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

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.

49 CFR 389.29 - Adoption of final rules.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Adoption of final rules. 389.29 Section 389.29 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY...-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.29 Adoption of final rules...

49 CFR 389.29 - Adoption of final rules.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Adoption of final rules. 389.29 Section 389.29 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY...-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.29 Adoption of final rules...

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

Superdense Coding over Optical Fiber Links with Complete Bell-State Measurements

DOE PAGES

Williams, Brian P.; Sadlier, Ronald J.; Humble, Travis S.

2017-02-01

Adopting quantum communication to modern networking requires transmitting quantum information through a fiber-based infrastructure. In this paper, we report the first demonstration of superdense coding over optical fiber links, taking advantage of a complete Bell-state measurement enabled by time-polarization hyperentanglement, linear optics, and common single-photon detectors. Finally, we demonstrate the highest single-qubit channel capacity to date utilizing linear optics, 1.665 ± 0.018, and we provide a full experimental implementation of a hybrid, quantum-classical communication protocol for image transfer.

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

76 FR 69333 - Derivatives Clearing Organization General Provisions and Core Principles

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-08

...The Commodity Futures Trading Commission (Commission) is adopting final regulations to implement certain provisions of Title VII and Title VIII of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act) governing derivatives clearing organization (DCO) activities. More specifically, the regulations establish the regulatory standards for compliance with DCO Core Principles A (Compliance), B (Financial Resources), C (Participant and Product Eligibility), D (Risk Management), E (Settlement Procedures), F (Treatment of Funds), G (Default Rules and Procedures), H (Rule Enforcement), I (System Safeguards), J (Reporting), K (Recordkeeping), L (Public Information), M (Information Sharing), N (Antitrust Considerations), and R (Legal Risk) set forth in Section 5b of the Commodity Exchange Act (CEA). The Commission also is updating and adding related definitions; adopting implementing rules for DCO chief compliance officers (CCOs); revising procedures for DCO applications including the required use of a new Form DCO; adopting procedural rules applicable to the transfer of a DCO registration; and adding requirements for approval of DCO rules establishing a portfolio margining program for customer accounts carried by a futures commission merchant (FCM) that is also registered as a securities broker-dealer (FCM/BD). In addition, the Commission is adopting certain technical amendments to parts 21 and 39, and is adopting certain delegation provisions under part 140.

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...

Early experiences with E-prescribing.

PubMed

Halamka, John

2006-01-01

Most physicians understand that e-prescribing will reduce medical errors and will be perceived by patients as making the prescription process easier. However, they are skeptical about a number of things. They worry whether their office processes will be improved or streamlined; e-prescribing will interface seamlessly with their existing practice management software; training and support will be available; e-prescribing data will be seamlessly transferable to an electronic health record when they implement a more advanced clinical record system for their practice; and if they will achieve a return on investment. Early adopting clinicians in Massachusetts can convince the majority of clinicians to adopt e-prescribing by sharing their motivations for adopting e-prescribing, the challenges that they needed to overcome, the hardware and software requirements, and integration into their office workflow. Finally, interaction with the physicians and practice managers in the audience makes the adoption of e-prescribing seem both reasonable and exciting. Resources such as vendor lists, questions to ask, and hardware and software requirements also need to be readily available and in a form that non-technical staff can read and understand. Physicians who know the "why" would also like to know

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)

DSA patterning options for logics and memory applications

NASA Astrophysics Data System (ADS)

Liu, Chi-Chun; Franke, Elliott; Mignot, Yann; LeFevre, Scott; Sieg, Stuart; Chi, Cheng; Meli, Luciana; Parnell, Doni; Schmidt, Kristin; Sanchez, Martha; Singh, Lovejeet; Furukawa, Tsuyoshi; Seshadri, Indira; De Silva, Ekmini Anuja; Tsai, Hsinyu; Lai, Kafai; Truong, Hoa; Farrell, Richard; Bruce, Robert; Somervell, Mark; Sanders, Daniel; Felix, Nelson; Arnold, John; Hetzer, David; Ko, Akiteru; Metz, Andrew; Colburn, Matthew; Corliss, Daniel

2017-03-01

The progress of three potential DSA applications, i.e. fin formation, via shrink, and pillars, were reviewed in this paper. For fin application, in addition to pattern quality, other important considerations such as customization and design flexibility were discussed. An electrical viachain study verified the DSA rectification effect on CD distribution by showing a tighter current distribution compared to that derived from the guiding pattern direct transfer without using DSA. Finally, a structural demonstration of pillar formation highlights the importance of pattern transfer in retaining both the CD and local CDU improvement from DSA. The learning from these three case studies can provide perspectives that may not have been considered thoroughly in the past. By including more important elements during DSA process development, the DSA maturity can be further advanced and move DSA closer to HVM adoption.

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

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…

Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme~Ubiquitin Conjugate

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

Pruneda, Jonathan N.; Stoll, Kate E.; Bolton, Laura J.

2011-03-15

Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2~Ub conjugate. Therefore, full characterization of the structure and dynamics of E2~Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2~Ub conjugates of two human enzymes, UbcH5c~Ub and Ubc13~Ub,more » in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5c~Ub conjugate populates an array of extended conformations, and the population of Ubc13~Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. Finally, we propose that the varied conformations adopted by Ub represent available binding modes of the E2~Ub species and thus provide insight into the diverse E2~Ub protein interactome, particularly with regard to interaction with Ub ligases.« less

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.

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…

40 CFR 1506.3 - Adoption.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) An agency may adopt a Federal draft or final environmental impact statement or portion thereof... are substantially the same, the agency adopting another agency's statement is not required to recirculate it except as a final statement. Otherwise the adopting agency shall treat the statement as a draft...

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

The ATLAS project: The effects of a constructionist digital laboratory project on undergraduate laboratory performance.

PubMed

Shoepe, Todd C; Cavedon, Dana K; Derian, Joseph M; Levy, Celine S; Morales, Amy

2015-01-01

Anatomical education is a dynamic field where developments in the implementation of constructive, situated-learning show promise in improving student achievement. The purpose of this study was to examine the effectiveness of an individualized, technology heavy project in promoting student performance in a combined anatomy and physiology laboratory course. Mixed-methods research was used to compare two cohorts of anatomy laboratories separated by the adoption of a new laboratory atlas project, which were defined as preceding (PRE) and following the adoption of the Anatomical Teaching and Learning Assessment Study (ATLAS; POST). The ATLAS project required the creation of a student-generated, photographic atlas via acquisition of specimen images taken with tablet technology and digital microscope cameras throughout the semester. Images were transferred to laptops, digitally labeled and photo edited weekly, and compiled into a digital book using Internet publishing freeware for final project submission. An analysis of covariance confirmed that student final examination scores were improved (P < 0.05) following the implementation of the laboratory atlas project (PRE, n = 75; POST, n = 90; means ± SE; 74.9 ± 0.9 versus 78.1 ± 0.8, respectively) after controlling for cumulative student grade point average. Analysis of questionnaires collected (n = 68) from the post group suggested students identified with atlas objectives, appreciated the comprehensive value in final examination preparation, and the constructionism involved, but recommended alterations in assignment logistics and the format of the final version. Constructionist, comprehensive term-projects utilizing student-preferred technologies could be used to improve performance toward student learning outcomes. © 2014 American Association of Anatomists.

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

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

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

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.

Software Engineering Technology Infusion Within NASA

NASA Technical Reports Server (NTRS)

Zelkowitz, Marvin V.

1996-01-01

Abstract technology transfer is of crucial concern to both government and industry today. In this paper, several software engineering technologies used within NASA are studied, and the mechanisms, schedules, and efforts at transferring these technologies are investigated. The goals of this study are: 1) to understand the difference between technology transfer (the adoption of a new method by large segments of an industry) as an industry-wide phenomenon and the adoption of a new technology by an individual organization (called technology infusion); and 2) to see if software engineering technology transfer differs from other engineering disciplines. While there is great interest today in developing technology transfer models for industry, it is the technology infusion process that actually causes changes in the current state of the practice.

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.

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.

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

The Scaling of Water Governance Tasks: A Comparative Federal Analysis of the European Union and Australia

NASA Astrophysics Data System (ADS)

Benson, David; Jordan, Andrew

2010-07-01

Conflicts over how to “scale” policy-making tasks have characterized environmental governance since time immemorial. They are particularly evident in the area of water policy and raise important questions over the democratic legitimacy, economic efficiency and effectiveness of allocating (or “scaling”) tasks to some administrative levels as opposed to others. This article adopts a comparative federalism perspective to assess the “optimality” of scaling—either upward or downward—in one issue area, namely coastal recreational water quality. It does so by comparing the scaling of recreational water quality tasks in the European Union (EU) and Australia. It reveals that the two systems have adopted rather different approaches to scaling and that this difference can partly be accounted for in federal theoretical terms. However, a much greater awareness of the inescapably political nature of scaling processes is nonetheless required. Finally, some words of caution are offered with regard to transferring policy lessons between these two jurisdictions.

76 FR 43477 - Debit Card Interchange Fees and Routing

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...The Board is adopting an interim final rule and requesting comment on provisions in Regulation II (Debit Card Interchange Fees and Routing) adopted in accordance with Section 920(a)(5) of the Electronic Fund Transfer Act, which governs adjustments to debit interchange transaction fees for fraud-prevention costs. The provisions allow an issuer to receive an adjustment of 1 cent to its interchange transaction fee if the issuer develops, implements, and updates policies and procedures reasonably designed to identify and prevent fraudulent electronic debit transactions; monitor the incidence of, reimbursements received for, and losses incurred from fraudulent electronic debit transactions; respond appropriately to suspicious electronic debit transactions so as to limit the fraud losses that may occur and prevent the occurrence of future fraudulent electronic debit transactions; and secure debit card and cardholder data. If an issuer meets these standards and wishes to receive the adjustment, it must certify its eligibility to receive the fraud-prevention adjustment to the payment card networks in which the issuer participates.

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

Adoptively transferred TRAIL+ T cells suppress GVHD and augment antitumor activity

PubMed Central

Ghosh, Arnab; Dogan, Yildirim; Moroz, Maxim; Holland, Amanda M.; Yim, Nury L.; Rao, Uttam K.; Young, Lauren F.; Tannenbaum, Daniel; Masih, Durva; Velardi, Enrico; Tsai, Jennifer J.; Jenq, Robert R.; Penack, Olaf; Hanash, Alan M.; Smith, Odette M.; Piersanti, Kelly; Lezcano, Cecilia; Murphy, George F.; Liu, Chen; Palomba, M. Lia; Sauer, Martin G.; Sadelain, Michel; Ponomarev, Vladimir; van den Brink, Marcel R.M.

2013-01-01

Current strategies to suppress graft-versus-host disease (GVHD) also compromise graft-versus-tumor (GVT) responses. Furthermore, most experimental strategies to separate GVHD and GVT responses merely spare GVT function without actually enhancing it. We have previously shown that endogenously expressed TNF-related apoptosis-inducing ligand (TRAIL) is required for optimal GVT activity against certain malignancies in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to model a donor-derived cellular therapy, we genetically engineered T cells to overexpress TRAIL and adoptively transferred donor-type unsorted TRAIL+ T cells into mouse models of allo-HSCT. We found that murine TRAIL+ T cells induced apoptosis of alloreactive T cells, thereby reducing GVHD in a DR5-dependent manner. Furthermore, murine TRAIL+ T cells mediated enhanced in vitro and in vivo antilymphoma GVT response. Moreover, human TRAIL+ T cells mediated enhanced in vitro cytotoxicity against both human leukemia cell lines and against freshly isolated chronic lymphocytic leukemia (CLL) cells. Finally, as a model of off-the-shelf, donor-unrestricted antitumor cellular therapy, in vitro–generated TRAIL+ precursor T cells from third-party donors also mediated enhanced GVT response in the absence of GVHD. These data indicate that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD. PMID:23676461

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.

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.

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

7 CFR 1794.72 - Adoption of an EIS.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Adoption of Environmental Documents § 1794.72... portion of the EIS as a part of its draft EIS. The circulation and notice provisions for a draft and final... agency's EIS is adequate, RUS shall adopt that agency's EIS as its final EIS. RUS and the applicant shall...

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.

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…

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.

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…

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.

The challenges of rescaling South African water resources management: Catchment Management Agencies and interbasin transfers

NASA Astrophysics Data System (ADS)

Bourblanc, Magalie; Blanchon, David

2014-11-01

The implementation of Catchment Management Agencies (CMAs) was supposed to be the cornerstone of the rescaling process of the South African water reform policy. Yet, less than 10 years after the adoption of the National Water Act, the process was suspended for 4 years and by 2012 only two CMAs had been established. Combining approaches in geography and political science, this paper investigates the reasons for the delays in CMAs' implementation in South Africa. It shows that the construction of interbasin transfers (IBTs) since the 1950s by the apartheid regime and nowadays the power struggles between CMAs and the Department of Water Affairs (DWA) are two of the main obstacles to the creation of CMAs planned by the 1998 National Water Act (NWA). Finally, the paper advocates taking the "hydrosocial cycle" as an analytical framework for designing new institutional arrangements that will include both rectifying the legacy of the past (the specific role of DWA) and acknowledging legitimate local interests.

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.

Graphene/h-BN/GaAs sandwich diode as solar cell and photodetector.

PubMed

Li, Xiaoqiang; Lin, Shisheng; Lin, Xing; Xu, Zhijuan; Wang, Peng; Zhang, Shengjiao; Zhong, Huikai; Xu, Wenli; Wu, Zhiqian; Fang, Wei

2016-01-11

In graphene/semiconductor heterojunction, the statistic charge transfer between graphene and semiconductor leads to decreased junction barrier height and limits the Fermi level tuning effect in graphene, which greatly affects the final performance of the device. In this work, we have designed a sandwich diode for solar cells and photodetectors through inserting 2D hexagonal boron nitride (h-BN) into graphene/GaAs heterostructure to suppress the static charge transfer. The barrier height of graphene/GaAs heterojunction can be increased from 0.88 eV to 1.02 eV by inserting h-BN. Based on the enhanced Fermi level tuning effect with interface h-BN, through adopting photo-induced doping into the device, power conversion efficiency (PCE) of 10.18% has been achieved for graphene/h-BN/GaAs compared with 8.63% of graphene/GaAs structure. The performance of graphene/h-BN/GaAs based photodetector is also improved with on/off ratio increased by one magnitude compared with graphene/GaAs structure.

Competency-Based Transfer Pilot Project--Final Report. Executive Summary [and] Competency-Based Transfer Pilot Project: Final Report on House Bill 1909

ERIC Educational Resources Information Center

Washington Higher Education Coordinating Board, 2006

2006-01-01

This publication contains the following: (1) Competency-Based Transfer Pilot Project--Final Report. Executive Summary (January 2006); and (2) Competency-Based Transfer Pilot Project: Final Report on House Bill 1909 (January 2005). In 2003, the legislature and governor enacted House Bill 1909 to create a pilot project on competency-based transfer…

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.

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.

[Nasal submicron emulsion of Scutellariae Radix extract preparation technology research based on phase transfer of solute technology].

PubMed

Shi, Ya-jun; Shi, Jun-hui; Chen, Shi-bin; Yang, Ming

2015-07-01

Based on the demand of nasal drug delivery high drug loadings, using the unique phase transfer of solute, integrating the phospholipid complex preparation and submicron emulsion molding process of Scutellariae Radix extract, the study obtained the preparation of the high drug loadings submicron emulsion of Scutellariae Radix extract. In the study of drug solution dispersion method, the uniformity of drug dispersed as the evaluation index, the traditional mixing method, grinding, homogenate and solute phase transfer technology were investigated, and the solute phase transfer technology was adopted in the last. With the adoption of new technology, the drug loading capacity reached 1.33% (phospholipid complex was 4%). The drug loading capacity was improved significantly. The transfer of solute method and timing were studied as follows,join the oil phase when the volume of phospholipid complex anhydrous ethanol solution remaining 30%, the solute phase transfer was completed with the continued recycling of anhydrous ethanol. After drug dissolved away to oil phase, the preparation technology of colostrum was determined with the evaluation index of emulsion droplet form. The particle size of submicron emulsion, PDI and stability parameters were used as evaluation index, orthogonal methodology were adopted to optimize the submicron emulsion ingredient and main influential factors of high pressure homogenization technology. The optimized preparation technology of Scutellariae Radix extract nasal submicron emulsion is practical and stable.

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.

Social contagions on correlated multiplex networks

NASA Astrophysics Data System (ADS)

Wang, Wei; Cai, Meng; Zheng, Muhua

2018-06-01

The existence of interlayer degree correlations has been disclosed by abundant multiplex network analysis. However, how they impose on the dynamics of social contagions are remain largely unknown. In this paper, we propose a non-Markovian social contagion model in multiplex networks with inter-layer degree correlations to delineate the behavior spreading, and develop an edge-based compartmental (EBC) theory to describe the model. We find that multiplex networks promote the final behavior adoption size. Remarkably, it can be observed that the growth pattern of the final behavior adoption size, versus the behavioral information transmission probability, changes from discontinuous to continuous once decreasing the behavior adoption threshold in one layer. We finally unravel that the inter-layer degree correlations play a role on the final behavior adoption size but have no effects on the growth pattern, which is coincidence with our prediction by using the suggested theory.

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.

Effects of Motion Cues on the Training of Multi-Axis Manual Control Skills

NASA Technical Reports Server (NTRS)

Zaal, Peter M. T.; Mobertz, Xander R. I.

2017-01-01

The study described in this paper investigated the effects of two different hexapod motion configurations on the training and transfer of training of a simultaneous roll and pitch control task. Pilots were divided between two groups which trained either under a baseline hexapod motion condition, with motion typically provided by current training simulators, or an optimized hexapod motion condition, with increased fidelity of the motion cues most relevant for the task. All pilots transferred to the same full-motion condition, representing motion experienced in flight. A cybernetic approach was used that gave insights into the development of pilots use of visual and motion cues over the course of training and after transfer. Based on the current results, neither of the hexapod motion conditions can unambiguously be chosen as providing the best motion for training and transfer of training of the used multi-axis control task. However, the optimized hexapod motion condition did allow pilots to generate less visual lead, control with higher gains, and have better disturbance-rejection performance at the end of the training session compared to the baseline hexapod motion condition. Significant adaptations in control behavior still occurred in the transfer phase under the full-motion condition for both groups. Pilots behaved less linearly compared to previous single-axis control-task experiments; however, this did not result in smaller motion or learning effects. Motion and learning effects were more pronounced in pitch compared to roll. Finally, valuable lessons were learned that allow us to improve the adopted approach for future transfer-of-training studies.

Strengthening Adoption Practice, Listening to Adoptive Families

ERIC Educational Resources Information Center

Atkinson, Anne; Gonet, Patricia

2007-01-01

In-depth interviews with 500 adoptive families who received postadoption services through Virginia's Adoptive Family Preservation (AFP) program paint a richly detailed picture of the challenges adoptive families face and what they need to sustain adoption for many years after finalization. Findings document the need for support in a variety of…

Regulatory T cells decrease invariant natural killer T cell-mediated pregnancy loss in mice.

PubMed

Li, L; Tu, J; Jiang, Y; Zhou, J; Schust, D J

2017-05-01

Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum. Adoptive transfer of iNKT cells from wild-type (WT) and IL-4 -/- mice but not IFN-γ -/- mice into αGC-treated iNKT cell-deficient Jα18 -/- mice restored αGC-induced pregnancy loss. Adoptive transfer of Treg cells downregulated α-GC-induced pregnancy loss in WT mice. Finally, co-culture with αGC-stimulated decidual iNKT cells decreased the production of IL-10 and TGF-β in decidual Treg cells and inhibited their suppressive activity. These findings suggest that activation of iNKT cells induces pregnancy loss in mice in an IFN-γ-dependent manner. In addition, inhibition of the function of decidual Treg cells has an important role in iNKT cell-mediated pregnancy loss.

Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

PubMed

Pomié, Céline; Blasco-Baque, Vincent; Klopp, Pascale; Nicolas, Simon; Waget, Aurélie; Loubières, Pascale; Azalbert, Vincent; Puel, Anthony; Lopez, Frédéric; Dray, Cédric; Valet, Philippe; Lelouvier, Benjamin; Servant, Florence; Courtney, Michael; Amar, Jacques; Burcelin, Rémy; Garidou, Lucile

2016-06-01

To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.

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).

Household-Level Determinants of Soil and Water Conservation Adoption Phases: Evidence from North-Western Ethiopian Highlands.

PubMed

Teshome, Akalu; de Graaff, Jan; Kassie, Menale

2016-03-01

Soil and water conservation (SWC) practices have been promoted in the highlands of Ethiopia during the last four decades. However, the level of adoption of SWC practices varies greatly. This paper examines the drivers of different stages of adoption of SWC technologies in the north-western highlands of Ethiopia. This study is based on a detailed farm survey among 298 households in three watersheds. Simple descriptive statistics were applied to analyze the stages of adoption. An ordered probit model was used to analyze the drivers of different stages of adoption of SWC. This model is used to analyze more than two outcomes of an ordinal dependent variable. The results indicate that sampled households are found in different phases of adoption, i.e., dis-adoption/non-adoption (18.5 %), initial adoption (30.5 %), actual adoption (20.1 %), and final adoption (30.9 %). The results of the ordered probit model show that some socio-economic and institutional factors affect the adoption phases of SWC differently. Farm labor, parcel size, ownership of tools, training in SWC, presence of SWC program, social capital (e.g., cooperation with adjacent farm owners), labor sharing scheme, and perception of erosion problem have a significant positive influence on actual and final adoption phases of SWC. In addition, the final adoption phase of SWC is positively associated with tenure security, cultivated land sizes, parcel slope, and perception on SWC profitability. Policy makers should take into consideration factors affecting (continued) adoption of SWC such as profitability, tenure security, social capital, technical support, and resource endowments (e.g., tools and labor) when designing and implementing SWC policies and programs.

Household-Level Determinants of Soil and Water Conservation Adoption Phases: Evidence from North-Western Ethiopian Highlands

NASA Astrophysics Data System (ADS)

Teshome, Akalu; de Graaff, Jan; Kassie, Menale

2016-03-01

Soil and water conservation (SWC) practices have been promoted in the highlands of Ethiopia during the last four decades. However, the level of adoption of SWC practices varies greatly. This paper examines the drivers of different stages of adoption of SWC technologies in the north-western highlands of Ethiopia. This study is based on a detailed farm survey among 298 households in three watersheds. Simple descriptive statistics were applied to analyze the stages of adoption. An ordered probit model was used to analyze the drivers of different stages of adoption of SWC. This model is used to analyze more than two outcomes of an ordinal dependent variable. The results indicate that sampled households are found in different phases of adoption, i.e., dis-adoption/non-adoption (18.5 %), initial adoption (30.5 %), actual adoption (20.1 %), and final adoption (30.9 %). The results of the ordered probit model show that some socio-economic and institutional factors affect the adoption phases of SWC differently. Farm labor, parcel size, ownership of tools, training in SWC, presence of SWC program, social capital (e.g., cooperation with adjacent farm owners), labor sharing scheme, and perception of erosion problem have a significant positive influence on actual and final adoption phases of SWC. In addition, the final adoption phase of SWC is positively associated with tenure security, cultivated land sizes, parcel slope, and perception on SWC profitability. Policy makers should take into consideration factors affecting (continued) adoption of SWC such as profitability, tenure security, social capital, technical support, and resource endowments (e.g., tools and labor) when designing and implementing SWC policies and programs.

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.

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.

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.

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.

Scoping Report: Advanced Technologies for Multi-Load Washers in Hospitality and Healthcare

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

Parker, Graham B.; Boyd, Brian K.; Petersen, Joseph M.

The purpose of this demonstration project is to quantify the energy savings and water efficiency potential of commercial laundry wastewater recycling systems and low-temperature detergent supply systems to help promote the adoption of these technologies in the commercial sector. This project will create a set of technical specifications for efficient multi-load laundry systems (both new and retrofit) tailored for specific applications and/or sectors (e.g., hospitality, health care). The specifications will be vetted with the appropriate Better Buildings Alliance (BBA) members (e.g., Commercial Real Estate Energy Alliance, Hospital Energy Alliance), finalized, published, and disseminated to enable widespread technology transfer in themore » industry and specifically among BBA partners.« less

The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies.

PubMed

Neal, Lillian R; Bailey, Stefanie R; Wyatt, Megan M; Bowers, Jacob S; Majchrzak, Kinga; Nelson, Michelle H; Haupt, Carl; Paulos, Chrystal M; Varela, Juan C

2017-01-01

Adoptive T cell transfer (ACT) can mediate objective responses in patients with advanced malignancies. There have been major advances in this field, including the optimization of the ex vivo generation of tumor-reactive lymphocytes to ample numbers for effective ACT therapy via the use of natural and artificial antigen presenting cells (APCs). Herein we review the basic properties of APCs and how they have been manufactured through the years to augment vaccine and T cell-based cancer therapies. We then discuss how these novel APCs impact the function and memory properties of T cells. Finally, we propose new ways to synthesize aAPCs to augment the therapeutic effectiveness of antitumor T cells for ACT therapy.

The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies

PubMed Central

Neal, Lillian R.; Bailey, Stefanie R.; Wyatt, Megan M.; Bowers, Jacob S.; Majchrzak, Kinga; Nelson, Michelle H.; Haupt, Carl; Paulos, Chrystal M.; Varela, Juan C.

2017-01-01

Adoptive T cell transfer (ACT) can mediate objective responses in patients with advanced malignancies. There have been major advances in this field, including the optimization of the ex vivo generation of tumor-reactive lymphocytes to ample numbers for effective ACT therapy via the use of natural and artificial antigen presenting cells (APCs). Herein we review the basic properties of APCs and how they have been manufactured through the years to augment vaccine and T cell-based cancer therapies. We then discuss how these novel APCs impact the function and memory properties of T cells. Finally, we propose new ways to synthesize aAPCs to augment the therapeutic effectiveness of antitumor T cells for ACT therapy. PMID:28825053

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.

Tissue-specific differentiation of a circulating CCR9- pDC-like common dendritic cell precursor.

PubMed

Schlitzer, Andreas; Heiseke, Alexander F; Einwächter, Henrik; Reindl, Wolfgang; Schiemann, Matthias; Manta, Calin-Petru; See, Peter; Niess, Jan-Hendrik; Suter, Tobias; Ginhoux, Florent; Krug, Anne B

2012-06-21

The ontogenic relationship between the common dendritic cell (DC) progenitor (CDP), the committed conventional DC precursor (pre-cDC), and cDC subpopulations in lymphoid and nonlymphoid tissues has been largely unraveled. In contrast, the sequential steps of plasmacytoid DC (pDC) development are less defined, and it is unknown at which developmental stage and location final commitment to the pDC lineage occurs. Here we show that CCR9(-) pDCs from murine BM which enter the circulation and peripheral tissues have a common DC precursor function in vivo in the steady state, in contrast to CCR9(+) pDCs which are terminally differentiated. On adoptive transfer, the fate of CCR9(-) pDC-like precursors is governed by the tissues they enter. In the BM and liver, most transferred CCR9(-) pDC-like precursors differentiate into CCR9(+) pDCs, whereas in peripheral lymphoid organs, lung, and intestine, they additionally give rise to cDCs. CCR9(-) pDC-like precursors which are distinct from pre-cDCs can be generated from the CDP. Thus, CCR9(-) pDC-like cells are novel CDP-derived circulating DC precursors with pDC and cDC potential. Their final differentiation into functionally distinct pDCs and cDCs depends on tissue-specific factors allowing adaptation to local requirements under homeostatic conditions.

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

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…

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…

The Effect of Uphill and Downhill Slopes on Weight Transfer, Alignment and Shot Outcome in Golf.

PubMed

Blenkinsop, Glen M; Liang, Ying; Gallimore, Nicholas J; Hiley, Michael J

2018-04-13

The aim of the study was to examine changes in weight transfer, alignment and shot outcome during golf shots from flat, uphill, and downhill slopes. Twelve elite male golfers hit 30 shots with a six-iron from a computer assisted rehabilitation environment (CAREN) used to create 5° slopes while collecting 3D kinematics and kinetics of the swing. A launch monitor measured performance outcomes. A shift in the centre of pressure was found throughout the swing when performed on a slope, with the mean position moving approximately 9% closer to the lower foot. The golfers attempted to remain perpendicular to the slope, resulting in the weight transfer towards the lower foot. The golfers adopted a wider stance in the sloped conditions and moved the ball towards the higher foot at address. Ball speed was not significantly affected by the slope, but launch angle and ball spin were. As predicted by the coaching literature, golfers were more likely to hit shots to the left from an uphill slope and to the right for a downhill slope. No consistent compensatory adjustments in alignment at address or azimuth were found, with the change in final shot dispersion due to the lateral spin of the ball.

Multi-resolution extension for transmission of geodata in a mobile context

NASA Astrophysics Data System (ADS)

Follin, Jean-Michel; Bouju, Alain; Bertrand, Frédéric; Boursier, Patrice

2005-03-01

A solution is proposed for the management of multi-resolution vector data in a mobile spatial information visualization system. The client-server architecture and the models of data and transfer of the system are presented first. The aim of this system is to reduce data exchanged between client and server by reusing data already present on the client side. Then, an extension of this system to multi-resolution data is proposed. Our solution is based on the use of increments in a multi-scale database. A database architecture where data sets for different predefined scales are precomputed and stored on the server side is adopted. In this model, each object representing the same real world entities at different levels of detail has to be linked beforehand. Increments correspond to the difference between two datasets with different levels of detail. They are transmitted in order to increase (or decrease) the detail to the client upon request. They include generalization and refinement operators allowing transitions between the different levels. Finally, a framework suited to the transfer of multi-resolution data in a mobile context is presented. This allows reuse of data locally available at different levels of detail and, in this way, reduces the amount of data transferred between client and server.

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.

Determination of heat transfer coefficient for an interaction of sub-cooled gas and metal

NASA Astrophysics Data System (ADS)

Zaidi Sidek, Mohd; Syahidan Kamarudin, Muhammad

2016-02-01

Heat transfer coefficient (HTC) for a hot metal surface and their surrounding is one of the need be defined parameter in hot forming process. This study has been conducted to determine the HTC for an interaction between sub-cooled gas sprayed on a hot metal surface. Both experiments and finite element have been adopted in this work. Initially, the designated experiment was conducted to obtain temperature history of spray cooling process. Then, an inverse method was adopted to calculate the HTC value before we validate in a finite element simulation model. The result shows that the heat transfer coefficient for interaction of subcooled gas and hot metal surface is 1000 W/m2K.

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.

76 FR 71465 - Defense Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-18

... Government procurement. Mary Overstreet, Editor, Defense Acquisition Regulations System. Interim Rule Adopted... Federal Acquisition Regulation Supplement: Management of Manufacturing Risk in Major Defense Acquisition...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the...

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 three lives of viral fusion peptides

PubMed Central

Apellániz, Beatriz; Huarte, Nerea; Largo, Eneko; Nieva, José L.

2014-01-01

Fusion peptides comprise conserved hydrophobic domains absolutely required for the fusogenic activity of glycoproteins from divergent virus families. After 30 years of intensive research efforts, the structures and functions underlying their high degree of sequence conservation are not fully elucidated. The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis. Firstly, the VFP sequence must fulfill the set of native interactions required for (meta) stable folding within the globular ectodomains of glycoprotein complexes. Secondly, at the onset of the fusion process, they get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Here we review different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions, and discuss briefly their potential as targets for clinical intervention. PMID:24704587

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.

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.

Adoptive Immunotherapy with T Lymphocytes Engineered for Enhanced Survival | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed a method of genetically engineering lymphocytes to expressed elevated levels of cytokine proteins. This technology is useful for improving cellular adoptive immunotherapies to treat a range of infectious diseases and cancers.

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

77 FR 40459 - Electronic Fund Transfers (Regulation E); Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

... Electronic Fund Transfers (Regulation E); Correction AGENCY: Bureau of Consumer Financial Protection. ACTION... published the Final Rule (77 FR 6194), which implements the Electronic Fund Transfer Act, and the official... Sec. 1005.3(a) in the interim final rule, Electronic Fund Transfers (Regulation E), published on...

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.

Characteristics and determinants of knowledge transfer policies at universities and public institutions in medical research--protocol for a systematic review of the qualitative research literature.

PubMed

Jahn, Rosa; Müller, Olaf; Bozorgmehr, Kayvan

2015-08-19

Universities, public institutions, and the transfer of knowledge to the private sector play a major role in the development of medical technologies. The decisions of universities and public institutions regarding the transfer of knowledge impact the accessibility of the final product, making it easier or more difficult for consumers to access these products. In the case of medical research, these products are pharmaceuticals, diagnostics, or medical procedures. The ethical dimension of access to these potentially lifesaving products is apparent and distinguishes the transfer of medical knowledge from the transfer of knowledge in other areas. While the general field of technology transfer from academic and public to private actors is attracting an increasing amount of scholarly attention, the specifications of knowledge transfer in the medical field are not as well explored. This review seeks to provide a systematic overview and analysis of the qualitative literature on the characteristics and determinants of knowledge transfer in medical research and development. The review systematically searches the literature for qualitative studies that focus on knowledge transfer characteristics and determinants at medical academic and public research institutions. It aims at identifying and analyzing the literature on the content and context of knowledge transfer policies, decision-making processes, and actors at academic and public institutions. The search strategy includes the databases PubMed, Web of Science, ProQuest, and DiVa. These databases will be searched based on pre-specified search terms. The studies selected for inclusion in the review will be critically assessed for their quality utilizing the Qualitative Research Checklist developed by the Clinical Appraisal Skills Programme. Data extraction and synthesis will be based on the meta-ethnographic approach. This review seeks to further the understanding of the kinds of transfer pathways that exist in medical knowledge transfer as well as what factors lead to the adoption of one pathway over another. The aim is to provide evidence for political and academic actors designing policies for the translation of medical knowledge and public-private cooperation. PROSPERO CRD42015014241 .

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…

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.

Creating Grander Families: Older Adults Adopting Younger Kin and Nonkin

ERIC Educational Resources Information Center

Hinterlong, James; Ryan, Scott

2008-01-01

Purpose: There is a dearth of research on older adoptive parents caring for minor children, despite a growing number of such adoptions finalized each year. This study offers a large-scale investigation of adoptive families headed by older parents. We describe these families and explore how preadoptive kinship between the adoptive parent and the…

Adoptive immunotherapy for acute leukemia: New insights in chimeric antigen receptors

PubMed Central

Heiblig, Maël; Elhamri, Mohamed; Michallet, Mauricette; Thomas, Xavier

2015-01-01

Relapses remain a major concern in acute leukemia. It is well known that leukemia stem cells (LSCs) hide in hematopoietic niches and escape to the immune system surveillance through the outgrowth of poorly immunogenic tumor-cell variants and the suppression of the active immune response. Despite the introduction of new reagents and new therapeutic approaches, no treatment strategies have been able to definitively eradicate LSCs. However, recent adoptive immunotherapy in cancer is expected to revolutionize our way to fight against this disease, by redirecting the immune system in order to eliminate relapse issues. Initially described at the onset of the 90’s, chimeric antigen receptors (CARs) are recombinant receptors transferred in various T cell subsets, providing specific antigens binding in a non-major histocompatibility complex restricted manner, and effective on a large variety of human leukocyte antigen-divers cell populations. Once transferred, engineered T cells act like an expanding “living drug” specifically targeting the tumor-associated antigen, and ensure long-term anti-tumor memory. Over the last decades, substantial improvements have been made in CARs design. CAR T cells have finally reached the clinical practice and first clinical trials have shown promising results. In acute lymphoblastic leukemia, high rate of complete and prolonged clinical responses have been observed after anti-CD19 CAR T cell therapy, with specific but manageable adverse events. In this review, our goal was to describe CAR structures and functions, and to summarize recent data regarding pre-clinical studies and clinical trials in acute leukemia. PMID:26328018

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

Recent developments in software tools for high-throughput in vitro ADME support with high-resolution MS.

PubMed

Paiva, Anthony; Shou, Wilson Z

2016-08-01

The last several years have seen the rapid adoption of the high-resolution MS (HRMS) for bioanalytical support of high throughput in vitro ADME profiling. Many capable software tools have been developed and refined to process quantitative HRMS bioanalysis data for ADME samples with excellent performance. Additionally, new software applications specifically designed for quan/qual soft spot identification workflows using HRMS have greatly enhanced the quality and efficiency of the structure elucidation process for high throughput metabolite ID in early in vitro ADME profiling. Finally, novel approaches in data acquisition and compression, as well as tools for transferring, archiving and retrieving HRMS data, are being continuously refined to tackle the issue of large data file size typical for HRMS analyses.

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.

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.

31 CFR Appendix A to Part 357 - Discussion of Final Rule

Code of Federal Regulations, 2011 CFR

2011-07-01

... as used in TRADES have been adopted. Section-By-Section Analysis Section 357.21Registration. The... final rules have adopted some of the existing practices applicable to commercial ACH payments, but it is... entities that are a part of the Government direct deposit network. See the discussion under paragraph (b)(2...

31 CFR Appendix A to Part 357 - Discussion of Final Rule

Code of Federal Regulations, 2013 CFR

2013-07-01

... as used in TRADES have been adopted. Section-By-Section Analysis Section 357.21Registration. The... final rules have adopted some of the existing practices applicable to commercial ACH payments, but it is... entities that are a part of the Government direct deposit network. See the discussion under paragraph (b)(2...

31 CFR Appendix A to Part 357 - Discussion of Final Rule

Code of Federal Regulations, 2012 CFR

2012-07-01

... as used in TRADES have been adopted. Section-By-Section Analysis Section 357.21Registration. The... final rules have adopted some of the existing practices applicable to commercial ACH payments, but it is... entities that are a part of the Government direct deposit network. See the discussion under paragraph (b)(2...

31 CFR Appendix A to Part 357 - Discussion of Final Rule

Code of Federal Regulations, 2014 CFR

2014-07-01

... as used in TRADES have been adopted. Section-By-Section Analysis Section 357.21Registration. The... final rules have adopted some of the existing practices applicable to commercial ACH payments, but it is... entities that are a part of the Government direct deposit network. See the discussion under paragraph (b)(2...

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…

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...

75 FR 31834 - Adoption of Environmental Impact Statement; Availability of an Environmental Reevaluation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-04

... DEPARTMENT OF TRANSPORTATION Federal Railroad Administration Adoption of Environmental Impact Statement; Availability of an Environmental Reevaluation AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Adoption and Recirculation of Final Environmental Impact...

24 CFR 58.52 - Adoption of other agencies' EISs.

Code of Federal Regulations, 2011 CFR

2011-04-01

... entity adopts an EIS prepared by another agency, the procedure in 40 CFR 1506.3 shall be followed. An adopted EIS may have to be revised and modified to adapt it to the particular environmental conditions and... other agencies' EISs. The responsible entity may adopt a draft or final EIS prepared by another agency...

What Works Clearinghouse Quick Review: "Transfer Incentives for High-Performing Teachers: Final Results from a Multisite Experiment"

ERIC Educational Resources Information Center

What Works Clearinghouse, 2014

2014-01-01

"Transfer Incentives for High-Performing Teachers: Final Results from a Multisite Experiment," examined the impact of the Talent Transfer Initiative (TTI) on both student achievement and teacher retention in 10 school districts across seven states. The initiative gave bonuses to high-performing teachers for them to transfer to and stay…

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

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.

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.

15 CFR 1180.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TECHNICAL INFORMATION SERVICE, DEPARTMENT OF COMMERCE TRANSFER BY FEDERAL AGENCIES OF SCIENTIFIC, TECHNICAL.... (a) The purpose of this regulation is to facilitate public access to the vast amount of scientific... regulation provides a variety of methods for federal agencies to adopt to ensure the timely transfer to the...

15 CFR 1180.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

...) TECHNOLOGY ADMINISTRATION, DEPARTMENT OF COMMERCE TRANSFER BY FEDERAL AGENCIES OF SCIENTIFIC, TECHNICAL AND... purpose of this regulation is to facilitate public access to the vast amount of scientific, technical and... variety of methods for federal agencies to adopt to ensure the timely transfer to the National Technical...

15 CFR 1180.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) TECHNOLOGY ADMINISTRATION, DEPARTMENT OF COMMERCE TRANSFER BY FEDERAL AGENCIES OF SCIENTIFIC, TECHNICAL AND... purpose of this regulation is to facilitate public access to the vast amount of scientific, technical and... variety of methods for federal agencies to adopt to ensure the timely transfer to the National Technical...

15 CFR 1180.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

...) TECHNOLOGY ADMINISTRATION, DEPARTMENT OF COMMERCE TRANSFER BY FEDERAL AGENCIES OF SCIENTIFIC, TECHNICAL AND... purpose of this regulation is to facilitate public access to the vast amount of scientific, technical and... variety of methods for federal agencies to adopt to ensure the timely transfer to the National Technical...

15 CFR 1180.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

...) TECHNOLOGY ADMINISTRATION, DEPARTMENT OF COMMERCE TRANSFER BY FEDERAL AGENCIES OF SCIENTIFIC, TECHNICAL AND... purpose of this regulation is to facilitate public access to the vast amount of scientific, technical and... variety of methods for federal agencies to adopt to ensure the timely transfer to the National Technical...

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…

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.

Thermal-hydraulic performance of metal foam heat exchangers under dry operating conditions

DOE PAGES

Nawaz, Kashif; Bock, Jessica; Jacobi, Anthony M.

2017-03-14

High porosity metal foams with novel thermal, mechanical, electrical, and acoustic properties are being more widely adopted for application. Due to their large surface-area-to-volume ratio and complex structure which induces better fluid mixing, boundary layer restarting and wake destruction, they hold promise for heat transfer applications. In this study, the thermal-hydraulic performance of open-cell aluminum metal foam heat exchanger has been evaluated. The impact of flow conditions and metal foam geometry on the heat transfer coefficient and gradient have been investigated. Metal foam heat exchanger with same geometry (face area, flow depth and fin dimensions) consisting of four different typemore » of metal foams have been built for the study. Experiments are conducted in a closed-loop wind tunnel at different flow rate under dry operating condition. Metal foams with a smaller pore size (40 PPI) have a larger heat transfer coefficient compared to foams with a larger pore size (5 PPI). However, foams with larger pores result in relatively smaller pressure gradients. Current thermal-hydraulic modeling practices have been reviewed and potential issues have been identified. Permeability and inertia coefficients are determined and compared to data reported in open literature. Finally, on the basis of the new experimental results, correlations are developed relating the foam characteristics and flow conditions through the friction factor f and the Colburn j factor.« less

Thermal-hydraulic performance of metal foam heat exchangers under dry operating conditions

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

Nawaz, Kashif; Bock, Jessica; Jacobi, Anthony M.

High porosity metal foams with novel thermal, mechanical, electrical, and acoustic properties are being more widely adopted for application. Due to their large surface-area-to-volume ratio and complex structure which induces better fluid mixing, boundary layer restarting and wake destruction, they hold promise for heat transfer applications. In this study, the thermal-hydraulic performance of open-cell aluminum metal foam heat exchanger has been evaluated. The impact of flow conditions and metal foam geometry on the heat transfer coefficient and gradient have been investigated. Metal foam heat exchanger with same geometry (face area, flow depth and fin dimensions) consisting of four different typemore » of metal foams have been built for the study. Experiments are conducted in a closed-loop wind tunnel at different flow rate under dry operating condition. Metal foams with a smaller pore size (40 PPI) have a larger heat transfer coefficient compared to foams with a larger pore size (5 PPI). However, foams with larger pores result in relatively smaller pressure gradients. Current thermal-hydraulic modeling practices have been reviewed and potential issues have been identified. Permeability and inertia coefficients are determined and compared to data reported in open literature. Finally, on the basis of the new experimental results, correlations are developed relating the foam characteristics and flow conditions through the friction factor f and the Colburn j factor.« less

22 CFR 96.50 - Placement and post-placement monitoring until final adoption in incoming cases.

Code of Federal Regulations, 2012 CFR

2012-04-01

... assumes responsibility for making another placement of the child. (e) The agency or person acts promptly... child's country of origin about any new prospective adoptive parent(s). (1) In all cases where removal... the referral of the child for adoption; (2) Informs the prospective adoptive parent(s) that they will...

22 CFR 96.50 - Placement and post-placement monitoring until final adoption in incoming cases.

Code of Federal Regulations, 2013 CFR

2013-04-01

... assumes responsibility for making another placement of the child. (e) The agency or person acts promptly... child's country of origin about any new prospective adoptive parent(s). (1) In all cases where removal... the referral of the child for adoption; (2) Informs the prospective adoptive parent(s) that they will...

22 CFR 96.50 - Placement and post-placement monitoring until final adoption in incoming cases.

Code of Federal Regulations, 2010 CFR

2010-04-01

... assumes responsibility for making another placement of the child. (e) The agency or person acts promptly... child's country of origin about any new prospective adoptive parent(s). (1) In all cases where removal... the referral of the child for adoption; (2) Informs the prospective adoptive parent(s) that they will...

22 CFR 96.50 - Placement and post-placement monitoring until final adoption in incoming cases.

Code of Federal Regulations, 2011 CFR

2011-04-01

... assumes responsibility for making another placement of the child. (e) The agency or person acts promptly... child's country of origin about any new prospective adoptive parent(s). (1) In all cases where removal... the referral of the child for adoption; (2) Informs the prospective adoptive parent(s) that they will...

22 CFR 96.50 - Placement and post-placement monitoring until final adoption in incoming cases.

Code of Federal Regulations, 2014 CFR

2014-04-01

... assumes responsibility for making another placement of the child. (e) The agency or person acts promptly... child's country of origin about any new prospective adoptive parent(s). (1) In all cases where removal... the referral of the child for adoption; (2) Informs the prospective adoptive parent(s) that they will...

Pattern uniformity control in integrated structures

NASA Astrophysics Data System (ADS)

Kobayashi, Shinji; Okada, Soichiro; Shimura, Satoru; Nafus, Kathleen; Fonseca, Carlos; Biesemans, Serge; Enomoto, Masashi

2017-03-01

In our previous paper dealing with multi-patterning, we proposed a new indicator to quantify the quality of final wafer pattern transfer, called interactive pattern fidelity error (IPFE). It detects patterning failures resulting from any source of variation in creating integrated patterns. IPFE is a function of overlay and edge placement error (EPE) of all layers comprising the final pattern (i.e. lower and upper layers). In this paper, we extend the use cases with Via in additional to the bridge case (Block on Spacer). We propose an IPFE budget and CD budget using simple geometric and statistical models with analysis of a variance (ANOVA). In addition, we validate the model with experimental data. From the experimental results, improvements in overlay, local-CDU (LCDU) of contact hole (CH) or pillar patterns (especially, stochastic pattern noise (SPN)) and pitch walking are all critical to meet budget requirements. We also provide a special note about the importance of the line length used in analyzing LWR. We find that IPFE and CD budget requirements are consistent to the table of the ITRS's technical requirement. Therefore the IPFE concept can be adopted for a variety of integrated structures comprising digital logic circuits. Finally, we suggest how to use IPFE for yield management and optimization requirements for each process.

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.

[Final Resolutions Adopted by the Conference on Planning of Rural Areas in Europe, 7 October 1978].

ERIC Educational Resources Information Center

Council of Europe, Strasbourg (France).

Two final resolutions were adopted by the Council of Europe at the October 1978 European Conference of Ministers Responsible for Regional Planning. Resolution 1 focused on guidelines for the planning of rural areas in Europe. Strategies and policies called for: a more balanced development which makes the living conditions of different regions as…

Web Service Architecture Framework for Embedded Devices

ERIC Educational Resources Information Center

Yanzick, Paul David

2009-01-01

The use of Service Oriented Architectures, namely web services, has become a widely adopted method for transfer of data between systems across the Internet as well as the Enterprise. Adopting a similar approach to embedded devices is also starting to emerge as personal devices and sensor networks are becoming more common in the industry. This…

[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.

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...

Optimal transfers between unstable periodic orbits using invariant manifolds

NASA Astrophysics Data System (ADS)

Davis, Kathryn E.; Anderson, Rodney L.; Scheeres, Daniel J.; Born, George H.

2011-03-01

This paper presents a method to construct optimal transfers between unstable periodic orbits of differing energies using invariant manifolds. The transfers constructed in this method asymptotically depart the initial orbit on a trajectory contained within the unstable manifold of the initial orbit and later, asymptotically arrive at the final orbit on a trajectory contained within the stable manifold of the final orbit. Primer vector theory is applied to a transfer to determine the optimal maneuvers required to create the bridging trajectory that connects the unstable and stable manifold trajectories. Transfers are constructed between unstable periodic orbits in the Sun-Earth, Earth-Moon, and Jupiter-Europa three-body systems. Multiple solutions are found between the same initial and final orbits, where certain solutions retrace interior portions of the trajectory. All transfers created satisfy the conditions for optimality. The costs of transfers constructed using manifolds are compared to the costs of transfers constructed without the use of manifolds. In all cases, the total cost of the transfer is significantly lower when invariant manifolds are used in the transfer construction. In many cases, the transfers that employ invariant manifolds are three times more efficient, in terms of fuel expenditure, than the transfer that do not. The decrease in transfer cost is accompanied by an increase in transfer time of flight.

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.

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

78 FR 49365 - Electronic Fund Transfers (Regulation E); Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-14

... BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Part 1005 [Docket No. CFPB-2012-0050] RIN 3170-AA33 Electronic Fund Transfers (Regulation E); Correction AGENCY: Bureau of Consumer Financial Protection. ACTION... 2013 Final Rule, which along with three other final rules \\1\\ implements the Electronic Fund Transfer...

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.

IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal Injury.

PubMed

Stremska, Marta E; Jose, Sheethal; Sabapathy, Vikram; Huang, Liping; Bajwa, Amandeep; Kinsey, Gilbert R; Sharma, Poonam R; Mohammad, Saleh; Rosin, Diane L; Okusa, Mark D; Sharma, Rahul

2017-09-01

CD4 + Foxp3 + regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4 + T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro , splenic Tregs from IL233-treated mice suppressed CD4 + T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential. Copyright © 2017 by the American Society of Nephrology.

Adoption Now: A Joint Initiative of New York's Courts and Child Welfare System

ERIC Educational Resources Information Center

DeCataldo, Kathleen R.; Carroll, Karen

2007-01-01

In November 2002, Chief Judge Judith Kaye attended the National Adoption Day festivities in Albany County and New York County (Manhattan). Although pleased that 600 adoptions were being finalized statewide on this special day, she was concerned to learn more than 6,000 other children were free for adoption but had not yet found permanent families.…

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.

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.

a Contemporary Approach for Evaluation of the best Measurement Capability of a Force Calibration Machine

NASA Astrophysics Data System (ADS)

Kumar, Harish

The present paper discusses the procedure for evaluation of best measurement capability of a force calibration machine. The best measurement capability of force calibration machine is evaluated by a comparison through the precision force transfer standards to the force standard machines. The force transfer standards are calibrated by the force standard machine and then by the force calibration machine by adopting the similar procedure. The results are reported and discussed in the paper and suitable discussion has been made for force calibration machine of 200 kN capacity. Different force transfer standards of nominal capacity 20 kN, 50 kN and 200 kN are used. It is found that there are significant variations in the .uncertainty of force realization by the force calibration machine according to the proposed method in comparison to the earlier method adopted.

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.

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.…

Comparison of Two Educational Methods on Nurses' Adoption of Safe Patient Handling Techniques

ERIC Educational Resources Information Center

Folami, Florence

2010-01-01

Musculoskeletal injuries caused by patient lifting and transfers are a concern to health care workers. The Safe Patient Handling Act calls for all health care organizations to move to mechanical assistance from previous manual methods of transfers. This research analyzed two different educational programs that addressed safe patient handling for…

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.

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

Adoptive parenting.

PubMed

Grotevant, Harold D; Lo, Albert Yh

2017-06-01

Challenges in adoptive parenting continue to emerge as adoption policies and practices evolve. We review three areas of research in adoptive parenting that reflect contemporary shifts in adoption. First, we highlight recent findings concerning openness in adoption contact arrangements, or contact between a child's families of birth and rearing. Second, we examine research regarding racial and cultural socialization in transracial and international adoptions. Finally, we review investigations of parenting experiences of lesbian and gay adoptive parents. Overall, parenting processes (e.g., supportive vs. problematic family interaction) are better predictors of child adjustment than are group differences (e.g., open vs. closed adoptions; adoption by heterosexual vs. same-sex parents). The distinctive needs of adopted children call for preparation of adoption-competent mental health, casework, education, and health care professionals. Copyright © 2017 Elsevier Ltd. 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.

Bridging the gap between the science and service of HIV prevention: transferring effective research-based HIV prevention interventions to community AIDS service providers.

PubMed Central

Kelly, J A; Somlai, A M; DiFranceisco, W J; Otto-Salaj, L L; McAuliffe, T L; Hackl, K L; Heckman, T G; Holtgrave, D R; Rompa, D

2000-01-01

OBJECTIVES: AIDS service organizations (ASOs) rarely have access to the information needed to implement research-based HIV prevention interventions for their clients. We compared the effectiveness of 3 dissemination strategies for transferring HIV prevention models from the research arena to community providers of HIV prevention services. METHODS: Interviews were conducted with the directors of 74 ASOs to assess current HIV prevention services. ASOs were randomized to programs that provided (1) technical assistance manuals describing how to implement research-based HIV prevention interventions, (2) manuals plus a staff training workshop on how to conduct the implementation, or (3) manuals, the training workshop, and follow-up telephone consultation calls. Follow-up interviews determined whether the intervention model had been adopted. RESULTS: The dissemination package that provided ASOs with implementation manuals, staff training workshops, and follow-up consultation resulted in more frequent adoption and use of the research-based HIV prevention intervention for gay men, women, and other client populations. CONCLUSIONS: Strategies are needed to quickly transfer research-based HIV prevention methods to community providers of HIV prevention services. Active collaboration between researchers and service agencies results in more successful program adoption than distribution of implementation packages alone. PMID:10897186

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

National Diffusion/Adoption Network: A First Year Formative Look. Final Report.

ERIC Educational Resources Information Center

Magi Educational Services, Inc., Port Chester, NY.

A basic function of the Diffusion/Adoption Network is to assist interested school districts in becoming aware of successfully demonstrated, innovative educational ideas, products, and programs; and in aquiring, through training, the competencies necessary to adopt or adapt a proven educational program. There are five basic components of the…

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…

Securing Real-Time Sessions in an IMS-Based Architecture

NASA Astrophysics Data System (ADS)

Cennamo, Paolo; Fresa, Antonio; Longo, Maurizio; Postiglione, Fabio; Robustelli, Anton Luca; Toro, Francesco

The emerging all-IP mobile network infrastructures based on 3rd Generation IP Multimedia Subsystem philosophy are characterised by radio access technology independence and ubiquitous connectivity for mobile users. Currently, great focus is being devoted to security issues since most of the security threats presently affecting the public Internet domain, and the upcoming ones as well, are going to be suffered by mobile users in the years to come. While a great deal of research activity, together with standardisation efforts and experimentations, is carried out on mechanisms for signalling protection, very few integrated frameworks for real-time multimedia data protection have been proposed in a context of IP Multimedia Subsystem, and even fewer experimental results based on testbeds are available. In this paper, after a general overview of the security issues arising in an advanced IP Multimedia Subsystem scenario, a comprehensive infrastructure for real-time multimedia data protection, based on the adoption of the Secure Real-Time Protocol, is proposed; then, the development of a testbed incorporating such functionalities, including mechanisms for key management and cryptographic context transfer, and allowing the setup of Secure Real-Time Protocol sessions is presented; finally, experimental results are provided together with quantitative assessments and comparisons of system performances for audio sessions with and without the adoption of the Secure Real-Time Protocol framework.

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.

A new BP Fourier algorithm and its application in English teaching evaluation

NASA Astrophysics Data System (ADS)

Pei, Xuehui; Pei, Guixin

2017-08-01

BP neural network algorithm has wide adaptability and accuracy when used in complicated system evaluation, but its calculation defects such as slow convergence have limited its practical application. The paper tries to speed up the calculation convergence of BP neural network algorithm with Fourier basis functions and presents a new BP Fourier algorithm for complicated system evaluation. First, shortages and working principle of BP algorithm are analyzed for subsequent targeted improvement; Second, the presented BP Fourier algorithm adopts Fourier basis functions to simplify calculation structure, designs new calculation transfer function between input and output layers, and conducts theoretical analysis to prove the efficiency of the presented algorithm; Finally, the presented algorithm is used in evaluating university English teaching and the application results shows that the presented BP Fourier algorithm has better performance in calculation efficiency and evaluation accuracy and can be used in evaluating complicated system practically.

Structure of the CLC-1 chloride channel from Homo sapiens.

PubMed

Park, Eunyong; MacKinnon, Roderick

2018-05-29

CLC channels mediate passive Cl - conduction, while CLC transporters mediate active Cl - transport coupled to H + transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its 'glutamate gate' residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl - conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl - at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl - affinity distinguish CLC channels and transporters. © 2018, Park & MacKinnon.

A call for a new approach towards midwifery practice.

PubMed

1993-01-01

According to the President of the Ghana Registered Midwives Association, a bold new approach is needed if the goal of Safe Birth for All by the Year 2000 is to be achieved. Lovia Owusu-Asiedu urged midwives to adopt a community-based, prevention-oriented approach to their work. Of utmost importance is health education aimed at modifying traditional norms (e.g., mistrust of contraception) that mitigate against women's health. As educators, midwives must transfer to the general population their knowledge about pregnancy, the causes of maternal and infant mortality, breastfeeding, and family planning. This can be accomplished, in part, through workshops on health and development. Midwives and the traditional birth attendants under their supervision need to increase their collaboration with other health professionals. Finally, Mrs. Owusu-Asiedu urged midwives to broaden their role definition to include the struggle against the high rate of female illiteracy, the subservient role of women, and early age at marriage and first birth.

A polyhedron made of tRNAs.

PubMed

Severcan, Isil; Geary, Cody; Chworos, Arkadiusz; Voss, Neil; Jacovetty, Erica; Jaeger, Luc

2010-09-01

Supramolecular assembly is a powerful strategy used by nature to build nanoscale architectures with predefined sizes and shapes. With synthetic systems, however, numerous challenges remain to be solved before precise control over the synthesis, folding and assembly of rationally designed three-dimensional nano-objects made of RNA can be achieved. Here, using the transfer RNA molecule as a structural building block, we report the design, efficient synthesis and structural characterization of stable, modular three-dimensional particles adopting the polyhedral geometry of a non-uniform square antiprism. The spatial control within the final architecture allows the precise positioning and encapsulation of proteins. This work demonstrates that a remarkable degree of structural control can be achieved with RNA structural motifs for the construction of thermostable three-dimensional nano-architectures that do not rely on helix bundles or tensegrity. RNA three-dimensional particles could potentially be used as carriers or scaffolds in nanomedicine and synthetic biology.

A polyhedron made of tRNAs

PubMed Central

Severcan, Isil; Geary, Cody; Chworos, Arkadiusz; Voss, Neil; Jacovetty, Erica; Jaeger, Luc

2010-01-01

Supra-molecular assembly is a powerful strategy used by nature for building nano-scale architectures with predefined sizes and shapes. Numerous challenges remain however to be solved in order to demonstrate precise control over the synthesis, folding and assembly of rationally designed three-dimensional (3D) nano-objects made of RNA. Using the transfer RNA molecule as a structural building block, we report the design, efficient synthesis and structural characterization of stable, modular 3D particles adopting the polyhedral geometry of a non-uniform square antiprism. The spatial control within the final architecture allows precise positioning and encapsulation of proteins. This work demonstrates that a remarkable degree of structural control can be achieved with RNA structural motifs to build thermostable 3D nano-architectures that do not rely on helix bundles or tensegrity. RNA 3D particles can potentially be used as carriers or scaffolds in nano-medicine and synthetic biology. PMID:20729899

Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

PubMed

Norelli, M; Casucci, M; Bonini, C; Bondanza, A

2016-01-01

Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors. Copyright © 2015. Published by Elsevier B.V.

Electrical-thermal-structural finite element simulation and experimental study of a plasma ion source for the production of radioactive ion beams

NASA Astrophysics Data System (ADS)

Manzolaro, M.; Meneghetti, G.; Andrighetto, A.; Vivian, G.

2016-03-01

The production target and the ion source constitute the core of the selective production of exotic species (SPES) facility. In this complex experimental apparatus for the production of radioactive ion beams, a 40 MeV, 200 μA proton beam directly impinges a uranium carbide target, generating approximately 1013 fissions per second. The transfer line enables the unstable isotopes generated by the 238U fissions in the target to reach the ion source, where they can be ionized and finally accelerated to the subsequent areas of the facility. In this work, the plasma ion source currently adopted for the SPES facility is analyzed in detail by means of electrical, thermal, and structural numerical models. Next, theoretical results are compared with the electric potential difference, temperature, and displacement measurements. Experimental tests with stable ion beams are also presented and discussed.

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.

Dynamics of social contagions with local trend imitation.

PubMed

Zhu, Xuzhen; Wang, Wei; Cai, Shimin; Stanley, H Eugene

2018-05-09

Research on social contagion dynamics has not yet included a theoretical analysis of the ubiquitous local trend imitation (LTI) characteristic. We propose a social contagion model with a tent-like adoption probability to investigate the effect of this LTI characteristic on behavior spreading. We also propose a generalized edge-based compartmental theory to describe the proposed model. Through extensive numerical simulations and theoretical analyses, we find a crossover in the phase transition: when the LTI capacity is strong, the growth of the final adoption size exhibits a second-order phase transition. When the LTI capacity is weak, we see a first-order phase transition. For a given behavioral information transmission probability, there is an optimal LTI capacity that maximizes the final adoption size. Finally we find that the above phenomena are not qualitatively affected by the heterogeneous degree distribution. Our suggested theoretical predictions agree with the simulation results.

Health information technology: initial set of standards, implementation specifications, and certification criteria for electronic health record technology. Interim final rule.

PubMed

2010-01-13

The Department of Health and Human Services (HHS) is issuing this interim final rule with a request for comments to adopt an initial set of standards, implementation specifications, and certification criteria, as required by section 3004(b)(1) of the Public Health Service Act. This interim final rule represents the first step in an incremental approach to adopting standards, implementation specifications, and certification criteria to enhance the interoperability, functionality, utility, and security of health information technology and to support its meaningful use. The certification criteria adopted in this initial set establish the capabilities and related standards that certified electronic health record (EHR) technology will need to include in order to, at a minimum, support the achievement of the proposed meaningful use Stage 1 (beginning in 2011) by eligible professionals and eligible hospitals under the Medicare and Medicaid EHR Incentive Programs.

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...

WWC Review of the Report "Transfer Incentives for High-Performing Teachers: Final Results from a Multisite Randomized Experiment." What Works Clearinghouse Single Study Review

ERIC Educational Resources Information Center

What Works Clearinghouse, 2015

2015-01-01

For the 2013 study, "Transfer Incentives for High-Performing Teachers: Final Results from a Multisite Randomized Experiment," researchers examined the impact of the Talent Transfer Initiative (TTI) on students' reading and mathematics achievement in 10 school districts. The TTI enabled principals of low-performing schools to provide…

Electron Capture Supernovae from Close Binary Systems

NASA Astrophysics Data System (ADS)

Poelarends, Arend J. T.; Wurtz, Scott; Tarka, James; Cole Adams, L.; Hills, Spencer T.

2017-12-01

We present the first detailed study of the Electron Capture Supernova Channel (ECSN Channel) for a primary star in a close binary star system. Progenitors of ECSN occupy the lower end of the mass spectrum of supernova progenitors and are thought to form the transition between white dwarf progenitors and core-collapse progenitors. The mass range for ECSN from close binary systems is thought to be wider than the range for single stars, because of the effects of mass transfer on the helium core. Using the MESA stellar evolution code, we explored the parameter space of initial primary masses between 8 and 17 {M}⊙ , using a large grid of models. We find that the initial primary mass and the mass transfer evolution are important factors in the final fate of stars in this mass range. Mass transfer due to Roche lobe overflow during and after carbon burning causes the core to cool down so that it avoids neon ignition, even in helium-free cores with masses up to 1.52 {M}⊙ , which in single stars would ignite neon. If the core is able to contract to high enough densities for electron captures to commence, we find that, for the adopted Ledoux convection criterion, the initial mass range for the primary to evolve into an ECSN is between 13.5 and 17.6 {M}⊙ . The mass ratio, initial period, and mass-loss efficiency only marginally affect the predicted ranges.

Three-Dimensional Mathematical Model of Oxygen Transport Behavior in Electroslag Remelting Process

NASA Astrophysics Data System (ADS)

Huang, Xuechi; Li, Baokuan; Liu, Zhongqiu

2018-04-01

A transient three-dimensional model has been proposed to investigate the oxygen transport behavior in electroslag remelting process. The electromagnetism, heat transfer, multiphase flow, and species transport were calculated simultaneously by finite volume method. The volume of fluid approach was adopted to trace the metal-slag-air three-phase flow. Based on the necessary thermodynamics of oxygen transport behavior, a kinetic model was established to predict the mass source terms in species transport equation. The kinetic correction factor was proposed to account for the effect of the oxide scale formed on the electrode on the FeO content in slag. Finally, the effect of applied current on the oxygen transfer was studied. The predicted result agrees well with the measured data when the kinetic correction factor is set to be 0.5. The temperature distribution that affects the thermodynamics differs at the interfaces. The oxygen in air is absorbed into slag due to the oxidation at the slag/air interface. The Fe2O3 in slag and the oxide scale contribute to the increase of FeO content in slag, and the latter one plays the leading role. The oxygen transfer from slag to metal mainly occurs during the formation of the droplet at the slag/metal droplet interface. With the current increasing from 1200 to 1800 A, the oxygen content increases from 76.4 to 89.8 ppm, and then slightly declines to 89.2 ppm when the current increases to 2100 A.

76 FR 40457 - Administrative Simplification: Adoption of Operating Rules for Eligibility for a Health Plan and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

... Plan and Health Care Claim Status Transactions; Interim Final Rule #0;#0;Federal Register / Vol. 76, No... Simplification: Adoption of Operating Rules for Eligibility for a Health Plan and Health Care Claim Status... rules for the health care industry and directed the Secretary of Health and Human Services to ``adopt a...

78 FR 65747 - Environmental Impact Statement: Adoption: St. Tammany Parish, LA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

...: Adoption: St. Tammany Parish, LA AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of... District for LA 3241, I-12 to Bush Highway in St. Tammany Parish, Louisiana. The FEIS will be supplemented...), intends to adopt an approved Final EIS for the I-12 to Bush Highway in St. Tammany Parish, Louisiana. The...

7 CFR 1794.72 - Adoption of an EIS.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Adoption of an EIS. 1794.72 Section 1794.72... Adoption of an EIS. (a) Where RUS determines that an existing Federal EIS requires additional information... portion of the EIS as a part of its draft EIS. The circulation and notice provisions for a draft and final...

States Adopt Standards at Fast Clip

ERIC Educational Resources Information Center

Gewertz, Catherine

2010-01-01

Nearly half the states have adopted a new set of common academic standards, barely a month after their final release and, in most cases, with little opposition. As of July 9, 23 states had decided to replace their mathematics and English/language arts standards with the common set. Another flurry of adoptions is expected by Aug. 2, since the $4…

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

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

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.

Surface PEGylation of mesoporous silica materials via surface-initiated chain transfer free radical polymerization: Characterization and controlled drug release.

PubMed

Huang, Long; Liu, Meiying; Mao, Liucheng; Huang, Qiang; Huang, Hongye; Wan, Qing; Tian, Jianwen; Wen, Yuanqing; Zhang, Xiaoyong; Wei, Yen

2017-12-01

As a new type of mesoporous silica materials with large pore diameter (pore size between 2 and 50nm) and high specific surface areas, SBA-15 has been widely explored for different applications especially in the biomedical fields. The surface modification of SBA-15 with functional polymers has demonstrated to be an effective way for improving its properties and performance. In this work, we reported the preparation of PEGylated SBA-15 polymer composites through surface-initiated chain transfer free radical polymerization for the first time. The thiol group was first introduced on SBA-15 via co-condensation with γ-mercaptopropyltrimethoxysilane (MPTS), that were utilized to initiate the chain transfer free radical polymerization using poly(ethylene glycol) methyl ether methacrylate (PEGMA) and itaconic acid (IA) as the monomers. The successful modification of SBA-15 with poly(PEGMA-co-IA) copolymers was evidenced by a series of characterization techniques, including 1 H NMR, FT-IR, TGA and XPS. The final SBA-15-SH- poly(PEGMA-co-IA) composites display well water dispersity and high loading capability towards cisplatin (CDDP) owing to the introduction of hydrophilic PEGMA and carboxyl groups. Furthermore, the CDDP could be released from SBA-15-SH-poly(PEGMA-co-IA)-CDDP complexes in a pH dependent behavior, suggesting the potential controlled drug delivery of SBA-15-SH-poly(PEGMA-co-IA). More importantly, the strategy should be also useful for fabrication of many other functional materials for biomedical applications owing to the advantages of SBA-15 and well monomer adoptability of chain transfer free radical polymerization. Copyright © 2017 Elsevier B.V. All rights reserved.

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 (CO 2) capture. In this study, to generate data for WWC model validation, CO 2 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 CO 2 in MEA. In addition,more » the overall mass transfer coefficient predicted 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 CO 2 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 (N 2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO 2 reaction rate constants after using the N 2O/CO 2 analogy method. Finally, the calibrated model can be used to predict the CO 2 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 (CO 2) capture. In this study, to generate data for WWC model validation, CO 2 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 CO 2 in MEA. In addition,more » the overall mass transfer coefficient predicted 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 CO 2 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 (N 2O)/MEA system obtained from Part 1 of this study, serves as priors for the calibration of CO 2 reaction rate constants after using the N 2O/CO 2 analogy method. Finally, the calibrated model can be used to predict the CO 2 mass transfer in a WWC for a wider range of operating conditions.« less

Nonlocal Quantum Information Transfer Without Superluminal Signalling and Communication

NASA Astrophysics Data System (ADS)

Walleczek, Jan; Grössing, Gerhard

2016-09-01

It is a frequent assumption that—via superluminal information transfers—superluminal signals capable of enabling communication are necessarily exchanged in any quantum theory that posits hidden superluminal influences. However, does the presence of hidden superluminal influences automatically imply superluminal signalling and communication? The non-signalling theorem mediates the apparent conflict between quantum mechanics and the theory of special relativity. However, as a `no-go' theorem there exist two opposing interpretations of the non-signalling constraint: foundational and operational. Concerning Bell's theorem, we argue that Bell employed both interpretations, and that he finally adopted the operational position which is associated often with ontological quantum theory, e.g., de Broglie-Bohm theory. This position we refer to as "effective non-signalling". By contrast, associated with orthodox quantum mechanics is the foundational position referred to here as "axiomatic non-signalling". In search of a decisive communication-theoretic criterion for differentiating between "axiomatic" and "effective" non-signalling, we employ the operational framework offered by Shannon's mathematical theory of communication, whereby we distinguish between Shannon signals and non-Shannon signals. We find that an effective non-signalling theorem represents two sub-theorems: (1) Non-transfer-control (NTC) theorem, and (2) Non-signification-control (NSC) theorem. Employing NTC and NSC theorems, we report that effective, instead of axiomatic, non-signalling is entirely sufficient for prohibiting nonlocal communication. Effective non-signalling prevents the instantaneous, i.e., superluminal, transfer of message-encoded information through the controlled use—by a sender-receiver pair —of informationally-correlated detection events, e.g., in EPR-type experiments. An effective non-signalling theorem allows for nonlocal quantum information transfer yet—at the same time—effectively denies superluminal signalling and communication.

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.

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.

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

Growth status of Korean orphans raised in the affluent West: anthropometric trend, multivariate determinants, and descriptive comparison with their North and South Korean peers.

PubMed

Schwekendiek, Daniel J

2017-04-01

This paper investigates the trend in height among adult Korean orphans who were adopted in early life into affluent Western nations. Final heights of 148 females were analyzed based on a Korean government survey conducted in 2008. Height of the orphans was descriptively compared against final heights of South and North Koreans. Furthermore, statistical determinants of orphan height were investigated in multivariate regressions. Mean height of Korean orphans was 160.44 cm (SD 5.89), which was higher than that of South Koreans at 158.83 cm (SD 5.01). Both Korean orphans and South Koreans were taller than North Koreans at 155.30 cm (SD 4.94). However, height of Korean orphans stagnated at around 160-161 cm while those of North and South Koreans improved over time. In the regression analysis, the socioeconomic status of the adoptive family was statistically significant in all models, while dummies for the adoptive nations and age at adoption were insignificant. This study shows that the mean final height of women experiencing extreme environmental improvements in early-life is capped at 160-161 cm, tentatively suggesting that social stress factors in the host nation or early-life factors in the birth nation might have offset some of the environmental enrichment effects achieved through intercountry adoption.

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

22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-Convention case, the reporting provider is the one that has child placement responsibility, as evidenced by... (generally the time the child is matched with adoptive parents); (2) Date of U.S. final adoption or date on... involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF...

22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States.

Code of Federal Regulations, 2014 CFR

2014-04-01

...-Convention case, the reporting provider is the one that has child placement responsibility, as evidenced by... (generally the time the child is matched with adoptive parents); (2) Date of U.S. final adoption or date on... involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF...

22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States.

Code of Federal Regulations, 2013 CFR

2013-04-01

...-Convention case, the reporting provider is the one that has child placement responsibility, as evidenced by... (generally the time the child is matched with adoptive parents); (2) Date of U.S. final adoption or date on... involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF...

22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-Convention case, the reporting provider is the one that has child placement responsibility, as evidenced by... (generally the time the child is matched with adoptive parents); (2) Date of U.S. final adoption or date on... involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF...

22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States.

Code of Federal Regulations, 2012 CFR

2012-04-01

...-Convention case, the reporting provider is the one that has child placement responsibility, as evidenced by... (generally the time the child is matched with adoptive parents); (2) Date of U.S. final adoption or date on... involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF...

Dynamics of social contagions with memory of nonredundant information

NASA Astrophysics Data System (ADS)

Wang, Wei; Tang, Ming; Zhang, Hai-Feng; Lai, Ying-Cheng

2015-07-01

A key ingredient in social contagion dynamics is reinforcement, as adopting a certain social behavior requires verification of its credibility and legitimacy. Memory of nonredundant information plays an important role in reinforcement, which so far has eluded theoretical analysis. We first propose a general social contagion model with reinforcement derived from nonredundant information memory. Then, we develop a unified edge-based compartmental theory to analyze this model, and a remarkable agreement with numerics is obtained on some specific models. We use a spreading threshold model as a specific example to understand the memory effect, in which each individual adopts a social behavior only when the cumulative pieces of information that the individual received from his or her neighbors exceeds an adoption threshold. Through analysis and numerical simulations, we find that the memory characteristic markedly affects the dynamics as quantified by the final adoption size. Strikingly, we uncover a transition phenomenon in which the dependence of the final adoption size on some key parameters, such as the transmission probability, can change from being discontinuous to being continuous. The transition can be triggered by proper parameters and structural perturbations to the system, such as decreasing individuals' adoption threshold, increasing initial seed size, or enhancing the network heterogeneity.

Technology Transfer Program (TTP). Quality Assurance System. Volume 2. Appendices

DTIC Science & Technology

1980-03-03

LSCo Report No. - 2X23-5.1-4-I TECHNOLOGY TRANSFER PROGRAM (TTP) FINAL REPORT QUALITY ASSURANCE SYSTEM Appendix A Accuracy Control System QUALITY...4-1 TECHNOLOGY TRANSFER PROGRAM (TTP) FINAL REPORT QUALITY ASSURANCE SYSTEM Appendix A Accuracy Control System QUALITY ASSURANCE VOLUME 2 APPENDICES...prepared by: Livingston Shipbuilding Company Orange, Texas March 3, 1980 APPENDIX A ACCURACY CONTROL SYSTEM . IIII MARINE TECHNOLOGY. INC. HP-121

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection.

PubMed

Booty, Matthew G; Barreira-Silva, Palmira; Carpenter, Stephen M; Nunes-Alves, Cláudio; Jacques, Miye K; Stowell, Britni L; Jayaraman, Pushpa; Beamer, Gillian; Behar, Samuel M

2016-11-07

IL-21 is produced predominantly by activated CD4 + T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γ c ) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8 + T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4 + and CD8 + T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R -/- mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R -/- T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

PubMed Central

Booty, Matthew G.; Barreira-Silva, Palmira; Carpenter, Stephen M.; Nunes-Alves, Cláudio; Jacques, Miye K.; Stowell, Britni L.; Jayaraman, Pushpa; Beamer, Gillian; Behar, Samuel M.

2016-01-01

IL-21 is produced predominantly by activated CD4+ T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (γc) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8+ T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4+ and CD8+ T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R−/− mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R−/− T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis. PMID:27819295

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.

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.

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

78 FR 33436 - 2013 Final Fee Rate and Fingerprint Fees

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission 2013 Final Fee Rate and Fingerprint... given, pursuant to 25 CFR 514.2, that the National Indian Gaming Commission has adopted its 2013 final... a certificate of self-regulation under 25 CFR part 518, the 2013 final fee rate on Class II revenues...

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.

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

Office of Inspector General; Medicare and state health care programs: fraud and abuse; issuance of advisory opinions by the OIG. Final rule.

PubMed

2008-07-17

OIG is adopting in final form, without change, an interim final rule published on March 26, 2008 (73 FR 15937). We received no comments to the interim final rule. The interim final rule revised the process for advisory opinion requestors to submit payments for advisory opinion costs.

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.

Transferring elements of a density matrix

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

Allahverdyan, Armen E.; Hovhannisyan, Karen V.; Yerevan State University, A. Manoogian Street 1, Yerevan

2010-01-15

We study restrictions imposed by quantum mechanics on the process of matrix-element transfer. This problem is at the core of quantum measurements and state transfer. Given two systems A and B with initial density matrices lambda and r, respectively, we consider interactions that lead to transferring certain matrix elements of unknown lambda into those of the final state r-tilde of B. We find that this process eliminates the memory on the transferred (or certain other) matrix elements from the final state of A. If one diagonal matrix element is transferred, r(tilde sign){sub aa}=lambda{sub aa}, the memory on each nondiagonal elementmore » lambda{sub an}ot ={sub b} is completely eliminated from the final density operator of A. Consider the following three quantities, Relambda{sub an}ot ={sub b}, Imlambda{sub an}ot ={sub b}, and lambda{sub aa}-lambda{sub bb} (the real and imaginary part of a nondiagonal element and the corresponding difference between diagonal elements). Transferring one of them, e.g., Rer(tilde sign){sub an}ot ={sub b}=Relambda{sub an}ot ={sub b}, erases the memory on two others from the final state of A. Generalization of these setups to a finite-accuracy transfer brings in a trade-off between the accuracy and the amount of preserved memory. This trade-off is expressed via system-independent uncertainty relations that account for local aspects of the accuracy-disturbance trade-off in quantum measurements. Thus, the general aspect of state disturbance in quantum measurements is elimination of memory on non-diagonal elements, rather than diagonalization.« less

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

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.

Impulsive time-free transfers between halo orbits

NASA Astrophysics Data System (ADS)

Hiday, L. A.; Howell, K. C.

1992-08-01

A methodology is developed to design optimal time-free impulsive transfers between three-dimensional halo orbits in the vicinity of the interior L1 libration point of the sun-earth/moon barycenter system. The transfer trajectories are optimal in the sense that the total characteristics velocity required to implement the transfer exhibits a local minimum. Criteria are established whereby the implementation of a coast in the initial orbit, a coast in the final orbit, or dual coasts accomplishes a reduction in fuel expenditure. The optimality of a reference two-impulse transfer can be determined by examining the slope at the endpoints of a plot of the magnitude of the primer vector on the reference trajectory. If the initial and final slopes of the primer magnitude are zero, the transfer trajectory is optimal; otherwise, the execution of coasts is warranted. The optimal time of flight on the time-free transfer, and consequently, the departure and arrival locations on the halo orbits are determined by the unconstrained minimization of a function of two variables using a multivariable search technique. Results indicate that the cost can be substantially diminished by the allowance for coasts in the initial and final libration-point orbits.

Impulsive Time-Free Transfers Between Halo Orbits

NASA Astrophysics Data System (ADS)

Hiday-Johnston, L. A.; Howell, K. C.

1996-12-01

A methodology is developed to design optimal time-free impulsive transfers between three-dimensional halo orbits in the vicinity of the interior L 1 libration point of the Sun-Earth/Moon barycenter system. The transfer trajectories are optimal in the sense that the total characteristic velocity required to implement the transfer exhibits a local minimum. Criteria are established whereby the implementation of a coast in the initial orbit, a coast in the final orbit, or dual coasts accomplishes a reduction in fuel expenditure. The optimality of a reference two-impulse transfer can be determined by examining the slope at the endpoints of a plot of the magnitude of the primer vector on the reference trajectory. If the initial and final slopes of the primer magnitude are zero, the transfer trajectory is optimal; otherwise, the execution of coasts is warranted. The optimal time of flight on the time-free transfer, and consequently, the departure and arrival locations on the halo orbits are determined by the unconstrained minimization of a function of two variables using a multivariable search technique. Results indicate that the cost can be substantially diminished by the allowance for coasts in the initial and final libration-point orbits.

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…

49 CFR 389.39 - Direct final rulemaking procedures

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Direct final rulemaking procedures 389.39 Section 389.39 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... PROCEDURES-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.39 Direct final...

49 CFR 389.39 - Direct final rulemaking procedures

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Direct final rulemaking procedures 389.39 Section 389.39 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER... PROCEDURES-FEDERAL MOTOR CARRIER SAFETY REGULATIONS Procedures for Adoption of Rules § 389.39 Direct final...

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.

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

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.

Medicare and Medicaid Programs; Fire Safety Requirements for Certain Health Care Facilities. Final rule.

PubMed

2016-05-04

This final rule will amend the fire safety standards for Medicare and Medicaid participating hospitals, critical access hospitals (CAHs), long-term care facilities, intermediate care facilities for individuals with intellectual disabilities (ICF-IID), ambulatory surgery centers (ASCs), hospices which provide inpatient services, religious non-medical health care institutions (RNHCIs), and programs of all-inclusive care for the elderly (PACE) facilities. Further, this final rule will adopt the 2012 edition of the Life Safety Code (LSC) and eliminate references in our regulations to all earlier editions of the Life Safety Code. It will also adopt the 2012 edition of the Health Care Facilities Code, with some exceptions.

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

Multiple burn fuel-optimal orbit transfers: Numerical trajectory computation and neighboring optimal feedback guidance

NASA Technical Reports Server (NTRS)

Chuang, C.-H.; Goodson, Troy D.; Ledsinger, Laura A.

1995-01-01

This report describes current work in the numerical computation of multiple burn, fuel-optimal orbit transfers and presents an analysis of the second variation for extremal multiple burn orbital transfers as well as a discussion of a guidance scheme which may be implemented for such transfers. The discussion of numerical computation focuses on the use of multivariate interpolation to aid the computation in the numerical optimization. The second variation analysis includes the development of the conditions for the examination of both fixed and free final time transfers. Evaluations for fixed final time are presented for extremal one, two, and three burn solutions of the first variation. The free final time problem is considered for an extremal two burn solution. In addition, corresponding changes of the second variation formulation over thrust arcs and coast arcs are included. The guidance scheme discussed is an implicit scheme which implements a neighboring optimal feedback guidance strategy to calculate both thrust direction and thrust on-off times.

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.

Medicare Program; FY 2017 Hospice Wage Index and Payment Rate Update and Hospice Quality Reporting Requirements. Final rule.

PubMed

2016-08-05

This final rule will update the hospice wage index, payment rates, and cap amount for fiscal year (FY) 2017. In addition, this rule changes the hospice quality reporting program, including adopting new quality measures. Finally, this final rule includes information regarding the Medicare Care Choices Model (MCCM).

46 CFR 112.20-15 - Transfer of emergency loads.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Systems Having a Temporary and a Final Emergency Power Source § 112.20-15 Transfer of emergency loads. (a) When the potential of the final emergency power source reaches 85 to 95...

46 CFR 112.20-15 - Transfer of emergency loads.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Systems Having a Temporary and a Final Emergency Power Source § 112.20-15 Transfer of emergency loads. (a) When the potential of the final emergency power source reaches 85 to 95...

46 CFR 112.20-15 - Transfer of emergency loads.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Systems Having a Temporary and a Final Emergency Power Source § 112.20-15 Transfer of emergency loads. (a) When the potential of the final emergency power source reaches 85 to 95...

46 CFR 112.20-15 - Transfer of emergency loads.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Systems Having a Temporary and a Final Emergency Power Source § 112.20-15 Transfer of emergency loads. (a) When the potential of the final emergency power source reaches 85 to 95...

46 CFR 112.20-15 - Transfer of emergency loads.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING EMERGENCY LIGHTING AND POWER SYSTEMS Emergency Systems Having a Temporary and a Final Emergency Power Source § 112.20-15 Transfer of emergency loads. (a) When the potential of the final emergency power source reaches 85 to 95...

Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice

PubMed Central

Hu, Zheng; Xia, Jinxing; Fan, Wei; Wargo, Jennifer; Yang, Yong-Guang

2016-01-01

A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy. PMID:26824989

Oxygen transport enhancement by functionalized magnetic nanoparticles (FMP) in bioprocesses

NASA Astrophysics Data System (ADS)

Ataide, Filipe Andre Prata

The enhancement of fluid properties, namely thermal conductivity and mass diffusivity for a wide range of applications, through the use of nanosized particles' suspensions has been gathering increasing interest in the scientific community. In previous studies, Olle et al. (2006) showed an enhancement in oxygen absorption to aqueous solutions of up to 6-fold through the use of functionalized nanosized magnetic particles with oleic acid coating. Krishnamurthy et al. (2006) showed a remarkable 26-fold enhancement in dye diffusion in water. These two publications are landmarks in mass transfer enhancement in chemical systems through the use of nanoparticles. The central goal of this Ph.D. thesis was to develop functionalized magnetic nanoparticles to enhance oxygen transport in bioprocesses. The experimental protocol for magnetic nanoparticles synthesis and purification adopted in this thesis is a modification of that reported by Olle et al. (2006). This is facilitated by employing twice the quantity of ammonia, added at a slower rate, and by filtering the final nanoparticle solution in a cross-flow filtration modulus against 55 volumes of distilled water. This modification in the protocol resulted in improved magnetic nanoparticles with measurably higher mass transfer enhancement. Magnetic nanoparticles with oleic acid and Hitenol-BC coating were screened for oxygen transfer enhancement, since these particles are relatively inexpensive and easy to synthesize. A glass 0.5-liter reactor was custom manufactured specifically for oxygen transport studies in magnetic nanoparticles suspensions. The reactor geometry, baffles and Rushton impeller are of standard dimensions. Mass transfer tests were conducted through the use of the sulphite oxidation method, applying iodometric back-titration. A 3-factor central composite circumscribed design (CCD) was adopted for design of experiments in order to generate sufficiently informative data to model the effect of magnetic nanoparticles on interfacial area and mass transfer coefficient. The parameters ranges used were: 250-750 rpm for stirring speed, 0-2 vvm for aeration and 0-0.00120 g g?1 magnetic nanoparticles mass fraction. It was found that 36 nm-sized nanoparticles produced during the course of this dissertation enhanced the volumetric mass transfer coefficient up to 3.3-fold and the interfacial area up to 3.3-fold in relation to gas-liquid dispersions without nanoparticles. These results are concordant with previously published enhancement data (kLa enhancement by 7.1-fold and a enhancement by 4.1-fold) (Olle et al. 2006). The magnetic nanoparticles synthesized in this thesis were stable (constant diameter) over a 1wide pH range (2-9). Statistical regression models showed that both kLa and a have high sensitivity to the nanoparticles loading. Empirical correlation models were derived for kLa and for interfacial area, a, as function of physical properties and nanoparticles loading. These correlations lay out a methodology that can help the scientific community to design and scale-up oxygen transfer systems that are based on nanoparticle suspensions. None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None None

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.

Effect of mass variation on dynamics of tethered system in orbital maneuvering

NASA Astrophysics Data System (ADS)

Sun, Liang; Zhao, Guowei; Huang, Hai

2018-05-01

In orbital maneuvering, the mass variation due to fuel consumption has an obvious impact on the dynamics of tethered system, which cannot be neglected. The contributions of the work are mainly shown in two aspects: 1) the improvement of the model; 2) the analysis of dynamics characteristics. As the mass is variable, and the derivative of the mass is directly considered in the traditional Lagrange equation, the expression of generalized force is complicated. To solve this problem, the coagulated derivative is adopted in the paper; besides, the attitude dynamics equations derived in this paper take into account the effect of mass variation and the drift of orbital trajectory at the same time. The bifurcation phenomenon, the pendular motion angular frequency, and amplitudes of tether vibration revealed in this paper can provide a reference for the parameters and controller design in practical engineering. In the article, a dumbbell model is adopted to analyze the dynamics of tethered system, in which the mass variation of base satellite is fully considered. Considering the practical application, the case of orbital transfer under a transversal thrust is mainly studied. Besides, compared with the analytical solutions of librational angles, the effects of mass variation on stability and librational characteristic are studied. Finally, in order to make an analysis of the effect on vibrational characteristic, a lumped model is introduced, which reveals a strong coupling of librational and vibrational characteristics.

Security and Policy for Group Collaboration

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

Ian Foster; Carl Kesselman

2006-07-31

“Security and Policy for Group Collaboration” was a Collaboratory Middleware research project aimed at providing the fundamental security and policy infrastructure required to support the creation and operation of distributed, computationally enabled collaborations. The project developed infrastructure that exploits innovative new techniques to address challenging issues of scale, dynamics, distribution, and role. To reduce greatly the cost of adding new members to a collaboration, we developed and evaluated new techniques for creating and managing credentials based on public key certificates, including support for online certificate generation, online certificate repositories, and support for multiple certificate authorities. To facilitate the integration ofmore » new resources into a collaboration, we improved significantly the integration of local security environments. To make it easy to create and change the role and associated privileges of both resources and participants of collaboration, we developed community wide authorization services that provide distributed, scalable means for specifying policy. These services make it possible for the delegation of capability from the community to a specific user, class of user or resource. Finally, we instantiated our research results into a framework that makes it useable to a wide range of collaborative tools. The resulting mechanisms and software have been widely adopted within DOE projects and in many other scientific projects. The widespread adoption of our Globus Toolkit technology has provided, and continues to provide, a natural dissemination and technology transfer vehicle for our results.« less

A Comparison of Grid-based and SPH Binary Mass-transfer and Merger Simulations

DOE PAGES

Motl, Patrick M.; Frank, Juhan; Staff, Jan; ...

2017-03-29

There is currently a great amount of interest in the outcomes and astrophysical implications of mergers of double degenerate binaries. In a commonly adopted approximation, the components of such binaries are represented by polytropes with an index of n = 3/2. We present detailed comparisons of stellar mass-transfer and merger simulations of polytropic binaries that have been carried out using two very different numerical algorithms—a finite-volume "grid" code and a smoothed-particle hydrodynamics (SPH) code. We find that there is agreement in both the ultimate outcomes of the evolutions and the intermediate stages if the initial conditions for each code aremore » chosen to match as closely as possible. We find that even with closely matching initial setups, the time it takes to reach a concordant evolution differs between the two codes because the initial depth of contact cannot be matched exactly. There is a general tendency for SPH to yield higher mass transfer rates and faster evolution to the final outcome. Here, we also present comparisons of simulations calculated from two different energy equations: in one series, we assume a polytropic equation of state and in the other series an ideal gas equation of state. In the latter series of simulations, an atmosphere forms around the accretor, which can exchange angular momentum and cause a more rapid loss of orbital angular momentum. In the simulations presented here, the effect of the ideal equation of state is to de-stabilize the binary in both SPH and grid simulations, but the effect is more pronounced in the grid code.« less

Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

DTIC Science & Technology

2015-12-21

SECURITY CLASSIFICATION OF: The overall goal of this project is to determine how electrode surface chemistry can be rationally designed to decrease...2015 Approved for Public Release; Distribution Unlimited Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for...ABSTRACT Final Report: Rational Design of Anode Surface Chemistry in Microbial Fuel Cells for Improved Exoelectrogen Attachment and Electron Transfer

Social contagions on time-varying community networks

NASA Astrophysics Data System (ADS)

Liu, Mian-Xin; Wang, Wei; Liu, Ying; Tang, Ming; Cai, Shi-Min; Zhang, Hai-Feng

2017-05-01

Time-varying community structures exist widely in real-world networks. However, previous studies on the dynamics of spreading seldom took this characteristic into account, especially those on social contagions. To study the effects of time-varying community structures on social contagions, we propose a non-Markovian social contagion model on time-varying community networks based on the activity-driven network model. A mean-field theory is developed to analyze the proposed model. Through theoretical analyses and numerical simulations, two hierarchical features of the behavior adoption processes are found. That is, when community strength is relatively large, the behavior can easily spread in one of the communities, while in the other community the spreading only occurs at higher behavioral information transmission rates. Meanwhile, in spatial-temporal evolution processes, hierarchical orders are observed for the behavior adoption. Moreover, under different information transmission rates, three distinctive patterns are demonstrated in the change of the whole network's final adoption proportion along with the growing community strength. Within a suitable range of transmission rate, an optimal community strength can be found that can maximize the final adoption proportion. Finally, compared with the average activity potential, the promoting or inhibiting of social contagions is much more influenced by the number of edges generated by active nodes.

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons

PubMed Central

Gunasekaran, Manojkumar; Chatterjee, Prodyot K.; Shih, Andrew; Imperato, Gavin H.; Addorisio, Meghan; Kumar, Gopal; Lee, Annette; Graf, John F.; Meyer, Dan; Marino, Michael; Puleo, Christopher; Ashe, Jeffrey; Cox, Maureen A.; Mak, Tak W.; Bouton, Chad; Sherry, Barbara; Diamond, Betty; Andersson, Ulf; Coleman, Thomas R.; Metz, Christine N.; Tracey, Kevin J.; Chavan, Sangeeta S.

2018-01-01

The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or μMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses. PMID:29755449

Empirical study of the perceived ease of use and relative advantage on load-bearing masonry (LBM) technology adoption

NASA Astrophysics Data System (ADS)

Ramli, Nor Azlinda; Abdullah, Che Sobry; Nawi, Mohd Nasrun Mohd

2017-11-01

Load-bearing masonry (LBM) technology has been identified as an alternative method that can potentially encourage the sustainability of the housing industry. The adoption of LBM technology is believed to bring beneficial effects to the housing industry as well as company productivity. The factors related to the adoption LBM technology was revealed to strongly influence the implementation of this system in the housing industry. The aim of this study is to determine the factors influencing the adoption of LBM technology among the developer firms in Malaysia as well as the factors that are highly related to perceived ease of use and relative advantage. A random sampling technique was applied and a questionnaire-based field survey was carried out to obtain the data from the respondents. All the data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM). The findings of this paper have revealed that perceived ease of use and relative advantage are related to the adoption of LBM technology. The findings also indicated the validity of Technology Acceptance Model TAM (perceived ease of use) and Innovation Diffusion Theory IDT (relative advantage) as the determinant factors in the adoption of LBM technology. Finally, some recommendations for future research are suggested in the final section of this paper.

Implementation of a Transition Model in a NASA Code and Validation Using Heat Transfer Data on a Turbine Blade

NASA Technical Reports Server (NTRS)

Ameri, Ali A.

2012-01-01

The purpose of this report is to summarize and document the work done to enable a NASA CFD code to model laminar-turbulent transition process on an isolated turbine blade. The ultimate purpose of the present work is to down-select a transition model that would allow the flow simulation of a variable speed power turbine to be accurately performed. The flow modeling in its final form will account for the blade row interactions and their effects on transition which would lead to accurate accounting for losses. The present work only concerns itself with steady flows of variable inlet turbulence. The low Reynolds number k- model of Wilcox and a modified version of the same model will be used for modeling of transition on experimentally measured blade pressure and heat transfer. It will be shown that the k- model and its modified variant fail to simulate the transition with any degree of accuracy. A case is thus made for the adoption of more accurate transition models. Three-equation models based on the work of Mayle on Laminar Kinetic Energy were explored. The three-equation model of Walters and Leylek was thought to be in a relatively mature state of development and was implemented in the Glenn-HT code. Two-dimensional heat transfer predictions of flat plate flow and two-dimensional and three-dimensional heat transfer predictions on a turbine blade were performed and reported herein. Surface heat transfer rate serves as sensitive indicator of transition. With the newly implemented model, it was shown that the simulation of transition process is much improved over the baseline k- model for the single Reynolds number and pressure ratio attempted; while agreement with heat transfer data became more satisfactory. Armed with the new transition model, total-pressure losses of computed three-dimensional flow of E3 tip section cascade were compared to the experimental data for a range of incidence angles. The results obtained, form a partial loss bucket for the chosen blade. In time the loss bucket will be populated with losses at additional incidences. Results obtained thus far will be discussed herein.

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.

78 FR 18285 - Direct Final Rulemaking Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... issue a direct final rule adopting amendments that become effective a number of days (specified in the... rules. NHTSA would not use direct final rule procedures for complex or controversial issues. [[Page... to http://www.regulations.gov and search by Docket ID number NHTSA-2013-0042 at any time. Follow the...

76 FR 38146 - Revision to the Final Principles of Integrated Resource Planning for Use in Resource Acquisition...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... DEPARTMENT OF ENERGY Western Area Power Administration Revision to the Final Principles of... Administration (Western) published proposed Principles for Integrated Resource planning (IRP) for use in its... December 6, 1994. After considering public comments on the proposed principles, Western adopted the Final...

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.

User's guide to four-body and three-body trajectory optimization programs

NASA Technical Reports Server (NTRS)

Pu, C. L.; Edelbaum, T. N.

1974-01-01

A collection of computer programs and subroutines written in FORTRAN to calculate 4-body (sun-earth-moon-space) and 3-body (earth-moon-space) optimal trajectories is presented. The programs incorporate a variable step integration technique and a quadrature formula to correct single step errors. The programs provide capability to solve initial value problem, two point boundary value problem of a transfer from a given initial position to a given final position in fixed time, optimal 2-impulse transfer from an earth parking orbit of given inclination to a given final position and velocity in fixed time and optimal 3-impulse transfer from a given position to a given final position and velocity in fixed time.

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.

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

Kar, Durga P.; Nayak, Praveen P.; Bhuyan, Satyanarayan

In order to power or charge electronic devices wirelessly, a bi-directional wireless power transfer method has been proposed and experimentally investigated. In the proposed design, two receiving coils are used on both sides of a transmitting coil along its central axis to receive the power wirelessly from the generated magnetic fields through strongly coupled magnetic resonance. It has been observed experimentally that the maximum power transfer occurs at the operating resonant frequency for optimum electric load connected across the receiving coils on both side. The optimum wireless power transfer efficiency is 88% for the bi-directional power transfer technique compared 84%more » in the one side receiver system. By adopting the developed bi-directional power transfer method, two electronic devices can be powered up or charged simultaneously instead of a single device through usual one side receiver system without affecting the optimum power transfer efficiency.« less

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.

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

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

2007 Wholesale Power Rate Adjustment Proceeding (WP-07) : Administrator's Final Record of Decision.

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

United States. Bonneville Power Administration.

2006-07-01

This Record of Decision (ROD) contains the decisions of the Bonneville Power Administration (BPA), based on the record compiled in this rate proceeding, with respect to the adoption of power rates for the three-year rate period commencing October 1, 2006, through September 30, 2009. This ''2007 Wholesale Power Rate Adjustment Proceeding'' is designed to establish replacement rate schedules and General Rate Schedule Provisions (GRSPs) for those that expire on September 30, 2006. This power rate case also establishes the General Transfer Agreement (GTA) Delivery Charge for the period of October 1, 2007, through September 30, 2009. BPA's Power Subscription Strategymore » and Record of Decision (Subscription Strategy), as well as other Agency processes, provide much of the policy context for this rate case and are described in Section 2. This ROD follows a full evidentiary hearing and briefing, including an Oral Argument before the BPA Administrator. Sections 3 through 18, including any appendices or attachments, present the issues raised by parties in this proceeding, the parties positions, BPA staff positions on the issues, BPA's evaluations of the positions, and the Administrator's decisions. Parties had the opportunity to file briefs on exceptions to the Draft ROD, before issuance of this Final Record of Decision.« less

76 FR 44761 - Remittance Transfers

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-27

...) (interim final rule); 72 FR 7927 (Feb. 22, 2007) (final rule). Section 1073 of the Dodd-Frank Act added a new Section 919 to the EFTA, entitled ``Remittance Transfers.'' Public Law 111-203, Sec. 1073, 124.... 1693o-1. Paragraph (d) of Section 1073 of Dodd-Frank amended the FCU Act to specify that a remittance...

78 FR 17053 - Indirect Stock Transfers and the Coordination Rule Exceptions; Transfers of Stock or Securities...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... IRS issued final regulations under section 367 (2009 final regulations) concerning gain recognition... without the recognition of a corresponding amount of gain or income inclusion. Notice 2008-10 announced... the revised regulations would confirm that to the extent the appropriate amount of built-in gain in...

77 FR 62431 - Adoption of Updated EDGAR Filer Manual

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

...-30227] Adoption of Updated EDGAR Filer Manual AGENCY: Securities and Exchange Commission. ACTION: Final... Electronic Data Gathering, Analysis, and Retrieval System (EDGAR) Filer Manual and related rules to reflect... Manual is approved by the Director of the Federal Register as of October 15, 2012. FOR FURTHER...

76 FR 52917 - Approval and Promulgation of Air Quality Implementation Plans; Pennsylvania; Adoption of Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-24

... Large Appliance and Metal Furniture Coatings AGENCY: Environmental Protection Agency (EPA). ACTION... Techniques Guidelines (CTG) standards for large appliance and metal furniture coatings. In the Final Rules...; Pennsylvania; Adoption of Control Techniques Guidelines for Large Appliance and Metal Furniture Coatings...

2010-11 NCAA[R] Division I Manual

ERIC Educational Resources Information Center

National Collegiate Athletic Association (NJ1), 2010

2010-01-01

This publication incorporates final legislative actions taken during the 2009-10 legislative cycle. Legislation adopted after August 1, 2009, interpretations incorporated by the Legislative Review/Interpretations Committee, modifications of wording and editorial revisions are set off by a gray background and also include an adoption or revision…

Heat and Mass Transfer in an L Shaped Porous Medium

NASA Astrophysics Data System (ADS)

Salman Ahmed, N. J.; Azeem; Yunus Khan, T. M.

2017-08-01

This article is an extension to the heat transfer in L-shaped porous medium by including the mass diffusion. The heat and mass transfer in the porous domain is represented by three coupled partial differential equations representing the fluid movement, energy transport and mass transport. The equations are converted into algebraic form of equations by the application of finite element method that can be conveniently solved by matrix method. An iterative approach is adopted to solve the coupled equations by setting suitable convergence criterion. The results are discussed in terms of heat transfer characteristics influenced by physical parameters such as buoyancy ratio, Lewis number, Rayleigh number etc. It is found that these physical parameters have significant effect on heat and mass transfer behavior of L-shaped porous medium.

Linear Polarization, Circular Polarization, and Depolarization of Gamma-ray Bursts: A Simple Case of Jitter Radiation

NASA Astrophysics Data System (ADS)

Mao, Jirong; Wang, Jiancheng

2017-04-01

Linear and circular polarizations of gamma-ray bursts (GRBs) have been detected recently. We adopt a simplified model to investigate GRB polarization characteristics in this paper. A compressed two-dimensional turbulent slab containing stochastic magnetic fields is considered, and jitter radiation can produce the linear polarization under this special magnetic field topology. Turbulent Faraday rotation measure (RM) of this slab makes strong wavelength-dependent depolarization. The jitter photons can also scatter with those magnetic clumps inside the turbulent slab, and a nonzero variance of the Stokes parameter V can be generated. Furthermore, the linearly and circularly polarized photons in the optical and radio bands may suffer heavy absorptions from the slab. Thus we consider the polarized jitter radiation transfer processes. Finally, we compare our model results with the optical detections of GRB 091018, GRB 121024A, and GRB 131030A. We suggest simultaneous observations of GRB multi-wavelength polarization in the future.

Trade brokerage property of industrial sectors on the global value chain

NASA Astrophysics Data System (ADS)

Xing, Lizhi; Xu, Xiaoyu; Guan, Jun; Dong, Xianlei

2017-08-01

ICIO data have proven itself to be a reliable source for the analysis of economic globalization, with which sectors all over the world could be constructed into a sophisticated GVC, bringing the advantages of simultaneous study on international and domestic economies in detail as a holistic network. This paper uses OECD-WTO TiVA data to set up GIVCN-TiVA networks as the general analytical framework, depicting the transferring process of intermediate goods among sectors of various countries/regions. Secondly, the conception of brokerage roles in SNA has been adopted to redefine sector’s function while linkage exists between its upstream providers and downstream consumers, referred to as “Trade Brokerage Property”, as well as to quantify the ratio of each types of the roles. Thirdly, a set of simulations have been defined to testify the contribution that different TBPs incur to the robustness of global economic system. Finally, analyses on TBPs and NTBPs have been carried out in the levels of industry and country/region, respectively.

Direct enzymatic bioelectrocatalysis: differentiating between myth and reality

PubMed Central

2017-01-01

Enzymatic bioelectrocatalysis is being increasingly exploited to better understand oxidoreductase enzymes, to develop minimalistic yet specific biosensor platforms, and to develop alternative energy conversion devices and bioelectrosynthetic devices for the production of energy and/or important chemical commodities. In some cases, these enzymes are able to electronically communicate with an appropriately designed electrode surface without the requirement of an electron mediator to shuttle electrons between the enzyme and electrode. This phenomenon has been termed direct electron transfer or direct bioelectrocatalysis. While many thorough studies have extensively investigated this fascinating feat, it is sometimes difficult to differentiate desirable enzymatic bioelectrocatalysis from electrocatalysis deriving from inactivated enzyme that may have also released its catalytic cofactor. This article will review direct bioelectrocatalysis of several oxidoreductases, with an emphasis on experiments that provide support for direct bioelectrocatalysis versus denatured enzyme or dissociated cofactor. Finally, this review will conclude with a series of proposed control experiments that could be adopted to discern successful direct electronic communication of an enzyme from its denatured counterpart. PMID:28637918

Recruited Monocytes and Type 2 Immunity Promote Lung Regeneration following Pneumonectomy.

PubMed

Lechner, Andrew J; Driver, Ian H; Lee, Jinwoo; Conroy, Carmen M; Nagle, Abigail; Locksley, Richard M; Rock, Jason R

2017-07-06

To investigate the role of immune cells in lung regeneration, we used a unilateral pneumonectomy model that promotes the formation of new alveoli in the remaining lobes. Immunofluorescence and single-cell RNA sequencing found CD115+ and CCR2+ monocytes and M2-like macrophages accumulating in the lung during the peak of type 2 alveolar epithelial stem cell (AEC2) proliferation. Genetic loss of function in mice and adoptive transfer studies revealed that bone marrow-derived macrophages (BMDMs) traffic to the lung through a CCL2-CCR2 chemokine axis and are required for optimal lung regeneration, along with Il4ra-expressing leukocytes. Our data suggest that these cells modulate AEC2 proliferation and differentiation. Finally, we provide evidence that group 2 innate lymphoid cells are a source of IL-13, which promotes lung regeneration. Together, our data highlight the potential for immunomodulatory therapies to stimulate alveologenesis in adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Linear Polarization, Circular Polarization, and Depolarization of Gamma-ray Bursts: A Simple Case of Jitter Radiation

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

Mao, Jirong; Wang, Jiancheng, E-mail: jirongmao@mail.ynao.ac.cn

Linear and circular polarizations of gamma-ray bursts (GRBs) have been detected recently. We adopt a simplified model to investigate GRB polarization characteristics in this paper. A compressed two-dimensional turbulent slab containing stochastic magnetic fields is considered, and jitter radiation can produce the linear polarization under this special magnetic field topology. Turbulent Faraday rotation measure (RM) of this slab makes strong wavelength-dependent depolarization. The jitter photons can also scatter with those magnetic clumps inside the turbulent slab, and a nonzero variance of the Stokes parameter V can be generated. Furthermore, the linearly and circularly polarized photons in the optical and radiomore » bands may suffer heavy absorptions from the slab. Thus we consider the polarized jitter radiation transfer processes. Finally, we compare our model results with the optical detections of GRB 091018, GRB 121024A, and GRB 131030A. We suggest simultaneous observations of GRB multi-wavelength polarization in the future.« less

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.

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.

77 FR 54663 - Administrative Simplification: Adoption of a Standard for a Unique Health Plan Identifier...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-05

...This final rule adopts the standard for a national unique health plan identifier (HPID) and establishes requirements for the implementation of the HPID. In addition, it adopts a data element that will serve as an other entity identifier (OEID), or an identifier for entities that are not health plans, health care providers, or individuals, but that need to be identified in standard transactions. This final rule also specifies the circumstances under which an organization covered health care provider must require certain noncovered individual health care providers who are prescribers to obtain and disclose a National Provider Identifier (NPI). Lastly, this final rule changes the compliance date for the International Classification of Diseases, 10th Revision, Clinical Modification (ICD- 10-CM) for diagnosis coding, including the Official ICD-10-CM Guidelines for Coding and Reporting, and the International Classification of Diseases, 10th Revision, Procedure Coding System (ICD-10-PCS) for inpatient hospital procedure coding, including the Official ICD-10-PCS Guidelines for Coding and Reporting, from October 1, 2013 to October 1, 2014.

78 FR 60684 - Adoption of Updated EDGAR Filer Manual

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

...-30722] Adoption of Updated EDGAR Filer Manual AGENCY: Securities and Exchange Commission. ACTION: Final... Electronic Data Gathering, Analysis, and Retrieval System (EDGAR) Filer Manual and related rules to reflect... the EDGAR Filer Manual is approved by the Director of the Federal Register as of October 2, 2013. FOR...

76 FR 1514 - Adoption of Updated EDGAR Filer Manual

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

... Filer Manual and the rule amendments is January 11, 2011. In accordance with the APA,\\8\\ we find that...-29547] Adoption of Updated EDGAR Filer Manual AGENCY: Securities and Exchange Commission. ACTION: Final... Electronic Data Gathering, Analysis, and Retrieval System (EDGAR) Filer Manual to reflect updates to the...

78 FR 29616 - Adoption of Updated EDGAR Filer Manual

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

... updated Filer Manual and the rule amendments is May 21, 2013. In accordance with the APA,\\7\\ we find that...-30515] Adoption of Updated EDGAR Filer Manual AGENCY: Securities and Exchange Commission. ACTION: Final... Electronic Data Gathering, Analysis, and Retrieval System (EDGAR) Filer Manual and related rules to reflect...

2010-11 NCAA[R] Division II Manual

ERIC Educational Resources Information Center

National Collegiate Athletic Association (NJ1), 2010

2010-01-01

This publication incorporates the final legislative actions of the 104th annual NCAA Convention, January 13-16, 2010. In addition, interpretations incorporated by the Legislative Review Subcommittee, noncontroversial amendments adopted by the Management Council, pursuant to Constitution 5.3.1.1.1, and modifications of wording adopted by the…

77 FR 2446 - Amendments to Regulations Regarding Eligibility for a Medicare Prescription Drug Subsidy

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-18

... Administration. ACTION: Final rule. SUMMARY: This final rule adopts, without change, the interim final rule with... incorporated changes to the Medicare prescription drug coverage low-income subsidy (Extra Help) program made by..., 2011. We also revised our regulations to incorporate changes made by the Medicare Improvements for...

75 FR 54526 - Defense Federal Acquisition Regulation Supplement; Payment of Costs Prior to Definitization...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-08

... in 48 CFR Part 217 Government procurement. Ynette R. Shelkin, Editor, Defense Acquisition Regulations...). ACTION: Final rule. SUMMARY: DoD is adopting as final, without change, an interim rule amending the... interim rule. Therefore, DoD is finalizing the interim rule without change. This rule was not subject to...

76 FR 446 - Supplemental Security Income (SSI) for the Aged, Blind, and Disabled; Dedicated Accounts and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... SOCIAL SECURITY ADMINISTRATION 20 CFR Part 416 [Docket No. SSA-2008-0050] RIN 0960-AE59... Payments for Certain Past- Due SSI Benefits AGENCY: Social Security Administration (SSA). ACTION: Final rules. SUMMARY: These final rules adopt, with some minor changes, the interim final rules with request...

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

Elucidating nitric oxide synthase domain interactions by molecular dynamics.

PubMed

Hollingsworth, Scott A; Holden, Jeffrey K; Li, Huiying; Poulos, Thomas L

2016-02-01

Nitric oxide synthase (NOS) is a multidomain enzyme that catalyzes the production of nitric oxide (NO) by oxidizing L-Arg to NO and L-citrulline. NO production requires multiple interdomain electron transfer steps between the flavin mononucleotide (FMN) and heme domain. Specifically, NADPH-derived electrons are transferred to the heme-containing oxygenase domain via the flavin adenine dinucleotide (FAD) and FMN containing reductase domains. While crystal structures are available for both the reductase and oxygenase domains of NOS, to date there is no atomic level structural information on domain interactions required for the final FMN-to-heme electron transfer step. Here, we evaluate a model of this final electron transfer step for the heme-FMN-calmodulin NOS complex based on the recent biophysical studies using a 105-ns molecular dynamics trajectory. The resulting equilibrated complex structure is very stable and provides a detailed prediction of interdomain contacts required for stabilizing the NOS output state. The resulting equilibrated complex model agrees well with previous experimental work and provides a detailed working model of the final NOS electron transfer step required for NO biosynthesis. © 2015 The Protein Society.

77 FR 69769 - Solid Waste Rail Transfer Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-21

.... SUMMARY: These final rules govern land-use-exemption permits for solid waste rail transfer facilities. The... ``land-use-exemption permits'' in certain circumstances. Under the CRA, a solid waste rail transfer... grants a land-use-exemption permit for a solid waste rail transfer facility, such permit would only...

Optimal high- and low-thrust geocentric transfer

NASA Technical Reports Server (NTRS)

Sackett, L. L.; Edelbaum, T. N.

1974-01-01

A computer code which rapidly calculates time optimal combined high- and low-thrust transfers between two geocentric orbits in the presence of a strong gravitational field has been developed as a mission analysis tool. The low-thrust portion of the transfer can be between any two arbitrary ellipses. There is an option for including the effect of two initial high-thrust impulses which would raise the spacecraft from a low, initially circular orbit to the initial orbit for the low-thrust portion of the transfer. In addition, the effect of a single final impulse after the low-thrust portion of the transfer may be included. The total Delta V for the initial two impulses must be specified as well as the Delta V for the final impulse. Either solar electric or nuclear electric propulsion can be assumed for the low-thrust phase of the transfer.

Immune response in pemphigus and beyond: progresses and emerging concepts.

PubMed

Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

2016-01-01

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

Contact Between Birth and Adoptive Families During the First Year Post-Placement: Perspectives of Lesbian, Gay, and Heterosexual Parents

PubMed Central

Goldberg, Abbie E.

2015-01-01

Despite growing visibility of lesbian- and gay-parent adoption, only one qualitative study has examined birth family contact among adoptive families with lesbian and gay parents (Goldberg, Kinkler, Richardson, & Downing, 2011). We studied adoptive parents’ (34 lesbian, 32 gay, and 37 heterosexual; N = 103 families) perspectives of birth family contact across the first year post-placement. Using questionnaire and interview data, we found few differences in openness dynamics by parental sexual orientation. Most reported some birth mother contact, most had legally finalized their adoption, and few described plans to withhold information from children. We discuss implications for clinical practice, policy, and research. PMID:26843808

Contact Between Birth and Adoptive Families During the First Year Post-Placement: Perspectives of Lesbian, Gay, and Heterosexual Parents.

PubMed

Farr, Rachel H; Goldberg, Abbie E

Despite growing visibility of lesbian- and gay-parent adoption, only one qualitative study has examined birth family contact among adoptive families with lesbian and gay parents (Goldberg, Kinkler, Richardson, & Downing, 2011). We studied adoptive parents' (34 lesbian, 32 gay, and 37 heterosexual; N = 103 families) perspectives of birth family contact across the first year post-placement. Using questionnaire and interview data, we found few differences in openness dynamics by parental sexual orientation. Most reported some birth mother contact, most had legally finalized their adoption, and few described plans to withhold information from children. We discuss implications for clinical practice, policy, and research.

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

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

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.

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.

75 FR 51934 - Telemarketing Sales Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-24

... FEDERAL TRADE COMMISSION 16 CFR Part 310 Telemarketing Sales Rule AGENCY: Federal Trade Commission. ACTION: Final rule; correction. SUMMARY: The Federal Trade Commission (``Commission'') published a final rule on August 10, 2010, adopting amendments to the Telemarketing Sales Rule that address the...

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

Transfer-appropriate processing in the testing effect.

PubMed

Veltre, Mary T; Cho, Kit W; Neely, James H

2015-01-01

The testing effect is the finding that taking a review test enhances performance on a final test relative to restudying the material. The present experiment investigated transfer-appropriate processing in the testing effect using semantic and orthographic cues to evoke conceptual and data-driven processing, respectively. After a study phase, subjects either restudied the material or took a cued-recall test consisting of half semantic and half orthographic cues in which the correct response was given as feedback. A final, cued-recall test consisted of the identical cue, or a new cue that was of the same type or different type of cue (semantic/orthographic or orthographic/semantic) as that used for that target in the review test. Testing enhanced memory in all conditions. When the review cues and final-test cues were identical, final recall was higher for semantic than orthographic cues. Consistent with test-based transfer-appropriate processing, memory performance improved as the review and final cues became more similar. These results suggest that the testing effect could potentially be caused by the episodic retrieval processes in a final memory test overlapping more with the episodic retrieval processes in a review test than with the encoding operations performed during restudy.

Recalibrating the BC Transfer System: Approved Final Report

ERIC Educational Resources Information Center

British Columbia Council on Admissions and Transfer, 2006

2006-01-01

In November 2005, the BC Council on Admissions and Transfer launched a consultation entitled Recalibrating the BC Transfer System with the institutional members of the BC Transfer System and other interested parties. This consultation was motivated in large part by significant changes in the BC post-secondary system over the last decade, and…

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.

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

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.

75 FR 58489 - Regulation Z; Truth in Lending

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

...The Board is publishing final rules amending Regulation Z (Truth in Lending). The final rule implements Section 131(g) of the Truth in Lending Act (TILA), which was enacted on May 20, 2009, as Section 404(a) of the Helping Families Save Their Homes Act. TILA Section 131(g) became effective immediately upon enactment and established a new requirement for notifying consumers of the sale or transfer of their mortgage loans. Consistent with the statute, the final rule requires a purchaser or assignee that acquires a loan to provide the disclosures in writing no later than 30 days after the date on which the loan was sold, transferred or assigned. Certain exceptions may apply if the covered person transfers or assigns the loan to another party on or before the 30th day.

Research on MMC-SST Oriented AC/DC Distribution System

NASA Astrophysics Data System (ADS)

Xie, Xifeng; Shi, Hua; Zuo, Jianglin; Zhang, Zhigang

2018-01-01

A modular multilevel converter-solid state transformer (MMC-SST) oriented AC/DC Distribution System is designed. Firstly, the topology structure is introduced, MMC is adopted in the input stage, multiple DC-DC converters are adopted in the isolation stage, and a Three-Phase Four-Leg inverter is adopted in the output stage. Then, the control strategy is analysed. Finally, simulation model and an experimental prototype of MMC-SST are built, simulation and experimental results show that topology and control strategy of MMC-SST are feasible.

A Comparison of Grid-based and SPH Binary Mass-transfer and Merger Simulations

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

Motl, Patrick M.; Frank, Juhan; Clayton, Geoffrey C.

2017-04-01

There is currently a great amount of interest in the outcomes and astrophysical implications of mergers of double degenerate binaries. In a commonly adopted approximation, the components of such binaries are represented by polytropes with an index of n  = 3/2. We present detailed comparisons of stellar mass-transfer and merger simulations of polytropic binaries that have been carried out using two very different numerical algorithms—a finite-volume “grid” code and a smoothed-particle hydrodynamics (SPH) code. We find that there is agreement in both the ultimate outcomes of the evolutions and the intermediate stages if the initial conditions for each code are chosen to matchmore » as closely as possible. We find that even with closely matching initial setups, the time it takes to reach a concordant evolution differs between the two codes because the initial depth of contact cannot be matched exactly. There is a general tendency for SPH to yield higher mass transfer rates and faster evolution to the final outcome. We also present comparisons of simulations calculated from two different energy equations: in one series, we assume a polytropic equation of state and in the other series an ideal gas equation of state. In the latter series of simulations, an atmosphere forms around the accretor, which can exchange angular momentum and cause a more rapid loss of orbital angular momentum. In the simulations presented here, the effect of the ideal equation of state is to de-stabilize the binary in both SPH and grid simulations, but the effect is more pronounced in the grid code.« less

A double-helix and cross-patterned solenoid used as a wirelessly powered receiver for medical implants

NASA Astrophysics Data System (ADS)

Mao, Shitong; Wang, Hao; Mao, Zhi-Hong; Sun, Mingui

2018-05-01

Many medical implants need to be designed in the shape of a cylinder (rod), a cuboid or a capsule in order to adapt to a specific site within the human body or facilitate the implantation procedure. In order to wirelessly power these types of implants, a pair of coils, one is located inside the human body and one is outside, is often used. Since most organs such as major muscles, blood vessels, and nerve bundles are anatomically parallel to the body surface, the most desired wireless power transfer (WPT) direction is from the external power transmission pad (a planar coil) to the lateral surface of the implant. However, to obtain optimal coupling, the currently used solenoid coil requires being positioned perpendicular to the body surface, which is often medically or anatomically unacceptable. In this research, a concentric double-helix (DH) coil with an air core is presented for use in implantable devices. Two helical coils are tilted at opposite angles (±45 degrees) to form a cross pattern. The WPT system is designed using the magnetic resonance concept for wireless power transfer (MR-WPT). The power transfer efficiency (PTE) relies on the near-field magnetic coupling which is closely related to the location and orientation of the DH coil. We explain how the novel structure of the DH solenoid magnifies the mutual inductance with the widely adopted circular planner coil and how the PTE is improved in comparison to the case of the conventional solenoid coil. We also study an important case where the double-helix power reception coil is laterally and angularly misaligned with the transmitter. Finally, our computational study using the finite element method and experimental study with actually constructed prototypes are presented which have proven our new double-helix coil design.

CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells.

PubMed

Legut, Mateusz; Dolton, Garry; Mian, Afsar Ali; Ottmann, Oliver G; Sewell, Andrew K

2018-01-18

Adoptive transfer of T cells genetically modified to express a cancer-specific T-cell receptor (TCR) has shown significant therapeutic potential for both hematological and solid tumors. However, a major issue of transducing T cells with a transgenic TCR is the preexisting expression of TCRs in the recipient cells. These endogenous TCRs compete with the transgenic TCR for surface expression and allow mixed dimer formation. Mixed dimers, formed by mispairing between the endogenous and transgenic TCRs, may harbor autoreactive specificities. To circumvent these problems, we designed a system where the endogenous TCR-β is knocked out from the recipient cells using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) technology, simultaneously with transduction with a cancer-reactive receptor of choice. This TCR replacement strategy resulted in markedly increased surface expression of transgenic αβ and γδ TCRs, which in turn translated to a stronger, and more polyfunctional, response of engineered T cells to their target cancer cell lines. Additionally, the TCR-plus-CRISPR-modified T cells were up to a thousandfold more sensitive to antigen than standard TCR-transduced T cells or conventional model proxy systems used for studying TCR activity. Finally, transduction with a pan-cancer-reactive γδ TCR used in conjunction with CRISPR/Cas9 knockout of the endogenous αβ TCR resulted in more efficient redirection of CD4 + and CD8 + T cells against a panel of established blood cancers and primary, patient-derived B-cell acute lymphoblastic leukemia blasts compared with standard TCR transfer. Our results suggest that TCR transfer combined with genome editing could lead to new, improved generations of cancer immunotherapies. © 2018 by The American Society of Hematology.

[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.

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.

75 FR 2013 - Health Information Technology: Initial Set of Standards, Implementation Specifications, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

...The Department of Health and Human Services (HHS) is issuing this interim final rule with a request for comments to adopt an initial set of standards, implementation specifications, and certification criteria, as required by section 3004(b)(1) of the Public Health Service Act. This interim final rule represents the first step in an incremental approach to adopting standards, implementation specifications, and certification criteria to enhance the interoperability, functionality, utility, and security of health information technology and to support its meaningful use. The certification criteria adopted in this initial set establish the capabilities and related standards that certified electronic health record (EHR) technology will need to include in order to, at a minimum, support the achievement of the proposed meaningful use Stage 1 (beginning in 2011) by eligible professionals and eligible hospitals under the Medicare and Medicaid EHR Incentive Programs.

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.

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

Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer

DTIC Science & Technology

2011-05-01

Briefly, the electron transfer activities of complex I/III (NADH dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from NADH to...ferricytochrome c) and complex II/III (succinate dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from succinate to ferricytochrome...The electron transfer activity of complex IV (cytochrome c oxidase: catalyzes the final step of the respiratory chain by transferring electrons from

75 FR 38725 - Service Performance Measurement

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-06

... of Customer Sastisfaction A. General Considerations B. Rule 3055.91--Consumer Access to Postal Services C. Rule 3055.92--Customer Experience Measurement Surveys D. Rule 3055.93--Mystery Shopper Program... Commission is adopting a final rule on service perfomance measurement and customer satisfaction. The final...

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.

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

External factors in hospital information system (HIS) adoption model: a case on Malaysia.

PubMed

Lee, Heng Wei; Ramayah, Thurasamy; Zakaria, Nasriah

2012-08-01

Studies related to healthcare ICT integration in Malaysia are relatively little, thus this paper provide a literature review of the integration of information and communication technologies (ICT) in the healthcare sector in Malaysia through the hospital information system (HIS). Our study emphasized on secondary data to investigate the factors related to ICT integration in healthcare through HIS. Therefore this paper aimed to gather an in depth understanding of issues related to HIS adoption, and contributing in fostering HIS adoption in Malaysia and other countries. This paper provides a direction for future research to study the correlation of factors affecting HIS adoption. Finally a research model is proposed using current adoption theories and external factors from human, technology, and organization perspectives.

Effects of multiple polyaniline layers immobilized on carbon nanotube and glutaraldehyde on performance and stability of biofuel cell

NASA Astrophysics Data System (ADS)

Christwardana, Marcelinus; Kwon, Yongchai

2015-12-01

Enzymatic biofuel cell (EBC) employing new catalyst for anode electrode is fabricated. The new catalyst consists of glucose oxidase (GOx), polyaniline (PANI) and carbon nanotube (CNT) that are multiply stacked together and finally the stack layer is surrounded by glutaraldehyde (GA) (GA/[GOx/PANI/CNT]n). To evaluate how the GA/[GOx/PANI/CNT]n layer affects EBC performance and stability, electrochemical characterizations are implemented. Regarding optimization, GA/[GOx/PANI/CNT]3 is determined. For elucidating reaction mechanism between glucose and flavin adenine dinucleotide (FAD) of GA/[GOx/PANI/CNT]3, associated investigations are performed. In the evaluations, drop in reduction current peak of FAD is observed with provisions of glucose and O2, while glucose does not influence FAD reaction without O2, confirming O2 makes mediator role. When the GA/[GOx/PANI/CNT]3 layer is adopted, superior catalytic activity and EBC performance are gained (electron transfer rate constant of 5.1 s-1, glucose sensitivity of 150 ìA mM-1 cm-2, and EBC maximum power density (MPD) of 0.29 mW cm-2). Regarding EBC stability, MPD of EBC adopting GA/[GOx/PANI/CNT]3 maintains up to 93% of their initial value even after four weeks. Although GA is little effective for improving EBC performance, EBC stability is helped by GA due to its adhesion promotion capability with [GOx/PANI/CNT]n layer.

Water footprint of Jing-Jin-Ji urban agglomeration in China

NASA Astrophysics Data System (ADS)

Zhao, D.

2017-12-01

A rapidly expanding economy and increasing water demand for economic production is placing enormous stress on water quantity and aquatic environment in Northern China, especially the so-called Jing-Jin-Ji (Beijing-Tianjin-Hebei) urban agglomeration. Several studies have focused on energy consumption, air pollution, CO2 emissions and regional blue water footprint (WF) following release of the Jing-Jin-Ji Integration Strategy by the China government. However, a comprehensive assessment distinguishing blue, green and grey WF amongst different industrial sectors, ascertaining how WF transfers internally and beyond the region and final demand consumption is not available. In this study, we quantified the WF and virtual water flow on a sectoral basis for the year 2010 through coupling the multi-regional input-output model (MRIO) with WF assessment. The results showed that Beijing and Tianjin are net importers of green, blue and grey water from Hebei and other provinces to support their needs. Conversely, Hebei exports all WF colors to Beijing, Tianjin and other provinces in China, more than 60% of WF is transferred as virtual water. For the overall Jing-Jin-Ji region a small amount of blue water (2,086 million m3) is exported, but huge amounts of green water (15,573 million m3) and grey water (30,620 million m3) are outsourced. A "Virtual Water Strategy" is one measure which could alleviate water stress at the regional scale, with consideration of financial compensation from water receiving regions made to water supplying regions for achieving water management targets. We also found that physical water transfer to Jing-Jin-Ji could not balance virtual blue water exports. Our research suggests that a continuation of an export-based economic development model will worsen Hebei's water stress. Reducing the dependency of Hebei's sectoral economy on export of water intensive and low value added agricultural products may be one strategy to reduce the pressure on regional water resources. In addition, the Integration Strategy drives industrial transfer from Beijing to Hebei resulting in the transfer of enterprises with low water utilization efficiency and producing heavy pollution. Thus, the government should consider incentivizing corporations to adopt technologies that reduce water consumption and pollution.

Closed-Form and Numerically-Stable Solutions to Problems Related to the Optimal Two-Impulse Transfer Between Specified Terminal States of Keplerian Orbits

NASA Technical Reports Server (NTRS)

Senent, Juan

2011-01-01

The first part of the paper presents some closed-form solutions to the optimal two-impulse transfer between fixed position and velocity vectors on Keplerian orbits when some constraints are imposed on the magnitude of the initial and final impulses. Additionally, a numerically-stable gradient-free algorithm with guaranteed convergence is presented for the minimum delta-v two-impulse transfer. In the second part of the paper, cooperative bargaining theory is used to solve some two-impulse transfer problems when the initial and final impulses are carried by different vehicles or when the goal is to minimize the delta-v and the time-of-flight at the same time.

Cost Evaluation of Evidence-Based Treatments

PubMed Central

Sindelar, Jody L.; Ball, Samuel A.

2010-01-01

Many treatment programs have adopted or are considering adopting evidence-based treatments (EBTs). When a program evaluates whether to adopt a new intervention, it must consider program objectives, operational goals, and costs. This article examines cost concepts, cost estimation, and use of cost information to make the final decision on whether to adopt an EBT. Cost categories, including variable and fixed, accounting and opportunity, and costs borne by patients and others, are defined and illustrated using the example of expenditures for contingency management. Ultimately, cost is one consideration in the overall determination of whether implementing an EBT is the best use of a program’s resources. PMID:22002453

An industry perspective: An update on the adoption of whole slide imaging.

PubMed

Montalto, Michael C

2016-01-01

This manuscript is an adaptation of the closing keynote presentation of the Digital Pathology Association Pathology Visions Conference 2015 in Boston, MA, USA. In this presentation, analogies are drawn between the adoption of whole slide imaging (WSI) and other mainstream digital technologies, including digital music and books. In doing so, it is revealed that the adoption of seemingly similar digital technologies does not follow the same adoption profiles and that understanding the unique aspects of value for each customer segment is critical. Finally, a call to action is given to academia and industry to study the value that WSI brings to the global healthcare community.

Advanced Air Transportation Technologies Project, Final Document Collection

NASA Technical Reports Server (NTRS)

Mogford, Richard H.; Wold, Sheryl (Editor)

2008-01-01

This CD ROM contains a compilation of the final documents of the Advanced Air Transportation Technologies (AAIT) project, which was an eight-year (1996 to 2004), $400M project managed by the Airspace Systems Program office, which was part of the Aeronautics Research Mission Directorate at NASA Headquarters. AAIT focused on developing advanced automation tools and air traffic management concepts that would help improve the efficiency of the National Airspace System, while maintaining or enhancing safety. The documents contained in the CD are final reports on AAIT tasks that serve to document the project's accomplishments over its eight-year term. Documents include information on: Advanced Air Transportation Technologies, Autonomous Operations Planner, Collaborative Arrival Planner, Distributed Air/Ground Traffic Management Concept Elements 5, 6, & 11, Direct-To, Direct-To Technology Transfer, Expedite Departure Path, En Route Data Exchange, Final Approach Spacing Tool - (Active and Passive), Multi-Center Traffic Management Advisor, Multi Center Traffic Management Advisor Technology Transfer, Surface Movement Advisor, Surface Management System, Surface Management System Technology Transfer and Traffic Flow Management Research & Development.

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

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

Final Requirements--School Improvement Grants--Title I of the Elementary and Secondary Education Act of 1965. Final Rule. Federal Register, Part IV, Department of Education, 34 CFR Chapter II

ERIC Educational Resources Information Center

National Archives and Records Administration, 2015

2015-01-01

The Assistant Secretary for Elementary and Secondary Education adopts final requirements for the School Improvement Grants (SIG) program, authorized under section 1003(g) of title I of the Elementary and Secondary Education Act of 1965, as amended (ESEA). These final requirements make changes to the current SIG program requirements and implement…

77 FR 40144 - Adoption of the Environmental Impact Statement (EIS) and Participation in the Section 106...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

...) obligations related to MTA's request for financing for the East Side Access project through the FRA Railroad... Statement (EIS) and Participation in the Section 106 Programmatic Agreement for the East Side Access Project... adoption and recirculation of the Final Environmental Impact Statement for the East Side Access Project and...

76 FR 29649 - Approval and Promulgation of Air Quality Implementation Plans; Pennsylvania; Adoption of Control...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... global warming, through regulations that will harm the economy of the United States,'' and asserts that EPA is attempting to take such action on the issue of global warming which Congress has ``decided that... purpose of addressing global warming. IV. Final Action EPA is approving Pennsylvania's adoption of the CTG...

75 FR 42270 - Adoption of Supplemental Standards of Ethical Conduct for Members and Employees of the Securities...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... Supplemental Standards of Ethical Conduct for Members and Employees of the Securities and Exchange Commission and Revisions to the Commission's Ethics Rules; Final Rule #0;#0;Federal Register / Vol. 75, No. 138... CFR Part 4401 and 17 CFR Part 200 [Release No. 34-62501] Adoption of Supplemental Standards of Ethical...

75 FR 42269 - Adoption of Supplemental Standards of Ethical Conduct for Members and Employees of the Securities...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-20

... Supplemental Standards of Ethical Conduct for Members and Employees of the Securities and Exchange Commission and Revisions to the Commission's Ethics Rules; Final Rule #0;#0;Federal Register / Vol. 75, No. 138... CFR Part 4401 and 17 CFR Part 200 [Release No. 34-62501] Adoption of Supplemental Standards of Ethical...

77 FR 44158 - Fees for Services Performed in Connection With Licensing and Related Services-2012 Update

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

... AGENCY: Surface Transportation Board, DOT. ACTION: Final rules. SUMMARY: The Board adopts its 2012 user... result of no wage & salary increases given in January 2012, no change to publication costs from their... 1002.3(d). The fee changes adopted here, reflect a combination of the unchanged wage and salary costs...

76 FR 46628 - Regulations Governing Fees for Services Performed in Connection With Licensing and Related...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

... Services--2011 Update AGENCY: Surface Transportation Board. ACTION: Final rule. SUMMARY: The Board adopts... decreased costs, resulting from a freeze on wage and salary increases in 2011, coupled with changes to the... adopted here reflect a combination of the unchanged wage and salary costs from the 2010 User Fee Update...

78 FR 13062 - Request for Public Comment on the Proposed Adoption of Administration for Native Americans...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

..., and rules of agency procedure or practice, and to give notice of the final adoption of such changes at... procedure or practice as they relate to the Fiscal Year (FY) 2013 Funding Opportunity Announcements (FOA... statements of policy, and rules of agency organization, procedure, or practice. The proposed clarifications...

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

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...

75 FR 60261 - Federal Acquisition Regulation; Award-Fee Language Revision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

...-AL42 Federal Acquisition Regulation; Award-Fee Language Revision AGENCIES: Department of Defense (DoD...: Final rule. SUMMARY: The Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council (Councils) have adopted as final, with changes, the interim rule amending the Federal Acquisition...

Federal employees health benefits acquisition regulation: Board of Contract Appeals. Final rule.

PubMed

2008-10-08

The Office of Personnel Management (OPM) is adopting as final,without change, the proposed rule published April 7, 2008 to remove the designation of the Armed Services Board of Contract Appeals (ASBCA)from the Federal Employees Health Benefits Acquisition Regulation(FEHBAR).

77 FR 38801 - Environmental Impacts Statements; Notice of Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

... Resource Management (VRM) Plan, Amendment, Class Designation, Carbon County, WY, Review Period Ends: 07/30... Final Vehicle Management Plan, Implementation, Denali National Park and Preserve, AK, Review Period Ends.... EIS No. 20120199, Final EIS, RUS, MS, ADOPTION--Kemper County Integrated Gasification Combined Cycle...

Representing the healthcare organization in a post-Sarbanes-Oxley world: new rules, new paradigms, new perils.

PubMed

Horton, William W

2004-01-01

The Sarbanes-Oxley Act (Act) significantly changed the expected corporate behavior of public companies. The Act governs the relationship between corporate organizations and their in-house or outside counsel. Under Section 307 of the Act, the Securities and Exchange Commission initially proposed expansive rules regarding counsel's duties. After comments and criticism from much of the bar, a final, narrower, version of rules under Section 307 (Final Rule) was adopted. The Final Rule contains alternative reporting procedures, attorney responsibilities, and sanctions for violations. In addition to the Act, the American Bar Association's (ABA) Task Force on Corporate Responsibility(Task Force), which was itself a reaction to Enron, reported on the importance of counsel's role in a corporate setting (Cheek Report). The ABA adopted amendments to its Model Rules of Professional Conduct (Model Rules) 1.6 and 1.13 as proposed in the Cheek Report. The Final Rule and amended Model Rules together suggest that attorneys may owe duties beyond those owed to their clients.

75 FR 7551 - Transfer of Accumulated Benefit Payments

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-22

... Transfer of Accumulated Benefit Payments AGENCY: Social Security Administration (SSA). ACTION: Final rule... that capacity to transfer accumulated benefit payments and interest directly to a beneficiary if we.... For information on eligibility or filing for benefits, call our national toll-free number, 1-800-772...

Structure of S-shaped growth in innovation diffusion

NASA Astrophysics Data System (ADS)

Shimogawa, Shinsuke; Shinno, Miyuki; Saito, Hiroshi

2012-05-01

A basic question on innovation diffusion is why the growth curve of the adopter population in a large society is often S shaped. From macroscopic, microscopic, and mesoscopic viewpoints, the growth of the adopter population is observed as the growth curve, individual adoptions, and differences among individual adoptions, respectively. The S shape can be explained if an empirical model of the growth curve can be deduced from models of microscopic and mesoscopic structures. However, even the structure of growth curve has not been revealed yet because long-term extrapolations by proposed models of S-shaped curves are unstable and it has been very difficult to predict the long-term growth and final adopter population. This paper studies the S-shaped growth from the viewpoint of social regularities. Simple methods to analyze power laws enable us to extract the structure of the growth curve directly from the growth data of recent basic telecommunication services. This empirical model of growth curve is singular at the inflection point and a logarithmic function of time after this point, which explains the unstable extrapolations obtained using previously proposed models and the difficulty in predicting the final adopter population. Because the empirical S curve can be expressed in terms of two power laws of the regularity found in social performances of individuals, we propose the hypothesis that the S shape represents the heterogeneity of the adopter population, and the heterogeneity parameter is distributed under the regularity in social performances of individuals. This hypothesis is so powerful as to yield models of microscopic and mesoscopic structures. In the microscopic model, each potential adopter adopts the innovation when the information accumulated by the learning about the innovation exceeds a threshold. The accumulation rate of information is heterogeneous among the adopter population, whereas the threshold is a constant, which is the opposite of previously proposed models. In the mesoscopic model, flows of innovation information incoming to individuals are organized as dimorphic and partially clustered. These microscopic and mesoscopic models yield the empirical model of the S curve and explain the S shape as representing the regularities of information flows generated through a social self-organization. To demonstrate the validity and importance of the hypothesis, the models of three level structures are applied to reveal the mechanism determining and differentiating diffusion speeds. The empirical model of S curves implies that the coefficient of variation of the flow rates determines the diffusion speed for later adopters. Based on this property, a model describing the inside of information flow clusters can be given, which provides a formula interconnecting the diffusion speed, cluster populations, and a network topological parameter of the flow clusters. For two recent basic telecommunication services in Japan, the formula represents the variety of speeds in different areas and enables us to explain speed gaps between urban and rural areas and between the two services. Furthermore, the formula provides a method to estimate the final adopter population.

Calculation of rates of exciton dissociation into hot charge-transfer states in model organic photovoltaic interfaces

NASA Astrophysics Data System (ADS)

Vázquez, Héctor; Troisi, Alessandro

2013-11-01

We investigate the process of exciton dissociation in ordered and disordered model donor/acceptor systems and describe a method to calculate exciton dissociation rates. We consider a one-dimensional system with Frenkel states in the donor material and states where charge transfer has taken place between donor and acceptor. We introduce a Green's function approach to calculate the generation rates of charge-transfer states. For disorder in the Frenkel states we find a clear exponential dependence of charge dissociation rates with exciton-interface distance, with a distance decay constant β that increases linearly with the amount of disorder. Disorder in the parameters that describe (final) charge-transfer states has little effect on the rates. Exciton dissociation invariably leads to partially separated charges. In all cases final states are “hot” charge-transfer states, with electron and hole located far from the interface.

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.

Laser Integration on Silicon Photonic Circuits Through Transfer Printing

DTIC Science & Technology

2017-03-10

AFRL-AFOSR-UK-TR-2017-0019 Laser integration on silicon photonic circuits through transfer printing Gunther Roelkens UNIVERSITEIT GENT VZW Final...TYPE Final 3. DATES COVERED (From - To) 15 Sep 2015 to 14 Sep 2016 4. TITLE AND SUBTITLE Laser integration on silicon photonic circuits through...parallel integration of III-V lasers on silicon photonic integrated circuits. The report discusses the technological process that has been developed as

Strategic Plan for Federal Research and Monitoring of Ocean Acidification

EPA Science Inventory

On July 19, 2010, the President signed an Executive Order establishing the nation’s first comprehensive National Policy for the Stewardship of the Ocean, Our Coasts, and Great Lakes and adopted the Final Recommendations of the Ocean Policy Task Force (OPTF 2010). The Final Recom...

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.

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

PubMed Central

Majewska-Szczepanik, Monika; Askenase, Philip W.; Lobo, Francis M.; Marcińska, Katarzyna; Wen, Li; Szczepanik, Marian

2017-01-01

Background Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy. Objective We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigen-specific manner. Methods Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization. Results Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) αβ+CD4+CD25− cells, whereas IgG2a production is dependent on both TCRαβ+ and TCRγδ+ T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-γ, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA-specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy. Conclusion Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases. PMID:26810716

75 FR 33681 - Electronic Fund Transfers

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... FEDERAL RESERVE SYSTEM 12 CFR Part 205 [Regulation E; Docket No. R-1343] Electronic Fund Transfers June 4, 2010. AGENCY: Board of Governors of the Federal Reserve System. ACTION: Final rule; correction..., published on June 4, 2010 (75 FR 31665) make the following correction: PART 205--ELECTRONIC FUND TRANSFERS...

Technology transfer: the key to fusion commercialization

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

Burnett, S.C.

1981-01-01

The paper brings to light some of the reasons why technology transfer is difficult in fusion, examines some of the impediments to the process, and finally looks at a successful example of technology transfer. The paper considers some subjective features of fusion - one might call them the sociology of fusion - that are none the less real and that serve as impediments to technology transfer.

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…

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.

Exceptions or alternatives to labeling requirements for products held by the Strategic National Stockpile. Final rule.

PubMed

2012-02-06

The Food and Drug Administration (FDA) is adopting as a final rule, without change, the interim final rule that issued regulations permitting FDA Center Directors to grant exceptions or alternatives to certain regulatory labeling requirements applicable to human drugs, biological products, or medical devices that are or will be included in the Strategic National Stockpile (SNS). FDA is taking this action to complete the rulemaking initiated with the interim final rule.

Energy conservation policy evaluation. Study module IA. Volume II. Technical appendix. Final report

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

Bergstresser, K.; Berney, R.E.; Carter, L.F.

1978-01-01

This volume contains detailed technical analyses of the 19 energy conservation measures which were discussed as regional policy options in the report proper (PB-274 337). For each measure there is a description of how the measure works to reduce consumption; an assessment of potential savings, costs, and returns to adopters; probable 'normal' adoption rates under present policies; and potential adoption rates if some additional conservation policy options are implemented. Report includes chapters on environmental residuals from energy end uses, and policy preferences of households and energy marketers.

The economics of integrated electronic medical record systems.

PubMed

Chismar, William G; Thomas, Sean M

2004-01-01

The decision to adopt electronic medical record systems in private practices is usually based on factors specific to the practice--the cost, cost and timesaving, and impact on quality of care. As evident by the low adoption rates, providers have not found these evaluations compelling. However, it is recognized that the widespread adoption of EMR systems would greatly benefit the health care system as a whole. One explanation for the lack of adoption is that there is a misalignment of the costs and benefits of EMR systems across the health care system. In this paper we present an economic model of the adoption of EMR systems that explicitly represents the distribution of costs and benefits across stakeholders (physicians, hospitals, insurers, etc.). We discuss incentive systems for balancing the costs and benefits and, thus, promoting the faster adoption of EMR systems. Finally, we describe our plan to extend the model and to use real-world data to evaluate our model.

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.

78 FR 36743 - Adoption of Final Environmental Assessment (UT-040-09-03) Prepared for the Upper Kanab Creek...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

... Assessment (UT-040-09-03) Prepared for the Upper Kanab Creek Watershed Vegetation Management Project AGENCY... (NRCS) announces its intent to adopt the Kanab Creek Watershed Vegetation Management Project EA, as... Management Project EA, request a copy of the EA, or submit comments on actions being taken by NRCS regarding...

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

76 FR 708 - Electronic Funds Transfer of Depository Taxes; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... DEPARTMENT OF THE TREASURY Internal Revenue Service 26 CFR Parts 1, 31, 40, and 301 [TD 9507] RIN 1545-BJ13 Electronic Funds Transfer of Depository Taxes; Correction AGENCY: Internal Revenue Service... Electronic Funds Transfer (EFT). The temporary and final regulations provide rules under which depositors...

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.

78 FR 33754 - Railroad Workplace Safety; Adjacent-Track On-Track Safety for Roadway Workers

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-05

... Workers AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Final... published November 30, 2011, and scheduled to take effect on July 1, 2013. The final rule mandates that roadway workers comply with specified on-track safety procedures that railroads must adopt to protect...

75 FR 47458 - TRICARE; Rare Diseases Definition

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... TRICARE; Rare Diseases Definition AGENCY: Office of the Secretary, DoD. ACTION: Final rule. SUMMARY: This final rule revises the definition of rare diseases to adopt the definition of a rare disease as promulgated by the National Institutes of Health, Office of Rare Diseases. The rule modification will result...

76 FR 72327 - NASA Federal Acquisition Regulation Supplement; Responsibility, Suspension and Debarment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

.... chapter 35). List of Subjects in 48 CFR Part 1809 Government procurement. Sheryl Goddard, Director... Space Administration (NASA). ACTION: Final rule. SUMMARY: NASA has adopted as final, without change, a... INFORMATION CONTACT: Leigh Pomponio, Procurement Analyst, at (202) 358-0592 or [email protected

76 FR 14570 - Federal Acquisition Regulation; Trade Agreements Thresholds

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-16

... application of the World Trade Organization Government Procurement Agreement and the Free Trade Agreements, as... Parts 22, 25, and 52 Government procurement. Dated: March 4, 2011. Millisa Gary, Acting Director, Office... (NASA). ACTION: Final rule. SUMMARY: DoD, GSA, and NASA have adopted as final, without change, an...

76 FR 35111 - Final Flood Elevation Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-16

... final for the communities listed below. The BFEs and modified BFEs are the basis for the floodplain management measures that each community is required either to adopt or to show evidence of being already in... BFEs for each community. This date may be obtained by contacting the office where the maps are...

75 FR 36395 - Guidance on Sound Incentive Compensation Policies

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-25

... response to comments. For example, the final guidance includes several provisions designed to reduce burden..., FDIC and OTS (collectively, the Agencies) are adopting final guidance designed to help ensure that... risks that are not consistent with the long-term health of the organization. For example, offering large...

76 FR 16531 - Country of Origin of Textile and Apparel Products; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-24

... RIN 1505-AB60) Country of Origin of Textile and Apparel Products; Correction AGENCIES: U.S. Customs and Border Protection, Department of Homeland Security; Department of the Treasury. ACTION: Final rule..., a document which adopted as a final rule, with some changes, interim amendments to the CBP...

76 FR 38552 - Amendments to Regulations Regarding Major Life-Changing Events Affecting Income-Related Monthly...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... to Regulations Regarding Major Life-Changing Events Affecting Income-Related Monthly Adjustment.... SUMMARY: This final rule adopts, without change, the interim final rule with request for comments we... consider major life-changing events for the Medicare Part B income- related monthly adjustment amount...

76 FR 1603 - Agency Information Collection Activities: Proposed Collection, Comment Request: Reporting of Pre...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-11

...The Commodity Futures Trading Commission (``Commission'' or ``CFTC'') is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act (``PRA''), 44 U.S.C. 3501 et seq., Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information and to allow 60 days for public comment. The Commission recently adopted an interim final rule, as required by the Wall Street Reform and Consumer Protection Act (``Dodd-Frank Act''), requiring counterparties to a pre-enactment unexpired swap to report such swaps according to such rules as the Commission may in the future adopt. This notice solicits comments on the record retention requirement that is embedded in the interim final rule's reporting requirement, which was recognized by the Commission in an interpretive note to the final rule.

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

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

Zachary-Fort Lauderdale pipeline construction and conversion project: final supplement to final environmental impact statement. Docket No. CP74-192

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

None

This Final Supplement to the Final Environmental Impact Statement (Final Supplement) evaluates the economic, engineering, and environmental aspects of newly developed alternatives to an abandonment/conversion project proposed by Florida Gas Transmission Company (Florida Gas). It also updates the staff's previous FEIS and studies revisions to the original proposal. Wherever possible, the staff has adopted portions of its previous FEIS in lieu of reprinting portions of that analysis which require no change. 60 references, 8 figures, 35 tables.

Current good manufacturing practices, quality control procedures, quality factors, notification requirements, and records and reports, for infant formula. Final rule.

PubMed

2014-06-10

The Food and Drug Administration (FDA or we) is issuing a final rule that adopts, with some modifications, the interim final rule (IFR) entitled "Current Good Manufacturing Practices, Quality Control Procedures, Quality Factors, Notification Requirements, and Records and Reports, for Infant Formula'' (February 10, 2014). This final rule affirms the IFR's changes to FDA's regulations and provides additional modifications and clarifications. The final rule also responds to certain comments submitted in response to the request for comments in the IFR.

Graphoepitaxy integration and pattern transfer of lamellar silicon-containing high-chi block copolymers

NASA Astrophysics Data System (ADS)

Bézard, P.; Chevalier, X.; Legrain, A.; Navarro, C.; Nicolet, C.; Fleury, G.; Cayrefourcq, I.; Tiron, R.; Zelsmann, M.

2018-03-01

In this work, we present our recent achievements on the integration and transfer etching of a novel silicon-containing high-χ block copolymer for lines/spaces applications. Developed carbo-silane BCPs are synthesized under industrial conditions and present periodicities as low as 14 nm. A full directed self-assembly by graphoepitaxy process is shown using standard photolithography stacks and all processes are performed on 300 mm wafer compatible tools. Specific plasma processes are developed to isolate perpendicular lamellae and sub-12 nm features are finally transferred into silicon substrates. The quality of the final BCP hard mask (CDU, LWR, LER) are also investigated. Finally, thanks to the development of dedicated neutral layers and top-coats allowing perpendicular orientations, it was possible to investigate plasma etching experiments on full-sheets at 7 nm resolution, opening the way to the integration of these polymers in chemoepitaxy stacks.

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)

What's new in the proton transfer reaction from pyranine to water? A femtosecond study of the proton transfer dynamics

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

Prayer, C.; Gustavsson, T.; Tran-Thi, T.-H.

1996-04-01

The proton transfer from excited pyranine to water is studied by the femtosecond fluorescence upconversion technique. It is shown for the first time that the proton transfer reaction in water proceeds by three successive steps: the solvent cage relaxation, the specific solute-solvent hydrogen-bond formation and finally the ion pair dissociation/diffusion.

"To Finally Understand How to Do Well Is the Hardest Part": Seeing the Transfer Journey, Research and Research-Inclusive Careers through the Eyes of Undergraduate Transfer Students Pursuing Science Majors

ERIC Educational Resources Information Center

Ewers, Tola Latola Marie

2014-01-01

This multi-case qualitative study explored how University of Wisconsin-Madison (UW-Madison) undergraduate science major transfer students' backgrounds, transfer journey, previous research and/or other academic experiences and future aspirations shaped perceptions and beliefs about research, research-inclusive careers and integration and engagement…

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.

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

Observations of Diurnal to Weekly Variations of Monoterpene-Dominated Fluxes of Volatile Organic Compounds from Mediterranean Forests: Implications for Regional Modeling

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

Fares, Silvano; Schnitzhofer, Ralf; Jiang, Xiaoyan

2013-10-01

The Estate of Castelporziano (Rome, Italy) hosts many ecosystems representative of Mediterranean vegetation, especially holm oak and pine forests and dune vegetation. In this work, basal emission factors (BEFs) of biogenic volatile organic compounds (BVOCs) obtained by Eddy Covariance in a field campaign using a proton transfer reaction–time-of-flight–mass spectrometer (PTR-TOF-MS) were compared to BEFs reported in previous studies that could not measure fluxes in real-time. Globally, broadleaf forests are dominated by isoprene emissions, but these Mediterranean ecosystems are dominated by strong monoterpene emitters, as shown by the new BEFs. The original and new BEFs were used to parametrize the modelmore » of emissions of gases and aerosols from nature (MEGAN v2.1), and model outputs were compared with measured fluxes. Results showed good agreement between modeled and measured fluxes when a model was used to predict radiative transfer and energy balance across the canopy. We then evaluated whether changes in BVOC emissions can affect the chemistry of the atmosphere and climate at a regional level. MEGAN was run together with the land surface model (community land model, CLM v4.0) of the community earth system model (CESM v1.0). Finally, results highlighted that tropospheric ozone concentration and air temperature predicted from the model are sensitive to the magnitude of BVOC emissions, thus demonstrating the importance of adopting the proper BEF values for model parametrization.« less

Sensing mechanism of SnO2/ZnO nanofibers for CH3OH sensors: heterojunction effects

NASA Astrophysics Data System (ADS)

Tang, Wei

2017-11-01

SnO2/ZnO composite nanofibers were synthesized by a simple electrospinning method. The prepared SnO2/ZnO gas sensors exhibited good linear and high response to methanol. The enhanced sensing behavior of SnO2/ZnO might be associated with the homotypic heterojunction effects formed in n-SnO2/n-ZnO nanograins boundaries. In addition, the possible sensing mechanisms of methanol on SnO2/ZnO surface were investigated by density functional theory in order to make the methanol adsorption and desorption process clear. Zn doped SnO2 model was adopted to approximate the SnO2/ZnO structure because of the calculation power limitations. Calculation results showed that when exposed to methanol, the methanol would react with bridge oxygen O2c , planar O3c and pre adsorbed oxygen vacancy on the lattice surface. The -CH3 and -OH of methanol molecule would both lose one H atom. The lost H atoms bonded with oxygen at the adsorption sites. The final products were HCHO and H2O. Electrons were transferred from methanol to the lattice surface to reduce the resistance of semiconductor gas sensitive materials, which is in agreement with the experimental phenomena. More adsorption models of other interfering gases, such as ethanol, formaldehyde and acetone will be built and calculated to explain the selectivity issue from the perspective of adsorption energy, transferred charge and density of states in the future work.

Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response

PubMed Central

Blasco-Baque, Vincent; Garidou, Lucile; Pomié, Céline; Escoula, Quentin; Loubieres, Pascale; Le Gall-David, Sandrine; Lemaitre, Mathieu; Nicolas, Simon; Klopp, Pascale; Waget, Aurélie; Azalbert, Vincent; Colom, André; Bonnaure-Mallet, Martine; Kemoun, Philippe; Serino, Matteo; Burcelin, Rémy

2017-01-01

Objective To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. Design We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Results Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. PMID:26838600

Transfer of Dicamba Tolerance from Sinapis arvensis to Brassica napus via Embryo Rescue and Recurrent Backcross Breeding.

PubMed

Jugulam, M; Ziauddin, Asma; So, Kenny K Y; Chen, Shu; Hall, J Christopher

2015-01-01

Auxinic herbicides (e.g. dicamba) are extensively used in agriculture to selectively control broadleaf weeds. Although cultivated species of Brassicaceae (e.g. Canola) are susceptible to auxinic herbicides, some biotypes of Sinapis arvensis (wild mustard) were found dicamba resistant in Canada. In this research, dicamba tolerance from wild mustard was introgressed into canola through embryo rescue followed by conventional breeding. Intergeneric hybrids between S. arvensis (2n = 18) and B. napus (2n = 38) were produced through embryo rescue. Embryo formation and hybrid plant regeneration was achieved. Transfer of dicamba tolerance from S. arvensis into the hybrid plants was determined by molecular analysis and at the whole plant level. Dicamba tolerance was introgressed into B. napus by backcrossing for seven generations. Homozygous dicamba-tolerant B. napus lines were identified. The ploidy of the hybrid progeny was assessed by flow cytometry. Finally, introgression of the piece of DNA possibly containing the dicamba tolerance gene into B. napus was confirmed using florescence in situ hybridization (FISH). This research demonstrates for the first time stable introgression of dicamba tolerance from S. arvensis into B. napus via in vitro embryo rescue followed by repeated backcross breeding. Creation of dicamba-tolerant B. napus varieties by this approach may have potential to provide options to growers to choose a desirable herbicide-tolerant technology. Furthermore, adoption of such technology facilitates effective weed control, less tillage, and possibly minimize evolution of herbicide resistant weeds.

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.

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

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