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

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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.

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.

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

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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.

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

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....

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....

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.

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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.

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...

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

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

2018-07-01

RNA transcriptional level and protein translational level in mud crab. Meantime, the phagocytosis rate and the expression of three phagocytosis related genes were declined after RNAi of SpCTL-B in hemocytes in mud crab. Collectively, our results suggest that SpCTL-B might play its roles as a pattern recognition receptor (PRR) in immune response towards pathogens infection through influencing the expression of AMPs and the phagocytosis of hemocytes in mud crab S. paramamosain. Copyright © 2018 Elsevier Ltd. All rights reserved.

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...

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

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

Long-term persistence of robust antibody and cytotoxic T cell responses in recovered patients infected with SARS coronavirus.

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Taisheng Li

2006-12-01

Full Text Available Most of the individuals infected with SARS coronavirus (SARS-CoV spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.

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

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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

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

DEFF Research Database (Denmark)

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...

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.

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

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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.

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

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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.

Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells

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Dalle-Donne Isabella

2008-10-01

Full Text Available Abstract Background Recent studies demonstrate that recombinant adeno-associated virus (rAAV-based antigen loading of dendritic cells (DCs generates in vitro, significant and rapid cytotoxic T-lymphocyte (CTL responses against viral antigens. Methods We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1, expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells. Results A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC after one, in vitro, stimulation. Conclusion In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.

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

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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.

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.

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.

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.

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.

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

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

Science.gov (United States)

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.

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

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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

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.

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

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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.

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.

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.

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

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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.

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.

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)

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....

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.

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

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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%.

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.

Factors influencing the vaccinia-specific cytotoxic response of thymocytes from normal and chimeric mice

International Nuclear Information System (INIS)

Doherty, P.C.; Schwartz, D.H.; Bennink, J.R.; Korngold, R.

1981-01-01

Following adoptive transfer into irradiated recipients, thymocytes can be induced to respond strongly to vaccinia virus. High levels of cytotoxic T-lymphocyte (CTL) activity may be generated from thymus, but not from spleen, of 3-day-old mice. The capacity of thymocytes to differentiate into effector CTL tends to be lost with age. Some of this loss may reflect positive suppression: a single, low dose of cyclophosphamide allows the reemergence of responsiveness in at least one mouse strain. Thymocytes from [A leads to (A x B)F1] and [(A x B)F1 leads to A] chimeras show the response patterns that would by predicted from previous studies of lymph node and spleen cells. However, thymic function seems to be rapidly lost in the [A leads to (A x B)F1] Chimeras

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...

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

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.

Improved humoral and cellular immune response against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatites B surface antigen

DEFF Research Database (Denmark)

Fomsgaard, A.; Nielsen, H.V.; Bryder, K.

1998-01-01

response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V2/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a `genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HbsAg plasmid...

Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen

DEFF Research Database (Denmark)

Fomsgaard, A; Nielsen, H V; Bryder, K

1998-01-01

response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL...... responses were induced in all mice against both MN V3 and HBsAg already within the first 3 weeks, lasting at least 11 weeks. Thus, HBsAg acts as a 'genetic vaccine adjuvant' augmenting and accelerating the cellular and humoral immune response against the inserted MN V3 loop. Such chimeric HIV-HBsAg plasmid...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.

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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.

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

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

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

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

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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.

Polymer nanoparticles for cross-presentation of exogenous antigens and enhanced cytotoxic T-lymphocyte immune response

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Song C

2016-08-01

Full Text Available Chanyoung Song,* Young-Woock Noh,* Yong Taik Lim SKKU Advanced Institute of Nanotechnology (SAINT, School of Chemical Engineering, Sungkyunkwan University, Suwon, South Korea *These authors contributed equally to this work Abstract: Effective induction of an antigen-specific cytotoxic T lymphocyte (CTL immune response is one of the key goals of cancer immunotherapy. We report the design and fabrication of polyethylenimine (PEI-coated polymer nanoparticles (NPs as efficient antigen-delivery carriers that can induce antigen cross-presentation and a strong CTL response. After synthesis of poly(d,l-lactide-co-glycolide (PLGA NPs containing ovalbumin (OVA by the double-emulsion solvent-evaporation method, cationic-charged PLGA NPs were generated by coating them with PEI. In a methyl tetrazolium salt assay, no discernible cytotoxic effect of PEI-coated PLGA (OVA NPs was observed. The capacity and mechanism of PEI-coated PLGA (OVA NPs for antigen delivery and cross-presentation on dendritic cells (DCs were determined by fluorescence microscopy and flow cytometry. PEI-coated PLGA (OVA NPs were internalized efficiently via phagocytosis or macropinocytosis in DCs and induced efficient cross-presentation of the antigen on MHC class I molecules via both endosome escape and a lysosomal processing mechanism. The DCs treated with PEI-coated PLGA (OVA NPs induced a release of IL-2 cytokine from OVA-specific CD8-OVA1.3 T cells more efficiently than DCs treated with PLGA (OVA NPs. Therefore, the PEI-coated PLGA (OVA NPs can induce antigen cross-presentation and are expected to be used for induction of a strong CTL immune response and for efficient anticancer immunotherapy. Keywords: antigen delivery, dendritic cells, polymer NPs, vaccine, cross-presentation

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

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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.

Transcutaneous immunization with a novel imiquimod nanoemulsion induces superior T cell responses and virus protection.

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Lopez, Pamela Aranda; Denny, Mark; Hartmann, Ann-Kathrin; Alflen, Astrid; Probst, Hans Christian; von Stebut, Esther; Tenzer, Stefan; Schild, Hansjörg; Stassen, Michael; Langguth, Peter; Radsak, Markus P

2017-09-01

Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses. Therefore we aimed to develop a novel imiquimod solid nanoemulsion (IMI-Sol) for TCI with superior vaccination properties suited to induce high quality T cell responses for enhanced protection against infections. TCI was performed by applying a MHC class I or II restricted epitope along with IMI-Sol or Aldara (each containing 5% Imiquimod) on the shaved dorsum of C57BL/6, IL-1R, Myd88, Tlr7 or Ccr7 deficient mice. T cell responses as well as DC migration upon TCI were subsequently analyzed by flow cytometry. To determine in vivo efficacy of TCI induced immune responses, CTL responses and frequency of peptide specific T cells were evaluated on day 8 or 35 post vaccination and protection in a lymphocytic choriomeningitis virus (LCMV) infection model was assessed. TCI with the imiquimod formulation IMI-Sol displayed equal skin penetration of imiquimod compared to Aldara, but elicited superior CD8 + as well as CD4 + T cell responses. The induction of T-cell responses induced by IMI-Sol TCI was dependent on the TLR7/MyD88 pathway and independent of IL-1R. IMI-Sol TCI activated skin-derived DCs in skin-draining lymph nodes more efficiently compared to Aldara leading to enhanced protection in a LCMV infection model. Our data demonstrate that IMI-Sol TCI can overcome current limitations of previous imiquimod based TCI approaches opening new perspectives for transcutaneous vaccination strategies and allowing the use of this

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

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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.

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.

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

Science.gov (United States)

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.

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

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

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

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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.

Antigen delivery by α2-macroglobulin enhances the cytotoxic T lymphocyte response

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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

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

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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.

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)

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

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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.

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....

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

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

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 .

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

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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.

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...

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

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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.

A T-cell response to a liver-stage Plasmodium antigen is not boosted by repeated sporozoite immunizations

Science.gov (United States)

Murphy, Sean C.; Kas, Arnold; Stone, Brad C.; Bevan, Michael J.

2013-01-01

Development of an antimalarial subunit vaccine inducing protective cytotoxic T lymphocyte (CTL)-mediated immunity could pave the way for malaria eradication. Experimental immunization with sporozoites induces this type of protective response, but the extremely large number of proteins expressed by Plasmodium parasites has so far prohibited the identification of sufficient discrete T-cell antigens to develop subunit vaccines that produce sterile immunity. Here, using mice singly immunized with Plasmodium yoelii sporozoites and high-throughput screening, we identified a unique CTL response against the parasite ribosomal L3 protein. Unlike CTL responses to the circumsporozoite protein (CSP), the population of L3-specific CTLs was not expanded by multiple sporozoite immunizations. CSP is abundant in the sporozoite itself, whereas L3 expression does not increase until the liver stage. The response induced by a single immunization with sporozoites reduces the parasite load in the liver so greatly during subsequent immunizations that L3-specific responses are only generated during the primary exposure. Functional L3-specific CTLs can, however, be expanded by heterologous prime-boost regimens. Thus, although repeat sporozoite immunization expands responses to preformed antigens like CSP that are present in the sporozoite itself, this immunization strategy may not expand CTLs targeting parasite proteins that are synthesized later. Heterologous strategies may be needed to increase CTL responses across the entire spectrum of Plasmodium liver-stage proteins. PMID:23530242

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

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.

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...

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. 

Viral suppression of multiple escape mutants by de novo CD8+ T cell responses in a human immunodeficiency virus-1 Infected elite suppressor

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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.

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.

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

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

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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.

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

Cytotoxic T lymphocyte responses by chimeric thymocytes. Self-recognition is determined early in T cell development

International Nuclear Information System (INIS)

Kruisbeek, A.M.; Hodes, R.J.; Singer, A.

1981-01-01

In this study the cytotoxic T lymphocyte (CTL) recognition pattern of thymocytes from recently reconstituted parent leads to F1 and F1 leads to parent radiation bone marrow chimeras was investigated. Chimeric thymocytes were entirely of donor origin approximately 4 weeks after irradiation and reconstitution but were not capable of autonomously generating either alloreactive or trinitrophenyl (TNP)-modified-self-reactive CTL responses. These experiments demonstrte that even at the earliest time CTL effectors of donor origin from the thymuses of chimeras can be studied, their self-receptor repertoire has already been restricted to recognition of host MHC determinants. These results support the cocept that the host environment influences the self-recognition capacity of T cells at the pre- or intrathymic stage of differentation

Genetic control of cell-mediated lympholysis to trinitrophenyl (TNP)-modified murine syngeneic cells. Expression of Ir gene function at the cytotoxic precursor and helper cell

International Nuclear Information System (INIS)

Fujiwara, H.; Shearer, G.M.

1981-01-01

The present study investigates some of the cellular mechanisms responsible for the defect in cytotoxic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified H-2/sup b/ self components in C57Bl/6(H-2/sup b/) or (C57BL/6 x C3H/He)(H-2/sup b/ x H-2/sup k/)F 1 mice. C3H/He, C57BL/6, and (C57BL/6 x C3H/He)F 1 mice were immunized to TNP-modified self by skin painting with trinitrochlorobenzene, and their spleen cells were used a) for in vitro secondary sensitization to syngeneic spleen cells conjugated with limiting concentrations of trinitrobenzene sulfonate (TNP-self) or b) as a source of radioresistant helper cells for augmenting the TNP-self CTL response generated by spleen cells from unimmunized C3H/He, C57Bl/6, and F 1 mice. The results indicate that strong or weak in vitro secondary CTL responses could be obtained in the H-2/sup k/ or H-2/sup b/ strain, respectively. This strain-dependent genetic difference was also observed in (H-2/sup b/ x H-2/sup k/)F 1 mice. These results permit the detection of the Ir gene defect in the anti-TNP-H-2/sup b/ self CTL response at both the helper and cytotoxic precursor cell levels

Interleukin 2 is not sufficient as helper component for the activation of cytotoxic T lymphocytes but synergizes with a late helper effect that is provided by irradiated T-region-incompatible stimulator cells

Energy Technology Data Exchange (ETDEWEB)

Reddehase, M.; Suessmith, W.; Moyers, C.; Falk, W.; Droege, W.

1982-01-01

Interleukin 2-containing supernatants from concanavalin A-activated spleen cells (CSCS) were found to provide strong helper activity for cytotoxic T lymphocyte (CTL) responses against allogeneic stimulator cells in microculture systems, but provided usually insufficient help for CTL responses against l-region compatible allogeneic or TNP-haptenated syngeneic stimulator cells. The interleukin 2-containing supernatant from HGG-activated AODH 7.1 hybridoma cells also mediated only relatively weak CTL responses against TNP-haptenated syngeneic cells in microcultures. Both types of supernatants, however, supported substantial responses against TNP-haptenated syngeneic stimulator cells if irradiated allogeneically activated syngeneic T cells or irradiated allogeneic spleen cells were added to the cultures. The allogeneic cells and the activated syngeneic T cells provided little helper activity if they were added in the absence of the interleukin 2-containing supernatants, thus demonstrating a synergistic effect between these 2 helper components. An l-region difference was sufficient for the helper effect of the allogeneic cells and control experiments showed that the presence of foreign l-region determinants could not be substituted for the TNP-haptenated stimulator cells.

Interleukin 2 is not sufficient as helper component for the activation of cytotoxic T lymphocytes but synergizes with a late helper effect that is provided by irradiated T-region-incompatible stimulator cells

International Nuclear Information System (INIS)

Reddehase, M.; Suessmith, W.; Moyers, C.; Falk, W.; Droege, W.

1982-01-01

Interleukin 2-containing supernatants from concanavalin A-activated spleen cells (CSCS) were found to provide strong helper activity for cytotoxic T lymphocyte (CTL) responses against allogeneic stimulator cells in microculture systems, but provided usually insufficient help for CTL responses against l-region compatible allogeneic or TNP-haptenated syngeneic stimulator cells. The interleukin 2-containing supernatant from HGG-activated AODH 7.1 hybridoma cells also mediated only relatively weak CTL responses against TNP-haptenated syngeneic cells in microcultures. Both types of supernatants, however, supported substantial responses against TNP-haptenated syngeneic stimulator cells if irradiated allogeneically activated syngeneic T cells or irradiated allogeneic spleen cells were added to the cultures. The allogeneic cells and the activated syngeneic T cells provided little helper activity if they were added in the absence of the interleukin 2-containing supernatants, thus demonstrating a synergistic effect between these 2 helper components. An l-region difference was sufficient for the helper effect of the allogeneic cells and control experiments showed that the presence of foreign l-region determinants could not be substituted for the TNP-haptenated stimulator cells

Bacterial CpG-DNA activates dendritic cells in vivo: T helper cell-independent cytotoxic T cell responses to soluble proteins.

Science.gov (United States)

Sparwasser, T; Vabulas, R M; Villmow, B; Lipford, G B; Wagner, H

2000-12-01

Receptors for conserved molecular patterns associated with microbial pathogens induce synthesis of co-stimulatory molecules and cytokines in immature dendritic cells (DC), as do antigen-reactive CD4 T helper cells via CD40 signaling. Once activated, antigen-presenting DC may activate CD8 T cell responses in a T helper cell-independent fashion. Using immunostimulatory CpG-oligonucleotides (ODN) mimicking bacterial CpG-DNA, we tested whether CpG-DNA bypasses the need for T helper cells in CTL responses towards proteins by directly activating antigen-presenting DC to transit into professional APC. We describe that immature DC in situ constitutively process soluble proteins and generate CD8 T cell determinants yet CD8 T cell responses remain abortive. Induction of primary antigen-specific CD8 cytotoxic T lymphocyte (CTL)-mediated responses becomes initiated in wild-type as well as T helper cell-deficient mice, provided soluble protein and CpG-ODN are draining into the same lymph node. Specifically we show that CpG-ODN trigger antigen-presenting immature DC within the draining lymph node to acutely up-regulate co-stimulatory molecules and produce IL-12. These results provide new insights for generating in vivo efficient CTL responses to soluble proteins which may influence vaccination strategies.

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.

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.

Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

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Kelly Lyn Warfield

2011-01-01

Full Text Available Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV, and Ebola virus (EBOV, leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks.

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

Science.gov (United States)

Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin

2018-06-05

CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Before and after retrofit - response of a building during ambient and strong motions

Science.gov (United States)

Celebi, M.; Liu, Huaibao P.; ,

1998-01-01

This paper presents results obtained from ambient vibration and strong-motion responses of a thirteen-story, moment-resisting steel framed Santa Clara County Office Building (SCCOB) before being retrofitted by visco-elastic dampers and from ambient vibration response following the retrofit. Understanding the cumulative structural and site characteristics that affect the response of SCCOB before and after the retrofit is important in assessing earthquake hazards to other similar buildings and decision making in retrofitting them. The results emphasize the need to better evaluate structural and site characteristics in developing earthquake resisting designs that avoid resonating effects. Various studies of the strong-motion response records from the SCCOB during the 24 April 1984 (MHE) Morgan Hill (MS = 6.1), the 31 March 1986 (MLE) Mt. Lewis (MS = 6.1) and the 17 October 1989 (LPE) Loma Prieta (MS = 7.1) earthquakes show that the dynamic characteristics of the building are such that it (a) resonated (b) responded with a beating effect due to close-coupling of its translational and torsional frequencies, and (c) had a long-duration response due to low-damping. During each of these earthquakes, there was considerable contents damage and the occupants felt the rigorous vibration of the building. Ambient tests of SCCOB performed following LPE showed that both translational and torsional periods of the building are smaller than those derived from strong motions. Ambient tests performed following the retrofit of the building with visco-elastic dampers show that the structural fundamental mode frequency of the building has increased. The increased frequency implies a stiffer structure. Strong-motion response of the building during future earthquakes will ultimately validate the effectiveness of the retrofit method.This paper presents results obtained from ambient vibration and strong-motion responses of a thirteen-story, moment-resisting steel framed Santa Clara County

Response of base isolated structure during strong ground motions beyond design earthquakes

International Nuclear Information System (INIS)

Yabana, Shuichi; Ishida, Katsuhiko; Shiojiri, Hiroo

1991-01-01

In Japan, some base isolated structures for fast breeder reactors (FBR) are tried to design. When a base isolated structure are designed, the relative displacement of isolators are generally limited so sa to be remain in linear state of those during design earthquakes. But to estimate safety margin of a base isolated structure, the response of that until the failure must be obtained experimentally to analytically during strong ground motions of beyond design earthquake. The aim of this paper is to investigate the response of a base isolated structure when the stiffness of the isolators hardens and to simulate the response during strong ground motions of beyond design earthquakes. The optimum characteristics of isolators, with which the margin of the structure are increased, are discussed. (author)

Short communication an interferon-γ ELISPOT assay with two cytotoxic T cell epitopes derived from HTLV-1 tax region 161-233 discriminates HTLV-1-associated myelopathy/tropical spastic paraparesis patients from asymptomatic HTLV-1 carriers in a Peruvian population.

Science.gov (United States)

Best, Ivan; López, Giovanni; Talledo, Michael; MacNamara, Aidan; Verdonck, Kristien; González, Elsa; Tipismana, Martín; Asquith, Becca; Gotuzzo, Eduardo; Vanham, Guido; Clark, Daniel

2011-11-01

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic and progressive disorder caused by the human T-lymphotropic virus type 1 (HTLV-1). In HTLV-1 infection, a strong cytotoxic T cell (CTL) response is mounted against the immunodominant protein Tax. Previous studies carried out by our group reported that increased IFN-γ enzyme-linked immunospot (ELISPOT) responses against the region spanning amino acids 161 to 233 of the Tax protein were associated with HAM/TSP and increased HTLV-1 proviral load (PVL). An exploratory study was conducted on 16 subjects with HAM/TSP, 13 asymptomatic carriers (AC), and 10 HTLV-1-seronegative controls (SC) to map the HAM/TSP-associated CTL epitopes within Tax region 161-233. The PVL of the infected subjects was determined and the specific CTL response was evaluated with a 6-h incubation IFN-γ ELISPOT assay using peripheral blood mononuclear cells (PBMCs) stimulated with 16 individual overlapping peptides covering the Tax region 161-233. Other proinflammatory and Th1/Th2 cytokines were also quantified in the supernatants by a flow cytometry multiplex assay. In addition, a set of human leukocyte antigen (HLA) class I alleles that bind with high affinity to the CTL epitopes of interest was determined using computational tools. Univariate analyses identified an association between ELISPOT responses to two new CTL epitopes, Tax 173-185 and Tax 181-193, and the presence of HAM/TSP as well as an increased PVL. The HLA-A*6801 allele, which is predicted to bind to the Tax 181-193 peptide, was overpresented in the HAM/TSP patients tested.

Arginine and vitamin E improve the immune response after a Salmonella challenge in broiler chicks.

Science.gov (United States)

Liu, X; Byrd, J A; Farnell, M; Ruiz-Feria, C A

2014-04-01

Two experiments were conducted to evaluate the effects of Arg, vitamin E (VE), and mannanoligosaccharide (MOS) on the immune response and clearance of Salmonella in broiler chickens. In each experiment, 1-d-old chicks (n = 160) were randomly distributed into 4 groups: antibiotic-free diet (negative control, CTL-), antibiotic-supplemented diet (positive control, CTL+), antibiotic free-diet plus Arg and VE (AVE), or antibiotic-free diet plus Arg, VE, and MOS (AVM). Birds were orally challenged with 10(6) cfu of a novobiocyn and nalidixic acid-resistant Salmonella enterica serovar Typhimurium strain at d 7 (experiment 1) or at d 3 (experiment 2). Heterophil- (HOB) and monocyte- (MOB) oxidative burst and lymphocyte proliferation (LPR), antibody titers, and Salmonella content in the ceca were measured at several intervals postinfection (PI). In experiment 1, both AVM and AVE decreased HOB compared with the controls 5 and 9 d PI, but increased LPR 9 d PI. In the same experiment, birds fed the AVE diet had higher MOB than birds fed CTL+ or the AVM diet at 7 d PI, whereas 9 d PI birds fed the AVM diet had the highest MOB. In experiment 2, birds fed the AVE diet had higher MOB, HOB, and LPR than birds in the other treatments 7 and 14 d PI, except at 7 d PI, when MOB was not different among treatments. Birds fed the AVM diet had the highest IgA antibody titer, and a higher IgM antibody titer than the CTL+ birds. In experiment 1, Salmonella Typhimurium content in the ceca was lower in birds fed the AVM diet compared with birds fed the CTL- diet 3 d PI, but later on (10 and 17 d PI), and in experiment 2 (7, 14, and 21 d PI), Salmonella Typhimurium concentrations were not different among treatments. Thus, Arg and VE improved immune response after a Salmonella Typhimurium challenge in young chicks, and although they did not reduce Salmonella Typhimurium concentrations in the ceca, they may improve bacterial resistance against other pathogens in commercial growing conditions.

Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization.

Science.gov (United States)

Reyes, L; Hartikka, J; Bozoukova, V; Sukhu, L; Nishioka, W; Singh, G; Ferrari, M; Enas, J; Wheeler, C J; Manthorpe, M; Wloch, M K

2001-06-14

Antigen specific immune responses were characterized after intramuscular immunization of BALB/c mice with 5 antigen encoding plasmid DNAs (pDNAs) complexed with Vaxfectin, a cationic lipid formulation. Vaxfectin increased IgG titers for all of the antigens with no effect on the CTL responses to the 2 antigens for which CTL assays were performed. Both antigen specific IgG1 and IgG2a were increased, although IgG2a remained greater than IgG1. Furthermore, Vaxfectin had no effect on IFN-gamma or IL-4 production by splenocytes re-stimulated with antigen, suggesting that the Th1 type responses typical of intramuscular pDNA immunization were not altered. Studies with IL-6 -/- mice suggest that the antibody enhancement is IL-6 dependent and results in a correlative increase in antigen specific antibody secreting cells.

Perceptual Sensitivity and Response to Strong Stimuli Are Related

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Anna C. Bolders

2017-09-01

Full Text Available To shed new light on the long-standing debate about the (independence of sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the relation between these tendencies within the neurobehavioral framework of the Predictive and Reactive Control Systems (PARCS theory (Tops et al., 2010, 2014. Whereas previous studies only considered overreactivity in terms of the individual tendency to experience unpleasant affect (punishment reactivity resulting from strong sensory stimulation, we also took the individual tendency to experience pleasant affect (reward reactivity resulting from strong sensory stimulation into account. According to PARCS theory, these temperamental tendencies overlap in terms of high reactivity toward stimulation, but oppose each other in terms of the response orientation (approach or avoid. PARCS theory predicts that both types of reactivity to strong stimuli relate to sensitivity to weak stimuli, but that these relationships are suppressed due to the opposing relationship between reward and punishment reactivity. We measured punishment and reward reactivity to strong stimuli and sensitivity to weak stimuli using scales from the Adult Temperament Questionnaire (Evans and Rothbart, 2007. Sensitivity was also measured more objectively using the masked auditory threshold. We found that sensitivity to weak stimuli (both self-reported and objectively assessed was positively associated with self-reported punishment and reward reactivity to strong stimuli, but only when these reactivity measures were controlled for each other, implicating a mutual suppression effect. These results are in line with PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are dependent, but this dependency is likely to be obscured if punishment and reward reactivity are not both taken into account.

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

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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

Induction of CML28-specific cytotoxic T cell responses using co-transfected dendritic cells with CML28 DNA vaccine and SOCS1 small interfering RNA expression vector

International Nuclear Information System (INIS)

Zhou Hongsheng; Zhang Donghua; Wang Yaya; Dai Ming; Zhang Lu; Liu Wenli; Liu Dan; Tan Huo; Huang Zhenqian

2006-01-01

CML28 is an attractive target for antigen-specific immunotherapy. SOCS1 represents an inhibitory control mechanism for DC antigen presentation and the magnitude of adaptive immunity. In this study, we evaluated the potential for inducing CML28-specific cytotoxic T lymphocytes (CTL) responses by dendritic cells (DCs)-based vaccination. We constructed a CML28 DNA vaccine and a SOCS1 siRNA vector and then cotransfect monocyte-derived DCs. Flow cytometry analysis showed gene silencing of SOCS1 resulted in higher expressions of costimulative moleculars in DCs. Mixed lymphocyte reaction (MLR) indicated downregulation of SOCS1 stronger capability to stimulate proliferation of responder cell in DCs. The CTL assay revealed transfected DCs effectively induced autologous CML28-specific CTL responses and the lytic activities induced by SOCS1-silenced DCs were significantly higher compared with those induced by SOCS1-expressing DCs. These results in our study indicates gene silencing of SOCS1 remarkably enhanced the cytotoxicity efficiency of CML28 DNA vaccine in DCs

Induction of Robust Immune Responses in Swine by Using a Cocktail of Adenovirus-Vectored African Swine Fever Virus Antigens.

Science.gov (United States)

Lokhandwala, Shehnaz; Waghela, Suryakant D; Bray, Jocelyn; Martin, Cameron L; Sangewar, Neha; Charendoff, Chloe; Shetti, Rashmi; Ashley, Clay; Chen, Chang-Hsin; Berghman, Luc R; Mwangi, Duncan; Dominowski, Paul J; Foss, Dennis L; Rai, Sharath; Vora, Shaunak; Gabbert, Lindsay; Burrage, Thomas G; Brake, David; Neilan, John; Mwangi, Waithaka

2016-11-01

The African swine fever virus (ASFV) causes a fatal hemorrhagic disease in domestic swine, and at present no treatment or vaccine is available. Natural and gene-deleted, live attenuated strains protect against closely related virulent strains; however, they are yet to be deployed and evaluated in the field to rule out chronic persistence and a potential for reversion to virulence. Previous studies suggest that antibodies play a role in protection, but induction of cytotoxic T lymphocytes (CTLs) could be the key to complete protection. Hence, generation of an efficacious subunit vaccine depends on identification of CTL targets along with a suitable delivery method that will elicit effector CTLs capable of eliminating ASFV-infected host cells and confer long-term protection. To this end, we evaluated the safety and immunogenicity of an adenovirus-vectored ASFV (Ad-ASFV) multiantigen cocktail formulated in two different adjuvants and at two immunizing doses in swine. Immunization with the cocktail rapidly induced unprecedented ASFV antigen-specific antibody and cellular immune responses against all of the antigens. The robust antibody responses underwent rapid isotype switching within 1 week postpriming, steadily increased over a 2-month period, and underwent rapid recall upon boost. Importantly, the primed antibodies strongly recognized the parental ASFV (Georgia 2007/1) by indirect fluorescence antibody (IFA) assay and Western blotting. Significant antigen-specific gamma interferon-positive (IFN-γ + ) responses were detected postpriming and postboosting. Furthermore, this study is the first to demonstrate induction of ASFV antigen-specific CTL responses in commercial swine using Ad-ASFV multiantigens. The relevance of the induced immune responses in regard to protection needs to be evaluated in a challenge study. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): Structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus

International Nuclear Information System (INIS)

Kerkvliet, N.I.; Baecher-Steppan, L.; Smith, B.B.; Youngberg, J.A.; Henderson, M.C.; Buhler, D.R.

1990-01-01

Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons

Evaluation of cellular responses for a chimeric HBsAg-HCV core DNA vaccine in BALB/c mice

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Maryam Yazdanian

2015-01-01

Conclusion: Fusion of HBsAg to HCVcp in the context of a DNA vaccine modality could augment Th1-oriented cellular and CTL responses toward a protective epitope, comparable to that of HCVcp (subunit HCV vaccine immunization.

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

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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.

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.

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

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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.

Simultaneous assessment of cytotoxic T lymphocyte responses against multiple viral infections by combined usage of optimal epitope matrices, anti- CD3 mAb T-cell expansion and "RecycleSpot"

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Wong Johnson T

2005-05-01

Full Text Available Abstract The assessment of cellular anti-viral immunity is often hampered by the limited availability of adequate samples, especially when attempting simultaneous, high-resolution determination of T cell responses against multiple viral infections. Thus, the development of assay systems, which optimize cell usage, while still allowing for the detailed determination of breadth and magnitude of virus-specific cytotoxic T lymphocyte (CTL responses, is urgently needed. This study provides an up-to-date listing of currently known, well-defined viral CTL epitopes for HIV, EBV, CMV, HCV and HBV and describes an approach that overcomes some of the above limitations through the use of peptide matrices of optimally defined viral CTL epitopes in combination with anti-CD3 in vitro T cell expansion and re-use of cells from negative ELISpot wells. The data show that, when compared to direct ex vivo cell preparations, antigen-unspecific in vitro T cell expansion maintains the breadth of detectable T cell responses and demonstrates that harvesting cells from negative ELISpot wells for re-use in subsequent ELISpot assays (RecycleSpot, further maximized the use of available cells. Furthermore when combining T cell expansion and RecycleSpot with the use of rationally designed peptide matrices, antiviral immunity against more than 400 different CTL epitopes from five different viruses can be reproducibly assessed from samples of less than 10 milliliters of blood without compromising information on the breadth and magnitude of these responses. Together, these data support an approach that facilitates the assessment of cellular immunity against multiple viral co-infections in settings where sample availability is severely limited.

Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

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Li-Xin Wang

Full Text Available Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC, a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS, acute myeloid leukemia (AML and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+, but not CD4(+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

Low Dose Decitabine Treatment Induces CD80 Expression in Cancer Cells and Stimulates Tumor Specific Cytotoxic T Lymphocyte Responses

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Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

2013-01-01

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8+, but not CD4+ T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy. PMID:23671644

Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses.

Science.gov (United States)

Wang, Li-Xin; Mei, Zhen-Yang; Zhou, Ji-Hao; Yao, Yu-Shi; Li, Yong-Hui; Xu, Yi-Han; Li, Jing-Xin; Gao, Xiao-Ning; Zhou, Min-Hang; Jiang, Meng-Meng; Gao, Li; Ding, Yi; Lu, Xue-Chun; Shi, Jin-Long; Luo, Xu-Feng; Wang, Jia; Wang, Li-Li; Qu, Chunfeng; Bai, Xue-Feng; Yu, Li

2013-01-01

Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.

Site classification of Indian strong motion network using response spectra ratios

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Chopra, Sumer; Kumar, Vikas; Choudhury, Pallabee; Yadav, R. B. S.

2018-03-01

In the present study, we tried to classify the Indian strong motion sites spread all over Himalaya and adjoining region, located on varied geological formations, based on response spectral ratio. A total of 90 sites were classified based on 395 strong motion records from 94 earthquakes recorded at these sites. The magnitude of these earthquakes are between 2.3 and 7.7 and the hypocentral distance for most of the cases is less than 50 km. The predominant period obtained from response spectral ratios is used to classify these sites. It was found that the shape and predominant peaks of the spectra at these sites match with those in Japan, Italy, Iran, and at some of the sites in Europe and the same classification scheme can be applied to Indian strong motion network. We found that the earlier schemes based on description of near-surface geology, geomorphology, and topography were not able to capture the effect of sediment thickness. The sites are classified into seven classes (CL-I to CL-VII) with varying predominant periods and ranges as proposed by Alessandro et al. (Bull Seismol Soc Am 102:680-695 2012). The effect of magnitudes and hypocentral distances on the shape and predominant peaks were also studied and found to be very small. The classification scheme is robust and cost-effective and can be used in region-specific attenuation relationships for accounting local site effect.

A high selective cataluminescence sensor for the determination of tetrahydrofuran vapor

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Cao, Xiaoan; Dai, Huimei; Chen, Suilin; Zeng, Jiayi; Zhang, Keke; Sun, Yan

2013-02-01

A novel tetrahydrofuran (THF) vapor sensor was designed based on the cataluminescence (CTL) of THF on nanosized γ-Al2O3/MgO (mol ratio = 1.5:1). SEM and XRD were applied for its characterization. We found that the CTL was strongly produced when THF vapor flowed through a nanosized Al-Mg mixed-metal oxide surface, while the CTL was weakly generated when THF vapor flowed through a single nanosized γ-Al2O3 or MgO surface. Quantitative analysis was performed at an optimal temperature of 279 °C, a wavelength of 460 nm and a flow rate of 360 mL min-1. The linear range of the CTL intensity versus concentrations of THF vapor was 1.0-3000 mL m-3 with a detection limit of 0.67 mL m-3. No (or only very low) interference was observed by formaldehyde, methanol, ethanol, benzene, toluene, ethyl acetate, ammonia, cyclohexane, chloroform, glycol armour ether, glycol ether, isopropyl ether and n-butyl ether or acetic acid. Since the response of the sensor was rapid and the system was easy to handle, we believe that the sensor has great potential for real-world use.

In vivo Ebola virus infection leads to a strong innate response in circulating immune cells.

Science.gov (United States)

Caballero, Ignacio S; Honko, Anna N; Gire, Stephen K; Winnicki, Sarah M; Melé, Marta; Gerhardinger, Chiara; Lin, Aaron E; Rinn, John L; Sabeti, Pardis C; Hensley, Lisa E; Connor, John H

2016-09-05

Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. In this study, we analyze RNA sequencing data to determine the host response to Ebola virus infection in circulating immune cells. Approximately half of the 100 genes with the strongest early increases in expression were interferon-stimulated genes, such as ISG15, OAS1, IFIT2, HERC5, MX1 and DHX58. Other highly upregulated genes included cytokines CXCL11, CCL7, IL2RA, IL2R1, IL15RA, and CSF2RB, which have not been previously reported to change during Ebola virus infection. Comparing this response in two different models of exposure (intramuscular and aerosol) revealed a similar signature of infection. The strong innate response in the aerosol model was seen not only in circulating cells, but also in primary and secondary target tissues. Conversely, the innate immune response of vaccinated macaques was almost non-existent. This suggests that the innate response is a major aspect of the cellular response to Ebola virus infection in multiple tissues. Ebola virus causes a severe infection in humans that is associated with high mortality. The host immune response to virus infection is thought to be an important aspect leading to severe pathology, but the components of this overactive response are not well characterized. Here, we analyzed how circulating immune cells respond to the virus and found that there is a strong innate response dependent on active virus replication. This finding is in stark contrast to in vitro evidence showing a suppression of innate immune signaling, and it suggests that the strong innate response we observe in infected animals may be an important contributor to pathogenesis.

The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype

NARCIS (Netherlands)

A.C.M. Boon (Adrianus); G. de Mutsert (Gerrie); Y.M.F. Graus; R.A.M. Fouchier (Ron); K. Sintnicolaas (Krijn); G.F. Rimmelzwaan (Guus); A.D.M.E. Osterhaus (Albert)

2002-01-01

textabstractThe repertoire of human cytotoxic T-lymphocytes (CTL) in response to influenza A viruses has been shown to be directed towards multiple epitopes, with a dominant response to the HLA-A2-restricted M1(58-66) epitope. These studies, however, were performed with peripheral blood mononuclear

Adaptation to human populations is revealed by within-host polymorphisms in HIV-1 and hepatitis C virus.

Directory of Open Access Journals (Sweden)

Art F Y Poon

2007-03-01

Full Text Available CD8(+ cytotoxic T-lymphocytes (CTLs perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1 and hepatitis C virus (HCV. As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately "toggle" in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1- (n > or = 3,000 and HCV-infected patients (n > or = 2,600 by screening bulk RT-PCR sequences for sequencing "mixtures" (i.e., ambiguous nucleotides, which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.

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.

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

GLA-SE, a Synthetic Toll-like Receptor 4 Agonist, Enhances T-Cell Responses to Influenza Vaccine in Older Adults

NARCIS (Netherlands)

Behzad, Hayedeh; Huckriede, Anke L. W.; Haynes, Laura; Gentleman, Beth; Coyle, Krysta; Wilschut, Jan C.; Kollmann, Tobias R.; Reed, Steven G.; McElhaney, Janet E.

2012-01-01

Background. The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza. Methods. The Toll-like receptor 4 agonist

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.

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.

Bone marrow cells from allogeneic bone marrow chimeras inhibit the generation of cytotoxic lymphocyte responses against both donor and recipient cells

International Nuclear Information System (INIS)

Ogasawara, M.; Iwabuchi, K.; Good, R.A.; Onoe, K.

1988-01-01

When added to a mixed lymphocyte culture, bone marrow cells suppress the generation of CTL activity against H-2 Ag shared by the BM cells and the stimulator cells. These cells have been referred to as veto cells and are thought to play a role in maintaining self-tolerance. We analyzed the H-2 specificity of the suppression expressed by the veto cells from H-2 incompatible bone marrow chimeras, because lymphocytes of such chimeras had been shown to be tolerant to both donor and recipient Ag when tested by CTL responses. We found that the bone marrow cells of such chimeras which were featured by non-T and non-B cell characteristics inhibited the generation of CTL directed against either donor or recipient Ag, but not against third-party Ag. These observations suggest that in allogeneic chimeras the veto or veto-like cells alter the inhibitory specificity exhibited in the recipient microenvironment and indicate that these cells are directly involved in the induction and maintenance of self-tolerance

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...

Regulatory effect of dietary intake of chromium propionate on the response of monocyte-derived macrophages from Holstein cows in mid lactation.

Science.gov (United States)

Garcia, M; Qu, Y; Scholte, C M; O'Connor, D; Rounds, W; Moyes, K M

2017-08-01

Chromium (Cr) has been reported to enhance immune function and improve insulin sensitivity and performance in beef and dairy cattle. However, its effect on bovine macrophage inflammatory and metabolic response is unknown. The objective of this study was to characterize the effect of dietary Cr on the inflammatory and metabolic response of polarized macrophages ex vivo. Twelve primiparous and 16 multiparous healthy Holstein cows in mid lactation (143 ± 37 d in milk) were enrolled in this study. Cows were fed a common total mixed ration once per day that was top-dressed with 200 g of ground corn containing 1 of 2 dietary treatments: control (CTL, no Cr supplementation) or Cr propionate (CrP, 8 mg of Cr/cow per day) for 35 d. At d 1, 17, and 35 of treatment, blood monocytes were isolated and cultured to obtain 3 monocyte-derived macrophage (MDM) phenotypes: M0 (non-polarized), M1 (pro-inflammatory; IFN-γ polarized) and M2 (anti-inflammatory; IL-4 polarized). The experiment was set in a randomized complete block design. Neither dry matter intake nor milk yield was affected by treatment. Plasma concentrations of metabolites and the metabolic and inflammatory response of MDM in spent media were not affected by treatment. Neither the whole blood cell population nor the specific proportion of leukocytes was affected by the main effect of treatment. However, we did observe a trend for fewer circulating neutrophils in cows fed CrP than in cows fed CTL for 35 d, which may be partly attributable to a greater influx of neutrophils into peripheral tissues, a reduced pro-inflammatory response during disease, or both; this warrants future study. Expression of IGFI was increased in MDM-M0, and expression of CXCL11 tended to increase in MDM-M2 from cows fed CrP compared with cows fed CTL. Expression of SLC2A3 also tended to increase in MDM-M2 from cows fed CrP compared with cows fed CTL at 17 d. Our results suggest that CrP has minimal effect on the inflammatory and metabolic

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.

Strong Antibody Responses Induced by Protein Antigens Conjugated onto the Surface of Lecithin-Based Nanoparticles

Science.gov (United States)

Sloat, Brian R.; Sandoval, Michael A.; Hau, Andrew M.; He, Yongqun; Cui, Zhengrong

2009-01-01

An accumulation of research over the years has demonstrated the utility of nanoparticles as antigen carriers with adjuvant activity. Herein we defined the adjuvanticity of a novel lecithin-based nanoparticle engineered from emulsions. The nanoparticles were spheres of around 200 nm. Model protein antigens, bovine serum albumin (BSA) or Bacillus anthracis protective antigen (PA) protein, were covalently conjugated onto the nanoparticles. Mice immunized with the BSA-conjugated nanoparticles developed strong anti-BSA antibody responses comparable to that induced by BSA adjuvanted with incomplete Freund's adjuvant and 6.5-fold stronger than that induced by BSA adsorbed onto aluminum hydroxide. Immunization of mice with the PA-conjugated nanoparticles elicited a quick, strong, and durable anti-PA antibody response that afforded protection of the mice against a lethal dose of anthrax lethal toxin challenge. The potent adjuvanticity of the nanoparticles was likely due to their ability to move the antigens into local draining lymph nodes, to enhance the uptake of the antigens by antigen-presenting cells (APCs), and to activate APCs. This novel nanoparticle system has the potential to serve as a universal protein-based vaccine carrier capable of inducing strong immune responses. PMID:19729045

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...

CD107a Expression and IFN-γ Production as Markers for Evaluation of Cytotoxic CD3+ CD8+ T Cell Response to CMV Antigen in Women with Recurrent Spontaneous Abortion.

Science.gov (United States)

Tarokhian, Batoul; Sherkat, Roya; Nasr Esfahani, Mohamma Hossein; Adib, Minoo; Kiani Esfahani, Abbas; Ataei, Behrooz

2014-01-01

Some evidence has shown a relationship between primary human cytomegalovirus (CMV) infection and pregnancy loss. The impact of CMV infection reactivation during pregnancy on adverse pregnancy outcomes is not completely understood. It is proposed that altered immune response, and therefore, recurrence or reactivation of latent CMV infection may relate to recurrent spontaneous abortion (RSA); however, few data are available in this regard. To find out about any cell mediated defect and reactivation of latent CMV infection in women with RPL, cellular immunity to the virus has been evaluated by specific cytotoxic T lymphocyte (CTL) response to CMV. In a case control study, CTL CD107a expression and in- tercellular IFN-γ production in response to CMV pp65 antigen and staphylococcus enterotoxin B (SEB) in women with RSA were assessed by flow cytometric analysis. Forty-four cases with history of recurrent pregnancy and forty-four controls with history of successful pregnancies were included. The FACSCaliber flow cytometer were used for analysis. No significant difference was observed between CD107a expression and IFN-γ production in response to CMV PP65 antigen in RPL patients and control group. How- ever, the cytotoxic response to SEB antigen in patients with RPL was significantly lower than control group (p=0.042). The results of this study show that impaired CD107a expression and IFN-γ production as CTL response to CMV does not appear to be a major contrib- uting and immune incompetence factor in patients with RPL, but cytotoxic T cell response defect to other antigens requires to be assessed further in these patients.

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.

Enhanced Wireless Power Transmission Using Strong Paramagnetic Response.

Science.gov (United States)

Ahn, Dukju; Kiani, Mehdi; Ghovanloo, Maysam

2014-03-01

A method of quasi-static magnetic resonant coupling has been presented for improving the power transmission efficiency (PTE) in near-field wireless power transmission, which improves upon the state of the art. The traditional source resonator on the transmitter side is equipped with an additional resonator with a resonance frequency that is tuned substantially higher than the magnetic field excitation frequency. This additional resonator enhances the magnetic dipole moment and the effective permeability of the power transmitter, owing to a phenomenon known as the strong paramagnetic response. Both theoretical calculations and experimental results show increased PTE due to amplification of the effective permeability. In measurements, the PTE was improved from 57.8% to 64.2% at the nominal distance of 15 cm when the effective permeability was 2.6. The power delivered to load was also improved significantly, with the same 10 V excitation voltage, from 0.38 to 5.26 W.

Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles

International Nuclear Information System (INIS)

Guo Lizheng; Lu Xiaoyan; Kang, S.-M.; Chen Changyi; Compans, Richard W.; Yao Qizhi

2003-01-01

To enhance mucosal immune responses using simian/human immunodeficiency virus-like particles (SHIV VLPs), we have produced novel phenotypically mixed chimeric influenza HA/SHIV VLPs and used them to immunize C57BL/6J mice intranasally. Antibody and cytotoxic T-cell (CTL) responses as well as cytokine production in both systemic and mucosal sites were compared after immunization with SHIV VLPs or chimeric HA/SHIV VLPs. By using enzyme-linked immunosorbent assay (ELISA), the levels of serum IgG and mucosal IgA to the HIV envelope protein (Env) were found to be highest in the group immunized with chimeric HA/SHIV VLPs. Furthermore, the highest titer of serum neutralizing antibody against HIV Env was found with the group immunized with chimeric HA/SHIV VLPs. Analysis of the IgG1/IgG2a ratio indicated that a T H 1-oriented immune response resulted from these VLP immunizations. HA/SHIV VLP-immunized mice also showed significantly higher CTL responses than those observed in SHIV VLP-immunized mice. Moreover, a MHC class I restricted T-cell activation ELISPOT assay showed a mixed type of T H 1/T H 2 cytokines in the HA/SHIV VLP-immunized mice, indicating that the chimeric VLPs can enhance both humoral and cellular immune responses to the HIV Env protein at multiple mucosal and systemic sites. The results indicate that incorporation of influenza HA into heterotypic VLPs may be highly effective for targeting vaccines to mucosal surfaces

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.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises

Energy Technology Data Exchange (ETDEWEB)

Deng, Mao-Lin; Zhu, Wei-Qiu, E-mail: wqzhu@zju.edu.cn [Department of Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Hangzhou 310027 (China)

2016-08-15

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises.

Science.gov (United States)

Deng, Mao-Lin; Zhu, Wei-Qiu

2016-08-01

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Response of MDOF strongly nonlinear systems to fractional Gaussian noises

International Nuclear Information System (INIS)

Deng, Mao-Lin; Zhu, Wei-Qiu

2016-01-01

In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

Attention Strongly Modulates Reliability of Neural Responses to Naturalistic Narrative Stimuli.

Science.gov (United States)

Ki, Jason J; Kelly, Simon P; Parra, Lucas C

2016-03-09

Attentional engagement is a major determinant of how effectively we gather information through our senses. Alongside the sheer growth in the amount and variety of information content that we are presented with through modern media, there is increased variability in the degree to which we "absorb" that information. Traditional research on attention has illuminated the basic principles of sensory selection to isolated features or locations, but it provides little insight into the neural underpinnings of our attentional engagement with modern naturalistic content. Here, we show in human subjects that the reliability of an individual's neural responses with respect to a larger group provides a highly robust index of the level of attentional engagement with a naturalistic narrative stimulus. Specifically, fast electroencephalographic evoked responses were more strongly correlated across subjects when naturally attending to auditory or audiovisual narratives than when attention was directed inward to a mental arithmetic task during stimulus presentation. This effect was strongest for audiovisual stimuli with a cohesive narrative and greatly reduced for speech stimuli lacking meaning. For compelling audiovisual narratives, the effect is remarkably strong, allowing perfect discrimination between attentional state across individuals. Control experiments rule out possible confounds related to altered eye movement trajectories or order of presentation. We conclude that reliability of evoked activity reproduced across subjects viewing the same movie is highly sensitive to the attentional state of the viewer and listener, which is aided by a cohesive narrative. Copyright © 2016 Ki et al.

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

International Nuclear Information System (INIS)

Zhao Ping; Cao Jie; Zhao Lanjuan; Qin Zhaolin; Ke Jinshan; Pan Wei; Ren Hao; Yu Jianguo; Qi Zhongtian

2005-01-01

The nucleocapsid (N) protein of SARS-coronavirus (SARS-CoV) is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membrane glycoprotein. In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5α and identified with pooled sera from patients in the convalescence phase of SARS. A plasmid pCI-N, encoding the full-length N gene of SARS-CoV, was constructed. Expression of the N protein was observed in COS1 cells following transfection with pCI-N. The immune responses induced by intramuscular immunization with pCI-N were evaluated in a murine model. Serum anti-N immunoglobulins and splenocytes proliferative responses against N protein were observed in immunized BALB/c mice. The major immunoglobulin G subclass recognizing N protein was immunoglobulin G2a, and stimulated splenocytes secreted high levels of gamma interferon and IL-2 in response to N protein. More importantly, the immunized mice produced strong delayed-type hypersensitivity (DTH) and CD8 + CTL responses to N protein. The study shows that N protein of SARS-CoV not only is an important B cell immunogen, but also can elicit broad-based cellular immune responses. The results indicate that the N protein may be of potential value in vaccine development for specific prophylaxis and treatment against SARS

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

HLA-Driven Convergence of HIV-1 Viral Subtypes B and F Toward the Adaptation to Immune Responses in Human Populations

Science.gov (United States)

Dilernia, Dario Alberto; Jones, Leandro; Rodriguez, Sabrina; Turk, Gabriela; Rubio, Andrea E.; Pampuro, Sandra; Gomez-Carrillo, Manuel; Bautista, Christian; Deluchi, Gabriel; Benetucci, Jorge; Lasala, María Beatriz; Lourtau, Leonardo; Losso, Marcelo Horacio; Perez, Héctor; Cahn, Pedro; Salomón, Horacio

2008-01-01

Background Cytotoxic T-Lymphocyte (CTL) response drives the evolution of HIV-1 at a host-level by selecting HLA-restricted escape mutations. Dissecting the dynamics of these escape mutations at a population-level would help to understand how HLA-mediated selection drives the evolution of HIV-1. Methodology/Principal Findings We undertook a study of the dynamics of HIV-1 CTL-escape mutations by analyzing through statistical approaches and phylogenetic methods the viral gene gag sequenced in plasma samples collected between the years 1987 and 2006 from 302 drug-naïve HIV-positive patients. By applying logistic regression models and after performing correction for multiple test, we identified 22 potential CTL-escape mutations (p-value<0.05; q-value<0.2); 10 of these associations were confirmed in samples biologically independent by a Bayesian Markov Chain Monte-Carlo method. Analyzing their prevalence back in time we found that escape mutations that are the consensus residue in samples collected after 2003 have actually significantly increased in time in one of either B or F subtype until becoming the most frequent residue, while dominating the other viral subtype. Their estimated prevalence in the viral subtype they did not dominate was lower than 30% for the majority of samples collected at the end of the 80's. In addition, when screening the entire viral region, we found that the 75% of positions significantly changing in time (p<0.05) were located within known CTL epitopes. Conclusions Across HIV Gag protein, the rise of polymorphisms from independent origin during the last twenty years of epidemic in our setting was related to an association with an HLA allele. The fact that these mutations accumulated in one of either B or F subtypes have also dominated the other subtype shows how this selection might be causing a convergence of viral subtypes to variants which are more likely to evade the immune response of the population where they circulate. PMID:18941505

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

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

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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.

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

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

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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.

Dielectric response of a relativistic degenerate electron plasma in a strong magnetic field

International Nuclear Information System (INIS)

Delsante, A.E.; Frankel, N.E.

1979-01-01

The longitudinal dielectric response of a relativistic ultradegenerate electron plasma in a strong magnetic field is obtained via a relativistic generalization of the Hartree self-consistent field method. Dispersion relations and damping conditions for plasma oscillations both parallel and perpendicular to the magnetic field are obtained. Detailed results for the zero-field case, and applications to white dwarf stars and pulsars are given

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.

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

JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

Science.gov (United States)

Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

2016-12-20

Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

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.

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.

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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.

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.

Sequential analysis of the virus-immune responder characteristics of thymocytes from F1→parent radiation chimeras

International Nuclear Information System (INIS)

Korngold, R.; Doherty, P.C.

1982-01-01

The virus-immune responder characteristics of thymocytes, spleen and lymph node (LN) cells from (P 1 x P 2 )F 1 →P 1 radiation chimeras have been examined sequentially at weekly intervals. Adoptively-transferred thymocytes generate strong cytotoxic thymus-derived lymphocyte (CTL) responses from 28 to 100 days after reconstitution with bone marrow, which are almost invariably restricted to recognition of virus presented in the context of P 1 . This pattern of H-2 restriction is also maintained for spleen and LN cells from the [(H-2sup(kxd)F 1 →H-2sup(k)] and [(H-2sup(kxb)F 1 →H-2sup(k)] combinations but there is random emergence of reactivity to H-2sup(k)+virus for peripheral lymphoid cells from [(H-2sup(kxb)F 1 →H-2sup(b)] chimeras. Treatment of established [(P 1 xP 2 )]F 1 →P 1 ] chimeras with a low dose of cyclophosphamide (Cy) did not lead to the emergence of significant CTL effector function for P2 + virus. Also, administration of a large dose of Cy prior to irradiation of the chimera recipients did not modify the H-2 restriction profile of the chimera, though the level of CTL responsiveness associated with the appropriate H-2 type was apparently enhanced. (Auth.)

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.

A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals

DEFF Research Database (Denmark)

Kasprowicz, V; Isa, Adiba; Jeffery, K

2006-01-01

Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF. All responders showed highly focused T-cell receptor (TCR) usage, using almost exclusively BV5.1. The BV5.1 TCR dominated...

Indoor noise annoyance due to 3-5 megawatt wind turbines-An exposure-response relationship.

Science.gov (United States)

Hongisto, Valtteri; Oliva, David; Keränen, Jukka

2017-10-01

The existing exposure-response relationships describing the association between wind turbine sound level and noise annoyance concern turbine sizes of 0.15-3.0 MW. The main purpose of this study was to determine a relationship concerning turbines with nominal power of 3-5 MW. A cross-sectional survey was conducted around three wind power areas in Finland. The survey involved all households within a 2 km distance from the nearest turbine. Altogether, 429 households out of 753 participated. The households were exposed to wind turbine noise having sound levels within 26.7-44.2 dB L Aeq . Standard prediction methods were applied to determine the sound level, L Aeq , in each participant's yard. The measured sound level agreed well with the predicted sound level. The exposure-response relationship was derived between L Aeq outdoors and the indoor noise annoyance. The relationship was in rather good agreement with two previous studies involving much smaller turbines (0.15-1.5 MW) under 40 dB L Aeq . The Community Tolerance Level (CTL), CTL 20  = 50 dB, was 3 dB lower than for two previous studies. Above 40 dB, a small number of participants prevented a reliable comparison to previous studies.

HIV: current opinion in escapology.

Science.gov (United States)

Klenerman, Paul; Wu, Ying; Phillips, Rodney

2002-08-01

Much recent work strongly supports the hypothesis that CD8(+) T lymphocytes (CTLs) exert important immune control over HIV and so are a major selective force in its evolution. We analyse this host-pathogen interplay and focus on new data that describe the overall 'effectiveness' of CTL responses (strength, spread, specificity and 'stamina') and the mechanisms by which HIV may evade this suppressive activity. CTLs directed against HIV recognise very large numbers of distinct epitopes across the genome, are largely functional, turn over rapidly, and possess a phenotype that is distinct from CD8(+) lymphocytes specific for other viruses. Mutation of HIV epitopes that alters or abolishes CTL recognition altogether appears to be the most important immune escape mechanism, as the variation that HIV generates defies the limits of the T cell repertoire. However, this immune evasion is still only well-studied in a few patients. The rules that govern immune escape, and the ultimate limits of CTL capacity to deal with the variant epitopes that currently circulate, are not understood. This information will determine the feasibility of current vaccine approaches that, so far, make no provision for the enormous antigenic plasticity of HIV.

Ionospheric convection response to changes of interplanetary magnetic field B-z component during strong B-y component

DEFF Research Database (Denmark)

Huang, C.S.; Murr, D.; Sofko, G.J.

2000-01-01

response to IMF Bz changes during strong IMF BZ. On March 23, 1995, B-x was small, B-y was strongly positive (7-11 nT), and the B-z polarity changed several times after 1300 UT. The dayside ionospheric convection is dominated by a large clockwise convection cell. The cell focus (the "eye" of the convection...... cell, or the largest change in the convection pattern, is limited roughly to the region between the previous cell focus and the new cell focus. Outside this region, the ionospheric flows could be greatly enhanced or weakened, while the convection pattern shape changes very little. When B-y is strong...... the dawn-dusk meridian plane, which is interpreted as propagation or expansion of newly generated convection cells in the cusp region. Other studies showed that the change in convection pattern in response to IMF reorientations is spatially fixed. In this paper, we investigate the ionospheric convection...

Extraordinary Photoluminescence and Strong Temperature/Angle-Dependent Raman Responses in Few-Layer Phosphorene

OpenAIRE

Zhang, Shuang; Yang, Jiong; Xu, Renjing; Wang, Fan; Li, Weifeng; Ghufran, Muhammad; Zhang, Yong-wei; Yu, Zongfu; Zhang, Gang; Qin, Qinghua; Lu, Yuerui

2014-01-01

Phosphorene is a new family member of two-dimensional materials. We observed strong and highly layer-dependent photoluminescence in few-layer phosphorene (2 to 5 layers). The results confirmed the theoretical prediction that few-layer phosphorene has a direct and layer-sensitive band gap. We also demonstrated that few-layer phosphorene is more sensitive to temperature modulation than graphene and MoS2 in Raman scattering. The anisotropic Raman response in few-layer phosphorene has enabled us ...

Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

DEFF Research Database (Denmark)

Kloverpris, Henrik; Karlsson, Ingrid; Bonde, Jesper

2009-01-01

OBJECTIVE:: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN:: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent...... epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). METHODS:: Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 x 10 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed......-cell counts was observed. CONCLUSION:: These data show that it is possible to generate new T-cell responses in treatment-naive HIV-1-infected individuals despite high viral loads, and thereby redirect immunity to target new multiple and rationally selected subdominant CTL epitopes. Further optimization could...

Chemokines: a new dendritic cell signal for T cell activation

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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.

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...

Immune markers and correlates of protection for vaccine induced immune responses

DEFF Research Database (Denmark)

Thakur, Aneesh; Pedersen, Lasse Eggers; Jungersen, Gregers

2012-01-01

of an appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against......-specific production of interferon-gamma (IFN-γ) has been promoted as a quantitative marker of protective cell-mediated immune responses over the past couple of decades. More recently, however, evidence from several infections has pointed towards the quality of the immune response, measured through increased levels...... of antigen-specific polyfunctional T cells capable of producing a triad of relevant cytokines, as a better correlate of sustained protective immunity against this type of infections. Also the possibilities to measure antigen-specific cytotoxic T cells (CTL) during infection or in response to vaccination...

Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

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Markus Haug

2018-04-01

Full Text Available Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

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

Divergent responses of tropical cyclone genesis factors to strong volcanic eruptions at different latitudes

Science.gov (United States)

Yan, Qing; Zhang, Zhongshi; Wang, Huijun

2018-03-01

To understand the behaviors of tropical cyclones (TCs), it is very important to explore how TCs respond to anthropogenic greenhouse gases and natural forcings. Volcanic eruptions are a major natural forcing mechanism because they inject sulphate aerosols into the stratosphere, which modulate the global climate by absorbing and scattering solar radiation. The number of Atlantic hurricanes is thought to be reduced following strong tropical eruptions, but whether the response of TCs varies with the locations of the volcanoes and the different ocean basins remains unknown. Here, we use the Community Earth System Model-Last Millennium Ensemble to investigate the response of the large-scale environmental factors that spawn TCs to strong volcanic eruptions at different latitudes. A composite analysis indicates that tropical and northern hemisphere volcanic eruptions lead to significantly unfavorable conditions for TC genesis over the whole Pacific basin and the North Atlantic during the 3 years post-eruption, relative to the preceding 3 years. Southern hemisphere volcanic eruptions result in obviously unfavorable conditions for TC formation over the southwestern Pacific, but more favorable conditions over the North Atlantic. The mean response over the Indian Ocean is generally muted and insignificant. It should be noted that volcanic eruptions impact on environmental conditions through both the direct effect (i.e. on radiative forcing) and the indirect effect (i.e. on El Niño-Southern Oscillation), which is not differentiated in this study. In addition, the spread of the TC genesis response is considerably large for each category of eruptions over each ocean basin, which is also seen in the observational/proxy-based records. This large spread is attributed to the differences in stratospheric aerosol distributions, initial states and eruption intensities, and makes the short-term forecast of TC activity following the next large eruption challenging.

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

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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

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.

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

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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

Evaluation of Immune Responses Mediated by Listeria-Stimulated Human Dendritic Cells: Implications for Cancer Vaccine Therapy

Science.gov (United States)

2013-07-01

transfected with RNA. NatBiotech. 1998;16:364-369. 20. Heiser A, Dahm P, Yancey DR, et al. Human dendritic cells transfected with RNA encoding prostate...specific antigen stimulate prostate-specific CTL responses in vitro. J Immunol. 2000;164(10):5508-5514. 21. Heiser A, Maurice MA, Yancey DR...primary and metastatic tumors. Cancer Res. 2001;61(8):3388-3393. 22. Heiser A, Coleman D, Dannull J, et al. Autologous dendritic cells transfected

Antigen Cross-Presentation of Immune Complexes

Science.gov (United States)

Platzer, Barbara; Stout, Madeleine; Fiebiger, Edda

2014-01-01

The ability of dendritic cells (DCs) to cross-present tumor antigens has long been a focus of interest to physicians, as well as basic scientists, that aim to establish efficient cell-based cancer immune therapy. A prerequisite for exploiting this pathway for therapeutic purposes is a better understanding of the mechanisms that underlie the induction of tumor-specific cytotoxic T-lymphocyte (CTL) responses when initiated by DCs via cross-presentation. The ability of humans DC to perform cross-presentation is of utmost interest, as this cell type is a main target for cell-based immunotherapy in humans. The outcome of a cross-presentation event is guided by the nature of the antigen, the form of antigen uptake, and the subpopulation of DCs that performs presentation. Generally, CD8α+ DCs are considered to be the most potent cross-presenting DCs. This paradigm, however, only applies to soluble antigens. During adaptive immune responses, immune complexes form when antibodies interact with their specific epitopes on soluble antigens. Immunoglobulin G (IgG) immune complexes target Fc-gamma receptors on DCs to shuttle exogenous antigens efficiently into the cross-presentation pathway. This receptor-mediated cross-presentation pathway is a well-described route for the induction of strong CD8+ T cell responses. IgG-mediated cross-presentation is intriguing because it permits the CD8− DCs, which are commonly considered to be weak cross-presenters, to efficiently cross-present. Engaging multiple DC subtypes for cross-presentation might be a superior strategy to boost CTL responses in vivo. We here summarize our current understanding of how DCs use IgG-complexed antigens for the efficient induction of CTL responses. Because of its importance for human cell therapy, we also review the recent advances in the characterization of cross-presentation properties of human DC subsets. PMID:24744762

Quantum correlations responsible for remote state creation: strong and weak control parameters

Science.gov (United States)

Doronin, S. I.; Zenchuk, A. I.

2017-03-01

We study the quantum correlations between the two remote qubits (sender and receiver) connected by the transmission line (homogeneous spin-1/2 chain) depending on the parameters of the sender's and receiver's initial states (control parameters). We consider two different measures of quantum correlations: the entanglement (a traditional measure) and the informational correlation (based on the parameter exchange between the sender and receiver). We find the domain in the control parameter space yielding (i) zero entanglement between the sender and receiver during the whole evolution period and (ii) non-vanishing informational correlation between the sender and receiver, thus showing that the informational correlation is responsible for the remote state creation. Among the control parameters, there are the strong parameters (which strongly effect the values of studied measures) and the weak ones (whose effect is negligible), therewith the eigenvalues of the initial state are given a privileged role. We also show that the problem of small entanglement (concurrence) in quantum information processing is similar (in certain sense) to the problem of small determinants in linear algebra. A particular model of 40-node spin-1/2 communication line is presented.

Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

Science.gov (United States)

Ichihashi, Toru; Satoh, Toshifumi; Sugimoto, Chihiro; Kajino, Kiichi

2013-01-01

To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs) in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL) induction capability. Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS) has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+)CD11b(+)MHCII(+) conventional dendritic cells (cDCs) compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

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...

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

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.

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

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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.

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.

Comparative Immunogenicity in Rhesus Monkeys of DNA Plasmid, Recombinant Vaccinia Virus, and Replication-Defective Adenovirus Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene

OpenAIRE

Casimiro, Danilo R.; Chen, Ling; Fu, Tong-Ming; Evans, Robert K.; Caulfield, Michael J.; Davies, Mary-Ellen; Tang, Aimin; Chen, Minchun; Huang, Lingyi; Harris, Virginia; Freed, Daniel C.; Wilson, Keith A.; Dubey, Sheri; Zhu, De-Min; Nawrocki, Denise

2003-01-01

Cellular immune responses, particularly those associated with CD3+ CD8+ cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defecti...

Nonlinear Site Response Validation Studies Using KIK-net Strong Motion Data

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Asimaki, D.; Shi, J.

2014-12-01

Earthquake simulations are nowadays producing realistic ground motion time-series in the range of engineering design applications. Of particular significance to engineers are simulations of near-field motions and large magnitude events, for which observations are scarce. With the engineering community slowly adopting the use of simulated ground motions, site response models need to be re-evaluated in terms of their capabilities and limitations to 'translate' the simulated time-series from rock surface output to structural analyses input. In this talk, we evaluate three one-dimensional site response models: linear viscoelastic, equivalent linear and nonlinear. We evaluate the performance of the models by comparing predictions to observations at 30 downhole stations of the Japanese network KIK-Net that have recorded several strong events, including the 2011 Tohoku earthquake. Velocity profiles are used as the only input to all models, while additional parameters such as quality factor, density and nonlinear dynamic soil properties are estimated from empirical correlations. We quantify the differences of ground surface predictions and observations in terms of both seismological and engineering intensity measures, including bias ratios of peak ground response and visual comparisons of elastic spectra, and inelastic to elastic deformation ratio for multiple ductility ratios. We observe that PGV/Vs,30 — as measure of strain— is a better predictor of site nonlinearity than PGA, and that incremental nonlinear analyses are necessary to produce reliable estimates of high-frequency ground motion components at soft sites. We finally discuss the implications of our findings on the parameterization of nonlinear amplification factors in GMPEs, and on the extensive use of equivalent linear analyses in probabilistic seismic hazard procedures.

Tumor Immunology meets…Immunology: Modified cancer cells as professional APC for priming naïve tumor-specific CD4+ T cells.

Science.gov (United States)

Bou Nasser Eddine, Farah; Ramia, Elise; Tosi, Giovanna; Forlani, Greta; Accolla, Roberto S

2017-01-01

Although recent therapeutic approaches have revitalized the enthusiasm of the immunological way to combat cancer, still the comprehension of immunity against tumors is largely incomplete. Due to their specific function, CD8+ T cells with cytolytic activity (CTL) have attracted the attention of most investigators because CTL are considered the main effectors against tumor cells. Nevertheless, CTL activity and persistence is largely dependent on the action of CD4+ T helper cells (TH). Thus establishment of tumor-specific TH cell response is key to the optimal response against cancer. Here we describe emerging new strategies to increase the TH cell recognition of tumor antigens. In particular, we review recent data indicating that tumor cells themselves can act as surrogate antigen presenting cells for triggering TH response and how these findings can help in constructing immunotherapeutic protocols for anti-cancer vaccine development.

The come back of liquid coal

International Nuclear Information System (INIS)

Caulier, S.

2010-01-01

The coal-to-liquid (CTL) process has made important progresses and is now perfectly mastered by the South-African company Sasol. At least 6 CTL facilities are under construction in China. Each will produce 80000 barrels/day of diesel fuel and the production is planned to start up by 2017 or 2018. The CTL process is profitable when the oil barrel price exceeds 100 US$ but it depends also of the coal price. However, the process itself is highly energy consuming and also highly polluting with strong CO 2 emissions. A solution to these drawbacks would come from the implementation of poly-generation (separate generation of energy, electricity and heat), and from the use of a combined cycle with integrated gasification. (J.S.)

Improved Cytotoxic T Lymphocyte Responses to Vaccination with Porcine Reproductive and Respiratory Syndrome Virus in 4-1BB Transgenic Pigs

Directory of Open Access Journals (Sweden)

Guangping Huang

2017-12-01

Full Text Available Vaccination is the most reliable measure to prevent infectious diseases in domestic animals. Development of novel vaccines demands extensive studies with new technologies, such as using novel adjuvants and immunomodulatory molecules. The co-stimulatory molecule 4-1BB provides a key signal that directs the fate of T cells during activation, and thus is important to their function in immune protection. To determine whether host immune responses to viral infection could be promoted by enhancing 4-1BB co-stimulation, in this study, we produced transgenic pig clones expressing an extra copy of the 4-1BB gene by clustered regularly interspaced short palindromic repeats/CRISPR-associated gene 9-mediated homologous recombination at the Rosa26 locus. The immune responses of transgenic pigs to porcine reproductive and respiratory syndrome virus (PRRSV vaccine were determined on day 14. We show that peripheral blood lymphocytes of transgenic pigs expressed around twice the level of 4-1BB mRNA than those of control pigs. We also found IL-2, TNF-α, and granzyme B mRNA levels as well as PRRSV-specific IFN-γ response were significantly upregulated in 4-1BB transgenic pigs, leading to more efficient cytotoxic T lymphocyte (CTL killing, whereas the expressions of IL-4, IL-17, and Foxp3 were not affected. These results indicate that higher levels of 4-1BB expression involve in promoting Th1 differentiation and enhancing specific CTL responses to PRRSV, and provide a novel approach to increase the efficacy of current vaccines to control the infectious diseases.

Emulsified phosphatidylserine, simple and effective peptide carrier for induction of potent epitope-specific T cell responses.

Directory of Open Access Journals (Sweden)

Toru Ichihashi

Full Text Available BACKGROUND: To induce potent epitope-specific T cell immunity by a peptide-based vaccine, epitope peptides must be delivered efficiently to antigen-presenting cells (APCs in vivo. Therefore, selecting an appropriate peptide carrier is crucial for the development of an effective peptide vaccine. In this study, we explored new peptide carriers which show enhancement in cytotoxic T lymphocyte (CTL induction capability. METHODOLOGY/PRINCIPAL FINDINGS: Data from an epitope-specific in vivo CTL assay revealed that phosphatidylserine (PS has a potent adjuvant effect among candidate materials tested. Further analyses showed that PS-conjugated antigens were preferentially and efficiently captured by professional APCs, in particular, by CD11c(+CD11b(+MHCII(+ conventional dendritic cells (cDCs compared to multilamellar liposome-conjugates or unconjugated antigens. In addition, PS demonstrated the stimulatory capacity of peptide-specific helper T cells in vivo. CONCLUSIONS/SIGNIFICANCE: This work indicates that PS is the easily preparable efficient carrier with a simple structure that delivers antigen to professional APCs effectively and induce both helper and cytotoxic T cell responses in vivo. Therefore, PS is a promising novel adjuvant for T cell-inducing peptide vaccines.

The response of the North Pacific Decadal Variability to strong tropical volcanic eruptions

Energy Technology Data Exchange (ETDEWEB)

Wang, Tao [Chinese Academy of Sciences, Nansen-Zhu International Research Center, Institute of Atmospheric Physics, Beijing (China); Otteraa, Odd Helge [Uni Bjerknes Centre, Uni Research, Bergen (Norway); Bjerknes Center for Climate Research, Bergen (Norway); Gao, Yongqi [Chinese Academy of Sciences, Nansen-Zhu International Research Center, Institute of Atmospheric Physics, Beijing (China); Bjerknes Center for Climate Research, Bergen (Norway); Nansen Environmental and Remote Sensing Center, Bergen (Norway); Wang, Huijun [Chinese Academy of Sciences, Nansen-Zhu International Research Center, Institute of Atmospheric Physics, Beijing (China); Chinese Academy of Sciences, Climate Change Research Center, Institute of Atmospheric Physics, Beijing (China)

2012-12-15

In this study, the effects of volcanic forcing on North Pacific climate variability, on interannual to decadal time scales, are examined using climate model simulations covering the last 600 years. The model used is the Bergen Climate Model, a fully coupled atmosphere-ocean general circulation model. It is found that natural external forcings, such as tropical strong volcanic eruptions (SVEs) and variations in total solar irradiance, play an important role in regulating North Pacific Decadal Variability (NPDV). In response to tropical SVEs the lower stratospheric pole-to-equator temperature gradient is enhanced. The North polar vortex is strengthened, which forces a significant positive Arctic Oscillation. At the same time, dipole zonal wind anomalies associated with strong polar vortex propagate downward from the lower stratosphere. Through positive feedbacks in the troposphere, the surface westerly winds across the central North Pacific are significantly weakened, and positive sea level pressure anomalies are formed in the North Pacific. This anomalous surface circulation results in changes in the net heat fluxes and the oceanic advection across the North Pacific. As a result of this, warm water converges in the subtropical western North Pacific, where the surface waters in addition are heated by significantly reduced latent and sensible heat fluxes from the ocean. In the eastern and high-latitude North Pacific the ocean loses more heat, and large-scale decreases in sea surface temperatures are found. The overall response of this chain of events is that the North Pacific enters a negative phase of the Pacific decadal oscillation (PDO), and this negative phase of the PDO is maintained for several years. It is thus concluded that the volcanic forcing plays a key role in the phasing of the PDO. The model results furthermore highlight the important role of troposphere-stratosphere coupling, tropical-extratropical teleconnections and extratropical ocean

Extraordinary photoluminescence and strong temperature/angle-dependent Raman responses in few-layer phosphorene.

Science.gov (United States)

Zhang, Shuang; Yang, Jiong; Xu, Renjing; Wang, Fan; Li, Weifeng; Ghufran, Muhammad; Zhang, Yong-Wei; Yu, Zongfu; Zhang, Gang; Qin, Qinghua; Lu, Yuerui

2014-09-23

Phosphorene is a new family member of two-dimensional materials. We observed strong and highly layer-dependent photoluminescence in few-layer phosphorene (two to five layers). The results confirmed the theoretical prediction that few-layer phosphorene has a direct and layer-sensitive band gap. We also demonstrated that few-layer phosphorene is more sensitive to temperature modulation than graphene and MoS2 in Raman scattering. The anisotropic Raman response in few-layer phosphorene has enabled us to use an optical method to quickly determine the crystalline orientation without tunneling electron microscopy or scanning tunneling microscopy. Our results provide much needed experimental information about the band structures and exciton nature in few-layer phosphorene.

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

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.

Cellular requirements for cutaneous sensitivity elicitation.

Science.gov (United States)

Aoki, I

1985-01-01

The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

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

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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.

Combined effect of Bacillus coagulans GBI-30, 6086 and HMB supplementation on muscle integrity and cytokine response during intense military training.

Science.gov (United States)

Gepner, Yftach; Hoffman, Jay R; Shemesh, Elad; Stout, Jeffrey R; Church, David D; Varanoske, Alyssa N; Zelicha, Hila; Shelef, Ilan; Chen, Yacov; Frankel, Hagai; Ostfeld, Ishay

2017-07-01

The purpose of this study was to compare the coadministration of the probiotic Bacillus coagulans GBI-30, 6086 (BC30) with β-hydroxy-β-methylbutyrate (HMB) calcium (CaHMB) to CaHMB alone on inflammatory response and muscle integrity during 40 days of intense military training. Soldiers were randomly assigned to one of two groups: CaHMB with BC30 (CaHMBBC30; n = 9) or CaHMB with placebo (CaHMBPL, n = 9). A third group of participants served as a control (CTL; n = 8). During the first 28 days soldiers were garrisoned on base and participated in the same training tasks. During the final 2 wk soldiers navigated 25-30 km per night in difficult terrain carrying ~35 kg of equipment. All assessments (blood draws and diffusion tensor imaging to assess muscle integrity) were conducted before and ~12 h after final supplement consumption. Analysis of covariance was used to analyze all blood and muscle measures. Significant attenuations were noted in IL-1β, IL-2, IL-6, CX3CL1, and TNF-α for both CaHMBBC30 and CaHMBPL compared with CTL. Plasma IL-10 concentrations were significantly attenuated for CaHMBBC30 compared with CTL only. A significant decrease in apparent diffusion coefficients was also observed for CaHMBBC30 compared with CaHMBPL. Results provide further evidence that HMB supplementation may attenuate the inflammatory response to intense training and that the combination of the probiotic BC30 with CaHMB may be more beneficial than CaHMB alone in maintaining muscle integrity during intense military training. NEW & NOTEWORTHY β-Hydroxy-β-methylbutyrate (HMB) in its free acid form was reported to attenuate inflammation and maintain muscle integrity during military training. However, this formulation was difficult to maintain in the field. In this investigation, soldiers ingested HMB calcium (CaHMB) with Bacillus coagulans (BC30) or CaHMB alone during 40 days of training. Results indicated that CaHMB attenuated the inflammatory response and that BC30 combined with

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.

Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

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Cheng-Yuk Lee

Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

Strongly correlating liquids and their isomorphs

OpenAIRE

Pedersen, Ulf R.; Gnan, Nicoletta; Bailey, Nicholas P.; Schröder, Thomas B.; Dyre, Jeppe C.

2010-01-01

This paper summarizes the properties of strongly correlating liquids, i.e., liquids with strong correlations between virial and potential energy equilibrium fluctuations at constant volume. We proceed to focus on the experimental predictions for strongly correlating glass-forming liquids. These predictions include i) density scaling, ii) isochronal superposition, iii) that there is a single function from which all frequency-dependent viscoelastic response functions may be calculated, iv) that...

Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen.

Science.gov (United States)

Arias, Mauricio A; Loxley, Andrew; Eatmon, Christy; Van Roey, Griet; Fairhurst, David; Mitchnick, Mark; Dash, Philip; Cole, Tom; Wegmann, Frank; Sattentau, Quentin; Shattock, Robin

2011-02-01

Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates. Copyright © 2010 Elsevier Ltd. All rights reserved.

Strong-coupling theory of superconductivity

International Nuclear Information System (INIS)

Rainer, D.; Sauls, J.A.

1995-01-01

The electronic properties of correlated metals with a strong electron-phonon coupling may be understood in terms of a combination of Landau''s Fermi liquid theory and the strong-coupling theory of Migdal and Eliashberg. In these lecture notes we discuss the microscopic foundations of this phenomenological Fermi-liquid model of correlated, strong-coupling metals. We formulate the basic equations of the model, which are quasiclassical transport equations that describe both equilibrium and non-equilibrium phenomena for the normal and superconducting states of a metal. Our emphasis is on superconductors close to equilibrium, for which we derive the general linear response theory. As an application we calculate the dynamical conductivity of strong-coupling superconductors. (author)

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

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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

Strong, sudden cooling alleviates the inflammatory responses in heat-stressed dairy cows based on iTRAQ proteomic analysis

Science.gov (United States)

Cheng, Jianbo; Min, Li; Zheng, Nan; Fan, Caiyun; Zhao, Shengguo; Zhang, Yangdong; Wang, Jiaqi

2018-02-01

This study was designed to investigate the effects of sudden cooling on the physiological responses of 12 heat-stressed Holstein dairy cows using an isobaric tags for relative and absolute quantification (iTRAQ) labeling approach. Plasma samples were collected from these cows during heat stress (HS), and after strong, sudden cooling in the summer (16 days later). We compared plasma proteomic data before and after sudden cooling to identify the differentially abundant proteins. The results showed that sudden cooling in summer effectively alleviated the negative consequences of HS on body temperature and production variables. Expressions of plasma hemoglobin alpha and hemoglobin beta were upregulated, whereas lipopolysaccharide-binding protein (LBP) and haptoglobin were downregulated in this process. The increase of hemoglobin after cooling may improve oxygen transport and alleviate the rise in respiration rates in heat-stressed dairy cows. The decrease of LBP and haptoglobin suggests that the inflammatory responses caused by HS are relieved after cooling. Our findings provide new insight into the physiological changes that occur when heat-stressed dairy cows experience strong, sudden cooling.

Human cold stress of strong local-wind "Hijikawa-arashi" in Japan, based on the UTCI index and thermo-physiological responses

Science.gov (United States)

Ohashi, Yukitaka; Katsuta, Takumi; Tani, Haruka; Okabayashi, Taiki; Miyahara, Satoshi; Miyashita, Ryoji

2018-03-01

We investigated the cold stress caused by a strong local wind called "Hijikawa-arashi," through in situ vital measurements and the Universal Thermal Climate Index (UTCI). This wind is a very interesting winter phenomenon, localized in an area within 1 km of the seashore in Ozu City, Ehime Prefecture in Japan. When a strong Hijikawa-arashi (HA) occurred at 14-15 m s-1, the UTCI decreased to - 30 °C along the bridge where commuting residents are the most exposed to strong and cold winds. On the bridge, most participants in our experiment felt "very cold" or "extremely cold." The UTCI of HA can be predicted from a multiple regression equation using wind speed and air temperature. The cold HA wind is also harmful to human thermo-physiological responses. It leads to higher blood pressure and increased heart rate, both of which act as cardiovascular stress triggers. Increases of 6-10 mmHg and 3-6 bpm for every 10 °C reduction in UTCI were seen on all observational days, including HA and non-HA days. In fact, the participants' body skin temperatures decreased by approximately 1.2 to 1.7 °C for every 10 °C reduction in UTCI. Thus, the UTCI variation due to the HA outbreak corresponded well with the cold sensation and thermo-physiological responses in humans. This result suggests that daily UTCI monitoring enables the prediction of thermo-physiological responses to the HA cold stress.

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

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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

Frictional Coulomb drag in strong magnetic fields

DEFF Research Database (Denmark)

Bønsager, Martin Christian; Flensberg, Karsten; Hu, Ben Yu-Kuang

1997-01-01

A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21) is eval......A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21...

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

Sekolah Hijau Sebagai Alternatif Pendidikan Lingkungan Hidup dengan Menggunakan Pendekatan Kontekstual

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Sumarmi Sumarmi

2016-02-01

Full Text Available Green school have the comitment to systematically develop school programs internalizing environmental values. As the environtment education is geared toward the development of knowledge, awareness, positive attitude, and responsible behavior toward environment, a joyful learning approach seemingly appropriate for green schools is contextual teaching and learning (CTL. Through CTL, green schools can create more meaningful lessons, making the environtment education real

Induction of complex immune responses and strong protection against retrovirus challenge by adenovirus-based immunization depends on the order of vaccine delivery.

Science.gov (United States)

Kaulfuß, Meike; Wensing, Ina; Windmann, Sonja; Hrycak, Camilla Patrizia; Bayer, Wibke

2017-02-06

In the Friend retrovirus mouse model we developed potent adenovirus-based vaccines that were designed to induce either strong Friend virus GagL 85-93 -specific CD8 + T cell or antibody responses, respectively. To optimize the immunization outcome we evaluated vaccination strategies using combinations of these vaccines. While the vaccines on their own confer strong protection from a subsequent Friend virus challenge, the simple combination of the vaccines for the establishment of an optimized immunization protocol did not result in a further improvement of vaccine effectivity. We demonstrate that the co-immunization with GagL 85-93 /leader-gag encoding vectors together with envelope-encoding vectors abrogates the induction of GagL 85-93 -specific CD8 + T cells, and in successive immunization protocols the immunization with the GagL 85-93 /leader-gag encoding vector had to precede the immunization with an envelope encoding vector for the efficient induction of GagL 85-93 -specific CD8 + T cells. Importantly, the antibody response to envelope was in fact enhanced when the mice were adenovirus-experienced from a prior immunization, highlighting the expedience of this approach. To circumvent the immunosuppressive effect of envelope on immune responses to simultaneously or subsequently administered immunogens, we developed a two immunizations-based vaccination protocol that induces strong immune responses and confers robust protection of highly Friend virus-susceptible mice from a lethal Friend virus challenge.

The role of natural killer T cells in dendritic cell licensing, cross-priming and memory CD8+ T cell generation

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Catherine eGottschalk

2015-07-01

Full Text Available New vaccination strategies focus on achieving CD8+ T cell (CTL immunity rather than on induction of protective antibody responses. While the requirement of CD4+ T (Th cell help in dendritic cell (DC activation and licensing, and in CTL memory induction has been described in several disease models, CTL responses may occur in a Th cell help independent manner. Natural Killer T cells (NKT cells can substitute for Th cell help and license DC as well. NKT cells produce a broad spectrum of Th1 and Th2 cytokines, thereby inducing a similar set of costimulatory molecules and cytokines in DC. This form of licensing differs from Th cell help by inducing other chemokines: while Th cell licensed DC produce CCR5 ligands, NKT cell-licensed DC produce CCL17 which attracts CCR4+ CD8+ T cells for subsequent activation. It has recently been shown that iNKT cells do not only enhance immune responses against bacterial pathogens or parasites, but also play a role in viral infections. The inclusion of NKT cell ligands in Influenza virus vaccines enhanced memory CTL generation and protective immunity in a mouse model. This review will focus on the role of iNKT cells in the cross-talk with cross-priming DC and memory CD8+ T cell formation.

Association of Neisseria gonorrhoeae Opa(CEA with dendritic cells suppresses their ability to elicit an HIV-1-specific T cell memory response.

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Qigui Yu

Full Text Available Infection with Neisseria gonorrhoeae (N. gonorrhoeae can trigger an intense local inflammatory response at the site of infection, yet there is little specific immune response or development of immune memory. Gonococcal surface epitopes are known to undergo antigenic variation; however, this is unlikely to explain the weak immune response to infection since individuals can be re-infected by the same serotype. Previous studies have demonstrated that the colony opacity-associated (Opa proteins on the N. gonorrhoeae surface can bind human carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 on CD4⁺ T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae infection is associated with impaired HIV-1 (human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte (CTL responses and with transient increases in plasma viremia in HIV-1-infected patients, suggesting that N. gonorrhoeae may also subvert immune responses to co-pathogens. Since dendritic cells (DCs are professional antigen presenting cells (APCs that play a key role in the induction of an adaptive immune response, we investigated the effects of N. gonorrhoeae Opa proteins on human DC activation and function. While morphological changes reminiscent of DC maturation were evident upon N. gonorrhoeae infection, we observed a marked downregulation of DC maturation marker CD83 when the gonococci expressing CEACAM1-specific Opa(CEA, but not other Opa variants. Consistent with a gonococcal-induced defect in maturation, Opa(CEA binding to CEACAM1 reduced the DCs' capacity to stimulate an allogeneic T cell proliferative response. Moreover, Opa(CEA-expressing N. gonorrhoeae showed the potential to impair DC-dependent development of specific adaptive immunity, since infection with Opa(CEA-positive gonococci suppressed the ability of DCs to stimulate HIV-1-specific memory CTL responses. These results reveal a novel mechanism to explain

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

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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

Clustered epitopes within the Gag-Pol fusion protein DNA vaccine enhance immune responses and protection against challenge with recombinant vaccinia viruses expressing HIV-1 Gag and Pol antigens

International Nuclear Information System (INIS)

Bolesta, Elizabeth; Gzyl, Jaroslaw; Wierzbicki, Andrzej; Kmieciak, Dariusz; Kowalczyk, Aleksandra; Kaneko, Yutaro; Srinivasan, Alagarsamy; Kozbor, Danuta

2005-01-01

We have generated a codon-optimized hGagp17p24-Polp51 plasmid DNA expressing the human immunodeficiency virus type 1 (HIV-1) Gag-Pol fusion protein that consists of clusters of highly conserved cytotoxic T lymphocyte (CTL) epitopes presented by multiple MHC class I alleles. In the hGagp17p24-Polp51 construct, the ribosomal frameshift site had been deleted together with the potentially immunosuppressive Gag nucleocapsid (p15) as well as Pol protease (p10) and integrase (p31). Analyses of the magnitude and breadth of cellular responses demonstrated that immunization of HLA-A2/K b transgenic mice with the hGagp17p24-Polp51 construct induced 2- to 5-fold higher CD8 + T-cell responses to Gag p17-, p24-, and Pol reverse transcriptase (RT)-specific CTL epitopes than the full-length hGag-PolΔFsΔPr counterpart. The increases were correlated with higher protection against challenge with recombinant vaccinia viruses (rVVs) expressing gag and pol gene products. Consistent with the profile of Gag- and Pol-specific CD8 + T cell responses, an elevated level of type 1 cytokine production was noted in p24- and RT-stimulated splenocyte cultures established from hGagp17p24-Polp51-immunized mice compared to responses induced with the hGag-PolΔFsΔPr vaccine. Sera of mice immunized with the hGagp17p24-Polp51 vaccine also exhibited an increased titer of p24- and RT-specific IgG2 antibody responses. The results from our studies provide insights into approaches for boosting the breadth of Gag- and Pol-specific immune responses

Human cold stress of strong local-wind "Hijikawa-arashi" in Japan, based on the UTCI index and thermo-physiological responses.

Science.gov (United States)

Ohashi, Yukitaka; Katsuta, Takumi; Tani, Haruka; Okabayashi, Taiki; Miyahara, Satoshi; Miyashita, Ryoji

2018-03-30

We investigated the cold stress caused by a strong local wind called "Hijikawa-arashi," through in situ vital measurements and the Universal Thermal Climate Index (UTCI). This wind is a very interesting winter phenomenon, localized in an area within 1 km of the seashore in Ozu City, Ehime Prefecture in Japan. When a strong Hijikawa-arashi (HA) occurred at 14-15 m s -1 , the UTCI decreased to - 30 °C along the bridge where commuting residents are the most exposed to strong and cold winds. On the bridge, most participants in our experiment felt "very cold" or "extremely cold." The UTCI of HA can be predicted from a multiple regression equation using wind speed and air temperature. The cold HA wind is also harmful to human thermo-physiological responses. It leads to higher blood pressure and increased heart rate, both of which act as cardiovascular stress triggers. Increases of 6-10 mmHg and 3-6 bpm for every 10 °C reduction in UTCI were seen on all observational days, including HA and non-HA days. In fact, the participants' body skin temperatures decreased by approximately 1.2 to 1.7 °C for every 10 °C reduction in UTCI. Thus, the UTCI variation due to the HA outbreak corresponded well with the cold sensation and thermo-physiological responses in humans. This result suggests that daily UTCI monitoring enables the prediction of thermo-physiological responses to the HA cold stress.

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

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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

Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8+ T Cells in a Diameter-Dependent Manner.

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Karuturi, Bala V K; Tallapaka, Shailendra B; Yeapuri, Pravin; Curran, Stephen M; Sanderson, Sam D; Vetro, Joseph A

2017-05-01

The diameter of biodegradable particles used to coencapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8 + T cells generated by systemic immunization. Possible effects on the magnitude of CD8 + T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles. We then compared total magnitude, effector/central memory (CD127/KRLG1/CD62L), and IFN-γ/TNF-α/IL-2 secreting subsets of pp89-specific CD8 + T cells as well as protection of naive female BALB/c mice against primary respiratory infection with MCMV 21 days after respiratory immunization. We found that decreasing the diameter of encapsulating particle from ∼5.4 μm to ∼350 nm (i) increased the magnitude of pp89-specific CD8 + T cells in the lungs and spleen; (ii) partially changed CD127/KLRG1 effector memory subsets in the lungs but not the spleen; (iii) changed CD127/KRLG1/CD62L effector/central memory subsets in the spleen; (iv) changed pp89-responsive IFN-γ/TNF-α/IL-2 secreting subsets in the lungs and spleen; (v) did not affect the extent to which encapsulation increased efficacy against primary MCMV respiratory infection over unencapsulated pp89-RR-EP67. Thus, although not observed under our current experimental conditions with MCMV, varying the diameter of nanoscale biodegradable particles may increase the efficacy of mucosal immunization with coencapsulated immunostimulant/subunit vaccines against certain pathogens by selectively increasing memory subset(s) of CD8 + T cells that correlate the strongest with protection.

Measuring T cell-mediated cytotoxicity using fluorogenic caspase substrates.

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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.

A Unique T-Cell Receptor Amino Acid Sequence Selected by Human T-Cell Lymphotropic Virus Type 1 Tax301-309-Specific Cytotoxic T Cells in HLA-A24:02-Positive Asymptomatic Carriers and Adult T-Cell Leukemia/Lymphoma Patients.

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Ishihara, Yuko; Tanaka, Yukie; Kobayashi, Seiichiro; Kawamura, Koji; Nakasone, Hideki; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Uchimaru, Kaoru; Kanda, Yoshinobu

2017-10-01

We previously reported that the T-cell receptor (TCR) repertoire of human T-cell lymphotropic virus type 1 (HTLV-1) Tax 301-309 -specific CD8 + cytotoxic T cells (Tax 301-309 -CTLs) was highly restricted and a particular amino acid sequence motif, the PDR motif, was conserved among HLA-A*24:02-positive (HLA-A*24:02 + ) adult T-cell leukemia/lymphoma (ATL) patients who had undergone allogeneic hematopoietic cell transplantation (allo-HSCT). Furthermore, we found that donor-derived PDR + CTLs selectively expanded in ATL long-term HSCT survivors with strong CTL activity against HTLV-1. On the other hand, the TCR repertoires in Tax 301-309 -CTLs of asymptomatic HTLV-1 carriers (ACs) remain unclear. In this study, we directly identified the DNA sequence of complementarity-determining region 3 (CDR3) of the TCR-β chain of Tax 301-309 -CTLs at the single-cell level and compared not only the TCR repertoires but also the frequencies and phenotypes of Tax 301-309 -CTLs between ACs and ATL patients. We did not observe any essential difference in the frequencies of Tax 301-309 -CTLs between ACs and ATL patients. In the single-cell TCR repertoire analysis of Tax 301-309 -CTLs, 1,458 Tax 301-309 -CTLs and 140 clones were identified in this cohort. Tax 301-309 -CTLs showed highly restricted TCR repertoires with a strongly biased usage of BV7, and PDR, the unique motif in TCR-β CDR3, was exclusively observed in all ACs and ATL patients. However, there was no correlation between PDR + CTL frequencies and HTLV-1 proviral load (PVL). In conclusion, we have identified, for the first time, a unique amino acid sequence, PDR, as a public TCR-CDR3 motif against Tax in HLA-A*24:02 + HTLV-1-infected individuals. Further investigations are warranted to elucidate the role of the PDR + CTL response in the progression from carrier state to ATL. IMPORTANCE ATL is an aggressive T-cell malignancy caused by HTLV-1 infection. The HTLV-1 regulatory protein Tax aggressively promotes the

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

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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.

Rapid upslope shifts in New Guinean birds illustrate strong distributional responses of tropical montane species to global warming

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Freeman, Benjamin G.; Class Freeman, Alexandra M.

2014-01-01

Temperate-zone species have responded to warming temperatures by shifting their distributions poleward and upslope. Thermal tolerance data suggests that tropical species may respond to warming temperatures even more strongly than temperate-zone species, but this prediction has yet to be tested. We addressed this data gap by conducting resurveys to measure distributional responses to temperature increases in the elevational limits of the avifaunas of two geographically and faunally independent New Guinean mountains, Mt. Karimui and Karkar Island, 47 and 44 y after they were originally surveyed. Although species richness is roughly five times greater on mainland Mt. Karimui than oceanic Karkar Island, distributional shifts at both sites were similar: upslope shifts averaged 113 m (Mt. Karimui) and 152 m (Karkar Island) for upper limits and 95 m (Mt. Karimui) and 123 m (Karkar Island) for lower limits. We incorporated these results into a metaanalysis to compare distributional responses of tropical species with those of temperate-zone species, finding that average upslope shifts in tropical montane species match local temperature increases significantly more closely than in temperate-zone montane species. That tropical species appear to be strong responders has global conservation implications and provides empirical support to hitherto untested models that predict widespread extinctions in upper-elevation tropical endemics with small ranges. PMID:24550460

Strong motion duration and earthquake magnitude relationships

International Nuclear Information System (INIS)

Salmon, M.W.; Short, S.A.; Kennedy, R.P.

1992-06-01

Earthquake duration is the total time of ground shaking from the arrival of seismic waves until the return to ambient conditions. Much of this time is at relatively low shaking levels which have little effect on seismic structural response and on earthquake damage potential. As a result, a parameter termed ''strong motion duration'' has been defined by a number of investigators to be used for the purpose of evaluating seismic response and assessing the potential for structural damage due to earthquakes. This report presents methods for determining strong motion duration and a time history envelope function appropriate for various evaluation purposes, for earthquake magnitude and distance, and for site soil properties. There are numerous definitions of strong motion duration. For most of these definitions, empirical studies have been completed which relate duration to earthquake magnitude and distance and to site soil properties. Each of these definitions recognizes that only the portion of an earthquake record which has sufficiently high acceleration amplitude, energy content, or some other parameters significantly affects seismic response. Studies have been performed which indicate that the portion of an earthquake record in which the power (average rate of energy input) is maximum correlates most closely with potential damage to stiff nuclear power plant structures. Hence, this report will concentrate on energy based strong motion duration definitions

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

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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.

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

DEFF Research Database (Denmark)

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin

2016-01-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... trachomatis SvD bacteria (UV-SvD/CAF01) or CAF01. The Hirep1+CTH93/CAF01 vaccine induced a strong CMI response against the vaccine antigens and high titers of antibodies, particularly against the VD4 region of MOMP. Sera from Hirep1+CTH93/CAF01 immunized pigs neutralized C. trachomatis SvD and SvF infectivity...

Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine

International Nuclear Information System (INIS)

Yoshikawa, Tomoaki; Imazu, Susumu; Gao Jianqing; Hayashi, Kazuyuki; Tsuda, Yasuhiro; Shimokawa, Mariko; Sugita, Toshiki; Niwa, Takako; Oda, Atushi; Akashi, Mitsuru; Tsutsumi, Yasuo; Mayumi, Tadanori; Nakagawa, Shinsaku

2004-01-01

In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen

In your eyes: does theory of mind predict impaired life functioning in bipolar disorder?

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Purcell, Amanda L; Phillips, Mary; Gruber, June

2013-12-01

Deficits in emotion perception and social functioning are strongly implicated in bipolar disorder (BD). Examining theory of mind (ToM) may provide one potential mechanism to explain observed socio-emotional impairments in this disorder. The present study prospectively investigated the relationship between theory of mind performance and life functioning in individuals diagnosed with BD compared to unipolar depression and healthy control groups. Theory of mind (ToM) performance was examined in 26 individuals with remitted bipolar I disorder (BD), 29 individuals with remitted unipolar depression (UD), and 28 healthy controls (CTL) using a well-validated advanced theory of mind task. Accuracy and response latency scores were calculated from the task. Life functioning was measured during a 12 month follow-up session. No group differences for ToM accuracy emerged. However, the BD group exhibited significantly shorter response times than the UD and CTL groups. Importantly, quicker response times in the BD group predicted greater life functioning impairment at a 12-month follow-up, even after controlling for baseline symptoms. The stimuli were static representations of emotional states and do not allow for evaluating the appropriateness of context during emotional communication; due to sample size, neither specific comorbidities nor medication effects were analyzed for the BD and UD groups; preliminary status of theory of mind as a construct. Results suggest that quickened socio-emotional decision making may represent a risk factor for future functional impairment in BD. Copyright © 2013 Elsevier B.V. All rights reserved.

Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

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Manns Michael P

2007-06-01

Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly.

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Costa, Eunice; Lloyd, Margaret M; Chopko, Caroline; Aguiar-Ricardo, Ana; Hammond, Paula T

2012-07-03

The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

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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.

Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

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Martin Kreutz

Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

DEFF Research Database (Denmark)

Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin

2016-01-01

Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1...

An Evaluation of the Brief Symptom Inventory-18 Using Item Response Theory: Which Items Are Most Strongly Related to Psychological Distress?

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Meijer, Rob R.; de Vries, Rivka M.; van Bruggen, Vincent

2011-01-01

The psychometric structure of the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a strong Mokken scale for outpatients and…

P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.

Science.gov (United States)

Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza

2014-12-01

Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation and summary of seismic response of above ground nuclear power plant piping to strong motion earthquakes

International Nuclear Information System (INIS)

Stevenson, J.D.

1985-01-01

The purpose of this paper is to summarize the observations and experience which has been developed relative to the seismic behavior of above-ground, building-supported, industrial type piping (similar to piping used in nuclear power plants) in strong motion earthquakes. The paper also contains observations regarding the response of piping in experimental tests which attempted to excite the piping to failure. Appropriate conclusions regarding the behavior of such piping in large earthquakes and recommendations as to future design of such piping to resist earthquake motion damage are presented based on observed behavior in large earthquakes and simulated shake table testing

HLA-A*0201 T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus nucleocapsid and spike proteins

International Nuclear Information System (INIS)

Tsao, Y.-P.; Lin, J.-Y.; Jan, J.-T.; Leng, C.-H.; Chu, C.-C.; Yang, Y.-C.; Chen, S.-L.

2006-01-01

The immunogenicity of HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) peptide in severe acute respiratory syndrome coronavirus (SARS-CoV) nuclear capsid (N) and spike (S) proteins was determined by testing the proteins' ability to elicit a specific cellular immune response after immunization of HLA-A2.1 transgenic mice and in vitro vaccination of HLA-A2.1 positive human peripheral blood mononuclearcytes (PBMCs). First, we screened SARS N and S amino acid sequences for allele-specific motif matching those in human HLA-A2.1 MHC-I molecules. From HLA peptide binding predictions (http://thr.cit.nih.gov/molbio/hla_bind/), ten each potential N- and S-specific HLA-A2.1-binding peptides were synthesized. The high affinity HLA-A2.1 peptides were validated by T2-cell stabilization assays, with immunogenicity assays revealing peptides N223-231, N227-235, and N317-325 to be First identified HLA-A*0201-restricted CTL epitopes of SARS-CoV N protein. In addition, previous reports identified three HLA-A*0201-restricted CTL epitopes of S protein (S978-986, S1203-1211, and S1167-1175), here we found two novel peptides S787-795 and S1042-1050 as S-specific CTL epitopes. Moreover, our identified N317-325 and S1042-1050 CTL epitopes could induce recall responses when IFN-γ stimulation of blood CD8 + T-cells revealed significant difference between normal healthy donors and SARS-recovered patients after those PBMCs were in vitro vaccinated with their cognate antigen. Our results would provide a new insight into the development of therapeutic vaccine in SARS

Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection

International Nuclear Information System (INIS)

Liu Yi; Mullins, James I.; Mittler, John E.

2006-01-01

The failure of HIV-1 to escape at some cytotoxic T-lymphocyte (CTL) epitopes has generally been explained in terms of viral fitness costs or ineffective or attenuated CTL responses. Relatively little attention has been paid to the evolutionary time required for escape mutants to be detected. This time is significantly affected by selection, mutation rates, the presence of other advantageous mutations, and the effective population size of HIV-1 in vivo (typically estimated to be ∼10 3 in chronically infected patients, though one study has estimated it to be ∼10 5 ). Here, we use a forward simulator with experimentally estimated HIV-1 parameters to show that these delays can be substantial. For an effective population size of 10 3 , even highly advantageous mutants (s = 0.5) may not be detected for a couple of years in chronically infected patients, while moderately advantageous escape mutants (s = 0.1) may not be detected for up to 10 years. Even with an effective population size of 10 5 , a moderately advantageous escape mutant (s = 0.1) may not be detected in the population within 2 years if it has to compete with other selectively advantageous mutants. Stochastic evolutionary forces, therefore, in addition to viral fitness costs and ineffective or attenuated CTL responses, must be taken into account when assessing the selection of CTL escape mutations

Students’ Creativity: Problem Posing in Structured Situation

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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.

Sensitive and selective cataluminescence-based sensor system for acetone and diethyl ether determination.

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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.

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

Low-pressure pulsed focused ultrasound with microbubbles promotes an anticancer immunological response.

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Liu, Hao-Li; Hsieh, Han-Yi; Lu, Li-An; Kang, Chiao-Wen; Wu, Ming-Fang; Lin, Chun-Yen

2012-11-11

High-intensity focused-ultrasound (HIFU) has been successfully employed for thermal ablation of tumors in clinical settings. Continuous- or pulsed-mode HIFU may also induce a host antitumor immune response, mainly through expansion of antigen-presenting cells in response to increased cellular debris and through increased macrophage activation/infiltration. Here we demonstrated that another form of focused ultrasound delivery, using low-pressure, pulsed-mode exposure in the presence of microbubbles (MBs), may also trigger an antitumor immunological response and inhibit tumor growth. A total of 280 tumor-bearing animals were subjected to sonographically-guided FUS. Implanted tumors were exposed to low-pressure FUS (0.6 to 1.4 MPa) with MBs to increase the permeability of tumor microvasculature. Tumor progression was suppressed by both 0.6 and 1.4-MPa MB-enhanced FUS exposures. We observed a transient increase in infiltration of non-T regulatory (non-Treg) tumor infiltrating lymphocytes (TILs) and continual infiltration of CD8+ cytotoxic T-lymphocytes (CTL). The ratio of CD8+/Treg increased significantly and tumor growth was inhibited. Our findings suggest that low-pressure FUS exposure with MBs may constitute a useful tool for triggering an anticancer immune response, for potential cancer immunotherapy.

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

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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.

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

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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.

Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

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Monica Poggianella

Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

Does programmed CTL proliferation optimize virus control?

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Wodarz, Dominik; Thomsen, Allan Randrup

2005-01-01

CD8 T-cell or cytotoxic T-lymphocyte responses develop through an antigen-independent proliferation and differentiation program. This is in contrast to the previous thinking, which was that continuous antigenic stimulation was required. This Opinion discusses why nature has chosen the proliferati...

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

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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.

Liposomes and nanotechnology in drug development: focus on oncotargets

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Kozako T

2012-09-01

antigen delivery vehicles to antigen-presenting cells. Oligomannose-coated liposomes (OML can eliminate established tumors in mouse cancer models. In addition, OMLs with an encased antigen can induce antigen-specific CTLs from peripheral blood mononuclear cells obtained from patients. Feasibility studies of OML-based vaccines have revealed their potential for clinical use as vaccines for diseases where CTLs act as effector cells. Furthermore, use of the hepatitis B core particle, in which tumor-antigen epitopes are set, has consistently been shown to induce strong CTL responses without the use of an adjuvant. Thus, nanoparticles may provide a new prophylactic strategy for infectious disease and therapeutic approaches for cancer via the induction of T-cell immunity.Keywords: adult T cell leukemia, cytotoxic T lymphocytes, oligomannose-coated liposomes, vaccine

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...

Enhancement of Th1 type cytokine production and primary T cell activation by PBI-1393.

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Allam, Mustapha; Julien, Nathalie; Zacharie, Boulos; Penney, Christopher; Gagnon, Lyne

2007-12-01

In previous reports, we have shown that PBI-1393 (formerly BCH-1393), N,N-Dimethylaminopurine pentoxycarbonyl D-arginine, stimulates cytotoxic T-lymphocyte (CTL) responses both in vitro and in vivo in normal immune status and immunosuppressed mice. Additionally, PBI-1393 was tested for anticancer activity in syngeneic mouse experimental tumor models and it displayed significant inhibition of tumor outgrowths when given in combination with sub-therapeutic doses of cytotoxic drugs (cyclophosphamide, 5-fluorouracil, doxorubicin and cis-platinum). However, the mechanism of action of PBI-1393 was still unknown. Here, we report that PBI-1393 enhances IL-2 and IFN-gamma production in human activated T cells by 51% and 46% respectively. PBI-1393 increases also IL-2 and IFN-gamma mRNA expression as shown by RT-PCR. The physiological relevance of IL-2 and IFN-gamma gene modulation by PBI-1393 is illustrated by the advantageous increase of T cell proliferation (39+/-0.3% above control) and human CTL response against prostate (PC-3) cancer cells (42+/-0.03%). The enhancement of human T cell proliferation and CTL activation by PBI-1393 demonstrates that this compound potentiates the immune response and in this regard, it could be used as an alternative approach to IL-2 and/or IFN-gamma therapy against cancer.

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

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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 CTL (ΔCTL) 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.

Coherent response of a two-level atom to a signal field with account of suppression of phase relaxation by a strong field

International Nuclear Information System (INIS)

Grishanin, B.A.; Shatalova, G.G.

1984-01-01

Calculation is made of a coherent part of response to a weak test field of an atom located in a strong resonance field. The latter bads to a suppression of phase relaxation. This response is shown to appear both at a test field freq uency ω and at a combination frequency 2ωsub(l)-ω, where ωsub(l) is a resona nce field frequency. The spectrum of test field absorption by such a system has a symmetric form and consist of two parts, one of which corresponds to a test f ield absorption and another - to its amplification

Revitalisation of Control and Data Acquisition Systems for Corrosion Test Loop

International Nuclear Information System (INIS)

Khairul Handono; Kiswanta; Edy Sumarno

2008-01-01

The replacement of control and data acquisition systems for Corrosion Test Loop (CTL) has been conducted. The aim of revitalisation for CTL is to increase controller system performance Kent 4000 which is based on PLC. On the other side revitalisation of acquisition data system is done to build computer based data retrieval system for transformation gauging of parameters in thermalhydraulic experiment of CTL. Previously, data collector system used indicator recorder analog, while data recording is done manually, which caused causing very slow response and the result is less accurate. To increase the user quality of data collector system, the data acquisition system is developed with application program Visual Basic and acquisition apparatus card of data. Result of the activity of revitalisation CTL is to obtain of control systems based on PLC and data acquisition system capable to present information in the form of temperature, pressure and cooling water level interactively, namely easy to read, quickly, realtime and accurate. This results give the improvement of control systems performance and data acquisition system which data storage of acquisition into hard disk in the form of file and further processed in the form of tables or graph to facilitate the analysis. (author)

Engaging Pre-Service Teachers to Teach Science Contextually with Scientific Approach Instructional Video

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Susantini, E.; Kurniasari, I.; Fauziah, A. N. M.; Prastowo, T.; Kholiq, A.; Rosdiana, L.

2018-01-01

Contextual teaching and learning/CTL presents new concepts in real-life experiences and situations where students can find out the meaningful relationship between abstract ideas and practical applications. Implementing contextual teaching by using scientific approach will foster teachers to find the constructive ways of delivering and organizing science content. This research developed an instructional video that represented a modeling of using a scientific approach in CTL. The aim of this research are to engage pre-service teachers in learning how to teach CTL and to show how pre-service teachers’ responses about learning how to teach CTL using an instructional video. The subjects of this research were ten pre-service teachers in Department of Natural Sciences, Universitas Negeri Surabaya, Indonesia. All subjects observed the instructional video which demonstrated contextual teaching and learning combined with the scientific approach as they completed a worksheet to analyze the video content. The results showed that pre-service teachers could learn to teach contextually as well as applying the scientific approach in science classroom through a modeling in the instructional video. They also responded that the instructional video could help them to learn to teach each component contextual teaching as well as scientific approach.

Mycobacterium vaccae induces a strong Th1 response that subsequently declines in C57BL/6 mice.

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Zhang, Lijiao; Jiang, Yanlong; Cui, Ziyin; Yang, Wentao; Yue, Limin; Ma, Yingcong; Shi, Shaohua; Wang, Chunfang; Wang, Chunfeng; Qian, Aidong

2016-12-30

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. bovis Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. bovis BCG revealed that M. vaccae was more malignant than M. bovis in mice. We also demonstrated that serum from the M. vaccae -infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.

Bioinformatics prediction of swine MHC class I epitopes from Porcine Reproductive and Respiratory Syndrome Virus

DEFF Research Database (Denmark)

Welner, Simon; Nielsen, Morten; Lund, Ole

an effective CTL response against PRRSV, we have taken a bioinformatics approach to identify common PRRSV epitopes predicted to react broadly with predominant swine MHC (SLA) alleles. First, the genomic integrity and sequencing method was examined for 334 available complete PRRSV type 2 genomes leaving 104...... by the PopCover algorithm, providing a final list of 54 epitopes prioritized according to maximum coverage of PRRSV strains and SLA alleles. This bioinformatics approach provides a rational strategy for selecting peptides for a CTL-activating vaccine with broad coverage of both virus and swine diversity...

Identification of swine influenza virus epitopes and analysis of multiple specificities expressed by cytotoxic T cell subsets

DEFF Research Database (Denmark)

Pedersen, Lasse Eggers; Breum, Solvej Østergaard; Riber, Ulla

2014-01-01

Background: Major histocompatibility complex (MHC) class I peptide binding and presentation are essential for antigen-specific activation of cytotoxic T lymphocytes (CTLs) and swine MHC class I molecules, also termed swine leukocyte antigens (SLA), thus play a crucial role in the process that leads...... to elimination of viruses such as swine influenza virus (SwIV). This study describes the identification of SLA-presented peptide epitopes that are targets for a swine CTL response, and further analyses multiple specificities expressed by SwIV activated CTL subsets. Findings: Four SwIV derived peptides were...

Genome-wide transcriptional response of silkworm (Bombyx mori to infection by the microsporidian Nosema bombycis.

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Zhengang Ma

Full Text Available Microsporidia have attracted much attention because they infect a variety of species ranging from protists to mammals, including immunocompromised patients with AIDS or cancer. Aside from the study on Nosema ceranae, few works have focused on elucidating the mechanism in host response to microsporidia infection. Nosema bombycis is a pathogen of silkworm pébrine that causes great economic losses to the silkworm industry. Detailed understanding of the host (Bombyx mori response to infection by N. bombycis is helpful for prevention of this disease. A genome-wide survey of the gene expression profile at 2, 4, 6 and 8 days post-infection by N. bombycis was performed and results showed that 64, 244, 1,328, 1,887 genes were induced, respectively. Up to 124 genes, which are involved in basal metabolism pathways, were modulated. Notably, B. mori genes that play a role in juvenile hormone synthesis and metabolism pathways were induced, suggesting that the host may accumulate JH as a response to infection. Interestingly, N. bombycis can inhibit the silkworm serine protease cascade melanization pathway in hemolymph, which may be due to the secretion of serpins in the microsporidia. N. bombycis also induced up-regulation of several cellular immune factors, in which CTL11 has been suggested to be involved in both spore recognition and immune signal transduction. Microarray and real-time PCR analysis indicated the activation of silkworm Toll and JAK/STAT pathways. The notable up-regulation of antimicrobial peptides, including gloverins, lebocins and moricins, strongly indicated that antimicrobial peptide defense mechanisms were triggered to resist the invasive microsporidia. An analysis of N. bombycis-specific response factors suggested their important roles in anti-microsporidia defense. Overall, this study primarily provides insight into the potential molecular mechanisms for the host-parasite interaction between B. mori and N. bombycis and may provide a

Granzyme B mediated function of Parvovirus B19-specific CD4+ T cells

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Kumar, Arun; Perdomo, Maria F; Kantele, Anu; Hedman, Lea; Hedman, Klaus; Franssila, Rauli

2015-01-01

A novel conception of CD4+ T cells with cytolytic potential (CD4+ CTL) is emerging. These cells appear to have a part in controlling malignancies and chronic infections. Human parvovirus B19 can cause a persistent infection, yet no data exist on the presence of B19-specific CD4+ CTLs. Such cells could have a role in the pathogenesis of some autoimmune disorders reported to be associated with B19. We explored the cytolytic potential of human parvovirus B19-specific T cells by stimulating peripheral blood mononuclear cell (PBMC) with recombinant B19-VP2 virus-like particles. The cytolytic potential was determined by enzyme immunoassay-based quantitation of granzyme B (GrB) and perforin from the tissue culture supernatants, by intracellular cytokine staining (ICS) and by detecting direct cytotoxicity. GrB and perforin responses with the B19 antigen were readily detectable in B19-seropositive individuals. T-cell depletion, HLA blocking and ICS experiments showed GrB and perforin to be secreted by CD4+ T cells. CD4+ T cells with strong GrB responses were found to exhibit direct cytotoxicity. As anticipated, ICS of B19-specific CD4+ T cells showed expected co-expression of GrB, perforin and interferon gamma (IFN-γ). Unexpectedly, also a strong co-expression of GrB and interleukin 17 (IL-17) was detected. These cells expressed natural killer (NK) cell surface marker CD56, together with the CD4 surface marker. To our knowledge, this is the first report on virus-specific CD4+ CTLs co-expressing CD56 antigen. Our results suggest a role for CD4+ CTL in B19 immunity. Such cells could function within both immune regulation and triggering of autoimmune phenomena such as systemic lupus erythematosus (SLE) or rheumatoid arthritis. PMID:26246896

Towards Integrated Marmara Strong Motion Network

Science.gov (United States)

Durukal, E.; Erdik, M.; Safak, E.; Ansal, A.; Ozel, O.; Alcik, H.; Mert, A.; Kafadar, N.; Korkmaz, A.; Kurtulus, A.

2009-04-01

Istanbul has a 65% chance of having a magnitude 7 or above earthquake within the next 30 years. As part of the preparations for the future earthquake, strong motion networks have been installed in and around Istanbul. The Marmara Strong Motion Network, operated by the Department of Earthquake Engineering of Kandilli Observatory and Earthquake Research Institute, encompasses permanent systems outlined below. It is envisaged that the networks will be run by a single entity responsible for technical management and maintanence, as well as for data management, archiving and dissemination through dedicated web-based interfaces. • Istanbul Earthquake Rapid Response and Early Warning System - IERREWS (one hundred 18-bit accelerometers for rapid response; ten 24-bit accelerometers for early warning) • IGDAŞ Gas Shutoff Network (100 accelerometers to be installed in 2010 and integrated with IERREWS) • Structural Monitoring Arrays - Fatih Sultan Mehmet Suspension Bridge (1200m-long suspension bridge across the Bosphorus, five 3-component accelerometers + GPS sensors) - Hagia Sophia Array (1500-year-old historical edifice, 9 accelerometers) - Süleymaniye Mosque Array (450-year-old historical edifice,9 accelerometers) - Fatih Mosque Array (237-year-old historical edifice, 9 accelerometers) - Kanyon Building Array (high-rise office building, 5 accelerometers) - Isbank Tower Array (high-rise office building, 5 accelerometers) - ENRON Array (power generation facility, 4 acelerometers) - Mihrimah Sultan Mosque Array (450-year-old historical edifice,9 accelerometers + tiltmeters, to be installed in 2009) - Sultanahmet Mosque Array, (390-year-old historical edifice, 9 accelerometers + tiltmeters, to be installed in 2009) • Special Arrays - Atakoy Vertical Array (four 3-component accelerometers at 25, 50, 75, and 150 m depths) - Marmara Tube Tunnel (1400 m long submerged tunnel, 128 ch. accelerometric data, 24 ch. strain data, to be installed in 2010) - Air-Force Academy

Rrsm: The European Rapid Raw Strong-Motion Database

Science.gov (United States)

Cauzzi, C.; Clinton, J. F.; Sleeman, R.; Domingo Ballesta, J.; Kaestli, P.; Galanis, O.

2014-12-01

We introduce the European Rapid Raw Strong-Motion database (RRSM), a Europe-wide system that provides parameterised strong motion information, as well as access to waveform data, within minutes of the occurrence of strong earthquakes. The RRSM significantly differs from traditional earthquake strong motion dissemination in Europe, which has focused on providing reviewed, processed strong motion parameters, typically with significant delays. As the RRSM provides rapid open access to raw waveform data and metadata and does not rely on external manual waveform processing, RRSM information is tailored to seismologists and strong-motion data analysts, earthquake and geotechnical engineers, international earthquake response agencies and the educated general public. Access to the RRSM database is via a portal at http://www.orfeus-eu.org/rrsm/ that allows users to query earthquake information, peak ground motion parameters and amplitudes of spectral response; and to select and download earthquake waveforms. All information is available within minutes of any earthquake with magnitude ≥ 3.5 occurring in the Euro-Mediterranean region. Waveform processing and database population are performed using the waveform processing module scwfparam, which is integrated in SeisComP3 (SC3; http://www.seiscomp3.org/). Earthquake information is provided by the EMSC (http://www.emsc-csem.org/) and all the seismic waveform data is accessed at the European Integrated waveform Data Archive (EIDA) at ORFEUS (http://www.orfeus-eu.org/index.html), where all on-scale data is used in the fully automated processing. As the EIDA community is continually growing, the already significant number of strong motion stations is also increasing and the importance of this product is expected to also increase. Real-time RRSM processing started in June 2014, while past events have been processed in order to provide a complete database back to 2005.

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

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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

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....

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)

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

Sensitive and selective system of benzene detection based on a cataluminescence sensor.

Science.gov (United States)

Li, Bo; Zhang, Yuejin; Liu, Juefu; Xie, Xin; Zou, Dan; Li, Minqiang; Liu, Jinhuai

2014-06-01

Au/La2 O3 nanomaterials were prepared through calcining Au-modified La(OH)3 precursors. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffractometry (XRD) were employed to characterize the as-prepared samples. Benzene, a common volatile organic compound, was selected as a model to investigate the cataluminescence (CTL)-sensing properties of the Au/La2 O3 nanomaterials. Results indicated that the as-prepared Au/La2 O3 exhibited outstanding CTL properties such as stable intensity, high signal-to-noise values, and short response and recovery times. Under optimized conditions, the benzene assay exhibited a broad linear range of 1-4000 ppm, with a limit of detection of 0.7 ppm, which was below the standard permitted concentrations. Furthermore, the gas sensor system showed outstanding selectivity for benzene compared with seven other types of common volatile organic compounds (VOCs). The proposed gas sensor showed good characteristics with high selectivity, fast response time and long lifetime, which suggested the promising application of the Au/La2 O3 nanomaterials as a novel highly efficient CTL-sensing material. Copyright © 2013 John Wiley & Sons, Ltd.

An item response theory analysis of Harter's Self-Perception Profile for children or why strong clinical scales should be distrusted.

Science.gov (United States)

Egberink, Iris J L; Meijer, Rob R

2011-06-01

The authors investigated the psychometric properties of the subscales of the Self-Perception Profile for Children with item response theory (IRT) models using a sample of 611 children. Results from a nonparametric Mokken analysis and a parametric IRT approach for boys (n = 268) and girls (n = 343) were compared. The authors found that most scales formed weak scales and that measurement precision was relatively low and only present for latent trait values indicating low self-perception. The subscales Physical Appearance and Global Self-Worth formed one strong scale. Children seem to interpret Global Self-Worth items as if they measure Physical Appearance. Furthermore, the authors found that strong Mokken scales (such as Global Self-Worth) consisted mostly of items that repeat the same item content. They conclude that researchers should be very careful in interpreting the total scores on the different Self-Perception Profile for Children scales. Finally, implications for further research are discussed.

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

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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.

Early dominance of irradiated host cells in the responder profiles of thymocytes from P → F1 radiation chimeras

International Nuclear Information System (INIS)

Korngold, R.; Bennink, J.R.; Doherty, P.C.

1981-01-01

The number of cells in the thymus of radiation (1000 rad) chimeras increases approximately 10-fold between 7 and 14 days after reconstitution with bone marrow. At least 50% of the cells in thymus on day 14 are of host origin and respond to virus presented in the context of both H-2/sup k/ and H-2/sup b/ when primed in irradiated, virus-infected (b x k)F 1 recipients. Strong CTL responses can be generated from thymocytes of donor origin on day 21. All evidence of a significant host thymocyte component has disappeared by day 28. The responsiveness of 14-day thymocytes is not abrogated by pretreatment of the mice used to make the chimeras with anti-thymocyte serum or by using doses of irradiation as high as 1200 rads to eliminate host components

Infection of goose with genotype VIId Newcastle disease virus of goose origin elicits strong immune responses at early stage

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Qianqian Xu

2016-10-01

Full Text Available Newcastle disease (ND, caused by virulent strains of Newcastle disease virus (NDV, is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06. The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR1–3, 5, 7 and 15, avian β-defensin (AvBD 5–7, 10, 12 and 16, cytokines interleukin (IL-8, IL-18, IL-1β and interferon-γ, inducible NO synthase (iNOS, and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10 and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus.

Science.gov (United States)

Kreijtz, J H C M; Bodewes, R; van den Brand, J M A; de Mutsert, G; Baas, C; van Amerongen, G; Fouchier, R A M; Osterhaus, A D M E; Rimmelzwaan, G F

2009-08-06

The transmission of highly pathogenic avian influenza (HPAI) A viruses of the H5N1 subtype from poultry to man and the high case fatality rate fuels the fear for a pandemic outbreak caused by these viruses. However, prior infections with seasonal influenza A/H1N1 and A/H3N2 viruses induce heterosubtypic immunity that could afford a certain degree of protection against infection with the HPAI A/H5N1 viruses, which are distantly related to the human influenza A viruses. To assess the protective efficacy of such heterosubtypic immunity mice were infected with human influenza virus A/Hong Kong/2/68 (H3N2) 4 weeks prior to a lethal infection with HPAI virus A/Indonesia/5/05 (H5N1). Prior infection with influenza virus A/Hong Kong/2/68 reduced clinical signs, body weight loss, mortality and virus replication in the lungs as compared to naive mice infected with HPAI virus A/Indonesia/5/05. Priming by infection with respiratory syncytial virus, a non-related virus did not have a beneficial effect on the outcome of A/H5N1 infections, indicating that adaptive immune responses were responsible for the protective effect. In mice primed by infection with influenza A/H3N2 virus cytotoxic T lymphocytes (CTL) specific for NP(366-374) epitope ASNENMDAM and PA(224-232) SCLENFRAYV were observed. A small proportion of these CTL was cross-reactive with the peptide variant derived from the influenza A/H5N1 virus (ASNENMEVM and SSLENFRAYV respectively) and upon challenge infection with the influenza A/H5N1 virus cross-reactive CTL were selectively expanded. These CTL, in addition to those directed to conserved epitopes, shared by the influenza A/H3N2 and A/H5N1 viruses, most likely contributed to accelerated clearance of the influenza A/H5N1 virus infection. Although also other arms of the adaptive immune response may contribute to heterosubtypic immunity, the induction of virus-specific CTL may be an attractive target for development of broad protective vaccines. Furthermore the

Characterization of the Apa antigen from M. avium subsp. paratuberculosis: a conserved Mycobacterium antigen that elicits a strong humoral response in cattle.

Science.gov (United States)

Gioffré, A; Echeverría-Valencia, G; Arese, A; Morsella, C; Garbaccio, S; Delgado, F; Zumárraga, M; Paolicchi, F; Cataldi, A; Romano, M I

2009-12-15

Johne's disease or paratuberculosis is widespread in almost all countries and remains difficult to eradicate. Nowadays, diagnosis of Mycobacterium avium subsp. paratuberculosis (MPTB) infection is one of the main concerns. In this work, we evaluated the expression, biochemical properties and antigenicity of the Apa antigen, encoded by the gene annotated as MAP1569, in the MPTB genome. We confirmed its expression in MPTB and its glycosylation by the ConA binding assay. Although the MPTB-Apa is not an immunodominant antigen, MPTB-infected cattle showed a strong humoral response to recombinant Apa by Western blot and ELISA. Milk was also a suitable sample to be tested by ELISA. We comparatively analysed the humoral cross-reactivity to the Apa from MPTB (MPTB-Apa) and the orthologue from Mycobacterium tuberculosis (MT-Apa, identical to that from Mycobacterium bovis) in both infected and control cows. Response of M. bovis- and MPTB-infected animals against MT-Apa was similar (P=0.6985) but the response of the M. bovis-infected ones to MPTB-Apa was differential, being significantly diminished (PApa stimulation in the IFNgamma release assay, we found no significant differences when compared infected herds with non-infected ones (P=0.34). This antigen, in contrast to bovine Purified Protein Derivative (PPDb), was strongly represented in avian PPD (PPDa), as shown by the recognition of BALB/c mice hyperimmune sera against MPTB-Apa by Dot-blot immunoassay. We therefore demonstrated the antigenicity of Apa in MPTB-infected animals and a differential response to the recombinant antigen when compared to M. bovis-infected animals. These traits herein described, added to the usefulness of milk samples to detect IgG anti-Apa, could be important for routine screening in dairy cattle, considering a multiantigenic approach to overcome the lack of immunodominance.

Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA

International Nuclear Information System (INIS)

Wyatt, Linda S.; Belyakov, Igor M.; Earl, Patricia L.; Berzofsky, Jay A.; Moss, Bernard

2008-01-01

During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermal (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines

Report of the U.S. Nuclear Regulatory Commission Piping Review Committee. Summary and evaluation of historical strong-motion earthquake seismic response and damage to aboveground industrial piping

International Nuclear Information System (INIS)

1985-04-01

The primary purpose of this report is to collect in one reference document the observation and experience that has been developed with regard to the seismic behavior of aboveground, building-supported, industrial-type process piping (similar to piping used in nuclear power plants) in strong-motion earthquakes. The report will also contain observations regarding the response of piping in strong-motion experimental tests and appropriate conclusions regarding the behavior of such piping in large earthquakes. Recommendations are included covering the future design of such piping to resist earthquake motion damage based on observed behavior in large earthquakes and simulated shake table testing. Since available detailed data on the behavior of aboveground (building-supported) piping are quite limited, this report will draw heavily on the observations and experiences of experts in the field. In Section 2 of this report, observed earthquake damage to aboveground piping in a number of large-motion earthquakes is summarized. In Section 3, the available experience from strong-motion testing of piping in experimental facilities is summarized. In Section 4 are presented some observations that attempt to explain the observed response of piping to strong-motion excitation from actual earthquakes and shake table testing. Section 5 contains the conclusions based on this study and recommendations regarding the future seismic design of piping based on the observed strong-motion behavior and material developed for the NPC Piping Review Committee. Finally, in Section 6 the references used in this study are presented. It should be understood that the use of the term piping in this report, in general, is limited to piping supported by building structures. It does not include behavior of piping buried in soil media. It is believed that the seismic behavior of buried piping is governed primarily by the deformation of the surrounding soil media and is not dependent on the inertial response

Enhanced suppressor cell activity as a mechanism of immunosuppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin

Energy Technology Data Exchange (ETDEWEB)

Clark, D.A.; Gauldie, J.; Szewczuk, M.R.; Sweeney, G.

1981-11-01

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a toxic halogenated aromatic hydrocarbon, acts in the body as a cumulative poison. The chronic immunotoxic effects of TCDD were studied in C57B1/6 male mice. Total doses of 100 ..mu..g/kg or greater produced cellular depletion in thymus, spleen, and lymph nodes, and the animals appeared sick. No cellular depletion was seen following 0.4 ..mu..g/kg, and only thymus was affected by 4 and 40 ..mu..g/kg. The antibody response to SRBC and TNP-Brucella abortus was impaired following ..mu..g/kg and the generation of alloantigen-specific cytotoxic T cells (CTL) was sensitive to as little as 0.004 ..mu..g/kg TCDD. In vitro analysis of the mechanism of suppression using limiting dilution techniques showed that TCDD did not deplete the precursors of CTL but generated cells capable of suppressing CTL generation in vitro.

Human Cytotoxic T Lymphocytes Form Dysfunctional Immune Synapses with B Cells Characterized by Non-Polarized Lytic Granule Release

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Anna Kabanova

2016-04-01

Full Text Available Suppression of the cytotoxic T cell (CTL immune response has been proposed as one mechanism for immune evasion in cancer. In this study, we have explored the underlying basis for CTL suppression in the context of B cell malignancies. We document that human B cells have an intrinsic ability to resist killing by freshly isolated cytotoxic T cells (CTLs, but are susceptible to lysis by IL-2 activated CTL blasts and CTLs isolated from immunotherapy-treated patients with chronic lymphocytic leukemia (CLL. Impaired killing was associated with the formation of dysfunctional non-lytic immune synapses characterized by the presence of defective linker for activation of T cells (LAT signaling and non-polarized release of the lytic granules transported by ADP-ribosylation factor-like protein 8 (Arl8. We propose that non-lytic degranulation of CTLs are a key regulatory mechanism of evasion through which B cells may interfere with the formation of functional immune synapses by CTLs.

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

Cell-mediated immune responses in rainbow trout after DNA immunization against the viral hemorrhagic septicemia virus

DEFF Research Database (Denmark)

Utke, Katrin; Kock, Holger; Schuetze, Heike

2008-01-01

injection site rather than to injection sites of heterologous vaccines, suggesting the antigen specificity of homing. By demonstrating CMC responses to distinct viral proteins and homing in rainbow trout, these results substantially contribute to the understanding of the teleost immune system.......To identify viral proteins that induce cell-mediated cytotoxicity (CMC) against viral hemorrhagic septicemia virus (VHSV)-infected cells, rainbow trout were immunized with DNA vectors encoding the glycoprotein G or the nucleocapsid protein N of VHSV. The G protein was a more potent trigger...... of cytotoxic cells than the N protein. Peripheral blood leukocytes (PBL) isolated from trout immunized against the G protein killed both VHSV-infected MHC class I matched (RTG-2) and VHSV-infected xenogeneic (EPC) target cells, suggesting the involvement of both cytotoxic T lymphocytes (CTL) and NK cells...

PRISM software—Processing and review interface for strong-motion data

Science.gov (United States)

Jones, Jeanne M.; Kalkan, Erol; Stephens, Christopher D.; Ng, Peter

2017-11-28

Rapidly available and accurate ground-motion acceleration time series (seismic recordings) and derived data products are essential to quickly providing scientific and engineering analysis and advice after an earthquake. To meet this need, the U.S. Geological Survey National Strong Motion Project has developed a software package called PRISM (Processing and Review Interface for Strong-Motion data). PRISM automatically processes strong-motion acceleration records, producing compatible acceleration, velocity, and displacement time series; acceleration, velocity, and displacement response spectra; Fourier amplitude spectra; and standard earthquake-intensity measures. PRISM is intended to be used by strong-motion seismic networks, as well as by earthquake engineers and seismologists.

Steel Moment-Resisting Frame Responses in Simulated Strong Ground Motions: or How I Learned to Stop Worrying and Love the Big One

OpenAIRE

Olsen, Anna

2008-01-01

This thesis studies the response of steel moment-resisting frame buildings in simulated strong ground motions. I collect 37 simulations of crustal earthquakes in California. These ground motions are applied to nonlinear finite element models of four types of steel moment frame buildings: six- or twenty-stories with either a stiffer, higherstrength design or a more flexible, lower-strength design. I also consider the presence of fracture-prone welds in each design. Since these b...

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

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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

Antigen-Specific Polyclonal Cytotoxic T Lymphocytes Induced by Fusions of Dendritic Cells and Tumor Cells

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Shigeo Koido

2010-01-01

Full Text Available The aim of cancer vaccines is induction of tumor-specific cytotoxic T lymphocytes (CTLs that can reduce the tumor mass. Dendritic cells (DCs are potent antigen-presenting cells and play a central role in the initiation and regulation of primary immune responses. Thus, DCs-based vaccination represents a potentially powerful strategy for induction of antigen-specific CTLs. Fusions of DCs and whole tumor cells represent an alternative approach to deliver, process, and subsequently present a broad spectrum of antigens, including those known and unidentified, in the context of costimulatory molecules. Once DCs/tumor fusions have been infused back into patient, they migrate to secondary lymphoid organs, where the generation of antigen-specific polyclonal CTL responses occurs. We will discuss perspectives for future development of DCs/tumor fusions for CTL induction.

Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

International Nuclear Information System (INIS)

Ordonhez Rigato, Paula; Maciel, Milton; Goldoni, Adriana Leticia; Piubelli, Orlando; Alves de Brito, Cyro; Fusaro, Ana Elisa; Eurico de Alencar, Liciana Xavier; August, Thomas; Torres Azevedo Marques, Ernesto; Silva Duarte, Alberto Jose da; Sato, Maria Notomi

2010-01-01

Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-γ, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric LAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory.

Temporal genetic stability in natural populations of the waterflea Daphnia magna in response to strong selection pressure.

Science.gov (United States)

Orsini, Luisa; Marshall, Hollie; Cuenca Cambronero, Maria; Chaturvedi, Anurag; Thomas, Kelley W; Pfrender, Michael E; Spanier, Katina I; De Meester, Luc

2016-12-01

Studies monitoring changes in genetic diversity and composition through time allow a unique understanding of evolutionary dynamics and persistence of natural populations. However, such studies are often limited to species with short generation times that can be propagated in the laboratory or few exceptional cases in the wild. Species that produce dormant stages provide powerful models for the reconstruction of evolutionary dynamics in the natural environment. A remaining open question is to what extent dormant egg banks are an unbiased representation of populations and hence of the species' evolutionary potential, especially in the presence of strong environmental selection. We address this key question using the water flea Daphnia magna, which produces dormant stages that accumulate in biological archives over time. We assess temporal genetic stability in three biological archives, previously used in resurrection ecology studies showing adaptive evolutionary responses to rapid environmental change. We show that neutral genetic diversity does not decline with the age of the population and it is maintained in the presence of strong selection. In addition, by comparing temporal genetic stability in hatched and unhatched populations from the same biological archive, we show that dormant egg banks can be consulted to obtain a reliable measure of genetic diversity over time, at least in the multidecadal time frame studied here. The stability of neutral genetic diversity through time is likely mediated by the buffering effect of the resting egg bank. © 2016 John Wiley & Sons Ltd.

Earthquake source model using strong motion displacement

Indian Academy of Sciences (India)

The strong motion displacement records available during an earthquake can be treated as the response of the earth as the a structural system to unknown forces acting at unknown locations. Thus, if the part of the earth participating in ground motion is modelled as a known finite elastic medium, one can attempt to model the ...

Influence of earthquake strong motion duration on nonlinear structural response

International Nuclear Information System (INIS)

Meskouris, K.

1983-01-01

The effects of motion duration on nonlinear structural response of high-rise, moment resisting frames are studied by subjecting shear beam models of a 10- and a 5-story frame to a series of synthetic accelerograms, all matching the same NEWMARK/HALL design spectrum. Two different hysteretic laws are used for the story springs, and calculations are carried out for target ductility values of 2 and 4. Maximum ductilities reached and energy-based damage indicators (maximum seismically input energy, hysteretically dissipated energy) are evaluated and correlated with the motion characteristics. A reasonable extrapolative determination of structural response characteristics based on these indicators seems possible. (orig.)

Strong and multi-antigen specific immunity by hepatitis B core antigen (HBcAg)-based vaccines in a murine model of chronic hepatitis B: HBcAg is a candidate for a therapeutic vaccine against hepatitis B virus.

Science.gov (United States)

Akbar, Sheikh Mohammad Fazle; Chen, Shiyi; Al-Mahtab, Mamun; Abe, Masanori; Hiasa, Yoichi; Onji, Morikazu

2012-10-01

Experimental evidence suggests that hepatitis B core antigen (HBcAg)-specific cytotoxic T lymphocytes (CTL) are essential for the control of hepatitis B virus (HBV) replication and prevention of liver damage in patients with chronic hepatitis B (CHB). However, most immune therapeutic approaches in CHB patients have been accomplished with hepatitis B surface antigen (HBsAg)-based prophylactic vaccines with unsatisfactory clinical outcomes. In this study, we prepared HBsAg-pulsed dendritic cells (DC) and HBcAg-pulsed DC by culturing spleen DC from HBV transgenic mice (HBV TM) and evaluated the immunomodulatory capabilities of these antigens, which may serve as a better therapy for CHB. The kinetics of HBsAg, antibody levels against HBsAg (anti-HBs), proliferation of HBsAg- and HBcAg-specific lymphocytes, production of antigen-specific CTL, and activation of endogenous DC were compared between HBV TM vaccinated with either HBsAg- or HBcAg-pulsed DC. Vaccination with HBsAg-pulsed DC induced HBsAg-specific immunity, but failed to induce HBcAg-specific immunity in HBV TM. However, immunization of HBV TM with HBcAg-pulsed DC resulted in: (1) HBsAg negativity, (2) production of anti-HBs, and (3) development of HBsAg- and HBcAg-specific T cells and CTL in the spleen and the liver. Additionally, significantly higher levels of activated endogenous DC were detected in HBV TM immunized with HBcAg-pulsed DC compared to HBsAg-pulsed DC (pdamage suggests that HBcAg should be an integral component of the therapeutic vaccine against CHB. Copyright © 2012 Elsevier B.V. All rights reserved.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

International Nuclear Information System (INIS)

Lubaczeuski, C.; Balbo, S.L.; Ribeiro, R.A.; Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M.; Bonfleur, M.L.

2015-01-01

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca 2+ mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca 2+ mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats

Altered frontocingulate activation during aversive interoceptive processing in young adults transitioning to problem stimulant use

Directory of Open Access Journals (Sweden)

Jennifer Lorraine Stewart

2013-11-01

Full Text Available Problems associated with stimulant use have been linked to frontocingulate, insular, and thalamic dysfunction during decision-making and alterations in interoceptive processing. However, little is known about how interoception and decision-making interact and contribute to dysfunctions that promote the transition from recreational drug use to abuse or dependence. Here, we investigate brain activation in response to reward, punishment, and uncertainty during an aversive interoceptive challenge in current and former stimulant (cocaine and amphetamine users using functional magnetic resonance imaging (fMRI. Young adults previously identified as recreational users (n=184 were followed up three years later. Of these, 18 individuals progressed to problem stimulant use (PSU, whereas 15 desisted stimulant use (DSU. PSU, DSU, and 14 healthy comparison subjects (CTL performed a two-choice prediction task at three fixed error rates (20%=reward, 50%=uncertainty, 80%=punishment during which they anticipated and experienced episodes of inspiratory breathing load. Although groups did not differ in insula activation or subjective breathing load ratings, PSU exhibited lower right inferior frontal gyrus (IFG and bilateral anterior cingulate (ACC activation than DSU and CTL during aversive interoceptive processing as well as lower right IFG in response to decision making involving uncertainty. However, PSU exhibited greater bilateral IFG activation than DSU and CTL while making choices within the context of punishing feedback, and both PSU and DSU showed lower thalamic activation during breathing load than CTL. Findings suggest that frontocingulate attenuation, reflecting reduced resources devoted to goal maintenance and action selection in the presence of uncertainty and interoceptive perturbations, may be a biomarker for susceptibility to problem stimulant use.

Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells

Directory of Open Access Journals (Sweden)

Stefania Varani

2015-11-01

Full Text Available Toscana virus (TOSV is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs and cytokine levels in plasma and cerebrospinal fluid (CSF from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.

Risk factors for admission and the role of respiratory syncytial virus ...

African Journals Online (AJOL)

disease and poor outcomes when exposed to the influenza virus. Studies of CTL responses ... (IL)8 and IL2) and human neutrophil elastase play a significant ~ role in the ..... Prophylaxis against respiratory syncytial virus in premature infants.

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.

Influence of HLA-D/DR antigen disparity in CTL generation in vitro

International Nuclear Information System (INIS)

Johnsen, H.E.; Madsen, M.; Mossin, J.; Kristensen, T.

1983-01-01

This report describes the influence of HLA-D/-DR antigen disparity upon the level of cytotoxicity in allogeneic in vitro cultures. Allogeneic cultures, between unrelated HLA-D/-DR full house donors, tested in CML gave three different levels of cytotoxicity, termed weak, intermediate and strong cytotoxicity. HLA-D/-DR compatibility predicts weak cytotoxicity and two HLA-B antigen incompatibility predicts strong cytotoxicity. On the contrary, HLA-A antigens have no major influence upon the strength of cytotoxicity. Accepting that the MLC/CML reaction is an in vitro parallel to the in vivo transplantation of allogeneic tissue, the observations are in accordance with the results of HLA-D/-DR matching for graft survival in human renal transplantation. (author)

T cells from fully H-2 allogeneic (A replaced by B) radiation bone marrow chimeras are functionally competent and host restricted but are alloreactive against hybrid Ia determinants expressed on (A x B)F1 cells

International Nuclear Information System (INIS)

Kruisbeek, A.M.; Hathcock, K.S.; Hodes, R.J.; Singer, A.

1982-01-01

In this communication it is demonstrated that T cells from fully allogeneic A replaced by B radiation bone marrow chimeras are alloreactive against the hybrid Ia molecules expressed on the surface of heterozygous A X B cells. These results suggested that previous failures to generate cytotoxic T lymphocyte (CTL) responses from fully allogeneic chimeras by sensitizing the chimeric T cells to antigen in an (A X B)F1-priming environment might have been confounded by an ongoing alloreaction against determinants created by hybrid Ia molecules expressed on F1 cells. Consequently, the ability to generate CTL responses from fully allogeneic chimeras was re-examined by sensitizing the chimeric T cells to antigen presented by homozygous rather that F1 stimulator cells. It was found that T cells of donor bone marrow origin that mediate cytotoxic responses to trinitrophenyl-modified self determinants do differentiate into functional competence in an H-2-incompatible host environment and are restricted to the host H-2 haplotype

Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)responsive Coating and their Application in Hyperthermia and Heat-Triggered Drug Delivery

KAUST Repository

Kakwere, Hamilton; Pernia Leal, Manuel; Materia, Maria-Elena; Curcio, Alberto; Guardia, Pablo; Niculaes, Dina; Marotta, Roberto; Falqui, Andrea; Pellegrino, Teresa

2015-01-01

Herein we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermo-responsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR) but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermo-responsive shell is composed of poly(N-isopropyl acrylamide-co-polyethylene glycolmethylether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.

Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)responsive Coating and their Application in Hyperthermia and Heat-Triggered Drug Delivery

KAUST Repository

Kakwere, Hamilton

2015-04-03

Herein we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermo-responsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR) but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermo-responsive shell is composed of poly(N-isopropyl acrylamide-co-polyethylene glycolmethylether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.

Immune hierarchy among HIV-1 CD8+ T cell epitopes delivered by dendritic cells depends on MHC-I binding irrespective of mode of loading and immunization in HLA-A*0201 mice

DEFF Research Database (Denmark)

Kloverpris, Henrik N; Karlsson, Ingrid; Thorn, Mette

2009-01-01

Recent human immunodeficiency virus type 1 (HIV-1) vaccination strategies aim at targeting a broad range of cytotoxic T lymphocyte (CTL) epitopes from different HIV-1 proteins by immunization with multiple CTL epitopes simultaneously. However, this may establish an immune hierarchical response......, where the immune system responds to only a small number of the epitopes administered. To evaluate the feasibility of such vaccine strategies, we used the human leukocyte antigen (HLA)-A*0201 transgenic (tg) HHD murine in vivo model and immunized with dendritic cells pulsed with seven HIV-1-derived HLA......-gamma)-producing CD8(+) T cells, mainly focused on two of seven administered epitopes. The magnitude of individual T-cell responses induced by immunization with multiple peptides correlated with their individual immunogenicity that depended on major histocompatibility class I binding and was not influenced by mode...

Induction of Foot-and-Mouth Disease Virus-Specific Cytotoxic T Cell Killing by Vaccination

DEFF Research Database (Denmark)

Patch, J.R.; Pedersen, Lasse Eggers; Toka, F.N.

2011-01-01

Foot-and-mouth disease (FMD) continues to be a significant threat to the health and economic value of livestock species. This acute infection is caused by the highly contagious FMD virus (FMDV), which infects cloven-hoofed animals including large and small ruminants and swine. Current vaccine...... cytopathic virus. Here, we have used recombinant human adenovirus vectors as a means of delivering FMDV antigens in a T cell-directed vaccine in pigs. We tested the hypothesis that impaired processing of the FMDV capsid would enhance cytolytic activity, presumably by targeting all proteins for degradation...... and effectively increasing the class I MHC/FMDV peptide concentration for stimulation of a CTL response. We compared such a T cell targeting vaccine with the parental vaccine, previously shown to effectively induce a neutralizing antibody response. Our results show induction of FMDV-specific CD8(+) CTL killing...

Holographic Floquet states I: a strongly coupled Weyl semimetal

International Nuclear Information System (INIS)

Hashimoto, Koji; Kinoshita, Shunichiro; Murata, Keiju; Oka, Takashi

2017-01-01

Floquet states can be realized in quantum systems driven by continuous time-periodic perturbations. It is known that a state known as the Floquet Weyl semimetal can be realized when free Dirac fermions are placed in a rotating electric field. What will happen if strong interaction is introduced to this system? Will the interaction wash out the characteristic features of Weyl semimetals such as the Hall response? Is there a steady state and what is its thermodynamic behavior? We answer these questions using AdS/CFT correspondence in the N=2 supersymmetric massless QCD in a rotating electric field in the large N c limit realizing the first example of a “holographic Floquet state”. In this limit, gluons not only mediate interaction, but also act as an energy reservoir and stabilize the nonequilibrium steady state (NESS). We obtain the electric current induced by a rotating electric field: in the high frequency region, the Ohm’s law is satisfied, while we recover the DC nonlinear conductivity at low frequency, which was obtained holographically in a previous work. The thermodynamic properties of the NESS, e.g., fluctuation-dissipation relation, is characterized by the effective Hawking temperature that is defined from the effective horizon giving a holographic meaning to the “periodic thermodynamic” concept. In addition to the strong (pump) rotating electric field, we apply an additional weak (probe) electric field in the spirit of the pump-probe experiments done in condensed matter experiments. Weak DC and AC probe analysis in the background rotating electric field shows Hall currents as a linear response, therefore the Hall response of Floquet Weyl semimetals survives at the strong coupling limit. We also find frequency mixed response currents, i.e., a heterodyning effect, characteristic to periodically driven Floquet systems.

Holographic Floquet states I: a strongly coupled Weyl semimetal

Energy Technology Data Exchange (ETDEWEB)

Hashimoto, Koji [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Kinoshita, Shunichiro [Department of Physics, Chuo University, Tokyo 112-8551 (Japan); Murata, Keiju [Keio University, 4-1-1 Hiyoshi, Yokohama 223-8521 (Japan); Oka, Takashi [Max-Planck-Institut für Physik komplexer Systeme (MPI-PKS), Nöthnitzer Straße 38, Dresden 01187 (Germany); Max-Planck-Institut für Chemische Physik fester Stoffe (MPI-CPfS),Nöthnitzer Straße 40, Dresden 01187 (Germany)

2017-05-23

Floquet states can be realized in quantum systems driven by continuous time-periodic perturbations. It is known that a state known as the Floquet Weyl semimetal can be realized when free Dirac fermions are placed in a rotating electric field. What will happen if strong interaction is introduced to this system? Will the interaction wash out the characteristic features of Weyl semimetals such as the Hall response? Is there a steady state and what is its thermodynamic behavior? We answer these questions using AdS/CFT correspondence in the N=2 supersymmetric massless QCD in a rotating electric field in the large N{sub c} limit realizing the first example of a “holographic Floquet state”. In this limit, gluons not only mediate interaction, but also act as an energy reservoir and stabilize the nonequilibrium steady state (NESS). We obtain the electric current induced by a rotating electric field: in the high frequency region, the Ohm’s law is satisfied, while we recover the DC nonlinear conductivity at low frequency, which was obtained holographically in a previous work. The thermodynamic properties of the NESS, e.g., fluctuation-dissipation relation, is characterized by the effective Hawking temperature that is defined from the effective horizon giving a holographic meaning to the “periodic thermodynamic” concept. In addition to the strong (pump) rotating electric field, we apply an additional weak (probe) electric field in the spirit of the pump-probe experiments done in condensed matter experiments. Weak DC and AC probe analysis in the background rotating electric field shows Hall currents as a linear response, therefore the Hall response of Floquet Weyl semimetals survives at the strong coupling limit. We also find frequency mixed response currents, i.e., a heterodyning effect, characteristic to periodically driven Floquet systems.

Holographic Floquet states I: a strongly coupled Weyl semimetal

Science.gov (United States)

Hashimoto, Koji; Kinoshita, Shunichiro; Murata, Keiju; Oka, Takashi

2017-05-01

Floquet states can be realized in quantum systems driven by continuous time-periodic perturbations. It is known that a state known as the Floquet Weyl semimetal can be realized when free Dirac fermions are placed in a rotating electric field. What will happen if strong interaction is introduced to this system? Will the interaction wash out the characteristic features of Weyl semimetals such as the Hall response? Is there a steady state and what is its thermodynamic behavior? We answer these questions using AdS/CFT correspondence in the N = 2 supersymmetric massless QCD in a rotating electric field in the large N c limit realizing the first example of a "holographic Floquet state". In this limit, gluons not only mediate interaction, but also act as an energy reservoir and stabilize the nonequilibrium steady state (NESS). We obtain the electric current induced by a rotating electric field: in the high frequency region, the Ohm's law is satisfied, while we recover the DC nonlinear conductivity at low frequency, which was obtained holographically in a previous work. The thermodynamic properties of the NESS, e.g., fluctuation-dissipation relation, is characterized by the effective Hawking temperature that is defined from the effective horizon giving a holographic meaning to the "periodic thermodynamic" concept. In addition to the strong (pump) rotating electric field, we apply an additional weak (probe) electric field in the spirit of the pump-probe experiments done in condensed matter experiments. Weak DC and AC probe analysis in the background rotating electric field shows Hall currents as a linear response, therefore the Hall response of Floquet Weyl semimetals survives at the strong coupling limit. We also find frequency mixed response currents, i.e., a heterodyning effect, characteristic to periodically driven Floquet systems.

Towards TDDFT for Strongly Correlated Materials

Directory of Open Access Journals (Sweden)

Shree Ram Acharya

2016-09-01

Full Text Available We present some details of our recently-proposed Time-Dependent Density-Functional Theory (TDDFT for strongly-correlated materials in which the exchange-correlation (XC kernel is derived from the charge susceptibility obtained using Dynamical Mean-Field Theory (the TDDFT + DMFT approach. We proceed with deriving the expression for the XC kernel for the one-band Hubbard model by solving DMFT equations via two approaches, the Hirsch–Fye Quantum Monte Carlo (HF-QMC and an approximate low-cost perturbation theory approach, and demonstrate that the latter gives results that are comparable to the exact HF-QMC solution. Furthermore, through a variety of applications, we propose a simple analytical formula for the XC kernel. Additionally, we use the exact and approximate kernels to examine the nonhomogeneous ultrafast response of two systems: a one-band Hubbard model and a Mott insulator YTiO3. We show that the frequency dependence of the kernel, i.e., memory effects, is important for dynamics at the femtosecond timescale. We also conclude that strong correlations lead to the presence of beats in the time-dependent electric conductivity in YTiO3, a feature that could be tested experimentally and that could help validate the few approximations used in our formulation. We conclude by proposing an algorithm for the generalization of the theory to non-linear response.

<strong>Mini-project>

DEFF Research Database (Denmark)

Katajainen, Jyrki

2008-01-01

In this project the goal is to develop the safe * family of containers for the CPH STL. The containers to be developed should be safer and more reliable than any of the existing implementations. A special focus should be put on strong exception safety since none of the existing prototypes available...

The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

Science.gov (United States)

Munier, C Mee Ling; van Bockel, David; Bailey, Michelle; Ip, Susanna; Xu, Yin; Alcantara, Sheilajen; Liu, Sue Min; Denyer, Gareth; Kaplan, Warren; Suzuki, Kazuo; Croft, Nathan; Purcell, Anthony; Tscharke, David; Cooper, David A; Kent, Stephen J; Zaunders, John J; Kelleher, Anthony D

2016-10-17

Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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.

On the strong CP problem

Energy Technology Data Exchange (ETDEWEB)

Dowrick, N.J. (Dept. of Physics, Oxford (United Kingdom)); McDougall, N.A. (National Lab. for High Energy Physics, Tsukuba, Ibaraki (Japan))

1992-07-09

We show that two well-known solutions to the strong CP problem, the axion and a massless quark, may be understood in terms of the mechanism recently proposed by Samuel where long-range interactions between topological charges may be responsible for the removal of CP violation. We explain how the axion and a QCD meson (identified as the {eta}' if all quarks are massless) suppress fluctuations in global topological charge by almost identical dynamical although the masses, couplings and relevant length scales are very different. Furthermore, we elucidate the precise origin of the {eta}' mass. (orig.).

The strong selective sweep candidate gene ADRA2C does not explain domestication related changes in the stress response of chickens.

Directory of Open Access Journals (Sweden)

Magnus Elfwing

Full Text Available Analysis of selective sweeps to pinpoint causative genomic regions involved in chicken domestication has revealed a strong selective sweep on chromosome 4 in layer chickens. The autoregulatory α-adrenergic receptor 2C (ADRA2C gene is the closest to the selective sweep and was proposed as an important gene in the domestication of layer chickens. The ADRA2C promoter region was also hypermethylated in comparison to the non-selected ancestor of all domesticated chicken breeds, the Red Junglefowl, further supporting its relevance. In mice the receptor is involved in the fight-or-flight response as it modulates epinephrine release from the adrenals. To investigate the involvement of ADRA2C in chicken domestication, we measured gene expression in the adrenals and radiolabeled receptor ligand in three brain regions comparing the domestic White Leghorn strain with the wild ancestor Red Junglefowl. In adrenals ADRA2C was twofold greater expressed than the related receptor gene ADRA2A, indicating that ADRA2C is the predominant modulator of epinephrine release but no strain differences were measured. In hypothalamus and amygdala, regions associated with the stress response, and in striatum, receptor binding pIC50 values ranged between 8.1-8.4, and the level was not influenced by the genotyped allele. Because chicken strains differ in morphology, physiology and behavior, differences attributed to a single gene may be lost in the noise caused by the heterogeneous genetic background. Therefore an F10 advanced intercross strain between White Leghorn and Red Junglefowl was used to investigate effects of ADRA2C alleles on fear related behaviors and fecundity. We did not find compelling genotype effects in open field, tonic immobility, aerial predator, associative learning or fecundity. Therefore we conclude that ADRA2C is probably not involved in the domestication of the stress response in chicken, and the strong selective sweep is probably caused by selection

The response of the Red Sea to a strong wind jet near the Tokar Gap in summer

KAUST Repository

Zhai, Ping

2013-01-01

[1] Remote sensing and in situ observations are used to investigate the ocean response to the Tokar Wind Jet in the Red Sea. The wind jet blows down the atmospheric pressure gradient through the Tokar Gap on the Sudanese coast, at about 19°N, during the summer monsoon season. It disturbs the prevailing along-sea (southeastward) winds with strong cross-sea (northeastward) winds that can last from days to weeks and reach amplitudes of 20-25 m/s. By comparing scatterometer winds with along-track and gridded sea level anomaly observations, it is observed that an intense dipolar eddy spins up in response to the wind jet. The eddy pair has a horizontal scale of 140 km. Maximum ocean surface velocities can reach 1 m/s and eddy currents extend more than 100 m into the water column. The eddy currents appear to cover the width of the sea, providing a pathway for rapid transport of marine organisms and other drifting material from one coast to the other. Interannual variability in the strength of the dipole is closely matched with variability in the strength of the wind jet. The dipole is observed to be quasi-stationary, although there is some evidence for slow eastward propagation in an idealized numerical model. Simulation of the dipole in an idealized high-resolution numerical model suggests that this is the result of self-advection. © 2012. American Geophysical Union. All Rights Reserved.

Rb2Na(NO33: A Congruently Melting UV-NLO Crystal with a Very Strong Second-Harmonic Generation Response

Directory of Open Access Journals (Sweden)

Guohong Zou

2016-04-01

Full Text Available Crystals of congruently melting noncentrosymmetric (NCS mixed alkali metal nitrate, Rb2Na(NO33, have been grown through solid state reactions. The material possesses layers with NaO8 hexagonal bipyramids and NO3 triangular units. Rb+ cations are residing in the interlayer space. Each NaO8 hexagonal bipyramid shares its corners and edges with two and three NO3 units, respectively, in order to fulfill a highly dense stacking in the unit cell. The NaO8 groups share their six oxygen atoms in equatorial positions with three different NO3 groups to generate a NaO6-NO3 layer with a parallel alignment. The optimized arrangement of the NO3 groups and their high density in the structure together produce a strong second-harmonic generation (SHG response. Powder SHG measurements indicate that Rb2Na(NO33 has a strong SHG efficiency of five times that of KH2PO4 (KDP and is type I phase-matchable. The calculated average nonlinear optical (NLO susceptibility of Rb2Na(NO33 turns out to be the largest value among the NLO materials composed of only [NO3]− anion. In addition, Rb2Na(NO33 exhibits a wide transparency region ranging from UV to near IR, which suggests that the compound is a promising NLO material.

Vagotomy ameliorates islet morphofunction and body metabolic homeostasis in MSG-obese rats

Energy Technology Data Exchange (ETDEWEB)

Lubaczeuski, C.; Balbo, S.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil); Ribeiro, R.A. [Universidade Federal do Rio de Janeiro, Macaé, RJ (Brazil); Vettorazzi, J.F.; Santos-Silva, J.C.; Carneiro, E.M. [Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP (Brazil); Bonfleur, M.L. [Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná, Cascavel, PR (Brazil)

2015-02-24

The parasympathetic nervous system is important for β-cell secretion and mass regulation. Here, we characterized involvement of the vagus nerve in pancreatic β-cell morphofunctional regulation and body nutrient homeostasis in 90-day-old monosodium glutamate (MSG)-obese rats. Male newborn Wistar rats received MSG (4 g/kg body weight) or saline [control (CTL) group] during the first 5 days of life. At 30 days of age, both groups of rats were submitted to sham-surgery (CTL and MSG groups) or subdiaphragmatic vagotomy (Cvag and Mvag groups). The 90-day-old MSG rats presented obesity, hyperinsulinemia, insulin resistance, and hypertriglyceridemia. Their pancreatic islets hypersecreted insulin in response to glucose but did not increase insulin release upon carbachol (Cch) stimulus, despite a higher intracellular Ca{sup 2+} mobilization. Furthermore, while the pancreas weight was 34% lower in MSG rats, no alteration in islet and β-cell mass was observed. However, in the MSG pancreas, increases of 51% and 55% were observed in the total islet and β-cell area/pancreas section, respectively. Also, the β-cell number per β-cell area was 19% higher in MSG rat pancreas than in CTL pancreas. Vagotomy prevented obesity, reducing 25% of body fat stores and ameliorated glucose homeostasis in Mvag rats. Mvag islets demonstrated partially reduced insulin secretion in response to 11.1 mM glucose and presented normalization of Cch-induced Ca{sup 2+} mobilization and insulin release. All morphometric parameters were similar among Mvag and CTL rat pancreases. Therefore, the higher insulin release in MSG rats was associated with greater β-cell/islet numbers and not due to hypertrophy. Vagotomy improved whole body nutrient homeostasis and endocrine pancreatic morphofunction in Mvag rats.

MUC1-specific CTLs are non-functional within a pancreatic tumor microenvironment.

Science.gov (United States)

Mukherjee, P; Ginardi, A R; Madsen, C S; Tinder, T L; Jacobs, F; Parker, J; Agrawal, B; Longenecker, B M; Gendler, S J

2001-01-01

Pancreatic cancer is a highly aggressive, treatment refractory disease and is the fourth leading cause of death in the United States. In humans, 90% of pancreatic adenocarcinomas over-express altered forms of a tumor-associated antigen, MUC1 (an epithelial mucin glycoprotein), which is a target for immunotherapy. Using a clinically relevant mouse model of pancreas cancer that demonstrates peripheral and central tolerance to human MUC1 and develops spontaneous tumors of the pancreas, we have previously reported the presence of functionally active, low affinity, MUC1-specific precursor cytotoxic T cells (pCTLs). Hypothesis for this study is that MUC1-based immunization may enhance the low level MUC1-specific immunity that may lead to an effective anti-tumor response. Data demonstrate that MUC1 peptide-based immunization elicits mature MUC1-specific CTLs in the peripheral lymphoid organs. The mature CTLs secrete IFN-gamma and are cytolytic against MUC1-expressing tumor cells in vitro. However, active CTLs that infiltrate the pancreas tumor microenvironment become cytolytically anergic and are tolerized to MUC1 antigen, allowing the tumor to grow. We demonstrate that the CTL tolerance could be reversed at least in vitro with the use of anti-CD40 co-stimulation. The pancreas tumor cells secrete immunosuppressive cytokines, including IL-10 and TGF-beta that are partly responsible for the down-regulation of CTL activity. In addition, they down-regulate their MHC class I molecules to avoid immune recognition. CD4+ CD25+ T regulatory cells, which secrete IL-10, were also found in the tumor environment. Together these data indicate the use of several immune evasion mechanisms by tumor cells to evade CTL killing. Thus altering the tumor microenvironment to make it more conducive to CTL killing may be key in developing a successful anti-cancer immunotherapy.

PEGylated graphene oxide elicits strong immunological responses despite surface passivation

Science.gov (United States)

Luo, Nana; Weber, Jeffrey K.; Wang, Shuang; Luan, Binquan; Yue, Hua; Xi, Xiaobo; Du, Jing; Yang, Zaixing; Wei, Wei; Zhou, Ruhong; Ma, Guanghui

2017-02-01

Engineered nanomaterials promise to transform medicine at the bio-nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

An attenuated herpes simplex virus type 1 (HSV1 encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

Directory of Open Access Journals (Sweden)

Mariaconcetta Sicurella

Full Text Available Herpes simplex virus types 1 and 2 (HSV1 and HSV2 are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat. In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ, induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1

An attenuated herpes simplex virus type 1 (HSV1) encoding the HIV-1 Tat protein protects mice from a deadly mucosal HSV1 challenge.

Science.gov (United States)

Sicurella, Mariaconcetta; Nicoli, Francesco; Gallerani, Eleonora; Volpi, Ilaria; Berto, Elena; Finessi, Valentina; Destro, Federica; Manservigi, Roberto; Cafaro, Aurelio; Ensoli, Barbara; Caputo, Antonella; Gavioli, Riccardo; Marconi, Peggy C

2014-01-01

Herpes simplex virus types 1 and 2 (HSV1 and HSV2) are common infectious agents in both industrialized and developing countries. They cause recurrent asymptomatic and/or symptomatic infections, and life-threatening diseases and death in newborns and immunocompromised patients. Current treatment for HSV relies on antiviral medications, which can halt the symptomatic diseases but cannot prevent the shedding that occurs in asymptomatic patients or, consequently, the spread of the viruses. Therefore, prevention rather than treatment of HSV infections has long been an area of intense research, but thus far effective anti-HSV vaccines still remain elusive. One of the key hurdles to overcome in anti-HSV vaccine development is the identification and effective use of strategies that promote the emergence of Th1-type immune responses against a wide range of epitopes involved in the control of viral replication. Since the HIV1 Tat protein has several immunomodulatory activities and increases CTL recognition of dominant and subdominant epitopes of heterologous antigens, we generated and assayed a recombinant attenuated replication-competent HSV1 vector containing the tat gene (HSV1-Tat). In this proof-of-concept study we show that immunization with this vector conferred protection in 100% of mice challenged intravaginally with a lethal dose of wild-type HSV1. We demonstrate that the presence of Tat within the recombinant virus increased and broadened Th1-like and CTL responses against HSV-derived T-cell epitopes and elicited in most immunized mice detectable IgG responses. In sharp contrast, a similarly attenuated HSV1 recombinant vector without Tat (HSV1-LacZ), induced low and different T cell responses, no measurable antibody responses and did not protect mice against the wild-type HSV1 challenge. These findings strongly suggest that recombinant HSV1 vectors expressing Tat merit further investigation for their potential to prevent and/or contain HSV1 infection and

Comparison of the inelastic response of steel building frames to strong earthquake and underground nuclear explosion ground motion

International Nuclear Information System (INIS)

Murray, R.C.; Tokarz, F.J.

1976-01-01

Analytic studies were made of the adequacy of simulating earthquake effects at the Nevada Test Site for structural testing purposes. It is concluded that underground nuclear explosion ground motion will produce inelastic behavior and damage comparable to that produced by strong earthquakes. The generally longer duration of earthquakes compared with underground nuclear explosions does not appear to significantly affect the structural behavior of the building frames considered. A comparison of maximum ductility ratios, maximum story drifts, and maximum displacement indicate similar structural behavior for both types of ground motion. Low yield (10 - kt) underground nuclear explosions are capable of producing inelastic behavior in large structures. Ground motion produced by underground nuclear explosions can produce inelastic earthquake-like effects in large structures and could be used for testing large structures in the inelastic response regime. The Nevada Test Site is a feasible earthquake simulator for testing large structures

Strong nonlinear harmonic generation in a PZT/Aluminum resonator

Energy Technology Data Exchange (ETDEWEB)

Parenthoine, D; Haumesser, L; Meulen, F Vander; Tran-Huu-Hue, L-P, E-mail: parenthoine@univ-tours.f [University Francois Rabelais of Tours, U 930 Imagerie et Cerveau, CNRS 2448, ENIVL, rue de la Chocolaterie, BP 3410, 41034 Blois (France)

2009-11-01

In this work, the extentional vibration mode of a coupled PZT/ Aluminum rod resonator is studied experimentally. Geometrical characteristics of the PZT are its 27 mm length and its 4x4 mm{sup 2} cross section area. The excitation voltage consists in sinusoidal bursts in the frequency range (20-80 kHz). Velocity measurements are performed at both ends of this system, using a laser probe. Strong harmonic distortions in the mechanical response (up to -20 dB with respect to the primary wave amplitude) have been observed. The corresponding input levels are far lower than those which are necessary to observe quadratic second harmonic generation in a free PZT resonator. The strong nonlinear effect can be explained as a super-harmonic resonance of the system due to a specific ratio between the eigen frequencies of the two parts of the resonator. Evolution of fundamental and harmonic responses are observed as a function of input levels, highlighting hysteretic behavior.

Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.

Science.gov (United States)

Suehiro, Youko; Hasegawa, Atsuhiko; Iino, Tadafumi; Sasada, Amane; Watanabe, Nobukazu; Matsuoka, Masao; Takamori, Ayako; Tanosaki, Ryuji; Utsunomiya, Atae; Choi, Ilseung; Fukuda, Tetsuya; Miura, Osamu; Takaishi, Shigeo; Teshima, Takanori; Akashi, Koichi; Kannagi, Mari; Uike, Naokuni; Okamura, Jun

2015-05-01

Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL. © 2015 John Wiley & Sons Ltd.

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)

Control of HIV-1 in Elite Suppressors despite Ongoing Replication and Evolution in Plasma Virus▿

Science.gov (United States)

O'Connell, Karen A.; Brennan, Timothy P.; Bailey, Justin R.; Ray, Stuart C.; Siliciano, Robert F.; Blankson, Joel N.

2010-01-01

A subset of HIV-1-infected patients known as elite controllers or suppressors (ES) control the virus naturally. We have previously demonstrated sequence discordance between proviral and plasma gag clones in ES, much of which can be attributed to selective pressure from the host (J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, J. Exp. Med. 203:1357-1369, 2006). However, it is not clear whether ongoing viral replication continues in ES once the control of viremia has been established or whether selective pressure impacts this evolution. The cytotoxic T-lymphocyte (CTL) response in ES often targets Gag and frequently is superior to that of HIV-1 progressors, partially due to the HLA class I alleles B*57/5801 and B*27, which are overrepresented in ES. We therefore examined longitudinal plasma and proviral gag sequences from HLA-B*57/5801 and -B*27 ES. Despite the highly conserved nature of gag, we observed clear evidence of evolution in the plasma virus, largely due to synonymous substitutions. In contrast, evolution was rare in proviral clones, suggesting that ongoing replication in ES does not permit the significant reseeding of the latent reservoir. Interestingly, there was little continual evolution in CTL epitopes, and we detected de novo CTL responses to autologous viral mutants. Thus, some ES control viremia despite ongoing replication and evolution. PMID:20444904

Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

NARCIS (Netherlands)

Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

2012-01-01

Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities

DEFF Research Database (Denmark)

Leitman, Ellen M.; Palmer, Christine D.; Buus, Søren

2017-01-01

Antigen-specific T-cells are highly variable, spanning potent antiviral efficacy and damaging auto-reactivity. In virus infections, identifying the most efficacious responses is critical to vaccine design. However, current methods depend on indirect measures or on ex vivo expanded CTL clones. We...

Induction of potent NK cell-dependent anti-myeloma cytotoxic T cells in response to combined mapatumumab and bortezomib.

Science.gov (United States)

Neeson, Paul J; Hsu, Andy K; Chen, Yin R; Halse, Heloise M; Loh, Joanna; Cordy, Reece; Fielding, Kate; Davis, Joanne; Noske, Josh; Davenport, Alex J; Lindqvist-Gigg, Camilla A; Humphreys, Robin; Tai, Tsin; Prince, H Miles; Trapani, Joseph A; Smyth, Mark J; Ritchie, David S

2015-09-01

There is increasing evidence that some cancer therapies can promote tumor immunogenicity to boost the endogenous antitumor immune response. In this study, we used the novel combination of agonistic anti-TRAIL-R1 antibody (mapatumumab, Mapa) with low dose bortezomib (LDB) for this purpose. The combination induced profound myeloma cell apoptosis, greatly enhanced the uptake of myeloma cell apoptotic bodies by dendritic cell (DC) and induced anti-myeloma cytotoxicity by both CD8 + T cells and NK cells. Cytotoxic lymphocyte expansion was detected within 24 h of commencing therapy and was maximized when myeloma-pulsed DC were co-treated with low dose bortezomib and mapatumumab (LDB+Mapa) in the presence of NK cells. This study shows that Mapa has two distinct but connected modes of action against multiple myeloma (MM). First, when combined with LDB, Mapa produced powerful myeloma cell apoptosis; secondly, it promoted DC priming and an NK cell-mediated expansion of anti-myeloma cytotoxic lymphocyte (CTL). Overall, this study indicates that Mapa can be used to drive potent anti-MM immune responses.

Advanced glycation end product (AGE) modified proteins in tears of diabetic patients.

Science.gov (United States)

Zhao, Zhenjun; Liu, Jingfang; Shi, Bingyin; He, Shuixiang; Yao, Xiaoli; Willcox, Mark D P

2010-08-11

High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with non-diabetic controls (CTL). Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1D- and 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30-60 kDa, PI 5.2-7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.

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.

Synthesis and strong optical limiting response of graphite oxide covalently functionalized with gallium phthalocyanine

Science.gov (United States)

Li, Yong-Xi; Zhu, Jinhui; Chen, Yu; Zhang, Jinjuan; Wang, Jun; Zhang, Bin; He, Ying; Blau, Werner J.

2011-05-01

A soluble graphite oxide (GO) axially substituted gallium phthalocyanine (PcGa) hybrid material (GO-PcGa) was for the first time synthesized by the reaction of tBu4PcGaCl with GO in anhydrous DMSO at 110 °C in the presence of K2CO3. The formation of a Ga-O bond between PcGa and GO has been confirmed by x-ray photoelectron spectroscopy. In contrast to GO, the D and G bands of GO-PcGa in the Raman spectrum are shifted to the lower wavenumbers by Δν = 11 and 18 cm - 1, respectively. At the same level of concentration of 0.1 g l - 1, GO-PcGa exhibit much larger nonlinear optical extinction coefficients and strong optical limiting performance than GO, tBu4PcGaCl and C60 at both 532 and 1064 nm, implying a remarkable accumulation effect as a result of the covalent link between GO and PcGa. GO-PcGa possesses three main mechanisms for the nonlinear optical response—nonlinear light scattering, two-photon absorption and reverse saturable absorption for the 532 nm pulses and nonlinear light scattering for the 1064 nm pulses. tBu4PcGaCl does not make any significant contribution to the optical limiting at 1064 nm, while GO-PcGa has a much greater optical limiting response than GO at this wavelength, this suggesting that the PcGa moiety could certainly play an unknown but important role in the GO-PcGa material system.

Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes

DEFF Research Database (Denmark)

Hofmann, Uta B; Voigt, Heike; Andersen, Mads H

2009-01-01

for potential binding K(b)-restricted octamer peptide epitopes. Two epitopes, which bind strongly to K(b), were selected to test their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature DC pulsed with these peptides displayed reactivity to the respective epitopes...

STRONG SOLAR WIND DYNAMIC PRESSURE PULSES: INTERPLANETARY SOURCES AND THEIR IMPACTS ON GEOSYNCHRONOUS MAGNETIC FIELDS

International Nuclear Information System (INIS)

Zuo, Pingbing; Feng, Xueshang; Wang, Yi; Xie, Yanqiong; Xu, Xiaojun

2015-01-01

In this investigation, we first present a statistical result of the interplanetary sources of very strong solar wind dynamic pressure pulses (DPPs) detected by WIND during solar cycle 23. It is found that the vast majority of strong DPPs reside within solar wind disturbances. Although the variabilities of geosynchronous magnetic fields (GMFs) due to the impact of positive DPPs have been well established, there appears to be no systematic investigations on the response of GMFs to negative DPPs. Here, we study both the decompression effects of very strong negative DPPs and the compression from strong positive DPPs on GMFs at different magnetic local time sectors. In response to the decompression of strong negative DPPs, GMFs on the dayside near dawn and near dusk on the nightside, are generally depressed. But near the midnight region, the responses of GMF are very diverse, being either positive or negative. For part of the events when GOES is located at the midnight sector, the GMF is found to abnormally increase as the result of magnetospheric decompression caused by negative DPPs. It is known that under certain conditions magnetic depression of nightside GMFs can be caused by the impact of positive DPPs. Here, we find that a stronger pressure enhancement may have a higher probability of producing the exceptional depression of GMF at the midnight region. Statistically, both the decompression effect of strong negative DPPs and the compression effect of strong positive DPPs depend on the magnetic local time, which are stronger at the noon sector

STRONG SOLAR WIND DYNAMIC PRESSURE PULSES: INTERPLANETARY SOURCES AND THEIR IMPACTS ON GEOSYNCHRONOUS MAGNETIC FIELDS

Energy Technology Data Exchange (ETDEWEB)

Zuo, Pingbing; Feng, Xueshang; Wang, Yi [SIGMA Weather Group, State Key Laboratory of Space Weather, National Space Science Center, Chinese Academy of Sciences, Beijing (China); Xie, Yanqiong [College of Meteorology and Oceanography, PLA University of Science and Technology, Nanjing (China); Xu, Xiaojun, E-mail: pbzuo@spaceweather.ac.cn, E-mail: fengx@spaceweather.ac.cn [Space Science Institute, Macau University of Science and Technology, Macao (China)

2015-10-20

In this investigation, we first present a statistical result of the interplanetary sources of very strong solar wind dynamic pressure pulses (DPPs) detected by WIND during solar cycle 23. It is found that the vast majority of strong DPPs reside within solar wind disturbances. Although the variabilities of geosynchronous magnetic fields (GMFs) due to the impact of positive DPPs have been well established, there appears to be no systematic investigations on the response of GMFs to negative DPPs. Here, we study both the decompression effects of very strong negative DPPs and the compression from strong positive DPPs on GMFs at different magnetic local time sectors. In response to the decompression of strong negative DPPs, GMFs on the dayside near dawn and near dusk on the nightside, are generally depressed. But near the midnight region, the responses of GMF are very diverse, being either positive or negative. For part of the events when GOES is located at the midnight sector, the GMF is found to abnormally increase as the result of magnetospheric decompression caused by negative DPPs. It is known that under certain conditions magnetic depression of nightside GMFs can be caused by the impact of positive DPPs. Here, we find that a stronger pressure enhancement may have a higher probability of producing the exceptional depression of GMF at the midnight region. Statistically, both the decompression effect of strong negative DPPs and the compression effect of strong positive DPPs depend on the magnetic local time, which are stronger at the noon sector.

Electron dynamics in metals and semiconductors in strong THz fields

DEFF Research Database (Denmark)

Jepsen, Peter Uhd

2017-01-01

Semiconductors and metals respond to strong electric fields in a highly nonlinear fashion. Using single-cycle THz field transients it is possible to investigate this response in regimes not accessible by transport-based measurements. Extremely high fields can be applied without material damage...

Nontrivial effects of high-frequency excitation for strongly damped mechanical systems

DEFF Research Database (Denmark)

Fidlin, Alexander; Thomsen, Jon Juel

Some nontrivial effects are investigated, which can occur if strongly damped mechanical systems are subjected to strong high-frequency (HF) excitation. The main result is a theoretical prediction, supported by numerical simulation, that for such systems the (quasi-)equilibrium states can change...... that can be substantial (depending on the strength of the HF excitation) for finite values of the damping. The analysis is focused on the differences between the classic results for weakly damped systems, and new effects for which the strong damping terms are responsible. The analysis is based...... on a slightly modified averaging technique, and includes an elementary example of an elliptically excited pendulum for illustration, alongside with a generalization to a broader class of strongly damped dynamical systems with HF excitation. As an application example, the nontrivial behavior of a classical...

Is It Possible to Predict Strong Earthquakes?

Science.gov (United States)

Polyakov, Y. S.; Ryabinin, G. V.; Solovyeva, A. B.; Timashev, S. F.

2015-07-01

The possibility of earthquake prediction is one of the key open questions in modern geophysics. We propose an approach based on the analysis of common short-term candidate precursors (2 weeks to 3 months prior to strong earthquake) with the subsequent processing of brain activity signals generated in specific types of rats (kept in laboratory settings) who reportedly sense an impending earthquake a few days prior to the event. We illustrate the identification of short-term precursors using the groundwater sodium-ion concentration data in the time frame from 2010 to 2014 (a major earthquake occurred on 28 February 2013) recorded at two different sites in the southeastern part of the Kamchatka Peninsula, Russia. The candidate precursors are observed as synchronized peaks in the nonstationarity factors, introduced within the flicker-noise spectroscopy framework for signal processing, for the high-frequency component of both time series. These peaks correspond to the local reorganizations of the underlying geophysical system that are believed to precede strong earthquakes. The rodent brain activity signals are selected as potential "immediate" (up to 2 weeks) deterministic precursors because of the recent scientific reports confirming that rodents sense imminent earthquakes and the population-genetic model of K irshvink (Soc Am 90, 312-323, 2000) showing how a reliable genetic seismic escape response system may have developed over the period of several hundred million years in certain animals. The use of brain activity signals, such as electroencephalograms, in contrast to conventional abnormal animal behavior observations, enables one to apply the standard "input-sensor-response" approach to determine what input signals trigger specific seismic escape brain activity responses.

Strong-motion observations of the M 7.8 Gorkha, Nepal, earthquake sequence and development of the N-shake strong-motion network

Science.gov (United States)

Dixit, Amod; Ringler, Adam; Sumy, Danielle F.; Cochran, Elizabeth S.; Hough, Susan E.; Martin, Stacey; Gibbons, Steven; Luetgert, James H.; Galetzka, John; Shrestha, Surya; Rajaure, Sudhir; McNamara, Daniel E.

2015-01-01

We present and describe strong-motion data observations from the 2015 M 7.8 Gorkha, Nepal, earthquake sequence collected using existing and new Quake-Catcher Network (QCN) and U.S. Geological Survey NetQuakes sensors located in the Kathmandu Valley. A comparison of QCN data with waveforms recorded by a conventional strong-motion (NetQuakes) instrument validates the QCN data. We present preliminary analysis of spectral accelerations, and peak ground acceleration and velocity for earthquakes up to M 7.3 from the QCN stations, as well as preliminary analysis of the mainshock recording from the NetQuakes station. We show that mainshock peak accelerations were lower than expected and conclude the Kathmandu Valley experienced a pervasively nonlinear response during the mainshock. Phase picks from the QCN and NetQuakes data are also used to improve aftershock locations. This study confirms the utility of QCN instruments to contribute to ground-motion investigations and aftershock response in regions where conventional instrumentation and open-access seismic data are limited. Initial pilot installations of QCN instruments in 2014 are now being expanded to create the Nepal–Shaking Hazard Assessment for Kathmandu and its Environment (N-SHAKE) network.

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.

Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant

DEFF Research Database (Denmark)

Korsholm, Karen Smith; Hansen, Jon; Karlsen, Kasper

2014-01-01

previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T...

Strong nonlinear photonic responses from microbiologically synthesized tellurium nanocomposites

Science.gov (United States)

Liao, K.-S.; Wang, Jingyuan; Dias, S.; Dewald, J.; Alley, N.J.; Baesman, S.M.; Oremland, R.S.; Blau, W.J.; Curran, S.A.

2010-01-01

A new class of nanomaterials, namely microbiologically-formed nanorods composed of elemental tellurium [Te(0)] that forms unusual nanocomposites when combined with poly(m-phenylenevinylene-co-2,5-dioctoxy-phenylenevinylene) (PmPV) is described. These bio-nanocomposites exhibit excellent broadband optical limiting at 532 and 1064 nm. Nonlinear scattering, originating from the laser induced solvent bubbles and microplasmas, is responsible for this nonlinear behavior. The use of bacterially-formed Te(0) when combined with an organic chemical host (e.g., PmPV) is a new green method of nanoparticle syntheses. This opens the possibilities of using unique, biologically synthesized materials to advance future nanoelectronic and nanophotonic applications. ?? 2009 Elsevier B.V. All rights reserved.

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.

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

Acupuncture Affects Autonomic and Endocrine but Not Behavioural Responses Induced by Startle in Horses

Directory of Open Access Journals (Sweden)

Julia Dias Villas-Boas

2015-01-01

Full Text Available Startle is a fast response elicited by sudden acoustic, tactile, or visual stimuli in a variety of animals and in humans. As the magnitude of startle response can be modulated by external and internal variables, it can be a useful tool to study reaction to stress. Our study evaluated whether acupuncture can change cardiac autonomic modulation (heart rate variability; and behavioural (reactivity and endocrine (cortisol levels parameters in response to startle. Brazilian Sport horses (n=6 were subjected to a model of startle in which an umbrella was abruptly opened near the horse. Before startle, the horses were subjected to a 20-minute session of acupuncture in acupoints GV1, HT7, GV20, and BL52 (ACUP and in nonpoints (NP or left undisturbed (CTL. For analysis of the heart rate variability, ultrashort-term (64 s heart rate series were interpolated (4 Hz and divided into 256-point segments and the spectra integrated into low (LF; 0.01–0.07 Hz; index of sympathetic modulation and high (HF; 0.07–0.50 Hz; index of parasympathetic modulation frequency bands. Acupuncture (ACUP changed the sympathovagal balance with a shift towards parasympathetic modulation, reducing the prompt startle-induced increase in LF/HF and reducing cortisol levels 30 min after startle. However, acupuncture elicited no changes in behavioural parameters.

Neutral Polymer Micelle Carriers with pH-Responsive, Endosome-Releasing Activity Modulate Antigen Trafficking to Enhance CD8 T-Cell Responses

Science.gov (United States)

Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

2014-01-01

Synthetic subunit vaccines need to induce CD8+ cytotoxic T-cell (CTL) responses for effective vaccination against intracellular pathogens. Most subunit vaccines primarily generate humoral immune responses, with a weaker than desired CD8+ cytotoxic T-cell response. Here, a neutral, pH-responsive polymer micelle carrier that alters intracellular antigen trafficking was shown to enhance CD8+ T-cell responses with a correlated increase in cytosolic delivery and a decrease in exocytosis. Polymer diblock carriers consisted of a N-(2-hydroxypropyl) methacrylamide corona block with pendant pyridyl disulfide groups for reversible conjugation of thiolated ovalbumin, and a tercopolymer ampholytic core-forming block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The diblock copolymers self-assembled into 25–30 nm diameter micellar nanoparticles. Conjugation of ovalbumin to the micelles significantly enhanced antigen cross-presentation in vitro relative to free ovalbumin, an unconjugated physical mixture of ovalbumin and polymer, and a non pH-responsive micelle-ovalbumin control. Mechanistic studies in a murine dendritic cell line (DC2.4) demonstrated micelle-mediated enhancements in intracellular antigen retention and cytosolic antigen accumulation. Approximately 90% of initially internalized ovalbumin-conjugated micelles were retained in cells after 1.5 h, compared to only ~40% for controls. Furthermore, cells dosed with conjugates displayed 67-fold higher cytosolic antigen levels relative to soluble ovalbumin 4 h post uptake. Subcutaneous immunization of mice with ovalbumin-polymer conjugates significantly enhanced antigen-specific CD8+ T cell responses (0.4 % IFN-γ+ of CD8+) compared to immunization with soluble protein, ovalbumin and polymer mixture, and the control micelle without endosome-releasing activity. Additionally, pH-responsive carrier facilitated antigen delivery to antigen presenting cells in the

Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8(+) T cell responses.

Science.gov (United States)

Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

2014-10-10

Synthetic subunit vaccines need to induce CD8(+) cytotoxic T cell (CTL) responses for effective vaccination against intracellular pathogens. Most subunit vaccines primarily generate humoral immune responses, with a weaker than desired CD8(+) cytotoxic T cell response. Here, a neutral, pH-responsive polymer micelle carrier that alters intracellular antigen trafficking was shown to enhance CD8(+) T cell responses with a correlated increase in cytosolic delivery and a decrease in exocytosis. Polymer diblock carriers consisted of a N-(2-hydroxypropyl) methacrylamide corona block with pendent pyridyl disulfide groups for reversible conjugation of thiolated ovalbumin, and a tercopolymer ampholytic core-forming block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The diblock copolymers self-assembled into 25-30nm diameter micellar nanoparticles. Conjugation of ovalbumin to the micelles significantly enhanced antigen cross-presentation in vitro relative to free ovalbumin, an unconjugated physical mixture of ovalbumin and polymer, and a non-pH-responsive micelle-ovalbumin control. Mechanistic studies in a murine dendritic cell line (DC 2.4) demonstrated micelle-mediated enhancements in intracellular antigen retention and cytosolic antigen accumulation. Approximately 90% of initially internalized ovalbumin-conjugated micelles were retained in cells after 1.5h, compared to only ~40% for controls. Furthermore, cells dosed with conjugates displayed 67-fold higher cytosolic antigen levels relative to soluble ovalbumin 4h post uptake. Subcutaneous immunization of mice with ovalbumin-polymer conjugates significantly enhanced antigen-specific CD8(+) T cell responses (0.4% IFN-γ(+) of CD8(+)) compared to immunization with soluble protein, ovalbumin and polymer mixture, and the control micelle without endosome-releasing activity. Additionally, pH-responsive carrier facilitated antigen delivery to antigen presenting cells

SEISMIC BEHAVIOR OF STEEL MONORAIL BRIDGES UNDER TRAIN LOAD DURING STRONG EARTHQUAKES

OpenAIRE

KIM, C. W.; KAWATANI, M.; KANBARA, T.; NISHIMURA, N.

2013-01-01

This paper investigated dynamic responses of steel monorail bridges incorporating train-bridge interaction under strong earthquakes. Two types of steel monorail bridges were considered in the study: a conventional type with steel track-girder; an advanced type with composite track-girder and simplified lateral bracing system. During strong earthquakes, monorail train was assumed standing on the track-girder of monorail bridges. Observations through the analytical study showed that considering...

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

Directory of Open Access Journals (Sweden)

Narcís Saubi

2011-01-01

Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

Science.gov (United States)

Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

2011-01-01

We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216

Strong piezoelectricity in bioinspired peptide nanotubes.

Science.gov (United States)

Kholkin, Andrei; Amdursky, Nadav; Bdikin, Igor; Gazit, Ehud; Rosenman, Gil

2010-02-23

We show anomalously strong shear piezoelectric activity in self-assembled diphenylalanine peptide nanotubes (PNTs), indicating electric polarization directed along the tube axis. Comparison with well-known piezoelectric LiNbO(3) and lateral signal calibration yields sufficiently high effective piezoelectric coefficient values of at least 60 pm/V (shear response for tubes of approximately 200 nm in diameter). PNTs demonstrate linear deformation without irreversible degradation in a broad range of driving voltages. The results open up a wide avenue for developing new generations of "green" piezoelectric materials and piezonanodevices based on bioactive tubular nanostructures potentially compatible with human tissue.

Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine

DEFF Research Database (Denmark)

De Groot, Anne S; Levitz, Lauren; Ardito, Matthew T

2012-01-01

Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8(+) cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response...

Strongly Enhanced Piezoelectric Response in Lead Zirconate Titanate Films with Vertically Aligned Columnar Grains

Science.gov (United States)

2017-01-01

Pb(Zr0.52Ti0.48)O3 (PZT) films with (001) orientation were deposited on Pt(111)/Ti/SiO2/Si(100) substrates using pulsed laser deposition. Variation of the laser pulse rate during the deposition of the PZT films was found to play a key role in the control of the microstructure and to change strongly the piezoelectric response of the thin film. The film deposited at low pulse rate has a denser columnar microstructure, which improves the transverse piezoelectric coefficient (d31f) and ferroelectric remanent polarization (Pr), whereas the less densely packed columnar grains in the film deposited at high pulse rates give rise to a significantly higher longitudinal piezoelectric coefficient (d33f) value. The effect of film thickness on the ferroelectric and piezoelectric properties of the PZT films was also investigated. With increasing film thickness, the grain column diameter gradually increases, and also the average Pr and d33f values become larger. The largest piezoelectric coefficient of d33f = 408 pm V–1 was found for a 4-μm film thickness. From a series of films in the thickness range 0.5–5 μm, the z-position dependence of the piezoelectric coefficient could be deduced. A local maximum value of 600 pm V–1 was deduced in the 3.5–4.5 μm section of the thickest films. The dependence of the film properties on film thickness is attributed to the decreasing effect of the clamping constraint imposed by the substrate and the increasing spatial separation between the grains with increasing film thickness. PMID:28247756

Nontrivial effects of high-frequency excitation for strongly damped mechanical systems

DEFF Research Database (Denmark)

Fidlin, Alexander; Thomsen, Jon Juel

2008-01-01

Some non-trivial effects are investigated, which can occur if strongly damped mechanical systems are subjected to strong high-frequency (HF) excitation. The main result is a theoretical prediction, supported by numerical simulation, that for such systems the (quasi-)equilibrium states can change...... that can be substantial depending on the strength of the HF excitation) for finite values of the damping. The analysis is focused on the differences between the classic results for weakly damped systems, and new effects for which the strong damping terms are responsible. The analysis is based on a slightly...... modified averaging technique, and includes an elementary example of an elliptically excited pendulum for illustration, alongside with a generalization to a broader class of strongly damped dynamical systems with HF excitation. As an application example, the nontrivial behavior of a classical optimally...

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

Earthquake strong ground motion studies at the Idaho National Engineering Laboratory

International Nuclear Information System (INIS)

Wong, Ivan; Silva, W.; Darragh, R.; Stark, C.; Wright, D.; Jackson, S.; Carpenter, G.; Smith, R.; Anderson, D.; Gilbert, H.; Scott, D.

1989-01-01

Site-specific strong earthquake ground motions have been estimated for the Idaho National Engineering Laboratory assuming that an event similar to the 1983 M s 7.3 Borah Peak earthquake occurs at epicentral distances of 10 to 28 km. The strong ground motion parameters have been estimated based on a methodology incorporating the Band-Limited-White-Noise ground motion model coupled with Random Vibration Theory. A 16-station seismic attenuation and site response survey utilizing three-component portable digital seismographs was also performed for a five-month period in 1989. Based on the recordings of regional earthquakes, the effects of seismic attenuation in the shallow crust and along the propagation path and local site response were evaluated. This data combined with a detailed geologic profile developed for each site based principally on borehole data, was used in the estimation of the strong ground motion parameters. The preliminary peak horizontal ground accelerations for individual sites range from approximately 0.15 to 0.35 g. Based on the authors analysis, the thick sedimentary interbeds (greater than 20 m) in the basalt section attenuate ground motions as speculated upon in a number of previous studies

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 ...

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 ...

The characterization of six auxin-induced tomato GH3 genes uncovers a member, SlGH3.4, strongly responsive to arbuscular mycorrhizal symbiosis.

Science.gov (United States)

Liao, Dehua; Chen, Xiao; Chen, Aiqun; Wang, Huimin; Liu, Jianjian; Liu, Junli; Gu, Mian; Sun, Shubin; Xu, Guohua

2015-04-01

In plants, the GH3 gene family is widely considered to be involved in a broad range of plant physiological processes, through modulation of hormonal homeostasis. Multiple GH3 genes have been functionally characterized in several plant species; however, to date, limited works to study the GH3 genes in tomato have been reported. Here, we characterize the expression and regulatory profiles of six tomato GH3 genes, SlGH3.2, SlGH3.3, SlGH3.4, SlGH3.7, SlGH3.9 and SlGH3.15, in response to different phytohormone applications and arbuscular mycorrhizal (AM) fungal colonization. All six GH3 genes showed inducible responses to external IAA, and three members were significantly up-regulated in response to AM symbiosis. In particular, SlGH3.4, the transcripts of which were barely detectable under normal growth conditions, was strongly activated in the IAA-treated and AM fungal-colonized roots. A comparison of the SlGH3.4 expression in wild-type plants and M161, a mutant with a defect in AM symbiosis, confirmed that SlGH3.4 expression is highly correlated to mycorrhizal colonization. Histochemical staining demonstrated that a 2,258 bp SlGH3.4 promoter fragment could drive β-glucuronidase (GUS) expression strongly in root tips, steles and cortical cells of IAA-treated roots, but predominantly in the fungal-colonized cells of mycorrhizal roots. A truncated 654 bp promoter failed to direct GUS expression in IAA-treated roots, but maintained the symbiosis-induced activity in mycorrhizal roots. In summary, our results suggest that a mycorrhizal signaling pathway that is at least partially independent of the auxin signaling pathway has evolved for the co-regulation of the auxin- and mycorrhiza-activated GH3 genes in plants. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Effective interactions in strongly-coupled quantum systems

International Nuclear Information System (INIS)

Chen, J.M.C.

1986-01-01

In this thesis, they study the role of effective interactions in strongly-coupled Fermi systems where the short-range correlations introduce difficulties requiring special treatment. The correlated basis function method provides the means to incorporate the short-range correlations and generate the matrix elements of the Hamiltonian and identity operators in a nonorthogonal basis of states which are so important to their studies. In the first half of the thesis, the particle-hole channel is examined to elucidate the effects of collective excitations. Proceeding from a least-action principle, a generalization of the random-phase approximation is developed capable of describing such strongly-interacting Fermi systems as nuclei, nuclear matter, neutron-star matter, and liquid 3 He. A linear response of dynamically correlated system to a weak external perturbation is also derived based on the same framework. In the second half of the thesis, the particle-particle channel is examined to elucidate the effects of pairing in nuclear and neutron-star matter

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

Topographic gradient based site characterization in India complemented by strong ground-motion spectral attributes

KAUST Repository

Nath, Sankar Kumar; Thingbaijam, Kiran Kumar; Adhikari, M. D.; Nayak, Avinash; Devaraj, N.; Ghosh, Soumalya K.; Mahajan, Arun K.

2013-01-01

We appraise topographic-gradient approach for site classification that employs correlations between 30. m column averaged shear-wave velocity and topographic gradients. Assessments based on site classifications reported from cities across India indicate that the approach is reasonably viable at regional level. Additionally, we experiment three techniques for site classification based on strong ground-motion recordings, namely Horizontal-to-Vertical Spectral Ratio (HVSR), Response Spectra Shape (RSS), and Horizontal-to-Vertical Response Spectral Ratio (HVRSR) at the strong motion stations located across the Himalayas and northeast India. Statistical tests on the results indicate that these three techniques broadly differentiate soil and rock sites while RSS and HVRSR yield better signatures. The results also support the implemented site classification in the light of strong ground-motion spectral attributes observed in different parts of the globe. © 2013 Elsevier Ltd.

Topographic gradient based site characterization in India complemented by strong ground-motion spectral attributes

KAUST Repository

Nath, Sankar Kumar

2013-12-01

We appraise topographic-gradient approach for site classification that employs correlations between 30. m column averaged shear-wave velocity and topographic gradients. Assessments based on site classifications reported from cities across India indicate that the approach is reasonably viable at regional level. Additionally, we experiment three techniques for site classification based on strong ground-motion recordings, namely Horizontal-to-Vertical Spectral Ratio (HVSR), Response Spectra Shape (RSS), and Horizontal-to-Vertical Response Spectral Ratio (HVRSR) at the strong motion stations located across the Himalayas and northeast India. Statistical tests on the results indicate that these three techniques broadly differentiate soil and rock sites while RSS and HVRSR yield better signatures. The results also support the implemented site classification in the light of strong ground-motion spectral attributes observed in different parts of the globe. © 2013 Elsevier Ltd.

Use of "one-pot, mix-and-read" peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

DEFF Research Database (Denmark)

Svitek, Nicholas; Hansen, Andreas Martin; Steinaa, Lucilla

2014-01-01

Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8(+) cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and re...

Leishmania mexicana Gp63 cDNA Using Gene Gun Induced Higher Immunity to L. mexicana Infection Compared to Soluble Leishmania Antigen in BALB/C

Science.gov (United States)

Rezvan, H; Rees, R; Ali, SA

2011-01-01

Background Leishmaniasis is a worldwide disease prevalent in tropical and sub tropical countries. Many attempts have been made and different strategies have been approached to develop a potent vaccine against Leishmania. DNA immunisation is a method, which is shown to be effective in Leishmania vaccination. Leishmania Soluble Antigen (SLA) has also recently been used Leishmania vaccination. Methods The immunity generated by SLA and L. mexicana gp63 cDNA was compared in groups of 6 mice, which were statistically analysed by student t- test with the P-value of 0.05. SLA was administered by two different methods; intramuscular injection and injection of dendritic cells (DCs) loaded with SLA. L. mexicana gp63 cDNA was administered by the gene gun. Results Immunisation of BALB/c mice with L. mexicana gp63 resulted in high levels of Th1-type immune response and cytotoxic T lymphocytes (CTL) activity, which were accompanied with protection induced by the immunisation against L. mexicana infection. In contrast, administration of SLA, produced a mixed Th1/Th2-type immune responses as well as a high level of CTL activity but did not protect mice from the infection. Conclusion The results indicate higher protection by DNA immunisation using L. mexicana gp63 cDNA compared to SLA, which is accompanied by a high level of Th1 immune response. However, the CTL activity does not necessarily correlate with the protection induced by the vaccine. Also, gene gun immunisation is a potential approach in Leishmania vaccination. These findings would be helpful in opening new windows in Leishmania vaccine research. PMID:22347315

A Unifying Perspective on Oxygen Vacancies in Wide Band Gap Oxides.

Science.gov (United States)

Linderälv, Christopher; Lindman, Anders; Erhart, Paul

2018-01-04

Wide band gap oxides are versatile materials with numerous applications in research and technology. Many properties of these materials are intimately related to defects, with the most important defect being the oxygen vacancy. Here, using electronic structure calculations, we show that the charge transition level (CTL) and eigenstates associated with oxygen vacancies, which to a large extent determine their electronic properties, are confined to a rather narrow energy range, even while band gap and the electronic structure of the conduction band vary substantially. Vacancies are classified according to their character (deep versus shallow), which shows that the alignment of electronic eigenenergies and CTL can be understood in terms of the transition between cavity-like localized levels in the large band gap limit and strong coupling between conduction band and vacancy states for small to medium band gaps. We consider both conventional and hybrid functionals and demonstrate that the former yields results in very good agreement with the latter provided that band edge alignment is taken into account.

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.

Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

Directory of Open Access Journals (Sweden)

Asanuma Hiroko

2008-05-01

Full Text Available Abstract Background We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer. Methods We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks. Results In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1, and another had general malaise (grade 1 and fever (grade 1. Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD. Immunologically, in 3 of the 10 patients (30%, an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%, although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols. Conclusion This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more

Equation of state of strongly coupled plasma mixtures

International Nuclear Information System (INIS)

DeWitt, H.E.

1984-01-01

Thermodynamic properties of strongly coupled (high density) plasmas of mixtures of light elements have been obtained by Monte Carlo simulations. For an assumed uniform charge background the equation of state of ionic mixtures is a simple extension of the one-component plasma EOS. More realistic electron screening effects are treated in linear response theory and with an appropriate electron dielectric function. Results have been obtained for the ionic pair distribution functions, and for the electric microfield distribution

Sorghum (Sorghum bicolor) varieties adopt strongly contrasting strategies in response to drought.

Science.gov (United States)

Ogbaga, Chukwuma C; Stepien, Piotr; Johnson, Giles N

2014-10-01

Sorghum is one of the most drought tolerant crops but surprisingly, little is known about the mechanisms achieving this. We have compared physiological and biochemical responses to drought in two sorghum cultivars with contrasting drought tolerance. These closely related cultivars have starkly contrasting responses to water deficit. In the less tolerant Samsorg 40, drought induced progressive loss of photosynthesis. The more drought tolerant Samsorg 17 maintained photosynthesis, transpiration and chlorophyll content until the most extreme conditions. In Samsorg 40, there was a highly specific down-regulation of selected proteins, with loss of PSII and Rubisco but maintenance of PSI and cytochrome b6 f, allowing plants to maintain ATP synthesis. The nitrogen released allows for accumulation of glycine betaine and proline. To the best of our knowledge, this is the first example of specific reengineering of the photosynthetic apparatus in response to drought. In contrast, in Samsorg 17 we detected no substantial change in the photosynthetic apparatus. Rather, plants showed constitutively high soluble sugar concentration, enabling them to maintain transpiration and photosynthesis, even in extremely dry conditions. The implications for these strikingly contrasted strategies are discussed in relation to agricultural and natural systems. © 2014 Scandinavian Plant Physiology Society.

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...

Strong-back safety latch

International Nuclear Information System (INIS)

DeSantis, G.N.

1995-01-01

The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

Nonlinear response of the quantum Hall system to a strong electromagnetic radiation

International Nuclear Information System (INIS)

Avetissian, H.K.; Mkrtchian, G.F.

2016-01-01

We study nonlinear response of a quantum Hall system in semiconductor-hetero-structures via third harmonic generation process and nonlinear Faraday effect. We demonstrate that Faraday rotation angle and third harmonic radiation intensity have a characteristic Hall plateaus feature. These nonlinear effects remain robust against the significant broadening of Landau levels. We predict realization of an experiment through the observation of the third harmonic signal and Faraday rotation angle, which are within the experimental feasibility. - Highlights: • Nonlinear optical response of a quantum Hall system has specific plateaus feature. • This effect remains robust against the significant broadening of Landau levels. • It can be observed via the third harmonic signal and the nonlinear Faraday effect.

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)

Strong-coupling approach to nematicity in the cuprates

Science.gov (United States)

Orth, Peter Philipp; Jeevanesan, Bhilahari; Schmalian, Joerg; Fernandes, Rafael

The underdoped cuprate superconductor YBa2Cu3O7-δ is known to exhibit an electronic nematic phase in proximity to antiferromagnetism. While nematicity sets in at large temperatures of T ~ 150 K, static spin density wave order only emerges at much lower temperatures. The magnetic response shows a strong in-plane anisotropy, displaying incommensurate Bragg peaks along one of the crystalline directions and a commensurate peak along the other one. Such an anisotropy persists even in the absence of long-range magnetic order at higher temperatures, marking the onset of nematic order. Here we theoretically investigate this situation using a strong-coupling method that takes into account both the localized Cu spins and the holes doped into the oxygen orbitals. We derive an effective spin Hamiltonian and show that charge fluctuations promote an enhancement of the nematic susceptibility near the antiferromagnetic transition temperature.

T Cell-Tumor Interaction Directs the Development of Immunotherapies in Head and Neck Cancer

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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.

Fulltext PDF

Indian Academy of Sciences (India)

Madhu Sudhan

HSP as danger signals produced and released when cells are under stress and as ... for specific CD8+ CTL responses (Srivastava et al 1994;. Srivastava 2000 .... to other infectious diseases such as malaria and HIV (Lehner and Anton 2002 ..... Army Knife' vaccines against cancers and infectious agents;. Vaccine 19 2590– ...

OVA-specific CD8(+)T cells do not express granzyme B during anterior chamber associated immune deviation

NARCIS (Netherlands)

Ren, Y.; Yang, P.; Li, B.; Gao, Y.; Zhou, H.; Huang, X.; Zhu, L.; Kijlstra, A.

2006-01-01

To examine antigen (Ag)-specific CTL response during anterior chamber associated immune deviation (ACAID). Methods OVA or OVA257-264 peptide was injected into the anterior chamber (AC) of C57BL/6 mice. There were 16 mice in each ACAID group induced with OVA or OVA257-264 peptide. The mice were

Expanding specificity of class I restricted CD8+ T cells for viral epitopes following multiple inoculations of swine with a human adenovirus vectored foot-and-mouth disease virus (FMDV) vaccine

DEFF Research Database (Denmark)

Pedersen, Lasse E.; Patch, Jared R; Kenney, Mary

2016-01-01

The immune response to the highly acute foot-and-mouth disease virus (FMDV) is routinely reported as a measure of serum antibody. However, a critical effector function of immune responses combating viral infection of mammals is the cytotoxic T lymphocyte (CTL) response mediated by virus specific CD...... show that the specificity of the CD8(+) T cell response to Ad5-FMDV-T varies between cohorts of genetically identical animals. Further, we demonstrate epitope specificity of CD8(+) T cells expands following multiple immunizations with this vaccine....

Strong congruence in tree and fern community turnover in response to soils and climate in central Panama

DEFF Research Database (Denmark)

Jones, Mirkka; Ferrier, Simon; Condit, Richard

2013-01-01

1. Plant species turnover in central Panamanian forests has been principally attributed to the effects of dispersal limitation and a strong Caribbean to Pacific gradient in rainfall seasonality. Despite marked geological heterogeneity, the role of soil variation has not been rigorously examined. 2....... We modelled the compositional turnover of trees and ferns in the Panama Canal watershed as a function of soil chemistry, climate and geographical separation, using generalized dissimilarity models (GDMs). 3. Predictability in both plant groups was strong, with 74% of turnover explained in trees...... and 49% in ferns. Major trends in the two plant groups were strikingly similar. The independent effects of soils, and of climate for trees, were sizeable, but those of geographical distance were minor. In both plant groups, distance and climatic effects on species turnover covaried strongly. 4. Including...

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.

Strong Broadband Terahertz Optical Activity through Control of the Blaschke Phase with Chiral Metasurfaces

Science.gov (United States)

Cole, Michael A.; Chen, Wen-chen; Liu, Mingkai; Kruk, Sergey S.; Padilla, Willie J.; Shadrivov, Ilya V.; Powell, David A.

2017-07-01

We demonstrate terahertz chiral metamaterials that achieve resonant transmission and strong optical activity. This response is realized in a metasurface coupled to its Babinet complement, with additional twist. Uniquely, the optical activity achieved in this type of metamaterial is weakly dispersive around the resonant transmission maxima, but it can be highly dispersive around the transmission minima. It has recently been shown that this unique optical activity response is closely related to zeros in the transmission spectra of circular polarizations through the Kramers-Kronig relations and strong resonant features in the optical activity spectrum corresponding to the Blaschke phase terms. Here we demonstrate how modifying the meta-atom geometry greatly affects the location and magnitude of these Blaschke phase terms. We study three different meta-atoms, which are variations on the simple cross structure. Their responses are measured using terahertz time-domain spectroscopy and analyzed via numerical simulations.

Strongly nonlinear optical glass fibers from noncentrosymmetric phase-change chalcogenide materials.

Science.gov (United States)

Chung, In; Jang, Joon I; Malliakas, Christos D; Ketterson, John B; Kanatzidis, Mercouri G

2010-01-13

We report that the one-dimensional polar selenophosphate compounds APSe(6) (A = K, Rb), which show crystal-glass phase-change behavior, exhibit strong second harmonic generation (SHG) response in both crystal and glassy forms. The crystalline materials are type-I phase-matchable with SHG coefficients chi((2)) of 151.3 and 149.4 pm V(-1) for K(+) and Rb(+) salts, respectively, which is the highest among phase-matchable nonlinear optical (NLO) materials with band gaps over 1.0 eV. The glass of APSe(6) exhibits comparable SHG intensities to the top infrared NLO material AgGaSe(2) without any poling treatments. APSe(6) exhibit excellent mid-IR transparency. We demonstrate that starting from noncentrosymmetric phase-change materials such as APSe(6) (A = K, Rb), we can obtain optical glass fibers with strong, intrinsic, and temporally stable second-order nonlinear optical (NLO) response. The as-prepared glass fibers exhibit SHG and difference frequency generation (DFG) responses over a wide range of wavelengths. Raman spectroscopy and pair distribution function (PDF) analyses provide further understanding of the local structure in amorphous state of KPSe(6) bulk glass and glass fiber. We propose that this approach can be widely applied to prepare permanent NLO glass from materials that undergo a phase-change process.

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.

A high and low noise model for strong motion accelerometers

Science.gov (United States)

Clinton, J. F.; Cauzzi, C.; Olivieri, M.

2010-12-01

We present reference noise models for high-quality strong motion accelerometer installations. We use continuous accelerometer data acquired by the Swiss Seismological Service (SED) since 2006 and other international high-quality accelerometer network data to derive very broadband (50Hz-100s) high and low noise models. The proposed noise models are compared to the Peterson (1993) low and high noise models designed for broadband seismometers; the datalogger self-noise; background noise levels at existing Swiss strong motion stations; and typical earthquake signals recorded in Switzerland and worldwide. The standard strong motion station operated by the SED consists of a Kinemetrics Episensor (2g clip level; flat acceleration response from 200 Hz to DC; insulated sensor / datalogger systems placed in vault quality sites. At all frequencies, there is at least one order of magnitude between the ALNM and the AHNM; at high frequencies (> 1Hz) this extends to 2 orders of magnitude. This study provides remarkable confirmation of the capability of modern strong motion accelerometers to record low-amplitude ground motions with seismic observation quality. In particular, an accelerometric station operating at the ALNM is capable of recording the full spectrum of near source earthquakes, out to 100 km, down to M2. Of particular interest for the SED, this study provides acceptable noise limits for candidate sites for the on-going Strong Motion Network modernisation.

Some Applications of Holography to Study Strongly Correlated Systems

Directory of Open Access Journals (Sweden)

Bhatnagar Neha

2018-01-01

Full Text Available In this work, we study the transport coefficients of strongly coupled condensed matter systems using gauge/gravity duality (holography. We consider examples from the real world and evaluate the conductivities from their gravity duals. Adopting the bottom-up approach of holography, we obtain the frequency response of the conductivity for (1+1-dimensional systems. We also evaluate the DC conductivities for non-relativistic condensed matter systems with hyperscaling violating geometry.

Strong Langmuir turbulence

International Nuclear Information System (INIS)

Goldman, M.V.

1984-01-01

After a brief discussion of beam-excited Langmuir turbulence in the solar wind, we explain the criteria for wave-particle, three-wave and strong turbulence interactions. We then present the results of a numerical integration of the Zakharov equations, which describe the strong turbulence saturation of a weak (low-density) high energy, bump-on-tail beam instability. (author)

Octodon Degus: A Strong Attractor for Alzheimer Research

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Rafael Castro-Fuentes

2013-01-01

Full Text Available   The most popular animal models of Alzheimer’s disease (AD are transgenic mice expressing human genes with known mutations which do not represent the most abundant sporadic form of the disease. An increasing number of genetic, vascular and psychosocial data strongly support that the Octodon degus, a moderate-sized and diurnal precocial rodent, provides a naturalistic model for the study of the early neurodegenerative process associated with sporadic AD. In this minireview we describe and analyze the risk factors that contribute to Alzheimer-like characteristics in the degus, following recent publications, and establish some guidelines for future studies in this model of natural aging associated with the disease. Given the heterogeneity of current data derived from the diverse transgenic animal models of AD, now may be the time for the degus to become a strong attractor for academic research labs and companies involved with AD. This may help to understand the mechanisms responsible for the early neurodegenerative process associated with this devastating disease.

Octodon Degus: A Strong Attractor for Alzheimer Research

Directory of Open Access Journals (Sweden)

Rafael Castro-Fuentes

2013-02-01

Full Text Available The most popular animal models of Alzheimer’s disease (AD are transgenic mice expressing human genes with known mutations which do not represent the most abundant sporadic form of the disease. An increasing number of genetic, vascular and psychosocial data strongly support that the Octodon degus, a moderate-sized and diurnal precocial rodent, provides a naturalistic model for the study of the early neurodegenerative process associated with sporadic AD. In this minireview we describe and analyze the risk factors that contribute to Alzheimer-like characteristics in the degus, following recent publications, and establish some guidelines for future studies in this model of natural aging associated with the disease. Given the heterogeneity of current data derived from the diverse transgenic animal models of AD, now may be the time for the degus to become a strong attractor for academic research labs and companies involved with AD. This may help to understand the mechanisms responsible for the early neurodegenerative process associated with this devastating disease.

Genetic adjuvantation of recombinant MVA with CD40L potentiates CD8 T cell mediated immunity

Directory of Open Access Journals (Sweden)

Henning eLauterbach

2013-08-01

Full Text Available Modified vaccinia Ankara (MVA is a safe and promising viral vaccine vector that is currently investigated in several clinical and pre-clinical trials. In contrast to inactivated or sub-unit vaccines, MVA is able to induce strong humoral as well as cellular immune responses. In order to further improve its CD8 T cell inducing capacity, we genetically adjuvanted MVA with the coding sequence of murine CD40L, a member of the tumor necrosis factor (TNF superfamily. Immunization of mice with this new vector led to strongly enhanced primary and memory CD8 T cell responses. Concordant with the enhanced CD8 T cell response, we could detect stronger activation of dendritic cells and higher systemic levels of innate cytokines (including IL-12p70 early after immunization. Interestingly, acquisition of memory characteristics (i.e., IL-7R expression was accelerated after immunization with MVA-CD40L in comparison to non-adjuvanted MVA. Furthermore, the generated CTLs also showed improved functionality as demonstrated by intracellular cytokine staining and in vivo killing activity. Importantly, the superior CTL response after a single MVA-CD40L immunization was able to protect B cell deficient mice against a fatal infection with ectromelia virus. Taken together, we show that genetic adjuvantation of MVA can change strength, quality and functionality of innate and adaptive immune responses. These data should facilitate a rational vaccine design with a focus on rapid induction of large numbers of CD8 T cells able to protect against specific diseases.

Strong Motion Earthquake Data Values of Digitized Strong-Motion Accelerograms, 1933-1994

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The Strong Motion Earthquake Data Values of Digitized Strong-Motion Accelerograms is a database of over 15,000 digitized and processed accelerograph records from...

Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

International Nuclear Information System (INIS)

Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

1999-01-01

Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

Mamu-A*01/Kb transgenic and MHC Class I knockout mice as a tool for HIV vaccine development

International Nuclear Information System (INIS)

Li Jinliang; Srivastava, Tumul; Rawal, Ravindra; Manuel, Edwin; Isbell, Donna; Tsark, Walter; La Rosa, Corinna; Wang Zhongde; Li Zhongqi; Barry, Peter A.; Hagen, Katharine D.; Longmate, Jeffrey; Diamond, Don J.

2009-01-01

We have developed a murine model expressing the rhesus macaque (RM) Mamu-A*01 MHC allele to characterize immune responses and vaccines based on antigens of importance to human disease processes. Towards that goal, transgenic (Tg) mice expressing chimeric RM (α1 and α2 Mamu-A*01 domains) and murine (α3, transmembrane, and cytoplasmic H-2K b domains) MHC Class I molecules were derived by transgenesis of the H-2K b D b double MHC Class I knockout strain. After immunization of Mamu-A*01/K b Tg mice with rVV-SIVGag-Pol, the mice generated CD8 + T-cell IFN-γ responses to several known Mamu-A*01 restricted epitopes from the SIV Gag and Pol antigen sequence. Fusion peptides of highly recognized CTL epitopes from SIV Pol and Gag and a strong T-help epitope were shown to be immunogenic and capable of limiting an rVV-SIVGag-Pol challenge. Mamu-A*01/K b Tg mice provide a model system to study the Mamu-A*01 restricted T-cell response for various infectious diseases which are applicable to a study in RM.

A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target.

Directory of Open Access Journals (Sweden)

Daniel M Appledorn

2010-03-01

Full Text Available Adenoviral based vectors remain promising vaccine platforms for use against numerous pathogens, including HIV. Recent vaccine trials utilizing Adenovirus based vaccines expressing HIV antigens confirmed induction of cellular immune responses, but these responses failed to prevent HIV infections in vaccinees. This illustrates the need to develop vaccine formulations capable of generating more potent T-cell responses to HIV antigens, such as HIV-Gag, since robust immune responses to this antigen correlate with improved outcomes in long-term non-progressor HIV infected individuals.In this study we designed a novel vaccine strategy utilizing an Ad-based vector expressing a potent TLR agonist derived from Eimeria tenella as an adjuvant to improve immune responses from a [E1-]Ad-based HIV-Gag vaccine. Our results confirm that expression of rEA elicits significantly increased TLR mediated innate immune responses as measured by the influx of plasma cytokines and chemokines, and activation of innate immune responding cells. Furthermore, our data show that the quantity and quality of HIV-Gag specific CD8(+ and CD8(- T-cell responses were significantly improved when coupled with rEA expression. These responses also correlated with a significantly increased number of HIV-Gag derived epitopes being recognized by host T cells. Finally, functional assays confirmed that rEA expression significantly improved antigen specific CTL responses, in vivo. Moreover, we show that these improved responses were dependent upon improved TLR pathway interactions.The data presented in this study illustrate the potential utility of Ad-based vectors expressing TLR agonists to improve clinical outcomes dependent upon induction of robust, antigen specific immune responses.

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

Immunogenicity of Recombinant Classic Swine Fever Virus CD8+ T Lymphocyte Epitope and Porcine Parvovirus VP2 Antigen Coexpressed by Lactobacillus casei in Swine via Oral Vaccination ▿

Science.gov (United States)

Xu, Yigang; Cui, Lichun; Tian, Changyong; Zhang, Guocai; Huo, Guicheng; Tang, Lijie; Li, Yijing

2011-01-01

Classical swine fever virus (CSFV) and porcine parvovirus (PPV) are highly contagious pathogens, resulting in enormous economic losses in pig industries worldwide. Because vaccines play an important role in disease control, researchers are seeking improved vaccines that could induce antiviral immune responses against CSFV and PPV at the mucosal and systemic levels simultaneously. In this study, a genetically engineered Lactobacillus strain coexpressing the CSFV-specific cytotoxic T lymphocyte (CTL) epitope 290 and the VP2 antigen of PPV was developed, and its immunopotentiating capacity as an oral vaccine in pigs was analyzed. The data demonstrated that in the absence of any adjuvant, the recombinant Lactobacillus strain can efficiently stimulate mucosal and systemic CSFV-specific CD8+ CTL responses to protect pigs against CSFV challenge. Moreover, anti-PPV-VP2 serum IgG and mucosal IgA were induced in pigs immunized orally with the recombinant Lactobacillus strain, showing a neutralizing effect on PPV infection. The results suggest that the recombinant Lactobacillus microecological agent may be a valuable component of a strategy for development of a vaccine against CSFV and PPV. PMID:21940406

Therapeutic Vaccine Against HIV, Viral Variability, Cytotoxic T Lymphocyte Epitopes, and Genetics of Patients.

Science.gov (United States)

Fleury, Herve; Tumiotto, Camille; Bellecave, Pantxika; Recordon-Pinson, Patricia

2018-01-01

The scientific and medical community is seeking to cure HIV. Several pathways have been or are being explored including therapeutic vaccination. Viroimmunological studies on primary infection as well as on elite controllers have demonstrated the importance of the cytotoxic CD8 response and have mainly oriented research on vaccine constructs toward this type of response. The results of these trials are clearly not commensurate with the hope placed in them. Might there be one or more uncontrolled variables? The genetics of patients need to be taken into consideration, especially their human lymphocyte antigen (HLA) alleles. There is a need to find a balance between the conservation of cytotoxic T lymphocyte (CTL) epitopes and presentation by HLA alleles. The pathway is a narrow one between adaptation of the virus to HLA I restriction and the definition of conserved proviral CTL epitopes presentable by HLA I alleles. It is likely that the genetics of patients will need to be considered for HIV-1 vaccine studies and that multidisciplinary collaboration will be essential in this field of infectious diseases.

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

Computational elucidation of potential antigenic CTL epitopes in Ebola virus.

Science.gov (United States)

Dikhit, Manas R; Kumar, Santosh; Vijaymahantesh; Sahoo, Bikash R; Mansuri, Rani; Amit, Ajay; Yousuf Ansari, Md; Sahoo, Ganesh C; Bimal, Sanjiva; Das, Pradeep

2015-12-01

Cell-mediated immunity is important for the control of Ebola virus infection. We hypothesized that those HLA A0201 and HLA B40 restricted epitopes derived from Ebola virus proteins, would mount a good antigenic response. Here we employed an immunoinformatics approach to identify specific 9mer amino acid which may be capable of inducing a robust cell-mediated immune response in humans. We identified a set of 28 epitopes that had no homologs in humans. Specifically, the epitopes derived from NP, RdRp, GP and VP40 share population coverage of 93.40%, 84.15%, 74.94% and 77.12%, respectively. Based on the other HLA binding specificity and population coverage, seven novel promiscuous epitopes were identified. These 7 promiscuous epitopes from NP, RdRp and GP were found to have world-wide population coverage of more than 95% indicating their potential significance as useful candidates for vaccine design. Epitope conservancy analysis also suggested that most of the peptides are highly conserved (100%) in other virulent Ebola strain (Mayinga-76, Kikwit-95 and Makona-G3816- 2014) and can therefore be further investigated for their immunological relevance and usefulness as vaccine candidates. Copyright © 2015 Elsevier B.V. All rights reserved.

John Strong (1941 - 2006)

CERN Multimedia

Wickens, F

Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

Diffraction analysis of materials under strong plastic deformation

International Nuclear Information System (INIS)

Pyzalla, A.

2001-01-01

The applicability of X-ray diffraction in analyses of the microstructure texture and intrinsic stresses of materials under strong plastic deformation is illustrated by examples and discussed. The experimental methods and findings are supplemented by numeric calculations. It is shown how the microstructure, texture and intrinsic stresses can thus be optimized already in the production process. Analyses of changes in materials during operation of a component provide information on loads and material response to loads which can then be used for optimization of the component, e.g. by constructional modifications or selective heat treatment [de

Earthquake Intensity and Strong Motion Analysis Within SEISCOMP3

Science.gov (United States)

Becker, J.; Weber, B.; Ghasemi, H.; Cummins, P. R.; Murjaya, J.; Rudyanto, A.; Rößler, D.

2017-12-01

Measuring and predicting ground motion parameters including seismic intensities for earthquakes is crucial and subject to recent research in engineering seismology.gempa has developed the new SIGMA module for Seismic Intensity and Ground Motion Analysis. The module is based on the SeisComP3 framework extending it in the field of seismic hazard assessment and engineering seismology. SIGMA may work with or independently of SeisComP3 by supporting FDSN Web services for importing earthquake or station information and waveforms. It provides a user-friendly and modern graphical interface for semi-automatic and interactive strong motion data processing. SIGMA provides intensity and (P)SA maps based on GMPE's or recorded data. It calculates the most common strong motion parameters, e.g. PGA/PGV/PGD, Arias intensity and duration, Tp, Tm, CAV, SED and Fourier-, power- and response spectra. GMPE's are configurable. Supporting C++ and Python plug-ins, standard and customized GMPE's including the OpenQuake Hazard Library can be easily integrated and compared. Originally tailored to specifications by Geoscience Australia and BMKG (Indonesia) SIGMA has become a popular tool among SeisComP3 users concerned with seismic hazard and strong motion seismology.

Iterative solutions of nonlinear equations with strongly accretive or strongly pseudocontractive maps

International Nuclear Information System (INIS)

Chidume, C.E.

1994-03-01

Let E be a real q-uniformly smooth Banach space. Suppose T is a strongly pseudo-contractive map with open domain D(T) in E. Suppose further that T has a fixed point in D(T). Under various continuity assumptions on T it is proved that each of the Mann iteration process or the Ishikawa iteration method converges strongly to the unique fixed point of T. Related results deal with iterative solutions of nonlinear operator equations involving strongly accretive maps. Explicit error estimates are also provided. (author). 38 refs

Semi-metallic, strong conductive polymer microfiber, method and fast response rate actuators and heating textiles

KAUST Repository

Zhou, Jian; Li, Er Qiang; Lubineau, Gilles; Thoroddsen, Sigurdur T; Mulle, Matthieu

2016-01-01

A method comprising: providing at least one first composition comprising at least one conjugated polymer and at least one solvent, wet spinning the at least one first composition to form at least one first fiber material, hot-drawing the at least one fiber to form at least one second fiber material. In lead embodiments, high-performance poly(3,4-ethylenedioxy- thiophene)/poly(styrenesulfonate) (PEDOT/PSS) conjugated polymer microfibers were fabricated via wet- spinning followed by hot-drawing. In these lead embodiments, due to the combined effects of the vertical hot-drawing process and doping/de-doping the microfibers with ethylene glycol (EG), a record electrical conductivity of 2804 S · cm-1 was achieved. This is believed to be a six-fold improvement over the best previously reported value for PEDOT/PSS fibers (467 S · cm-1) and a twofold improvement over the best values for conductive polymer films treated by EG de-doping (1418 S · cm-1). Moreover, these lead, highly conductive fibers experience a semiconductor-metal transition at 313 K. They also have superior mechanical properties with a Young's modulus up to 8.3 GPa, a tensile strength reaching 409.8 MPa and a large elongation before failure (21%). The most conductive fiber also demonstrates an extraordinary electrical performance during stretching/unstretching: the conductivity increased by 25% before the fiber rupture point with a maximum strain up to 21%. Simple fabrication of the semi-metallic, strong and stretchable wet-spun PEDOT/PSS microfibers can make them available for conductive smart electronics. A dramatic improvement in electrical conductivity is needed to make conductive polymer fibers viable candidates in applications such as flexible electrodes, conductive textiles, and fast-response sensors and actuators.

Semi-metallic, strong conductive polymer microfiber, method and fast response rate actuators and heating textiles

KAUST Repository

Zhou, Jian

2016-06-09

A method comprising: providing at least one first composition comprising at least one conjugated polymer and at least one solvent, wet spinning the at least one first composition to form at least one first fiber material, hot-drawing the at least one fiber to form at least one second fiber material. In lead embodiments, high-performance poly(3,4-ethylenedioxy- thiophene)/poly(styrenesulfonate) (PEDOT/PSS) conjugated polymer microfibers were fabricated via wet- spinning followed by hot-drawing. In these lead embodiments, due to the combined effects of the vertical hot-drawing process and doping/de-doping the microfibers with ethylene glycol (EG), a record electrical conductivity of 2804 S · cm-1 was achieved. This is believed to be a six-fold improvement over the best previously reported value for PEDOT/PSS fibers (467 S · cm-1) and a twofold improvement over the best values for conductive polymer films treated by EG de-doping (1418 S · cm-1). Moreover, these lead, highly conductive fibers experience a semiconductor-metal transition at 313 K. They also have superior mechanical properties with a Young\\'s modulus up to 8.3 GPa, a tensile strength reaching 409.8 MPa and a large elongation before failure (21%). The most conductive fiber also demonstrates an extraordinary electrical performance during stretching/unstretching: the conductivity increased by 25% before the fiber rupture point with a maximum strain up to 21%. Simple fabrication of the semi-metallic, strong and stretchable wet-spun PEDOT/PSS microfibers can make them available for conductive smart electronics. A dramatic improvement in electrical conductivity is needed to make conductive polymer fibers viable candidates in applications such as flexible electrodes, conductive textiles, and fast-response sensors and actuators.

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.

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...

Strong intrinsic motivation

OpenAIRE

Dessi, Roberta; Rustichini, Aldo

2015-01-01

A large literature in psychology, and more recently in economics, has argued that monetary rewards can reduce intrinsic motivation. We investigate whether the negative impact persists when intrinsic motivation is strong, and test this hypothesis experimentally focusing on the motivation to undertake interesting and challenging tasks, informative about individual ability. We find that this type of task can generate strong intrinsic motivation, that is impervious to the effect of monetary incen...

The INGV Real Time Strong Motion Database

Science.gov (United States)

Massa, Marco; D'Alema, Ezio; Mascandola, Claudia; Lovati, Sara; Scafidi, Davide; Gomez, Antonio; Carannante, Simona; Franceschina, Gianlorenzo; Mirenna, Santi; Augliera, Paolo

2017-04-01

The INGV real time strong motion data sharing is assured by the INGV Strong Motion Database. ISMD (http://ismd.mi.ingv.it) was designed in the last months of 2011 in cooperation among different INGV departments, with the aim to organize the distribution of the INGV strong-motion data using standard procedures for data acquisition and processing. The first version of the web portal was published soon after the occurrence of the 2012 Emilia (Northern Italy), Mw 6.1, seismic sequence. At that time ISMD was the first European real time web portal devoted to the engineering seismology community. After four years of successfully operation, the thousands of accelerometric waveforms collected in the archive need necessary a technological improvement of the system in order to better organize the new data archiving and to make more efficient the answer to the user requests. ISMD 2.0 was based on PostgreSQL (www.postgresql.org), an open source object- relational database. The main purpose of the web portal is to distribute few minutes after the origin time the accelerometric waveforms and related metadata of the Italian earthquakes with ML≥3.0. Data are provided both in raw SAC (counts) and automatically corrected ASCII (gal) formats. The web portal also provide, for each event, a detailed description of the ground motion parameters (i.e. Peak Ground Acceleration, Velocity and Displacement, Arias and Housner Intensities) data converted in velocity and displacement, response spectra up to 10.0 s and general maps concerning the recent and the historical seismicity of the area together with information about its seismic hazard. The focal parameters of the events are provided by the INGV National Earthquake Center (CNT, http://cnt.rm.ingv.it). Moreover, the database provides a detailed site characterization section for each strong motion station, based on geological, geomorphological and geophysical information. At present (i.e. January 2017), ISMD includes 987 (121

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

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.

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

Science.gov (United States)

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.

Phase transition transistors based on strongly-correlated materials

Science.gov (United States)

Nakano, Masaki

2013-03-01

The field-effect transistor (FET) provides electrical switching functions through linear control of the number of charges at a channel surface by external voltage. Controlling electronic phases of condensed matters in a FET geometry has long been a central issue of physical science. In particular, FET based on a strongly correlated material, namely ``Mott transistor,'' has attracted considerable interest, because it potentially provides gigantic and diverse electronic responses due to a strong interplay between charge, spin, orbital and lattice. We have investigated electric-field effects on such materials aiming at novel physical phenomena and electronic functions originating from strong correlation effects. Here we demonstrate electrical switching of bulk state of matter over the first-order metal-insulator transition. We fabricated FETs based on VO2 with use of a recently developed electric-double-layer transistor technique, and found that the electrostatically induced carriers at a channel surface drive all preexisting localized carriers of 1022 cm-3 even inside a bulk to motion, leading to bulk carrier delocalization beyond the electrostatic screening length. This non-local switching of bulk phases is achieved with just around 1 V, and moreover, a novel non-volatile memory like character emerges in a voltage-sweep measurement. These observations are apparently distinct from those of conventional FETs based on band insulators, capturing the essential feature of collective interactions in strongly correlated materials. This work was done in collaboration with K. Shibuya, D. Okuyama, T. Hatano, S. Ono, M. Kawasaki, Y. Iwasa, and Y. Tokura. This work was supported by the Japan Society for the Promotion of Science (JSAP) through its ``Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program).''

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.

Testing strong interaction theories

International Nuclear Information System (INIS)

Ellis, J.

1979-01-01

The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

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

The type of adjuvant strongly influences the T-cell response during nanoparticle-based immunization

Science.gov (United States)

Knuschke, Torben; Epple, Matthias; Westendorf, Astrid M

2014-01-01

Potent vaccines require the ability to effectively induce immune responses. Especially for the control of infectious diseases with intracellular pathogens, like viruses or bacteria, potent T-cell responses are indispensable. Several delivery systems such as nanoparticles have been considered to boost the immunogenicity of pathogen derived peptides or subunits for the induction of potent T-cell responses. Since they can be further functionalized with immunostimulants, like Toll-like receptor (TLR) agonists, they improve the response by enhanced activation of the innate immune system. Currently, TLR agonists like unmethylated CpG oligonucleotides and the synthetic dsRNA derivate polyriboinosinic acid-polyribocytidylic acid (poly[I:C]) are widely used as vaccine adjuvants. CpG and poly(I:C) trigger different TLRs and therefore show differential signal transduction. Recently, we established biodegradable calcium phosphate (CaP) nanoparticles as potent T cell inducing vaccination vehicles. In this commentary we discuss the role of CpG and poly(I:C) for the effective induction of virus-specific T cells during immunization with CaP nanoparticles. The presented results underline the importance of the right formulation of vaccines for specific immunization purpose. PMID:23982325

The cryo-thermal therapy eradicated melanoma in mice by eliciting CD4+ T-cell-mediated antitumor memory immune response.

Science.gov (United States)

He, Kun; Liu, Ping; Xu, Lisa X

2017-03-23

Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used. The cryo-thermal therapy induced regression of implanted melanoma and prolonged long-term survival while inhibiting lung metastasis. It also promoted the activation of CD4 + CD25 - conventional T cells, while reduced the percentage of CD4 + CD25 + regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the spleen, lung and blood. Furthermore, the cryo-thermal therapy enhanced the cytolytic function of CD8 + T cells and induced differentiation of CD8 + T cells into memory stem T cell (T SCM ), and differentiation of CD4 + T cells into dominant CD4-CTL, Th1 and Tfh subsets in the spleen for 90 days after the treatment. It was found that good therapeutic effect was mainly dependent on CD4 + T cells providing a durable memory antitumor immune response. At the same time, significant increase of serum IFN-γ was also observed to provide an ideal microenvironment of antitumor immunity. Further study showed that the rejection of re-challenge of B16F10 but not GL261 tumor in the treated mice in 45 or 60 days after the treatment, implied a strong systemic and melanoma-specific memory antitumor immunity induced by the treatment. Thus the cryo-thermal therapy would be considered as a new therapeutic strategy to prevent tumor recurrence and metastasis with potential clinical applications in the near future.

Memory CD8+ T cells protect dendritic cells from CTL killing

NARCIS (Netherlands)

Watchmaker, Payal B.; Urban, Julie A.; Berk, Erik; Nakamura, Yutaro; Mailliard, Robbie B.; Watkins, Simon C.; van Ham, S. Marieke; Kalinski, Pawel

2008-01-01

CD8(+) T cells have been shown to be capable of either suppressing or promoting immune responses. To reconcile these contrasting regulatory functions, we compared the ability of human effector and memory CD8(+) T cells to regulate survival and functions of dendritic cells (DC). We report that, in

The Electron-Phonon Interaction in Strongly Correlated Systems

International Nuclear Information System (INIS)

Castellani, C.; Grilli, M.

1995-01-01

We analyze the effect of strong electron-electron repulsion on the electron-phonon interaction from a Fermi-liquid point of view and show that the electron-electron interaction is responsible for vertex corrections, which generically lead to a strong suppression of the electron-phonon coupling in the v F q/ω >>1 region, while such effect is not present when v F q/ω F is the Fermi velocity and q and ω are the transferred momentum and frequency respectively. In particular the e-ph scattering is suppressed in transport properties which are dominated by low-energy-high-momentum processes. On the other hand, analyzing the stability criterion for the compressibility, which involves the effective interactions in the dynamical limit, we show that a sizable electron-phonon interaction can push the system towards a phase-separation instability. Finally a detailed analysis of these ideas is carried out using a slave-boson approach for the infinite-U three-band Hubbard model in the presence of a coupling between the local hole density and a dispersionless optical phonon. (author)

Fortune favours the brave: Movement responses shape demographic dynamics in strongly competing populations.

Science.gov (United States)

Potts, Jonathan R; Petrovskii, Sergei V

2017-05-07

Animal movement is a key mechanism for shaping population dynamics. The effect of interactions between competing animals on a population's survival has been studied for many decades. However, interactions also affect an animal's subsequent movement decisions. Despite this, the indirect effect of these decisions on animal survival is much less well-understood. Here, we incorporate movement responses to foreign animals into a model of two competing populations, where inter-specific competition is greater than intra-specific competition. When movement is diffusive, the travelling wave moves from the stronger population to the weaker. However, by incorporating behaviourally induced directed movement towards the stronger population, the weaker one can slow the travelling wave down, even reversing its direction. Hence movement responses can switch the predictions of traditional mechanistic models. Furthermore, when environmental heterogeneity is combined with aggressive movement strategies, it is possible for spatially segregated co-existence to emerge. In this situation, the spatial patterns of the competing populations have the unusual feature that they are slightly out-of-phase with the environmental patterns. Finally, incorporating dynamic movement responses can also enable stable co-existence in a homogeneous environment, giving a new mechanism for spatially segregated co-existence. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

Direct Microbicidal Activity of Cytotoxic T-Lymphocytes

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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.

The impact of acute high-intensity interval exercise on biomarkers of cardiovascular health in type 2 diabetes.

Science.gov (United States)

Francois, Monique E; Little, Jonathan P

2017-08-01

High-intensity interval training (HIIT) interventions improve cardiovascular health, yet the acute effects on circulating and functional biomarkers of cardiovascular function are unclear in individuals with type 2 diabetes (T2D). To explore this, we conducted two investigations to examine the acute response to HIIT in individuals with T2D. Study 1 measured blood pressure, endothelial-dependent dilation, circulating measures of endothelial activation, and troponin T, 30 min and 2 h after HIIT (7 × 1-min intervals) in T2D (n = 8) and age-matched normoglycemic controls (CTL; n = 8). Study 2 assessed circulating measures of endothelial activation and troponin T, 30 min, and 24 h after HIIT (10 × 1-min intervals) in ten previously trained T2D men. In study 1, markers of endothelial function and activation within the first 2 h after HIIT did not differ from baseline between T2D and CTL participants, except at 30 min after HIIT for glucose, which was reduced more in T2D than CTL (by -0.8 ± 1.2 mmol/L, p = 0.04), and VCAM-1, which was reduced more 30 min after HIIT in CTL compared to T2D (by -187 ± 221 ng/mL, p = 0.05). Study 2 saw no significant difference in any circulating markers of endothelial activation and troponin T, 30 min, and 24 h after HIIT in trained T2D males. Exploratory findings from these two studies suggest that acute HIIT does not substantially alter circulating and functional markers of cardio(vascular) health in individuals with T2D who are unaccustomed (study 1) and accustomed to HIIT (study 2).

Discovery of novel targets for multi-epitope vaccines: Screening of HIV-1 genomes using association rule mining

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Piontkivska Helen

2009-07-01

Full Text Available Abstract Background Studies have shown that in the genome of human immunodeficiency virus (HIV-1 regions responsible for interactions with the host's immune system, namely, cytotoxic T-lymphocyte (CTL epitopes tend to cluster together in relatively conserved regions. On the other hand, "epitope-less" regions or regions with relatively low density of epitopes tend to be more variable. However, very little is known about relationships among epitopes from different genes, in other words, whether particular epitopes from different genes would occur together in the same viral genome. To identify CTL epitopes in different genes that co-occur in HIV genomes, association rule mining was used. Results Using a set of 189 best-defined HIV-1 CTL/CD8+ epitopes from 9 different protein-coding genes, as described by Frahm, Linde & Brander (2007, we examined the complete genomic sequences of 62 reference HIV sequences (including 13 subtypes and sub-subtypes with approximately 4 representative sequences for each subtype or sub-subtype, and 18 circulating recombinant forms. The results showed that despite inclusion of recombinant sequences that would be expected to break-up associations of epitopes in different genes when two different genomes are recombined, there exist particular combinations of epitopes (epitope associations that occur repeatedly across the world-wide population of HIV-1. For example, Pol epitope LFLDGIDKA is found to be significantly associated with epitopes GHQAAMQML and FLKEKGGL from Gag and Nef, respectively, and this association rule is observed even among circulating recombinant forms. Conclusion We have identified CTL epitope combinations co-occurring in HIV-1 genomes including different subtypes and recombinant forms. Such co-occurrence has important implications for design of complex vaccines (multi-epitope vaccines and/or drugs that would target multiple HIV-1 regions at once and, thus, may be expected to overcome challenges

Reexamination of the role of Lyt-2-positive T cells in murine skin graft rejection

International Nuclear Information System (INIS)

LeFrancois, L.; Bevan, M.J.

1984-01-01

The authors have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. The authors found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process

Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes.

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Ulrich D Kadolsky

2010-11-01

Full Text Available HIV-1 escape from the cytotoxic T-lymphocyte (CTL response leads to a weakening of viral control and is likely to be detrimental to the patient. To date, the impact of escape on viral load and CD4(+ T cell count has not been quantified, primarily because of sparse longitudinal data and the difficulty of separating cause and effect in cross-sectional studies. We use two independent methods to quantify the impact of HIV-1 escape from CTLs in chronic infection: mathematical modelling of escape and statistical analysis of a cross-sectional cohort. Mathematical modelling revealed a modest increase in log viral load of 0.051 copies ml(-1 per escape event. Analysis of the cross-sectional cohort revealed a significant positive association between viral load and the number of "escape events", after correcting for length of infection and rate of replication. We estimate that a single CTL escape event leads to a viral load increase of 0.11 log copies ml(-1 (95% confidence interval: 0.040-0.18, consistent with the predictions from the mathematical modelling. Overall, the number of escape events could only account for approximately 6% of the viral load variation in the cohort. Our findings indicate that although the loss of the CTL response for a single epitope results in a highly statistically significant increase in viral load, the biological impact is modest. We suggest that this small increase in viral load is explained by the small growth advantage of the variant relative to the wildtype virus. Escape from CTLs had a measurable, but unexpectedly low, impact on viral load in chronic infection.

Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro

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Caixia Gao

2017-12-01

Full Text Available Swine leukocyte antigen (SLA class I molecules play a crucial role in generating specific cellular immune responses against viruses and other intracellular pathogens. They mainly bind and present antigens of intracellular origin to circulating MHC I-restricted cytotoxic T lymphocytes (CTLs. Binding of an appropriate epitope to an SLA class I molecule is the single most selective event in antigen presentation and the first step in the killing of infected cells by CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA molecules. In this study, we constructed SLA class I complexes in vitro comprising viral epitope peptides, the extracellular region of the SLA-1 molecules, and β2-microglobulin (β2m using splicing overlap extension polymerase chain reaction (SOE-PCR. The protein complexes were induced and expressed in an Escherichia coli prokaryotic expression system and subsequently purified and refolded. Specific binding of seven SLA-1 proteins to one classical swine fever virus (CSFV and four porcine reproductive and respiratory syndrome virus (PRRSV epitope peptides was detected by enzyme-linked immunosorbent assay (ELISA-based method. The SLA-1∗13:01, SLA-1∗11:10, and SLA-1∗11:01:02 proteins were able to bind specifically to different CTL epitopes of CSFV and PRRSV and the MHC restrictions of the five epitopes were identified. The fixed combination of Asn151Val152 residues was identified as the potentially key amino acid residues influencing the binding of viral several CTL epitope peptides to SLA-1∗13:01 and SLA-1∗04:01:01 proteins. The more flexible pocket E in the SLA-1∗13:01 protein might have fewer steric limitations and therefore be able to accommodate more residues of viral CTL epitope peptides, and may thus play a critical biochemical role in determining the peptide-binding motif of SLA-1∗13:01. Characterization of the binding specificity of peptides to SLA class I molecules provides an

Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1.

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Zabrina L Brumme

2007-07-01

Full Text Available Despite the formidable mutational capacity and sequence diversity of HIV-1, evidence suggests that viral evolution in response to specific selective pressures follows generally predictable mutational pathways. Population-based analyses of clinically derived HIV sequences may be used to identify immune escape mutations in viral genes; however, prior attempts to identify such mutations have been complicated by the inability to discriminate active immune selection from virus founder effects. Furthermore, the association between mutations arising under in vivo immune selection and disease progression for highly variable pathogens such as HIV-1 remains incompletely understood. We applied a viral lineage-corrected analytical method to investigate HLA class I-associated sequence imprinting in HIV protease, reverse transcriptase (RT, Vpr, and Nef in a large cohort of chronically infected, antiretrovirally naïve individuals. A total of 478 unique HLA-associated polymorphisms were observed and organized into a series of "escape maps," which identify known and putative cytotoxic T lymphocyte (CTL epitopes under selection pressure in vivo. Our data indicate that pathways to immune escape are predictable based on host HLA class I profile, and that epitope anchor residues are not the preferred sites of CTL escape. Results reveal differential contributions of immune imprinting to viral gene diversity, with Nef exhibiting far greater evidence for HLA class I-mediated selection compared to other genes. Moreover, these data reveal a significant, dose-dependent inverse correlation between HLA-associated polymorphisms and HIV disease stage as estimated by CD4(+ T cell count. Identification of specific sites and patterns of HLA-associated polymorphisms across HIV protease, RT, Vpr, and Nef illuminates regions of the genes encoding these products under active immune selection pressure in vivo. The high density of HLA-associated polymorphisms in Nef compared to other

Abortion: Strong's counterexamples fail

DEFF Research Database (Denmark)

Di Nucci, Ezio

2009-01-01

This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally...

Responsible nations

DEFF Research Database (Denmark)

Lippert-Rasmussen, Kasper

2009-01-01

In National Responsibility and Global Justice, David Miller defends the view that a member of a nation can be collectively responsible for an outcome despite the fact that: (i) she did not control it; (ii) she actively opposed those of her nation's policies that produced the outcome; and (iii......) actively opposing the relevant policy was costly for her. I argue that Miller's arguments in favor of this strong externalist view about responsibility and control are insufficient. Specifically, I show that Miller's two models of synchronic collective responsibility*the like-minded group model...

The role of HLA-E polymorphism in immunological response

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Milena Iwaszko

2011-09-01

Full Text Available The HLA-E protein is one of the most extensively studied MHC class Ib antigens and the least polymorphic one compared to other MHC class I molecules. In the human population there have been reported just ten alleles encoding three different peptides. Only two of these alleles, namely HLA-E*0101 and HLA-E*0103, are widely distributed (around 50�0each. The proteins encoded by these alleles differ from each other in one amino acid at position 107. In HLA-E*0101 it is arginine and in HLA-E*0103 it is glycine. The difference between these proteins manifests itself in surface expression levels, affinities to leader peptides and thermal stabilities of their complexes.The HLA-E molecule is a ligand for CD94/NKG2 receptors on NK cells and TCR receptors on NK-CTL (NK-cytotoxic T lymphocyte cells, so it plays a double role in both innate and adaptive immunity. This paper reviews the knowledge on the role of the HLA-E molecule in the immunological response. Aspects related to polymorphism of the HLA-E gene and the course of several diseases including type I diabetes, ankylosing spondylitis, HCV and HIV infections, nasopharyngeal cancer and recurrent spontaneous abortions, as well as the outcome of hematopoietic stem cell transplantation, are presented and discussed in more detail.

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

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.

Simultaneous approach using systemic, mucosal and transcutaneous routes of immunization for development of protective HIV-1 vaccines.

Science.gov (United States)

Belyakov, I M; Ahlers, J D

2011-01-01

Mucosal tissues are major sites of HIV entry and initial infection. Induction of a local mucosal cytotoxic T lymphocyte response is considered an important goal in developing an effective HIV vaccine. In addition, activation and recruitment of memory CD4(+) and CD8(+) T cells in systemic lymphoid circulation to mucosal effector sites might provide the firewall needed to prevent virus spread. Therefore a vaccine that generates CD4(+) and CD8(+) responses in both mucosal and systemic tissues might be required for protection against HIV. However, optimal routes and number of vaccinations required for the generation of long lasting CD4(+) and CD8(+) CTL effector and memory responses are not well understood especially for mucosal T cells. A number of studies looking at protective immune responses against diverse mucosal pathogens have shown that mucosal vaccination is necessary to induce a compartmentalized immune response including maximum levels of mucosal high-avidity CD8(+) CTL, antigen specific mucosal antibodies titers (especially sIgA), as well as induction of innate anti-viral factors in mucosa tissue. Immune responses are detectable at mucosal sites after systemic delivery of vaccine, and prime boost regimens can amplify the magnitude of immune responses in mucosal sites and in systemic lymphoid tissues. We believe that the most optimal mucosal and systemic HIV/SIV specific protective immune responses and innate factors might best be achieved by simultaneous mucosal and systemic prime and boost vaccinations. Similar principals of vaccination may be applied for vaccine development against cancer and highly invasive pathogens that lead to chronic infection.

Light-intensity and high-intensity interval training improve cardiometabolic health in rats.

Science.gov (United States)

Batacan, Romeo B; Duncan, Mitch J; Dalbo, Vincent J; Connolly, Kylie J; Fenning, Andrew S

2016-09-01

Physical activity has the potential to reduce cardiometabolic risk factors but evaluation of different intensities of physical activity and the mechanisms behind their health effects still need to be fully established. This study examined the effects of sedentary behaviour, light-intensity training, and high-intensity interval training on biometric indices, glucose and lipid metabolism, inflammatory and oxidative stress markers, and vascular and cardiac function in adult rats. Rats (12 weeks old) were randomly assigned to 1 of 4 groups: control (CTL; no exercise), sedentary (SED; no exercise and housed in small cages to reduce activity), light-intensity trained (LIT; four 30-min exercise bouts/day at 8 m/min separated by 2-h rest period, 5 days/week), and high-intensity interval trained (HIIT, four 2.5-min work bouts/day at 50 m/min separated by 3-min rest periods, 5 days/week). After 12 weeks of intervention, SED had greater visceral fat accumulation (p HIIT demonstrated beneficial changes in body weight, visceral and epididymal fat weight, glucose regulation, low-density lipoprotein cholesterol, total cholesterol, and mesenteric vessel contractile response compared with the CTL group (p HIIT had significant improvements in systolic blood pressure and endothelium-independent vasodilation to aorta and mesenteric artery compared with the CTL group (p HIIT induce health benefits by improving traditional cardiometabolic risk factors. LIT improves cardiac health while HIIT promotes improvements in vascular health.

Poly-ϵ-caprolactone/chitosan nanoparticles provide strong adjuvant effect for hepatitis B antigen.

Science.gov (United States)

Jesus, Sandra; Soares, Edna; Borchard, Gerrit; Borges, Olga

2017-10-01

This work aims to investigate the adjuvant effect of poly-ϵ-caprolactone/chitosan nanoparticles (NPs) for hepatitis B surface antigen (HBsAg) and the plasmid DNA encoding HBsAg (pRC/CMV-HBs). Both antigens were adsorbed onto preformed NPs. Vaccination studies were performed in C57BL/6 mice. Transfection efficiency was investigated in A549 cell line. HBsAg-adsorbed NPs generated strong anti-HBsAg IgG titers, mainly of IgG1 isotype, and induced antigen-specific IFN-γ and IL-17 secretion by spleen cells. The addition of pRC/CMV-HBs to the HBsAg-adsorbed NPs inhibited IL-17 secretion but had minor effect on IFN-γ levels. Lastly, pRC/CMV-HBs-loaded NPs generated a weak serum antibody response. Poly-ϵ-caprolactone/chitosan NPs provide a strong humoral adjuvant effect for HBsAg and induce a Th1/Th17-mediated cellular immune responses worth explore for hepatitis B virus vaccination.

Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

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Fei Jiang

Full Text Available Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu and heat shock protein 70 (HSP 70 are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70, IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

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.

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.

Depletion of CD4+ T cells precipitates immunopathology in immunodeficient mice infected with a noncytocidal virus

DEFF Research Database (Denmark)

Christensen, Jan Pravsgaard; Bartholdy, C; Wodarz, D

2001-01-01

investigated whether CD4(+) Th cells are required to establish and maintain this new equilibrium. The absence of IFN-gamma does not impair the generation of IL-2-producing CD4(+) cells, and depletion of these cells precipitates severe CD8(+) T cell-mediated immunopathology in IFN-gamma(-/-) mice, indicating...... an important role of CD4(+) T cells in preventing this syndrome. Analysis of organ virus levels revealed a further impairment of virus control in IFN-gamma(-/-) mice following CD4(+) cell depletion. Initially the antiviral CTL response did not require CD4(+) cells, but with time an impaired reactivity toward...... especially the glycoprotein 33--41 epitope was noted. Enumeration of epitope-specific (glycoprotein 33--41 and nucleoprotein 396--404) CD8(+) T cells by use of tetramers gave similar results. Finally, limiting dilution analysis of CTL precursors reveal an impaired capacity to sustain this population in CD4...

77 FR 16131 - Establishing a White House Council on Strong Cities, Strong Communities

Science.gov (United States)

2012-03-20

... Order 13602 of March 15, 2012 Establishing a White House Council on Strong Cities, Strong Communities By... enable them to develop and implement economic strategies to become more competitive, sustainable, and... resources to develop and implement their economic vision and strategies. Sec. 2. White House Council on...

Instabilities in strongly coupled plasmas

CERN Document Server

Kalman, G J

2003-01-01

The conventional Vlasov treatment of beam-plasma instabilities is inappropriate when the plasma is strongly coupled. In the strongly coupled liquid state, the strong correlations between the dust grains fundamentally affect the conditions for instability. In the crystalline state, the inherent anisotropy couples the longitudinal and transverse polarizations, and results in unstable excitations in both polarizations. We summarize analyses of resonant and non-resonant, as well as resistive instabilities. We consider both ion-dust streaming and dust beam-plasma instabilities. Strong coupling, in general, leads to an enhancement of the growth rates. In the crystalline phase, a resonant transverse instability can be excited.

Strong dietary restrictions protect Drosophila against anoxia/reoxygenation injuries.

Directory of Open Access Journals (Sweden)

Paul Vigne

Full Text Available Reoxygenation of ischemic tissues is a major factor that determines the severity of cardiovascular diseases. This paper describes the consequences of anoxia/reoxygenation (A/R stresses on Drosophila, a useful, anoxia tolerant, model organism.Newly emerged adult male flies were exposed to anoxic conditions (<1% O2 for 1 to 6 hours, reoxygenated and their survival was monitored.A/R stresses induced a transient increase in mortality which peaked at the time of reoxygenation. Then flies recovered low mortality rates similar to those of control flies. A/R induced mortality was strongly dependent on dietary conditions during the 48 h that preceded anoxia. Well fed flies were anoxia sensitive. Strong dietary restrictions and starvation conditions protected flies against A/R injuries. The tolerance to anoxia was associated to large decreases in glycogen, protein, and ATP contents. During anoxia, anoxia tolerant flies produced more lactate, less phosphate and they maintained more stable ATP levels than anoxia sensitive flies. Moderate dietary restrictions, which increased the longevity of normoxic flies, did not promote resistance to A/R stresses. Diet dependent A/R injuries were still observed in sigma loss of function mutants and they were insensitive to dietary rapamycin or resveratrol. AICAR (5-aminoimidazole-4-carboxamide-1-beta-D-ribose-furanoside, an activator AMP kinase decreased A/R injuries. Mutants in the insulin signalling pathway were more anoxia tolerant in a fed state.Long A/R stresses induce a transient increase in mortality in Drosophila. This mortality is highly dependent on dietary conditions prior to the stress. Strong dietary restrictions and starvation conditions protect flies against A/R injuries, probably by inducing a major remodelling of energy metabolism. The results also indicate that mechanistically different responses develop in response to dietary restrictions of different strengths. AMP kinase and the insulin signalling

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.

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

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

Strongly interacting Fermi gases

Directory of Open Access Journals (Sweden)

Bakr W.

2013-08-01

Full Text Available Strongly interacting gases of ultracold fermions have become an amazingly rich test-bed for many-body theories of fermionic matter. Here we present our recent experiments on these systems. Firstly, we discuss high-precision measurements on the thermodynamics of a strongly interacting Fermi gas across the superfluid transition. The onset of superfluidity is directly observed in the compressibility, the chemical potential, the entropy, and the heat capacity. Our measurements provide benchmarks for current many-body theories on strongly interacting fermions. Secondly, we have studied the evolution of fermion pairing from three to two dimensions in these gases, relating to the physics of layered superconductors. In the presence of p-wave interactions, Fermi gases are predicted to display toplogical superfluidity carrying Majorana edge states. Two possible avenues in this direction are discussed, our creation and direct observation of spin-orbit coupling in Fermi gases and the creation of fermionic molecules of 23Na 40K that will feature strong dipolar interactions in their absolute ground state.

Quantum electrodynamics of strong fields

International Nuclear Information System (INIS)

Greiner, W.

1983-01-01

Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

International Nuclear Information System (INIS)

Muthumani, Karuppiah; Zhang Donghui; Dayes, Nathanael S.; Hwang, Daniel S.; Calarota, Sandra A.; Choo, Andrew Y.; Boyer, Jean D.; Weiner, David B.

2003-01-01

HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

Development of tipping-over analysis of cask subjected to earthquake strong motion

International Nuclear Information System (INIS)

Shirai, Koji; Ito, Chihiro; Ryu, Hiroshi

1993-01-01

Since a cask is vertically oriented during loading in cask-storage, it is necessary to investigate the integrity of the cask against tipping-over during strong earthquakes. The rocking and sliding behavior of the cask during strong earthquakes can be analyzed as a dynamic vibration problem for a rigid cylinder. In this paper, in order to clarify the tipping-over characteristics of a cask during strong earthquakes, the authors applied the Distinct Element Method (DEM) to the seismic response analysis of the cask. DEM was introduced by Cundall P.A. in 1971. It is based on the use of an explicit numerical scheme. The cask was considered to be a rigid polygonal element, which satisfied the equation of motion and the law of action and reaction. They examined the applicability of this code by comparison with experimental results obtained from shaking table tests using scale model casks considering the dimension of a 100 ton class full-scale cask

Strongly Deterministic Population Dynamics in Closed Microbial Communities

Directory of Open Access Journals (Sweden)

Zak Frentz

2015-10-01

Full Text Available Biological systems are influenced by random processes at all scales, including molecular, demographic, and behavioral fluctuations, as well as by their interactions with a fluctuating environment. We previously established microbial closed ecosystems (CES as model systems for studying the role of random events and the emergent statistical laws governing population dynamics. Here, we present long-term measurements of population dynamics using replicate digital holographic microscopes that maintain CES under precisely controlled external conditions while automatically measuring abundances of three microbial species via single-cell imaging. With this system, we measure spatiotemporal population dynamics in more than 60 replicate CES over periods of months. In contrast to previous studies, we observe strongly deterministic population dynamics in replicate systems. Furthermore, we show that previously discovered statistical structure in abundance fluctuations across replicate CES is driven by variation in external conditions, such as illumination. In particular, we confirm the existence of stable ecomodes governing the correlations in population abundances of three species. The observation of strongly deterministic dynamics, together with stable structure of correlations in response to external perturbations, points towards a possibility of simple macroscopic laws governing microbial systems despite numerous stochastic events present on microscopic levels.

Into the intracellular logistics of cross-presentation

Directory of Open Access Journals (Sweden)

Charlotte eSadaka

2012-02-01

Full Text Available The induction of cytotoxic CD8+ T cell responses requires the presentation of antigenic peptides by MHC class I molecules (MHC I. MHC I usually present peptides derived from endogenous proteins. However, some subtypes of dendritic cells (DCs have developed the ability to efficiently present peptides derived from exogenous antigens on MHC I via a process called cross-presentation. Cross-presentation is intimately linked to the induction of anti-viral, -bacterial and -tumor cytotoxic T cell (CTL responses, as well as a wide variety of CTL-mediated diseases and transplant rejections. The molecular and cellular mechanisms underlying cross-presentation have been studied intensively since its original description, yet understanding of this process is incomplete and on the forefront of immunological research. Numerous pathways and models, some of them conflicting, have been described so far. Here, we review the various pathways reported as involved in cross-presentation, highlighting the complexity of this process. We also discuss in detail the different intracellular steps required, from antigen capture and routing, to processing and finally peptide loading, emphasizing the need for a better understanding of the cell biology of this phenomenon.

Suppression of immune surveillance in melanoma [Immunotherapy of metastatic melanoma by reversal of immune suppression

Energy Technology Data Exchange (ETDEWEB)

Biggs, M. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Eiselein, J. E. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2001-06-01

In this paper we develop the hypothesis that a significant fraction of patients with advanced melanoma can be successfully treated with immunotherapy. Reversal of antigen-specific immune suppression to melanoma polypeptide antigens is an essential, first step. We postulate the key regulation of CTL responses resides within the CD4+ T-lymphocytes and macrophage/dendritic cells. There is a pluri-potential cell within this regulatory arm that functions either as a Th1 cell or as a suppressor T-cell, Ths, depending on how antigen is presented. We have shown that poliovirus 1 Sabin will lyse human melanoma cells in tissue culture, and a special "vaccine" prepared from this lysis actively stimulates Ths cell function. The Ths arm of the regulatory system can be down-regulated with cyclophosphamide given 24 hours after the vaccine. The capacity to generate a CTL response is retained. The summary conclusion is that a phase 1 clinical trial in advanced melanoma using the special viral-tumor-lysate followed by cyclophosphamide, plus expanded autologous dendritic cells sensitized with the polypeptide epitopes captained in the viral-lysate will produce beneficial results.

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...

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.

Strong Bisimilarity of Simple Process Algebras

DEFF Research Database (Denmark)

Srba, Jirí

2003-01-01

We study bisimilarity and regularity problems of simple process algebras. In particular, we show PSPACE-hardness of the following problems: (i) strong bisimilarity of Basic Parallel Processes (BPP), (ii) strong bisimilarity of Basic Process Algebra (BPA), (iii) strong regularity of BPP, and (iv......) strong regularity of BPA. We also demonstrate NL-hardness of strong regularity problems for the normed subclasses of BPP and BPA. Bisimilarity problems of simple process algebras are introduced in a general framework of process rewrite systems, and a uniform description of the new techniques used...

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.

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...

Milk protein responses to balanced amino acid and removal of Leucine and Arginine supplied from jugular-infused amino acid mixture in lactating dairy cows.

Science.gov (United States)

Tian, W; Wang, H R; Wu, T Y; Ding, L Y; Zhao, R; Khas, E; Wang, C F; Zhang, F Q; Mi, F Y; Wang, L; Ning, L T

2017-10-01

This study was undertaken to evaluate the milk protein response when cows were supplied a balanced AA profile and to determine whether a deficiency of Leucine (Leu) or Arginine (Arg) had a negative effect on milk protein. Eight mid-lactation Holstein cows were randomly assigned to 5-day continuous jugular infusions of saline (CTL), EAA mixture prepared on the profile of casein and supplied (in % of lysine (Lys)) 100% of Lys, 33.3% of methionine (Met), 110.2% of Leu, 43.6% of Arg, 50.8% of threonine (Thr), 81.6% of valine (Val), 69.7% of isoleucine (Ile), 61.4% of phenylalanine (Phe) and 34.2% of histidine (His) (Casein, 160 g/d), EAA mixture excluding Leu (-Leu, 163 g/d) or EAA mixture excluding Arg (-Arg, 158 g/d) in a duplicated 4 × 4 Latin square design with four infusion periods separated by 7-day interval period. The basal diet supplied 1.6 Mcal NE L and 94.4 g MP per 1 kg DM to meet requirements for lactation. The Casein treatment provided a balanced supply (in % of MP) of 10.3% Leu and 5.3% Arg, whereas in the two subsequent -Leu and -Arg treatments, the concentration of Leu and Arg was reduced to 8.4 and 4.6% respectively. Dry matter intake (15.4 kg/day) was not affected by treatments. The Casein treatment increased milk yield (14.9%, p < 0.001), milk protein yield (120 g, p < 0.001) and milk protein efficiency (0.03, p = 0.099) than CTL treatment. However, the -Leu treatment decreased the responses of above-measured parameters by 6.25%, 70 g, 0.05 (p < 0.06) (compared with Casein). These effects of Leu were related to decreased Leu concentration and improved concentration of Ile and Val in plasma. The -Arg treatment decreased the plasma Arg concentration than the Casein treatment, whereby resulted in the decrease of milk yield (5.7%, p = 0.073), milk protein yield (60 g, p = 0.011) and milk protein efficiency (0.04, p = 0.037). In conclusion, supply of EAA profile of casein can increase the lactation production in dairy cows, and 8

Rejection of unfair offers in the ultimatum game is no evidence of strong reciprocity

Science.gov (United States)

Yamagishi, Toshio; Horita, Yutaka; Mifune, Nobuhiro; Hashimoto, Hirofumi; Li, Yang; Shinada, Mizuho; Miura, Arisa; Inukai, Keigo; Takagishi, Haruto; Simunovic, Dora

2012-01-01

The strong reciprocity model of the evolution of human cooperation has gained some acceptance, partly on the basis of support from experimental findings. The observation that unfair offers in the ultimatum game are frequently rejected constitutes an important piece of the experimental evidence for strong reciprocity. In the present study, we have challenged the idea that the rejection response in the ultimatum game provides evidence of the assumption held by strong reciprocity theorists that negative reciprocity observed in the ultimatum game is inseparably related to positive reciprocity as the two sides of a preference for fairness. The prediction of an inseparable relationship between positive and negative reciprocity was rejected on the basis of the results of a series of experiments that we conducted using the ultimatum game, the dictator game, the trust game, and the prisoner’s dilemma game. We did not find any correlation between the participants’ tendencies to reject unfair offers in the ultimatum game and their tendencies to exhibit various prosocial behaviors in the other games, including their inclinations to positively reciprocate in the trust game. The participants’ responses to postexperimental questions add support to the view that the rejection of unfair offers in the ultimatum game is a tacit strategy for avoiding the imposition of an inferior status. PMID:23188801

Rejection of unfair offers in the ultimatum game is no evidence of strong reciprocity.

Science.gov (United States)

Yamagishi, Toshio; Horita, Yutaka; Mifune, Nobuhiro; Hashimoto, Hirofumi; Li, Yang; Shinada, Mizuho; Miura, Arisa; Inukai, Keigo; Takagishi, Haruto; Simunovic, Dora

2012-12-11

The strong reciprocity model of the evolution of human cooperation has gained some acceptance, partly on the basis of support from experimental findings. The observation that unfair offers in the ultimatum game are frequently rejected constitutes an important piece of the experimental evidence for strong reciprocity. In the present study, we have challenged the idea that the rejection response in the ultimatum game provides evidence of the assumption held by strong reciprocity theorists that negative reciprocity observed in the ultimatum game is inseparably related to positive reciprocity as the two sides of a preference for fairness. The prediction of an inseparable relationship between positive and negative reciprocity was rejected on the basis of the results of a series of experiments that we conducted using the ultimatum game, the dictator game, the trust game, and the prisoner's dilemma game. We did not find any correlation between the participants' tendencies to reject unfair offers in the ultimatum game and their tendencies to exhibit various prosocial behaviors in the other games, including their inclinations to positively reciprocate in the trust game. The participants' responses to postexperimental questions add support to the view that the rejection of unfair offers in the ultimatum game is a tacit strategy for avoiding the imposition of an inferior status.

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.

Strong cosmic censorship and the strong curvature singularities

International Nuclear Information System (INIS)

Krolak, A.

1987-01-01

Conditions are given under which any asymptotically simple and empty space-time that has a partial Cauchy surface with an asymptotically simple past is globally hyperbolic. It is shown that this result suggests that the Cauchy horizons of the type occurring in Reissner--Nordstroem and Kerr space-times are unstable. This in turn gives support for the validity of the strong cosmic censorship hypothesis

PRISM, Processing and Review Interface for Strong Motion Data Software

Science.gov (United States)

Kalkan, E.; Jones, J. M.; Stephens, C. D.; Ng, P.

2016-12-01

A continually increasing number of high-quality digital strong-motion records from stations of the National Strong Motion Project (NSMP) of the U.S. Geological Survey (USGS), as well as data from regional seismic networks within the U.S., calls for automated processing of strong-motion records with human review limited to selected significant or flagged records. The NSMP has developed the Processing and Review Interface for Strong Motion data (PRISM) software to meet this need. PRISM automates the processing of strong-motion records by providing batch-processing capabilities. The PRISM software is platform-independent (coded in Java), open-source, and does not depend on any closed-source or proprietary software. The software consists of two major components: a record processing engine composed of modules for each processing step, and a graphical user interface (GUI) for manual review and processing. To facilitate the use by non-NSMP earthquake engineers and scientists, PRISM (both its processing engine and GUI components) is easy to install and run as a stand-alone system on common operating systems such as Linux, OS X and Windows. PRISM was designed to be flexible and extensible in order to accommodate implementation of new processing techniques. Input to PRISM currently is limited to data files in the Consortium of Organizations for Strong-Motion Observation Systems (COSMOS) V0 format, so that all retrieved acceleration time series need to be converted to this format. Output products include COSMOS V1, V2 and V3 files as: (i) raw acceleration time series in physical units with mean removed (V1), (ii) baseline-corrected and filtered acceleration, velocity, and displacement time series (V2), and (iii) response spectra, Fourier amplitude spectra and common earthquake-engineering intensity measures (V3). A thorough description of the record processing features supported by PRISM is presented with examples and validation results. All computing features have been

Advanced Technologies Addressing Asia-Pacific Infectious Diseases

Science.gov (United States)

2011-01-01

outbreak in Malaysia in 1998-1999 threaten to spread beyond borders as finally demonstrated by the outbreak of severe acute respiratory syndrome (SARS) in...independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human...former smokers. By history, 5 had dyslipidemia (all diet controlled), 3 had a diagnosis of hypertension (all treated with anti-hypertensive

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.

A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate

DEFF Research Database (Denmark)