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

PubMed Central

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

2016-01-01

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

Adoptive transfer of acute lung injury.

PubMed

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

2000-11-01

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

The Transfer of Training at Macro Level in Least Developed Countries: A Case Study of the "Brain-Drain" in Eritrea

ERIC Educational Resources Information Center

Tessema, Mussie T.; Winrow, Brian P.; Teclezion, Mussie M.

2012-01-01

Over the past four decades, governments in the least developed countries (LDCs--a categorization adopted by the United Nations) have been attempting to improve the skills and knowledge of their public servants by providing local and international training programs. Despite these training activities, however, many LDCs continue to experience acute…

Effetive methods in educating extension agents and farmers on conservation farming technology

USDA-ARS?s Scientific Manuscript database

Adoption of new technologies requires transfer of information from developers to end users. Efficiency of the transfer process influences the rate of adoption and ultimate impact of the technology. Various channels are used to transfer technology from researchers to farmers. Two commonly used ones ...

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

Cost Savings Associated with the Adoption of a Cloud Computing Data Transfer System for Trauma Patients.

PubMed

Feeney, James M; Montgomery, Stephanie C; Wolf, Laura; Jayaraman, Vijay; Twohig, Michael

2016-09-01

Among transferred trauma patients, challenges with the transfer of radiographic studies include problems loading or viewing the studies at the receiving hospitals, and problems manipulating, reconstructing, or evalu- ating the transferred images. Cloud-based image transfer systems may address some ofthese problems. We reviewed the charts of patients trans- ferred during one year surrounding the adoption of a cloud computing data transfer system. We compared the rates of repeat imaging before (precloud) and af- ter (postcloud) the adoption of the cloud-based data transfer system. During the precloud period, 28 out of 100 patients required 90 repeat studies. With the cloud computing transfer system in place, three out of 134 patients required seven repeat films. There was a statistically significant decrease in the proportion of patients requiring repeat films (28% to 2.2%, P < .0001). Based on an annualized volume of 200 trauma patient transfers, the cost savings estimated using three methods of cost analysis, is between $30,272 and $192,453.

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

PubMed

Masterson, Kate; Brenner, Maria

2016-05-01

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

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

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

PubMed Central

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

2013-01-01

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

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.

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

PubMed Central

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

2014-01-01

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

18 CFR 341.6 - Adoption rule.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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

PubMed

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

2017-07-01

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

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

PubMed Central

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

2017-01-01

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

Natural convection during heat energy accumulation by substances that change their state of aggregation

NASA Astrophysics Data System (ADS)

Chukaev, A. G.; Kuks, A. M.

Heat transfer calculations are presented for a heat accumulator using the melting heat of a substance which changes its state of aggregation. It is shown that the approach adopted here makes it possible to evaluate the efficiency of using heat-storage materials in the pipe-tank system. The calculations, which allow for the effect of free convection in the liquid phase, have been made using the Boussinesq approximation. Results of a numerical experiment for NaNO3 salt show that the effect of natural convection on heat transfer is significant and that the heat flux to the material decreases as heat accumulates.

Natural convection during heat accumulation by substances with change of aggregate state

NASA Astrophysics Data System (ADS)

Chukayev, A. G.; Kuks, A. M.

1985-03-01

Heat transfer calculations are presented for a heat accumulator using the melting heat of a substance which changes its state of aggregation. It is shown that the approach adopted here makes it possible to evaluate the efficiency of using heat-storage materials in the pipe-tank system. The calculations, which allow for the effect of free convection in the liquid phase, have been made using the Boussinesq approximation. Results of a numerical experiment for NaNO3 salt show that the effect of natural convection on heat transfer is significant and that the heat flux to the material decreases as heat accumulates.

A conceptual framework for transferring research to practice.

PubMed

Simpson, D Dwayne

2002-06-01

Systematic evaluations of efforts to transfer research-based interventions and procedures into general practice at community drug treatment programs have been limited. However, practical experiences as well as results from studies of technology transfer and organizational behavior in related fields provide a basis for proposing a heuristic model of key factors that influence this process. The successful completion of four stages of activity typically involved in program change (exposure, adoption, implementation, and practice of new interventions) appears to be influenced by several organizational considerations (e.g., institutional readiness for change, resources, and climate) as well as staff attributes. Assessment instruments for measuring organizational functioning (based on ratings aggregated for staff and patients in a program) are introduced, along with preliminary evidence for their validity. A better conceptual understanding of the process of program change and common barriers that may be encountered is needed for effectively transferring research to practice.

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

Early development of abstract language knowledge: evidence from perception–production transfer of birth-language memory

PubMed Central

Cutler, Anne; Broersma, Mirjam

2017-01-01

Children adopted early in life into another linguistic community typically forget their birth language but retain, unaware, relevant linguistic knowledge that may facilitate (re)learning of birth-language patterns. Understanding the nature of this knowledge can shed light on how language is acquired. Here, international adoptees from Korea with Dutch as their current language, and matched Dutch-native controls, provided speech production data on a Korean consonantal distinction unlike any Dutch distinctions, at the outset and end of an intensive perceptual training. The productions, elicited in a repetition task, were identified and rated by Korean listeners. Adoptees' production scores improved significantly more across the training period than control participants' scores, and, for adoptees only, relative production success correlated significantly with the rate of learning in perception (which had, as predicted, also surpassed that of the controls). Of the adoptee group, half had been adopted at 17 months or older (when talking would have begun), while half had been prelinguistic (under six months). The former group, with production experience, showed no advantage over the group without. Thus the adoptees' retained knowledge of Korean transferred from perception to production and appears to be abstract in nature rather than dependent on the amount of experience. PMID:28280567

T cells targeting a neuronal paraneoplastic antigen mediate tumor rejection and trigger CNS autoimmunity with humoral activation.

PubMed

Blachère, Nathalie E; Orange, Dana E; Santomasso, Bianca D; Doerner, Jessica; Foo, Patricia K; Herre, Margaret; Fak, John; Monette, Sébastien; Gantman, Emily C; Frank, Mayu O; Darnell, Robert B

2014-11-01

Paraneoplastic neurologic diseases (PND) involving immune responses directed toward intracellular antigens are poorly understood. Here, we examine immunity to the PND antigen Nova2, which is expressed exclusively in central nervous system (CNS) neurons. We hypothesized that ectopic expression of neuronal antigen in the periphery could incite PND. In our C57BL/6 mouse model, CNS antigen expression limits antigen-specific CD4+ and CD8+ T-cell expansion. Chimera experiments demonstrate that this tolerance is mediated by antigen expression in nonhematopoietic cells. CNS antigen expression does not limit tumor rejection by adoptively transferred transgenic T cells but does limit the generation of a memory population that can be expanded upon secondary challenge in vivo. Despite mediating cancer rejection, adoptively transferred transgenic T cells do not lead to paraneoplastic neuronal targeting. Preliminary experiments suggest an additional requirement for humoral activation to induce CNS autoimmunity. This work provides evidence that the requirements for cancer immunity and neuronal autoimmunity are uncoupled. Since humoral immunity was not required for tumor rejection, B-cell targeting therapy, such as rituximab, may be a rational treatment option for PND that does not hamper tumor immunity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Adoption research, practice, and societal trends: Ten years of progress.

PubMed

Wiley, Mary O'Leary

2017-12-01

Adoption involves the legal transfer of parental rights and responsibilities from a child's birth parents to adults who will raise the child (Reitz & Watson, 1992). Research related to adoption has expanded over the past 10 years and has incorporated more focus on implications for practice and public policy. This expansion has reflected increased awareness of the lived experience of adopted individuals, in addition to that of adoptive families and birth or first parents and families, collectively known as the adoption kinship network (Grotevant & McRoy, 1998). Trends discussed included research and social trends or movements (2007-2017) since the publication of the final article in a series of articles in the psychological literature related to adoption in The Counseling Psychologist (Baden & Wiley, 2007; Lee, 2003; O'Brien & Zamostny, 2003; Wiley & Baden, 2005; Zamostny, O'Brien, Baden, & Wiley, 2003; Zamostny, Wiley, O'Brien, Lee, & Baden, 2003). This article summarizes the social trends and research related to adoption over the last 10 years, including longitudinal and meta-analytic studies, increased research and conceptualization of ethnic and racial identity development, research on microaggressions, and research on diverse adoptive families, including those with gay and lesbian parents. Social trends included increased knowledge related to Internet accessibility, genetic information, continued focus on openness, and viewing adoption through a more critical lens. Implications are discussed for the development of programs that enhance competence of mental health professionals and adoption professionals in adoption-competent practice. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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)

The importance of training strategy adaptation: a learner-oriented approach for improving older adults' memory and transfer.

PubMed

Bottiroli, Sara; Cavallini, Elena; Dunlosky, John; Vecchi, Tomaso; Hertzog, Christopher

2013-09-01

We investigated the benefits of strategy-adaptation training for promoting transfer effects. This learner-oriented approach--which directly encourages the learner to generalize strategic behavior to new tasks--helps older adults appraise new tasks and adapt trained strategies to them. In Experiment 1, older adults in a strategy-adaptation training group used 2 strategies (imagery and sentence generation) while practicing 2 tasks (list and associative learning); they were then instructed on how to do a simple task analysis to help them adapt the trained strategies for 2 different unpracticed tasks (place learning and text learning) that were discussed during training. Two additional criterion tasks (name-face associative learning and grocery-list learning) were never mentioned during training. Two other groups were included: A strategy training group (who received strategy training and transfer instructions but not strategy-adaptation training) and a waiting-list control group. Both training procedures enhanced older adults' performance on the trained tasks and those tasks that were discussed during training, but transfer was greatest after strategy-adaptation training. Experiment 2 found that strategy-adaptation training conducted via a manual that older adults used at home also promoted transfer. These findings demonstrate the importance of adopting a learner-oriented approach to promote transfer of strategy training. PsycINFO Database Record (c) 2013 APA, all rights reserved.

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)

[Reaction time tests in Leipzig, Paris and Würzburg. The Franco-German history of a psychological experiment, 1890-1910].

PubMed

Carroy, Jacqueline; Schmidgen, Henning

2004-01-01

This article diiscusses from a comparative perspective the complex history of the reaction experiment with the Hipp chronoscope, one of the central experiments of late 19th-century psychology. It focuses on Wilhelm Wundt's (1832-1920) Institute for Experimental Psychology in Leipzig and on the Paris Laboratory for Physiological Psychology at the Sorbonne, which was initially directed by Henry Beaunis (1830-1921), but soon came to be dominated by the research activities of Alfred Binet (1857-1911). When the Paris psychologists founded their Laboratory in 1889, they took the Leipzig Institute as their model. In the early 1890s they adopted the reaction time experiment that had been central to Wundt's psychology. Shortly after, they modified this experiment according to their own specific interests. For Binet, it no longer served as a method for identifying the elementary components of "general" consciousness (as in Wundt), but for classifying "individual" personalities. The methodological and technological changes that Binet introduced into the experimental practice of psychology had no immediate impact on the research work in Leipzig. However, they influenced the "Wurzburg School" of psychology under Wundt's former assistant, Oswald Külpe (1862-1915). This illustrates that the comparative history of transfers of "experimental systems" (Rheinberger) across national borders is not simply a history of mere transports. Rather, it is a history of transferences that sometimes includes surprising "re-transferences".

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…

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…

Experimental and numerical investigation on heat transfer augmentation in a circular tube under forced convection with annular differential blockages/inserts

NASA Astrophysics Data System (ADS)

Waghole, D. R.

2018-06-01

Investigation on heat transfer by generating turbulence in the fluid stream inside the circular tube is an innovative area of research for researchers. Hence, many techniques are been investigated and adopted for enhancement of heat transfer rate to reduce the size and the cost of the heat exchanger/circular tube. In the present study the effect of differential solid ring inserts /turbulators on heat transfer, friction factor of heat exchanger/circular tube was evaluated through experimentally and numerically. The experiments were conducted in range of 3000 ≤Re≤ 6500 and annular blockages 0 ≤ɸ≤50 %. The heat transfer rate was higher for differential combination of inserts as compared to tube fitted with uniform inserts. The maximum heat transfer was obtained by the use of differential metal circular ring inserts/blockages. From this study, Nusselt number, friction factor and enhancement factor are found as 2.5-3.5 times, 12% - 50.5% and 155% - 195%, respectively with water. Finally new possible correlations for predicting heat transfer and friction factor in the flow of water through the circular tube with differential blockages/inserts are proposed.

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

Aberrant muscle antigen exposure in mice is sufficient to cause myositis in a Treg cell-deficient milieu.

PubMed

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

2013-12-01

Myositis is associated with muscle-targeted inflammation and is observed in some Treg cell-deficient mouse models. Because an autoimmune pathogenesis has been strongly implicated, the aim of this study was to investigate the hypothesis that abnormal exposure to muscle antigens, as observed in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts. FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII) mutant mice, which resulted in a new mouse strain that combines impaired membrane resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant mice were adoptively transferred intraperitoneally, with or without purified Treg cells, into recombination-activating gene 1 (RAG-1)-null recipients. Lymph node cells from mice with the FoxP3 mutation were transferred into RAG-1-null mice either 1) intraperitoneally in conjunction with muscle homogenate or purified myosin protein or 2) intramuscularly with or without cotransfer of purified Treg cells. FoxP3-deficient mouse lymph node cells transferred in conjunction with myosin protein or muscle homogenate induced robust skeletal muscle inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a limited number of macrophages, and no B cells. Significant inflammation was also seen in similar experiments using lymph node cells from FoxP3/Syt VII double-mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant mouse cells alone. The cotransfer of Treg cells completely suppressed myositis. These data, derived from a new, reproducible model, demonstrate the critical roles of Treg cell deficiency and aberrant muscle antigen exposure in the priming of autoreactive cells to induce myositis. This mouse system has multifaceted potential for examining the interplay in vivo between tissue injury and autoimmunity. © 2013 The Authors. Arthritis & Rheumatism is published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

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

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.

Multiagent Reinforcement Learning With Sparse Interactions by Negotiation and Knowledge Transfer.

PubMed

Zhou, Luowei; Yang, Pei; Chen, Chunlin; Gao, Yang

2017-05-01

Reinforcement learning has significant applications for multiagent systems, especially in unknown dynamic environments. However, most multiagent reinforcement learning (MARL) algorithms suffer from such problems as exponential computation complexity in the joint state-action space, which makes it difficult to scale up to realistic multiagent problems. In this paper, a novel algorithm named negotiation-based MARL with sparse interactions (NegoSIs) is presented. In contrast to traditional sparse-interaction-based MARL algorithms, NegoSI adopts the equilibrium concept and makes it possible for agents to select the nonstrict equilibrium-dominating strategy profile (nonstrict EDSP) or meta equilibrium for their joint actions. The presented NegoSI algorithm consists of four parts: 1) the equilibrium-based framework for sparse interactions; 2) the negotiation for the equilibrium set; 3) the minimum variance method for selecting one joint action; and 4) the knowledge transfer of local Q -values. In this integrated algorithm, three techniques, i.e., unshared value functions, equilibrium solutions, and sparse interactions are adopted to achieve privacy protection, better coordination and lower computational complexity, respectively. To evaluate the performance of the presented NegoSI algorithm, two groups of experiments are carried out regarding three criteria: 1) steps of each episode; 2) rewards of each episode; and 3) average runtime. The first group of experiments is conducted using six grid world games and shows fast convergence and high scalability of the presented algorithm. Then in the second group of experiments NegoSI is applied to an intelligent warehouse problem and simulated results demonstrate the effectiveness of the presented NegoSI algorithm compared with other state-of-the-art MARL algorithms.

VOLATILIZATION RATES FROM WATER TO INDOOR AIR ...

EPA Pesticide Factsheets

Contaminated water can lead to volatilization of chemicals to residential indoor air. Previous research has focused on only one source (shower stalls) and has been limited to chemicals in which gas-phase resistance to mass transfer is of marginal significance. As a result, attempts to extrapolate chemical emissions from high-volatility chemicals to lower volatility chemicals, or to sources other than showers, have been difficult or impossible. This study involved the development of two-phase, dynamic mass balance models for estimating chemical emissions from washing machines, dishwashers, and bathtubs. An existing model was adopted for showers only. Each model required the use of source- and chemical-specific mass transfer coefficients. Air exchange (ventilation) rates were required for dishwashers and washing machines as well. These parameters were estimated based on a series of 113 experiments involving 5 tracer chemicals (acetone, ethyl acetate, toluene, ethylbenzene, and cyclohexane) and 4 sources (showers, bathtubs, washing machines, and dishwashers). Each set of experiments led to the determination of chemical stripping efficiencies and mass transfer coefficients (overall, liquid-phase, gas-phase), and to an assessment of the importance of gas- phase resistance to mass transfer. Stripping efficiencies ranged from 6.3% to 80% for showers, 2.6% to 69% for bathtubs, 18% to 100% for dishwashers, and 3.8% to 100% for washing machines. Acetone and cyclohexane al

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Endogenous T-Cell Therapy: Clinical Experience.

PubMed

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

2015-01-01

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

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

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.

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.

The Study of Micro-Pressure Inner-Loop Bioreactor Oxygen Mass Transfer Characteristics

NASA Astrophysics Data System (ADS)

Wan, L. G.; Lin, Q.; Bian, D. J.; Ren, Q. K.; Xiao, Y. B.; Lu, W. X.

2018-03-01

The oxygen mass transfer characteristics in a Micro-Pressure Inner-Loop bioreactor (MPR) were studied by clean water oxygenation experiment, the results show that when the aeration adopt by 0.1, 0.2, 0.4, 0.6 m3·h-1, respectively, the oxygen mass transfer coefficient KLa(20) in the reactor increases with the increase of the aeration. KLa(20) shows a good linear correlation with the aeration. The rate is 0.2128 h·m-3·min-1 and the correlation coefficient R=0.993. However, the trend of EO2 increases first and then decreases with the increase of aeration. When the aeration increased to 0.4 m3·h-1, the EO2 reaches the maximum. If aeration increases constantly, EO2 begin to decrease excessive aeration may lead to an increase in energy waste during reactor operation.

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

Keren, Y.; Bemporad, G.A.; Rubin, H.

This paper concerns an experimental evaluation of the basic aspects of operation of the advanced solar pond (ASP). Experiments wee carried out in a laboratory test section in order to assess the feasibility of the density gradient maintenance in stratified flowing layers. The density stratification was caused by a non uniform distribution of temperatures in the flow field. Results of the experiments are reported and analyzed in the paper. Experimental data were used in order to calibrate the numerical model able to simulate heat and momentum transfer in the ASP. The numerical results confirmed the validity of the numerical modelmore » adopted, and proved the latter applicability for the simulation of the ASP performance.« less

Solar power satellite system definition study. Volume 5: Space transportation analysis, phase 3

NASA Technical Reports Server (NTRS)

1980-01-01

A small Heavy Lift Launch Vehicle (HLLV) for the Solar Power Satellites (SPS) System was analyzed. It is recommended that the small HLLV with a payload of 120 metric tons be adopted as the SPS launch vehicle. The reference HLLV, a shuttle-derived option with a payload of 400 metric tons, should serve as a backup and be examined further after initial flight experience. The electric orbit transfer vehicle should be retained as the reference orbit-to-orbit cargo system.

Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

PubMed Central

Oka, Hisaki

2016-01-01

Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature. PMID:27173144

Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

NASA Astrophysics Data System (ADS)

Oka, Hisaki

2016-05-01

Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation.

PubMed

Oka, Hisaki

2016-05-13

Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

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.

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.

The interaction between practice and performance pressure on the planning and control of fast target directed movement.

PubMed

Allsop, Jonathan E; Lawrence, Gavin P; Gray, Robert; Khan, Michael A

2017-09-01

Pressure to perform often results in decrements to both outcome accuracy and the kinematics of motor skills. Furthermore, this pressure-performance relationship is moderated by the amount of accumulated practice or the experience of the performer. However, the interactive effects of performance pressure and practice on the underlying processes of motor skills are far from clear. Movement execution involves both an offline pre-planning process and an online control process. The present experiment aimed to investigate the interaction between pressure and practice on these two motor control processes. Two groups of participants (control and pressure; N = 12 and 12, respectively) practiced a video aiming amplitude task and were transferred to either a non-pressure (control group) or a pressure condition (pressure group) both early and late in practice. Results revealed similar accuracy and movement kinematics between the control and pressure groups at early transfer. However, at late transfer, the introduction of pressure was associated with increased performance compared to control conditions. Analysis of kinematic variability throughout the movement suggested that the performance increase was due to participants adopting strategies to improve movement planning in response to pressure reducing the effectiveness of the online control system.

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

PubMed Central

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

2007-01-01

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

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

DTIC Science & Technology

1976-05-01

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

Use of the Delay-Tolerant Networking Bundle Protocol from Space

NASA Technical Reports Server (NTRS)

Wood, Lloyd; Ivancic, William D.; Eddy, Wesley M.; Stewart, Dave; Northam, James; Jackson, Chris; daSilvaCuriel, Alex

2009-01-01

The Disaster Monitoring Constellation (DMC), constructed by Survey Satellite Technology Ltd (SSTL), is a multisatellite Earth-imaging low-Earth-orbit sensor network where captured image swaths are stored onboard each satellite and later downloaded from the satellite payloads to a ground station. Store-and-forward of images with capture and later download gives each satellite the characteristics of a node in a Delay/Disruption Tolerant Network (DTN). Originally developed for the Interplanetary Internet, DTNs are now under investigation in an Internet Research Task Force (IRTF) DTN research group (RG), which has developed a bundle architecture and protocol. The DMC is currently unique in its adoption of the Internet Protocol (IP) for its imaging payloads and for satellite command and control, based around reuse of commercial networking and link protocols. These satellites use of IP has enabled earlier experiments with the Cisco router in Low Earth Orbit (CLEO) onboard the constellation's UK-DMC satellite. Earth images are downloaded from the satellites using a custom IPbased high-speed transfer protocol developed by SSTL, Saratoga, which tolerates unusual link environments. Saratoga has been documented in the Internet Engineering Task Force (IETF) for wider adoption. We experiment with use of DTNRG bundle concepts onboard the UKDMC satellite, by examining how Saratoga can be used as a DTN convergence layer to carry the DTNRG Bundle Protocol, so that sensor images can be delivered to ground stations and beyond as bundles. This is the first successful use of the DTNRG Bundle Protocol in a space environment. We use our practical experience to examine the strengths and weaknesses of the Bundle Protocol for DTN use, paying attention to fragmentation, custody transfer, and reliability issues.

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

Development of a software for the design of custom-made hip prostheses using an open-source rapid application development environment.

PubMed

Viceconti, M; Testi, D; Gori, R; Zannoni, C

2000-01-01

The present work describes a technology transfer project called HIPCOM devoted to the re-engineering of the process used by a medical devices manufacturer to design custom-made hip prostheses. Although it started with insufficient support from the end-user management, a very tight scheduling and a moderate budget, the project developed into what is considered by all partners a success story. In particular, the development of the design software, called HIPCOM Interactive Design Environment (HIDE) was completed in a time shorter than any optimistic expectation. The software was quite stable since its first beta version, and once introduced at the user site it fully replaced the original procedure in less than two months. One year after the early adoption, more than 80 custom-made prostheses had been designed with HIDE and the user had reported only two bugs, both cosmetics. The scope of the present work was to report the development experience and to investigate the reasons for these positive results, with particular reference to the development procedure and the software architecture. The choice of TCL/TK as development language and the adoption of well-defined software architecture were found to be the success key factors. Other important determinants were found to be the adoption of an incremental software engineering strategy, well suited for small to medium projects and the presence in the development staff of a technology transfer expert.

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

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

PubMed Central

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

2015-01-01

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

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

The critical success factors and impact of prior knowledge to nursing students when transferring nursing knowledge during nursing clinical practise.

PubMed

Tsai, Ming-Tien; Tsai, Ling-Long

2005-11-01

Nursing practise plays an important role in transferring nursing knowledge to nursing students. From the related literature review, prior knowledge will affect how learners gain new knowledge. There has been no direct examination of the prior knowledge interaction effect on students' performance and its influence on nursing students when evaluating the knowledge transfer success factors. This study explores (1) the critical success factors in transferring nursing knowledge, (2) the impact of prior knowledge when evaluating the success factors for transferring nursing knowledge. This research utilizes in-depth interviews to probe the initial success factor phase. A total of 422 valid questionnaires were conducted by the authors. The data were analysed by comparing the mean score and t-test between two groups. Seventeen critical success factors were identified by the two groups of students. Twelve items were selected to examine the diversity in the two groups. Students with prior knowledge were more independent than the other group. They also preferred self-directed learning over students without prior knowledge. Students who did not have prior knowledge were eager to take every opportunity to gain experience and more readily adopted new knowledge.

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

PubMed

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

2018-01-01

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

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…

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

ERIC Educational Resources Information Center

Beauregard, Caroline; Rousseau, Cécile; Mustafa, Sally

2015-01-01

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

Immunotherapeutic Strategies in Breast Cancer: Preclinical and Clinical Trials

DTIC Science & Technology

2005-09-01

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

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

PubMed

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

2015-10-01

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

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

PubMed

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

2017-09-01

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

Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

PubMed Central

Brody, Joshua; Levy, Ronald

2017-01-01

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

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

PubMed

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

2010-03-26

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

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.

Mode-of-action, efficacy, and safety of a homologous multi-epitope vaccine in a murine model for adjuvant treatment of renal cell carcinoma.

PubMed

Doehn, Christian; Esser, Norbert; Pauels, Hans-Gerd; Kiessig, Stephan T; Stelljes, Matthias; Grossmann, Armin; Jocham, Dieter; Drevs, Joachim

2009-07-01

In a phase-III trial it was recently shown that an adjuvant renal cell carcinoma (RCC) vaccine (Reniale) reduces the risk of tumour progression following nephrectomy. This clinical trial focused on efficacy and did not investigate end-points relating to mode-of-action of the vaccine. In a murine model we investigated mode-of-action, efficacy, and safety of a homologous RENCA cell-based vaccine. Six groups with 12 BALB/c mice per group received five vaccinations (lysate of 1x10(6)-1x10(7) RENCA cells, manufactured with or without prior IFN-gamma incubation) at 3-wk intervals before tumour transplantation and one vaccination 14 d afterwards. Controls (12 mice) received only solvent. All mice were sacrificed 21 d after tumour transplantation. Animal welfare, tumour growth, number of metastases, and the presence of cytotoxic T-lymphocytes as determined by a (51)chromium-release assay. Adoptive immune transfer experiments (vaccination of nine mice with the RENCA vaccine or saline and transfer of serum, spleen cells, and CD4 and/or CD8 depleted spleen cells into five recipient mice each) were carried out to demonstrate involvement of different immune mechanisms. All controls developed a renal tumour, compared to 7/72 animals (9.7%) in the vaccine groups. The mean number of lung metastases was 100 (range 3-750) in controls and 4 (range 0-196) in the vaccine groups, respectively. Tumour uptake and number of metastases were not related to the vaccine dose. The (51)chromium-release assay confirmed a significant tumour-specific cytolytic activity and marginally increased NK activity of splenocytes from vaccinated mice against RENCA cells compared to controls. Adoptive immune transfer experiments showed that the antitumoural effective immune mechanisms are cell-based. We could demonstrate the mode-of-action, efficacy, and safety of a homologous tumour vaccine in a RENCA model. These findings support the positive results from a phase-III trial with Reniale.

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.

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

NASA Astrophysics Data System (ADS)

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

2009-05-01

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

Impaired antibody response against T-dependent antigens in rhino mice.

PubMed

Takaoki, M; Kawaji, H

1980-05-01

The antibody response in rhino mice, which carry a mutant gene hrrh, to thymus-dependent (TD) or thymus-independent (TI) antigens was compared with that of phenotypically normal littermates. The magnitude of antibody response to TD antigens in rhino mice decreased as they grew up, whereas the antibody response to TI antigens in rhino mice was indistinguishable from that of littermates. A transfer of thymus cells from littermates to rhino mice resulted in the partial restoration of the responsiveness to TD antigens. The experiments employing adoptive transfer of spleen cells from rhino mice to the irradiated normal mice suggested that the hyporesponsiveness of TD antigens of adult rhino mice was mainly due to the defect in the T helper cell activities rather than either the increase of the suppressor cells or defects in other cell types.

The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

PubMed

Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

2004-11-15

Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

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.

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

PubMed

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

2009-03-01

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

Heat transfer in fish: are short excursions between habitats a thermoregulatory behaviour to exploit resources in an unfavourable thermal environment?

PubMed

Pépino, Marc; Goyer, Katerine; Magnan, Pierre

2015-11-01

Temperature is the primary environmental factor affecting physiological processes in ectotherms. Heat-transfer models describe how the fish's internal temperature responds to a fluctuating thermal environment. Specifically, the rate coefficient (k), defined as the instantaneous rate of change in body temperature in relation to the difference between ambient and body temperature, summarizes the combined effects of direct thermal conduction through body mass, passive convection (intracellular and intercellular fluids) and forced convective heat transfer (cardiovascular system). The k-coefficient is widely used in fish ecology to understand how body temperature responds to changes in water temperature. The main objective of this study was to estimate the k-coefficient of brook charr equipped with internal temperature-sensitive transmitters in controlled laboratory experiments. Fish were first transferred from acclimation tanks (10°C) to tanks at 14, 19 or 23°C (warming experiments) and were then returned to the acclimation tanks (10°C; cooling experiments), thus producing six step changes in ambient temperature. We used non-linear mixed models to estimate the k-coefficient. Model comparisons indicated that the model incorporating the k-coefficient as a function of absolute temperature difference (dT: 4, 9 and 13°C) best described body temperature change. By simulating body temperature in a heterogeneous thermal environment, we provide theoretical predictions of maximum excursion duration between feeding and resting areas. Our simulations suggest that short (i.e. <60 min) excursions could be a common thermoregulatory behaviour adopted by cold freshwater fish species to sustain body temperature below a critical temperature threshold, enabling them to exploit resources in an unfavourable thermal environment. © 2015. Published by The Company of Biologists Ltd.

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon’s perspective

PubMed Central

ZIPPEL, DOUGLAS B.; BESSER, MICHAL; SHAPIRA, RONI; BEN-NUN, ALON; GOITEIN, DAVID; DAVIDSON, TIMA; TREVES, ABRAHAM J.; MARKEL, GAL; SCHACHTER, JACOB; PAPA, MOSHE Z.

2012-01-01

Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel. Eligible patients underwent surgical consultation to determine what tumorectomy would be beneficial for harvesting appropriate tissue. Factors involved in the decision included tumor mass size, location and morbidity of the procedure. Between January 2006 and May 2010, 44 patients underwent 47 procedures of adoptive transfer of TILs. Three patients underwent the procedure twice for recurrence after initial good responses, including an additional surgical procedure to produce fresh tumor. Thirty-seven excisions were with general anesthesia and 10 were with local anesthesia. Of the 37 general anesthesia procedures, 27 were open procedures involving a thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical mortality and major morbidity was 0%. Minor morbidity included only wound complications. Maximal number of TILs were derived from lymph node specimens, while liver metastasis procured the fewest TILs. Adoptive cell transfer technology affords a maximal tumor response with minimal surgical morbidity in metastatic patients. PMID:22969990

The Danish Adoption Register.

PubMed

Petersen, Liselotte; Sørensen, Thorkild I A

2011-07-01

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

BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy

PubMed Central

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

2012-01-01

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

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

Cancer.gov

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

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

PubMed

Hasin, Afroza; Smith, Sylvia

2018-01-01

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

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.

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.

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.

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

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

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Best practices for health and safety technology transfer in construction.

PubMed

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

2015-08-01

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

Adapting Knowledge Translation Strategies for Rare Rheumatic Diseases.

PubMed

Cellucci, Tania; Lee, Shirley; Webster, Fiona

2016-08-01

Rare rheumatic diseases present unique challenges to knowledge translation (KT) researchers. There is often an urgent need to transfer knowledge from research findings into clinical practice to facilitate earlier diagnosis and better outcomes. However, existing KT frameworks have not addressed the specific considerations surrounding rare diseases for which gold standard evidence is not available. Several widely adopted models provide guidance for processes and problems associated with KT. However, they do not address issues surrounding creation or synthesis of knowledge for rare diseases. Additional problems relate to lack of awareness or experience in intended knowledge users, low motivation, and potential barriers to changing practice or policy. Strategies to address the challenges of KT for rare rheumatic diseases include considering different levels of evidence available, linking knowledge creation and transfer directly, incorporating patient and physician advocacy efforts to generate awareness of conditions, and selecting strategies to address barriers to practice or policy change.

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.

Genetic analysis of a bacterial genetic exchange element: The gene transfer agent of Rhodobacter capsulatus

PubMed Central

Lang, Andrew S.; Beatty, J. T.

2000-01-01

An unusual system of genetic exchange exists in the purple nonsulfur bacterium Rhodobacter capsulatus. DNA transmission is mediated by a small bacteriophage-like particle called the gene transfer agent (GTA) that transfers random 4.5-kb segments of the producing cell's genome to recipient cells, where allelic replacement occurs. This paper presents the results of gene cloning, analysis, and mutagenesis experiments that show that GTA resembles a defective prophage related to bacteriophages from diverse genera of bacteria, which has been adopted by R. capsulatus for genetic exchange. A pair of cellular proteins, CckA and CtrA, appear to constitute part of a sensor kinase/response regulator signaling pathway that is required for expression of GTA structural genes. This signaling pathway controls growth-phase-dependent regulation of GTA gene messages, yielding maximal gene expression in the stationary phase. We suggest that GTA is an ancient prophage remnant that has evolved in concert with the bacterial genome, resulting in a genetic exchange process controlled by the bacterial cell. PMID:10639170

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.

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

A methodology to determine boundary conditions from forced convection experiments using liquid crystal thermography

NASA Astrophysics Data System (ADS)

Jakkareddy, Pradeep S.; Balaji, C.

2017-02-01

This paper reports the results of an experimental study to estimate the heat flux and convective heat transfer coefficient using liquid crystal thermography and Bayesian inference in a heat generating sphere, enclosed in a cubical Teflon block. The geometry considered for the experiments comprises a heater inserted in a hollow hemispherical aluminium ball, resulting in a volumetric heat generation source that is placed at the center of the Teflon block. Calibrated thermochromic liquid crystal sheets are used to capture the temperature distribution at the front face of the Teflon block. The forward model is the three dimensional conduction equation which is solved within the Teflon block to obtain steady state temperatures, using COMSOL. Match up experiments are carried out for various velocities by minimizing the residual between TLC and simulated temperatures for every assumed loss coefficient, to obtain a correlation of average Nusselt number against Reynolds number. This is used for prescribing the boundary condition for the solution to the forward model. A surrogate model obtained by artificial neural network built upon the data from COMSOL simulations is used to drive a Markov Chain Monte Carlo based Metropolis Hastings algorithm to generate the samples. Bayesian inference is adopted to solve the inverse problem for determination of heat flux and heat transfer coefficient from the measured temperature field. Point estimates of the posterior like the mean, maximum a posteriori and standard deviation of the retrieved heat flux and convective heat transfer coefficient are reported. Additionally the effect of number of samples on the performance of the estimation process has been investigated.

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.

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

The role of siblings in adoption outcomes and experiences from adolescence to emerging adulthood.

PubMed

Farr, Rachel H; Flood, Margaux E; Grotevant, Harold D

2016-04-01

In many families, siblings play important roles in shaping each other's outcomes and experiences across development. In adoptive families, siblings may affect adoptees' feelings about adoption and birth family contact. Among "target adoptees" (i.e., 1 participating adopted individual within adoptive families) with siblings who may have also been adopted or the biological children of the adoptive parents, we examined how adoption experiences and individual adjustment from adolescence into emerging adulthood were associated with sibling relationship dynamics. We present 3 studies using longitudinal, mixed method data within the same overarching sample of adoptive families. Study 1 was a follow-up to Berge et al.'s (2006) study of adolescent adoptees and their adopted siblings with birth family contact; we found evidence of changes in the status of contact collectively experienced by 26 adopted sibling pairs when target adoptees were emerging adults. In Study 2, we found that target adoptees (n = 91) with siblings (adopted or not) who were more involved with target adoptees' birth family contact demonstrated more favorable behavioral outcomes than target adoptees who had uninvolved siblings. Finally in Study 3, for target adoptees with siblings who were also adopted (n = 51), results showed that target adoptees felt more positively about their own adoption when siblings expressed similar positive feelings about individual adoption experiences. Implications of our findings are discussed in terms of the enduring contributions of sibling relationships from childhood into adulthood and the unique ways in which adoptive siblings are important in shaping one another's experiences of adoption. (c) 2016 APA, all rights reserved).

The Role of Siblings in Adoption Outcomes and Experiences from Adolescence to Emerging Adulthood

PubMed Central

Farr, Rachel H.; Flood, Margaux E.; Grotevant, Harold D.

2015-01-01

In many families, siblings play important roles in shaping each other’s outcomes and experiences across development. In adoptive families, siblings may affect adoptees’ feelings about adoption and birth family contact. Among “target adoptees” (i.e., one participating adopted individual within adoptive families) with siblings who may have also been adopted or the biological children of the adoptive parents, we examined how adoption experiences and individual adjustment from adolescence into emerging adulthood were associated with sibling relationship dynamics. We present three studies using longitudinal, mixed method data within the same overarching sample of adoptive families. Study 1 was a follow-up to Berge et al.’s (2006) study of adolescent adoptees and their adopted siblings with birth family contact; we found evidence of changes in the status of contact collectively experienced by 26 adopted sibling pairs when target adoptees were emerging adults. In Study 2, we found that target adoptees (n = 91) with siblings (adopted or not) who were more involved with target adoptees’ birth family contact demonstrated more favorable behavioral outcomes than target adoptees who had uninvolved siblings. Finally in Study 3, for target adoptees with siblings who were also adopted (n = 51), results showed that target adoptees felt more positively about their own adoption when siblings expressed similar positive feelings about individual adoption experiences. Implications of our findings are discussed in terms of the enduring contributions of sibling relationships from childhood into adulthood, and the unique ways in which adoptive siblings are important in shaping one another’s experiences of adoption. PMID:26651349

Restoring tactile and erogenous penile sensation in low-spinal-lesion patients: procedural and technical aspects following 43 TOMAX nerve transfer procedures.

PubMed

Overgoor, Max L E; de Jong, Tom P V M; Kon, Moshe

2014-08-01

The "TOMAX" (TO MAX-imize sensation, sexuality, and quality of life) procedure restores genital sensation in men with low spinal lesions, improving sexual health, as shown previously. It connects the dorsal nerve of the penis to the intact ipsilateral ilioinguinal nerve, unilaterally or bilaterally. This study reports on the technical aspects based on 43 TOMAX nerve transfers. In 40 patients with no penile but intact groin sensation, 43 nerve transfers were performed. Data on patient selection, surgical history, anatomy of the ilioinguinal nerve and dorsal nerve of the penis, unilateral or bilateral surgery, surgical technique, complications, and patient information were collected prospectively. Regardless of origin, all patients with no penile but good groin sensation are eligible for the procedure, provided the ilioinguinal nerve is not damaged because of former inguinal surgery or absent because of anatomical variations. Selection of a unilateral or bilateral procedure depends on the presence or absence of reflex erections and bulbocavernosus reflex. Preliminary experience with the first three bilateral cases shows that it is technically feasible, with encouraging results. The surgical technique has evolved (described in detail, including video) to enhance outcome and reduce complications. Patients are better informed, resulting in realistic expectations. This article synthesizes the procedural and technical experience of 43 TOMAX nerve transfers. Anyone skilled in peripheral nerve surgery and microsurgery can adopt this concept and further develop it. The TOMAX procedure can then be used to restore erogenous penile sensation and improve the quality of sexual health in patients with absent penile but good groin sensation.

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.

A journey of restoring self-confidence: the life experiences of women recipients of augmentation mammaplasty.

PubMed

Wu, Wan-Ru; Chung, Ue-Lin; Chang, Sophia C N

2007-06-01

The purpose of this qualitative research study was to explore the preoperative through postoperative phase experience of women who had undergone augmentation mammaplasty. Nine women undergoing augmentation mammaplasty were selected by purposive sampling and interviewed using semi- structured, open-ended interview guidelines. Researchers used Symbolic interactionism to frame their overall perspective and analyzed data with the content analysis method. Rigors of data analysis were adopted credibility, transferability, dependability and confirmability proposed by Guba and Lincoln. The main theme of living experience of women who received augmentation mammaplasty could be summarized as "a journey to restore self-confidence". The categories identified within this journey included: (1) the invisible standards of breast beauty; (2) Taking courageous action to make changes; (3) conflicts between the natural and artificial. The above findings provided initial qualitative data from Taiwanese women's perspective. By better understanding their experience, nurses can become increasingly sensitive to patients' psychosocial adjustment and provide prudential nursing care.

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.

Age at placement, adoption experience and adult adopted people's contact with their adoptive and birth mothers: an attachment perspective.

PubMed

Howe, D

2001-09-01

Adoption holds particular interest for attachment researchers. Although children adopted as babies experience almost continuous care by their adoptive parents, older placed children experience at least one major change of caregiver when they join their adoptive family. Moreover, in the majority of cases, older placed children have generally suffered a pre-adoption history of abuse, neglect and/or rejection. It is now being recognized that older placed children's attachment histories and internal working models (IWMs) established in relationship with their initial carers remain active in relationship with their new carers. Transactional models have helped both researchers and practitioners to understand the dynamics of parent-child relationships in cases where insecure children with histories of neglect, abuse and rejection find themselves in new caregiving environments. The present study examines the childhood experiences of adult adopted people and their current levels of contact with their adoptive mothers, and in cases where people had searched for and found a birth relative, current levels of contact with their birth mother. Although no information was collected on the adopted adult's pre-placement history, age at placement was used as a proxy measure to examine whether older placed children reported different adoption experiences and what their current levels of contact were with their adoptive and birth mothers. The findings show that age at placement was associated with adopted people's reported experiences of being adopted and current rates of contact with their adoptive and birth mothers, with those placed at older ages most likely to report that they (1) did not feel they belonged in their adoptive families while growing up, (2) did not feel loved by their adoptive mother, (3) were least likely to remain in high-frequency contact with their adoptive mother, and (4) were least likely to remain in high-frequency contact with their birth mother. An attachment perspective is used to interpret the findings. Children adopted at older ages appear more likely to have experienced an insecure attachment relationship with their adoptive mother.

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

Transfer of Mindfulness Training to the Work Setting: A Qualitative Study in a Health Care System.

PubMed

Lyddy, Christopher J; Schachter, Yotam; Reyer, Amy; Julliard, Kell

2016-01-01

Mindfulness training is now commonly offered as professional development for health care practitioners. Understanding how health care practitioners adopt mindfulness practices is limited, which poses a hurdle to the development of effective mindfulness training programs. To explore how health professionals use and perceive mindfulness practices at work, we conducted an exploratory qualitative study at a large multicomponent inner-city health system. All participants were self-selected health professionals who attended at least one mindfulness training. Training content was derived from the Tergar Meditation Community's nonsectarian Joy of Living program and focused on calming the mind using a flexible and broadly applicable approach. Transcribed interview data were examined using thematic analysis. Individuals receiving mindfulness training varied substantially in their subsequent adoption and utilization of these practices. Interviewees' experiences overall suggest that the workplace presents a relatively challenging but nonetheless viable environment for being mindful. Health care workers relied on more informal practice models than on formal meditation practice routines while at work. Factors reported by some individuals to inhibit effective mindfulness practice supported mindfulness for others, and overall displayed equivocal effects. Adoption and integration of mindfulness practices within the workplace are feasible yet vary significantly by practice type, situation, and the individual. Greater understanding of how individuals adopt workplace mindfulness training could improve future intervention research while clarifying optimal mindfulness training approaches.

NKG2D is Required for Regulation of Lung Pathology and Dendritic Cell Function Following RSV Infection.

PubMed

Liu, Huan; Osterburg, Andrew R; Flury, Jennifer; Huang, Shuo; McCormack, Francis X; Cormier, Stephania A; Borchers, Michael T

2018-03-15

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infection in vulnerable populations. Natural killer (NK) cells and dendritic cells (DC) are important for the effector functions of both cell types following infection. Wild type and NKG2D deficient mice were infected with RSV. Lung pathology, was assessed by histology. DC function and phenotype was evaluated by ELISA and flow cytometry. The expression of NKG2D ligands on lung and lymph node DCs was measured by immunostaining and flow cytometry. Adoptive transfer experiments were performed to assess the importance of NKG2D dependent DC function in RSV infection. NKG2D deficient mice exhibited greater lung pathology, marked by the accumulation of DCs following RSV infection.  DCs isolated from NKG2D deficient mice had impaired responses towards TLR ligands. DCs expressed NKG2D ligands on their surface, which was further increased in NKG2D deficient mice and during RSV infection. Adoptive transfer of DCs isolated from WT mice into the airways of NKG2D deficient mice ameliorated the enhanced inflammation in NKG2D deficient mice after RSV infection. NKG2D-dependent interactions with DCs control the phenotype and function of DCs and play a critical role in pulmonary host defenses against RSV infection.

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.

Integrating developed and developing world knowledge into global discussions and strategies for sustainability. 2. Economics and governance.

PubMed

Ramaswami, Anu; Zimmerman, Julie B; Mihelcic, James R

2007-05-15

Knowledge transfer from the developing to the developed world is described in the domain of economics and governance for sustainable development. Three system areas are explored: the structure of commons governance institutions, the process of community-based participatory action research, and the role of microfinance and microenterprise for the development, adoption, and diffusion of sustainable technologies. Case studies from both the developed and developing world demonstrate the effectiveness of social networks and community cooperative strategies in a wide range of sectors. Developing world experiences are shown to be particularly rich in the application of local knowledge and social capital toward sustainable development.

A critical review of the core medical training curriculum in the UK: A medical education perspective.

PubMed

Laskaratos, Faidon-Marios; Gkotsi, Despoina; Panteliou, Eleftheria

2014-01-01

This paper represents a systematic evaluation of the Core Medical Training Curriculum in the UK. The authors critically review the curriculum from a medical education perspective based mainly on the medical education literature as well as their personal experience of this curriculum. They conclude in practical recommendations and suggestions which, if adopted, could improve the design and implementation of this postgraduate curriculum. The systematic evaluation approach described in this paper is transferable to the evaluation of other undergraduate or postgraduate curricula, and could be a helpful guide for medical teachers involved in the delivery and evaluation of any medical curriculum.

Invariant NKT cells inhibit development of the Th17 lineage

PubMed Central

Mars, Lennart T.; Araujo, Luiza; Kerschen, Philippe; Diem, Séverine; Bourgeois, Elvire; Van, Linh Pham; Carrié, Nadège; Dy, Michel; Liblau, Roland S.; Herbelin, André

2009-01-01

T cells differentiate into functionally distinct effector subsets in response to pathogen encounter. Cells of the innate immune system direct this process; CD1d-restricted invariant natural killer T (iNKT) cells, for example, can either promote or inhibit Th1 and Th2 responses. Recently, a new subset of CD4+ T helper cells, called Th17, was identified that is implicated in mucosal immunity and autoimmune disorders. To investigate the influence of iNKT cells on the differentiation of naïve T cells we used an adoptive transfer model of traceable antigen-specific CD4+ T cells. Transferred naïve CD25−CD62L+ CD4+ T cells were primed by antigen immunization of the recipient mice, permitting their expansion and Th17 differentiation. This study establishes that in vivo activation of iNKT cells during T-cell priming impedes the commitment of naïve T cells to the Th17 lineage. In vivo cytokine neutralization experiments revealed a role for IL-4, IL-10, and IFN-γ in the iNKT-cell-mediated regulation of T-cell lineage development. Moreover, by comparing IL-17 production by antigen-experienced T cells from unmanipulated wild-type mice and iNKT-cell-deficient mice, we demonstrate an enhanced Th17 response in mice lacking iNKT cells. This invigorated Th17 response reverts to physiological levels when iNKT cells are introduced into Jα18−/− mice by adoptive transfer, indicating that iNKT cells control the Th17 compartment at steady state. We conclude that iNKT cells play an important role in limiting development of the Th17 lineage and suggest that iNKT cells provide a natural barrier against Th17 responses. PMID:19325124

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

Attitudes and Actions That Adoptive Parents Perceive as Helpful in the Process of Raising Their Internationally Adopted Adolescent

ERIC Educational Resources Information Center

Kuzmina, Marina V.

2017-01-01

This phenomenological dissertation study explored the lived experiences of adoptive parents in the process of raising their internationally adopted adolescents. The researcher interviewed 9 participants. Criteria for selection of the research sample included having personal experience with parenting one or more international adolescents adopted at…

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...

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

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

PubMed

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

2012-03-01

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

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.

The Adoption Experience: Families Who Give Children a Second Chance.

ERIC Educational Resources Information Center

Morris, Ann

This book examines the adoption process in Great Britain, recounting first-hand experiences to take the reader through each stage of the process from the adopter's point of view. The book also examines the success and failure of several types of adoption. The chapters are: (1) "You Want to Adopt"; (2) "First Meetings, First Months,…

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.

On the advantage of an external focus of attention: a benefit to learning or performance?

PubMed

Lohse, Keith R; Sherwood, David E; Healy, Alice F

2014-02-01

Although there is general agreement in the sport science community that the focus of attention (FOA) has significant effects on performance, there is some debate about whether or not the FOA adopted during training affects learning. A large number of studies on the focus of attention have shown that subjects who train with an external FOA perform better on subsequent retention and transfer tests. However, the FOA in these studies was not experimentally controlled during testing. Therefore, the current study used a dart-throwing paradigm in which the FOA was experimentally manipulated at both acquisition and testing over very short and long training times. Performance at test, in terms of accuracy and precision, was improved by adopting an external focus at test regardless of the focus instructed during acquisition, in both Experiment 1 and 2. Although an effect of acquisition focus during testing in Experiment 2 provides some evidence that FOA affects learning, the current data demonstrate a much stronger effect for performance than learning, and stronger effects of attention on precision than accuracy. Theoretical implications of these results are discussed, but in general these data provide a more nuanced understanding of how attentional focus instructions influence motor learning and performance. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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

NASA Astrophysics Data System (ADS)

Klotz, Daniel; Herrnegger, Mathew; Schulz, Karsten

2015-04-01

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

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…

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.

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.

Effect of government actions on technological innovation for SO2 control.

PubMed

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

2003-10-15

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

Insights into the Mechanism of a Covalently Linked Organic Dye–Cobaloxime Catalyst System for Dye‐Sensitized Solar Fuel Devices

PubMed Central

Pati, Palas Baran; Zhang, Lei; Philippe, Bertrand; Fernández‐Terán, Ricardo; Ahmadi, Sareh; Tian, Lei; Rensmo, Håkan; Hammarström, Leif

2017-01-01

Abstract A covalently linked organic dye–cobaloxime catalyst system based on mesoporous NiO is synthesized by a facile click reaction for mechanistic studies and application in a dye‐sensitized solar fuel device. The system is systematically investigated by photoelectrochemical measurements, density functional theory, time‐resolved fluorescence, transient absorption spectroscopy, and photoelectron spectroscopy. The results show that irradiation of the dye–catalyst on NiO leads to ultrafast hole injection into NiO from the excited dye, followed by a fast electron transfer process to reduce the catalyst. Moreover, the dye adopts different structures with different excited state energies, and excitation energy transfer occurs between neighboring molecules on the semiconductor surface. The photoelectrochemical experiments also show hydrogen production by this system. The axial chloride ligands of the catalyst are released during photocatalysis to create the active sites for proton reduction. A working mechanism of the dye–catalyst system on the photocathode is proposed on the basis of this study. PMID:28338295

DUSP3 genetic deletion confers M2-like−macrophage-dependent tolerance to septic shock

PubMed Central

Singh, Pratibha; Dejager, Lien; Amand, Mathieu; Theatre, Emilie; Vandereyken, Maud; Zurashvilli, Tinatin; Singh, Maneesh; Mack, Matthias; Timmermans, Steven; Musumeci, Lucia; Dejardin, Emmanuel; Mustelin, Tomas; Van Ginderachter, Jo A.; Moutschen, Michel; Oury, Cécile; Libert, Claude; Rahmouni, Souad

2015-01-01

DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages and that its deficiency in mice promotes tolerance to lipopolysaccharide (LPS)-induced endotoxin shock and to polymicrobial septic shock following cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage-dependent and transferable and that this protection is associated with a striking increase of M2-like macrophages in DUSP3−/− mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3−/− mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and non-redundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion and macrophage polarization. PMID:25876765

[Interdisciplinary longitudinal curriculum "Medical Psychology, Psychotherapy and Psychosomatics." Experiences from the preclinical segment].

PubMed

Schüppel, R; Bayer, A; Hrabal, V; Hölzer, M; Allert, G; Tiedemann, G; Hochkirchen, B; Stephanos, S; Kächele, H; Zenz, H

1998-05-01

The departments of Medical Psychology, Psychosomatics and Psychotherapy developed an interdisciplinary longitudinal curriculum in order to coach medical students for the whole length of their medical education. Experiences from the first four undergraduate semesters are reported. 46 students (33 females, 13 males), mean age 22.3 +/- 2.6 years, attended 60 hours of interdisciplinary group sessions. Frequent motives to join the course were interest in psychosocial disciplines and relevant previous experience. The students expected to benefit from this project in their study, their future practice as a physician, and in their personal development. Important educational goals that could be attained were the adoption of a patient-centred view in medicine as well as strengthening of the students' critical capacities and sensitivity. The students especially appreciated the possibility of group discussions and the opportunity to participate actively in the course. Based on a critical review of the evaluation, the possibility of a transfer of our model is considered and perspectives for the future are developed.

12 CFR 611.501 - Procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

PubMed

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

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

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

PubMed

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

2013-01-01

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

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

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.

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.

"School Adopts an Experiment": The Magnetic Levitation of Superconductors

ERIC Educational Resources Information Center

Gallitto, Aurelio Agliolo

2010-01-01

The event "School adopts an experiment" is an event targeted at high schools and secondary schools. It is based on a tight and direct collaboration between researchers and school students and teachers. Several schools were involved in the event by "adopting" an experiment in physics research laboratories. Groups of selected students were first…

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.

Comparison of Requirements for Composite Structures for Aircraft and Space Applications

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

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

Bass, H.; Mosmann, T.; Strober, S.

Purified CD4+ BALB/c spleen T cells obtained 4-6 wk after total lymphoid irradiation (TLI) helped normal syngeneic B cells to produce a vigorous antibody response to TNP keyhole limpet hemocyanin in adoptive cell transfer experiments. However, the same cells failed to transfer delayed-type hypersensitivity to the adoptive hosts as measured by a foot pad swelling assay. In addition, purified CD4+ cells from TLI-treated mice were unable to induce graft vs. host disease in lethally irradiated allogeneic C57BL/Ka recipient mice. In response to mitogen stimulation, unfractionated spleen cells obtained from TLI mice secreted normal levels of IL-4 and IL-5, but markedlymore » reduced levels of IL-2 and INF-gamma. A total of 229 CD4+ clones from spleen cells of both normal and TLI-treated mice were established, and the cytokine secretion pattern from each clone was analyzed. The results demonstrate that the ratio of Th1- and Th2-like clones in the spleens of normal BALB/c mice is 1:0.6, whereas the ratio in TLI mice is approximately 1:7. These results suggest that Th2-like cells recover rapidly (at approximately 4-6 wk) after TLI treatment and account for the early return of antibody helper activity and secretion of IL-4 and IL-5, but Th1-like cells recover more slowly (in approximately 3 mo) after irradiation, and this accounts for the deficit in cell-mediated immunity and the reduced amount of IL-2 and IFN-gamma secretion.« less

Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF

PubMed Central

De Kleer, Ismé; Henri, Sandrine; Post, Sijranke; Vanhoutte, Leen; De Prijck, Sofie; Deswarte, Kim; Malissen, Bernard; Hammad, Hamida; Lambrecht, Bart N.

2013-01-01

Tissue-resident macrophages can develop from circulating adult monocytes or from primitive yolk sac–derived macrophages. The precise ontogeny of alveolar macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis experiments in adult mice, we found that circulating monocytes contributed minimally to the steady-state AMF pool. Mature AMFs were undetectable before birth and only fully colonized the alveolar space by 3 d after birth. Before birth, F4/80hiCD11blo primitive macrophages and Ly6ChiCD11bhi fetal monocytes sequentially colonized the developing lung around E12.5 and E16.5, respectively. The first signs of AMF differentiation appeared around the saccular stage of lung development (E18.5). Adoptive transfer identified fetal monocytes, and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes transferred to the lung of neonatal mice acquired an AMF phenotype via defined developmental stages over the course of one week, and persisted for at least three months. Early AMF commitment from fetal monocytes was absent in GM-CSF–deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy rescued AMF development for weeks, although the resulting AMFs displayed an immature phenotype. This demonstrates that tissue-resident macrophages can also develop from fetal monocytes that adopt a stable phenotype shortly after birth in response to instructive cytokines, and then self-maintain throughout life. PMID:24043763

The setting up and running of a cross-county out-of-hours gastrointestinal bleed service: a possible blueprint for the future.

PubMed

Shokouhi, Bahman N; Khan, Mohammad; Carter, Martyn J; Khan, Nasser Q; Mills, Philip; Morris, Danielle; Rowlands, David E; Samsheer, Kote; Sargeant, Ian R; McIntyre, Peter B; Greenfield, Simon M

2013-07-01

Acute upper gastrointestinal bleeding (AUGIB) results in 25 000 hospital admissions annually. Patients admitted at weekends with AUGIB have increased mortality, and guidelines advise out-of-hours endoscopy. We present retrospective data from our service involving the interhospital transfer of patients. We pooled resources of two neighbouring general hospitals, just north of London. Emergency endoscopy is performed at the start of the list followed by elective endoscopy in the endoscopy unit on Saturday and Sunday mornings. From Friday evening to Sunday morning, patients admitted to Queen Elizabeth II Hospital (QEII) are medically stabilised and transferred to Lister Hospital by ambulance. 240 endoscopies were performed out of hours from December 2007 to March 2011. Of these, 54 patients were transferred: nine had emergency endoscopy at QEII as they were medically unstable; eight of the patients transferred required therapeutic intervention for active bleeding. The mean pre-endoscopy Rockall score of those transferred was 2.5. We examined the records of 51 of the 54 patients transferred. There were three deaths within 30 days after endoscopy not associated with the transfer process. 19 (37%) patients had reduced hospitalisation after having their endoscopy at the weekend. The introduction of the out-of-hours endoscopy service in our trust has had multiple benefits, including patients consistently receiving timely emergency endoscopy, significantly reduced disruption to emergency operating theatres, and participation of endoscopy nurses ensures a better and safer experience for patients, and better endoscopy decontamination. We suggest our model is safe and feasible for other small units wishing to set up their own out-of-hours endoscopy service to adopt.

The setting up and running of a cross-county out-of-hours gastrointestinal bleed service: a possible blueprint for the future

PubMed Central

Shokouhi, Bahman N; Khan, Mohammad; Carter, Martyn J; Khan, Nasser Q; Mills, Philip; Morris, Danielle; Rowlands, David E; Samsheer, Kote; Sargeant, Ian R; McIntyre, Peter B; Greenfield, Simon M

2013-01-01

Objective Acute upper gastrointestinal bleeding (AUGIB) results in 25 000 hospital admissions annually. Patients admitted at weekends with AUGIB have increased mortality, and guidelines advise out-of-hours endoscopy. We present retrospective data from our service involving the interhospital transfer of patients. Design We pooled resources of two neighbouring general hospitals, just north of London. Emergency endoscopy is performed at the start of the list followed by elective endoscopy in the endoscopy unit on Saturday and Sunday mornings. From Friday evening to Sunday morning, patients admitted to Queen Elizabeth II Hospital (QEII) are medically stabilised and transferred to Lister Hospital by ambulance. Results 240 endoscopies were performed out of hours from December 2007 to March 2011. Of these, 54 patients were transferred: nine had emergency endoscopy at QEII as they were medically unstable; eight of the patients transferred required therapeutic intervention for active bleeding. The mean pre-endoscopy Rockall score of those transferred was 2.5. We examined the records of 51 of the 54 patients transferred. There were three deaths within 30 days after endoscopy not associated with the transfer process. 19 (37%) patients had reduced hospitalisation after having their endoscopy at the weekend. Conclusions The introduction of the out-of-hours endoscopy service in our trust has had multiple benefits, including patients consistently receiving timely emergency endoscopy, significantly reduced disruption to emergency operating theatres, and participation of endoscopy nurses ensures a better and safer experience for patients, and better endoscopy decontamination. We suggest our model is safe and feasible for other small units wishing to set up their own out-of-hours endoscopy service to adopt. PMID:28839729

Intensive care survivors' experiences of ward-based care: Meleis' theory of nursing transitions and role development among critical care outreach services.

PubMed

Ramsay, Pam; Huby, Guro; Thompson, Andrew; Walsh, Tim

2014-03-01

To explore the psychosocial needs of patients discharged from intensive care, the extent to which they are captured using existing theory on transitions in care and the potential role development of critical care outreach, follow-up and liaison services. Intensive care patients are at an increased risk of adverse events, deterioration or death following ward transfer. Nurse-led critical care outreach, follow-up or liaison services have been adopted internationally to prevent these potentially avoidable sequelae. The need to provide patients with psychosocial support during the transition to ward-based care has also been identified, but the evidence base for role development is currently limited. Twenty participants were invited to discuss their experiences of ward-based care as part of a broader study on recovery following prolonged critical illness. Psychosocial distress was a prominent feature of their accounts, prompting secondary data analysis using Meleis et al.'s mid-range theory on experiencing transitions. Participants described a sense of disconnection in relation to profound debilitation and dependency and were often distressed by a perceived lack of understanding, indifference or insensitivity among ward staff to their basic care needs. Negotiating the transition between dependence and independence was identified as a significant source of distress following ward transfer. Participants varied in the extent to which they were able to express their needs and negotiate recovery within professionally mediated boundaries. These data provide new insights into the putative origins of the psychosocial distress that patients experience following ward transfer. Meleis et al.'s work has resonance in terms of explicating intensive care patients' experiences of psychosocial distress throughout the transition to general ward-based care, such that the future role development of critical care outreach, follow-up and liaison services may be more theoretically informed. © 2013 John Wiley & Sons Ltd.

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.

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.

Parental Cultural Competence for Transracial Adoptive Parents: Effect of Experiences of Oppression, Perceived Support, and Multicultural Experiences

ERIC Educational Resources Information Center

Rootes, Katie M. Heiden

2014-01-01

This study sought to understand how parental cultural competence (PCC) develops for transracial adoptive parents. PCC refers to the use of cultural socialization by parents for supporting the racial and ethnic identity development of their transracially-adopted children. PCC remains an under researched area within transracial adoption research…

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…

Adoption and Usage of mHealth Technology on Quality and Experience of Care Provided by Frontline Workers: Observations From Rural India.

PubMed

Kaphle, Sangya; Chaturvedi, Sharad; Chaudhuri, Indrajit; Krishnan, Ram; Lesh, Neal

2015-05-28

mHealth apps are deployed with the aim of improving access, quality, and experience of health care. It is possible that any mHealth intervention can yield differential impacts for different types of users. Mediating and determining factors, including personal and socioeconomic factors, affect technology adoption, the way health workers leverage and use the technology, and subsequently the quality and experience of care they provide. To develop a framework to assess whether mHealth platforms affect the quality and experience of care provided by frontline workers, and whether these effects on quality and experience are different depending on the level of technology adoption and individual characteristics of the health worker. Literacy, education, age, and previous mobile experience are identified as individual factors that affect technology adoption and use, as well as factors that affect the quality and experience of care directly and via the technology. Formative research was conducted with 15 community health workers (CHWs) using CommCare, an mHealth app for maternal and newborn care, in Bihar, India. CHWs were first classified on the level of CommCare adoption using data from CommCareHQ and were then shadowed on home visits to evaluate their levels of technology proficiency, and the quality and experience of care provided. Regression techniques were employed to test the relationships. Out of all the CHWs, 2 of them refused to participate in the home visits, however, we did have information on their levels of technology adoption and background characteristics, which were included in the analysis as relevant. Level of technology adoption was important for both quality and experience of care. The quality score for high users of CommCare was higher by 33.4% (P=.04), on average, compared to low users of CommCare. Those who scored higher on CommCare proficiency also provided significantly higher quality and experience of care, where an additional point in CommCare proficiency score increased the quality score by around half a point (0.541, P=.07), and experience score by around a third of a point (0.308, P=.03). Age affected CommCare user type negatively, with an increase in age increasing the likelihood of belonging to a lower category of CommCare adoption (-0.105, P=.08). Other individual characteristics did not affect adoption or the predicted values estimating the relationship between adoption and quality and experience of care, although illiteracy was able to affect the relationship negatively. mHealth technology adoption by frontline workers can positively impact the quality and experience of care they provide. Individual characteristics, especially literacy and age, can be important elements affecting technology adoption and the way users leverage the technology for their work. Our formative study provides informed hypotheses and methods for further research.

Adoption and Usage of mHealth Technology on Quality and Experience of Care Provided by Frontline Workers: Observations From Rural India

PubMed Central

Chaturvedi, Sharad; Chaudhuri, Indrajit; Krishnan, Ram; Lesh, Neal

2015-01-01

Background mHealth apps are deployed with the aim of improving access, quality, and experience of health care. It is possible that any mHealth intervention can yield differential impacts for different types of users. Mediating and determining factors, including personal and socioeconomic factors, affect technology adoption, the way health workers leverage and use the technology, and subsequently the quality and experience of care they provide. Objective To develop a framework to assess whether mHealth platforms affect the quality and experience of care provided by frontline workers, and whether these effects on quality and experience are different depending on the level of technology adoption and individual characteristics of the health worker. Literacy, education, age, and previous mobile experience are identified as individual factors that affect technology adoption and use, as well as factors that affect the quality and experience of care directly and via the technology. Methods Formative research was conducted with 15 community health workers (CHWs) using CommCare, an mHealth app for maternal and newborn care, in Bihar, India. CHWs were first classified on the level of CommCare adoption using data from CommCareHQ and were then shadowed on home visits to evaluate their levels of technology proficiency, and the quality and experience of care provided. Regression techniques were employed to test the relationships. Out of all the CHWs, 2 of them refused to participate in the home visits, however, we did have information on their levels of technology adoption and background characteristics, which were included in the analysis as relevant. Results Level of technology adoption was important for both quality and experience of care. The quality score for high users of CommCare was higher by 33.4% (P=.04), on average, compared to low users of CommCare. Those who scored higher on CommCare proficiency also provided significantly higher quality and experience of care, where an additional point in CommCare proficiency score increased the quality score by around half a point (0.541, P=.07), and experience score by around a third of a point (0.308, P=.03). Age affected CommCare user type negatively, with an increase in age increasing the likelihood of belonging to a lower category of CommCare adoption (-0.105, P=.08). Other individual characteristics did not affect adoption or the predicted values estimating the relationship between adoption and quality and experience of care, although illiteracy was able to affect the relationship negatively. Conclusions mHealth technology adoption by frontline workers can positively impact the quality and experience of care they provide. Individual characteristics, especially literacy and age, can be important elements affecting technology adoption and the way users leverage the technology for their work. Our formative study provides informed hypotheses and methods for further research. PMID:26023001

'School adopts an experiment': the magnetic levitation of superconductors

NASA Astrophysics Data System (ADS)

Agliolo Gallitto, Aurelio

2010-09-01

The event 'School adopts an experiment' is an event targeted at high schools and secondary schools. It is based on a tight and direct collaboration between researchers and school students and teachers. Several schools were involved in the event by 'adopting' an experiment in physics research laboratories. Groups of selected students were first trained by university researchers, then they demonstrated the experiments to other students and teachers during the event. Students who adopted an experiment acquired knowledge of the subjects connected with the experiment in a most impressive way compared with the usual didactics at school. Further positive points were: (i) to establish a close and direct collaboration between university researchers and high-school students and teachers; (ii) to give school students the opportunity to visit physics research laboratories.

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.

The experience of adoptive parents in adoption reunion relationships: a qualitative study.

PubMed

Petta, Gabrielle A; Steed, Lyndall G

2005-04-01

The issues experienced by adoptive parents when faced with an adult child's searching or reunion relationship with his or her birth family, how adoptive parents place themselves within this process, and the factors that influence their experience at this time were explored in a qualitative study of 21 adoptive parents. Themes derived from semistructured interviews are discussed, and implications for clinical practice and future research are suggested. Copyright (c) 2005 APA, all rights reserved.

Development of New Cooling System Using Gm/jt Cryocoolers for the SKS Magnet

NASA Astrophysics Data System (ADS)

Aoki, K.; Haruyama, T.; Makida, Y.; Araoka, O.; Kasami, K.; Takahashi, T.; Nagae, T.; Kakiguchi, Y.; Sekimoto, M.; Tosaka, T.; Miyazaki, H.; Kuriyama, T.; Ono, M.; Orikasa, T.; Tsuchihashi, T.; Hirata, Y.

2008-03-01

We plan to develop a new improved cooling system for the Superconducting Kaon Spectrometer (SKS) magnet and transfer the magnet to the K1.8 beamline of the Hadron Hall of the Japan Proton Accelerator Research Complex (J-PARC) for further use in nuclear physics experiments. To replace the present 300 W cryogenic system, we will adopt a new cooling method that uses 4 K Gifford-McMahon/Joule-Thomson (GM/JT) cryocoolers. In order to decide a practical design for the new liquid helium reservoir of the magnet, which will be equipped with GM/JT cryocoolers, cooling tests on a GM/JT cryocooler were performed from February to March 2007. We constructed a new cooling test stand with a GM/JT cryocooler and measured the cooling capacities under several thermal shield temperatures with or without a baffle, which helped prevent convection. Based on the test results, we have finally decided to adopt three GM/JT cryocoolers for the new SKS along with a baffle and an additional dedicated GM cooler to cool the thermal shield of the GM/JT ports.

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

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…

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.

Experiences of Adopting Blended Pedagogies in Health Assessment Course in Post RN Baccalaureate Program of Nursing in Karachi, Pakistan

ERIC Educational Resources Information Center

Cassum, Shanaz Hussein; Allana, Saleema; Dias, Jacqueline

2016-01-01

Purpose: There is little known about whether faculty and students in a resource constricted context experience a change in learning due to the adoption of blended learning (BL) pedagogies in a lab based course. The study aimed to understand the experiences of faculty and students' related to the adoption of BL pedagogies in health assessment…

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.

Control of repulsive force in a virtual environment using an electrorheological haptic master for a surgical robot application

NASA Astrophysics Data System (ADS)

Oh, Jong-Seok; Choi, Seung-Hyun; Choi, Seung-Bok

2014-01-01

This paper presents control performances of a new type of four-degrees-of-freedom (4-DOF) haptic master that can be used for robot-assisted minimally invasive surgery (RMIS). By adopting a controllable electrorheological (ER) fluid, the function of the proposed master is realized as a haptic feedback as well as remote manipulation. In order to verify the efficacy of the proposed master and method, an experiment is conducted with deformable objects featuring human organs. Since the use of real human organs is difficult for control due to high cost and moral hazard, an excellent alternative method, the virtual reality environment, is used for control in this work. In order to embody a human organ in the virtual space, the experiment adopts a volumetric deformable object represented by a shape-retaining chain linked (S-chain) model which has salient properties such as fast and realistic deformation of elastic objects. In haptic architecture for RMIS, the desired torque/force and desired position originating from the object of the virtual slave and operator of the haptic master are transferred to each other. In order to achieve the desired torque/force trajectories, a sliding mode controller (SMC) which is known to be robust to uncertainties is designed and empirically implemented. Tracking control performances for various torque/force trajectories from the virtual slave are evaluated and presented in the time domain.

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...

Direct numerical simulation of viscoelastic-fluid-based nanofluid turbulent channel flow with heat transfer

NASA Astrophysics Data System (ADS)

Yang, Juan-Cheng; Li, Feng-Chen; Cai, Wei-Hua; Zhang, Hong-Na; Yu, Bo

2015-08-01

Our previous experimental studies have confirmed that viscoelastic-fluid-based nanofluid (VFBN) prepared by suspending nanoparticles in a viscoelastic base fluid (VBF, behaves drag reduction at turbulent flow state) can reduce turbulent flow resistance as compared with water and enhance heat transfer as compared with VBF. Direct numerical simulation (DNS) is performed in this study to explore the mechanisms of heat transfer enhancement (HTE) and flow drag reduction (DR) for the VFBN turbulent flow. The Giesekus model is used as the constitutive equation for VFBN. Our previously proposed thermal dispersion model is adopted to take into account the thermal dispersion effects of nanoparticles in the VFBN turbulent flow. The DNS results show similar behaviors for flow resistance and heat transfer to those obtained in our previous experiments. Detailed analyses are conducted for the turbulent velocity, temperature, and conformation fields obtained by DNSs for different fluid cases, and for the friction factor with viscous, turbulent, and elastic contributions and heat transfer rate with conductive, turbulent and thermal dispersion contributions of nanoparticles, respectively. The mechanisms of HTE and DR of VFBN turbulent flows are then discussed. Based on analogy theory, the ratios of Chilton-Colburn factor to friction factor for different fluid flow cases are investigated, which from another aspect show the significant enhancement in heat transfer performance for some cases of water-based nanofluid and VFBN turbulent flows. Project supported by the National Natural Science Foundation of China (Grant No. 51276046), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20112302110020), the China Postdoctoral Science Foundation (Grant No. 2014M561037), and the President Fund of University of Chinese Academy of Sciences, China (Grant No. Y3510213N00).

Experience with Delay-Tolerant Networking from Orbit

NASA Technical Reports Server (NTRS)

Ivancic, W.; Eddy, W. M.; Stewart, D.; Wood, L.; Northam, J.; Jackson, C.

2010-01-01

We describe the first use from space of the Bundle Protocol for Delay-Tolerant Networking (DTN) and lessons learned from experiments made and experience gained with this protocol. The Disaster Monitoring Constellation (DMC), constructed by Surrey Satellite Technology Ltd (SSTL), is a multiple-satellite Earth-imaging low-Earth-orbit sensor network in which recorded image swaths are stored onboard each satellite and later downloaded from the satellite payloads to a ground station. Store-and-forward of images with capture and later download gives each satellite the characteristics of a node in a disruption-tolerant network. Originally developed for the Interplanetary Internet, DTNs are now under investigation in an Internet Research Task Force (IRTF) DTN research group (RG), which has developed a bundle architecture and protocol. The DMC is technically advanced in its adoption of the Internet Protocol (IP) for its imaging payloads and for satellite command and control, based around reuse of commercial networking and link protocols. These satellites use of IP has enabled earlier experiments with the Cisco router in Low Earth Orbit (CLEO) onboard the constellation s UK-DMC satellite. Earth images are downloaded from the satellites using a custom IP-based high-speed transfer protocol developed by SSTL, Saratoga, which tolerates unusual link environments. Saratoga has been documented in the Internet Engineering Task Force (IETF) for wider adoption. We experiment with the use of DTNRG bundle concepts onboard the UK-DMC satellite, by examining how Saratoga can be used as a DTN convergence layer to carry the DTNRG Bundle Protocol, so that sensor images can be delivered to ground stations and beyond as bundles. Our practical experience with the first successful use of the DTNRG Bundle Protocol in a space environment gives us insights into the design of the Bundle Protocol and enables us to identify issues that must be addressed before wider deployment of the Bundle Protocol. Published in 2010 by John Wiley & Sons, Ltd. KEY WORDS: Internet; UK-DMC; satellite; Delay-Tolerant Networking (DTN); Bundle Protocol

Themes of Hope and Healing: Infertile Couples' Experiences of Adoption.

ERIC Educational Resources Information Center

Daniluk, Judith C.; Hurtig-Mitchell, Joss

2003-01-01

Using qualitative approach, authors explored the experiences of becoming parents through adoption after unsuccessful infertility treatments. Analysis of data revealed three overarching themes. Findings are discussed in terms of their implications for counselors who work with infertile couples considering adoption, clients engaged in adoption…

AIEgens for dark through-bond energy transfer: design, synthesis, theoretical study and application in ratiometric Hg2+ sensing.

PubMed

Chen, Yuncong; Zhang, Weijie; Cai, Yuanjing; Kwok, Ryan T K; Hu, Yubing; Lam, Jacky W Y; Gu, Xinggui; He, Zikai; Zhao, Zheng; Zheng, Xiaoyan; Chen, Bin; Gui, Chen; Tang, Ben Zhong

2017-03-01

A novel dark through-bond energy transfer (DTBET) strategy is proposed and applied as the design strategy to develop ratiometric Hg 2+ sensors with high performance. Tetraphenylethene ( TPE ) derivatives with aggregation-induced emission (AIE) characteristics are selected as dark donors to eliminate emission leakage from the donors. The TBET mechanism has been adopted since it experiences less influence from spectral overlapping than Förster resonance energy transfer (FRET), making it more flexible for developing cassettes with large pseudo-Stokes shifts. In this work, energy transfer from the TPE derivatives (dark donor) to a rhodamine moiety (acceptor) was illustrated through photophysical spectroscopic studies and the energy transfer efficiency (ETE) was found to be up to 99%. In the solution state, no emission from the donors was observed and large pseudo-Stokes shifts were achieved (>280 nm), which are beneficial for biological imaging. Theoretical calculations were performed to gain a deeper mechanistic insight into the DTBET process and the structure-property relationship of the DTBET cassettes. Ratiometric Hg 2+ sensors were rationally constructed based on the DTBET mechanism by taking advantage of the intense emission of TPE aggregates. The Hg 2+ sensors exhibited well resolved emission peaks. >6000-fold ratiometric fluorescent enhancement is also achieved and the detection limit was found to be as low as 0.3 ppb. This newly proposed DTBET mechanism could be used to develop novel ratiometric sensors for various analytes and AIEgens with DTBET characteristics will have great potential in various areas including light harvesting materials, environmental science, chemical sensing, biological imaging and diagnostics.

US/China Energy and Environmental Technology Center (EETC) international business development and technology transfer

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

Hsieh, S.T.; Atwood, T.; Qiu Daxiong

1997-12-31

Since January 1997, the US/China Energy and Environmental Technology Center (EETC) in Beijing has been jointly operated by Tulane University and Tsinghua University. EETC is established to encourage the adoption of technologies for energy production with improved environmental performance which are essential for supporting economic growth and managing the Global Warming and Climate Change issues. International cooperation is critical to insure the environmental and energy security on a global basis. For example, the US has acquired a great deal of useful experience in clean coal technology which has been demonstrated with major utilities in commercial operations. The adaption of, andmore » the installation of, clean coal technology should be given high priority. Worldwide, the continuous exchange of information and technology between developed and developing nations relating to the current and future clean coal technologies is of great importance. Developed nations which possess environmental responsive technologies and financial resources should work closely with developing nations to facilitate technology transfer and trade of technologies. International cooperation will lower the cost of deploying clean coal technologies directed toward the clean production of energy. This paper presents the updated activities of EETC on facilitating technology transfer and promoting the clean use of coal to satisfy growing energy demand in China.« less

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

Comparison of Requirements for Composite Structures for Aircraft and Space Applications

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

Current advances in T-cell-based cancer immunotherapy

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2017-01-01

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

Current advances in T-cell-based cancer immunotherapy.

PubMed

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

2014-01-01

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

Portable oil bath for high-accuracy resistance transfer and maintenance

NASA Astrophysics Data System (ADS)

Shiota, Fuyuhiko

1999-10-01

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

How the adoption of impression management goals alters impression formation.

PubMed

Gibson, Bryan; Poposki, Elizabeth M

2010-11-01

Five experiments (N = 390) tested the hypothesis that adopting an impression management goal leads the impression manager to view an interaction partner as having less of the trait he or she is attempting to express. This hypothesis was confirmed for the impression management goals of appearing introverted, extraverted, smart, confident, and happy. Experiment 2 shows that adoption of the impression goal could alter judgments even when participants could not act on the goal. Experiment 3 provides evidence that adopting an impression management goal prompted a comparison mind-set and that this comparison mind-set activation mediated target judgments. Experiment 4 rules out a potential alternative explanation and provides more direct evidence that comparison of the impression manager's self-concept mediates the impression of the target. Experiment 5 eliminates a potential confound and extends the effect to another impression goal. These experiments highlight the dynamic interplay between impression management and impression formation.

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

Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice

PubMed Central

Jin, Rong; Zhu, Xiaolei; Liu, Lin; Nanda, Anil; Granger, D Neil; Li, Guohong

2013-01-01

Background and Purpose Statins are widely used in the primary and secondary prevention of ischemic stroke, but their effects on stroke-induced immunodeppression and post-stroke infections are elusive. We investigated effects of simvastatin treatment on stroke-induced splenic atrophy and lung susceptibility to bacterial infection in acute experimental stroke in mice. Methods Ischemic stroke was induced by transient occlusion of middle cerebral artery (MCAO) followed by reperfusion. In some experiments, splenectomies were performed 2 weeks prior to MCAO. Animals were randomly assigned to sham and MCAO groups treated subcutaneously with vehicle or simvastatin (20 mg/kg/day). Brain infarction, neurological function, brain interferon-γ expression, splenic atrophy and apoptosis, and lung infection were examined. Results Simvastatin reduced stroke-induced spleen atrophy and splenic apoptosis via increased mitochrondrial anti-apoptotic Bcl-2 expression and decreased pro-apoptotic Bax translocation from cytosol into mitochondria. Splenectomy reduced brain interferon-γ (3d) and infarct size (5d) after stroke and these effects were reversed by adoptive transfer of splenocytes. Simvastatin inhibited brain interferon-γ (3d) and reduced infarct volume and neurological deficits (5d) after stroke, and these protective effects were observed not only in naïve stroke mice but also in splenectomied stroke mice adoptively transferred with splenocytes. Simvastatin also decreased the stroke-associated lung susceptibility to spontaneous bacterial infection. Conclusions Results provide the first direct experimental evidence that simvastatin ameliorates stroke-induced peripheral immunodepression by attenuating spleen atrophy and lung bacterial infection. These findings contribute to a better understanding of beneficial effects of statins in the treatment of stroke. PMID:23391769

Ex vivo Akt inhibition promotes the generation of potent CD19CAR T cells for adoptive immunotherapy.

PubMed

Urak, Ryan; Walter, Miriam; Lim, Laura; Wong, ChingLam W; Budde, Lihua E; Thomas, Sandra; Forman, Stephen J; Wang, Xiuli

2017-01-01

Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. Generating potent CAR T cells is of increasing importance in the field. Studies have demonstrated the importance of the Akt pathway in the regulation of T cell differentiation and memory formation. We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model. Various T cell subsets including CD8+ T cells, bulk T cells, central memory T cells and naïve/memory T cells were isolated from PBMC of healthy donors, activated with CD3/CD28 beads, and transduced with a lentiviral vector encoding a second-generation CD19CAR containing a CD28 co-stimulatory domain. The transduced CD19CAR T cells were expanded in the presence of IL-2 (50U/mL) and Akt inhibitor (Akti) (1 μM) that were supplemented every other day. Proliferative/expansion potential, phenotypical characteristics and functionality of the propagated CD19CAR T cells were analyzed in vitro and in vivo after 17-21 day ex vivo expansion. Anti-tumor activity was evaluated after adoptive transfer of the CD19CAR T cells into CD19+ tumor-bearing immunodeficient mice. Tumor signals were monitored with biophotonic imaging, and survival rates were analyzed by the end of the experiments. We found that Akt inhibition did not compromise CD19CAR T cell proliferation and expansion in vitro, independent of the T cell subsets, as comparable CD19CAR T cell expansion was observed after culturing in the presence or absence of Akt inhibitor. Functionally, Akt inhibition did not dampen cell-mediated effector function, while Th1 cytokine production increased. With respect to phenotype, Akti-treated CD19CAR T cells expressed higher levels of CD62L and CD28 as compared to untreated CD19CAR T cells. Once adoptively transferred into CD19+ tumor-bearing mice, Akti treated CD19CAR T cells exhibited more antitumor activity than did untreated CD19CAR T cells. Inhibition of Akt signaling during ex vivo priming and expansion gives rise to CD19CAR T cell populations that display comparatively higher antitumor activity.

Adopted children and education: the experiences of a specialist CAMHS team.

PubMed

Barratt, Sara

2012-01-01

The education system makes special provision for "looked after children". However, once adopted these children become invisible. Adopted children are often placed in their new families when they are already of school age. School is yet another transition alongside that of home, food, language and social milieu which an adopted child has to manage together the pain of the loss of the biological family and its culture. This article focuses on the importance for CAMHS practitioners to work closely with schools and adoptive parents to help children manage their lives in school. Alongside the difficulties they face in learning, many adopted children need help in managing friendships and in concentrating on what is required of them in school. Adults may be ignorant of the day to day experiences of racism and questions about mothers, fathers, brothers and sisters that can throw an adopted child into confusion. This chapter draws on clinical experience to describe some of the difficulties that arise for parents and children in managing the education system.

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

NASA Technical Reports Server (NTRS)

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

1976-01-01

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

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

ERIC Educational Resources Information Center

Riccio, James A.

2013-01-01

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

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

PubMed

Taylor, Jude Matthew

2017-12-15

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

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

PubMed Central

Kim, Sang-Ha

2017-01-01

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

Insights into the Mechanism of a Covalently Linked Organic Dye-Cobaloxime Catalyst System for Dye-Sensitized Solar Fuel Devices.

PubMed

Pati, Palas Baran; Zhang, Lei; Philippe, Bertrand; Fernández-Terán, Ricardo; Ahmadi, Sareh; Tian, Lei; Rensmo, Håkan; Hammarström, Leif; Tian, Haining

2017-06-09

A covalently linked organic dye-cobaloxime catalyst system based on mesoporous NiO is synthesized by a facile click reaction for mechanistic studies and application in a dye-sensitized solar fuel device. The system is systematically investigated by photoelectrochemical measurements, density functional theory, time-resolved fluorescence, transient absorption spectroscopy, and photoelectron spectroscopy. The results show that irradiation of the dye-catalyst on NiO leads to ultrafast hole injection into NiO from the excited dye, followed by a fast electron transfer process to reduce the catalyst. Moreover, the dye adopts different structures with different excited state energies, and excitation energy transfer occurs between neighboring molecules on the semiconductor surface. The photoelectrochemical experiments also show hydrogen production by this system. The axial chloride ligands of the catalyst are released during photocatalysis to create the active sites for proton reduction. A working mechanism of the dye-catalyst system on the photocathode is proposed on the basis of this study. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Online Learning Adoption: Effects of Neuroticism, Openness to Experience, and Perceived Values

ERIC Educational Resources Information Center

Watjatrakul, Boonlert

2016-01-01

Purpose: Individual differences and perceived values of technology have received much attention in technology adoption literature. However, there is a lack of understanding of their relationships and effects on online learning adoption. The study aims to investigate the effects of two important personality traits (i.e. openness to experience and…

Lesbian, Gay, and Heterosexual Adoptive Parents' Experiences in Preschool Environments

PubMed Central

Goldberg, Abbie E.

2014-01-01

Little research has examined the school experiences of lesbian/gay (LG) parent families or adoptive parent families. The current exploratory study examined the experiences of 79 lesbian, 75 gay male, and 112 heterosexual adoptive parents of preschool-age children with respect to their (a) level of disclosure regarding their LG parent and adoptive family status at their children's schools; (b) perceived challenges in navigating the preschool environment and advocating on behalf of their children and families; and (c) recommendations to teachers and schools about how to create affirming school environments with respect to family structure, adoption, and race/ethnicity. Findings revealed that the majority of parents were open about their LG and adoptive family status, and had not encountered challenges related to family diversity. Those parents who did experience challenges tended to describe implicit forms of marginalization, such as insensitive language and school assignments. Recommendations for teachers included discussing and reading books about diverse families, tailoring assignments to meet the needs of diverse families, and offering school community-building activities and events to help bridge differences across families. PMID:25414543

Lesbian, Gay, and Heterosexual Adoptive Parents' Experiences in Preschool Environments.

PubMed

Goldberg, Abbie E

2014-01-01

Little research has examined the school experiences of lesbian/gay (LG) parent families or adoptive parent families. The current exploratory study examined the experiences of 79 lesbian, 75 gay male, and 112 heterosexual adoptive parents of preschool-age children with respect to their (a) level of disclosure regarding their LG parent and adoptive family status at their children's schools; (b) perceived challenges in navigating the preschool environment and advocating on behalf of their children and families; and (c) recommendations to teachers and schools about how to create affirming school environments with respect to family structure, adoption, and race/ethnicity. Findings revealed that the majority of parents were open about their LG and adoptive family status, and had not encountered challenges related to family diversity. Those parents who did experience challenges tended to describe implicit forms of marginalization, such as insensitive language and school assignments. Recommendations for teachers included discussing and reading books about diverse families, tailoring assignments to meet the needs of diverse families, and offering school community-building activities and events to help bridge differences across families.

Through the client's eyes: using narratives to explore experiences of care transfers during pregnancy, childbirth, and the neonatal period.

PubMed

van Stenus, Cherelle M V; Gotink, Mark; Boere-Boonekamp, Magda M; Sools, Anneke; Need, Ariana

2017-06-12

The client experience is an important outcome in the evaluation and development of perinatal healthcare. But because clients meet different professionals, measuring such experiences poses a challenge. This is especially the case in the Netherlands, where pregnant women are often transferred between professionals due to the nation's approach to risk selection. This paper explores questions around how clients experience transfers of care during pregnancy, childbirth, and the neonatal period, as well as how these experiences compare to the established quality of care aspects the Dutch Patient Federation developed. Narratives from 17 Dutch women who had given birth about their experiences with transfers were collected in the Netherlands. The narratives, for which informed consent was obtained, were collected on paper and online. Storyline analysis was used to identify story types. Story types portray patterns that indicate how clients experience transfers between healthcare providers. A comparative analysis was performed to identify differences and similarities between existing quality criteria and those clients mentioned. Four story types were identified: 1) Disconnected transfers of care lead to uncertainties; 2) Seamless transfers of care due to proper collaboration lead to positive experiences; 3) Transfers of care lead to disruption of patient-provider connectedness; 4) Transfer of care is initiated by the client to make pregnancy and childbirth dreams come true. Most of the quality aspects derived from these story types were identified as being similar or complementary to the Dutch Patient Federation list. A 'new' aspect identified in the clients' stories was the influencing role of prior experiences with transfers of care on current expectations, fears, and wishes. Transfers of care affect clients greatly and influence their experiences. Good communication, seamless transfers, and maintaining autonomy contribute to more positive experiences. The stories also show that previous experiences influence client's expectations for the next pregnancy, childbirth, and transfers of care.

Adoption: A Lifelong Journey for Children & Families.

ERIC Educational Resources Information Center

McManus, Marilyn, C., Ed.

1996-01-01

Several issues surrounding adoption are addressed in this journal. "Openness in Adoption," by Ruth G. McRoy and others, explores the movement away from confidentiality in adoption. "Mid-Life Reflections on Adoption" by Carol Yttri and "An Adoption Journey" by Shannon Latimer detail the experiences of adults who were…

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.

"Choosing Life": Birth Mothers on Abortion and Reproductive Choice.

PubMed

Sisson, Gretchen

2015-01-01

As the least-chosen option when faced with an unplanned pregnancy, adoption remains largely unexamined as a reproductive choice. Although the anti-abortion movement promotes adoption as its preferred alternative to abortion, little is known of birth mothers' pregnancy decision making and whether adoption was chosen in lieu of abortion. I conducted in-depth interviews with 40 women who had placed infants for adoption from 1962 to 2009. Participants were asked about all aspects of their adoption experiences, including their pregnancy decision making and thoughts on abortion. Interview transcripts were analyzed using grounded theory to find unifying themes speaking to reproductive choice. Participants' stories revealed widely varying ideas about abortion. Many were opposed to abortion, but a greater number supported abortion as a reproductive choice, although one they did not choose for themselves. Birth mothers were most often choosing between adoption and parenting, not adoption and abortion. Most participants would have preferred to parent, but did not because of external variables. Mixed experiences with adoption also influenced participants' long-term ideas about reproductive choice. Findings suggest that the anti-abortion framing of adoption as a preferable alternative to abortion is inconsistent with birth mothers' pregnancy decision-making experiences and their feelings about adoption. Reducing social barriers to both abortion and parenting will ensure that adoption is situated as a true reproductive choice. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

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.

Improving text comprehension strategies in upper primary school children: a design experiment.

PubMed

De Corte, E; Verschaffel, L; Van De Ven, A

2001-12-01

With respect to the acquisition of competence in reading, new standards for primary education stress more than before the importance of learning and teaching cognitive and metacognitive strategies that facilitate text comprehension. Therefore, there is a need to design a research-based instructional approach to strategic reading comprehension. The design experiment aimed at developing, implementing and evaluating a research-based, but also practically applicable learning environment for enhancing skilled strategy use in upper primary school children when reading a text. Four text comprehension strategies (activating prior knowledge, clarifying difficult words, making a schematic representation of the text, and formulating the main idea) and a metacognitive strategy (regulating one's own reading process) were trained through a variety of highly interactive instructional techniques, namely modelling, whole class discussion, and small group work in the format of reciprocal teaching. Participants in the study were four experimental 5th grade classes (79 children) and eight comparable control classes (149 pupils). The effects of the learning environment were measured using a pretest-post-test-retention design. Multilevel hierarchical linear regression models were used to analyse the quantitative data of a Reading Strategy Test, a standardised Reading Comprehension Test, a Reading Attitude Scale, a Transfer Test and an interview about strategy use during reading. The data of the Reading Strategy Test, the Transfer Test and the interviews about strategy use showed that the experimental group out-performed the control group in terms of the strategy adoption and application during text reading. Whilst the experimental group also scored higher on the Reading Comprehension Test than the control group, the difference was not significant. This design experiment shows that it is possible to foster pupils' use and transfer of strategic reading comprehension skills in regular classrooms by immersing them in a powerful learning environment. But this intervention does not automatically result in improvement of performance on a standardised reading comprehension test.

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

'She didn't have a word of English; we didn't have a word of Vietnamese': Exploring parent experiences of communication with toddlers who were adopted internationally.

PubMed

McAndrew, Brid; Malley-Keighran, Mary-Pat O

2017-07-01

The purpose of this study was to explore in detail parents' experiences of communicating with toddlers who were adopted internationally. Often, there is a mismatch between parents and children in terms of language, particularly in the early post-adoption period. There is a gap in the literature regarding parent experiences of this phase of their lives. Changing patterns in international adoption have led to an increase in adoptions of toddlers and older children. Due to institutional care, these toddlers and older children often lack exposure to their native language which may lead to language delay. When they are brought home, they are immersed in English. As well beginning to acquire English, these children are also forming an attachment with their parents. While research has investigated speech and language skills in this population, there is a lack of literature exploring the experiences of parents regarding communicating with toddlers who are adopted internationally in the early months following adoption. This is a qualitative study where interviews and thematic analysis were used to explore the experiences of 12 parents of 12 toddlers who were adopted internationally. Three main themes: 'Getting ready', 'Support', and 'Challenges' emerged from the data. The results highlight the ways in which adoptive parents facilitated communication with their toddlers, supporting their acquisition of English. The results also reveal gaps in service provision for this population. Results also illustrate the proactive way in which parents dealt with challenges, even in the presence of limited support services. Gaps in service provision where intense focus pre-adoption was followed by a lack of support post-adoption were identified by parents. The dual needs of developing attachment and common language development strategies were also described by parents. The study demonstrates the need for pre- and post-adoptive speech and language services for this client group. It highlights the importance of the role of speech and language pathology in working with parents of toddlers and children who were adopted internationally. This role is in health promotion and prevention, as well as providing a service to this population as part of a multidisciplinary team, post-adoption. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Immunotherapy for Cervical Cancer

Cancer.gov

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

Adoptive Cell 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

CLAHRCs in practice: combined knowledge transfer and exchange strategies, cultural change, and experimentation.

PubMed

Soper, Bryony; Yaqub, Ohid; Hinrichs, Saba; Marjanovich, Sonja; Drabble, Samuel; Hanney, Stephen; Nolte, Ellen

2013-10-01

The nine NIHR CLAHRCs are collaborations between universities and local NHS organizations that seek to improve patient outcomes through the conduct and application of applied health research. The theoretical and practical context within which the CLAHRCs were set up was characterized by a considerable degree of uncertainty, and the CLAHRCs were established as a natural experiment. We adopted a formative and emergent evaluation approach. Drawing on in-depth, multi-method case studies of two CLAHRCs we explored how they pursued their remit by supporting efforts to increase the relevance and use of health research, and building relationships. Both CLAHRCs: strengthened local networks and relationships; built capacity in their local academic and NHS communities to undertake and use research that meets the needs of the service; developed research and implementation methodologies; and added to understanding of the complex relation between research and implementation. There was evidence of impact of CLAHRC projects on health and social care services. Informed by the literature on implementing collaborative research initiatives, knowledge transfer and exchange and cultural change, some key lessons can be drawn. The CLAHRCs pursued a strategy that can be categorized as one of flexible comprehensiveness; i.e. their programmes have been flexible and responsive and they have used a range of approaches that seek to match the diverse aspects of the complex issues they face. Key features include their work on combining a range of knowledge transfer and exchange strategies, their efforts to promote cultural change, and the freedom to experiment, learn and adapt. Although the CLAHRCs do not, by themselves, have the remit or resources to bring about wholesale service improvement in health care, they do have features that would allow them to play a key role in some of the wider initiatives that encourage innovation.

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

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…

From birth mothers to first mothers: toward a compassionate understanding of the life-long act of adoption placement.

PubMed

Coleman, Priscilla K; Garratt, Debbie

2016-01-01

Women who place a child for adoption have historically been far less actively researched than the other individuals in the adoption triad (adoptees and adoptive parents). They often have unmet psychological needs related to the decision to place for adoption, the placement experience, and as they endeavor to move forward post-adoption. In this review an effort is made to provide a description and analysis of the professional literature on women's placement experiences, with attention to methodological challenges inherent in deriving valid results. Next an overview of the results of a mixed method pilot study on birth mothers' decision-making and adjustment is shared. Finally, the most pressing future research needs on the topic of adoption placement from the birth mother's perspective are outlined. Data sources and extraction: Employing the following search terms: adoption, open-adoption, closed adoption, birth-mother, biological mother, relinquishment, and adoption placement, an exhaustive search for empirical journal articles, reviews, and edited book chapters was conducted yielding over 80 publications. Sources spanning a 50 year period (1974-2014) were identified via MEDLINE, PUBMED, and PsycINFO. Based on an in-depth analysis of the best available evidence on the psychological lives of women who choose adoption, an argument is made for more focused research attention and enhanced sensitivity to the unmet needs of birth mothers in our communities. As the experiences of birth mothers are more fully understood, more substantive and compassionate counseling before, during, and after adoption will become more feasible.

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.

Is Early Experience Destiny? Review of Research on Long-Term Outcomes following International Adoption with Special Reference to the British Chinese Adoption Study.

PubMed

Grant, Margaret; Rushton, Alan; Simmonds, John

2016-01-01

The pathway from adverse early experience to adulthood for internationally adopted children is complex in identifying key influences, impacts, and outcomes. This review arose from the authors' involvement in the British Chinese Adoption Study, a recent outcomes study that explored the links between early orphanage care, adoptive experiences, and midadulthood. It differs from previous reviews in focusing on a greater length of time since adoption. Both quantitative and qualitative studies were included to allow for examination of a fuller range of adult-related outcomes rather than mental health scores alone. The sampling, methods, and results of reviewed articles are summarised and a critical commentary is provided. Despite methodological differences and identified strengths and weaknesses, conclusions are drawn on the basis of the evidence available. Special attention is paid to the interpretation of negative outcomes. Findings identify areas that should be explored further in order to gain a fuller understanding of midlife outcomes of people who experienced a poor start in life followed by international adoption. Such studies help in refining lifespan developmental theories.

Dog owners show experience-based viewing behaviour in judging dog face approachability.

PubMed

Gavin, Carla Jade; Houghton, Sarah; Guo, Kun

2017-01-01

Our prior visual experience plays a critical role in face perception. We show superior perceptual performance for differentiating conspecific (vs non-conspecific), own-race (vs other-race) and familiar (vs unfamiliar) faces. However, it remains unclear whether our experience with faces of other species would influence our gaze allocation for extracting salient facial information. In this eye-tracking study, we asked both dog owners and non-owners to judge the approachability of human, monkey and dog faces, and systematically compared their behavioural performance and gaze pattern associated with the task. Compared to non-owners, dog owners assessed dog faces with shorter time and fewer fixations, but gave higher approachability ratings. The gaze allocation within local facial features was also modulated by the ownership. The averaged proportion of the fixations and viewing time directed at the dog mouth region were significantly less for the dog owners, and more experienced dog owners tended to look more at the dog eyes, suggesting the adoption of a prior experience-based viewing behaviour for assessing dog approachability. No differences in behavioural performance and gaze pattern were observed between dog owners and non-owners when judging human and monkey faces, implying that the dog owner's experience-based gaze strategy for viewing dog faces was not transferable across faces of other species.

Organizational Processes and Patient Experiences in the Patient-centered Medical Home.

PubMed

Aysola, Jaya; Schapira, Marilyn M; Huo, Hairong; Werner, Rachel M

2018-06-01

There is increasing emphasis on the use of patient-reported experience data to assess practice performance, particularly in the setting of patient-centered medical homes. Yet we lack understanding of what organizational processes relate to patient experiences. Examine associations between organizational processes practices adopt to become PCMH and patient experiences with care. We analyzed visit data from patients (n=8356) at adult primary care practices (n=22) in a large health system. We evaluated the associations between practice organizational processes and patient experience using generalized estimating equations (GEE) with an exchangeable correlation structure to account for patient clustering by practice in multivariate models, adjusting for several practice-level and patient-level characteristics. We evaluated if these associations varied by race/ethnicity, insurance type, and the degree of patient comorbidity MEASURES:: Predictors include overall PCMH adoption and adoption of six organizational processes: access and communications, patient tracking and registry, care management, test referral tracking, quality improvement and external coordination. Primary outcome was overall patient experience. In our full sample, overall PCMH adoption score was not significantly associated with patient experience outcomes. However, among subpopulations with higher comorbidities, the overall PCMH adoption score was positively associated with overall patient experience measures [0.2 (0.06, 0.4); P=0.006]. Differences by race/ethnicity and insurance type in associations between specific organizational processes and patient experience were noted. Although some organizational processes relate to patients' experiences with care irrespective of the background of the patient, further efforts are needed to align practice efforts with patient experience.

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

The transition into adoptive parenthood: Adoption as a process of continued unsafe uncertainty when family scripts collide.

PubMed

Tasker, Fiona; Wood, Sally

2016-10-01

Our prospective study investigated couples' expectations of adoptive parenthood and explored how these changed with their actual experience of parenthood. Six heterosexual couples were interviewed just before placement began and 6 months after the children had arrived. Interpretative Phenomenological Analysis (IPA) was used to analyse both sets of interview data. Expectations of adoptive parenthood mostly transformed smoothly into adoption experience for couples, but challenges were experienced when family scripts collided and a continued feeling of unsafe uncertainty then prevailed within these newly formed family systems. Family script collision seemed a particular problem for couples adopting sibling pairs. To further professional practice in working with families over the transition to adoptive parenting, we suggest that professionals keep in mind a framework that includes the following: Internal and external world influences on family members, Intergenerational issues, Family scripts and the Structural challenges of adoption (IIFS). © The Author(s) 2016.

Transitions of Adoptive Parents: A Longitudinal Mixed Methods Analysis.

PubMed

Foli, Karen J; Hebdon, Megan; Lim, Eunjung; South, Susan C

2017-10-01

As adoptive parents create a new family, they face myriad changes both pre-and post-placement of their child. The aim of this study was to describe parent perceptions and depressive symptoms during this transition via reports collected with an online survey. Using content analysis, we analyzed a total of 110 responses from 64 parents at three time points: 4-6weeks pre-placement, and 4-6weeks and 5-6months post-placement. Five main themes were revealed: Transition from uncertainty to a new normal; unique experiences related to adoption; rest/fatigue: out of balance; life stressors; and faith/spirituality. Two subthemes were also identified: previous losses (pre-placement) and joy and love (post-placement). During the transition from pre-to post-placement, adoptive parents experience a unique passage, with both challenges and strengths exclusive to this group of parents. While acknowledging the commonalities of some parenting experiences, healthcare and adoption professionals should recognize the unique dynamics that adoption brings to families. Copyright © 2017 Elsevier Inc. All rights reserved.

Lesbian, Gay, and Heterosexual Adoptive Parents' Perceptions of Inclusivity and Receptiveness in Early Childhood Education Settings

ERIC Educational Resources Information Center

Goldberg, Abbie E.; Black, Kaitlin; Sweeney, Kristin; Moyer, April

2017-01-01

Little research has examined the experiences of lesbian/gay (LG) parent families or adoptive parent families in early childhood education settings. This study uses interview data to examine the perceptions and experiences of 45 lesbian, gay, and heterosexual couples (90 individuals) with 10 adopted children with respect to their (1) openness with…

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.

Simultaneous transfer of optical frequency and time over 306 km long-haul optical fibre link

NASA Astrophysics Data System (ADS)

Hucl, Vaclav; Cizek, Martin; Pravdova, Lenka; Rerucha, Simon; Hrabina, Jan; Mikel, Bretislav; Smotlacha, Vladimir; Vojtech, Josef; Lazar, Josef; Cip, Ondrej

2016-12-01

Optical fibre links for distributing optical frequencies and time stamps were researched and experimentally tested in the past fifteen years. They have been used mainly for stability comparison of experimental optical clocks. But recent development puts demands on a technology transfer from laboratory experiments to the real industry. The remote calibration of interrogators of Fibre Bragg Grating strain sensory networks is one of important examples. The first step of the adoption the time and frequency broadcasting should be the drop-out free long-term operation of this technology between research laboratories connected via long-haul fibre links. We present a 306 km long-haul optical fibre link between the cities of Prague and Brno in the Czech Republic where a coherent transfer of stable optical frequency and a stable time signal has been firstly demonstrated. The link between ISI CAS Brno and CESNET Prague uses an internet communication fibre where a window of 1540-1546 nm is dedicated for the coherent transfer and 1PPS signal. The link is equipped with 6 bidirectional EDFA amplifiers. The optical frequency standard based on the highly-coherent laser Koheras Adjustik working at 1540.5 nm and stabilized with a saturation absorption spectroscopy technique was used for the coherent wave transfer. The suppression of the Doppler shift induced by the optical fibre was based on an accoustooptical modulator with a servo-loop including a fast PID controller processing the beat-note frequency given by mixing of the Adjustik laser (Brno) and the reflected frequency of this laser from the far end of 306 km long-haul fibre link (Prague). We verified the Doppler shift suppression for the coherent wave with a measuring method analysing the transport delay of the 1PPS signal.

Physiological numbers of CD4+ T cells generate weak recall responses following influenza virus challenge.

PubMed

Thomas, Paul G; Brown, Scott A; Morris, Melissa Y; Yue, Wen; So, Jenny; Reynolds, Cory; Webby, Richard J; Doherty, Peter C

2010-02-15

Naive and recall CD4(+) T cell responses were probed with recombinant influenza A viruses incorporating the OVA OT-II peptide. The extent of OT-II-specific CD4(+) T cell expansion was greater following primary exposure, with secondary challenge achieving no significant increase in numbers, despite higher precursor frequencies. Adoptive transfer experiments with OT-II TCR-transgenic T cells established that the predominant memory set is CD62L(hi), whereas the CD62L(lo) precursors make little contribution to the recall response. Unlike the situation described by other investigators, in which the transfer of very large numbers of in vitro-activated CD4 effectors can modify the disease process, providing CD62L(hi) or CD62L(lo) OT-II-specific T cells at physiological levels neither enhanced virus clearance nor altered clinical progression. Some confounding effects of the transgenic model were observed, with decreasing primary expansion efficiency correlating with greater numbers of transferred cells. This was associated with increased levels of mRNA for the proapoptotic molecule Bim in cells recovered following high-dose transfer. However, even with very low numbers of transferred cells, memory T cells did not expand significantly following secondary challenge. A similar result was recorded in mice primed and boosted to respond to an endogenous IA(b)-restricted epitope derived from the influenza virus hemagglutinin glycoprotein. Depletion of CD8(+) T cells during secondary challenge generated an increased accumulation of OT-II-specific T cells but only at the site of infection. Taken together, significant expansion was not a feature of these secondary influenza-specific CD4 T cell responses and the recall of memory did not enhance recovery.

Interleukin-15-transferred cytokine-induced killer cells elevated anti-tumor activity in a gastric tumor-bearing nude mice model.

PubMed

Peng, Zheng; Liang, Wentao; Li, Zexue; Xu, Yingxin; Chen, Lin

2016-02-01

Gastric cancer is the second leading cause of cancer-related mortality worldwide. Adoptive cell therapy (ACT) for gastric cancer is a novel therapy modality. However, the therapeutic effectiveness in vivo is still limited. The objective of this study was to assess the value of interleukin-15 (IL-15)-transferred cytokine-induced killer (CIK) cells in ACT for gastric cancer. IL-15-IRES-TK retroviral vector was constructed and transferred into the CIK cells. A gastric tumor-bearing nude mice model was constructed by subcutaneously injecting gastric cancer cells, BGC-823. Gastric tumor-bearing nude mice were randomly divided into three groups (five mice each group) and injected with physiological saline, CIK cells, and IL-15-IRES-TK-transfected CIK cells for 2 weeks, respectively. IL-15-IRES-TK-transferred CIK cells were prepared successfully and flow cytometry (FCM) analysis indicated that the transfection rate reached 85.7% after 5 days culture. In vivo experiment, we found that CIK cells retarded tumor growth by reducing tumor volume and tumor weight, as well as increasing tumor inhibition rate. Furthermore, IL-15-IRES-TK-transferred CIK cells showed a much stronger inhibition on tumor growth than CIK cells alone. Tumor morphology observation and growth indexes also showed that IL-15-transfected CIK cells had stronger cytotoxicity to tumor tissue than CIK cells. IL-15-IRES-TK transfection could elevate the effects of CIK cells to gastric carcinoma. The engineered CIK cells carrying IL-15-IRES-TK may be used in the ACT for gastric carcinoma, but prudent clinical trial is still indispensable. © 2015 International Federation for Cell Biology.

Effect of cold atmospheric pressure He-plasma jet on DNA change and mutation

NASA Astrophysics Data System (ADS)

Yaopromsiri, C.; Yu, L. D.; Sarapirom, S.; Thopan, P.; Boonyawan, D.

2015-12-01

Cold atmospheric pressure plasma jet (CAPPJ) effect on DNA change was studied for assessment of its safety. The experiment utilized a home-developed CAPPJ using 100% helium to directly treat naked DNA plasmid pGFP (plasmid green fluorescent protein). A traversal electric field was applied to separate the plasma components and both dry and wet sample conditions were adopted to investigate various factor roles in changing DNA. Plasma species were measured by using optical emission spectroscopy. DNA topological form change was analyzed by gel electrophoresis. The plasma jet treated DNA was transferred into bacterial Escherichia coli cells for observing mutation. The results show that the He-CAPPJ could break DNA strands due to actions from charge, radicals and neutrals and potentially cause genetic modification of living cells.

The SPES surface ionization source

NASA Astrophysics Data System (ADS)

Manzolaro, M.; D'Agostini, F.; Monetti, A.; Andrighetto, A.

2017-09-01

Ion sources and target systems play a crucial role in isotope separation on line facilities, determining the main characteristics of the radioactive ion beams available for experiments. In the context of the selective production of exotic species (SPES) facility, a 40 MeV, 200 μA proton beam directly impinges a uranium carbide target, generating approximately 1013 fissions per second. The radioactive isotopes produced by the 238U fissions are delivered to the 1+ ion source by means of a tubular transfer line. Here they can be ionized and subsequently accelerated toward the experimental areas. In this work, the characterization of the surface ionization source currently adopted for the SPES facility is presented, taking as a reference ionization efficiency and transversal emittance measurements. The effects of long term operation at high temperature are also illustrated and discussed.

Towards single embryo transfer? Modelling clinical outcomes of potential treatment choices using multiple data sources: predictive models and patient perspectives.

PubMed

Roberts, Sa; McGowan, L; Hirst, Wm; Brison, Dr; Vail, A; Lieberman, Ba

2010-07-01

In vitro fertilisation (IVF) treatments involve an egg retrieval process, fertilisation and culture of the resultant embryos in the laboratory, and the transfer of embryos back to the mother over one or more transfer cycles. The first transfer is usually of fresh embryos and the remainder may be cryopreserved for future frozen cycles. Most commonly in UK practice two embryos are transferred (double embryo transfer, DET). IVF techniques have led to an increase in the number of multiple births, carrying an increased risk of maternal and infant morbidity. The UK Human Fertilisation and Embryology Authority (HFEA) has adopted a multiple birth minimisation strategy. One way of achieving this would be by increased use of single embryo transfer (SET). To collate cohort data from treatment centres and the HFEA; to develop predictive models for live birth and twinning probabilities from fresh and frozen embryo transfers and predict outcomes from treatment scenarios; to understand patients' perspectives and use the modelling results to investigate the acceptability of twin reduction policies. A multidisciplinary approach was adopted, combining statistical modelling with qualitative exploration of patients' perspectives: interviews were conducted with 27 couples at various stages of IVF treatment at both UK NHS and private clinics; datasets were collated of over 90,000 patients from the HFEA registry and nearly 9000 patients from five clinics, both over the period 2000-5; models were developed to determine live birth and twin outcomes and predict the outcomes of policies for selecting patients for SET or DET in the fresh cycle following egg retrieval and fertilisation, and the predictions were used in simulations of treatments; two focus groups were convened, one NHS and one web based on a patient organisation's website, to present the results of the statistical analyses and explore potential treatment policies. The statistical analysis revealed no characteristics that specifically predicted multiple birth outcomes beyond those that predicted treatment success. In the fresh transfer following egg retrieval, SET would lead to a reduction of approximately one-third in the live birth probability compared with DET, a result consistent with the limited data from clinical trials. From the population or clinic perspective, selection of patients based on prognostic indicators might mitigate about half of the loss in live births associated with SET in the initial fresh transfer while achieving a twin rate of 10% or less. Data-based simulations suggested that, if all good-quality embryos are replaced over multiple frozen embryo transfers, repeated SET has the potential to produce more live birth events than repeated DET. However, this would depend on optimising cryopreservation procedures. Universal SET could both reduce the number of twin births and lead to more couples having a child, but at an average cost of one more embryo transfer procedure per egg retrieval. The interview and focus group data suggest that, despite the potential to maintain overall success rates, patients would prefer DET: the potential for twins was seen as positive, while additional transfer procedures can be emotionally, physically and financially draining. For any one transfer, SET has about a one-third loss of success rate relative to DET. This can be only partially mitigated by patient and treatment cycle selection, which may be criticised as unfair as all patients receiving SET will have a lower chance of success than they would with DET. However, considering complete cycles (fresh plus frozen transfers), it is possible for repeat SET to produce more live births than repeat DET. Such a strategy would require support from funders and acceptance by patients of both cryopreservation and the burden of additional transfer cycles. Future work should include development of improved clinical and regulatory database systems, surveys to quantify the extent of patients' beliefs and experiences and develop approaches to meet their information needs, and, ideally, randomised controlled trials comparing policies of repeated SET with repeated DET.

Exploring Community College Students' Transfer Experiences and Perceptions and What They Believe Administration Can Do to Improve Their Experiences

ERIC Educational Resources Information Center

Walker, Kimberly Young; Okpala, Comfort

2017-01-01

This study explored the interconnectedness of the transfer student experience and used it as a foundational framework to inform the administrative leadership on a North Carolina, midsized, historically Black college of the existing transfer students' experiences. This study focused on (a) how transfer students at a midsized historically black…

[The adopted child and his problems. Pedo-psychiatric point of view].

PubMed

Schachter, M

1980-12-01

After a survey of the recent pedopsychiatric literature concerning the difficulties exhibited by young adoptees, we describe our own experience with 35 adopted children. The subjects were divided in two groups: a) the first group of 26 cases (74%) concerning clinical disturbances with no evident relation to the situation derived by the adoption; b) the second group of 9 cases (26%) concerning: 1. four cases ou rebellious behaviour against the adopters et 2. fives cases of camouflaged rejection of the adoptees by their adopters. These 9 cases are given with details; the characteristics of the other 26 cases are summarized. Our pedopsychiatric experience has shown that adoption was a failure in 26% of the cases related in the present study.

All in: expansion of the acquisition of data for outcomes and procedure transfer (ADOPT) program to an entire SAGES annual meeting hands-on hernia course.

PubMed

Dort, Jonathan; Trickey, Amber; Paige, John; Schwarz, Erin; Cecil, Tom; Coleman, Mark; Dunkin, Brian

2018-05-01

Continuing professional development (CPD) for the surgeon has been challenging because of a lack of standardized approaches of hands-on courses, resulting in poor post-course outcomes. To remedy this situation, SAGES has introduced the ADOPT program, implementing a standardized, long-term mentoring program as part of its hernia hands-on course. Previous work evaluating the pilot program showed increased adoption of learned procedures as well as increased confidence of the mentored surgeons. This manuscript describes the impact of such a program when it is instituted across an entire hands-on course. Following collection of pre-course benchmark data, all participants in the 2016 SAGES hands-on hernia course underwent structured, learner-focused instruction during the cadaveric lab. All faculty had completed a standardized teaching course in the Lapco TT format. Subsequently, course participants were enrolled in a year-long program involving longitudinal mentorship, webinars, conference calls, and coaching. Information about participant demographics, training, experience, self-reported case volumes, and confidence levels related to procedures were collected via survey 3 months prior to 9 months after the course. Twenty surgeons participated in the SAGES ADOPT 2016 hands-on hernia program. Of these, seventeen completed pre-course questionnaires (85%), ten completed the 3-month questionnaire (50%), and four completed the 9-month questionnaire (20%). Nine of ten respondents of the 3-month survey (90%) reported changes in their practice. In the 9-month survey, significant increases in the annualized procedural volumes were reported for open primary ventral hernia repair, open components separation, and mesh insertion for ventral hernia repair (p < 0.001). The expansion of the ADOPT program to an entire hands-on hernia course is both feasible and beneficial, with evidence of Kirkpatrick Levels 1-4a training effectiveness. This expanded success suggests that it is a useful blueprint for the CPD of surgeons wishing to learn new techniques and procedures for their patients.

Age at adoption from institutional care as a window into the lasting effects of early experiences

PubMed Central

Julian, Megan M.

2013-01-01

One of the major questions of human development is how early experience impacts the course of development years later. Children adopted from institutional care experience varying levels of deprivation in their early life followed by qualitatively better care in an adoptive home, providing a unique opportunity to study the lasting effects of early deprivation and its timing. The effects of age at adoption from institutional care are discussed for multiple domains of social and behavioral development within the context of several prominent developmental hypotheses about the effects of early deprivation (cumulative effects, experience-expectant developmental programming, and experience-adaptive developmental programming). Age at adoption effects are detected in a majority of studies, particularly when children experienced global deprivation and were assessed in adolescence. For most outcomes, institutionalization beyond a certain age is associated with a step-like increase in risk for lasting social and behavioral problems, with the step occurring at an earlier age for children who experienced more severe levels of deprivation. Findings are discussed in terms of their concordance and discordance with our current hypotheses, and speculative explanations for the findings are offered. PMID:23576122

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

PubMed

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

2018-05-01

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

National Aerospace Leadership Initiative - Phase I

DTIC Science & Technology

2008-09-30

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2014-12-16

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

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

PubMed

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

2014-05-01

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

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

PubMed

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

2016-11-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed

Dodlova, Marina; Giolbas, Anna; Lay, Jann

2018-02-01

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

Adoptive immunotherapy for cancer.

PubMed

Ruella, Marco; Kalos, Michael

2014-01-01

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

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

Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice.

PubMed

Kapoor, A K; Buckmaster, A; Nash, A A; Field, H J; Wildy, P

1982-11-01

Congenitally athymic nude mice were infected with 10(4) p.f.u. herpes simplex type 1 (strain SC16). Following the passive transfer of neutralizing monoclonal antibodies (AP7, AP8 and AP12) it was observed that AP7 alone reduced the virus infectivity in the nervous system; AP8 and AP12 failed to protect mice probably due to poor in vivo binding to the neutralization site on the virus. Latent ganglionic infection could be established in nude mice following adoptive transfer of optimum number (2 x 10(7) cells/mouse) of immune lymph node cells from day 7 herpes virus-infected hairy immunocompetent donor mice. Moreover, in some of the immune lymph node cell protected nudes, latency could be maintained even in complete absence of neutralizing antibodies. Results of ear-ablation experiments revealed that removal of primary source of infection after day 5 of infection reduced the amount of virus in the ganglia and spinal cord. Acute neurological infection was not detected following transfer of protective anti-gp-D neutralizing antibody (LP2) in combination with removal of infected pinna. These data suggest that continuous seeding of virus occurs in related ganglia via the axonal route from infected ear pinna. It appears that local T-cell-mediated immune mechanisms are involved in maintenance of latency.

Cognitive and emotional processing of pleasant and unpleasant experiences in major depression: A matter of vantage point?

PubMed

Pfaltz, Monique C; Wu, Gwyneth W Y; Liu, Guanyu; Tankersley, Amelia P; Stilley, Ashley M; Plichta, Michael M; McNally, Richard J

2017-03-01

In nonclinical populations, adopting a third-person perspective as opposed to a first-person perspective while analyzing negative emotional experiences fosters understanding of these experiences and reduces negative emotional reactivity. We assessed whether this generalizes to people with major depression (MD). Additionally, we assessed whether the emotion-reducing effects of adopting a third-person perspective also occur when subjects with MD and HC subjects analyze positive experiences. Seventy-two MD subjects and 82 HC subjects analyzed a happy and a negative experience from either a first-person or a third-person perspective. Unexpectedly, we found no emotion-reducing effects of third-person perspective in either group thinking about negative events. However, across groups, third-person perspective was associated with less recounting of negative experiences and with a clearer, more coherent understanding of them. Negative affect decreased and positive affect increased in both groups analyzing happy experiences. In MD subjects, decreases in depressive affect were stronger for the third-person perspective. In both groups, positive affect increased and negative affect decreased more strongly for the third-person perspective. While reflecting on their positive memory, MD subjects adopted their assigned perspective for a shorter amount of time (70%) than HC subjects (78%). However, percentage of time participants adopted their assigned perspective was unrelated to the significant effects we found. Both people suffering from MD and healthy individuals may benefit from processing pleasant experiences, especially when adopting a self-distant perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

OX40 signaling is involved in the autoactivation of CD4+CD28- T cells and contributes to the pathogenesis of autoimmune arthritis.

PubMed

Jiang, Juean; Liu, Cuiping; Liu, Mi; Shen, Yu; Hu, Xiaohan; Wang, Qin; Wu, Jian; Wu, Min; Fang, Qi; Zhang, Xueguang

2017-03-21

CD4 + CD28 - T cells exhibit autoreactive potential in autoimmune disorders, including rheumatoid arthritis (RA). It is not well known which costimulator functions as an alternative second signal in the activation of this subset after CD28 expression is downregulated. Tumor necrosis factor receptor superfamily member OX40 is a key costimulator in the activation of T cells. The aim of this study was to investigate the costimulatory effects of OX40 on CD4 + CD28 - T cells in autoimmune arthritis. Clinical samples were collected from patients with RA and control subjects. Collagen-induced arthritis (CIA) was induced with collagen type II (CII) in DBA/1 mice. The CD4 + CD28 - OX40 + T-cell subset and its cytokine production were detected by flow cytometry. After T-cell purification, adoptive transfer was performed in CIA mice. The regulatory role of OX40 was determined by blocking experiments in vitro and in vivo. OX40 and OX40L were abnormally expressed in patients with RA and CIA mice. Further analysis showed that CD4 + CD28 - OX40 + T cells accumulated in patients with RA and in animal models. These cells produced higher levels of proinflammatory cytokines and were closely correlated with the clinicopathological features of the affected individuals. Adoptive transfer of CII-specific CD4 + CD28 - OX40 + T cells remarkably aggravated arthritic development and joint pathology in CIA mice. Moreover, OX40 blockade significantly reduced the proinflammatory responses and ameliorated arthritis development. OX40 acts as an alternative costimulator of CD4 + CD28 - T cells and plays a pathogenic role in autoimmune arthritic development, suggesting that it is a potential target for immunomodulatory therapy of RA.

Worm Proteins of Schistosoma mansoni Reduce the Severity of Experimental Chronic Colitis in Mice by Suppressing Colonic Proinflammatory Immune Responses

PubMed Central

Heylen, Marthe; Ruyssers, Nathalie E.; De Man, Joris G.; Timmermans, Jean-Pierre; Pelckmans, Paul A.; Moreels, Tom G.; De Winter, Benedicte Y.

2014-01-01

Although helminthic therapy as a possible new option to treat inflammatory bowel disease is a well-established concept by now, the search for immunomodulatory helminth-derived compounds and their mechanisms of action is still ongoing. We investigated the therapeutic potential and the underlying immunological mechanisms of Schistosoma mansoni soluble worm proteins (SmSWP) in an adoptive T cell transfer mouse model of chronic colitis. Both a curative and a preventive treatment protocol were included in this study. The curative administration of SmSWP (started when colitis was established), resulted in a significant improvement of the clinical disease score, colonoscopy, macroscopic and microscopic inflammation score, colon length and myeloperoxidase activity. The therapeutic potential of the preventive SmSWP treatment (started before colitis was established), was less pronounced compared with the curative SmSWP treatment but still resulted in an improved clinical disease score, body weight loss, colon length and microscopic inflammation score. Both the curative and preventive SmSWP treatment downregulated the mRNA expression of the proinflammatory cytokines IFN-γ and IL-17A and upregulated the mRNA expression of the anti-inflammatory cytokine IL-4 in the colon at the end of the experiment. This colonic immunomodulatory effect of SmSWP could not be confirmed at the protein level. Moreover, the effect of SmSWP appeared to be a local colonic phenomenon, since the flow cytometric T cell characterization of the mesenteric lymph nodes and the cytokine measurements in the serum did not reveal any effect of SmSWP treatment. In conclusion, SmSWP treatment reduced the severity of colitis in the adoptive transfer mouse model via the suppression of proinflammatory cytokines and the induction of an anti-inflammatory response in the colon. PMID:25313594

Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

PubMed Central

Behler, Friederike; Maus, Regina; Bohling, Jennifer; Knippenberg, Sarah; Kirchhof, Gabriele; Nagata, Masahiro; Jonigk, Danny; Izykowski, Nicole; Mägel, Lavinia; Welte, Tobias; Yamasaki, Sho

2014-01-01

The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTR mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice. PMID:25332121

Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent process.

PubMed

Lee, Hyun Soo; Schlereth, Simona; Khandelwal, Payal; Saban, Daniel R

2013-01-01

A reproducible method to inhibit allergic immune responses is accomplished with hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is whether such modulation extends to ocular allergy. We therefore determined herein whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+ FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 µg) versus hi-dose (1000 µg) ovalbumin (OVA), in aluminum hydroxide (1 mg) and pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg during sensitization. In another experiment, Treg from hi-dose sensitized mice were adoptively transferred into low-dose sensitized mice. Once daily OVA challenges were administered. Clinical signs, IgE, T cell cytokines, and eosinophils were assessed. Data revealed that hi-dose, but not low-dose, sensitization led to allergy modulation, indicated by decreased clinical signs, serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg from these mice were able to efficiently suppress effector T cell proliferation in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to adoptively transfer allergy modulation to their low-dose sensitized counterparts. Collectively, these findings indicate that modulation to hi-dose sensitization, which is extended to ocular allergy, occurs in a Treg-dependent manner. In addition, our data suggest that hi-dose sensitization may henceforth facilitate the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease.

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.

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

“When You’re Sitting on the Fence, Hope’s the Hardest Part”: Challenges and Experiences of Heterosexual and Same-Sex Couples Adopting Through the Child Welfare System

PubMed Central

Moyer, April M.; Kinkler, Lori A.; Richardson, Hannah B.

2012-01-01

Foster-to-adopt families can be viewed as systems that are influenced by many other systems (e.g., the legal system, the social service agency, and the birth family). The current qualitative study of 84 foster-to-adopt parents (members of 42 lesbian, gay, and heterosexual couples) examined the types of challenges that parents faced as they navigated multiple systems during the initial post-placement period. Some participants described the legal insecurity associated with their role as foster-to-adopt parents as impacting their personal well-being and their attachment to their children. Lack of support services and disorganization within social service agencies, as well as strained relationships with birth parents, were also identified as stressors for foster-to-adopt parents. Importantly, lesbian and gay participants faced additional concerns regarding the security of their placement, due to the possibility for discrimination within the various systems involved with the foster-to-adopt process. Participants as a whole also identified positive aspects of their experiences within various systems; for example, they appreciated child care subsidies, state-provided health insurance, and supportive social workers. Our findings provide insights into foster-to-adopt parents’ experiences during the initial post-placement period, and have implications for adoption services aimed to improve placement stability and enhance family functioning in foster-to-adopt families. PMID:23226935

Responding to the Needs of the Adopted Child

ERIC Educational Resources Information Center

Gajda, Rebecca

2004-01-01

In today's societal landscape, "adoption," the legal process by which a child becomes a full and permanent member of a new family, is becoming commonplace. Even though most people have had a personal experience with adoption in some capacity, those most closely associated with adoption (birth parents, adoptees, and adoptive parents) continue to be…

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

PubMed

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

2016-01-01

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

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

PubMed

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

2013-09-01

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

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.

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.

A Phenomenological Exploration of Adoption

ERIC Educational Resources Information Center

Baltimore, Diana L.; Crase, Sedahlia Jasper

2009-01-01

This qualitative analysis explored children's and adults' experiences with adoption. We used phenomenological methodology and individually interviewed 25 participants and included adoptive mothers and fathers, and their children, each adopted before 18 months of age. Two research questions guided the data analysis: (a) What are children's and…

'School adopts an experiment': the photoluminescence in extra-virgin olive oil and in tonic water

NASA Astrophysics Data System (ADS)

Agliolo Gallitto, A.; Agnello, S.; Cannas, M.

2011-09-01

We report a laboratory activity, carried out along with high- and secondary-school students, that can be done to increase the interest of the young in scientific studies. Groups of selected students 'adopted' experiments at physics research laboratories, under the guidance of university researchers. Subsequently, the students demonstrated the experiments to the public at large during the annual science festival organized in Palermo by the association PalermoScienza, in collaboration with the University of Palermo. Experiments on the magnetic levitation of superconductors and on the photoluminescence of several substances were proposed. We discuss the experiment on photoluminescence as a case study. The students who adopted the experiments reinforced their commitment to learning. They acquired a physics-based knowledge of the topics connected with the experiments in a much better way compared with the usual didactics in school.

Correlates and Predictors of Parenting Stress among Internationally Adopting Mothers: A Longitudinal Investigation

ERIC Educational Resources Information Center

Viana, Andres G.; Welsh, Janet A.

2010-01-01

This study examined correlates and predictors of parenting stress among internationally adopting (IA) mothers with the goal of expanding the knowledge base on the experiences of adoptive parents. One hundred and forty-three IA mothers completed pre-adoption (Time 0) and six months post-adoption (Time 1) surveys with questions regarding child-,…

Processes of local alcohol policy-making in England: Does the theory of policy transfer provide useful insights into public health decision-making?

PubMed

Gavens, Lucy; Holmes, John; Buykx, Penny; de Vocht, Frank; Egan, Matt; Grace, Daniel; Lock, Karen; Mooney, John D; Brennan, Alan

2017-06-13

Recent years have seen a rise in new and innovative policies to reduce alcohol consumption and related harm in England, which can be implemented by local, as opposed to national, policy-makers. The aim of this paper is to explore the processes that underpin the adoption of these alcohol policies within local authorities. In particular, it aims to assess whether the concept of policy transfer (i.e. a process through which knowledge about policies in one place is used in the development of policies in another time or place) provides a useful model for understanding local alcohol policy-making. Qualitative data generated through in-depth interviews and focus groups from five case study sites across England were used to explore stakeholder experiences of alcohol policy transfer between local authorities. The purposive sample of policy actors included representatives from the police, trading standards, public health, licensing, and commissioning. Thematic analysis was used inductively to identify key features in the data. Themes from the policy transfer literature identified in the data were: policy copying, emulating, hybridization, and inspiration. Participants described a multitude of ways in which learning was shared between places, ranging from formal academic evaluation to opportunistic conversations in informal settings. Participants also described facilitators and constraints to policy transfer, such as the historical policy context and the local cultural, economic, and bureaucratic context, which influenced whether or not a policy that was perceived to work in one place might be transferred successfully to another context. Theories of policy transfer provide a promising framework for characterising processes of local alcohol policy-making in England, extending beyond debates regarding evidence-informed policy to account for a much wider range of considerations. Applying a policy transfer lens enables us to move beyond simple (but still important) questions of what is supported by 'robust' research evidence by paying greater attention to how policy making is carried out in practice and the multiple methods by which policies diffuse across jurisdictions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Grower networks support adoption of innovations in pollination management: The roles of social learning, technical learning, and personal experience.

PubMed

Garbach, Kelly; Morgan, Geoffrey P

2017-12-15

Management decisions underpinning availability of ecosystem services and the organisms that provide them in agroecosystems, such as pollinators and pollination services, have emerged as a foremost consideration for both conservation and crop production goals. There is growing evidence that innovative management practices can support diverse pollinators and increase crop pollination. However, there is also considerable debate regarding factors that support adoption of these innovative practices. This study investigated pollination management practices and related knowledge systems in a major crop producing region of southwest Michigan in the United States, where 367 growers were surveyed to evaluate adoption of three innovative practices that are at various stages of adoption. The goals of this quantitative, social survey were to investigate grower experience with concerns and benefits associated with each practice, as well as the influence of grower networks, which are comprised of contacts that reflect potential pathways for social and technical learning. The results demonstrated that 17% of growers adopted combinations of bees (e.g. honey bees, Apis mellifera, with other species), representing an innovation in use by early adopters; 49% of growers adopted flowering cover crops, an innovation in use by the early majority 55% of growers retained permanent habitat for pollinators, an innovation in use by the late majority. Not all growers adopted innovative practices. We found that growers' personal experience with potential benefits and concerns related to the management practices had significant positive and negative relationships, respectively, with adoption of all three innovations. The influence of these communication links likely has different levels of importance, depending on the stage of the adoption that a practice is experiencing in the agricultural community. Social learning was positively associated with adopting the use of combinations of bees, highlighting the potentially critical roles of peer-to-peer networks and social learning in supporting early stages of adoption of innovations. Engaging with grower networks and understanding grower experience with benefits and concerns associated with innovative practices is needed to inform outreach, extension, and policy efforts designed to stimulate management innovations in agroecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Input-output mapping reconstruction of spike trains at dorsal horn evoked by manual acupuncture

NASA Astrophysics Data System (ADS)

Wei, Xile; Shi, Dingtian; Yu, Haitao; Deng, Bin; Lu, Meili; Han, Chunxiao; Wang, Jiang

2016-12-01

In this study, a generalized linear model (GLM) is used to reconstruct mapping from acupuncture stimulation to spike trains driven by action potential data. The electrical signals are recorded in spinal dorsal horn after manual acupuncture (MA) manipulations with different frequencies being taken at the “Zusanli” point of experiment rats. Maximum-likelihood method is adopted to estimate the parameters of GLM and the quantified value of assumed model input. Through validating the accuracy of firings generated from the established GLM, it is found that the input-output mapping of spike trains evoked by acupuncture can be successfully reconstructed for different frequencies. Furthermore, via comparing the performance of several GLMs based on distinct inputs, it suggests that input with the form of half-sine with noise can well describe the generator potential induced by acupuncture mechanical action. Particularly, the comparison of reproducing the experiment spikes for five selected inputs is in accordance with the phenomenon found in Hudgkin-Huxley (H-H) model simulation, which indicates the mapping from half-sine with noise input to experiment spikes meets the real encoding scheme to some extent. These studies provide us a new insight into coding processes and information transfer of acupuncture.

[Adoptive parents' satisfaction with the adoption experience and with its impact on family life].

PubMed

Sánchez-Sandoval, Yolanda

2011-11-01

In this study, we discuss the relevance of adoptive families' satisfaction in the assessment of adoption processes. The effects of adoption on a sample group of 272 adoptive families are analyzed. Most families show high levels of satisfaction as to: their decision to adopt, the features of their adopted children and how adoption has affected them as individuals and as a family. Statistical analyses show that these families can have different satisfaction levels depending on certain features of the adoptees, of the adoptive families or of their educational style. Life satisfaction of the adoptees is also related to how their adoptive parents evaluate the adoption.

[The qualitative research on social inequalities in health: the life courses].

PubMed

Roy, Bernard; De Koninck, Maria

2013-02-11

Adopting a lifecourse perspective is more and more frequent in the health inequalities research field. This article describes such an approach, as applied in a study on poverty and social exclusion. In this study, life histories were collected through open interviews and focused on the meaning of lived experiences. An original analysis table was used, in which words are grouped within categories identifying the different components of a lifecourse. Whether it refers to experiences lived in childhood or adulthood, the life history enables the placing of these within the individual's lifecourse. The horizontal analysis of different individual stories makes it possible to identify experiences that have harmful, or conversely, beneficial effects. When transferring results, reporting the experiences lived by the populations using the same words they did to describe them can help those responsible for program development or implementation understand the genesis of social health inequities. The analysis of life histories, based on the different components of a lifecourse, allows the identification of key moments in the interviewees' life evolution and, in an action perspective, to do so while taking health and social intervention fields into account. Such results make it easier to design actions to counter social health inequities - and above all their chronic nature - that are suited to the realities encountered.

A sequential assignment procedure for proteins that have intermediate line widths in MAS NMR spectra: amyloid fibrils of human CA150.WW2.

PubMed

Becker, Johanna; Ferguson, Neil; Flinders, Jeremy; van Rossum, Barth-Jan; Fersht, Alan R; Oschkinat, Hartmut

2008-08-11

The second WW domain (WW2) of CA150, a human transcriptional activator, forms amyloid fibrils in vitro under physiological conditions. Based on experimental constraints from MAS NMR spectroscopy experiments, alanine scanning and electron microscopy, a structural model of CA150.WW2 amyloid fibrils was calculated earlier. Here, the assignment strategy is presented and suggested as a general approach for proteins that show intermediate line width. The (13)C,(13)C correlation experiments were recorded on fully or partially (13)C-labelled fibrils. The earlier (13)C assignment (26 residues) was extended to 34 of the 40 residues by direct (13)C-excitation experiments by using a deuterated sample that showed strongly improved line width. A 3D HNC-TEDOR (transferred-echo double-resonance) experiment with deuterated CA150.WW2 fibrils yielded 14 amide nitrogen and proton resonance assignments. The obtained chemical shifts were compared with the chemical shifts determined with the natively folded WW domain. TALOS (Torsion angle likelihood obtained from shift and sequence similarity) predictions confirmed that, under physiological conditions, the fibrillar form of CA150.WW2 adopts a significantly different beta structure than the native WW-domain fold.

Product diffusion through on-demand information-seeking behaviour.

PubMed

Riedl, Christoph; Bjelland, Johannes; Canright, Geoffrey; Iqbal, Asif; Engø-Monsen, Kenth; Qureshi, Taimur; Sundsøy, Pål Roe; Lazer, David

2018-02-01

Most models of product adoption predict S-shaped adoption curves. Here we report results from two country-scale experiments in which we find linear adoption curves. We show evidence that the observed linear pattern is the result of active information-seeking behaviour: individuals actively pulling information from several central sources facilitated by modern Internet searches. Thus, a constant baseline rate of interest sustains product diffusion, resulting in a linear diffusion process instead of the S-shaped curve of adoption predicted by many diffusion models. The main experiment seeded 70 000 (48 000 in Experiment 2) unique voucher codes for the same product with randomly sampled nodes in a social network of approximately 43 million individuals with about 567 million ties. We find that the experiment reached over 800 000 individuals with 80% of adopters adopting the same product-a winner-take-all dynamic consistent with search engine driven rankings that would not have emerged had the products spread only through a network of social contacts. We provide evidence for (and characterization of) this diffusion process driven by active information-seeking behaviour through analyses investigating (a) patterns of geographical spreading; (b) the branching process; and (c) diffusion heterogeneity. Using data on adopters' geolocation we show that social spreading is highly localized, while on-demand diffusion is geographically independent. We also show that cascades started by individuals who actively pull information from central sources are more effective at spreading the product among their peers. © 2018 The Authors.

Product diffusion through on-demand information-seeking behaviour

PubMed Central

Bjelland, Johannes; Canright, Geoffrey; Iqbal, Asif; Qureshi, Taimur; Sundsøy, Pål Roe

2018-01-01

Most models of product adoption predict S-shaped adoption curves. Here we report results from two country-scale experiments in which we find linear adoption curves. We show evidence that the observed linear pattern is the result of active information-seeking behaviour: individuals actively pulling information from several central sources facilitated by modern Internet searches. Thus, a constant baseline rate of interest sustains product diffusion, resulting in a linear diffusion process instead of the S-shaped curve of adoption predicted by many diffusion models. The main experiment seeded 70 000 (48 000 in Experiment 2) unique voucher codes for the same product with randomly sampled nodes in a social network of approximately 43 million individuals with about 567 million ties. We find that the experiment reached over 800 000 individuals with 80% of adopters adopting the same product—a winner-take-all dynamic consistent with search engine driven rankings that would not have emerged had the products spread only through a network of social contacts. We provide evidence for (and characterization of) this diffusion process driven by active information-seeking behaviour through analyses investigating (a) patterns of geographical spreading; (b) the branching process; and (c) diffusion heterogeneity. Using data on adopters' geolocation we show that social spreading is highly localized, while on-demand diffusion is geographically independent. We also show that cascades started by individuals who actively pull information from central sources are more effective at spreading the product among their peers. PMID:29467257

Caucasian Parents and Korean Adoptees: A Survey of Parents' Perceptions.

ERIC Educational Resources Information Center

Bergquist, Kathleen Ja Sook; Campbell, Mary E.; Unrau, Yvonne A.

2003-01-01

Explored the transracial adoption experiences of Caucasian parents adopting children from Korea, comparing mothers' and fathers' perceptions regarding reasons for adopting, family adjustment related to the adoption, and racial identity of adoptees. Found that mothers' and fathers' perceptions were more similar than different, and parents…

Experience of in vitro fertilization surrogacy in Finland.

PubMed

Söderström-Anttila, Viveca; Blomqvist, Tom; Foudila, Tuija; Hippeläinen, Maritta; Kurunmäki, Henri; Siegberg, Rita; Tulppala, Maija; Tuomi-Nikula, Merja; Vilska, Sirpa; Hovatta, Outi

2002-08-01

In vitro fertilization (IVF) surrogacy makes it possible for women who do not have a functional uterus to have their own genetic offspring. We describe here our experience of IVF surrogacy in Finland over a 10-year period. This retrospective study included 17 women who underwent ovarian stimulation in connection with surrogacy in 1991-2001 at four clinics. The surrogate mothers were unpaid volunteers: six sisters, three mothers, one husband's sister, one cousin, four friends and three other volunteers. Thorough counseling was given to the commissioning couples and to the surrogate mothers and their partners. The commissioning couples were prepared to adopt their biological children. Twenty-eight surrogate IVF cycles were started in 17 women. One couple received donated oocytes. Trans-vaginal oocyte retrieval was feasible in every case, including those five women with congenital absence of the vagina and uterus. An average of 1.8 embryos was transferred at a time, and 11 pregnancies were achieved [50% per fresh embryo transfer (ET) and 16% per frozen-thawed ET]. Nine healthy singletons and one set of twins were born. One pregnancy ended in miscarriage. The mean birth weight of singleton infants was 3498 g (2270-4650 g). The birth weights of the twins were 2900 and 2400 g. In all cases the genetic parents took care of the infant immediately after birth. Two surrogate mothers had postpartum depression. Altruistic IVF surrogacy works well, but careful counseling of all parties involved is essential.

A seesaw-type approach for enhancing nonlinear energy harvesting

NASA Astrophysics Data System (ADS)

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

2018-05-01

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

Knowledge transfer to builders in post-disaster housing reconstruction in West-Sumatra of Indonesia

NASA Astrophysics Data System (ADS)

Hidayat, Benny; Afif, Zal

2017-11-01

Housing is the most affected sector by disasters as can be observed after the 2009 earthquake in West Sumatra province in Indonesia. As in Indonesian construction industry, the housing post-disaster reconstruction is influenced by knowledge and skills of builders or laborers, or locally known as `tukang'. After the earthquake there were trainings to transfer knowledge about earthquake-safe house structure for the builders in the post-disaster reconstruction. This study examined the effectiveness of the training in term of understanding of the builders and application of the new knowledge. Ten semi-structured interviews with the builders were conducted in this study. The results indicate that the builders with prior housing construction experience can absorb and understand the new knowledge about earthquake-safe house structure. Combination of lecturing and practice sessions also help the builders to understand the knowledge. However, findings of this research also suggest there is a problem in implementation of the new knowledge. Utilization of earthquake-safe house structure may leads to a rise in house cost. As a result, some house owners prefer to save money than to adopt the new knowledge.

Antibody treatment of human tumor xenografts elicits active anti-tumor immunity in nude mice

PubMed Central

Liebman, Meredith A.; Roche, Marly I.; Williams, Brent R.; Kim, Jae; Pageau, Steven C.; Sharon, Jacqueline

2007-01-01

Athymic nude mice bearing subcutaneous tumor xenografts of the human anti-colorectal cancer cell line SW480 were used as a preclinical model to explore anti-tumor immunotherapies. Intratumor or systemic treatment of the mice with murine anti-SW480 serum, recombinant anti-SW480 polyclonal antibodies, or the anti-colorectal cancer monoclonal antibody CO17-1A, caused retardation or regression of SW480 tumor xenografts. Interestingly, when mice that had regressed their tumors were re-challenged with SW480 cells, these mice regressed the new tumors without further antibody treatment. Adoptive transfer of spleen cells from mice that had regressed their tumors conferred anti-tumor immunity to naïve nude mice. Pilot experiments suggest that the transferred anti-tumor immunity is mediated by T cells of both γδ and αβ lineages. These results demonstrate that passive anti-tumor immunotherapy can elicit active immunity and support a role for extra-thymic γδ and αβ T cells in tumor rejection. Implications for potential immunotherapies include injection of tumor nodules in cancer patients with anti-tumor antibodies to induce anti-tumor T cell immunity. PMID:17920694

Beyond "Initiate-Build-Operate-Transfer" strategy for creating sustainable telemedicine programs: lesson from the first decade.

PubMed

Latifi, Rifat; Dasho, Erion; Lecaj, Ismet; Latifi, Kalterina; Bekteshi, Flamur; Hadeed, Molly; Doarn, Charles R; Merrell, Ronald C

2012-06-01

December 10, 2012 will mark the 10th anniversary of the implementation of telemedicine in the Balkans. This first decade of development and function is due to the passion, creativity, experience, and implementation know-how of the award-winning concept of the International Virtual e-Hospital (IVeH) Foundation. The objective of this article is to analyze the results of the IVeH's core strategy, "Initiate-Build-Operate-Transfer" (IBOT), which has been instrumental in establishing telemedicine in the Balkans and has been adopted by many other countries worldwide, and to describe the lessons learned that go beyond IBOT. A retrospective review of the results of IVeH engagement in establishing telemedicine in developing countries was conducted. Using IBOT, the IVeH has successfully established two national programs: one in Kosova and one in Albania. Together, they have connected 16 hospitals. Currently IVeH is in the process of creating such programs in many countries around the world. During the analysis of the first decade, we have identified eight factors that should be considered when establishing telemedicine programs. IBOT has been successful, but further studies are needed to demonstrate its effectiveness in countries beyond the Balkans.

T cell-independent and T cell-dependent immunoglobulin G responses to polyomavirus infection are impaired in complement receptor 2-deficient mice.

PubMed

Szomolanyi-Tsuda, Eva; Seedhom, Mina O; Carroll, Michael C; Garcea, Robert L

2006-08-15

Polyomavirus (PyV) infection induces protective T cell-independent (TI) IgM and IgG antibody responses in T cell-deficient mice, but these responses are not generated by immunization with viral proteins or virus like particles. We hypothesized that innate signals contribute to the generation of isotype-switched antiviral antibody responses. We studied the role of complement receptor (CR2) engagement in TI and T cell-dependent (TD) antibody responses to PyV using CR2-deficient mice. Antiviral IgG responses were reduced by 80-40% in CR2-/- mice compared to wild type. Adoptive transfer experiments demonstrated the need for CR2 not only in TD, but also in TI IgG responses to PyV. Transfer of CR2-/- B lymphocytes to SCID mice resulted in TI antiviral IgG responses that corresponded to 10% of that seen in wild-type B cell-reconstituted mice. Thus, our studies revealed a profound dependence of TI and TD antiviral antibody responses on CR2-mediated signals in PyV-infected mice, where the viral antigen is abundant and persistent.

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

Bass, H.Z.

As observed from a large panel of mouse T helper clones, there are at least two subsets of CD4{sup +} T cells that both differ in function and demonstrate distinct patterns of cytokine secretion after antigen or mitogen stimulation. Th1 cells synthesize IL-2, INF-{gamma} and lymphotoxin. They produce a DTH reaction in the footpads of naive mice. In addition, Th1 cells are required for the generation of CTL, and they appear to augment IgG2a antibody production. In contrast, by secreting IL-4, IL-5, and IL-6, Th2 cells play an essential role in humoral immunity. TLI consists of high dose, fractionated irradiationmore » delivered selectively to the major lymphoid tissues. Four to six weeks after TLI, the CD4{sup +} cells of the treated mice (counted as a percentage of the total spleen lymphocytes) recover to the similar levels as those in normal BALB/c mice. These CD4{sup +} cells can help normal syngeneic B cells to produce a vigorous antibody response to TNP-KLH in adoptive cell transfer experiments, but the same cells are inactive in the MLR, and they fail to transfer DTH in TNP-KLH primed syngeneic BALB/c mice.« less

Skill Learning and Skill Transfer Mediated by Cooperative Haptic Interaction.

PubMed

Avila Mireles, Edwin Johnatan; Zenzeri, Jacopo; Squeri, Valentina; Morasso, Pietro; De Santis, Dalia

2017-07-01

It is known that physical coupling between two subjects may be advantageous in joint tasks. However, little is known about how two people mutually exchange information to exploit the coupling. Therefore, we adopted a reversed, novel perspective to the standard one that focuses on the ability of physically coupled subjects to adapt to cooperative contexts that require negotiating a common plan: we investigated how training in pairs on a novel task affects the development of motor skills of each of the interacting partners. The task involved reaching movements in an unstable dynamic environment using a bilateral non-linear elastic tool that could be used bimanually or dyadically. The main result is that training with an expert leads to the greatest performance in the joint task. However, the performance in the individual test is strongly affected by the initial skill level of the partner. Moreover, practicing with a peer rather than an expert appears to be more advantageous for a naive; and motor skills can be transferred to a bimanual context, after training with an expert, only if the non-expert subject had prior experience of the dynamics of the novel task.

The design and evaluation of a master of science program in anatomical sciences at Queen's University Canada.

PubMed

Kolomitro, Klodiana; MacKenzie, Leslie W; Wiercigroch, David; Godden, Lorraine

2018-05-15

The purpose of this study was to describe the design and evolution of a unique and successful Master of Science program in anatomical sciences at one Canadian post-secondary institution and to evaluate its long-term impact on student learning. This program prepares students to teach anatomy and design curricula in the anatomical sciences and is structured around three pillars of competency-content (disciplinary knowledge and transferable skills), pedagogy, and inquiry. Graduates of the program from the last ten years were surveyed, to better understand the knowledge, skills, and habits of mind they have adopted and implemented since completion. Interest was taken in identifying aspects of the program that students found particularly beneficial and areas that needed to be further developed. Based on the findings, this program has been a highly valuable experience for the graduates especially in helping them develop transferable skills, and grow as individuals. The hope is that other institutions that have similar programs in place or are considering developing them would benefit from this description of the program design and the sharing of the lessons learned. Anat Sci Educ. © 2018 American Association of Anatomists. © 2018 American Association of Anatomists.

Nontransmission of porcine circovirus 2 (PCV2) by embryo transfer.

PubMed

Bielanski, A; Algire, J; Lalonde, A; Garceac, A; Pollard, J W; Plante, C

2013-07-15

Two experiments were conducted to determine the association of porcine circovirus type 2 (PCV2) with embryos and the risk of viral transmission by embryo transfer. In the first experiment, 240 embryos from uninfected donors were exposed to PCV2a 10(4)TCID50/mL in vitro before transfer to seronegative recipients; in the second experiment, 384 embryos recovered from infected donors, 10 days after donor inoculation with PCV2, were transferred to seronegative recipients. In total, 1120 embryos and/or ova were collected from 37 viral-free donors (experiment 1) and 1019 from 59 PCV2-infected donors (experiment 2) (P < 0.01). The washing and/or disinfection procedure recommended by the International Embryo Transfer Society was applied to embryos in both experiments. Transfer of embryos experimentally exposed in vitro to high titers of virus caused seroconversion of recipients (58%; N = 7/12) and their piglets (81%; N = 13/16). Postmortem, PCV2 DNA was detected in various organs of embryo transfer recipients and their embryo transfer-derived piglets. In contrast, the transfer of embryos recovered from infectious PCV2 donors did not result in the seroconversion of embryo recipients (N = 24) or their embryo transfer-derived piglets (N = 76). Neither PCV2 DNA nor infectious virus was detected in the tissues of either recipients or embryo transfer-derived piglets collected postmortem in the second experiment. The results obtained in this study indicate that the transmission of PCV2 from infected donors by embryo transfer is unlikely if the sanitary recommendations of the International Embryo Transfer Society are followed. In practical terms, this means that embryo transfer can be successfully used for the intentional elimination of PCV2 and to create virus-free offspring for the safe exchange of swine genetic materials. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

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

Promoting Transfer of Learning: Connecting General Education Courses

ERIC Educational Resources Information Center

Benander, Ruth; Lightner, Robin

2005-01-01

General education programs rely on students transferring learning from one context to another. This transfer cannot be taken for granted. Faculty must see individual courses as elements of a larger experience and focus on specific techniques promoting transfer. Classroom experiences serve to illustrate the elements of transfer that require…

Exploring the Lived Experiences and Intersectionalities of Mexican Community College Transfer Students: Qualitative Insights toward Expanding a Transfer Receptive Culture

ERIC Educational Resources Information Center

Castro, Erin L.; Cortez, Edén

2017-01-01

This qualitative study examines the experiences of six Mexican community college transfer students attending a research-intensive institution in the Pacific Northwest. Using semi-structured interviews, the objectives of this study were to 1) understand how Mexican students made meaning of their transfer experiences and 2) how those experiences…

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.

A Thematic Analysis of Health Care Workers' Adoption of Mindfulness Practices.

PubMed

Valley, Morgan; Stallones, Lorann

2018-05-01

Mindfulness training, which teaches individuals to bring awareness and acceptance to the present moment, has been effective in improving the well-being of health care workers. Limited research examines the adoption of mindfulness practices using health behavior theories. The current study sought to conceptualize hospital health care workers' experiences in adopting mindfulness practices using the Health Belief Model (HBM), a theoretical framework used by health promotion practitioners to design and implement health behavior change interventions. Hospital health care workers in Colorado participated in an 8-week Mindfulness-Based Stress Reduction (MBSR) course. Participants ( n = 19) answered open-ended questions about their experiences adopting mindfulness practices. A theory-driven thematic analysis approach was used to analyze data with key constructs of the HBM acting as the framework for the analysis. Results showed that HBM constructs, including internal cues to action, perceived benefits and barriers, and self-efficacy, helped portray the participants' experiences and challenges in adopting and adhering to the mindfulness practices taught in the MBSR course.

Alternative methods of reproduction. Effects on the child.

PubMed

Sokoloff, B Z

1987-01-01

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

Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science.

PubMed

Cañete-Valdeón, José M; Wieringa, Roel; Smallbone, Kieran

2012-12-01

There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants.

PubMed

Yoshida, S; Haque, A; Mizobuchi, T; Iwata, T; Chiyo, M; Webb, T J; Baldridge, L A; Heidler, K M; Cummings, O W; Fujisawa, T; Blum, J S; Brand, D D; Wilkes, D S

2006-04-01

Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.

Cell intrinsic abrogation of TGFβ signaling delays but does not prevent dysfunction of self/tumor specific CD8 T cells in a murine model of autochthonous prostate cancer

PubMed Central

Chou, Cassie K.; Schietinger, Andrea; Liggitt, H. Denny; Tan, Xiaoxia; Funk, Sarah; Freeman, Gordon J.; Ratliff, Timothy L.; Greenberg, Norman M.; Greenberg, Philip D.

2012-01-01

Adoptive T cell therapy (ACT) for the treatment of established cancers is actively being pursued in clinical trials. However, poor in vivo persistence and maintenance of anti-tumor activity of transferred T cells remain major problems. Transforming growth factor beta (TGFβ) is a potent immunosuppressive cytokine that is often expressed at high levels within the tumor microenvironment, potentially limiting T cell mediated anti-tumor activity. Here, we used a model of autochthonous murine prostate cancer to evaluate the effect of cell intrinsic abrogation of TGFβ signaling in self/tumor specific CD8 T cells used in ACT to target the tumor in situ. We found that persistence and anti-tumor activity of adoptively transferred effector T cells deficient in TGFβ signaling was significantly improved in the cancerous prostate. However, over time, despite persistence in peripheral lymphoid organs, the numbers of transferred cells in the prostate decreased and the residual prostate infiltrating T cells were no longer functional. These findings reveal that TGFβ negatively regulates the accumulation and effector function of transferred self/tumor specific CD8 T cells and highlight that, when targeting a tumor antigen that is also expressed as a self-protein, additional substantive obstacles are operative within the tumor microenvironment, potentially hampering the success of ACT for solid tumors. PMID:22984076

European two-way satellite time transfer experiments using the INTELSAT (VA-F13) satellite at 307{degree}E

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

Davis, J.A.; Pearce, P.R.; Kirchner, D.

1994-12-31

A Two Way Satellite Time and Frequency Transfer (TWSTFT) experiment performed between six European laboratories is reported. The characteristics of the time transfers undertaken between each pair of laboratory earth stations has been determined. Multiple time transfer and ranging experiments were performed to determine both systematic errors and delay instabilities in the TWSTFT system.

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.

[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.

Does the early adopter catch the worm or choke on it? A reflective journey of the challenges of technology adoption in a health sciences education institution.

PubMed

Botha-Ravyse, Chrisna; Blignaut, Seugnet

2017-01-01

Early adoption of technology is a struggle well known to early adopters and now to me. Since the demand to use and implement technology in health professions' education has increased, I have been led to adopt various technologies, leading to many headaches. This paper addresses my experiences in developing and implementing technology in health science classrooms in a setting not adequately equipped to do so. After reflecting on my experiences, I conclude that it is crucial that systems help innovators and early adopters as they work to develop and implement teaching and learning technology. Technical decisions should address the needs of the higher education educator. In addition, once an institution chooses a specific technological approach, such as using e-guides, there should be resources in place to support the forerunners of these initiatives.

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.

Post-Adoption Depression: Clinical Windows on an Emerging Concept

ERIC Educational Resources Information Center

Speilman, Eda

2011-01-01

In recent years, the concept of post-adoption depression--with both parallels and differences from postpartum depression--has emerged as a salient descriptor of the experience of a significant minority of newly adoptive parents. This article offers a clinical perspective on post-adoption depression through the stories of several families seen in…

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

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.

Associations between Discussions of Racial and Ethnic Differences in Internationally Adoptive Families and Delinquent Behavior among Korean Adopted Adolescents.

PubMed

Anderson, Kayla N; Lee, Richard M; Rueter, Martha A; Kim, Oh Myo

2015-04-01

Internationally adopted adolescents may have more delinquent behavior than non-adopted adolescents. One explanation is these adolescents experience discrimination and loss of culture, and adoptive parents are not adequately addressing these experiences. However, studies have not examined the effects of family discussions of racial and ethnic differences within adoptive families on adopted adolescents' delinquent behavior. To test this relationship, this study utilized data from 111 U.S. internationally adoptive families with 185 South Korean adopted adolescents (55% female, M age = 17.75). During an observational assessment, families discussed the importance of their racial and ethnic differences, and adolescents completed a delinquent behavior questionnaire. Analysis of covariance showed differences in adolescent delinquent behavior across three ways adoptive families discussed racial and ethnic differences; adolescents whose families acknowledged differences had the fewest mean delinquent behaviors. There were no significant differences in delinquent behavior between adolescents whose families acknowledged or rejected the importance of racial and ethnic differences. However, adopted adolescents whose families held discrepant views of differences had significantly more problem behavior than adolescents whose families either acknowledged or rejected the importance of racial and ethnic differences. Clinicians, adoption professionals, and other parenting specialists should focus on building cohesive family identities about racial and ethnic differences, as discrepant views of differences are associated with the most adoptee delinquent behavior.

Associations between Discussions of Racial and Ethnic Differences in Internationally Adoptive Families and Delinquent Behavior among Korean Adopted Adolescents

PubMed Central

Anderson, Kayla N.; Lee, Richard M.; Rueter, Martha A.; Kim, Oh Myo

2015-01-01

Internationally adopted adolescents may have more delinquent behavior than non-adopted adolescents. One explanation is these adolescents experience discrimination and loss of culture, and adoptive parents are not adequately addressing these experiences. However, studies have not examined the effects of family discussions of racial and ethnic differences within adoptive families on adopted adolescents’ delinquent behavior. To test this relationship, this study utilized data from 111 U.S. internationally adoptive families with 185 South Korean adopted adolescents (55% female, M age = 17.75). During an observational assessment, families discussed the importance of their racial and ethnic differences, and adolescents completed a delinquent behavior questionnaire. Analysis of covariance showed differences in adolescent delinquent behavior across three ways adoptive families discussed racial and ethnic differences; adolescents whose families acknowledged differences had the fewest mean delinquent behaviors. There were no significant differences in delinquent behavior between adolescents whose families acknowledged or rejected the importance of racial and ethnic differences. However, adopted adolescents whose families held discrepant views of differences had significantly more problem behavior than adolescents whose families either acknowledged or rejected the importance of racial and ethnic differences. Clinicians, adoption professionals, and other parenting specialists should focus on building cohesive family identities about racial and ethnic differences, as discrepant views of differences are associated with the most adoptee delinquent behavior. PMID:25729119

Advancing Pre-Health Humanities as Intensive Research Practice: Principles and Recommendations from a Cross-Divisional Baccalaureate Setting.

PubMed

Singer, Sarah Ann; Weed, Kym; Edwell, Jennifer; Jack, Jordynn; Thrailkill, Jane F

2017-12-01

This essay argues that pre-health humanities programs should focus on intensive research practice for baccalaureate students and provides three guiding principles for implementing it. Although the interdisciplinary nature of health humanities permits baccalaureate students to use research methods from the natural sciences, social sciences, and humanities, pre-health humanities coursework tends to force students to adopt only one of many disciplinary identities. Alternatively, an intensive research approach invites students to critically select and combine methods from multiple (and seemingly opposing) disciplines to ask and answer questions about health problems more innovatively. Using the authors' experiences with implementing health humanities baccalaureate research initiatives at The University of North Carolina at Chapel Hill, the authors contend that pre-health humanities programs should teach and study multiple disciplinary research methods and their values; examine how health humanities research might transfer across disciplines; and focus on mentoring opportunities for funding, presenting, and publishing research. These recommendations have the potential to create unprecedented research experiences for baccalaureate students as they prepare to enter careers within and beyond the allied health professions.

Nanosecond time transfer via shuttle laser ranging experiment

NASA Technical Reports Server (NTRS)

Reinhardt, V. S.; Premo, D. A.; Fitzmaurice, M. W.; Wardrip, S. C.; Cervenka, P. O.

1978-01-01

A method is described to use a proposed shuttle laser ranging experiment to transfer time with nanosecond precision. All that need be added to the original experiment are low cost ground stations and an atomic clock on the shuttle. It is shown that global time transfer can be accomplished with 1 ns precision and transfer up to distances of 2000 km can be accomplished with better than 100 ps precision.

Generalizing attentional control across dimensions and tasks: evidence from transfer of proportion-congruent effects.

PubMed

Wühr, Peter; Duthoo, Wout; Notebaert, Wim

2015-01-01

Three experiments investigated transfer of list-wide proportion congruent (LWPC) effects from a set of congruent and incongruent items with different frequency (inducer task) to a set of congruent and incongruent items with equal frequency (diagnostic task). Experiments 1 and 2 mixed items from horizontal and vertical Simon tasks. Tasks always involved different stimuli that varied on the same dimension (colour) in Experiment 1 and on different dimensions (colour, shape) in Experiment 2. Experiment 3 mixed trials from a manual Simon task with trials from a vocal Stroop task, with colour being the relevant stimulus in both tasks. There were two major results. First, we observed transfer of LWPC effects in Experiments 1 and 3, when tasks shared the relevant dimension, but not in Experiment 2. Second, sequential modulations of congruency effects transferred in Experiment 1 only. Hence, the different transfer patterns suggest that LWPC effects and sequential modulations arise from different mechanisms. Moreover, the observation of transfer supports an account of LWPC effects in terms of list-wide cognitive control, while being at odds with accounts in terms of stimulus-response (contingency) learning and item-specific control.

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

Non-Traditional Transfer Student Attrition

ERIC Educational Resources Information Center

Monroe, Anne

2006-01-01

Current literature focuses on traditional student attrition and on transfer transition, but little information is available on the non-traditional transfer student experience. The following study explores the process of non-traditional transfer student attrition through an investigation that illustrates the importance of past student experiences,…

The subscale orbital fluid transfer experiment

NASA Technical Reports Server (NTRS)

Collins, Frank G.; Antar, Basil N.; Menzel, Reinhard W.; Meserole, Jere S.; Meserole, Jere S.; Jones, Ogden

1990-01-01

The Subscale Orbital Fluid Transfer Experiment (SOFTE) is a planned Shuttle Orbiter fluid transfer experiment. CASP (Center for Advanced Space Propulsion) performed certain aspects of the conceptual design of this experiment. The CASP work consisted of the conceptual design of the optical system, the search for alternative experimental fluids, the determination of the flow meter specifications and the examination of materials to use for a bladder that will empty one of the tanks in the experiment.

The Subscale Orbital Fluid Transfer Experiment

NASA Technical Reports Server (NTRS)

Meserole, J. S.; Collins, Frank G.; Jones, Ogden; Antar, Basil; Menzel, Reinhard; Gray, Perry

1989-01-01

The Center for Advanced Spacecraft Propulsion (CASP) is a subcontractor to Boeing Aerospace Corporation to provide support for the concept definition and design of a subscale orbital fluid transfer experiment (SOFTE). SOFTE is an experiment that will look at the fluid mechanics of the process of transfer of a saturated fluid between two tanks. The experiment will be placed in two get away special (GAS) can containers; the tanks will be in one container and the power and electronics will be in a second container. Since GAS cans are being used, the experiment will be autonomous. The work during the present year consisted of examining concepts for visual observation of the fluid transfer process, methods for accurately metering the amount of fluid transferred between the two tanks, possible test fluids, and materials for the elastomeric diaphragm.

Factors affecting the adoption of home-heating energy-conservation measures: a behavioral approach

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

Macey, S.M.

1982-01-01

The basic aim of this research is to better understand homeowners' adoption of home-heating energy-conservation measures by analyzing a number of factors that are thought to be underlying determinants of adoption behavior. The basic approach is behavioral drawing on the knowledge built up in behavioral geography through studies on natural hazards and innovation diffusion, and borrowing from psychological theories of attitude formation and decision making. In particular, six factors (information, environmental personality, socio-economic and demographic factors, dwelling unit characteristics, psychological variables, and past experience) are shown to directly and indirectly affect adoption behavior. By this means, differences between adopters andmore » nonadopters in the underlying cognitive structures and in the situational factors that affect their decisions are identified. The study focuses on the adoption of three measures: reducing winter night-time thermostat settings, changing or cleaning furnace filters, and installing an automatic setback thermostat. Personal interviews with a random sample of 159 homeowners in Decatur, Illinois serve as the main data base. Results indicate that adoption behavior is determined more by past experience, than by intention. Beliefs, attitudes, and social influences affect behavior indirectly through intention. These psychological variables also act as mediators between information, knowledge, environmental personality, situational variables and behavior. In particular, respondent's age, previous home ownership, and length of residence act indirectly on adoption behavior. Each of these reflects the amount of past experience the respondent is likely to have.« less

A Cross-Sectional Online Survey of HIV Pre-Exposure Prophylaxis Adoption Among Primary Care Physicians.

PubMed

Blackstock, Oni J; Moore, Brent A; Berkenblit, Gail V; Calabrese, Sarah K; Cunningham, Chinazo O; Fiellin, David A; Patel, Viraj V; Phillips, Karran A; Tetrault, Jeanette M; Shah, Minesh; Edelman, E Jennifer

2017-01-01

Among health care providers, prescription of HIV pre-exposure prophylaxis (PrEP) has been low. Little is known specifically about primary care physicians (PCPs) with regard to PrEP awareness and adoption (i.e., prescription or referral), and factors associated with adoption. To assess PrEP awareness, PrEP adoption, and factors associated with adoption among PCPs. Cross-sectional online survey conducted in April and May 2015. Members of a national professional organization for academic primary care physicians (n = 266). PrEP awareness, PrEP adoption (ever prescribed or referred a patient for PrEP [yes/no]), provider and practice characteristics, and self-rated knowledge, attitudes, and beliefs associated with adoption. The survey response rate was 8.6 % (266/2093). Ninety-three percent of respondents reported prior awareness of PrEP. Of these, 34.9 % reported PrEP adoption. In multivariable analysis of provider and practice characteristics, compared with non-adopters, adopters were more likely to provide care to more than 50 HIV-positive patients (vs. 0, aOR = 6.82, 95 % CI 2.06-22.52). Compared with non-adopters, adopters were also more likely to report excellent, very good, or good self-rated PrEP knowledge (15.1 %, 33.7 %, 30.2 % vs. 2.5 %, 18.1 %, 23.8 %, respectively; p < 0.001) and to perceive PrEP as extremely safe (35.1 % vs. 10.7 %; p = 0.002). Compared with non-adopters, adopters were less likely to perceive PrEP as being moderately likely to increase risk behaviors ("risk compensation") (12.8 % vs. 28.8 %, p = 0.02). While most respondents were aware of PrEP, only one-third of PrEP-aware PCPs reported adoption. Adopters were more likely to have experience providing HIV care and to perceive PrEP as extremely safe, and were less likely to perceive PrEP use as leading to risk compensation. To enhance PCP adoption of PrEP, educational efforts targeting PCPs without HIV care experience should be considered, as well as training those with HIV care experience to be PrEP "clinical champions". Concerns about safety and risk compensation must also be addressed.

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

Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling.

PubMed

Kido, Masahiro; Watanabe, Norihiko; Okazaki, Taku; Akamatsu, Takuji; Tanaka, Junya; Saga, Kazuyuki; Nishio, Akiyoshi; Honjo, Tasuku; Chiba, Tsutomu

2008-10-01

Because of the lack of animal models developing spontaneous autoimmune hepatitis (AIH), the molecular mechanisms involved in the development of AIH are still unclear. This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH. To induce a concurrent loss of Treg cells and PD-1-mediated signaling, neonatal thymectomy (NTx), which severely reduces the number of Treg cells, was performed on PD-1(-/-) mice. After the NTx, we performed histologic examination, assessed autoantibody production and infiltrating cells in the liver, and conducted adoptive transfer experiments. In contrast to NTx mice and PD-1(-/-) mice, NTx-PD-1(-/-) mice produced antinuclear antibodies and developed fatal hepatitis characterized by a CD4(+) and CD8(+) T-cell infiltration invading the parenchyma with massive lobular necrosis. Induction of AIH in NTx-PD-1(-/-) mice was suppressed by transfer of Treg cells, even derived from PD-1(-/-) mice. Transfer of total but not CD4(+) T-cell-depleted splenocytes from NTx-PD-1(-/-) mice into RAG2(-/-) mice induced the development of severe hepatitis. In contrast, the transfer of CD8(+) T-cell-depleted splenocytes triggered only mononuclear infiltrates without massive necrosis of the parenchyma. NTx-PD-1(-/-) mice are the first mouse model of spontaneous fatal AIH. The concurrent loss of Treg cells and PD-1-mediated signaling can induce the development of fatal AIH. Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage.

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.

Behavioral and Emotional Symptoms of Post-Institutionalized Children in Middle Childhood

ERIC Educational Resources Information Center

Wiik, Kristen L.; Loman, Michelle M.; Van Ryzin, Mark J.; Armstrong, Jeffrey M.; Essex, Marilyn J.; Pollak, Seth D.; Gunnar, Megan R.

2011-01-01

Background: Experience in institutional/orphanage care has been linked to increased mental health problems. Research suggests that children adopted from institutions experience specific difficulties related to inattention/overactivity. Evidence of internalizing and conduct problems relative to non-adopted peers has been found in early childhood…

22 CFR 96.37 - Education and experience requirements for social service personnel.

Code of Federal Regulations, 2010 CFR

2010-04-01

... social service personnel. 96.37 Section 96.37 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED... § 96.37 Education and experience requirements for social service personnel. (a) The agency or person... Convention adoption, adoption-related social service functions that require the application of clinical...

22 CFR 96.37 - Education and experience requirements for social service personnel.

Code of Federal Regulations, 2011 CFR

2011-04-01

... social service personnel. 96.37 Section 96.37 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED... § 96.37 Education and experience requirements for social service personnel. (a) The agency or person... Convention adoption, adoption-related social service functions that require the application of clinical...

22 CFR 96.37 - Education and experience requirements for social service personnel.

Code of Federal Regulations, 2013 CFR

2013-04-01

... social service personnel. 96.37 Section 96.37 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED... § 96.37 Education and experience requirements for social service personnel. (a) The agency or person... Convention adoption, adoption-related social service functions that require the application of clinical...

22 CFR 96.37 - Education and experience requirements for social service personnel.

Code of Federal Regulations, 2014 CFR

2014-04-01

... social service personnel. 96.37 Section 96.37 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED... § 96.37 Education and experience requirements for social service personnel. (a) The agency or person... Convention adoption, adoption-related social service functions that require the application of clinical...

22 CFR 96.37 - Education and experience requirements for social service personnel.

Code of Federal Regulations, 2012 CFR

2012-04-01

... social service personnel. 96.37 Section 96.37 Foreign Relations DEPARTMENT OF STATE LEGAL AND RELATED... § 96.37 Education and experience requirements for social service personnel. (a) The agency or person... Convention adoption, adoption-related social service functions that require the application of clinical...

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...

Participation in the Adoption Mentoring Partnership: Mentors' Experiences of Ethnic Identity

ERIC Educational Resources Information Center

Garber, Karin J.; French, Quade Y. S.; Grotevant, Harold D.

2015-01-01

The Adoption Mentoring Partnership (AMP) matches preadolescent adoptees with adopted college students, prioritizing matches of the same ethnic background. As part of AMP, participants actively discuss issues of ethnicity and adoption with a cohort of mentors over a period of 1 to 3 years in mentor group meetings (MGMs). This study focuses on…

Analyzing ex-ante agroforestry adoption decisions with attribute based choice experiments

Treesearch

Evan Mercer; Ann Snook

2004-01-01

Although many cases of successful agroforestry extension efforts exist (for examples, see Chapter 2), all too often attempts to promote agroforestry have resulted in low adoption rates, with farmers reluctant to adopt new or improved agroforestry systems or abandoning agroforestry shortly after establishment. As a result, the recent increase in research on the adoption...

A Longitudinal Study of Service Use in Families of Children Adopted from Romanian Orphanages

ERIC Educational Resources Information Center

Le Mare, Lucy; Audet, Karyn; Kurytnik, Karen

2007-01-01

Post-adoption service use and unmet service needs were examined longitudinally in three matched groups of children: children adopted from Romanian orphanages following a minimum of eight months' institutional experience (RO: n = 36); children from Romania who were destined for orphanages but were adopted early in infancy (EA: n = 25); and Canadian…

Metro passengers’ route choice model and its application considering perceived transfer threshold

PubMed Central

Jin, Fanglei; Zhang, Yongsheng; Liu, Shasha

2017-01-01

With the rapid development of the Metro network in China, the greatly increased route alternatives make passengers’ route choice behavior and passenger flow assignment more complicated, which presents challenges to the operation management. In this paper, a path sized logit model is adopted to analyze passengers’ route choice preferences considering such parameters as in-vehicle time, number of transfers, and transfer time. Moreover, the “perceived transfer threshold” is defined and included in the utility function to reflect the penalty difference caused by transfer time on passengers’ perceived utility under various numbers of transfers. Next, based on the revealed preference data collected in the Guangzhou Metro, the proposed model is calibrated. The appropriate perceived transfer threshold value and the route choice preferences are analyzed. Finally, the model is applied to a personalized route planning case to demonstrate the engineering practicability of route choice behavior analysis. The results show that the introduction of the perceived transfer threshold is helpful to improve the model’s explanatory abilities. In addition, personalized route planning based on route choice preferences can meet passengers’ diversified travel demands. PMID:28957376

The personal and professional: nurses' lived experiences of adoption.

PubMed

Foli, Karen J; Schweitzer, Roberta; Wells, Courtenay

2013-03-01

Nurses provide healthcare services to members of the adoption triad (AT; birth parents, adoptive parents, and the child) in a number of settings. However, nurses' perceptions of and interactions with members of the AT have not been investigated. This study describes the lived experiences of nurses and the care rendered to the AT using a descriptive phenomenological approach. In response to an invitation published in a national electronic newsletter, nurses were asked to submit narratives about their experiences in caring for members of the AT. Researchers coded 17 narratives using Colaizzi's phenomenological method. Four themes emerged from the texts: (1) Where the personal and professional selves meet ("I see so many issues from both sides"); (2) The paradox of adoption ("...an emotional rollercoaster"); (3) Unique contexts of adoptive families ("We all have a story"); and (4) Reframing nurses' perceptions surrounding adoption ("There are several areas we could improve"). Nurses often have a personal connection to adoption and this potentiates the care delivered to AT members. Serving as role models for their peers and advocates for a better understanding of the dynamics of relinquishment and placement, nurses can improve clinical practices for these patients. Themes reflected insights gained from both personal and professional roles and offer specific interventions that enhance care of the AT. Nursing education and practice guidelines should include care rendered to the AT.

Beyond Transfer Shock: Dimensions of Transfer Students' Adjustment.

ERIC Educational Resources Information Center

Laanan, Frankie Santos

This study examined the adjustment process of 727 students who transferred to the University of California, Los Angeles (UCLA) in fall 1994 or fall 1995. The Transfer Students' Questionnaire (TSQ) was organized into three main sections: social demographics, perceptions of the community college experience, and perception of the UCLA experience. The…

Flight Simulation for the Study of Skill Transfer.

ERIC Educational Resources Information Center

Lintern, Gavan

1992-01-01

Discusses skill transfer as a human performance issue based on experiences with computerized flight simulators. Highlights include the issue of similarity; simulation and the design of training devices; an information theory of transfer; invariants for flight control; and experiments involving the transfer of flight skills. (21 references) (LRW)

Function Transfer in Human Operant Experiments: The Role of Stimulus Pairings

ERIC Educational Resources Information Center

Tonneau, Francois; Gonzalez, Carmen

2004-01-01

Although function transfer often has been studied in complex operant procedures (such as matching to sample), whether operant reinforcement actually produces function transfer in such settings has not been established. The present experiments, with high school students as subjects, suggest that stimulus pairings can promote function transfer in…

Identifying Transfer Student Subgroups by Academic and Social Adjustment: A Latent Class Analysis

ERIC Educational Resources Information Center

Fematt, Veronica Lavenant

2017-01-01

Community college transfer students often experience "transfer shock" at receiving four-year institutions, which includes a variety of academic, social, and institutional challenges associated with the first-year transfer experience. Research has demonstrated that first-year program interventions can facilitate the transition of…

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.

The ovine uterus as a host for in vitro-produced bovine embryos.

PubMed

Rexroad, C E; Powell, A M

1999-07-15

A series of experiments were conducted to determine whether bovine blastocysts would develop beyond the blastocyst stage in the ovine uterine environment. In Experiment 1, in vitro matured, fertilized and cultured (IVM/IVF/IVC) expanded bovine blastocysts were transferred into uteri of ewes on Day 7 or 9 of the estrous cycle and collected on Day 14 or 15 to determine if the bovine blastocysts would elongate and form an embryonic disk. Springtime trials with ewes that were synchronized with a medroxyprogesterone acetate (MAP) sponge resulted in a 78% blastocyst recovery rate, and 68% of the recovered spherical or elongated embryos had embryonic disks. In Experiment 2, transfer of 4-cell bovine embryos to the oviducts of ewes at Day 3 resulted in a lower recovery (47 vs 80%) than the transfer of blastocysts at Day 7 when embryos were recovered at Day 14. However, the percentage of embryos containing embryonic disks was higher for embryos transferred at the 4-cell stage (71%) than for embryos transferred as blastocysts (50%). In Experiment 3, IVF embryos from super-ovulated cows or Day 8 in vitro produced embryos transferred to cows were collected at Day 14 and were found to be similar in size to those produced by transfer to ewes in Experiment 2. In Experiment 4, the transfer of bovine blastocysts to ewes did not prolong the ovine estrous cycle. In Experiment 5, extension of the ovine estrous cycle by administration of a MAP releasing intravaginal device allowed bovine embryos to elongate extensively and to become filamentous. In Experiment 6, uterine flushings on Day 14 or Day 16 contained elevated levels of interferon-tau when bovine blastocyst were transferred on Day 7. Transfer of bovine embryos to the reproductive tract of a ewe allows some embryos to develop normally to advanced perimplantation stages and may be a useful tool for studying critical stages of embryo development and the developmental capacity of experimental embryos.

Intercountry Adoption: A Comparison between France and England.

ERIC Educational Resources Information Center

Greenfield, Joanna

1995-01-01

Examined the intercountry adoption experiences of 100 French and 100 English families, comparing policy in each country. Found a lack of effective and sensitive management of the introductory meetings between prospective parents and adoptive children, and of adequate birth records information. (HTH)

Learning to Disclose: A Postcolonial Autoethnography of Transracial Adoption

ERIC Educational Resources Information Center

Schwartz, Joni; Schwartz, Rebecca

2018-01-01

This autoethnographic research project examines the transformational learning of a transracial adoptive adult mother and daughter through the lens of postcolonialism. As collaborative researchers, adult adoptee and adoptive mother, examine this lifelong learning experience through critical self-reflection, qualitative meta-analysis, and…

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.

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

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.

Technology transfer needs and experiences: The NASA Research Center perspective

NASA Technical Reports Server (NTRS)

Gross, Anthony R.

1992-01-01

Viewgraphs on technology transfer needs and experiences - the NASA Research Center perspective are provided. Topics covered include: functions of NASA, incentives and benefits, technology transfer mechanisms, economics of technology commercialization, examples, and conclusions.

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…

The Nature and Role of Thought Experiments in Solving Conceptual Physics Problems

ERIC Educational Resources Information Center

Kösem, Sule Dönertas; Özdemir, Ömer Faruk

2014-01-01

This study describes the possible variations of thought experiments in terms of their nature, purpose, and reasoning resources adopted during the solution of conceptual physics problems. A phenomenographic research approach was adopted for this study. Three groups of participants with varying levels of physics knowledge--low, medium, and high…

Alternative Student Growth Measures for Teacher Evaluation: Implementation Experiences of Early-Adopting Districts. REL 2015-093

ERIC Educational Resources Information Center

McCullough, Moira; English, Brittany; Angus, Megan Hague; Gill, Brian

2015-01-01

Alternative student growth measures for teacher evaluation: Implementation experiences of early-adopting districts: State requirements to include student achievement growth in teacher evaluations are prompting the development of alternative ways to measure growth in grades and subjects not covered by state assessments. These alternative growth…

Towards a Theory of the Ecology of Reflection: Reflective Practice for Experiential Learning in Higher Education

ERIC Educational Resources Information Center

Harvey, Marina; ; Coulson, Debra; McMaugh, Anne

2016-01-01

Reflective practice is widely adopted across the field of experience-based learning subjects in higher education, including practicums, work-integrated learning, internships, service learning and community participation. This adoption of reflective practice implies that it supports student learning through experience. When reviewing the evidence…

"School Adopts an Experiment": The Photoluminescence in Extra-Virgin Olive Oil and in Tonic Water

ERIC Educational Resources Information Center

Gallitto, A. Agliolo; Agnello, S.; Cannas, M.

2011-01-01

We report a laboratory activity, carried out along with high- and secondary-school students, that can be done to increase the interest of the young in scientific studies. Groups of selected students "adopted" experiments at physics research laboratories, under the guidance of university researchers. Subsequently, the students…

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.

Test facility for investigation of heat transfer of promising coolants for the nuclear power industry

NASA Astrophysics Data System (ADS)

Belyaev, I. A.; Sviridov, V. G.; Batenin, V. M.; Biryukov, D. A.; Nikitina, I. S.; Manchkha, S. P.; Pyatnitskaya, N. Yu.; Razuvanov, N. G.; Sviridov, E. V.

2017-11-01

The results are presented of experimental investigations into liquid metal heat transfer performed by the joint research group consisting of specialist in heat transfer and hydrodynamics from NIU MPEI and JIHT RAS. The program of experiments has been prepared considering the concept of development of the nuclear power industry in Russia. This concept calls for, in addition to extensive application of water-cooled, water-moderated (VVER-type) power reactors and BN-type sodium cooled fast reactors, development of the new generation of BREST-type reactors, fusion power reactors, and thermonuclear neutron sources. The basic coolants for these nuclear power installations will be heavy liquid metals, such as lead and lithium-lead alloy. The team of specialists from NRU MPEI and JIHT RAS commissioned a new RK-3 mercury MHD-test facility. The major components of this test facility are a unique electrical magnet constructed at Budker Nuclear Physics Institute and a pressurized liquid metal circuit. The test facility is designed for investigating upward and downward liquid metal flows in channels of various cross-sections in a transverse magnetic field. A probe procedure will be used for experimental investigation into heat transfer and hydrodynamics as well as for measuring temperature, velocity, and flow parameter fluctuations. It is generally adopted that liquid metals are the best coolants for the Tokamak reactors. However, alternative coolants should be sought for. As an alternative to liquid metal coolants, molten salts, such as fluorides of lithium and beryllium (so-called FLiBes) or fluorides of alkali metals (so-called FLiNaK) doped with uranium fluoride, can be used. That is why the team of specialists from NRU MPEI and JIHT RAS, in parallel with development of a mercury MHD test facility, is designing a test facility for simulating molten salt heat transfer and hydrodynamics. Since development of this test facility requires numerical predictions and verification of numerical codes, all examined configurations of the MHD flow are also investigated numerically.

Telling the Truth to Your Adopted or Foster Child: Making Sense of the Past.

ERIC Educational Resources Information Center

Keefer, Betsy; Schooler, Jayne E.

Many individuals who grew up as adopted or foster children felt that they were reared under the shadow of secrecy, silence, and shame, finding it difficult to build an identity and feel secure. Because of the connection to troublesome experiences that resulted in the adoption plan such as alcoholism or teen pregnancy, adoptive and foster parents…

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

Lu, Dingjie; Xie, Yi Min; Huang, Xiaodong

Analytical studies on the size effects of a simply-shaped beam fixed at both ends have successfully explained the sudden changes of effective Young's modulus as its diameter decreases below 100 nm. Yet they are invalid for complex nanostructures ubiquitously existing in nature. In accordance with a generalized Young-Laplace equation, one of the representative size effects is transferred to non-uniformly distributed pressure against an external surface due to the imbalance of inward and outward loads. Because the magnitude of pressure depends on the principal curvatures, iterative steps have to be adopted to gradually stabilize the structure in finite element analysis. Computational resultsmore » are in good agreement with both experiment data and theoretical prediction. Furthermore, the investigation on strengthened and softened Young's modulus for two complex nanostructures demonstrates that the proposed computational method provides a general and effective approach to analyze the size effects for nanostructures in arbitrary shape.« less

Education, outreach and the future of remote sensing in human health

NASA Technical Reports Server (NTRS)

Wood, B. L.; Beck, L. R.; Lobitz, B. M.; Bobo, M. R.

2000-01-01

The human health community has been slow to adopt remote sensing technology for research, surveillance, or control activities. This chapter presents a brief history of the National Aeronautics and Space Administration's experiences in the use of remotely sensed data for health applications, and explores some of the obstacles, both real and perceived, that have slowed the transfer of this technology to the health community. These obstacles include the lack of awareness, which must be overcome through outreach and proper training in remote sensing, and inadequate spatial, spectral and temporal data resolutions, which are being addressed as new sensor systems are launched and currently overlooked (and underutilized) sensors are newly discovered by the health community. A basic training outline is presented, along with general considerations for selecting training candidates. The chapter concludes with a brief discussion of some current and future sensors that show promise for health applications.

T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice

PubMed Central

Clarkson, Benjamin D.S.; Ling, Changying; Shi, Yejie; Harris, Melissa G.; Rayasam, Aditya; Sun, Dandan; Salamat, M. Shahriar; Kuchroo, Vijay; Lambris, John D.; Sandor, Matyas

2014-01-01

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke. PMID:24616379

Selective effect of irradiation on responses to thymus-independent antigen.

PubMed

Lee, S K; Woodland, R T

1985-02-01

Low doses of ionizing radiation have a selective immunosuppressive effect on in vivo B cell responses to thymus-independent (TI) antigens. The B cell response, assayed as direct anti-trinitrophenyl (TNP)-specific plaque-forming cells (PFC), induced by type 2, TI antigens (TNP-Ficoll or TNP-Dextran), was reduced, on the average, by 10-fold in animals exposed to 200 rad of ionizing radiation 24 hr before antigen challenge. In contrast, PFC responses to type 1, TI antigens (TNP-lipopolysaccharide or TNP-Brucella abortus) are unaffected in mice exposed to the same dose of radiation. Adoptive transfers showed that this selective immunosuppression is a result of the specific inactivation of the B cell subpopulation responding to type 2, TI antigens. These experiments suggest that physiologic differences exist in the B cell subpopulations of normal mice which respond to type 1, or type 2, TI antigens.

Synergi and E&P forum HSE management system helps companies improve HSE performance and reduce losses

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

Grundt, H.J.

1996-12-31

This paper discusses the use of information on accidents and near-misses to improve HSE performance and reduce losses in Exploration and Production activities. Incidents are considered a result of management system failure. To avoid incidents and recurrence of incidents, companies should adopt an integrated HSE Management System and software especially designed for recording, analyzing and following up events. The E&P Forum has issued guidelines to support current company HSE Management systems and practices. Concurrently, the Synergi Project has been established to facilitate experience transfer and effective handling of incidents as part of an integrated HSE Management System. The paper describesmore » how important it is to learn from past mistakes, to have a management system which facilitates the implementation of the required corrective action, and that tools for improved loss control are available.« less

Experimental and Computational Investigations of Phase Change Thermal Energy Storage Canisters

NASA Technical Reports Server (NTRS)

Ibrahim, Mounir; Kerslake, Thomas; Sokolov, Pavel; Tolbert, Carol

1996-01-01

Two sets of experimental data are examined in this paper, ground and space experiments, for cylindrical canisters with thermal energy storage applications. A 2-D computational model was developed for unsteady heat transfer (conduction and radiation) with phase-change. The radiation heat transfer employed a finite volume method. The following was found in this study: (1) Ground Experiments: the convection heat transfer is equally important to that of the radiation heat transfer; radiation heat transfer in the liquid is found to be more significant than that in the void; including the radiation heat transfer in the liquid resulted in lower temperatures (about 15 K) and increased the melting time (about 10 min.); generally, most of the heat flow takes place in the radial direction. (2) Space Experiments: radiation heat transfer in the void is found to be more significant than that in the liquid (exactly the opposite to the Ground Experiments); accordingly, the location and size of the void affects the performance considerably; including the radiation heat transfer in the void resulted in lower temperatures (about 40 K).

Parents' experiences of neonatal transfer. A meta-study of qualitative research 2000-2017.

PubMed

Aagaard, Hanne; Hall, Elisabeth O C; Ludvigsen, Mette S; Uhrenfeldt, Lisbeth; Fegran, Liv

2018-02-15

Transfers of critically ill neonates are frequent phenomena. Even though parents' participation is regarded as crucial in neonatal care, a transfer often means that parents and neonates are separated. A systematic review of the parents' experiences of neonatal transfer is lacking. This paper describes a meta-study addressing qualitative research about parents' experiences of neonatal transfer. Through deconstruction and reflections of theories, methods, and empirical data, the aim was to achieve a deeper understanding of theoretical, empirical, contextual, historical, and methodological issues of qualitative studies concerning parents' experiences of neonatal transfer over the course of this meta-study (2000-2017). Meta-theory and meta-method analyses showed that caring, transition, and family-centered care were main theoretical frames applied and that interviewing with a small number of participants was the preferred data collection method. The meta-data-analysis showed that transfer was a scary, unfamiliar, and threatening experience for the parents; they were losing familiar context, were separated from their neonate, and could feel their parenthood disrupted. We identified 'wavering and wandering' as a metaphoric representation of the parents' experiences. The findings add knowledge about meta-study as an approach for comprehensive qualitative research and point at the value of meta-theory and meta-method analyses. © 2018 John Wiley & Sons Ltd.

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.

Phenotype and function of T cells infiltrating visceral metastases from gastrointestinal cancers and melanoma: implications for adoptive cell transfer therapy.

PubMed

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S; Wunderlich, John R; Dudley, Mark E; Rosenberg, Steven A

2013-09-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3(+) T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8(+) cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ~50 × 10(9) T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3(+)CD8(+) cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I-mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I-mediated up-regulation of CD137 (4-1BB) expression on CD8(+) cells suggested that 0-3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells.

Phenotype and Function of T Cells Infiltrating Visceral Metastases from Gastrointestinal Cancers and Melanoma: Implications for Adoptive Cell Transfer Therapy

PubMed Central

Turcotte, Simon; Gros, Alena; Hogan, Katherine; Tran, Eric; Hinrichs, Christian S.; Wunderlich, John R.; Dudley, Mark E.

2013-01-01

Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) can mediate cancer regression in patients with metastatic melanoma, but whether this approach can be applied to common epithelial malignancies remains unclear. In this study, we compared the phenotype and function of TILs derived from liver and lung metastases from patients with gastrointestinal (GI) cancers (n = 14) or melanoma (n = 42). Fewer CD3+ T cells were found to infiltrate GI compared with melanoma metastases, but the proportions of CD8+ cells, T cell differentiation stage, and expression of costimulatory molecules were similar for both tumor types. Clinical-scale expansion up to ∼50 × 109 T cells on average was obtained for all patients with GI cancer and melanoma. From GI tumors, however, TIL outgrowth in high-dose IL-2 yielded 22 ± 1.4% CD3+CD8+ cells compared with 63 ± 2.4% from melanoma (p < 0.001). IFN-γ ELISA demonstrated MHC class I–mediated reactivity of TIL against autologous tumor in 5 of 7 GI cancer patients tested (9% of 188 distinct TIL cultures) and in 9 of 10 melanoma patients (43% of 246 distinct TIL cultures). In these assays, MHC class I–mediated up-regulation of CD137 (4-1BB) expression on CD8+ cells suggested that 0–3% of TILs expanded from GI cancer metastases were tumor-reactive. This study implies that the main challenge to the development of TIL adoptive cell transfer for metastatic GI cancers may not be the in vitro expansion of bulk TILs, but the ability to select and enrich for tumor-reactive T cells. PMID:23904171

Toll-like receptor-2 agonist-allergen coupling efficiently redirects Th2 cell responses and inhibits allergic airway eosinophilia.

PubMed

Krishnaswamy, Jayendra Kumar; Jirmo, Adan Chari; Baru, Abdul Mannan; Ebensen, Thomas; Guzmán, Carlos A; Sparwasser, Tim; Behrens, Georg M N

2012-12-01

Toll-like receptor (TLR) agonists beneficially modulate allergic airway inflammation. However, the efficiency of TLR agonists varies considerably, and their exact cellular mechanisms (especially of TLR 2/6 agonists) are incompletely understood. We investigated at a cellular level whether the administration of the pharmacologically improved TLR2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPP) conjugated to antigenic peptide (BPP-OVA) could divert an existing Th2 response and influence airway eosinophilia. The effects of BPP-OVA on airway inflammation were assessed in a classic murine sensitization/challenge model and an adoptive transfer model, which involved the adoptive transfer of in vitro differentiated ovalbumin (OVA)-specific Th2 cells. Functional T-cell stimulation by lung dendritic cells (DCs) was determined both in vitro and in vivo, combined with a cytokine secretion analysis. A single mucosal application of BPP-OVA efficiently delivered antigen, led to TLR2-mediated DC activation, and resulted in OVA-specific T-cell proliferation via lung DCs in vivo. In alternative models of allergic airway disease, a single administration of BPP-OVA before OVA challenge (but not BPP alone) significantly reduced airway eosinophilia, most likely through altered antigen-specific T-cell stimulation via DCs. Analyses of adoptively transferred Th2-biased cells after BPP-OVA administration in vivo suggested that BPP-OVA guides antigen-specific Th2 cells to produce significantly higher amounts of IFN-γ upon allergen challenge. In conclusion, our data show for the first time that a single mucosal administration of a TLR 2/6 agonist-allergen conjugate can provoke IFN-γ responses in Th2-biased cells and alleviate allergic airway inflammation.

Adoptive transfer of Epstein-Barr virus-specific cytotoxic T-lymphocytes for the treatment of angiocentric lymphomas.

PubMed

Cho, Hyun-Il; Hong, Young Seon; Lee, Myung Ah; Kim, Eun-Kyung; Yoon, Sung-Hee; Kim, Chun-Choo; Kim, Tai-Gyu

2006-01-01

Angiocentric lymphoma, known as natural killer (NK)/T-cell non-Hodgkin's lymphoma, has been reported to be associated with the Epstein-Barr virus (EBV). We performed adoptive transfer of EBV-specific polyclonal T-cell lines in 3 patients with extranodal NK/T-cell lymphoma, nasal type, and evaluated the treatment for safety, immunologic reconstitution, and clinical outcomes. The tissue samples collected from the 3 patients were confirmed by polymerase chain reaction analysis to be EBV positive. In the cases of the first and second patients, EBV-transformed B-lymphoblastoid cell lines (LCLs) and T-cell lines were generated from peripheral lymphocytes of HLA-matched sibling donors. The third patient's T-cell lines were induced with autologous lymphocytes. Polyclonal T-cell infusion was carried out after high-dose radiotherapy because active relapsed disease remained in all of the patients. The first patient received 4 weekly infusions of 2 3 10(7) cells/m(2), and the second and third patients underwent treatment with 2 cycles of infusions of the same dosage. All T-cell lines showed >60% NK activity, cytotoxic T-lymphocyte (CTL) responses of >40% against autologous LCLs, and no CTL activity against patient-derived lymphoblasts. The level of cytotoxicity increased substantially in all patients after cell infusion. The 2 patients who received T-cell therapy twice had stabilized disease for more than 3 years. These safe treatments exhibited no severe inflammatory response, and no serious toxicity developed during T-cell therapy. Our findings demonstrate that adoptively transferred cells may provide reconstitution of EBV-specific CTL responses in patients with active relapsed angiocentric lymphoma. These results provide a rationale for the immunotherapy of angiocentric lymphoma.

Adoptive transfer of nontransgenic mesenteric lymph node cells induces colitis in athymic HLA-B27 transgenic nude rats

PubMed Central

Hoentjen, F; Tonkonogy, S L; Liu, B; Sartor, R B; Taurog, J D; Dieleman, L A

2006-01-01

HLA-B27 transgenic (TG) rats develop spontaneous colitis when colonized with intestinal bacteria, whereas athymic nude (rnu/rnu) HLA-B27 TG rats remain disease free. The present study was designed to determine whether or not HLA-B27 expression on T cells is required for development of colitis after transfer of mesenteric lymph node (MLN) cells into rnu/rnu HLA-B27 recipients. Athymic nontransgenic (non-TG) and HLA-B27 TG recipients received MLN cells from either TG or non-TG rnu/+ heterozygous donor rats that contain T cells. HLA-B27 TG rnu/rnu recipients receiving either non-TG or TG MLN cells developed severe colitis and had higher caecal MPO and IL-1β levels, and their MLN cells produced more IFN-γ and less IL-10 after in vitro stimulation with caecal bacterial lysate compared to rnu/rnu non-TG recipients that remained disease free after receiving either TG or non-TG cells. Interestingly, proliferating donor TG T cells were detectable one week after adoptive transfer into rnu/rnu TG recipients but not after transfer into non-TG recipients. T cells from either non-TG or TG donors induce colitis in rnu/rnu TG but not in non-TG rats, suggesting that activation of effector T cells by other cell types that express HLA-B27 is pivotal for the pathogenesis of colitis in this model. PMID:16487247

Defective natural killer cell activity in a mouse model of eczema herpeticum.

PubMed

Kawakami, Yuko; Ando, Tomoaki; Lee, Jong-Rok; Kim, Gisen; Kawakami, Yu; Nakasaki, Tae; Nakasaki, Manando; Matsumoto, Kenji; Choi, Youn Soo; Kawakami, Toshiaki

2017-03-01

Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. We sought to establish and characterize a mouse model of EH. We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Transfer of movement sequences: bigger is better.

PubMed

Dean, Noah J; Kovacs, Attila J; Shea, Charles H

2008-02-01

Experiment 1 was conducted to determine if proportional transfer from "small to large" scale movements is as effective as transferring from "large to small." We hypothesize that the learning of larger scale movement will require the participant to learn to manage the generation, storage, and dissipation of forces better than when practicing smaller scale movements. Thus, we predict an advantage for transfer of larger scale movements to smaller scale movements relative to transfer from smaller to larger scale movements. Experiment 2 was conducted to determine if adding a load to a smaller scale movement would enhance later transfer to a larger scale movement sequence. It was hypothesized that the added load would require the participants to consider the dynamics of the movement to a greater extent than without the load. The results replicated earlier findings of effective transfer from large to small movements, but consistent with our hypothesis, transfer was less effective from small to large (Experiment 1). However, when a load was added during acquisition transfer from small to large was enhanced even though the load was removed during the transfer test. These results are consistent with the notion that the transfer asymmetry noted in Experiment 1 was due to factors related to movement dynamics that were enhanced during practice of the larger scale movement sequence, but not during the practice of the smaller scale movement sequence. The findings that the movement structure is unaffected by transfer direction but the movement dynamics are influenced by transfer direction is consistent with hierarchal models of sequence production.

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.

Transition of late-stage effector T cells to CD27+ CD28+ tumor-reactive effector memory T cells in humans after adoptive cell transfer therapy

PubMed Central

Powell, Daniel J.; Dudley, Mark E.; Robbins, Paul F.; Rosenberg, Steven A.

2007-01-01

In humans, the pathways of memory T-cell differentiation remain poorly defined. Recently, adoptive cell transfer (ACT) of tumor-reactive T lymphocytes to metastatic melanoma patients after nonmyeloablative chemotherapy has resulted in persistence of functional, tumor-reactive lymphocytes, regression of disease, and induction of melanocyte-directed autoimmunity in some responding patients. In the current study, longitudinal phenotypic analysis was performed on melanoma antigen–specific CD8+ T cells during their transition from in vitro cultured effector cells to long-term persistent memory cells following ACT to 6 responding patients. Tumor-reactive T cells used for therapy were generally late-stage effector cells with a CD27Lo CD28Lo CD45RA− CD62 ligand− (CD62L−) CC chemokine receptor 7− (CCR7−) interleukin-7 receptor αLo (IL-7RαLo) phenotype. After transfer, rapid up-regulation and continued expression of IL-7Rα in vivo suggested an important role for IL-7R in immediate and long-term T-cell survival. Although the tumor antigen–specific T-cell population contracted between 1 and 4 weeks after transfer, stable numbers of CD27+ CD28+ tumor-reactive T cells were maintained, demonstrating their contribution to the development of long-term, melanoma-reactive memory CD8+ T cells in vivo. At 2 months after transfer, melanoma-reactive T cells persisted at high levels and displayed an effector memory phenotype, including a CD27+ CD28+ CD62L− CCR7− profile, which may explain in part their ability to mediate tumor destruction. PMID:15345595

Large-scale Isolation of Highly Pure "Untouched" Regulatory T Cells in a GMP Environment for Adoptive Cell Therapy.

PubMed

Haase, Doreen; Puan, Kia Joo; Starke, Mireille; Lai, Tuck Siong; Soh, Melissa Yan Ling; Karunanithi, Iyswariya; San Luis, Boris; Poh, Tuang Yeow; Yusof, Nurhashikin; Yeap, Chun Hsien; Phang, Chew Yen; Chye, Willis Soon Yuan; Chan, Marieta; Koh, Mickey Boon Chai; Goh, Yeow Tee; Bertin-Maghit, Sebastien; Nardin, Alessandra; Ho, Liam Pock; Rotzschke, Olaf

2015-01-01

Adoptive cell therapy is an emerging treatment strategy for a number of serious diseases. Regulatory T (Treg) cells represent 1 cell type of particular interest for therapy of inflammatory conditions, as they are responsible for controlling unwanted immune responses. Initial clinical trials of adoptive transfer of Treg cells in patients with graft-versus-host disease were shown to be safe. However, obtaining sufficient numbers of highly pure and functional Treg cells with minimal contamination remains a challenge. We developed a novel approach to isolate "untouched" human Treg cells from healthy donors on the basis of negative selection using the surface markers CD49d and CD127. This procedure, which uses an antibody cocktail and magnetic beads for separation in an automated system (RoboSep), was scaled up and adapted to be compatible with good manufacturing practice conditions. With this setup we performed 9 Treg isolations from large-scale leukapheresis samples in a good manufacturing practice facility. These runs yielded sufficient numbers of "untouched" Treg cells for immediate use in clinical applications. The cell preparations consisted of viable highly pure FoxP3-positive Treg cells that were functional in suppressing the proliferation of effector T cells. Contamination with CD4 effector T cells was <10%. All other cell types did not exceed 2% in the final product. Remaining isolation reagents were reduced to levels that are considered safe. Treg cells isolated with this procedure will be used in a phase I clinical trial of adoptive transfer into leukemia patients developing graft-versus-host disease after stem cell transplantation.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting.

PubMed

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J Michael; Kanerva, Anna; Hemminki, Akseli

2016-05-01

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8(+) T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors.

Syngeneic syrian hamster tumors feature tumor-infiltrating lymphocytes allowing adoptive cell therapy enhanced by oncolytic adenovirus in a replication permissive setting

PubMed Central

Siurala, Mikko; Vähä-Koskela, Markus; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Parviainen, Suvi; Mathis, J. Michael; Kanerva, Anna; Hemminki, Akseli

2016-01-01

ABSTRACT Adoptive transfer of tumor-infiltrating lymphocytes (TIL) has shown promising yet sometimes suboptimal results in clinical trials for advanced cancer, underscoring the need for approaches improving efficacy and safety. Six implantable syngeneic tumor cell lines of the Syrian hamster were used to initiate TIL cultures. TIL generated from tumor fragments cultured in human interleukin-2 (IL-2) for 10 d were adoptively transferred into tumor-bearing hamsters with concomitant intratumoral injections of oncolytic adenovirus (Ad5-D24) for the assessment of antitumor efficacy. Pancreatic cancer (HapT1) and melanoma (RPMI 1846) TIL exhibited potent and tumor-specific cytotoxicity in effector-to-target (E/T) assays. MHC Class I blocking abrogated the cell killing of RPMI 1846 TIL, indicating cytotoxic CD8+ T-cell activity. When TIL were combined with Ad5-D24 in vitro, HapT1 tumor cell killing was significantly enhanced over single agents. In vivo, the intratumoral administration of HapT1 TIL and Ad5-D24 resulted in improved tumor growth control compared with either treatment alone. Additionally, splenocytes derived from animals treated with the combination of Ad5-D24 and TIL killed autologous tumor cells more efficiently than monotherapy-derived splenocytes, suggesting that systemic antitumor immunity was induced. For the first time, TIL of the Syrian hamster have been cultured, characterized and used therapeutically together with oncolytic adenovirus for enhancing the efficacy of TIL therapy. Our results support human translation of oncolytic adenovirus as an enabling technology for adoptive T-cell therapy of solid tumors. PMID:27467954

Enabling Grid Computing resources within the KM3NeT computing model

NASA Astrophysics Data System (ADS)

Filippidis, Christos

2016-04-01

KM3NeT is a future European deep-sea research infrastructure hosting a new generation neutrino detectors that - located at the bottom of the Mediterranean Sea - will open a new window on the universe and answer fundamental questions both in particle physics and astrophysics. International collaborative scientific experiments, like KM3NeT, are generating datasets which are increasing exponentially in both complexity and volume, making their analysis, archival, and sharing one of the grand challenges of the 21st century. These experiments, in their majority, adopt computing models consisting of different Tiers with several computing centres and providing a specific set of services for the different steps of data processing such as detector calibration, simulation and data filtering, reconstruction and analysis. The computing requirements are extremely demanding and, usually, span from serial to multi-parallel or GPU-optimized jobs. The collaborative nature of these experiments demands very frequent WAN data transfers and data sharing among individuals and groups. In order to support the aforementioned demanding computing requirements we enabled Grid Computing resources, operated by EGI, within the KM3NeT computing model. In this study we describe our first advances in this field and the method for the KM3NeT users to utilize the EGI computing resources in a simulation-driven use-case.

Introducing Students to Basic ChE Concepts: Four Simple Experiments.

ERIC Educational Resources Information Center

Fraser, Duncan M.

1999-01-01

Describes an Introduction to Chemical Engineering course with particular reference to the development, use, and evaluation of four simple experiments centered around the fundamental principles of heat transfer, mass transfer, reaction kinetics, and momentum transfer. (WRM)

Development and Adoption of a Watershed Approach to Compensatory Mitigation: Experiences in Colorado and California

EPA Science Inventory

In this article, we examine the adoption of the watershed approach and its technical methods into regulatory programs in Colorado and California. Specific steps and motives for the adoption are explained. Through close collaboration, regulators have systematically been made aware...

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)

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

Touring DNS Open Houses for Trends and Configurations

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

Kalafut, Prof. Andrew; Shue, Craig A; Gupta, Prof. Minaxi

2011-01-01

DNS is a critical component of the Internet. It maps domain names to IP addresses and serves as a distributed database for various other applications, including mail, Web, and spam filtering. This paper examines DNS zones in the Internet for diversity, adoption rates of new technologies, and prevalence of configuration issues. To gather data, we sweep 60% of the Internet's domains in June - August 2007 for zone transfers. 6.6% of them allow us to transfer their complete information. Surprisingly, this includes a large fraction of the domains deploying DNSSEC. We find that DNS zones vary significantly in size andmore » some span many ASes. Also, while anti-spam technologies appear to be getting deployed, the adoption rates of DNSSEC and IPv6 continue to be low. Finally, we also find that carelessness in handing DNS records can lead to reduced availability of name servers, email, and Web servers. This also undermines anti-spam efforts and the efforts to shut down phishing sites or to contain malware infections.« less

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…

Using Assessments of Contextual Learning to Identify Characteristics of Adaptive Transfer in Medical Students

ERIC Educational Resources Information Center

Baer, Tom

2013-01-01

Transfer of learning from curricular experiences to non-academic settings is a primary goal of any academic institution. In cases where skills, knowledge, and attitudes learned in curricular experiences are used to solve complex problems, transfer is especially difficult to define and measure. This study attempts to better define transfer in…

Community College Transfer and the Pathway to a Baccalaureate Degree: The Lived Experiences of Transfer Students

ERIC Educational Resources Information Center

Peters, Stephannie Rae

2018-01-01

Many students who start at the community college with the intention of transferring and earning a baccalaureate degree fail to accomplish this goal. This study, using IPA methodology, explored the experiences of seven community college transfer students currently enrolled at a public 4-year institution to identify how community college transfer…

Cross-Fostering of Male Mice Subtly Affects Female Olfactory Preferences

PubMed Central

Liu, Ying-Juan; Zhang, Yao-Hua; Li, Lai-Fu; Du, Rui-Qing; Zhang, Jin-Hua; Zhang, Jian-Xu

2016-01-01

The maternal environment has been shown to influence female olfactory preferences through early chemosensory experience. However, little is known about the influence of the maternal environment on chemosignals. In this study, we used two inbred mouse strains, C57BL/6 (C57) and BALB/c (BALB), and explored whether adoption could alter male chemosignals and thus influence female olfactory preferences. In Experiment 1, C57 pups were placed with BALB dams. Adult BALB females then served as the subjects in binary choice tests between paired male urine odours (BALB vs. C57, BALB vs. adopted C57 and C57 vs. adopted C57). In Experiment 2, BALB pups were placed with C57 dams, and C57 females served as the subjects in binary choice tests between paired male urine odours (C57 vs. BALB, C57 vs. adopted BALB, and BALB vs. adopted BALB). In both experiments, we found that females preferred the urine of males from different genetic backgrounds, suggesting that female olfactory preferences may be driven by genetic compatibility. Cross-fostering had subtle effects on female olfactory preferences. Although the females showed no preference between the urine odours of adopted and non-adopted males of the other strain, the BALB females preferred the urine odour of BALB males to that of adopted C57 males, whereas the C57 females showed no preference between the urine odour of C57 and adopted BALB males. Using gas chromatography-mass spectrometry (GC-MS) and stepwise discriminant analysis, we found that the ratios of volatile chemicals from urine and preputial gland secretions were altered in the fostered male mice; these changes may have resulted in the behavioural changes observed in the females. Overall, the results suggest that female mice prefer urine odours from males with different genetic backgrounds; this preference may be driven by genetic compatibility. The early maternal environment influences the chemosignals of males and thus may influence the olfactory preferences of females. Our study provides additional evidence in support of genotype-dependent maternal influences on phenotypic variability in adulthood. PMID:26756471

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.

Neurophysiological evidence for transfer appropriate processing of memory: processing versus feature similarity.

PubMed

Schendan, Haune E; Kutas, Malra

2007-08-01

Transfer appropriate processing (TAP) accounts propose that memory is a function of the degree to which the same neural processes transfer appropriately from the study experience to the memory test. However, in prior research, study and test stimuli were often similar physically. In two experiments, event-related brain potentials (ERPs) were recorded to fragmented objects during an indirect memory test to isolate transfer of a specific perceptual process from overlap of physical features between experiences. An occipitotemporoparietal P2(00) at 200 msec showed implicit memory effects only when similar perceptual grouping processes of good continuation were repeatedly engaged-despite physical feature differences--as TAP accounts hypothesize. This result provides direct neurophysiological evidence for the critical role of process transfer across experiences for memory.

Guaranteeing Isochronous Control of Networked Motion Control Systems Using Phase Offset Adjustment

PubMed Central

Kim, Ikhwan; Kim, Taehyoun

2015-01-01

Guaranteeing isochronous transfer of control commands is an essential function for networked motion control systems. The adoption of real-time Ethernet (RTE) technologies may be profitable in guaranteeing deterministic transfer of control messages. However, unpredictable behavior of software in the motion controller often results in unexpectedly large deviation in control message transmission intervals, and thus leads to imprecise motion. This paper presents a simple and efficient heuristic to guarantee the end-to-end isochronous control with very small jitter. The key idea of our approach is to adjust the phase offset of control message transmission time in the motion controller by investigating the behavior of motion control task. In realizing the idea, we performed a pre-runtime analysis to determine a safe and reliable phase offset and applied the phase offset to the runtime code of motion controller by customizing an open-source based integrated development environment (IDE). We also constructed an EtherCAT-based motion control system testbed and performed extensive experiments on the testbed to verify the effectiveness of our approach. The experimental results show that our heuristic is highly effective even for low-end embedded controller implemented in open-source software components under various configurations of control period and the number of motor drives. PMID:26076407

The Lived Experiences of Faculty Who Use Instructional Technology: A Phenomenological Study

ERIC Educational Resources Information Center

Tuttle, Heath V.

2012-01-01

This qualitative phenomenological study was designed to gain an in-depth understanding of the lived experiences of university faculty who adopt technology for teaching and learning purposes and to determine if adoption affected the way a person taught, worked, and lived. A review of the literature found a gap in the understanding of the lived…

An Examination of the Impact of Permanency on Young Adults' Special Education Experiences

ERIC Educational Resources Information Center

Hill, Katharine; Koester, Shannon

2015-01-01

Educational outcomes for youths in foster care are poor compared with those of their peers who are not child welfare involved. This qualitative study examined the impact of adoption on the educational experiences of older youths with disabilities who were adopted from the child welfare system. Researchers conducted interviews with families of…

Gaining a Child: Comparing the Experiences of Biological Parents, Adoptive Parents, and Stepparents

ERIC Educational Resources Information Center

Ceballo, Rosario; Lansford, Jennifer E.; Abbey, Antonia; Stewart, Abigail J.

2004-01-01

This study compares the experience of gaining a child through birth, adoption, or marriage, extending the focus of investigation beyond biological parenthood and the transition made by first-time parents. Using a subsample from the National Survey of Families and Households N=204, we compared reasons for having children, parental well-being,…

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

A fragile bond: adoptive parents' experiences of caring for children with a diagnosis of reactive attachment disorder.

PubMed

Follan, Michael; McNamara, Martin

2014-04-01

To understand how adoptive parents caring for children with a diagnosis of reactive attachment disorder (RAD) make sense of their life-worlds by establishing the meanings that underlie and structure their experiences of their everyday lives. Reactive attachment disorder is a serious psychosocial disorder of childhood that causes short- and long-term relationship, health and social consequences for children. It is more likely to be observed in children being cared for by foster carers, kinship carers or adoptive parents. Exploration of adoption from parents' perspectives is not well documented, and no previous work has been undertaken to understand the challenges of caring for children with a diagnosis of reactive attachment disorder. The study was guided by Husserl's phenomenology, which aims to uncover the underlying essential meanings intrinsic to a phenomenon. Three concepts are central to this approach: essences, intuiting and eidetic reduction. Semi-structured interviews were conducted with eight adoptive parents. Data were analysed using an adaptation of Colaizzi's method. Four essential elements fundamental to participants' lived experiences of caring for a child with a diagnosis of RAD were uncovered: being profoundly unprepared, being insecure, being assailed by unexpected emotions and being committed. The parent-child relationship is a fragile bond developed at an unexpectedly high personal cost; it is a committed relationship but vulnerable to continual destabilisation. The involvement in the preparation of adoptive parents of child and adolescent mental health (CAMH) staff with expertise in the impact of early neglect or separation on children should be considered. The development of systems to prepare, screen and identify potential challenges and problems prior to adoption might help adoptive parents. Access to a CAMH professional in the pre and postadoption phases might assist potential adoptive parents in making informed decisions around the choice of a child for adoption. © 2013 John Wiley & Sons Ltd.

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

PubMed

Kuipers, Derek A; Terlouw, Gijs; Wartena, Bard O; van 't Veer, Job Tb; Prins, Jelle T; Pierie, Jean Pierre En

2017-11-24

The usefulness and importance of serious games and simulations in learning and behavior change for health and health-related issues are widely recognized. Studies have addressed games and simulations as interventions, mostly in comparison with their analog counterparts. Numerous complex design choices have to be made with serious games and simulations for health, including choices that directly contribute to the effects of the intervention. One of these decisions is the way an intervention is expected to lead to desirable transfer effects. Most designs adopt a first-class transfer rationale, whereas the second class of transfer types seems a rarity in serious games and simulations for health. This study sought to review the literature specifically on the second class of transfer types in the design of serious games and simulations. Focusing on game-like interventions for health and health care, this study aimed to (1) determine whether the second class of transfer is recognized as a road for transfer in game-like interventions, (2) review the application of the second class of transfer type in designing game-like interventions, and (3) assess studies that include second-class transfer types reporting transfer outcomes. A total of 6 Web-based databases were systematically searched by titles, abstracts, and keywords using the search strategy (video games OR game OR games OR gaming OR computer simulation*) AND (software design OR design) AND (fidelity OR fidelities OR transfer* OR behaviour OR behavior). The databases searched were identified as relevant to health, education, and social science. A total of 15 relevant studies were included, covering a range of game-like interventions, all more or less mentioning design parameters aimed at transfer. We found 9 studies where first-class transfer was part of the design of the intervention. In total, 8 studies dealt with transfer concepts and fidelity types in game-like intervention design in general; 3 studies dealt with the concept of second-class transfer types and reported effects, and 2 of those recognized transfer as a design parameter. In studies on game-like interventions for health and health care, transfer is regarded as a desirable effect but not as a basic principle for design. None of the studies determined the second class of transfer or instances thereof, although in 3 cases a nonliteral transfer type was present. We also found that studies on game-like interventions for health do not elucidate design choices made and rarely provide design principles for future work. Games and simulations for health abundantly build upon the principles of first-class transfer, but the adoption of second-class transfer types proves scarce. It is likely to be worthwhile to explore the possibilities of second-class transfer types, as they may considerably influence educational objectives in terms of future serious game design for health. ©Derek A Kuipers, Gijs Terlouw, Bard O Wartena, Job TB van 't Veer, Jelle T Prins, Jean Pierre EN Pierie. Originally published in JMIR Serious Games (http://games.jmir.org), 24.11.2017.

Long-term follow-up of women and men after unsuccessful IVF.

PubMed

Filetto, Juliana N; Makuch, Maria Y

2005-10-01

The experience of 92 couples, who had unsuccessfully undergone one or more IVF cycles at a university clinic, was evaluated 3-8 years following their last failed attempt. One member of each couple completed a telephone questionnaire regarding life events during their last IVF cycle performed at the clinic and at the time of the interview. Some couples had continued further treatment and some had not. Multivariate correspondence analysis was used to analyse the data. Regarding the long-term experience of couples who had undergone further treatment, for men the main experiences were psychological problems and having adopted a child. For women, the main experiences were related to problems of self-image, psychological problems, loss of hope, and having adopted a child. These women also presented a strong association with problems in their marital relationship and with adoption. For the group that did not undergo further treatment, the women showed a strong association with considering adoption, and a less intense association with psychological problems and loss of hope. The men presented psychological problems and having adopted a child as associated variables. Comparison between men and women showed that recognizing the impossibility of conceiving a child and giving up treatment were strongly associated. Men and women who had not continued with further treatment were more affected in the long term than those who had undergone further treatment after IVF failure.

A statewide teleradiology system reduces radiation exposure and charges in transferred trauma patients.

PubMed

Watson, Justin J J; Moren, Alexis; Diggs, Brian; Houser, Ben; Eastes, Lynn; Brand, Dawn; Bilyeu, Pamela; Schreiber, Martin; Kiraly, Laszlo

2016-05-01

Trauma transfer patients routinely undergo repeat imaging because of inefficiencies within the radiology system. In 2009, the virtual private network (VPN) telemedicine system was adopted throughout Oregon allowing virtual image transfer between hospitals. The startup cost was a nominal $3,000 per hospital. A retrospective review from 2007 to 2012 included 400 randomly selected adult trauma transfer patients based on a power analysis (200 pre/200 post). The primary outcome evaluated was reduction in repeat computed tomography (CT) scans. Secondary outcomes included cost savings, emergency department (ED) length of stay (LOS), and spared radiation. All data were analyzed using Mann-Whitney U and chi-square tests. P less than .05 indicated significance. Spared radiation was calculated as a weighted average per body region, and savings was calculated using charges obtained from Oregon Health and Science University radiology current procedural terminology codes. Four-hundred patients were included. Injury Severity Score, age, ED and overall LOS, mortality, trauma type, and gender were not statistically different between groups. The percentage of patients with repeat CT scans decreased after VPN implementation: CT abdomen (13.2% vs 2.8%, P < .01) and cervical spine (34.4% vs 18.2%, P < .01). Post-VPN, the total charges saved in 2012 for trauma transfer patients was $333,500, whereas the average radiation dose spared per person was 1.8 mSV. Length of stay in the ED for patients with Injury Severity Score less than 15 transferring to the ICU was decreased (P < .05). Implementation of a statewide teleradiology network resulted in fewer total repeat CT scans, significant savings, decrease in radiation exposure, and decreased LOS in the ED for patients with less complex injuries. The potential for health care savings by widespread adoption of a VPN is significant. Copyright © 2016 Elsevier Inc. All rights reserved.

Powering the High-Luminosity Triplets

NASA Astrophysics Data System (ADS)

Ballarino, A.; Burnet, J. P.

The powering of the magnets in the LHC High-Luminosity Triplets requires production and transfer of more than 150 kA of DC current. High precision power converters will be adopted, and novel High Temperature Superconducting (HTS) current leads and MgB2 based transfer lines will provide the electrical link between the power converters and the magnets. This chapter gives an overview of the systems conceived in the framework of the LHC High-Luminosity upgrade for feeding the superconducting magnet circuits. The focus is on requirements, challenges and novel developments.

CCR 20th Anniversary Commentary: Autologous T Cells-The Ultimate Personalized Drug for the Immunotherapy of Human Cancer.

PubMed

Rosenberg, Steven A

2015-12-15

The article by Rosenberg and colleagues, which was published in the July 1, 2011, issue of Clinical Cancer Research, demonstrated the power of the adoptive transfer of autologous antitumor T cells to mediate the complete, durable, and likely curative regression of cancer in patients with heavily pretreated metastatic melanoma. It also provided a stimulus to the development of cell transfer approaches for other cancer types using both natural and genetically engineered lymphocytes. ©2015 American Association for Cancer Research.

Computation of Flow and Heat Transfer in Flow Around a 180 deg Bend.

DTIC Science & Technology

1984-04-01

be required if a more elaborate closure were adopted.[I- 9 Enayet et al [14] in a 900 bend with a radius:diameter ratio of I only 2.8:1 giving a Dean...Figure 9 indicates, however, that a satisfactory numerical simulation is nevertheless obtained. Enayet et al [14] also measured the development of...computations of the 2.P:1 90o bend of Enayet et al [1h] indicate a five-fold variation of local heat transfer coefficient around the bend at 750 . The