Passing the baton: Mentoring for adoption of active-learning pedagogies by research-active junior faculty.

PubMed

Grimes, Catherine Leimkuhler; White, Harold B

2015-01-01

There are barriers to adoption of research-based teaching methods. Professional development workshops may inform faculty of these methods, but effective adoption often does not follow. In addition, newly-minted research-active faculty are often overwhelmed by the many new responsibilities (grant writing, group management, laboratory setup, teaching) that accompany the position and normally do not have the time to consider novel teaching approaches. This case study documents how over a three-year period, the responsibility for teaching a nontraditional "Introduction to Biochemistry" course in a problem-based learning format was successfully transferred from a senior faculty member nearing retirement (HBW) to a newly-hired research-active assistant professor (CLG). We describe our apprenticeship project involving modeling, scaffolding, fading, and coaching. We suggest that involving faculty in active-learning pedagogy early in their career with mentoring by senior faculty overcomes barriers to adopting these methods. This case describes a specific example from which potentially useful elements can be adopted and adapted wherever biochemistry is taught. © 2015 The International Union of Biochemistry and Molecular Biology.

Adoptive transfer of acute lung injury.

PubMed

Moxley, M A; Baird, T L; Corbett, J A

2000-11-01

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.

Studying Neutrophil Migration In Vivo Using Adoptive Cell Transfer.

PubMed

Miyabe, Yoshishige; Kim, Nancy D; Miyabe, Chie; Luster, Andrew D

2016-01-01

Adoptive cell transfer experiments can be used to study the roles of cell trafficking molecules on the migratory behavior of specific immune cell populations in vivo. Chemoattractants and their G protein-coupled seven-transmembrane-spanning receptors regulate migration of cells in vivo, and dysregulated expression of chemoattractants and their receptors is implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. We have used adoptive neutrophil transfer to define the contributions of chemoattractant receptors, cytokines, and activation receptors expressed on neutrophils that critically regulate their entry into the inflamed joint. In this review, we describe the procedure of neutrophil adoptive transfer to study the influence of neutrophil-specific receptors or mediators upon the their recruitment into the joint using the K/BxN model of inflammatory arthritis as a model of how adoptive cell transfer studies can be used to study immune cell migration in vivo.

Least-squares collocation meshless approach for radiative heat transfer in absorbing and scattering media

NASA Astrophysics Data System (ADS)

Liu, L. H.; Tan, J. Y.

2007-02-01

A least-squares collocation meshless method is employed for solving the radiative heat transfer in absorbing, emitting and scattering media. The least-squares collocation meshless method for radiative transfer is based on the discrete ordinates equation. A moving least-squares approximation is applied to construct the trial functions. Except for the collocation points which are used to construct the trial functions, a number of auxiliary points are also adopted to form the total residuals of the problem. The least-squares technique is used to obtain the solution of the problem by minimizing the summation of residuals of all collocation and auxiliary points. Three numerical examples are studied to illustrate the performance of this new solution method. The numerical results are compared with the other benchmark approximate solutions. By comparison, the results show that the least-squares collocation meshless method is efficient, accurate and stable, and can be used for solving the radiative heat transfer in absorbing, emitting and scattering media.

Irradiated and activated autologous PBMCs induce expansion of highly cytotoxic human NK cells in vitro.

PubMed

Ahn, Yong-Oon; Kim, Saerom; Kim, Tae Min; Song, Eun Young; Park, Myoung Hee; Heo, Dae Seog

2013-09-01

Adoptive cell transfer of ex vivo-activated natural killer (NK) cells is a promising therapy for cancer treatment. Because of inhibitory signaling through killer immunoglobulin-like receptor (KIR)-KIR ligands, KIR-mismatched allogeneic NK cell transfer is considered to be a more effective strategy than is autologous transfer. However, purified NK cells do not expand well enough in vitro with good manufacturing practice-compliant components for clinical use. Some investigators have developed selective expansion of NK cells from peripheral blood mononuclear cells, but these cells have the risk of graft-versus-host disease in allogeneic settings because of T cells contamination. In this study, we developed a novel method for NK cell activation and expansion. Using only good manufacturing practice-compliant components and autologous feeder cells, once purified NK cells were effectively expanded (2500-fold at day 17). The expanded cells were highly purified NK cells, and the use of these cells is suitable for allogeneic transfer without the risk of graft-versus-host disease induction. Importantly, the expanded NK cells also showed enhanced cytotoxicity compared with NK cells conventionally expanded by recombinant human interleukin 2. Finally, induction of NKG2D ligand expression on feeder cells implies that the NKG2D-NKG2DL interaction may play a role in NK cell expansion. In conclusion, this method can be used to obtain NK cells for more successful allogeneic NK cell adoptive transfer for use in antitumor immune therapy.

AlGaAs/Si dual-junction tandem solar cells by epitaxial lift-off and print-transfer-assisted direct bonding

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

Xiong, Kanglin; Mi, Hongyi; Chang, Tzu-Hsuan

A novel method is developed to realize a III-V/Si dual-junction photovoltaic cell by combining epitaxial lift-off (ELO) and print-transfer-assisted bonding methods. The adoption of ELO enables III-V wafers to be recycled and reused, which can further lower the cost of III-V/Si photovoltaic panels. For demonstration, high crystal quality, micrometer-thick, GaAs/AlGaAs/GaAs films are lifted off, transferred, and directly bonded onto Si wafer without the use of any adhesive or bonding agents. The bonding interface is optically transparent and conductive both thermally and electrically. Prototype AlGaAs/Si dual-junction tandem solar cells have been fabricated and exhibit decent performance.

AlGaAs/Si dual-junction tandem solar cells by epitaxial lift-off and print-transfer-assisted direct bonding

DOE PAGES

Xiong, Kanglin; Mi, Hongyi; Chang, Tzu-Hsuan; ...

2018-01-04

A novel method is developed to realize a III-V/Si dual-junction photovoltaic cell by combining epitaxial lift-off (ELO) and print-transfer-assisted bonding methods. The adoption of ELO enables III-V wafers to be recycled and reused, which can further lower the cost of III-V/Si photovoltaic panels. For demonstration, high crystal quality, micrometer-thick, GaAs/AlGaAs/GaAs films are lifted off, transferred, and directly bonded onto Si wafer without the use of any adhesive or bonding agents. The bonding interface is optically transparent and conductive both thermally and electrically. Prototype AlGaAs/Si dual-junction tandem solar cells have been fabricated and exhibit decent performance.

Restoration of Viral Immunity in Immunodeficient Humans by the Adoptive Transfer of T Cell Clones

NASA Astrophysics Data System (ADS)

Riddell, Stanley R.; Watanabe, Kathe S.; Goodrich, James M.; Li, Cheng R.; Agha, Mounzer E.; Greenberg, Philip D.

1992-07-01

The adoptive transfer of antigen-specific T cells to establish immunity is an effective therapy for viral infections and tumors in animal models. The application of this approach to human disease would require the isolation and in vitro expansion of human antigen-specific T cells and evidence that such T cells persist and function in vivo after transfer. Cytomegalovirus-specific CD8^+ cytotoxic T cell (CTL) clones could be isolated from bone marrow donors, propagated in vitro, and adoptively transferred to immunodeficient bone marrow transplant recipients. No toxicity developed and the clones provided persistent reconstitution of CD8^+ cytomegalovirus-specific CTL responses.

ADOPTIVE-CELL-TRANSFER THERAPY FOR THE TREATMENT OF PATIENTS WITH CANCER

PubMed Central

Dudley, Mark E.; Rosenberg, Steven A.

2008-01-01

Adoptive immunotherapy — the isolation of antigen-specific cells, their ex vivo expansion and activation, and subsequent autologous administration — is a promising approach to inducing antitumour immune responses. The molecular identification of tumour antigens and the ability to monitor the persistence and transport of transferred cells has provided new insights into the mechanisms of tumour immunotherapy. Recent studies have shown the effectiveness of cell-transfer therapies for the treatment of patients with selected metastatic cancers. These studies provide a blueprint for the wider application of adoptive-cell-transfer therapy, and emphasize the requirement for in vivo persistence of the cells for therapeutic efficacy. PMID:12951585

T lymphocyte-mediated protection against Pseudomonas aeruginosa infection in granulocytopenic mice.

PubMed Central

Powderly, W G; Pier, G B; Markham, R B

1986-01-01

BALB/c mice immunized with Pseudomonas aeruginosa immunotype 1 polysaccharide develop protective T cell immunity to bacterial challenge. In vitro, T cells from immunized mice kill P. aeruginosa by production of a bactericidal lymphokine. The present study demonstrates that adoptive transfer of T cells from immunized BALB/c mice to granulocytopenic mice resulted in 97% survival on challenge with P. aeruginosa, compared with 17% survival with adoptive transfer of T cells from nonimmune BALB/c mice. This protection is specifically elicited by reexposure to the original immunizing antigen; adoptive recipients cannot withstand challenge with immunotype 3 P. aeruginosa. However, the adoptive recipients do survive simultaneous infection with both P. aeruginosa immunotypes 1 and 3. Adoptive transfer of T cells from the congenic CB.20 mice, which are unable to kill P. aeruginosa in vitro, provides only 20% protection to granulocytopenic mice. These studies indicate that transfer of specific immune T lymphocytes can significantly enhance the resistance to P. aeruginosa infection in granulocytopenic mice. PMID:2426306

Adoptive Cell Transfer Therapy

PubMed Central

Dudley, Mark E.; Rosenberg, Steven A.

2008-01-01

Adoptive cell transfer therapy has developed into a potent and effective treatment for patients with metastatic melanoma. Current application of this therapy relies on the ex vivo generation of highly active, highly avid tumor-reactive lymphocyte cultures from endogenous tumor infiltrating lymphocytes or on the genetic engineering of cells using antigen receptor genes to express de novo tumor antigen recognition. When anti-tumor lymphocyte cultures are administered to autologous patients with high dose interleukin-2 following a lymphodepleting conditioning regimen, the cells can expand in vivo, traffic to tumor, and mediate tumor regression and durable objective clinical responses. Current investigation seeks to improve the methods for generating and administering the lymphocyte cultures, and future clinical trials aim to improve durable response rates and extend the patient populations that are candidates for treatment. PMID:18083376

Simple, green, and clean removal of a poly(methyl methacrylate) film on chemical vapor deposited graphene

NASA Astrophysics Data System (ADS)

Park, J.-H.; Jung, W.; Cho, D.; Seo, J.-T.; Moon, Y.; Woo, S. H.; Lee, C.; Park, C.-Y.; Ahn, J. R.

2013-10-01

The clean removal of a poly(methyl methacrylate) (PMMA) film on graphene has been an essential part of the process of transferring chemical vapor deposited graphene to a specific substrate, influencing the quality of the transferred graphene. Here we demonstrate that the clean removal of PMMA can be achieved by a single heat-treatment process without the chemical treatment that was adopted in other methods of PMMA removal. The cleanness of the transferred graphene was confirmed by four-point probe measurements, synchrotron radiation x-ray photoemission spectroscopy, optical images, and Raman spectroscopy.

CTLA-4 blockade plus adoptive T cell transfer promotes optimal melanoma immunity in mice

PubMed Central

Mahvi, David A.; Meyers, Justin V.; Tatar, Andrew J.; Contreras, Amanda; Suresh, M.; Leverson, Glen E.; Sen, Siddhartha; Cho, Clifford S.

2014-01-01

Immunotherapeutic approaches to the treatment of advanced melanoma have relied on strategies that augment the responsiveness of endogenous tumor-specific T cell populations (e.g., CTLA-4 blockade-mediated checkpoint inhibition) or introduce exogenously-prepared tumor-specific T cell populations (e.g., adoptive cell transfer). Although both approaches have shown considerable promise, response rates to these therapies remain suboptimal. We hypothesized that a combinatorial approach to immunotherapy using both CTLA-4 blockade and non-lymphodepletional adoptive cell transfer could offer additive therapeutic benefit. C57BL/6 mice were inoculated with syngeneic B16F10 melanoma tumors transfected to express low levels of the lymphocytic choriomeningitis virus peptide GP33 (B16GP33), and treated with no immunotherapy, CTLA-4 blockade, adoptive cell transfer, or combination immunotherapy of CTLA-4 blockade with adoptive cell transfer. Combination immunotherapy resulted in optimal control of B16GP33 melanoma tumors. Combination immunotherapy promoted a stronger local immune response reflected by enhanced tumor-infiltrating lymphocyte populations, as well as a stronger systemic immune responses reflected by more potent tumor antigen-specific T cell activity in splenocytes. In addition, whereas both CTLA-4 blockade and combination immunotherapy were able to promote long-term immunity against B16GP33 tumors, only combination immunotherapy was capable of promoting immunity against parental B16F10 tumors as well. Our findings suggest that a combinatorial approach using CTLA-4 blockade with non-lymphodepletional adoptive cell transfer may promote additive endogenous and exogenous T cell activities that enable greater therapeutic efficacy in the treatment of melanoma. PMID:25658614

18 CFR 341.6 - Adoption rule.

Code of Federal Regulations, 2010 CFR

2010-04-01

... properties is transferred, the adopting carrier must file and post an adoption notice, numbered in its own FERC Tariff series, reading as follows: The [legal name of adopting carrier] hereby adopts and makes its own all tariff publications of [name of adopted carrier], effective [date]. (2) The adopting...

Clinical scale rapid expansion of lymphocytes for adoptive cell transfer therapy in the WAVE® bioreactor

PubMed Central

2012-01-01

Background To simplify clinical scale lymphocyte expansions, we investigated the use of the WAVE®, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. Methods We have developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant numbers of cells for our adoptive cell transfer clinical protocols. Results TIL and genetically modified PBL were rapidly expanded to clinically relevant scales in both static bags and the WAVE bioreactor. Both bioreactors produced comparable numbers of cells; however the cultures generated in the WAVE bioreactor had a higher percentage of CD4+ cells and had a less activated phenotype. Conclusions The WAVE bioreactor simplifies the process of rapidly expanding tumor reactive lymphocytes under GMP conditions, and provides an alternate approach to cell generation for ACT protocols. PMID:22475724

A Novel Diffusion MRI Phantom, and a Method for Enhancing MR Image Quality | NCI Technology Transfer Center | TTC

Cancer.gov

The use of Polyvinyl Pyrrolidone (PVP) solutions of varying concentrations as phantoms for diffusion MRI calibration and quality control is disclosed. This diffusion MRI phantom material is already being adopted by radiologists for quality control and assurance in clinical studies.

Combining Antiangiogenic Therapy with Adoptive Cell Immunotherapy Exerts Better Antitumor Effects in Non-Small Cell Lung Cancer Models

PubMed Central

Shi, Shujing; Wang, Rui; Chen, Yitian; Song, Haizhu; Chen, Longbang; Huang, Guichun

2013-01-01

Introduction Cytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. Methods We combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. Results Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. Conclusions Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung carcinomas and unmask the mechanisms of the synergistic antitumor efficacy, providing a new rationale for combining antiangiogenesis therapy with immunotherapy in the treatment of lung cancer. PMID:23799045

Adoptive transfer of induced-Treg cells effectively attenuates murine airway allergic inflammation.

PubMed

Xu, Wei; Lan, Qin; Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

2012-01-01

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4(+)FoxP3(+)) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma.

Adoptive Transfer of Induced-Treg Cells Effectively Attenuates Murine Airway Allergic Inflammation

PubMed Central

Chen, Maogen; Chen, Hui; Zhu, Ning; Zhou, Xiaohui; Wang, Julie; Fan, Huimin; Yan, Chun-Song; Kuang, Jiu-Long; Warburton, David; Togbe, Dieudonnée; Ryffel, Bernhard; Zheng, Song-Guo; Shi, Wei

2012-01-01

Both nature and induced regulatory T (Treg) lymphocytes are potent regulators of autoimmune and allergic disorders. Defects in endogenous Treg cells have been reported in patients with allergic asthma, suggesting that disrupted Treg cell-mediated immunological regulation may play an important role in airway allergic inflammation. In order to determine whether adoptive transfer of induced Treg cells generated in vitro can be used as an effective therapeutic approach to suppress airway allergic inflammation, exogenously induced Treg cells were infused into ovalbumin-sensitized mice prior to or during intranasal ovalbumin challenge. The results showed that adoptive transfer of induced Treg cells prior to allergen challenge markedly reduced airway hyperresponsiveness, eosinophil recruitment, mucus hyper-production, airway remodeling, and IgE levels. This effect was associated with increase of Treg cells (CD4+FoxP3+) and decrease of dendritic cells in the draining lymph nodes, and with reduction of Th1, Th2, and Th17 cell response as compared to the controls. Moreover, adoptive transfer of induced Treg cells during allergen challenge also effectively attenuate airway inflammation and improve airway function, which are comparable to those by natural Treg cell infusion. Therefore, adoptive transfer of in vitro induced Treg cells may be a promising therapeutic approach to prevent and treat severe asthma. PMID:22792275

Information Transfer and the Adoption of Agricultural Innovations.

ERIC Educational Resources Information Center

Longo, Rose Mary Juliano

1990-01-01

Data collected in the Federal District of Brazil were analyzed in terms of information transfer through mass media and interpersonal communication and how they influence farmers in the Federal District of Brazil in their decisions to adopt agricultural innovations. (42 references) (EAM)

Making Our Nonpoint Source Pollution Education Programs Effective.

ERIC Educational Resources Information Center

Shepard, Robin

1999-01-01

The rate of adoption of nutrient management by farmers in Wisconsin watersheds was compared for a program using diffuse communication strategies and one using one-to-one information transfer. Information transfer increased adoption of specific practices and decreased application of excessive nitrogen and phosphorus. (SK)

Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model

PubMed Central

Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W.; Kasper, Dennis L.

1998-01-01

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules. PMID:9573085

A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy

PubMed Central

Spielmann, Guillaume; Bollard, Catherine M.; Kunz, Hawley; Hanley, Patrick J.; Simpson, Richard J.

2016-01-01

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy. PMID:27181409

A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy.

PubMed

Spielmann, Guillaume; Bollard, Catherine M; Kunz, Hawley; Hanley, Patrick J; Simpson, Richard J

2016-05-16

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections remain a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). The adoptive transfer of donor-derived viral-specific cytotoxic T-cells (VSTs) is an effective treatment for controlling CMV and EBV infections after HSCT; however, new practical methods are required to augment the ex vivo manufacture of multi-VSTs from healthy donors. This study investigated the effects of a single exercise bout on the ex vivo manufacture of multi-VSTs. PBMCs isolated from healthy CMV/EBV seropositive participants before (PRE) and immediately after (POST) 30-minutes of cycling exercise were stimulated with CMV (pp65 and IE1) and EBV (LMP2A and BMLF1) peptides and expanded over 8 days. The number (fold difference from PRE) of T-cells specific for CMV pp65 (2.6), EBV LMP2A (2.5), and EBV BMLF1 (4.4) was greater among the VSTs expanded POST. VSTs expanded PRE and POST had similar phenotype characteristics and were equally capable of MHC-restricted killing of autologous target cells. We conclude that a single exercise bout enhances the manufacture of multi-VSTs from healthy donors without altering their phenotype or function and may serve as a simple and economical adjuvant to boost the production of multi-VSTs for allogeneic adoptive transfer immunotherapy.

Immune Rejection after Pancreatic Islet Cell Transplantation: In Vivo Dual Contrast-enhanced MR Imaging in a Mouse Model

PubMed Central

Wang, Ping; Schuetz, Christian; Ross, Alana; Dai, Guangping; Markmann, James F.

2013-01-01

Purpose: To detect adoptively transferred immune attack in a mouse model of islet cell transplantation by using a long-circulating paramagnetic T1 contrast agent, a protected graft copolymer (PGC) that is covalently linked to gadolinium–diethylenetriaminepentaacetic acid with fluorescein isothiocyanate (Gd-DTPA-F), which accumulates in the sites of inflammation that are characterized by vascular disruption. Materials and Methods: All animal experiments were performed in compliance with institutional guidelines and approved by the subcommittee on research animal care. Six nonobese diabetic severe combined immunodeficiency mice received transplanted human islet cells under the kidney capsule and adoptively transferred 5 × 106 splenocytes from 6-week-old nonobese diabetic mice. These mice also served as control subjects for comparison of pre- and postadoptive transfer MR imaging results. Mice that received phosphate-buffered saline solution only were included as nonadoptive-transfer control subjects (n = 2). In vivo magnetic resonance (MR) imaging was performed before and 17 hours after intravenous injections of PGC-Gd-DTPA-F, followed by histologic examination. Statistical differences were analyzed by means of a paired Student t test and repeated two-way analysis of variance. Results: MR imaging results showed significantly greater accumulation of PGC-Gd-DTPA-F in the graft area after immune attack initiated by adoptive transfer of splenocytes compared with that of the same area before the transfer (T1, 137.2 msec ± 39.3 and 239.5 msec ± 17.6, respectively; P < .001). These results were confirmed at histologic examination, which showed considerable leakage of the contrast agent into the islet cell interstitium. Conclusion: PGC-Gd-DTPA-F–enhanced MR imaging allows for the in vivo assessment of vascular damage of the graft T cell challenge. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12121129/-/DC1 PMID:23264346

Is Transferring an Educational Innovation Actually a Process of Transformation?

ERIC Educational Resources Information Center

Varpio, Lara; Bell, Robert; Hollingworth, Gary; Jalali, Alireza; Haidet, Paul; Levine, Ruth; Regehr, Glenn

2012-01-01

Recent debates question the extent to which adopting an educational innovation requires compromise between the innovation's original design and the adoption site's context. Through compromises, the innovation's fundamental principles may be transferred, transformed, or abandoned. This paper analyzes such compromises during the piloting of…

Community-based technology transfer in rural aquaculture: the case of mudcrab Scylla serrata nursery in ponds in Northern Samar, Central Philippines.

PubMed

Baticados, Didi B; Agbayani, Renato F; Quinitio, Emilia T

2014-12-01

Finding aquaculture development approaches to open up livelihood opportunities for the rural poor and in mainstreaming smallholder fish farmers to reduce poverty remain a challenge. This paper examines the community-based technology transfer mechanism of mudcrab nursery in ponds and its socioeconomic impacts on smallholder mudcrab growers in Northern Samar, Philippines. Results indicated that the technology is a viable enterprise done by a straight culture system method, which is the rearing of crablets from <1.0 to 4.0 cm for 42 days, or by-phases. However, technology adoption hinges on many factors like area ownership, farm distance from household, and market including the type of strategy needed to enhance technology uptake. Collaboration among research and development institutions and local partners is critical in training and empowering rural communities to adopt aquaculture technologies.

Endogenous T-Cell Therapy: Clinical Experience.

PubMed

Yee, Cassian; Lizee, Greg; Schueneman, Aaron J

2015-01-01

Adoptive cellular therapy represents a robust means of augmenting the tumor-reactive effector population in patients with cancer by adoptive transfer of ex vivo expanded T cells. Three approaches have been developed to achieve this goal: the use of tumor-infiltrating lymphocytes or tumor-infiltrating lymphocytess extracted from patient biopsy material; the redirected engineering of lymphocytes using vectors expressing a chimeric antigen receptor and T-cell receptor; and third, the isolation and expansion of often low-frequency endogenous T cells (ETCs) reactive to tumor antigens from the peripheral blood of patients. This last form of adoptive transfer of T cells, known as ETC therapy, requires specialized methods to isolate and expand from peripheral blood the very low-frequency tumor-reactive T cells, methods that have been developed over the last 2 decades, to the point where such an approach may be broadly applicable not only for the treatment of melanoma but also for that of other solid tumor malignancies. One compelling feature of ETC is the ability to rapidly deploy clinical trials following identification of a tumor-associated target epitope, a feature that may be exploited to develop personalized antigen-specific T-cell therapy for patients with almost any solid tumor. With a well-validated antigen discovery pipeline in place, clinical studies combining ETC with agents that modulate the immune microenvironment can be developed that will transform ETC into a feasible treatment modality.

On new scaling group of transformation for Prandtl-Eyring fluid model with both heat and mass transfer

NASA Astrophysics Data System (ADS)

Rehman, Khalil Ur; Malik, Aneeqa Ashfaq; Malik, M. Y.; Tahir, M.; Zehra, Iffat

2018-03-01

A short communication is structured to offer a set of scaling group of transformation for Prandtl-Eyring fluid flow yields by stretching flat porous surface. The fluid flow regime is carried with both heat and mass transfer characteristics. To seek solution of flow problem a set of scaling group of transformation is proposed by adopting Lie approach. These transformations are used to step down the partial differential equations into ordinary differential equations. The reduced system is solved by numerical method termed as shooting method. A self-coded algorithm is executed in this regard. The obtain results are elaborated by means of figures and tables.

Hands-on 2.0: improving transfer of training via the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Acquisition of Data for Outcomes and Procedure Transfer (ADOPT) program.

PubMed

Dort, Jonathan; Trickey, Amber; Paige, John; Schwarz, Erin; Dunkin, Brian

2017-08-01

Practicing surgeons commonly learn new procedures and techniques by attending a "hands-on" course, though trainings are often ineffective at promoting subsequent procedure adoption in practice. We describe implementation of a new program with the SAGES All Things Hernia Hands-On Course, Acquisition of Data for Outcomes and Procedure Transfer (ADOPT), which employs standardized, proven teaching techniques, and 1-year mentorship. Attendee confidence and procedure adoption are compared between standard and ADOPT programs. For the pilot ADOPT course implementation, a hands-on course focusing on abdominal wall hernia repair was chosen. ADOPT participants were recruited among enrollees for the standard Hands-On Hernia Course. Enrollment in ADOPT was capped at 10 participants and limited to a 2:1 student-to-faculty ratio, compared to the standard course 22 participants with a 4:1 student-to-faculty ratio. ADOPT mentors interacted with participants through webinars, phone conferences, and continuous email availability throughout the year. All participants were asked to provide pre- and post-course surveys inquiring about the number of targeted hernia procedures performed and related confidence level. Four of 10 ADOPT participants (40%) and six of 22 standard training participants (27%) returned questionnaires. Over the 3 months following the course, ADOPT participants performed more ventral hernia mesh insertion procedures than standard training participants (median 13 vs. 0.5, p = 0.010) and considerably more total combined procedures (median 26 vs. 7, p = 0.054). Compared to standard training, learners who participated in ADOPT reported greater confidence improvements in employing a components separation via an open approach (p = 0.051), and performing an open transversus abdominis release, though the difference did not achieve statistical significance (p = 0.14). These results suggest that the ADOPT program, with standardized and structured teaching, telementoring, and a longitudinal educational approach, is effective and leads to better transfer of learned skills and procedures to clinical practice.

Policy Borrowing and Transfer, and Policy Convergence: Justifications for the Adoption of the Bologna Process in the CEMAC Region and the Cameroonian Higher Education System through the LMD Reform

ERIC Educational Resources Information Center

Eta, Elizabeth Agbor

2015-01-01

The borrowing and transfer of policies, ideas and practices from one system to another may in part explain the convergence of educational systems. Using text documents as research material, this paper examines the adoption and transfer of Bologna Process (BP) ideas in the Economic and Monetary Community of Central Africa (CEMAC) and in the…

Spectral collocation method with a flexible angular discretization scheme for radiative transfer in multi-layer graded index medium

NASA Astrophysics Data System (ADS)

Wei, Linyang; Qi, Hong; Sun, Jianping; Ren, Yatao; Ruan, Liming

2017-05-01

The spectral collocation method (SCM) is employed to solve the radiative transfer in multi-layer semitransparent medium with graded index. A new flexible angular discretization scheme is employed to discretize the solid angle domain freely to overcome the limit of the number of discrete radiative direction when adopting traditional SN discrete ordinate scheme. Three radial basis function interpolation approaches, named as multi-quadric (MQ), inverse multi-quadric (IMQ) and inverse quadratic (IQ) interpolation, are employed to couple the radiative intensity at the interface between two adjacent layers and numerical experiments show that MQ interpolation has the highest accuracy and best stability. Variable radiative transfer problems in double-layer semitransparent media with different thermophysical properties are investigated and the influence of these thermophysical properties on the radiative transfer procedure in double-layer semitransparent media is also analyzed. All the simulated results show that the present SCM with the new angular discretization scheme can predict the radiative transfer in multi-layer semitransparent medium with graded index efficiently and accurately.

Performance analysis of cross-seeding WDM-PON system using transfer matrix method

NASA Astrophysics Data System (ADS)

Simatupang, Joni Welman; Pukhrambam, Puspa Devi; Huang, Yen-Ru

2016-12-01

In this paper, a model based on the transfer matrix method is adopted to analyze the effects of Rayleigh backscattering and Fresnel multiple reflections on a cross-seeding WDM-PON system. As part of analytical approximation methods, this time-independent model is quite simple but very efficient when it is applied to various WDM-PON transmission systems, including the cross-seeding scheme. The cross seeding scheme is most beneficial for systems with low loop-back ONU gain or low reflection loss at the drop fiber for upstream data in bidirectional transmission. However for downstream data transmission, multiple reflections power could destroy the usefulness of the cross-seeding scheme when the reflectivity is high enough and the RN is positioned near OLT or close to ONU.

CpG Oligodeoxynucleotides Enhance the Efficacy of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes by Modifying the Th1 Polarization and Local Infiltration of Th17 Cells

PubMed Central

Xu, Lin; Wang, Chunhong; Wen, Zhenke; Zhou, Ya; Liu, Zhongmin; Liang, Yongjie; Xu, Zengguang; Ren, Tao

2010-01-01

Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs) was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8+ T cells and CD8+ T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs. PMID:20981279

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment

PubMed Central

Bathe, Oliver F; Dalyot-Herman, Nava; Malek, Thomas R

2003-01-01

Background 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. Methods 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. Results 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. Conclusions 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 antigens when developing vaccine strategies for cancer. PMID:12882650

Transfer Efficiency and Cooling Cost by Thermal Loss based on Nitrogen Evaporation Method for Superconducting MAGLEV System

NASA Astrophysics Data System (ADS)

Chung, Y. D.; Kim, D. W.; Lee, C. Y.

2017-07-01

This paper presents the feasibility of technical fusion between wireless power transfer (WPT) and superconducting technology to improve the transfer efficiency and evaluate operating costs such as refrigerant consumption. Generally, in WPT technology, the various copper wires have been adopted. From this reason, the transfer efficiency is limited since the copper wires of Q value are intrinsically critical point. On the other hand, as superconducting wires keep larger current density and relatively higher Q value, the superconducting resonance coil can be expected as a reasonable option to deliver large transfer power as well as improve the transfer ratio since it exchanges energy at a much higher rate and keeps stronger magnetic fields out. However, since superconducting wires should be cooled indispensably, the cooling cost of consumed refrigerant for resonance HTS wires should be estimated. In this study, the transmission ratios using HTS resonance receiver (Rx) coil and various cooled and noncooled copper resonance Rx coils were presented under non cooled copper antenna within input power of 200 W of 370 kHz respectively. In addition, authors evaluated cooling cost of liquid nitrogen for HTS resonance coil and various cooled copper resonance coils based on nitrogen evaporation method.

Viscous dissipation effects on MHD slip flow and heat transfer in porous micro duct with LTNE assumptions using modified lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Rabhi, R.; Amami, B.; Dhahri, H.; Mhimid, A.

2017-11-01

This paper deals with heat transfer and fluid flow in a porous micro duct under local thermal non equilibrium conditions subjected to an external oriented magnetic field. The considered sample is a micro duct filled with porous media assumed to be homogenous, isotropic and saturated. The slip velocity and the temperature jump were uniformly imposed to the wall. In modeling the flow, the Brinkmann-Forchheimer extended Darcy model was incorporated into the momentum equations. In the energy equation, the local thermal non equilibrium between the two phases was adopted. A modified axisymmetric lattice Boltzmann method was used to solve the obtained governing equation system. Attention was focused on the influence of the emerging parameters such as Knudsen number, Kn, Hartmann number, Ha, Eckert number, Ec, Biot number, Bi and the magnetic field inclination γ on flow and heat transfer throughout this paper.

Influenza virus-specific TCR-transduced T cells as a model for adoptive immunotherapy

PubMed Central

Berdien, Belinda; Reinhard, Henrike; Meyer, Sabrina; Spöck, Stefanie; Kröger, Nicolaus; Atanackovic, Djordje; Fehse, Boris

2013-01-01

Adoptive transfer of T lymphocytes equipped with tumor-antigen specific T-cell receptors (TCRs) represents a promising strategy in cancer immunotherapy, but the approach remains technically demanding. Using influenza virus (Flu)-specific T-cell responses as a model system we compared different methods for the generation of T-cell clones and isolation of antigen-specific TCRs. Altogether, we generated 12 CD8+ T-cell clones reacting to the Flu matrix protein (Flu-M) and 6 CD4+ T-cell clones reacting to the Flu nucleoprotein (Flu-NP) from 4 healthy donors. IFN-γ-secretion-based enrichment of antigen-specific cells, optionally combined with tetramer staining, was the most efficient way for generating T-cell clones. In contrast, the commonly used limiting dilution approach was least efficient. TCR genes were isolated from T-cell clones and cloned into both a previously used gammaretroviral LTR-vector, MP91 and the novel lentiviral self-inactivating vector LeGO-MP that contains MP91-derived promotor and regulatory elements. To directly compare their functional efficiencies, we in parallel transduced T-cell lines and primary T cells with the two vectors encoding identical TCRs. Transduction efficiencies were approximately twice higher with the gammaretroviral vector. Secretion of high amounts of IFN-γ, IL-2 and TNF-α by transduced cells after exposure to the respective influenza target epitope proved efficient specificity transfer of the isolated TCRs to primary T-cells for both vectors, at the same time indicating superior functionality of MP91-transduced cells. In conclusion, we have developed optimized strategies to obtain and transfer antigen-specific TCRs as well as designed a novel lentiviral vector for TCR-gene transfer. Our data may help to improve adoptive T-cell therapies. PMID:23428899

Adoptive cell transfer in autoimmune hepatitis.

PubMed

Czaja, Albert J

2015-06-01

Adoptive cell transfer is an intervention in which autologous immune cells that have been expanded ex vivo are re-introduced to mitigate a pathological process. Tregs, mesenchymal stromal cells, dendritic cells, macrophages and myeloid-derived suppressor cells have been transferred in diverse immune-mediated diseases, and Tregs have been the focus of investigations in autoimmune hepatitis. Transferred Tregs have improved histological findings in animal models of autoimmune hepatitis and autoimmune cholangitis. Key challenges relate to discrepant findings among studies, phenotypic instability of the transferred population, uncertain side effects and possible need for staged therapy involving anti-inflammatory drugs. Future investigations must resolve issues about the purification, durability and safety of these cells and consider alternative populations if necessary.

Improving the outcome of adoptive cell transfer by targeting tumor escape

PubMed Central

Kaluza, Karen M.; Vile, Richard

2013-01-01

Adoptive T-cell transfer is among the most promising immunotherapies against cancer. To continue increasing the potential of this therapy, our studies focus on the inhibition of tumor recurrence. Recently, we have demonstrated several ways in which combination therapies involving multiple T-cell populations and immunostimulatory chemotherapy can enhance long-term survival. PMID:23483796

Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care.

PubMed

Riccione, Katherine; Suryadevara, Carter M; Snyder, David; Cui, Xiuyu; Sampson, John H; Sanchez-Perez, Luis

2015-02-16

Adoptive T cell immunotherapy offers a promising strategy for specifically targeting and eliminating malignant gliomas. T cells can be engineered ex vivo to express chimeric antigen receptors specific for glioma antigens (CAR T cells). The expansion and function of adoptively transferred CAR T cells can be potentiated by the lymphodepletive and tumoricidal effects of standard of care chemotherapy and radiotherapy. We describe a method for generating CAR T cells targeting EGFRvIII, a glioma-specific antigen, and evaluating their efficacy when combined with a murine model of glioblastoma standard of care. T cells are engineered by transduction with a retroviral vector containing the anti-EGFRvIII CAR gene. Tumor-bearing animals are subjected to host conditioning by a course of temozolomide and whole brain irradiation at dose regimens designed to model clinical standard of care. CAR T cells are then delivered intravenously to primed hosts. This method can be used to evaluate the antitumor efficacy of CAR T cells in the context of standard of care.

Large-scale expansion of γδ T cells and peptide-specific cytotoxic T cells using zoledronate for adoptive immunotherapy.

PubMed

Yoshikawa, Toshiaki; Takahara, Masashi; Tomiyama, Mai; Nieda, Mie; Maekawa, Ryuji; Nakatsura, Tetsuya

2014-11-01

Specific cellular immunotherapy for cancer requires efficient generation and expansion of cytotoxic T lymphocytes (CTLs) that recognize tumor-associated antigens. However, it is difficult to isolate and expand functionally active T-cells ex vivo. In this study, we investigated the efficacy of a new method to induce expansion of antigen-specific CTLs for adoptive immunotherapy. We used tumor-associated antigen glypican-3 (GPC3)-derived peptide and cytomegalovirus (CMV)-derived peptide as antigens. Treatment of human peripheral blood mononuclear cells (PBMCs) with zoledronate is a method that enables large-scale γδ T-cell expansion. To induce expansion of γδ T cells and antigen-specific CTLs, the PBMCs of healthy volunteers or patients vaccinated with GPC3 peptide were cultured with both peptide and zoledronate for 14 days. The expansion of γδ T cells and peptide-specific CTLs from a few PBMCs using zoledronate yields cell numbers sufficient for adoptive transfer. The rate of increase of GPC3‑specific CTLs was approximately 24- to 170,000-fold. These CD8(+) cells, including CTLs, showed GPC3-specific cytotoxicity against SK-Hep-1/hGPC3 and T2 pulsed with GPC3 peptide, but not against SK-Hep-1/vec and T2 pulsed with human immunodeficiency virus peptide. On the other hand, CD8(-) cells, including γδ T cells, showed cytotoxicity against SK-Hep-1/hGPC3 and SK-Hep-1/vec, but did not show GPC3 specificity. Furthermore, adoptive cell transfer of CD8(+) cells, CD8(-) cells, and total cells after expansion significantly inhibited tumor growth in an NOD/SCID mouse model. This study indicates that simultaneous expansion of γδ T cells and peptide-specific CTLs using zoledronate is useful for adoptive immunotherapy.

Improvements of the Radiation Code "MstrnX" in AORI/NIES/JAMSTEC Models

NASA Astrophysics Data System (ADS)

Sekiguchi, M.; Suzuki, K.; Takemura, T.; Watanabe, M.; Ogura, T.

2015-12-01

There is a large demand for an accurate yet rapid radiation transfer scheme accurate for general climate models. The broadband radiative transfer code "mstrnX", ,which was developed by Atmosphere and Ocean Research Institute (AORI) and was implemented in several global and regional climate models cooperatively developed in the Japanese research community, for example, MIROC (the Model for Interdisciplinary Research on Climate) [Watanabe et al., 2010], NICAM (Non-hydrostatic Icosahedral Atmospheric Model) [Satoh et al, 2008], and CReSS (Cloud Resolving Storm Simulator) [Tsuboki and Sakakibara, 2002]. In this study, we improve the gas absorption process and the scattering process of ice particles. For update of gas absorption process, the absorption line database is replaced by the latest versions of the Harvard-Smithsonian Center, HITRAN2012. An optimization method is adopted in mstrnX to decrease the number of integration points for the wavenumber integration using the correlated k-distribution method and to increase the computational efficiency in each band. The integration points and weights of the correlated k-distribution are optimized for accurate calculation of the heating rate up to altitude of 70 km. For this purpose we adopted a new non-linear optimization method of the correlated k-distribution and studied an optimal initial condition and the cost function for the non-linear optimization. It is known that mstrnX has a considerable bias in case of quadrapled carbon dioxide concentrations [Pincus et al., 2015], however, the bias is decreased by this improvement. For update of scattering process of ice particles, we adopt a solid column as an ice crystal habit [Yang et al., 2013]. The single scattering properties are calculated and tabulated in advance. The size parameter of this table is ranged from 0.1 to 1000 in mstrnX, we expand the maximum to 50000 in order to correspond to large particles, like fog and rain drop. Those update will be introduced to MIROC and adopted for CMIP6 experiment.

Efficient Radiative Transfer for Dynamically Evolving Stratified Atmospheres

NASA Astrophysics Data System (ADS)

Judge, Philip G.

2017-12-01

We present a fast multi-level and multi-atom non-local thermodynamic equilibrium radiative transfer method for dynamically evolving stratified atmospheres, such as the solar atmosphere. The preconditioning method of Rybicki & Hummer (RH92) is adopted. But, pressed for the need of speed and stability, a “second-order escape probability” scheme is implemented within the framework of the RH92 method, in which frequency- and angle-integrals are carried out analytically. While minimizing the computational work needed, this comes at the expense of numerical accuracy. The iteration scheme is local, the formal solutions for the intensities are the only non-local component. At present the methods have been coded for vertical transport, applicable to atmospheres that are highly stratified. The probabilistic method seems adequately fast, stable, and sufficiently accurate for exploring dynamical interactions between the evolving MHD atmosphere and radiation using current computer hardware. Current 2D and 3D dynamics codes do not include this interaction as consistently as the current method does. The solutions generated may ultimately serve as initial conditions for dynamical calculations including full 3D radiative transfer. The National Center for Atmospheric Research is sponsored by the National Science Foundation.

Numerical Investigation of Radiative Heat Transfer in Laser Induced Air Plasmas

NASA Technical Reports Server (NTRS)

Liu, J.; Chen, Y. S.; Wang, T. S.; Turner, James E. (Technical Monitor)

2001-01-01

Radiative heat transfer is one of the most important phenomena in the laser induced plasmas. This study is intended to develop accurate and efficient methods for predicting laser radiation absorption and plasma radiative heat transfer, and investigate the plasma radiation effects in laser propelled vehicles. To model laser radiation absorption, a ray tracing method along with the Beer's law is adopted. To solve the radiative transfer equation in the air plasmas, the discrete transfer method (DTM) is selected and explained. The air plasma radiative properties are predicted by the LORAN code. To validate the present nonequilibrium radiation model, several benchmark problems are examined and the present results are found to match the available solutions. To investigate the effects of plasma radiation in laser propelled vehicles, the present radiation code is coupled into a plasma aerodynamics code and a selected problem is considered. Comparisons of results at different cases show that plasma radiation plays a role of cooling plasma and it lowers the plasma temperature by about 10%. This change in temperature also results in a reduction of the coupling coefficient by about 10-20%. The present study indicates that plasma radiation modeling is very important for accurate modeling of aerodynamics in a laser propelled vehicle.

Transferring Data from Smartwatch to Smartphone through Mechanical Wave Propagation.

PubMed

Kim, Seung-Chan; Lim, Soo-Chul

2015-08-28

Inspired by the mechanisms of bone conduction transmission, we present a novel sensor and actuation system that enables a smartwatch to securely communicate with a peripheral touch device, such as a smartphone. Our system regards hand structures as a mechanical waveguide that transmits particular signals through mechanical waves. As a signal, we used high-frequency vibrations (18.0-20.0 kHz) so that users cannot sense the signals either tactually or audibly. To this end, we adopted a commercial surface transducer, which is originally developed as a bone-conduction actuator, for mechanical signal generation. At the receiver side, a piezoelement was adopted for picking up the transferred mechanical signals. Experimental results have shown that the proposed system can successfully transfer data using mechanical waves. We also validate dual-frequency actuations under which high-frequency signals (18.0-20.0 kHz) are generated along with low-frequency (up to 250 Hz) haptic vibrations. The proposed method has advantages in terms of security in that it does not reveal the signals outside the body, meaning that it is not possible for attackers to eavesdrop on the signals. To further illustrate the possible application spaces, we conclude with explorations of the proposed approach.

Photonic band structures solved by a plane-wave-based transfer-matrix method.

PubMed

Li, Zhi-Yuan; Lin, Lan-Lan

2003-04-01

Transfer-matrix methods adopting a plane-wave basis have been routinely used to calculate the scattering of electromagnetic waves by general multilayer gratings and photonic crystal slabs. In this paper we show that this technique, when combined with Bloch's theorem, can be extended to solve the photonic band structure for 2D and 3D photonic crystal structures. Three different eigensolution schemes to solve the traditional band diagrams along high-symmetry lines in the first Brillouin zone of the crystal are discussed. Optimal rules for the Fourier expansion over the dielectric function and electromagnetic fields with discontinuities occurring at the boundary of different material domains have been employed to accelerate the convergence of numerical computation. Application of this method to an important class of 3D layer-by-layer photonic crystals reveals the superior convergency of this different approach over the conventional plane-wave expansion method.

Compression and Transmission of RF Signals for Telediagnosis

NASA Astrophysics Data System (ADS)

Seko, Toshihiro; Doi, Motonori; Oshiro, Osamu; Chihara, Kunihiro

2000-05-01

Health care is a critical issue nowadays. Much emphasis is given to quality care for all people. Telediagnosis has attracted public attention. We propose a new method of ultrasound image transmission for telediagnosis. In conventional methods, video image signals are transmitted. In our method, the RF signals which are acquired by an ultrasound probe, are transmitted. The RF signals can be transformed to color Doppler images or high-resolution images by a receiver. Because a stored form is adopted, the proposed system can be realized with existent technology such as hyper text transfer protocol (HTTP) and file transfer protocol (FTP). In this paper, we describe two lossless compression methods which specialize in the transmission of RF signals. One of the methods uses the characteristics of the RF signal. In the other method, the amount of the data is reduced. Measurements were performed in water targeting an iron block and triangular Styrofoam. Additionally, abdominal fat measurement was performed. Our method achieved a compression rate of 13% with 8 bit data.

CMV-Specific CD8 T Cell Differentiation and Localization: Implications for Adoptive Therapies.

PubMed

Smith, Corinne J; Quinn, Michael; Snyder, Christopher M

2016-01-01

Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8 + T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8 + T cell immunity. The aim of this review is to briefly summarize the role of these T cell subsets in CMV immunity and to describe how current adoptive immunotherapy practices might affect their reconstitution in patients. The bulk of the CMV-specific CD8 + T cell population is made up of terminally differentiated effector T cells with immediate effector function and a short life span. Self-renewing memory T cells within the CMV-specific population retain the capacity to expand and differentiate upon challenge and are important for the long-term persistence of the CD8 + T cell response. Finally, mucosal organs, which are frequent sites of CMV reactivation, are primarily inhabited by tissue-resident memory T cells, which do not recirculate. Future work on adoptive transfer strategies may need to focus on striking a balance between the formation of these subsets to ensure the development of long lasting and protective immune responses that can access the organs affected by CMV disease.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

PubMed

Zhang, Hua; Wu, Yue; Wang, Jing; Tang, Zhongmin; Ren, Yan; Ni, Dalong; Gao, Hongbo; Song, Ruixue; Jin, Teng; Li, Qiao; Bu, Wenbo; Yao, Zhenwei

2018-01-01

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T 1 MR-based nanoprobes, NaGdF 4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm -1 s -1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF 4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF 4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 10 7 labeled T-cells by T 1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF 4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma.

PubMed

Siurala, Mikko; Havunen, Riikka; Saha, Dipongkor; Lumen, Dave; Airaksinen, Anu J; Tähtinen, Siri; Cervera-Carrascon, Víctor; Bramante, Simona; Parviainen, Suvi; Vähä-Koskela, Markus; Kanerva, Anna; Hemminki, Akseli

2016-08-01

Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFα, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of (111)In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies.

Identification of factors that affect the adoption of an ergonomic intervention among Emergency Medical Service workers.

PubMed

Weiler, Monica R; Lavender, Steven A; Crawford, J Mac; Reichelt, Paul A; Conrad, Karen M; Browne, Michael W

2012-01-01

This study explored factors contributing to intervention adoption decisions among Emergency Medical Service (EMS) workers. Emergency Medical Service workers (n = 190), from six different organisations, participated in a two-month longitudinal study following the introduction of a patient transfer-board (also known as slide-board) designed to ease lateral transfers of patients to and from ambulance cots. Surveys administered at baseline, after one month and after two months sampled factors potentially influencing the EMS providers' decision process. 'Ergonomics Advantage' and 'Patient Advantage' entered into a stepwise regression model predicting 'intention to use' at the end of month one (R (2 )= 0.78). After the second month, the stepwise regression indicated only two factors were predictive of intention to use: 'Ergonomics Advantage,' and 'Endorsed by Champions' (R (2 )= 0.58). Actual use was predicted by: 'Ergonomics Advantage' and 'Previous Tool Experience.' These results relate to key concepts identified in the diffusion of innovation literature and have the potential to further ergonomics intervention adoption efforts. Practitioner Summary. This study explored factors that potentially facilitate the adoption of voluntarily used ergonomics interventions. EMS workers were provided with foldable transfer-boards (slideboards) designed to reduce the physical demands when laterally transferring patients. Factors predictive of adoption measures included perceived ergonomics advantage, the endorsement by champions, and prior tool experience.

Fiscal Rules and the Composition of Government Expenditures in OECD Countries

ERIC Educational Resources Information Center

Dahan, Momi; Strawczynski, Michel

2013-01-01

Since the 1990s many OECD countries have adopted fiscal rules. After the adoption of these rules, the ratio of social transfers to government consumption substantially declined, and it recovered following the global economic crisis. Using a sample of 22 OECD countries, we found a negative effect of fiscal rules on the ratio of social transfers to…

Hit parade for adoptive cell transfer therapy: the best T cells for superior clinical responses.

PubMed

Speiser, Daniel E

2013-04-01

Adoptive cell transfer (ACT) of T cells has great clinical potential, but the numerous variables of this therapy make choices difficult. A new study takes advantage of a novel technology for characterizing the T-cell responses of patients. If applied systematically, this approach may identify biomedical correlates of protection, thereby supporting treatment optimization. ©2013 AACR.

Architecture of a prehospital emergency patient care report system (PEPRS).

PubMed

Majeed, Raphael W; Stöhr, Mark R; Röhrig, Rainer

2013-01-01

In recent years, prehospital emergency care adapted to the technology shift towards tablet computers and mobile computing. In particular, electronic patient care report (e-PCR) systems gained considerable attention and adoption in prehospital emergency medicine [1]. On the other hand, hospital information systems are already widely adopted. Yet, there is no universal solution for integrating prehospital emergency reports into electronic medical records of hospital information systems. Previous projects either relied on proprietary viewing workstations or examined and transferred only data for specific diseases (e.g. stroke patients[2]). Using requirements engineering and a three step software engineering approach, this project presents a generic architecture for integrating prehospital emergency care reports into hospital information systems. Aim of this project is to describe a generic architecture which can be used to implement data transfer and integration of pre hospital emergency care reports to hospital information systems. In summary, the prototype was able to integrate data in a standardized manner. The devised methods can be used design generic software for prehospital to hospital data integration.

17 CFR 190.06 - Transfers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... transfer is made fails to respond within a reasonable time to a margin call for the difference between the... 17 Commodity and Securities Exchanges 1 2011-04-01 2011-04-01 false Transfers. 190.06 Section 190... Transfers. (a) Transfer rules. No self-regulatory organization or clearing organization may adopt, maintain...

17 CFR 190.06 - Transfers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... transfer is made fails to respond within a reasonable time to a margin call for the difference between the... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Transfers. 190.06 Section 190... Transfers. (a) Transfer rules. No self-regulatory organization or clearing organization may adopt, maintain...

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

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

Zhang, Han; Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp; Hijioka, Kuniaki

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV,more » with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.« less

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization.

PubMed

Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8+ T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

Quantitative phase microscopy via optimized inversion of the phase optical transfer function.

PubMed

Jenkins, Micah H; Gaylord, Thomas K

2015-10-01

Although the field of quantitative phase imaging (QPI) has wide-ranging biomedical applicability, many QPI methods are not well-suited for such applications due to their reliance on coherent illumination and specialized hardware. By contrast, methods utilizing partially coherent illumination have the potential to promote the widespread adoption of QPI due to their compatibility with microscopy, which is ubiquitous in the biomedical community. Described herein is a new defocus-based reconstruction method that utilizes a small number of efficiently sampled micrographs to optimally invert the partially coherent phase optical transfer function under assumptions of weak absorption and slowly varying phase. Simulation results are provided that compare the performance of this method with similar algorithms and demonstrate compatibility with large phase objects. The accuracy of the method is validated experimentally using a microlens array as a test phase object. Lastly, time-lapse images of live adherent cells are obtained with an off-the-shelf microscope, thus demonstrating the new method's potential for extending QPI capability widely in the biomedical community.

Quinazoline derivatives: synthesis and bioactivities

PubMed Central

2013-01-01

Owing to the significant biological activities, quinazoline derivatives have drawn more and more attention in the synthesis and bioactivities research. This review summarizes the recent advances in the synthesis and biological activities investigations of quinazoline derivatives. According to the main method the authors adopted in their research design, those synthetic methods were divided into five main classifications, including Aza-reaction, Microwave-assisted reaction, Metal-mediated reaction, Ultrasound-promoted reaction and Phase-transfer catalysis reaction. The biological activities of the synthesized quinazoline derivatives also are discussed. PMID:23731671

Persistence of Multiple Tumor-Specific T-Cell Clones Is Associated with Complete Tumor Regression in a Melanoma Patient Receiving Adoptive Cell Transfer Therapy

PubMed Central

Zhou, Juhua; Dudley, Mark E.; Rosenberg, Steven A.; Robbins, Paul F.

2007-01-01

Summary The authors recently reported that adoptive immunotherapy with autologous tumor-reactive tumor infiltrating lymphocytes (TILs) immediately following a conditioning nonmyeloablative chemotherapy regimen resulted in an enhanced clinical response rate in patients with metastatic melanoma. These observations led to the current studies, which are focused on a detailed analysis of the T-cell antigen reactivity as well as the in vivo persistence of T cells in melanoma patient 2098, who experienced a complete regression of all metastatic lesions in lungs and soft tissues following therapy. Screening of an autologous tumor cell cDNA library using transferred TILs resulted in the identification of novel mutated growth arrest-specific gene 7 (GAS7) and glyceral-dehyde-3-phosphate dehydrogenase (GAPDH) gene transcripts. Direct sequence analysis of the expressed T-cell receptor beta chain variable regions showed that the transferred TILs contained multiple T-cell clonotypes, at least six of which persisted in peripheral blood for a month or more following transfer. The persistent T cells recognized both the mutated GAS7 and GAPDH. These persistent tumor-reactive T-cell clones were detected in tumor cell samples obtained from the patient following adoptive cell transfer and appeared to be represented at higher levels in the tumor sample obtained 1 month following transfer than in the peripheral blood obtained at the same time. Overall, these results indicate that multiple tumor-reactive T cells can persist in the peripheral blood and at the tumor site for prolonged times following adoptive transfer and thus may be responsible for the complete tumor regression in this patient. PMID:15614045

Viral Vaccine Immunogenicity in Relation to Host Cell-Mediated and Humoral Immune Responses.

DTIC Science & Technology

1976-05-01

adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring adoptive immunity...vac- cine combined with adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring...Freund’s adjuvant and Bordetella pertussis , are consistently capable of producing early and brisk serum neutralizing antibody responses in adoptively

An inducible model of abacterial prostatitis induces antigen specific inflammatory and proliferative changes in the murine prostate

PubMed Central

Haverkamp, Jessica M.; Charbonneau, Bridget; Meyerholz, David K.; Cohen, Michael B.; Snyder, Paul W.; Svensson, Robert U.; Henry, Michael D.; Wang, Hsing- Hui

2011-01-01

Background Prostatitis is a poorly understood disease and increasing evidence suggests inflammation is involved in other prostatic diseases, including prostate cancer. Methods The ability of pre-activated CD8 T cells to induce prostatitis was examined by adoptive transfer into POET-3 mice or POET-3/Luc/Pten−/+ mice. Characterization of the inflammatory response was determined by examining leukocyte infiltration by histological analysis, flow cytometry and by evaluating cytokine and chemokine levels in prostate tissue. The impact of inflammation on the prostate was evaluated by monitoring epithelial cell proliferation over time. Results Initiation of inflammation by ovalbumin specific CD8+ T cells (OT-I cells) resulted in development of acute prostatitis in the anterior, dorsolateral and anterior prostate of POET-3 and POET-3/Luc/Pten−/+ mice. Acute prostatitis was characterized by recruitment of adoptively transferred OT-I cells and importantly, autologous CD4+ and CD8+ T cells, myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg). In concert with leukocyte infiltration elevated levels of pro-inflammatory cytokines and chemokines were observed. Inflammation also resulted in marked epithelial cell proliferation that was sustained up to 80 days post adoptive-transfer of OT-I cells. Conclusions The POET-3 model represents a novel mouse model to study both acute and chronic prostate inflammation in an antigen-specific system. Further, the POET-3 mouse model can be crossed with other genetic models of disease such as the C57/Luc/Pten−/− model of prostate cancer, allowing the impact of prostatitis on other prostatic diseases to be evaluated. PMID:21656824

Hydrodynamic models of a cepheid atmosphere. Ph.D. Thesis - Maryland Univ., College Park

NASA Technical Reports Server (NTRS)

Karp, A. H.

1974-01-01

A method for including the solution of the transfer equation in a standard Henyey type hydrodynamic code was developed. This modified Henyey method was used in an implicit hydrodynamic code to compute deep envelope models of a classical Cepheid with a period of 12(d) including radiative transfer effects in the optically thin zones. It was found that the velocity gradients in the atmosphere are not responsible for the large microturbulent velocities observed in Cepheids but may be responsible for the occurrence of supersonic microturbulence. It was found that the splitting of the cores of the strong lines is due to shock induced temperature inversions in the line forming region. The adopted light, color, and velocity curves were used to study three methods frequently used to determine the mean radii of Cepheids. It is concluded that an accuracy of 10% is possible only if high quality observations are used.

Adenoviral Delivery of Tumor Necrosis Factor-α and Interleukin-2 Enables Successful Adoptive Cell Therapy of Immunosuppressive Melanoma

PubMed Central

Siurala, Mikko; Havunen, Riikka; Saha, Dipongkor; Lumen, Dave; Airaksinen, Anu J.; Tähtinen, Siri; Cervera-Carrascon, Víctor; Bramante, Simona; Parviainen, Suvi; Vähä-Koskela, Markus; Kanerva, Anna; Hemminki, Akseli

2016-01-01

Adoptive T-cell transfer is a promising treatment approach for metastatic cancer, but efficacy in solid tumors has only been achieved with toxic pre- and postconditioning regimens. Thus, adoptive T-cell therapies would benefit from complementary modalities that enable their full potential without excessive toxicity. We aimed to improve the efficacy and safety of adoptive T-cell transfer by using adenoviral vectors for direct delivery of immunomodulatory murine cytokines into B16.OVA melanoma tumors with concomitant T-cell receptor transgenic OT-I T-cell transfer. Armed adenoviruses expressed high local and low systemic levels of cytokine when injected into B16.OVA tumors, suggesting safety of virus-mediated cytokine delivery. Antitumor efficacy was significantly enhanced with adenoviruses coding for murine interleukin-2 (mIL-2) and tumor necrosis factor-α (mTNFα) when compared with T-cell transfer alone or viruses alone. Further improvement in efficacy was achieved with a triple combination of mIL-2, mTNFα, and OT-I T-cells. Mechanistic studies suggest that mIL-2 has an important role in activating T-cells at the tumor, while mTNFα induces chemokine expression. Furthermore, adenovirus treatments enhanced tumor-infiltration of OT-I T-cells as demonstrated by SPECT/CT imaging of 111In-labeled cells. Our results suggest the utility of cytokine-coding adenoviruses for improving the efficacy of adoptive T-cell therapies. PMID:27357626

The Relationships between Selected Organizational Variables and ATM Technology Adoption in Campus Networking.

ERIC Educational Resources Information Center

Yao, Engui

1998-01-01

Determines the relationships between ATM (Asynchronous Transfer Mode) adoption and four organizational variables: university size, type, finances, and information-processing maturity. Identifies the current status of ATM adoption in campus networking in the United States. Contains 33 references. (DDR)

Antigen-specific T-cell lines transfer protective immunity against Trichinella spiralis in vivo.

PubMed Central

Riedlinger, J; Grencis, R K; Wakelin, D

1986-01-01

T-cell lines specific for infective muscle larvae antigens of the intestinal nematode Trichinella spiralis have been generated in vitro. These antigen-specific T-cell lines express the L3T4+ Ly2- phenotype and secrete the lymphokines IL-2, IL-3 and gamma-IFN. They are stable in culture for up to 15 weeks and are protective when adoptively transferred into naive recipients. As few as 2 x 10(5) T. spiralis-specific tract. In addition, intestinal mastocytosis and peripheral blood eosinophilia were accelerated after adoptive transfer of T. spiralis-specific T-cell lines. PMID:2423438

Synergy of brief activation of CD8 T-cells in the presence of IL-12 and adoptive transfer into lymphopenic hosts promotes tumor clearance and anti-tumor memory

PubMed Central

Díaz-Montero, C Marcela; Naga, Osama; Zidan, Abdel-Aziz A; Salem, Mohamed L; Pallin, Maria; Parmigiani, Anita; Walker, Gail; Wieder, Eric; Komanduri, Krishna; Cole, David J; Montero, Alberto J; Lichtenheld, Mathias G

2011-01-01

Adoptive T-cell therapy holds great promise for the treatment of metastatic melanoma. However, prohibitive costs associated with current technology required for culture and expansion of tumor-reactive T-cells, the need for intense preconditioning regimens to induce lymphopenia, and the unpredictable anti-tumor effect of adoptively transferred T-cells remain significant impediments for its clinical implementation. Here we report a simplified combinatorial approach that involves short activation of CD8+ T cells in the presence of IL-12 followed by adoptive transfer into tumor bearing animals after a single injection of cyclophosphamide. This approach resulted in complete eradication of B16 melanoma, and the establishment of long term immunological memory capable of fully protecting mice after a second B16 melanoma challenge. The activated donor cells were unique because they simultaneously exhibited traits for cytotoxic effector function, central memory-like, homing, and senescence. After tumor eradication and within three months after transfer, CD8+ cells exhibited a conventional memory CTL phenotype. Moreover, these memory CTLs acquired functional attributes characteristic of memory stem cells, including the ability to resist chemotherapy-induced toxicity. Our results suggest that short-term T-cell receptor signaling in the presence of IL-12 promotes promiscuous qualities in naïve CTL which - upon transfer into lymphopenic hosts- are sufficient to eradicate tumors and generate life-long tumor-specific memory. PMID:21915391

Transfer in Virginia--an Update. Transfer Connection, 1996.

ERIC Educational Resources Information Center

Virginia State Dept. of Community Colleges, Richmond.

The "State Policy on Transfer", adopted in 1991, continues to be highly effective in helping students transfer from two-year to four-year institutions. In addition, the policy has promoted cooperation between institutions, most of which have progressed beyond questions of policy compliance to practices that facilitate equitable admission…

Persistence, immune specificity, and functional ability of murine mutant ras epitope-specific CD4(+) and CD8(+) T lymphocytes following in vivo adoptive transfer.

PubMed

Bristol, J A; Schlom, J; Abrams, S I

1999-05-25

Adoptive T-cell transfer has been shown to be a potentially effective strategy for cellular immunotherapy in some murine models of disease. However, several issues remain unresolved regarding some of the basic features involved in effective adoptive transfer, such as the influence of specific peptide antigen (Ag) boost after T-cell transfer, the addition of IL-2 post-T-cell transfer, the trafficking of transferred T cells to lymphoid and nonlymphoid tissues, and the functional stability of recoverable CD4(+) and CD8(+) T cells. We investigated several of these parameters, particularly as they relate to the persistence and maintenance of effector functions of murine CD4(+) and/or CD8(+) T lymphocytes after adoptive cellular transfer into partially gamma-irradiated syngeneic hosts. Our laboratory previously identified murine (H-2(d)) immunogenic CD4(+) and CD8(+) T-cell peptide epitopes reflecting codon 12 ras mutations as tumor-specific Ag. Therefore, the model system chosen here employed epitope-specific MHC class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells produced from previously immunized BALB/c mice. Between 2 and 7 days after T-cell transfer, recipient mice received various combinations of peptide boosts and/or IL-2 treatments. At different times after the T-cell transfer, spleen and lung tissues were analyzed phenotypically to monitor the persistence of the immune T cells and functionally (via proliferation or cytotoxicity assays) to assess the maintenance of peptide specificity. The results showed that immune donor T lymphocytes (uncultured immune T cells or cloned T cells) were recoverable from the spleens and lungs of recipient mice after transfer. The recovery of Ag-specific T-cell responses was greatest from recipient mice that received peptide boosts and IL-2 treatment. However, mice that received a peptide boost without IL-2 treatment responded nearly as well, which suggested that including a peptide boost after T-cell transfer was more obligatory than exogenous IL-2 treatment to sustain adoptively transferred T cells in vivo. Ag-specific T-cell responses were weak in mice that either received IL-2 alone or did not receive the cognate peptide boost after T-cell transfer. The T-cell clones were also monitored by flow cytometry or RT-PCR based on expression of the T-cell receptor Vbeta-chain, which was previously characterized. Ag-specific T cells were recovered from both spleens and lungs of recipient mice, demonstrating that the T-cell clones could localize to both lymphoid and nonlymphoid tissues. This study demonstrates that both uncultured and in vitro-cloned T lymphocytes can migrate to lymphoid tissues and nonlymphoid (e.g., lung) tissues in recipient hosts and that their functional activities can be maintained at these sites after transfer, if they are exposed to peptide Ag in vivo. Copyright 1999 Academic Press.

The effect of the PROSPER partnership model on cultivating local stakeholder knowledge of evidence-based programs: a five-year longitudinal study of 28 communities.

PubMed

Crowley, D Max; Greenberg, Mark T; Feinberg, Mark E; Spoth, Richard L; Redmond, Cleve R

2012-02-01

A substantial challenge in improving public health is how to facilitate the local adoption of evidence-based interventions (EBIs). To do so, an important step is to build local stakeholders' knowledge and decision-making skills regarding the adoption and implementation of EBIs. One EBI delivery system, called PROSPER (PROmoting School-community-university Partnerships to Enhance Resilience), has effectively mobilized community prevention efforts, implemented prevention programming with quality, and consequently decreased youth substance abuse. While these results are encouraging, another objective is to increase local stakeholder knowledge of best practices for adoption, implementation and evaluation of EBIs. Using a mixed methods approach, we assessed local stakeholder knowledge of these best practices over 5 years, in 28 intervention and control communities. Results indicated that the PROSPER partnership model led to significant increases in expert knowledge regarding the selection, implementation, and evaluation of evidence-based interventions. Findings illustrate the limited programming knowledge possessed by members of local prevention efforts, the difficulty of complete knowledge transfer, and highlight one method for cultivating that knowledge.

Transferring Data from Smartwatch to Smartphone through Mechanical Wave Propagation

PubMed Central

Kim, Seung-Chan; Lim, Soo-Chul

2015-01-01

Inspired by the mechanisms of bone conduction transmission, we present a novel sensor and actuation system that enables a smartwatch to securely communicate with a peripheral touch device, such as a smartphone. Our system regards hand structures as a mechanical waveguide that transmits particular signals through mechanical waves. As a signal, we used high-frequency vibrations (18.0–20.0 kHz) so that users cannot sense the signals either tactually or audibly. To this end, we adopted a commercial surface transducer, which is originally developed as a bone-conduction actuator, for mechanical signal generation. At the receiver side, a piezoelement was adopted for picking up the transferred mechanical signals. Experimental results have shown that the proposed system can successfully transfer data using mechanical waves. We also validate dual-frequency actuations under which high-frequency signals (18.0–20.0 kHz) are generated along with low-frequency (up to 250 Hz) haptic vibrations. The proposed method has advantages in terms of security in that it does not reveal the signals outside the body, meaning that it is not possible for attackers to eavesdrop on the signals. To further illustrate the possible application spaces, we conclude with explorations of the proposed approach. PMID:26343674

ATM Technology Adoption in U.S. Campus Networking.

ERIC Educational Resources Information Center

Yao, Engui; Perry, John F.; Anderson, Larry S.; Brook, R. Dan; Hare, R. Dwight; Moore, Arnold J.; Xu, Xiaohe

This study examined the relationships between ATM (asynchronous transfer mode) adoption in universities and four organizational variables: university size, type, finances, and information processing maturity. Another purpose of the study was to identify the current status of ATM adoption in campus networking. Subjects were university domain LAN…

Evaluation of a Novel Dog Adoption Program in Two US Communities

PubMed Central

Mohan-Gibbons, Heather; Weiss, Emily; Garrison, Laurie; Allison, Meg

2014-01-01

Millions of dogs enter animal welfare organizations every year and only a fraction of them are adopted. Despite the most recent American Pet Products Association (APPA) data that nearly half the US population owns a dog, only 20% acquired their dog from an animal welfare organization. Studies show that people consider adopting from an animal shelter more often than they actually do, which indicates a potential market increase if programs can make shelter dogs more visible to adopters. This research focused on a novel adoption program where shelter dogs were transferred into foster homes who were tasked with finding an adopter. Shelter dogs were placed in the path of potential adopters and bypassed the need for the adopter to go to the shelter. The results show that this novel program was effective in a variety of ways including getting dogs adopted. Although length of stay was significantly longer for dogs in the program, the dogs were in a home environment, not taking up kennel space in the shelter. The program also had a lower rate of returns than dogs adopted at the shelter. The foster program tapped adopters in different geographical segments of the community than the dogs adopted from the shelter. By bringing shelter dogs to where adopters spend their time (ex: restaurants, parks, hair salons), the program potentially captured a segment of the population who might have obtained their dog from other sources besides the shelter (such as breeders or pet stores). This novel approach can be an effective method for adoption, has many benefits for shelters, and can tap into a new adopter market by engaging their community in a new way. PMID:24663804

Improvement of the Asia-Pacific TWSTFT network solutions by using DPN results.

PubMed

Lin, Huang-Tien; Huang, Yi-Jiun; Liao, Chia-Shu; Chu, Fang-Dar; Tseng, Wen-Hung

2012-03-01

Two major time and frequency transfer techniques, two-way satellite time and frequency transfer (TWSTFT) and global navigation satellite systems (GNSS: GPS, GALILEO, GLONASS, etc.), are used for the generation of Coordinated Universal Time (UTC)/International Atomic Time (TAI). These time and frequency transfer links comprise a worldwide network and the utilization of the highly redundant time and frequency data is an important topic. Two methods, either TW-only network (i.e., TWSTFT) or single-link combination of TW and Global Positioning System (GPS), have been developed for combining the redundant data from different techniques. In our previous study, we have proposed a feasible method, utilizing full time-transfer network data, to improve the results of TWSTFT network. The National Institute of Information and Communications Technology (NICT) has recently developed a software-based two-way time-transfer modem using a dual pseudo-random noise (DPN) signal. The first international DPN TWSTFT experiment, using these modems, was performed between NICT (Japan) and Telecommunication Laboratories (TL; Taiwan)and its ability to improve the time transfer precision was demonstrated. In comparison with the conventional NICT–TLTWSTFT link, the DPN time transfer results have higher precision and lower diurnal effects. The estimation also shows that DPN is comparable to GPS precise point positioning (PPP).Because the DPN results show better performance than the conventional TWSTFT results, we would adopt the DPN data for the NICT–TL link and solve the TW+DPN network solutions by using our proposed method. The concept of this application is similar to the so-called multi-technique-network time/frequency transfer. The encouraging results confirm that the TWSTFT network performance can benefit from DPN data by improving short-term stabilities and reducing diurnal effects.The results of TW+PPP network solutions are also illustrated.

The Use of Video in Knowledge Transfer of Teacher-Led Psychosocial Interventions: Feeling Competent to Adopt a Different Role in the Classroom (L'utilisation de la vidéo dans le transfert de connaissances dans les interventions psychosociales menées par les enseignants : sentir que l'on a la compétence d'adopter un rôle différent dans la salle de classe)

ERIC Educational Resources Information Center

Beauregard, Caroline; Rousseau, Cécile; Mustafa, Sally

2015-01-01

Because they propose a form of modeling, videos have been recognised to be useful to transfer knowledge about practices requiring teachers to adopt a different role. This paper describes the results of a satisfaction survey with 98 teachers, school administrators and professionals regarding their appreciation of training videos showing teacher-led…

Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials

DTIC Science & Technology

2005-09-01

M.K. Brenner, and C.M. Rooney, Long-term restoration of immunity against Epstein - Barr virus infection by adoptive transfer of gene-modified virus ...R.A. Krance, M.K. Brenner, and C.M. Rooney, Long-term restoration of immunity against Epstein - Barr virus infection by adoptive transfer of gene...immunity will result in anti-tumor immunity. We propose to develop an optimal cancer vaccine using epithelial cell mucin MUCI peptides or protein or MUCl

T-cell-based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition.

PubMed

Houot, Roch; Schultz, Liora Michal; Marabelle, Aurélien; Kohrt, Holbrook

2015-10-01

Tumor immunotherapy has had demonstrable efficacy in patients with cancer. The most promising results have been with T-cell-based therapies. These include adoptive cell transfer of tumor-infiltrating lymphocytes, genetically engineered T cells, and immune checkpoint inhibitor antibodies. In this review, we describe the different T-cell-based strategies currently in clinical trials and put their applications, present and future, into perspective. ©2015 American Association for Cancer Research.

Two is better than one: advances in pathogen-boosted immunotherapy and adoptive T-cell therapy.

PubMed

Xin, Gang; Schauder, David M; Zander, Ryan; Cui, Weiguo

2017-09-01

The recent tremendous successes in clinical trials take cancer immunotherapy into a new era and have attracted major attention from both academia and industry. Among the variety of immunotherapy strategies developed to boost patients' own immune systems to fight against malignant cells, the pathogen-based and adoptive cell transfer therapies have shown the most promise for treating multiple types of cancer. Pathogen-based therapies could either break the immune tolerance to enhance the effectiveness of cancer vaccines or directly infect and kill cancer cells. Adoptive cell transfer can induce a strong durable antitumor response, with recent advances including engineering dual specificity into T cells to recognize multiple antigens and improving the metabolic fitness of transferred cells. In this review, we focus on the recent prospects in these two areas and summarize some ongoing studies that represent potential advancements for anticancer immunotherapy, including testing combinations of these two strategies.

Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

PubMed Central

Brody, Joshua; Levy, Ronald

2017-01-01

Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

Tumor-targeting CTL expressing a single-chain Fv specific for VEGFR2.

PubMed

Kanagawa, Naoko; Yanagawa, Tatsuya; Mukai, Yohei; Yoshioka, Yasuo; Okada, Naoki; Nakagawa, Shinsaku

2010-03-26

Cytotoxic T lymphocytes (CTL) are critical effector cells in tumor immunity. Adoptive transfer therapy with in vitro-expanded tumor-specific CTL is a promising approach for preventing cancer metastasis and recurrence. Transferred CTL are not effective in clinical trials, however, due to inadequate tumor-infiltration. Therefore, the development of functionally modified CTL, such as tumor-targeting CTL, is widely desired. Here, we designed the tumor-targeting CTL expressing a single-chain antibody fragment (scFv-CTL) specific for vascular endothelial growth factor receptor 2 (VEGFR2/flk1) by transducing the CTL with a retroviral vector. The scFv-CTL bound to VEGFR2/flk1-expressing cells and retained their cytotoxic activity against tumor cells. In addition, adoptive transfer of scFv-CTL into tumor-bearing mice effectively suppressed tumor growth due to the augmented accumulation of the transferred CTL in the tumor tissue. These findings indicate that the creation of CTL capable of targeting tumor vascular endothelial cells by scFv-expression technique is considerably promising for improvement of efficacy in adoptive immunotherapy. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Excitonic energy transfer in light-harvesting complexes in purple bacteria

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

Ye Jun; Sun Kewei; Zhao Yang

Two distinct approaches, the Frenkel-Dirac time-dependent variation and the Haken-Strobl model, are adopted to study energy transfer dynamics in single-ring and double-ring light-harvesting (LH) systems in purple bacteria. It is found that the inclusion of long-range dipolar interactions in the two methods results in significant increase in intra- or inter-ring exciton transfer efficiency. The dependence of exciton transfer efficiency on trapping positions on single rings of LH2 (B850) and LH1 is similar to that in toy models with nearest-neighbor coupling only. However, owing to the symmetry breaking caused by the dimerization of BChls and dipolar couplings, such dependence has beenmore » largely suppressed. In the studies of coupled-ring systems, both methods reveal an interesting role of dipolar interactions in increasing energy transfer efficiency by introducing multiple intra/inter-ring transfer paths. Importantly, the time scale (4 ps) of inter-ring exciton transfer obtained from polaron dynamics is in good agreement with previous studies. In a double-ring LH2 system, non-nearest neighbor interactions can induce symmetry breaking, which leads to global and local minima of the average trapping time in the presence of a non-zero dephasing rate, suggesting that environment dephasing helps preserve quantum coherent energy transfer when the perfect circular symmetry in the hypothetic system is broken. This study reveals that dipolar coupling between chromophores may play an important role in the high energy transfer efficiency in the LH systems of purple bacteria and many other natural photosynthetic systems.« less

Trial-by-trial analysis of intermanual transfer during visuomotor adaptation

PubMed Central

Wojaczynski, Greg J.; Ivry, Richard B.

2011-01-01

Studies of intermanual transfer have been used to probe representations formed during skill acquisition. We employ a new method that provides a continuous assay of intermanual transfer, intermixing right- and left-hand trials while limiting visual feedback to right-hand movements. We manipulated the degree of awareness of the visuomotor rotation, introducing a 22.5° perturbation in either an abrupt single step or gradually in ∼1° increments every 10 trials. Intermanual transfer was observed with the direction of left-hand movements shifting in the opposite direction of the rotation over the course of training. The transfer on left-hand trials was less than that observed in the right hand. Moreover, the magnitude of transfer was larger in our mixed-limb design compared with the standard blocked design in which transfer is only probed at the end of training. Transfer was similar in the abrupt and gradual groups, suggesting that awareness of the perturbation has little effect on intermanual transfer. In a final experiment, participants were provided with a strategy to offset an abrupt rotation, a method that has been shown to increase error over the course of training due to the operation of sensorimotor adaptation. This deterioration was also observed on left-hand probe trials, providing further support that awareness has little effect on intermanual transfer. These results indicate that intermanual transfer is not dependent on the implementation of cognitively assisted strategies that participants might adopt when they become aware that the visuomotor mapping has been perturbed. Rather, the results indicate that the information available to processes involved in adaptation entails some degree of effector independence. PMID:21917998

Understanding the biology of ex vivo-expanded CD8 T cells for adoptive cell therapy: role of CD62L.

PubMed

Díaz-Montero, C Marcela; Zidan, Abdel-Aziz; Pallin, Maria F; Anagnostopoulos, Vasileios; Salem, Mohamed L; Wieder, Eric; Komanduri, Krishna; Montero, Alberto J; Lichtenheld, Mathias G

2013-12-01

CD62L governs the circulation of CD8(+) T cells between lymph nodes and peripheral tissues, whereby the expression of CD62L by CD8(+) T cells promotes their recirculation through lymph nodes. As such, CD62L participates in the fate of adoptively transferred CD8(+) T cells and may control their effectiveness for cancer immunotherapy, including settings in which host preconditioning results in the acute lymphopenia-induced proliferation of the transferred cells. Indeed, previous studies correlated CD62L expression by donor CD8(+) cells with the success rate of adoptive cell therapy (ACT). Here, we analyzed the functions and fate of ex vivo-activated, tumor-specific CD62L(-/-) CD8(+) T cells in a mouse melanoma model for ACT. Unexpectedly, we observed that CD62L(-/-) CD8(+) T cells were functionally indistinguishable from CD62L(+/+) CD8(+) T cells, i.e., both greatly expanded in cyclophosphamide preconditioned animals, controlled subcutaneously and hematogenously spreading tumors, and generated anti-tumor-specific CD8(+) T cell memory. Moreover, even in hosts with rudimentary secondary lymphoid organs (LT(-/-) animals), CD8(+) T cells with and without CD62L expanded equivalently to those adoptively transferred into wild-type animals. These results put into question the utility of CD62L as a predictive biomarker for the efficacy of ex vivo-expanded T cells after ACT in lymphopenic conditions and also offer new insights into the homing, engraftment, and memory generation of adoptively transferred ex vivo-activated CD8(+) T cells.

Development of RWHet to Simulate Contaminant Transport in Fractured Porous Media

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

Zhang, Yong; LaBolle, Eric; Reeves, Donald M

2012-07-01

Accurate simulation of matrix diffusion in regional-scale dual-porosity and dual-permeability media is a critical issue for the DOE Underground Test Area (UGTA) program, given the prevalence of fractured geologic media on the Nevada National Security Site (NNSS). Contaminant transport through regional-scale fractured media is typically quantified by particle-tracking based Lagrangian solvers through the inclusion of dual-domain mass transfer algorithms that probabilistically determine particle transfer between fractures and unfractured matrix blocks. UGTA applications include a wide variety of fracture aperture and spacing, effective diffusion coefficients ranging four orders of magnitude, and extreme end member retardation values. This report incorporates the currentmore » dual-domain mass transfer algorithms into the well-known particle tracking code RWHet [LaBolle, 2006], and then tests and evaluates the updated code. We also develop and test a direct numerical simulation (DNS) approach to replace the classical transfer probability method in characterizing particle dynamics across the fracture/matrix interface. The final goal of this work is to implement the algorithm identified as most efficient and effective into RWHet, so that an accurate and computationally efficient software suite can be built for dual-porosity/dual-permeability applications. RWHet is a mature Lagrangian transport simulator with a substantial user-base that has undergone significant development and model validation. In this report, we also substantially tested the capability of RWHet in simulating passive and reactive tracer transport through regional-scale, heterogeneous media. Four dual-domain mass transfer methodologies were considered in this work. We first developed the empirical transfer probability approach proposed by Liu et al. [2000], and coded it into RWHet. The particle transfer probability from one continuum to the other is proportional to the ratio of the mass entering the other continuum to the mass in the current continuum. Numerical examples show that this method is limited to certain ranges of parameters, due to an intrinsic assumption of an equilibrium concentration profile in the matrix blocks in building the transfer probability. Subsequently, this method fails in describing mass transfer for parameter combinations that violate this assumption, including small diffusion coefficients (i.e., the free-water molecular diffusion coefficient 1×10-11 meter2/second), relatively large fracture spacings (such as meter), and/or relatively large matrix retardation coefficients (i.e., ). These “outliers” in parameter range are common in UGTA applications. To address the above limitations, we then developed a Direct Numerical Simulation (DNS)-Reflective method. The novel DNS-Reflective method can directly track the particle dynamics across the fracture/matrix interface using a random walk, without any empirical assumptions. This advantage should make the DNS-Reflective method feasible for a wide range of parameters. Numerical tests of the DNS-Reflective, however, show that the method is computationally very demanding, since the time step must be very small to resolve particle transfer between fractures and matrix blocks. To improve the computational efficiency of the DNS approach, we then adopted Roubinet et al.’s method [2009], which uses first passage time distributions to simulate dual-domain mass transfer. The DNS-Roubinet method was found to be computationally more efficient than the DNS-Reflective method. It matches the analytical solution for the whole range of major parameters (including diffusion coefficient and fracture aperture values that are considered “outliers” for Liu et al.’s transfer probability method [2000]) for a single fracture system. The DNS-Roubinet method, however, has its own disadvantage: for a parallel fracture system, the truncation of the first passage time distribution creates apparent errors when the fracture spacing is small, and thus it tends to erroneously predict breakthrough curves (BTCs) for the parallel fracture system. Finally, we adopted the transient range approach proposed by Pan and Bodvarsson [2002] in RWHet. In this method, particle transfer between fractures and matrix blocks can be resolved without using very small time steps. It does not use any truncation of the first passage time distribution for particles. Hence it does not have the limitation identified above for the DNS-Reflective method and the DNS-Roubinet method. Numerical results were checked against analytical solutions, and also compared to DCPTV2.0 [Pan, 2002]. This version of RWHet (called RWHet-Pan&Bodvarsson in this report) can accurately capture contaminant transport in fractured porous media for a full range of parameters without any practical or theoretical limitations.« less

Adoptive transfer of paternal antigen-hyporesponsive T cells facilitates a Th2 bias in peripheral lymphocytes and at materno-fetal interface in murine abortion-prone matings.

PubMed

Jin, Li-Ping; Zhou, Yue-Hua; Zhu, Xiao-Yong; Wang, Ming-Yan; Li, Da-Jin

2006-10-01

To investigate the Th1/Th2 cytokine changes in abortion-prone recipient mice adoptively transferred by the paternal antigen-hyporesponsive T cells. The paternal antigen-hyporesponsive T cells were generated by the anti-B7 monoclonal antibody (mAb) treatment and adoptively transferred into pregnant CBA/J mice of abortion-prone matings on day 4 of gestation. The intracellular expressions of Th1 cell-derived cytokine, tumor necrosis factor-alpha, gamma-interferon and interleukin-2 (IL-2) and Th2 cell-derived cytokine, IL-4 and IL-10 in the maternal spleen were analyzed by flow cytometry, and secretions of the Th1 and Th2 cytokines in supernatant of the feto-placental unit culture were analyzed by an enzyme-linked immunosorbent assay. Our findings showed the increased secretion of Th1 cytokines and the decreased secretion of Th2 cytokines in abortion-prone matings. Treatment with anti-B7 mAbs on day 4 of gestation enhanced Th2 and reduced Th1 cytokine production in abortion-prone matings. Similarly, adoptive transfer of paternal antigen-hyporesponsive T cells induced maternal tolerance to the fetus and displayed a Th2 bias both in the peripheral lymphocytes and at the materno-fetal interface of the abortion-prone matings. These findings indicate that the Th2 cytokine bias and an increase in fetal viability induced by the anti-B7 mAb treatment can be transferred to other pregnant mice of the abortion-prone matings.

Comprehensive genetic assessment of the human embryo: can empiric application of microarray comparative genomic hybridization reduce multiple gestation rate by single fresh blastocyst transfer?

PubMed

Sills, Eric Scott; Yang, Zhihong; Walsh, David J; Salem, Shala A

2012-09-01

The unacceptable multiple gestation rate currently associated with in vitro fertilization (IVF) would be substantially alleviated if the routine practice of transferring more than one embryo were reconsidered. While transferring a single embryo is an effective method to reduce the clinical problem of multiple gestation, rigid adherence to this approach has been criticized for negatively impacting clinical pregnancy success in IVF. In general, single embryo transfer is viewed cautiously by IVF patients although greater acceptance would result from a more effective embryo selection method. Selection of one embryo for fresh transfer on the basis of chromosomal normalcy should achieve the dual objective of maintaining satisfactory clinical pregnancy rates and minimizing the multiple gestation problem, because embryo aneuploidy is a major contributing factor in implantation failure and miscarriage in IVF. The initial techniques for preimplantation genetic screening unfortunately lacked sufficient sensitivity and did not yield the expected results in IVF. However, newer molecular genetic methods could be incorporated with standard IVF to bring the goal of single embryo transfer within reach. Aiming to make multiple embryo transfers obsolete and unnecessary, and recognizing that array comparative genomic hybridization (aCGH) will typically require an additional 12 h of laboratory time to complete, we propose adopting aCGH for mainstream use in clinical IVF practice. As aCGH technology continues to develop and becomes increasingly available at lower cost, it may soon be considered unusual for IVF laboratories to select a single embryo for fresh transfer without regard to its chromosomal competency. In this report, we provide a rationale supporting aCGH as the preferred methodology to provide a comprehensive genetic assessment of the single embryo before fresh transfer in IVF. The logistics and cost of integrating aCGH with IVF to enable fresh embryo transfer are also discussed.

Comparison of Transformer Winding Methods for Contactless Power Transfer Systems of Electric Vehicle

NASA Astrophysics Data System (ADS)

Kaneko, Yasuyoshi; Ehara, Natsuki; Iwata, Takuya; Abe, Shigeru; Yasuda, Tomio; Ida, Kazuhiko

This paper describes the comparison of the characteristics of double- and single-sided windings of contactless power transfer systems used in electric vehicles. The self-inductance changes with the electric current when the gap length is fixed in single-sided windings. The issue is resolved by maintaining the secondary voltage constant. In the case of double-sided windings, the transformer can be miniaturized in comparison with the single-sided winding transformer. However, the coupling factor is small, and appropriate countermeasures must be adopted to reduce the back leakage flux. The leakage flux is reduced by placing an aluminum board behind the transformer. Thus, the coupling factor increases.

Improved Personalized Cancer Immunotherapy | NCI Technology Transfer Center | TTC

Cancer.gov

The National Cancer Institute’s Surgery Branch seeks partners interested in collaborative research to co-develop adoptive transfer of tumor infiltrating leukocytes (TIL) for cancers other than melanoma.

T-Cell-Based Immunotherapy for Osteosarcoma: Challenges and Opportunities

PubMed Central

Wang, Zhan; Li, Binghao; Ren, Yingqing; Ye, Zhaoming

2016-01-01

Even though combining surgery with chemotherapy has significantly improved the prognosis of osteosarcoma patients, advanced, metastatic, or recurrent osteosarcomas are often non-responsive to chemotherapy, making development of novel efficient therapeutic methods an urgent need. Adoptive immunotherapy has the potential to be a useful non-surgical modality for treatment of osteosarcoma. Recently, alternative strategies, including immunotherapies using naturally occurring or genetically modified T cells, have been found to hold promise in the treatment of hematologic malignancies and solid tumors. In this review, we will discuss possible T-cell-based therapies against osteosarcoma with a special emphasis on combination strategies to improve the effectiveness of adoptive T cell transfer and, thus, to provide a rationale for the clinical development of immunotherapies. PMID:27683579

The Danish Adoption Register.

PubMed

Petersen, Liselotte; Sørensen, Thorkild I A

2011-07-01

The Danish Adoption Register was established in 1963-1964 to explore the genetic and environmental contribution to familial aggregation of schizophrenia. The register encompass information on all 14,425 non-familial adoptions of Danish children legally granted in Denmark 1924-1947. It includes name and date of birth of each adoptee and his or her biological and adoptive parents, date of transfer to adoptive parents and date of formal adoption. The linkage to biological and adoptive parents is close to complete, even biological fathers are registered for 91.4% of the adoptees. Adoption registers are a unique source allowing disentangling of genetic and familial environmental influences on traits, risk of diseases, and mortality.

BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy

PubMed Central

Koya, Richard C.; Mok, Stephen; Otte, Nicholas; Blacketor, Kevin J.; Comin-Anduix, Begonya; Tumeh, Paul C.; Minasyan, Aspram; Graham, Nicholas A.; Graeber, Thomas G.; Chodon, Thinle; Ribas, Antoni

2012-01-01

Combining immunotherapy with targeted therapy blocking oncogenic BRAFV600 may result in improved treatments for advanced melanoma. Here, we developed a BRAFV600E-driven murine model of melanoma, SM1, which is syngeneic to fully immunocompetent mice. SM1 cells exposed to the BRAF inhibitor vemurafenib (PLX4032) showed partial in vitro and in vivo sensitivity resulting from the inhibition of MAPK pathway signaling. Combined treatment of vemurafenib plus adoptive cell transfer (ACT) therapy with lymphocytes genetically modified with a T cell receptor (TCR) recognizing chicken ovalbumin (OVA) expressed by SM1-OVA tumors, or pmel-1 TCR transgenic lymphocytes recognizing gp100 endogenously expressed by SM1, resulted in superior antitumor responses compared with either therapy alone. T cell analysis demonstrated that vemurafenib did not significantly alter the expansion, distribution, or tumor accumulation of the adoptively transferred cells. However, vemurafenib paradoxically increased MAPK signaling, in vivo cytotoxic activity, and intratumoral cytokine secretion by adoptively transferred cells. Together, our findings, derived from two independent models combining BRAF-targeted therapy with immunotherapy, support the testing of this therapeutic combination in patients with BRAFV600 mutant metastatic melanoma. PMID:22693252

Tumor infiltrating BRAFV600E-specific CD4 T cells correlated with complete clinical response in melanoma. | Office of Cancer Genomics

Cancer.gov

T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL).

Farmers' Market Manager's Level of Communication and Influence on Electronic Benefits Transfer (EBT) Adoption at Midwest Farmers' Markets.

PubMed

Hasin, Afroza; Smith, Sylvia

2018-01-01

To understand market managers' level of communication and use of technology that might influence decision to adopt Electronic Benefits Transfer (EBT) at farmers' markets. Cross-sectional study using the Theory of Diffusion of Innovation. Electronic survey administered in midwest states of Illinois, Michigan, and Wisconsin. Farmers' market managers in Illinois, Michigan, and Wisconsin. Information on EBT adoption, market managers' communication, and technology use. Binary logistic regression analysis with EBT adoption as the dependent variable and frequency of technology use, partnership with organizations, farmers' market association (FMA) membership, Facebook page and Web site for the market, and primary source of information as independent variables. Chi-square tests and ANOVA were used to compare states and adopter categories. Logistic regression results showed that the odds of adopting EBT was 7.5 times higher for markets that had partnership with other organizations. Compared with non-adopters, a significantly greater number of early adopters had partnership, FMA membership, and a Facebook page and Web site for market, and reported to a board of directors. Markets that had partnership, FMA membership, a Facebook page and Web site, and mandatory reporting to a board of directors were important factors that influenced EBT adoption at midwest farmers' markets. Copyright © 2017 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Fully Transparent Quantum Dot Light-Emitting Diode with a Laminated Top Graphene Anode.

PubMed

Yao, Li; Fang, Xin; Gu, Wei; Zhai, Wenhao; Wan, Yi; Xie, Xixi; Xu, Wanjin; Pi, Xiaodong; Ran, Guangzhao; Qin, Guogang

2017-07-19

A new method to employ graphene as top electrode was introduced, and based on that, fully transparent quantum dot light-emitting diodes (T-QLEDs) were successfully fabricated through a lamination process. We adopted the widely used wet transfer method to transfer bilayer graphene (BG) on polydimethylsiloxane/polyethylene terephthalate (PDMS/PET) substrate. The sheet resistance of graphene reduced to ∼540 Ω/□ through transferring BG for 3 times on the PDMS/PET. The T-QLED has an inverted device structure of glass/indium tin oxide (ITO)/ZnO nanoparticles/(CdSSe/ZnS quantum dots (QDs))/1,1-bis[(di-4-tolylamino)phenyl] cyclohexane (TAPC)/MoO 3 /graphene/PDMS/PET. The graphene anode on PDMS/PET substrate can be directly laminated on the MoO 3 /TAPC/(CdSSe/ZnS QDs)/ZnO nanoparticles/ITO/glass, which relied on the van der Waals interaction between the graphene/PDMS and the MoO 3 . The transmittance of the T-QLED is 79.4% at its main electroluminescence peak wavelength of 622 nm.

The interplay between experiential and traditional learning for competency development.

PubMed

Bonesso, Sara; Gerli, Fabrizio; Pizzi, Claudio

2015-01-01

Extensive research demonstrated that firms may pursue several advantages in hiring individuals with the set of emotional, social, and cognitive (ESC) competencies that are most critical for business success. Therefore, the role of education for competency development is becoming paramount. Prior studies have questioned the traditional methods, grounded in the lecture format, as a way to effectively develop ESC competencies. Alternatively, they propose experiential learning techniques that involve participants in dedicated courses or activities. Despite the insights provided by these studies, they do not take into account a comprehensive set of learning methods and their combined effect on the individual's competency portfolio within educational programs that aim to transfer primarily professional skills. Our study aims to fill these gaps by investigating the impact of the interplay between different learning methods on ESC competencies through a sample of students enrolled in the first year of a master's degree program. After providing a classification of three learning methods [traditional learning (TL), individual experiential learning (IEL), and social experiential learning (SEL)], the study delves into their combined influence on ESC competencies, adopting the Artificial Neural Network. Contrary to prior studies, our results provide counterintuitive evidence, suggesting that TL needs to be implemented together, on the one hand, with IEL to achieve a significant effect on emotional competencies and, on the other hand, with SEL to have an impact on social competencies. Moreover, IEL plays a prominent role in stimulating cognitive competencies. Our research contributes to educational literature by providing new insights on the effective combination of learning methods that can be adopted into programs that transfer technical knowledge and skills to promote behavioral competencies.

The interplay between experiential and traditional learning for competency development

PubMed Central

Bonesso, Sara; Gerli, Fabrizio; Pizzi, Claudio

2015-01-01

Extensive research demonstrated that firms may pursue several advantages in hiring individuals with the set of emotional, social, and cognitive (ESC) competencies that are most critical for business success. Therefore, the role of education for competency development is becoming paramount. Prior studies have questioned the traditional methods, grounded in the lecture format, as a way to effectively develop ESC competencies. Alternatively, they propose experiential learning techniques that involve participants in dedicated courses or activities. Despite the insights provided by these studies, they do not take into account a comprehensive set of learning methods and their combined effect on the individual's competency portfolio within educational programs that aim to transfer primarily professional skills. Our study aims to fill these gaps by investigating the impact of the interplay between different learning methods on ESC competencies through a sample of students enrolled in the first year of a master's degree program. After providing a classification of three learning methods [traditional learning (TL), individual experiential learning (IEL), and social experiential learning (SEL)], the study delves into their combined influence on ESC competencies, adopting the Artificial Neural Network. Contrary to prior studies, our results provide counterintuitive evidence, suggesting that TL needs to be implemented together, on the one hand, with IEL to achieve a significant effect on emotional competencies and, on the other hand, with SEL to have an impact on social competencies. Moreover, IEL plays a prominent role in stimulating cognitive competencies. Our research contributes to educational literature by providing new insights on the effective combination of learning methods that can be adopted into programs that transfer technical knowledge and skills to promote behavioral competencies. PMID:26388810

The fine tuning of carotenoid-chlorophyll interactions in light-harvesting complexes: an important requisite to guarantee efficient photoprotection via triplet-triplet energy transfer in the complex balance of the energy transfer processes

NASA Astrophysics Data System (ADS)

Di Valentin, Marilena; Carbonera, Donatella

2017-08-01

Triplet-triplet energy transfer (TTET) from the chlorophyll to the carotenoid triplet state is the process exploited by photosynthetic systems to protect themselves from singlet oxygen formation under light-stress conditions. A deep comprehension of the molecular strategies adopted to guarantee TTET efficiency, while at the same time maintaining minimal energy loss and efficient light-harvesting capability, is still lacking. The paramagnetic nature of the triplet state makes electron paramagnetic resonance (EPR) the method of choice when investigating TTET. In this review, we focus on our extended comparative study of two photosynthetic antenna complexes, the Peridinin-chlorophyll a-protein of dinoflagellates and the light-harvesting complex II of higher plants, in order to point out important aspects of the molecular design adopted in the photoprotection strategy. We have demonstrated that a proper analysis of the EPR data allows one to identify the pigments involved in TTET and, consequently, gain an insight into the structure of the photoprotective sites. The structural information has been complemented by a detailed description of the electronic structure provided by hyperfine spectroscopy. All these elements represent the fundamental building blocks toward a deeper understanding of the requirements for efficient photoprotection, which is fundamental to guarantee the prolonged energy conversion action of photosynthesis.

Adoptive Cell Transfer Therapy Following Non-Myeloablative but Lymphodepleting Chemotherapy for the Treatment of Patients With Refractory Metastatic Melanoma

PubMed Central

Dudley, Mark E.; Wunderlich, John R.; Yang, James C.; Sherry, Richard M.; Topalian, Suzanne L.; Restifo, Nicholas P.; Royal, Richard E.; Kammula, Udai; White, Don E.; Mavroukakis, Sharon A.; Rogers, Linda J.; Gracia, Gerald J.; Jones, Stephanie A.; Mangiameli, David P.; Pelletier, Michelle M.; Gea-Banacloche, Juan; Robinson, Michael R.; Berman, David M.; Filie, Armando C.; Abati, Andrea; Rosenberg, Steven A.

2006-01-01

Purpose We investigated the combination of lymphodepleting chemotherapy followed by the adoptive transfer of autologous tumor reactive lymphocytes for the treatment of patients with refractory metastatic melanoma. Patients and Methods Thirty-five patients with metastatic melanoma, all but one with disease refractory to treatment with high-dose interleukin (IL)-2 and many with progressive disease after chemotherapy, underwent lymphodepleting conditioning with two days of cyclophosphamide (60 mg/kg) followed by five days of fludarabine (25 mg/m2). On the day following the final dose of fludarabine, all patients received cell infusion with autologous tumor-reactive, rapidly expanded tumor infiltrating lymphocyte cultures and high-dose IL-2 therapy. Results Eighteen (51%) of 35 treated patients experienced objective clinical responses including three ongoing complete responses and 15 partial responses with a mean duration of 11.5 ± 2.2 months. Sites of regression included metastases to lung, liver, lymph nodes, brain, and cutaneous and subcutaneous tissues. Toxicities of treatment included the expected hematologic toxicities of chemotherapy including neutropenia, thrombocytopenia, and lymphopenia, the transient toxicities of high-dose IL-2 therapy, two patients who developed Pneumocystis pneumonia and one patient who developed an Epstein-Barr virus-related lymphoproliferation. Conclusion Lymphodepleting chemotherapy followed by the transfer of highly avid antitumor lymphocytes can mediate significant tumor regression in heavily pretreated patients with IL-2 refractory metastatic melanoma. PMID:15800326

Drug Resistance in Salmonella Typhimurium and its Implications*

PubMed Central

Anderson, E. S.

1968-01-01

A rise in Salmonella typhimurium infection was observed in calves in Britain during 1964–6, follwing the adoption of the intensive farming method. A single phage type of S. typhimurium, type 29, was incriminated as the major pathogen. Attempts to treat and control the disease with a range of antibiotics were ineffective, but resulted in the acquisition of transferable multiple drug resistance by type 29. The transmission of drug-resistant type 29, directly or indirectly, from bovines to man resulted in many human infections. Transferable drug resistance reaching man from enterobacteria of animal origin may ultimately enter specifically human pathogens. Infections such as that caused by type 29 can be eliminated, not by the massive use of antibiotics but by improvement in conditions of animal husbandry and reduction in the opportunities for the initiation and spread of the disease. A reappraisal is needed of the methods of using antibiotics to determine how these methods can be improved, in order to conserve the long-term efficacy of the antibiotics. PMID:4874171

Adoptive Transfer of Dying Cells Causes Bystander-Induced Apoptosis

PubMed Central

Schwulst, Steven J.; Davis, Christopher G.; Coopersmith, Craig M.; Hotchkiss, Richard S.

2009-01-01

The anti-apoptotic Bcl-2 protein has the remarkable ability to prevent cell death from several noxious stimuli. Intriguingly, Bcl-2 overexpression in one cell type has been reported to protect against cell death in neighboring non-Bcl-2 overexpressing cell types. The mechanism of this “trans” protection has been speculated to be secondary to the release of a cytoprotective factor by Bcl-2 overexpressing cells. We employed a series of adoptive transfer experiments in which lymphocytes that overexpress Bcl-2 were administered to either wild type mice or mice lacking mature T and B cells (Rag-1-/-) to detect the presence or absence of the putative protective factor. We were unable to demonstrate “trans” protection. However, adoptive transfer of apoptotic or necrotic cells exacerbated the degree of apoptotic death in neighboring non-Bcl-2 overexpressing cells (p≤0.05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e. a “trans” destructive effect. PMID:17194455

Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

PubMed Central

Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

2014-01-01

Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

PubMed

Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

2008-02-01

The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

N-S/DSMC hybrid simulation of hypersonic flow over blunt body including wakes

NASA Astrophysics Data System (ADS)

Li, Zhonghua; Li, Zhihui; Li, Haiyan; Yang, Yanguang; Jiang, Xinyu

2014-12-01

A hybrid N-S/DSMC method is presented and applied to solve the three-dimensional hypersonic transitional flows by employing the MPC (modular Particle-Continuum) technique based on the N-S and the DSMC method. A sub-relax technique is adopted to deal with information transfer between the N-S and the DSMC. The hypersonic flows over a 70-deg spherically blunted cone under different Kn numbers are simulated using the CFD, DSMC and hybrid N-S/DSMC method. The present computations are found in good agreement with DSMC and experimental results. The present method provides an efficient way to predict the hypersonic aerodynamics in near-continuum transitional flow regime.

Beyond the standard two-film theory: Computational fluid dynamics simulations for carbon dioxide capture in a wetted wall column

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

Wang, Chao; Xu, Zhijie; Lai, Canhai

The standard two-film theory (STFT) is a diffusion-based mechanism that can be used to describe gas mass transfer across liquid film. Fundamental assumptions of the STFT impose serious limitations on its ability to predict mass transfer coefficients. To better understand gas absorption across liquid film in practical situations, a multiphase computational fluid dynamics (CFD) model fully equipped with mass transport and chemistry capabilities has been developed for solvent-based carbon dioxide (CO 2) capture to predict the CO 2 mass transfer coefficient in a wetted wall column. The hydrodynamics is modeled using a volume of fluid method, and the diffusive andmore » reactive mass transfer between the two phases is modeled by adopting a one-fluid formulation. We demonstrate that the proposed CFD model can naturally account for the influence of many important factors on the overall mass transfer that cannot be quantitatively explained by the STFT, such as the local variation in fluid velocities and properties, flow instabilities, and complex geometries. The CFD model also can predict the local mass transfer coefficient variation along the column height, which the STFT typically does not consider.« less

Beyond the standard two-film theory: Computational fluid dynamics simulations for carbon dioxide capture in a wetted wall column

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

Wang, Chao; Xu, Zhijie; Lai, Canhai

The standard two-film theory (STFT) is a diffusion-based mechanism that can be used to describe gas mass transfer across liquid film. Fundamental assumptions of the STFT impose serious limitations on its ability to predict mass transfer coefficients. To better understand gas absorption across liquid film in practical situations, a multiphase computational fluid dynamics (CFD) model fully equipped with mass transport and chemistry capabilities has been developed for solvent-based carbon dioxide (CO2) capture to predict the CO2 mass transfer coefficient in a wetted wall column. The hydrodynamics is modeled using a volume of fluid method, and the diffusive and reactive massmore » transfer between the two phases is modeled by adopting a one-fluid formulation. We demonstrate that the proposed CFD model can naturally account for the influence of many important factors on the overall mass transfer that cannot be quantitatively explained by the STFT, such as the local variation in fluid velocities and properties, flow instabilities, and complex geometries. The CFD model also can predict the local mass transfer coefficient variation along the column height, which the STFT typically does not consider.« less

Beyond the standard two-film theory: Computational fluid dynamics simulations for carbon dioxide capture in a wetted wall column

DOE PAGES

Wang, Chao; Xu, Zhijie; Lai, Canhai; ...

2018-03-27

The standard two-film theory (STFT) is a diffusion-based mechanism that can be used to describe gas mass transfer across liquid film. Fundamental assumptions of the STFT impose serious limitations on its ability to predict mass transfer coefficients. To better understand gas absorption across liquid film in practical situations, a multiphase computational fluid dynamics (CFD) model fully equipped with mass transport and chemistry capabilities has been developed for solvent-based carbon dioxide (CO 2) capture to predict the CO 2 mass transfer coefficient in a wetted wall column. The hydrodynamics is modeled using a volume of fluid method, and the diffusive andmore » reactive mass transfer between the two phases is modeled by adopting a one-fluid formulation. We demonstrate that the proposed CFD model can naturally account for the influence of many important factors on the overall mass transfer that cannot be quantitatively explained by the STFT, such as the local variation in fluid velocities and properties, flow instabilities, and complex geometries. The CFD model also can predict the local mass transfer coefficient variation along the column height, which the STFT typically does not consider.« less

Machine-Thermal Coupling Stresses Analysis of the Fin-Type Structural Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Zhang, Zheng; Yue, Hao; Chen, Dongbo; Qin, Delei; Chen, Zijian

2017-05-01

The design structure and heat-transfer mechanism of a thermoelectric generator (TEG) determine its body temperature state. Thermal stress and thermal deformation generated by the temperature variation directly affect the stress state of thermoelectric modules (TEMs). Therefore, the rated temperature and pressing force of TEMs are important parameters in TEG design. Here, the relationships between structural of a fin-type TEG (FTEG) and these parameters are studied by modeling and "machine-thermal" coupling simulation. An indirect calculation method is adopted in the coupling simulation. First, numerical heat transfer calculations of a three-dimensional FTEG model are conducted according to an orthogonal simulation table. The influences of structural parameters for heat transfer in the channel and outer fin temperature distribution are analyzed. The optimal structural parameters are obtained and used to simulate temperature field of the outer fins. Second, taking the thermal calculation results as the initial condition, the thermal-solid coupling calculation is adopted. The thermal stresses of outer fin, mechanical force of spring-angle pressing mechanism, and clamping force on a TEM are analyzed. The simulation results show that the heat transfer area of the inner fin and the physical parameters of the metal materials are the keys to determining the FTEG temperature field. The pressing mechanism's mechanical force can be reduced by reducing the outer fin angle. In addition, a corrugated cooling water pipe, which has cooling and spring functionality, is conducive to establishing an adaptable clamping force to avoid the TEMs being crushed by the thermal stresses in the body.

Adoptive cell transfer therapy for malignant gliomas.

PubMed

Ishikawa, Eiichi; Takano, Shingo; Ohno, Tadao; Tsuboi, Koji

2012-01-01

To date, various adoptive immunotherapies have been attempted for treatment of malignant gliomas using nonspecific and/or specific effector cells. Since the late 1980s, with the development of rIL-2, the efficacy of lymphokine-activated killer (LAK) cell therapy with or without rIL-2 for malignant gliomas had been tested with some modifications in therapeutic protocols. With advancements in technology, ex vivo expanded tumor specific cytotoxic T-lymphocytes (CTL) or those lineages were used in clinical trials with higher tumor response rates. In addition, combinations of those adoptive cell transfer using LAK cells, CTLs or natural killer (NK) cells with autologous tumor vaccine (ATV) therapy were attempted. Also, a strategy of high-dose (or lymphodepleting) chemotherapy followed by adoptive cell transfer has been drawing attentions recently. The most important role of these clinical studies using cell therapy was to prove that these ex vivo expanded effector cells could kill tumor cells in vivo. Although recent clinical results could demonstrate radiologic tumor shrinkage in a number of cases, cell transfer therapy alone has been utilized less frequently, because of the high cost of ex vivo cell expansion, the short duration of antitumor activity in vivo, and the recent shift of interest to vaccine immunotherapy. Nevertheless, NK cell therapy using specific feeder cells or allergenic NK cell lines have potentials to be a good choice of treatment because of easy ex vivo expansion and their efficacy especially when combined with vaccine therapy as they are complementary to each other. Also, further studies are expected to clarify the efficacy of the high-dose chemotherapy followed by a large scale cell transfer therapy as a new therapeutic strategy for malignant gliomas.

Immune Cell-Mediated Protection against Vaginal Candidiasis: Evidence for a Major Role of Vaginal CD4+ T Cells and Possible Participation of Other Local Lymphocyte Effectors

PubMed Central

Santoni, Giorgio; Boccanera, Maria; Adriani, Daniela; Lucciarini, Roberta; Amantini, Consuelo; Morrone, Stefania; Cassone, Antonio; De Bernardis, Flavia

2002-01-01

The protective roles of different lymphocyte subsets were investigated in a rat vaginal candidiasis model by adoptive transfer of vaginal lymphocytes (VL) or sorted, purified CD3+ T cells, CD4+ or CD8+ T cells, or CD3− CD5+ B cells from the vaginas of naïve or immune rats following three rounds of Candida albicans infection. The adoptive transfer of total VL from nonimmune animals did not alter the course of vaginal candidiasis of the recipient rats. In contrast, the animals receiving total VL or CD3+ T cells from immune rats showed a highly significant acceleration of fungus clearance compared with animals which received nonimmune VL. The animals with vaginal CD3− CD5+ B cells transferred from immune rats also had fewer Candida CFU than the controls, but fungal clearance was significantly retarded with respect to the animals administered immune T cells. Sorted, purified CD4+ and CD8+ vaginal T cells from immune rats were also adoptively transferred to naïve animals. Although both populations were seen to accelerate the clearance of the fungus from the vagina, CD4+ T cells were much more effective than CD8+ T cells. Overall, there was no difference between the antifungal effects of immune vaginal CD4+ T cells and those achievable with the transfer of whole, immune VL. Histological observations of the vaginal tissues of rats with adoptively transferred immune T cells demonstrated a remarkable accumulation of lymphocytes in the subepithelial lamina propria and also infiltrating the mucosal epithelium. These results strongly suggest that distinct vaginal lymphocyte subsets participate in the adaptive anti-Candida immunity at the vaginal level, with the vaginal CD4+ T cells probably playing a major role. PMID:12183521

Valid methods: the quality assurance of test method development, validation, approval, and transfer for veterinary testing laboratories.

PubMed

Wiegers, Ann L

2003-07-01

Third-party accreditation is a valuable tool to demonstrate a laboratory's competence to conduct testing. Accreditation, internationally and in the United States, has been discussed previously. However, accreditation is only I part of establishing data credibility. A validated test method is the first component of a valid measurement system. Validation is defined as confirmation by examination and the provision of objective evidence that the particular requirements for a specific intended use are fulfilled. The international and national standard ISO/IEC 17025 recognizes the importance of validated methods and requires that laboratory-developed methods or methods adopted by the laboratory be appropriate for the intended use. Validated methods are therefore required and their use agreed to by the client (i.e., end users of the test results such as veterinarians, animal health programs, and owners). ISO/IEC 17025 also requires that the introduction of methods developed by the laboratory for its own use be a planned activity conducted by qualified personnel with adequate resources. This article discusses considerations and recommendations for the conduct of veterinary diagnostic test method development, validation, evaluation, approval, and transfer to the user laboratory in the ISO/IEC 17025 environment. These recommendations are based on those of nationally and internationally accepted standards and guidelines, as well as those of reputable and experienced technical bodies. They are also based on the author's experience in the evaluation of method development and transfer projects, validation data, and the implementation of quality management systems in the area of method development.

Transfer Students in Higher Education: Building Foundations for Policies, Programs, and Services that Foster Student Success. The First-Year Experience Monograph Series No. 54

ERIC Educational Resources Information Center

Poisel, Mark Allen, Ed.; Joseph, Sonya, Ed.

2011-01-01

"Transfer Students in Higher Education" presents what individuals know about transfer students, addresses assumptions and myths about the transfer experience, and explores the changing demographics of this student group. Adopting a student-centered approach, the monograph offers strategies to begin (and continue) the work of serving students and…

How do CARs work?

PubMed Central

Davila, Marco L.; Brentjens, Renier; Wang, Xiuyan; Rivière, Isabelle; Sadelain, Michel

2012-01-01

Second-generation chimeric antigen receptors (CARs) are powerful tools to redirect antigen-specific T cells independently of HLA-restriction. Recent clinical studies evaluating CD19-targeted T cells in patients with B-cell malignancies demonstrate the potency of CAR-engineered T cells. With results from 28 subjects enrolled by five centers conducting studies in patients with chronic lymphocytic leukemia (CLL) or lymphoma, some insights into the parameters that determine T-cell function and clinical outcome of CAR-based approaches are emerging. These parameters involve CAR design, T-cell production methods, conditioning chemotherapy as well as patient selection. Here, we discuss the potential relevance of these findings and in particular the interplay between the adoptive transfer of T cells and pre-transfer patient conditioning. PMID:23264903

Proposal for probing energy transfer pathway by single-molecule pump-dump experiment.

PubMed

Tao, Ming-Jie; Ai, Qing; Deng, Fu-Guo; Cheng, Yuan-Chung

2016-06-09

The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex had long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent modified Redfield theory and non-Markovian quantum jump method to simulate EET dynamics. This scheme provides a practical approach of detecting the realistic EET pathway in BChl complexes with currently available experimental technology. And it may assist optimizing design of artificial light-harvesting devices.

Proposal for probing energy transfer pathway by single-molecule pump-dump experiment

NASA Astrophysics Data System (ADS)

Tao, Ming-Jie; Ai, Qing; Deng, Fu-Guo; Cheng, Yuan-Chung

2016-06-01

The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex had long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent modified Redfield theory and non-Markovian quantum jump method to simulate EET dynamics. This scheme provides a practical approach of detecting the realistic EET pathway in BChl complexes with currently available experimental technology. And it may assist optimizing design of artificial light-harvesting devices.

Proposal for probing energy transfer pathway by single-molecule pump-dump experiment

PubMed Central

Tao, Ming-Jie; Ai, Qing; Deng, Fu-Guo; Cheng, Yuan-Chung

2016-01-01

The structure of Fenna-Matthews-Olson (FMO) light-harvesting complex had long been recognized as containing seven bacteriochlorophyll (BChl) molecules. Recently, an additional BChl molecule was discovered in the crystal structure of the FMO complex, which may serve as a link between baseplate and the remaining seven molecules. Here, we investigate excitation energy transfer (EET) process by simulating single-molecule pump-dump experiment in the eight-molecules complex. We adopt the coherent modified Redfield theory and non-Markovian quantum jump method to simulate EET dynamics. This scheme provides a practical approach of detecting the realistic EET pathway in BChl complexes with currently available experimental technology. And it may assist optimizing design of artificial light-harvesting devices. PMID:27277702

Combined natural convection and non-gray radiation heat transfer in a horizontal annulus

NASA Astrophysics Data System (ADS)

Sun, Yujia; Zhang, Xiaobing; Howell, John R.

2018-02-01

Natural convection and non-gray radiation in an annulus containing a radiative participating gas is investigated. To determine the effect of non-gray radiation, the spectral line based weighted sum of gray gas is adopted to model the gas radiative properties. Case with only surface radiation (transparent medium) is also considered to see the relative contributions of surface radiation and gas radiation. The finite volume method is used to solve the mass, momentum, energy and radiative transfer equations. Comparisons between pure convection, case considering only surface radiation and case considering both gas radiation and surface radiation are made and the results show that radiation is not negligible and gas radiation becomes more important with increasing Rayleigh number (and the annulus size).

Pathways to Engineering: The Validation Experiences of Transfer Students

ERIC Educational Resources Information Center

Zhang, Yi; Ozuna, Taryn

2015-01-01

Community college engineering transfer students are a critical student population of engineering degree recipients and technical workforce in the United States. Focusing on this group of students, we adopted Rendón's (1994) validation theory to explore the students' experiences in community colleges prior to transferring to a four-year…

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies

PubMed Central

Wang, X; Rivière, I

2015-01-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic. PMID:25721207

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies.

PubMed

Wang, X; Rivière, I

2015-03-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic.

Numerical investigation of mist/air impingement cooling on ribbed blade leading-edge surface.

PubMed

Bian, Qingfei; Wang, Jin; Chen, Yi-Tung; Wang, Qiuwang; Zeng, Min

2017-12-01

The working gas turbine blades are exposed to the environment of high temperature, especially in the leading-edge region. The mist/air two-phase impingement cooling has been adopted to enhance the heat transfer on blade surfaces and investigate the leading-edge cooling effectiveness. An Euler-Lagrange particle tracking method is used to simulate the two-phase impingement cooling on the blade leading-edge. The mesh dependency test has been carried out and the numerical method is validated based on the available experimental data of mist/air cooling with jet impingement on a concave surface. The cooling effectiveness on three target surfaces is investigated, including the smooth and the ribbed surface with convex/concave columnar ribs. The results show that the cooling effectiveness of the mist/air two-phase flow is better than that of the single-phase flow. When the ribbed surfaces are used, the heat transfer enhancement is significant, the surface cooling effectiveness becomes higher and the convex ribbed surface presents a better performance. With the enhancement of the surface heat transfer, the pressure drop in the impingement zone increases, but the incremental factor of the flow friction is smaller than that of the heat transfer enhancement. Copyright © 2017 Elsevier Ltd. All rights reserved.

TIME-DEPENDENT MULTI-GROUP MULTI-DIMENSIONAL RELATIVISTIC RADIATIVE TRANSFER CODE BASED ON SPHERICAL HARMONIC DISCRETE ORDINATE METHOD

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

Tominaga, Nozomu; Shibata, Sanshiro; Blinnikov, Sergei I., E-mail: tominaga@konan-u.ac.jp, E-mail: sshibata@post.kek.jp, E-mail: Sergei.Blinnikov@itep.ru

We develop a time-dependent, multi-group, multi-dimensional relativistic radiative transfer code, which is required to numerically investigate radiation from relativistic fluids that are involved in, e.g., gamma-ray bursts and active galactic nuclei. The code is based on the spherical harmonic discrete ordinate method (SHDOM) which evaluates a source function including anisotropic scattering in spherical harmonics and implicitly solves the static radiative transfer equation with ray tracing in discrete ordinates. We implement treatments of time dependence, multi-frequency bins, Lorentz transformation, and elastic Thomson and inelastic Compton scattering to the publicly available SHDOM code. Our code adopts a mixed-frame approach; the source functionmore » is evaluated in the comoving frame, whereas the radiative transfer equation is solved in the laboratory frame. This implementation is validated using various test problems and comparisons with the results from a relativistic Monte Carlo code. These validations confirm that the code correctly calculates the intensity and its evolution in the computational domain. The code enables us to obtain an Eddington tensor that relates the first and third moments of intensity (energy density and radiation pressure) and is frequently used as a closure relation in radiation hydrodynamics calculations.« less

Retargeted human avidin-CAR T cells for adoptive immunotherapy of EGFRvIII expressing gliomas and their evaluation via optical imaging.

PubMed

Liu, Kaiyu; Liu, Xujie; Peng, Zhiping; Sun, Haojie; Zhang, Mingzhi; Zhang, Jianning; Liu, Shuang; Hao, Limin; Lu, Guoqiu; Zheng, Kangcheng; Gong, Xikui; Wu, Di; Wang, Fan; Shen, Li

2015-09-15

There has been significant progress in the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. However, the challenge of monitoring the therapy in real time has been continually ignored. To address this issue, we developed optical molecular imaging approaches to evaluate a recently reported novel CAR strategy for adoptive immunotherapy against glioma xenografts expressing EGFRvIII. We initially biotinylated a novel anti-EGFRvIII monoclonal antibody (biotin-4G1) to pre-target EGFRvIII+ gliomas and then redirect activated avidin-CAR expressing T cells against the pre-targeted biotin-4G1. By optical imaging study and bio-distribution analysis, we confirmed the specificity of pre-target and target and determined the optimal time for T cells adoptive transfer in vivo. The results showed this therapeutic strategy offered efficient therapy effect to EGFRvIII+ glioma-bearing mice and implied that optical imaging is a highly useful tool in aiding in the instruction of clinical CAR-T cells adoptive transfer in future.

Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors.

PubMed

Xin, Gang; Schauder, David M; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S; Johnson, Bryon; Cui, Weiguo

2017-01-24

Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors.

Multiple Scattering in Planetary Regoliths Using Incoherent Interactions

NASA Astrophysics Data System (ADS)

Muinonen, K.; Markkanen, J.; Vaisanen, T.; Penttilä, A.

2017-12-01

We consider scattering of light by a planetary regolith using novel numerical methods for discrete random media of particles. Understanding the scattering process is of key importance for spectroscopic, photometric, and polarimetric modeling of airless planetary objects, including radar studies. In our modeling, the size of the spherical random medium can range from microscopic to macroscopic sizes, whereas the particles are assumed to be of the order of the wavelength in size. We extend the radiative transfer and coherent backscattering method (RT-CB) to the case of dense packing of particles by adopting the ensemble-averaged first-order incoherent extinction, scattering, and absorption characteristics of a volume element of particles as input. In the radiative transfer part, at each absorption and scattering process, we account for absorption with the help of the single-scattering albedo and peel off the Stokes parameters of radiation emerging from the medium in predefined scattering angles. We then generate a new scattering direction using the joint probability density for the local polar and azimuthal scattering angles. In the coherent backscattering part, we utilize amplitude scattering matrices along the radiative-transfer path and the reciprocal path. Furthermore, we replace the far-field interactions of the RT-CB method with rigorous interactions facilitated by the Superposition T-matrix method (STMM). This gives rise to a new RT-RT method, radiative transfer with reciprocal interactions. For microscopic random media, we then compare the new results to asymptotically exact results computed using the STMM, succeeding in the numerical validation of the new methods.Acknowledgments. Research supported by European Research Council with Advanced Grant No. 320773 SAEMPL, Scattering and Absorption of ElectroMagnetic waves in ParticuLate media. Computational resources provided by CSC - IT Centre for Science Ltd, Finland.

Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells

PubMed Central

Liu, Ting; Ren, Jun; Wang, Wei; Wei, Xia-wei; Shen, Guo-bo; Liu, Yan-tong; Luo, Min; Xu, Guang-chao; Shao, Bin; Deng, Sen-yi; He, Zhi-yao; Liang, Xiao; Liu, Yu; Wen, Yan-Zhu; Xiang, Rong; Yang, Li; Deng, Hong-xin; Wei, Yu-quan

2015-01-01

The adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF−κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy. PMID:26565726

The Role of Transfer in Designing Games and Simulations for Health: Systematic Review

PubMed Central

Terlouw, Gijs; Wartena, Bard O; van 't Veer, Job TB; Prins, Jelle T; Pierie, Jean Pierre EN

2017-01-01

Background The usefulness and importance of serious games and simulations in learning and behavior change for health and health-related issues are widely recognized. Studies have addressed games and simulations as interventions, mostly in comparison with their analog counterparts. Numerous complex design choices have to be made with serious games and simulations for health, including choices that directly contribute to the effects of the intervention. One of these decisions is the way an intervention is expected to lead to desirable transfer effects. Most designs adopt a first-class transfer rationale, whereas the second class of transfer types seems a rarity in serious games and simulations for health. Objective This study sought to review the literature specifically on the second class of transfer types in the design of serious games and simulations. Focusing on game-like interventions for health and health care, this study aimed to (1) determine whether the second class of transfer is recognized as a road for transfer in game-like interventions, (2) review the application of the second class of transfer type in designing game-like interventions, and (3) assess studies that include second-class transfer types reporting transfer outcomes. Methods A total of 6 Web-based databases were systematically searched by titles, abstracts, and keywords using the search strategy (video games OR game OR games OR gaming OR computer simulation*) AND (software design OR design) AND (fidelity OR fidelities OR transfer* OR behaviour OR behavior). The databases searched were identified as relevant to health, education, and social science. Results A total of 15 relevant studies were included, covering a range of game-like interventions, all more or less mentioning design parameters aimed at transfer. We found 9 studies where first-class transfer was part of the design of the intervention. In total, 8 studies dealt with transfer concepts and fidelity types in game-like intervention design in general; 3 studies dealt with the concept of second-class transfer types and reported effects, and 2 of those recognized transfer as a design parameter. Conclusions In studies on game-like interventions for health and health care, transfer is regarded as a desirable effect but not as a basic principle for design. None of the studies determined the second class of transfer or instances thereof, although in 3 cases a nonliteral transfer type was present. We also found that studies on game-like interventions for health do not elucidate design choices made and rarely provide design principles for future work. Games and simulations for health abundantly build upon the principles of first-class transfer, but the adoption of second-class transfer types proves scarce. It is likely to be worthwhile to explore the possibilities of second-class transfer types, as they may considerably influence educational objectives in terms of future serious game design for health. PMID:29175812

Mending the Gap, An Effort to Aid the Transfer of Formal Methods Technology

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly

2009-01-01

Formal methods can be applied to many of the development and verification activities required for civil avionics software. RTCA/DO-178B, Software Considerations in Airborne Systems and Equipment Certification, gives a brief description of using formal methods as an alternate method of compliance with the objectives of that standard. Despite this, the avionics industry at large has been hesitant to adopt formal methods, with few developers have actually used formal methods for certification credit. Why is this so, given the volume of evidence of the benefits of formal methods? This presentation will explore some of the challenges to using formal methods in a certification context and describe the effort by the Formal Methods Subgroup of RTCA SC-205/EUROCAE WG-71 to develop guidance to make the use of formal methods a recognized approach.

Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection.

PubMed

Moeller, Maria; Haynes, Nicole M; Kershaw, Michael H; Jackson, Jacob T; Teng, Michele W L; Street, Shayna E; Cerutti, Loretta; Jane, Stephen M; Trapani, Joseph A; Smyth, Mark J; Darcy, Phillip K

2005-11-01

Because CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an antitumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4+ and CD8+ cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4+ and CD8+ T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.

Rethinking the role of myeloid-derived suppressor cells in adoptive T-cell therapy for cancer

PubMed Central

Arina, Ainhoa

2014-01-01

The expansion of cancer-induced myeloid cells is thought to be one of the main obstacles to successful immunotherapy. Nevertheless, in murine tumors undergoing immune-mediated destruction by adoptively transferred T cells, we have recently shown that such cells maintain their immunosuppressive properties. Therefore, adoptive T-cell therapy can, under certain conditions, overcome myeloid cell immunosuppression. PMID:25050213

In vivo programming of tumor antigen-specific T lymphocytes from pluripotent stem cells to promote cancer immunosurveillance.

PubMed

Lei, Fengyang; Zhao, Baohua; Haque, Rizwanul; Xiong, Xiaofang; Budgeon, Lynn; Christensen, Neil D; Wu, Yuzhang; Song, Jianxun

2011-07-15

Adoptive T-cell immunotherapy has garnered wide attention, but its effective use is limited by the need of multiple ex vivo manipulations and infusions that are complex and expensive. In this study, we show how highly reactive antigen (Ag)-specific CTLs can be generated from induced pluripotent stem (iPS) cells to provide an unlimited source of functional CTLs for adoptive immunotherapy. iPS cell-derived T cells can offer the advantages of avoiding possible immune rejection and circumventing ethical and practical issues associated with other stem cell types. iPS cells can be differentiated into progenitor T cells in vitro by stimulation with the Notch ligand Delta-like 1 (DL1) overexpressed on bone marrow stromal cells, with complete maturation occurring upon adoptive transfer into Rag1-deficient mice. Here, we report that these iPS cells can be differentiated in vivo into functional CTLs after overexpression of MHC I-restricted Ag-specific T-cell receptors (TCR). In this study, we generated murine iPS cells genetically modified with ovalbumin (OVA)-specific and MHC-I restricted TCR (OT-I) by retrovirus-mediated transduction. After their adoptive transfer into recipient mice, the majority of OT-I/iPS cells underwent differentiation into CD8+ CTLs. TCR-transduced iPS cells developed in vivo responded in vitro to peptide stimulation by secreting interleukin 2 and IFN-γ. Most importantly, adoptive transfer of TCR-transduced iPS cells triggered infiltration of OVA-reactive CTLs into tumor tissues and protected animals from tumor challenge. Taken together, our findings offer proof of concept for a potentially more efficient approach to generate Ag-specific T lymphocytes for adoptive immunotherapy. ©2011 AACR.

Knowledge Transfer and Capacity for Dissemination: A Review and Proposals for Further Research on Academic Knowledge Transfer

ERIC Educational Resources Information Center

Kuiken, Janna; van der Sijde, Peter

2011-01-01

The process of knowledge transfer has been extensively studied in the context of a variety of theoretical considerations. In this paper the authors adopt a communication theory perspective and focus on capacity for dissemination. Many studies assume that universities are able to disseminate and commercialize their knowledge (and technology).…

Enhancing Transfer of Knowledge in Physics through Effective Teaching Strategies

ERIC Educational Resources Information Center

Akinbobola, Akinyemi Olufunminiyi

2015-01-01

The study assessed the enhancement of transfer of knowledge in physics through the use of effective teaching strategies in Nigerian senior secondary schools. Non-randomized pretest-posttest control group design was adopted for the study. A total of 278 physics students took part in the study. Transfer of Knowledge Test in Physics (TKTP) with the…

Repairing Student Misconceptions in Heat Transfer Using Inquiry-Based Activities

ERIC Educational Resources Information Center

Prince, Michael; Vigeant, Margot; Nottis, Katharyn

2016-01-01

Eight inquiry-based activities, described here in sufficient detail for faculty to adopt in their own courses, were designed to teach students fundamental concepts in heat transfer. The concept areas chosen were (1) factors affecting the rate vs. amount of heat transfer, (2) temperature vs. perceptions of hot and cold, (3) temperature vs. energy…

ULTRA-SHARP nonoscillatory convection schemes for high-speed steady multidimensional flow

NASA Technical Reports Server (NTRS)

Leonard, B. P.; Mokhtari, Simin

1990-01-01

For convection-dominated flows, classical second-order methods are notoriously oscillatory and often unstable. For this reason, many computational fluid dynamicists have adopted various forms of (inherently stable) first-order upwinding over the past few decades. Although it is now well known that first-order convection schemes suffer from serious inaccuracies attributable to artificial viscosity or numerical diffusion under high convection conditions, these methods continue to enjoy widespread popularity for numerical heat transfer calculations, apparently due to a perceived lack of viable high accuracy alternatives. But alternatives are available. For example, nonoscillatory methods used in gasdynamics, including currently popular TVD schemes, can be easily adapted to multidimensional incompressible flow and convective transport. This, in itself, would be a major advance for numerical convective heat transfer, for example. But, as is shown, second-order TVD schemes form only a small, overly restrictive, subclass of a much more universal, and extremely simple, nonoscillatory flux-limiting strategy which can be applied to convection schemes of arbitrarily high order accuracy, while requiring only a simple tridiagonal ADI line-solver, as used in the majority of general purpose iterative codes for incompressible flow and numerical heat transfer. The new universal limiter and associated solution procedures form the so-called ULTRA-SHARP alternative for high resolution nonoscillatory multidimensional steady state high speed convective modelling.

The rank correlated SLW model of gas radiation in non-uniform media

NASA Astrophysics Data System (ADS)

Solovjov, Vladimir P.; Andre, Frederic; Lemonnier, Denis; Webb, Brent W.

2017-08-01

A comprehensive theoretical development of possible reference approaches in modelling of radiation transfer in non-uniform gaseous media is developed within the framework of the Generalized SLW Model. The notion of absorption spectrum ;correlation; adopted currently for global methods in gas radiation is critically revisited and replaced by a less restrictive concept of rank correlated spectrum. Within this framework it is shown that eight different reference approaches are possible, of which only three have been reported in the literature. Among the approaches presented is a novel Rank Correlated SLW Model, which is distinguished by the fact that i) it does not require the specification of a reference gas thermodynamic state, and ii) it preserves the emission term in the spectrally integrated Radiative Transfer Equation. Construction of this reference model requires only two absorption line blackbody distribution functions, and subdivision into gray gases can be performed using standard quadratures. Consequently, this new reference approach appears to have significant advantages over all other methods, and is, in general, a significant improvement in the global modelling of gas radiation. All reference approaches are summarized in the present work, and their use in radiative transfer prediction is demonstrated for simple example cases. Further, a detailed rigorous theoretical development of the improved methods is provided.

Transfer of in vitro expanded T lymphocytes after activation with dendritomas prolonged survival of mice challenged with EL4 tumor cells.

PubMed

Li, Jinhua; Theofanous, Leigh; Stickel, Sara; Bouton-Verville, Hilary; Burgin, Kelly E; Jakubchak, Susan; Wagner, Thomas E; Wei, Yanzhang

2007-07-01

Adoptive T cell transfer after in vitro expansion represents an attractive cancer immunotherapy. The majority of studies so far have been focusing on the expansion of tumor infiltrated lymphocytes (TIL) and some have shown very encouraging results. Recently, we have developed a unique tumor immune response activator, dendritomas, by fusion of dendritic cells and tumor cells. Animal studies and early clinical trials have shown that dendritomas are able to activate tumor specific immune responses. In this study, we hypothesized that naïve T cells can be primed with dendritomas and expanded in vitro to develop an adoptive transfer therapy for patients who do not have solid tumors, such as leukemia. T cells were isolated and purified from lymph nodes of mice. The cells were then incubated with dendritomas made from syngeneic DCs and tumor cells and expanded in vitro using Dynabeads mouse CD3/CD28 T cell expander for approximately three weeks. The in vitro primed and expanded T cells showed tumor cell specific CTL activity and increased secretion of IFN-gamma. Tumor bearing mice receiving the in vitro expanded T cells survived significantly longer than control mice. Furthermore, the depletion of regulator T cells enhanced the survival of the mice that received the adoptive transfer therapy.

V3885 Sagittarius: A Comparison With a Range of Standard Model Accretion Disks

NASA Technical Reports Server (NTRS)

Linnell, Albert P.; Godon, Patrick; Hubeny, Ivan; Sion, Edward M; Szkody, Paula; Barrett, Paul E.

2009-01-01

A chi-squared analysis of standard model accretion disk synthetic spectrum fits to combined Far Ultraviolet Spectroscopic Explorer and Space Telescope Imaging Spectrograph spectra of V3885 Sagittarius, on an absolute flux basis, selects a model that accurately represents the observed spectral energy distribution. Calculation of the synthetic spectrum requires the following system parameters. The cataclysmic variable secondary star period-mass relation calibrated by Knigge in 2006 and 2007 sets the secondary component mass. A mean white dwarf (WD) mass from the same study, which is consistent with an observationally determined mass ratio, sets the adopted WD mass of 0.7M(solar mass), and the WD radius follows from standard theoretical models. The adopted inclination, i = 65 deg, is a literature consensus, and is subsequently supported by chi-squared analysis. The mass transfer rate is the remaining parameter to set the accretion disk T(sub eff) profile, and the Hipparcos parallax constrains that parameter to mas transfer = (5.0 +/- 2.0) x 10(exp -9) M(solar mass)/yr by a comparison with observed spectra. The fit to the observed spectra adopts the contribution of a 57,000 +/- 5000 K WD. The model thus provides realistic constraints on mass transfer and T(sub eff) for a large mass transfer system above the period gap.

The effect of burn injury on CD8+ and CD4+ T cells in an irradiation model of homeostatic proliferation.

PubMed

Buchanan, Ian B; Maile, Robert; Frelinger, Jeffrey A; Fair, Jeffrey H; Meyer, Anthony A; Cairns, Bruce A

2006-11-01

Homeostatic proliferation of T cells has recently been shown to be an important mechanism in the host response to infection. However, its role in the T cell response to burn injury is unknown. In this study, we examine the effect of burn injury on CD4+ and CD8+ T cell homeostatic proliferation after irradiation. Wild-type C57BL/6 female mice were irradiated with six grays ionizing radiation and 48 hours later, syngeneic whole splenocytes or purified CD4+ or CD8+ T cells labeled with carboxy-fluorescein diacetate, succinimidyl ester were adoptively transferred. Two days later, mice underwent a 20% burn injury, followed by splenocyte harvest 3 and 10 days after injury. Burn mice demonstrate increased splenic cellularity and CD8+ T cell proliferation after adoptive transfer of either purified CD8+ cells or whole spleen populations compared with unburned (sham) mice. In contrast, CD4+ T cell proliferation after burn injury is unchanged after adoptive transfer of whole spleen cells and drastically decreased after adoptive transfer of a purified CD4+ population compared with sham mice. Ten days after burn injury CD8+ T cells continue to demonstrate greater proliferation than CD4+ T cells. CD8+ T cells are more robust than CD4+ T cells in their proliferative response after burn injury. In addition, CD8+ T cell proliferation appears less reliant on other immune cells than purified CD4+ T cell proliferation. These data reiterate the importance of CD8+ T cells in the initial immune response to burn injury.

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.

PubMed

Uribe-Herranz, Mireia; Bittinger, Kyle; Rafail, Stavros; Guedan, Sonia; Pierini, Stefano; Tanes, Ceylan; Ganetsky, Alex; Morgan, Mark A; Gill, Saar; Tanyi, Janos L; Bushman, Frederic D; June, Carl H; Facciabene, Andrea

2018-02-22

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12

PubMed Central

Bittinger, Kyle; Rafail, Stavros; Pierini, Stefano; Tanes, Ceylan; Ganetsky, Alex; Morgan, Mark A.; Gill, Saar; Tanyi, Janos L.; Bushman, Frederic D.; June, Carl H.

2018-01-01

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12–dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota. PMID:29467322

Aberrant Muscle Antigen Exposure in Mice Is Sufficient to Cause Myositis in a Treg Cell–Deficient Milieu

PubMed Central

Young, Nicholas A; Sharma, Rahul; Friedman, Alexandra K; Kaffenberger, Benjamin H; Bolon, Brad; Jarjour, Wael N

2013-01-01

Objective Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell–deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. Methods FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)–null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1–null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. Results FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. Conclusion These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity. PMID:24022275

National responses to global health targets: exploring policy transfer in the context of the UNAIDS ‘90–90–90’ treatment targets in Ghana and Uganda

PubMed Central

McRobie, Ellen; Matovu, Fred; Nanyiti, Aisha; Nonvignon, Justice; Abankwah, Daniel Nana Yaw; Case, Kelsey K; Hallett, Timothy B; Hanefeld, Johanna; Conteh, Lesong

2018-01-01

Abstract Global health organizations frequently set disease-specific targets with the goal of eliciting adoption at the national-level; consideration of the influence of target setting on national policies, programme and health budgets is of benefit to those setting targets and those intended to respond. In 2014, the Joint United Nations Programme on HIV/AIDS set ‘ambitious’ treatment targets for country adoption: 90% of HIV-positive persons should know their status; 90% of those on treatment; 90% of those achieving viral suppression. Using case studies from Ghana and Uganda, we explore how the target and its associated policy content have been adopted at the national level. That is whether adoption is in rhetoric only or supported by programme, policy or budgetary changes. We review 23 (14 from Ghana, 9 from Uganda) national policy, operational and strategic documents for the HIV response and assess commitments to ‘90–90–90’. In-person semi-structured interviews were conducted with purposively sampled key informants (17 in Ghana, 20 in Uganda) involved in programme-planning and resource allocation within HIV to gain insight into factors facilitating adoption of 90–90–90. Interviews were transcribed and analysed thematically, inductively and deductively, guided by pre-existing policy theories, including Dolowitz and Marsh’s policy transfer framework to describe features of the transfer and the Global Health Advocacy and Policy Project framework to explain observations. Regardless of notable resource constraints, transfer of the 90–90–90 targets was evident beyond rhetoric with substantial shifts in policy and programme activities. In both countries, there was evidence of attempts to minimize resource constraints by seeking programme efficiencies, prioritization of programme activities and devising domestic financing mechanisms; however, significant resource gaps persist. An effective health network, comprised of global and local actors, mediated the adoption and adaptation, facilitating a shift in the HIV programme from ‘business as usual’ to approaches targeting geographies and populations. PMID:29040476

National responses to global health targets: exploring policy transfer in the context of the UNAIDS '90-90-90' treatment targets in Ghana and Uganda.

PubMed

McRobie, Ellen; Matovu, Fred; Nanyiti, Aisha; Nonvignon, Justice; Abankwah, Daniel Nana Yaw; Case, Kelsey K; Hallett, Timothy B; Hanefeld, Johanna; Conteh, Lesong

2018-01-01

Global health organizations frequently set disease-specific targets with the goal of eliciting adoption at the national-level; consideration of the influence of target setting on national policies, programme and health budgets is of benefit to those setting targets and those intended to respond. In 2014, the Joint United Nations Programme on HIV/AIDS set 'ambitious' treatment targets for country adoption: 90% of HIV-positive persons should know their status; 90% of those on treatment; 90% of those achieving viral suppression. Using case studies from Ghana and Uganda, we explore how the target and its associated policy content have been adopted at the national level. That is whether adoption is in rhetoric only or supported by programme, policy or budgetary changes. We review 23 (14 from Ghana, 9 from Uganda) national policy, operational and strategic documents for the HIV response and assess commitments to '90-90-90'. In-person semi-structured interviews were conducted with purposively sampled key informants (17 in Ghana, 20 in Uganda) involved in programme-planning and resource allocation within HIV to gain insight into factors facilitating adoption of 90-90-90. Interviews were transcribed and analysed thematically, inductively and deductively, guided by pre-existing policy theories, including Dolowitz and Marsh's policy transfer framework to describe features of the transfer and the Global Health Advocacy and Policy Project framework to explain observations. Regardless of notable resource constraints, transfer of the 90-90-90 targets was evident beyond rhetoric with substantial shifts in policy and programme activities. In both countries, there was evidence of attempts to minimize resource constraints by seeking programme efficiencies, prioritization of programme activities and devising domestic financing mechanisms; however, significant resource gaps persist. An effective health network, comprised of global and local actors, mediated the adoption and adaptation, facilitating a shift in the HIV programme from 'business as usual' to approaches targeting geographies and populations. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

a Marker-Based Eulerian-Lagrangian Method for Multiphase Flow with Supersonic Combustion Applications

NASA Astrophysics Data System (ADS)

Fan, Xiaofeng; Wang, Jiangfeng

2016-06-01

The atomization of liquid fuel is a kind of intricate dynamic process from continuous phase to discrete phase. Procedures of fuel spray in supersonic flow are modeled with an Eulerian-Lagrangian computational fluid dynamics methodology. The method combines two distinct techniques and develops an integrated numerical simulation method to simulate the atomization processes. The traditional finite volume method based on stationary (Eulerian) Cartesian grid is used to resolve the flow field, and multi-component Navier-Stokes equations are adopted in present work, with accounting for the mass exchange and heat transfer occupied by vaporization process. The marker-based moving (Lagrangian) grid is utilized to depict the behavior of atomized liquid sprays injected into a gaseous environment, and discrete droplet model 13 is adopted. To verify the current approach, the proposed method is applied to simulate processes of liquid atomization in supersonic cross flow. Three classic breakup models, TAB model, wave model and K-H/R-T hybrid model, are discussed. The numerical results are compared with multiple perspectives quantitatively, including spray penetration height and droplet size distribution. In addition, the complex flow field structures induced by the presence of liquid spray are illustrated and discussed. It is validated that the maker-based Eulerian-Lagrangian method is effective and reliable.

Distribution of adoptively transferred porcine T-lymphoblasts tracked by (18)F-2-fluoro-2-deoxy-D-glucose and position emission tomography.

PubMed

Eriksson, Olof; Sadeghi, Arian; Carlsson, Björn; Eich, Torsten; Lundgren, Torbjörn; Nilsson, Bo; Tötterman, Thomas; Korsgren, Olle; Sundin, Anders

2011-08-01

Autologous or allogeneic transfer of tumor-infiltrating T-lymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-lymphoblasts in a porcine model by (18)F-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and positron emission tomography. T-lymphoblasts were labeled with the positron-emitting tracer [(18)F]FDG through incubation. The T-lymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preincubating and coadministrating the T-lymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [(18)F]FDG-labeled T-lymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications. Copyright © 2011 Elsevier Inc. All rights reserved.

Architecture of the nitric-oxide synthase holoenzyme reveals large conformational changes and a calmodulin-driven release of the FMN domain.

PubMed

Yokom, Adam L; Morishima, Yoshihiro; Lau, Miranda; Su, Min; Glukhova, Alisa; Osawa, Yoichi; Southworth, Daniel R

2014-06-13

Nitric-oxide synthase (NOS) is required in mammals to generate NO for regulating blood pressure, synaptic response, and immune defense. NOS is a large homodimer with well characterized reductase and oxygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize l-arginine and generate NO. Ca(2+)-calmodulin (CaM) binds between the reductase and oxygenase domains to activate NO synthesis. Although NOS has long been proposed to adopt distinct conformations that alternate between interflavin and FMN-heme electron transfer steps, structures of the holoenzyme have remained elusive and the CaM-bound arrangement is unknown. Here we have applied single particle electron microscopy (EM) methods to characterize the full-length of the neuronal isoform (nNOS) complex and determine the structural mechanism of CaM activation. We have identified that nNOS adopts an ensemble of open and closed conformational states and that CaM binding induces a dramatic rearrangement of the reductase domain. Our three-dimensional reconstruction of the intact nNOS-CaM complex reveals a closed conformation and a cross-monomer arrangement with the FMN domain rotated away from the NADPH-FAD center, toward the oxygenase dimer. This work captures, for the first time, the reductase-oxygenase structural arrangement and the CaM-dependent release of the FMN domain that coordinates to drive electron transfer across the domains during catalysis. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Adoptive Cell Therapy for Patients With Metastatic Melanoma: Evaluation of Intensive Myeloablative Chemoradiation Preparative Regimens

PubMed Central

Dudley, Mark E.; Yang, James C.; Sherry, Richard; Hughes, Marybeth S.; Royal, Richard; Kammula, Udai; Robbins, Paul F.; Huang, JianPing; Citrin, Deborah E.; Leitman, Susan F.; Wunderlich, John; Restifo, Nicholas P.; Thomasian, Armen; Downey, Stephanie G.; Smith, Franz O.; Klapper, Jacob; Morton, Kathleen; Laurencot, Carolyn; White, Donald E.; Rosenberg, Steven A.

2008-01-01

Purpose The two approved treatments for patients with metastatic melanoma, interleukin (IL)-2 and dacarbazine, mediate objective response rates of 12% to 15%. We previously reported that adoptive cell therapy (ACT) with autologous antitumor lymphocytes in lymphodepleted hosts mediated objective responses in 51% of 35 patients. Here, we update that study and evaluate the safety and efficacy of two increased-intensity myeloablative lymphodepleting regimens. Patients and Methods We performed two additional sequential trials of ACT with autologous tumor-infiltrating lymphocytes (TIL) in patients with metastatic melanoma. Increasing intensity of host preparative lymphodepletion consisting of cyclophosphamide and fludarabine with either 2 (25 patients) or 12 Gy (25 patients) of total-body irradiation (TBI) was administered before cell transfer. Objective response rates by Response Evaluation Criteria in Solid Tumors (RECIST) and survival were evaluated. Immunologic correlates of effective treatment were studied. Results Although nonmyeloablative chemotherapy alone showed an objective response rate of 49%, when 2 or 12 Gy of TBI was added, the response rates were 52% and 72% respectively. Responses were seen in all visceral sites including brain. There was one treatment-related death in the 93 patients. Host lymphodepletion was associated with increased serum levels of the lymphocyte homeostatic cytokines IL-7 and IL-15. Objective responses were correlated with the telomere length of the transferred cells. Conclusion Host lymphodepletion followed by autologous TIL transfer and IL-2 results in objective response rates of 50% to 70% in patients with metastatic melanoma refractory to standard therapies. PMID:18809613

Improving the durability of the optical fiber sensor based on strain transfer analysis

NASA Astrophysics Data System (ADS)

Wang, Huaping; Jiang, Lizhong; Xiang, Ping

2018-05-01

To realize the reliable and long-term strain detection, the durability of optical fiber sensors has attracted more and more attention. The packaging technique has been considered as an effective method, which can enhance the survival ratios of optical fiber sensors to resist the harsh construction and service environment in civil engineering. To monitor the internal strain of structures, the embedded installation is adopted. Due to the different material properties between host material and the protective layer, the monitored structure embedded with sensors can be regarded as a typical model containing inclusions. Interfacial characteristic between the sensor and host material exists obviously, and the contacted interface is prone to debonding failure induced by the large interfacial shear stress. To recognize the local interfacial debonding damage and extend the effective life cycle of the embedded sensor, strain transfer analysis of a general three-layered sensing model is conducted to investigate the failure mechanism. The perturbation of the embedded sensor on the local strain field of host material is discussed. Based on the theoretical analysis, the distribution of the interfacial shear stress along the sensing length is characterized and adopted for the diagnosis of local interfacial debonding, and the sensitive parameters influencing the interfacial shear stress are also investigated. The research in this paper explores the interfacial debonding failure mechanism of embedded sensors based on the strain transfer analysis and provides theoretical basis for enhancing the interfacial bonding properties and improving the durability of embedded optical fiber sensors.

Scalable transfer of vertical graphene nanosheets for flexible supercapacitor applications

NASA Astrophysics Data System (ADS)

Sahoo, Gopinath; Ghosh, Subrata; Polaki, S. R.; Mathews, Tom; Kamruddin, M.

2017-10-01

Vertical graphene nanosheets (VGN) are the material of choice for application in next-generation electronic devices. The growing demand for VGN-based flexible devices for the electronics industry brings in restriction on VGN growth temperature. The difficulty associated with the direct growth of VGN on flexible substrates can be overcome by adopting an effective strategy of transferring the well-grown VGN onto arbitrary flexible substrates through a soft chemistry route. In the present study, we report an inexpensive and scalable technique for the polymer-free transfer of VGN onto arbitrary substrates without disrupting its morphology, structure, and properties. After transfer, the morphology, chemical structure, and electrical properties are analyzed by scanning electron microscopy, Raman spectroscopy, x-ray photoelectron spectroscopy, and four-probe resistive methods, respectively. The wetting properties are studied from the water contact angle measurements. The observed results indicate the retention of morphology, surface chemistry, structure, and electronic properties. Furthermore, the storage capacity of the transferred VGN-based binder-free and current collector-free flexible symmetric supercapacitor device is studied. A very low sheet resistance of 670 Ω/□ and excellent supercapacitance of 158 μF cm-2 with 86% retention after 10 000 cycles show the prospect of the damage-free VGN transfer approach for the fabrication of flexible nanoelectronic devices.

Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.

PubMed

O'Sullivan, Timothy E; Sun, Joseph C

2018-01-01

Innate lymphoid cells are a heterogeneous family of tissue-resident and circulating lymphocytes that play an important role in host immunity. Recent studies have profiled the developmental pathways of mature ILCs and have identified ILC progenitors in the bone marrow through the use of transcription factor reporter mice. Here we describe methodology to identify and isolate bone marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker expression for adoptive transfer into lymphopenic mice to track the fate of developing ILCs.

Allotype suppression in an adoptive transfer system in adult mice: the specificity and feedback effects of a monoclonal IgG3 anti-(Igh-1b) allotype antibody.

PubMed Central

Curling, E M; Dresser, D W

1984-01-01

Using an adoptive transfer system in mice, an allotype-specific suppression has been induced by a monoclonal IgG3 anti-Igh-1b (Hyb 5.7) reagent. Suppression was specific for IgG2a (Igh-1b) and led to a compensatory increase of the Igh-1a response in irradiated mice reconstituted with allotype heterozygous (Igha/b) spleen cells. Suppression, which was not antigen-specific, lasted for at least 1 month after anti-allotype treatment. PMID:6365744

Adoptive transfer of dendritic cells expressing CD11c reduces the immunological response associated with experimental colitis in BALB/c mice.

PubMed

Paiatto, Lisiery N; Silva, Fernanda G D; Yamada, Áureo T; Tamashiro, Wirla M S C; Simioni, Patricia U

2018-01-01

In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms. To induce oral tolerance, BALB/c mice were fed 4mg/mL OVA solution for seven consecutive days. Spleen DCs were isolated from tolerant (tDC) and naïve (nDC) mice, and then adoptively transferred to syngeneic mice. Three days later, colitis was induced in DC treated mice by intrarectal instillation of 100μg2,4,6-trinitrobenzenesulfonic acid (TNBS) dissolved in 50% ethanol. Control subjects received only intrarectal instillation of either TNBS solution or a vehicle. Five days later, mice from all groups were euthanized and examined for physiological and immunological parameters. Regarding the phenotype, we observed that the frequencies of CD11+ MHC II+ and CD11+ MHCII+ CD86+ cells were significantly lower in DCs isolated from tolerant mice than in those from naive mice. However, pretreatment with both types of DCs was able to significantly reduce clinical signs of colitis such as diarrhea, rectal prolapse, bleeding, and cachexia, although only treatment with tDCs was able to prevent weight loss from instillation of TNBS. In vitro proliferation of spleen cells from mice treated with either type of DCs was significantly lower than that observed in splenic cell cultures of naïve mice. Although no significant difference was observed in the frequencies of Treg cells in the experimental groups, the frequency of Th17+CD4+cellsand the secretion of IL-17 were more reduced in the cultures of spleen cells from mice treated with either type of DCs. The levels of IL-9 and IFN-γ were lower in supernatants of cells from mice treated with nDCs. The results allow us to conclude that the adoptive transfer of cells expressing CD11c is able to reduce the clinical and immunological signs of drug-induced colitis. Adoptive transfer of CD11c+DC isolated from both naive and tolerant mice altered the proliferative and T cell responses. To the best of our knowledge, there is no previously published data showing the protective effects of DCs from naïve or tolerant mice in the treatment of colitis.

A Conceptual Framework for Educational Design at Modular Level to Promote Transfer of Learning

ERIC Educational Resources Information Center

Botma, Yvonne; Van Rensburg, G. H.; Coetzee, I. M.; Heyns, T.

2015-01-01

Students bridge the theory-practice gap when they apply in practice what they have learned in class. A conceptual framework was developed that can serve as foundation to design for learning transfer at modular level. The framework is based on an adopted and adapted systemic model of transfer of learning, existing learning theories, constructive…

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

Gao, Zhiming; Abdelaziz, Omar; Qu, Ming

This paper introduces a first-order physics-based model that accounts for the fundamental heat and mass transfer between a humid-air vapor stream on feed side to another flow stream on permeate side. The model comprises a few optional submodels for membrane mass transport; and it adopts a segment-by-segment method for discretizing heat and mass transfer governing equations for flow streams on feed and permeate sides. The model is able to simulate both dehumidifiers and energy recovery ventilators in parallel-flow, cross-flow, and counter-flow configurations. The predicted tresults are compared reasonably well with the measurements. The open-source codes are written in C++. Themore » model and open-source codes are expected to become a fundament tool for the analysis of membrane-based dehumidification in the future.« less

Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer

PubMed Central

Ward-Kavanagh, Lindsay K.; Zhu, Junjia; Cooper, Timothy K.; Schell, Todd D.

2014-01-01

Adoptive immunotherapy has demonstrated efficacy in a subset of clinical and preclinical studies, but the T cells used for therapy often are rendered rapidly non-functional in tumor-bearing hosts. Recent evidence indicates that prostate cancer can be susceptible to immunotherapy, but most studies using autochthonous tumor models demonstrate only short-lived T-cell responses in the tolerogenic prostate microenvironment. Here, we assessed the efficacy of sublethal whole-body irradiation (WBI) to enhance the magnitude and duration of adoptively transferred CD8+ T cells in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. We demonstrate that WBI promoted high-level accumulation of granzyme B (GzB)-expressing donor T cells both in lymphoid organs and in the prostate of TRAMP mice. Donor T cells remained responsive to vaccination in irradiated recipients, but a single round of WBI-enhanced adoptive immunotherapy failed to impact significantly the existing disease. Addition of a second round of immunotherapy promoted regression of established disease in half of the treated mice, with no progressions observed. Regression was associated with long-term persistence of effector/memory phenotype CD8+ donor cells. Administration of the second round of adoptive immunotherapy led to reacquisition of GzB expression by persistent T cells from the first transfer. These results indicate that WBI conditioning amplifies tumor-specific T cells in the TRAMP prostate and lymphoid tissue, and suggest that the initial treatment alters the tolerogenic microenvironment to increase antitumor activity by a second wave of donor cells. PMID:24801834

Embryo transfer: a comparative biosecurity advantage in international movements of germplasm.

PubMed

Thibier, M

2011-04-01

This paper uses cattle as a model to provide an overview of the hazards involved in the transfer of in vivo-derived and in vitro-produced embryos. While scientific studies in recent decades have led to the identification of pathogens that may be associated with both in vivo- and in vitro-derived embryos, those studies have also been the basis of appropriate disease control measures to reduce the risks to a negligible level. These disease control measures have been identified and assessed by the International Embryo Transfer Society's (lETS) Health and Safety Advisory Committee, the expert body that advises the World Organisation for Animal Health (OIE) on matters related to the safety of embryo transfer. Through the OIE's processes for developing and adopting international standards, the disease control measures identified by the IETS have been incorporated into the Terrestrial Animal Health Code. The basic principles rely on the crucial ethical roles of the embryo collection team and embryo transfer team, under the leadership of approved veterinarians. Decades of experience, with nearly 10 million embryos transferred, have demonstrated the very significant biosecurity advantage that embryo transfer technology has when moving germplasm internationally, provided that the international standards developed by the IETS and adopted by the OIE are strictly followed.

22 CFR 96.51 - Post-adoption services in incoming cases.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

22 CFR 96.51 - Post-adoption services in incoming cases.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

22 CFR 96.51 - Post-adoption services in incoming cases.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

22 CFR 96.51 - Post-adoption services in incoming cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

22 CFR 96.51 - Post-adoption services in incoming cases.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the agency's or person's responsibilities. (c) When post-adoption reports are required by the child's... Accreditation and Approval Standards for Cases in Which A Child Is Immigrating to the United States (incoming... measures to ensure that the transfer of the child takes place in secure and appropriate circumstances, with...

Direct integration of polycrystalline graphene into light emitting diodes by plasma-assisted metal-catalyst-free synthesis.

PubMed

Kim, Yong Seung; Joo, Kisu; Jerng, Sahng-Kyoon; Lee, Jae Hong; Moon, Daeyoung; Kim, Jonghak; Yoon, Euijoon; Chun, Seung-Hyun

2014-03-25

The integration of graphene into devices is a challenging task because the preparation of a graphene-based device usually includes graphene growth on a metal surface at elevated temperatures (∼1000 °C) and a complicated postgrowth transfer process of graphene from the metal catalyst. Here we report a direct integration approach for incorporating polycrystalline graphene into light emitting diodes (LEDs) at low temperature by plasma-assisted metal-catalyst-free synthesis. Thermal degradation of the active layer in LEDs is negligible at our growth temperature, and LEDs could be fabricated without a transfer process. Moreover, in situ ohmic contact formation is observed between DG and p-GaN resulting from carbon diffusion into the p-GaN surface during the growth process. As a result, the contact resistance is reduced and the electrical properties of directly integrated LEDs outperform those of LEDs with transferred graphene electrodes. This relatively simple method of graphene integration will be easily adoptable in the industrialization of graphene-based devices.

Analytical Model of Large Data Transactions in CoAP Networks

PubMed Central

Ludovici, Alessandro; Di Marco, Piergiuseppe; Calveras, Anna; Johansson, Karl H.

2014-01-01

We propose a novel analytical model to study fragmentation methods in wireless sensor networks adopting the Constrained Application Protocol (CoAP) and the IEEE 802.15.4 standard for medium access control (MAC). The blockwise transfer technique proposed in CoAP and the 6LoWPAN fragmentation are included in the analysis. The two techniques are compared in terms of reliability and delay, depending on the traffic, the number of nodes and the parameters of the IEEE 802.15.4 MAC. The results are validated trough Monte Carlo simulations. To the best of our knowledge this is the first study that evaluates and compares analytically the performance of CoAP blockwise transfer and 6LoWPAN fragmentation. A major contribution is the possibility to understand the behavior of both techniques with different network conditions. Our results show that 6LoWPAN fragmentation is preferable for delay-constrained applications. For highly congested networks, the blockwise transfer slightly outperforms 6LoWPAN fragmentation in terms of reliability. PMID:25153143

A vector radiative transfer model for coupled atmosphere and ocean systems based on successive order of scattering method.

PubMed

Zhai, Peng-Wang; Hu, Yongxiang; Trepte, Charles R; Lucker, Patricia L

2009-02-16

A vector radiative transfer model has been developed for coupled atmosphere and ocean systems based on the Successive Order of Scattering (SOS) Method. The emphasis of this study is to make the model easy-to-use and computationally efficient. This model provides the full Stokes vector at arbitrary locations which can be conveniently specified by users. The model is capable of tracking and labeling different sources of the photons that are measured, e.g. water leaving radiances and reflected sky lights. This model also has the capability to separate florescence from multi-scattered sunlight. The delta - fit technique has been adopted to reduce computational time associated with the strongly forward-peaked scattering phase matrices. The exponential - linear approximation has been used to reduce the number of discretized vertical layers while maintaining the accuracy. This model is developed to serve the remote sensing community in harvesting physical parameters from multi-platform, multi-sensor measurements that target different components of the atmosphere-oceanic system.

Research on soundproof properties of cylindrical shells of generalized phononic crystals

NASA Astrophysics Data System (ADS)

Liu, Ru; Shu, Haisheng; Wang, Xingguo

2017-04-01

Based on the previous studies, the concept of generalized phononic crystals (GPCs) is further introduced into the cylindrical shell structures in this paper. And a type of cylindrical shells of generalized phononic crystals (CS-GPCs) is constructed, the structural field and acoustic-structural coupled field of the composite cylindrical shells are examined respectively. For the structural field, the transfer matrix method of mechanical state vector is adopted to build the transfer matrix of radial waves propagating from inside to outside. For the acoustic-structural coupled field, the expressions of the acoustic transmission/reflection coefficients and the sound insulation of acoustic waves with the excitation of center line sound source are set up. And the acoustic transmission coefficient and the frequency response of sound insulation in this mode were numerical calculated. Furthermore, the theoretical analysis results are verified by using the method of combining the numerical calculation and finite element simulation. Finally, the effects of inner and outer fluid parameters on the transmission/reflection coefficients of CS-GPCs are analyzed in detail.

Extending amulti-scale parameter regionalization (MPR) method by introducing parameter constrained optimization and flexible transfer functions

NASA Astrophysics Data System (ADS)

Klotz, Daniel; Herrnegger, Mathew; Schulz, Karsten

2015-04-01

A multi-scale parameter-estimation method, as presented by Samaniego et al. (2010), is implemented and extended for the conceptual hydrological model COSERO. COSERO is a HBV-type model that is specialized for alpine-environments, but has been applied over a wide range of basins all over the world (see: Kling et al., 2014 for an overview). Within the methodology available small-scale information (DEM, soil texture, land cover, etc.) is used to estimate the coarse-scale model parameters by applying a set of transfer-functions (TFs) and subsequent averaging methods, whereby only TF hyper-parameters are optimized against available observations (e.g. runoff data). The parameter regionalisation approach was extended in order to allow for a more meta-heuristical handling of the transfer-functions. The two main novelties are: 1. An explicit introduction of constrains into parameter estimation scheme: The constraint scheme replaces invalid parts of the transfer-function-solution space with valid solutions. It is inspired by applications in evolutionary algorithms and related to the combination of learning and evolution. This allows the consideration of physical and numerical constraints as well as the incorporation of a priori modeller-experience into the parameter estimation. 2. Spline-based transfer-functions: Spline-based functions enable arbitrary forms of transfer-functions: This is of importance since in many cases the general relationship between sub-grid information and parameters are known, but not the form of the transfer-function itself. The contribution presents the results and experiences with the adopted method and the introduced extensions. Simulation are performed for the pre-alpine/alpine Traisen catchment in Lower Austria. References: Samaniego, L., Kumar, R., Attinger, S. (2010): Multiscale parameter regionalization of a grid-based hydrologic model at the mesoscale, Water Resour. Res., doi: 10.1029/2008WR007327 Kling, H., Stanzel, P., Fuchs, M., and Nachtnebel, H. P. (2014): Performance of the COSERO precipitation-runoff model under non-stationary conditions in basins with different climates, Hydrolog. Sci. J., doi: 10.1080/02626667.2014.959956.

Sinusoidal synthesis based adaptive tracking for rotating machinery fault detection

NASA Astrophysics Data System (ADS)

Li, Gang; McDonald, Geoff L.; Zhao, Qing

2017-01-01

This paper presents a novel Sinusoidal Synthesis Based Adaptive Tracking (SSBAT) technique for vibration-based rotating machinery fault detection. The proposed SSBAT algorithm is an adaptive time series technique that makes use of both frequency and time domain information of vibration signals. Such information is incorporated in a time varying dynamic model. Signal tracking is then realized by applying adaptive sinusoidal synthesis to the vibration signal. A modified Least-Squares (LS) method is adopted to estimate the model parameters. In addition to tracking, the proposed vibration synthesis model is mainly used as a linear time-varying predictor. The health condition of the rotating machine is monitored by checking the residual between the predicted and measured signal. The SSBAT method takes advantage of the sinusoidal nature of vibration signals and transfers the nonlinear problem into a linear adaptive problem in the time domain based on a state-space realization. It has low computation burden and does not need a priori knowledge of the machine under the no-fault condition which makes the algorithm ideal for on-line fault detection. The method is validated using both numerical simulation and practical application data. Meanwhile, the fault detection results are compared with the commonly adopted autoregressive (AR) and autoregressive Minimum Entropy Deconvolution (ARMED) method to verify the feasibility and performance of the SSBAT method.

Pathogen boosted adoptive cell transfer immunotherapy to treat solid tumors

PubMed Central

Xin, Gang; Schauder, David M.; Jing, Weiqing; Jiang, Aimin; Joshi, Nikhil S.; Johnson, Bryon; Cui, Weiguo

2017-01-01

Because of insufficient migration and antitumor function of transferred T cells, especially inside the immunosuppressive tumor microenvironment (TME), the efficacy of adoptive cell transfer (ACT) is much curtailed in treating solid tumors. To overcome these challenges, we sought to reenergize ACT (ReACT) with a pathogen-based cancer vaccine. To bridge ACT with a pathogen, we genetically engineered tumor-specific CD8 T cells in vitro with a second T-cell receptor (TCR) that recognizes a bacterial antigen. We then transferred these dual-specific T cells in combination with intratumoral bacteria injection to treat solid tumors in mice. The dual-specific CD8 T cells expanded vigorously, migrated to tumor sites, and robustly eradicated primary tumors. The mice cured from ReACT also developed immunological memory against tumor rechallenge. Mechanistically, we have found that this combined approach reverts the immunosuppressive TME and recruits CD8 T cells with an increased number and killing ability to the tumors. PMID:28069963

Immunologic Effects Of Peritoneal Photodynamic Treatment

NASA Astrophysics Data System (ADS)

Lynch, David H.; Haddad, Sandra; Jolles, Christopher J.; King, Vernon J.; Ott, Mark J.; Robertson, Bekkie; Straight, Richard C.

1989-06-01

One of the side effects of peritoneal photodynamic treatment (PDT) of mice is a systemic suppression of contact hypersensitivity (CH) responses. Treatment with either laser alone or the photosensitizer, Photofrin II (PFII), alone does not cause suppression of CH responses. Immunosuppression of CH responses is an active process that is adoptively transferable using viable cells, but not serum, from PDT-treated mice. The induction of adoptively transferable suppressor cells in PDT-treated mice requires exposure to an antigenic stimulus, yet the suppressor cells are antigen non-specific in their function. T cell function in PDT-treated mice, as measured by the ability of splenic lymphoid cells to generate allogeneic cytotoxic T lymphocyte responses, is comparable to that detected in normal mice. However, the ability of spleen cells from PDT-treated mice to act as stimulators in a mixed lymhocyte reaction is dramatically impaired, suggesting that the major cell type affected by peritoneal PDT is of the macrophage lineage. Support for this concept is provided by experiments in which spleen cells from PDT-treated mice were chromatographically separated into populations of T cells, B cells and macrophages prior to adoptive transfer into naive recipients. The results indicate that the cell type mediating adoptively transferable suppression of CH responsiveness is of the macrophage lineage. Analysis of hematologic parameters revealed that induction of suppression by PDT-treatment was associated with a marked neutrophilia and lymphocytosis, and was also accompanied by a 5-fold increase in concentration of the acute phase protein, Serum Amyloid P. Finally, attempts to ameliorate PDT-induced immunosuppression by pharmacologic intervention have proved successful using implants of pellets that release indomethacin at a rate of 1.25µg/day. Thus, the data suggest that PDT-treatment induces macrophages to produce factors (e.g., prostaglandins) that are known to be potently immunosuppressive.

IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia.

PubMed

Xu, Aizhang; Bhanumathy, Kalpana Kalyanasundaram; Wu, Jie; Ye, Zhenmin; Freywald, Andrew; Leary, Scot C; Li, Rongxiu; Xiang, Jim

2016-01-01

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia. We demonstrate that transferred T-cells prolong their survival and enhance their memory in lymphopenic mice, in a manner that depends on IL-15 signaling, but not IL-7. We determine that in vitro stimulation of naïve or effector T-cells with IL-7 and IL-15 reduces IL-7Rα, and increases and/or maintains IL-15Rβ expression, respectively. Consistent with these findings, the expression of IL-7Rα and IL-15Rβ is down- and up-regulated, respectively, in vivo on transferred T-cells in an early phase post T-cell transfer in lymphopenia. We further show that in vitro IL-15 restimulation-induced memory T-cells (compared to IL-2 restimulation-induced effector T-cells) and in vivo transferred T-cells in irradiated IL-15-sufficient C57BL/6 mice (compared to IL-15-deficient IL-15 KO mice) have increased mitochondrial content, but less NADH and lower mitochondrial potential (ΔΨm), and demonstrate greater phosphorylation of signal transducers and activators of transcription-5 (STAT5) and Unc-51-like kinase-1 (ULK1), and higher expression of B-cell leukemia/lymphoma-2 (Bcl2) and memory-, autophagy- and mitochondrial biogenesis-related molecules. Irradiation-induced lymphopenia promotes effector T-cell survival via IL-15 signaling the STAT5/Bcl2 pathway, enhances T-cell memory formation via IL-15 activation of the forkhead-box family of transcription factor (FOXO)/eomesodermin (Eomes) memory and ULK1/autophagy-related gene-7 (ATG7) autophagy pathways, and via IL-15 activation of the mitochondrial remodeling. Our data thus identify some important targets to consider when designing potent adoptive T-cell immunotherapies of cancer.

Numerical investigation of flow and heat transfer in a novel configuration multi-tubular fixed bed reactor for propylene to acrolein process

NASA Astrophysics Data System (ADS)

Jiang, Bin; Hao, Li; Zhang, Luhong; Sun, Yongli; Xiao, Xiaoming

2015-01-01

In the present contribution, a numerical study of fluid flow and heat transfer performance in a pilot-scale multi-tubular fixed bed reactor for propylene to acrolein oxidation reaction is presented using computational fluid dynamics (CFD) method. Firstly, a two-dimensional CFD model is developed to simulate flow behaviors, catalytic oxidation reaction, heat and mass transfer adopting porous medium model on tube side to achieve the temperature distribution and investigate the effect of operation parameters on hot spot temperature. Secondly, based on the conclusions of tube-side, a novel configuration multi-tubular fixed-bed reactor comprising 790 tubes design with disk-and-doughnut baffles is proposed by comparing with segmental baffles reactor and their performance of fluid flow and heat transfer is analyzed to ensure the uniformity condition using molten salt as heat carrier medium on shell-side by three-dimensional CFD method. The results reveal that comprehensive performance of the reactor with disk-and-doughnut baffles is better than that of with segmental baffles. Finally, the effects of operating conditions to control the hot spots are investigated. The results show that the flow velocity range about 0.65 m/s is applicable and the co-current cooling system flow direction is better than counter-current flow to control the hottest temperature.

Real-time PCR to determine transgene copy number and to quantitate the biolocalization of adoptively transferred cells from EGFP-transgenic mice.

PubMed

Joshi, Molishree; Keith Pittman, H; Haisch, Carl; Verbanac, Kathryn

2008-09-01

Quantitative real-time PCR (qPCR) is a sensitive technique for the detection and quantitation of specific DNA sequences. Here we describe a Taqman qPCR assay for quantification of tissue-localized, adoptively transferred enhanced green fluorescent protein (EGFP)-transgenic cells. A standard curve constructed from serial dilutions of a plasmid containing the EGFP transgene was (i) highly reproducible, (ii) detected as few as two copies, and (iii) was included in each qPCR assay. qPCR analysis of genomic DNA was used to determine transgene copy number in several mouse strains. Fluorescent microscopy of tissue sections showed that adoptively transferred vascular endothelial cells (VEC) from EGFP-transgenic mice specifically localized to tissue with metastatic tumors in syngeneic recipients. VEC microscopic enumeration of liver metastases strongly correlated with qPCR analysis of identical sections (Pearson correlation 0.81). EGFP was undetectable in tissue from control mice by qPCR. In another study using intra-tumor EGFP-VEC delivery to subcutaneous tumors, manual cell count and qPCR analysis of alternating sections also strongly correlated (Pearson correlation 0.82). Confocal microscopy of the subcutaneous tumor sections determined that visual fluorescent signals were frequently tissue artifacts. This qPCR methodology offers specific, objective, and rapid quantitation, uncomplicated by tissue autofluorescence, and should be readily transferable to other in vivo models to quantitate the biolocalization of transplanted cells.

Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

NASA Astrophysics Data System (ADS)

Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.

2006-10-01

Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

Transfer of myelin-specific cells deviated in vitro towards IL-4 production ameliorates ongoing experimental allergic neuritis

PubMed Central

Ekerfelt, C; Dahle, C; Weissert, R; Kvarnström, M; Olsson, T; Ernerudh, J

2001-01-01

A causal role of IL-4 (Th2) production for recovery in experimental allergic neuritis (EAN) was indicated by experiments where Th1-like autoreactive cell populations, taken from the induction phase of the disease, were deviated to extensive secretion of IL-4 in a selective fashion, by ex vivo stimulation with autoantigen in the presence of IL-4. The deviated cells were adoptively transferred to EAN rats at a time just prior to the onset of clinical signs. This treatment ameliorated EAN compared with sham treatment. This therapeutic approach, with generation of autoreactive IL-4-secreting cells ex vivo followed by subsequent adoptive transfer, may become a new selective treatment of organ-specific autoimmune diseases since, in contrast to previous attempts, it is done in a physiological and technically easy way. PMID:11168007

CXCR1 as a novel target for directing reactive T cells toward melanoma: implications for adoptive cell transfer immunotherapy.

PubMed

Sapoznik, Sivan; Ortenberg, Rona; Galore-Haskel, Gilli; Kozlovski, Stav; Levy, Daphna; Avivi, Camila; Barshack, Iris; Cohen, Cyrille J; Besser, Michal J; Schachter, Jacob; Markel, Gal

2012-10-01

Adoptive cell transfer therapy with reactive T cells is one of the most promising immunotherapeutic modalities for metastatic melanoma patients. Homing of the transferred T cells to all tumor sites in sufficient numbers is of great importance. Here, we seek to exploit endogenous chemotactic signals in order to manipulate and enhance the directional trafficking of transferred T cells toward melanoma. Chemokine profiling of 15 melanoma cultures shows that CXCL1 and CXCL8 are abundantly expressed and secreted from melanoma cultures. However, the complimentary analysis on 40 melanoma patient-derived tumor-infiltrating lymphocytes (TIL) proves that the corresponding chemokine receptors are either not expressed (CXCR2) or expressed at low levels (CXCR1). Using the in vitro transwell system, we demonstrate that TIL cells preferentially migrate toward melanoma and that endogenously expressing CXCR1 TIL cells are significantly enriched among the migrating lymphocytes. The role of the chemokines CXCL1 and CXCL8 is demonstrated by partial abrogation of this enrichment with anti-CXCL1 and anti-CXCL8 neutralizing antibodies. The role of the chemokine receptor CXCR1 is validated by the enhanced migration of CXCR1-engineered TIL cells toward melanoma or recombinant CXCL8. Cytotoxicity and IFNγ secretion activity are unaltered by CXCR1 expression profile. Taken together, these results mark CXCR1 as a candidate for genetic manipulations to enhance trafficking of adoptively transferred T cells. This approach is complimentary and potentially synergistic with other genetic strategies designed to enhance anti-tumor potency.

The influence of training and experience on memory strategy.

PubMed

Patrick, John; Morgan, Phillip L; Smy, Victoria; Tiley, Leyanne; Seeby, Helen; Patrick, Tanya; Evans, Jonathan

2015-07-01

This paper investigates whether, and if so how much, prior training and experience overwrite the influence of the constraints of the task environment on strategy deployment. This evidence is relevant to the theory of soft constraints that focuses on the role of constraints in the task environment (Gray, Simms, Fu, & Schoelles, Psychological Review, 113: 461-482, 2006). The theory explains how an increase in the cost of accessing information induces a more memory-based strategy involving more encoding and planning. Experiments 1 and 3 adopt a traditional training and transfer design using the Blocks World Task in which participants were exposed to training trials involving a 2.5-s delay in accessing goal-state information before encountering transfer trials in which there was no access delay. The effect of prior training was assessed by the degree of memory-based strategy adopted in the transfer trials. Training with an access delay had a substantial carry-over effect and increased the subsequent degree of memory-based strategy adopted in the transfer environment. However, such effects do not necessarily occur if goal-state access cost in training is less costly than in transfer trials (Experiment 2). Experiment 4 used a fine-grained intra-trial design to examine the effect of experiencing access cost on one, two, or three occasions within the same trial and found that such experience on two consecutive occasions was sufficient to induce a more memory-based strategy. This paper establishes some effects of training that are relevant to the soft constraints theory and also discusses practical implications.

Knowledge Transfer Partnerships and the Entrepreneurial University

ERIC Educational Resources Information Center

Wynn, Martin; Jones, Peter

2017-01-01

This article outlines one way in which less research-intensive universities can contribute to entrepreneurship by examining the achievements of several Knowledge Transfer Partnerships (KTPs) in the University of Gloucestershire. The article adopts a qualitative case study approach: four case studies of KTPs at, respectively, Beacons Business…

The Potential of Cellular- and Viral-Based Immunotherapies for Malignant Glioma-Dendritic Cell Vaccines, Adoptive Cell Transfer, and Oncolytic Viruses.

PubMed

Maxwell, Russell; Luksik, Andrew S; Garzon-Muvdi, Tomas; Lim, Michael

2017-06-01

Malignant gliomas, including glioblastoma and anaplastic astrocytoma, are the most frequent primary brain tumors and present with many treatment challenges. In this review, we discuss the potential of cellular- and viral-based immunotherapies in the treatment of malignant glioma, specifically focusing on dendritic cell vaccines, adoptive cell therapy, and oncolytic viruses. Diverse cellular- and viral-based strategies have been engineered and optimized to generate either a specific or broad antitumor immune response in malignant glioma. Due to their successes in the preclinical arena, many of these therapies have undergone phase I and II clinical testing. These early clinical trials have demonstrated the feasibility, safety, and efficacy of these immunotherapies. Dendritic cell vaccines, adoptive cell transfer, and oncolytic viruses may have a potential role in the treatment of malignant glioma. However, these modalities must be investigated in well-designed phase III trials to prove their efficacy.

[Adoptive transfer of Epstein-Barr virus-specific T-lymphocytes in chronic active Epstein-Barr infection].

PubMed

Babel, N; Hammer, M H; Reinke, P

2003-03-14

A 27-year-old man was admitted because of intermittent fever, fatigue, lymphadenopathy and splenomegaly for 20 years. Chronic administration of 6 - 8 g aspirin per day (self-prescribed) resulted in limited control of symptoms and in the development of analgesic nephropathy. The patient had prominent splenomegaly and lymphadenopathy without histological signs of malignancy. Monocytosis and T-lymphopenia were also present. Infectious disease testing revealed IgG+/IgM- EBV serology and EA-EBV-mRNA nested PCR clearly demonstrated the presence of lytic EBV-proteins in PBMCs. As chronic active Epstein-Barr virus infection (CAEBV) was highly probable, treatment with aciclovir, gancilovir and steroids was started. Because treatment failed adoptive T-cell transfer with autologous EBV-specific T-cells was performed. After three consecutive infusions the patient responded with a complete remission of fever, fatigue, lymphadenopathy and splenomegaly without adverse effects. Retrospective real-time PCR analysis showed a decrease in viral load from 62847 copies/ microg DNA to 45 - 250 copies after treatment. The patient remains in stable remission without signs of CAEBV (> 4 years). Adoptive transfer of autologous, EBV-specific T-lymphocytes is a promising treatment in CAEBV.

Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE−/− Reporter Mouse—Brief Report

PubMed Central

Iqbal, Asif J.; Jones, Daniel; Patel, Jyoti; Coutinho, Patricia; Taylor, Lewis; Greaves, David R.; Channon, Keith M.

2017-01-01

Objective— To create a model of atherosclerosis using green fluorescent protein (GFP)–targeted monocytes/macrophages, allowing analysis of both endogenous GFP+ and adoptively transferred GFP+ myeloid cells in arterial inflammation. Approach and Results— hCD68GFP reporter mice were crossed with ApoE−/− mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II–induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP+ expression in CD11b+/CD64+, CD11c+/MHC-IIHI, and CD11b+/F4/80+ myeloid cells. Adoptive transfer of GFP+ monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2−/− monocytes to sites of inflammation. Conclusions— hCD68GFP/ApoE−/− mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes. PMID:27908893

Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression

PubMed Central

Lu, Yong-Chen; Yao, Xin; Li, Yong F.; El-Gamil, Mona; Dudley, Mark E.; Yang, James C.; Almeida, Jorge R.; Douek, Daniel C.; Samuels, Yardena; Rosenberg, Steven A.; Robbins, Paul F.

2013-01-01

Adoptive cell therapy with tumor infiltrating lymphocytes (TILs) represents an effective treatment for patients with metastatic melanoma. However, most of the antigen targets recognized by effective melanoma reactive TILs remain elusive. In this study, patient 2369 experienced a complete response, including regressions of bulky liver tumor masses ongoing beyond seven years following adoptive TILs transfer. The screening of a cDNA library generated from the autologous melanoma cell line resulted in the isolation of a mutated PPP1R3B (protein phosphatase 1, regulatory (inhibitor) subunit 3B) gene product. The mutated PPP1R3B peptide represents the immunodominant epitope recognized by tumor reactive T cells in TIL 2369. Five years following adoptive transfer, peripheral blood T lymphocytes obtained from patient 2369 recognized the mutated PPP1R3B epitope. These results demonstrate that adoptive T cell therapy targeting a tumor-specific antigen can mediate long-term survival for a patient with metastatic melanoma. This study also provides an impetus to develop personalized immunotherapy targeting tumor-specific, mutated antigens. PMID:23690473

Effective adoptive transfer of haploidentical tumor-specific T cells in B16-melanoma bearing mice.

PubMed

Cui, Nai-peng; Xie, Shao-jian; Han, Jin-sheng; Ma, Zhen-feng; Chen, Bao-ping; Cai, Jian-hui

2012-03-01

Adoptive transfer of allogeneic tumor-specific T cells often results in severe graft-versus-host disease (GVHD). Here, we sought to maximize graft-versus-tumor and minimize GVHD by using haploidentical T cells in pre-irradiated B16-melanoma bearing mice. C57BL/6 mice bearing B16-melanoma tumors were irradiated with 0, 5, or 7 Gy total body irradiation (TBI), or 7 Gy TBI plus bone marrow transplantation. Tumor areas were measured every 3 days to assess the influence of irradiation treatment on tumor regression. B16-melanoma bearing mice were irradiated with 7 Gy TBI; sera and spleens were harvested at days 1, 3, 5, 7, 9, 11, and 13 after irradiation. White blood cell levels were measured and transforming growth factor β1 (TGF-b1) and interleukin 10 (IL-10) levels in serum were detected using enzyme-linked immunosorbent assay (ELISA) kits. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry were performed to test TGF-b1, IL-10 and Foxp3 mRNA levels and the proportion of CD4+CD25+Foxp3+ T-regulatory cells (Tregs) in spleens. B16-melanoma bearing C57BL/6 mice were irradiated with 7 Gy TBI followed by syngeneic (Syn1/Syn2) or haploidentical (Hap1/Hap2), dendritic cell-induced cytotoxic T lymphocytes (DC-CTLs) treatment, tumor areas and system GVHD were observed every 3 days. Mice were killed 21 days after the DC-CTLs adoptive transfer; histologic analyses of eyes, skin, liver, lungs, and intestine were then performed. Irradiation with 7 Gy TBI on the B16-melanoma-bearing mice did not influence tumor regression compared to the control group; however, it down-regulated the proportion of Tregs in spleens and the TGF-b1 and IL-10 levels in sera and spleens, suggesting inhibition of autoimmunity and intervention of tumor microenvironment. Adoptive transfer of haploidentical DC-CTLs significantly inhibited B16-melanoma growth. GVHD assessment and histology analysis showed no significant difference among the groups. Adoptive transfer of haploidentical tumor-specific T cells in irradiation-pretreated B16-melanoma bearing mice preserved antitumor capacity without causing a GVHD response.

Adoption Factors of the Electronic Health Record: A Systematic Review

PubMed Central

2016-01-01

Background The Health Information Technology for Economic and Clinical Health (HITECH) was a significant piece of legislation in America that served as a catalyst for the adoption of health information technology. Following implementation of the HITECH Act, Health Information Technology (HIT) experienced broad adoption of Electronic Health Records (EHR), despite skepticism exhibited by many providers for the transition to an electronic system. A thorough review of EHR adoption facilitator and barriers provides ongoing support for the continuation of EHR implementation across various health care structures, possibly leading to a reduction in associated economic expenditures. Objective The purpose of this review is to compile a current and comprehensive list of facilitators and barriers to the adoption of the EHR in the United States. Methods Authors searched Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE, 01/01/2012–09/01/2015, core clinical/academic journals, MEDLINE full text, and evaluated only articles germane to our research objective. Team members selected a final list of articles through consensus meetings (n=31). Multiple research team members thoroughly read each article to confirm applicability and study conclusions, thereby increasing validity. Results Group members identified common facilitators and barriers associated with the EHR adoption process. In total, 25 adoption facilitators were identified in the literature occurring 109 times; the majority of which were efficiency, hospital size, quality, access to data, perceived value, and ability to transfer information. A total of 23 barriers to adoption were identified in the literature, appearing 95 times; the majority of which were cost, time consuming, perception of uselessness, transition of data, facility location, and implementation issues. Conclusions The 25 facilitators and 23 barriers to the adoption of the EHR continue to reveal a preoccupation on cost, despite incentives in the HITECH Act. Limited financial backing and outdated technology were also common barriers frequently mentioned during data review. Future public policy should include incentives commensurate with those in the HITECH Act to maintain strong adoption rates. PMID:27251559

A transfer of technology from engineering: use of ROC curves from signal detection theory to investigate information processing in the brain during sensory difference testing.

PubMed

Wichchukit, Sukanya; O'Mahony, Michael

2010-01-01

This article reviews a beneficial effect of technology transfer from Electrical Engineering to Food Sensory Science. Specifically, it reviews the recent adoption in Food Sensory Science of the receiver operating characteristic (ROC) curve, a tool that is incorporated in the theory of signal detection. Its use allows the information processing that takes place in the brain during sensory difference testing to be studied and understood. The review deals with how Signal Detection Theory, also called Thurstonian modeling, led to the adoption of a more sophisticated way of analyzing the data from sensory difference tests, by introducing the signal-to-noise ratio, d', as a fundamental measure of perceived small sensory differences. Generally, the method of computation of d' is a simple matter for some of the better known difference tests like the triangle, duo-trio and 2-AFC. However, there are occasions when these tests are not appropriate and other tests like the same-different and the A Not-A test are more suitable. Yet, for these, it is necessary to understand how the brain processes information during the test before d' can be computed. It is for this task that the ROC curve has a particular use. © 2010 Institute of Food Technologists®

12 CFR 611.501 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Procedures. 611.501 Section 611.501 Banks and... Procedures. (a) The boards of directors of a bank and an association which seek to transfer authorities may adopt appropriate resolutions approving such transfer and providing for the submission of such a...

Stakeholder analysis for adopting a personal health record standard in Korea.

PubMed

Kang, Min-Jeoung; Jung, Chai Young; Kim, Soyoun; Boo, Yookyung; Lee, Yuri; Kim, Sundo

Interest in health information exchanges (HIEs) is increasing. Several countries have adopted core health data standards with appropriate strategies. This study was conducted to determine the feasibility of a continuity of care record (CCR) as the standard for an electronic version of the official transfer note and the HIE in Korean healthcare. A technical review of the CCR standard and analysis of stakeholders' views were undertaken. Transfer notes were reviewed and matched with CCR standard categories. The standard for the Korean coding system was selected. Stakeholder analysis included an online survey of members of the Korean Society of Medical Informatics, a public hearing to derive opinions of consumers, doctors, vendors, academic societies and policy makers about the policy process, and a focus group meeting with EMR vendors to determine which HIE objects were technically applicable. Data objects in the official transfer note form matched CCR standards. Korean Classification of Diseases, Korean Standard Terminology of Medicine, Electronic Data Interchange code (EDI code), Logical Observation Identifiers Names and Codes, and Korean drug codes (KD code) were recommended as the Korean coding standard.'Social history', 'payers', and 'encounters' were mostly marked as optional or unnecessary sections, and 'allergies', 'alerts', 'medication list', 'problems/diagnoses', 'results',and 'procedures' as mandatory. Unlike the US, 'social history' was considered optional and 'advance directives' mandatory.At the public hearing there was some objection from the Korean Medical Association to the HIE on legal grounds in termsof intellectual property and patients' personal information. Other groups showed positive or neutral responses. Focus group members divided CCR data objects into three phases based onpredicted adoption time in CCR: (i) immediate adoption; (ii) short-term adoption ('alerts', 'family history'); and (iii) long-term adoption ('results', 'advanced directives', 'functional status', 'medical equipment', 'vital signs', 'plan of care', 'social history'). There were no technical problems in generating the CCR standard document from EMRs. Matters of concern that arose from study results should be resolved with time and consultation.

Combining antiangiogenic therapy with adoptive cell immunotherapy exerts better antitumor effects in non-small cell lung cancer models.

PubMed

Shi, Shujing; Wang, Rui; Chen, Yitian; Song, Haizhu; Chen, Longbang; Huang, Guichun

2013-01-01

Cytokine-induced killer cells (CIK cells) are a heterogeneous subset of ex-vivo expanded T lymphocytes which are characterized with a MHC-unrestricted tumor-killing activity and a mixed T-NK phenotype. Adoptive CIK cells transfer, one of the adoptive immunotherapy represents a promising nontoxic anticancer therapy. However, in clinical studies, the therapeutic activity of adoptive CIK cells transfer is not as efficient as anticipated. Possible explanations are that abnormal tumor vasculature and hypoxic tumor microenvironment could impede the infiltration and efficacy of lymphocytes. We hypothesized that antiangiogenesis therapy could improve the antitumor activity of CIK cells by normalizing tumor vasculature and modulating hypoxic tumor microenvironment. We combined recombinant human endostatin (rh-endostatin) and CIK cells in the treatment of lung carcinoma murine models. Intravital microscopy, dynamic contrast enhanced magnetic resonance imaging, immunohistochemistry, and flow cytometry were used to investigate the tumor vasculature and hypoxic microenvironment as well as the infiltration of immune cells. Our results indicated that rh-endostatin synergized with adoptive CIK cells transfer to inhibit the growth of lung carcinoma. We found that rh-endostatin normalized tumor vasculature and reduced hypoxic area in the tumor microenvironment. Hypoxia significantly inhibited the proliferation, cytotoxicity and migration of CIK cells in vitro and impeded the homing of CIK cells into tumor parenchyma ex vivo. Furthermore, we found that treatment with rh-endostatin significantly increased the homing of CIK cells and decreased the accumulation of suppressive immune cells in the tumor tissue. In addition, combination therapy produced higher level of tumor-infiltration lymphocytes compared with other treatments. Our results demonstrate that rh-endostatin improves the therapeutic effect of adoptive CIK cells therapy against lung carcinomas and unmask the mechanisms of the synergistic antitumor efficacy, providing a new rationale for combining antiangiogenesis therapy with immunotherapy in the treatment of lung cancer.

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

PubMed

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

Design of a CAN bus interface for photoelectric encoder in the spaceflight camera

NASA Astrophysics Data System (ADS)

Sun, Ying; Wan, Qiu-hua; She, Rong-hong; Zhao, Chang-hai; Jiang, Yong

2009-05-01

In order to make photoelectric encoder usable in a spaceflight camera which adopts CAN bus as the communication method, CAN bus interface of the photoelectric encoder is designed in this paper. CAN bus interface hardware circuit of photoelectric encoder consists of CAN bus controller SJA 1000, CAN bus transceiver TJA1050 and singlechip. CAN bus interface controlling software program is completed in C language. A ten-meter shield twisted pair line is used as the transmission medium in the spaceflight camera, and speed rate is 600kbps.The experiments show that: the photoelectric encoder with CAN bus interface which has the advantages of more reliability, real-time, transfer rate and transfer distance overcomes communication line's shortcomings of classical photoelectric encoder system. The system works well in automatic measuring and controlling system.

Detailed performance analysis of the A.A.D. - concept B

NASA Technical Reports Server (NTRS)

Sekar, R.; Tozzi, L.

1983-01-01

New concepts for engine performance improvement are seen through the adoption of heat regeneration techniques; advanced methods to enhance the combustion; and higher efficiency air handling machinery, such as the positive displacement helical screw expander and compressor. Each of these concepts plays a particular role in engine performance improvement. First regeneration has a great potential for achieving higher engine thermal efficiency through the recovery of waste energy. Although the concept itself is not new (this technique is used in the gas turbine), the application to reciprocating internal combustion engines is quite unusual and presents conceptual difficulties. The second important area is better control of the combustion process in terms of heat transfer characteristics, combustion products, and heat release rate. The third area for performance improvement is in the adoption of high efficiency air handling machinery. In particular, positive displacement helical expander and compressor exhibit an extremely high efficiency over a wide range of operating conditions.

Optimizing physicians' instruction of PACS through e-learning: cognitive load theory applied.

PubMed

Devolder, P; Pynoo, B; Voet, T; Adang, L; Vercruysse, J; Duyck, P

2009-03-01

This article outlines the strategy used by our hospital to maximize the knowledge transfer to referring physicians on using a picture archiving and communication system (PACS). We developed an e-learning platform underpinned by the cognitive load theory (CLT) so that in depth knowledge of PACS' abilities becomes attainable regardless of the user's prior experience with computers. The application of the techniques proposed by CLT optimizes the learning of the new actions necessary to obtain and manipulate radiological images. The application of cognitive load reducing techniques is explained with several examples. We discuss the need to safeguard the physicians' main mental processes to keep the patient's interests in focus. A holistic adoption of CLT techniques both in teaching and in configuration of information systems could be adopted to attain this goal. An overview of the advantages of this instruction method is given both on the individual and organizational level.

[Present status and trend of heart fluid mechanics research based on medical image analysis].

PubMed

Gan, Jianhong; Yin, Lixue; Xie, Shenghua; Li, Wenhua; Lu, Jing; Luo, Anguo

2014-06-01

With introduction of current main methods for heart fluid mechanics researches, we studied the characteristics and weakness for three primary analysis methods based on magnetic resonance imaging, color Doppler ultrasound and grayscale ultrasound image, respectively. It is pointed out that particle image velocity (PIV), speckle tracking and block match have the same nature, and three algorithms all adopt block correlation. The further analysis shows that, with the development of information technology and sensor, the research for cardiac function and fluid mechanics will focus on energy transfer process of heart fluid, characteristics of Chamber wall related to blood fluid and Fluid-structure interaction in the future heart fluid mechanics fields.

Genetic algorithm to optimize the design of main combustor and gas generator in liquid rocket engines

NASA Astrophysics Data System (ADS)

Son, Min; Ko, Sangho; Koo, Jaye

2014-06-01

A genetic algorithm was used to develop optimal design methods for the regenerative cooled combustor and fuel-rich gas generator of a liquid rocket engine. For the combustor design, a chemical equilibrium analysis was applied, and the profile was calculated using Rao's method. One-dimensional heat transfer was assumed along the profile, and cooling channels were designed. For the gas-generator design, non-equilibrium properties were derived from a counterflow analysis, and a vaporization model for the fuel droplet was adopted to calculate residence time. Finally, a genetic algorithm was adopted to optimize the designs. The combustor and gas generator were optimally designed for 30-tonf, 75-tonf, and 150-tonf engines. The optimized combustors demonstrated superior design characteristics when compared with previous non-optimized results. Wall temperatures at the nozzle throat were optimized to satisfy the requirement of 800 K, and specific impulses were maximized. In addition, the target turbine power and a burned-gas temperature of 1000 K were obtained from the optimized gas-generator design.

BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models.

PubMed

Kagoya, Yuki; Nakatsugawa, Munehide; Yamashita, Yuki; Ochi, Toshiki; Guo, Tingxi; Anczurowski, Mark; Saso, Kayoko; Butler, Marcus O; Arrowsmith, Cheryl H; Hirano, Naoto

2016-09-01

Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription factor BATF in CD8+ T cells, which was associated with differentiation of T cells into an effector memory phenotype. JQ1-treated T cells showed enhanced persistence and antitumor effects in murine T cell receptor and chimeric antigen receptor gene therapy models. Furthermore, we found that histone acetyltransferase p300 supported the recruitment of BRD4 to the BATF promoter region, and p300 inhibition similarly augmented antitumor effects of the adoptively transferred T cells. These results demonstrate that targeting the BRD4-p300 signaling cascade supports the generation of superior antitumor T cell grafts for adoptive immunotherapy.

Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

PubMed

Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

2013-09-01

Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

An analytical solution for modeling thermal energy transfer in a confined aquifer system

NASA Astrophysics Data System (ADS)

Shaw-Yang, Yang; Hund-der, Yeh

2008-12-01

A mathematical model is developed for simulating the thermal energy transfer in a confined aquifer with different geological properties in the underlying and overlying rocks. The solutions for temperature distributions in the aquifer, underlying rock, and overlying rock are derived by the Laplace transforms and their corresponding time-domain solutions are evaluated by the modified Crump method. Field data adopted from the literature are used as examples to demonstrate the applicability of the solutions in modeling the heat transfer in an aquifer thermal energy storage (ATES) system. The results show that the aquifer temperature increases with time, injection flow rate, and water temperature. However, the temperature decreases with increasing radial and vertical distances. The heat transfer in the rocks is slow and has an effect on the aquifer temperature only after a long period of injection time. The influence distance depends on the aquifer physical and thermal properties, injection flow rate, and injected water temperature. A larger value of thermal diffusivity or injection flow rate will result in a longer influence distance. The present solution can be used as a tool for designing the heat injection facilities for an ATES system.

Visualization of natural convection heat transfer on a sphere

NASA Astrophysics Data System (ADS)

Lee, Dong-Young; Chung, Bum-Jin

2017-12-01

Natural convection heat transfer phenomena on spheres were investigated by adopting mass transfer experiments based on analogy concept. The diameters of spheres were varied from 0.01 m to 0.12 m, which correspond to the Rayleigh numbers of 1.69×108-2.91×1011. The measured mass transfer coefficients agreed well with the existing correlations. The copper electroplating patterns on the spheres visualized the local heat transfer depending on angular distance. The streak plating patterns were observed on the upper part of the sphere, resulting from the wavy flow patterns caused by the instability.

Enhancing Chinese Agribusiness Supply Chains with Internet Technologies: A Transnational Knowledge Transfer Approach

ERIC Educational Resources Information Center

Duan, Yanqing; Bentley, Yongmei; Fu, Zetian; Zografos, Konstantinos; Bemeleit, Boris

2008-01-01

This paper reports research findings from a project funded by the European Commission. The research used case studies and surveys to identify gaps between Europe and China in the level of Internet adoption in fresh-produce supply chains. The project reveals barriers to Internet adoption in China in this industry, and employs a transnational…

Transferring Aviation Practices into Clinical Medicine for the Promotion of High Reliability.

PubMed

Powell-Dunford, Nicole; McPherson, Mark K; Pina, Joseph S; Gaydos, Steven J

2017-05-01

Aviation is a classic example of a high reliability organization (HRO)-an organization in which catastrophic events are expected to occur without control measures. As health care systems transition toward high reliability, aviation practices are increasingly transferred for clinical implementation. A PubMed search using the terms aviation, crew resource management, and patient safety was undertaken. Manuscripts authored by physician pilots and accident investigation regulations were analyzed. Subject matter experts involved in adoption of aviation practices into the medical field were interviewed. A PubMed search yielded 621 results with 22 relevant for inclusion. Improved clinical outcomes were noted in five research trials in which aviation practices were adopted, particularly with regard to checklist usage and crew resource-management training. Effectiveness of interventions was influenced by intensity of application, leadership involvement, and provision of staff training. The usefulness of incorporating mishap investigation techniques has not been established. Whereas aviation accident investigation is highly standardized, the investigation of medical error is characterized by variation. The adoption of aviation practices into clinical medicine facilitates an evolution toward high reliability. Evidence for the efficacy of the checklist and crew resource-management training is robust. Transference of aviation accident investigation practices is preliminary. A standardized, independent investigation process could facilitate the development of a safety culture commensurate with that achieved in the aviation industry.Powell-Dunford N, McPherson MK, Pina JS, Gaydos SJ. Transferring aviation practices into clinical medicine for the promotion of high reliability. Aerosp Med Hum Perform. 2017; 88(5):487-491.

Dendritic cell internalization of α-galactosylceramide from CD8 T cells induces potent antitumor CD8 T-cell responses.

PubMed

Choi, Dong Hoon; Kim, Kwang Soon; Yang, Se Hwan; Chung, Doo Hyun; Song, Boyeong; Sprent, Jonathan; Cho, Jae Ho; Sung, Young Chul

2011-12-15

Dendritic cells (DC) present α-galactosylceramide (αGalCer) to invariant T-cell receptor-expressing natural killer T cells (iNKT) activating these cells to secrete a variety of cytokines, which in turn results in DC maturation and activation of other cell types, including NK cells, B cells, and conventional T cells. In this study, we showed that αGalCer-pulsing of antigen-activated CD8 T cells before adoptive transfer to tumor-bearing mice caused a marked increase in donor T-cell proliferation, precursor frequency, and cytotoxic lymphocyte activity. This effect was interleukin (IL)-2 dependent and involved both natural killer T cells (NKT) and DCs, as mice lacking IL-2, NKTs, and DCs lacked any enhanced response to adoptively transferred αGalCer-loaded CD8 T cells. iNKT activation was mediated by transfer of αGalCer from the cell membrane of the donor CD8 T cells onto the αGalCer receptor CD1d which is present on host DCs. αGalCer transfer was increased by prior activation of the donor CD8 T cells and required AP-2-mediated endocytosis by host DCs. In addition, host iNKT cell activation led to strong IL-2 synthesis, thereby increasing expansion and differentiation of donor CD8 T cells. Transfer of these cells led to improved therapeutic efficacy against established solid tumors in mice. Thus, our findings illustrate how αGalCer loading of CD8 T cells after antigen activation in vitro may leverage the therapeutic potential of adoptive T-cell therapies.

Surface, Deep, and Transfer? Considering the Role of Content Literacy Instructional Strategies

ERIC Educational Resources Information Center

Frey, Nancy; Fisher, Douglas; Hattie, John

2017-01-01

This article provides an organizational review of content literacy instructional strategies to forward a claim that some strategies work better for surface learning, whereas others are more effective for deep learning and still others for transfer learning. The authors argue that the failure to adopt content literacy strategies by disciplinary…

Towards a Taxonomy of Intergenerational Knowledge Transfer Practices: Insights from an International Comparison (Germany-Quebec)

ERIC Educational Resources Information Center

Kuyken, Kerstin; Ebrahimi, Mehran; Saives, Anne-Laure

2018-01-01

Purpose: This paper aims to develop a better understanding of intergenerational knowledge transfer (IKT) practices by adopting a context-related and comparative perspective. Design/methodology/approach: A qualitative case study design involving 83 interviews and non-participative observation in German and Quebec organizations has been chosen.…

Design Thinking and Metacognitive Reflective Scaffolds: A Graphic Design-Industrial Design Transfer Case Study

ERIC Educational Resources Information Center

Lee, Chien-Sing; Wong, Kuok-Shoong Daniel

2015-01-01

Scaffolding is crucial as transfer of learning does not occur naturally and teaching-learning strategies found to be effective for experts may not be suitably adopted as is for novice learners. Furthermore, opportunities are often "found" or "made." The quality of solutions, however, is mediated by different conceptualizations…

Immunologic memory response induced by a meningococcal serogroup C conjugate vaccine using the P64k recombinant protein as carrier.

PubMed

Guirola, María; Urquiza, Dioslaida; Alvarez, Anabel; Cannan-Haden, Leonardo; Caballero, Evelin; Guillén, Gerardo

2006-03-01

In this study, we used an adoptive lymphocyte transfer experiment to evaluate the ability of the P64k recombinant protein to recruit T-helper activity and induce immunologic memory response to the polysaccharide moiety in a meningococcal serogroup C conjugate vaccine. Adoptive transfer of splenocytes from mice immunized with the glycoconjugate conferred antipolysaccharide immunologic memory to naive recipient mice. The observed anamnestic immune response was characterized by more rapid kinetics, isotype switching from IgM to IgG and higher antipolysaccharide antibody titers compared with those reached in groups transferred with splenocytes from plain polysaccharide or phosphate-immunized mice. The memory response generated was also long lasting. Sera from mice transferred with cells from conjugate-immunized mice were the only protective in the infant rat passive protection assay, and also showed higher bactericidal titers. We demonstrated that priming the mice immune system with the glycoconjugate using the P64k protein as carrier induced a memory response to the polysaccharide, promoting a switch of the T-cell-independent response to a T-cell dependent one.

'Don't put the parent out': parents' perspectives of being present during an inter-hospital transfer.

PubMed

Masterson, Kate; Brenner, Maria

2016-05-01

To understand Irish parents' experiences of the inter-hospital transfer of their acutely ill child from a regional hospital to a tertiary children's hospital. Much of the literature on inter-hospital transfer focuses on the medical outcome of children who have been transferred for specialist care. While parental presence during this journey is the focus of discussion papers, little is known about the experience of parents as service users. A qualitative design using a Husserlian phenomenological approach was adopted for this study. Semi-structured interviews were conducted with ten parents between March and October 2014 to explore their experiences of parental presence during the transfer of an acutely ill child. Data were analysed using the modified Van Kaam method. Two key themes emerged 'don't put the parent out' and 'being a parent'. Given a choice, all parents interviewed would have wished to stay with their child during transfer and the findings portray the specific contribution of parents during the journey. Not being permitted to travel with their acutely ill child had a negative effect on parents' perceptions of their ability to continue to parent their child during transfer to specialist paediatric services. To address this there is a need for parents to have the choice, when at all possible, to stay with their child at this time. There is a need to maximise the facilitation of parental presence in an Irish context through the introduction of guidelines to support staff involved in the transfer of an acutely ill child. © 2016 John Wiley & Sons Ltd.

Method translation and full metadata transfer from thermal to differential flow modulated comprehensive two dimensional gas chromatography: Profiling of suspected fragrance allergens.

PubMed

Cordero, Chiara; Rubiolo, Patrizia; Reichenbach, Stephen E; Carretta, Andrea; Cobelli, Luigi; Giardina, Matthew; Bicchi, Carlo

2017-01-13

The possibility to transfer methods from thermal to differential-flow modulated comprehensive two-dimensional gas chromatographic (GC×GC) platforms is of high interest to improve GC×GC flexibility and increase the compatibility of results from different platforms. The principles of method translation are here applied to an original method, developed for a loop-type thermal modulated GC×GC-MS/FID system, suitable for quali-quantitative screening of suspected fragrance allergens. The analysis conditions were translated to a reverse-injection differential flow modulated platform (GC×2GC-MS/FID) with a dual-parallel secondary column and dual detection. The experimental results, for a model mixture of suspected volatile allergens and for raw fragrance mixtures of different composition, confirmed the feasibility of translating methods by preserving 1 D elution order, as well as the relative alignment of resulting 2D peak patterns. A correct translation produced several benefits including an effective transfer of metadata (compound names, MS fragmentation pattern, response factors) by automatic template transformation and matching from the original/reference method to its translated counterpart. The correct translation provided: (a) 2D pattern repeatability, (b) MS fragmentation pattern reliability for identity confirmation, and (c) comparable response factors and quantitation accuracy within a concentration range of three orders of magnitude. The adoption of a narrow bore (i.e. 0.1mm d c ) first-dimension column to operate under close-to-optimal conditions with the differential-flow modulation GC×GC platform was also advantageous in halving the total analysis under the translated conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Objective measures of adoption of patient lift and transfer devices to reduce nursing staff injuries in the hospital setting.

PubMed

Schoenfisch, Ashley L; Pompeii, Lisa A; Myers, Douglas J; James, Tamara; Yeung, Yeu-Li; Fricklas, Ethan; Pentico, Marissa; Lipscomb, Hester J

2011-12-01

Interventions to reduce patient-handling injuries in the hospital setting are often evaluated based on their effect on outcomes such as injury rates. Measuring intervention adoption could address how and why observed trends in the outcome occurred. Unit-level data related to adoption of patient lift equipment were systematically collected at several points in time over 5 years on nursing units at two hospitals, including hours of lift equipment use, equipment accessibility, and supply purchases and availability. Various measures of adoption highlighted the adoption process' gradual nature and variability by hospital and between units. No single measure adequately assessed adoption. Certain measures appear well-correlated. Future evaluation of primary preventive efforts designed to prevent patient-handling injuries would be strengthened by objective data on intermediate measures that reflect intervention implementation and adoption. Copyright © 2011 Wiley Periodicals, Inc.

Estimation of photosynthetically available radiation (PAR) from OCEANSAT-I OCM using a simple atmospheric radiative transfer model

NASA Astrophysics Data System (ADS)

Tripathy, Madhumita; Raman, Mini; Chauhan, Prakash

2015-10-01

Photosynthetically available radiation (PAR) is an important variable for radiation budget, marine and terrestrial ecosystem models. OCEANSAT-1 Ocean Color Monitor (OCM) PAR was estimated using two different methods under both clear and cloudy sky conditions. In the first approach, aerosol optical depth (AOD) and cloud optical depth (COD) were estimated from OCEANSAT-1 OCM TOA (top-of-atmosphere) radiance data on a pixel by pixel basis and PAR was estimated from extraterrestrial solar flux for fifteen spectral bands using a radiative transfer model. The second approach used TOA radiances measured by OCM in the PAR spectral range to compute PAR. This approach also included surface albedo and cloud albedo as inputs. Comparison between OCEANSAT-1 OCM PAR at noon with in situ measured PAR shows that root mean square difference was 5.82% for the method I and 7.24% for the method II in daily time scales. Results indicate that methodology adopted to estimate PAR from OCEANSAT-1 OCM can produce reasonably accurate PAR estimates over the tropical Indian Ocean region. This approach can be extended to OCEANSAT-2 OCM and future OCEANSAT-3 OCM data for operational estimation of PAR for regional marine ecosystem applications.

Gradient Augmented Level Set Method for Two Phase Flow Simulations with Phase Change

NASA Astrophysics Data System (ADS)

Anumolu, C. R. Lakshman; Trujillo, Mario F.

2016-11-01

A sharp interface capturing approach is presented for two-phase flow simulations with phase change. The Gradient Augmented Levelset method is coupled with the two-phase momentum and energy equations to advect the liquid-gas interface and predict heat transfer with phase change. The Ghost Fluid Method (GFM) is adopted for velocity to discretize the advection and diffusion terms in the interfacial region. Furthermore, the GFM is employed to treat the discontinuity in the stress tensor, velocity, and temperature gradient yielding an accurate treatment in handling jump conditions. Thermal convection and diffusion terms are approximated by explicitly identifying the interface location, resulting in a sharp treatment for the energy solution. This sharp treatment is extended to estimate the interfacial mass transfer rate. At the computational cell, a d-cubic Hermite interpolating polynomial is employed to describe the interface location, which is locally fourth-order accurate. This extent of subgrid level description provides an accurate methodology for treating various interfacial processes with a high degree of sharpness. The ability to predict the interface and temperature evolutions accurately is illustrated by comparing numerical results with existing 1D to 3D analytical solutions.

Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms

PubMed Central

Bagnara, Davide; Ibatici, Adalberto; Corselli, Mirko; Sessarego, Nadia; Tenca, Claudya; De Santanna, Amleto; Mazzarello, Andrea; Daga, Antonio; Corvò, Renzo; De Rossi, Giulio; Frassoni, Francesco; Ciccone, Ermanno; Fais, Franco

2009-01-01

Background CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha-galactosylceramide (α-GalCer) is a glycolipid that can be presented to cytotoxic CD1d-restricted T cells. These reagents represent a potentially powerful tool for cell mediated immunotherapy. Design and Methods We set up an experimental model to evaluate the use of adoptively transferred cytotoxic CD1d-restricted T cells and α-GalCer in the treatment of mice engrafted with CD1d+ lymphoid neoplastic cells. To this end the C1R cell line was transfected with CD1c or CD1d molecules. In addition, upon retroviral infection firefly luciferase was expressed on C1R transfected cell lines allowing the evaluation of tumor growth in xenografted immunodeficient NOD/SCID mice. Results The C1R-CD1d cell line was highly susceptible to specific CD1d-restricted T cell cytotoxicity in the presence α-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and α-GalCer to mice engrafted with both C1R-CD1c and C1R-CD1d, a reduction in tumor growth was observed only in CD1d+ masses. In addition, CD1d-restricted T-cell treatment plus α-GalCer eradicated small C1R-CD1d+ nodules. Immunohistochemical analysis revealed that infiltrating NKT cells were mainly observed in CD1d nodules. Conclusions Our results indicate that ex vivo expanded cytotoxic CD1d-restricted T cells and α-GalCer may represent a new immunotherapeutic tool for treatment of CD1d+ hematologic malignancies. PMID:19454494

HCV T Cell Receptor Chain Modifications to Enhance Expression, Pairing, and Antigen Recognition in T Cells for Adoptive Transfer.

PubMed

Foley, Kendra C; Spear, Timothy T; Murray, David C; Nagato, Kaoru; Garrett-Mayer, Elizabeth; Nishimura, Michael I

2017-06-16

T cell receptor (TCR)-gene-modified T cells for adoptive cell transfer can mediate objective clinical responses in melanoma and other malignancies. When introducing a second TCR, mispairing between the endogenous and introduced α and β TCR chains limits expression of the introduced TCR, which can result in impaired efficacy or off-target reactivity and autoimmunity. One approach to promote proper TCR chain pairing involves modifications of the introduced TCR genes: introducing a disulfide bridge, substituting murine for human constant regions, codon optimization, TCR chain leucine zipper fusions, and a single-chain TCR. We have introduced these modifications into our hepatitis C virus (HCV) reactive TCR and utilize a marker gene, CD34t, which allows us to directly compare transduction efficiency with TCR expression and T cell function. Our results reveal that of the TCRs tested, T cells expressing the murine Cβ2 TCR or leucine zipper TCR have the highest levels of expression and the highest percentage of lytic and interferon-γ (IFN-γ)-producing T cells. Our studies give us a better understanding of how TCR modifications impact TCR expression and T cell function that may allow for optimization of TCR-modified T cells for adoptive cell transfer to treat patients with malignancies.

Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA–peptide tetramers

PubMed Central

Cobbold, Mark; Khan, Naeem; Pourgheysari, Batoul; Tauro, Sudhir; McDonald, Dorothy; Osman, Husam; Assenmacher, Mario; Billingham, Lucinda; Steward, Colin; Crawley, Charles; Olavarria, Eduardo; Goldman, John; Chakraverty, Ronjon; Mahendra, Premini; Craddock, Charles; Moss, Paul A.H.

2005-01-01

Stem cell transplantation is used widely in the management of a range of diseases of the hemopoietic system. Patients are immunosuppressed profoundly in the early posttransplant period, and reactivation of cytomegalovirus (CMV) remains a significant cause of morbidity and mortality. Adoptive transfer of donor-derived CMV-specific CD8+ T cell clones has been shown to reduce the rate of viral reactivation; however, the complexity of this approach severely limits its clinical application. We have purified CMV-specific CD8+ T cells from the blood of stem cell transplant donors using staining with HLA–peptide tetramers followed by selection with magnetic beads. CMV-specific CD8+ cells were infused directly into nine patients within 4 h of selection. Median cell dosage was 8.6 × 103/kg with a purity of 98% of all T cells. CMV-specific CD8+ T cells became detectable in all patients within 10 d of infusion, and TCR clonotype analysis showed persistence of infused cells in two patients studied. CMV viremia was reduced in every case and eight patients cleared the infection, including one patient who had a prolonged history of CMV infection that was refractory to antiviral therapy. This novel approach to adoptive transfer has considerable potential for antigen-specific T cell therapy. PMID:16061727

A role for B cells in the development of T cell helper function in a malaria infection in mice

PubMed Central

Langhorne, Jean; Cross, Caroline; Seixas, Elsa; Li, Ching; von der Weid, Thierry

1998-01-01

B cell knockout mice are unable to clear a primary erythrocytic infection of Plasmodium chabaudi chabaudi. However, the early acute infection is controlled to some extent, giving rise to a chronic relapsing parasitemia that can be reduced either by drug treatment or by adoptive transfer of B cells. Similar to mice rendered B-cell deficient by lifelong treatment with anti-μ antibodies, B cell knockout mice (μMT) retain a predominant CD4+ Th1-like response to malarial antigens throughout a primary infection. This contrasts with the response seen in control C57BL/6 mice in which the CD4+ T-cell response has switched to that characteristic of Th2 cells at the later stages of infection, manifesting efficient help for specific antibodies in vitro and interleukin 4 production. Both chloroquine and adoptive transfer of immune B cells reduced parasite load. However, the adoptive transfer of B cells resulted in a Th2 response in recipient μMT mice, as indicated by a relative increase in the precursor frequency of helper cells for antibody production. These data support the idea that B cells play a role in the regulation of CD4+ T subset responses. PMID:9465085

Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease

PubMed Central

Pierini, Antonio; Baker, Jeanette; Armstrong, Randall; Pan, Yuqiong; Leveson-Gower, Dennis; Negrin, Robert; Meyer, Everett

2015-01-01

The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in murine models of allogeneic hematopoietic cell transplantation (HCT) has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD) and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L), which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies. PMID:26693907

Tumor-promoting desmoplasia is disrupted by depleting FAP-expressing stromal cells

PubMed Central

Scholler, John; Monslow, James; Avery, Diana; Newick, Kheng; O'Brien, Shaun; Evans, Rebecca A.; Bajor, David J.; Clendenin, Cynthia; Durham, Amy C; Buza, Elizabeth L; Vonderheide, Robert H; June, Carl H

2015-01-01

Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASCs) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP+ cells inhibits tumor growth by augmenting anti-tumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP+ CASCs are required for maintenance of the provisional tumor stroma since depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP+ CASCs from other CASC subsets and provide support for further development of FAP+ stromal cell-targeted therapies for the treatment of solid tumors. PMID:25979873

Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells.

PubMed

Lo, Albert; Wang, Liang-Chuan S; Scholler, John; Monslow, James; Avery, Diana; Newick, Kheng; O'Brien, Shaun; Evans, Rebecca A; Bajor, David J; Clendenin, Cynthia; Durham, Amy C; Buza, Elizabeth L; Vonderheide, Robert H; June, Carl H; Albelda, Steven M; Puré, Ellen

2015-07-15

Malignant cells drive the generation of a desmoplastic and immunosuppressive tumor microenvironment. Cancer-associated stromal cells (CASC) are a heterogeneous population that provides both negative and positive signals for tumor cell growth and metastasis. Fibroblast activation protein (FAP) is a marker of a major subset of CASCs in virtually all carcinomas. Clinically, FAP expression serves as an independent negative prognostic factor for multiple types of human malignancies. Prior studies established that depletion of FAP(+) cells inhibits tumor growth by augmenting antitumor immunity. However, the potential for immune-independent effects on tumor growth have not been defined. Herein, we demonstrate that FAP(+) CASCs are required for maintenance of the provisional tumor stroma because depletion of these cells, by adoptive transfer of FAP-targeted chimeric antigen receptor (CAR) T cells, reduced extracellular matrix proteins and glycosaminoglycans. Adoptive transfer of FAP-CAR T cells also decreased tumor vascular density and restrained growth of desmoplastic human lung cancer xenografts and syngeneic murine pancreatic cancers in an immune-independent fashion. Adoptive transfer of FAP-CAR T cells also restrained autochthonous pancreatic cancer growth. These data distinguish the function of FAP(+) CASCs from other CASC subsets and provide support for further development of FAP(+) stromal cell-targeted therapies for the treatment of solid tumors. ©2015 American Association for Cancer Research.

Influence of the boundary conditions on heat and mass transfer in spacer-filled channels

NASA Astrophysics Data System (ADS)

Ciofalo, M.; La Cerva, M. F.; Di Liberto, M.; Tamburini, A.

2017-11-01

The purpose of this study is to discuss some problems which arise in heat or mass transfer in complex channels, with special reference to the spacer-filled channels adopted in membrane processes. Among the issues addressed are the consistent definition of local and mean heat or mass transfer coefficients; the influence of the wall boundary conditions; the influence of one-side versus two-side heat/mass transfer. Most of the results discussed were obtained by finite volume CFD simulations concerning heat transfer in Membrane Distillation or mass transfer in Electrodialysis and Reverse Electrodialysis, but many of the conclusions apply also to different processes involving geometrically complex channels

Cytotoxic T Cell Adoptive Immunotherapy as a Treatment for Nasopharyngeal Carcinoma

PubMed Central

Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E.; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B.; Coman, Scott; Moss, Denis J.

2014-01-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress. PMID:24351754

Cytotoxic T cell adoptive immunotherapy as a treatment for nasopharyngeal carcinoma.

PubMed

Lutzky, Viviana P; Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B; Coman, Scott; Moss, Denis J

2014-02-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.

Three Cs of Translating Evidence-Based Programs for Youth and Families to Practice Settings

ERIC Educational Resources Information Center

Freire, Kimberley E.; Perkinson, Leah; Morrel-Samuels, Susan; Zimmerman, Marc A.

2015-01-01

Despite the growing number of evidence-based programs (EBPs) for youth and families, few are well-integrated in service systems or widely adopted by communities. One set of challenges to widespread adoption of EBPs relates to the transfer of programs from research and development to practice settings. This is often because program developers have…

Driving techniques for high frame rate CCD camera

NASA Astrophysics Data System (ADS)

Guo, Weiqiang; Jin, Longxu; Xiong, Jingwu

2008-03-01

This paper describes a high-frame rate CCD camera capable of operating at 100 frames/s. This camera utilizes Kodak KAI-0340, an interline transfer CCD with 640(vertical)×480(horizontal) pixels. Two output ports are used to read out CCD data and pixel rates approaching 30 MHz. Because of its reduced effective opacity of vertical charge transfer registers, interline transfer CCD can cause undesired image artifacts, such as random white spots and smear generated in the registers. To increase frame rate, a kind of speed-up structure has been incorporated inside KAI-0340, then it is vulnerable to a vertical stripe effect. The phenomena which mentioned above may severely impair the image quality. To solve these problems, some electronic methods of eliminating these artifacts are adopted. Special clocking mode can dump the unwanted charge quickly, then the fast readout of the images, cleared of smear, follows immediately. Amplifier is used to sense and correct delay mismatch between the dual phase vertical clock pulses, the transition edges become close to coincident, so vertical stripes disappear. Results obtained with the CCD camera are shown.

Best practices for health and safety technology transfer in construction.

PubMed

Welch, Laura S; Russell, Dustin; Weinstock, Deborah; Betit, Eileen

2015-08-01

Construction continues to be a dangerous industry, yet solutions that would prevent injury and illness do exist. Prevention of injury and illness among construction workers requires dissemination, adoption, and implementation of these effective interventions, or "research to practice" (r2p). CPWR recruited participants with experience and insight into effective methods for diffusion of health and safety technologies in this industry for a symposium with 3 group sessions and 3 breakout groups. The organizers reviewed session notes and identified 141 recommendations, which were then assigned to 13 over-arching themes. Recommendations included a guide for researchers on patenting and licensing, a business case model, and in-depth case studies including development, testing, manufacturing, marketing, and diffusion. A more comprehensive understanding of the health and safety technology transfer landscape, the various actors, and their motivators and goals will help to foster the successful commercialization and diffusion of health and safety innovations. © 2015 Wiley Periodicals, Inc.

Adoptive transfer of murine T cells expressing a chimeric-PD1-Dap10 receptor as an immunotherapy for lymphoma.

PubMed

Lynch, Adam; Hawk, William; Nylen, Emily; Ober, Sean; Autin, Pierre; Barber, Amorette

2017-11-01

Adoptive transfer of T cells is a promising cancer therapy and expression of chimeric antigen receptors can enhance tumour recognition and T-cell effector functions. The programmed death protein 1 (PD1) receptor is a prospective target for a chimeric antigen receptor because PD1 ligands are expressed on many cancer types, including lymphoma. Therefore, we developed a murine chimeric PD1 receptor (chPD1) consisting of the PD1 extracellular domain fused to the cytoplasmic domain of CD3ζ. Additionally, chimeric antigen receptor therapies use various co-stimulatory domains to enhance efficacy. Hence, the inclusion of a Dap10 or CD28 co-stimulatory domain in the chPD1 receptor was compared to determine which domain induced optimal anti-tumour immunity in a mouse model of lymphoma. The chPD1 T cells secreted pro-inflammatory cytokines and lysed RMA lymphoma cells. Adoptive transfer of chPD1 T cells significantly reduced established tumours and led to tumour-free survival in lymphoma-bearing mice. When comparing chPD1 receptors containing a Dap10 or CD28 domain, both receptors induced secretion of pro-inflammatory cytokines; however, chPD1-CD28 T cells also secreted anti-inflammatory cytokines whereas chPD1-Dap10 T cells did not. Additionally, chPD1-Dap10 induced a central memory T-cell phenotype compared with chPD1-CD28, which induced an effector memory phenotype. The chPD1-Dap10 T cells also had enhanced in vivo persistence and anti-tumour efficacy compared with chPD1-CD28 T cells. Therefore, adoptive transfer of chPD1 T cells could be a novel therapy for lymphoma and inclusion of the Dap10 co-stimulatory domain in chimeric antigen receptors may induce a preferential cytokine profile and T-cell differentiation phenotype for anti-tumour therapies. © 2017 John Wiley & Sons Ltd.

Self-catalyzed photo-initiated RAFT polymerization for fabrication of fluorescent polymeric nanoparticles with aggregation-induced emission feature.

PubMed

Zeng, Guangjian; Liu, Meiying; Jiang, Ruming; Huang, Qiang; Huang, Long; Wan, Qing; Dai, Yanfeng; Wen, Yuanqing; Zhang, Xiaoyong; Wei, Yen

2018-02-01

In recent years, the fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) feature have been extensively exploited in various biomedical fields owing to their advantages, such as low toxicity, biodegradation, excellent biocompatibility, good designability and optical properties. Therefore, development of a facile, efficient and well designable strategy should be of great importance for the biomedical applications of these AIE-active FPNs. In this work, a novel method for the fabrication of AIE-active FPNs has been developed through the self-catalyzed photo-initiated reversible addition fragmentation chain transfer (RAFT) polymerization using an AIE dye containing chain transfer agent (CTA), which could initiate the RAFT polymerization under light irradiation. The results suggested that the final AIE-active FPNs (named as TPE-poly(St-PEGMA)) showed great potential for biomedical applications owing to their optical and biological properties. More importantly, the method described in the work is rather simple and effective and can be further extended to prepare many other different AIE-active FPNs owing to the good monomer adoptability of RAFT polymerization. Copyright © 2017 Elsevier B.V. All rights reserved.

The infiltration of experimentally induced lung metastases of colon carcinoma CC531 by adoptively transferred interleukin-2-activated natural killer cells in Wag rats.

PubMed

Kuppen, P J; Basse, P H; Goldfarb, R H; Van De Velde, C J; Fleuren, G J; Eggermont, A M

1994-02-15

The number of IL-2-activated natural killer (A-NK) cells reaching the tumor site in vivo may be crucial for their anti-tumor effect following adoptive immunotherapy. We investigated in a syngeneic rat model the infiltration of established lung metastases by adoptively transferred A-NK cells. The Wag rat colon carcinoma CC531 was injected via a tail vein to induce pulmonary metastases. Syngeneic A-NK cells were labeled with the fluorescent dye rhodamine (TRITC) and next injected via a tail vein in rats bearing day-12 lung tumors. The number of A-NK cells in tumor and in normal tissue per rat was counted in sections after administration of A-NK cells. At all time points tested, a significant linear relationship between the cross-section area of the tumor and the number of infiltrating cells was observed, but small tumor areas became fully infiltrated earlier than larger areas. At 24 hr after injection, approximately 10% of the injected cells were found in the tumor tissue and the average A-NK-cell-to-tumor-cell ratio was estimated to be 1:3. A-NK cells were found in the liver too, although the number of cells per mm2 tissue was low compared with the pulmonary tumor tissue. Very low numbers of A-NK cells were found in kidney, adrenal gland, spleen, and blood. We conclude that, in this syngeneic rat model, adoptively transferred A-NK cells are able to find and specifically infiltrate pulmonary metastases in a time-dependent fashion.

At the bench: adoptive cell therapy for melanoma.

PubMed

Urba, Walter J

2014-06-01

The cellular and molecular principles that furnish the foundation for ACT of melanoma and their implications for further clinical research are reviewed. The parallel advances in basic immunology, preclinical animal studies, and clinical trials over the last two decades have been integrated successfully with improvements in technology to produce an effective ACT strategy for patients with melanoma. From the initial observation that tumors could be treated effectively by the transfer of immune cells to current strategies using preconditioning with myeloablative therapy before adoptive transfer of native or genetically altered T cells, the role of preclinical animal models is discussed. The importance of the pmel transgenic mouse model in the determination of the mechanisms of lymphodepletion, the ongoing work to identify the optimal T cells for adoptive immunotherapy, and the early impact of the emerging discipline of synthetic biology are highlighted. The clinical consequences of the research described herein are reviewed in the companion manuscript. © 2014 Society for Leukocyte Biology.

Analysis of technical spin-off effects of space-related R&D by means of patent indicators

NASA Astrophysics Data System (ADS)

Schmoch, U.; Kirsch, N.; Ley, W.; Plescher, E.; Jung, K. O.

In view of increasing European activity in the field of manned space travel, intense discussion has arisen on the significance of associated spin-off effects. Alongside this predominantly political debate, however, there is also a purely pragmatic interest in transferring wherever possible the successful results from space research to other branches of industry, in order to achieve optimum exploitation of all the resources available. Until now, spin-offs from space technology have been analyzed by means of interviews conducted in the firms involved, a process harbouring a whole series of uncertainty factors. Potential spin-off fields are frequently ignored, and alleged transfers from space research often in reality stem from other sources. This survey develops an objective method of describing technology transfer based on patent indicators. The first step was to establish on line a total of some 3000 space patents filed since 1975 with destination to the European and American markets. This record is sufficient to permit an analysis of the R&D activities undertaken by the leading industrial nations in the space sector. With further assistance provided by the method of analyzing patent citations, however, it is then possible to discover spin-off effects in areas outside space technology, which are nevertheless closely related in technical terms to the basic space patents with which they are associated. In this way, it is possible to define areas which are particularly suited to adopt space technologies in earthbound applications. This method of analyzing citations, which in principle is familiar for describing technology transfer within any one technical field, has thus been successfully employed for the first time for analyzing spin-offs.

Nonlinear equation of the modes in circular slab waveguides and its application.

PubMed

Zhu, Jianxin; Zheng, Jia

2013-11-20

In this paper, circularly curved inhomogeneous waveguides are transformed into straight inhomogeneous waveguides first by a conformal mapping. Then, the differential transfer matrix method is introduced and adopted to deduce the exact dispersion relation for modes. This relation itself is complex and difficult to solve, but it can be approximated by a simpler nonlinear equation in practical applications, which is close to the exact relation and quite easy to analyze. Afterward, optimized asymptotic solutions are obtained and act as initial guesses for the following Newton's iteration. Finally, very accurate solutions are achieved in the numerical experiment.

Design and synthesis study of the thermo-sensitive poly (N-vinylpyrrolidone-b- N, N-diethylacrylamide).

PubMed

Zhang, Xiayun; Yang, Zhongduo; Xie, Dengmin; Liu, Donglei; Chen, Zhenbin; Li, Ke; Li, Zhizhong; Tichnell, Brandon; Liu, Zhen

2018-01-01

The reversible addition fragmentation chain transfer (RAFT) polymerization method was adopted here to prepare a series of thermo-sensitive copolymers, poly (N,N-diethyl- acrylamide-b-N-vinylpyrrolidone). Their structures, molecular weight distribution and temperature sensitivity performances were characterized by the nuclear magnetic resonance ( 1 HNMR), the gel permeation chromatography (GPC) and the fluorescence spectrophotometer, respectively. It has been identified that the synthesis reaction of the block copolymer was living polymerization. The thermo-sensitivity study suggested that N-vinylpyrrolidone (NVP), played a key role on the lower critical solution temperature (LCST) performance.

Optical roughness BRDF model for reverse Monte Carlo simulation of real material thermal radiation transfer.

PubMed

Su, Peiran; Eri, Qitai; Wang, Qiang

2014-04-10

Optical roughness was introduced into the bidirectional reflectance distribution function (BRDF) model to simulate the reflectance characteristics of thermal radiation. The optical roughness BRDF model stemmed from the influence of surface roughness and wavelength on the ray reflectance calculation. This model was adopted to simulate real metal emissivity. The reverse Monte Carlo method was used to display the distribution of reflectance rays. The numerical simulations showed that the optical roughness BRDF model can calculate the wavelength effect on emissivity and simulate the real metal emissivity variance with incidence angles.

Doing Knowledge Transfer: Engaging Management and Labor with Research on Employee Health and Safety

ERIC Educational Resources Information Center

Kramer, Desre M.; Cole, Donald C.; Leithwood, Kenneth

2004-01-01

In workplace health interventions, engaging management and union decision makers is considered important for the success of the project, yet little research has described the process of making this happen. A case study of a knowledge-transfer process is presented to describe the practices and processes adopted by a knowledge broker who engaged…

From a social marketing perspective: a proposed customer relationship management technology transfer model

Treesearch

Delton Alderman; Kent Nakamoto; David Briberg

2007-01-01

Technology and knowledge transfer (TKT) is practiced for a plethora of causes, ranging from AIDS prevention to manufacturing competitiveness. The number of government, university, and association TKT efforts is exhausting and fraught with problems; we know anecdotally that the adoption of technology or knowledge is minimal across all contexts. There are a myriad of...

The Practical Obstacles of Data Transfer: Why researchers still love scp

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

Nam, Hai Ah; Hill, Jason J; Parete-Koon, Suzanne T

The importance of computing facilities is heralded every six months with the announcement of the new Top500 list, showcasing the world s fastest supercomputers. Unfortu- nately, with great computing capability does not come great long-term data storage capacity, which often means users must move their data to their local site archive, to remote sites where they may be doing future computation or anal- ysis, or back to their home institution, else face the dreaded data purge that most HPC centers employ to keep utiliza- tion of large parallel filesystems low to manage performance and capacity. At HPC centers, data transfermore » is crucial to the scientific workflow and will increase in importance as computing systems grow in size. The Energy Sciences Net- work (ESnet) recently launched its fifth generation network, a 100 Gbps high-performance, unclassified national network connecting more than 40 DOE research sites to support scientific research and collaboration. Despite the tenfold increase in bandwidth to DOE research sites amenable to multiple data transfer streams and high throughput, in prac- tice, researchers often under-utilize the network and resort to painfully-slow single stream transfer methods such as scp to avoid the complexity of using multiple stream tools such as GridFTP and bbcp, and contend with frustration from the lack of consistency of available tools between sites. In this study we survey and assess the data transfer methods pro- vided at several DOE supported computing facilities, includ- ing both leadership-computing facilities, connected through ESnet. We present observed transfer rates, suggested opti- mizations, and discuss the obstacles the tools must overcome to receive wide-spread adoption over scp.« less

NY-ESO-1 antigen-reactive T cell receptors exhibit diverse therapeutic capability

PubMed Central

Sommermeyer, Daniel; Conrad, Heinke; Krönig, Holger; Gelfort, Haike; Bernhard, Helga; Uckert, Wolfgang

2013-01-01

The cancer-testis antigen NY-ESO-1 has been used as a target for different immunotherapies like vaccinations and adoptive transfer of antigen-specific cytotoxic T cells, as it is expressed in various tumor types and has limited expression in normal cells. The in vitro generation of T cells with defined antigen specificity by T cell receptor (TCR) gene transfer is an established method to create cells for immunotherapy. However, an extensive characterization of TCR which are candidates for treatment of patients is crucial for successful therapies. The TCR has to be efficiently expressed, their affinity to the desired antigen should be high enough to recognize low amounts of endogenously processed peptides on tumor cells, and the TCR should not be cross-reactive to other antigens. We characterized three NY-ESO-1 antigen-reactive cytotoxic T lymphocyte clones which were generated by different approaches of T cell priming (autologous, allogeneic), and transferred their TCR into donor T cells for more extensive evaluations. Although one TCR most efficiently bound MHC-multimers loaded with NY-ESO-1 peptide, T cells expressing this transgenic TCR were not able to recognize endogenously processed antigen. A second TCR recognized HLA-A2 independent of the bound peptide beside its much stronger recognition of NY-ESO-1 bound to HLA-A2. A third TCR displayed an intermediate but peptide-specific performance in all functional assays and, therefore, is the most promising candidate TCR for further clinical development. Our data indicate that multiple parameters of TCR gene-modified T cells have to be evaluated to identify an optimal TCR candidate for adoptive therapy. PMID:22907642

Engineered T cells for pancreatic cancer treatment

PubMed Central

Katari, Usha L; Keirnan, Jacqueline M; Worth, Anna C; Hodges, Sally E; Leen, Ann M; Fisher, William E; Vera, Juan F

2011-01-01

Objective Conventional chemotherapy and radiotherapy produce marginal survival benefits in pancreatic cancer, underscoring the need for novel therapies. The aim of this study is to develop an adoptive T cell transfer approach to target tumours expressing prostate stem cell antigen (PSCA), a tumour-associated antigen that is frequently expressed by pancreatic cancer cells. Methods Expression of PSCA on cell lines and primary tumour samples was confirmed by immunohistochemistry. Healthy donor- and patient-derived T cells were isolated, activated in vitro using CD3/CD28, and transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) targeting PSCA. The ability of these cells to kill tumour cells was analysed by chromium-51 (Cr51) release. Results Prostate stem cell antigen was expressed on >70% of the primary tumour samples screened. Activated, CAR-modified T cells could be readily generated in clinically relevant numbers and were specifically able to kill PSCA-expressing pancreatic cancer cell lines with no non-specific killing of PSCA-negative target cells, thus indicating the potential efficacy and safety of this approach. Conclusions Prostate stem cell antigen is frequently expressed on pancreatic cancer cells and can be targeted for immune-mediated destruction using CAR-modified, adoptively transferred T cells. The safety and efficacy of this approach indicate that it deserves further study and may represent a promising novel treatment for patients with pancreatic cancer. PMID:21843265

The Interaction between Regulatory T Cells and NKT Cells in the Liver: A CD1d Bridge Links Innate and Adaptive Immunity

PubMed Central

Webb, Tonya J.; Potter, James P.; Li, Zhiping

2011-01-01

Background/Aims Regulatory T cells (Tregs) and natural killer T (NKT) cells are two distinct lymphocyte subsets that independently regulate hepatic adaptive and innate immunity, respectively. In the current study, we examine the interaction between Tregs and NKT cells to understand the mechanisms of cross immune regulation by these cells. Methods The frequency and function of Tregs were evaluated in wild type and NKT cell deficient (CD1dko) mice. In vitro lymphocyte proliferation and apoptosis assays were performed with NKT cells co-cultured with Tregs. The ability of Tregs to inhibit NKT cells in vivo was examined by adoptive transfer of Tregs in a model of NKT cell mediated hepatitis. Results CD1dko mice have a significant reduction in hepatic Tregs. Although, the Tregs from CD1dko mice remain functional and can suppress conventional T cells, their ability to suppress activation induced NKT cell proliferation and to promote NKT cell apoptosis is greatly diminished. These effects are CD1d dependent and require cell to cell contact. Adoptive transfer of Tregs inhibits NKT cell-mediated liver injury. Conclusions NKT cells promote Tregs, and Tregs inhibit NKT cells in a CD1d dependent manner requiring cell to cell contact. These cross-talk immune regulations provide a linkage between innate and adaptive immunity. PMID:22073248

Dilemmas of Transfer Pricing Comparability Analysis in Manufacturing Entities. Polish-Czech Case Study

NASA Astrophysics Data System (ADS)

Sulik-Górecka, Aleksandra

2018-06-01

Modern manufacturing entities often operate in capital groups, and their role is sometimes limited to the function of cost centers. From the legal point of view, however, they are separate entities obliged to apply transfer pricing regulations. Meeting the requirements of the arm's length principle can be very difficult at this time, given the relationships and conflicts of interest in the capital group. Complexity increases in capital groups operating in different countries, due to differences in tax regulations. The main purpose of the paper is to demonstrate that the need to valuate the sale of finished goods to a manufacturing entity, which is a subject to a different tax jurisdiction, may lead to a problem of compliance with the arm's length principle. In addition, the paper proposes a methodology for comparability analysis that may be used by manufacturing entities to defend conditions of setting transfer pricing. The paper presents the different functional profiles of manufacturing entities and points out the difficulties that they may encounter when preparing the comparability analysis. It has also been noted that there are differences in transfer pricing regulations in different countries, for example by analyzing Polish and Czech regulations. The lack of uniform benchmarking legislation can cause inconsistencies in the selection of comparable data, resulting in differences in transfer pricing. The paper uses the method of legal regulation review and analysis of results of published studies concerning the scope of transfer pricing and comparability analysis. The paper also adopts a case study analysis.

LUT observations of the mass-transferring binary AI Dra

NASA Astrophysics Data System (ADS)

Liao, Wenping; Qian, Shengbang; Li, Linjia; Zhou, Xiao; Zhao, Ergang; Liu, Nianping

2016-06-01

Complete UV band light curve of the eclipsing binary AI Dra was observed with the Lunar-based Ultraviolet Telescope (LUT) in October 2014. It is very useful to adopt this continuous and uninterrupted light curve to determine physical and orbital parameters of the binary system. Photometric solutions of the spot model are obtained by using the W-D (Wilson and Devinney) method. It is confirmed that AI Dra is a semi-detached binary with secondary component filling its critical Roche lobe, which indicates that a mass transfer from the secondary component to the primary one should happen. Orbital period analysis based on all available eclipse times suggests a secular period increase and two cyclic variations. The secular period increase was interpreted by mass transfer from the secondary component to the primary one at a rate of 4.12 ×10^{-8}M_{⊙}/yr, which is in agreement with the photometric solutions. Two cyclic oscillations were due to light travel-time effect (LTTE) via the presence of two cool stellar companions in a near 2:1 mean-motion resonance. Both photometric solutions and orbital period analysis confirm that AI Dra is a mass-transferring binary, the massive primary is filling 69 % of its critical Roche lobe. After the primary evolves to fill the critical Roche lobe, the mass transfer will be reversed and the binary will evolve into a contact configuration.

Dynamic impedance compensation for wireless power transfer using conjugate power

NASA Astrophysics Data System (ADS)

Liu, Suqi; Tan, Jianping; Wen, Xue

2018-02-01

Wireless power transfer (WPT) via coupled magnetic resonances has been in development for over a decade. However, the frequency splitting phenomenon occurs in the over-coupled region. Thus, the output power of the two-coil system achieves the maximum output power at the two splitting angular frequencies, and not at the natural resonant angular frequency. According to the maximum power transfer theorem, the impedance compensation method was adopted in many WPT projects. However, it remains a challenge to achieve the maximum output power and transmission efficiency in a fixed-frequency mode. In this study, dynamic impedance compensation for WPT was presented by utilizing the compensator within a virtual three-coil WPT system. First, the circuit model was established and transfer characteristics of a system were studied by utilizing circuit theories. Second, the power superposition of the WPT system was carefully researched. When a pair of compensating coils was inserted into the transmitter loop, the conjugate power of the compensator loop was created via magnetic coupling of the two compensating coils that insert into the transmitter loop. The mechanism for dynamic impedance compensation for wireless power transfer was then provided by investigating a virtual three-coil WPT system. Finally, the experimental circuit of a virtual three-coil WPT system was designed, and experimental results are consistent with the theoretical analysis, which achieves the maximum output power and transmission efficiency.

Inflammatory impact of IFN-γ in CD8+ T cell-mediated lung injury is mediated by both Stat1-dependent and -independent pathways

PubMed Central

Ramana, Chilakamarti V.; DeBerge, Matthew P.; Kumar, Aseem; Alia, Christopher S.; Durbin, Joan E.

2015-01-01

Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8+ T cell effector functions. To isolate the specific contribution of CD8+ T cells to lung immunopathology, we utilized a nonviral murine model in which alveolar epithelial cells express an influenza antigen and injury is initiated by adoptive transfer of influenza-specific CD8+ T cells. We report that IFN-γ production by adoptively transferred influenza-specific CD8+ T cells is a significant contributor to acute lung injury following influenza antigen recognition, in isolation from its impact on viral clearance. CD8+ T cell production of IFN-γ enhanced lung epithelial cell expression of chemokines and the subsequent recruitment of inflammatory cells into the airways. Surprisingly, Stat1 deficiency in the adoptive-transfer recipients exacerbated the lung injury that was mediated by the transferred influenza-specific CD8+ T cells but was still dependent on IFN-γ production by these cells. Loss of Stat1 resulted in sustained activation of Stat3 signaling, dysregulated chemokine expression, and increased infiltration of the airways by inflammatory cells. Taken together, these data identify important roles for IFN-γ signaling and Stat1-independent IFN-γ signaling in regulating CD8+ T cell-mediated acute lung injury. This is the first study to demonstrate an anti-inflammatory effect of Stat1 on CD8+ T cell-mediated lung immunopathology without the complication of differences in viral load. PMID:25617378

Adoptive transfer of MART-1 T cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma

PubMed Central

Chodon, Thinle; Comin-Anduix, Begonya; Chmielowski, Bartosz; Koya, Richard C; Wu, Zhongqi; Auerbach, Martin; Ng, Charles; Avramis, Earl; Seja, Elizabeth; Villanueva, Arturo; McCannel, Tara A.; Ishiyama, Akira; Czernin, Johannes; Radu, Caius G.; Wang, Xiaoyan; Gjertson, David W.; Cochran, Alistair J.; Cornetta, Kenneth; Wong, Deborah J.L.; Kaplan-lefko, Paula; Hamid, Omid; Samlowski, Wolfram; Cohen, Peter A.; Daniels, Gregory A.; Mukherji, Bijay; Yang, Lili; Zack, Jerome A.; Kohn, Donald B.; Heath, James R.; Glaspy, John A.; Witte, Owen N.; Baltimore, David; Economou, James S.; Ribas, Antoni

2014-01-01

Purpose It has been demonstrated that large numbers of tumor-specific T cells for adoptive cell transfer (ACT) can be manufactured by retroviral genetic engineering of autologous peripheral blood lymphocytes and expanding them over several weeks. In mouse models, this therapy is optimized when administered with dendritic cell (DC) vaccination. We developed a short one-week manufacture protocol to determine the feasibility, safety and antitumor efficacy of this double cell therapy. Experimnetal Design A clinical trial (NCT00910650) adoptively transferring MART-1 T cell receptor (TCR) transgenic lymphocytes together with MART-1 peptide pulsed DC vaccination in HLA-A2.1 patients with metastatic melanoma. Autologous TCR transgenic cells were manufactured in 6 to 7 days using retroviral vector gene transfer, and re-infused with (n = 10) or without (n = 3) prior cryopreservation. Results 14 patients with metastatic melanoma were enrolled and nine out of 13 treated patients (69%) showed evidence of tumor regression. Peripheral blood reconstitution with MART-1-specific T cells peaked within two weeks of ACT indicating rapid in vivo expansion. Administration of freshly manufactured TCR transgenic T cells resulted in a higher persistence of MART-1-specific T cells in the blood as compared to cryopreserved. Evidence that DC vaccination could cause further in vivo expansion was only observed with ACT using non-cryopreserved T cells. Conclusion Double cell therapy with ACT of TCR engineered T cells with a very short ex vivo manipulation and DC vaccines is feasible and results in antitumor activity, but improvements are needed to maintain tumor responses. PMID:24634374

Current advances in T-cell-based cancer immunotherapy

PubMed Central

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2015-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy. PMID:25524383

The Rise of Allogeneic Natural Killer Cells As a Platform for Cancer Immunotherapy: Recent Innovations and Future Developments

PubMed Central

Veluchamy, John P.; Kok, Nina; van der Vliet, Hans J.; Verheul, Henk M. W.; de Gruijl, Tanja D.; Spanholtz, Jan

2017-01-01

Natural killer (NK) cells are critical immune effector cells in the fight against cancer. As NK cells in cancer patients are highly dysfunctional and reduced in number, adoptive transfer of large numbers of cytolytic NK cells and their potential to induce relevant antitumor responses are widely explored in cancer immunotherapy. Early studies from autologous NK cells have failed to demonstrate significant clinical benefit. In this review, the clinical benefits of adoptively transferred allogeneic NK cells in a transplant and non-transplant setting are compared and discussed in the context of relevant NK cell platforms that are being developed and optimized by various biotech industries with a special focus on augmenting NK cell functions. PMID:28620386

Current advances in T-cell-based cancer immunotherapy.

PubMed

Wang, Mingjun; Yin, Bingnan; Wang, Helen Y; Wang, Rong-Fu

2014-01-01

Cancer is a leading cause of death worldwide; due to the lack of ideal cancer biomarkers for early detection or diagnosis, most patients present with late-stage disease at the time of diagnosis, thus limiting the potential for successful treatment. Traditional cancer treatments, including surgery, chemotherapy and radiation therapy, have demonstrated very limited efficacy for patients with late-stage disease. Therefore, innovative and effective cancer treatments are urgently needed for cancer patients with late-stage and refractory disease. Cancer immunotherapy, particularly adoptive cell transfer, has shown great promise in the treatment of patients with late-stage disease, including those who are refractory to standard therapies. In this review, we will highlight recent advances and discuss future directions in adoptive cell transfer based cancer immunotherapy.

Portable oil bath for high-accuracy resistance transfer and maintenance

NASA Astrophysics Data System (ADS)

Shiota, Fuyuhiko

1999-10-01

A portable oil bath containing one standard resistor for high-accuracy resistance transfer and maintenance was developed and operated for seven years in the National Research Laboratory of Metrology. The aim of the bath is to save labor and apparatus for high-accuracy resistance transfer and maintenance by consistently keeping the standard resistor in an optimum environmental condition. The details of the prototype system, including its performance, are described together with some suggestions for a more practical bath design, which adopts the same concept.

Learning better by repetition or variation? Is transfer at odds with task specific training?

PubMed Central

Bonney, Emmanuel; Ferguson, Gillian D.; Smits-Engelsman, Bouwien C. M.

2017-01-01

Objective Transfer of motor skills is the ultimate goal of motor training in rehabilitation practice. In children with Developmental Coordination Disorder (DCD), very little is known about how skills are transferred from training situations to real life contexts. In this study we examined the influence of two types of practice on transfer of motor skills acquired in a virtual reality (VR) environment. Method One hundred and eleven children with DCD and their typically developing (TD) peers, aged 6–10 years (M = 8.0 SD = 1.0) were randomly assigned to either variable (n = 56) or repetitive practice (n = 55). Participants in the repetitive practice played the same exergame (ski slalom) twice weekly for 20 minutes, over a period of 5 weeks, while those in the variable group played 10 different games. Motor skills such as balance tasks (hopping), running and agility tasks, ball skills and functional activities were evaluated before and after 5 weeks of training. Results ANOVA repeated measures indicated that both DCD and TD children demonstrated transfer effects to real life skills with identical and non-identical elements at exactly the same rate, irrespective of the type of practice they were assigned to. Conclusion Based on these findings, we conclude that motor skills acquired in the VR environment, transfers to real world contexts in similar proportions for both TD and DCD children. The type of practice adopted does not seem to influence children’s ability to transfer skills acquired in an exergame to life situations but the number of identical elements does. PMID:28333997

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

PubMed Central

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-01-01

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses—the so-called transfer function—and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. PMID:25404136

Adoptive transfer of T regulatory cells inhibits lipopolysaccharide-induced inflammation in fetal brain tissue in a late-pregnancy preterm birth mouse model.

PubMed

Wang, Fan; Xiao, Mi; Chen, Ru-Juan; Lin, Xiao-Jie; Siddiq, Muhammad; Liu, Li

2017-02-01

To evaluate the effect of regulatory T cells (Tregs) on the inflammation resulting from lipopolysaccharide (LPS) challenge in prenatal brain tissue, Tregs isolated from pregnant mice were transferred into model mice, and the expression levels of fork head family transcription factor (Foxp3), interleukin-6 (IL-6), CD68 (a marker of microglia), and toll-like receptor 4 (TLR-4) were assessed in the fetal brain tissue. Foxp3, IL-6, and TLR-4 expression were detected by polymerase chain reaction and Western blot; CD68 expression level was detected using immunochemical analysis. Foxp3, IL-6, TLR-4, and CD68 expressions in fetal brain were significantly induced by maternal LPS administration, and the increased expression levels were markedly reduced by adoptive transfer of Tregs. Maternal LPS exposure significantly induced inflammation in perinatal brain tissue, and Tregs negatively regulated this LPS-induced inflammation. © 2016 International Federation for Cell Biology.

Alternative methods of reproduction. Effects on the child.

PubMed

Sokoloff, B Z

1987-01-01

Artificial donor insemination (DI), surrogate parenting, in vitro fertilization, and embryo transfer are alternative methods of reproduction being utilized with increasing frequency. Technological developments are being studied in detail. Because of the secrecy inherent in the families involved, there has been little written describing the emotional and psychological well-being of the participants. Significant factors, such as unlimited pregnancies per donor, lack of recordkeeping of the genetic background of each insemination, need for psychological counseling of the parents, the impact of the "family secret" of the pregnancy, and the well-being of the offspring, have not been adequately addressed. There has been little effort to make use of our experience in adoption in relation to many of these same areas. No medical guidelines or legislation exist. The inherent problems associated with these parenting methods and practices are discussed along with recommendations for improvement.

Application research of computational mass-transfer differential equation in MBR concentration field simulation.

PubMed

Li, Chunqing; Tie, Xiaobo; Liang, Kai; Ji, Chanjuan

2016-01-01

After conducting the intensive research on the distribution of fluid's velocity and biochemical reactions in the membrane bioreactor (MBR), this paper introduces the use of the mass-transfer differential equation to simulate the distribution of the chemical oxygen demand (COD) concentration in MBR membrane pool. The solutions are as follows: first, use computational fluid dynamics to establish a flow control equation model of the fluid in MBR membrane pool; second, calculate this model by adopting direct numerical simulation to get the velocity field of the fluid in membrane pool; third, combine the data of velocity field to establish mass-transfer differential equation model for the concentration field in MBR membrane pool, and use Seidel iteration method to solve the equation model; last but not least, substitute the real factory data into the velocity and concentration field model to calculate simulation results, and use visualization software Tecplot to display the results. Finally by analyzing the nephogram of COD concentration distribution, it can be found that the simulation result conforms the distribution rule of the COD's concentration in real membrane pool, and the mass-transfer phenomenon can be affected by the velocity field of the fluid in membrane pool. The simulation results of this paper have certain reference value for the design optimization of the real MBR system.

Technology transfer potential of an automated water monitoring system. [market research

NASA Technical Reports Server (NTRS)

Jamieson, W. M.; Hillman, M. E. D.; Eischen, M. A.; Stilwell, J. M.

1976-01-01

The nature and characteristics of the potential economic need (markets) for a highly integrated water quality monitoring system were investigated. The technological, institutional and marketing factors that would influence the transfer and adoption of an automated system were studied for application to public and private water supply, public and private wastewater treatment and environmental monitoring of rivers and lakes.

New Findings on New York City's Conditional Cash Transfer Program. Fast Focus. No. 18-2013

ERIC Educational Resources Information Center

Riccio, James A.

2013-01-01

The Earned Income Tax Credit (EITC) and Temporary Assistance for Needy Families (TANF) are long-standing policies that link cash assistance to low-income families to work effort. A new policy being tested in New York City adopts this "conditional cash transfer" principle and extends it to a broader set of family efforts to build their…

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

PubMed

Taylor, Jude Matthew

2017-12-15

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients. These observations suggest that during EAN in Lewis rats actively induced by immunization with peripheral nerve myelin, phagocytic macrophages originating from the resident endoneurial population may be sufficient to engage in demyelination initiated by anti-myelin antibodies in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

Transfer-Efficient Face Routing Using the Planar Graphs of Neighbors in High Density WSNs

PubMed Central

Kim, Sang-Ha

2017-01-01

Face routing has been adopted in wireless sensor networks (WSNs) where topological changes occur frequently or maintaining full network information is difficult. For message forwarding in networks, a planar graph is used to prevent looping, and because long edges are removed by planarization and the resulting planar graph is composed of short edges, and messages are forwarded along multiple nodes connected by them even though they can be forwarded directly. To solve this, face routing using information on all nodes within 2-hop range was adopted to forward messages directly to the farthest node within radio range. However, as the density of the nodes increases, network performance plunges because message transfer nodes receive and process increased node information. To deal with this problem, we propose a new face routing using the planar graphs of neighboring nodes to improve transfer efficiency. It forwards a message directly to the farthest neighbor and reduces loads and processing time by distributing network graph construction and planarization to the neighbors. It also decreases the amount of location information to be transmitted by sending information on the planar graph nodes rather than on all neighboring nodes. Simulation results show that it significantly improves transfer efficiency. PMID:29053623

Physicians’ experience adopting the electronic transfer of care communication tool: barriers and opportunities

PubMed Central

de Grood, Chloe; Eso, Katherine; Santana, Maria Jose

2015-01-01

Purpose The purpose of this study was to assess physicians’ perceptions on a newly developed electronic transfer of care (e-TOC) communication tool and identify barriers and opportunities toward its adoption. Participants and methods The study was conducted in a tertiary care teaching center as part of a randomized controlled trial assessing the efficacy of an e-TOC communication tool. The e-TOC technology was developed through iterative consultation with stakeholders. This e-TOC summary was populated by acute care physicians (AcPs) and communicated electronically to community care physicians (CcPs). The AcPs consisted of attending physicians, resident trainees, and medical students rotating through the Medical Teaching Unit. The CcPs were health care providers caring for patients discharged from hospital to the community. AcPs and CcPs completed validated surveys assessing their experience with the newly developed e-TOC tool. Free text questions were added to gather general comments from both groups of physicians. Units of analysis were individual physicians. Data from the surveys were analyzed using mixed methods. Results AcPs completed 138 linked pre- and post-rotation surveys. At post-rotation, each AcP completed an average of six e-TOC summaries, taking an average of 37 minutes per e-TOC summary. Over 100 CcPs assessed the quality of the TOC summaries, with an overall rating of 8.3 (standard deviation: 1.48; on a scale of 1–10). Thematic analyses revealed barriers and opportunities encountered by physicians toward the adoption of the e-TOC tool. While the AcPs highlighted issues with timeliness, usability, and presentation, the CcPs identified barriers accessing the web-based TOC summaries, emphasizing that the summaries were timely and the quality of information supported continuity of care. Conclusion Despite the barriers identified by both groups of physicians, the e-TOC communication tool was well received. Our experience can serve as a template for other health research teams considering the implementation of e-health technologies into health care systems. PMID:25609977

Design of ocular for optical sight with long exit pupil distance

NASA Astrophysics Data System (ADS)

Zhu, Zhongyao; Li, Yuyao; Tian, Ailing

2017-02-01

In order to solve the injury of optical sight to shooters, which is produced by recoil for using artillery or firearms, and the usage problems of shooters' eye mask, headband and gas mask, the ocular with long exit pupil distance has been designed based on optical sighting system. The optical properties and aberration characteristics of ocular with long exit pupil distance has been analyzed, the structural style with positive-positive-negative three lens groups has been put forward. According to the aberration theory and the isoplanatic image formation principle, the focal power assignment expression has been deduced by adopting analytical method. By using of optical design software ZEMAX, the ocular with long exit pupil distance has been designed, the focal length of system is 20mm, the exit pupil diameter is 4mm, the field angle is 40°, the distance of exit pupil is 41mm, and the relative eye relief is greater than 2. The design results show if this method has been adopted, the transfer functions of each field are all greater than 0.15 when the ocular with long exit pupil distance locates on 45lp/mm, which can meet the use requirements of visual optical instruments.

Cervical spine motion in manual versus Jackson table turning methods in a cadaveric global instability model.

PubMed

DiPaola, Matthew J; DiPaola, Christian P; Conrad, Bryan P; Horodyski, MaryBeth; Del Rossi, Gianluca; Sawers, Andrew; Bloch, David; Rechtine, Glenn R

2008-06-01

A study of spine biomechanics in a cadaver model. To quantify motion in multiple axes created by transfer methods from stretcher to operating table in the prone position in a cervical global instability model. Patients with an unstable cervical spine remain at high risk for further secondary injury until their spine is adequately surgically stabilized. Previous studies have revealed that collars have significant, but limited benefit in preventing cervical motion when manually transferring patients. The literature proposes multiple methods of patient transfer, although no one method has been universally adopted. To date, no study has effectively evaluated the relationship between spine motion and various patient transfer methods to an operating room table for prone positioning. A global instability was surgically created at C5-6 in 4 fresh cadavers with no history of spine pathology. All cadavers were tested both with and without a rigid cervical collar in the intact and unstable state. Three headrest permutations were evaluated Mayfield (SM USA Inc), Prone View (Dupaco, Oceanside, CA), and Foam Pillow (OSI, Union City, CA). A trained group of medical staff performed each of 2 transfer methods: the "manual" and the "Jackson table" transfer. The manual technique entailed performing a standard rotation of the supine patient on a stretcher to the prone position on the operating room table with in-line manual cervical stabilization. The "Jackson" technique involved sliding the supine patient to the Jackson table (OSI, Union City, CA) with manual in-line cervical stabilization, securing them to the table, then initiating the table's lock and turn mechanism and rotating them into a prone position. An electromagnetic tracking device captured angular motion between the C5 and C6 vertebral segments. Repeated measures statistical analysis was performed to evaluate the following conditions: collar use (2 levels), headrest (3 levels), and turning technique (2 levels). For all measures, there was significantly more cervical spine motion during manual prone positioning compared with using the Jackson table. The use of a collar provided a slight reduction in motion in all the planes of movement; however, this was only significantly different from the no collar condition in axial rotation. Differences in gross motion between the headrest type were observed in lateral bending (Foam Pillow

Implementation of Medical Information Exchange System Based on EHR Standard

PubMed Central

Han, Soon Hwa; Kim, Sang Guk; Jeong, Jun Yong; Lee, Bi Na; Choi, Myeong Seon; Kim, Il Kon; Park, Woo Sung; Ha, Kyooseob; Cho, Eunyoung; Kim, Yoon; Bae, Jae Bong

2010-01-01

Objectives To develop effective ways of sharing patients' medical information, we developed a new medical information exchange system (MIES) based on a registry server, which enabled us to exchange different types of data generated by various systems. Methods To assure that patient's medical information can be effectively exchanged under different system environments, we adopted the standardized data transfer methods and terminologies suggested by the Center for Interoperable Electronic Healthcare Record (CIEHR) of Korea in order to guarantee interoperability. Regarding information security, MIES followed the security guidelines suggested by the CIEHR of Korea. This study aimed to develop essential security systems for the implementation of online services, such as encryption of communication, server security, database security, protection against hacking, contents, and network security. Results The registry server managed information exchange as well as the registration information of the clinical document architecture (CDA) documents, and the CDA Transfer Server was used to locate and transmit the proper CDA document from the relevant repository. The CDA viewer showed the CDA documents via connection with the information systems of related hospitals. Conclusions This research chooses transfer items and defines document standards that follow CDA standards, such that exchange of CDA documents between different systems became possible through ebXML. The proposed MIES was designed as an independent central registry server model in order to guarantee the essential security of patients' medical information. PMID:21818447

Umbilical cord blood-derived natural killer cells combined with Bevacizumab for colorectal cancer treatment.

PubMed

Xu, Chen; Liu, Dongning; Chen, Zhixin; Zhuo, Fan; Sun, Huankui; Hu, Jiaping; Li, Taiyuan

2018-06-19

Colorectal cancer (CRC) is among cancers with highest incidence globally and currently ranks fourth as the leading cause of cancer-related deaths worldwide. It remains an urgent need for novel strategies in the management of patients with advanced CRC. Adoptive transfer of allogeneic natural killer (NK) cells represent an attractive option in the treatment of patients with CRC. In this study, we successfully expanded NK cells from umbilical cord blood (UCB) with membrane-bound IL-21, termed eUCB-NK cells. eUCB-NK cells efficiently lysed CRC cell lines in vitro and secreted significantly higher levels of IFN-γ, TNF-α, GM-CSF and CCL3 compared with IL-2 stimulated NK cells. Adoptive transfer of these NK cells significantly inhibited the growth of HT29 xenografts, whereas LoVo tumors were not effectively controlled with eUCB-NK cells. More NK cells inside HT29 tumors, not seen in LoVo tumors, might contribute to the differences in response to eUCB-NK cells. Combination of bevacizumab can increase extravasation of adoptively transferred NK cells into the LoVo tumors and improve the therapeutic activity of eUCB-NK cells. These results justified clinical translation of this UCB-derived NK cell-based therapeutics, either used alone or combined with bevacizumab, as a novel treatment option for patients with CRC.

Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer.

PubMed

Shrimali, Rajeev K; Yu, Zhiya; Theoret, Marc R; Chinnasamy, Dhanalakshmi; Restifo, Nicholas P; Rosenberg, Steven A

2010-08-01

Adoptive cell transfer (ACT)-based immunotherapies can mediate objective cancer regression in animal models and in up to 70% of patients with metastatic melanoma; however, it remains unclear whether the tumor vasculature impedes the egress of tumor-specific T cells, thus hindering this immunotherapy. Disruption of the proangiogenic interaction of vascular endothelial growth factor (VEGF) with its receptor (VEGFR-2) has been reported to "normalize" tumor vasculature, enhancing the efficacy of chemotherapeutic agents by increasing their delivery to the tumor intersitium. We thus sought to determine whether disrupting VEGF/VEGFR-2 signaling could enhance the effectiveness of ACT in a murine cancer model. The administration of an antibody against mouse VEGF synergized with ACT to enhance inhibition of established, vascularized, B16 melanoma (P = 0.009) and improve survival (P = 0.003). Additive effects of an antibody against VEGFR-2 in conjunction with ACT were seen in this model (P = 0.013). Anti-VEGF, but not anti-VEGFR-2, antibody significantly increased infiltration of transferred cells into the tumor. Thus, normalization of tumor vasculature through disruption of the VEGF/VEGFR-2 axis can increase extravasation of adoptively transferred T cells into the tumor and improve ACT-based immunotherapy. These studies provide a rationale for the exploration of combining antiangiogenic agents with ACT for the treatment of patients with cancer.

D Semantic Labeling of ALS Data Based on Domain Adaption by Transferring and Fusing Random Forest Models

NASA Astrophysics Data System (ADS)

Wu, J.; Yao, W.; Zhang, J.; Li, Y.

2018-04-01

Labeling 3D point cloud data with traditional supervised learning methods requires considerable labelled samples, the collection of which is cost and time expensive. This work focuses on adopting domain adaption concept to transfer existing trained random forest classifiers (based on source domain) to new data scenes (target domain), which aims at reducing the dependence of accurate 3D semantic labeling in point clouds on training samples from the new data scene. Firstly, two random forest classifiers were firstly trained with existing samples previously collected for other data. They were different from each other by using two different decision tree construction algorithms: C4.5 with information gain ratio and CART with Gini index. Secondly, four random forest classifiers adapted to the target domain are derived through transferring each tree in the source random forest models with two types of operations: structure expansion and reduction-SER and structure transfer-STRUT. Finally, points in target domain are labelled by fusing the four newly derived random forest classifiers using weights of evidence based fusion model. To validate our method, experimental analysis was conducted using 3 datasets: one is used as the source domain data (Vaihingen data for 3D Semantic Labelling); another two are used as the target domain data from two cities in China (Jinmen city and Dunhuang city). Overall accuracies of 85.5 % and 83.3 % for 3D labelling were achieved for Jinmen city and Dunhuang city data respectively, with only 1/3 newly labelled samples compared to the cases without domain adaption.

Blockade of PD-1/PD-L1 Promotes Adoptive T-Cell Immunotherapy in a Tolerogenic Environment

PubMed Central

Kenna, Tony J.; Galea, Ryan; Large, Justin; Yagita, Hideo; Steptoe, Raymond J.

2015-01-01

Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells. PMID:25741704

Blockade of PD-1/PD-L1 promotes adoptive T-cell immunotherapy in a tolerogenic environment.

PubMed

Blake, Stephen J P; Ching, Alan L H; Kenna, Tony J; Galea, Ryan; Large, Justin; Yagita, Hideo; Steptoe, Raymond J

2015-01-01

Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells.

Tumor relapse prevented by combining adoptive T cell therapy with Salmonella typhimurium

PubMed Central

Binder, David C.; Arina, Ainhoa; Wen, Frank; Tu, Tony; Zhao, Ming; Hoffman, Robert M.; Wainwright, Derek A.; Schreiber, Hans

2016-01-01

ABSTRACT We recently reported that therapeutic vaccination with live tumor antigen-producing Salmonella typhimurium rescues dysfunctional endogenous T cell responses and eradicates long-established tumors refractory to αCTLA-4 and αPD-L1 checkpoint inhibitor blockade. Here, we show that live intravenously injected or heat-killed (HK) intratumorally injected Salmonella typhimurium, even when not producing tumor antigen, synergize with adoptive T cell therapy to eradicate tumors. These data demonstrate that the combination of adoptive T cell transfer with the injection of live or dead Salmonella typhimurium is a promising approach for cancer treatment. PMID:27471609

Identification and characterization of B cell precursors in rat lymphoid tissues. I. Adoptive transfer assays for precursors of TI-1, TI-2, and TD antigen-reactive B cells.

PubMed

Whalen, B J; Goldschneider, I

1993-10-01

Quantitative adoptive transfer assays were developed to detect the precursors of TI-1, TI-2, and TD antigen-reactive B cells in rat lymphoid tissues. Studies on the immune responses in normal and athymic nude rats validate the use of TNP-lipopolysaccharide as a TI-1 antigen, TNP-Ficoll as a TI-2 antigen, and SRBC as a TD antigen in rats. The precursors to these immunologically competent B cells are detected, following transfer into irradiated histocompatible recipients, by their ability to generate expanded populations of antigen-reactive B cells capable of mounting antibody responses (splenic IgM plaque-forming cells) to these antigens. Maximal numbers of antigen-reactive B cells emerge in antigenically naive rats after an interval of 7-12 days following transfer of donor lymphoid cells and decline rapidly thereafter. The delayed responses in adoptive recipients reconstituted with spleen cells are proportional to the numbers of spleen cells transferred and are shown to be primarily donor derived using histocompatible Ig kappa chain alloantigen disparate rat strain combinations. The precursors of TI-1, TI-2, and TD antigen-reactive B cells are present in both donor spleen and bone marrow. However, precursor cells to TI-1 and TD antigens are largely absent from donor lymph node cells, whereas precursors to the TI-2 antigen are as prevalent in donor lymph node as in donor spleen. These results support the hypothesis that newly formed virginal B cells represent transient populations of precursor cells that undergo further proliferation and differentiation in the spleen before acquiring immunological competence. The results also suggest that the precursors of TI-2 antigen-reactive B cells differ developmentally from those of TI-1 and TD antigen-reactive B cells, and that the antigen-reactive progeny of these precursors require additional stimulation in order to join the pool of long-lived peripheral B cells.

Broad spectrum antibiotic enrofloxacin modulates contact sensitivity through gut microbiota in a murine model.

PubMed

Strzępa, Anna; Majewska-Szczepanik, Monika; Lobo, Francis M; Wen, Li; Szczepanik, Marian

2017-07-01

Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. Oral treatment with enrofloxacin suppresses CS and production of anti-trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αβ + CD4 + CD25 + FoxP3 + Treg, CD19 + B220 + CD5 + IL-10 + , IL-10 + Tr1, and IL-10 + TCR γδ + cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides-Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Pertussis Maternal Immunization: Narrowing the Knowledge Gaps on the Duration of Transferred Protective Immunity and on Vaccination Frequency

PubMed Central

Gaillard, María Emilia; Bottero, Daniela; Zurita, María Eugenia; Carriquiriborde, Francisco; Martin Aispuro, Pablo; Bartel, Erika; Sabater-Martínez, David; Bravo, María Sol; Castuma, Celina; Hozbor, Daniela Flavia

2017-01-01

Maternal safety through pertussis vaccination and subsequent maternal–fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP) vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4–5 logs, p < 0.001) in the colony-forming-units recovered from the lungs of 16-week-old offspring. Moreover, maternal-vaccination-acquired immunity from the first pregnancy still conferred protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results—though admittedly not necessarily immediately extrapolatable to humans—nevertheless enabled us to test hypotheses under controlled conditions through detailed sampling and data collection. These findings will hopefully refine hypotheses that can then be validated in subsequent human studies. PMID:28932228

Immunotherapy for Cervical Cancer

Cancer.gov

In an early phase NCI clinical trial, two patients with metastatic cervical cancer had a complete disappearance of their tumors after receiving treatment with a form of immunotherapy called adoptive cell transfer.

Adoptive cell therapy: genetic modification to redirect effector cell specificity.

PubMed

Morgan, Richard A; Dudley, Mark E; Rosenberg, Steven A

2010-01-01

Building on the principals that the adoptive transfer of T cells can lead to the regression of established tumors in humans, investigators are now further manipulating these cells using genetic engineering. Two decades of human gene transfer experiments have resulted in the translation of laboratory technology into robust clinical applications. The purpose of this review is to give the reader an introduction to the 2 major approaches being developed to redirect effector T-cell specificity. Primary human T cells can be engineered to express exogenous T-cell receptors or chimeric antigen receptors directed against multiple human tumor antigens. Initial clinical trial results have demonstrated that both T-cell receptor- and chimeric antigen receptor-engineered T cells can be administered to cancer patients and mediate tumor regression.

The art of successful implementation of psychosocial interventions in residential dementia care: a systematic review of the literature based on the RE-AIM framework.

PubMed

Boersma, Petra; van Weert, Julia C M; Lakerveld, Jeroen; Dröes, Rose-Marie

2015-01-01

In the past decades many psychosocial interventions for elderly people with dementia have been developed and implemented. Relatively little research has been done on the extent to which these interventions were implemented in the daily care. The aim of this study was to obtain insight into strategies for successful implementation of psychosocial interventions in the daily residential dementia care. Using a modified RE-AIM framework, the indicators that are considered important for effective and sustainable implementation were defined. A systematic literature search was undertaken in PubMed, PsycINFO, and Cinahl, followed by a hand search for key papers. The included publications were mapped based on the dimensions of the RE-AIM framework: Reach, Effectiveness, Adoption, Implementation, and Maintenance. Fifty-four papers met the inclusion criteria and described various psychosocial interventions. A distinction was made between studies that used one and studies that used multiple implementation strategies. This review shows that to improve their knowledge, caregivers needed at least multiple implementation strategies, only education is not enough. For increasing a more person-centered attitude, different types of knowledge transfer can be effective. Little consideration is given to the adoption of the method by caregivers and to the long-term sustainability (maintenance). This review shows that in order to successfully implement a psychosocial method the use of multiple implementation strategies is recommended. To ensure sustainability of a psychosocial care method in daily nursing home care, innovators as well as researchers should specifically pay attention to the dimensions Adoption, Implementation, and Maintenance of the RE-AIM implementation framework.

Knowledge Transfer between SMEs and Higher Education Institutions: Differences between Universities and Colleges of Higher Education in the Netherlands

ERIC Educational Resources Information Center

Delfmann, Heike; Koster, Sierdjan

2012-01-01

Knowledge transfer (KT) between higher education institutions (HEIs) and businesses is seen as a key element of innovation in knowledge-driven economies: HEIs generate knowledge that can be adopted in the regional economy. This process of valorization has been studied extensively, mainly with a focus on universities. In the Netherlands, there is a…

The Role of Community Sports Coaches in Creating Optimal Social Conditions for Life Skill Development and Transferability--A Salutogenic Perspective

ERIC Educational Resources Information Center

Super, Sabina; Verkooijen, Kirsten; Koelen, Maria

2018-01-01

Sport is widely recognised as having the potential to enhance the personal development of socially vulnerable youth, yet there is very limited knowledge on how community sports coaches can create optimal social conditions for life skill development and transferability. We adopt a salutogenic approach in order to study whether and how community…

Polysaccharides derived from Ganoderma lucidum fungus mycelia ameliorate indomethacin-induced small intestinal injury via induction of GM-CSF from macrophages.

PubMed

Nagai, Kenta; Ueno, Yoshitaka; Tanaka, Shinji; Hayashi, Ryohei; Shinagawa, Kei; Chayama, Kazuaki

2017-10-01

Non-steroidal anti-inflammatory drugs often cause ulcers in the human small intestine, but few effective agents exist to treat such injury. Ganoderma lucidum Karst, also known as "Reishi" or "Lingzhi", is a mushroom. We previously reported that a water-soluble extract from G. lucidum fungus mycelia (MAK) has anti-inflammatory effects in murine colitis induced by trinitrobenzene sulfonic acid, and induction of granulocyte macrophage colony-stimulating factor (GM-CSF) by MAK may provide anti-inflammatory effects. However, its effects on indomethacin-induced small intestinal injuries are unknown. The present study investigated the preventative effects of MAK via immunological function and the polysaccharides from MAK on indomethacin-induced ileitis in mice. Peritoneal macrophages (PMs) were stimulated in vitro with MAK and adoptively transferred to C57BL/6 mice intraperitoneally, which were then given indomethacin. Intestinal inflammation was evaluated after 24h. We performed in vivo antibody blockade to investigate the preventive role of GM-CSF, which derived from PMs stimulated with MAK. We then used PMs stimulated with MAK pre-treated by pectinase in an adoptive transfer assay to determine the preventive role of polysaccharides. Indomethacin-induced small intestinal injury was inhibited by adoptive transfer of PMs stimulated in vitro with MAK. In this transfer model, pre-treatment with anti-GM-CSF antibody but not with control antibody reversed the improvement of small intestinal inflammation by indomethacin. Pectinase pretreatment impaired the anti-inflammatory effect of MAK. PMs stimulated by MAK appear to contribute to the anti-inflammatory response through GM-CSF in small intestinal injury induced by indomethacin. The polysaccharides may be the components that elicit the anti-inflammatory effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Constant-current control method of multi-function electromagnetic transmitter.

PubMed

Xue, Kaichang; Zhou, Fengdao; Wang, Shuang; Lin, Jun

2015-02-01

Based on the requirements of controlled source audio-frequency magnetotelluric, DC resistivity, and induced polarization, a constant-current control method is proposed. Using the required current waveforms in prospecting as a standard, the causes of current waveform distortion and current waveform distortion's effects on prospecting are analyzed. A cascaded topology is adopted to achieve 40 kW constant-current transmitter. The responsive speed and precision are analyzed. According to the power circuit of the transmitting system, the circuit structure of the pulse width modulation (PWM) constant-current controller is designed. After establishing the power circuit model of the transmitting system and the PWM constant-current controller model, analyzing the influence of ripple current, and designing an open-loop transfer function according to the amplitude-frequency characteristic curves, the parameters of the PWM constant-current controller are determined. The open-loop transfer function indicates that the loop gain is no less than 28 dB below 160 Hz, which assures the responsive speed of the transmitting system; the phase margin is 45°, which assures the stabilization of the transmitting system. Experimental results verify that the proposed constant-current control method can keep the control error below 4% and can effectively suppress load change caused by the capacitance of earth load.

Constant-current control method of multi-function electromagnetic transmitter

NASA Astrophysics Data System (ADS)

Xue, Kaichang; Zhou, Fengdao; Wang, Shuang; Lin, Jun

2015-02-01

Based on the requirements of controlled source audio-frequency magnetotelluric, DC resistivity, and induced polarization, a constant-current control method is proposed. Using the required current waveforms in prospecting as a standard, the causes of current waveform distortion and current waveform distortion's effects on prospecting are analyzed. A cascaded topology is adopted to achieve 40 kW constant-current transmitter. The responsive speed and precision are analyzed. According to the power circuit of the transmitting system, the circuit structure of the pulse width modulation (PWM) constant-current controller is designed. After establishing the power circuit model of the transmitting system and the PWM constant-current controller model, analyzing the influence of ripple current, and designing an open-loop transfer function according to the amplitude-frequency characteristic curves, the parameters of the PWM constant-current controller are determined. The open-loop transfer function indicates that the loop gain is no less than 28 dB below 160 Hz, which assures the responsive speed of the transmitting system; the phase margin is 45°, which assures the stabilization of the transmitting system. Experimental results verify that the proposed constant-current control method can keep the control error below 4% and can effectively suppress load change caused by the capacitance of earth load.

[Magnetic field numerical calculation and analysis for magnetic coupling of centrifugal blood pump for extracorporeal circulation].

PubMed

Hu, Zhaoyan; Lu, Lijun; Zhang, Tianyi; Chen, Zhenglong; Zhang, Tao

2013-12-01

This paper mainly studies the driving system of centrifugal blood pump for extracorporeal circulation, with the core being disc magnetic coupling. Structure parameters of disc magnetic coupling are related to the ability of transferring magnetic torque. Therefore, it is necessary to carry out disc magnetic coupling permanent magnet pole number (n), air gap length (L(g)), permanent magnet thickness (L(m)), permanent magnet body inside diameter (R(i)) and outside diameter (R(o)), etc. thoroughly. This paper adopts the three-dimensional static magnetic field edge element method of Ansys for numerical calculation, and analyses the relations of magnetic coupling each parameter to transmission magnetic torque. It provides a good theory basis and calculation method for further optimization of the disc magnetic coupling.

Immunotherapies: Exploiting the Immune System for Cancer Treatment

PubMed Central

Cato, Caleb; Geiger, Joseph; Henry, Denise; Hernandez, Jennifer; Kaur, Preet; Teskey, Garrett; Tran, Andrew

2018-01-01

Cancer is a condition that has plagued humanity for thousands of years, with the first depictions dating back to ancient Egyptian times. However, not until recent decades have biological therapeutics been developed and refined enough to safely and effectively combat cancer. Three unique immunotherapies have gained traction in recent decades: adoptive T cell transfer, checkpoint inhibitors, and bivalent antibodies. Each has led to clinically approved therapies, as well as to therapies in preclinical and ongoing clinical trials. In this review, we outline the method by which these 3 immunotherapies function as well as any major immunotherapeutic drugs developed for treating a variety of cancers. PMID:29725606

A national survey of organizational transfer practices in chronic disease prevention in Canada.

PubMed

Hanusaik, Nancy; O'Loughlin, Jennifer L; Paradis, Gilles; Kishchuk, Natalie

2011-08-01

Underuse of best practices in chronic disease prevention (CDP) represents missed opportunities to promote healthy living and prevent chronic disease. Better understanding of how CDP programs, practices and policies (PPPs) are transferred from 'resource' organizations that develop them to 'user' organizations that implement them is crucial. The objectives of this work were to develop psychometrically sound measures of transfer practices occurring within resource organizations; describe the use of these transfer practices and identify correlates of the transfer process. Cross-sectional data were collected in structured telephone interviews with the person most knowledgeable about PPP transfer in 77 Canadian organizations that develop PPPs. Independent correlates of transfer were identified using multiple linear regression. The transfer practices most commonly used included: identification of barriers to PPP adoption/implementation, tailoring transfer strategies and designing a transfer plan. Skill at planning/implementing transfer, external sources of funding specifically allocated for transfer, type of resource organization, attitude toward process of collaboration and user-centeredness were all positively associated with the transfer process. These factors represent possible targets for interventions to improve transfer of CDP PPPs.

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors.

PubMed

Grenier, Jeremy M; Yeung, Stephen T; Qiu, Zhijuan; Jellison, Evan R; Khanna, Kamal M

2017-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1 b , on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1 b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection.

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors

PubMed Central

Grenier, Jeremy M.; Yeung, Stephen T.; Qiu, Zhijuan; Jellison, Evan R.; Khanna, Kamal M.

2018-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1b, on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection. PMID:29387061

Optical model potentials for 6He+64Zn from 63Cu(7Li,6He)64Zn reactions

NASA Astrophysics Data System (ADS)

Yang, L.; Lin, C. J.; Jia, H. M.; Wang, D. X.; Sun, L. J.; Ma, N. R.; Yang, F.; Wu, Z. D.; Xu, X. X.; Zhang, H. Q.; Liu, Z. H.; Bao, P. F.

2017-03-01

Angular distributions of the transfer reaction 63Cu(7Li,6He )64Zn were measured at Elab(7Li) =12.67 , 15.21, 16.33, 23.30, 27.30, and 30.96 MeV. With the interaction potentials of the entrance channel 7Li+63Cu obtained from elastic scattering data as input, the optical potentials of the halo nuclear system 6He+64Zn in the exit channel were extracted by fitting the experimental data with the distorted-wave Born approximation (DWBA) and coupled reaction channels (CRC) methods, respectively. The results show that the threshold anomaly presents in the weakly bound system of 7Li+63Cu and the dispersion relation can be adopted to describe the connection between the real and imaginary potentials, while both the real and imaginary potentials nearly keep constant within the researched energy region for the halo system of 6He+64Zn . Moreover, calculations by the potentials extracted from the CRC method can reproduce the experimental elastic scattering of the 6He+64Zn system rather well, but those by the potentials from the DWBA method cannot, where the couplings between 7Li and 6He are absent. This work verifies the validity of the transfer method in the medium-mass target region and lays a solid foundation for the further study of optical potentials for exotic nuclear systems.

Numerical investigation of heat transfer in parallel channels with water at supercritical pressure.

PubMed

Shitsi, Edward; Kofi Debrah, Seth; Yao Agbodemegbe, Vincent; Ampomah-Amoako, Emmanuel

2017-11-01

Thermal phenomena such as heat transfer enhancement, heat transfer deterioration, and flow instability observed at supercritical pressures as a result of fluid property variations have the potential to affect the safety of design and operation of Supercritical Water-cooled Reactor SCWR, and also challenge the capabilities of both heat transfer correlations and Computational Fluid Dynamics CFD physical models. These phenomena observed at supercritical pressures need to be thoroughly investigated. An experimental study was carried out by Xi to investigate flow instability in parallel channels at supercritical pressures under different mass flow rates, pressures, and axial power shapes. Experimental data on flow instability at inlet of the heated channels were obtained but no heat transfer data along the axial length was obtained. This numerical study used 3D numerical tool STAR-CCM+ to investigate heat transfer at supercritical pressures along the axial lengths of the parallel channels with water ahead of experimental data. Homogeneous axial power shape HAPS was adopted and the heating powers adopted in this work were below the experimental threshold heating powers obtained for HAPS by Xi. The results show that the Fluid Centre-line Temperature FCLT increased linearly below and above the PCT region, but flattened at the PCT region for all the system parameters considered. The inlet temperature, heating power, pressure, gravity and mass flow rate have effects on WT (wall temperature) values in the NHT (normal heat transfer), EHT (enhanced heat transfer), DHT (deteriorated heat transfer) and recovery from DHT regions. While variation of all other system parameters in the EHT and PCT regions showed no significant difference in the WT and FCLT values respectively, the WT and FCLT values respectively increased with pressure in these regions. For most of the system parameters considered, the FCLT and WT values obtained in the two channels were nearly the same. The numerical study was not quantitatively compared with experimental data along the axial lengths of the parallel channels, but it was observed that the numerical tool STAR-CCM+ adopted was able to capture the trends for NHT, EHT, DHT and recovery from DHT regions. The heating powers used for the various simulations were below the experimentally observed threshold heating powers, but heat transfer deterioration HTD was observed, confirming the previous finding that HTD could occur before the occurrence of unstable behavior at supercritical pressures. For purposes of comparing the results of numerical simulations with experimental data, the heat transfer data on temperature oscillations obtained at the outlet of the heated channels and instability boundary results obtained at the inlet of the heated channels were compared. The numerical results obtained quite well agree with the experimental data. This work calls for provision of experimental data on heat transfer in parallel channels at supercritical pressures for validation of similar numerical studies.

MHD natural convection of hybrid nanofluid in an open wavy cavity

NASA Astrophysics Data System (ADS)

Ashorynejad, Hamid Reza; Shahriari, Alireza

2018-06-01

In this paper, natural convection heat transfer of Al2O3-Cu/water hybrid nanofluid within open wavy cavity and subjected to a uniform magnetic field is examined by adopting the lattice Boltzmann method scheme. The left wavy wall is heated sinusoidal, while the right wall is open and maintained to the ambient conditions. The top and the bottom horizontal walls are smooth and insulated against heat and mass. The influence of solid volume fraction of nanoparticles (φ = 0, 0.02, 0.04), Rayleigh number (Ra = 103, 104, 105), Hartmann number (Ha = 0, 30, 60, 90) and phase deviation (Φ = 0, π/4, π/2, 3π/4) are investigated on flow and heat transfer fields. The results proved that the Nusselt number decreases with the increase of the Hartmann number, but it increases by the increment of Rayleigh number and nanoparticle volume fraction. The magnetic field rises or falls the effect produced by the presence of nanoparticles with respect to Rayleigh number. At Ra = 103, the effect of the raising phase deviation on heat transfer is erratic while it has a positive role in the improvement of nanoparticles effect at Ra = 105.

Mechanical Flexibility of Zinc Oxide Thin-Film Transistors Prepared by Transfer Printing Method

NASA Astrophysics Data System (ADS)

Eun, K. T.; Hwang, W. J.; Sharma, B. K.; Ahn, J. H.; Lee, Y. K.; Choa, S. H.

In the present study, we demonstrate the performance of Zinc oxide thin film transistors (ZnO TFTs) array subjected to the strain under high bending test and the reliability of TFTs was confirmed for the bending fatigue test of 2000 cycles. Initially, ZnO TFTs were fabricated on Si substrate and subsequently transferred on flexible PET substrate using transfer printing process. It was observed that when the bending radius reached ≥ 11 mm then cracks start to initiate first at SiO2 bridges, acting as interconnecting layers among individual TFT. Whatever the strain is applied to the devices, it is almost equivalently adopted by the SiO2 bridges, as they are relatively weak compared to rest of the part. The initial cracking of destructed SiO2 bridge leads to the secondary cracks to the ITO electrodes upon further increment of bending radius. Numerical simulation suggested that the strain of SiO2 layer reached to fracture level of 0.55% which was concentrated at the edge of SiO2 bridge layer. It also suggests that the round shape of SiO2 bridge can be more fruitful to compensate the stress concentration and to prevent failure of device.

Is it time for a paradigm shift in understanding embryo selection?

PubMed

Gleicher, Norbert; Kushnir, Vitaly A; Barad, David H

2015-01-11

Embryo selection has been an integral feature of in vitro fertilization (IVF) almost since its inception. Since the advent of extended blastocyst stage embryo culture, and especially with increasing popularity of elective single embryo transfer (eSET), the concept of embryo selection has increasingly become a mainstay of routine IVF. We here, however, argue that embryo selection via blastocyst stage embryo transfer (BSET), as currently practiced, at best improves IVF outcomes only for a small minority of patients undergoing IVF cycles. For a large majority BSET is either ineffective or, indeed, may actually be harmful by decreasing IVF pregnancy chances. Overall, only a small minority of patients, thus, benefit from prolonged embryo culture, while BSET, as a tool to enhance IVF outcomes, is increasingly utilized as routine care in IVF for all patients. Since newer methods of embryo selection, like preimplantation genetic screening (PGS) and closed system embryo incubation with time-lapse photography are practically dependent on BSET, these concepts of embryo selection, currently increasingly adopted in mainstream IVF, require reconsideration. They, automatically, transfer the downsides of BSET, including decreases in IVF pregnancy chances in some patients, to these new procedures, and in addition raise serious questions about cost-effectiveness.

Lattice Boltzmann simulation of the gas-solid adsorption process in reconstructed random porous media.

PubMed

Zhou, L; Qu, Z G; Ding, T; Miao, J Y

2016-04-01

The gas-solid adsorption process in reconstructed random porous media is numerically studied with the lattice Boltzmann (LB) method at the pore scale with consideration of interparticle, interfacial, and intraparticle mass transfer performances. Adsorbent structures are reconstructed in two dimensions by employing the quartet structure generation set approach. To implement boundary conditions accurately, all the porous interfacial nodes are recognized and classified into 14 types using a proposed universal program called the boundary recognition and classification program. The multiple-relaxation-time LB model and single-relaxation-time LB model are adopted to simulate flow and mass transport, respectively. The interparticle, interfacial, and intraparticle mass transfer capacities are evaluated with the permeability factor and interparticle transfer coefficient, Langmuir adsorption kinetics, and the solid diffusion model, respectively. Adsorption processes are performed in two groups of adsorbent media with different porosities and particle sizes. External and internal mass transfer resistances govern the adsorption system. A large porosity leads to an early time for adsorption equilibrium because of the controlling factor of external resistance. External and internal resistances are dominant at small and large particle sizes, respectively. Particle size, under which the total resistance is minimum, ranges from 3 to 7 μm with the preset parameters. Pore-scale simulation clearly explains the effect of both external and internal mass transfer resistances. The present paper provides both theoretical and practical guidance for the design and optimization of adsorption systems.

Lattice Boltzmann simulation of the gas-solid adsorption process in reconstructed random porous media

NASA Astrophysics Data System (ADS)

Zhou, L.; Qu, Z. G.; Ding, T.; Miao, J. Y.

2016-04-01

The gas-solid adsorption process in reconstructed random porous media is numerically studied with the lattice Boltzmann (LB) method at the pore scale with consideration of interparticle, interfacial, and intraparticle mass transfer performances. Adsorbent structures are reconstructed in two dimensions by employing the quartet structure generation set approach. To implement boundary conditions accurately, all the porous interfacial nodes are recognized and classified into 14 types using a proposed universal program called the boundary recognition and classification program. The multiple-relaxation-time LB model and single-relaxation-time LB model are adopted to simulate flow and mass transport, respectively. The interparticle, interfacial, and intraparticle mass transfer capacities are evaluated with the permeability factor and interparticle transfer coefficient, Langmuir adsorption kinetics, and the solid diffusion model, respectively. Adsorption processes are performed in two groups of adsorbent media with different porosities and particle sizes. External and internal mass transfer resistances govern the adsorption system. A large porosity leads to an early time for adsorption equilibrium because of the controlling factor of external resistance. External and internal resistances are dominant at small and large particle sizes, respectively. Particle size, under which the total resistance is minimum, ranges from 3 to 7 μm with the preset parameters. Pore-scale simulation clearly explains the effect of both external and internal mass transfer resistances. The present paper provides both theoretical and practical guidance for the design and optimization of adsorption systems.

Studying NK cell responses to ectromelia virus infections in mice.

PubMed

Fang, Min; Sigal, Luis

2010-01-01

Here we describe methods for the in vivo study of antiviral NK cell responses using the mouse Orthopoxvirus ectromelia virus as a model, the agent of mousepox. The methods include those specific for the preparation and use of ectromelia virus such as the production of virus stocks in tissue culture and in live mice, the purification of virus stocks, the titration of virus stocks and virus loads in organs, and the infection of mice. The chapter also includes methods for the specific study of NK cell responses in infected mice such as the preparation of organs (lymph nodes, spleen, and liver) for analysis, the study of NK cell responses by flow cytometry, the adoptive transfer of NK cells, the measurement of NK cell cytolytic activity ex vivo and in vivo, and the determination of NK cell proliferation by bromodeoxyuridine loading or by dilution of carboxyfluorescein diacetate succinimidyl ester (CFSE).

Analysis of temperature rise for piezoelectric transformer using finite-element method.

PubMed

Joo, Hyun-Woo; Lee, Chang-Hwan; Rho, Jong-Seok; Jung, Hyun-Kyo

2006-08-01

Analysis of heat problem and temperature field of a piezoelectric transformer, operated at steady-state conditions, is described. The resonance frequency of the transformer is calculated from impedance and electrical gain analysis using a finite-element method. Mechanical displacement and electric potential of the transformer at the calculated resonance frequency are used to calculate the loss distribution of the transformer. Temperature distribution using discretized heat transfer equation is calculated from the obtained losses of the transformer. Properties of the piezoelectric material, dependent on the temperature field, are measured to recalculate the losses, temperature distribution, and new resonance characteristics of the transformer. Iterative method is adopted to recalculate the losses and resonance frequency due to the changes of the material constants from temperature increase. Computed temperature distributions and new resonance characteristics of the transformer at steady-state temperature are verified by comparison with experimental results.

A seesaw-type approach for enhancing nonlinear energy harvesting

NASA Astrophysics Data System (ADS)

Deng, Huaxia; Wang, Zhemin; Du, Yu; Zhang, Jin; Ma, Mengchao; Zhong, Xiang

2018-05-01

Harvesting sustainable mechanical energy is the ultimate objective of nonlinear energy harvesters. However, overcoming potential barriers, especially without the use of extra excitations, poses a great challenge for the development of nonlinear generators. In contrast to the existing methods, which typically modify the barrier height or utilize additional excitations, this letter proposes a seesaw-type approach to facilitate escape from potential wells by transfer of internal energy, even under low-intensity excitation. This approach is adopted in the design of a seesaw-type nonlinear piezoelectric energy harvester and the energy transfer process is analyzed by deriving expressions for the energy to reveal the working mechanism. Comparison experiments demonstrate that this approach improves energy harvesting in terms of an increase in the working frequency bandwidth by a factor of 60.14 and an increase in the maximum output voltage by a factor of 5.1. Moreover, the output power is increased by a factor of 51.3, which indicates that this approach significantly improves energy collection efficiency. This seesaw-type approach provides a welcome boost to the development of renewable energy collection methods by improving the efficiency of harvesting of low-intensity ambient mechanical energy.

Impact of Safety Training and Interventions on Training-Transfer: Targeting Migrant Construction Workers.

PubMed

Hussain, Rahat; Pedro, Akeem; Lee, Do Yeop; Pham, Hai Chien; Park, Chan Sik

2018-05-01

Despite substantial efforts to improve construction safety training, the accident rate of migrant workers is still high. One of the primary factors contributing to the inefficacy of training includes information delivery gaps during training sessions (knowledge-transfer). In addition, there is insufficient evidence that these training programs alone are effective enough to enable migrant workers to transfer their skills to jobsite (training-transfer). This research attempts to identify and evaluate additional interventions to improve the transfer of acquired knowledge to workplace. For this purpose, this study presents the first known experimental effort to assess the effect of interventions on migrant work groups in a multinational construction project in Qatar. Data analysis reveals that the adoption of training programs with the inclusion of interventions significantly improves training-transfer. Construction safety experts can leverage the findings of this study to enhance training-transfer by increasing worker's safety performance and hazard identification ability.

National Aerospace Leadership Initiative - Phase I

DTIC Science & Technology

2008-09-30

Devised and validated CFD code for operation of a micro-channel heat exchanger. The work was published at the 2008 AIAA Annual Meeting and Exposition...and (3) preparation to implement this algorithm in TURBO. Heat Transfer Capability In the short and medium term, the following plan has been adopted...to provide heat transfer capability to the TURBO code: • Incorporation of a constant wall temperature boundary condition. This capability will be

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia

PubMed Central

Paszkiewicz, Paulina J.; Fräßle, Simon P.; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C.; Riddell, Stanley R.; Busch, Dirk H.

2016-01-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies. PMID:27760047

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.

PubMed

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-12-16

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

T-cell receptor transfer into human T cells with ecotropic retroviral vectors.

PubMed

Koste, L; Beissert, T; Hoff, H; Pretsch, L; Türeci, Ö; Sahin, U

2014-05-01

Adoptive T-cell transfer for cancer immunotherapy requires genetic modification of T cells with recombinant T-cell receptors (TCRs). Amphotropic retroviral vectors (RVs) used for TCR transduction for this purpose are considered safe in principle. Despite this, TCR-coding and packaging vectors could theoretically recombine to produce replication competent vectors (RCVs), and transduced T-cell preparations must be proven free of RCV. To eliminate the need for RCV testing, we transduced human T cells with ecotropic RVs so potential RCV would be non-infectious for human cells. We show that transfection of synthetic messenger RNA encoding murine cationic amino-acid transporter 1 (mCAT-1), the receptor for murine retroviruses, enables efficient transient ecotropic transduction of human T cells. mCAT-1-dependent transduction was more efficient than amphotropic transduction performed in parallel, and preferentially targeted naive T cells. Moreover, we demonstrate that ecotropic TCR transduction results in antigen-specific restimulation of primary human T cells. Thus, ecotropic RVs represent a versatile, safe and potent tool to prepare T cells for the adoptive transfer.

Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia.

PubMed

Paszkiewicz, Paulina J; Fräßle, Simon P; Srivastava, Shivani; Sommermeyer, Daniel; Hudecek, Michael; Drexler, Ingo; Sadelain, Michel; Liu, Lingfeng; Jensen, Michael C; Riddell, Stanley R; Busch, Dirk H

2016-11-01

The adoptive transfer of T cells that have been genetically modified to express a CD19-specific chimeric antigen receptor (CAR) is effective for treating human B cell malignancies. However, the persistence of functional CD19 CAR T cells causes sustained depletion of endogenous CD19+ B cells and hypogammaglobulinemia. Thus, there is a need for a mechanism to ablate transferred T cells after tumor eradication is complete to allow recovery of normal B cells. Previously, we developed a truncated version of the epidermal growth factor receptor (EGFRt) that is coexpressed with the CAR on the T cell surface. Here, we show that targeting EGFRt with the IgG1 monoclonal antibody cetuximab eliminates CD19 CAR T cells both early and late after adoptive transfer in mice, resulting in complete and permanent recovery of normal functional B cells, without tumor relapse. EGFRt can be incorporated into many clinical applications to regulate the survival of gene-engineered cells. These results support the concept that EGFRt represents a promising approach to improve safety of cell-based therapies.

Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells

PubMed Central

Herrmann, Andreas; Kortylewski, Marcin; Kujawski, Maciej; Zhang, Chunyan; Reckamp, Karen; Armstrong, Brian; Wang, Lin; Kowolik, Claudia; Deng, Jiehui; Robert, Figlin; Yu, Hua

2010-01-01

Improving effector T cell functions is highly desirable for preventive or therapeutic interventions of diverse diseases. Stat3 in the myeloid compartment constrains Th-1 type immunity, dampening natural and induced antitumor immune responses. We have recently developed an in vivo siRNA delivery platform by conjugating a TLR9 agonist with siRNA that efficiently targets myeloid and B cells. Here we show that either ablating the Stat3 alleles in the myeloid compartment and B cells combined with CpG triggering or administrating the CpG-Stat3siRNA conjugates drastically augments effector functions of adoptively transferred CD8+ T cells. Specifically, we demonstrate that both approaches are capable of increasing dendritic cell and CD8+ T cell engagement in tumor draining lymph nodes. Furthermore, both approaches can significantly activate the transferred CD8+ T cells in vivo, upregulating effector molecules such as perforin, granzyme B and IFN-γ. Intravital multiphoton microscopy reveals that Stat3 silencing combined with CpG triggering greatly increases killing activity and tumor infiltration of transferred T cells. These results suggest the use of CpG-Stat3siRNA, and possibly other Stat3 inhibitors, as a potent adjuvant to improve T cell therapies. PMID:20841481

Non-contributory social transfer programs in developing countries: A new dataset and research agenda.

PubMed

Dodlova, Marina; Giolbas, Anna; Lay, Jann

2018-02-01

Social transfer programs in developing countries are designed to contribute to poverty reduction by increasing the income of the poor in order to ensure minimal living standards. In addition, social transfers provide a safety net for the vulnerable, who are typically not covered by contributory social security. The question of how effective such programs are in achieving these aims has been the subject of numerous impact evaluations. However, the optimal design of such programs is still unclear. Even less is known about whether the adoption and implementation of transfer programs is really driven by poverty and neediness or whether other factors also have an influence. To investigate these and other research questions, we have developed a new dataset entitled Non-Contributory Social Transfer Programs (NSTP) in Developing Countries. One advantage of this dataset is that it traces 186 non-contributory programs from 101 countries back in time and presents them in panel form for the period up until 2015. The second advantage is that it contains all the details regarding the various programs' designs as well as information on costs and coverage in a coded format and thus facilitates both comparative quantitative and in-depth qualitative analyses. While describing the data we discuss a number of examples of how the dataset can be used to explore different issues related to social policies in developing countries. We present suggestive evidence that the adoption of social transfer programs is not based only on pro-poor motives, but rather that social policy choices differ between political regimes.

Adoptive immunotherapy for cancer.

PubMed

Ruella, Marco; Kalos, Michael

2014-01-01

Recent clinical success has underscored the potential for immunotherapy based on the adoptive cell transfer (ACT) of engineered T lymphocytes to mediate dramatic, potent, and durable clinical responses. This success has led to the broader evaluation of engineered T-lymphocyte-based adoptive cell therapy to treat a broad range of malignancies. In this review, we summarize concepts, successes, and challenges for the broader development of this promising field, focusing principally on lessons gleaned from immunological principles and clinical thought. We present ACT in the context of integrating T-cell and tumor biology and the broader systemic immune response. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of government actions on technological innovation for SO2 control.

PubMed

Taylor, Margaret R; Rubin, Edward S; Hounshell, David A

2003-10-15

The relationship between government actions and innovation in environmental control technology is important for the design of cost-effective policies to achieve environmental goals. This paper examines such relationships for the case of sulfur dioxide control technology for U.S. coal-fired power plants. The study employs several complementary research methods, including analyses of key government actions, technology patenting activity, technology performance and cost trends, knowledge transfer activities, and expert elicitations. Our results indicate that government regulation appears to be a greater stimulus to inventive activity than government-sponsored research support alone, and that the anticipation of regulation also spurs inventive activity. Regulatory stringency focuses this activity along particular technical pathways and is a key factor in creating markets for environmental technologies. We also find that with greater technology adoption, both new and existing systems experience notable efficiency improvements and capital cost reductions. The important role of government in fostering knowledge transfer via technical conferences and other measures is also seen as an important factor in promoting environmental technology innovation.

Geological occurrence response to trace elemental migration in coal liquefaction based on SPSS: take no. 11 coalbed in Antaibao mine for example

NASA Astrophysics Data System (ADS)

Xia, Xiaohong; Qin, Yong; Yang, Weifeng

2013-03-01

Coal liquefaction is an adoptable method to transfer the solid fossil energy into liquid oil in large scale, but the dirty material in which will migrate to different step of liquefaction. The migration rule of some trace elements is response to the react activity of macerals in coal and the geological occurrence of the element nature of itself. In this paper, from the SPSS data correlation analysis and hierarchical clustering dendrogram about the trace elements with macerals respond to coal liquefaction yield, it shows the trace elements in No.11 Antaibao coal seam originated from some of lithophile and sulphophle elements. Correlation coefficient between liquefaction yield of three organic macerals and migration of the elements in liquefaction residue indicated that the lithophile are easy to transfer to residue, while sulphophle are apt to in the liquid products. The activated macerals are response to sulphophle trace elements. The conclusion is useful to the coal blending and environmental effects on coal direct liquefaction.

Fabrication of flexible gold nanorods polymer metafilm via phase transfer method as SERS substrate for detecting food contaminants.

PubMed

Yang, Nan; You, Ting-Ting; Gao, Yu-Kun; Zhang, Chen-Meng; Yin, Penggang

2018-06-08

Surface enhanced Raman scattering (SERS) has been widely used in detection of food safety due to the nondestructive examination property. Here, we reported a flexible SERS film based on polymer immobilized gold nanorods polymer metafilm. Polystyrene-polyisoprene-polystyrene (SIS), a transparent and flexible along with excellent elasticity polymer was chosen as main support of gold nanorods. A simple phase transfer progress was adopted to mix the gold nanorods with polymer which can further used in most water-insoluble polymers. The SERS film performed satisfactorily while tested in a series of standard Raman probes like crystal violet (CV) and malachite green (MG). Moreover, the excellent reproducibility and elastic properties make the film promising substrates in practical detection. Hence, the MG detection on fish surface and trace thiram detection on orange pericarp were inspected with the detection result of 1 × 10-10 M and 1 × 10-6 M which below the demand of National standard of China, exactly matching the realistic application requirements.

Photoactive layered nanocomposites obtained by direct transferring of anodic TiO2 nanotubes to commodity thermoplastics

NASA Astrophysics Data System (ADS)

Sanz, Ruy; Buccheri, Maria Antonietta; Zimbone, Massimo; Scuderi, Viviana; Amiard, Guillaume; Impellizzeri, Giuliana; Romano, Lucia; Privitera, Vittorio

2017-03-01

TiO2 nanotubes demonstrated to be a versatile nanostructure for biomaterials, clean energy and water remediation applications. However, the cost of titanium and the poor mechanical properties of the nanotubes hinder their adoption at large scale. This work presents a straightforward and scalable method for transferring photoactive anodic TiO2 nanotubes from titanium foils to commodity thermoplastic polymers, polypropylene, polyethylene terephthalate, polycarbonate, and polymethylmetacrylate, allowing the reusing of the remaining titanium. The obtained flexible nanocomposites reach a maximum photonic efficiencies of 0.038% (ISO-10678:2010) representing the 93% of photonic efficiency of TiO2 nanotubes on titanium. In addition, the nanocomposites and TiO2 nanotubes on titanium present similar antibacterial properties under 1 mW cm-2 UV-A, 60% of Escherichia coli survival after 1 h of exposition. The final objective of this work is to point out main concepts and key parameters for a low-cost fabrication of a photoactive nanocomposite material.

Numerical Modeling of Fluid Flow, Heat Transfer and Arc-Melt Interaction in Tungsten Inert Gas Welding

NASA Astrophysics Data System (ADS)

Li, Linmin; Li, Baokuan; Liu, Lichao; Motoyama, Yuichi

2017-04-01

The present work develops a multi-region dynamic coupling model for fluid flow, heat transfer and arc-melt interaction in tungsten inert gas (TIG) welding using the dynamic mesh technique. The arc-weld pool unified model is developed on basis of magnetohydrodynamic (MHD) equations and the interface is tracked using the dynamic mesh method. The numerical model for arc is firstly validated by comparing the calculated temperature profiles and essential results with the former experimental data. For weld pool convection solution, the drag, Marangoni, buoyancy and electromagnetic forces are separately validated, and then taken into account. Moreover, the model considering interface deformation is adopted in a stationary TIG welding process with SUS304 stainless steel and the effect of interface deformation is investigated. The depression of weld pool center and the lifting of pool periphery are both predicted. The results show that the weld pool shape calculated with considering the interface deformation is more accurate.

Assessing the transferability of a hybrid Taguchi-objective function method to optimize image segmentation for detecting and counting cave roosting birds using terrestrial laser scanning data

NASA Astrophysics Data System (ADS)

Idrees, Mohammed Oludare; Pradhan, Biswajeet; Buchroithner, Manfred F.; Shafri, Helmi Zulhaidi Mohd; Khairunniza Bejo, Siti

2016-07-01

As far back as early 15th century during the reign of the Ming Dynasty (1368 to 1634 AD), Gomantong cave in Sabah (Malaysia) has been known as one of the largest roosting sites for wrinkle-lipped bats (Chaerephon plicata) and swiftlet birds (Aerodramus maximus and Aerodramus fuciphagus) in very large colonies. Until recently, no study has been done to quantify or estimate the colony sizes of these inhabitants in spite of the grave danger posed to this avifauna by human activities and potential habitat loss to postspeleogenetic processes. This paper evaluates the transferability of a hybrid optimization image analysis-based method developed to detect and count cave roosting birds. The method utilizes high-resolution terrestrial laser scanning intensity image. First, segmentation parameters were optimized by integrating objective function and the statistical Taguchi methods. Thereafter, the optimized parameters were used as input into the segmentation and classification processes using two images selected from Simud Hitam (lower cave) and Simud Putih (upper cave) of the Gomantong cave. The result shows that the method is capable of detecting birds (and bats) from the image for accurate population censusing. A total number of 9998 swiftlet birds were counted from the first image while 1132 comprising of both bats and birds were obtained from the second image. Furthermore, the transferability evaluation yielded overall accuracies of 0.93 and 0.94 (area under receiver operating characteristic curve) for the first and second image, respectively, with p value of <0.0001 at 95% confidence level. The findings indicate that the method is not only efficient for the detection and counting cave birds for which it was developed for but also useful for counting bats; thus, it can be adopted in any cave.

Two eras of globalization and hardwood sawtimber demand

Treesearch

William G. Luppold; Matthew S. Bumgardner

2006-01-01

In the early 1970s, the adoption of floating exchange rates resulted in more fluid transfers between international currencies and spurred increased international demand for hardwood lumber produced in the United States.

Boosting Natural Killer Cell-Based Immunotherapy with Anticancer Drugs: a Perspective.

PubMed

Cifaldi, Loredana; Locatelli, Franco; Marasco, Emiliano; Moretta, Lorenzo; Pistoia, Vito

2017-12-01

Natural killer (NK) cells efficiently recognize and kill tumor cells through several mechanisms including the expression of ligands for NK cell-activating receptors on target cells. Different clinical trials indicate that NK cell-based immunotherapy represents a promising antitumor treatment. However, tumors develop immune-evasion strategies, including downregulation of ligands for NK cell-activating receptors, that can negatively affect antitumor activity of NK cells, which either reside endogenously, or are adoptively transferred. Thus, restoration of the expression of NK cell-activating ligands on tumor cells represents a strategic therapeutic goal. As discussed here, various anticancer drugs can fulfill this task via different mechanisms. We envision that the combination of selected chemotherapeutic agents with NK cell adoptive transfer may represent a novel strategy for cancer immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adoptive Cellular Gene Therapy for the Treatment of Experimental Autoimmune Polychondritis Ear Disease.

PubMed

Zhou, Bin; Liao, Yonggan; Guo, Yunkai; Tarner, Ingo H; Liao, Chunfen; Chen, Sisi; Kermany, Mohammad Habiby; Tu, Hanjun; Zhong, Sen; Chen, Peijie

2017-01-01

In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation. © 2017 S. Karger AG, Basel.

Adoptive transfer of ex vivo expanded Vγ9Vδ2 T cells in combination with zoledronic acid inhibits cancer growth and limits osteolysis in a murine model of osteolytic breast cancer.

PubMed

Zysk, Aneta; DeNichilo, Mark O; Panagopoulos, Vasilios; Zinonos, Irene; Liapis, Vasilios; Hay, Shelley; Ingman, Wendy; Ponomarev, Vladimir; Atkins, Gerald; Findlay, David; Zannettino, Andrew; Evdokiou, Andreas

2017-02-01

Bone metastases occur in over 75% of patients with advanced breast cancer and are responsible for high levels of morbidity and mortality. In this study, ex vivo expanded cytotoxic Vγ9Vδ2 T cells isolated from human peripheral blood were tested for their anti-cancer efficacy in combination with zoledronic acid (ZOL), using a mouse model of osteolytic breast cancer. In vitro, expanded Vγ9Vδ2 T cells were cytotoxic against a panel of human breast cancer cell lines, and ZOL pre-treatment further sensitised breast cancer cells to killing by Vγ9Vδ2 T cells. Vγ9Vδ2 T cells adoptively transferred into NOD/SCID mice localised to osteolytic breast cancer lesions in the bone, and multiple infusions of Vγ9Vδ2 T cells reduced tumour growth in the bone. ZOL pre-treatment potentiated the anti-cancer efficacy of Vγ9Vδ2 T cells, with mice showing further reductions in tumour burden. Mice treated with the combination also had reduced tumour burden of secondary pulmonary metastases, and decreased bone degradation. Our data suggests that adoptive transfer of Vγ9Vδ2 T cell in combination with ZOL may prove an effective immunotherapeutic approach for the treatment of breast cancer bone metastases. Copyright © 2016. Published by Elsevier Ireland Ltd.

Recovery from Cyclophosphamide-Induced Lymphopenia Results in Expansion of Immature Dendritic Cells Which Can Mediate Enhanced Prime-Boost Vaccination Antitumor Responses In Vivo When Stimulated with the TLR3 Agonist Poly(I:C)1

PubMed Central

Salem, Mohamed L.; Díaz-Montero, C. Marcela; Al-Khami, Amir A.; El-Naggar, Sabry A.; Naga, Osama; Montero, Alberto J.; Khafagy, Ahmed; Cole, David J.

2011-01-01

Recent preclinical studies suggest that vaccination following adoptive transfer of CD8+ T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8+ T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8–16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp10025–33 melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8+ T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies. PMID:19201856

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies.

PubMed

Tsukahara, T; Iwase, N; Kawakami, K; Iwasaki, M; Yamamoto, C; Ohmine, K; Uchibori, R; Teruya, T; Ido, H; Saga, Y; Urabe, M; Mizukami, H; Kume, A; Nakamura, M; Brentjens, R; Ozawa, K

2015-02-01

Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.

Treatment of malignant pleural mesothelioma by fibroblast activation protein-specific re-directed T cells

PubMed Central

2013-01-01

Introduction Malignant pleural mesothelioma (MPM) is an incurable malignant disease, which results from chronic exposition to asbestos in at least 70% of the cases. Fibroblast activation protein (FAP) is predominantly expressed on the surface of reactive tumor-associated fibroblasts as well as on particular cancer types. Because of its expression on the cell surface, FAP is an attractive target for adoptive T cell therapy. T cells can be re-directed by retroviral transfer of chimeric antigen receptors (CAR) against tumor-associated antigens (TAA) and therefore represent a therapeutic strategy of adoptive immunotherapy. Methods To evaluate FAP expression immunohistochemistry was performed in tumor tissue from MPM patients. CD8+ human T cells were retrovirally transduced with an anti-FAP-F19-∆CD28/CD3ζ-CAR. T cell function was evaluated in vitro by cytokine release and cytotoxicity assays. In vivo function was tested with an intraperitoneal xenograft tumor model in immunodeficient mice. Results FAP was found to be expressed in all subtypes of MPM. Additionally, FAP expression was evaluated in healthy adult tissue samples and was only detected in specific areas in the pancreas, the placenta and very weakly for cervix and uterus. Expression of the anti-FAP-F19-∆CD28/CD3ζ-CAR in CD8+ T cells resulted in antigen-specific IFNγ release. Additionally, FAP-specific re-directed T cells lysed FAP positive mesothelioma cells and inflammatory fibroblasts in an antigen-specific manner in vitro. Furthermore, FAP-specific re-directed T cells inhibited the growth of FAP positive human tumor cells in the peritoneal cavity of mice and significantly prolonged survival of mice. Conclusion FAP re-directed CD8+ T cells showed antigen-specific functionality in vitro and in vivo. Furthermore, FAP expression was verified in all MPM histotypes. Therefore, our data support performing a phase I clinical trial in which MPM patients are treated with adoptively transferred FAP-specific re-directed T cells. PMID:23937772

One size fits all? Challenges faced by physicians during shift handovers in a hospital with high sender/recipient ratio

PubMed Central

Yang, Xi Jessie; Park, Taezoon; Siah, Tien Ho Kewin; Ang, Bee Leng Sophia; Donchin, Yoel

2015-01-01

INTRODUCTION The aim of the present study was to investigate the challenges faced by physicians during shift handovers in a university hospital that has a high handover sender/recipient ratio. METHODS We adopted a multifaceted approach, comprising recording and analysis of handover information, rating of handover quality, and shadowing of handover recipients. Data was collected at the general medical ward of a university hospital in Singapore for a period of three months. Handover information transfer (i.e. senders’ and recipients’ verbal communication, and recipients’ handwritten notes) and handover environmental factors were analysed. The relationship between ‘to-do’ tasks and information transfer, handover quality and handover duration was examined using analysis of variance. RESULTS Verbal handovers for 152 patients were observed. Handwritten notes on 102 (67.1%) patients and handover quality ratings for 98 (64.5%) patients were collected. Although there was good task prioritisation (information transfer: p < 0.005, handover duration: p < 0.01), incomplete information transfer and poor implementation of non-modifiable identifiers were observed. The high sender/recipient ratio of the hospital made face-to-face and/or bedside handover difficult to implement. Although the current handover method (i.e. use of telephone communication) allowed for interactive communication, it resulted in systemic information loss due to the lack of written information. The handover environment was chaotic in the high sender/recipient ratio setting, and the physicians had no designated handover time or location. CONCLUSION Handovers in high sender/recipient ratio settings are challenging. Efforts should be made to improve the handover processes in such situations, so that patient care is not compromised. PMID:25532519

Numerical and experimental analysis of heat transfer in injector plate of hydrogen peroxide hybrid rocket motor

NASA Astrophysics Data System (ADS)

Cai, Guobiao; Li, Chengen; Tian, Hui

2016-11-01

This paper is aimed to analyze heat transfer in injector plate of hydrogen peroxide hybrid rocket motor by two-dimensional axisymmetric numerical simulations and full-scale firing tests. Long-time working, which is an advantage of hybrid rocket motor over conventional solid rocket motor, puts forward new challenges for thermal protection. Thermal environments of full-scale hybrid rocket motors designed for long-time firing tests are studied through steady-state coupled numerical simulations of flow field and heat transfer in chamber head. The motor adopts 98% hydrogen peroxide (98HP) oxidizer and hydroxyl-terminated poly-butadiene (HTPB) based fuel as the propellants. Simulation results reveal that flowing liquid 98HP in head oxidizer chamber could cool the injector plate of the motor. The cooling of 98HP is similar to the regenerative cooling in liquid rocket engines. However, the temperature of the 98HP in periphery portion of the head oxidizer chamber is higher than its boiling point. In order to prevent the liquid 98HP from unexpected decomposition, a thermal protection method for chamber head utilizing silica-phenolics annular insulating board is proposed. The simulation results show that the annular insulating board could effectively decrease the temperature of the 98HP in head oxidizer chamber. Besides, the thermal protection method for long-time working hydrogen peroxide hybrid rocket motor is verified through full-scale firing tests. The ablation of the insulating board in oxygen-rich environment is also analyzed.

Applications of aerospace technology in industry, a technology transfer profile: Contamination control

NASA Technical Reports Server (NTRS)

1971-01-01

The strong influence NASA-sponsored research has had on the development of solutions to difficult contamination problems is considered. The contamination control field is comprised of an industrial base, supplying the tools of control; a user base, adopting control techniques; and a technical base, expanding the concepts of control. Both formal and informal mechanisms used by NASA to communicate a variety of technical advances are reviewed and certain examples of the expansion of the user base through technology transfer are given. Issues related to transfer of NASA-generated contamination control technology are emphasized.

Reasons for adopting technological innovations reducing physical workload in bricklaying.

PubMed

de Jong, A M; Vink, P; de Kroon, J C A

2003-09-15

In this paper the adoption of technological innovations to improve the work of bricklayers and bricklayers' assistants is evaluated. Two studies were performed among 323 subjects to determine the adoption of the working methods, the perceived workload, experiences with the working methods, and the reasons for adopting the working methods. Furthermore, a comparison of the results of the studies was made with those of two similar studies in the literature. The results show that more than half of the sector adopted the innovations. The perceived workload was reduced. The employees and employers are satisfied with the working methods and important reasons for adoption were cost/benefit advantages, improvement of work and health, and increase in productivity. Problems preventing the adoption were the use of the working methods at specific sites, for instance in renovation work. The adoption of the new working methods could perhaps have been higher or faster if more attention had been paid to the active participation of bricklayers and bricklayers' assistants during the development of the new working methods and to the use of modern media techniques, such as the Internet and CD/DVD.

Assessment of the Accuracy of the Conventional Ray-Tracing Technique: Implications in Remote Sensing and Radiative Transfer Involving Ice Clouds.

NASA Technical Reports Server (NTRS)

Bi, Lei; Yang, Ping; Liu, Chao; Yi, Bingqi; Baum, Bryan A.; Van Diedenhoven, Bastiaan; Iwabuchi, Hironobu

2014-01-01

A fundamental problem in remote sensing and radiative transfer simulations involving ice clouds is the ability to compute accurate optical properties for individual ice particles. While relatively simple and intuitively appealing, the conventional geometric-optics method (CGOM) is used frequently for the solution of light scattering by ice crystals. Due to the approximations in the ray-tracing technique, the CGOM accuracy is not well quantified. The result is that the uncertainties are introduced that can impact many applications. Improvements in the Invariant Imbedding T-matrix method (II-TM) and the Improved Geometric-Optics Method (IGOM) provide a mechanism to assess the aforementioned uncertainties. The results computed by the II-TMþIGOM are considered as a benchmark because the IITM solves Maxwell's equations from first principles and is applicable to particle size parameters ranging into the domain at which the IGOM has reasonable accuracy. To assess the uncertainties with the CGOM in remote sensing and radiative transfer simulations, two independent optical property datasets of hexagonal columns are developed for sensitivity studies by using the CGOM and the II-TMþIGOM, respectively. Ice cloud bulk optical properties obtained from the two datasets are compared and subsequently applied to retrieve the optical thickness and effective diameter from Moderate Resolution Imaging Spectroradiometer (MODIS) measurements. Additionally, the bulk optical properties are tested in broadband radiative transfer (RT) simulations using the general circulation model (GCM) version of the Rapid Radiative Transfer Model (RRTMG) that is adopted in the National Center for Atmospheric Research (NCAR) Community Atmosphere Model (CAM, version 5.1). For MODIS retrievals, the mean bias of uncertainties of applying the CGOM in shortwave bands (0.86 and 2.13 micrometers) can be up to 5% in the optical thickness and as high as 20% in the effective diameter, depending on cloud optical thickness and effective diameter. In the MODIS infrared window bands centered at 8.5, 11, and 12 micrometers biases in the optical thickness and effective diameter are up to 12% and 10%, respectively. The CGOM-based simulation errors in ice cloud radiative forcing calculations are on the order of 10Wm(exp 2).

Fault-tolerant bandwidth reservation strategies for data transfers in high-performance networks

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

Zuo, Liudong; Zhu, Michelle M.; Wu, Chase Q.

2016-11-22

Many next-generation e-science applications need fast and reliable transfer of large volumes of data with guaranteed performance, which is typically enabled by the bandwidth reservation service in high-performance networks. One prominent issue in such network environments with large footprints is that node and link failures are inevitable, hence potentially degrading the quality of data transfer. We consider two generic types of bandwidth reservation requests (BRRs) concerning data transfer reliability: (i) to achieve the highest data transfer reliability under a given data transfer deadline, and (ii) to achieve the earliest data transfer completion time while satisfying a given data transfer reliabilitymore » requirement. We propose two periodic bandwidth reservation algorithms with rigorous optimality proofs to optimize the scheduling of individual BRRs within BRR batches. The efficacy of the proposed algorithms is illustrated through extensive simulations in comparison with scheduling algorithms widely adopted in production networks in terms of various performance metrics.« less

Structure-aware depth super-resolution using Gaussian mixture model

NASA Astrophysics Data System (ADS)

Kim, Sunok; Oh, Changjae; Kim, Youngjung; Sohn, Kwanghoon

2015-03-01

This paper presents a probabilistic optimization approach to enhance the resolution of a depth map. Conventionally, a high-resolution color image is considered as a cue for depth super-resolution under the assumption that the pixels with similar color likely belong to similar depth. This assumption might induce a texture transferring from the color image into the depth map and an edge blurring artifact to the depth boundaries. In order to alleviate these problems, we propose an efficient depth prior exploiting a Gaussian mixture model in which an estimated depth map is considered to a feature for computing affinity between two pixels. Furthermore, a fixed-point iteration scheme is adopted to address the non-linearity of a constraint derived from the proposed prior. The experimental results show that the proposed method outperforms state-of-the-art methods both quantitatively and qualitatively.

Conjugate heat transfer analysis of an ultrasonic molten metal treatment system

NASA Astrophysics Data System (ADS)

Zhu, Youli; Bian, Feilong; Wang, Yanli; Zhao, Qian

2014-09-01

In piezoceramic ultrasonic devices, the piezoceramic stacks may fail permanently or function improperly if their working temperatures overstep the Curie temperature of the piezoceramic material. While the end of the horn usually serves near the melting point of the molten metal and is enclosed in an airtight chamber, so that it is difficult to experimentally measure the temperature of the transducer and its variation with time, which bring heavy difficulty to the design of the ultrasonic molten metal treatment system. To find a way out, conjugate heat transfer analysis of an ultrasonic molten metal treatment system is performed with coupled fluid and heat transfer finite element method. In modeling of the system, the RNG model and the SIMPLE algorithm are adopted for turbulence and nonlinear coupling between the momentum equation and the energy equation. Forced air cooling as well as natural air cooling is analyzed to compare the difference of temperature evolution. Numerical results show that, after about 350 s of working time, temperatures in the surface of the ceramic stacks in forced air cooling drop about 7 K compared with that in natural cooling. At 240 s, The molten metal surface emits heat radiation with a maximum rate of about 19 036 W/m2, while the heat insulation disc absorbs heat radiation at a maximum rate of about 7922 W/m2, which indicates the effectiveness of heat insulation of the asbestos pad. Transient heat transfer film coefficient and its distribution, which are difficult to be measured experimentally are also obtained through numerical simulation. At 240 s, the heat transfer film coefficient in the surface of the transducer ranges from -17.86 to 20.17 W/(m2 · K). Compared with the trial and error method based on the test, the proposed research provides a more effective way in the design and analysis of the temperature control of the molten metal treatment system.

Comparison of Requirements for Composite Structures for Aircraft and Space Applications

NASA Technical Reports Server (NTRS)

Raju, Ivatury S.; Elliott, Kenny B.; Hampton, Roy W.; Knight, Norman F., Jr.; Aggarwal, Pravin; Engelstad, Stephen P.; Chang, James B.

2010-01-01

In this paper, the aircraft and space vehicle requirements for composite structures are compared. It is a valuable exercise to study composite structural design approaches used in the airframe industry, and to adopt methodology that is applicable for space vehicles. The missions, environments, analysis methods, analysis validation approaches, testing programs, build quantities, inspection, and maintenance procedures used by the airframe industry, in general, are not transferable to spaceflight hardware. Therefore, while the application of composite design approaches from other industries is appealing, many aspects cannot be directly utilized. Nevertheless, experiences and research for composite aircraft structures may be of use in unexpected arenas as space exploration technology develops, and so continued technology exchanges are encouraged.

One-Dimensional Modelling of Internal Ballistics

NASA Astrophysics Data System (ADS)

Monreal-González, G.; Otón-Martínez, R. A.; Velasco, F. J. S.; García-Cascáles, J. R.; Ramírez-Fernández, F. J.

2017-10-01

A one-dimensional model is introduced in this paper for problems of internal ballistics involving solid propellant combustion. First, the work presents the physical approach and equations adopted. Closure relationships accounting for the physical phenomena taking place during combustion (interfacial friction, interfacial heat transfer, combustion) are deeply discussed. Secondly, the numerical method proposed is presented. Finally, numerical results provided by this code (UXGun) are compared with results of experimental tests and with the outcome from a well-known zero-dimensional code. The model provides successful results in firing tests of artillery guns, predicting with good accuracy the maximum pressure in the chamber and muzzle velocity what highlights its capabilities as prediction/design tool for internal ballistics.

Evaluating knowledge transfer practices among construction organization in Malaysia

NASA Astrophysics Data System (ADS)

Zaidi, Mohd Azian; Baharuddin, Mohd Nurfaisal; Bahardin, Nur Fadhilah; Yasin, Mohd Fadzil Mat; Nawi, Mohd Nasrun Mohd; Deraman, Rafikullah

2016-08-01

The aims of this paper is to identify a key dimension of knowledge transfer component to improve construction organization performance. It investigates the effectiveness of present knowledge transfer practices currently adopted by the Malaysian construction organizations and examines the relationship between knowledge transfer factors and organizational factors. A survey among 151 respondents including a different contractor registration grade was employed for the study. The survey shows that a seven-teen (17) factors known as creating shared awareness for information sharing, communication, personal skills,individual attitude,training, organizational culture, information technology,motivation, monitoring and supervision, service quality,information accessibility, information supply, socialization process,knowledge tools, coaching and monitoring, staff briefing and information sharing were identify as a key dimension for knowledge transfer success. This finding suggest that through improvement of each factor, the recognition of the whole strategic knowledge transfer process can be increase thus helping to strengthen the Malaysian construction organization for competitive advantages.

The effects of techno-economic and organizational factors on the adoption of NASA-innovations by commercial firms in the U.S

NASA Technical Reports Server (NTRS)

Chakrabarti, A. K.

1974-01-01

The present work reports on the effects of several organizational and techno-economic factors which tend to facilitate or inhibit the successful transfer and commercial utilization of technology generated outside the organizational setting of a potential industrial user. Innovations were regarded as either product cases or process cases, and successful adoption of these innovations was related to systematic data on the relation between innovator and user and on channels of communication.

Generating and Expanding Autologous Chimeric Antigen Receptor T Cells from Patients with Acute Myeloid Leukemia.

PubMed

Kenderian, Saad S; June, Carl H; Gill, Saar

2017-01-01

Adoptive transfer of genetically engineered T cells can lead to profound and durable responses in patients with hematologic malignancies, generating enormous enthusiasm among scientists, clinicians, patients, and biotechnology companies. The success of adoptive cellular immunotherapy depends upon the ability to manufacture good quality T cells. We discuss here the methodologies and reagents that are used to generate T cells for the preclinical study of chimeric antigen receptor T cell therapy for acute myeloid leukemia (AML).

Worldwide Emerging Environmental Issues Affecting the U.S. Military. May 2007 Report

DTIC Science & Technology

2007-05-01

Change…………………………….…….4 6.2 Nuclear Nonproliferation Treaty Stalemate Continues…………………………..…..5 6.3 Stockholm Convention on POPs Adopts Evaluation but...cooperation and implementation of the Convention on Desertification; and strengthen international cooperation in scientific research and technology transfer...Environmental Security Issues––May 2007 5 AC/UNU Millennium Project 6.3 Stockholm Convention on POPs Adopts

Transferability of genome-wide associated loci for asthma in African Americans

PubMed Central

Faruque, Mezbah U.; Chen, Guanjie; Doumatey, Ayo P.; Zhou, Jie; Huang, Hanxia; Shriner, Daniel; Adeyemo, Adebowale A.; Rotimi, Charles N.; Dunston, Georgia M.

2017-01-01

Objective Transferability of significantly associated loci or GWAS “hits” adds credibility to genotype-disease associations and provides evidence for generalizability across different ancestral populations. We sought evidence of association of known asthma-associated single nucleotide polymorphisms (SNPs) in an African American population. Methods Subjects comprised 661 participants (261 asthma cases and 400 controls) from the Howard University Family Study. Forty-eight SNPs previously reported to be associated with asthma by GWAS were selected for testing. We adopted a combined strategy by first adopting an “exact” approach where we looked-up only the reported index SNP. For those index SNPs missing form our dataset, we used a “local” approach that examined all the regional SNPs in LD with the index SNP. Results Out of the 48 SNPs, our cohort had genotype data available for 27, which were examined for exact replication. Of these, two SNPs were found positively associated with asthma. These included: rs10508372 (OR = 1.567 [95%CI, 1.133–2.167], P = 0.0066) and rs2378383 (OR = 2.147 [95%CI, 1.149–4.013], P = 0.0166), located on chromosomal bands 10p14 and 9q21.31, respectively. Local replication of the remaining 21 loci showed association at two chromosomal loci (9p24.1-rs2381413 and 6p21.32-rs3132947; Bonferroni-corrected P values: 0.0033 and 0.0197, respectively). Of note, multiple SNPs in LD with rs2381413 located upstream of IL33 were significantly associated with asthma. Conclusions This study has successfully transferred four reported asthma-associated loci in an independent African American population. Identification of several asthma-associated SNPs in the upstream of the IL33, a gene previously implicated in allergic inflammation of asthmatic airway, supports the generalizability of this finding. PMID:27177148

Key Points to Facilitate the Adoption of Computer-Based Assessments.

PubMed

Burr, S A; Chatterjee, A; Gibson, S; Coombes, L; Wilkinson, S

2016-01-01

There are strong pedagogical arguments in favor of adopting computer-based assessment. The risks of technical failure can be managed and are offset by improvements in cost-effectiveness and quality assurance capability. Academic, administrative, and technical leads at an appropriately senior level within an institution need to be identified, so that they can act as effective advocates. All stakeholder groups need to be represented in undertaking a detailed appraisal of requirements and shortlisting software based on core functionality, summative assessment life cycle needs, external compatibility, security, and usability. Any software that is a candidate for adoption should be trialed under simulated summative conditions, with all stakeholders having a voice in agreeing the optimum solution. Transfer to a new system should be carefully planned and communicated, with a programme of training established to maximize the success of adoption.

Key Points to Facilitate the Adoption of Computer-Based Assessments

PubMed Central

Burr, S.A.; Chatterjee, A.; Gibson, S.; Coombes, L.; Wilkinson, S.

2016-01-01

There are strong pedagogical arguments in favor of adopting computer-based assessment. The risks of technical failure can be managed and are offset by improvements in cost-effectiveness and quality assurance capability. Academic, administrative, and technical leads at an appropriately senior level within an institution need to be identified, so that they can act as effective advocates. All stakeholder groups need to be represented in undertaking a detailed appraisal of requirements and shortlisting software based on core functionality, summative assessment life cycle needs, external compatibility, security, and usability. Any software that is a candidate for adoption should be trialed under simulated summative conditions, with all stakeholders having a voice in agreeing the optimum solution. Transfer to a new system should be carefully planned and communicated, with a programme of training established to maximize the success of adoption. PMID:29349322

A Radiation Transfer Solver for Athena Using Short Characteristics

NASA Astrophysics Data System (ADS)

Davis, Shane W.; Stone, James M.; Jiang, Yan-Fei

2012-03-01

We describe the implementation of a module for the Athena magnetohydrodynamics (MHD) code that solves the time-independent, multi-frequency radiative transfer (RT) equation on multidimensional Cartesian simulation domains, including scattering and non-local thermodynamic equilibrium (LTE) effects. The module is based on well known and well tested algorithms developed for modeling stellar atmospheres, including the method of short characteristics to solve the RT equation, accelerated Lambda iteration to handle scattering and non-LTE effects, and parallelization via domain decomposition. The module serves several purposes: it can be used to generate spectra and images, to compute a variable Eddington tensor (VET) for full radiation MHD simulations, and to calculate the heating and cooling source terms in the MHD equations in flows where radiation pressure is small compared with gas pressure. For the latter case, the module is combined with the standard MHD integrators using operator splitting: we describe this approach in detail, including a new constraint on the time step for stability due to radiation diffusion modes. Implementation of the VET method for radiation pressure dominated flows is described in a companion paper. We present results from a suite of test problems for both the RT solver itself and for dynamical problems that include radiative heating and cooling. These tests demonstrate that the radiative transfer solution is accurate and confirm that the operator split method is stable, convergent, and efficient for problems of interest. We demonstrate there is no need to adopt ad hoc assumptions of questionable accuracy to solve RT problems in concert with MHD: the computational cost for our general-purpose module for simple (e.g., LTE gray) problems can be comparable to or less than a single time step of Athena's MHD integrators, and only few times more expensive than that for more general (non-LTE) problems.

Longitudinal study of ITS implementation : decision factors and effects.

DOT National Transportation Integrated Search

2013-04-01

The Intelligent Transportation Systems (ITS) Joint Program Office (JPO) is placing increasing emphasis on transferring ITS technology from research to deployment, and on accelerating the rate of ITS technology adoption. As part of these efforts, the ...

Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

PubMed

Mukai, S; Kato, H; Kimura, S; Asai, K; Kawahito, Y; Inoue, M; Yamamura, Y; Sano, H; Sugino, S; Shu, S; Kondo, M

1996-02-01

We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Small RNA Enhances Antitumor T-cell Therapy | Center for Cancer Research

Cancer.gov

Adoptive T-cell transfer is an effective form of anticancer immunotherapy in which patients receive infusions of cytotoxic T cells that seek out and destroy targeted cancer cells. This type of therapy is usually preceded by a lymphodepleting chemotherapy regimen and combined with high doses of the cytokine interleukin-2 (IL-2) to eliminate immunosuppressive and other immune cells and to enhance the survival and activity of the transplanted cells. Unfortunately, these high-intensity treatments often lead to severe side effects, such as a prolonged reduction of white blood cells, an increased risk of clotting events, or an accumulation of fluid in the tissues, which limit the pool of patients healthy enough to receive the treatment and can result in prolonged hospitalization and higher health care costs. New approaches that are less toxic but equally effective could allow for more widespread use of adoptive T-cell transfer.

Genetically engineered T cells to target EGFRvIII expressing glioblastoma.

PubMed

Bullain, Szofia S; Sahin, Ayguen; Szentirmai, Oszkar; Sanchez, Carlos; Lin, Ning; Baratta, Elizabeth; Waterman, Peter; Weissleder, Ralph; Mulligan, Richard C; Carter, Bob S

2009-09-01

Glioblastoma remains a significant therapeutic challenge, warranting further investigation of novel therapies. We describe an immunotherapeutic strategy to treat glioblastoma based on adoptive transfer of genetically modified T-lymphocytes (T cells) redirected to kill EGFRvIII expressing gliomas. We constructed a chimeric immune receptor (CIR) specific to EGFRvIII, (MR1-zeta). After in vitro selection and expansion, MR1-zeta genetically modified primary human T-cells specifically recognized EGFRvIII-positive tumor cells as demonstrated by IFN-gamma secretion and efficient tumor lysis compared to control CIRs defective in EGFRvIII binding (MRB-zeta) or signaling (MR1-delzeta). MR1-zeta expressing T cells also inhibited EGFRvIII-positive tumor growth in vivo in a xenografted mouse model. Successful targeting of EGFRvIII-positive tumors via adoptive transfer of genetically modified T cells may represent a new immunotherapy strategy with great potential for clinical applications.

Adoption research, practice, and societal trends: Ten years of progress.

PubMed

Wiley, Mary O'Leary

2017-12-01

Adoption involves the legal transfer of parental rights and responsibilities from a child's birth parents to adults who will raise the child (Reitz & Watson, 1992). Research related to adoption has expanded over the past 10 years and has incorporated more focus on implications for practice and public policy. This expansion has reflected increased awareness of the lived experience of adopted individuals, in addition to that of adoptive families and birth or first parents and families, collectively known as the adoption kinship network (Grotevant & McRoy, 1998). Trends discussed included research and social trends or movements (2007-2017) since the publication of the final article in a series of articles in the psychological literature related to adoption in The Counseling Psychologist (Baden & Wiley, 2007; Lee, 2003; O'Brien & Zamostny, 2003; Wiley & Baden, 2005; Zamostny, O'Brien, Baden, & Wiley, 2003; Zamostny, Wiley, O'Brien, Lee, & Baden, 2003). This article summarizes the social trends and research related to adoption over the last 10 years, including longitudinal and meta-analytic studies, increased research and conceptualization of ethnic and racial identity development, research on microaggressions, and research on diverse adoptive families, including those with gay and lesbian parents. Social trends included increased knowledge related to Internet accessibility, genetic information, continued focus on openness, and viewing adoption through a more critical lens. Implications are discussed for the development of programs that enhance competence of mental health professionals and adoption professionals in adoption-competent practice. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Development of New Cooling System Using Gm/jt Cryocoolers for the SKS Magnet

NASA Astrophysics Data System (ADS)

Aoki, K.; Haruyama, T.; Makida, Y.; Araoka, O.; Kasami, K.; Takahashi, T.; Nagae, T.; Kakiguchi, Y.; Sekimoto, M.; Tosaka, T.; Miyazaki, H.; Kuriyama, T.; Ono, M.; Orikasa, T.; Tsuchihashi, T.; Hirata, Y.

2008-03-01

We plan to develop a new improved cooling system for the Superconducting Kaon Spectrometer (SKS) magnet and transfer the magnet to the K1.8 beamline of the Hadron Hall of the Japan Proton Accelerator Research Complex (J-PARC) for further use in nuclear physics experiments. To replace the present 300 W cryogenic system, we will adopt a new cooling method that uses 4 K Gifford-McMahon/Joule-Thomson (GM/JT) cryocoolers. In order to decide a practical design for the new liquid helium reservoir of the magnet, which will be equipped with GM/JT cryocoolers, cooling tests on a GM/JT cryocooler were performed from February to March 2007. We constructed a new cooling test stand with a GM/JT cryocooler and measured the cooling capacities under several thermal shield temperatures with or without a baffle, which helped prevent convection. Based on the test results, we have finally decided to adopt three GM/JT cryocoolers for the new SKS along with a baffle and an additional dedicated GM cooler to cool the thermal shield of the GM/JT ports.

Advanced Computational Aeroacoustics Methods for Fan Noise Prediction

NASA Technical Reports Server (NTRS)

Envia, Edmane (Technical Monitor); Tam, Christopher

2003-01-01

Direct computation of fan noise is presently not possible. One of the major difficulties is the geometrical complexity of the problem. In the case of fan noise, the blade geometry is critical to the loading on the blade and hence the intensity of the radiated noise. The precise geometry must be incorporated into the computation. In computational fluid dynamics (CFD), there are two general ways to handle problems with complex geometry. One way is to use unstructured grids. The other is to use body fitted overset grids. In the overset grid method, accurate data transfer is of utmost importance. For acoustic computation, it is not clear that the currently used data transfer methods are sufficiently accurate as not to contaminate the very small amplitude acoustic disturbances. In CFD, low order schemes are, invariably, used in conjunction with unstructured grids. However, low order schemes are known to be numerically dispersive and dissipative. dissipative errors are extremely undesirable for acoustic wave problems. The objective of this project is to develop a high order unstructured grid Dispersion-Relation-Preserving (DRP) scheme. would minimize numerical dispersion and dissipation errors. contains the results of the funded portion of the project. scheme on an unstructured grid has been developed. constructed in the wave number space. The characteristics of the scheme can be improved by the inclusion of additional constraints. Stability of the scheme has been investigated. Stability can be improved by adopting the upwinding strategy.

Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants.

PubMed

Yoshida, S; Haque, A; Mizobuchi, T; Iwata, T; Chiyo, M; Webb, T J; Baldridge, L A; Heidler, K M; Cummings, O W; Fujisawa, T; Blum, J S; Brand, D D; Wilkes, D S

2006-04-01

Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.

Cell intrinsic abrogation of TGFβ signaling delays but does not prevent dysfunction of self/tumor specific CD8 T cells in a murine model of autochthonous prostate cancer

PubMed Central

Chou, Cassie K.; Schietinger, Andrea; Liggitt, H. Denny; Tan, Xiaoxia; Funk, Sarah; Freeman, Gordon J.; Ratliff, Timothy L.; Greenberg, Norman M.; Greenberg, Philip D.

2012-01-01

Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of anti-tumor activity of transferred T cells remain major problems. Transforming growth factor beta (TGFβ) is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell mediated anti-tumor activity. Here, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell intrinsic abrogation of TGFβ signaling in self/tumor specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and anti-tumor activity of adoptively transferred effector T cells deficient in TGFβ signaling was significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate infiltrating T cells were no longer functional. These findings reveal that TGFβ negatively regulates the accumulation and effector function of transferred self/tumor specific CD8 T cells and highlight that, when targeting a tumor antigen that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. PMID:22984076

T Cells Prevent Hemorrhagic Transformation in Ischemic Stroke by P-Selectin Binding.

PubMed

Salas-Perdomo, Angélica; Miró-Mur, Francesc; Urra, Xabier; Justicia, Carles; Gallizioli, Mattia; Zhao, Yashu; Brait, Vanessa H; Laredo, Carlos; Tudela, Raúl; Hidalgo, Andrés; Chamorro, Ángel; Planas, Anna M

2018-06-14

Hemorrhagic transformation is a serious complication of ischemic stroke after recanalization therapies. This study aims to identify mechanisms underlying hemorrhagic transformation after cerebral ischemia/reperfusion. We used wild-type mice and Selplg -/- and Fut7 -/- mice defective in P-selectin binding and lymphopenic Rag2 -/- mice. We induced 30-minute or 45-minute ischemia by intraluminal occlusion of the middle cerebral artery and assessed hemorrhagic transformation at 48 hours with a hemorrhage grading score, histological means, brain hemoglobin content, or magnetic resonance imaging. We depleted platelets and adoptively transferred T cells of the different genotypes to lymphopenic mice. Interactions of T cells with platelets in blood were studied by flow cytometry and image stream technology. We show that platelet depletion increased the bleeding risk only after large infarcts. Lymphopenia predisposed to hemorrhagic transformation after severe stroke, and adoptive transfer of T cells prevented hemorrhagic transformation in lymphopenic mice. CD4 + memory T cells were the subset of T cells binding P-selectin and platelets through functional P-selectin glycoprotein ligand-1. Mice defective in P-selectin binding had a higher hemorrhagic score than wild-type mice. Adoptive transfer of T cells defective in P-selectin binding into lymphopenic mice did not prevent hemorrhagic transformation. The study identifies lymphopenia as a previously unrecognized risk factor for secondary hemorrhagic transformation in mice after severe ischemic stroke. T cells prevent hemorrhagic transformation by their capacity to bind platelets through P-selectin. The results highlight the role of T cells in bridging immunity and hemostasis in ischemic stroke. © 2018 American Heart Association, Inc.

Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma.

PubMed

Grange, Magali; Buferne, Michel; Verdeil, Grégory; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie

2012-01-01

Immunotherapy based on adoptive transfer of tumor antigen-specific CD8(+) T cell (TC) is generally limited by poor in vivo expansion and tumor infiltration. In this study, we report that activated STAT5 transcription factors (STAT5CA) confer high efficiency on CD8(+) effector T cells (eTC) for host colonization after adoptive transfer. Engineered expression of STAT5CA in antigen-experienced TCs with poor replicative potential was also sufficient to convert them into long-lived antigen-responsive eTCs. In transplanted mastocytoma- or melanoma-bearing hosts, STAT5CA greatly enhanced the ability of eTCs to accumulate in tumors, become activated by tumor antigens, and to express the cytolytic factor granzyme B. Taken together, these properties contributed to an increase in tumor regression by STAT5CA-transduced, as compared with untransduced, TCs including when the latter control cells were combined with infusion of interleukin (IL)-2/anti-IL-2 complexes. In tumors arising in the autochthonous TiRP transgenic model of melanoma associated with systemic chronic inflammation, endogenous CD8(+) TCs were nonfunctional. In this setting, adoptive transfer of STAT5CA-transduced TCs produced superior antitumor effects compared with nontransduced TCs. Our findings imply that STAT5CA expression can render TCs resistant to the immunosuppressive environment of melanoma tumors, enhancing their ability to home to tumors and to maintain high granzyme B expression, as well as their capacity to stimulate granzyme B expression in endogenous TCs. ©2011 AACR.

Active antitumor immunity elicited by vaccine based on recombinant form of epidermal growth factor receptor.

PubMed

Hu, Bing; Wei, Yuquan; Tian, Ling; Zhao, Xia; Lu, You; Wu, Yang; Yao, Bing; Liu, Jiyan; Niu, Ting; Wen, Yanjun; He, Qiuming; Su, Jingmei; Huang, Meijuan; Lou, Yanyan; Luo, Yan; Kan, Bing

2005-01-01

Active immunotherapy targeting epidermal growth factor receptor (EGFR) should be another attractive approach to the treatment of EGFR-positive tumors. To test this concept, the authors evaluated the potential immune responses and antitumor activities elicited by dendritic cells pulsed with recombinant ectodomain of mouse EGFR (DC-edMER). Spleen cells isolated from DC-edMER-vaccinated mice showed a high quantity of EGFR-specific antibody-producing cells. EGFR-reactive antibody in sera isolated from vaccinated mice was identified and shown to be effective against tumors in vitro and in vivo by adoptive transfer. DC-edMER vaccine also elicited cytotoxic T-lymphocyte responses that could mediate antitumor effects in vitro and adoptive transfer in vivo. In addition, EGFR-specific cytokines responses were elicited by DC-edMER vaccine. Immunization with DC-edMER resulted in tumor regression and prolonged survival in mice challenged with Lewis lung carcinomas and mammary cancer models. Depletion of CD4+ T lymphocytes could completely abrogate the antitumor activity and EGFR-specific antibody responses, whereas the depletion of CD8+ T lymphocytes showed partial abrogation of the antitumor activity but antibody was still detected. Furthermore, tumor-induced angiogenesis was suppressed in DC-edMER-vaccinated mice or mice treated with antibody adoptive transfer. Taken together, these findings suggest the antitumor immunity could be induced by DC-edMER, which may involve both humoral and cellular immunity, and may provide insight into the treatment of EGFR-positive tumors through the induction of active immunity against EGFR.

Motivations for enterprise system adoption in transition economies: insights from Poland

NASA Astrophysics Data System (ADS)

Soja, Piotr; Weistroffer, Heinz Roland

2016-06-01

Enterprise system (ES) adoption can bring many benefits, but may also put tremendous strain on an organisation or business, sometimes with disastrous outcomes. The specific motivations and expectations that lead to ES adoption may impact the success or failure of these endeavours, and understanding these motivations may be useful in predicting the success of ES projects. Most of the published research on ES adoption motivation has been in the context of highly developed countries. The social, cultural, economic and political conditions in developing, emerging and transition economies make for a different business environment, and insights obtained from developed countries may not always transfer to these settings. This study seeks to identify and help understand the motivations for ES adoption specifically in transition economies, as these economies play a significant role in the global market, but have not been receiving adequate research attention. Drawing on the experience of 129 ES adopters in Poland, a transition economy, this study categorises motivations into coherent groups of issues and evaluates the influence of discovered motivations on ES adoption success. Further, motivations revealed by this study are compared with motivations reported by prior research conducted in developed countries.

[Eimeria tenella and Eimeria acervulina: an antigenic stimulation in vitro of cells from immune chickens induced by adoptive transfer of protection against avian coccidiosis].

PubMed

Rhalem, A; Sahibi, H; Kazanji, M; Laurent, F; Berrag, B; Péry, P

1993-01-01

The transfer of 5 x 10(7) or 10(8) spleen cells from E tenella-infected chickens to virgin animals after 12-20-h in vitro stimulation with whole sporozoite homogenates confers significant protection to recipients. The oocyst contents of ceca on d 7 post-infection with 20,000 E tenella oocysts were (1.33 +/- 1.10) x 10(6) in chickens which received 5 x 10(7) immune cells after 20-h in vitro stimulation and (4.64 +/- 2.85) x 10(6) in chickens receiving 5 x 10(7) stimulated cells from normal chickens (85% protection). Adoptive transfer by spleen cells revealed an asymmetric cross-protection between E tenella and E acervulina. Spleen cells from E tenella immune chickens protected only against a subsequent infection with the same parasite, while spleen cells from E acervulina immune chickens protected against infection with E acervulina (78%) but also against infection with E tenella (68% protection). The common antigen permits better stimulation, but common surface sporozoite antigens purified from E tenella sporozoites via anti-E acervulina biliary antibodies are capable of stimulating both types of cells without, however, changing their properties.

Thermal protection system gap analysis using a loosely coupled fluid-structural thermal numerical method

NASA Astrophysics Data System (ADS)

Huang, Jie; Li, Piao; Yao, Weixing

2018-05-01

A loosely coupled fluid-structural thermal numerical method is introduced for the thermal protection system (TPS) gap thermal control analysis in this paper. The aerodynamic heating and structural thermal are analyzed by computational fluid dynamics (CFD) and numerical heat transfer (NHT) methods respectively. An interpolation algorithm based on the control surface is adopted for the data exchanges on the coupled surface. In order to verify the analysis precision of the loosely coupled method, a circular tube example was analyzed, and the wall temperature agrees well with the test result. TPS gap thermal control performance was studied by the loosely coupled method successfully. The gap heat flux is mainly distributed in the small region at the top of the gap which is the high temperature region. Besides, TPS gap temperature and the power of the active cooling system (CCS) calculated by the traditional uncoupled method are higher than that calculated by the coupled method obviously. The reason is that the uncoupled method doesn't consider the coupled effect between the aerodynamic heating and structural thermal, however the coupled method considers it, so TPS gap thermal control performance can be analyzed more accurately by the coupled method.

CXCL16-positive dendritic cells enhance invariant natural killer T cell-dependent IFNγ production and tumor control

PubMed Central

Veinotte, Linnea; Gebremeskel, Simon; Johnston, Brent

2016-01-01

ABSTRACT Crosstalk interactions between dendritic cells (DCs) and invariant natural killer T (iNKT) cells are important in regulating antitumor responses elicited by glycolipid antigens. iNKT cells constitutively express the chemokine receptor CXCR6, while cytokine-activated DCs upregulate the transmembrane chemokine ligand, CXCL16. This study examined the co-stimulatory role of CXCR6/CXCL16 interactions in glycolipid-dependent iNKT cell activation and tumor control. Spleen and liver DCs in wild-type mice, but not iNKT cell deficient (Jα18−/−) mice, transiently upregulated surface CXCL16 following in vivo administration of the glycolipid antigen α-galactosylceramide. Recombinant CXCL16 did not directly induce iNKT cell activation in vitro but enhanced interferon (IFN)-γ production when mouse or human iNKT cells were stimulated with plate-bound anti-CD3. Compared with glycolipid-loaded CXCL16neg DCs, CXCL16hi DCs induced higher levels of IFNγ production in iNKT cell cultures and following adoptive transfer in vivo. The number of IFNγ+ iNKT cells and expansion of T-bet+ iNKT cells were reduced in vivo when CXCL16−/− DCs were used to activate iNKT cells. Enhanced IFNγ production in vivo was not dependent on CXCR6 expression on natural killer (NK) cells. Adoptive transfer of glycolipid-loaded CXCL16hi DCs provided superior protection against tumor metastasis compared to CXCL16neg DC transfers. Similarly, wild-type DCs provided superior protection against metastasis compared with CXCL16−/− DCs. These experiments implicate an important role for CXCR6/CXCL16 interactions in regulating iNKT cell IFNγ production and tumor control. The selective use of CXCL16hi DCs in adoptive transfer immunotherapies may prove useful for enhancing T helper (Th) type 1 responses and clinical outcomes in cancer patients. PMID:27471636

7 CFR 1466.27 - Conservation Innovation Grants (CIG).

Code of Federal Regulations, 2011 CFR

2011-01-01

... lead to the transfer of conservation technologies, management systems, and innovative approaches (such... to stimulate the development and adoption of innovative conservation approaches and technologies... focus. Applications for CIG should demonstrate the use of innovative approaches and technologies to...

Synergistic effects of the xid gene in X chromosome congenic mice. I. Inability of C3.CBA/N mice to respond to thymus-dependent antigens in adoptive transfer assays.

PubMed

Kenny, J J; Guelde, G; Hansen, C; Mond, J J

1987-03-01

The xid gene, which causes a B lymphocyte immune defect in CBA/N mice, has been bred onto the C3H/HeN background. The resulting X chromosome congenic mice (C3.CBA/N) exhibit immunologic defects that are much more profound than the defect exhibited by CBA/N mice; thus, the B cells from C3.CBA/N mice not only fail to respond to thymus-independent (TI) type 2 antigens such as TNP-Ficoll, but they fail to respond in vitro to TI-type 1 antigens such as TNP-Brucella abortus (BA) and B cell mitogens such as LPS and Nocardia water-soluble mitogen. In this paper we show that the synergistic defect seen in C3.CBA/N B cells is also elicited in adoptive transfer assays to thymus-dependent (TD) antigens such as TNP-KLH and PC-KLH, antigens to which both parental strains respond. Thus, the secondary adoptive transfer response of C3.CBA/N spleen cells is generally less than 5% of the immune response produced by CBA/N or C3H/HeN spleen cells. This synergistic defect is restricted to the C3.CBA/N B cells, since C3.CBA/N T cells can provide help to CBA/N B cells that is equivalent to the help obtained with CBA/N T cells. The low responsiveness of C3.CBA/N spleen cells to TD antigens, which is elicited in adoptive transfer assays, is not seen when the intact animal is immunized with antigen in CFA; this, intact C3.CBA/N mice produce anti-PC-KLH and anti-TNP-KLH responses only slightly lower than the responses of CBA/N mice to these same antigens. In contrast, when these mice are immunized with phenol-extracted LPS, a TI-type 1 antigen, their antibody responses are severely depressed. These data suggest that under conditions in which T cell help may be limiting or in which the intact physiology of the T and B cells has been disrupted, C3.CBA/N B cells demonstrate profound immunologic impairment; however, when adequate T cell help is available and the splenic architecture is not disrupted, their immune responses appear to progress in a normal fashion.

NOX2 Deficiency Protects Against Streptozotocin-Induced β-Cell Destruction and Development of Diabetes in Mice

PubMed Central

Xiang, Fu-Li; Lu, Xiangru; Strutt, Brenda; Hill, David J.; Feng, Qingping

2010-01-01

OBJECTIVE The role of NOX2-containing NADPH oxidase in the development of diabetes is not fully understood. We hypothesized that NOX2 deficiency decreases reactive oxygen species (ROS) production and immune response and protects against streptozotocin (STZ)-induced β-cell destruction and development of diabetes in mice. RESEARCH DESIGN AND METHODS Five groups of mice—wild-type (WT), NOX2−/−, WT treated with apocynin, and WT adoptively transferred with NOX2−/− or WT splenocytes—were treated with multiple-low-dose STZ. Blood glucose and insulin levels were monitored, and an intraperitoneal glucose tolerance test was performed. Isolated WT and NOX2−/− pancreatic islets were treated with cytokines for 48 h. RESULTS Significantly lower blood glucose levels, higher insulin levels, and better glucose tolerance was observed in NOX2−/− mice and in WT mice adoptively transferred with NOX2−/− splenocytes compared with the respective control groups after STZ treatment. Compared with WT, β-cell apoptosis, as determined by TUNEL staining, and insulitis were significantly decreased, whereas β-cell mass was significantly increased in NOX2−/− mice. In response to cytokine stimulation, ROS production was significantly decreased, and insulin secretion was preserved in NOX2−/− compared with WT islets. Furthermore, proinflammatory cytokine release induced by concanavalin A was significantly decreased in NOX2−/− compared with WT splenocytes. CONCLUSIONS NOX2 deficiency decreases β-cell destruction and preserves islet function in STZ-induced diabetes by reducing ROS production, immune response, and β-cell apoptosis. PMID:20627937

Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice

PubMed Central

Jin, Rong; Zhu, Xiaolei; Liu, Lin; Nanda, Anil; Granger, D Neil; Li, Guohong

2013-01-01

Background and Purpose Statins are widely used in the primary and secondary prevention of ischemic stroke, but their effects on stroke-induced immunodeppression and post-stroke infections are elusive. We investigated effects of simvastatin treatment on stroke-induced splenic atrophy and lung susceptibility to bacterial infection in acute experimental stroke in mice. Methods Ischemic stroke was induced by transient occlusion of middle cerebral artery (MCAO) followed by reperfusion. In some experiments, splenectomies were performed 2 weeks prior to MCAO. Animals were randomly assigned to sham and MCAO groups treated subcutaneously with vehicle or simvastatin (20 mg/kg/day). Brain infarction, neurological function, brain interferon-γ expression, splenic atrophy and apoptosis, and lung infection were examined. Results Simvastatin reduced stroke-induced spleen atrophy and splenic apoptosis via increased mitochrondrial anti-apoptotic Bcl-2 expression and decreased pro-apoptotic Bax translocation from cytosol into mitochondria. Splenectomy reduced brain interferon-γ (3d) and infarct size (5d) after stroke and these effects were reversed by adoptive transfer of splenocytes. Simvastatin inhibited brain interferon-γ (3d) and reduced infarct volume and neurological deficits (5d) after stroke, and these protective effects were observed not only in naïve stroke mice but also in splenectomied stroke mice adoptively transferred with splenocytes. Simvastatin also decreased the stroke-associated lung susceptibility to spontaneous bacterial infection. Conclusions Results provide the first direct experimental evidence that simvastatin ameliorates stroke-induced peripheral immunodepression by attenuating spleen atrophy and lung bacterial infection. These findings contribute to a better understanding of beneficial effects of statins in the treatment of stroke. PMID:23391769

Multiagent Reinforcement Learning With Sparse Interactions by Negotiation and Knowledge Transfer.

PubMed

Zhou, Luowei; Yang, Pei; Chen, Chunlin; Gao, Yang

2017-05-01

Reinforcement learning has significant applications for multiagent systems, especially in unknown dynamic environments. However, most multiagent reinforcement learning (MARL) algorithms suffer from such problems as exponential computation complexity in the joint state-action space, which makes it difficult to scale up to realistic multiagent problems. In this paper, a novel algorithm named negotiation-based MARL with sparse interactions (NegoSIs) is presented. In contrast to traditional sparse-interaction-based MARL algorithms, NegoSI adopts the equilibrium concept and makes it possible for agents to select the nonstrict equilibrium-dominating strategy profile (nonstrict EDSP) or meta equilibrium for their joint actions. The presented NegoSI algorithm consists of four parts: 1) the equilibrium-based framework for sparse interactions; 2) the negotiation for the equilibrium set; 3) the minimum variance method for selecting one joint action; and 4) the knowledge transfer of local Q -values. In this integrated algorithm, three techniques, i.e., unshared value functions, equilibrium solutions, and sparse interactions are adopted to achieve privacy protection, better coordination and lower computational complexity, respectively. To evaluate the performance of the presented NegoSI algorithm, two groups of experiments are carried out regarding three criteria: 1) steps of each episode; 2) rewards of each episode; and 3) average runtime. The first group of experiments is conducted using six grid world games and shows fast convergence and high scalability of the presented algorithm. Then in the second group of experiments NegoSI is applied to an intelligent warehouse problem and simulated results demonstrate the effectiveness of the presented NegoSI algorithm compared with other state-of-the-art MARL algorithms.

Adoptive cell therapy using PD-1+ myeloma-reactive T cells eliminates established myeloma in mice.

PubMed

Jing, Weiqing; Gershan, Jill A; Blitzer, Grace C; Palen, Katie; Weber, James; McOlash, Laura; Riese, Matthew; Johnson, Bryon D

2017-01-01

Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers. PD-1 + and PD-1 - T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT. Myeloma-reactive T cells were enriched in the PD-1 + cell subset. Similar results were also observed in a mouse AML model. PD-1 + T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1 + T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1 + T cells persisted in recipient mice and were able to mount an adaptive memory immune response. These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1 + T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers.

Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells.

PubMed

Ager, Ann; Watson, H Angharad; Wehenkel, Sophie C; Mohammed, Rebar N

2016-04-15

The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8(+)T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8(+)T-cell infiltration of tumours and increase the efficacy of adoptive CD8(+)T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy 'normalizes' (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients. © 2016 Authors; published by Portland Press Limited.

Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells

PubMed Central

Ager, Ann; Watson, H. Angharad; Wehenkel, Sophie C.; Mohammed, Rebar N.

2016-01-01

The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8+ T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8+ T-cell infiltration of tumours and increase the efficacy of adoptive CD8+ T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy ‘normalizes’ (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients. PMID:27068943

Exploring inter-task transfer following a CO-OP approach with four children with DCD: A single subject multiple baseline design.

PubMed

Capistran, Julie; Martini, Rose

2016-10-01

Cognitive Orientation to daily Occupational Performance (CO-OP) approach has been shown to be effective for improving the performance of tasks worked on in therapy and the use of cognitive strategies. No study to date seems to have explored its effectiveness for improving performance of untrained tasks (inter-task transfer) in children with Developmental Coordination Disorder (DCD). This study aimed to determine whether CO-OP leads to improved performance in an untrained task. A single-subject design with multiple baselines across skills was adopted, with three replications. Four children with DCD (7-12years) received 10 sessions of CO-OP intervention where each child worked on three tasks during therapy sessions and a fourth task was identified, but not worked on, to verify inter-task transfer. Task performance was rated over four phases (baseline, intervention, post-intervention, follow-up) using the Performance Quality Rating Scale (PQRS-OD). Graphed data was statistically analyzed using a two or three standard deviation band method. Significant improvement was obtained for 11 of 12 tasks worked on during therapy and for two of the four untrained tasks. These results indicate that the effectiveness of CO-OP to improve untrained tasks in children merit further exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

Tumor vessel-injuring ability improves antitumor effect of cytotoxic T lymphocytes in adoptive immunotherapy.

PubMed

Kanagawa, N; Yanagawa, T; Nakagawa, T; Okada, N; Nakagawa, S

2013-01-01

Angiogenesis is required for normal physiologic processes, but it is also involved in tumor growth, progression and metastasis. Here, we report the development of an immune-based antiangiogenic strategy based on the generation of T lymphocytes that possess killing specificity for cells expressing vascular endothelial growth factor receptor 2 (VEGFR2). To target VEGFR2-expressing cells, we engineered cytotoxic T lymphocyte (CTL) expressing chimeric T-cell receptors (cTCR-CTL) comprised of a single-chain variable fragment (scFv) against VEGFR2 linked to an intracellular signaling sequence derived from the CD3ζ chain of the TCR and CD28 by retroviral gene transduction methods. The cTCR-CTL exhibited efficient killing specificity against VEGFR2 and a tumor-targeting function in vitro and in vivo. Reflecting such abilities, we confirmed that the cTCR-CTL strongly inhibited the growth of a variety of syngeneic tumors after adoptive transfer into tumor-bearing mice without consequent damage to normal tissue. In addition, CTL expressing both cTCR and tumor-specific TCR induced complete tumor regression due to enhanced tumor infiltration by the CTL and long-term antigen-specific function. These findings provide evidence that the tumor vessel-injuring ability improved the antitumor effect of CTLs in adoptive immunotherapy for a broad range of cancers by inducing immune-mediated destruction of the tumor neovasculature.

The challenge of technology transfer: Buying in without selling out

PubMed Central

Pennypacker, H. S.

1986-01-01

Highly effective technologies flowing from the discipline of behavior analysis have not been widely adopted, thus threatening the survival of the discipline itself. An analysis of the contingencies underlying successful technology transfer suggests the need for direct, empirical involvement in the marketplace in order to insure that the maximum demonstrable benefits reach the ultimate users. A successful example of this strategy of technology transfer is provided. Three areas of intense national concern—urban violence, illiteracy, and declining industrial productivity—provide immediate opportunities for the technologies of behavior analysis to secure the place of the discipline in the intellectual mosaic of the 21st century. PMID:22478656

Photoinduced charge-transfer electronic excitation of tetracyanoethylene/tetramethylethylene complex in dichloromethane

NASA Astrophysics Data System (ADS)

Xu, Long-Kun; Bi, Ting-Jun; Ming, Mei-Jun; Wang, Jing-Bo; Li, Xiang-Yuan

2017-07-01

Based on the previous work on nonequilibrium solvation model by the authors, Intermolecular charge-transfer electronic excitation of tetracyanoethylene (TCE)/tetramethylethylene (TME) π -stacked complex in dichloromethane (DCM) has been investigated. For weak interaction correction, dispersion corrected functional DFT-D3 is adopted for geometry optimization. In order to identify the excitation metric, dipole moment components of each Cartesian direction, atomic charge, charge separation and Δr index are analyzed for TCE/TME complex. Calculation shows that the calculated excitation energy is dependent on the functional choice, when conjuncted with suitable time-dependent density functional, the modified nonequilibrium expression gives satisfied results for intermolecular charge-transfer electronic excitation.

A Kalman Filter for SINS Self-Alignment Based on Vector Observation.

PubMed

Xu, Xiang; Xu, Xiaosu; Zhang, Tao; Li, Yao; Tong, Jinwu

2017-01-29

In this paper, a self-alignment method for strapdown inertial navigation systems based on the q -method is studied. In addition, an improved method based on integrating gravitational apparent motion to form apparent velocity is designed, which can reduce the random noises of the observation vectors. For further analysis, a novel self-alignment method using a Kalman filter based on adaptive filter technology is proposed, which transforms the self-alignment procedure into an attitude estimation using the observation vectors. In the proposed method, a linear psuedo-measurement equation is adopted by employing the transfer method between the quaternion and the observation vectors. Analysis and simulation indicate that the accuracy of the self-alignment is improved. Meanwhile, to improve the convergence rate of the proposed method, a new method based on parameter recognition and a reconstruction algorithm for apparent gravitation is devised, which can reduce the influence of the random noises of the observation vectors. Simulations and turntable tests are carried out, and the results indicate that the proposed method can acquire sound alignment results with lower standard variances, and can obtain higher alignment accuracy and a faster convergence rate.

A Kalman Filter for SINS Self-Alignment Based on Vector Observation

PubMed Central

Xu, Xiang; Xu, Xiaosu; Zhang, Tao; Li, Yao; Tong, Jinwu

2017-01-01

In this paper, a self-alignment method for strapdown inertial navigation systems based on the q-method is studied. In addition, an improved method based on integrating gravitational apparent motion to form apparent velocity is designed, which can reduce the random noises of the observation vectors. For further analysis, a novel self-alignment method using a Kalman filter based on adaptive filter technology is proposed, which transforms the self-alignment procedure into an attitude estimation using the observation vectors. In the proposed method, a linear psuedo-measurement equation is adopted by employing the transfer method between the quaternion and the observation vectors. Analysis and simulation indicate that the accuracy of the self-alignment is improved. Meanwhile, to improve the convergence rate of the proposed method, a new method based on parameter recognition and a reconstruction algorithm for apparent gravitation is devised, which can reduce the influence of the random noises of the observation vectors. Simulations and turntable tests are carried out, and the results indicate that the proposed method can acquire sound alignment results with lower standard variances, and can obtain higher alignment accuracy and a faster convergence rate. PMID:28146059

Using shared goal setting to improve access and equity: a mixed methods study of the Good Goals intervention in children's occupational therapy.

PubMed

Kolehmainen, Niina; MacLennan, Graeme; Ternent, Laura; Duncan, Edward A S; Duncan, Eilidh M; Ryan, Stephen B; McKee, Lorna; Francis, Jill J

2012-08-16

Access and equity in children's therapy services may be improved by directing clinicians' use of resources toward specific goals that are important to patients. A practice-change intervention (titled 'Good Goals') was designed to achieve this. This study investigated uptake, adoption, and possible effects of that intervention in children's occupational therapy services. Mixed methods case studies (n = 3 services, including 46 therapists and 558 children) were conducted. The intervention was delivered over 25 weeks through face-to-face training, team workbooks, and 'tools for change'. Data were collected before, during, and after the intervention on a range of factors using interviews, a focus group, case note analysis, routine data, document analysis, and researchers' observations. Factors related to uptake and adoptions were: mode of intervention delivery, competing demands on therapists' time, and leadership by service manager. Service managers and therapists reported that the intervention: helped therapists establish a shared rationale for clinical decisions; increased clarity in service provision; and improved interactions with families and schools. During the study period, therapists' behaviours changed: identifying goals, odds ratio 2.4 (95% CI 1.5 to 3.8); agreeing goals, 3.5 (2.4 to 5.1); evaluating progress, 2.0 (1.1 to 3.5). Children's LoT decreased by two months [95% CI -8 to +4 months] across the services. Cost per therapist trained ranged from £1,003 to £1,277, depending upon service size and therapists' salary bands. Good Goals is a promising quality improvement intervention that can be delivered and adopted in practice and may have benefits. Further research is required to evaluate its: (i) impact on patient outcomes, effectiveness, cost-effectiveness, and (ii) transferability to other clinical contexts.

Computational Models for Nanoscale Fluid Dynamics and Transport Inspired by Nonequilibrium Thermodynamics1

PubMed Central

Radhakrishnan, Ravi; Yu, Hsiu-Yu; Eckmann, David M.; Ayyaswamy, Portonovo S.

2017-01-01

Traditionally, the numerical computation of particle motion in a fluid is resolved through computational fluid dynamics (CFD). However, resolving the motion of nanoparticles poses additional challenges due to the coupling between the Brownian and hydrodynamic forces. Here, we focus on the Brownian motion of a nanoparticle coupled to adhesive interactions and confining-wall-mediated hydrodynamic interactions. We discuss several techniques that are founded on the basis of combining CFD methods with the theory of nonequilibrium statistical mechanics in order to simultaneously conserve thermal equipartition and to show correct hydrodynamic correlations. These include the fluctuating hydrodynamics (FHD) method, the generalized Langevin method, the hybrid method, and the deterministic method. Through the examples discussed, we also show a top-down multiscale progression of temporal dynamics from the colloidal scales to the molecular scales, and the associated fluctuations, hydrodynamic correlations. While the motivation and the examples discussed here pertain to nanoscale fluid dynamics and mass transport, the methodologies presented are rather general and can be easily adopted to applications in convective heat transfer. PMID:28035168

Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation

PubMed Central

Bleakley, Marie; Turtle, Cameron J; Riddell, Stanley R

2012-01-01

Allogeneic hematopoietic stem cell transplantation (HCT) is currently the standard of care for most patients with high-risk acute leukemias and some other hematologic malignancies. Although HCT can be curative, many patients who undergo allogeneic HCT will later relapse. There is, therefore, a critical need for the development of novel post-HCT therapies for patients who are at high risk for disease recurrence following HCT. One potentially efficacious approach is adoptive T-cell immunotherapy, which is currently undergoing a renaissance that has been inspired by scientific insight into the key issues that impeded its previous clinical application. Translation of the next generation of adoptive T-cell therapies to the allogeneic HCT setting, using donor T cells of defined specificity and function, presents a unique set of challenges and opportunities. The challenges, progress and future of adoptive T-cell therapy following allogeneic HCT are discussed in this review. PMID:22992235

CCR 20th Anniversary Commentary: Autologous T Cells—The Ultimate Personalized Drug for the Immunotherapy of Human Cancer

PubMed Central

Rosenberg, Steven A.

2015-01-01

Summary The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. PMID:26672082

New frontiers for zebrafish management.

PubMed

Lawrence, C

2016-01-01

The zebrafish (Danio rerio) is a preeminent model organism with a wide and expanding utility for numerous scientific disciplines. The same features that once endeared this small freshwater minnow to developmental biologists combined with its relatively high genetic similarity to mammals and the advent of new, more efficient methods for genome editing are now helping to spur expanded growth in its usage in various fields, including toxicology, drug discovery, transplant biology, disease modeling, and even aquaculture. Continued maturation and adoption of the zebrafish model system in these and other fields of science will require that methods and approaches for husbandry and management of these fish in controlled settings be refined and improved to the extent that, ultimately, zebrafish research becomes more reproducible, defined, cost-effective, and accessible to the masses. Knowledge and technology transfer from laboratory animal science and commercial aquaculture will be a necessary part of this development. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of goods and valuation of ecosystem services (AGAVES) San Pedro River Basin, United States and Mexico

USGS Publications Warehouse

Semmens, Darius; Kepner, William; Goodrich, David

2010-01-01

A consortium of federal, academic, and nongovernment organization (NGO) partners have established a collaborative research enterprise in the San Pedro River Basin to develop methods, standards, and tools to assess and value ecosystem goods and services. The central premise of ecosystem services research is that human condition is intrinsically linked to the environment. Human health and well-being (including economic prosperity) depend on important supporting, regulating, provisioning, and cultural services that we derive from our surrounding ecosystems. The AGAVES project is intended as a demonstration study for incorporating ecosystem services information into resource management policy and decisionmaking. Accordingly, a nested, multiscale project design has been adopted to address a range of stakeholder information requirements. This design will further facilitate an evaluation of how well methods developed in this project can be transferred to other areas.

Evaluating the use of transfers for improving demand responsive systems adopting zoning strategies.

DOT National Transportation Integrated Search

2011-08-01

Due to widely dispersed population density over large and sparsely suburban/rural areas, : conventional fixed route transit services hardly satisfy the travel needs of their residents. As an : alternative, demand responsive transit (DRT) systems have...

Metro passengers’ route choice model and its application considering perceived transfer threshold

PubMed Central

Jin, Fanglei; Zhang, Yongsheng; Liu, Shasha

2017-01-01

With the rapid development of the Metro network in China, the greatly increased route alternatives make passengers’ route choice behavior and passenger flow assignment more complicated, which presents challenges to the operation management. In this paper, a path sized logit model is adopted to analyze passengers’ route choice preferences considering such parameters as in-vehicle time, number of transfers, and transfer time. Moreover, the “perceived transfer threshold” is defined and included in the utility function to reflect the penalty difference caused by transfer time on passengers’ perceived utility under various numbers of transfers. Next, based on the revealed preference data collected in the Guangzhou Metro, the proposed model is calibrated. The appropriate perceived transfer threshold value and the route choice preferences are analyzed. Finally, the model is applied to a personalized route planning case to demonstrate the engineering practicability of route choice behavior analysis. The results show that the introduction of the perceived transfer threshold is helpful to improve the model’s explanatory abilities. In addition, personalized route planning based on route choice preferences can meet passengers’ diversified travel demands. PMID:28957376

Thermal stability analysis of a superconducting magnet considering heat flow between magnet surface and liquid helium

NASA Astrophysics Data System (ADS)

Jang, J. Y.; Hwang, Y. J.; Ahn, M. C.; Choi, Y. S.

2018-07-01

This paper represents a numerical calculation method that enables highly-accurate simulations on temperature analysis of superconducting magnets considering the heat flow between the magnet and liquid helium during a quench. A three-dimensional (3D) superconducting magnet space was divided into many cells and the finite-difference method (FDM) was adopted to calculate the superconducting magnet temperatures governed by the heat transfer and joule heating of the each cell during a quench. To enhance the accuracy of the temperature calculations during a quench, the heat flow between the superconducting magnet surface and liquid helium, which lowers the magnet temperatures, was considered in this work. The electrical equation coupled with the governing thermal equation was also applied to calculate the change of the decay of the magnet current related to the joule heating. The proposed FDM method for temperatures calculation of a superconducting magnet during a quench process achieved results that were in good agreement with those obtained from an experiment.

Particle behavior simulation in thermophoresis phenomena by direct simulation Monte Carlo method

NASA Astrophysics Data System (ADS)

Wada, Takao

2014-07-01

A particle motion considering thermophoretic force is simulated by using direct simulation Monte Carlo (DSMC) method. Thermophoresis phenomena, which occur for a particle size of 1 μm, are treated in this paper. The problem of thermophoresis simulation is computation time which is proportional to the collision frequency. Note that the time step interval becomes much small for the simulation considering the motion of large size particle. Thermophoretic forces calculated by DSMC method were reported, but the particle motion was not computed because of the small time step interval. In this paper, the molecule-particle collision model, which computes the collision between a particle and multi molecules in a collision event, is considered. The momentum transfer to the particle is computed with a collision weight factor, where the collision weight factor means the number of molecules colliding with a particle in a collision event. The large time step interval is adopted by considering the collision weight factor. Furthermore, the large time step interval is about million times longer than the conventional time step interval of the DSMC method when a particle size is 1 μm. Therefore, the computation time becomes about one-millionth. We simulate the graphite particle motion considering thermophoretic force by DSMC-Neutrals (Particle-PLUS neutral module) with above the collision weight factor, where DSMC-Neutrals is commercial software adopting DSMC method. The size and the shape of the particle are 1 μm and a sphere, respectively. The particle-particle collision is ignored. We compute the thermophoretic forces in Ar and H2 gases of a pressure range from 0.1 to 100 mTorr. The results agree well with Gallis' analytical results. Note that Gallis' analytical result for continuum limit is the same as Waldmann's result.

Blending addiction research and practice: strategies for technology transfer.

PubMed

Condon, Timothy P; Miner, Lucinda L; Balmer, Curtis W; Pintello, Denise

2008-09-01

Consistent with traditional conceptions of technology transfer, efforts to translate substance abuse and addiction research into treatment practice have typically relied on the passive dissemination of research findings. The large gap between addiction research and practice, however, indicates that there are many barriers to successful technology transfer and that dissemination alone is not sufficient to produce lasting changes in addiction treatment. To accelerate the translation of research into practice, the National Institute on Drug Abuse launched the Blending Initiative in 2001. In part a collaboration with the Substance Abuse and Mental Health Services Administration/Center for Substance Abuse Treatment's Addiction Technology Transfer Center program, this initiative aims to improve the development, effectiveness, and usability of evidence-based practices and reduce the obstacles to their timely adoption and implementation.

Flying Lessons for Clinicians: Developing System 2 Practice.

PubMed

Gregoire, Jerome N; Alfes, Celeste M; Reimer, Andrew P; Terhaar, Mary F

There is a long history of adopting lessons learned from aviation to improve health care practice. Two of the major practices that have successfully transferred include using a checklist and simulation. Training and simulation technology is currently underdeveloped for nurses and health care providers entering critical care transport. This article describes a pedagogical approach adopted from aviation to develop a new simulation platform and program of research to develop the science of critical care transport nursing education. Copyright © 2017 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.

Evaluation of tunnel seismic prediction (TSP) result using the Japanese highway rock mass classification system for Pahang-Selangor Raw Water Transfer Tunnel

NASA Astrophysics Data System (ADS)

Von, W. C.; Ismail, M. A. M.

2017-10-01

The knowing of geological profile ahead of tunnel face is significant to minimize the risk in tunnel excavation work and cost control in preventative measure. Due to mountainous area, site investigation with vertical boring is not recommended to obtain the geological profile for Pahang-Selangor Raw Water Transfer project. Hence, tunnel seismic prediction (TSP) method is adopted to predict the geological profile ahead of tunnel face. In order to evaluate the TSP results, IBM SPSS Statistic 22 is used to run artificial neural network (ANN) analysis to back calculate the predicted Rock Grade Points (JH) from actual Rock Grade Points (JH) using Vp, Vs and Vp/Vs from TSP. The results show good correlation between predicted Rock Grade points and actual Rock Grade Points (JH). In other words, TSP can provide geological profile prediction ahead of tunnel face significantly while allowing continuously TBM excavation works. Identifying weak zones or faults ahead of tunnel face is crucial for preventative measures to be carried out in advance for a safer tunnel excavation works.

Analysis of antigen-specific B-cell memory directly ex vivo.

PubMed

McHeyzer-Williams, Louise J; McHeyzer-Williams, Michael G

2004-01-01

Helper T-cell-regulated B-cell memory develops in response to initial antigen priming as a cellular product of the germinal center (GC) reaction. On antigen recall, memory response precursors expand rapidly with exaggerated differentiation into plasma cells to produce the high-titer, high-affinity antibody(Ab) that typifies the memory B-cell response in vivo. We have devised a high-resolution flow cytometric strategy to quantify the emergence and maintenance of antigen-specific memory B cells directly ex vivo. Extended cell surface phenotype establishes a level of cellular diversity not previously appreciated for the memory B-cell compartment. Using an "exclusion transfer" strategy, we ascertain the capacity of two distinct memory B-cell populations to transfer antigen-specific memory into naive adoptive hosts. Finally, we sequence expressed messenger ribonucleic acid (mRNA) from single cells within the population to estimate the level of somatic hypermutation as the best molecular indicator of B-cell memory. In this chapter, we describe the methods used in each of these four sections that serve to provide high-resolution quantification of antigen-specific B-cell memory responses directly ex vivo.

Helicity conservation by flow across scales in reconnecting vortex links and knots

PubMed Central

Scheeler, Martin W.; Kleckner, Dustin; Kindlmann, Gordon L.; Irvine, William T. M.

2014-01-01

The conjecture that helicity (or knottedness) is a fundamental conserved quantity has a rich history in fluid mechanics, but the nature of this conservation in the presence of dissipation has proven difficult to resolve. Making use of recent advances, we create vortex knots and links in viscous fluids and simulated superfluids and track their geometry through topology-changing reconnections. We find that the reassociation of vortex lines through a reconnection enables the transfer of helicity from links and knots to helical coils. This process is remarkably efficient, owing to the antiparallel orientation spontaneously adopted by the reconnecting vortices. Using a new method for quantifying the spatial helicity spectrum, we find that the reconnection process can be viewed as transferring helicity between scales, rather than dissipating it. We also infer the presence of geometric deformations that convert helical coils into even smaller scale twist, where it may ultimately be dissipated. Our results suggest that helicity conservation plays an important role in fluids and related fields, even in the presence of dissipation. PMID:25326419

IDO and galectin-3 hamper the ex vivo generation of clinical grade tumor-specific T cells for adoptive cell therapy in metastatic melanoma.

PubMed

Melief, Sara M; Visser, Marten; van der Burg, Sjoerd H; Verdegaal, Els M E

2017-07-01

Adoptive T cell transfer (ACT) with ex vivo-expanded tumor-reactive T cells proved to be successful for the treatment of metastatic melanoma patients. Mixed lymphocyte tumor cell cultures (MLTC) can be used to generate tumor-specific T cells for ACT; however, in a number of cases tumor-reactive T cell, expansion is far from optimal. We hypothesized that this is due to tumor intrinsic and extrinsic factors and aimed to identify and manipulate these factors so to optimize our clinical, GMP-compliant MLTC protocol. We found that the tumor cell produced IDO and/or galectin-3, and the accumulation of CD4 + CD25 hi FoxP3 + T cells suppressed the expansion of tumor-specific T cells in the MLTC. Strategies to eliminate CD4 + CD25 hi FoxP3 + T cells during culture required the depletion of the whole CD4 + T cell population and were found to be undesirable. Blocking of IDO and galectin-3 was feasible and resulted in improved efficiency of the MLTC. Implementation of these findings in clinical protocols for ex vivo expansion of tumor-reactive T cells holds promise for an increased therapeutic potential of adoptive cell transfer treatments with tumor-specific T cells.

Experimental and numerical investigation of a packed-bed thermal energy storage device

NASA Astrophysics Data System (ADS)

Yang, Bei; Wang, Yan; Bai, Fengwu; Wang, Zhifeng

2017-06-01

This paper presents a pilot-scale setup built to study a packed bed thermal energy storage device based on ceramic balls randomly poured into a cylindrical tank while using air as heat transfer fluid. Temperature distribution of ceramic balls throughout the packed bed is investigated both experimentally and numerically. Method of characteristic is adopted to improve the numerical computing efficiency, and mesh independence is verified to guarantee the accuracy of numerical solutions and the economy of computing time cost at the same time. Temperature in tests is as high as over 600 °C, and modeling prediction shows good agreements with experimental results under various testing conditions when heat loss is included and thermal properties of air are considered as temperature dependent.

[Nudge in prevention… an alternative approach or a dead end?].

PubMed

Cambon, Linda

2016-01-01

Prevention policies need to be more effective. Practitioners and decision-makers therefore need to innovate in the field of prevention policies and interventions by adapting methods or strategies used in other domains. Nudges, considered to be an attractive technique in view of its efficacy, are one of these innovations.However, the use of nudges in prevention policies raises ethical debates which will be summarized in this article. After recalling the definition of nudging, this article describes the ethical debates concerning three issues and emphasizes the way they can reflect a beneficial, democratic, freedom-based and autonomous society.In conclusion, this article encourages prevention practitioners and decision-makers to adopt a larger view before transferring strategies from other sectors and especially to consider all ethical issues.

Comparison of Requirements for Composite Structures for Aircraft and Space Applications

NASA Technical Reports Server (NTRS)

Raju, Ivatury S.; Elliot, Kenny B.; Hampton, Roy W.; Knight, Norman F., Jr.; Aggarwal, Pravin; Engelstad, Stephen P.; Chang, James B.

2010-01-01

In this report, the aircraft and space vehicle requirements for composite structures are compared. It is a valuable exercise to study composite structural design approaches used in the airframe industry and to adopt methodology that is applicable for space vehicles. The missions, environments, analysis methods, analysis validation approaches, testing programs, build quantities, inspection, and maintenance procedures used by the airframe industry, in general, are not transferable to spaceflight hardware. Therefore, while the application of composite design approaches from aircraft and other industries is appealing, many aspects cannot be directly utilized. Nevertheless, experiences and research for composite aircraft structures may be of use in unexpected arenas as space exploration technology develops, and so continued technology exchanges are encouraged.

A wideband analog correlator system for AMiBA

NASA Astrophysics Data System (ADS)

Li, Chao-Te; Kubo, Derek; Han, Chih-Chiang; Chen, Chung-Cheng; Chen, Ming-Tang; Lien, Chun-Hsien; Wang, Huei; Wei, Ray-Ming; Yang, Chia-Hsiang; Chiueh, Tzi-Dar; Peterson, Jeffrey; Kesteven, Michael; Wilson, Warwick

2004-10-01

A wideband correlator system with a bandwidth of 16 GHz or more is required for Array for Microwave Background Anisotropy (AMiBA) to achieve the sensitivity of 10μK in one hour of observation. Double-balanced diode mixers were used as multipliers in 4-lag correlator modules. Several wideband modules were developed for IF signal distribution between receivers and correlators. Correlator outputs were amplified, and digitized by voltage-to-frequency converters. Data acquisition circuits were designed using field programmable gate arrays (FPGA). Subsequent data transfer and control software were based on the configuration for Australia Telescope Compact Array. Transform matrix method will be adopted during calibration to take into account the phase and amplitude variations of analog devices across the passband.

Reference dosimetry study for 3 MEV electron beam accelerator in malaysia

NASA Astrophysics Data System (ADS)

Ali, Noriah Mod; Sunaga, Hiromi; Tanaka, Ryuichi

1995-09-01

An effective quality assurance programme is initiated for the use of the electron beam with energies up to 3 MeV. The key element of the programme is the establishment of a relationship between the standardised beam to the routine technique which is employed to verify the beam parameter. A total absorbing calorimeter was adopted as a suitable reference system and when used in combination with the electron current densitymeter (ECD) will enable to determine the mean energy for electron with energies between 1 to 3 MeV. An appropriate method of transfering the standard parameter is studied and the work that is expected to optimise the accuracy attainable with routine check-up of the irradiation parameter are presented.

Phylomemetics—Evolutionary Analysis beyond the Gene

PubMed Central

Howe, Christopher J.; Windram, Heather F.

2011-01-01

Genes are propagated by error-prone copying, and the resulting variation provides the basis for phylogenetic reconstruction of evolutionary relationships. Horizontal gene transfer may be superimposed on a tree-like evolutionary pattern, with some relationships better depicted as networks. The copying of manuscripts by scribes is very similar to the replication of genes, and phylogenetic inference programs can be used directly for reconstructing the copying history of different versions of a manuscript text. Phylogenetic methods have also been used for some time to analyse the evolution of languages and the development of physical cultural artefacts. These studies can help to answer a range of anthropological questions. We propose the adoption of the term “phylomemetics” for phylogenetic analysis of reproducing non-genetic elements. PMID:21655311

22 CFR 96.93 - Reports to the Secretary about accredited agencies and approved persons and their activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... accrediting entity must report to the Secretary within thirty days of the time it learns that an accredited agency or approved person: (1) Has ceased to provide adoption services; or (2) Has transferred its...

22 CFR 96.93 - Reports to the Secretary about accredited agencies and approved persons and their activities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accrediting entity must report to the Secretary within thirty days of the time it learns that an accredited agency or approved person: (1) Has ceased to provide adoption services; or (2) Has transferred its...

22 CFR 96.93 - Reports to the Secretary about accredited agencies and approved persons and their activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... accrediting entity must report to the Secretary within thirty days of the time it learns that an accredited agency or approved person: (1) Has ceased to provide adoption services; or (2) Has transferred its...

22 CFR 96.93 - Reports to the Secretary about accredited agencies and approved persons and their activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... accrediting entity must report to the Secretary within thirty days of the time it learns that an accredited agency or approved person: (1) Has ceased to provide adoption services; or (2) Has transferred its...

22 CFR 96.93 - Reports to the Secretary about accredited agencies and approved persons and their activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... accrediting entity must report to the Secretary within thirty days of the time it learns that an accredited agency or approved person: (1) Has ceased to provide adoption services; or (2) Has transferred its...

Conditions That Facilitate the Implementation of Educational Technology Innovations.

ERIC Educational Resources Information Center

Ely, Donald P.

1990-01-01

Describes eight conditions that facilitate the adoption, implementation, and institutionalization of educational technology innovations and suggests applications to the transfer of portable software. Applications of these conditions involving educational technology in Indonesia, Chile, and Peru are evaluated, and guidelines for successful…

3D-SIFT-Flow for atlas-based CT liver image segmentation

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

Xu, Yan, E-mail: xuyan04@gmail.com; Xu, Chenchao, E-mail: chenchaoxu33@gmail.com; Kuang, Xiao, E-mail: kuangxiao.ace@gmail.com

Purpose: In this paper, the authors proposed a new 3D registration algorithm, 3D-scale invariant feature transform (SIFT)-Flow, for multiatlas-based liver segmentation in computed tomography (CT) images. Methods: In the registration work, the authors developed a new registration method that takes advantage of dense correspondence using the informative and robust SIFT feature. The authors computed the dense SIFT features for the source image and the target image and designed an objective function to obtain the correspondence between these two images. Labeling of the source image was then mapped to the target image according to the former correspondence, resulting in accurate segmentation.more » In the fusion work, the 2D-based nonparametric label transfer method was extended to 3D for fusing the registered 3D atlases. Results: Compared with existing registration algorithms, 3D-SIFT-Flow has its particular advantage in matching anatomical structures (such as the liver) that observe large variation/deformation. The authors observed consistent improvement over widely adopted state-of-the-art registration methods such as ELASTIX, ANTS, and multiatlas fusion methods such as joint label fusion. Experimental results of liver segmentation on the MICCAI 2007 Grand Challenge are encouraging, e.g., Dice overlap ratio 96.27% ± 0.96% by our method compared with the previous state-of-the-art result of 94.90% ± 2.86%. Conclusions: Experimental results show that 3D-SIFT-Flow is robust for segmenting the liver from CT images, which has large tissue deformation and blurry boundary, and 3D label transfer is effective and efficient for improving the registration accuracy.« less

A general solution strategy of modified power method for higher mode solutions

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

Zhang, Peng; Lee, Hyunsuk; Lee, Deokjung, E-mail: deokjung@unist.ac.kr

2016-01-15

A general solution strategy of the modified power iteration method for calculating higher eigenmodes has been developed and applied in continuous energy Monte Carlo simulation. The new approach adopts four features: 1) the eigen decomposition of transfer matrix, 2) weight cancellation for higher modes, 3) population control with higher mode weights, and 4) stabilization technique of statistical fluctuations using multi-cycle accumulations. The numerical tests of neutron transport eigenvalue problems successfully demonstrate that the new strategy can significantly accelerate the fission source convergence with stable convergence behavior while obtaining multiple higher eigenmodes at the same time. The advantages of the newmore » strategy can be summarized as 1) the replacement of the cumbersome solution step of high order polynomial equations required by Booth's original method with the simple matrix eigen decomposition, 2) faster fission source convergence in inactive cycles, 3) more stable behaviors in both inactive and active cycles, and 4) smaller variances in active cycles. Advantages 3 and 4 can be attributed to the lower sensitivity of the new strategy to statistical fluctuations due to the multi-cycle accumulations. The application of the modified power method to continuous energy Monte Carlo simulation and the higher eigenmodes up to 4th order are reported for the first time in this paper. -- Graphical abstract: -- Highlights: •Modified power method is applied to continuous energy Monte Carlo simulation. •Transfer matrix is introduced to generalize the modified power method. •All mode based population control is applied to get the higher eigenmodes. •Statistic fluctuation can be greatly reduced using accumulated tally results. •Fission source convergence is accelerated with higher mode solutions.« less

Direct determination of resonance energy transfer in photolyase: structural alignment for the functional state.

PubMed

Tan, Chuang; Guo, Lijun; Ai, Yuejie; Li, Jiang; Wang, Lijuan; Sancar, Aziz; Luo, Yi; Zhong, Dongping

2014-11-13

Photoantenna is essential to energy transduction in photoinduced biological machinery. A photoenzyme, photolyase, has a light-harvesting pigment of methenyltetrahydrofolate (MTHF) that transfers its excitation energy to the catalytic flavin cofactor FADH¯ to enhance DNA-repair efficiency. Here we report our systematic characterization and direct determination of the ultrafast dynamics of resonance energy transfer from excited MTHF to three flavin redox states in E. coli photolyase by capturing the intermediates formed through the energy transfer and thus excluding the electron-transfer quenching pathway. We observed 170 ps for excitation energy transferring to the fully reduced hydroquinone FADH¯, 20 ps to the fully oxidized FAD, and 18 ps to the neutral semiquinone FADH(•), and the corresponding orientation factors (κ(2)) were determined to be 2.84, 1.53 and 1.26, respectively, perfectly matching with our calculated theoretical values. Thus, under physiological conditions and over the course of evolution, photolyase has adopted the optimized orientation of its photopigment to efficiently convert solar energy for repair of damaged DNA.

A Three-Dimensional Model of the Yeast Genome

NASA Astrophysics Data System (ADS)

Noble, William; Duan, Zhi-Jun; Andronescu, Mirela; Schutz, Kevin; McIlwain, Sean; Kim, Yoo Jung; Lee, Choli; Shendure, Jay; Fields, Stanley; Blau, C. Anthony

Layered on top of information conveyed by DNA sequence and chromatin are higher order structures that encompass portions of chromosomes, entire chromosomes, and even whole genomes. Interphase chromosomes are not positioned randomly within the nucleus, but instead adopt preferred conformations. Disparate DNA elements co-localize into functionally defined aggregates or factories for transcription and DNA replication. In budding yeast, Drosophila and many other eukaryotes, chromosomes adopt a Rabl configuration, with arms extending from centromeres adjacent to the spindle pole body to telomeres that abut the nuclear envelope. Nonetheless, the topologies and spatial relationships of chromosomes remain poorly understood. Here we developed a method to globally capture intra- and inter-chromosomal interactions, and applied it to generate a map at kilobase resolution of the haploid genome of Saccharomyces cerevisiae. The map recapitulates known features of genome organization, thereby validating the method, and identifies new features. Extensive regional and higher order folding of individual chromosomes is observed. Chromosome XII exhibits a striking conformation that implicates the nucleolus as a formidable barrier to interaction between DNA sequences at either end. Inter-chromosomal contacts are anchored by centromeres and include interactions among transfer RNA genes, among origins of early DNA replication and among sites where chromosomal breakpoints occur. Finally, we constructed a three-dimensional model of the yeast genome. Our findings provide a glimpse of the interface between the form and function of a eukaryotic genome.

Identifying Pathways for Improving Household Food Self-Sufficiency Outcomes in the Hills of Nepal

PubMed Central

Karki, Tika B.; Sah, Shrawan K.; Thapa, Resam B.; McDonald, Andrew J.; Davis, Adam S.

2015-01-01

Maintaining and improving household food self-sufficiency (FSS) in mountain regions is an ongoing challenge. There are many facets to the issue, including comparatively high levels of land fragmentation, challenging terrain and transportation bottlenecks, declining labor availability due to out-migration, and low technical knowledge, among others. Using a nonparametric multivariate approach, we quantified primary associations underlying current levels of FSS in the mid-hills of Nepal. A needs assessment survey was administered to 77 households in Lungaun (Baglung District), Pang (Parbat District), and Pathlekhet (Myagdi District), with a total of 80 variables covering five performance areas; resulting data were analyzed using Classification and Regression Trees. The most parsimonious statistical model for household FSS highlighted associations with agronomic management, including yields of maize and fingermillet within a relay cropping system and adoption of improved crop cultivars. Secondary analyses of the variables retained in the first model again focused primarily on crop and livestock management. It thus appears that continued emphasis on technical agricultural improvements is warranted, independent of factors such as land holding size that, in any case, are very difficult to change through development interventions. Initiatives to increase household FSS in the mid-hills of Nepal will benefit from placing a primary focus on methods of agricultural intensification to improve crop yields and effective technology transfer to increase adoption of these methods. PMID:26047508

Control of repulsive force in a virtual environment using an electrorheological haptic master for a surgical robot application

NASA Astrophysics Data System (ADS)

Oh, Jong-Seok; Choi, Seung-Hyun; Choi, Seung-Bok

2014-01-01

This paper presents control performances of a new type of four-degrees-of-freedom (4-DOF) haptic master that can be used for robot-assisted minimally invasive surgery (RMIS). By adopting a controllable electrorheological (ER) fluid, the function of the proposed master is realized as a haptic feedback as well as remote manipulation. In order to verify the efficacy of the proposed master and method, an experiment is conducted with deformable objects featuring human organs. Since the use of real human organs is difficult for control due to high cost and moral hazard, an excellent alternative method, the virtual reality environment, is used for control in this work. In order to embody a human organ in the virtual space, the experiment adopts a volumetric deformable object represented by a shape-retaining chain linked (S-chain) model which has salient properties such as fast and realistic deformation of elastic objects. In haptic architecture for RMIS, the desired torque/force and desired position originating from the object of the virtual slave and operator of the haptic master are transferred to each other. In order to achieve the desired torque/force trajectories, a sliding mode controller (SMC) which is known to be robust to uncertainties is designed and empirically implemented. Tracking control performances for various torque/force trajectories from the virtual slave are evaluated and presented in the time domain.

Targeting CD6 for the treatment of experimental autoimmune uveitis.

PubMed

Zhang, Lingjun; Li, Yan; Qiu, Wen; Bell, Brent A; Dvorina, Nina; Baldwin, William M; Singer, Nora; Kern, Timothy; Caspi, Rachel R; Fox, David A; Lin, Feng

2018-06-01

CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells. Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

High-efficiency lysis of cervical cancer by allogeneic NK cells derived from umbilical cord progenitors is independent of HLA status.

PubMed

Veluchamy, John P; Heeren, A Marijne; Spanholtz, Jan; van Eendenburg, Jaap D H; Heideman, Daniëlle A M; Kenter, Gemma G; Verheul, Henk M; van der Vliet, Hans J; Jordanova, Ekaterina S; de Gruijl, Tanja D

2017-01-01

Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK). Whereas CET monotherapy was ineffective against the panel of cervical cancer cell lines, irrespective of their EGFR expression levels and despite their RAS wt status, it significantly enhanced the in vitro cytotoxic efficacy of activated PBNK (P = 0.002). Equally superior cytotoxicity over activated PBNK alone was achieved by UCB-NK (P < 0.001). Both PBNK- and UCB-NK-mediated cytotoxic activity was dependent on the NK-activating receptors natural killer group 2, member D receptor (NKG2D) and DNAX accessory molecule-1 (DNAM-1) (P < 0.05) and unrelated to expression levels of the inhibitory receptors HLA-E and/or HLA-G. Most strikingly, whereas the PBNK's cytotoxic activity was inversely correlated with HLA-ABC levels (P = 0.036), PBNK + CET and UCB-NK cytotoxicity were entirely independent of HLA-ABC expression. In conclusion, this study provides a rationale to initiate a clinical trial for cervical cancer with adoptively transferred allogeneic NK cells, employing either UCB-NK or PBNK + CET for EGFR-expressing tumors. Adoptive transfer of UCB-NK might serve as a generally applicable treatment for cervical cancer, enabled by HLA-, histology- and HPV-independent killing mechanisms.

Whole-Killed Blood-Stage Vaccine-Induced Immunity Suppresses the Development of Malaria Parasites in Mosquitoes.

PubMed

Zhu, Feng; Liu, Taiping; Zhao, Chenhao; Lu, Xiao; Zhang, Jian; Xu, Wenyue

2017-01-01

As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection. The depletion of CD4 + T cells prior to the adoptive transfer of parasites into WKV-immunized mice has no effect on the development of the malaria parasite in the mosquito, but the adoptive transfer of the serum from the immunized mice into the parasite-inoculated mice remarkably suppresses the development of malaria parasites in mosquitoes. Furthermore, immunized mice challenged with the malaria parasite generate higher levels of parasite-specific Abs and the inflammatory cytokines MCP-1 and IFN-γ. However, the adoptive transfer of parasite-specific IgG or the depletion of MCP-1, but not IFN-γ, to some extent is closely associated with the suppression of malaria parasite development in mosquitoes. These data strongly suggest that WKV-induced immune responses confer protection against the mosquito stage, which is largely dependent on malaria parasite-specific Abs and MCP-1. This finding sheds new light on blocking malaria transmission through the immunization of individuals with the WKV. Copyright © 2016 by The American Association of Immunologists, Inc.

Cross-talk between T Cells and Hematopoietic Stem Cells during Adoptive Cellular Therapy for Malignant Glioma.

PubMed

Wildes, Tyler J; Grippin, Adam; Dyson, Kyle A; Wummer, Brandon M; Damiani, David J; Abraham, Rebecca S; Flores, Catherine T; Mitchell, Duane A

2018-04-30

Purpose: Adoptive T-cell immunotherapy (ACT) has emerged as a viable therapeutic for peripheral and central nervous system (CNS) tumors. In peripheral cancers, optimal efficacy of ACT is reliant on dendritic cells (DCs) in the tumor microenvironment. However, the CNS is largely devoid of resident migratory DCs to function as antigen-presenting cells during immunotherapy. Herein, we demonstrate that cellular interactions between adoptively transferred tumor-reactive T cells and bone marrow-derived hematopoietic stem and progenitor cells (HSPCs) lead to the generation of potent intratumoral DCs within the CNS compartment. Experimental Design: We evaluated HSPC differentiation during ACT in vivo in glioma-bearing hosts and HSPC proliferation and differentiation in vitro using a T-cell coculture system. We utilized FACS, ELISAs, and gene expression profiling to study the phenotype and function of HSPC-derived cells ex vivo and in vivo. To demonstrate the impact of HSPC differentiation and function on antitumor efficacy, we performed survival experiments. Results: Transfer of HSPCs with concomitant ACT led to the production of activated CD86 + CD11c + MHCII + cells consistent with DC phenotype and function within the brain tumor microenvironment. These intratumoral DCs largely supplanted abundant host myeloid-derived suppressor cells. We determined that during ACT, HSPC-derived cells in gliomas rely on T-cell-released IFNγ to differentiate into DCs, activate T cells, and reject intracranial tumors. Conclusions: Our data support the use of HSPCs as a novel cellular therapy. Although DC vaccines induce robust immune responses in the periphery, our data demonstrate that HSPC transfer uniquely generates intratumoral DCs that potentiate T-cell responses and promote glioma rejection in situ Clin Cancer Res; 1-12. ©2018 AACR. ©2018 American Association for Cancer Research.

Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy.

PubMed

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S; Wunderlich, John R; Dudley, Mark E; Rosenberg, Steven A

2013-09-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ~50 × 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3(+)CD8(+) cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

PubMed Central

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S.; Wunderlich, John R.; Dudley, Mark E.

2013-01-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3+ T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8+ cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ∼50 × 109 T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3+CD8+ cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I–mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I–mediated up-regulation of CD137 (4-1BB) expression on CD8+ cells suggested that 0–3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells. PMID:23904171

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

PubMed

Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

2012-12-01

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

Adoptive transfer of Epstein-Barr virus-specific cytotoxic T-lymphocytes for the treatment of angiocentric lymphomas.

PubMed

Cho, Hyun-Il; Hong, Young Seon; Lee, Myung Ah; Kim, Eun-Kyung; Yoon, Sung-Hee; Kim, Chun-Choo; Kim, Tai-Gyu

2006-01-01

Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin's lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient's T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 3 10(7) cells/m(2), and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lymphoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.

Adoptive transfer of nontransgenic mesenteric lymph node cells induces colitis in athymic HLA-B27 transgenic nude rats

PubMed Central

Hoentjen, F; Tonkonogy, S L; Liu, B; Sartor, R B; Taurog, J D; Dieleman, L A

2006-01-01

HLA-B27 transgenic (TG) rats develop spontaneous colitis when colonized with intestinal bacteria, whereas athymic nude (rnu/rnu) HLA-B27 TG rats remain disease free. The present study was designed to determine whether or not HLA-B27 expression on T cells is required for development of colitis after transfer of mesenteric lymph node (MLN) cells into rnu/rnu HLA-B27 recipients. Athymic nontransgenic (non-TG) and HLA-B27 TG recipients received MLN cells from either TG or non-TG rnu/+ heterozygous donor rats that contain T cells. HLA-B27 TG rnu/rnu recipients receiving either non-TG or TG MLN cells developed severe colitis and had higher caecal MPO and IL-1β levels, and their MLN cells produced more IFN-γ and less IL-10 after in vitro stimulation with caecal bacterial lysate compared to rnu/rnu non-TG recipients that remained disease free after receiving either TG or non-TG cells. Interestingly, proliferating donor TG T cells were detectable one week after adoptive transfer into rnu/rnu TG recipients but not after transfer into non-TG recipients. T cells from either non-TG or TG donors induce colitis in rnu/rnu TG but not in non-TG rats, suggesting that activation of effector T cells by other cell types that express HLA-B27 is pivotal for the pathogenesis of colitis in this model. PMID:16487247

Development and characterization of microsatellite markers for Morus spp. and assessment of their transferability to other closely related species

PubMed Central

2013-01-01

Background Adoption of genomics based breeding has emerged as a promising approach for achieving comprehensive crop improvement. Such an approach is more relevant in the case of perennial species like mulberry. However, unavailability of genomic resources of co-dominant marker systems has been the major constraint for adopting molecular breeding to achieve genetic enhancement of Mulberry. The goal of this study was to develop and characterize a large number of locus specific genic and genomic SSR markers which can be effectively used for molecular characterization of mulberry species/genotypes. Result We analyzed a total of 3485 DNA sequences including genomic and expressed sequences (ESTs) of mulberry (Morus alba L.) genome. We identified 358 sequences to develop appropriate microsatellite primer pairs representing 222 genomic and 136 EST regions. Primers amplifying locus specific regions of Dudia white (a genotype of Morus alba L), were identified and 137 genomic and 51 genic SSR markers were standardized. A two pronged strategy was adopted to assess the applicability of these SSR markers using mulberry species and genotypes along with a few closely related species belonging to the family Moraceae viz., Ficus, Fig and Jackfruit. While 100% of these markers amplified specific loci on the mulberry genome, 79% were transferable to other related species indicating the robustness of these markers and the potential they hold in analyzing the molecular and genetic diversity among mulberry germplasm as well as other related species. The inherent ability of these markers in detecting heterozygosity combined with a high average polymorphic information content (PIC) of 0.559 ranging between 0.076 and 0.943 clearly demonstrates their potential as genomic resources in diversity analysis. The dissimilarity coefficient determined based on Neighbor joining method, revealed that the markers were successful in segregating the mulberry species, genotypes and other related species into distinct clusters. Conclusion We report a total of 188 genomic and genic SSR markers in Morus alba L. A large proportion of these markers (164) were polymorphic both among mulberry species and genotypes. A substantial number of these markers (149) were also transferable to other related species like Ficus, Fig and Jackfruit. The extent of polymorphism revealed and the ability to detect heterozygosity among the cross pollinated mulberry species and genotypes render these markers an invaluable genomic resource that can be utilized in assessing molecular diversity as well as in QTL mapping and subsequently mulberry crop improvement through MAS. PMID:24289047

Simultaneous transfer of optical frequency and time over 306 km long-haul optical fibre link

NASA Astrophysics Data System (ADS)

Hucl, Vaclav; Cizek, Martin; Pravdova, Lenka; Rerucha, Simon; Hrabina, Jan; Mikel, Bretislav; Smotlacha, Vladimir; Vojtech, Josef; Lazar, Josef; Cip, Ondrej

2016-12-01

Optical fibre links for distributing optical frequencies and time stamps were researched and experimentally tested in the past fifteen years. They have been used mainly for stability comparison of experimental optical clocks. But recent development puts demands on a technology transfer from laboratory experiments to the real industry. The remote calibration of interrogators of Fibre Bragg Grating strain sensory networks is one of important examples. The first step of the adoption the time and frequency broadcasting should be the drop-out free long-term operation of this technology between research laboratories connected via long-haul fibre links. We present a 306 km long-haul optical fibre link between the cities of Prague and Brno in the Czech Republic where a coherent transfer of stable optical frequency and a stable time signal has been firstly demonstrated. The link between ISI CAS Brno and CESNET Prague uses an internet communication fibre where a window of 1540-1546 nm is dedicated for the coherent transfer and 1PPS signal. The link is equipped with 6 bidirectional EDFA amplifiers. The optical frequency standard based on the highly-coherent laser Koheras Adjustik working at 1540.5 nm and stabilized with a saturation absorption spectroscopy technique was used for the coherent wave transfer. The suppression of the Doppler shift induced by the optical fibre was based on an accoustooptical modulator with a servo-loop including a fast PID controller processing the beat-note frequency given by mixing of the Adjustik laser (Brno) and the reflected frequency of this laser from the far end of 306 km long-haul fibre link (Prague). We verified the Doppler shift suppression for the coherent wave with a measuring method analysing the transport delay of the 1PPS signal.

Soret and Dufour effects on MHD peristaltic flow of Prandtl fluid in a rotating channel

NASA Astrophysics Data System (ADS)

Hayat, Tasawar; Zahir, Hina; Tanveer, Anum; Alsaedi, Ahmed

2018-03-01

An analysis has been arranged to study the magnetohydrodynamics (MHD) peristaltic flow of Prandtl fluid in a channel with flexible walls. Both fluid and channel are in a state of solid body rotation. Simultaneous effects of heat and mass transfer with thermal-diffusion (Soret) and diffusion-thermo (Dufour) effects are considered. Convective conditions for heat and mass transfer in the formulation are adopted. Ordinary differential systems using low Reynolds number and long wavelength approximation are obtained. Resulting equations have been solved numerically. The discussion of axial and secondary velocities, temperature, concentration and heat transfer coefficient with respect to emerging parameters embedded in the flow model is presented after sketching plots.

K β to K α X-ray intensity ratios and K to L shell vacancy transfer probabilities of Co, Ni, Cu, and Zn

NASA Astrophysics Data System (ADS)

Anand, L. F. M.; Gudennavar, S. B.; Bubbly, S. G.; Kerur, B. R.

2015-12-01

The K to L shell total vacancy transfer probabilities of low Z elements Co, Ni, Cu, and Zn are estimated by measuring the K β to K α intensity ratio adopting the 2π-geometry. The target elements were excited by 32.86 keV barium K-shell X-rays from a weak 137Cs γ-ray source. The emitted K-shell X-rays were detected using a low energy HPGe X-ray detector coupled to a 16 k MCA. The measured intensity ratios and the total vacancy transfer probabilities are compared with theoretical results and others' work, establishing a good agreement.

Counterheroism, Common Knowledge, and Ergonomics: Concepts from Aviation That Could Improve Patient Safety

PubMed Central

Lewis, Geraint H; Vaithianathan, Rhema; Hockey, Peter M; Hirst, Guy; Bagian, James P

2011-01-01

Context: Many safety initiatives have been transferred successfully from commercial aviation to health care. This article develops a typology of aviation safety initiatives, applies this to health care, and proposes safety measures that might be adopted more widely. It then presents an economic framework for determining the likely costs and benefits of different patient safety initiatives. Methods: This article describes fifteen examples of error countermeasures that are used in public transport aviation, many of which are not routinely used in health care at present. Examples are the sterile cockpit rule, flight envelope protection, the first-names-only rule, and incentivized no-fault reporting. It develops a conceptual schema that is then used to argue why analogous initiatives might be usefully applied to health care and why physicians may resist them. Each example is measured against a set of economic criteria adopted from the taxation literature. Findings: The initiatives considered in the article fall into three themes: safety concepts that seek to downplay the role of heroic individuals and instead emphasize the importance of teams and whole organizations; concepts that seek to increase and apply group knowledge of safety information and values; and concepts that promote safety by design. The salient costs to be considered by organizations wishing to adopt these suggestions are the compliance costs to clinicians, the administration costs to the organization, and the costs of behavioral distortions. Conclusions: This article concludes that there is a range of safety initiatives used in commercial aviation that could have a positive impact on patient safety, and that adopting such initiatives may alter the safety culture of health care teams. The desirability of implementing each initiative, however, depends on the projected costs and benefits, which must be assessed for each situation. PMID:21418311

Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy

PubMed Central

Powell, Daniel J.; Dudley, Mark E.; Robbins, Paul F.; Rosenberg, Steven A.

2007-01-01

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen–specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA− CD62 ligand− (CD62L−) CC chemokine receptor 7− (CCR7−) interleukin-7 receptor αLo (IL-7RαLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Rα in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen–specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+ CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L− CCR7− profile, which may explain in part their ability to mediate tumor destruction. PMID:15345595

Large-scale Isolation of Highly Pure "Untouched" Regulatory T Cells in a GMP Environment for Adoptive Cell Therapy.

PubMed

Haase, Doreen; Puan, Kia Joo; Starke, Mireille; Lai, Tuck Siong; Soh, Melissa Yan Ling; Karunanithi, Iyswariya; San Luis, Boris; Poh, Tuang Yeow; Yusof, Nurhashikin; Yeap, Chun Hsien; Phang, Chew Yen; Chye, Willis Soon Yuan; Chan, Marieta; Koh, Mickey Boon Chai; Goh, Yeow Tee; Bertin-Maghit, Sebastien; Nardin, Alessandra; Ho, Liam Pock; Rotzschke, Olaf

2015-01-01

Adoptive cell therapy is an emerging treatment strategy for a number of serious diseases. Regulatory T (Treg) cells represent 1 cell type of particular interest for therapy of inflammatory conditions, as they are responsible for controlling unwanted immune responses. Initial clinical trials of adoptive transfer of Treg cells in patients with graft-versus-host disease were shown to be safe. However, obtaining sufficient numbers of highly pure and functional Treg cells with minimal contamination remains a challenge. We developed a novel approach to isolate "untouched" human Treg cells from healthy donors on the basis of negative selection using the surface markers CD49d and CD127. This procedure, which uses an antibody cocktail and magnetic beads for separation in an automated system (RoboSep), was scaled up and adapted to be compatible with good manufacturing practice conditions. With this setup we performed 9 Treg isolations from large-scale leukapheresis samples in a good manufacturing practice facility. These runs yielded sufficient numbers of "untouched" Treg cells for immediate use in clinical applications. The cell preparations consisted of viable highly pure FoxP3-positive Treg cells that were functional in suppressing the proliferation of effector T cells. Contamination with CD4 effector T cells was <10%. All other cell types did not exceed 2% in the final product. Remaining isolation reagents were reduced to levels that are considered safe. Treg cells isolated with this procedure will be used in a phase I clinical trial of adoptive transfer into leukemia patients developing graft-versus-host disease after stem cell transplantation.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

PubMed

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

2016-05-01

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

PubMed Central

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J. Michael; Kanerva, Anna; Hemminki, Akseli

2016-01-01

ABSTRACT Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8+ T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors. PMID:27467954

Diagnosis before treatment: Identifying dairy farmers' determinants for the adoption of sustainable practices in gastrointestinal nematode control.

PubMed

Vande Velde, F; Claerebout, E; Cauberghe, V; Hudders, L; Van Loo, H; Vercruysse, J; Charlier, J

2015-09-15

Anthelmintic resistance is emerging in dairy cattle and this can result in a lack of effective control and production losses. Therefore, sustainable control strategies, such as targeted treatments (TT) and targeted selected treatments (TST), should be adopted by the industry. TT and TST approaches require the use of diagnostic methods to take informed treatment decisions. To understand the factors affecting the farmers' intention to adopt diagnostic methods before implementing anthelmintic drugs ('adoption intention'), a cross-sectional survey was carried out in dairy farms in Belgium (Flanders). A framework was constructed to predict adoption intentions based on two fundamental theories in the field of behavioural psychology and health psychology: the Theory of Planned Behaviour and the Health Belief Model. In the tested model, adoption intentions were predicted based on attitudes towards anthelminthics, attitudes towards diagnostic methods, subjective norms, behavioural control and perceived risk. Structural equation modelling was used for analyses. The model fitted the data well and explained 46% of the variance in adoption intention of diagnostics. The factors 'attitude towards diagnostic methods' and 'subjective norm'; i.e. the influence of significant others, had the strongest, positive influence on adoption intention of diagnostic methods. 'Perceived behavioural control' had a weak, positive effect on intention. Further, 'attitude towards the use of anthelmintic drugs' had a negative effect on adoption intention of the diagnostic methods. This implicates an effect of current behaviour on future adoption, which should be considered in future research. Factors measuring risk perception of anthelmintic resistance; perceived severity and perceived susceptibility, had no effect on the adoption intention of diagnostic methods. The threat of anthelmintic resistance is perceived to be low for dairy herds. The study further did not find any differences in the effects of the predictors for young stock and adult dairy cows. The results of this study can be used to develop communication strategies to advertise sustainable nematode control on dairy farms. Copyright © 2015 Elsevier B.V. All rights reserved.

A study on the use of near-infrared spectroscopy for the rapid quantification of major compounds in Tanreqing injection

NASA Astrophysics Data System (ADS)

Li, Wenlong; Cheng, Zhiwei; Wang, Yuefei; Qu, Haibin

2013-01-01

In this paper we describe the strategy used in the development and validation of a near infrared spectroscopy method for the rapid determination of baicalin, chlorogenic acid, ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), and the total solid contents (TSCs) in the Tanreqing injection. To increase the representativeness of calibration sample set, a concentrating-diluting method was adopted to artificially prepare samples. Partial least square regression (PLSR) was used to establish calibration models, with which the five quality indicators can be determined with satisfied accuracy and repeatability. In addition, the slope/bias (S/B) method was used for the models transfer between two different types of NIR instruments from the same manufacturer, which is contributing to enlarge the application range of the established models. With the presented method, a great deal of time, effort and money can be saved when large amounts of Tanreqing injection samples need to be analyzed in a relatively short period of time, which is of great significance to the traditional Chinese medicine (TCM) industries.

40 CFR 52.320 - Identification of plan.

Code of Federal Regulations, 2012 CFR

2012-07-01

... of Group II VOC sources were submitted on January 6, 1981, and the supplemental information received... Gasoline Transfer at Bulk Plants-Vapor Balance System), and D (Test Procedures for Annual Pressure/Vacuum... recent EPA capture efficiency protocols, and the commitment to adopt federal capture efficiency test...

Making Childhood Asthma Management Education Happen in the Community: Translating Health Behavioral Research into Local Program.

ERIC Educational Resources Information Center

Krutzch, Christine B.; And Others

1987-01-01

A technology transfer project for getting initial community adoption of childhood asthma management programs is described. The evolution of the project, including development of programs, packaging considerations, establishment of partnerships, implementation, and evaluation are discussed. (Author/CH)

New Zealand Dairy Farmers as Organisational Leaders.

ERIC Educational Resources Information Center

Massey, Claire; Hurley, Evelyn

2001-01-01

A strategy for improving learning and competitiveness in the New Zealand dairy industry examined barriers to farmers' learning and adopted action research with a group of women farmers. This form of participant involvement appeared to facilitate individual learning and technology transfer. (Contains 30 references.) (SK)

Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen

PubMed Central

Tian, Chaorui; Yuan, Xueli; Jindra, Peter T.; Bagley, Jessamyn; Sayegh, Mohamed H.; Iacomini, John

2010-01-01

Induction of transplantation tolerance has the potential to allow for allograft acceptance without the need for life-long immunosuppression. Here we describe a novel approach that uses delivery of alloantigen by mature T cells to induce tolerance to fully allogeneic cardiac grafts. Adoptive transfer of mature alloantigen-expressing T cells into myeloablatively conditioned mice results in long-term acceptance of fully allogeneic heart transplants without evidence of chronic rejection. Since myeloablative conditioning is clinically undesirable we further demonstrated that adoptive transfer of mature alloantigen-expressing T cells alone into mice receiving non-myeloablative conditioning resulted in long-term acceptance of fully allogeneic heart allografts with minimal evidence of chronic rejection. Mechanistically, tolerance induction involved both deletion of donor-reactive host T cells and the development of regulatory T cells. Thus, delivery of alloantigen by mature T cells induces tolerance to fully allogeneic organ allografts in non-myeloablatively conditioned recipients, representing a novel approach for tolerance induction in transplantation. PMID:20452826

Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia

PubMed Central

Schmidt, Stanislaw; Tramsen, Lars; Hanisch, Mitra; Latgé, Jean-Paul; Huenecke, Sabine; Koehl, Ulrike

2011-01-01

Because natural killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to hematopoietic stem cell recipients. Unfortunately, in humans, the activity of NK cells against Aspergillus species, the major cause of invasive fungal infection in stem cell recipients, are poorly characterized. Our results show that unstimulated and interleukin-2 prestimulated human NK cells kill Aspergillus fumigatus hyphae but do not affect resting conidia. Killing is also induced by the supernatant of prestimulated NK cells and human perforin. The high levels of interferon-γ and granulocyte macrophage colony-stimulating factor produced by prestimulated NK cells are significantly reduced by Aspergillus, indicating an immunosuppressive effect of the fungus. Whereas Aspergillus hyphae activate NK cells, resting, and germinating, conidia and conidia of ΔrodA mutants lacking the hydrophobic surface layer do not. Our results suggest that adoptively transferred human NK cells may be a potential antifungal tool in the transplantation context. PMID:21208932

Touring DNS Open Houses for Trends and Configurations

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

Kalafut, Prof. Andrew; Shue, Craig A; Gupta, Prof. Minaxi

2011-01-01

DNS is a critical component of the Internet. It maps domain names to IP addresses and serves as a distributed database for various other applications, including mail, Web, and spam filtering. This paper examines DNS zones in the Internet for diversity, adoption rates of new technologies, and prevalence of configuration issues. To gather data, we sweep 60% of the Internet's domains in June - August 2007 for zone transfers. 6.6% of them allow us to transfer their complete information. Surprisingly, this includes a large fraction of the domains deploying DNSSEC. We find that DNS zones vary significantly in size andmore » some span many ASes. Also, while anti-spam technologies appear to be getting deployed, the adoption rates of DNSSEC and IPv6 continue to be low. Finally, we also find that carelessness in handing DNS records can lead to reduced availability of name servers, email, and Web servers. This also undermines anti-spam efforts and the efforts to shut down phishing sites or to contain malware infections.« less

Study on an antagonist differentiated heated lid driven-cavity enclosing a tube: lattice Boltzmann method

NASA Astrophysics Data System (ADS)

Ma, Xiaoyan; Pellerin, Nicolas; Reggio, Marcelo; Bennacer, Rachid

2017-05-01

The method of lattice-Boltzmann multiple relaxation time (MRT) is commonly applied to study the conversion system consisting in a combination of forced convection and natural convection occurred in a cavity. Moving the top surface horizontally at a fixed speed, while two vertical walls are applied with constant different temperatures, assuming adiabatic case on both bottom and top walls. We consider a "non-cooperating" situation, where dynamics and buoyancy forces counterbalance. The cavity contains a circular cylinder placed at various positions. Boundary conditions for velocity and temperature have been applied to handle the non-Cartesian boundary of the cylinder. In lattice Boltzmann methods we adopt the double distribution model for calculating both the thermal and hydrodynamic fields. The D2Q5 and D2Q9 lattice are chosen to perform the simulations for a wide range of Reynolds and Rayleigh numbers. By calculating the average Nusselt number, we also investigated the influence of different obstacle positions on characteristics of flow and heat transfer. The results show the influence of the obstacle position on the dimensionless numbers, so as to effect the heat transfer behaviors inside the cavity. It is also indicates that the governing parameters are also related to driven power for the upper surface sliding. Contribution to the topical issue "Materials for Energy harvesting, conversion and storage II (ICOME 2016)", edited by Jean-Michel Nunzi, Rachid Bennacer and Mohammed El Ganaoui

A Frequency-Domain Multipath Parameter Estimation and Mitigation Method for BOC-Modulated GNSS Signals

PubMed Central

Sun, Chao; Feng, Wenquan; Du, Songlin

2018-01-01

As multipath is one of the dominating error sources for high accuracy Global Navigation Satellite System (GNSS) applications, multipath mitigation approaches are employed to minimize this hazardous error in receivers. Binary offset carrier modulation (BOC), as a modernized signal structure, is adopted to achieve significant enhancement. However, because of its multi-peak autocorrelation function, conventional multipath mitigation techniques for binary phase shift keying (BPSK) signal would not be optimal. Currently, non-parametric and parametric approaches have been studied specifically aiming at multipath mitigation for BOC signals. Non-parametric techniques, such as Code Correlation Reference Waveforms (CCRW), usually have good feasibility with simple structures, but suffer from low universal applicability for different BOC signals. Parametric approaches can thoroughly eliminate multipath error by estimating multipath parameters. The problems with this category are at the high computation complexity and vulnerability to the noise. To tackle the problem, we present a practical parametric multipath estimation method in the frequency domain for BOC signals. The received signal is transferred to the frequency domain to separate out the multipath channel transfer function for multipath parameter estimation. During this process, we take the operations of segmentation and averaging to reduce both noise effect and computational load. The performance of the proposed method is evaluated and compared with the previous work in three scenarios. Results indicate that the proposed averaging-Fast Fourier Transform (averaging-FFT) method achieves good robustness in severe multipath environments with lower computational load for both low-order and high-order BOC signals. PMID:29495589

More than just a question of technology: factors related to hospitals' adoption and implementation of health information exchange.

PubMed

Vest, Joshua R

2010-12-01

The provisions of the American Recovery & Reinvestment Act increased the likelihood of more widespread health information exchange (HIE), the electronic transfer of patient-level information between organizations, by essentially mandating the use of electronic health record systems. While important, the sparse body of research on HIE efforts and anecdotal reports indicate the barriers to HIE adoption and implementation include factors beyond simply the presence or absence of a specific technology. This paper examines those technological, organizational, and environmental factors that are associated with both HIE adoption and implementation in a sample of 4830 U.S. hospitals. Factors associated with adoption and implementation were modeled using random-intercept logistic regression. Consistent with a perspective that adoption and implementation are different phenomena, many factors associated with an increased odds of adoption, were unassociated with implementation and vice versa. Non-profit status, public hospitals, more live and operation applications, more emergency room visits, network membership, and the presence of physician portals all increased hospitals' odds of HIE adoption. However, only network membership increased the odds of HIE implementation, whereas competition decreased those odds significantly. This study agreed with earlier case-studies and anecdotal reports that factors beyond technology were important to both adoption and implementation. While current U.S. policy on healthcare information technology adoption focuses on technological barriers, many other non-technological factors may ultimately hinder effective HIE. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Antigen-specific T cell therapies for cancer

PubMed Central

Manzo, Teresa; Heslop, Helen E.; Rooney, Cliona M.

2015-01-01

Adoptively transferred antigen-specific T cells that recognize tumor antigens through their native receptors have many potential benefits as treatment for virus-associated diseases and malignancies, due to their ability to selectively recognize tumor antigens, expand and persist to provide long-term protection. Infusions of T cells targeting Epstein–Barr virus (EBV) antigens have shown encouraging response rates in patients with post-transplant lymphoproliferative disease as well as EBV-positive lymphomas and nasopharyngeal cancer, although a recent study also showed that human papilloma virus-reactive T cells can induce complete regression of metastatic cervical cancer. This strategy is also being evaluated to target non-viral tumor-associated antigens. Targeting these less immunogenic antigens is more challenging, as tumor antigens are generally weak, and high avidity T cells specific for self-antigens are deleted in the thymus, but tumor responses have been reported. Current research focusses on defining factors that promote in vivo persistence of transferred cells and ameliorate the immunosuppressive microenvironment. To this end, investigators are evaluating the effects of combining adoptive transfer of antigen-specific T cells with other immunotherapy moieties such as checkpoint inhibitors. Genetic modification of infused T cells may also be used to overcome tumor evasion mechanisms, and vaccines may be used to promote in vivo proliferation. PMID:26160910

The Role of Transfer in Designing Games and Simulations for Health: Systematic Review.

PubMed

Kuipers, Derek A; Terlouw, Gijs; Wartena, Bard O; van 't Veer, Job Tb; Prins, Jelle T; Pierie, Jean Pierre En

2017-11-24

The usefulness and importance of serious games and simulations in learning and behavior change for health and health-related issues are widely recognized. Studies have addressed games and simulations as interventions, mostly in comparison with their analog counterparts. Numerous complex design choices have to be made with serious games and simulations for health, including choices that directly contribute to the effects of the intervention. One of these decisions is the way an intervention is expected to lead to desirable transfer effects. Most designs adopt a first-class transfer rationale, whereas the second class of transfer types seems a rarity in serious games and simulations for health. This study sought to review the literature specifically on the second class of transfer types in the design of serious games and simulations. Focusing on game-like interventions for health and health care, this study aimed to (1) determine whether the second class of transfer is recognized as a road for transfer in game-like interventions, (2) review the application of the second class of transfer type in designing game-like interventions, and (3) assess studies that include second-class transfer types reporting transfer outcomes. A total of 6 Web-based databases were systematically searched by titles, abstracts, and keywords using the search strategy (video games OR game OR games OR gaming OR computer simulation*) AND (software design OR design) AND (fidelity OR fidelities OR transfer* OR behaviour OR behavior). The databases searched were identified as relevant to health, education, and social science. A total of 15 relevant studies were included, covering a range of game-like interventions, all more or less mentioning design parameters aimed at transfer. We found 9 studies where first-class transfer was part of the design of the intervention. In total, 8 studies dealt with transfer concepts and fidelity types in game-like intervention design in general; 3 studies dealt with the concept of second-class transfer types and reported effects, and 2 of those recognized transfer as a design parameter. In studies on game-like interventions for health and health care, transfer is regarded as a desirable effect but not as a basic principle for design. None of the studies determined the second class of transfer or instances thereof, although in 3 cases a nonliteral transfer type was present. We also found that studies on game-like interventions for health do not elucidate design choices made and rarely provide design principles for future work. Games and simulations for health abundantly build upon the principles of first-class transfer, but the adoption of second-class transfer types proves scarce. It is likely to be worthwhile to explore the possibilities of second-class transfer types, as they may considerably influence educational objectives in terms of future serious game design for health. ©Derek A Kuipers, Gijs Terlouw, Bard O Wartena, Job TB van 't Veer, Jelle T Prins, Jean Pierre EN Pierie. Originally published in JMIR Serious Games (http://games.jmir.org), 24.11.2017.

A novel end-to-end classifier using domain transferred deep convolutional neural networks for biomedical images.

PubMed

Pang, Shuchao; Yu, Zhezhou; Orgun, Mehmet A

2017-03-01

Highly accurate classification of biomedical images is an essential task in the clinical diagnosis of numerous medical diseases identified from those images. Traditional image classification methods combined with hand-crafted image feature descriptors and various classifiers are not able to effectively improve the accuracy rate and meet the high requirements of classification of biomedical images. The same also holds true for artificial neural network models directly trained with limited biomedical images used as training data or directly used as a black box to extract the deep features based on another distant dataset. In this study, we propose a highly reliable and accurate end-to-end classifier for all kinds of biomedical images via deep learning and transfer learning. We first apply domain transferred deep convolutional neural network for building a deep model; and then develop an overall deep learning architecture based on the raw pixels of original biomedical images using supervised training. In our model, we do not need the manual design of the feature space, seek an effective feature vector classifier or segment specific detection object and image patches, which are the main technological difficulties in the adoption of traditional image classification methods. Moreover, we do not need to be concerned with whether there are large training sets of annotated biomedical images, affordable parallel computing resources featuring GPUs or long times to wait for training a perfect deep model, which are the main problems to train deep neural networks for biomedical image classification as observed in recent works. With the utilization of a simple data augmentation method and fast convergence speed, our algorithm can achieve the best accuracy rate and outstanding classification ability for biomedical images. We have evaluated our classifier on several well-known public biomedical datasets and compared it with several state-of-the-art approaches. We propose a robust automated end-to-end classifier for biomedical images based on a domain transferred deep convolutional neural network model that shows a highly reliable and accurate performance which has been confirmed on several public biomedical image datasets. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the CPU time for solving the radiative transfer equation with high-order resolution schemes applying the normalized weighting-factor method

NASA Astrophysics Data System (ADS)

Xamán, J.; Zavala-Guillén, I.; Hernández-López, I.; Uriarte-Flores, J.; Hernández-Pérez, I.; Macías-Melo, E. V.; Aguilar-Castro, K. M.

2018-03-01

In this paper, we evaluated the convergence rate (CPU time) of a new mathematical formulation for the numerical solution of the radiative transfer equation (RTE) with several High-Order (HO) and High-Resolution (HR) schemes. In computational fluid dynamics, this procedure is known as the Normalized Weighting-Factor (NWF) method and it is adopted here. The NWF method is used to incorporate the high-order resolution schemes in the discretized RTE. The NWF method is compared, in terms of computer time needed to obtain a converged solution, with the widely used deferred-correction (DC) technique for the calculations of a two-dimensional cavity with emitting-absorbing-scattering gray media using the discrete ordinates method. Six parameters, viz. the grid size, the order of quadrature, the absorption coefficient, the emissivity of the boundary surface, the under-relaxation factor, and the scattering albedo are considered to evaluate ten schemes. The results showed that using the DC method, in general, the scheme that had the lowest CPU time is the SOU. In contrast, with the results of theDC procedure the CPU time for DIAMOND and QUICK schemes using the NWF method is shown to be, between the 3.8 and 23.1% faster and 12.6 and 56.1% faster, respectively. However, the other schemes are more time consuming when theNWFis used instead of the DC method. Additionally, a second test case was presented and the results showed that depending on the problem under consideration, the NWF procedure may be computationally faster or slower that the DC method. As an example, the CPU time for QUICK and SMART schemes are 61.8 and 203.7%, respectively, slower when the NWF formulation is used for the second test case. Finally, future researches to explore the computational cost of the NWF method in more complex problems are required.

Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

PubMed

Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

2013-01-01

A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes

PubMed Central

Mircheff, Austin K.; Wang, Yanru; Schechter, Joel E.; Li, Meng; Tong, Warren; Attar, Mayssa; Chengalvala, Murty; Harmuth, Joe; Prusakiewicz, Jeffery J.

2016-01-01

Purpose To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity. Methods Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1° ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA). Results Immunizing Pi dose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1° ATD-eyes and exacerbated 1° ATD-LG atrophy. IMIP were evident in 2° ATD-LG as well as 1° ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IA scores. Conclusions The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms. PMID:27423911

A statewide teleradiology system reduces radiation exposure and charges in transferred trauma patients.

PubMed

Watson, Justin J J; Moren, Alexis; Diggs, Brian; Houser, Ben; Eastes, Lynn; Brand, Dawn; Bilyeu, Pamela; Schreiber, Martin; Kiraly, Laszlo

2016-05-01

Trauma transfer patients routinely undergo repeat imaging because of inefficiencies within the radiology system. In 2009, the virtual private network (VPN) telemedicine system was adopted throughout Oregon allowing virtual image transfer between hospitals. The startup cost was a nominal $3,000 per hospital. A retrospective review from 2007 to 2012 included 400 randomly selected adult trauma transfer patients based on a power analysis (200 pre/200 post). The primary outcome evaluated was reduction in repeat computed tomography (CT) scans. Secondary outcomes included cost savings, emergency department (ED) length of stay (LOS), and spared radiation. All data were analyzed using Mann-Whitney U and chi-square tests. P less than .05 indicated significance. Spared radiation was calculated as a weighted average per body region, and savings was calculated using charges obtained from Oregon Health and Science University radiology current procedural terminology codes. Four-hundred patients were included. Injury Severity Score, age, ED and overall LOS, mortality, trauma type, and gender were not statistically different between groups. The percentage of patients with repeat CT scans decreased after VPN implementation: CT abdomen (13.2% vs 2.8%, P < .01) and cervical spine (34.4% vs 18.2%, P < .01). Post-VPN, the total charges saved in 2012 for trauma transfer patients was $333,500, whereas the average radiation dose spared per person was 1.8 mSV. Length of stay in the ED for patients with Injury Severity Score less than 15 transferring to the ICU was decreased (P < .05). Implementation of a statewide teleradiology network resulted in fewer total repeat CT scans, significant savings, decrease in radiation exposure, and decreased LOS in the ED for patients with less complex injuries. The potential for health care savings by widespread adoption of a VPN is significant. Copyright © 2016 Elsevier Inc. All rights reserved.

Powering the High-Luminosity Triplets

NASA Astrophysics Data System (ADS)

Ballarino, A.; Burnet, J. P.

The powering of the magnets in the LHC High-Luminosity Triplets requires production and transfer of more than 150 kA of DC current. High precision power converters will be adopted, and novel High Temperature Superconducting (HTS) current leads and MgB2 based transfer lines will provide the electrical link between the power converters and the magnets. This chapter gives an overview of the systems conceived in the framework of the LHC High-Luminosity upgrade for feeding the superconducting magnet circuits. The focus is on requirements, challenges and novel developments.

CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate Personalized Drug for the Immunotherapy of Human Cancer.

PubMed

Rosenberg, Steven A

2015-12-15

The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. ©2015 American Association for Cancer Research.

Computation of Flow and Heat Transfer in Flow Around a 180 deg Bend.

DTIC Science & Technology

1984-04-01

be required if a more elaborate closure were adopted.[I- 9 Enayet et al [14] in a 900 bend with a radius:diameter ratio of I only 2.8:1 giving a Dean...Figure 9 indicates, however, that a satisfactory numerical simulation is nevertheless obtained. Enayet et al [14] also measured the development of...computations of the 2.P:1 90o bend of Enayet et al [1h] indicate a five-fold variation of local heat transfer coefficient around the bend at 750 . The

Cell-mediated immunity in herpes simplex virus-infected mice: H-2 mapping of the delayed-type hypersensitivity response and the antiviral T cell response.

PubMed

Nash, A A; Phelan, J; Wildy, P

1981-04-01

An adoptive transfer system was used to investigate the H-2 restriction of delayed-type hypersensitivity (DTH) to herpes simplex virus. A successful DTH transfer was achieved when donor and recipient were compatible at the I-A region, with K and D region compatibility unnecessary. However, the rapid clearance of infectious virus from the inoculation site was found only when the donor and recipients were compatible at H-2K (and presumably D) and I-A regions.

Finding Safety in Small Numbers.

ERIC Educational Resources Information Center

McPartland, James; Jordan, Will; Legters, Nettie; Balfanz, Robert

1997-01-01

A large Baltimore high school has shown how personalizing relationships and focusing the curriculum can turn around an unsafe school and create a climate conducive to learning. The school adopted the Talent Development model, which created six smaller units or academies. Instead of suspending or transferring ill-behaved students, Patterson…

Revenue Sharing: An Assessment of Current Policies at UK Universities

ERIC Educational Resources Information Center

Gazzard, James; Brown, Sarah A.

2012-01-01

The transfer of academic technologies to industry is an important process underpinning innovation and economic development. Various approaches have been adopted by universities to encourage academics to participate in commercial activities. Many have implemented revenue sharing policies, through which the revenues generated from university-owned…

A basic study on Thermosyphon-type thermal storage unit (TSU) using Nanofluid as the heat transfer medium

NASA Astrophysics Data System (ADS)

Li, Shuang-Fei; Wang, Ping-Yang; Liu, Zhen-hua

2018-05-01

This study proposed a novel thermosyphon-type thermal storage unit using water-based CuO nanofluid as the phase-change heat transfer medium. Seven tubular canisters containing solid-liquid phase-change material (PCM) with peak melting temperature of 100 °C were placed vertically into the center of the TSU which is a vertical cylindrical vessel made of stainless steel. Coat formed by depositing nanoparticles during the phase-change process was adopted to increase the wettability of the heat transfer surfaces of the canisters. We investigated the phase-change heat transfer, as well as the heat-storage and heat-release properties, of the TSU through experimental and computational analysis. Our results demonstrate that this thermal storage unit construction can propose good heat transfer and heat-storage/heat-release performance. The coating of nanoparticles onto the heat transfer surfaces increases the surface wettability and improves both the evaporation and condensation heat transfer. The main thermal resistance in the TSU results from the conductive heat transfer inside of the PCM. All phase-change thermal resistance of liquid film in charging and discharging processes can be ignored in this TSU.

Numerical investigation of MHD flow of blood and heat transfer in a stenosed arterial segment

NASA Astrophysics Data System (ADS)

Majee, Sreeparna; Shit, G. C.

2017-02-01

A numerical investigation of unsteady flow of blood and heat transfer has been performed with an aim to provide better understanding of blood flow through arteries under stenotic condition. The blood is treated as Newtonian fluid and the arterial wall is considered to be rigid having deposition of plaque in its lumen. The heat transfer characteristic has been analyzed by taking into consideration of the dissipation of energy due to applied magnetic field and the viscosity of blood. The vorticity-stream function formulation has been adopted to solve the problem using implicit finite difference method by developing well known Peaceman-Rachford Alternating Direction Implicit (ADI) scheme. The quantitative profile analysis of velocity, temperature and wall shear stress as well as Nusselt number is carried out over the entire arterial segment. The streamline and temperature contours have been plotted to understand the flow pattern in the diseased artery, which alters significantly in the downstream of the stenosis in the presence of magnetic field. Both the wall shear stress and Nusselt number increases with increasing magnetic field strength. However, wall shear stress decreases and Nusselt number enhances with Reynolds number. The results show that with an increase in the magnetic field strength upto 8 T, does not causes any damage to the arterial wall, but the study is significant for assessing temperature rise during hyperthermic treatment.

LEO cooperative multi-spacecraft refueling mission optimization considering J2 perturbation and target's surplus propellant constraint

NASA Astrophysics Data System (ADS)

Zhao, Zhao; Zhang, Jin; Li, Hai-yang; Zhou, Jian-yong

2017-01-01

The optimization of an LEO cooperative multi-spacecraft refueling mission considering the J2 perturbation and target's surplus propellant constraint is studied in the paper. First, a mission scenario is introduced. One service spacecraft and several target spacecraft run on an LEO near-circular orbit, the service spacecraft rendezvouses with some service positions one by one, and target spacecraft transfer to corresponding service positions respectively. Each target spacecraft returns to its original position after obtaining required propellant and the service spacecraft returns to its original position after refueling all target spacecraft. Next, an optimization model of this mission is built. The service sequence, orbital transfer time, and service position are used as deign variables, whereas the propellant cost is used as the design objective. The J2 perturbation, time constraint and the target spacecraft's surplus propellant capability constraint are taken into account. Then, a hybrid two-level optimization approach is presented to solve the formulated mixed integer nonlinear programming (MINLP) problem. A hybrid-encoding genetic algorithm is adopted to seek the near optimal solution in the up-level optimization, while a linear relative dynamic equation considering the J2 perturbation is used to obtain the impulses of orbital transfer in the low-level optimization. Finally, the effectiveness of the proposed model and method is validated by numerical examples.

A Knowledge Transfer Study of the Utility of the Nova Scotia Seniors’ Mental Health Network in Implementing Seniors’ Mental Health National Guidelines

PubMed Central

Bosma, Mark; Cassidy, Keri-Leigh; Le Clair, J Kenneth; Helsdingen, Sherri; Devichand, Pratima

2011-01-01

Background The Canadian Coalition for Seniors’ Mental Health (CCSMH) developed national best-practice guidelines in seniors’ mental health. Promoting adoption of new guidelines is challenging, as paper dissemination alone has limited impact on practice change. Purpose We hypothesized that the existing knowledge transfer (KT) mechanisms of the Nova Scotia Seniors’ Mental Health Network would prove useful in transferring the CCSMH best-practice guidelines. Methods In this observational KT study, CCSMH best-practice guidelines were delivered through two interactive, case-based teaching modules on Depression & Suicide, and Delirium via a provincial tele-education program and local face-to-face sessions. Usefulness of KT was measured using self-report evaluations of material quality and learning. Evaluation results from the two session topics and from tele-education versus face-to-face sessions were compared. Results Sessions were well attended (N = 347), with a high evaluation return rate (287, 83%). Most participants reported enhanced knowledge in seniors’ mental health and intended to apply knowledge to practice. Ratings did not differ significantly between KT session topics or modes of delivery. Conclusions The KT mechanisms of a provincial seniors’ mental health network facilitated knowledge acquisition and the intention of using national guidelines on seniors’ mental health among Nova Scotian clinicians. Key elements of accelerating KT used in this initiative are discussed. PMID:23251305

A transfer function type of simplified electrochemical model with modified boundary conditions and Padé approximation for Li-ion battery: Part 1. lithium concentration estimation

NASA Astrophysics Data System (ADS)

Yuan, Shifei; Jiang, Lei; Yin, Chengliang; Wu, Hongjie; Zhang, Xi

2017-06-01

To guarantee the safety, high efficiency and long lifetime for lithium-ion battery, an advanced battery management system requires a physics-meaningful yet computationally efficient battery model. The pseudo-two dimensional (P2D) electrochemical model can provide physical information about the lithium concentration and potential distributions across the cell dimension. However, the extensive computation burden caused by the temporal and spatial discretization limits its real-time application. In this research, we propose a new simplified electrochemical model (SEM) by modifying the boundary conditions for electrolyte diffusion equations, which significantly facilitates the analytical solving process. Then to obtain a reduced order transfer function, the Padé approximation method is adopted to simplify the derived transcendental impedance solution. The proposed model with the reduced order transfer function can be briefly computable and preserve physical meanings through the presence of parameters such as the solid/electrolyte diffusion coefficients (Ds&De) and particle radius. The simulation illustrates that the proposed simplified model maintains high accuracy for electrolyte phase concentration (Ce) predictions, saying 0.8% and 0.24% modeling error respectively, when compared to the rigorous model under 1C-rate pulse charge/discharge and urban dynamometer driving schedule (UDDS) profiles. Meanwhile, this simplified model yields significantly reduced computational burden, which benefits its real-time application.

Implementation of Medical Information Exchange System Based on EHR Standard.

PubMed

Han, Soon Hwa; Lee, Min Ho; Kim, Sang Guk; Jeong, Jun Yong; Lee, Bi Na; Choi, Myeong Seon; Kim, Il Kon; Park, Woo Sung; Ha, Kyooseob; Cho, Eunyoung; Kim, Yoon; Bae, Jae Bong

2010-12-01

To develop effective ways of sharing patients' medical information, we developed a new medical information exchange system (MIES) based on a registry server, which enabled us to exchange different types of data generated by various systems. To assure that patient's medical information can be effectively exchanged under different system environments, we adopted the standardized data transfer methods and terminologies suggested by the Center for Interoperable Electronic Healthcare Record (CIEHR) of Korea in order to guarantee interoperability. Regarding information security, MIES followed the security guidelines suggested by the CIEHR of Korea. This study aimed to develop essential security systems for the implementation of online services, such as encryption of communication, server security, database security, protection against hacking, contents, and network security. The registry server managed information exchange as well as the registration information of the clinical document architecture (CDA) documents, and the CDA Transfer Server was used to locate and transmit the proper CDA document from the relevant repository. The CDA viewer showed the CDA documents via connection with the information systems of related hospitals. This research chooses transfer items and defines document standards that follow CDA standards, such that exchange of CDA documents between different systems became possible through ebXML. The proposed MIES was designed as an independent central registry server model in order to guarantee the essential security of patients' medical information.

[Reaction time tests in Leipzig, Paris and Würzburg. The Franco-German history of a psychological experiment, 1890-1910].

PubMed

Carroy, Jacqueline; Schmidgen, Henning

2004-01-01

This article diiscusses from a comparative perspective the complex history of the reaction experiment with the Hipp chronoscope, one of the central experiments of late 19th-century psychology. It focuses on Wilhelm Wundt's (1832-1920) Institute for Experimental Psychology in Leipzig and on the Paris Laboratory for Physiological Psychology at the Sorbonne, which was initially directed by Henry Beaunis (1830-1921), but soon came to be dominated by the research activities of Alfred Binet (1857-1911). When the Paris psychologists founded their Laboratory in 1889, they took the Leipzig Institute as their model. In the early 1890s they adopted the reaction time experiment that had been central to Wundt's psychology. Shortly after, they modified this experiment according to their own specific interests. For Binet, it no longer served as a method for identifying the elementary components of "general" consciousness (as in Wundt), but for classifying "individual" personalities. The methodological and technological changes that Binet introduced into the experimental practice of psychology had no immediate impact on the research work in Leipzig. However, they influenced the "Wurzburg School" of psychology under Wundt's former assistant, Oswald Külpe (1862-1915). This illustrates that the comparative history of transfers of "experimental systems" (Rheinberger) across national borders is not simply a history of mere transports. Rather, it is a history of transferences that sometimes includes surprising "re-transferences".

Processes of local alcohol policy-making in England: Does the theory of policy transfer provide useful insights into public health decision-making?

PubMed

Gavens, Lucy; Holmes, John; Buykx, Penny; de Vocht, Frank; Egan, Matt; Grace, Daniel; Lock, Karen; Mooney, John D; Brennan, Alan

2017-06-13

Recent years have seen a rise in new and innovative policies to reduce alcohol consumption and related harm in England, which can be implemented by local, as opposed to national, policy-makers. The aim of this paper is to explore the processes that underpin the adoption of these alcohol policies within local authorities. In particular, it aims to assess whether the concept of policy transfer (i.e. a process through which knowledge about policies in one place is used in the development of policies in another time or place) provides a useful model for understanding local alcohol policy-making. Qualitative data generated through in-depth interviews and focus groups from five case study sites across England were used to explore stakeholder experiences of alcohol policy transfer between local authorities. The purposive sample of policy actors included representatives from the police, trading standards, public health, licensing, and commissioning. Thematic analysis was used inductively to identify key features in the data. Themes from the policy transfer literature identified in the data were: policy copying, emulating, hybridization, and inspiration. Participants described a multitude of ways in which learning was shared between places, ranging from formal academic evaluation to opportunistic conversations in informal settings. Participants also described facilitators and constraints to policy transfer, such as the historical policy context and the local cultural, economic, and bureaucratic context, which influenced whether or not a policy that was perceived to work in one place might be transferred successfully to another context. Theories of policy transfer provide a promising framework for characterising processes of local alcohol policy-making in England, extending beyond debates regarding evidence-informed policy to account for a much wider range of considerations. Applying a policy transfer lens enables us to move beyond simple (but still important) questions of what is supported by 'robust' research evidence by paying greater attention to how policy making is carried out in practice and the multiple methods by which policies diffuse across jurisdictions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advances in evidence-based cancer adoptive cell therapy.

PubMed

Ge, Chunlei; Li, Ruilei; Song, Xin; Qin, Shukui

2017-04-01

Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic.

Moving receptor redirected adoptive cell therapy toward fine tuning of antitumor responses.

PubMed

Chicaybam, Leonardo; Bonamino, Martin Hernan

2014-10-01

Adoptive cell transfer (ACT) is emerging as a powerful modality of cancer treatment. While ACT has proved able to induce massive clinical responses, genetic modification of T lymphocytes further improved clinical responses obtained. One of the major current limitations of ACT is the inability to discern healthy from malignant cells, leading to on target/off tumor responses that can limit its application. We here discuss some of the approaches currently under development and potential solutions to circumvent these limitations and extend this potentially curative therapy to different tumors by targeting a variety of antigens.

Adoptive cell transfer: a clinical path to effective cancer immunotherapy

PubMed Central

Rosenberg, Steven A.; Restifo, Nicholas P.; Yang, James C.; Morgan, Richard A.; Dudley, Mark E.

2008-01-01

Adoptive cell therapy (ACT) using autologous tumour-infiltrating lymphocytes has emerged as the most effective treatment for patients with metastatic melanoma and can mediate objective cancer regression in approximately 50% of patients. The use of donor lymphocytes for ACT is an effective treatment for immunosuppressed patients who develop post-transplant lymphomas. The ability to genetically engineer human lymphocytes and use them to mediate cancer regression in patients, which has recently been demonstrated, has opened possibilities for the extension of ACT immunotherapy to patients with a wide variety of cancer types and is a promising new approach to cancer treatment. PMID:18354418

Adoptive cell therapy for sarcoma

PubMed Central

Mata, Melinda; Gottschalk, Stephen

2015-01-01

Current therapy for sarcomas, though effective in treating local disease, is often ineffective for patients with recurrent or metastatic disease. To improve outcomes, novel approaches are needed and cell therapy has the potential to meet this need since it does not rely on the cytotoxic mechanisms of conventional therapies. The recent successes of T-cell therapies for hematological malignancies have led to renewed interest in exploring cell therapies for solid tumors such as sarcomas. In this review, we will discuss current cell therapies for sarcoma with special emphasis on genetic approaches to improve the effector function of adoptively transferred cells. PMID:25572477

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

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

Wang, Chao; Xu, Zhijie; Lai, Kevin

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO2) capture. To generate data for WWC model validation, CO2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO2 in MEA. In addition, the overall mass transfer coefficient predictedmore » using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO2 reaction rate constants after using the N2O/CO2 analogy method. The calibrated model can be used to predict the CO2 mass transfer in a WWC for a wider range of operating conditions.« less

Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations for solvent-based carbon capture. Part 2: Chemical absorption across a wetted wall column: Original Research Article: Hierarchical calibration and validation framework of bench-scale computational fluid dynamics simulations

DOE PAGES

Wang, Chao; Xu, Zhijie; Lai, Kevin; ...

2017-10-24

Part 1 of this paper presents a numerical model for non-reactive physical mass transfer across a wetted wall column (WWC). In Part 2, we improved the existing computational fluid dynamics (CFD) model to simulate chemical absorption occurring in a WWC as a bench-scale study of solvent-based carbon dioxide (CO2) capture. To generate data for WWC model validation, CO2 mass transfer across a monoethanolamine (MEA) solvent was first measured on a WWC experimental apparatus. The numerical model developed in this work can account for both chemical absorption and desorption of CO2 in MEA. In addition, the overall mass transfer coefficient predictedmore » using traditional/empirical correlations is conducted and compared with CFD prediction results for both steady and wavy falling films. A Bayesian statistical calibration algorithm is adopted to calibrate the reaction rate constants in chemical absorption/desorption of CO2 across a falling film of MEA. The posterior distributions of the two transport properties, i.e., Henry's constant and gas diffusivity in the non-reacting nitrous oxide (N2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO2 reaction rate constants after using the N2O/CO2 analogy method. The calibrated model can be used to predict the CO2 mass transfer in a WWC for a wider range of operating conditions.« less

Deployed communication between the Role 3 and Role 1.

PubMed

Parsons, Iain T

2015-06-01

The discharge summary is the most common method for documenting a patient's diagnostic findings, hospital management and arrangements for post-discharge follow up. After being discharged from hospital, patients are routinely reviewed without a discharge summary being available. A recent review revealed that a significant proportion of patients discharged from the Role 3 had no evidence of their admission on their permanent medical record. The aim of this audit was to assess the transition of discharge summaries from Role 3 to Role 1 during Op HERRICK 18. The intention was to review where errors in the transfer of discharge information between Role 3 and Role 1 might be occurring with a view to implementing improvements. Two audits assessed the delivery of discharge information. A re-audit was performed 1 month after a system was implemented. The transfer of discharge information was poor with only 1/40 (2.5%) summaries arriving from R3 to R1. Following implementation of a system the transfer of discharge information improved to 24/30 (80%). The adoption of a system to transit discharge information from R3 to R1 resulted in a drastic improvement. Ideally, a future electronic patient record system used by all facets of Defence Medical Services would limit the potential for future adverse events due to communication failure. Regular audits assessing the transfer of discharge information should form part of standard audit cycles in future contingency operations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Temporal Effect of Training Utility Perceptions on Adopting a Trained Method: The Role of Perceived Organizational Support

ERIC Educational Resources Information Center

Madera, Juan M.; Steele, Stacey T.; Beier, Margaret

2011-01-01

The current study examined the temporal effect of perceived training utility on adoption of a trained method and how perceived organizational support influences the relationship between perceived training utility perceptions and adoption of a trained method. With the use of a correlational-survey-based design, this longitudinal study required…

Resources Available for Hazards Analysis of Aerospace Fluids

NASA Technical Reports Server (NTRS)

Woods, S. S.; Stewart, W. F.; Baker, D. L.

2001-01-01

In recent years, the legislative and executive branches of the federal government have pushed to make government more efficient and responsive to the needs of the marketplace. One of these initiatives, Public Law 104-113, also known as the National Technology Transfer and Advancement Act of 1995 (NTTAA), is designed to accelerate technology transfer to industry and promote government-industry partnership. Summarized, NTTAA states that '... all Federal agencies and departments shall use technical standards that are developed or adopted by voluntary consensus standards bodies, using such technical standards as a means to carry out policy objectives or activities determined by the agencies and departments. Government agencies must now determine if their in-house requirement-setting activities are sufficiently unique that no public interest is served by having them adopted by a voluntary consensus organization (VCO), or if not, to use or develop voluntary consensus standards. The Office of Management and Budget (OMB) is chartered by the law to monitor federal agency progress and report the results to Congress. In response to NTTAA, agency-wide oxygen and hydrogen safety standards sponsored by the NASA Headquarters (HQ) Office of Safety and Mission Assurance (OSMA) were obvious choices for early adoption by VCOs. In 1996, HQ sought assistance from the Johnson Space Center (JSC) White Sands Test Facility (WSTF), the technical lead for development of these safety standards, to evaluate their adoption by VCOs. At that time, WSTF-developed propellant hazards manuals were likewise identified for possible VCO adoption. Subsequently, WSTF was asked to represent NASA for development of an international ISO safety standard for hydrogen use. Concurrent with these WSTF standards activities are related efforts to develop and publish propellant hazards analysis protocols and safety courses for the industrial, propellant use of oxygen, hydrogen, and hypergols. This paper reports on these efforts and describes WSTF's overall voluntary consensus standards program to coordinate the interchange of NASA's propellant hazards and safety information with industry.

Optimal design of the first stage of the plate-fin heat exchanger for the EAST cryogenic system

NASA Astrophysics Data System (ADS)

Qingfeng, JIANG; Zhigang, ZHU; Qiyong, ZHANG; Ming, ZHUANG; Xiaofei, LU

2018-03-01

The size of the heat exchanger is an important factor determining the dimensions of the cold box in helium cryogenic systems. In this paper, a counter-flow multi-stream plate-fin heat exchanger is optimized by means of a spatial interpolation method coupled with a hybrid genetic algorithm. Compared with empirical correlations, this spatial interpolation algorithm based on a kriging model can be adopted to more precisely predict the Colburn heat transfer factors and Fanning friction factors of offset-strip fins. Moreover, strict computational fluid dynamics simulations can be carried out to predict the heat transfer and friction performance in the absence of reliable experimental data. Within the constraints of heat exchange requirements, maximum allowable pressure drop, existing manufacturing techniques and structural strength, a mathematical model of an optimized design with discrete and continuous variables based on a hybrid genetic algorithm is established in order to minimize the volume. The results show that for the first-stage heat exchanger in the EAST refrigerator, the structural size could be decreased from the original 2.200 × 0.600 × 0.627 (m3) to the optimized 1.854 × 0.420 × 0.340 (m3), with a large reduction in volume. The current work demonstrates that the proposed method could be a useful tool to achieve optimization in an actual engineering project during the practical design process.

Experimental study on the monomer structure of solar semiconductor cold wall

NASA Astrophysics Data System (ADS)

Fu, Yuanyuan; Liu, Qiuxin; Chen, Tianshou

2018-06-01

In this paper, solar semiconductor cold wall structure was adopted in the net-zero energy buildings, NZEB for short. The heat transfer and refrigeration effect of the monomer structure of semiconductor cold wall were tested, we get that the monomer structure of semiconductor cold wall has certain cooling effect. However, the heat exchange effect is not good of the cold and hot aluminum plate only through natural convection and radiation heat transfer. It is necessary to further study the process of semiconductor refrigeration and heat transfer and the factors that affect the cooling effect. At the same time, it put forward a series of suggestions and improvement opinion for NZEB in hot summer and cold winter areas.

K{sub β} to K{sub α} X-ray intensity ratios and K to L shell vacancy transfer probabilities of Co, Ni, Cu, and Zn

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

Anand, L. F. M.; Gudennavar, S. B., E-mail: shivappa.b.gudennavar@christuniversity.in; Bubbly, S. G.

The K to L shell total vacancy transfer probabilities of low Z elements Co, Ni, Cu, and Zn are estimated by measuring the K{sub β} to K{sub α} intensity ratio adopting the 2π-geometry. The target elements were excited by 32.86 keV barium K-shell X-rays from a weak {sup 137}Cs γ-ray source. The emitted K-shell X-rays were detected using a low energy HPGe X-ray detector coupled to a 16 k MCA. The measured intensity ratios and the total vacancy transfer probabilities are compared with theoretical results and others’ work, establishing a good agreement.

Adoptive cell transfer of resistance to Mycobacterium leprae infections in mice.

PubMed Central

Lowe, C; Brett, S J; Rees, R J

1985-01-01

Cells were transferred from mice intradermally vaccinated with killed Mycobacterium leprae to sublethally irradiated recipients. Unseparated cells from lymph nodes or spleens of M. leprae vaccinated mice were found to cause significant inhibition of the growth of a subsequent M. leprae challenge in mouse footpads for up to 26 weeks after vaccination. Vaccination with live BCG and cells transferred from BCG-vaccinated mice caused no significant inhibition of M. leprae growth in mouse footpads. Cell separation into fractions containing predominantly B and T lymphocytes showed that the inhibition of growth was due to M. leprae-sensitized T lymphocytes. M. leprae vaccinated mice were also skin tested with soluble M. leprae antigen and showed maximum delayed hypersensitivity responses 4 weeks after vaccination. PMID:3876183

Experimental immunotherapy shows promise in treating metastatic uveal melanoma | Center for Cancer Research

Cancer.gov

A team led by Udai S. Kammula, M.D., Investigator in the Surgery Branch, has shown that an immunotherapy known as adoptive cell transfer (ACT) is a promising approach to treating a rare form of melanoma that affects the eye.  Learn more...

United States Air Force Computer-Aided Acquisition & Logistics Support (CALS): CAD/CAM/CAE Current and Future Environment (1988 - 1998). Version 3.0

DOT National Transportation Integrated Search

1988-11-01

The diffusion and adoption of new technologies across national, sectoral, and : organizational boundaries has been a topic of considerable research. While the : exact transfer mechanism remains a matter of hypothesis, it seems clear that the : direct...

Chimeric Antigen Receptors to CD276 for Treating Cancer | NCI Technology Transfer Center | TTC

Cancer.gov

This licensing opportunity from the National Cancer Institute concerns the development of CARs comprising an antigen-binding fragment derived from the MGA271 antibody. The resulting CARs can be used in adoptive cell therapy treatment for neuroblastoma and other tumors that express CD276.

Routine Principal Transfers Invigorate School Management.

ERIC Educational Resources Information Center

Aquila, Frank D.

1989-01-01

A systematic rotation of principals can spark a willingness to tackle new challenges. Recommends the following strategies: (1) adopt a systematic rotation policy; (2) avoid random school assignments; (3) be prepared for a strong reaction from administrative staff; and (4) review personnel policies that might conflict with a rotation policy. (MLF)

Copyright in Context: The OCLC Database.

ERIC Educational Resources Information Center

Mason, Marilyn Gell

1988-01-01

Discusses topics related to OCLC adoption of guidelines for the use and transfer of OCLC-derived records, including the purpose of OCLC; the legal basis of copyrighting; technological change; compilation copyright; rationale for copyright of the OCLC database; impact on libraries; impact on networks; and relationships between OCLC and libraries. A…

Energy Innovation Portal Bridging Information Gap - Continuum Magazine |

Science.gov Websites

NASA and Sandia National Laboratories have adopted its architecture for their own tech transfer sites : Battelle Memorial Institute Colorado School of Mines Great Lakes Bioenergy Research Center NASA Naval Research Laboratory University of Colorado. NASA, which became a partner after Ringer approached them

An Assessment of the ECTS in Software Engineering: A Teaching Experience

ERIC Educational Resources Information Center

Salas-Morera, L.; Berral-Yeron, J.; Serrano-Gomez, I.; Martinez-Jimenez, P.

2009-01-01

Spain is currently implementing the regulatory modifications promulgated by the Declaration of Bologna, which should result in the updating of the structure of university degrees, and the inclusion of the European Credit Transfer and Accumulation System (ECTS) methodology. In some Spanish universities, the experimental adoption of this methodology…

DEVELOPMENT OF SUSTAINABLE AQUACULTURE PRACTICES IN TABASCO, MEXICO USING NOVEL RIAA TECHNOLOGY

EPA Science Inventory

We anticipate that several of the indigenous farmers will adopt fish farming in the context of their small irrigated farms. Fish farming is a non-consumptive use of water and irrigation will transfer the wastes from the fish into the fertilizers needed for crop production. W...

42 CFR 1001.1001 - Exclusion of entities owned or controlled by a sanctioned person.

Code of Federal Regulations, 2010 CFR

2010-10-01

... longer so described because of a transfer of ownership or control interest to an immediate family member... on behalf of an entity. Immediate family member means, a person's husband or wife; natural or adoptive parent; child or sibling; stepparent, stepchild, stepbrother or stepsister; father-, mother...

Vocation, Motivation and Approaches to Learning: A Comparative Study

ERIC Educational Resources Information Center

Arquero, Jose Luis; Fernández-Polvillo, Carmen; Hassall, Trevor; Joyce, John

2015-01-01

Purpose: The individual characteristics of students can have a strong influence on the success of the adopted innovations in terms of their transferability and sustainability. The purpose of this paper is to compare the motivations and approaches to learning on degrees with differing vocational components. Design/methodology/approach:…

The current status and future of commercial embryo transfer in cattle.

PubMed

Hasler, John F

2003-12-15

A commercially viable cattle embryo transfer (ET) industry was established in North America during the early 1970s, approximately 80 years after the first successful embryo transfer was reported in a mammal. Initially, techniques for recovering and transferring cattle embryos were exclusively surgical. However, by the late 1970s, most embryos were recovered and transferred nonsurgically. Successful cryopreservation of embryos was widespread by the early 1980s, followed by the introduction of embryo splitting, in vitro procedures, direct transfer of frozen embryos and sexing of embryos. The wide spread adoption of ethylene glycol as a cryoprotectant has simplified the thaw-transfer procedures for frozen embryos. The number of embryos recovered annually has not grown appreciably over the last 10 years in North America and Europe; however, there has been significant growth of commercial ET in South America. Within North America, ET activity has been relatively constant in Holstein cattle, whereas there has been a large ET increase in the Angus breed and a concomitant ET decrease in some other beef breeds. Although a number of new technologies have been adopted within the ET industry in the last decade, the basic procedure of superovulation of donor cattle has undergone little improvement over the last 20 years. The export-import of frozen cattle embryos has become a well-established industry, governed by specific health regulations. The international movement of embryos is subject to sudden and dramatic disturbances, as exemplified by the 2001 outbreak of foot and mouth disease in Great Britain. It is probable that there will be an increased influence of animal rights issues on the ET industry in the future. Several companies in North America are currently commercially producing cloned cattle. The sexing of bovine semen with the use of flow cytometry is extremely accurate and moderate pregnancy rates in heifers have been achieved in field trials, but sexed semen currently is available in only a few countries and on an extremely limited basis. As of yet, all programs involving the production of transgenic cattle are experimental in nature.

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

Peeters, S.H.; Carter, B.G.

An adoptive cell transfer system was defined for studying the long-term IgE anti-ovalbumin (OA) response of B6D2F/sub 1/ mice. The primary IgE anti-OA response given by this strain persisted for more than 8 months and the half-life of the IgE anti-OA in circulation was 10.5 hr as measured by residual passive cutaneous anaphylaxis (PCA) in rat skin. The system described for studying cell recruitment patterns in this response involves the transfer of primed spleen cells to irradiated recipients and the production in these recipients of IgE and hemagglutinating antibody without further overt antigenic challenge. The capacity of primed spleen cellsmore » to transfer the response was detectable 10 days after immunization and increased for the next 6 weeks. After this time the ability of primed cells to transfer the response declined steadily, but was still evident 8 months after immunization of the donor animals. The transferred response itself persisted in the recipients for many months.« less

Oral Gene Application Using Chitosan-DNA Nanoparticles Induces Transferable Tolerance

PubMed Central

Ensminger, Stephan M.; Spriewald, Bernd M.

2012-01-01

Oral tolerance is a promising approach to induce unresponsiveness to various antigens. The development of tolerogenic vaccines could be exploited in modulating the immune response in autoimmune disease and allograft rejection. In this study, we investigated a nonviral gene transfer strategy for inducing oral tolerance via antigen-encoding chitosan-DNA nanoparticles (NP). Oral application of ovalbumin (OVA)-encoding chitosan-DNA NP (OVA-NP) suppressed the OVA-specific delayed-type hypersensitivity (DTH) response and anti-OVA antibody formation, as well as spleen cell proliferation following OVA stimulation. Cytokine expression patterns following OVA stimulation in vitro showed a shift from a Th1 toward a Th2/Th3 response. The OVA-NP-induced tolerance was transferable from donor to naïve recipient mice via adoptive spleen cell transfer and was mediated by CD4+CD25+ T cells. These findings indicate that nonviral oral gene transfer can induce regulatory T cells for antigen-specific immune modulation. PMID:22933401

A generalized groundwater fluctuation model based on precipitation for estimating water table levels of deep unconfined aquifers

NASA Astrophysics Data System (ADS)

Jeong, Jina; Park, Eungyu; Shik Han, Weon; Kim, Kue-Young; Suk, Heejun; Beom Jo, Si

2018-07-01

A generalized water table fluctuation model based on precipitation was developed using a statistical conceptualization of unsaturated infiltration fluxes. A gamma distribution function was adopted as a transfer function due to its versatility in representing recharge rates with temporally dispersed infiltration fluxes, and a Laplace transformation was used to obtain an analytical solution. To prove the general applicability of the model, convergences with previous water table fluctuation models were shown as special cases. For validation, a few hypothetical cases were developed, where the applicability of the model to a wide range of unsaturated zone conditions was confirmed. For further validation, the model was applied to water table level estimations of three monitoring wells with considerably thick unsaturated zones on Jeju Island. The results show that the developed model represented the pattern of hydrographs from the two monitoring wells fairly well. The lag times from precipitation to recharge estimated from the developed system transfer function were found to agree with those from a conventional cross-correlation analysis. The developed model has the potential to be adopted for the hydraulic characterization of both saturated and unsaturated zones by being calibrated to actual data when extraneous and exogenous causes of water table fluctuation are limited. In addition, as it provides reference estimates, the model can be adopted as a tool for surveilling groundwater resources under hydraulically stressed conditions.

The cognitive therapy of depression rests on substantial theoretical, empirical and clinical foundations: a reply to Dr Gipps

PubMed Central

Moorey, Stirling

2017-01-01

Dr Gipps claims that the cognitive therapy for depression rests on a mistake. But his anachronistic analysis of Beck's early research from the perspective of current psychoanalytic theory misses the point. The value of the research was not that it disproved psychoanalytic theory, but that it generated a model of depression that has revolutionised psychotherapy research. Psychoanalysts are belatedly adopting research methods that Beck pioneered half a century ago. The cognitive model of depression has explanatory power for both maintenance and vulnerability and has substantial research underpinning it. Cognitive therapy for depression has a larger body of evidence for its efficacy and relapse prevention effect than any other psychotherapy. Transference-focused approaches to depression have yet to establish themselves in the same way. PMID:29018552

Computational Simulation of the Formation and Material Behavior of Ice

NASA Technical Reports Server (NTRS)

Tong, Michael T.; Singhal, Surendra N.; Chamis, Christos C.

1994-01-01

Computational methods are described for simulating the formation and the material behavior of ice in prevailing transient environments. The methodology developed at the NASA Lewis Research Center was adopted. A three dimensional finite-element heat transfer analyzer was used to predict the thickness of ice formed under prevailing environmental conditions. A multi-factor interaction model for simulating the material behavior of time-variant ice layers is presented. The model, used in conjunction with laminated composite mechanics, updates the material properties of an ice block as its thickness increases with time. A sample case of ice formation in a body of water was used to demonstrate the methodology. The results showed that the formation and the material behavior of ice can be computationally simulated using the available composites technology.

A complexity-scalable software-based MPEG-2 video encoder.

PubMed

Chen, Guo-bin; Lu, Xin-ning; Wang, Xing-guo; Liu, Ji-lin

2004-05-01

With the development of general-purpose processors (GPP) and video signal processing algorithms, it is possible to implement a software-based real-time video encoder on GPP, and its low cost and easy upgrade attract developers' interests to transfer video encoding from specialized hardware to more flexible software. In this paper, the encoding structure is set up first to support complexity scalability; then a lot of high performance algorithms are used on the key time-consuming modules in coding process; finally, at programming level, processor characteristics are considered to improve data access efficiency and processing parallelism. Other programming methods such as lookup table are adopted to reduce the computational complexity. Simulation results showed that these ideas could not only improve the global performance of video coding, but also provide great flexibility in complexity regulation.

Power optimization of ultrasonic friction-modulation tactile interfaces.

PubMed

Wiertlewski, Michael; Colgate, J Edward

2015-01-01

Ultrasonic friction-modulation devices provide rich tactile sensation on flat surfaces and have the potential to restore tangibility to touchscreens. To date, their adoption into consumer electronics has been in part limited by relatively high power consumption, incompatible with the requirements of battery-powered devices. This paper introduces a method that optimizes the energy efficiency and performance of this class of devices. It considers optimal energy transfer to the impedance provided by the finger interacting with the surface. Constitutive equations are determined from the mode shape of the interface and the piezoelectric coupling of the actuator. The optimization procedure employs a lumped parameter model to simplify the treatment of the problem. Examples and an experimental study show the evolution of the optimal design as a function of the impedance of the finger.

A revised B(E2;2+ 1 → 0+ 1) value in the semi-magic nucleus 210Po

NASA Astrophysics Data System (ADS)

Kocheva, D.; Rainovski, G.; Jolie, J.; Pietralla, N.; Blazhev, A.; Astier, A.; Altenkirch, R.; Ansari, S.; Braunroth, Th.; Cortés, M. L.; Dewald, A.; Diel, F.; Djongolov, M.; Fransen, C.; Gladnishki, K.; Hennig, A.; Karayonchev, V.; Keatings, J. M.; Kluge, E.; Litzinger, J.; Müller-Gatermann, C.; Petkov, P.; Rudigier, M.; Scheck, M.; Scholz, Ph.; Spagnoletti, P.; Spieker, M.; Stahl, C.; Stegmann, R.; Stoyanova, M.; Thöle, P.; Warr, N.; Werner, V.; Witt, W.; Wölk, D.; Zell, K. O.; Van Isacker, P.; Ponomarev, V. Yu.

2017-09-01

The lifetimes of the 2^+_1 , the 2^+_2 and the 3^-_1 states of 210Po have been measured in the 208Pb(12C,10Be)210Po transfer reaction by the Doppler-shift attenuation method. The result for the lifetime of the 2^+_1 state is about three times shorter than the adopted value. However, the new value still does not allow for a consistent description of the properties of the yrast 2^+_1 , 4^+_1 , 6^+_1 , and 8^+_1 states of 210Po in the framework of nuclear shell models. Quasi-particle Phonon Model (QPM) calculations also cannot overcome this problem thus indicating the existence of a peculiarity which is neglected in both theoretical approaches.

Ultrafast direct electron transfer at organic semiconductor and metal interfaces.

PubMed

Xiang, Bo; Li, Yingmin; Pham, C Huy; Paesani, Francesco; Xiong, Wei

2017-11-01

The ability to control direct electron transfer can facilitate the development of new molecular electronics, light-harvesting materials, and photocatalysis. However, control of direct electron transfer has been rarely reported, and the molecular conformation-electron dynamics relationships remain unclear. We describe direct electron transfer at buried interfaces between an organic polymer semiconductor film and a gold substrate by observing the first dynamical electric field-induced vibrational sum frequency generation (VSFG). In transient electric field-induced VSFG measurements on this system, we observe dynamical responses (<150 fs) that depend on photon energy and polarization, demonstrating that electrons are directly transferred from the Fermi level of gold to the lowest unoccupied molecular orbital of organic semiconductor. Transient spectra further reveal that, although the interfaces are prepared without deliberate alignment control, a subensemble of surface molecules can adopt conformations for direct electron transfer. Density functional theory calculations support the experimental results and ascribe the observed electron transfer to a flat-lying polymer configuration in which electronic orbitals are found to be delocalized across the interface. The present observation of direct electron transfer at complex interfaces and the insights gained into the relationship between molecular conformations and electron dynamics will have implications for implementing novel direct electron transfer in energy materials.

Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering an In Situ Inflammatory Immune Response.

PubMed

Lorvik, Kristina Berg; Hammarström, Clara; Fauskanger, Marte; Haabeth, Ole Audun Werner; Zangani, Michael; Haraldsen, Guttorm; Bogen, Bjarne; Corthay, Alexandre

2016-12-01

Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8 + T cells; however, the potential of CD4 + T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8 + T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type II inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer. Cancer Res; 76(23); 6864-76. ©2016 AACR. ©2016 American Association for Cancer Research.