Our findings generally support the high cognitive abilities hypothesis, but this ability can be acquired during a relatively short period in the life of an individual as a result of interactions between individual birds and humans.

  1. A survey of exposures related to recognized occupational contact dermatitis in Denmark in 2010

    DEFF Research Database (Denmark)

    Carøe, Tanja Korfitsen; Ebbehøj, Niels; Agner, Tove

    2014-01-01

    BACKGROUND: Skin diseases are the most commonly recognized occupational diseases in Denmark, and occupational contact dermatitis (OCD) comprises ∼95% of all cases. OBJECTIVES: To prevent occupational contact dermatitis, it is important to specifically identify exposures and work routines related...... to outbreak of the disease. The aim of this study was to give an overview of exposures for patients with occupational contact dermatitis in Denmark in 2010, and relate this to line of work and disease severity. MATERIAL AND METHODS: The study was a descriptive, register-based study including patients......, 1020 women and 484 men, were included in the study. Irritant contact dermatitis accounted for 70% of all cases; 68% of these were caused by wet work. Forty-six per cent of all patients were employed either in the healthcare sector, in cleaning, or as kitchen workers. Among contact allergies, the most...

  2. UPAYA PENINGKATAN KEAKTIFAN DAN HASIL BELAJAR MATEMATIKAMELALUI PENDEKATAN CONTEXTUAL TEACHING AND LEARNING (CTL BERBANTUAN ALAT PERAGA PADA SISWA KELAS 5 SDN LODOYONG 03 – AMBARAWA TAHUN PELAJARAN 2013/2014

    Directory of Open Access Journals (Sweden)

    Nova Dinda Taurina

    2015-12-01

    Full Text Available Penelitian ini didasarkan pada kenyataan bahwa guru kurang optimal dalam pembelajaran matematika. Metode pembelajaran yang sering digunakan adalah ceramah, dan guru tidak menggunakan alat peraga dalam pembelajaran. Hal tersebut menyebabkan rendahnya keaktifan siswa dan berdampak pada rendahnya hasil belajar mereka. Sebanyak 62% atau 13 siswa dari 21 siswa tidak dapat mencapai nilai ≥ KKM sebesar 70. Berdasar dari permasalahan tersebut, maka penelitian ini bertujuan untuk meningkatkan keaktifan dan hasil belajar matematika pada siswa kelas 5 SDN Lodoyong 03 Kecamatan Ambarawa Tahun Pelajaran 2013/2014 melalui pendekatan CTL berbantuan alat peraga. Jenis penelitian ini adalah penelitian tindakan kelas atau PTK. Model PTK yang digunakan adalah model Kemmis dan Taggart yang terdiri dari empat tahapan yaitu tahap perencanaan, pelaksanaan, observasi, dan refleksi. Adapun yang menjadi subyek penelitian ini adalah siswa kelas 5 SDN Lodoyong 03 berjumlah 21 siswa, yang terdiri dari 14 siswa laki-laki dan 7 siswa perempuan. Teknik pengumpulan data menggunakan teknik tes, observasi, wawancara dan dokumentasi. Instrumen penelitiannya berupa lembar evaluasi berbentuk isian dan uraian, lembar observasi aktivitas guru dan siswa, serta lembar wawancara guru dan siswa. Indikator keberhasilan penelitian ini sebesar 80% atau sekitar 17 siswa harus mencapai nilai ≥ KKM sebesar 70 dan harus aktif dalam pembelajaran. Adapun teknik analisis data yang digunakan adalah analisis ketuntasan dan analisis komparatif. Hasil penelitian menunjukkan adanya peningkatan hasil belajar siswa. Pada pra siklus hanya 8 siswa (38% yang tuntas dan 13 siswa lainnya (62% belum tuntas. Pada siklus I jumlah siswa yang tuntas meningkat menjadi 13 siswa (62%, sedangkan 8 siswa (38% belum tuntas. Kemudian pada siklus II meningkat lagi menjadi 17 siswa (81% yang tuntas, dan hanya 4 siswa (19% yang belum tuntas. Hal tersebut berarti bahwa penelitian ini berhasil, karena telah mencapai

  3. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby; Lundegaard, Claus; Lamberth, K.

    2007-01-01

    BACKGROUND: Reliable predictions of Cytotoxic T lymphocyte (CTL) epitopes are essential for rational vaccine design. Most importantly, they can minimize the experimental effort needed to identify epitopes. NetCTL is a web-based tool designed for predicting human CTL epitopes in any given protein....... of the other methods achieved a sensitivity of 0.64. The NetCTL-1.2 method is available at http://www.cbs.dtu.dk/services/NetCTL.All used datasets are available at http://www.cbs.dtu.dk/suppl/immunology/CTL-1.2.php....

  4. A NON-ISOTHERMAL THEORY FOR INTERPRETING SODIUM LINES IN TRANSMISSION SPECTRA OF EXOPLANETS

    Energy Technology Data Exchange (ETDEWEB)

    Heng, Kevin; Lavie, Baptiste [University of Bern, Physics Institute, Center for Space and Habitability, Sidlerstrasse 5, CH-3012 Bern (Switzerland); Wyttenbach, Aurélien; Ehrenreich, David; Lovis, Christophe [Observatoire de l’Université de Genève, 51 chemin des Maillettes, CH-1290 Sauverny (Switzerland); Sing, David K., E-mail: kevin.heng@csh.unibe.ch [Astrophysics Group, School of Physics, University of Exeter, Stocker Road, Exeter EX4 4QL (United Kingdom)

    2015-04-10

    We present a theory for interpreting the sodium lines detected in transmission spectra of exoplanetary atmospheres. Previous analyses employed the isothermal approximation and dealt only with the transit radius. By recognizing the absorption depth and the transit radius as being independent observables, we develop a theory for jointly interpreting both quantities, which allows us to infer the temperatures and number densities associated with the sodium lines. We are able to treat a non-isothermal situation with a constant temperature gradient. Our novel diagnostics take the form of simple-to-use algebraic formulae and require measurements of the transit radii (and their corresponding absorption depths) at line center and in the line wing for both sodium lines. We apply our diagnostics to the HARPS data of HD 189733b, confirm the upper atmospheric heating reported by Huitson et al., derive a temperature gradient of 0.4376 ± 0.0154 K km{sup −1}, and find densities ∼1–10{sup 4} cm{sup −3}.

  5. Production of interferon-¿ and interleukin-4 by human T cells recognizing Leishmania lipophosphoglycan-associated protein

    DEFF Research Database (Denmark)

    Kemp, M; Kurtzhals, J A; Christensen, C B

    1993-01-01

    The Leishmania protein LPGAP which is co-isolated with lipophosphoglycan is a specific activator of T cells from individuals who have recovered from American leishmaniasis. We have tested the effect of LPGAP on peripheral blood mononuclear cells (PBMC) from Kenyan donors cured from L. donovani in....... The results show that both IFN-gamma producing (Th1-like) and IL-4 producing (Th2-like) T cells recognizing LPGAP are expanded after infection with L. donovani in humans....... infections. LPGAP induced vigorous proliferation and production of interferon-gamma (IFN-gamma) by the cells. In addition PBMC incubated with LPGAP released interleukin-4 (IL-4) after pulsing with ionomycin and phorbol myristate acetate. Single cells were isolated from LPGAP-stimulated cell lines...

  6. B-CLL cells acquire APC- and CTL-like phenotypic characteristics after stimulation with CpG ODN and IL-21

    Science.gov (United States)

    Hagn, Magdalena; Blackwell, Sue E.; Beyer, Thamara; Ebel, Verena; Fabricius, Dorit; Lindner, Stefanie; Stilgenbauer, Stefan; Simmet, Thomas; Tam, Constantine; Neeson, Paul; Trapani, Joseph A.; Schrezenmeier, Hubert; Weiner, George J.

    2014-01-01

    CpG oligodeoxynucleotides (CpG) and IL-21 are two promising agents for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). Recently, we reported that the combination of CpG and IL-21 (CpG/IL-21) can induce granzyme B (GrB)-dependent apoptosis in B-CLL cells. Here, we demonstrate that treatment of B-CLL cells with CpG and IL-21 results in the development of antigen-presenting cell (APC)-like cells with cytotoxic features. These properties eventually give rise to B-CLL cell apoptosis, independently of their cytogenetic phenotype, whereas normal B-cell survival is not negatively affected by CpG/IL-21. APC- and CTL-typical molecules found to be up-regulated in CpG/IL-21-stimulated B-CLL cells include GrB, perforin, T-bet, monokine-induced by IFN-γ and IFN-γ-inducible protein 10 (IP-10), as well as molecules important for cell adhesion, antigen cross-presentation and costimulation. Also induced are molecules involved in GrB induction, trafficking and processing, whereas the GrB inhibitor Serpin B9 [formerly proteinase inhibitor-9 (PI-9)] is down-modulated by CpG/IL-21. In conclusion, CpG/IL-21-stimulated B-CLL cells acquire features that are reminiscent of killer dendritic cells, and which result in enhanced immunogenicity, cytotoxicity and apoptosis. Our results provide novel insights into the aberrant immune state of B-CLL cells and may establish a basis for the development of an innovative cellular vaccination approach in B-CLL. PMID:24497611

  7. A High Performance Banknote Recognition System Based on a One-Dimensional Visible Light Line Sensor.

    Science.gov (United States)

    Park, Young Ho; Kwon, Seung Yong; Pham, Tuyen Danh; Park, Kang Ryoung; Jeong, Dae Sik; Yoon, Sungsoo

    2015-06-15

    An algorithm for recognizing banknotes is required in many fields, such as banknote-counting machines and automatic teller machines (ATM). Due to the size and cost limitations of banknote-counting machines and ATMs, the banknote image is usually captured by a one-dimensional (line) sensor instead of a conventional two-dimensional (area) sensor. Because the banknote image is captured by the line sensor while it is moved at fast speed through the rollers inside the banknote-counting machine or ATM, misalignment, geometric distortion, and non-uniform illumination of the captured images frequently occur, which degrades the banknote recognition accuracy. To overcome these problems, we propose a new method for recognizing banknotes. The experimental results using two-fold cross-validation for 61,240 United States dollar (USD) images show that the pre-classification error rate is 0%, and the average error rate for the final recognition of the USD banknotes is 0.114%.

  8. A High Performance Banknote Recognition System Based on a One-Dimensional Visible Light Line Sensor

    Directory of Open Access Journals (Sweden)

    Young Ho Park

    2015-06-01

    Full Text Available An algorithm for recognizing banknotes is required in many fields, such as banknote-counting machines and automatic teller machines (ATM. Due to the size and cost limitations of banknote-counting machines and ATMs, the banknote image is usually captured by a one-dimensional (line sensor instead of a conventional two-dimensional (area sensor. Because the banknote image is captured by the line sensor while it is moved at fast speed through the rollers inside the banknote-counting machine or ATM, misalignment, geometric distortion, and non-uniform illumination of the captured images frequently occur, which degrades the banknote recognition accuracy. To overcome these problems, we propose a new method for recognizing banknotes. The experimental results using two-fold cross-validation for 61,240 United States dollar (USD images show that the pre-classification error rate is 0%, and the average error rate for the final recognition of the USD banknotes is 0.114%.

  9. Strain differences in the expression of an H-2K/sup k/ gene product by epidermal and spleen cells

    International Nuclear Information System (INIS)

    Hadley, G.A.; Steinmuller, D.

    1986-01-01

    Cytotoxic T lymphocytes (CTL) directed against Epa-1, a non-H-2 alloantigen expressed by epidermal cells (EC) but no lymphoid cells, lyse EC of different H-2/sup k/, Epa-1 + strains at different levels. For example, the mean percent lysis values for EC of strains CBA, AKR, C58, and RF are 60, 46, 41, and 35 respectively. Since the CTL used to obtain these values recognize Epa-1 only in the context of H-2K/sup k/, the different levels of lysis could reflect differences in either Epa-1 or K/sup k/ antigens. The goal of this investigation was to test the second alternative. For this purpose, the authors obtained hybridoma 16-1-11N that secretes a K/sup k/-specific MoAb. They first demonstrated the capacity of MoAb 16-1-11N to block the lysis of CBA EC by Epa-1-specific CTL. They then utilized it as the probe in a cellar RIA, with 125 I-protein A as the second reagent, to quantitate the expression of K/sup k/ antigens on EC of strains CBA, AKR, C58, and RF. They found that C58 and RF EC bound significantly less of the K/sup k/ MoAb than CBA EC. Although AKR EC also bound less of the MoAb than CBA EC, the difference was not significant. Nonetheless, these data support the hypothesis that the differential susceptibility of the strains to lysis by Epa-1-specific CTL is due to differences in the expression of the H-2 restricting element. The authors also tested spleen cells (SC) of the four strains in the RIA described above and found that SC of RF, but not of C58 or AKR, express reduced levels of K/sup k/ antigens compared to CBA SC

  10. Multi-UAV joint target recognizing based on binocular vision theory

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-01-01

    Full Text Available Target recognizing of unmanned aerial vehicle (UAV based on image processing take the advantage of 2D information containing in the image for identifying the target. Compare to single UAV with electrical optical tracking system (EOTS, multi-UAV with EOTS is able to take a group of image focused on the suspected target from multiple view point. Benefit from matching each couple of image in this group, points set constituted by matched feature points implicates the depth of each point. Coordinate of target feature points could be computing from depth of feature points. This depth information makes up a cloud of points and reconstructed an exclusive 3D model to recognizing system. Considering the target recognizing do not require precise target model, the cloud of feature points was regrouped into n subsets and reconstructed to a semi-3D model. Casting these subsets in a Cartesian coordinate and applying these projections in convolutional neural networks (CNN respectively, the integrated output of networks is the improved result of recognizing.

  11. Mining Emerging Patterns for Recognizing Activities of Multiple Users in Pervasive Computing

    DEFF Research Database (Denmark)

    Gu, Tao; Wu, Zhanqing; Wang, Liang

    2009-01-01

    Understanding and recognizing human activities from sensor readings is an important task in pervasive computing. Existing work on activity recognition mainly focuses on recognizing activities for a single user in a smart home environment. However, in real life, there are often multiple inhabitants...... activity models, and propose an Emerging Pattern based Multi-user Activity Recognizer (epMAR) to recognize both single-user and multiuser activities. We conduct our empirical studies by collecting real-world activity traces done by two volunteers over a period of two weeks in a smart home environment...... sensor readings in a home environment, and propose a novel pattern mining approach to recognize both single-user and multi-user activities in a unified solution. We exploit Emerging Pattern – a type of knowledge pattern that describes significant changes between classes of data – for constructing our...

  12. Resilience and work-life balance in first-line nurse manager.

    Science.gov (United States)

    Kim, Miyoung; Windsor, Carol

    2015-03-01

    The aim of this study was to explore how first-line nurse managers constructed the meaning of resilience and its relationship to work-life balance for nurses in Korea. Participants were 20 first-line nurse managers working in six university hospitals. Data were collected through in-depth interviews from December 2011 to August 2012, and analyzed using Strauss and Corbin's grounded theory method. Analysis revealed that participants perceived work-life balance and resilience to be shaped by dynamic, reflective processes. The features consisting resilience included "positive thinking", "flexibility", "assuming responsibility", and "separating work and life". This perception of resilience has the potential to facilitate a shift in focus from negative to positive experiences, from rigidity to flexibility, from task-centered to person-centered thinking, and from the organization to life. Recognizing the importance of work-life balance in producing and sustaining resilience in first-line nurse managers could increase retention in the Korean nursing workforce. Copyright © 2015. Published by Elsevier B.V.

  13. The Fragile X Mental Retardation Protein, FMRP, Recognizes G-Quartets

    Science.gov (United States)

    Darnell, Jennifer C.; Warren, Stephen T.; Darnell, Robert B.

    2004-01-01

    Fragile X mental retardation is a disease caused by the loss of function of a single RNA-binding protein, FMRP. Identifying the RNA targets recognized by FMRP is likely to reveal much about its functions in controlling some aspects of memory and behavior. Recent evidence suggests that one of the predominant RNA motifs recognized by the FMRP…

  14. Transformation and Tumorigenicity Testing of Simian Cell Lines and Evaluation of Poliovirus Replication.

    Directory of Open Access Journals (Sweden)

    Silvia Dotti

    Full Text Available The key role of cell cultures in different scientific fields is worldwide recognized, both as in vitro research models alternative to laboratory animals and substrates for biological production. However, many safety concerns rise from the use of animal/human cell lines that may be tumorigenic, leading to potential adverse contaminations in cell-derived biologicals. In order to evaluate the suitability of 13 different cell lines for Poliovirus vaccine production, safety and quality, in vitro/in vivo tumorigenicity and Poliovirus propagation properties were evaluated. Our results revealed that non-human primate cell lines CYNOM-K1, FRhK-4, 4MBr-5 and 4647 are free of tumorigenic features and represent highly susceptible substrates for attenuated Sabin Poliovirus strains. In particular, FRhK-4 and 4647 cell lines are characterized by a higher in vitro replication, resulting indicated for the use in large-scale production field.

  15. The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma

    Directory of Open Access Journals (Sweden)

    Guo Yajun

    2006-01-01

    Full Text Available Abstract Background Previously we have generated the monoclonal antibody SM5-1 by using a subtractive immunization protocol of human melanoma. This antibody exhibits a high sensitivity for primary melanomas of 99% (248/250 tested and for metastatic melanoma of 96% (146/151 tested in paraffin embedded sections. This reactivity is superior to the one obtained by HMB-45, anti-MelanA or anti-Tyrosinase and is comparable to anti-S100. However, as compared to anti-S100, the antibody SM5-1 is highly specific for melanocytic lesions since 40 different neoplasms were found to be negative for SM5-1 by immunohistochemistry. The antigen recognized by SM5-1 is unknown. Methods In order to characterize the antigen recognized by mAb SM5-1, a cDNA library was constructed from the metastatic human melanoma cell line SMMUpos in the Uni-ZAP lambda phage and screened by mAb SM5-1. The cDNA clones identified by this approach were then sequenced and subsequently analyzed. Results Sequence analysis of nine independent overlapping clones (length 3100–5600 bp represent fibronectin cDNA including the ED-A, but not the ED-B region which are produced by alternative splicing. The 89aa splicing variant of the IIICS region was found in 8/9 clones and the 120aa splicing variant in 1/9 clones, both of which are included in the CS1 region of fibronectin being involved in melanoma cell adhesion and spreading. Conclusion The molecule recognized by SM5-1 is a melanoma associated FN variant expressed by virtually all primary and metastatic melanomas and may play an important role in melanoma formation and progression. This antibody is therefore not only of value in immunohistochemistry, but potentially also for diagnostic imaging and immunotherapy.

  16. Framework for benchmarking FA-based string recognizers

    CSIR Research Space (South Africa)

    Ngassam, EK

    2010-10-01

    Full Text Available of suggested algorithms by domain-specific FA-implementers requires prior knowledge of the behaviour (performance-wise) of each algorithm in order to make an informed choice. The authors propose a based string recognizers such that FA-implementers could capture...

  17. The effect of color on the recognition and use of line drawings by children with severe intellectual disabilities.

    Science.gov (United States)

    Stephenson, Jennifer

    2007-03-01

    Line drawings are commonly used as communication symbols for individuals with severe intellectual disabilities. This study investigated the effect of color on the recognition and use of line drawings by young children with severe intellectual disabilities and poor verbal comprehension who were beginning picture users. Drawings where the color of the picture matched the object and where the color of the drawing did not match the object were used, as well as black and white line drawings. Tentative findings suggest that some students with intellectual disabilities may find it more difficult to recognize and line drawings where the color does not match the object compared to line drawings where the color of the drawing does match the color of the object.

  18. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.

    Directory of Open Access Journals (Sweden)

    Yukiko Kiniwa

    Full Text Available Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+ T helper (Th cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1 as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+ T cell-mediated immunotherapy in melanoma.

  19. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.

    Science.gov (United States)

    Kiniwa, Yukiko; Li, Jiang; Wang, Mingjun; Sun, Chuang; Lee, Jeffrey E; Wang, Rong-Fu; Wang, Helen Y

    2015-01-01

    Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+) T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+) T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+) T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+) Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+) T cell-mediated immunotherapy in melanoma.

  20. Recognizing Multi-user Activities using Wearable Sensors in a Smart Home

    DEFF Research Database (Denmark)

    Wang, Liang; Gu, Tao; Tao, Xianping

    2010-01-01

    The advances of wearable sensors and wireless networks oer many opportunities to recognize human activities from sensor readings in pervasive computing. Existing work so far focuses mainly on recognizing activities of a single user in a home environment. However, there are typically multiple inha...

  1. Robust and accurate vectorization of line drawings.

    Science.gov (United States)

    Hilaire, Xavier; Tombre, Karl

    2006-06-01

    This paper presents a method for vectorizing the graphical parts of paper-based line drawings. The method consists of separating the input binary image into layers of homogeneous thickness, skeletonizing each layer, segmenting the skeleton by a method based on random sampling, and simplifying the result. The segmentation method is robust with a best bound of 50 percent noise reached for indefinitely long primitives. Accurate estimation of the recognized vector's parameters is enabled by explicitly computing their feasibility domains. Theoretical performance analysis and expression of the complexity of the segmentation method are derived. Experimental results and comparisons with other vectorization systems are also provided.

  2. Product line based ontology reuse in context-aware e-business environment

    DEFF Research Database (Denmark)

    Zhang, Weishan; Kunz, Thomas

    2006-01-01

    Improving the reusability of ontology is recognized as increasingly important due to the prevalence of OWL research and applications. But there exists no convincing methodology and tool support in this direction yet. In this paper, we apply ideas from the research and practice with software product...... lines in order to explore this issue. The ontology is developed and managed according to the commonalities and variabilities underlying a specific problem domain. Meta-ontology is used in order to improve the reusability, evolve-ability and customizability of ontology. Another advantage is being able...... to generate needed ontology with the created meta-ontology implemented with XVCL (XML based Variant Configuration Language) technology. We demonstrate our product line based reuse approach with an example B2C application....

  3. Cytotoxic T lymphocyte response to herpes simplex virus type 1 is composed of both CD8+ and CD4+ T cell phenotypes in acute and memory states

    International Nuclear Information System (INIS)

    Niemialtowski, Marek G.; Rouse, Barry T.

    1994-01-01

    Mice were infected via the cornea with HSV-1. Next, draining lymph nodes (DLN) and spleen cells were analyzed at various times post infection for the presence of cytotoxic T lymphocyte precursors (CTL-p) of both the CD8 + and CD4 + phenotypes. Responses were greatest in the DLN, but memory CTL persisted in the spleen and were undetectable in DLN by 60 days. On all occasions, the frequency of CD8 + CTL outnumbered CD4 + CTL. The murine CTL responses to HSV-1 differ from those in man where CD4 + MHC class II restricted CTL appear to dominate the response at least in the memory phase. (author). 28 refs, 2 figs, 1 tab

  4. Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

    Science.gov (United States)

    Hatano, Manabu; Kuwashima, Naruo; Tatsumi, Tomohide; Dusak, Jill E; Nishimura, Fumihiko; Reilly, Karlyne M; Storkus, Walter J; Okada, Hideho

    2004-01-01

    Background A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. Methods C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2671–679, mEphA2682–689) and CD4+ (mEphA230–44) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed. Results Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. Conclusions These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells. PMID:15563374

  5. Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

    Directory of Open Access Journals (Sweden)

    Hatano Manabu

    2004-11-01

    Full Text Available Abstract Background A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. Methods C57BL/6 mice received subcutaneous (s.c. vaccinations with bone marrow-derived dendritic cells (DCs pulsed with synthetic peptides recognized by CD8+ (mEphA2671–679, mEphA2682–689 and CD4+ (mEphA230–44 T cells. Splenocytes (SPCs were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6 establishment/progression was then assessed. Results Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. Conclusions These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells.

  6. Recognizing the Stranger: Recognition Scenes in the Gospel of John

    DEFF Research Database (Denmark)

    Larsen, Kasper Bro

    Recognizing the Stranger is the first monographic study of recognition scenes and motifs in the Gospel of John. The recognition type-scene (anagnōrisis) was a common feature in ancient drama and narrative, highly valued by Aristotle as a touching moment of truth, e.g., in Oedipus’ tragic self...... structures of the type-scene in order to show how Jesus’ true identity can be recognized behind the half-mask of his human appearance....

  7. A Weighing Algorithm for Checking Missing Components in a Pharmaceutical Line

    Directory of Open Access Journals (Sweden)

    Alessandro Silvestri

    2014-11-01

    image. The goal of the present work is the development of an algorithm able to optimize the production line of a pharmaceutical firm. In particular, the proposed weighing procedure allows both checking missing components in packaging and minimizing false rejects of packages by dynamic scales. The main problem is the presence at the same time, in the same package, of different components with different variable weights. The consequence is uncertainty in recognizing the absence of one or more components.

  8. Pooling Objects for Recognizing Scenes without Examples

    NARCIS (Netherlands)

    Kordumova, S.; Mensink, T.; Snoek, C.G.M.

    2016-01-01

    In this paper we aim to recognize scenes in images without using any scene images as training data. Different from attribute based approaches, we do not carefully select the training classes to match the unseen scene classes. Instead, we propose a pooling over ten thousand of off-the-shelf object

  9. Good Practices for Learning to Recognize Actions Using FV and VLAD.

    Science.gov (United States)

    Wu, Jianxin; Zhang, Yu; Lin, Weiyao

    2016-12-01

    High dimensional representations such as Fisher vectors (FV) and vectors of locally aggregated descriptors (VLAD) have shown state-of-the-art accuracy for action recognition in videos. The high dimensionality, on the other hand, also causes computational difficulties when scaling up to large-scale video data. This paper makes three lines of contributions to learning to recognize actions using high dimensional representations. First, we reviewed several existing techniques that improve upon FV or VLAD in image classification, and performed extensive empirical evaluations to assess their applicability for action recognition. Our analyses of these empirical results show that normality and bimodality are essential to achieve high accuracy. Second, we proposed a new pooling strategy for VLAD and three simple, efficient, and effective transformations for both FV and VLAD. Both proposed methods have shown higher accuracy than the original FV/VLAD method in extensive evaluations. Third, we proposed and evaluated new feature selection and compression methods for the FV and VLAD representations. This strategy uses only 4% of the storage of the original representation, but achieves comparable or even higher accuracy. Based on these contributions, we recommend a set of good practices for action recognition in videos for practitioners in this field.

  10. Super-Memorizers Are Not Super-Recognizers

    OpenAIRE

    Ramon, M.; Miellet, S.; Dzieciol, A.M.; Konrad, B.N; Dresler, M.; Caldara, R.

    2016-01-01

    Humans have a natural expertise in recognizing faces. However, the nature of the interaction between this critical visual biological skill and memory is yet unclear. Here, we had the unique opportunity to test two individuals who have had exceptional success in the World Memory Championships, including several world records in face-name association memory. We designed a range of face processing tasks to determine whether superior/expert face memory skills are associated with distinctive perce...

  11. Markerless tracking in nuclear power plants. A line segment-based approach

    International Nuclear Information System (INIS)

    Ishii, Hirotake; Kimura, Taro; Tokumaru, Hiroki; Shimoda, Hiroshi; Koda, Yuya

    2017-01-01

    To develop augmented reality-based support systems, a tracking method that measures the camera's position and orientation in real time is indispensable. A relocalization is one step that is used to (re)start the tracking. A line-segment-based relocalization method that uses a RGB-D camera and coarse-to-fine approach was developed and evaluated for this study. In the preparation stage, the target environment is scanned with a RGB-D camera. Line segments are recognized. Then three-dimensional positions of the line segments are calculated, and statistics of the line segments are calculated and stored in a database. In the relocalization stage, a few images that closely resemble the current RGB-D camera image are chosen from the database by comparing the statistics of the line segments. Then the most similar image is chosen using Normalized Cross-Correlation. This coarse-to-fine approach reduces the computational load to find the most similar image. The method was evaluated in the water purification room of the Fugen nuclear power plant. Results showed that the success rate of the relocalization is 93.6% and processing time is 45.7 ms per frame on average, which is promising for practical use. (author)

  12. Federally-Recognized Tribes of the Columbia-Snake Basin.

    Energy Technology Data Exchange (ETDEWEB)

    United States. Bonneville Power Administration

    1997-11-01

    This is an omnibus publication about the federally-recognized Indian tribes of the Columbia-Snake river basin, as presented by themselves. It showcases several figurative and literal snapshots of each tribe, bits and pieces of each tribe`s story. Each individual tribe or tribal confederation either submitted its own section to this publication, or developed its own section with the assistance of the writer-editor. A federally-recognized tribe is an individual Indian group, or confederation of Indian groups, officially acknowledged by the US government for purposes of legislation, consultation and benefits. This publication is designed to be used both as a resource and as an introduction to the tribes. Taken together, the sections present a rich picture of regional indian culture and history, as told by the tribes.

  13. Recognizing team formation in american football

    KAUST Repository

    Atmosukarto, Indriyati

    2014-01-01

    Most existing software packages for sports video analysis require manual annotation of important events in the video. Despite being the most popular sport in the United States, most American football game analysis is still done manually. Line of scrimmage and offensive team formation recognition are two statistics that must be tagged by American Football coaches when watching and evaluating past play video clips, a process which takesmanyman hours per week. These two statistics are the building blocks for more high-level analysis such as play strategy inference and automatic statistic generation. In this chapter, we propose a novel framework where given an American football play clip, we automatically identify the video frame in which the offensive team lines in formation (formation frame), the line of scrimmage for that play, and the type of player formation the offensive team takes on. The proposed framework achieves 95% accuracy in detecting the formation frame, 98% accuracy in detecting the line of scrimmage, and up to 67%accuracy in classifying the offensive team’s formation. To validate our framework, we compiled a large dataset comprising more than 800 play-clips of standard and high definition resolution from real-world football games. This dataset will be made publicly available for future comparison.

  14. 78 FR 7460 - Stakeholder Meeting on the Nationally Recognized Testing Laboratory Program

    Science.gov (United States)

    2013-02-01

    ...] Stakeholder Meeting on the Nationally Recognized Testing Laboratory Program AGENCY: Occupational Safety and Health Administration (OSHA), Labor. ACTION: Notice of stakeholder meeting. SUMMARY: OSHA invites interested parties to attend an informal stakeholder meeting concerning Nationally Recognized Testing...

  15. Selective attention in vision: recognition memory for superimposed line drawings.

    Science.gov (United States)

    Goldstein, E B; Fink, S I

    1981-10-01

    These experiments show that observers can selectively attend to one of two stationary superimposed pictures. If superimposed line drawings are presented to observers who are told to attend to one line drawing in the pair and to ignore the other line drawing in the pair, then a subsequent recognition test in which the pictures are presently singly, the attended picture in each pair is recognized much more frequently than the unattended picture in each pair. This selective recognition occurs both with large (11 degrees-22 degrees) displays in which observers are free to make eye movements during a 3-sec exposure and with small (1 degree) displays in which observers are instructed to fixate steadily on a point during a 1-sec exposure. The results of the steady fixation experiments show that in the absence of eye movements, attention to one of two superimposed stimuli can cause an observer to remember the attended image and not to remember the other, clearly visible, unattended image in a superimposed pair.

  16. Recognition of facial expressions by cortical multi-scale line and edge coding

    OpenAIRE

    Sousa, R.; Rodrigues, J. M. F.; du Buf, J. M. H.

    2010-01-01

    Face-to-face communications between humans involve emotions, which often are unconsciously conveyed by facial expressions and body gestures. Intelligent human-machine interfaces, for example in cognitive robotics, need to recognize emotions. This paper addresses facial expressions and their neural correlates on the basis of a model of the visual cortex: the multi-scale line and edge coding. The recognition model links the cortical representation with Paul Ekman's Action Units which are relate...

  17. A novel approach in recognizing magnetic material with simplified algorithm

    KAUST Repository

    Talukdar, Abdul Hafiz Ibne

    2011-04-01

    In this article a cost-effective and simple system (circuit and algorithm) which allows recognizing different kinds of films by their magneto-field conductive properties is demonstrated. The studied signals are generated by a proposed circuit. This signal was further analyzed (recognized) in frequency domain creating the Fourier frequency spectrum which is easily used to detect the response of magnetic sample. The novel algorithm in detecting magnetic field is presented here with both simulation and experimental results. © 2011 IEEE.

  18. Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease.

    Science.gov (United States)

    Manuel, Sharrón L; Schell, Todd D; Acheampong, Edward; Rahman, Saifur; Khan, Zafar K; Jain, Pooja

    2009-11-01

    HTLV-1 is the etiologic agent of a debilitating neurologic disorder, HAM/TSP. This disease features a robust immune response including the oligoclonal expansion of CD8+ CTLs specific for the viral oncoprotein Tax. The key pathogenic process resulting in the proliferation of CTLs and the presentation of Tax peptide remains uncharacterized. We have investigated the role of APCs, particularly DCs, in priming of the anti-Tax CTL response under in vitro and in vivo conditions. We investigated two routes (direct vs. indirect) of Tax presentation using live virus, infected primary CD4+/CD25+ T cells, and the CD4+ T cell line (C8166, a HTLV-1-mutated line that only expresses Tax). Our results indicated that DCs are capable of priming a pronounced Tax-specific CTL response in cell cultures consisting of naïve PBLs as well as in HLA-A*0201 transgenic mice (line HHD II). DCs were able to direct the presentation of Tax successfully through infected T cells, live virus, and cell-free Tax. These observations were comparable with those made with a known stimulant of DC maturation, a combination of CD40L and IFN-gamma. Our studies clearly establish a role for this important immune cell component in HTLV-1 immuno/neuropathogenesis and suggest that modulation of DC functions could be an important tool for therapeutic interventions.

  19. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  20. Modeling and techno-economic analysis of shale-to-liquid and coal-to-liquid fuels processes

    International Nuclear Information System (INIS)

    Zhou, Huairong; Yang, Siyu; Xiao, Honghua; Yang, Qingchun; Qian, Yu; Gao, Li

    2016-01-01

    To alleviate the conflict between oil supply and demand, Chinese government has accelerated exploration and exploitation of alternative oil productions. STL (Shale-to-liquid) processes and CTL (coal-to-liquid) processes are promising choices to supply oil. However, few analyses have been made on their energy efficiency and economic performance. This paper conducts a detailed analysis of a STL process and a CTL process based on mathematical modeling and simulation. Analysis shows that low efficiency of the STL process is due to low oil yield of the Fushun-type retorting technology. For the CTL process, the utility system provides near to 34% energy consumption of the total. This is because that CTL technologies are in early development and no heat integration between units is implemented. Economic analysis reveals that the total capital investment of the CTL process is higher than that of the STL process. The production cost of the CTL process is right on the same level as that of the STL process. For better techno-economic performance, it is suggested to develop a new retorting technology of high oil yield for the STL process. The remaining retorting gas should be converted to hydrogen and then used for shale oil hydrogenation. For the CTL process, developing an appropriate heat network is an efficient way to apply heat integration. In addition, the CTL process is intended to be integrated with hydrogen rich gas to adjust H_2/CO for better resource utilization. - Highlights: • Aspen Plus software is used for modeling and simulation of a shale-to-liquid (STL) and a coal-to-liquid (CTL) processes. • Techno-economic analysis of STL and CTL processes is conducted. • Suggestions are given for improving energy efficiency and economic performance of STL and CTL processes.

  1. Realistic Creativity Training for Innovation Practitioners: The Know-Recognize-React Model

    DEFF Research Database (Denmark)

    Valgeirsdóttir, Dagný; Onarheim, Balder

    2017-01-01

    As creativity becomes increasingly recognized as important raw material for innovation, the importance of identifying ways to increase practitioners’ creativity through rigorously designed creativity training programs is highlighted. Therefore we sat out to design a creativity training program sp...... the transdisciplinary study described in this paper. Co-creation was employed as a method to ensure the three layers of focus would be taken into consideration. The result is a program called Creative Awareness Training which is based on the new Know-Recognize-React model.......As creativity becomes increasingly recognized as important raw material for innovation, the importance of identifying ways to increase practitioners’ creativity through rigorously designed creativity training programs is highlighted. Therefore we sat out to design a creativity training program...

  2. Recognizing Risk and Vulnerability in Research Ethics: Imagining the "What Ifs?"

    Science.gov (United States)

    Peter, Elizabeth; Friedland, Judith

    2017-04-01

    Research ethics committees (RECs) may misunderstand the vulnerability of participants, given their distance from the field. What RECs identify as the vulnerabilities that were not adequately recognized in protocols and how they attempt to protect the perceived vulnerability of participants and mitigate risks were examined using the response letters sent to researchers by three university-based RECs. Using a critical qualitative method informed by feminist ethics, we identified an overarching theme of recognizing and responding to cascading vulnerabilities and four subthemes: identifying vulnerable groups, recognizing potentially risky research, imagining the "what ifs," and mitigating perceived risks. An ethics approach that is up-close, as opposed to distant, is needed to foster closer relationships among participants, researchers, and RECs and to understand participant vulnerability and strength better.

  3. A practical approach for writer-dependent symbol recognition using a writer-independent symbol recognizer.

    Science.gov (United States)

    LaViola, Joseph J; Zeleznik, Robert C

    2007-11-01

    We present a practical technique for using a writer-independent recognition engine to improve the accuracy and speed while reducing the training requirements of a writer-dependent symbol recognizer. Our writer-dependent recognizer uses a set of binary classifiers based on the AdaBoost learning algorithm, one for each possible pairwise symbol comparison. Each classifier consists of a set of weak learners, one of which is based on a writer-independent handwriting recognizer. During online recognition, we also use the n-best list of the writer-independent recognizer to prune the set of possible symbols and thus reduce the number of required binary classifications. In this paper, we describe the geometric and statistical features used in our recognizer and our all-pairs classification algorithm. We also present the results of experiments that quantify the effect incorporating a writer-independent recognition engine into a writer-dependent recognizer has on accuracy, speed, and user training time.

  4. Residue analysis of a CTL epitope of SARS-CoV spike protein by IFN-gamma production and bioinformatics prediction

    Directory of Open Access Journals (Sweden)

    Huang Jun

    2012-09-01

    Full Text Available Abstract Background Severe acute respiratory syndrome (SARS is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epitopes. Analysis of the functional importance of side-chains by mutational study may exaggerate the effect by imposing a structural disturbance or an unusual steric, electrostatic or hydrophobic interaction. Results We demonstrated that N50 could induce significant IFN-gamma response from SARS-CoV S DNA immunized mice splenocytes by the means of ELISA, ELISPOT and FACS. Moreover, S366-374 was predicted to be an optimal epitope by bioinformatics tools: ANN, SMM, ARB and BIMAS, and confirmed by IFN-gamma response induced by a series of S358-374-derived peptides. Furthermore, each of S366-374 was replaced by alanine (A, lysine (K or aspartic acid (D, respectively. ANN was used to estimate the binding affinity of single S366-374 mutants to H-2 Kd. Y367 and L374 were predicated to possess the most important role in peptide binding. Additionally, these one residue mutated peptides were synthesized, and IFN-gamma production induced by G368, V369, A371, T372 and K373 mutated S366-374 were decreased obviously. Conclusions We demonstrated that S366-374 is an optimal H-2 Kd CTL epitope in the SARS CoV S protein. Moreover, Y367, S370, and L374 are anchors in the epitope, while C366, G368, V369, A371, T372, and K373 may directly interact with TCR on the surface of CD8-T cells.

  5. Ants recognize foes and not friends

    Science.gov (United States)

    Guerrieri, Fernando J.; Nehring, Volker; Jørgensen, Charlotte G.; Nielsen, John; Galizia, C. Giovanni; d'Ettorre, Patrizia

    2009-01-01

    Discriminating among individuals and rejecting non-group members is essential for the evolution and stability of animal societies. Ants are good models for studying recognition mechanisms, because they are typically very efficient in discriminating ‘friends’ (nest-mates) from ‘foes’ (non-nest-mates). Recognition in ants involves multicomponent cues encoded in cuticular hydrocarbon profiles. Here, we tested whether workers of the carpenter ant Camponotus herculeanus use the presence and/or absence of cuticular hydrocarbons to discriminate between nest-mates and non-nest-mates. We supplemented the cuticular profile with synthetic hydrocarbons mixed to liquid food and then assessed behavioural responses using two different bioassays. Our results show that (i) the presence, but not the absence, of an additional hydrocarbon elicited aggression and that (ii) among the three classes of hydrocarbons tested (unbranched, mono-methylated and dimethylated alkanes; for mono-methylated alkanes, we present a new synthetic pathway), only the dimethylated alkane was effective in eliciting aggression. Our results suggest that carpenter ants use a fundamentally different mechanism for nest-mate recognition than previously thought. They do not specifically recognize nest-mates, but rather recognize and reject non-nest-mates bearing odour cues that are novel to their own colony cuticular hydrocarbon profile. This begs for a reappraisal of the mechanisms underlying recognition systems in social insects. PMID:19364750

  6. Responsibilities and commitment of top management and first line management in organizational-level interventions - what difference does it make?

    DEFF Research Database (Denmark)

    Gish, Liv; Ipsen, Christine; Poulsen, Signe

    Researchers advocate that interventions should apply a participatory approach i.e. employee participation. It is also widely recognized that top management’s support is an important part of a successful intervention implementation. Lately there has been a request for multi-level intervention...... momentum and increase chances of successful implementation. Four SMEs participated in the study. The typical intervention construct was that top management initiated the intervention and first line managers had to manage the intervention on a daily basis together with two selected employees who acted as in...... between top management and first line management. The top manager’s most important responsibilities were to ensure that the first line manager understood the purpose of the intervention, and to support the first line manager’s dispositions through the intervention. The first line manager’s most important...

  7. Can Independent Judges Recognize Different Psychotherapies? An Experience with Manual-Guided Therapies.

    Science.gov (United States)

    Luborsky, Lester; And Others

    1982-01-01

    Tested whether independent judges could recognize three different manual-guided psychotherapies, drug counseling, supportive-expressive psychotherapy, and cognitive-behavioral using a special rating form containing scales for the characteristic aspects of each type. Results indicated that manual-guided therapies can be reliably recognized.…

  8. Visual agnosia for line drawings and silhouettes without apparent impairment of real-object recognition: a case report.

    Science.gov (United States)

    Hiraoka, Kotaro; Suzuki, Kyoko; Hirayama, Kazumi; Mori, Etsuro

    2009-01-01

    We report on a patient with visual agnosia for line drawings and silhouette pictures following cerebral infarction in the region of the right posterior cerebral artery. The patient retained the ability to recognize real objects and their photographs, and could precisely copy line drawings of objects that she could not name. This case report highlights the importance of clinicians and researchers paying special attention to avoid overlooking agnosia in such cases. The factors that lead to problems in the identification of stimuli other than real objects in agnosic cases are discussed.

  9. Visual Agnosia for Line Drawings and Silhouettes without Apparent Impairment of Real-Object Recognition: A Case Report

    Directory of Open Access Journals (Sweden)

    Kotaro Hiraoka

    2009-01-01

    Full Text Available We report on a patient with visual agnosia for line drawings and silhouette pictures following cerebral infarction in the region of the right posterior cerebral artery. The patient retained the ability to recognize real objects and their photographs, and could precisely copy line drawings of objects that she could not name. This case report highlights the importance of clinicians and researchers paying special attention to avoid overlooking agnosia in such cases. The factors that lead to problems in the identification of stimuli other than real objects in agnosic cases are discussed.

  10. Holliday junction–recognizing protein promotes cell proliferation and correlates with unfavorable clinical outcome of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hu B

    2017-05-01

    Full Text Available Baohong Hu,1,2,* Qianli Wang,3,* Yueju Wang,4 Jian Chen,2 Peng Li,2 Mingyong Han1 1Department of Health Care Oncology, East District of Shandong Provincial Hospital of Shandong University, Jinan, 2Department of Medical Oncology, 3Department of Intensive Care Unit, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong, 4Department of Geriatrics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China *These authors contributed equally to this work Aim: To investigate the expression and clinical significance of Holliday junction–recognizing protein (HJURP in hepatocellular carcinoma (HCC. Methods: In this study, we detected the expression of HJURP protein in samples of 164 patients with HCC, and based on this, we divided the patients into two cohorts: high expression of HJURP and low expression of HJURP. We analyzed the correlation between HJURP expression and the clinicopathological factors using chi-square test. Survival significance of HJURP was defined by Kaplan–Meier method and log-rank test, and the independent prognostic factors were identified by Cox regression model. Using function assays of HCC cell lines, we investigated the influence of HJURP on the proliferation of HCC cells. Results: In our study, the proportion of patients with high HJURP expression was 25.6%, which was significantly associated with the tumor size and Barcelona clinic liver cancer stage. Univariate analysis confirmed that high HJURP expression was remarkably associated with poorer overall survival rates (P=0.003, as well as tumor number (P=0.016, tumor differentiation (P=0.047, TNM stage (P=0.005, and Barcelona clinic liver cancer stage (P=0.004. Multivariate analysis confirmed that high HJURP expression (P<0.001 acted as an independent prognostic risk factor of unfavorable prognosis. Real-time polymerase chain reaction analysis revealed that the expression of HJURP was significantly higher in

  11. Slice&Dice: Recognizing Food Preparation Activities Using Embedded Accelerometers

    Science.gov (United States)

    Pham, Cuong; Olivier, Patrick

    Within the context of an endeavor to provide situated support for people with cognitive impairments in the kitchen, we developed and evaluated classifiers for recognizing 11 actions involved in food preparation. Data was collected from 20 lay subjects using four specially designed kitchen utensils incorporating embedded 3-axis accelerometers. Subjects were asked to prepare a mixed salad in our laboratory-based instrumented kitchen environment. Video of each subject's food preparation activities were independently annotated by three different coders. Several classifiers were trained and tested using these features. With an overall accuracy of 82.9% our investigation demonstrated that a broad set of food preparation actions can be reliably recognized using sensors embedded in kitchen utensils.

  12. Production of antibodies which recognize opiate receptors on murine leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.

    1988-01-01

    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  13. Switch from perforin-expressing to perforin-deficient CD8(+) T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo.

    Science.gov (United States)

    Meiraz, Avihai; Garber, Orit Gal; Harari, Shaul; Hassin, David; Berke, Gideon

    2009-09-01

    Although CD8(+) cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8(+) CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8(+) T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8(+) cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8(+) CTL have two killing strategies.

  14. Switch from perforin-expressing to perforin-deficient CD8+ T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo

    Science.gov (United States)

    Meiraz, Avihai; Garber, Orit Gal; Harari, Shaul; Hassin, David; Berke, Gideon

    2009-01-01

    Although CD8+ cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8+ CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8+ T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8+ cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8+ CTL have two killing strategies. PMID:19689737

  15. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.

    Science.gov (United States)

    Davenport, A J; Cross, R S; Watson, K A; Liao, Y; Shi, W; Prince, H M; Beavis, P A; Trapani, J A; Kershaw, M H; Ritchie, D S; Darcy, P K; Neeson, P J; Jenkins, M R

    2018-02-27

    Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell. Copyright © 2018 the Author(s). Published by PNAS.

  16. Structural elements recognized by abacavir-induced T cells

    DEFF Research Database (Denmark)

    Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J.

    2017-01-01

    of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context...

  17. QMODULE: CAMAC modules recognized by the QAL compiler

    International Nuclear Information System (INIS)

    Kellogg, M.; Minor, M.M.; Shlaer, S.; Spencer, N.; Thomas, R.F. Jr.; van der Beken, H.

    1977-10-01

    The compiler for the Q Analyzer Language, QAL, recognizes a certain set of CAMAC modules as having known characteristics. The conventions and procedures used to describe these modules are discussed as well as the tools available to the user for extending this set as required

  18. How biological soil crusts became recognized as a functional unit: a selective history

    Science.gov (United States)

    Lange, Otto L.; Belnap, Jayne

    2016-01-01

    It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

  19. Local Attitudes Towards AN International Project: a Study of Residents' Attitudes Towards a Future High Speed Rail Line in General and Towards Annoyance in Particular

    Science.gov (United States)

    Schaap, D.

    1996-05-01

    Plans for a high speed rail line in Holland generate concerns about the impact on the living environment. Residents living near the planned track have an extremely negative attitude towards the high speed rail line. Most of them do not see the need for the line and they expect a great deal of noise annoyance. There is a disparity between the expectations of the residents and those of the government: the residents expect much more noise that the government does, on the basis of scientific research. The image that residents have of the noise of a high speed train is probably too negative. Therefore the government should supply the residents with better and more detailed information about the noise and the possible annoyance. Furthermore, for a positive attitude, it is important that residents not only recognize the disadvantages of the rail line, but that they recognize some local advantages too. For instances, the government can guarantee compensation for the affected green space, or that other noise sources will be removed. Finally, the residents have the feeling they cannot influence the decision-making process. To reduce this feeling of powerlessness, the government can involve the residents; for example, in the decision-making about the local plans for the high speed rail line.

  20. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez

    2017-12-16

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  1. A reference genome and methylome for the Plasmodium knowlesi A1-H.1 line

    KAUST Repository

    Benavente, Ernest Diez; de Sessions, Paola Florez; Moon, Robert W.; Grainger, Munira; Holder, Anthony A; Blackman, Michael J.; Roper, Cally; Drakeley, Christopher J.; Pain, Arnab; Sutherland, Colin J.; Hibberd, Martin L.; Campino, Susana; Clark, Taane G

    2017-01-01

    Plasmodium knowlesi, a common parasite of macaques, is recognized as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites. The PkA1-H.1 reference will enhance the capabilities of the in vitro model to improve the understanding of P. knowlesi infection in humans.

  2. Evaluation of speech recognizers for use in advanced combat helicopter crew station research and development

    Science.gov (United States)

    Simpson, Carol A.

    1990-01-01

    The U.S. Army Crew Station Research and Development Facility uses vintage 1984 speech recognizers. An evaluation was performed of newer off-the-shelf speech recognition devices to determine whether newer technology performance and capabilities are substantially better than that of the Army's current speech recognizers. The Phonetic Discrimination (PD-100) Test was used to compare recognizer performance in two ambient noise conditions: quiet office and helicopter noise. Test tokens were spoken by males and females and in isolated-word and connected-work mode. Better overall recognition accuracy was obtained from the newer recognizers. Recognizer capabilities needed to support the development of human factors design requirements for speech command systems in advanced combat helicopters are listed.

  3. Smart responsive microcapsules capable of recognizing heavy metal ions.

    Science.gov (United States)

    Pi, Shuo-Wei; Ju, Xiao-Jie; Wu, Han-Guang; Xie, Rui; Chu, Liang-Yin

    2010-09-15

    Smart responsive microcapsules capable of recognizing heavy metal ions are successfully prepared with oil-in-water-in-oil double emulsions as templates for polymerization in this study. The microcapsules are featured with thin poly(N-isopropylacrylamide-co-benzo-18-crown-6-acrylamide) (P(NIPAM-co-BCAm)) membranes, and they can selectively recognize special heavy metal ions such as barium(II) or lead(II) ions very well due to the "host-guest" complexation between the BCAm receptors and barium(II) or lead(II) ions. The stable BCAm/Ba(2+) or BCAm/Pb(2+) complexes in the P(NIPAM-co-BCAm) membrane cause a positive shift of the volume phase transition temperature of the crosslinked P(NIPAM-co-BCAm) hydrogel to a higher temperature, and the repulsion among the charged BCAm/Ba(2+) or BCAm/Pb(2+) complexes and the osmotic pressure within the P(NIPAM-co-BCAm) membranes result in the swelling of microcapsules. Induced by recognizing barium(II) or lead(II) ions, the prepared microcapsules with P(NIPAM-co-BCAm) membranes exhibit isothermal and significant swelling not only in outer and inner diameters but also in the membrane thickness. The proposed microcapsules in this study are highly attractive for developing smart sensors and/or carriers for detection and/or elimination of heavy metal ions. Copyright 2010 Elsevier Inc. All rights reserved.

  4. LINEs Contribute to the Origins of Middle Bodies of SINEs besides 3′ Tails

    Science.gov (United States)

    2018-01-01

    Abstract Short interspersed elements (SINEs), which are nonautonomous transposable elements, require the transposition machinery of long interspersed elements (LINEs) to mobilize. SINEs are composed of two or more independently originating parts. The 5′ region is called the “head” and is derived mainly from small RNAs, and the 3′ region (“tail”) originates from the 3′ region of LINEs and is responsible for being recognized by counterpart LINE proteins. The origin of the middle “body” of SINEs is enigmatic, although significant sequence similarities among SINEs from very diverse species have been observed. Here, a systematic analysis of the similarities among SINEs and LINEs deposited on Repbase, a comprehensive database of eukaryotic repeat sequences was performed. Three primary findings are described: 1) The 5′ regions of only two clades of LINEs, RTE and Vingi, were revealed to have contributed to the middle parts of SINEs; 2) The linkage of the 5′ and 3′ parts of LINEs can be lost due to occasional tail exchange of SINEs; and 3) The previously proposed Ceph-domain was revealed to be a fusion of a CORE-domain and a 5′ part of RTE clade of LINE. Based on these findings, a hypothesis that the 5′ parts of bipartite nonautonomous LINEs, which possess only the 5′ and 3′ regions of the original LINEs, can contribute to the undefined middle part of SINEs is proposed. PMID:29325122

  5. A new theory of cytotoxic T-lymphocyte memory: implications for HIV treatment

    DEFF Research Database (Denmark)

    Wodarz, D; Page, K M; Arnaout, R A

    2000-01-01

    result in the failure to establish CTL memory which in turn leads to viral persistence. Based on our models we suggest conceptual treatment regimes which ensure establishment of CTL memory. This would allow the immune response to control HIV in the long term in the absence of continued therapy....... reinfection is only effective in a restricted set of circumstances, we find that resolution of the primary infection requires persistence of CTL precursors (GTLp), as well as a fast rate of activation of the CTLp. Since these are commonly the defining characteristics of CTL memory, we propose that CTL memory...... may have evolved in order to clear the virus during primary challenge. We show experimental data from lymphocytic choriomeningitis virus infection in mice, supporting our theory on CTL memory. We adapt our models to HIV and find that immune impairment during the primary phase of the infection may...

  6. Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model

    Directory of Open Access Journals (Sweden)

    Takashi Ohashi

    2014-01-01

    Full Text Available Adult T cell leukemia (ATL is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I. To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV, LC16m8Δ (m8Δ, and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.

  7. Parsley: a Command-Line Parser for Astronomical Applications

    Science.gov (United States)

    Deich, William

    Parsley is a sophisticated keyword + value parser, packaged as a library of routines that offers an easy method for providing command-line arguments to programs. It makes it easy for the user to enter values, and it makes it easy for the programmer to collect and validate the user's entries. Parsley is tuned for astronomical applications: for example, dates entered in Julian, Modified Julian, calendar, or several other formats are all recognized without special effort by the user or by the programmer; angles can be entered using decimal degrees or dd:mm:ss; time-like intervals as decimal hours, hh:mm:ss, or a variety of other units. Vectors of data are accepted as readily as scalars.

  8. 76 FR 28954 - International Conservation and Management Measures Recognized by the United States

    Science.gov (United States)

    2011-05-19

    ... International Conservation and Management Measures Recognized by the United States AGENCY: National Marine... international conservation and management measures recognized by the United States. To fulfill this requirement, a list of agreements resulting in international conservation and management measures was first...

  9. Establishment and characterization of Epstein-Barr virus-specific human CD4+ T lymphocyte clones

    International Nuclear Information System (INIS)

    Honda, S.; Okuno, K.; Yasutomi, M.; Takasaki, T.; Kurane, I.

    1998-01-01

    We developed a simple method for establishing Epstein-Barr virus (EBV)-specific, human CD4+ T cell clones. The method originates from our experience that the regression of cell growth in in vitro EBV transformation of B cells occurs when round lymphoid cells appear in the culture. Peripheral blood mononuclear cells were cultured with EBV; and IL-2 (20 U/ml) was added to the culture on day 17 after the virus addition. The phenotype of the growing cells was CD3+ , CD4+ , and CD8-. The cells were cytotoxic for autologous lymphoblastoid B cell line (LCL) and EBV-super-infected autologous LCL. The cytotoxic T lymphocytes (CTLs) were confirmed to be CD4+ T cells but not CD8+ T cells in the culture. CTL clones were established by a limiting dilution method. All the CTL clones had the phenotype of CD3+ , CD4+ and CD8-, and proliferated in response to autologous LCL. They produced interferon (IFN)-gamma, interleukin 2 (IL-2) and tumour necrosis factor (TNF)-beta but not IL-4. All but one clone responded to both autologous, EBV-super-infected and non-super-infected LCLs. Proliferative and cytotoxic responses to allogeneic LCLs were heterogeneous. These results suggest that this method induces heterogeneous, EBV-specific CD4+ CTL clones and is useful for analysis of CD4+ T cells in EBV infections. (authors)

  10. Recognizing Risk-of-Failure in Communication Design Projects

    Science.gov (United States)

    Yee, Joyce; Lievesley, Matthew; Taylor, Louise

    2009-01-01

    The pace of commercial graphic design practice presents very few opportunities to conduct user research after a project's launch. This makes the design team's ability to anticipate and address risks during the design development phase even more important, recognized in the astute observation from Tim Brown, CEO of leading international design…

  11. Realistic Creativity Training for Innovation Practitioners: The Know-Recognize-React Model

    DEFF Research Database (Denmark)

    Valgeirsdóttir, Dagný; Onarheim, Balder

    2017-01-01

    As creativity becomes increasingly recognized as important raw material for innovation, the importance of identifying ways to increase practitioners’ creativity through rigorously designed creativity training programs is highlighted. Therefore we sat out to design a creativity training program...... the transdisciplinary study described in this paper. Co-creation was employed as a method to ensure the three layers of focus would be taken into consideration. The result is a program called Creative Awareness Training which is based on the new Know-Recognize-React model....

  12. Recognizing and managing sapstreak disease of sugar maple

    Science.gov (United States)

    David R. Houston; David R. Houston

    1993-01-01

    Sapstreak disease, a potentially serious problem of sugarbushes and forest stands, occurs when the causal fungus, Ceratocystis virescens, invades the sapwood of roots and bases of stems through wounds inflicted during logging, saphauling, or other activities. Describes how to recognize the disease, the factors that affect its occurrence and development, and management...

  13. Recognizing and Treating Malaria in U.S. Residents

    Centers for Disease Control (CDC) Podcasts

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: It's a Small World After All: Dengue and Malaria in U.S. Residents - Recognizing and Treating These Mosquito-borne Diseases. CDC's David Townes discusses clinical presentation, transmission, prevention strategies, new treatments, and malaria resources available to health care providers.

  14. Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation

    DEFF Research Database (Denmark)

    Yusim, K.; Kesmir, Can; Gaschen, B.

    2002-01-01

    The human cytotoxic T-lymphocyte (CTL) response to human immunodeficiency virus type 1 (HIV-1) has been intensely studied, and hundreds of CTL epitopes have been experimentally defined, published, and compiled in the HIV Molecular Immunology Database. Maps of CTL epitopes on HIV-1 protein sequenc...

  15. Cytolytic T lymphocyte precursor cells in congenitally athymic C57BL/6 nu/nu mice: Quantitation, enrichment, and specificity

    Energy Technology Data Exchange (ETDEWEB)

    Maryanski, J.L. (Ludwig Inst. for Cancer Research, Epalinges, Switzerland); MacDonald, H.R.; Sordat, B.; Cerottini, J.C.

    1981-03-01

    A sensitive limiting dilution microculture system was used to obtain minimal estimates of the frequency of CTL precursor cells (CTL-P) in spleens from 5- to 14-mo-old C57BL/6 nu/nu mice. Frequency determinations of CTL-P directed against H-2delta alloantigens ranged from 1/159,000 to 1/12,400. The relatively low frequency of CTL-P was enriched nearly 10-fold (to 1/2300) by passage of nude spleen cells over a column of nylon wool. After priming nude spleen cells for 7 days in conventional MLC, 1 to 3% of the MLC cells could be operationally identified as CTL-P. Furthermore, the progeny of MLC-primed nude CTL-P were specifically cytolytic for target cells of the strain used for priming. Such a system may be useful for analyzing the specificity repertoires of cells of the T cell lineage that have not undergone thymic influence.

  16. Proctalgia fugax: would you recognize it?

    Science.gov (United States)

    Babb, R R

    1996-04-01

    Proctalgia fugax is characterized by sudden and sometimes severe rectal pain that occurs by day or night at irregular intervals. The pain results from dysfunction of the internal anal sphincter. Proctalgia fugax has a uniform clinical picture, and it can be easily diagnosed when recognized. The patient can be assured that nothing serious is wrong. Expensive tests, such as computed tomography or magnetic resonance imaging of the pelvis, are not required. Treatment may be difficult, but if the attacks of pain are numerous and severe,, a calcium channel blocker such as nifedipine (Adalat, Procardia) should be tried.

  17. The U-line line balancing problem

    NARCIS (Netherlands)

    Miltenburg, G.J.; Wijngaard, J.

    1994-01-01

    The traditional line balancing (LB) problem considers a production line in which stations are arranged consecutively in a line. A balance is determined by grouping tasks into stations while moving forward (or backward) through a precedence network. Recently many production lines are being arranged

  18. Evaluation of Spring Wheat Recombinant Inbred Lines under Drought Stress

    Directory of Open Access Journals (Sweden)

    M. Moghaddaszadeh-Ahrabi

    2012-07-01

    Full Text Available Iran is one of arid and semi-arid regions of the world. Wheat as a strategic agricultural products faces water deficiency in most areas of the country. Therefore, identification of the resistant varieties to drought stress is one of main aims for breeders. To assess effect of drought stress at heading on 72 spring wheat recombinant inbred lines derived from American Yecora Rojo (high yielder, dwarf and early maturity as paternal parent and Iranian No. 49 line (tall and late maturiting as maternal parent cross were studied. The experiment was conducted at the Research Station of the University of Tabriz using a randomized complete block design with two replications during 2009 growing season. Based on the results from combined analysis of variance significant difference was observed among lines for all of traits studied, except for harvest index, grain number per spike and days to heading. There was significant difference between normal and drought stress conditions. Since the interaction between line and conditions was insignificant for all traits, it does therefore, provide the possibility of comparing the lines without regard to irrigation levels. Based on the means of, the traits it was found that the lines 96, 122, 123 and 155 were superior. MP, GMP and STI indices were recognized to be suitable indices to identify superior lines. With respect to these indices, lines 96, 122, 123, 138, 149 and 155 were found superior as compared with remaining lines. Based on stepwise regression analysis of grain yield with other traits, respectively grain number per spike, number of spikes/m2 and 1000 kernel weight were inserted into final model as effective variables on grain yield, which made 81/9 percent of the grain yield variation. Path analysis of grain yield and related traits, based on stepwise regression, demonstrated the significant positive direct effect for grain number per spike, number of spikes/m2 and 1000 kernel weight on grain yield

  19. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro

    NARCIS (Netherlands)

    E.G.M. Berkhoff (Eufemia); A.C.M. Boon (Adrianus); N.J. Nieuwkoop; R.A.M. Fouchier (Ron); K. Sintnicolaas (Krijn); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

    2004-01-01

    textabstractViruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus

  20. Multiwavelet packet entropy and its application in transmission line fault recognition and classification.

    Science.gov (United States)

    Liu, Zhigang; Han, Zhiwei; Zhang, Yang; Zhang, Qiaoge

    2014-11-01

    Multiwavelets possess better properties than traditional wavelets. Multiwavelet packet transformation has more high-frequency information. Spectral entropy can be applied as an analysis index to the complexity or uncertainty of a signal. This paper tries to define four multiwavelet packet entropies to extract the features of different transmission line faults, and uses a radial basis function (RBF) neural network to recognize and classify 10 fault types of power transmission lines. First, the preprocessing and postprocessing problems of multiwavelets are presented. Shannon entropy and Tsallis entropy are introduced, and their difference is discussed. Second, multiwavelet packet energy entropy, time entropy, Shannon singular entropy, and Tsallis singular entropy are defined as the feature extraction methods of transmission line fault signals. Third, the plan of transmission line fault recognition using multiwavelet packet entropies and an RBF neural network is proposed. Finally, the experimental results show that the plan with the four multiwavelet packet energy entropies defined in this paper achieves better performance in fault recognition. The performance with SA4 (symmetric antisymmetric) multiwavelet packet Tsallis singular entropy is the best among the combinations of different multiwavelet packets and the four multiwavelet packet entropies.

  1. Simple biophysical model of tumor evasion from immune system control

    Science.gov (United States)

    D'Onofrio, Alberto; Ciancio, Armando

    2011-09-01

    The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated.

  2. Natural killer cells facilitate PRAME-specific T-cell reactivity against neuroblastoma

    Science.gov (United States)

    Spel, Lotte; Boelens, Jaap-Jan; van der Steen, Dirk M.; Blokland, Nina J.G.; van Noesel, Max M.; Molenaar, Jan J.; Heemskerk, Mirjam H.M.

    2015-01-01

    Neuroblastoma is the most common solid tumor in children with an estimated 5-year progression free survival of 20–40% in stage 4 disease. Neuroblastoma actively avoids recognition by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Although immunotherapy has gained traction for neuroblastoma treatment, these immune escape mechanisms restrain clinical results. Therefore, we aimed to improve neuroblastoma immunogenicity to further the development of antigen-specific immunotherapy against neuroblastoma. We found that neuroblastoma cells significantly increase surface expression of MHC I upon exposure to active NK cells which thereby readily sensitize neuroblastoma cells for recognition by CTLs. We show that oncoprotein PRAME serves as an immunodominant antigen for neuroblastoma as NK-modulated neuroblastoma cells are recognized by PRAMESLLQHLIGL/A2-specific CTL clones. Furthermore, NK cells induce MHC I upregulation in neuroblastoma through contact-dependent secretion of IFNγ. Our results demonstrate remarkable plasticity in the peptide/MHC I surface expression of neuroblastoma cells, which is reversed when neuroblastoma cells experience innate immune attack by sensitized NK cells. These findings support the exploration of NK cells as adjuvant therapy to enforce neuroblastoma-specific CTL responses. PMID:26452036

  3. Recognizing the needs – Student teachers´ learning to teach from teaching

    Directory of Open Access Journals (Sweden)

    Pernilla Nilsson

    2012-06-01

    Full Text Available This paper is based on an exploration of the ways in which primary science student teachers recognize and learn about issues that shape their own professional learning. The paper discusses different perspectives of “knowledgebase needed for teaching” and Shulman’s concept of pedagogical content knowledge, and explores how elements of knowledge are to be recognized and further developed within primary teacher education. Primary science student teacher participants (n = 25 were stimulated to use portfolios as a tool to reflect upon situations within their six weeks teaching practice in pre- and primary schools in order to facilitate recognizing their knowledge needs. The results give an insight into what situations within the teaching practice that student teachers consider as important for their own learning to teach primary maths and science.

  4. TL transgenic mouse strains

    International Nuclear Information System (INIS)

    Obata, Y.; Matsudaira, Y.; Hasegawa, H.; Tamaki, H.; Takahashi, T.; Morita, A.; Kasai, K.

    1993-01-01

    As a result of abnormal development of the thymus of these mice, TCR αβ lineage of the T cell differentiation is disturbed and cells belonging to the TCR γδ CD4 - CD8 - double negative (DN) lineage become preponderant. The γδ DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, indicating that the γδ cells are incapable of participating in these reactions. Molecular and serological analyses of T-cell lymphomas reveal that they belong to the γδ lineage. Tg.Tla a -3-1 mice should be useful in defining the role of TL in normal and abnormal T cell differentiation as well as in the development of T-cell lymphomas, and further they should facilitate studies on the differentiation and function of γδ T cells. We isolated T3 b -TL gene from B6 mice and constructed a chimeric gene in which T3 b -TL is driven by the promoter of H-2K b . With the chimeric gene, two transgenic mouse strains, Tg. Con.3-1 and -2 have been derived in C3H background. Both strains express TL antigen in various tissues including skin. The skin graft of transgenic mice on C3H and (B6 X C3H)F 1 mice were rejected. In the mice which rejected the grafts, CD8 + TCRαβ cytotoxic T cells (CTL) against TL antigens were recognized. The recognition of TL by CTL did not require the antigen presentation by H-2 molecules. The results indicated that TL antigen in the skin becomes a transplantation antigen and behaves like a typical allogeneic MHC class I antigen. The facts that (B6 X C3H)F 1 mice rejected the skin expressing T3 b -TL antigen and induced CTL that killed TL + lymphomas of B6 origin revealed that TL antigen encoded by T3 b -TL is recognized as non-self in B6 mice. Experiments are now extended to analyze immune responses to TL antigen expressed on autochthonous T cell lymphomas. (J.P.N.)

  5. Efficient Banknote Recognition Based on Selection of Discriminative Regions with One-Dimensional Visible-Light Line Sensor.

    Science.gov (United States)

    Pham, Tuyen Danh; Park, Young Ho; Kwon, Seung Yong; Park, Kang Ryoung; Jeong, Dae Sik; Yoon, Sungsoo

    2016-03-04

    Banknote papers are automatically recognized and classified in various machines, such as vending machines, automatic teller machines (ATM), and banknote-counting machines. Previous studies on automatic classification of banknotes have been based on the optical characteristics of banknote papers. On each banknote image, there are regions more distinguishable than others in terms of banknote types, sides, and directions. However, there has been little previous research on banknote recognition that has addressed the selection of distinguishable areas. To overcome this problem, we propose a method for recognizing banknotes by selecting more discriminative regions based on similarity mapping, using images captured by a one-dimensional visible light line sensor. Experimental results with various types of banknote databases show that our proposed method outperforms previous methods.

  6. Efficient Banknote Recognition Based on Selection of Discriminative Regions with One-Dimensional Visible-Light Line Sensor

    Directory of Open Access Journals (Sweden)

    Tuyen Danh Pham

    2016-03-01

    Full Text Available Banknote papers are automatically recognized and classified in various machines, such as vending machines, automatic teller machines (ATM, and banknote-counting machines. Previous studies on automatic classification of banknotes have been based on the optical characteristics of banknote papers. On each banknote image, there are regions more distinguishable than others in terms of banknote types, sides, and directions. However, there has been little previous research on banknote recognition that has addressed the selection of distinguishable areas. To overcome this problem, we propose a method for recognizing banknotes by selecting more discriminative regions based on similarity mapping, using images captured by a one-dimensional visible light line sensor. Experimental results with various types of banknote databases show that our proposed method outperforms previous methods.

  7. Discovery of HeLa Cell Contamination in HES Cells: Call for Cell Line Authentication in Reproductive Biology Research.

    Science.gov (United States)

    Kniss, Douglas A; Summerfield, Taryn L

    2014-08-01

    Continuous cell lines are used frequently in reproductive biology research to study problems in early pregnancy events and parturition. It has been recognized for 50 years that many mammalian cell lines contain inter- or intraspecies contaminations with other cells. However, most investigators do not routinely test their culture systems for cross-contamination. The most frequent contributor to cross-contamination of cell lines is the HeLa cell isolated from an aggressive cervical adenocarcinoma. We report on the discovery of HeLa cell contamination of the human endometrial epithelial cell line HES isolated in our laboratory. Short tandem repeat analysis of 9 unique genetic loci demonstrated molecular identity between HES and HeLa cells. In addition, we verified that WISH cells, isolated originally from human amnion epithelium, were also contaminated with HeLa cells. Inasmuch as our laboratory did not culture HeLa cells at the time of HES cell derivations, the source of contamination was the WISH cell line. These data highlight the need for continued diligence in authenticating cell lines used in reproductive biology research. © The Author(s) 2014.

  8. The costs of using unauthenticated, over-passaged cell lines: how much more data do we need?

    Science.gov (United States)

    Hughes, Peyton; Marshall, Damian; Reid, Yvonne; Parkes, Helen; Gelber, Cohava

    2007-11-01

    Increasing data demonstrate that cellular cross-contamination, misidentified cell lines, and the use of cultures at high-passage levels contribute to the generation of erroneous and misleading results as well as wasted research funds. Contamination of cell lines by other lines has been recognized and documented back to the 1950s. Based on submissions to major cell repositories in the last decade, it is estimated that between 18% and 36% of cell lines may be contaminated or misidentified. More recently, problems surrounding practices of over-subculturing cells are being identified. As a result of selective pressures and genetic drift, cell lines, when kept in culture too long, exhibit reduced or altered key functions and often no longer represent reliable models of their original source material. A review of papers showing significant experimental variances between low- and high-passage cell culture numbers, as well as contaminated lines, makes a strong case for using verified, tested cell lines at low- or defined passage numbers. In the absence of cell culture guidelines, mandates from the National Institutes of Health (NIH) and other funding agencies or journal requirements, it becomes the responsibility of the scientific community to perform due diligence to ensure the integrity of cell cultures used in research.

  9. Cross-protective peptide vaccine against influenza A viruses developed in HLA-A*2402 human immunity model.

    Directory of Open Access Journals (Sweden)

    Toru Ichihashi

    Full Text Available BACKGROUND: The virus-specific cytotoxic T lymphocyte (CTL induction is an important target for the development of a broadly protective human influenza vaccine, since most CTL epitopes are found on internal viral proteins and relatively conserved. In this study, the possibility of developing a strain/subtype-independent human influenza vaccine was explored by taking a bioinformatics approach to establish an immunogenic HLA-A24 restricted CTL epitope screening system in HLA-transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: HLA-A24 restricted CTL epitope peptides derived from internal proteins of the H5N1 highly pathogenic avian influenza A virus were predicted by CTL epitope peptide prediction programs. Of 35 predicted peptides, six peptides exhibited remarkable cytotoxic activity in vivo. More than half of the mice which were subcutaneously vaccinated with the three most immunogenic and highly conserved epitopes among three different influenza A virus subtypes (H1N1, H3N2 and H5N1 survived lethal influenza virus challenge during both effector and memory CTL phases. Furthermore, mice that were intranasally vaccinated with these peptides remained free of clinical signs after lethal virus challenge during the effector phase. CONCLUSIONS/SIGNIFICANCE: This CTL epitope peptide selection system can be used as an effective tool for the development of a cross-protective human influenza vaccine. Furthermore this vaccine strategy can be applicable to the development of all intracellular pathogens vaccines to induce epitope-specific CTL that effectively eliminate infected cells.

  10. Recognition of melanoma-derived antigens by CTL: possible mechanisms involved in down-regulating anti-tumor T-cell reactivity

    DEFF Research Database (Denmark)

    Rivoltini, L; Loftus, D J; Squarcina, P

    1998-01-01

    Several T cell-recognized epitopes presented by melanoma cells have been identified recently. Despite the large array of epitopes potentially available for clinical use, it is still unclear which of these antigens could be effective in mediating anti-tumor responses when used as a vaccine...

  11. The role and mechanics of dendritic cells in tumor antigen acquisition and presentation following laser immunotherapy

    Science.gov (United States)

    Laverty, Sean M.; Dawkins, Bryan A.; Chen, Wei R.

    2018-02-01

    We extend our model of the antitumor immune response initiated by laser-immunotherapy treatment to more closely examine key steps in the immune response 1) tumor antigen acquisition by antigen-presenting dendritic cells (DCs) and 2) cytotoxic T cell (CTL) priming by lymphatic DCs. Specifically we explore the formation of DC-CTL complexes that lead to CTL priming. We find that the bias in the dissociation rate of the complex influences the outcome of treatment. In particular, a bias towards priming favors a rapid activated CTL response and the clearance of tumors.

  12. Lessons from Tiananmen Square: Recognizing Bias in News Reporting.

    Science.gov (United States)

    Braun, Joseph A., Jr.

    1990-01-01

    Recommends teaching students to recognize bias in news reports and how personal preferences infringe on objective judgment. Provides two class activities designed to help students understand this concept. Uses the Cinderella story from three cultures and group discussion to illustrate this technique. (NL)

  13. Design of an Adaptive Human-Machine System Based on Dynamical Pattern Recognition of Cognitive Task-Load.

    Science.gov (United States)

    Zhang, Jianhua; Yin, Zhong; Wang, Rubin

    2017-01-01

    This paper developed a cognitive task-load (CTL) classification algorithm and allocation strategy to sustain the optimal operator CTL levels over time in safety-critical human-machine integrated systems. An adaptive human-machine system is designed based on a non-linear dynamic CTL classifier, which maps a set of electroencephalogram (EEG) and electrocardiogram (ECG) related features to a few CTL classes. The least-squares support vector machine (LSSVM) is used as dynamic pattern classifier. A series of electrophysiological and performance data acquisition experiments were performed on seven volunteer participants under a simulated process control task environment. The participant-specific dynamic LSSVM model is constructed to classify the instantaneous CTL into five classes at each time instant. The initial feature set, comprising 56 EEG and ECG related features, is reduced to a set of 12 salient features (including 11 EEG-related features) by using the locality preserving projection (LPP) technique. An overall correct classification rate of about 80% is achieved for the 5-class CTL classification problem. Then the predicted CTL is used to adaptively allocate the number of process control tasks between operator and computer-based controller. Simulation results showed that the overall performance of the human-machine system can be improved by using the adaptive automation strategy proposed.

  14. Thymectomized, irradiated, and bone marrow-reconstituted chimeras have normal cytolytic T lymphocyte precursors but a defect in lymphokine production

    International Nuclear Information System (INIS)

    Duprez, V.; Maziarz, R.; Weinberger, O.; Burakoff, S.J.

    1984-01-01

    A model system has been developed to study extrathymic T cell differentiation; mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1 + cells. After 8 wk, the spleen cells of these athymic, bone marrow-reconstituted chimeras contain Thy-1 + precytolytic T lymphocytes (CTL) that are able to respond to antigen only if supernatant from Con A-activated T cells is added to culture. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be immature T cells. Initial evaluation of the CTL repertoire of these athymic mice demonstrated that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2-restricted, and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal mice but not in nude mice. In this report, the authors demonstrate a helper T cell defect in these thymectomized chimeras. These chimeras lack an Ly-1 + helper cell required for thymocytes to differentiate to CTL. Further studies revealed that when spleen cells from these thymectomized chimeras were stimulated with Con A, they produced normal levels of interleukin 2. However, these splenocytes were defective in the production of another factor needed for CTL differentiation

  15. Expression of blood group I and i active carbohydrate sequences on cultured human and animal cell lines assessed by radioimmunoassays with monoclonal cold agglutinins

    International Nuclear Information System (INIS)

    Childs, R.A.; Kapadia, A.; Feizi, T.

    1980-01-01

    Human monoclonal anti-I and anti-i, reactive with known carbohydrate sequences, have been used as reagents to quantitate (by radioimmunoassay) and visualize (by immunofluorescence) the expression of the various blood group I and i antigenic determinants in a variety of cultured cell lines commonly used in laboratory investigations. It has been shown that the antigens they recognize are widely distributed on the surface of human and animal cell lines, expressed in varying amounts in different cell lines and on individual cells within a given cell line. In two cell lines, a transformation-associated increase in the expression of I antigen was observed. Because of their precise specificity for defined carbohydrate chain domains, these autoantibodies have become valuable reagents in biological chemistry. (orig.) [de

  16. Regulation of primary cytotoxic T lymphocyte responses generated during mixed leukocyte culture with H-2d identical Qa-1-disparate cells

    International Nuclear Information System (INIS)

    Huston, D.P.; Tavana, G.; Rich, R.R.; Gressens, S.E.

    1986-01-01

    Cytotoxic lymphocyte (CTL) responses are not usually generated during primary mixed leukocyte culture (MLC) with H-2 identical cells. Thus NZB mice are unusual in that their spleen cells do mount CTL responses during primary MLC with H-2d identical stimulator cells; the predominant target antigen for these NZB responses is Qa-1b. Considering the numerous immunoregulatory defects in NZB mice, we postulated that these NZB anti-Qa-1 primary CTL responses were due to an abnormality in T suppressor cell activity. Cellular interactions capable of suppressing NZB anti-Qa-1 primary CTL responses were investigated by using one-way and two-way MLC with spleen cells from NZB mice and other H-2d strains. Although H-2d identical one-way MLC with the use of NZB responders resulted in substantial CTL responses, only minimal CTL responses were detected from two-way MLC with the use of NZB spleen cells plus nonirradiated spleen cells from other H-2d mice. Thus the presence of non-NZB spleen cells in the two-way H-2d identical MLC prevented the generation of NZB CTL. Noncytotoxic mechanisms were implicated in the suppression of the NZB CTL responses during two-way MLC, because only minimal CTL activity was generated when NZB spleen cells were cultured with semiallogeneic, H-2d identical (e.g., NZB X BALB) F1 spleen cells. The observed suppression could be abrogated with as little as 100 rad gamma-irradiation to the non-NZB spleen cells. The phenotype of these highly radiosensitive spleen cells was Thy-1+, Lyt-1+, Lyt-2-, L3T4+. The functional presence of these cells in the spleens of semiallogeneic, H-2d identical F1 mice indicated that their deficiency in NZB mice was a recessive trait. These data suggest that NZB mice lack an L3T4+ cell present in the spleens of normal mice that is capable of suppressing primary anti-Qa-1 CTL responses

  17. Establishment and characterization of a novel osteosarcoma cell line: CHOS.

    Science.gov (United States)

    Liu, Yunlu; Feng, Xiaobo; Zhang, Yukun; Jiang, Hongyan; Cai, Xianyi; Yan, Xinxin; Huang, Zengfa; Mo, Fengbo; Yang, Wen; Yang, Cao; Yang, Shuhua; Liu, Xianzhe

    2016-12-01

    Osteosarcoma has a well-recognized bimodal distribution, with the first peak in adolescence and another in the elderly age-group. The elderly patients have different clinical features and a poorer prognosis as compared to adolescents. To better understand the biological features of osteosarcoma in the elderly population, we established a new human osteosarcoma cell line from a 58-year-old man with primary chondroblastic osteosarcoma. After 6 months of continuous culture in vitro for over 50 passages, an immortalized cell line CHOS was established. The cell line was well-characterized by cytogenetic, biomarker, functional, and histological analyses. The CHOS cells exhibited a spindle-shaped morphology and a doubling time of 36 h. Cytogenetic analysis of CHOS cells revealed the loss of chromosome Y and the gain of chromosome 12. Quantitative real-time polymerase chain reaction (RT-PCR), Western blotting and/or immunofluorescence revealed the expression of chondroblastic, mesenchymal and tumor metastasis markers in the CHOS cells. Compared with the osteosarcoma cell line, the CHOS cells were found to be more sensitive to cisplatin and doxorubicin, but were resistant to methotrexate. The cell line was highly tumorigenic and maintained the histological characteristics and invasive nature of the original tumor. Furthermore, on immunohistochemical analysis, the xenografts and metastases were found to co-express collagen II, aggrecan, vimentin and S100A4 that resembled the original tumor cells. Our results indicate, the potential of CHOS cell line to serve as a useful tool for further studies on the molecular biology of osteosarcoma, especially in the elderly patients. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2116-2125, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Literature Review: Is the Emotional Expression of Contempt Recognized Universally or Culturally?

    OpenAIRE

    Phoukhao, Julianna

    2017-01-01

    The universal facial expression of contempt is often described as one lip corner raised and tightened. This literature reviews whether or not this expression is recognized universally. After examining theories and methods, low agreement of this expression recognized as contempt was found across cultures. Evidence so far is not sufficient enough to support the unilateral lip corner as an universal expression for contempt. The expression and recognition of contempt is highly dependent on cultur...

  19. Craig Reynolds: Recognized for Excellence in Medicine | Poster

    Science.gov (United States)

    The Distinguished Alumni Award is one of the most prestigious awards at the University of Iowa Roy J. and Lucille A. Carver College of Medicine. This award recognizes influential alumni who have achieved excellence in the art and science of medicine. One of this year’s recipients is Craig Reynolds, Ph.D., associate director, NCI. When asked how he felt about receiving this

  20. Quasar outflow energetics from broad absorption line variability

    Science.gov (United States)

    McGraw, S. M.; Shields, J. C.; Hamann, F. W.; Capellupo, D. M.; Herbst, H.

    2018-03-01

    Quasar outflows have long been recognized as potential contributors to the co-evolution between supermassive black holes (SMBHs) and their host galaxies. The role of outflows in active galactic nucleus (AGN) feedback processes can be better understood by placing observational constraints on wind locations and kinetic energies. We utilize broad absorption line (BAL) variability to investigate the properties of a sample of 71 BAL quasars with P V broad absorption. The presence of P V BALs indicates that other BALs like C IV are saturated, such that variability in those lines favours clouds crossing the line of sight. We use these constraints with measurements of BAL variability to estimate outflow locations and energetics. Our data set consists of multiple-epoch spectra from the Sloan Digital Sky Survey and MDM Observatory. We detect significant (4σ) BAL variations from 10 quasars in our sample over rest-frame time-scales between ≤0.2-3.8 yr. Our derived distances for the 10 variable outflows are nominally ≲ 1-10 pc from the SMBH using the transverse-motion scenario, and ≲ 100-1000 pc from the central source using ionization-change considerations. These distances, in combination with the estimated high outflow column densities (i.e. NH ≳ 1022 cm-2), yield outflow kinetic luminosities between ˜ 0.001 and 1 times the bolometric luminosity of the quasar, indicating that many absorber energies within our sample are viable for AGN feedback.

  1. Development of contextual teaching and learning based science module for junior high school for increasing creativity of students

    Science.gov (United States)

    Kurniasari, H.; Sukarmin; Sarwanto

    2018-03-01

    The purpose of this research are to analyze the the properness of contextual teaching and learning (CTL)-based science module for Junior High School for increasing students’ creativity and using CTL-based science module to increase students’ learning creativity. Development of CTL-based science module for Junior High School is Research and Development (R&D) using 4D Model consist of 4 steps: define, design, develop, and disseminate. Module is validated by 3 expert validators (Material, media, and language experts), 2 reviewer and 1 peer reviewer. . Based on the results of data analysis, it can be concluded that: the results of the validation, the average score of CTL-based science module is 88.28%, the value exceeded the value of the cut off score of 87.5%, so the media declared eligible for the study. Research shows that the gain creativity class that uses CTL-based science module has a gain of 0.72. Based on the results of the study showed that CTL-based science module effectively promotes creativity of students

  2. Analysis of Gait Pattern to Recognize the Human Activities

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    2014-09-01

    Full Text Available Human activity recognition based on the computer vision is the process of labelling image sequences with action labels. Accurate systems for this problem are applied in areas such as visual surveillance, human computer interaction and video retrieval. The challenges are due to variations in motion, recording settings and gait differences. Here we propose an approach to recognize the human activities through gait. Activity recognition through Gait is the process of identifying an activity by the manner in which they walk. The identification of human activities in a video, such as a person is walking, running, jumping, jogging etc are important activities in video surveillance. We contribute the use of Model based approach for activity recognition with the help of movement of legs only. Experimental results suggest that our method are able to recognize the human activities with a good accuracy rate and robust to shadows present in the videos.

  3. Recognizing intentions in infant-directed speech: evidence for universals.

    Science.gov (United States)

    Bryant, Gregory A; Barrett, H Clark

    2007-08-01

    In all languages studied to date, distinct prosodic contours characterize different intention categories of infant-directed (ID) speech. This vocal behavior likely exists universally as a species-typical trait, but little research has examined whether listeners can accurately recognize intentions in ID speech using only vocal cues, without access to semantic information. We recorded native-English-speaking mothers producing four intention categories of utterances (prohibition, approval, comfort, and attention) as both ID and adult-directed (AD) speech, and we then presented the utterances to Shuar adults (South American hunter-horticulturalists). Shuar subjects were able to reliably distinguish ID from AD speech and were able to reliably recognize the intention categories in both types of speech, although performance was significantly better with ID speech. This is the first demonstration that adult listeners in an indigenous, nonindustrialized, and nonliterate culture can accurately infer intentions from both ID speech and AD speech in a language they do not speak.

  4. How legumes recognize rhizobia.

    Science.gov (United States)

    Via, Virginia Dalla; Zanetti, María Eugenia; Blanco, Flavio

    2016-01-01

    Legume plants have developed the capacity to establish symbiotic interactions with soil bacteria (known as rhizobia) that can convert N2 to molecular forms that are incorporated into the plant metabolism. The first step of this relationship is the recognition of bacteria by the plant, which allows to distinguish potentially harmful species from symbiotic partners. The main molecular determinant of this symbiotic interaction is the Nod Factor, a diffusible lipochitooligosaccharide molecule produced by rhizobia and perceived by LysM receptor kinases; however, other important molecules involved in the specific recognition have emerged over the years. Secreted exopolysaccharides and the lipopolysaccharides present in the bacterial cell wall have been proposed to act as signaling molecules, triggering the expression of specific genes related to the symbiotic process. In this review we will briefly discuss how transcriptomic analysis are helping to understand how multiple signaling pathways, triggered by the perception of different molecules produced by rhizobia, control the genetic programs of root nodule organogenesis and bacterial infection. This knowledge can help to understand how legumes have evolved to recognize and establish complex ecological relationships with particular species and strains of rhizobia, adjusting gene expression in response to identity determinants of bacteria.

  5. Natural killer cells for immunotherapy – Advantages of cell lines over blood NK cells

    Directory of Open Access Journals (Sweden)

    Hans eKlingemann

    2016-03-01

    Full Text Available Natural killer cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells form a patient’s blood since they represent only 10% of the lymphocytes. Especially, cancer patients are known to have dysfunctional NK cells. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T-cells. Establishing cell lines from donor blood NK cells have not been successful, in contrast to blood NK cells obtained from patients with a clonal NK cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. However, except for the NK-92 cell line none of the other six known cell lines has consistent and reproducibly high anti-tumor cytotoxicity, nor can they be easily genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through ADCC. NK-92 is also the only cell line product that has been widely given to patients with advanced cancer with demonstrated efficiency and minimal side effects.

  6. Pinus saw timber tree optimisation in South Africa: a comparison of ...

    African Journals Online (AJOL)

    Both Cut to Length (CTL) and Full Tree/Tree Length (FT/TL) ground-based systems are used to harvest pine in South Africa. The fully mechanised CTL system is the most recently introduced system in South Africa. One of the reasons for the limited use of CTL harvesting systems in South Africa is the perceived inability of the ...

  7. Ethanol extract of Carthamus tinctorius L. shows anti-thrombosis ...

    African Journals Online (AJOL)

    TXB2 decreased and 6-keto-PGF1α increased with CTL and aspirin, with an association between 6-keto-PGF1α/TXB2 and arterial or venous thrombus weight for all products, and for occlusion time with CTL but not for aspirin. Conclusion: The experimental effects of CTL on thrombosis in rats were confirmed. Again, further ...

  8. Comprehensive Context Recognizer Based on Multimodal Sensors in a Smartphone

    Directory of Open Access Journals (Sweden)

    Sungyoung Lee

    2012-09-01

    Full Text Available Recent developments in smartphones have increased the processing capabilities and equipped these devices with a number of built-in multimodal sensors, including accelerometers, gyroscopes, GPS interfaces, Wi-Fi access, and proximity sensors. Despite the fact that numerous studies have investigated the development of user-context aware applications using smartphones, these applications are currently only able to recognize simple contexts using a single type of sensor. Therefore, in this work, we introduce a comprehensive approach for context aware applications that utilizes the multimodal sensors in smartphones. The proposed system is not only able to recognize different kinds of contexts with high accuracy, but it is also able to optimize the power consumption since power-hungry sensors can be activated or deactivated at appropriate times. Additionally, the system is able to recognize activities wherever the smartphone is on a human’s body, even when the user is using the phone to make a phone call, manipulate applications, play games, or listen to music. Furthermore, we also present a novel feature selection algorithm for the accelerometer classification module. The proposed feature selection algorithm helps select good features and eliminates bad features, thereby improving the overall accuracy of the accelerometer classifier. Experimental results show that the proposed system can classify eight activities with an accuracy of 92.43%.

  9. Bridges to Excellence--recognizing high-quality care: analysis of physician quality and resource use.

    Science.gov (United States)

    Rosenthal, Meredith B; de Brantes, Francois S; Sinaiko, Anna D; Frankel, Matthew; Robbins, Russell D; Young, Sara

    2008-10-01

    To examine whether physicians who sought and received Bridges to Excellence (BTE) recognition performed better than similar physicians on a standardized set of population-based performance measures. Cross-sectional comparison of performance data. Using a claims dataset of all commercially insured members from 6 health plans in Massachusetts, we examined population-based measures of quality and resource use for physicians recognized by the BTE programs Physician Office Link and Diabetes Care Link, compared with nonrecognized physicians in the same specialties. Differences in performance were tested using generalized linear models. Physician Office Link-recognized physicians performed significantly better than their nonrecognized peers on measures of cervical cancer screening, mammography, and glycosylated hemoglobin testing. Diabetes Care Link-recognized physicians performed significantly better on all 4 diabetes process measures of quality, with the largest differences observed in microalbumin screening (17.7%). Patients of Physician Office Link-recognized physicians had a significantly greater percentage of their resource use accounted for by evaluation and management services (3.4%), and a smaller percentage accounted for by facility (-1.6%), inpatient ancillary (-0.1%), and nonmanagement outpatient services (-1.0%). After adjustment for patient age and sex, and case mix, Physician Office Link-recognized physicians had significantly fewer episodes per patient (0.13) and lower resource use per episode (dollars 130), but findings were mixed for Diabetes Care Link-recognized physicians. Our findings suggest that the BTE approach to ascertaining physician quality identifies physicians who perform better on claims-based quality measures and primary care physicians who use a less resource-intensive practice style.

  10. Recognizing team formation in american football

    KAUST Repository

    Atmosukarto, Indriyati; Ghanem, Bernard; Nasef Saadalla, Mohamed Magdy Mohamed; Ahuja, Narendra

    2014-01-01

    Most existing software packages for sports video analysis require manual annotation of important events in the video. Despite being the most popular sport in the United States, most American football game analysis is still done manually. Line

  11. Recognizing limitations in eddy current testing

    International Nuclear Information System (INIS)

    Van Drunen, G.; Cecco, V.S.

    1981-11-01

    This paper addresses known limitations and constraints in eddy current nondestructive testing. Incomplete appreciation for eddy current limitations is believed to have contributed to both under-utilization and misapplication of the technique. Neither situation need arise if known limitations are recognized. Some, such as the skin depth effect, are inherent to electromagnetic test methods and define the role of eddy current testing. Others can be overcome with available technology such as surface probes to find circumferential cracks in tubes and magnetic saturation of ferromagnetic alloys to eliminate permeability effects. The variables responsible for limitations in eddy current testing are discussed and where alternative approaches exist, these are presented. Areas with potential for further research and development are also identified

  12. NREL: News - Students Recognized for Creativity during Energy Education

    Science.gov (United States)

    Event Recognized for Creativity during Energy Education Event Golden, Colo., May 13, 2002 Tapping the power of the sun was the theme of the May 11 Solarbrate Education event at the U.S. Department Assistance Foundation, Oakwood Homes, Home Depot, E-Star Colorado, Governor's Office of Energy Management

  13. Automated Facial Coding Software Outperforms People in Recognizing Neutral Faces as Neutral from Standardized Datasets

    Directory of Open Access Journals (Sweden)

    Peter eLewinski

    2015-09-01

    Full Text Available Little is known about people’s accuracy of recognizing neutral faces as neutral. In this paper, I demonstrate the importance of knowing how well people recognize neutral faces. I contrasted human recognition scores of 100 typical, neutral front-up facial images with scores of an arguably objective judge – automated facial coding (AFC software. I hypothesized that the software would outperform humans in recognizing neutral faces because of the inherently objective nature of computer algorithms. Results confirmed this hypothesis. I provided the first-ever evidence that computer software (90% was more accurate in recognizing neutral faces than people were (59%. I posited two theoretical mechanisms, i.e. smile-as-a-baseline and false recognition of emotion, as possible explanations for my findings.

  14. Recognizing and responding to uncertainty: a grounded theory of nurses' uncertainty.

    Science.gov (United States)

    Cranley, Lisa A; Doran, Diane M; Tourangeau, Ann E; Kushniruk, Andre; Nagle, Lynn

    2012-08-01

    There has been little research to date exploring nurses' uncertainty in their practice. Understanding nurses' uncertainty is important because it has potential implications for how care is delivered. The purpose of this study is to develop a substantive theory to explain how staff nurses experience and respond to uncertainty in their practice. Between 2006 and 2008, a grounded theory study was conducted that included in-depth semi-structured interviews. Fourteen staff nurses working in adult medical-surgical intensive care units at two teaching hospitals in Ontario, Canada, participated in the study. The theory recognizing and responding to uncertainty characterizes the processes through which nurses' uncertainty manifested and how it was managed. Recognizing uncertainty involved the processes of assessing, reflecting, questioning, and/or being unable to predict aspects of the patient situation. Nurses' responses to uncertainty highlighted the cognitive-affective strategies used to manage uncertainty. Study findings highlight the importance of acknowledging uncertainty and having collegial support to manage uncertainty. The theory adds to our understanding the processes involved in recognizing uncertainty, strategies and outcomes of managing uncertainty, and influencing factors. Tailored nursing education programs should be developed to assist nurses in developing skills in articulating and managing their uncertainty. Further research is needed to extend, test and refine the theory of recognizing and responding to uncertainty to develop strategies for managing uncertainty. This theory advances the nursing perspective of uncertainty in clinical practice. The theory is relevant to nurses who are faced with uncertainty and complex clinical decisions, to managers who support nurses in their clinical decision-making, and to researchers who investigate ways to improve decision-making and care delivery. ©2012 Sigma Theta Tau International.

  15. T cells recognizing a peptide contaminant undetectable by mass spectrometry

    DEFF Research Database (Denmark)

    Brezar, Vedran; Culina, Slobodan; Østerbye, Thomas

    2011-01-01

    Synthetic peptides are widely used in immunological research as epitopes to stimulate their cognate T cells. These preparations are never completely pure, but trace contaminants are commonly revealed by mass spectrometry quality controls. In an effort to characterize novel major histocompatibility...... complex (MHC) Class I-restricted ß-cell epitopes in non-obese diabetic (NOD) mice, we identified islet-infiltrating CD8+ T cells recognizing a contaminating peptide. The amount of this contaminant was so small to be undetectable by direct mass spectrometry. Only after concentration by liquid...... chromatography, we observed a mass peak corresponding to an immunodominant islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214) epitope described in the literature. Generation of CD8+ T-cell clones recognizing IGRP(206-214) using a novel method confirmed the identity...

  16. The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral CD8+ T Cells via SHIP-1

    Directory of Open Access Journals (Sweden)

    Jennifer L. Hope

    2017-12-01

    Full Text Available We report here that the expression of the transcription factor T-bet, which is known to be required for effector cytotoxic CD8+ T lymphocytes (CTL generation and effector memory cell formation, is regulated in CTL by microRNA-155 (miR-155. Importantly, we show that the proliferative effect of miR-155 on CD8+ T cells is mediated by T-bet. T-bet levels in CTL were controlled in vivo by miR-155 via SH2 (Src homology 2-containing inositol phosphatase-1 (SHIP-1, a known direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies reveal an important and unexpected signaling axis between miR-155, T-bet, and SHIP-1 in in vivo CTL responses and suggest an important signaling module that regulates effector CTL immunity.

  17. Generation of specific antitumor cytotoxic T-lymphocytes in the monoculture

    International Nuclear Information System (INIS)

    Lupatov, A.Yu.; Brondz, B.D.

    1992-01-01

    A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2 + , Lyt2 + , L3T4 - phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. The release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors

  18. Do Preschoolers Recognize The Emotional Expressiveness of Colors in Realistic and Abstract Art Paintings?

    Science.gov (United States)

    Pouliou, Dimitra; Bonoti, Fotini; Nikonanou, Niki

    2018-01-01

    The present study was designed to examine preschoolers' ability to recognize the emotional expressiveness of an art painting, through its colors. To attain this aim 78 children, 3-5 years old were presented with realistic and abstract paintings conveying either happiness or sadness and were asked to choose those which matched the appropriate emotion. In total 16 paintings were used, which varied in color, while their subject matter was held as constant as possible after they had been previously rated by a group of adults to ensure that they conveyed the two emotions under investigation. Results showed that children's ability to recognize the emotional expressiveness of a painting through its colors appears at 3 years old and increases significantly at 4 and 5 years old. It was also found that the mood of happiness was more easily recognized than that of sadness, while the style of art paintings (realistic vs. abstract) did not affect children's ability to recognize emotions.

  19. Poly(ADP-ribosyl)ation is recognized by ECT2 during mitosis.

    Science.gov (United States)

    Li, Mo; Bian, Chunjing; Yu, Xiaochun

    2014-01-01

    Poly(ADP-ribosyl)ation is an unique posttranslational modification and required for spindle assembly and function during mitosis. However, the molecular mechanism of poly(ADP-ribose) (PAR) in mitosis remains elusive. Here, we show the evidence that PAR is recognized by ECT2, a key guanine nucleotide exchange factor in mitosis. The BRCT domain of ECT2 directly binds to PAR both in vitro and in vivo. We further found that α-tubulin is PARylated during mitosis. PARylation of α-tubulin is recognized by ECT2 and recruits ECT2 to mitotic spindle for completing mitosis. Taken together, our study reveals a novel mechanism by which PAR regulates mitosis.

  20. Effect of Cudrania tricuspidata and Kaempferol in Endoplasmic Reticulum Stress-Induced Inflammation and Hepatic Insulin Resistance in HepG2 Cells.

    Science.gov (United States)

    Kim, Ok-Kyung; Jun, Woojin; Lee, Jeongmin

    2016-01-21

    In this study, we quantitated kaempferol in water extract from Cudrania tricuspidata leaves (CTL) and investigated its effects on endoplasmic reticulum (ER) stress-induced inflammation and insulin resistance in HepG2 cells. The concentration of kaempferol in the CTL was 5.07 ± 0.08 mg/g. The HepG2 cells were treated with 300 µg/mL of CTL, 500 µg/mL of CTL, 1.5 µg/mL of kaempferol or 2.5 µg/mL of kaempferol, followed immediately by stimulation with 100 nM of thapsigargin for ER stress induction for 24 h. There was a marked increase in the activation of the ER stress and inflammation response in the thapsigargin-stimulated control group. The CTL treatment interrupted the ER stress response and ER stress-induced inflammation. Kaempferol partially inhibited the ER stress response and inflammation. There was a significant increase in serine phosphorylation of insulin receptor substrate (IRS)-1 and the expression of C/EBPα and gluconeogenic genes in the thapsigargin-stimulated control group compared to the normal control. Both CTL and kaempferol suppressed serine phosphorylation of IRS-1, and the treatments did not interrupt the C/EBPα/gluconeogenic gene pathway. These results suggest that kaempferol might be the active compound of CTL and that it might protect against ER stress-induced inflammation and hyperglycemia.

  1. A novel C-type lectin identified by EST analysis in tissue migratory larvae of Ascaris suum.

    Science.gov (United States)

    Yoshida, Ayako; Nagayasu, Eiji; Horii, Yoichiro; Maruyama, Haruhiko

    2012-04-01

    C-type lectins (CTLs) are a group of proteins which bind to carbohydrate epitopes in the presence of Ca(2+), which have been described in a wide range of species. In this study, a cDNA sequence coding a putative CTL has been identified from the cDNA library constructed from the pig round worm Ascaris suum lung L3 (LL3) larvae, which was designated as A. suum C-type lectin-1 (As-CTL-1). The 510 nucleotide open reading frame of As-CTL-1 cDNA encoded the predicted 169 amino acid protein including a putative signal peptide of 23 residues and C-type lectin/C-type lectin-like domain (CLECT) at residue 26 to 167. As-CTL-1 was most similar to Toxocara canis C-type lectin-1 and 4 (Tc-CTL-1 and 4), and highly homologous to namatode CTLs and mammalian CTLs as well, such as human C-type lectin domain family 4 member G (CLECG4). In addition, As-CTL-1 was strongly expressed in tissue migrating LL3 and the L4 larvae, which were developmental larvae stages within the mammalian host. These results suggest that A. suum larvae might utilize As-CTL-1 to avoid pathogen recognition mechanisms in mammalian hosts due to it is similarity to host immune cell receptors.

  2. Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT

    International Nuclear Information System (INIS)

    Oh, Seungjong; Stewart, James; Moseley, Joanne; Kelly, Valerie; Lim, Karen; Xie, Jason; Fyles, Anthony; Brock, Kristy K.; Lundin, Anna; Rehbinder, Henrik; Milosevic, Michael; Jaffray, David

    2014-01-01

    Purpose: Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. Materials and method: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3 mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. Results: Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases

  3. “An Unexpected Sound”: Recognizing Diverse Voices in Postcolonial Literary Interpretation

    Directory of Open Access Journals (Sweden)

    Joanne Nystrom Janssen

    2012-04-01

    Full Text Available This article explores expectations about the ways in which readers from each side of the colonial/colonized divide might approach texts. Pedagogical articles about world and postcolonial literature frequently classify readers in one of two categories—Western or non-Western. Since I teach women from a dozen Asian countries at the Asian University for Women in Chittagong, Bangladesh, I had imagined that my world literature students would embody expectations about readers from the developing world: that they would relate to the characters and themes in the course’s contemporary texts. When I began teaching Marjane Satrapi’s "Persepolis" (2003 last spring, however, I learned that my students’ responses to the text varied considerably from what I had expected. As a result, I began questioning my assumptions: why exactly did I expect certain responses from my students, and what is the significance of the alternate responses with which I was confronted? I argue that the assumed interpretive binary does not always exist. In addition to failing to recognize the diverse points of view that readers may bring to texts, the assumption frequently presupposes that postcolonial authors have imagined only Western readers as their audiences—a view that runs the risk of reinforcing oppositional lines of thinking rather than eradicating them. Using Persepolis as a case study, I propose avoiding the Western/non-Western binary when considering readers of literature, which requires paying greater attention to “minority” voices—an ironic assertion, considering the field’s alleged attention to diversity, heterogeneity, and cultural and historical specificity.

  4. Diagnosis and treatment of leukemia recognized in atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Ichimaru, M [Nagasaki Univ. (Japan). School of Medicine

    1978-05-01

    Out of atomic bomb survivors in Hiroshima and Nagasaki, 256 patients which were diagnosed as having leukemia by 1975 and of which exposure dose was estimated as over 1 rad were described. Chronic myelocytic leukemia (CGL) was plentiful in Hiroshima, and acute myelocytic leukemia (AGL) was comparatively plentiful in Nagasaki. Chronic lymphatic leukemia (CLL) was not recognized in the atomic bomb survivors exposed at places near the center of the explosion, but CLL was recognized plentifully in the atomic bomb survivors exposed to radiation of under 1 rad. The incidence of leukemia according to the total dose was higher in Hiroshima than in Nagasaki. When RBE of neutron on the occurrence of leukemia was considered to be five times that of gamma-ray, the occurrence curves in both cities were consistent well. As to a relationship between leukemia in the atomic bomb survivors and the age at the exposure time, CGL occurred early in the atomic bomb survivors exposed at an early age. A specific lesion of leukemia in the atomic bomb survivors was not recognized, but cases of which leukemia cells were negative to peroxidase and were very difficult to be identified were plentiful in the atomic bomb survivors exposed within 2 km from the explosion center. The treatment of leukemia in atomic bomb survivors does not differ from that of general leukemia, but a method of treatment, administration dosage, a method and a kind of supportive care must be discussed according to each case.

  5. A novel approach in recognizing magnetic material with simplified algorithm

    KAUST Repository

    Talukdar, Abdul Hafiz Ibne; Sultana, Mahbuba Q.; Useinov, Arthur

    2011-01-01

    . This signal was further analyzed (recognized) in frequency domain creating the Fourier frequency spectrum which is easily used to detect the response of magnetic sample. The novel algorithm in detecting magnetic field is presented here with both simulation

  6. Action of the city of Schweinfurt against Kernkraftwerk Grafenrheinfeld recognized

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    In the appeal proceedings, the Bavarian Administrative Court with its interim decision of April 9, 1979 - No. 167 VI 74 - has recognized the action of the city of Schweinfurt against the state of Bavaria to set aside the 1st part license for the construction of Kernkraftwerk Grafenrheinfeld, although the right for action was limited to the city's legal position concerning planning authority, drinking water supply, and a city-owned lake used for swimming. Appeal was allowed. The city has lodged an appeal. The decision of the Administrative Court of Wuerzburg of March 25, 1977, which was contested by the appeal, had also recognized the city's rights but dismissed the action as being unfounded. Guidelines and reasons for the decision of the Bavarian Administrative Court are given in full wording. (orig./HP) 891 HP/orig.- 892 HIS [de

  7. Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity

    International Nuclear Information System (INIS)

    Golding, H.; Munitz, T.I.; Singer, A.

    1985-01-01

    The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. The authors found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, the authors utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus

  8. HIV-specific CD8+ T cells: serial killers condemned to die?

    Science.gov (United States)

    Petrovas, Constantinos; Mueller, Yvonne M; Katsikis, Peter D

    2004-04-01

    An increasing body of evidence supports a key role for cytotoxic CD8+ T cells (CTL) in controlling HIV infection. Although a vigorous HIV-specific CD8+ T cell response is raised during the primary infection, these cells ultimately fail to control virus and prevent disease progression. The failure of CTL to control HIV infection has been attributed to a number of strategies HIV employs to evade the immune system. Recently, intrinsic defects in the CTL themselves have been proposed to contribute to the failure of CTL to control HIV. HIV-specific CD8+ T cells differ in their effector/memory phenotype from other virus-specific CD8+ T cells indicating that their differentiation status differs. This altered differentiation may affect effector functions as well as homing properties of these cells. Other studies have indicated that activation of HIV-specific CTL may be impaired and this contributes to their dysfunction. The effector function of these CTL may also be affected. There are conflicting reports about their ability to kill, whereas IFNgamma production does not appear to be impaired in these cells. In this review we focus on recent work indicating that apoptosis may be an important mechanism through which HIV evades the CTL response. In particular, HIV-specific CD8+ T cells are highly susceptible to CD95/Fas-induced apoptosis. This leads to the hypothesis that virus-specific cytotoxic T cells can be eliminated upon binding CD95L/FasL on HIV-infected cells. Understanding the intrinsic defects of CTL in HIV infection could lead to new therapeutic strategies and optimized vaccination protocols that enhance the HIV-specific cytotoxic response.

  9. Patient Selection in Plastic Surgery: Recognizing Body Dysmorphic Disorder

    Directory of Open Access Journals (Sweden)

    Cihan Sahin

    2013-04-01

    Full Text Available Plastic surgery is a branch of medicine that provides significant improvements to the people with positive changes. But first of all, this branch has a characteristic which requires analysing patients' psychological situation very carefully. Plastic surgeons are often confronted by patients with mental disorders seeking aesthetic surgery. It is imperative for surgeons to recognize possible underlying psychiatric illnesses. Common psychiatric conditions seen in cosmetic surgery patients include body dysmorphic disorder (BDD, narcissistic personality disorder and histrionic personality disorders. BDD is of particular importance to plastic surgeons. Because outrageous dissatisfaction with one's appearance may conceal psychopathologic traits that are not always easily recognizable, and which, if neglected, may result in serious iatrogenic and medicolegal consequences, we hope that this paper will help plastic surgeons in ultimately preventing patient and surgeon dissatisfaction within the population of patients with psychiatric disorders, and should recognize the diagnostic features of body dysmorphic disorder and screen psychologically unstable patients who may never be satisfied with surgery. [Arch Clin Exp Surg 2013; 2(2.000: 109-115

  10. Model Checking as Static Analysis

    DEFF Research Database (Denmark)

    Zhang, Fuyuan

    fairness problems can be encoded into ALFP as well. To deal with multi-valued model checking problems, we have proposed multivalued ALFP. A Moore Family result for multi-valued ALFP is also established, which ensures the existence and uniqueness of the least model. When the truth values in multi-valued...... of states satisfying a CTL formula can be characterized as the least model of ALFP clauses specifying this CTL formula. The existence of the least model of ALFP clauses is ensured by the Moore Family property of ALFP. Then, we take fairness assumptions in CTL into consideration and have shown that CTL...... ALFP constitute a nite distributive complete lattice, multi-valued ALFP can be reduced to two-valued ALFP. This result enables to implement a solver for multi-valued ALFP by reusing existing solvers for twovalued ALFP. Our ALFP-based technique developed for the two-valued CTL naturally generalizes...

  11. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

    Directory of Open Access Journals (Sweden)

    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  12. Shady strategic behavior : Recognizing strategic behavior of Dark Triad followers

    NARCIS (Netherlands)

    Schyns, Birgit; Wisse, Barbara; Sanders, Stacey

    2018-01-01

    The importance of strategic behavior in organizations has long been recognized. However, so far the literature has primarily focused on leaders’ strategic behavior, largely ignoring followers’ strategic behavior. In the present paper, we take a follower trait perspective to strategic follower

  13. A Safe Education for All: Recognizing and Stemming Harassment in Music Classes and Ensembles

    Science.gov (United States)

    Carter, Bruce Allen

    2011-01-01

    This article addresses the pervasiveness of harassment in schools in the United States and presents ways to recognize and stem bullying in music classrooms. Music educators are in a unique position to recognize atypical behaviors in their students. Music educators who teach middle and high school ensembles often retain the same students in their…

  14. A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Marina Antelo

    Full Text Available Early-onset colorectal cancer (CRC represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously.We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188, a group of sporadic CRC >50 years (MSS n=89; MSI n=46, and a group of Lynch syndrome CRCs (n=20. Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated.Mean LINE-1 methylation levels (± SD in the five study groups were early-onset CRC, 56.6% (8.6; sporadic MSI, 67.1% (5.5; sporadic MSS, 65.1% (6.3; Lynch syndrome, 66.3% (4.5 and normal mucosa, 76.5% (1.5. Early-onset CRC had significantly lower LINE-1 methylation than any other group (p<0.0001. Compared to patients with <65% LINE-1 methylation in tumors, those with ≥ 65% LINE-1 methylation had significantly better overall survival (p=0.026, log rank test.LINE-1 hypomethylation constitutes a potentially important feature of early-onset CRC, and suggests a distinct molecular subtype. Further studies are needed to assess the potential of LINE-1 methylation status as a prognostic biomarker for young people with CRC.

  15. Epstein-Barr virus nuclear antigen 1 (EBNA1) induced cytotoxicity in epithelial cells is associated with EBNA1 degradation and processing

    International Nuclear Information System (INIS)

    Jones, Richard J.; Smith, Laura J.; Dawson, Christopher W.; Haigh, Tracy; Blake, Neil W.; Young, Lawrence S.

    2003-01-01

    Epstein-Barr virus nuclear antigen 1 (EBNA1) has a central role in the maintenance and segregation of the Epstein-Barr virus (EBV) episome and by virtue of a glycine-alanine repeat domain is prevented from being endogenously processed for recognition by HLA class I restricted cytotoxic T lymphocytes (CTLs). We found that EBNA1 expression resulted in growth inhibition and a G2/M arrest in human squamous epithelial cell lines (SCC12F, SVK) but not epithelial cell lines of glandular origin (Hela, Ad/AH). The cytotoxicity of EBNA1 was associated with EBNA1 degradation and both these effects were blocked in SCC12F cells expressing either the anti-apoptotic bcl-2 protein or the EBV homolog of bcl-2, BHRF1. The endogenous degradation of EBNA1 in SVK epithelial cells was associated with specific CTL recognition, an effect not evident in EBNA1-expressing Hela cells. Consistent with the inability of SVK cells to tolerate EBNA1 expression, studies with a recombinant EBV demonstrated that SVK cells are unable to maintain stable virus infection, whereas Hela cells are able to efficiently establish latent EBV infection. These data have important implications for both the cellular requirements necessary to sustain a stable EBV infection and for the possible role of CTL responses in controlling EBV infection of epithelial cells

  16. 75 FR 9953 - Definition and Requirements for a Nationally Recognized Testing Laboratory (NRTL); Extension of...

    Science.gov (United States)

    2010-03-04

    ...] Definition and Requirements for a Nationally Recognized Testing Laboratory (NRTL); Extension of the Office of Management and Budget's (OMB) Approval of Information Collection (Paperwork) Requirements AGENCY... its Regulation on the Definition and Requirements for a Nationally Recognized Testing Laboratory (29...

  17. Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

    International Nuclear Information System (INIS)

    Ganusov, Vitaly V; Neher, Richard A; Perelson, Alan S

    2013-01-01

    Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2–3 weeks postinfection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4–12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Indeed, the viral population ‘escapes’ from about half of the CTL responses by mutation in the first year. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the model fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with

  18. Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice.

    Directory of Open Access Journals (Sweden)

    Susu Duan

    2015-02-01

    Full Text Available The recent emergence of a novel H7N9 influenza A virus (IAV causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+ cytotoxic T lymphocyte (CTL memory specific for epitopes conserved between H7N9 and previously encountered IAVs. In the present study, the heterosubtypic immunity generated by prior H9N2 or H1N1 infections significantly, but variably, reduced morbidity and mortality, pulmonary virus load and time to clearance in mice challenged with the H7N9 virus. In all cases, the recall of established CTL memory was characterized by earlier, greater airway infiltration of effectors targeting the conserved or cross-reactive H7N9 IAV peptides; though, depending on the priming IAV, each case was accompanied by distinct CTL epitope immunodominance hierarchies for the prominent K(bPB(1703, D(bPA(224, and D(bNP(366 epitopes. While the presence of conserved, variable, or cross-reactive epitopes between the priming H9N2 and H1N1 and the challenge H7N9 IAVs clearly influenced any change in the immunodominance hierarchy, the changing patterns were not tied solely to epitope conservation. Furthermore, the total size of the IAV-specific memory CTL pool after priming was a better predictor of favorable outcomes than the extent of epitope conservation or secondary CTL expansion. Modifying the size of the memory CTL pool significantly altered its subsequent protective efficacy on disease severity or virus clearance, confirming the important role of heterologous priming. These findings establish that both the protective efficacy of heterosubtypic immunity and CTL immunodominance hierarchies are reflective of the immunological history of the host, a finding that has implications for understanding human CTL responses and the rational design of CTL-mediated vaccines.

  19. Recommendations for recognizing video events by concept vocabularies

    Science.gov (United States)

    2014-06-01

    represents a video in terms of low-level audiovisual features [16,38,50,35,15,19,37]. In general, these methods first extract from the video various types of...interpretable, but is also reported to outperform the state-of-the-art low-level audiovisual features in recognizing events [31,33]. Rather than training...concept detector accuracy. As a consequence, the vocabulary concepts do not necessarily have a semantic interpreta- tion needed to explain the video content

  20. Professional Development Recognizing Technology Integration Modeled after the TPACK Framework

    Science.gov (United States)

    McCusker, Laura

    2017-01-01

    Public school teachers within a Pennsylvania intermediate unit are receiving inadequate job-embedded professional development that recognizes knowledge of content, pedagogy, and technology integration, as outlined by Mishra and Koehler's Technological Pedagogical Content Knowledge (TPACK) framework (2006). A school environment where teachers are…

  1. Effect of radiation on the induction of anti-hapten cytotoxic T-lymphocytes

    International Nuclear Information System (INIS)

    Ito, Shinichi; Hachisu, Reiko.

    1987-01-01

    Effect of ionizing radiation on the induction process of cytotoxic T lymphocytes was studied. We used trinitrophenyl (TNP) as hapten to modify the syngeneic spleen cells. Anti-TNP cytotoxic T lymphocytes (TNP-CTL) were induced from normal spleen cells of C3H mice. The spleen cells were stimulated with TNP-modified spleen cells and cultured for five days in CO 2 incubator (37 deg C, 5 % CO 2 ). Then, the activity of TNP-CTL was measured with 51 Cr release assay. Syngeneic tumor cells, X5563 cells, were labeled with 51 Cr and used as target cells in the assay. The spleen cells were irradiated with 0, 0.5, or 2Gy in course of five days culture. The activity of TNP-CTL was greatly reduced when the spleen cells were irradiated by two days after the initiation of the culture. On the other hand, irradiation was less effective to reduce the TNP-CTL activity on the spleen cells which were cultured longer than three days. Therefore efficacy of the irradiation to suppress the generation of TNP-CTL was gradually reduced with the passing of the culture day. This suggests that the radiosensitivity of the spleen cells which probably include precursor cells of CTL and helper T cells were decreased with the matuation of these cells. The results supported that matured TNP-CTL was radioresistant, for it's activity did not decrease after the irradiation up to 42Gy. (author)

  2. Modular Bayesian Networks with Low-Power Wearable Sensors for Recognizing Eating Activities

    Directory of Open Access Journals (Sweden)

    Kee-Hoon Kim

    2017-12-01

    Full Text Available Recently, recognizing a user’s daily activity using a smartphone and wearable sensors has become a popular issue. However, in contrast with the ideal definition of an experiment, there could be numerous complex activities in real life with respect to its various background and contexts: time, space, age, culture, and so on. Recognizing these complex activities with limited low-power sensors, considering the power and memory constraints of the wearable environment and the user’s obtrusiveness at once is not an easy problem, although it is very crucial for the activity recognizer to be practically useful. In this paper, we recognize activity of eating, which is one of the most typical examples of a complex activity, using only daily low-power mobile and wearable sensors. To organize the related contexts systemically, we have constructed the context model based on activity theory and the “Five W’s”, and propose a Bayesian network with 88 nodes to predict uncertain contexts probabilistically. The structure of the proposed Bayesian network is designed by a modular and tree-structured approach to reduce the time complexity and increase the scalability. To evaluate the proposed method, we collected the data with 10 different activities from 25 volunteers of various ages, occupations, and jobs, and have obtained 79.71% accuracy, which outperforms other conventional classifiers by 7.54–14.4%. Analyses of the results showed that our probabilistic approach could also give approximate results even when one of contexts or sensor values has a very heterogeneous pattern or is missing.

  3. Modular Bayesian Networks with Low-Power Wearable Sensors for Recognizing Eating Activities.

    Science.gov (United States)

    Kim, Kee-Hoon; Cho, Sung-Bae

    2017-12-11

    Recently, recognizing a user's daily activity using a smartphone and wearable sensors has become a popular issue. However, in contrast with the ideal definition of an experiment, there could be numerous complex activities in real life with respect to its various background and contexts: time, space, age, culture, and so on. Recognizing these complex activities with limited low-power sensors, considering the power and memory constraints of the wearable environment and the user's obtrusiveness at once is not an easy problem, although it is very crucial for the activity recognizer to be practically useful. In this paper, we recognize activity of eating, which is one of the most typical examples of a complex activity, using only daily low-power mobile and wearable sensors. To organize the related contexts systemically, we have constructed the context model based on activity theory and the "Five W's", and propose a Bayesian network with 88 nodes to predict uncertain contexts probabilistically. The structure of the proposed Bayesian network is designed by a modular and tree-structured approach to reduce the time complexity and increase the scalability. To evaluate the proposed method, we collected the data with 10 different activities from 25 volunteers of various ages, occupations, and jobs, and have obtained 79.71% accuracy, which outperforms other conventional classifiers by 7.54-14.4%. Analyses of the results showed that our probabilistic approach could also give approximate results even when one of contexts or sensor values has a very heterogeneous pattern or is missing.

  4. Modular Bayesian Networks with Low-Power Wearable Sensors for Recognizing Eating Activities

    Science.gov (United States)

    Kim, Kee-Hoon

    2017-01-01

    Recently, recognizing a user’s daily activity using a smartphone and wearable sensors has become a popular issue. However, in contrast with the ideal definition of an experiment, there could be numerous complex activities in real life with respect to its various background and contexts: time, space, age, culture, and so on. Recognizing these complex activities with limited low-power sensors, considering the power and memory constraints of the wearable environment and the user’s obtrusiveness at once is not an easy problem, although it is very crucial for the activity recognizer to be practically useful. In this paper, we recognize activity of eating, which is one of the most typical examples of a complex activity, using only daily low-power mobile and wearable sensors. To organize the related contexts systemically, we have constructed the context model based on activity theory and the “Five W’s”, and propose a Bayesian network with 88 nodes to predict uncertain contexts probabilistically. The structure of the proposed Bayesian network is designed by a modular and tree-structured approach to reduce the time complexity and increase the scalability. To evaluate the proposed method, we collected the data with 10 different activities from 25 volunteers of various ages, occupations, and jobs, and have obtained 79.71% accuracy, which outperforms other conventional classifiers by 7.54–14.4%. Analyses of the results showed that our probabilistic approach could also give approximate results even when one of contexts or sensor values has a very heterogeneous pattern or is missing. PMID:29232937

  5. Line facilities outline

    International Nuclear Information System (INIS)

    1998-08-01

    This book deals with line facilities. The contents of this book are outline line of wire telecommunication ; development of line, classification of section of line and theory of transmission of line, cable line ; structure of line, line of cable in town, line out of town, domestic cable and other lines, Optical communication ; line of optical cable, transmission method, measurement of optical communication and cable of the sea bottom, Equipment of telecommunication line ; telecommunication line facilities and telecommunication of public works, construction of cable line and maintenance and Regulation of line equipment ; regulation on technique, construction and maintenance.

  6. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

    Directory of Open Access Journals (Sweden)

    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  7. Discriminative latent models for recognizing contextual group activities.

    Science.gov (United States)

    Lan, Tian; Wang, Yang; Yang, Weilong; Robinovitch, Stephen N; Mori, Greg

    2012-08-01

    In this paper, we go beyond recognizing the actions of individuals and focus on group activities. This is motivated from the observation that human actions are rarely performed in isolation; the contextual information of what other people in the scene are doing provides a useful cue for understanding high-level activities. We propose a novel framework for recognizing group activities which jointly captures the group activity, the individual person actions, and the interactions among them. Two types of contextual information, group-person interaction and person-person interaction, are explored in a latent variable framework. In particular, we propose three different approaches to model the person-person interaction. One approach is to explore the structures of person-person interaction. Differently from most of the previous latent structured models, which assume a predefined structure for the hidden layer, e.g., a tree structure, we treat the structure of the hidden layer as a latent variable and implicitly infer it during learning and inference. The second approach explores person-person interaction in the feature level. We introduce a new feature representation called the action context (AC) descriptor. The AC descriptor encodes information about not only the action of an individual person in the video, but also the behavior of other people nearby. The third approach combines the above two. Our experimental results demonstrate the benefit of using contextual information for disambiguating group activities.

  8. Human L-ficolin recognizes phosphocholine moieties of pneumococcal teichoic acid

    DEFF Research Database (Denmark)

    Vassal-Stermann, Emilie; Lacroix, Monique; Gout, Evelyne

    2014-01-01

    Human L-ficolin is a soluble protein of the innate immune system able to sense pathogens through its fibrinogen (FBG) recognition domains and to trigger activation of the lectin complement pathway through associated serine proteases. L-Ficolin has been previously shown to recognize pneumococcal c...

  9. Cultural characters of a newly recognized group of hospital staphylococci.

    Science.gov (United States)

    Jevons, M P; John, M; Parker, M T

    1966-07-01

    Members of a newly recognized group of hospital staphylococci, which are believed to have arisen from 83A staphylococci by lysogenization, differ from them in several cultural characters. Some but not all of these characters appear to be determined by the carriage of phage.

  10. T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    A. E. Albers

    2010-01-01

    Full Text Available The competent immune system controls disease effectively due to induction, function, and regulation of effector lymphocytes. Immunosurveillance is exerted mostly by cytotoxic T-lymphocytes (CTLs while specific immune suppression is associated with tumor malignancy and progression. In squamous cell carcinoma of the head and neck, the presence, activity, but also suppression of tumor-specific CTL have been demonstrated. Functional CTL may exert a selection pressure on the tumor cells that consecutively escape by a combination of molecular and cellular evasion mechanisms. Certain of these mechanisms target antitumor effector cells directly or indirectly by affecting cells that regulate CTL function. This results in the dysfunction or apoptosis of lymphocytes and dysregulated lymphocyte homeostasis. Another important tumor-escape mechanism is to avoid recognition by dysregulation of antigen processing and presentation. Thus, both induction of functional CTL and susceptibility of the tumor and its microenvironment to become T cell targets should be considered in CTL-based immunotherapy.

  11. Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response

    International Nuclear Information System (INIS)

    Chandra, Subhash; Kaur, Manpreet; Midha, Shuchi; Bhatnagar, Rakesh; Banerjee-Bhatnagar, Nirupama

    2006-01-01

    We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine

  12. 17 CFR 240.17g-3 - Annual financial reports to be furnished by nationally recognized statistical rating organizations.

    Science.gov (United States)

    2010-04-01

    ... financial statements of the nationally recognized statistical rating organization or audited consolidated financial statements of its parent if the nationally recognized statistical rating organization is a...) of this section are consolidated financial statements of the parent of the nationally recognized...

  13. Dendritic cells fused with different pancreatic carcinoma cells induce different T-cell responses

    Directory of Open Access Journals (Sweden)

    Andoh Y

    2013-01-01

    Full Text Available Yoshiaki Andoh,1,2 Naohiko Makino,2 Mitsunori Yamakawa11Department of Pathological Diagnostics, 2Department of Gastroenterology, Yamagata University School of Medicine, Yamagata, JapanBackground: It is unclear whether there are any differences in the induction of cytotoxic T lymphocytes (CTL and CD4+CD25high regulatory T-cells (Tregs among dendritic cells (DCs fused with different pancreatic carcinomas. The aim of this study was to compare the ability to induce cytotoxicity by human DCs fused with different human pancreatic carcinoma cell lines and to elucidate the causes of variable cytotoxicity among cell lines.Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells (PBMCs, were fused with carcinoma cells such as Panc-1, KP-1NL, QGP-1, and KP-3L. The induction of CTL and Tregs, and cytokine profile of PBMCs stimulated by fused DCs were evaluated.Results: The cytotoxicity against tumor targets induced by PBMCs cocultured with DCs fused with QGP-1 (DC/QGP-1 was very low, even though PBMCs cocultured with DCs fused with other cell lines induced significant cytotoxicity against the respective tumor target. The factors causing this low cytotoxicity were subsequently investigated. DC/QGP-1 induced a significant expansion of Tregs in cocultured PBMCs compared with DC/KP-3L. The level of interleukin-10 secreted in the supernatants of PBMCs cocultured with DC/QGP-1 was increased significantly compared with that in DC/KP-3L. Downregulation of major histocompatibility complex class I expression and increased secretion of vascular endothelial growth factor were observed with QGP-1, as well as in the other cell lines.Conclusion: The present study demonstrated that the cytotoxicity induced by DCs fused with pancreatic cancer cell lines was different between each cell line, and that the reduced cytotoxicity of DC/QGP-1 might be related to the increased secretion of interleukin-10 and the extensive induction of Tregs

  14. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

    Science.gov (United States)

    Gasper, David J.; Neldner, Brandon; Plisch, Erin H.; Rustom, Hani; Imai, Hirotaka; Kawaoka, Yoshihiro; Suresh, M.

    2016-01-01

    CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the

  15. Establishment and characterization of equine fibroblast cell lines transformed in vivo and in vitro by BPV-1: Model systems for equine sarcoids

    International Nuclear Information System (INIS)

    Yuan, Z.Q.; Gault, E.A.; Gobeil, P.; Nixon, C.; Campo, M.S.; Nasir, L.

    2008-01-01

    It is now widely recognized that BPV-1 and less commonly BPV-2 are the causative agents of equine sarcoids. Here we present the generation of equine cell lines harboring BPV-1 genomes and expressing viral genes. These lines have been either explanted from sarcoid biopsies or generated in vitro by transfection of primary fibroblasts with BPV-1 DNA. Previously detected BPV-1 genome variations in equine sarcoids are also found in sarcoid cell lines, and only variant BPV-1 genomes can transform equine cells. These equine cell lines are morphologically transformed, proliferate faster than parental cells, have an extended life span and can grow independently of substrate. These characteristics are more marked the higher the level of viral E5, E6 and E7 gene expression. These findings confirm that the virus has an active role in the induction of sarcoids and the lines will be invaluable for further studies on the role of BPV-1 in sarcoid pathology

  16. Similarity law for Widom lines and coexistence lines.

    Science.gov (United States)

    Banuti, D T; Raju, M; Ihme, M

    2017-05-01

    The coexistence line of a fluid separates liquid and gaseous states at subcritical pressures, ending at the critical point. Only recently, it became clear that the supercritical state space can likewise be divided into regions with liquidlike and gaslike properties, separated by an extension to the coexistence line. This crossover line is commonly referred to as the Widom line, and is characterized by large changes in density or enthalpy, manifesting as maxima in the thermodynamic response functions. Thus, a reliable representation of the coexistence line and the Widom line is important for sub- and supercritical applications that depend on an accurate prediction of fluid properties. While it is known for subcritical pressures that nondimensionalization with the respective species critical pressures p_{cr} and temperatures T_{cr} only collapses coexistence line data for simple fluids, this approach is used for Widom lines of all fluids. However, we show here that the Widom line does not adhere to the corresponding states principle, but instead to the extended corresponding states principle. We resolve this problem in two steps. First, we propose a Widom line functional based on the Clapeyron equation and derive an analytical, species specific expression for the only parameter from the Soave-Redlich-Kwong equation of state. This parameter is a function of the acentric factor ω and compares well with experimental data. Second, we introduce the scaled reduced pressure p_{r}^{*} to replace the previously used reduced pressure p_{r}=p/p_{cr}. We show that p_{r}^{*} is a function of the acentric factor only and can thus be readily determined from fluid property tables. It collapses both subcritical coexistence line and supercritical Widom line data over a wide range of species with acentric factors ranging from -0.38 (helium) to 0.34 (water), including alkanes up to n-hexane. By using p_{r}^{*}, the extended corresponding states principle can be applied within

  17. Coal-to-liquids bill introduced in the Senate

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, L.

    2006-06-15

    Of immense importance to the coal industry is the announcement, on 7 June 2006 by US Senators Barack Obama (D-IL) and Jim Bunning (R-KY) of S.3325, the 'Coal-to-Liquid Fund Promotion Act of 2006'. This legislation creates tax incentives for coal-to-liquids (CTL) technologies and construction of CTL plants. If passed, this will create the infrastructure needed to make CTL a viable energy resource throughout America. The article gives comment and background to this proposed legislation. Illinois Basin coal is well suited for CTL because of its high Btu content. If Sasol constructs a proposed plant in Illinois it would increase coal production in the state by 10 mt. 1 fig.

  18. Discovering Activities to Recognize and Track in a Smart Environment.

    Science.gov (United States)

    Rashidi, Parisa; Cook, Diane J; Holder, Lawrence B; Schmitter-Edgecombe, Maureen

    2011-01-01

    The machine learning and pervasive sensing technologies found in smart homes offer unprecedented opportunities for providing health monitoring and assistance to individuals experiencing difficulties living independently at home. In order to monitor the functional health of smart home residents, we need to design technologies that recognize and track activities that people normally perform as part of their daily routines. Although approaches do exist for recognizing activities, the approaches are applied to activities that have been pre-selected and for which labeled training data is available. In contrast, we introduce an automated approach to activity tracking that identifies frequent activities that naturally occur in an individual's routine. With this capability we can then track the occurrence of regular activities to monitor functional health and to detect changes in an individual's patterns and lifestyle. In this paper we describe our activity mining and tracking approach and validate our algorithms on data collected in physical smart environments.

  19. A Pilot Directional Protection for HVDC Transmission Line Based on Relative Entropy of Wavelet Energy

    Directory of Open Access Journals (Sweden)

    Sheng Lin

    2015-07-01

    Full Text Available On the basis of analyzing high-voltage direct current (HVDC transmission system and its fault superimposed circuit, the direction of the fault components of the voltage and the current measured at one end of transmission line is certified to be different for internal faults and external faults. As an estimate of the differences between two signals, relative entropy is an effective parameter for recognizing transient signals in HVDC transmission lines. In this paper, the relative entropy of wavelet energy is applied to distinguish internal fault from external fault. For internal faults, the directions of fault components of voltage and current are opposite at the two ends of the transmission line, indicating a huge difference of wavelet energy relative entropy; for external faults, the directions are identical, indicating a small difference. The simulation results based on PSCAD/EMTDC show that the proposed pilot protection system acts accurately for faults under different conditions, and its performance is not affected by fault type, fault location, fault resistance and noise.

  20. Recognized focused practice: Does sub-specialty designation offer value to the neurosurgeon?

    Directory of Open Access Journals (Sweden)

    Maya A Babu

    Full Text Available Vehicles for life-long assessment such as Maintenance of Certification tend to focus on generalist neurosurgical knowledge. However, as neurosurgeons advance in their careers, they tend to narrow their practice and increase volumes in certain specific types of operations. Failing to test the type of procedures most relevant to the practitioner is a lost opportunity to improve the knowledge and practice of the individual neurosurgeon. In this study, we assess the neurosurgical community's appetite for designations of board-recognized Recognized Focused Practice (RFP. We administered a validated, online, confidential survey to 4,899 neurosurgeons (2,435 American Board of Neurological Surgery (ABNS Diplomates participating in MOC, 1,440 Diplomates certified prior to 1999 (grandfathered, and 1,024 retired Diplomates. We received 1,449 responses overall (30% response rate. A plurality of respondents were in practice 11-15 years (18.5%, in private practice (40% and participate in MOC (61%. 49% of respondents felt that a RFP designation would not be helpful. For the 30% who felt that RFP would be helpful, 61.3% felt that it would support recognition by their hospital or practice, it would motivate them to stay current on medical knowledge (53.4%, or it would help attract patients (46.4%;. The most popular suggestions for RFP were Spine (56.2%, Cerebrovascular (62.9%, Pediatrics (64.1%, and Functional/Stereotactic (52%. A plurality of neurosurgeons (35.7% felt that RFP should recognize neurosurgeons with accredited and non-accredited fellowship experience and sub-specialty experience. Ultimately, Recognized Focused Practice may provide value to individual neurosurgeons, but the neurosurgical community shows tepid interest for pursuing this designation.

  1. Recognized focused practice: Does sub-specialty designation offer value to the neurosurgeon?

    Science.gov (United States)

    Babu, Maya A; Liau, Linda M; Meyer, Fredric B

    2017-01-01

    Vehicles for life-long assessment such as Maintenance of Certification tend to focus on generalist neurosurgical knowledge. However, as neurosurgeons advance in their careers, they tend to narrow their practice and increase volumes in certain specific types of operations. Failing to test the type of procedures most relevant to the practitioner is a lost opportunity to improve the knowledge and practice of the individual neurosurgeon. In this study, we assess the neurosurgical community's appetite for designations of board-recognized Recognized Focused Practice (RFP). We administered a validated, online, confidential survey to 4,899 neurosurgeons (2,435 American Board of Neurological Surgery (ABNS) Diplomates participating in MOC, 1,440 Diplomates certified prior to 1999 (grandfathered), and 1,024 retired Diplomates). We received 1,449 responses overall (30% response rate). A plurality of respondents were in practice 11-15 years (18.5%), in private practice (40%) and participate in MOC (61%). 49% of respondents felt that a RFP designation would not be helpful. For the 30% who felt that RFP would be helpful, 61.3% felt that it would support recognition by their hospital or practice, it would motivate them to stay current on medical knowledge (53.4%), or it would help attract patients (46.4%;). The most popular suggestions for RFP were Spine (56.2%), Cerebrovascular (62.9%), Pediatrics (64.1%), and Functional/Stereotactic (52%). A plurality of neurosurgeons (35.7%) felt that RFP should recognize neurosurgeons with accredited and non-accredited fellowship experience and sub-specialty experience. Ultimately, Recognized Focused Practice may provide value to individual neurosurgeons, but the neurosurgical community shows tepid interest for pursuing this designation.

  2. Derivation from an alloreactive T-cell line of a clone which cross-reacts with a self H2-E-restricted minor alloantigen

    DEFF Research Database (Denmark)

    Owens, T; Liddell, M E; Crispe, I N

    1984-01-01

    An alloreactive T-helper-cell line [(A.TH X Balb/c) anti-A.TL] was shown to recognize both H2-Ek and H2-Ed. Both proliferation and polyclonal B-cell activation (protein A plaques) were used in the analyses of specificity. On cloning, the H2-Ek/Ed cross-reaction was shown by one clonotype...

  3. The assessment of the nutritional value of meals consumed by patients with recognized schizophrenia

    Science.gov (United States)

    Stefańska, Ewa; Wendołowicz, Agnieszka; Lech, Magdalena; Wilczyńska, Karolina; Konarzewska, Beata; Zapolska, Joanna; Ostrowska, Lucyna

    2018-01-01

    As studies show, changes in diet - so important in the therapy of psychiatric disorders and related to changes in appetite and nutritional preferences, including avoiding of the consumption of specific groups of products and dishes - are much more frequent among patients affected by schizophrenia. The aim of the study was to assess the chosen nutritional habits, including the number and type of meals usually consumed during a day, snacking between meals and the energy value and content of the chosen nutrients in the diets of persons with recognized schizophrenia. The study was carried out in a group of 85 patients with recognized schizophrenia, and 70 healthy volunteers ranging in age from 18-65 years without mental or nutritional disorders. For the purpose of the study, we used a questionnaire containing questions on nutritional habits. A 24-hour diet recall was used in the quantitative nutritional assessment with the use of the computer program Dieta 5.0. Female patients with recognized schizophrenia were having 3 meals a day significantly more frequently as compared to healthy women. They were also having an afternoon snack much more frequently as compared to the control group. The food rations of female patients were characterized by a significantly higher energy value and the content of most of the assessed nutrients as compared to the food rations of healthy women. The food rations of men with recognized schizophrenia were characterized by a much lower energy intake and the content of the majority of assessed nutrients as compared to the food rations of healthy men. In all compared groups, we observed an energetic structure of food rations with the breakdown by specific meals that was inconsistent with the applicable recommendations. Despite of differences between the nutritional value of the meals of patients with recognized schizophrenia and those of healthy subjects, it seems advisable to involve patients with recognized schizophrenia in the education of

  4. A new mathematical formulation of the line-by-line method in case of weak line overlapping

    Science.gov (United States)

    Ishov, Alexander G.; Krymova, Natalie V.

    1994-01-01

    A rigorous mathematical proof is presented for multiline representation on the equivalent width of a molecular band which consists in the general case of n overlapping spectral lines. The multiline representation includes a principal term and terms of minor significance. The principal term is the equivalent width of the molecular band consisting of the same n nonoverlapping spectral lines. The terms of minor significance take into consideration the overlapping of two, three and more spectral lines. They are small in case of the weak overlapping of spectral lines in the molecular band. The multiline representation can be easily generalized for optically inhomogeneous gas media and holds true for combinations of molecular bands. If the band lines overlap weakly the standard formulation of line-by-line method becomes too labor-consuming. In this case the multiline representation permits line-by-line calculations to be performed more effectively. Other useful properties of the multiline representation are pointed out.

  5. Passive wireless sensor systems can recognize activites of daily living.

    Science.gov (United States)

    Urwyler, Prabitha; Stucki, Reto; Muri, Rene; Mosimann, Urs P; Nef, Tobias

    2015-08-01

    The ability to determine what activity of daily living a person performs is of interest in many application domains. It is possible to determine the physical and cognitive capabilities of the elderly by inferring what activities they perform in their houses. Our primary aim was to establish a proof of concept that a wireless sensor system can monitor and record physical activity and these data can be modeled to predict activities of daily living. The secondary aim was to determine the optimal placement of the sensor boxes for detecting activities in a room. A wireless sensor system was set up in a laboratory kitchen. The ten healthy participants were requested to make tea following a defined sequence of tasks. Data were collected from the eight wireless sensor boxes placed in specific places in the test kitchen and analyzed to detect the sequences of tasks performed by the participants. These sequence of tasks were trained and tested using the Markov Model. Data analysis focused on the reliability of the system and the integrity of the collected data. The sequence of tasks were successfully recognized for all subjects and the averaged data pattern of tasks sequences between the subjects had a high correlation. Analysis of the data collected indicates that sensors placed in different locations are capable of recognizing activities, with the movement detection sensor contributing the most to detection of tasks. The central top of the room with no obstruction of view was considered to be the best location to record data for activity detection. Wireless sensor systems show much promise as easily deployable to monitor and recognize activities of daily living.

  6. Accelerated production of antigen-specific T-cells for pre-clinical and clinical applications using Gas-permeable Rapid Expansion cultureware (G-Rex)

    Science.gov (United States)

    Vera, Juan F.; Brenner, Lara J.; Gerdemann, Ulrike; Ngo, Minhtran C.; Sili, Uluhan; Liu, Hao; Wilson, John; Dotti, Gianpietro; Heslop, Helen E.; Leen, Ann M.; Rooney, Cliona M.

    2009-01-01

    The clinical manufacture of antigen-specific cytotoxic T lymphocytes (CTL) for adoptive immunotherapy is limited by the complexity and time required to produce large numbers with the desired function and specificity. The culture conditions required are rigorous, and in some cases only achieved in 2cm2 wells in which cell growth is limited by gas exchange, nutrients and waste accumulation. Bioreactors developed to overcome these issues tend to be complex, expensive and not always conducive to CTL growth. We observed that antigen-specific CTL undergo seven to ten divisions post-stimulation. However the expected CTL numbers were achieved only in the first week of culture. By recreating the culture conditions present during this first week - low frequency of antigen-specific T-cells and high frequency of feeder cells - we were able to increase CTL expansion to expected levels which could be sustained for several weeks without affecting phenotype or function. However, the number of 24-well plates needed was excessive and cultures required frequent media changes, increasing complexity and manufacturing costs. Therefore, we evaluated novel gas-permeable culture devices (G-Rex) with a silicone membrane at the base allowing gas exchange to occur uninhibited by depth of medium above. This system effectively supports the expansion of CTL and actually increases output by up to 20-fold while decreasing required technician time. Importantly, this amplified cell expansion is not due to more cell divisions but to reduced cell death. This bioprocess optimization increased T-cell output while decreasing the complexity and cost of CTL manufacture, making cell therapy more accessible. PMID:20445351

  7. 76 FR 51367 - China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A...

    Science.gov (United States)

    2011-08-18

    ... FEDERAL MARITIME COMMISSION [Docket No. 11-12] China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company Limited; Evergreen Line A Joint Service Agreement; Hanjin Shipping Co., Ltd... Maritime Commission (Commission) by China Shipping Container Lines Co., Ltd.; COSCO Container Lines Company...

  8. Recognizing, explaining and countering norm transgressive behaviour on social media

    NARCIS (Netherlands)

    Padje, E.D.H.

    2016-01-01

    In this thesis, it is researched how norm transgressive behaviour exhibited on the Dutch domains of social media can be recognized, explained and countered. An analysis of four comment threads is conducted, of which the comments can be found on the Facebook pages of three Dutch news sites and on a

  9. Effects of a yeast-dried milk product in creep and phase-1 nursery diets on growth performance, circulating immunoglobulin A, and fecal microbiota of nursing and nursery pigs.

    Science.gov (United States)

    Tran, H; Bundy, J W; Hinkle, E E; Walter, J; Burkey, T E; Miller, P S

    2014-10-01

    Four experiments were conducted to evaluate effects of yeast-dried milk (YDM) product in creep and phase-1 nursery diets. In Exp. 1, 24 parity-4 litters were allotted to 3 dietary treatments (8 litters/treatment) including no creep (NC), control creep (CTL), and experimental creep (EC; 10% YDM). Creep diets were fed twice daily from d 7 after birth until weaning (23.6 ± 1.8 d). In Exp. 2, 108 weaned pigs were selected based on mean BW of pigs from the respective treatments in Exp. 1. For phase 1 (d 0 to 7 postweaning) of Exp. 2, NC and CTL pigs were fed the CTL diet and EC pigs continued to receive the EC diet. For phase 2 and 3 (d 7 to 28 postweaning) of Exp. 2, all pigs received a common diet containing antibiotics. Blood and fecal samples were collected on d 0, 7, 14, and 21 postweaning to evaluate serum IgA and fecal microbiota. In Exp. 1, pigs fed EC and CTL tended to have greater (P < 0.10) weaning BW compared with NC pigs. Pigs fed EC had greater (P < 0.05) ADFI compared with CTL pigs. In Exp. 2, pigs fed EC tended to have greater BW (P < 0.10) and greater ADG (P < 0.05) and ADFI (P < 0.01) compared with CTL and NC pigs (d 0 to 28). For serum IgA, EC and CTL pigs tended (P < 0.10) to have greater IgA compared with NC pigs. For microbial data, EC pigs had greater (P < 0.01) microbial diversity compared with CTL (d 7 postweaning). On d 7 and 21 postweaning, microbial similarity decreased (P < 0.01) in pigs fed EC compared with NC and CTL. Overall (d 0 to 14), lactobacilli gene copy numbers tended (P < 0.10) to be greater in EC (7.3 log10) compared with NC pigs (6.9 log10). In Exp. 3, 23 parity-1 litters were allotted to 3 dietary treatments as described for Exp. 1. In Exp. 4, 108 weaned pigs were selected based on mean BW of all pigs from Exp. 3 and dietary treatments were the same as described for Exp. 2 except no antibiotic was included in phase-2 diet. In Exp. 3, there were no treatment effects on litter ADFI, ADG, and serum IgA, but a tendency (P < 0

  10. Recognizing and Treating Malaria in U.S. Residents

    Centers for Disease Control (CDC) Podcasts

    2010-06-09

    This podcast is an overview of the Clinician Outreach and Communication Activity (COCA) Call: It's a Small World After All: Dengue and Malaria in U.S. Residents - Recognizing and Treating These Mosquito-borne Diseases. CDC's David Townes discusses clinical presentation, transmission, prevention strategies, new treatments, and malaria resources available to health care providers.  Created: 6/9/2010 by Division of Parasitic Diseases and Malaria, Center for Global Health and Emergency Communication System (ECS)/Joint Information Center (JIC); Office of Public Health Preparedness and Response (OPHPR).   Date Released: 6/15/2010.

  11. Recognize and classify pneumoconiosis

    International Nuclear Information System (INIS)

    Hering, K.G.; Hofmann-Preiss, K.

    2014-01-01

    In the year 2012, out of the 10 most frequently recognized occupational diseases 6 were forms of pneumoconiosis. With respect to healthcare and economic aspects, silicosis and asbestos-associated diseases are of foremost importance. The latter are to be found everywhere and are not restricted to large industrial areas. Radiology has a central role in the diagnosis and evaluation of occupational lung disorders. In cases of known exposure mainly to asbestos and quartz, the diagnosis of pneumoconiosis, with few exceptions will be established primarily by the radiological findings. As these disorders are asymptomatic for a long time they are quite often detected as incidental findings in examinations for other reasons. Therefore, radiologists have to be familiar with the pattern of findings of the most frequent forms of pneumoconiosis and the differential diagnoses. For reasons of equal treatment of the insured a quality-based, standardized performance, documentation and evaluation of radiological examinations is required in preventive procedures and evaluations. Above all, a standardized low-dose protocol has to be used in computed tomography (CT) examinations, although individualized concerning the dose, in order to keep radiation exposure as low as possible for the patient. The International Labour Office (ILO) classification for the coding of chest X-rays and the international classification of occupational and environmental respiratory diseases (ICOERD) classification used since 2004 for CT examinations meet the requirements of the insured and the occupational insurance associations as a means of reproducible and comparable data for decision-making. (orig.) [de

  12. Recognizing Family Dynamics in the Treatment of Chronic Fatigue Syndrome

    Science.gov (United States)

    Sperry, Len

    2012-01-01

    Chronic fatigue syndrome (CFS) is an increasingly common chronic medical condition that affects not only patients but also their families. Because family dynamics, particularly the family life cycle, can and does influence the disease process, those providing counseling to CFS patients and their families would do well to recognize these dynamics.…

  13. Recognizing Job Health Hazards. Module SH-08. Safety and Health.

    Science.gov (United States)

    Center for Occupational Research and Development, Inc., Waco, TX.

    This student module on recognizing job health hazards is one of 50 modules concerned with job safety and health. This module presents the four general categories of environmental conditions or stresses: chemical, physical, biological, and ergonomic. Following the introduction, 14 objectives (each keyed to a page in the text) the student is…

  14. Questioning the "big assumptions". Part II: recognizing organizational contradictions that impede institutional change.

    Science.gov (United States)

    Bowe, Constance M; Lahey, Lisa; Kegan, Robert; Armstrong, Elizabeth

    2003-08-01

    Well-designed medical curriculum reforms can fall short of their primary objectives during implementation when unanticipated or unaddressed organizational resistance surfaces. This typically occurs if the agents for change ignore faculty concerns during the planning stage or when the provision of essential institutional safeguards to support new behaviors are neglected. Disappointing outcomes in curriculum reforms then result in the perpetuation of or reversion to the status quo despite the loftiest of goals. Institutional resistance to change, much like that observed during personal development, does not necessarily indicate a communal lack of commitment to the organization's newly stated goals. It may reflect the existence of competing organizational objectives that must be addressed before substantive advances in a new direction can be accomplished. The authors describe how the Big Assumptions process (see previous article) was adapted and applied at the institutional level during a school of medicine's curriculum reform. Reform leaders encouraged faculty participants to articulate their reservations about considered changes to provided insights into the organization's competing commitments. The line of discussion provided an opportunity for faculty to appreciate the gridlock that existed until appropriate test of the school's long held Big Assumptions could be conducted. The Big Assumptions process proved useful in moving faculty groups to recognize and questions the validity of unchallenged institutional beliefs that were likely to undermine efforts toward change. The process also allowed the organization to put essential institutional safeguards in place that ultimately insured that substantive reforms could be sustained.

  15. The TESS Input Catalog and Selection of Targets for the TESS Transit Search

    Science.gov (United States)

    Pepper, Joshua; Stassun, Keivan G.; Paegert, Martin; Oelkers, Ryan; De Lee, Nathan Michael; Torres, Guillermo; TESS Target Selection Working Group

    2018-01-01

    The TESS mission will photometrically survey millions of the brightest stars over almost the entire the sky to detect transiting exoplanets. A key step to enable that search is the creation of the TESS Input Catalog (TIC), a compiled catalog of 700 million stars and galaxies with observed and calculated parameters. From the TIC we derive the Candidate Target List (CTL) to identify target stars for the 2-minute TESS postage stamps. The CTL is designed to identify the best stars for the detection of small planets, which includes all bright cool dwarf stars in the sky. I will describe the target selection strategy, the distribution of stars in the current CTL, and how both the TIC and CTL will expand and improve going forward.

  16. In vitro analysis of cytotoxic T cell recruitment mediated by the DC-derived chemokine CCL17

    OpenAIRE

    sprotocols

    2015-01-01

    Dendritic cell (DC) licensing in cross-priming requires physical interaction of several rare immune cells, i.e. cytotoxic T cells (CTL), and cross-presenting DCs. Here we describe a novel in vitro method of analyzing chemokine effects on complex recruitment events in a multi-cellular system. To study CTL recruitment towards CCL17-producing DCs, we established a co-culture system of murine splenic DCs with polyclonal splenic CTL from donor mice, which enables visualization of cell motility and...

  17. Chemokines: a new dendritic cell signal for T cell activation

    Directory of Open Access Journals (Sweden)

    Christoph A Thaiss

    2011-08-01

    Full Text Available Dendritic cells (DCs are the main inducers and regulators of cytotoxic T lymphocyte (CTL responses against viruses and tumors. One checkpoint to avoid misguided CTL activation, which might damage healthy cells of the body, is the necessity for multiple activation signals, involving both antigenic as well as additional signals that reflect the presence of pathogens. DCs provide both signals when activated by ligands of pattern recognition receptors and licensed by helper lymphocytes. Recently, it has been established that such T cell licensing can be facilitated by CD4+ T helper cells (classical licensing or by NKT cells (alternative licensing. Licensing regulates the DC/CTL cross-talk at multiple layers. Direct recruitment of CTLs through chemokines released by licensed DCs has recently emerged as a common theme and has a crucial impact on the efficiency of CTL responses. Here, we discuss recent advances in our understanding of DC licensing for cross-priming and implications for the temporal and spatial regulation underlying this process. Future vaccination strategies will benefit from a deeper insight into the mechanisms that govern CTL activation.

  18. Features of target cell lysis by class I and class II MHC restricted cytolytic T lymphocytes

    International Nuclear Information System (INIS)

    Maimone, M.M.; Morrison, L.A.; Braciale, V.L.; Braciale, T.J.

    1986-01-01

    The lytic activity of influenza virus-specific muvine cytolytic T lymphocyte (CTL) clones that are restricted by either H-2K/D (class I) or H-2I (class II) major histocompatibility (MHC) locus products was compared on an influenza virus-infected target cell expressing both K/D and I locus products. With the use of two in vitro measurements of cytotoxicity, conventional 51 Cr release, and detergent-releasable radiolabeled DNA (as a measure of nuclear disintegration in the early post-lethal hit period), the authors found no difference between class I and class II MHC-restricted CTL in the kinetics of target cell destruction. In addition, class II MHC-restricted antiviral CTL failed to show any lysis of radiolabeled bystander cells. Killing of labeled specific targets by these class II MHC-restricted CTL was also efficiently inhibited by unlabeled specific competitor cells in a cold target inhibition assay. In sum, these data suggest that class I and class II MHC-restricted CTL mediate target cell destruction by an essentially similar direct mechanism

  19. Assistant director of intramural sports and technology recognized for innovative contributions

    OpenAIRE

    Kropff, Catherine L.

    2009-01-01

    Jennifer Rezac, assistant director of intramural sports and technology at Virginia Tech, was recognized at the National Intramural-Recreational Sports Association (NIRSA) Annual Conference in Charlotte, N.C., in April for her contributions to the Virginia Tech Recreational Sports department.

  20. Measurement of the ability of science students to recognize business opportunities

    NARCIS (Netherlands)

    Nab, J.|info:eu-repo/dai/nl/304827614; Oost, H.|info:eu-repo/dai/nl/11394229X; Pilot, A.|info:eu-repo/dai/nl/068350880; van Keulen, H.|info:eu-repo/dai/nl/138693587

    2008-01-01

    This paper describes the development of an instrument measuring students’ ability to recognize business opportunities. Recognition of business opportunities where others do not is one of the basic qualities of entrepreneurs, and therefore needs attention in entrepreneurship education. However, only

  1. Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex

    DEFF Research Database (Denmark)

    Stryhn, A; Andersen, P S; Pedersen, L O

    1996-01-01

    Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide...... each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T...... cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody....

  2. From Off-line to On-line Handwriting Recognition

    NARCIS (Netherlands)

    Lallican, P.; Viard-Gaudin, C.; Knerr, S.

    2004-01-01

    On-line handwriting includes more information on time order of the writing signal and on the dynamics of the writing process than off-line handwriting. Therefore, on-line recognition systems achieve higher recognition rates. This can be concluded from results reported in the literature, and has been

  3. Induced pluripotent stem cells: challenges and opportunities for cancer immunotherapy.

    Science.gov (United States)

    Sachamitr, Patty; Hackett, Simon; Fairchild, Paul Jonathan

    2014-01-01

    Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumor-associated antigens (TAA) are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focused on the administration of autologous monocyte-derived dendritic cells (moDC) pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumor-infiltrating lymphocytes (TIL) as a source of TAA-specific cytotoxic T cells (CTL). Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross present exogenous TAA to the CD8(+) T-cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here, we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS) cells as well as minor subsets of dendritic cells (DCs) with therapeutic potential, including CD141(+)XCR1(+) DC, capable of cross presenting TAA to naïve CD8(+) T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  4. Induced pluripotent stem cells: Challenges and opportunities for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Patty eSachamitr

    2014-04-01

    Full Text Available Despite recent advances in cancer treatment over the past 30 years, therapeutic options remain limited and do not always offer a cure for malignancy. Given that tumour associated antigens (TAA are, by definition, self-proteins, the need to productively engage autoreactive T cells remains at the heart of strategies for cancer immunotherapy. These have traditionally focussed on the administration of autologous monocyte-derived dendritic cells (moDC pulsed with TAA, or the ex vivo expansion and adoptive transfer of tumour infiltrating lymphocytes (TIL as a source of TAA-specific cytotoxic T cells (CTL. Although such approaches have shown some efficacy, success has been limited by the poor capacity of moDC to cross-present exogenous TAA to the CD8+ T cell repertoire and the potential for exhaustion of CTL expanded ex vivo. Recent advances in induced pluripotency offer opportunities to generate patient-specific stem cell lines with the potential to differentiate in vitro into cell types whose properties may help address these issues. Here we review recent success in the differentiation of NK cells from human induced pluripotent stem (iPS cells as well as minor subsets of DC with therapeutic potential, including CD141+XCR1+ DC, capable of cross-presenting TAA to naïve CD8+ T cells. Furthermore, we review recent progress in the use of TIL as the starting material for the derivation of iPSC lines, thereby capturing their antigen specificity in a self-renewing stem cell line, from which potentially unlimited numbers of naïve TAA-specific T cells may be differentiated, free of the risks of exhaustion.

  5. Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

    Directory of Open Access Journals (Sweden)

    CAROLYNE D.S. SANTOS

    Full Text Available ABSTRACT Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT, Brown Adipose Tissue (BAT, and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation. After birth, only male offspring (F1 were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA. According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

  6. VT Digital Line Graph Miscellaneous Transmission Lines

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This datalayer is comprised of Miscellaineous Transmission Lines. Digital line graph (DLG) data are digital representations of cartographic...

  7. Identification of the base-pairing requirements for repression of hctA translation by the small RNA IhtA leads to the discovery of a new mRNA target in Chlamydia trachomatis.

    Directory of Open Access Journals (Sweden)

    Nicole A Grieshaber

    Full Text Available The non-coding small RNA, IhtA expressed by the obligate intracellular human pathogen Chlamydia trachomatis modulates the translation of HctA, a key protein involved in replicative to infectious cell type differentiation. Using a combination of bioinformatics and mutagenesis we sought to identify the base pairing requirement for functional repression of HctA protein expression, with an eye to applying our findings towards the identification of additional targets. IhtA is predicted to fold into a three stem:loop structure. We found that loop 1 occludes the initiation codon of hctA, while loop 2 and 3 are not required for function. This 7 nucleotide region forms G/C rich interactions surrounding the AUG of hctA. Two additional genes in the chlamydial genome, CTL0322 and CTL0097, contained some elements of the hctA:IhtA recognition sequence. The mRNA of both CTL0322and CTL0097 interacted with IhtA in vitro as measured by biolayer interferometry. However, using a CheZ reporter expression system, IhtA only inhibited the translation of CTL0322. The proposed IhtA recognition site in the CTL0322 message contains significant G/C base pairing on either side of the initiation codon while CTL0097 only contains G/C base pairing 3' to the AUG initiation codon. These data suggest that as the functional interacting region is only 6-7nt in length that full translation repression is dependent on the degree of G/C base pairing. Additionally our results indicate that IhtA may regulate multiple mRNAs involved in the chlamydial infectious cycle.

  8. Using Noninvasive Wearable Computers to Recognize Human Emotions from Physiological Signals

    Directory of Open Access Journals (Sweden)

    Nasoz Fatma

    2004-01-01

    Full Text Available We discuss the strong relationship between affect and cognition and the importance of emotions in multimodal human computer interaction (HCI and user modeling. We introduce the overall paradigm for our multimodal system that aims at recognizing its users' emotions and at responding to them accordingly depending upon the current context or application. We then describe the design of the emotion elicitation experiment we conducted by collecting, via wearable computers, physiological signals from the autonomic nervous system (galvanic skin response, heart rate, temperature and mapping them to certain emotions (sadness, anger, fear, surprise, frustration, and amusement. We show the results of three different supervised learning algorithms that categorize these collected signals in terms of emotions, and generalize their learning to recognize emotions from new collections of signals. We finally discuss possible broader impact and potential applications of emotion recognition for multimodal intelligent systems.

  9. Super-Memorizers Are Not Super-Recognizers.

    Directory of Open Access Journals (Sweden)

    Meike Ramon

    Full Text Available Humans have a natural expertise in recognizing faces. However, the nature of the interaction between this critical visual biological skill and memory is yet unclear. Here, we had the unique opportunity to test two individuals who have had exceptional success in the World Memory Championships, including several world records in face-name association memory. We designed a range of face processing tasks to determine whether superior/expert face memory skills are associated with distinctive perceptual strategies for processing faces. Superior memorizers excelled at tasks involving associative face-name learning. Nevertheless, they were as impaired as controls in tasks probing the efficiency of the face system: face inversion and the other-race effect. Super memorizers did not show increased hippocampal volumes, and exhibited optimal generic eye movement strategies when they performed complex multi-item face-name associations. Our data show that the visual computations of the face system are not malleable and are robust to acquired expertise involving extensive training of associative memory.

  10. Super-Memorizers Are Not Super-Recognizers.

    Science.gov (United States)

    Ramon, Meike; Miellet, Sebastien; Dzieciol, Anna M; Konrad, Boris Nikolai; Dresler, Martin; Caldara, Roberto

    2016-01-01

    Humans have a natural expertise in recognizing faces. However, the nature of the interaction between this critical visual biological skill and memory is yet unclear. Here, we had the unique opportunity to test two individuals who have had exceptional success in the World Memory Championships, including several world records in face-name association memory. We designed a range of face processing tasks to determine whether superior/expert face memory skills are associated with distinctive perceptual strategies for processing faces. Superior memorizers excelled at tasks involving associative face-name learning. Nevertheless, they were as impaired as controls in tasks probing the efficiency of the face system: face inversion and the other-race effect. Super memorizers did not show increased hippocampal volumes, and exhibited optimal generic eye movement strategies when they performed complex multi-item face-name associations. Our data show that the visual computations of the face system are not malleable and are robust to acquired expertise involving extensive training of associative memory.

  11. Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

    International Nuclear Information System (INIS)

    Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

    2003-01-01

    Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. OT-I CTL were adoptively transferred to C57BL/6 mice 21 – 28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several

  12. The status of intercellular junctions in established lens epithelial cell lines.

    Science.gov (United States)

    Dave, Alpana; Craig, Jamie E; Sharma, Shiwani

    2012-01-01

    Cataract is the major cause of vision-related disability worldwide. Mutations in the crystallin genes are the most common known cause of inherited congenital cataract. Mutations in the genes associated with intercellular contacts, such as Nance-Horan Syndrome (NHS) and Ephrin type A receptor-2 (EPHA2), are other recognized causes of congenital cataract. The EPHA2 gene has been also associated with age-related cataract, suggesting that intercellular junctions are important in not only lens development, but also in maintaining lens transparency. The purpose of this study was to analyze the expression and localization of the key cell junction and cytoskeletal proteins, and of NHS and EPHA2, in established lens epithelial cell lines to determine their suitability as model epithelial systems for the functional investigation of genes involved in intercellular contacts and implicated in cataract. The expression and subcellular localization of occludin and zona occludens protein-1 (ZO-1), which are associated with tight junctions; E-cadherin, which is associated with adherence junctions; and the cytoskeletal actin were analyzed in monolayers of a human lens epithelial cell line (SRA 01/04) and a mouse lens epithelial cell line (αTN4). In addition, the expression and subcellular localization of the NHS and EPHA2 proteins were analyzed in these cell lines. Protein or mRNA expression was respectively determined by western blotting or reverse transcription-polymerase chain reaction (RT-PCR), and localization was determined by immunofluorescence labeling. Human SRA 01/04 and mouse αTN4 lens epithelial cells expressed either the proteins of interest or their encoding mRNA. Occludin, ZO-1, and NHS proteins localized to the cellular periphery, whereas E-cadherin, actin, and EPHA2 localized in the cytoplasm in these cell lines. The human SRA 01/04 and mouse αTN4 lens epithelial cells express the key junctional proteins. The localization patterns of these proteins suggest that

  13. Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines

    DEFF Research Database (Denmark)

    Netchiporouk, Elena; Gantchev, Jennifer; Tsang, Matthew

    2017-01-01

    HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome...... (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV- 1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis......, TP53 sequencing in the 11 patient-derived HTLV- 1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors...

  14. Recognizing the signs of time in the perspective of Jesus’ call to the evangelization

    Directory of Open Access Journals (Sweden)

    Dariusz Adamczyk

    2008-12-01

    Full Text Available The call of Jesus to recognize the signs of time from Mt 16, 3 has a timeless character. The investigation and explanation of the Gospel light is the duty of the Church. This has a fundamental importance for the effectiveness of evangelization. The signs of time can be correlated directly with God’s initiative to save us. The sign of time can be considered the sign of God in which God’s freedom addresses our freedom, calling us to create history. God, thanks to the signs of time, not so much manifests his definite will, but rather directs us towards freedom. The signs of time show the direction of behaviour for the development of the world which is unanimous with the thought of God. They are God’s calls, which are directed towards men, therefore, recognizing the signs of time has mainly a practical dimen- sion, not a theoretical one. Recognizing signs nowadays allows us to discover new and current elements in the Gospel.

  15. Analysis of some coplanar transmission lines: coplanar coupled lines, coplanar coupled striplines, and coplanar coupled lines with rectangular microshield

    Science.gov (United States)

    Yuan, Naichang; He, Jianguo; Yao, Demiao; Dai, Qin; Lin, Weigan

    1995-06-01

    Two types of coplanar transmission lines, rectangular microshield coplanar coupled lines (RMCCL) and coplanar coupled rectangular microshield lines (CCRML), are proposed for MMIC applications. These are developed from coplanar coupled lines (CCL) and coplanar coupled strip lines (CCS). Analytic formulas are presented for calculating the quasistatic TEM parameters of these coupled lines by means of exact conformal mapping techniques. Numerical results are also presented to illustrate the properties of these coplanar transmission lines.

  16. 46 CFR 159.010-7 - Recognized independent laboratory: Memorandum of Understanding.

    Science.gov (United States)

    2010-10-01

    ... independent laboratory and the Coast Guard; (7) An agreement to conduct comparison testing with other... for conducting comparison tests with other recognized laboratories. (d) Copies of MOUs signed by the... Understanding. 159.010-7 Section 159.010-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED...

  17. Should the United Nations Framework Convention on Climate Change recognize climate migrants?

    Science.gov (United States)

    Gibb, Christine; Ford, James

    2012-12-01

    Climate change is expected to increase migration flows, especially from socially and environmentally vulnerable populations. These ‘climate migrants’ do not have any official protection under international law, which has implications for the human security of migrants. This work argues that the United Nations Framework Convention on Climate Change (UNFCCC) can and should recognize climate migrants, and is the most relevant international framework for doing so. While not legally binding, the acknowledgment of climate displacement, migration and planned relocation issues in the UNFCCC’s Cancun Adaptation Framework indicates a willingness to address the issue through an adaptation lens. Herein, the paper proposes a framework for setting the institutional groundwork for recognizing climate migrants, focusing on the most vulnerable, promoting targeted research and policy agendas, and situating policies within a comprehensive strategy.

  18. Should the United Nations Framework Convention on Climate Change recognize climate migrants?

    International Nuclear Information System (INIS)

    Gibb, Christine; Ford, James

    2012-01-01

    Climate change is expected to increase migration flows, especially from socially and environmentally vulnerable populations. These ‘climate migrants’ do not have any official protection under international law, which has implications for the human security of migrants. This work argues that the United Nations Framework Convention on Climate Change (UNFCCC) can and should recognize climate migrants, and is the most relevant international framework for doing so. While not legally binding, the acknowledgment of climate displacement, migration and planned relocation issues in the UNFCCC’s Cancun Adaptation Framework indicates a willingness to address the issue through an adaptation lens. Herein, the paper proposes a framework for setting the institutional groundwork for recognizing climate migrants, focusing on the most vulnerable, promoting targeted research and policy agendas, and situating policies within a comprehensive strategy. (letter)

  19. Recognizing pedestrian's unsafe behaviors in far-infrared imagery at night

    Science.gov (United States)

    Lee, Eun Ju; Ko, Byoung Chul; Nam, Jae-Yeal

    2016-05-01

    Pedestrian behavior recognition is important work for early accident prevention in advanced driver assistance system (ADAS). In particular, because most pedestrian-vehicle crashes are occurred from late of night to early of dawn, our study focus on recognizing unsafe behavior of pedestrians using thermal image captured from moving vehicle at night. For recognizing unsafe behavior, this study uses convolutional neural network (CNN) which shows high quality of recognition performance. However, because traditional CNN requires the very expensive training time and memory, we design the light CNN consisted of two convolutional layers and two subsampling layers for real-time processing of vehicle applications. In addition, we combine light CNN with boosted random forest (Boosted RF) classifier so that the output of CNN is not fully connected with the classifier but randomly connected with Boosted random forest. We named this CNN as randomly connected CNN (RC-CNN). The proposed method was successfully applied to the pedestrian unsafe behavior (PUB) dataset captured from far-infrared camera at night and its behavior recognition accuracy is confirmed to be higher than that of some algorithms related to CNNs, with a shorter processing time.

  20. Generally Recognized as Safe: Uncertainty Surrounding E-Cigarette Flavoring Safety

    Directory of Open Access Journals (Sweden)

    Clara G. Sears

    2017-10-01

    Full Text Available Despite scientific uncertainty regarding the relative safety of inhaling e-cigarette aerosol and flavorings, some consumers regard the U.S. Food and Drug Administration’s “generally recognized as safe” (GRAS designation as evidence of flavoring safety. In this study, we assessed how college students’ perceptions of e-cigarette flavoring safety are related to understanding of the GRAS designation. During spring 2017, an online questionnaire was administered to college students. Chi-square p-values and multivariable logistic regression were employed to compare perceptions among participants considering e-cigarette flavorings as safe and those considering e-cigarette flavorings to be unsafe. The total sample size was 567 participants. Only 22% knew that GRAS designation meant that a product is safe to ingest, not inhale, inject, or use topically. Of participants who considered flavorings to be GRAS, the majority recognized that the designation meant a product is safe to ingest but also considered it safe to inhale. Although scientific uncertainty on the overall safety of flavorings in e-cigarettes remains, health messaging can educate the public about the GRAS designation and its irrelevance to e-cigarette safety.

  1. Optimization of line configuration and balancing for flexible machining lines

    Science.gov (United States)

    Liu, Xuemei; Li, Aiping; Chen, Zurui

    2016-05-01

    Line configuration and balancing is to select the type of line and allot a given set of operations as well as machines to a sequence of workstations to realize high-efficiency production. Most of the current researches for machining line configuration and balancing problems are related to dedicated transfer lines with dedicated machine workstations. With growing trends towards great product variety and fluctuations in market demand, dedicated transfer lines are being replaced with flexible machining line composed of identical CNC machines. This paper deals with the line configuration and balancing problem for flexible machining lines. The objective is to assign operations to workstations and find the sequence of execution, specify the number of machines in each workstation while minimizing the line cycle time and total number of machines. This problem is subject to precedence, clustering, accessibility and capacity constraints among the features, operations, setups and workstations. The mathematical model and heuristic algorithm based on feature group strategy and polychromatic sets theory are presented to find an optimal solution. The feature group strategy and polychromatic sets theory are used to establish constraint model. A heuristic operations sequencing and assignment algorithm is given. An industrial case study is carried out, and multiple optimal solutions in different line configurations are obtained. The case studying results show that the solutions with shorter cycle time and higher line balancing rate demonstrate the feasibility and effectiveness of the proposed algorithm. This research proposes a heuristic line configuration and balancing algorithm based on feature group strategy and polychromatic sets theory which is able to provide better solutions while achieving an improvement in computing time.

  2. How do GPs recognize needs for palliative care in their patients?

    NARCIS (Netherlands)

    Claessen, S.J.; Francke, A.L.; Deliens, L.

    2012-01-01

    Aim: The aim of this study was to explore how GPs in the Netherlands recognize patients’ needs for palliative care. Methods: We conducted qualitative semi-structured interviews with about 25 GPs. These GPs were interviewed about recognition of the needs for palliative care in their patients and how

  3. 46 CFR 8.230 - Minimum standards for a recognized classification society.

    Science.gov (United States)

    2010-10-01

    ... the United States that provides a continuous management and administrative presence; (15) Maintain an... required end-results; (19) Maintain and ensure compliance with a Code of Ethics that recognizes the...) Not have any business interest in, or share of ownership of, any vessel in its classed fleet; and (23...

  4. LINE FUSION GENES: a database of LINE expression in human genes

    Directory of Open Access Journals (Sweden)

    Park Hong-Seog

    2006-06-01

    Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line

  5. Cable line engineering

    International Nuclear Information System (INIS)

    Jang, Hak Sin; Kim, Sin Yeong

    1998-02-01

    This book is about cable line engineering. It is comprised of nine chapters, which deals with summary of cable communication such as way, process of cable communication and optical communication, Line constant of transmission on primary constant, reflection and crosstalk, communication cable line of types like flat cable, coaxial cable and loaded cable, Install of communication line with types and facility of aerial line, construction method of communication line facility, Measurement of communication line, Carrier communication of summary, PCM communication with Introduction, regeneration relay system sampling and quantization and Electric communication service and general information network with mobile communication technique and satellite communication system.

  6. Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells

    International Nuclear Information System (INIS)

    Bradley, S.M.; Kruisbeek, A.M.; Singer, A.

    1982-01-01

    The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors

  7. Concrete material characterization reinforced concrete tank structure Multi-Function Waste Tank Facility

    International Nuclear Information System (INIS)

    Winkel, B.V.

    1995-01-01

    The purpose of this report is to document the Multi-Function Waste Tank Facility (MWTF) Project position on the concrete mechanical properties needed to perform design/analysis calculations for the MWTF secondary concrete structure. This report provides a position on MWTF concrete properties for the Title 1 and Title 2 calculations. The scope of the report is limited to mechanical properties and does not include the thermophysical properties of concrete needed to perform heat transfer calculations. In the 1970's, a comprehensive series of tests were performed at Construction Technology Laboratories (CTL) on two different Hanford concrete mix designs. Statistical correlations of the CTL data were later generated by Pacific Northwest Laboratories (PNL). These test results and property correlations have been utilized in various design/analysis efforts of Hanford waste tanks. However, due to changes in the concrete design mix and the lower range of MWTF operating temperatures, plus uncertainties in the CTL data and PNL correlations, it was prudent to evaluate the CTL data base and PNL correlations, relative to the MWTF application, and develop a defendable position. The CTL test program for Hanford concrete involved two different mix designs: a 3 kip/in 2 mix and a 4.5 kip/in 2 mix. The proposed 28-day design strength for the MWTF tanks is 5 kip/in 2 . In addition to this design strength difference, there are also differences between the CTL and MWTF mix design details. Also of interest, are the appropriate application of the MWTF concrete properties in performing calculations demonstrating ACI Code compliance. Mix design details and ACI Code issues are addressed in Sections 3.0 and 5.0, respectively. The CTL test program and PNL data correlations focused on a temperature range of 250 to 450 F. The temperature range of interest for the MWTF tank concrete application is 70 to 200 F

  8. Biofuel feedstock and blended coproducts compared with deoiled corn distillers grains in feedlot diets: Effects on cattle growth performance, apparent total tract nutrient digestibility, and carcass characteristics.

    Science.gov (United States)

    Opheim, T L; Campanili, P R B; Lemos, B J M; Ovinge, L A; Baggerman, J O; McCuistion, K C; Galyean, M L; Sarturi, J O; Trojan, S J

    2016-01-01

    Crossbred steers (British × Continental; = 192; initial BW 391 ± 28 kg) were used to evaluate the effects of feeding ethanol coproducts on feedlot cattle growth performance, apparent nutrient digestibility, and carcass characteristics. Steers were blocked by initial BW and assigned randomly to 1 of 6 dietary treatments within block. Treatments (replicated in 8 pens with 4 steers/pen) included 1) control, steam-flaked corn-based diet (CTL), 2) corn dried distillers grains with solubles (DGS; DRY-C), 3) deoiled corn dried DGS (DRY-CLF), 4) blended 50/50 corn/sorghum dried DGS (DRY-C/S), 5) sorghum dried DGS (DRY-S), and 6) sorghum wet DGS (WET-S). Inclusion of DGS was 25% (DM basis). The DGS diets were isonitrogenous, CTL was formulated for 13.5% CP, and all diets were balanced for ether extract. Final shrunk BW, ADG, and DMI did not differ among CTL and DGS treatments ( ≥ 0.19). Overall G:F did not differ from CTL for DRY-C, DRY-CLF, or WET-S ( ≥ 0.12); however, G:F was 9.6% less for DRY-S compared with CTL ( carcass-adjusted G:F vs. DRY-S. For WET-S, final BW and ADG were greater ( Carcass weight, dressing percent, and marbling score did not differ between CTL and DGS diets ( ≥ 0.23). For DRY-S, HCW was lower than for DRY-C ( = 0.02); however, compared with DRY-S, HCW tended to be greater for DRY-C/S ( = 0.10) and WET-S ( = 0.07). At a moderately high (25% DM) inclusion, blending C/S or feeding WET-S resulted in cattle growth performance and carcass characteristics similar to those of CTL and corn-based coproducts.

  9. Fabrication a new modified electrochemical sensor based on Au–Pd bimetallic nanoparticle decorated graphene for citalopram determination

    Energy Technology Data Exchange (ETDEWEB)

    Daneshvar, Leili [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Rounaghi, Gholam Hossein, E-mail: ghrounaghi@yahoo.com [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Es' haghi, Zarrin [Department of Chemistry, Faculty of Sciences, Payame Noor University, Mashhad (Iran, Islamic Republic of); Chamsaz, Mahmoud; Tarahomi, Somayeh [Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of)

    2016-12-01

    This paper proposes a simple approach for sensing of citalopram (CTL) using gold–palladium bimetallic nanoparticles (Au–PdNPs) decorated graphene modified gold electrode. Au–PdNPs were deposited at the surface of a graphene modified gold electrode with simple electrodeposition method. The morphology and the electrochemical properties of the modified electrode were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), energy dispersion spectroscopy (EDS), electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square wave voltammetry (SWV). The novel sensor exhibited an excellent catalytic activity towards the oxidation of CTL. The oxidation peak current of CTL, was linear in the range of 0.5–50 μM with a detection limit 0.049 μM with respect to concentration of citalopram. The proposed sensor was successfully applied for determination of CTL tablet and human plasma samples with satisfactory results. - Highlights: • A novel sensor based on Au-PdNPs deposited graphene modified gold electrode was fabricated. • The morphology and the electrochemical properties of the sensor were characterized by several methods. • The fabricated sensor was employed for the detection of antidepressant drug CTL with satisfactory results.

  10. A virus-sensitive suppressor cell is involved in the regulation of human allospecific T cell-mediated cytotoxicity

    International Nuclear Information System (INIS)

    Muluk, S.C.; Bernstein, D.C.; Shearer, G.M.

    1989-01-01

    The in vitro generation of allospecific CTL by human PBMC was enhanced 4- to 16-fold by sequential plastic and nylon wool adherence, which depleted the PBMC of macrophages and B cells. The enhanced CTL response was suppressed by adding back irradiated, unfractionated PBMC or adherent cells to the depleted cells. This finding suggests that the enhanced CTL response was not simply a consequence of enrichment of T cells, but was instead due to active suppression by radioresistant cells contained in the adherent fraction. Of note is the finding that, unlike the CTL response, the proliferative response to allostimulation was not affected by the removal of adherent cells. The suppressor function could be abrogated by preincubation of irradiated PBMC with influenza A virus before the coculture with depleted cells. Furthermore, costimulation of unfractionated PBMC with influenza A virus and allogeneic stimulators augmented allospecific CTL activity. Thus, in the adherent fraction of human PBMC, there appears to be a native suppressor population that can be functionally inactivated by virus. This result may account for the clinical observation of increased allograft rejection after certain viral infections

  11. Measuring T cell-mediated cytotoxicity using fluorogenic caspase substrates.

    Science.gov (United States)

    Chahroudi, A; Silvestri, G; Feinberg, M B

    2003-10-01

    Cytotoxic T lymphocytes (CTLs) play a major role in the immune response against viruses and other intracellular pathogens. In addition, CTLs are implicated in the control of tumor cells in certain settings. Accurate measures of CTL function are of critical importance to study the pathogenesis of infectious diseases and to evaluate the efficacy of new vaccines and immunotherapies. To this end, we have recently developed a flow cytometry-based CTL (FCC) assay that measures the CTL-induced caspase activation within target cells using cell permeable fluorogenic caspase substrates. This novel assay reliably detects, by flow cytometry or fluorescence/confocal microscopy, antigen-specific CTLs in a wide variety of human and murine systems, and is safer and more informative than the standard 51Cr-release assay. In addition, the flow cytometric CTL (FCC) assay provides an alternative method that is often more sensitive and physiologically informative when compared to previously described FCC assays, as it measures a biological indicator of apoptosis within the target cell. The FCC assay may thus represent a useful tool to further understand the molecular and cellular mechanisms that underlie CTL-mediated killing during tumorigenesis or following infection with viruses or other intracellular pathogens.

  12. Development of a rectal sexually transmitted infection (STI) Model in Rhesus macaques using Chlamydia trachomatis serovars E and L2.

    Science.gov (United States)

    Henning, Tara R; Morris, Monica; Ellis, Shanon; Kelley, Kristen; Phillips, Christi; Ritter, Jana; Jones, Tara; Nachamkin, Eli; Chen, Cheng Y; Hong, Jaeyoung; Kang, Joseph; Patton, Dorothy; McNicholl, Janet; Papp, John; Kersh, Ellen N

    2017-10-01

    Rectal STI coinfection models enhance the understanding of rectal HIV transmission risk factors. Rhesus macaques (n=9) were exposed to one of three rectal Chlamydia trachomatis (CT) challenges: C. trachomatis L 2 (CT-L 2 ); C. trachomatis serovar E (CT-E), followed by CT-L 2 ; or CT-E, treatment/clearance, then CT-L 2 . Infections were monitored by PCR. Weekly blood and rectal secretion/lavage samples were collected for cytokine analyzes and/or epithelial sloughing, occult, and overt blood determinations. Chlamydial infections were successfully established in each animal, with varying degrees of persistence. Mucosal IL-1beta was upregulated in animals consecutively infected with CT-E then CT-L 2 (P=.05). Epithelial sloughing was also significantly increased post-infection in this group (P=.0003). This study demonstrates successful rectal infection of rhesus macaques with CT-E and CT-L 2 and describes measures of assessing rectal inflammation and pathology. Different infection strategies yield varying inflammatory and pathologic outcomes, providing well-described models for future SIV/SHIV susceptibility studies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Cytotoxic Activity of Selected Iranian Traditional Medicinal Plants on Colon, Colorectal and Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Leila Mohammad Taghizadeh Kashani

    2014-11-01

    Full Text Available Background: Many natural products from plants have been recognized to exert anticancer activity. In this study, ethanolic extracts of selected medicinal herbs from Iranian flora including Alyssum homolocarpum Fisch. (from seeds, Urtica dioica L. (from aerial parts, Cichorium intybus L. (from roots and Solanum nigrum L. (from fruits, were evaluated for their cytotoxic effect on different cell lines.Methods: Cytotoxic effect of these extracts was studied on three different cancer cell lines; colon carcinoma (HT-29, colorectal adenocarcinoma (Caco-2 and breast ductal carcinoma (T47D. In addition, Swiss mouse embryo fibroblasts (NIH 3T3 were used as normal nonmalignant cells. MTT assay (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide was utilized for calculating the cytotoxicity of extracts on cell lines.Results: Results showed the potent cytotoxic activity of U. dioica ethanolic extract against T47D cell line with IC50 value of 46.14±4.55 µg/ml. Other extracts showed poor activity with IC50>100 µg/ml.Conclusions: Cytotoxic activity recorded in the present study revealed high potential antiproliferative activity of U. dioica ethanolic extract against T47D cell line. The real IC50 values of this extract may be considerably lower than the IC50 measured in our study if its pharmacological active compounds become pure. The results emphasize the importance of studies on U. dioica ethanolic extract to characterize potential components as cytotoxic natural medicines.

  14. The "Finding Physics" Project: Recognizing and Exploring Physics outside the Classroom

    Science.gov (United States)

    Beck, Judith; Perkins, James

    2016-01-01

    Students in introductory physics classes often have difficulty recognizing the relevance of physics concepts outside the confines of the physics classroom, lab, and textbook. Even though textbooks and instructors often provide examples of physics applications from a wide array of areas, students have difficulty relating physics to their own lives.…

  15. Dogs recognize dog and human emotions.

    Science.gov (United States)

    Albuquerque, Natalia; Guo, Kun; Wilkinson, Anna; Savalli, Carine; Otta, Emma; Mills, Daniel

    2016-01-01

    The perception of emotional expressions allows animals to evaluate the social intentions and motivations of each other. This usually takes place within species; however, in the case of domestic dogs, it might be advantageous to recognize the emotions of humans as well as other dogs. In this sense, the combination of visual and auditory cues to categorize others' emotions facilitates the information processing and indicates high-level cognitive representations. Using a cross-modal preferential looking paradigm, we presented dogs with either human or dog faces with different emotional valences (happy/playful versus angry/aggressive) paired with a single vocalization from the same individual with either a positive or negative valence or Brownian noise. Dogs looked significantly longer at the face whose expression was congruent to the valence of vocalization, for both conspecifics and heterospecifics, an ability previously known only in humans. These results demonstrate that dogs can extract and integrate bimodal sensory emotional information, and discriminate between positive and negative emotions from both humans and dogs. © 2016 The Author(s).

  16. Anti-Thrombotic Effect of Carthamus tinctorius Linn Extracts in Rats

    African Journals Online (AJOL)

    HP

    PGF1α/TXB2 and arterial or venous thrombus weight for all treatments, and also with occlusion time for. CTL treatment but not for aspirin. Conclusion: CTL has a significant effect on thrombosis in rats. ..... Thrombolysis for experimental deep.

  17. HTGR-Integrated Coal To Liquids Production Analysis

    International Nuclear Information System (INIS)

    Gandrik, Anastasia M.; Wood, Rick A.

    2010-01-01

    As part of the DOE's Idaho National Laboratory (INL) nuclear energy development mission, the INL is leading a program to develop and design a high temperature gas-cooled reactor (HTGR), which has been selected as the base design for the Next Generation Nuclear Plant. Because an HTGR operates at a higher temperature, it can provide higher temperature process heat, more closely matched to chemical process temperatures, than a conventional light water reactor. Integrating HTGRs into conventional industrial processes would increase U.S. energy security and potentially reduce greenhouse gas emissions (GHG), particularly CO2. This paper focuses on the integration of HTGRs into a coal to liquids (CTL) process, for the production of synthetic diesel fuel, naphtha, and liquefied petroleum gas (LPG). The plant models for the CTL processes were developed using Aspen Plus. The models were constructed with plant production capacity set at 50,000 barrels per day of liquid products. Analysis of the conventional CTL case indicated a potential need for hydrogen supplementation from high temperature steam electrolysis (HTSE), with heat and power supplied by the HTGR. By supplementing the process with an external hydrogen source, the need to 'shift' the syngas using conventional water-gas shift reactors was eliminated. HTGR electrical power generation efficiency was set at 40%, a reactor size of 600 MWth was specified, and it was assumed that heat in the form of hot helium could be delivered at a maximum temperature of 700 C to the processes. Results from the Aspen Plus model were used to perform a preliminary economic analysis and a life cycle emissions assessment. The following conclusions were drawn when evaluating the nuclear assisted CTL process against the conventional process: (1) 11 HTGRs (600 MWth each) are required to support production of a 50,000 barrel per day CTL facility. When compared to conventional CTL production, nuclear integration decreases coal consumption by 66

  18. HTGR-INTEGRATED COAL TO LIQUIDS PRODUCTION ANALYSIS

    Energy Technology Data Exchange (ETDEWEB)

    Anastasia M Gandrik; Rick A Wood

    2010-10-01

    As part of the DOE’s Idaho National Laboratory (INL) nuclear energy development mission, the INL is leading a program to develop and design a high temperature gas-cooled reactor (HTGR), which has been selected as the base design for the Next Generation Nuclear Plant. Because an HTGR operates at a higher temperature, it can provide higher temperature process heat, more closely matched to chemical process temperatures, than a conventional light water reactor. Integrating HTGRs into conventional industrial processes would increase U.S. energy security and potentially reduce greenhouse gas emissions (GHG), particularly CO2. This paper focuses on the integration of HTGRs into a coal to liquids (CTL) process, for the production of synthetic diesel fuel, naphtha, and liquefied petroleum gas (LPG). The plant models for the CTL processes were developed using Aspen Plus. The models were constructed with plant production capacity set at 50,000 barrels per day of liquid products. Analysis of the conventional CTL case indicated a potential need for hydrogen supplementation from high temperature steam electrolysis (HTSE), with heat and power supplied by the HTGR. By supplementing the process with an external hydrogen source, the need to “shift” the syngas using conventional water-gas shift reactors was eliminated. HTGR electrical power generation efficiency was set at 40%, a reactor size of 600 MWth was specified, and it was assumed that heat in the form of hot helium could be delivered at a maximum temperature of 700°C to the processes. Results from the Aspen Plus model were used to perform a preliminary economic analysis and a life cycle emissions assessment. The following conclusions were drawn when evaluating the nuclear assisted CTL process against the conventional process: • 11 HTGRs (600 MWth each) are required to support production of a 50,000 barrel per day CTL facility. When compared to conventional CTL production, nuclear integration decreases coal

  19. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors

    DEFF Research Database (Denmark)

    Yang, Liang; Rybtke, Morten Theil; Jakobsen, Tim Holm

    2009-01-01

    R, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related...

  20. Disseminating treatment for anxiety disorders: step 1: recognizing the problem as a precursor to seeking help.

    Science.gov (United States)

    Coles, Meredith E; Schubert, Jessica R; Heimberg, Richard G; Weiss, Barry D

    2014-12-01

    Untreated mental illness is a substantial public health issue in the United States, with only approximately 1/3 of the estimated 46 million adults in the US with mental illness receiving treatment. Many of the individuals with mental illness suffer from excessive anxiety, as over 25% of Americans experience an anxiety disorder during their lifetime and most of these individuals remain untreated. Building from the premise that recognizing one's symptoms precedes requests for help, the current paper presents data from 577 adults (50% Caucasian, 50% African American) in the US regarding their ability to recognize anxiety disorders. Findings from a national survey showed that when presented with detailed vignettes portraying symptoms and their impact, 50% of respondents correctly recognized depression, whereas less than 20% correctly recognized the anxiety disorders. Recognition that the symptoms were a cause for concern was much more common, with 75% or more of the sample noting concern. Responses were surprisingly similar across the two races, and few consistent moderators were found. In conclusion, increasing recognition of anxiety disorders may be a useful first step toward increasing service utilization. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Alternative Liquid Fuels Simulation Model (AltSim).

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Ryan; Baker, Arnold Barry; Drennen, Thomas E.

    2009-12-01

    The Alternative Liquid Fuels Simulation Model (AltSim) is a high-level dynamic simulation model which calculates and compares the production and end use costs, greenhouse gas emissions, and energy balances of several alternative liquid transportation fuels. These fuels include: corn ethanol, cellulosic ethanol from various feedstocks (switchgrass, corn stover, forest residue, and farmed trees), biodiesel, and diesels derived from natural gas (gas to liquid, or GTL), coal (coal to liquid, or CTL), and coal with biomass (CBTL). AltSim allows for comprehensive sensitivity analyses on capital costs, operation and maintenance costs, renewable and fossil fuel feedstock costs, feedstock conversion ratio, financial assumptions, tax credits, CO{sub 2} taxes, and plant capacity factor. This paper summarizes the structure and methodology of AltSim, presents results, and provides a detailed sensitivity analysis. The Energy Independence and Security Act (EISA) of 2007 sets a goal for the increased use of biofuels in the U.S., ultimately reaching 36 billion gallons by 2022. AltSim's base case assumes EPA projected feedstock costs in 2022 (EPA, 2009). For the base case assumptions, AltSim estimates per gallon production costs for the five ethanol feedstocks (corn, switchgrass, corn stover, forest residue, and farmed trees) of $1.86, $2.32, $2.45, $1.52, and $1.91, respectively. The projected production cost of biodiesel is $1.81/gallon. The estimates for CTL without biomass range from $1.36 to $2.22. With biomass, the estimated costs increase, ranging from $2.19 per gallon for the CTL option with 8% biomass to $2.79 per gallon for the CTL option with 30% biomass and carbon capture and sequestration. AltSim compares the greenhouse gas emissions (GHG) associated with both the production and consumption of the various fuels. EISA allows fuels emitting 20% less greenhouse gases (GHG) than conventional gasoline and diesels to qualify as renewable fuels. This allows several of the

  2. Human NOD2 Recognizes Structurally Unique Muramyl Dipeptides from Mycobacterium leprae.

    Science.gov (United States)

    Schenk, Mirjam; Mahapatra, Sebabrata; Le, Phuonganh; Kim, Hee Jin; Choi, Aaron W; Brennan, Patrick J; Belisle, John T; Modlin, Robert L

    2016-09-01

    The innate immune system recognizes microbial pathogens via pattern recognition receptors. One such receptor, NOD2, via recognition of muramyl dipeptide (MDP), triggers a distinct network of innate immune responses, including the production of interleukin-32 (IL-32), which leads to the differentiation of monocytes into dendritic cells (DC). NOD2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether Mycobacterium leprae, which has a distinct MDP structure, can activate this pathway. We investigated the effect of MDP structure on the innate immune response, finding that infection of monocytes with M. leprae induces IL-32 and DC differentiation in a NOD2-dependent manner. The presence of the proximal l-Ala instead of Gly in the common configuration of the peptide side chain of M. leprae did not affect recognition by NOD2 or cytokine production. Furthermore, amidation of the d-Glu residue did not alter NOD2 activation. These data provide experimental evidence that NOD2 recognizes naturally occurring structural variants of MDP. Copyright © 2016 Schenk et al.

  3. Evolution of Src Homology 2 (SH2) Domain to Recognize Sulfotyrosine.

    Science.gov (United States)

    Ju, Tong; Niu, Wei; Guo, Jiantao

    2016-09-16

    Protein tyrosine O-sulfation is considered as the most common type of post-translational tyrosine modification in nature and plays important roles in extracellular biomolecular interactions. To facilitate the mapping, biological study, and medicinal application of this type of post-translational modification, we seek to evolve a small protein scaffold that recognizes sulfotyrosine with high affinity. We focused our efforts on the engineering of the Src Homology 2 (SH2) domain, which represents the largest class of known phosphotyrosine-recognition domain in nature and has a highly evolvable binding pocket. By using phage display, we successfully engineered the SH2 domain to recognize sulfotyrosine with high affinity. The best mutant, SH2-60.1, displayed more than 1700 fold higher sulfotyrosine-binding affinity than that of the wild-type SH2 domain. We also demonstrated that the evolved SH2 domain mutants could be used to detect sulfoprotein levels on the cell surface. These evolved SH2 domain mutants can be potentially applied to the study of protein tyrosine O-sulfation with proper experimental designs.

  4. Effects of Facial Expressions on Recognizing Emotions in Dance Movements

    Directory of Open Access Journals (Sweden)

    Nao Shikanai

    2011-10-01

    Full Text Available Effects of facial expressions on recognizing emotions expressed in dance movements were investigated. Dancers expressed three emotions: joy, sadness, and anger through dance movements. We used digital video cameras and a 3D motion capturing system to record and capture the movements. We then created full-video displays with an expressive face, full-video displays with an unexpressive face, stick figure displays (no face, or point-light displays (no face from these data using 3D animation software. To make point-light displays, 13 markers were attached to the body of each dancer. We examined how accurately observers were able to identify the expression that the dancers intended to create through their dance movements. Dance experienced and inexperienced observers participated in the experiment. They watched the movements and rated the compatibility of each emotion with each movement on a 5-point Likert scale. The results indicated that both experienced and inexperienced observers could identify all the emotions that dancers intended to express. Identification scores for dance movements with an expressive face were higher than for other expressions. This finding indicates that facial expressions affect the identification of emotions in dance movements, whereas only bodily expressions provide sufficient information to recognize emotions.

  5. The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus.

    Directory of Open Access Journals (Sweden)

    Chad Steele

    2005-12-01

    Full Text Available Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical for innate immunity to A. fumigatus. Acknowledging that the A. fumigatus cell wall contains a high beta-1,3-glucan content, we questioned whether the beta-glucan receptor dectin-1 played a role in this recognition process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated that the alveolar macrophage inflammatory response, specifically the production of tumor necrosis factor-alpha (TNF-alpha, interleukin-1alpha (IL-1alpha, IL-1beta, IL-6, CXCL2/macrophage inflammatory protein-2 (MIP-2, CCL3/macrophage inflammatory protein-1alpha (MIP-1alpha, granulocyte-colony stimulating factor (G-CSF, and granulocyte monocyte-CSF (GM-CSF, to live A. fumigatus was dependent on recognition via the beta-glucan receptor dectin-1. The inflammatory response was triggered at the highest level by A. fumigatus swollen conidia and early germlings and correlated to the levels of surface-exposed beta glucans, indicating that dectin-1 preferentially recognizes specific morphological forms of A. fumigatus. Intratracheal administration of A. fumigatus conidia to mice in the presence of a soluble dectin-Fc fusion protein reduced both lung proinflammatory cytokine/chemokine levels and cellular recruitment while modestly increasing the A. fumigatus fungal burden, illustrating the importance of beta-glucan-initiated dectin-1 signaling in defense against this pathogen. Collectively, these data show that dectin-1 is centrally required for the generation of alveolar macrophage proinflammatory responses to A. fumigatus and to our knowledge provides the first in vivo evidence for the role of dectin-1 in fungal innate defense.

  6. Identification of MHC class II restricted T‐cell‐mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

    DEFF Research Database (Denmark)

    Wang, Mingjun; Tang, Sheila Tuyet; Stryhn, Anette

    2011-01-01

    Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide...

  7. Assessing the feasibility and profitability of cut-to-length harvests in eastern hardwoods

    Science.gov (United States)

    Chris B. LoDoux

    2002-01-01

    Cut-to-length (CTL) logging applications are becoming more popular in hardwood forests. CTL harvesting causes much less damage to the residual stand than conventional harvesting because logs and trees are not pulled through the stand and trees can be felled directionally.

  8. 25 CFR 115.422 - As a custodial parent, the legal guardian, the person who BIA has recognized as having control...

    Science.gov (United States)

    2010-04-01

    ... BIA has recognized as having control and custody of the minor, or an emancipated minor, what are your... BIA has recognized as having control and custody of the minor, or an emancipated minor, what are your... legal guardian, the person who BIA has recognized as having control and custody of the minor, or an...

  9. Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines

    Directory of Open Access Journals (Sweden)

    Kaski Samuel

    2007-03-01

    Full Text Available Abstract Background Asbestos has been shown to cause chromosomal damage and DNA aberrations. Exposure to asbestos causes many lung diseases e.g. asbestosis, malignant mesothelioma, and lung cancer, but the disease-related processes are still largely unknown. We exposed the human cell lines A549, Beas-2B and Met5A to crocidolite asbestos and determined time-dependent gene expression profiles by using Affymetrix arrays. The hybridization data was analyzed by using an algorithm specifically designed for clustering of short time series expression data. A canonical correlation analysis was applied to identify correlations between the cell lines, and a Gene Ontology analysis method for the identification of enriched, differentially expressed biological processes. Results We recognized a large number of previously known as well as new potential asbestos-associated genes and biological processes, and identified chromosomal regions enriched with genes potentially contributing to common responses to asbestos in these cell lines. These include genes such as the thioredoxin domain containing gene (TXNDC and the potential tumor suppressor, BCL2/adenovirus E1B 19kD-interacting protein gene (BNIP3L, GO-terms such as "positive regulation of I-kappaB kinase/NF-kappaB cascade" and "positive regulation of transcription, DNA-dependent", and chromosomal regions such as 2p22, 9p13, and 14q21. We present the complete data sets as Additional files. Conclusion This study identifies several interesting targets for further investigation in relation to asbestos-associated diseases.

  10. Recognizing mid-career productivity: the 2008 Retrovirology Prize, call for nomination

    Directory of Open Access Journals (Sweden)

    Jeang Kuan-Teh

    2008-09-01

    Full Text Available Abstract A recent analysis suggested a narrow age range for productivity of innovative work by researchers. The Retrovirology Prize seeks to recognize the research of a mid-career retrovirologist between the ages of 45 and 60. The 2007 Retrovirology Prize was awarded to Dr. Karen Beemon. Nominations are being solicited for the 2008 prize.

  11. Hidden Abuse within the Home: Recognizing and Responding to Sibling Abuse

    Science.gov (United States)

    Stutey, Diane; Clemens, Elysia V.

    2015-01-01

    Sibling abuse is a serious phenomenon in our society that often goes unaddressed. Victims of sibling abuse experience psychological effects similar to those of child abuse (Caspi, 2012; Wiehe, 2002). The purpose of this article is to provide school counselors with a definition of sibling abuse and a five-step model to recognize and respond. A…

  12. Generally Recognized as Safe: Uncertainty Surrounding E-Cigarette Flavoring Safety

    OpenAIRE

    Sears, Clara G.; Hart, Joy L.; Walker, Kandi L.; Robertson, Rose Marie

    2017-01-01

    Despite scientific uncertainty regarding the relative safety of inhaling e-cigarette aerosol and flavorings, some consumers regard the U.S. Food and Drug Administration’s “generally recognized as safe” (GRAS) designation as evidence of flavoring safety. In this study, we assessed how college students’ perceptions of e-cigarette flavoring safety are related to understanding of the GRAS designation. During spring 2017, an online questionnaire was administered to college students. Chi-square p-v...

  13. LKM-1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P-450 monooxygenase.

    OpenAIRE

    Manns, M P; Griffin, K J; Sullivan, K F; Johnson, E F

    1991-01-01

    LKM-1 autoantibodies, which are associated with autoimmune chronic active hepatitis, recognize P450IID6, a cytochrome P-450 monooxygenase. The reactivities of 26 LKM-1 antisera were tested with a panel of deletion mutants of P450IID6 expressed in Escherichia coli. 22 sera recognize a 33-amino acid segment of P450IID6, and 11 of these recognize a shorter segment, DPAQPPRD. PAQPPR is also found in IE175 of herpes simplex virus type 1 (HSV-1). Antibodies for HSV-1 proteins were detected by ELISA...

  14. IMPLEMENTASI PENDEKATAN KONTEKSTUAL DENGAN VARIASI METODE BERBASIS MASALAH UNTUK MENINGKATKAN KUALITAS PEMBELAJARAN BIOLOGI

    Directory of Open Access Journals (Sweden)

    S. Sudarisman

    2013-04-01

    Full Text Available Tujuan dari penelitian ini adalah meningkatkan kualitas pembelajaran biologi ditinjau dari 5 aspek pembelajaran yang meliputi: performance guru, fasilitas pembelajaran, iklim kelas, sikap dan motivasi belajar siswa melalui pene-rapan pendekatan CTL dengan metode problem solving. Hasil penelitian menunjukkan implementasi pendekatan CTL dengan metode problem solving dapat meningkatkan kelima aspek kualitas pembelajaran, meliputi performance guru, fasilitas pembelajaran, iklim kelas, sikap dan motivasi belajar siswa. The purpose of this research is to improve the quality of biology learning in terms of five aspects of learning which include: performance of teachers, learning facilities, classroom climate, learning attitude and motivation of students through the implementation of CTL approach with problem solving methods. The results showed that implementation of CTL approach with problem solving method can improve the quality of the five aspects of learning, include performance of teachers, learning facilities, classroom climate, students’ attitudes and motivation.

  15. Prediction of T-cell Epitopes for Therapeutic and Prophylactic Vaccines

    DEFF Research Database (Denmark)

    Larsen, Mette Voldby

    2007-01-01

    : The bacteria Mycobacterium tuberculosis, Influenza A virus, HIV, Yellow fever virus, and West Nile virus. For each of the above-mentioned viruses, a number of predicted CTL epitopes was subsequently selected in such a way that they together constitute a broad coverage of the available viral strains. Part IV......The spread of existing infectious diseases and the emergence of new ones call for efficient methods for vaccine development. Some of the important players in conferring immunity against pathogens are the Cytotoxic T Lymphocytes (CTL), which eliminate infected cells. Due to their deleterious effects...... vaccine design as well as for diagnostic purposes and is the centre of focus of this thesis: Part I of the thesis is an introduction to the field. In part II, I describe how we generated a method, NetCTL, for predicting CTL epitopes by integrating existing methods for predicting proteasomal cleavage, TAP...

  16. Metabolomics Characterization of U.S. and Japanese F-15 and C-130 Flight Line Crews Exposed to Jet Fuel Volatile Organic Compounds and Aerosols

    Science.gov (United States)

    2014-09-30

    been recognized as the single largest source of chemical exposure for U.S. and NATO military personnel (Carlton and Smith, 2000) where inhalation and...flight line, 2) exposure to spills, 3) inhalation exposure (primarily exhaust), and 4) total measured VOCs. The total VOC value was calculated by...chemical and primary metals industries, biomass burning, gasoline and oil combustion, tobacco smoking, the use of mothballs, fumigants and deodorizers

  17. Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

    Science.gov (United States)

    Kawamura, Junichiro; Sugiura, Fumiaki; Sukegawa, Yasushi; Yoshioka, Yasumasa; Hida, Jin-Ichi; Hazama, Shoichi; Okuno, Kiyotaka

    2018-02-23

    We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34-kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil-tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination-induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA-masked fashion. After the disclosure of HLA, 28 patients were in the HLA-A*2402-matched and 16 were in the unmatched group. In the HLA-matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA-unmatched group, 10 CTL responses were positive and 2 negative. In the HLA-matched group, 3-year relapse-free survival (RFS) was significantly better in the positive CTL subgroup than in the negative-response subgroup. Patients with negative vaccination-induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA-unmatched group, the positive CTL response subgroup showed an equally good 3-year RFS as in the HLA-matched group. In conclusion, vaccination-induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  18. Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope

    DEFF Research Database (Denmark)

    Iversen, Astrid K N; Stewart-Jones, Guillaume; Learn, Gerald H

    2006-01-01

    two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which...

  19. Alloreactive cytotoxic T lymphocytes from aged mice express increased lysis of autologous and third-party target cells

    NARCIS (Netherlands)

    Kruisbeek, A.M.; Steinmeier, F.A.

    1980-01-01

    Much data support the notion that with increasing age a decline in T cell effector function occurs. In the present study, qualitative rather than quantitative age-related changes in vitro alloreactive cytotoxic T lymphocyte (CTL) responses were observed. The level of specific alloreactive CTL

  20. Minimizing performance degradation induced by interfacial recombination in perovskite solar cells through tailoring of the transport layer electronic properties

    Directory of Open Access Journals (Sweden)

    Liang Xu

    2018-03-01

    Full Text Available The performance of hybrid organic-inorganic metal halide perovskite solar cells is investigated using one-dimensional drift-diffusion device simulations. We study the effects of interfacial defect density, doping concentration, and electronic level positions of the charge transport layer (CTL. Choosing CTLs with a favorable band alignment, rather than passivating CTL-perovskite interfacial defects, is shown to be beneficial for maintaining high power-conversion efficiency, due to reduced minority carrier density arising from a favorable local electric field profile. Insights from this study provide theoretical guidance on practical selection of CTL materials for achieving high-performance perovskite solar cells.

  1. DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

    Science.gov (United States)

    Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

    2016-09-01

    Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4 + (nTh) and CD8 + (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

  2. Antioxidant and lipoxygenase activities of polyphenol extracts from oat brans treated with polysaccharide degrading enzymes

    Directory of Open Access Journals (Sweden)

    Nisita Ratnasari

    2017-07-01

    Full Text Available This study used polysaccharide degrading enzymes and protein precipitation to extract polyphenols from oats and to determine their bioactivity. Duplicate oat brans were treated with viscozyme (Vis, cellulase (Cel or no enzyme (control, CTL then, proteins were removed in one set (Vis1, Cel1, CTL1 and not in the other (Vis2, Cel2, CTL2. HPLC analyses showed that for cellulase treated brans, precipitation of proteins increased phenolic acids and avenanthramides by 14%. Meanwhile, a decreased of 67% and 20% respectively was found for viscozyme and control brans. The effect of protein precipitation on soluble polyphenols is therefore dependent of the carbohydrase, as proteins with different compositions will interact differently with other molecules. Radical scavenging data showed that Cel1 and Vis1 had higher quenching effects on ROO• radicals with activities of 22.1 ± 0.8 and 23.5 ± 1.2 μM Trolox Equivalents/g defatted brans. Meanwhile, CTL2 had the highest HO• radicals inhibition (49.4 ± 2.8% compared to 10.8–32.3% for others. Samples that highly inhibited lipoxygenase (LOX, an enzyme involved in lipid oxidation were Cel1 (23.4 ± 2.3% and CTL1 (18 ± 0.4%.

  3. Transmission Line Ampacity Improvements of AltaLink Wind Plant Overhead Tie-Lines Using Weather-Based Dynamic Line Rating

    Energy Technology Data Exchange (ETDEWEB)

    Bhattarai, Bishnu P.; Gentle, Jake P.; Hill, Porter; McJunkin, Tim; Myers, Kurt S.; Abbound, Alex; Renwick, Rodger; Hengst, David

    2017-07-01

    Abstract—Overhead transmission lines (TLs) are conventionally given seasonal ratings based on conservative environmental assumptions. Such an approach often results in underutilization of the line ampacity as the worst conditions prevail only for a short period over a year/season. We presents dynamic line rating (DLR) as an enabling smart grid technology that adaptively computes ratings of TLs based on local weather conditions to utilize additional headroom of existing lines. In particular, general line ampacity state solver utilizes measured weather data for computing the real-time thermal rating of the TLs. The performance of the presented method is demonstrated from a field study of DLR technology implementation on four TL segments at AltaLink, Canada. The performance is evaluated and quantified by comparing the existing static and proposed dynamic line ratings, and the potential benefits of DLR for enhanced transmission assets utilization. For the given line segments, the proposed DLR results in real-time ratings above the seasonal static ratings for most of the time; up to 95.1% of the time, with a mean increase of 72% over static rating.

  4. Beacon- and Schema-Based Method for Recognizing Algorithms from Students' Source Code

    Science.gov (United States)

    Taherkhani, Ahmad; Malmi, Lauri

    2013-01-01

    In this paper, we present a method for recognizing algorithms from students programming submissions coded in Java. The method is based on the concept of "programming schemas" and "beacons". Schemas are high-level programming knowledge with detailed knowledge abstracted out, and beacons are statements that imply specific…

  5. Male tawny dragons use throat patterns to recognize rivals.

    Science.gov (United States)

    Osborne, Louise; Umbers, Kate D L; Backwell, Patricia R Y; Keogh, J Scott

    2012-10-01

    The ability to distinguish between familiar and unfamiliar conspecifics is important for many animals, especially territorial species since it allows them to avoid unnecessary interactions with individuals that pose little threat. There are very few studies, however, that identify the proximate cues that facilitate such recognition in visual systems. Here, we show that in tawny dragons (Ctenophorus decresii), males can recognize familiar and unfamiliar conspecific males based on morphological features alone, without the aid of chemical or behavioural cues. We further show that it is the colour pattern of the throat patches (gular) that facilitates this recognition.

  6. Recognizing and labeling sex-based and sexual harassment in the health care workplace.

    Science.gov (United States)

    Madison, J; Minichiello, V

    2000-01-01

    To explore how registered nurses (RNs) recognized and labeled incidents of sex-based and sexual harassment in the Australian health care workplace. Qualitative, using 16 unstructured interviews with registered nurses in Australia. Verbatim transcripts were analyzed largely by inductive analysis. Key categories were identified as themes or concepts for analysis. RNs reported several indicators of sexual harassment, including the invasion of space, confirmation from others, lack of respect, the deliberate nature of the behavior, perceived power or control, overly friendly behavior, and a sexualized workplace. RNs rarely labeled harassing behaviors as sex-based or sexual harassment. Many forces reduce the likelihood that RNs will correctly recognize and label unwelcome sexualized behavior as sexual harassment. Recognition is associated with a variety of workplace behaviors that sometimes precede harassment. Implications for the health care workplace are discussed.

  7. Directed line liquids

    International Nuclear Information System (INIS)

    Kamien, R.D.

    1992-01-01

    This thesis is devoted to the study of ensembles of dense directed lines. These lines are principally to be thought of as polymers, though they also have the morphology of flux lines in high temperature superconductors, strings of colloidal spheres in electrorheological fluids and the world lines of quantum mechanical bosons. The authors discuss how directed polymer melts, string-like formations in electrorheological and ferro-fluids, flux lines in high temperature superconductors and the world lines of quantum mechanical bosons all share similar descriptions. They study a continuous transition in all of these systems, and then study the critical mixing properties of binary mixtures of directed polymers through the renormalization group. They predict the exponents for a directed polymer blend consolute point and a novel two-phase superfluid liquid-gas critical point

  8. Recognizing Induced Emotions of Happiness and Sadness from Dance Movement

    Science.gov (United States)

    Van Dyck, Edith; Vansteenkiste, Pieter; Lenoir, Matthieu; Lesaffre, Micheline; Leman, Marc

    2014-01-01

    Recent research revealed that emotional content can be successfully decoded from human dance movement. Most previous studies made use of videos of actors or dancers portraying emotions through choreography. The current study applies emotion induction techniques and free movement in order to examine the recognition of emotional content from dance. Observers (N = 30) watched a set of silent videos showing depersonalized avatars of dancers moving to an emotionally neutral musical stimulus after emotions of either sadness or happiness had been induced. Each of the video clips consisted of two dance performances which were presented side-by-side and were played simultaneously; one of a dancer in the happy condition and one of the same individual in the sad condition. After every film clip, the observers were asked to make forced-choices concerning the emotional state of the dancer. Results revealed that observers were able to identify the emotional state of the dancers with a high degree of accuracy. Moreover, emotions were more often recognized for female dancers than for their male counterparts. In addition, the results of eye tracking measurements unveiled that observers primarily focus on movements of the chest when decoding emotional information from dance movement. The findings of our study show that not merely portrayed emotions, but also induced emotions can be successfully recognized from free dance movement. PMID:24587026

  9. Different signaling pathways induced by alpha-CD3 monoclonal antibody versus alloantigen on the basis of differential ornithine sensitivity.

    Science.gov (United States)

    Mehrotra nee Tandon, P; Lind, D S; Bear, H D; Susskind, B M

    1992-08-01

    Previously we reported that 10 mM ornithine (Orn) selectively inhibits the development of CD8+ CTL in MLC. Herein we show that induction by alpha-CD3 mAb of CD8+ killer cells which manifest antibody-redirected cytotoxicity (ARC) of FcR+ targets is not Orn sensitive. Orn resistance was independent of activation kinetics or alpha-CD3 mAb concentration. alpha-CD3 mAb added to the cytotoxicity assay did not reveal a cytolytic potential in CTL from an Orn-treated MLC when the target cells bore both the inducing alloantigen and FcR. Addition of alpha-CD3 mAb to MLC failed to overcome Orn inhibition of CTL and yet induced ARC activity in the same culture. Expression of mRNA for pore-forming proteins (PFP) and granzyme B was inhibited by Orn in CTL but not in ARC killer cells. Our results demonstrate differences in the T cell activation process stimulated by alloantigen or alpha-CD3 mAb.

  10. Power Lines and Crops Can Be Good Neighbors

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-08-01

    Two of the Pacific Northwest’s greatest economic assets are its wealth of agriculture and its clean and reliable electricity fueled largely by hydropower. Sometimes the two intersect. Transmission lines carrying electricity to the region’s farms, businesses and homes must, of necessity, span large areas where people grow crops and orchards. To ensure a safe and reliable flow of electricity across these expanses, trees and other vegetation must be managed to certain standards. At the same time, the Bonneville Power Administration — which owns and operates three-quarters of the region’s high-voltage transmission — recognizes the importance of our region’s agricultural bounty. We are committed to working with individuals and agricultural communities to facilitate ongoing land-use activities in transmission rights-of-way as long as those uses are compatible with transmission safety and reliability standards. Our goal with vegetation management is to keep you and your property safe while protecting the reliability of our region’s electricity system. By working together, BPA and landowners can protect the system and public safety.

  11. Stress fractures of the rib arising from the manufactory assembly line

    International Nuclear Information System (INIS)

    Arima, Toru; Iwasaki, Masayuki

    2007-01-01

    We investigated stress injuries of the rib arising from the assembly line. The patients, all males, were 20 in number and divided into two groups; those with stress fracture (n=13) and those with ''pre-fracture'' (n=7). The former group with the average age of 37 years was involved by a single fracture in 10 patients and multiple fractures in 3, ranging from 5th to 8th ribs, with the affected side on the right in 9 and the left in 4. All 13 fractures occurred in the posterior half of the rib, in which 5 were located in its lateral portion, 5 in the middle, and 3 in the posterior. The latter group with the average age of 32 years were involved on the right side in 4 and the left in 3. The working pattern causing rib injuries was either repeated raising of the upper extremity or forward pushing of the shoulder girdle. The symptom was back pain, and aggravated especially in elevation of the arm, deep breathing and sneezing. Local tenderness over the fracture site was noted in all cases. X-ray findings at initial examination revealed fractures in most cases and 3D-CT was employed in 9 questionable cases to assess fracture conditions. In the ''pre-fracture'' group, although the fracture was not recognized on X-ray, the diagnosis was made as an impending fracture based on the localized tenderness on the rib. As to treatment, bust band fixation and work load reduction were performed. Stress fractures of the rib have been occasionally reported in sports medicine, but not so much in industrial medicine. This specific injury has been treated in literature as muscle strain because of the absence of apparent trauma. It is important to recognize the underlying pathology to make the correct diagnosis. In the early stage of rib fractures, 3D-CT was more useful than X-ray in making diagnosis and assessing the bony union. As to the pathomechanism of this condition, it was postulated that repeated raising or forward pushing of the arm applying excessive traction to the origin of the

  12. SET-NUP214 fusion in acute myeloid leukemia- and T-cell acute lymphoblastic leukemia-derived cell lines

    Directory of Open Access Journals (Sweden)

    Zaborski Margarete

    2009-01-01

    Full Text Available Abstract Background SET-NUP214 fusion resulting from a recurrent cryptic deletion, del(9(q34.11q34.13 has recently been described in T-cell acute lymphoblastic leukemia (T-ALL and in one case of acute myeloid leukemia (AML. The fusion protein appears to promote elevated expression of HOXA cluster genes in T-ALL and may contribute to the pathogenesis of the disease. We screened a panel of ALL and AML cell lines for SET-NUP214 expression to find model systems that might help to elucidate the cellular function of this fusion gene. Results Of 141 human leukemia/lymphoma cell lines tested, only the T-ALL cell line LOUCY and the AML cell line MEGAL expressed the SET(TAF-Iβ-NUP214 fusion gene transcript. RT-PCR analysis specifically recognizing the alternative first exons of the two TAF-I isoforms revealed that the cell lines also expressed TAF-Iα-NUP214 mRNA. Results of fluorescence in situ hybridization (FISH and array-based copy number analysis were both consistent with del(9(q34.11q34.13 as described. Quantitative genomic PCR also confirmed loss of genomic material between SET and NUP214 in both cell lines. Genomic sequencing localized the breakpoints of the SET gene to regions downstream of the stop codon and to NUP214 intron 17/18 in both LOUCY and MEGAL cells. Both cell lines expressed the 140 kDa SET-NUP214 fusion protein. Conclusion Cell lines LOUCY and MEGAL express the recently described SET-NUP214 fusion gene. Of special note is that the formation of the SET exon 7/NUP214 exon 18 gene transcript requires alternative splicing as the SET breakpoint is located downstream of the stop codon in exon 8. The cell lines are promising model systems for SET-NUP214 studies and should facilitate investigating cellular functions of the the SET-NUP214 protein.

  13. Pisotriquetral joint disorders: an under-recognized cause of ulnar side wrist pain

    Energy Technology Data Exchange (ETDEWEB)

    Moraux, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Imagerie Medicale Jacquemars Gielee, Lille (France); Lefebvre, G.; Pansini, V.; Aucourt, J.; Vandenbussche, L.; Cotten, A. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Demondion, X. [Hopital Roger Salengro, Service d' Imagerie Musculo-Squelettique, Centre de Consultation de l' Appareil Locomoteur, CHRU Lille (France); Pole Recherche Faculte de Medecine de Lille, Laboratoire d' Anatomie, Lille (France)

    2014-06-15

    Pisotriquetral joint disorders are often under-recognized in routine clinical practice. They nevertheless represent a significant cause of ulnar side wrist pain. The aim of this article is to present the main disorders of this joint and discuss the different imaging modalities that can be useful for its assessment. (orig.)

  14. Facial Asymmetry-Based Age Group Estimation: Role in Recognizing Age-Separated Face Images.

    Science.gov (United States)

    Sajid, Muhammad; Taj, Imtiaz Ahmad; Bajwa, Usama Ijaz; Ratyal, Naeem Iqbal

    2018-04-23

    Face recognition aims to establish the identity of a person based on facial characteristics. On the other hand, age group estimation is the automatic calculation of an individual's age range based on facial features. Recognizing age-separated face images is still a challenging research problem due to complex aging processes involving different types of facial tissues, skin, fat, muscles, and bones. Certain holistic and local facial features are used to recognize age-separated face images. However, most of the existing methods recognize face images without incorporating the knowledge learned from age group estimation. In this paper, we propose an age-assisted face recognition approach to handle aging variations. Inspired by the observation that facial asymmetry is an age-dependent intrinsic facial feature, we first use asymmetric facial dimensions to estimate the age group of a given face image. Deeply learned asymmetric facial features are then extracted for face recognition using a deep convolutional neural network (dCNN). Finally, we integrate the knowledge learned from the age group estimation into the face recognition algorithm using the same dCNN. This integration results in a significant improvement in the overall performance compared to using the face recognition algorithm alone. The experimental results on two large facial aging datasets, the MORPH and FERET sets, show that the proposed age group estimation based on the face recognition approach yields superior performance compared to some existing state-of-the-art methods. © 2018 American Academy of Forensic Sciences.

  15. Deficits in recognizing disgust facial expressions and Internet addiction: Perceived stress as a mediator.

    Science.gov (United States)

    Chen, Zhongting; Poon, Kai-Tak; Cheng, Cecilia

    2017-08-01

    Studies have examined social maladjustment among individuals with Internet addiction, but little is known about their deficits in specific social skills and the underlying psychological mechanisms. The present study filled these gaps by (a) establishing a relationship between deficits in facial expression recognition and Internet addiction, and (b) examining the mediating role of perceived stress that explains this hypothesized relationship. Ninety-seven participants completed validated questionnaires that assessed their levels of Internet addiction and perceived stress, and performed a computer-based task that measured their facial expression recognition. The results revealed a positive relationship between deficits in recognizing disgust facial expression and Internet addiction, and this relationship was mediated by perceived stress. However, the same findings did not apply to other facial expressions. Ad hoc analyses showed that recognizing disgust was more difficult than recognizing other facial expressions, reflecting that the former task assesses a social skill that requires cognitive astuteness. The present findings contribute to the literature by identifying a specific social skill deficit related to Internet addiction and by unveiling a psychological mechanism that explains this relationship, thus providing more concrete guidelines for practitioners to strengthen specific social skills that mitigate both perceived stress and Internet addiction. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Pan-specific prediction of peptide-MHC Class I complex stability, a correlate of T cell immunogenicity

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Fenoy, Emilio; Harndahl, Mikkel

    2016-01-01

    Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in the processing and presentation of Ags to CTL, and insights into the mechanisms that govern peptide-MHC-I binding should facilitate our understanding of CTL biology. Peptide-MHC-I interactions have traditionally b...

  17. Promotion of European coal to liquids R&D activities

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-06-15

    The IEA Clean Coal Centre, with its partners Fuel Consult GmbH (Germany), Glowny Instytut Gornictwa (Poland), Tallinn University of Technology (Estonia) and Stredisko Pro Efektivni Vyuzivani Energie O.P.S. (Czech Republic) is undertaking a promotion and dissemination project. This is supported with a financial grant from the Research Programme of the Research Fund for Coal and Steel under contract number RFC2-CT-2008-00006. The aim is to undertake an overall assessment of the competitiveness and environmental performance of coal to liquids technology from a European perspective. The major deliverable is this report, which comprises a review of CTL activities, worldwide and a consideration of possible future CTL R, D & D needs for Europe, building both on the global state of the art arising from work undertaken previously and the current worldwide activities including the planned and ongoing demonstration programmes in the USA and China respectively. This is complemented with comment on the capabilities and expertise in EU universities as well as EU industry should there be a need to implement larger-scale development and demonstration programmes and ultimately to build large CTL plant. Finally the benefits of seeking international cooperation on CTL R, D & D with stakeholders outside of Europe rather than limiting activities to EU member states is discussed. The information is being promoted and disseminated to all European stakeholders, in particular to those major coal- and oil shale-using member states, Poland, the Czech Republic and Estonia, in which there is significant potential for an uptake of CTL technology and where industry is now starting to reconsider the development of CTL processes.

  18. Producing and Recognizing Analogical Relations

    Science.gov (United States)

    Lipkens, Regina; Hayes, Steven C

    2009-01-01

    Analogical reasoning is an important component of intelligent behavior, and a key test of any approach to human language and cognition. Only a limited amount of empirical work has been conducted from a behavior analytic point of view, most of that within Relational Frame Theory (RFT), which views analogy as a matter of deriving relations among relations. The present series of four studies expands previous work by exploring the applicability of this model of analogy to topography-based rather than merely selection-based responses and by extending the work into additional relations, including nonsymmetrical ones. In each of the four studies participants pretrained in contextual control over nonarbitrary stimulus relations of sameness and opposition, or of sameness, smaller than, and larger than, learned arbitrary stimulus relations in the presence of these relational cues and derived analogies involving directly trained relations and derived relations of mutual and combinatorial entailment, measured using a variety of productive and selection-based measures. In Experiment 1 participants successfully recognized analogies among stimulus networks containing same and opposite relations; in Experiment 2 analogy was successfully used to extend derived relations to pairs of novel stimuli; in Experiment 3 the procedure used in Experiment 1 was extended to nonsymmetrical comparative relations; in Experiment 4 the procedure used in Experiment 2 was extended to nonsymmetrical comparative relations. Although not every participant showed the effects predicted, overall the procedures occasioned relational responses consistent with an RFT account that have not yet been demonstrated in a behavior-analytic laboratory setting, including productive responding on the basis of analogies. PMID:19230515

  19. HLA-A2–Restricted Cytotoxic T Lymphocyte Epitopes from Human Heparanase as Novel Targets for Broad-Spectrum Tumor Immunotherapy

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2008-09-01

    Full Text Available Peptide vaccination for cancer immunotherapy requires identification of peptide epitopes derived from antigenic proteins associated with tumors. Heparanase (Hpa is broadly expressed in various advanced tumors and seems to be an attractive new tumor-associated antigen. The present study was designed to predict and identify HLA-A2– restricted cytotoxic T lymphocyte (CTL epitopes in the protein of human Hpa. For this purpose, HLA-A2–restricted CTL epitopes were identified using the following four-step procedure: 1 a computer-based epitope prediction from the amino acid sequence of human Hpa, 2 a peptide-binding assay to determine the affinity of the predicted protein with the HLA-A2 molecule, 3 stimulation of the primary T-cell response against the predicted peptides in vitro, and 4 testing of the induced CTLs toward different kinds of carcinoma cells expressing Hpa antigens and/or HLA-A2. The results demonstrated that, of the tested peptides, effectors induced by peptides of human Hpa containing residues 525-533 (PAFSYSFFV, Hpa525, 277-285 (KMLKSFLKA, Hpa277, and 405-413 (WLSLLFKKL, Hpa405 could effectively lyse various tumor cell lines that were Hpa-positive and HLA-A2-matched. We also found that these peptide-specific CTLs could not lyse autologous lymphocytes with low Hpa activity. Further study revealed that Hpa525, Hpa277, and Hpa405 peptides increased the frequency of IFN-γ–producing T cells compared to a negative peptide. Our results suggest that Hpa525, Hpa277, and Hpa405 peptides are new HLA-A2–restricted CTL epitopes capable of inducing Hpa-specific CTLs in vitro. Because Hpa is expressed in most advanced malignant tumors, Hpa525, Hpa277, and Hpa405 peptide–based vaccines may be useful for the immunotherapy for patients with advanced tumors.

  20. Wavefront holoscopy: application of digital in-line holography for the inspection of engraved marks in progressive addition lenses.

    Science.gov (United States)

    Perucho, Beatriz; Micó, Vicente

    2014-01-01

    Progressive addition lenses (PALs) are engraved with permanent marks at standardized locations in order to guarantee correct centering and alignment throughout the manufacturing and mounting processes. Out of the production line, engraved marks provide useful information about the PAL as well as act as locator marks to re-ink again the removable marks. Even though those marks should be visible by simple visual inspection with the naked eye, engraving marks are often faint and weak, obscured by scratches, and partially occluded and difficult to recognize on tinted or antireflection-coated lenses. Here, we present an extremely simple optical device (named as wavefront holoscope) for visualization and characterization of permanent marks in PAL based on digital in-line holography. Essentially, a point source of coherent light illuminates the engraved mark placed just before a CCD camera that records a classical Gabor in-line hologram. The recorded hologram is then digitally processed to provide a set of high-contrast images of the engraved marks. Experimental results are presented showing the applicability of the proposed method as a new ophthalmic instrument for visualization and characterization of engraved marks in PALs.

  1. MICROLENSING OF QUASAR BROAD EMISSION LINES: CONSTRAINTS ON BROAD LINE REGION SIZE

    Energy Technology Data Exchange (ETDEWEB)

    Guerras, E.; Mediavilla, E. [Instituto de Astrofisica de Canarias, Via Lactea S/N, La Laguna E-38200, Tenerife (Spain); Jimenez-Vicente, J. [Departamento de Fisica Teorica y del Cosmos, Universidad de Granada, Campus de Fuentenueva, E-18071 Granada (Spain); Kochanek, C. S. [Department of Astronomy and the Center for Cosmology and Astroparticle Physics, The Ohio State University, 4055 McPherson Lab, 140 West 18th Avenue, Columbus, OH 43221 (United States); Munoz, J. A. [Departamento de Astronomia y Astrofisica, Universidad de Valencia, E-46100 Burjassot, Valencia (Spain); Falco, E. [Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Motta, V. [Departamento de Fisica y Astronomia, Universidad de Valparaiso, Avda. Gran Bretana 1111, Valparaiso (Chile)

    2013-02-20

    We measure the differential microlensing of the broad emission lines between 18 quasar image pairs in 16 gravitational lenses. We find that the broad emission lines are in general weakly microlensed. The results show, at a modest level of confidence (1.8{sigma}), that high ionization lines such as C IV are more strongly microlensed than low ionization lines such as H{beta}, indicating that the high ionization line emission regions are more compact. If we statistically model the distribution of microlensing magnifications, we obtain estimates for the broad line region size of r{sub s} = 24{sup +22} {sub -15} and r{sub s} = 55{sup +150} {sub -35} lt-day (90% confidence) for the high and low ionization lines, respectively. When the samples are divided into higher and lower luminosity quasars, we find that the line emission regions of more luminous quasars are larger, with a slope consistent with the expected scaling from photoionization models. Our estimates also agree well with the results from local reveberation mapping studies.

  2. Lining seam elimination algorithm and surface crack detection in concrete tunnel lining

    Science.gov (United States)

    Qu, Zhong; Bai, Ling; An, Shi-Quan; Ju, Fang-Rong; Liu, Ling

    2016-11-01

    Due to the particularity of the surface of concrete tunnel lining and the diversity of detection environments such as uneven illumination, smudges, localized rock falls, water leakage, and the inherent seams of the lining structure, existing crack detection algorithms cannot detect real cracks accurately. This paper proposed an algorithm that combines lining seam elimination with the improved percolation detection algorithm based on grid cell analysis for surface crack detection in concrete tunnel lining. First, check the characteristics of pixels within the overlapping grid to remove the background noise and generate the percolation seed map (PSM). Second, cracks are detected based on the PSM by the accelerated percolation algorithm so that the fracture unit areas can be scanned and connected. Finally, the real surface cracks in concrete tunnel lining can be obtained by removing the lining seam and performing percolation denoising. Experimental results show that the proposed algorithm can accurately, quickly, and effectively detect the real surface cracks. Furthermore, it can fill the gap in the existing concrete tunnel lining surface crack detection by removing the lining seam.

  3. Topographic antigenic determinants recognized by monoclonal antibodies on human choriogonadotropin beta-subunit

    International Nuclear Information System (INIS)

    Bidart, J.M.; Troalen, F.; Salesse, R.; Bousfield, G.R.; Bohuon, C.J.; Bellet, D.H.

    1987-01-01

    We describe a first attempt to study the antibody-combining sites recognized by monoclonal antibodies raised against the beta-subunit of human choriogonadotropin (hCG). Two groups of antibodies were first defined by their ability to recognize only the free beta-subunit or the free and combined subunit. Antibodies FBT-11 and FBT-11-L bind only to hCG beta-subunit but not to hCG, whereas antibodies FBT-10 and D1E8 bind to both the beta-subunit and the hormone. In both cases, the antigenic determinants were localized to the core of the protein (residues 1-112), indicating the weak immunogenicity of the specific carboxyl-terminal extension of hCG-beta. Nine synthetic peptides spanning different regions of hCG-beta and lutropin-beta were assessed for their capacity to inhibit antibody binding. A synthetic peptide inclusive of the NH2-terminal region (residues 1-7) of the hCG beta-subunit was found to inhibit binding to the radiolabeled subunit of a monoclonal antibody specific for free hCG-beta (FBT-11). Further delineation of the antigenic site recognized by this antibody provided evidence for the involvement of fragment 82-92. Moreover, monoclonal antibody FBT-11 inhibited the recombination of hCG-beta to hCG-alpha, indicating that its antigenic determinant might be located nearby or in the hCG-beta portion interacting with the alpha-subunit. Binding of monoclonal antibody FBT-10, corresponding to the second antigenic determinant, was weakly inhibited by fragment 82-105 and did not impair the recombination of the hCG beta-subunit to the hCG alpha-subunit. Its combining site appeared to be located in a region of the intact native choriogonadotropin present at the surface of the hormone-receptor complex

  4. Recognition and Diagnosis. Adolescent Alcoholism: Recognizing, Intervening, and Treating Series No. 3.

    Science.gov (United States)

    Siegal, Harvey A.; Fahey, Patrick J.

    This document is one of seven publications contained in a series of materials for physicians on recognizing, intervening with, and treating adolescent alcoholism. The goals of this unit of study are to provide an overview of the problem of of teenage alcoholism and substance abuse and to facilitate the diagnosis of adolescent alcoholism. The…

  5. Comparison of concept recognizers for building the Open Biomedical Annotator

    Directory of Open Access Journals (Sweden)

    Rubin Daniel

    2009-09-01

    Full Text Available Abstract The National Center for Biomedical Ontology (NCBO is developing a system for automated, ontology-based access to online biomedical resources (Shah NH, et al.: Ontology-driven indexing of public datasets for translational bioinformatics. BMC Bioinformatics 2009, 10(Suppl 2:S1. The system's indexing workflow processes the text metadata of diverse resources such as datasets from GEO and ArrayExpress to annotate and index them with concepts from appropriate ontologies. This indexing requires the use of a concept-recognition tool to identify ontology concepts in the resource's textual metadata. In this paper, we present a comparison of two concept recognizers – NLM's MetaMap and the University of Michigan's Mgrep. We utilize a number of data sources and dictionaries to evaluate the concept recognizers in terms of precision, recall, speed of execution, scalability and customizability. Our evaluations demonstrate that Mgrep has a clear edge over MetaMap for large-scale service oriented applications. Based on our analysis we also suggest areas of potential improvements for Mgrep. We have subsequently used Mgrep to build the Open Biomedical Annotator service. The Annotator service has access to a large dictionary of biomedical terms derived from the United Medical Language System (UMLS and NCBO ontologies. The Annotator also leverages the hierarchical structure of the ontologies and their mappings to expand annotations. The Annotator service is available to the community as a REST Web service for creating ontology-based annotations of their data.

  6. Do pediatricians recognize cognitive developmental problems in preterm children at age 5 years?

    NARCIS (Netherlands)

    Sondaar, M.; Kessel, B.J.M. van; Kleine, M.J.K. de; Briët, J.M.; Ouden, A.L. den; Baar, A. van

    2008-01-01

    Often developmental psychologists see children only after referral from physicians. Do pediatricians recognize which children in a known risk group are in need of a cognitive evaluation? A judgment by pediatricians, based on an assessment using a parent questionnaire, the Denver Developmental

  7. Semi-automated limit-dilution assay and clonal expansion of all T-cell precursors of cytotoxic lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, A.; Chen, W.F.; Scollay, R.; Shortman, K. (Walter and Eliza Hall Inst. of Medical Research, Parkville (Australia))

    1982-08-13

    A limit-dilution microculture system is described, where almost all precursor T cells of the cytotoxic lineage (CTL-p) develop into extended clones of cytotoxic T cells (CTL), which are then detected with a new radio-autographic /sup 111/In-release assay. The principle is to polyclonally activate all T cells with concanavalin A, to expand the resultant clones over an 8-9 day period in cultures saturated with growth factors, then to detect all clones with cytotoxic function by phytohaemagglutinin mediated lysis of P815 tumour cells. The key variables for obtaining high cloning efficiency are the use of flat-bottomed 96-well culture trays, the use of appropriately irradiated spleen filler cells, and the inclusion of a T-cell growth factor supplement. Cultures are set up at input levels of around one T cell per well. Forty percent of T cells then form CTL clones readily detected by the cytotoxic assay. The lytic activity of the average clone is equivalent to 3000 CTL, but clone size appears to be much larger. The precursor cells are predominantly if not entirely from the Lyt 2/sup +/ T-cell subclass and almost all cells of this subclass form cytolytic clones. Analysis of the frequency of positive cultures shows a good fit to the expected Poisson distribution, with no evidence of the CTL-p frequency estimates being distorted by helper or suppressor effects.

  8. Semi-automated limit-dilution assay and clonal expansion of all T-cell precursors of cytotoxic lymphocytes

    International Nuclear Information System (INIS)

    Wilson, A.; Chen, W.-F.; Scollay, R.; Shortman, K.

    1982-01-01

    A limit-dilution microculture system is described, where almost all precursor T cells of the cytotoxic lineage (CTL-p) develop into extended clones of cytotoxic T cells (CTL), which are then detected with a new radio-autographic 111 In-release assay. The principle is to polyclonally activate all T cells with concanavalin A, to expand the resultant clones over an 8-9 day period in cultures saturated with growth factors, then to detect all clones with cytotoxic function by phytohaemagglutinin mediated lysis of P815 tumour cells. The key variables for obtaining high cloning efficiency are the use of flat-bottomed 96-well culture trays, the use of appropriately irradiated spleen filler cells, and the inclusion of a T-cell growth factor supplement. Cultures are set up at input levels of around one T cell per well. Forty percent of T cells then form CTL clones readily detected by the cytotoxic assay. The lytic activity of the average clone is equivalent to 3000 CTL, but clone size appears to be much larger. The precursor cells are predominantly if not entirely from the Lyt 2 + T-cell subclass and almost all cells of this subclass form cytolytic clones. Analysis of the frequency of positive cultures shows a good fit to the expected Poisson distribution, with no evidence of the CTL-p frequency estimates being distorted by helper or suppressor effects. (Auth.)

  9. HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients.

    Science.gov (United States)

    Wang, Jiajun; Liu, Li; Qu, Yang; Xi, Wei; Xia, Yu; Bai, Qi; Xiong, Ying; Long, Qilai; Xu, Jiejie; Guo, Jianming

    2018-01-01

    Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients. A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. HLA class I expression and cytotoxic T lymphocyte (CTL) density was assessed by immunohistochemistry on tissue microarrays. Association between HLA class I and CTL was also assessed in the TCGA KIRC cohort. In the TKI cohort, down-regulated HLA class I was associated with lower objective response rate of TKI therapy (P = 0.004), shorter overall survival (OS) (P = 0.001), and shorter progression free survival (PFS) (P class I was not significantly associated with survival. HLA class I expression was associated with CTL infiltration and function, and its prognostic value was more predominant in CTL high-density tumors (P class I expression can serve as a potential predictive biomarker for TKI therapy in mRCC patients. Its predictive value was restricted in CTL high-density tumors. However, further external validations and functional investigations are still required.

  10. High Line

    DEFF Research Database (Denmark)

    Kiib, Hans

    2015-01-01

    At just over 10 meters above street level, the High Line extends three kilometers through three districts of Southwestern Manhattan in New York. It consists of simple steel construction, and previously served as an elevated rail line connection between Penn Station on 34th Street and the many....... The High Line project has been carried out as part of an open conversion strategy. The result is a remarkable urban architectural project, which works as a catalyst for the urban development of Western Manhattan. The greater project includes the restoration and reuse of many old industrial buildings...

  11. Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.

    Science.gov (United States)

    Hanon, E; Hall, S; Taylor, G P; Saito, M; Davis, R; Tanaka, Y; Usuku, K; Osame, M; Weber, J N; Bangham, C R

    2000-02-15

    The role of the cellular immune response in human T-cell leukemia virus type I (HTLV-I) infection is not fully understood. A persistently activated cytotoxic T lymphocyte (CTL) response to HTLV-I is found in the majority of infected individuals. However, it remains unclear whether this CTL response is protective or causes tissue damage. In addition, several observations paradoxically suggest that HTLV-I is transcriptionally silent in most infected cells and, therefore, not detectable by virus-specific CTLs. With the use of a new flow cytometric procedure, we show here that a high proportion of naturally infected CD4+ peripheral blood mononuclear cells (PBMC) (between 10% and 80%) are capable of expressing Tax, the immunodominant target antigen recognized by virus-specific CTLs. Furthermore, we provide direct evidence that autologous CD8+ T cells rapidly kill CD4+ cells naturally infected with HTLV-I and expressing Tax in vitro by a perforin-dependent mechanism. Consistent with these observations, we observed a significant negative correlation between the frequency of Tax(11-19)-specific CD8+ T cells and the percentage of CD4+ T cells in peripheral blood of patients infected with HTLV-I. Those results are in accordance with the view that virus-specific CTLs participate in a highly efficient immune surveillance mechanism that persistently destroys Tax-expressing HTLV-I-infected CD4+ T cells in vivo. (Blood. 2000;95:1386-1392)

  12. An ultrafast line-by-line algorithm for calculating spectral transmittance and radiance

    International Nuclear Information System (INIS)

    Tan, X.

    2013-01-01

    An ultrafast line-by-line algorithm for calculating spectral transmittance and radiance of gases is presented. The algorithm is based on fast convolution of the Voigt line profile using Fourier transform and a binning technique. The algorithm breaks a radiative transfer calculation into two steps: a one-time pre-computation step in which a set of pressure independent coefficients are computed using the spectral line information; a normal calculation step in which the Fourier transform coefficients of the optical depth are calculated using the line of sight information and the coefficients pre-computed in the first step, the optical depth is then calculated using an inverse Fourier transform and the spectral transmittance and radiance are calculated. The algorithm is significantly faster than line-by-line algorithms that do not employ special speedup techniques by a factor of 10 3 –10 6 . A case study of the 2.7 μm band of H 2 O vapor is presented. -- Highlights: •An ultrafast line-by-line model based on FFT and a binning technique is presented. •Computationally expensive calculations are factored out into a pre-computation step. •It is 10 3 –10 8 times faster than LBL algorithms that do not employ speedup techniques. •Good agreement with experimental data for the 2.7 μm band of H 2 O

  13. Blue petrels recognize the odor of their egg.

    Science.gov (United States)

    Leclaire, Sarah; Bourret, Vincent; Bonadonna, Francesco

    2017-09-01

    Most studies on avian olfactory communication have focused on mate choice, and the importance of olfaction in subsequent nesting stages has been poorly explored. In particular, the role of olfactory cues in egg recognition has received little attention, despite eggs potentially being spread with parental odorous secretions known to elicit individual discrimination. Here, we used behavioral choice tests to determine whether female blue petrels ( Halobaena caerulea ) can discriminate the odor of their own egg from the odor of a conspecific egg. Females preferentially approached the odor of their own egg, suggesting that blue petrels can recognize their own egg using odor cues. This finding raises the question of the adaptive value of this mechanism, and may inspire further research on odor-based egg discrimination in species suffering brood parasitism. © 2017. Published by The Company of Biologists Ltd.

  14. Perceptron Genetic to Recognize Openning Strategy Ruy Lopez

    Science.gov (United States)

    Azmi, Zulfian; Mawengkang, Herman

    2018-01-01

    The application of Perceptron method is not effective for coding on hardware based systems because it is not real time learning. With Genetic algorithm approach in calculating and searching the best weight (fitness value) system will do learning only one iteration. And the results of this analysis were tested in the case of the introduction of the opening pattern of chess Ruy Lopez. The Analysis with Perceptron Model with Algorithm Approach Genetics from group Artificial Neural Network for open Ruy Lopez. The data is processed with base open chess, with step eight a position white Pion from end open chess. Using perceptron method have many input and one output process many weight and refraction until output equal goal. Data trained and test with software Matlab and system can recognize the chess opening Ruy Lopez or Not open Ruy Lopez with Real time.

  15. Modeling and Recognizing Driver Behavior Based on Driving Data: A Survey

    OpenAIRE

    Wang, Wenshuo; Xi, Junqiang; Chen, Huiyan

    2014-01-01

    In recent years, modeling and recognizing driver behavior have become crucial to understanding intelligence transport systems, human-vehicle systems, and intelligent vehicle systems. A wide range of both mathematical identification methods and modeling methods of driver behavior are presented from the control point of view in this paper based on the driving data, such as the brake/throttle pedal position and the steering wheel angle, among others. Subsequently, the driver’s characteristics de...

  16. Covariant electromagnetic field lines

    Science.gov (United States)

    Hadad, Y.; Cohen, E.; Kaminer, I.; Elitzur, A. C.

    2017-08-01

    Faraday introduced electric field lines as a powerful tool for understanding the electric force, and these field lines are still used today in classrooms and textbooks teaching the basics of electromagnetism within the electrostatic limit. However, despite attempts at generalizing this concept beyond the electrostatic limit, such a fully relativistic field line theory still appears to be missing. In this work, we propose such a theory and define covariant electromagnetic field lines that naturally extend electric field lines to relativistic systems and general electromagnetic fields. We derive a closed-form formula for the field lines curvature in the vicinity of a charge, and show that it is related to the world line of the charge. This demonstrates how the kinematics of a charge can be derived from the geometry of the electromagnetic field lines. Such a theory may also provide new tools in modeling and analyzing electromagnetic phenomena, and may entail new insights regarding long-standing problems such as radiation-reaction and self-force. In particular, the electromagnetic field lines curvature has the attractive property of being non-singular everywhere, thus eliminating all self-field singularities without using renormalization techniques.

  17. STUDENTS’ DIFFICULTIES IN BIOCHEMISTRY LEARNING ANALYZED THROUGH AN ON LINE ACADEMIC DROP-IN CENTER

    Directory of Open Access Journals (Sweden)

    F. Schoenmaker

    2007-05-01

    Full Text Available The biochemistry discipline integrates the curriculum of all graduation courses onthe Biological Area and is a basis for other disciplines. The students’ difficulties inthis discipline are already widely recognized. To investigate these difficulties, wecreated a drop-in on line service that has two purposes: (1 To give support tostudents’ learning by answering their questions and solving their problemswhenever they appear and (2 to analyze the questions presented, as a strategy todiagnose the most prevalent difficulties. After two semesters of this service on line,217 questions were received and answered. There were few conceptual questionsbeing the majority related to problems and exercises. The most frequent questionsdealt with cell metabolism (54,4%, mainly lipid metabolism and aerobicmetabolism; basic concepts (11,5% such as about amino acids and buffer, proteinstructure (8,3% and enzymes (7,8%. These percentages are correlated to thenumber of hours dedicated to each subjects in the disciplines. The main difficultiesfounded were: integration of metabolic processes in different tissues, induction ofenergy reserve oxidation, reciprocal regulation between glycolysis andgluconeogenesis. We suppose that the lack of laboratory practice difficults thelearning of basic concepts. A more in-deep analysis will be necessary toinvestigate the causes of the pointed difficulties.

  18. The End of the Lines for OX 169: No Binary Broad-Line Region

    Science.gov (United States)

    Halpern, J. P.; Eracleous, M.

    2000-03-01

    We show that unusual Balmer emission-line profiles of the quasar OX 169, frequently described as either self-absorbed or double peaked, are actually neither. The effect is an illusion resulting from two coincidences. First, the forbidden lines are quite strong and broad. Consequently, the [N II] λ6583 line and the associated narrow-line component of Hα present the appearance of twin Hα peaks. Second, the redshift of 0.2110 brings Hβ into coincidence with Na I D at zero redshift, and ISM absorption in Na I D divides the Hβ emission line. In spectra obtained over the past decade, we see no substantial change in the character of the line profiles and no indication of intrinsic double-peaked structure. The Hγ, Mg II, and Lyα emission lines are single peaked, and all of the emission-line redshifts are consistent once they are correctly attributed to their permitted and forbidden-line identifications. A systematic shift of up to 700 km s-1 between broad and narrow lines is seen, but such differences are common and could be due to gravitational and transverse redshift in a low-inclination disk. Stockton & Farnham had called attention to an apparent tidal tail in the host galaxy of OX 169 and speculated that a recent merger had supplied the nucleus with a coalescing pair of black holes that was now revealing its existence in the form of two physically distinct broad-line regions. Although there is no longer any evidence for two broad emission-line regions in OX 169, binary black holes should form frequently in galaxy mergers, and it is still worthwhile to monitor the radial velocities of emission lines that could supply evidence of their existence in certain objects.

  19. 48 CFR 1642.1204 - Agreement to recognize a successor in interest (novation agreement).

    Science.gov (United States)

    2010-10-01

    ... that the corporate name of (insert old corporate name) was changed to (insert new corporate name) on... MANAGEMENT CONTRACT ADMINISTRATION Novation and Change-of-Name Agreements 1642.1204 Agreement to recognize a... corporate name) (Transferor), a corporation duly organized and existing under the laws of (insert State...

  20. [A method of recognizing biology surface spectrum using cascade-connection artificial neural nets].

    Science.gov (United States)

    Shi, Wei-Jie; Yao, Yong; Zhang, Tie-Qiang; Meng, Xian-Jiang

    2008-05-01

    A method of recognizing the visible spectrum of micro-areas on the biological surface with cascade-connection artificial neural nets is presented in the present paper. The visible spectra of spots on apples' pericarp, ranging from 500 to 730 nm, were obtained with a fiber-probe spectrometer, and a new spectrum recognition system consisting of three-level cascade-connection neural nets was set up. The experiments show that the spectra of rotten, scar and bumped spot on an apple's pericarp can be recognized by the spectrum recognition system, and the recognition accuracy is higher than 85% even when noise level is 15%. The new recognition system overcomes the disadvantages of poor accuracy and poor anti-noise with the traditional system based on single cascade neural nets. Finally, a new method of expression of recognition results was proved. The method is based on the conception of degree of membership in fuzzing mathematics, and through it the recognition results can be expressed exactly and objectively.

  1. Antigen delivery by α2-macroglobulin enhances the cytotoxic T lymphocyte response

    Science.gov (United States)

    Bowers, Edith V.; Horvath, Jeffrey J.; Bond, Jennifer E.; Cianciolo, George J.; Pizzo, Salvatore V.

    2009-01-01

    α2M* targets antigens to APCs for rapid internalization, processing, and presentation. When used as an antigen-delivery vehicle, α2M* amplifies MHC class II presentation, as demonstrated by increased antibody titers. Recent evidence, however, suggests that α2M* encapsulation may also enhance antigen-specific CTL immunity. In this study, we demonstrate that α2M*-delivered antigen (OVA) enhances the production of specific in vitro and in vivo CTL responses. Murine splenocytes expressing a transgenic TCR specific for CTL peptide OVA257–264 (SIINFEKL) demonstrated up to 25-fold greater IFN-γ and IL-2 secretion when treated in vitro with α2M*-OVA compared with soluble OVA. The frequency of IFN-γ-producing cells was increased ∼15-fold, as measured by ELISPOT. Expansion of the OVA-specific CD8+ T cell population, as assayed by tetramer binding and [3H]thymidine incorporation, and OVA-specific cell-mediated cytotoxicity, as determined by a flow cytometric assay, were also enhanced significantly by α2M*-OVA. Furthermore, significant CTL responses were observed at antigen doses tenfold lower than those required with OVA alone. Finally, we also observed enhanced humoral and CTL responses by naïve mice following intradermal immunization with α2M*-OVA. These α2M*-OVA-immunized mice demonstrated increased protection against a s.c.-implanted, OVA-expressing tumor, as demonstrated by delayed tumor growth and prolonged animal survival. The observation that α2M*-mediated antigen delivery elicits specific CTL responses suggests the cross-presentation of antigen onto MHC class I. These results support α2M* as an effective antigen-delivery system that may be particularly useful for vaccines based on weakly immunogenic subunits or requiring dose sparing. PMID:19652028

  2. Aralia elata inhibits neurodegeneration by downregulating O-GlcNAcylation of NF-κB in diabetic mice

    Directory of Open Access Journals (Sweden)

    Seong-Jae Kim

    2017-08-01

    Full Text Available AIM: To investigate the role of O-GlcNAcylation of nuclear factor-kappa B (NF-κB in retinal ganglion cell (RGC death and analysedthe effect of Aralia elata (AE on neurodegeneration in diabetic mice. METHODS: C57BL/6mice with streptozotocin-induced diabetes were fed daily with AE extract or control (CTL diet at the onset of diabetes mellitus (DM. Two months after injection of streptozotocin or saline, the degree of cell death and the expression of O-GlcNAc transferase (OGT, N-acetyl-b-D-glucosaminidase (OGA, O-GlcNAcylated proteins, and O-GlcNAcylation of NF-κB were examined. RESULTS: AE did not affect the metabolic status of diabetic mice. The decrease in the inner retinal thickness (P<0.001 vs CTL, P<0.01 vs DM and increases in RGCs with terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (P<0.001 vs CTL, P<0.0001 vs DM, glial activation, and active caspase-3 (P<0.0001 vs CTL, P<0.0001 vs DM were blocked in diabetic retinas of AE extract-fed mice. Expression levels of protein O-GlcNAcylation and OGT were increased in diabetic retinas (P<0.0001 vs CTL, and the level of O-GlcNAcylation of the NF-κB p65 subunit was higher in diabetic retinas than in controls (P<0.0001 vs CTL. AE extract downregulated O-GlcNAcylation of NF-κB and prevented neurodegeneration induced by hyperglycemia (P<0.0001 vs DM. CONCLUSION: O-GlcNAcylation of NF-κB is concerned in neuronal degeneration and that AE prevents diabetes-induced RGC apoptosis via downregulation of NF-κB O-GlcNAcylation. Hence, O-GlcNAcylation may be a new object for the treatment of DR, and AE may have therapeutic possibility to prevent diabetes-induced neurodegeneration.

  3. Nasca Lines, Peru

    Science.gov (United States)

    2001-01-01

    The Nasca Lines are located in the Pampa region of Peru, the desolate plain of the Peruvian coast 400 km south of Lima. The Lines were first spotted when commercial airlines began flying across the Peruvian desert in the 1920's. Passengers reported seeing 'primitive landing strips' on the ground below. The Lines were made by removing the iron-oxide coated pebbles which cover the surface of the desert. When the gravel is removed, they contrast with the light color underneath. In this way the lines were drawn as furrows of a lighter color. On the pampa, south of the Nasca Lines, archaeologists have now uncovered the lost city of the line-builders, Cahuachi. It was built nearly two thousand years ago and was mysteriously abandoned 500 years later. This ASTER sub-image covers an area of 14 x 18 km, was acquired on December 22, 2000, and is located at 14.7 degrees south latitude and 75.1 degrees west longitude. The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  4. Predictors of social instability stress effects on social interaction and anxiety in adolescent male rats.

    Science.gov (United States)

    Hodges, Travis E; Baumbach, Jennet L; McCormick, Cheryl M

    2018-06-21

    Adolescence is an important phase of development of social behaviors, which may be disrupted by the experience of stressors. We previously reported that exposure to social instability stress in adolescence (SS; postnatal day [PND] 30-45) in rats reduced social interactions with unfamiliar peers compared with non-stressed controls (CTL). In experiment 1, we replicated the effect of SS on social interaction and found that the pattern of neural activations based on Fos immunohistochemistry in brain regions during social interactions differed for SS and CTL rats. In experiment 2, we found that individual differences in novelty-seeking behavior on PND 30 and SS exposure were unique predictors of anxiety in the elevated plus maze on PND 46, and interacted to predict social interaction on PND 47; among high novelty-seeking rats, SS and CTL rats do not differ, whereas among low-novelty seeking rats, SS rats engaged in less social interaction than did CTL rats. Thus, high novelty-seeking may be a resilience factor against the effects of social stressors in adolescence. © 2018 Wiley Periodicals, Inc.

  5. Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

    International Nuclear Information System (INIS)

    Herd, Karen A.; Harvey, Tracey; Khromykh, Alexander A.; Tindle, Robert W.

    2004-01-01

    The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses

  6. Students’ Creativity: Problem Posing in Structured Situation

    Science.gov (United States)

    Amalina, I. K.; Amirudin, M.; Budiarto, M. T.

    2018-01-01

    This is a qualitative research concerning on students’ creativity on problem posing task. The study aimed at describing the students’ creative thinking ability to pose the mathematics problem in structured situations with varied condition of given problems. In order to find out the students’ creative thinking ability, an analysis of mathematics problem posing test based on fluency, novelty, and flexibility and interview was applied for categorizing students’ responses on that task. The data analysis used the quality of problem posing and categorized in 4 level of creativity. The results revealed from 29 secondary students grade 8, a student in CTL (Creative Thinking Level) 1 met the fluency. A student in CTL 2 met the novelty, while a student in CTL 3 met both fluency and novelty and no one in CTL 4. These results are affected by students’ mathematical experience. The findings of this study highlight that student’s problem posing creativity are dependent on their experience in mathematics learning and from the point of view of which students start to pose problem.

  7. Sensitive and selective cataluminescence-based sensor system for acetone and diethyl ether determination.

    Science.gov (United States)

    Wang, Qihui; Li, Bo; Wang, Yuhuai; Shou, Zhouxiang; Shi, Guolong

    2015-05-01

    A three-dimensional hierarchical CdO nanostructure with a novel bio-inspired morphology is reported. The field emission scanning electronic microscopy, transmission electron microscopy and X-ray diffractometer were employed to characterize the as-prepared samples. In gas-sensing measurements, acetone and diethyl ether were employed as target gases to investigate cataluminescence (CTL) sensing properties of the CdO nanostructure. The results show that the as-fabricated CdO nanostructure exhibited outstanding CTL properties such as stable intensity, high signal/noise values, short response and recovery time. The limit of detection of acetone and diethyl ether was ca. 6.5 ppm and 6.7 ppm, respectively, which was below the standard permitted concentrations. Additionally, a principal components analysis method was used to investigate the recognizable ability of the CTL sensor, and it was found that acetone and diethyl ether can be distinguished clearly. The performance of the bio-inspired CdO nanostructure-based sensor system suggested the promising application of the CdO nanostructure as a novel highly efficient CTL sensing material. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Arabic word recognizer for mobile applications

    Science.gov (United States)

    Khanna, Nitin; Abdollahian, Golnaz; Brame, Ben; Boutin, Mireille; Delp, Edward J.

    2011-03-01

    When traveling in a region where the local language is not written using a "Roman alphabet," translating written text (e.g., documents, road signs, or placards) is a particularly difficult problem since the text cannot be easily entered into a translation device or searched using a dictionary. To address this problem, we are developing the "Rosetta Phone," a handheld device (e.g., PDA or mobile telephone) capable of acquiring an image of the text, locating the region (word) of interest within the image, and producing both an audio and a visual English interpretation of the text. This paper presents a system targeted for interpreting words written in Arabic script. The goal of this work is to develop an autonomous, segmentation-free Arabic phrase recognizer, with computational complexity low enough to deploy on a mobile device. A prototype of the proposed system has been deployed on an iPhone with a suitable user interface. The system was tested on a number of noisy images, in addition to the images acquired from the iPhone's camera. It identifies Arabic words or phrases by extracting appropriate features and assigning "codewords" to each word or phrase. On a dictionary of 5,000 words, the system uniquely mapped (word-image to codeword) 99.9% of the words. The system has a 82% recognition accuracy on images of words captured using the iPhone's built-in camera.

  9. An OCD perspective of line edge and line width roughness metrology

    Science.gov (United States)

    Bonam, Ravi; Muthinti, Raja; Breton, Mary; Liu, Chi-Chun; Sieg, Stuart; Seshadri, Indira; Saulnier, Nicole; Shearer, Jeffrey; Patlolla, Raghuveer; Huang, Huai

    2017-03-01

    Metrology of nanoscale patterns poses multiple challenges that range from measurement noise, metrology errors, probe size etc. Optical Metrology has gained a lot of significance in the semiconductor industry due to its fast turn around and reliable accuracy, particularly to monitor in-line process variations. Apart from monitoring critical dimension, thickness of films, there are multiple parameters that can be extracted from Optical Metrology models3. Sidewall angles, material compositions etc., can also be modeled to acceptable accuracy. Line edge and Line Width roughness are much sought of metrology following critical dimension and its uniformity, although there has not been much development in them with optical metrology. Scanning Electron Microscopy is still used as a standard metrology technique for assessment of Line Edge and Line Width roughness. In this work we present an assessment of Optical Metrology and its ability to model roughness from a set of structures with intentional jogs to simulate both Line edge and Line width roughness at multiple amplitudes and frequencies. We also present multiple models to represent roughness and extract relevant parameters from Optical metrology. Another critical aspect of optical metrology setup is correlation of measurement to a complementary technique to calibrate models. In this work, we also present comparison of roughness parameters extracted and measured with variation of image processing conditions on a commercially available CD-SEM tool.

  10. Modification of the U-line of the RHIC injection line

    International Nuclear Information System (INIS)

    Xu, Jianming.

    1991-09-01

    The parameters of the U-line of the RHIC injection line with low β waist are described. In that lattice, the location of SA is not dispersion free and 14 quadrupoles are needed. This line has been modified to move SA to a dispersion free region (after the 8-degree bend), the length and maximum gradient of quadrupoles have been adjusted to fit the existing quadrupole parameters and the number of quadrupoles is reduced to 12. 2 refs., 3 tabs

  11. Difference in membrane repair capacity between cancer cell lines and a normal cell line

    DEFF Research Database (Denmark)

    Frandsen, Stine Krog; McNeil, Anna K.; Novak, Ivana

    2016-01-01

    repair was investigated by disrupting the plasma membrane using laser followed by monitoring fluorescent dye entry over time in seven cancer cell lines, an immortalized cell line, and a normal primary cell line. The kinetics of repair in living cells can be directly recorded using this technique...... cancer cell lines (p immortalized cell line (p

  12. Contextual Teaching and Learning for Practitioners

    Directory of Open Access Journals (Sweden)

    Clemente Charles Hudson

    2008-08-01

    Full Text Available Contextual Teaching and Learning (CTL is defined as a way to introduce content using a variety of activelearning techniques designed to help students connect what they already know to what they are expected to learn, and to construct new knowledge from the analysis and synthesis of this learning process. A theoretical basis for CTL is outlined, with a focus on Connection, Constructivist, and Active Learning theories. A summary of brain activity during the learning process illustrates the physiological changes and connections that occur during educational activities. Three types of learning scenarios (project-based, goal-based, and inquiry-oriented are presented to illustrate how CTL can be applied by practitioners.

  13. Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

    Directory of Open Access Journals (Sweden)

    Siliciano Robert F

    2011-08-01

    Full Text Available Abstract Elite suppressors or controllers (ES are HIV-1 infected patients who maintain undetectable viral loads without treatment. While HLA-B*57-positive ES are usually infected with virus that is unmutated at CTL epitopes, a single, dominant variant containing CTL escape mutations is typically seen in plasma during chronic infection. We describe an ES who developed seven distinct and rare escape variants at an HLA-B*57-restricted Gag epitope over a five year period. Interestingly, he developed proliferative, de novo CTL responses that suppressed replication of each of these variants. These responses, in combination with low viral fitness of each variant, may contribute to sustained elite control in this ES.

  14. The necessity of recognizing all events in x-ray detection

    International Nuclear Information System (INIS)

    Papp, T.; Maxwell, J.A.; Papp, A.T.

    2008-01-01

    Full text: In our work in studying properties of inner shell ionization, we stumbled upon the problems that the basic parameters of x-ray physics have a large and unexplainable scatter. If we look deep into the problems many of them contradict simple logic, elemental arithmetic, even parity and angular conservation laws. We have identified that the main source of the problems, other than the human factor, is rooted in the signal processing electronics. To overcome these problems, we have developed a fully digital signal processor, which not only has excellent resolution and line shape but also allows proper accounting. It is achieved by processing all events and separating them into two or more spectra, maximum sixteen, where the first spectrum is the accepted or good spectrum and the second spectrum is the rejected spectrum. Depending on the request of the analysis further spectra can be generated to supply all the information needed for the analysis. It is not enough to know that an event was rejected, and increment the input counter, it is necessary to know, what why and when it happened, whether it was a noise, noisy or disturbed event, or an event, and any pile up combination of them, accounting properly as input and at the dead time as well. This can be determined from the spectra of properly processed rejected events. We will demonstrate that the direct comparison of the results of the detector simulation model with a partial spectrum, what the various signal recognition and discrimination methods of the signal processor have created, is ambiguous. We will present the difference between pile up and sum peaks, demonstrate the proper accounting of pile up, dead time and what compromises are made in general to warrant the good resolution. We will demonstrate why it is mandatory to recognize all the events, how to interpret the rejected spectrum, what advantage it has in training the industrial analyst, and how it reduces the demands for human expertise in x

  15. The ability of IgY to recognize surface proteins of Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Basri A. Gani

    2009-12-01

    Full Text Available Background: Streptococcus mutans are gram positive bacteria classified into viridians group, and have a role in pathogenesis of dental caries. It’s adhesion to the tooth surface is mediated by cell surface proteins, which interact with specific receptor located in tooth pellicle. Glucan binding protein, Glukosyltransferase, and antigen I/II are basic proteins of S. mutans, which have a role in initiating the interaction. A previous study showed that chicken’s IgY can interfere the interaction. Purpose: The objective of this study was to assess the ability of IgY in recognizing the surface molecule of Streptococcus mutans expressed by various serotypes (c, d, e, f and a strain derived from IPB, Bogor. Method: Western blot was used as a method to determine such capability. Result: The result showed that IgY has a potency to recognize antigen I/II, but not the other proteins on the cell surface of all bacteria tested. Conclusion: The ability of IgY to bind the surface protein, antigen I/II, indicates that this avian antibody could be used as a candidate for anti-adhesion in preventing dental caries.

  16. Anti-liver-kidney microsome antibody type 1 recognizes human cytochrome P450 db1.

    Science.gov (United States)

    Gueguen, M; Yamamoto, A M; Bernard, O; Alvarez, F

    1989-03-15

    Anti-liver-kidney microsome antibody type 1 (LKM1), present in the sera of a group of children with autoimmune hepatitis, was recently shown to recognize a 50 kDa protein identified as rat liver cytochromes P450 db1 and db2. High homology between these two members of the rat P450 IID subfamily and human P450 db1 suggested that anti-LKM1 antibody is directed against this human protein. To test this hypothesis, a human liver cDNA expression library in phage lambda GT-11 was screened using rat P450 db1 cDNA as a probe. Two human cDNA clones were found to be identical to human P450 db1 by restriction mapping. Immunoblot analysis using as antigen, the purified fusion protein from one of the human cDNA clones showed that only anti-LKM1 with anti-50 kDa reactivity recognized the fusion protein. This fusion protein was further used to develop an ELISA test that was shown to be specific for sera of children with this disease. These results: 1) identify the human liver antigen recognized by anti-LKM1 auto-antibodies as cytochrome P450 db1, 2) allow to speculate that mutation on the human P450 db1 gene could alter its expression in the hepatocyte and make it auto-antigenic, 3) provide a simple and specific diagnostic test for this disease.

  17. Structure-function analysis of the self-recognizing Antigen 43 autotransporter protein from Escherichia coli

    DEFF Research Database (Denmark)

    Klemm, Per; Hjerrild, L.; Gjermansen, Morten

    2004-01-01

    Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Expression of Ag43 confers aggregation and fluffing of cells, promotes biofilm formation and is associated with enhanced resistance to antimicrobial agents. Ag43 is an autotransporter protein and consi......Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Expression of Ag43 confers aggregation and fluffing of cells, promotes biofilm formation and is associated with enhanced resistance to antimicrobial agents. Ag43 is an autotransporter protein......-clumping variants, we have pinpointed the region of the protein responsible for autoaggregation to be located within the N-terminal one-third of the passenger domain. Our data suggest that ionic interactions between charged residues residing in interacting pairs of Ag43(alpha) domains may be important for the self...

  18. PMab-38 Recognizes Canine Podoplanin of Squamous Cell Carcinomas.

    Science.gov (United States)

    Kaneko, Mika K; Honma, Ryusuke; Ogasawara, Satoshi; Fujii, Yuki; Nakamura, Takuro; Saidoh, Noriko; Takagi, Michiaki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2016-10-01

    Podoplanin, a type I transmembrane protein, is expressed in lymphatic endothelial cells. Although we previously developed an anticanine podoplanin monoclonal antibody (mAb), PMab-38, immunohistochemistry (IHC) showed that it did not react with canine lymphatic endothelial cells. Here, we determined whether PMab-38 recognizes canine podoplanin of squamous cell carcinomas (SCCs) and clarified its epitope. In IHC, PMab-38 reacted with 83% of SCCs (15/18 cases). Flow cytometry showed that the epitope of PMab-38 was different from that of the platelet aggregation-stimulating domain of the N-terminus, which was detected by almost all antipodoplanin mAbs such as D2-40 or NZ-1. PMab-38 is expected to be useful for investigating the function of podoplanin in canine tumors.

  19. Development and characterization of anti-glycopeptide monoclonal antibodies against human podoplanin, using glycan-deficient cell lines generated by CRISPR/Cas9 and TALEN.

    Science.gov (United States)

    Kaneko, Mika K; Nakamura, Takuro; Honma, Ryusuke; Ogasawara, Satoshi; Fujii, Yuki; Abe, Shinji; Takagi, Michiaki; Harada, Hiroyuki; Suzuki, Hiroyoshi; Nishioka, Yasuhiko; Kato, Yukinari

    2017-02-01

    Human podoplanin (hPDPN), which binds to C-type lectin-like receptor-2 (CLEC-2), is involved in platelet aggregation and cancer metastasis. The expression of hPDPN in cancer cells or cancer-associated fibroblasts indicates poor prognosis. Human lymphatic endothelial cells, lung-type I alveolar cells, and renal glomerular epithelial cells express hPDPN. Although numerous monoclonal antibodies (mAbs) against hPDPN are available, they recognize peptide epitopes of hPDPN. Here, we generated a novel anti-hPDPN mAb, LpMab-21. To characterize the hPDPN epitope recognized by the LpMab-21, we established glycan-deficient CHO-S and HEK-293T cell lines, using the CRISPR/Cas9 or TALEN. Flow cytometric analysis revealed that the minimum hPDPN epitope, in which sialic acid is linked to Thr76, recognized by LpMab-21 is Thr76-Arg79. LpMab-21 detected hPDPN expression in glioblastoma, oral squamous carcinoma, and seminoma cells as well as in normal lymphatic endothelial cells. However, LpMab-21 did not react with renal glomerular epithelial cells or lung type I alveolar cells, indicating that sialylation of hPDPN Thr76 is cell-type-specific. LpMab-21 combined with other anti-hPDPN antibodies that recognize different epitopes may therefore be useful for determining the physiological function of sialylated hPDPN. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  20. Interleukins 1alpha and 1beta secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens.

    Science.gov (United States)

    Kholmanskikh, Olga; van Baren, Nicolas; Brasseur, Francis; Ottaviani, Sabrina; Vanacker, Julie; Arts, Nathalie; van der Bruggen, Pierre; Coulie, Pierre; De Plaen, Etienne

    2010-10-01

    We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4- to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1beta. This effect is NF-kappaB and JNK-dependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1beta reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1alpha or IL-1beta secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that approximately 13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.