| 71. |
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| 72. |
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| 73. |
- Andhill, Carl Johan, et al.
(författare)
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ViPCity
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Today simulation studies in ViP are mainly carried out in countryside driving environments. There is a lack of city environments. This is probably due to the fact that creating and running countryside environments in some aspects are easier than creating and running city environments. Another reason might be that countryside driving is very relevant in Swedish studies.As projects, and markets, become more international the need for city simulator studies becomes more important. Many drivers around the world do most of their driving in cities.In the ViPCity project software has been developed which facilitates the generation of driving environments for city simulations on the ViP platform. The project result is a number of assets (software, file formats and 3D components) which integrates well with the ViP platform. These assets together give simulator users the possibility to design city environments in a fast and easy way. The software has been implemented and tested successfully in Scania’s truck simulator.
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| 74. |
- Aniander, Gustav
(författare)
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Improved candidate screening through tailored co-culture assays and precise tuning of protein expression
- 2024
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of biopharmaceuticals is a rapidly growing one. In the last ten years the number of approved biopharmaceuticals has more than doubled. A major hurdle to overcome for increased availability of all the new, effective biopharmaceuticals is the cost of treatment. Much of this can be attributed to the sheer time required for their development. Owing to this, interest in improvements to the biopharmaceuticals and their development process has also rapidly increased. As costs increase the further into development a drug candidate progresses, increasing the fidelity of screening at early stages could alleviate some of the exorbitant costs of development.In paper I, we showcase a novel way of targeting the tumor microenvironment (TME) to allow for TMElocalized CD40 activation. This is of interest as CD40 agonists have shown great potential for immune activation, but with systemic activation leading to severe adverse effects. The localized activation is achieved through the construction of an affinity fusion protein termed an AffiMab through fusion of a platelet derived growth factor receptor beta (PDGFRβ) targeting affibody to the heavy chain of a CD40 agonistic monoclonal antibody (mAb). We demonstrate PDGFRβ-dependent activation in a variety of assays, showing that the approach merits further investigation.Building on the activation assays set up in paper I, we aim to generate an in vitro screening platform for immune cell engagers in paper II. Screening candidates for on-target off-tumor activation is essential, as such activation would lead to adverse effects and be a doselimiting factor. To screen for this, we construct a series of plasmids which upon transfecting cells allow for different levels of a cell-surface target protein to be expressed, a so-called target density panel. This is achieved through the use of hairpin forming elements in the 5’ untranslated region of the mRNA dubbed regulatory elements (RgEs). Through use of different RgEs, we show that a target density panel can be generated and validate it in activation assays with the AffiMab developed in paper I. The platforms’ uniform cell surface background due to all different levels of target being expressed in the same host cell line and tunability through use of different RgEs are features that make it interesting for further research.Finally in paper III, we construct and test an improved translation initiation site (TIS) sequence. Using previous studies on the impact of the nucleotides in the sequence on the efficacy of the TIS, we constructed a novel sequence, TISNOV. This sequence enhanced titer and quality for recombinant production of IgG1 and IgG4 in both stable and transient settings. Further research into other TIS sequences and their uses in regulating protein expression, as well as usage of the TISNOV to improve expression of difficult to express proteins such as bispecifics remain interesting.In conclusion this thesis focuses on different manners to improve and hasten development of new biopharmaceuticals through usage of new workflows, platforms, and genetic engineering strategies.
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| 75. |
- Asp, Julia, 1973, et al.
(författare)
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CHCHD7-PLAG1 and TCEA1-PLAG1 gene fusions resulting from cryptic, intrachromosomal 8q rearrangements in pleomorphic salivary gland adenomas.
- 2006
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 45:9, s. 820-8
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Tidskriftsartikel (refereegranskat)abstract
- Pleomorphic salivary gland adenomas are characterized by recurrent chromosome rearrangements of 8q12, leading to activation of the PLAG1 oncogene. Here we demonstrate that CHCHD7-PLAG1 is a novel and recurrent gene fusion generated by a cytogenetically cryptic rearrangement in pleomorphic adenomas. CHCHD7 is a newly identified member of a multifamily of proteins containing a conserved (coiled coil 1)-(helix 1)-(coiled coil 2)-(helix 2) domain. Northern blot analysis revealed that the gene is ubiquitously expressed. Its biological function is unknown and the gene has hitherto not been associated with neoplasia. CHCHD7 and PLAG1 are located head-to-head about 500 bp apart in 8q12. Molecular analyses of 27 tumors revealed CHCHD7-PLAG1 fusions in three tumors, two of which had t(6;8) and t(8;15) translocations as the sole anomalies and one a normal karyotype. FISH analyses of interphase nuclei and nuclear chromatin fibers of a fourth adenoma with a normal karyotype revealed that a second fusion partner gene, TCEA1, located about 2 Mb centromeric to PLAG1, also is fused to PLAG1 as a result of a cryptic 8q rearrangement. The breakpoints in both fusions occur in the 5'-noncoding regions of the genes, leading to activation of PLAG1 by promoter swapping/substitution. Western blot and immunohistochemical analyses demonstrated that the PLAG1 protein was overexpressed in epithelial, myoepithelial, and mesenchymal-like tumor cells in tumors with both fusions. Our findings further emphasize the significance of PLAG1 activation in pleomorphic adenomas and demonstrate that the gene is more frequently activated than previously anticipated.
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| 76. |
- Aspenberg, Magnus, et al.
(författare)
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On the asymptotics of the scenery flow
- 2015
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Ingår i: Discrete and Continuous Dynamical Systems. Series A. - : American Institute of Mathematical Sciences (AIMS). - 1553-5231. ; 35:7, s. 2797-2815
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Tidskriftsartikel (refereegranskat)abstract
- We study the asymptotics of the scenery flow. We give corrected versions with proofs of a certain lemma by Hochman, and study some related phenomena.
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| 77. |
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| 78. |
- Balaz, Martina, et al.
(författare)
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Protein-surface Interactions and Functional Geometry of Surface-adsorbed Myosin Motor Fragments
- 2009
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Ingår i: Biophysical Journal. - : Biophysical Society. - 0006-3495 .- 1542-0086. ; 96:3 Suppl. 1, s. 495A-495A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Biophysical studies with myosin motor fragments (heavy meromyosin; HMM and subfragment 1; S1) adsorbed to artificial surfaces, are important for elucidation of actomyosin function. In spite of the widespread use of such in vitro motility assays and single molecule studies, little is known about the adsorption geometry and effects of protein-surface interactions on the motor properties. Here, we investigate these factors with focus on HMM using quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) spectroscopy based ATPase assays. In the latter, we monitored the turnover of Alexa-fluor647-ATP (Alexa-ATP) by surface adsorbed HMM. Studies were performed with HMM/S1 adsorbed to model hydrophilic (SiO2) or hydrophobic (trimethyl-chlorosilane [TMCS] - derivatized) surfaces. The results suggest that adsorption of HMM is weakened on SiO2 (but not on TMCS) at high (245 mM) compared to low (65 mM) ionic strengths. The changes in ionic strength were also associated with structural changes in the protein layer according to QCM-D studies. Moreover, the TIRF based ATPase assay suggested a larger fraction of HMM molecules with low catalytic activity on SiO2. These and other TIRF and QCM-D results, suggest that HMM preferentially adsorbs to negatively charged hydrophilic surfaces via the actin-binding region. In contrast, the majority of the HMM molecules seem to adsorb via their C-terminal tail on moderately hydrophobic surfaces. In the latter case the catalytic sites appear to be close to, but not immobilized on the surface. The results with HMM were compared to, and found consistent with, QCM-D and TIRF-data obtained with S1 motor fragments.
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| 79. |
- Bashir, Tariq, 1981-, et al.
(författare)
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Cellulosic Smart Textile Fibers based on Organic Electronics
- 2016
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Konferensbidrag (refereegranskat)abstract
- The paradigm shift of merging structural properties of materials with other functionalities prevails and cellulose based fibres are no exception. For the realisation of so called smart materials, including smart textiles, electrical conductivity is of special importance, enabling sensorics, signal transmission, energy supply, energy generation, and actuation. We here discuss taking use of the advancement within the organic electronics community of conjugated polymeric systems producing smart textile fibres for inclusion into garment as well as interior and technical textiles. Specifically, poly(3,4-ethylenedioxythiophene) known as PEDOT is studied as a model system. PEDOT has relevance being a working horse within the organic electronics community. Our emerging pilot line is based on creating conductivity by vapour polymerization of EDOT monomers on an oxidant coated textile fibre where these could be taken from arrange of materials. Here we focus on cellulose based fibres. It is shown that Tencell-Lyocell is a suitable substrate offering many anchoring sites and that multiple depositions with layers deposited directly on each other decreased the resistance from 5.1 (± 1.6) kΩ/10 cm to 1.0 (± 0.1) kΩ/10 cm, for one layer and multiple layers respectively. Furthermore, adding 15 wt. % of the copolymer PEG-PPG-PEG to the oxidant solution decreased the resistance from 6.8 (± 1.2) kΩ/10 cm to 3.9 (± 0.8) kΩ/10 cm.
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| 80. |
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