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- Reinke, Beth A, et al.
(författare)
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Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
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Tidskriftsartikel (refereegranskat)abstract
- Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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- Silva, DN, et al.
(författare)
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Process Development for Adoptive Cell Therapy in Academia: A Pipeline for Clinical-Scale Manufacturing of Multiple TCR-T Cell Products
- 2022
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Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 13, s. 896242-
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Tidskriftsartikel (refereegranskat)abstract
- Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipeline for process development and clinical-scale manufacturing of TCR-T cells in academia. We utilized two TCRs specific for hepatitis C virus (HCV) as models because of their marked differences in avidity and functional profile in TCR-redirected cells. With our clinical-scale pipeline, we reproduced the functional profile associated with each TCR. Moreover, the two TCR-T cell products demonstrated similar yield, purity, transduction efficiency as well as phenotype. The TCR-T cell products had a highly reproducible yield of over 1.4 × 109 cells, with an average viability of 93%; 97.8–99% of cells were CD3+, of which 47.66 ± 2.02% were CD8+ T cells; the phenotype was markedly associated with central memory (CD62L+CD45RO+) for CD4+ (93.70 ± 5.23%) and CD8+ (94.26 ± 4.04%). The functional assessments in 2D and 3D cell culture assays showed that TCR-T cells mounted a polyfunctional response to the cognate HCV peptide target in tumor cell lines, including killing. Collectively, we report a solid strategy for the efficient large-scale manufacturing of TCR-T cells.
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- Mazzotti, L, et al.
(författare)
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T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer
- 2022
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Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 23:15
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Tidskriftsartikel (refereegranskat)abstract
- The immune system is a dynamic feature of each individual and a footprint of our unique internal and external exposures. Indeed, the type and level of exposure to physical and biological agents shape the development and behavior of this complex and diffuse system. Many pathological conditions depend on how our immune system responds or does not respond to a pathogen or a disease or on how the regulation of immunity is altered by the disease itself. T-cells are important players in adaptive immunity and, together with B-cells, define specificity and monitor the internal and external signals that our organism perceives through its specific receptors, TCRs and BCRs, respectively. Today, high-throughput sequencing (HTS) applied to the TCR repertoire has opened a window of opportunity to disclose T-cell repertoire development and behavior down to the clonal level. Although TCR repertoire sequencing is easily accessible today, it is important to deeply understand the available technologies for choosing the best fit for the specific experimental needs and questions. Here, we provide an updated overview of TCR repertoire sequencing strategies, providers and applications to infectious diseases and cancer to guide researchers’ choice through the multitude of available options. The possibility of extending the TCR repertoire to HLA characterization will be of pivotal importance in the near future to understand how specific HLA genes shape T-cell responses in different pathological contexts and will add a level of comprehension that was unthinkable just a few years ago.
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- Abel, S, et al.
(författare)
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Two-fraction and three-fraction continuous simulated moving bed separation of nucleosides
- 2004
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Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1043:2, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- A new experimental set-up and a new simulated moving bed (SMB) operation are presented in this work. A desktop SMB unit developed as a modification of the commercial AKTA(TM) explorer working platform has been utilized for the separation of different mixtures of nucleosides. Both two fraction and three fraction SMB separations have been carried out, the latter made possible by the adoption of a new SMB configuration and operating mode (three fraction SMB, 3F-SMB, operation). Experiments demonstrate the feasibility of the 3F-SMB operation, and confirm the trends predicted based on considerations about retention of the components to be separated along the unit.
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- Codan, L., et al.
(författare)
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Phase diagram of a chiral substance exhibiting oiling out. 2. Racemic compound forming ibuprofen in water
- 2012
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Ingår i: Crystal Growth & Design. - : American Chemical Society (ACS). - 1528-7483 .- 1528-7505. ; 12:11, s. 5298-5310
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Tidskriftsartikel (refereegranskat)abstract
- This work investigates the ternary phase behavior of the two enantiomers of ibuprofen and water. The two enantiomers crystallize as a racemic compound and exhibit a thermodynamically stable liquid-liquid phase separation (LLPS), which extends over the entire enantiomeric composition range. First, the generic phase behavior of racemic compound forming systems exhibiting a stable LLPS is derived by exploiting the consolidated knowledge of conglomerate forming systems obtained in the first part of this series. Below the onset temperature of the LLPS, the system behaves like a typical racemic compound forming system. As for conglomerate forming systems, the onset of the LLPS is found to occur through a ternary monotectic equilibrium, where a new, solute-rich liquid phase emerges inside each solid-solid-liquid phase region. Then, the ternary phase diagram of the ibuprofen/water system in the temperature range from 40 to 82 °C is presented together with the outcome of a thorough experimental investigation. Our theoretical considerations are in excellent agreement with experimental results.
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- Grilli, Simonetta, et al.
(författare)
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Visualization of optical deflection and switching operations by a domain-engineered-based LiNbO electro-optic device
- 2003
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Ingår i: Optics express. - 1094-4087. ; 11, s. 1212-
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Tidskriftsartikel (refereegranskat)abstract
- An electro-optic device applied as an optical beam deflector and switch at different wavelengths has been built and tested. The electro-optic device is based on domain-engineered lithium niobate (LiNbO3). In this paper, for the first time, its operation has been visualized by an imaging camera. The device has been characterized both at the visible wavelength (632.8 nm) and at a typical telecom wavelength (1532 nm). Furthermore, the device has been tested as an amplitude modulator in the mid-infrared region as well, at a wavelength of similar to4.3 mum, where no Pockels cells are available. A detailed description of this device is given, and the experimental results are discussed.
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