981 resultados para policy transfer
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Doctoral dissertation, University of Tampere
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Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies.
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Selostus: Hevosen alkioiden värjääminen DAPI:lla ennen vastaanottajaan siirtoa
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Selostus: Radiocesiumin kulkeutuminen eri laidunekosysteemien maa-ruoho-lammas -ravintoketjussa
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Selostus: Vasikoiden tuottaminen tuoreilla ja kylmäsäilytetyillä halkaistuilla alkioilla
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Vertebroplasty and kyphoplasty have been reported to alter the mechanical behavior of the treated and adjacent-level segments, and have been suggested to increase the risk for adjacent-level fractures. The intervertebral disc (IVD) plays an important role in the mechanical behavior of vertebral motion segments. Comparisons between normal and degenerative IVD motion segments following cement augmentation have yet to be reported. A microstructural finite element model of a degenerative IVD motion segment was constructed from micro-CT images. Microdamage within the vertebral body trabecular structure was used to simulate a slightly (I = 83.5% of intact stiffness), moderately (II = 57.8% of intact stiffness), and severely (III = 16.0% of intact stiffness) damaged motion segment. Six variable geometry single-segment cement repair strategies (models A-F) were studied at each damage level (I-III). IVD and bone stresses, and motion segment stiffness, were compared with the intact and baseline damage models (untreated), as well as, previous findings using normal IVD models with the same repair strategies. Overall, small differences were observed in motion segment stiffness and average stresses between the degenerative and normal disc repair models. We did however observe a reduction in endplate bulge and a redistribution in the microstructural tissue level stresses across both endplates and in the treated segment following early stage IVD degeneration. The cement augmentation strategy placing bone cement along the periphery of the vertebra (model E) proved to be the most advantageous in treating the degenerative IVD models by showing larger reductions in the average bone stresses (vertebral and endplate) as compared to the normal IVD models. Furthermore, only this repair strategy, and the complete cement fill strategy (model F), were able to restore the slightly damaged (I) motion segment stiffness above pre-damaged (intact) levels. Early stage IVD degeneration does not have an appreciable effect in motion segment stiffness and average stresses in the treated and adjacent-level segments following vertebroplasty and kyphoplasty. Placing bone cement in the periphery of the damaged vertebra in a degenerative IVD motion segment, minimizes load transfer, and may reduce the likelihood of adjacent-level fractures.
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Selostus: Alkionsiirtojalostusohjelma "ASMO", sen tavoitteet ja yhteenveto alkuvalinnan tuloksista
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The first part of a three year plan to evaluate and recommend improvements to Iowa's Juvenile Courts.
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The provision of free appropriate public education (FAPE), an Individualized Education Program (IEP), and the least restrictive environment (LRE) have been important cornerstones of educating students with disabilities since the enactment of the Education of All Handicapped Children Act (EAHCA), Public Law 94-142, in 1975, and its subsequent reauthorizations, the Individuals with Disabilities Education Act (IDEA) in 1990, 1997, and 2004. It is impossible to consider any one of these cornerstones without the others, when determining an appropriate educational placement for a student with a disability. The Iowa Department of Education has identified several practice issues regarding the interplay between FAPE, LRE, and the IEP in placement decisions for students with disabilities. To that end, this document will provide guidance for administrators of local education agencies (LEAs) and area education agencies (AEAs), as well as IEP teams (or other placement teams) within Iowa LEAs and AEAs when making placement decisions for eligible children with disabilities. This guidance will specifically discuss ten LRE and FAPE placement/program policy questions that have been identified by the Iowa Department of Education as needing attention. The policy discussions are consistent with the legal provisions of the 2004 reauthorization of IDEA (IDEA 2004) and its 2006 final federal implementing regulations issued by the U.S. Department of Education, Office of Special Education Programs (OSEP). This document is also consistent with the Iowa Administrative Rules of Special Education (2007) [hereinafter “Iowa Rules”]. In addition, the term local education agency (LEA) is used interchangeably for school district throughout this document. Prior to the discussion of specific policy questions, a federal and state legal framework for providing FAPE for students with disabilities within the LRE is briefly outlined. Pertinent FAPE and LRE court decisions that impact Iowa LEAs and AEAs are also included within Section II.
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Stimulation of resident cells by NF-κB activating cytokines is a central element of inflammatory and degenerative disorders of the central nervous system (CNS). This disease-mediated NF-κB activation could be used to drive transgene expression selectively in affected cells, using adeno-associated virus (AAV)-mediated gene transfer. We have constructed a series of AAV vectors expressing GFP under the control of different promoters including NF-κB -responsive elements. As an initial screen, the vectors were tested in vitro in HEK-293T cells treated with TNF-α. The best profile of GFP induction was obtained with a promoter containing two blocks of four NF-κB -responsive sequences from the human JCV neurotropic polyoma virus promoter, fused to a new tight minimal CMV promoter, optimally distant from each other. A therapeutical gene, glial cell line-derived neurotrophic factor (GDNF) cDNA under the control of serotype 1-encapsidated NF-κB -responsive AAV vector (AAV-NF) was protective in senescent cultures of mouse cortical neurons. AAV-NF was then evaluated in vivo in the kainic acid (KA)-induced status epilepticus rat model for temporal lobe epilepsy, a major neurological disorder with a central pathophysiological role for NF-κB activation. We demonstrate that AAV-NF, injected in the hippocampus, responded to disease induction by mediating GFP expression, preferentially in CA1 and CA3 neurons and astrocytes, specifically in regions where inflammatory markers were also induced. Altogether, these data demonstrate the feasibility to use disease-activated transcription factor-responsive elements in order to drive transgene expression specifically in affected cells in inflammatory CNS disorders using AAV-mediated gene transfer.