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32 result(s) for "Wetzel, Keith"
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Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells
Adoptive cellular therapy using chimeric antigen receptor (CAR) T cell therapies have produced significant objective responses in patients with CD19+ hematological malignancies, including durable complete responses. Although the majority of clinical trials to date have used autologous patient cells as the starting material to generate CAR T cells, this strategy poses significant manufacturing challenges and, for some patients, may not be feasible because of their advanced disease state or difficulty with manufacturing suitable numbers of CAR T cells. Alternatively, T cells from a healthy donor can be used to produce an allogeneic CAR T therapy, provided the cells are rendered incapable of eliciting graft versus host disease (GvHD). One approach to the production of these cells is gene editing to eliminate expression of the endogenous T cell receptor (TCR). Here we report a streamlined strategy for generating allogeneic CAR T cells by targeting the insertion of a CAR transgene directly into the native TCR locus using an engineered homing endonuclease and an AAV donor template. We demonstrate that anti-CD19 CAR T cells produced in this manner do not express the endogenous TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19+ tumors in an in vivo mouse model. MacLeod and colleagues use a homing endonuclease and an AAV vector to insert an anti-CD19 CAR into the TRAC gene to create universal allogeneic CAR T cells. Targeted insertion of a CAR transgene may allow the generation of more homogeneous CAR T cell products with more predictable safety and efficacy profiles.
Vibrio fischeri‐derived outer membrane vesicles trigger host development
Summary Outer membrane vesicles (OMV) are critical elements in many host‐cell/microbe interactions. Previous studies of the symbiotic association between Euprymna scolopes and Vibrio fischeri had shown that within 12 h of colonizing crypts deep within the squid's light organ, the symbionts trigger an irreversible programme of tissue development in the host. Here, we report that OMV produced by V. fischeri are powerful contributors to this process. The first detectable host response to the OMV is an increased trafficking of macrophage‐like cells called haemocytes into surface epithelial tissues. We showed that exposing the squid to other Vibrio species fails to induce this trafficking; however, addition of a high concentration of their OMV, which can diffuse into the crypts, does. We also provide evidence that tracheal cytotoxin released by the symbionts, which can induce haemocyte trafficking, is not part of the OMV cargo, suggesting two distinct mechanisms to induce the same morphogenesis event. By manipulating the timing and localization of OMV signal delivery, we showed that haemocyte trafficking is fully induced only when V. fischeri, the sole species able to reach and grow in the crypts, succeeds in establishing a sustained colonization. Further, our data suggest that the host's detection of OMV serves as a symbiotic checkpoint prior to inducing irreversible morphogenesis.
Electronic Portfolios in Teacher Education
At a time when implementation of electronic portfolios (EPs) is expanding, the issues of clarifying their purposes continue to plague teacher education programs. Are student-centered uses of EPs compatible with program assessment and accreditation efforts? Is this an either/or situation, or can a productive middle ground be forged? This article reviews the compatibility of key purposes for EPs in light of the changing landscape of their use in teacher education. It explores theoretical perspectives, analyzes policy implications and challenges, and provides recommendations that support current adoption and implementation decisions. It concludes that it is possible to effectively use EPs for varied purposes and provides specific recommendations for doing so.
The Diffusion of Electronic Portfolios in Teacher Education
This descriptive study investigates the diffusion of electronic portfolios in preservice teacher education by documenting the context and emergent practices in six programs identified as mature in their implementation. Context variables examined include prior use of paper portfolios, pressures for standards-based assessment, and leadership and governance issues. Variations in program implementation are also explored including the portfolio tools employed, artifact selection, evaluation of student work, and the role of reflection. Findings of the study suggest that amidst the common themes across programs, there are numerous variations in approaches to e-portfolio use. The authors conclude that further research is needed to examine the future directions for e-portfolios envisioned as well as specific advice for those in earlier stages of adoption or implementation.
Electronic Portfolios in Teacher Education: Forging a Middle Ground
At a time when implementation of electronic portfolios (EPs) is expanding, the issues of clarifying their purposes continue to plague teacher education programs. Are student-centered uses of EPs compatible with program assessment and accreditation efforts? Is this an either/or situation, or can a productive middle ground be forged? This article reviews the compatibility of key purposes for EPs in light of the changing landscape of their use in teacher education. It explores theoretical perspectives, analyzes policy implications and challenges, and provides recommendations that support current adoption and implementation decisions. It concludes that it is possible to effectively use EPs for varied purposes and provides specific recommendations for doing so. (Contains 2 tables.)
The Diffusion of Electronic Portfolios In Teacher Education
This is the second part of a two-part article on the diffusion of electronic portfolios in preservice teacher education. The first part addressed issues of adoption and implementation; this part documents \"next steps\" and key recommendations by informants from the six programs studied. Next steps included streamlining requirements, addressing reliability of technology and access, and planning for data aggregation and program evaluation. Key recommendations were to involve a broad base of participants in the planning process, clarify the purposes for electronic portfolios, move forward incrementally, and provide sufficient technology access, training, and support. The study concludes that a range of research is needed to inform future decisions pertaining to the large-scale implementation of electronic portfolios in teacher education.
Lessons from Exemplary Colleges of Education: Factors Affecting Technology Integration in Preservice Programs
This study focused on efforts in four colleges of education deemed exemplary in their approaches to prepare preservice teachers to use technology. The study addressed one overarching question: What are the important pieces of the puzzle that make up the current technology integration efforts at these exemplary sites? Data were gathered during the 1997—98 academic year. Findings suggest that there is a web of enabling factors that supports student learning opportunities and desired technology-related outcomes for preservice teachers. The informed leadership of deans and other administrative and faculty leaders appears to be especially critical to sustain and expand technology-integration efforts. Leadership issues, along with a wide range of other factors, are systematically examined across the four case studies. The authors conclude that while each of the four cases is unique, many of the recommended practices explored in this study would likely prove beneficial f employed in other settings.
The Negotiated Project Approach: Project-Based Learning without Leaving the Standards Behind
The purpose this study was to explore how a veteran first-grade teacher collaboratively negotiated the implementation of a project with her students while, at the same time, addressed grade-level standards. Researchers investigated the teacher’s strategies for integrating the district’s standards into project topics, investigative activities, and final presentations. They also examined the teacher’s strategies for promoting students’ participation in project planning and independent problem-solving. Data sources included field notes, teacher interviews, videotaped observations, and transcribed teacher, and student interviews. As an extension to teacher-directed approaches to implementing the project approach, the results of this study revealed a collaborative approach to implementing projects that allowed the teacher and the students to work together for project planning and learning. The teacher felt successful with meeting grade level learning needs, and the students were given the opportunity to fuel their learning by expressing their natural interests and curiosities, and become problem solvers.