| 1. |
- Aad, G., et al.
(författare)
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- 2015
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Blokhuis, Harry
(författare)
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Advances in poultry welfare
- 2018
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Ingår i: Animal Welfare. - 0962-7286 .- 2054-1538. ; 27, s. 398-399
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Patel, M., et al.
(författare)
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Language for learning complex human-object interactions
- 2013
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Ingår i: 2013 IEEE International Conference on Robotics and Automation (ICRA). - : IEEE Computer Society. - 9781467356411 ; , s. 4997-5002
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Konferensbidrag (refereegranskat)abstract
- In this paper we use a Hierarchical Hidden Markov Model (HHMM) to represent and learn complex activities/task performed by humans/robots in everyday life. Action primitives are used as a grammar to represent complex human behaviour and learn the interactions and behaviour of human/robots with different objects. The main contribution is the use of a probabilistic model capable of representing behaviours at multiple levels of abstraction to support the proposed hypothesis. The hierarchical nature of the model allows decomposition of the complex task into simple action primitives. The framework is evaluated with data collected for tasks of everyday importance performed by a human user.
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| 4. |
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| 5. |
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| 6. |
- Liu, Chenxiao, et al.
(författare)
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Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level
- 2022
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Ingår i: Biology Open. - : The Company of Biologists. - 2046-6390. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Vγ9Vδ2 T cells is the dominant γδ T cell subset in human blood. They are cytotoxic and activated by phosphoantigens whose concentrations are increased in cancer cells, making the cancer cells targets for Vγ9Vδ2 T cell immunotherapy. For successful immunotherapy, it is important both to characterise Vγ9Vδ2 T cell proliferation and optimise the assessment of their cytotoxic potential, which is the aim of this study. We found that supplementation with freshly thawed human serum potentiated Vγ9Vδ2 T cell proliferation from peripheral mononuclear cells (PBMCs) stimulated with (E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) and consistently enabled Vγ9Vδ2 T cell proliferation from cryopreserved PBMCs. In cryopreserved PBMCs the proliferation was higher than in freshly prepared PBMCs. In a panel of short-chain prenyl alcohols, monophosphates and diphosphates, most diphosphates and also dimethylallylmonophosphate stimulated Vγ9Vδ2 T cell proliferation.We developed a method where the cytotoxicity of Vγ9Vδ2 T cells towards adherent cells is assessed at the single cell level using flow cytometry, which gives more clear-cut results than the traditional bulk release assays. Moreover, we found that HMBPP enhances the Vγ9Vδ2 T cell cytotoxicity towards colon cancer cells. In summary, we have developed an easily interpretable method to assess the cytotoxicity of Vγ9Vδ2 T cells towards adherent cells, found that Vγ9Vδ2 T cell proliferation can be potentiated by media-supplementation and how misclassification of non-responders may be avoided. Our findings will be useful in the further development of Vγ9Vδ2 T cell immunotherapy. © 2022. Published by The Company of Biologists Ltd.
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| 7. |
- Butler, C.C., et al.
(författare)
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Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection
- 2011
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 38:1, s. 119-125
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p=0.68) or green (coefficient -0.01; p=0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p=0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.
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| 8. |
- Stafford, William C
(författare)
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Elucidation of thioredoxin reductase 1 as an anticancer drug target
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer constantly finds ways to survive, so we must find new ways to stop it. A major attribute of cancer cells is increased oxidative stress, occurring in the form of reactive oxygen species (ROS). Basal ROS generation commonly occurs in all types of cells and is essential for normal cellular growth and function. However, in contrast to its beneficial attributes when generated at low concentrations, excessive production of ROS is harmful to the cell. High levels of ROS can damage cellular function to the point of cell senescence or cell death. Certain cells are able to effectively adapt to increased ROS levels, activating endogenous antioxidant pathways as a way to survive the aberrant onslaught of oxidative stress. One antioxidant pathway that is often found to be upregulated in cancer cells is the thioredoxin pathway, and within the thioredoxin pathway exists a highly reactive selenocysteine-containing enzyme called thioredoxin reductase 1 (TrxR1). The observed overexpression of the antioxidant enzyme TrxR1 in cancer cells suggests that the enzyme serves as an integral combatant to increased oxidative stress levels, allowing cancer cells to survive and even thrive in the nocuous environment of elevated ROS. The studies comprising this thesis further examine the ability to inhibit TrxR1 function with small molecule drug candidates, the role such inhibition has on modulating ROS levels, and whether such inhibition is sufficient to elicit anticancer therapeutic effects. Paper I established a novel recombinant TrxR1 assay designed for high-throughput screening capabilities. The assay was designed to be dual-purpose, with the ability to detect TrxR1 substrate or inhibitory activity of the test compound within a single test sample. Using the library of pharmacologically active compounds (LOPAC1280), known substrates and inhibitors of TrxR1 in the library validated the assay. Protoporphyrin IX (PpIX), a previously unknown inhibitor of TrxR1, was discovered to inhibit the enzyme in the screen. PpIX and two of its analogs displayed irreversible inhibition to the enzyme, with the capacity to inhibit cellular TrxR1 activity and inhibit cancer cell viability. The three porphyrin compounds illustrated how slight chemical modifications to the porphyrin ring core of PpIX could alter the inhibitory activity of TrxR1. Paper II examined various pharmacodymics and activities of the proteasome inhibitor b-AP15. b- AP15 was found to be rapidly taken up in cancer cells and quickly induce cell death irrespective of brief exposure times. The reactive site of b-AP15 was determined to exist at the α,β-unsaturated carbonyl Michael acceptor moiety of the compound. The half-life of b-AP15 in plasma was determined to be short, but coincided with the observed rapid uptake of the compound into cells. In human hepatocytes, over 17 different metabolites were observed after compound treatment. b-AP15 and many of its analogs, as opposed to bortezomib, were also found to be potent inhibitors of TrxR1. b-AP15 was also successfully able to inhibit TrxR1 in a cellular context. Paper III describes the effects of MJ25, a novel p53 transactivator and TrxR1 inhibitor, and Auranofin against malignant melanoma. Both compounds were found to be effective inhibitors of malignant melanoma cell growth and viability. In redox profiling, both compounds irreversibly inhibited of TrxR1, displayed selenium compromised thioredoxin reductase-derived apoptotic protein (SecTRAP) activity, and caused increased cellular ROS production. Paper IV screened for novel TrxR1 inhibitors on a large scale and tested whether the newly discovered inhibitors would elicit anticancer effects. A structure activity relationship analysis of the two top TrxR1 inhibitors (TRi-1 and TRi-2) correlated enzyme inhibition to inhibition of cell viability. Both compounds exhibited potency across multiple cancer cell types in the NCI60 cell panel and individual cell line testing. Differential SecTRAP forming capabilities of the two compounds, compared with Auranofin, correlated a SecTRAP dependent cellular induction of H2O2 while lacking effects on mitochondrial function. TRi-1 effectively inhibited tumor growth, decreased tumor metabolic activity, and was well tolerated in mouse models. TRi-1 and Auranofin effectively inhibited tumor growth in syngenic mouse models. These studies reinforce the candidacy of TrxR1 as an anticancer drug target through the introduction of novel inhibitors of the enzyme displaying anticancer effects in vitro and in vivo, and through the exposition of anticancer drug candidates as inhibitors of the enzyme.
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| 9. |
- Charlier, Christophe, et al.
(författare)
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Large Gap Asymptotics for Airy Kernel Determinants with Discontinuities
- 2020
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Ingår i: Communications in Mathematical Physics. - : Springer Science and Business Media LLC. - 0010-3616 .- 1432-0916. ; 375:2, s. 1299-1339
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Tidskriftsartikel (refereegranskat)abstract
- We obtain large gap asymptotics for Airy kernel Fredholm determinants with any number m of discontinuities. These m-point determinants are generating functions for the Airy point process and encode probabilistic information about eigenvalues near soft edges in random matrix ensembles. Our main result is that the m-point determinants can be expressed asymptotically as the product of m 1-point determinants, multiplied by an explicit constant pre-factor which can be interpreted in terms of the covariance of the counting function of the process.
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| 10. |
- Charlier, Christophe, et al.
(författare)
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Higher Order Large Gap Asymptotics at the Hard Edge for Muttalib–Borodin Ensembles
- 2021
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Ingår i: Communications in Mathematical Physics. - : Springer Nature. - 0010-3616 .- 1432-0916. ; 384:2, s. 829-907
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Tidskriftsartikel (refereegranskat)abstract
- We consider the limiting process that arises at the hard edge of Muttalib–Borodin ensembles. This point process depends on θ> 0 and has a kernel built out of Wright’s generalized Bessel functions. In a recent paper, Claeys, Girotti and Stivigny have established first and second order asymptotics for large gap probabilities in these ensembles. These asymptotics take the form P(gapon[0,s])=Cexp(-as2ρ+bsρ+clns)(1+o(1))ass→+∞,where the constants ρ, a, and b have been derived explicitly via a differential identity in s and the analysis of a Riemann–Hilbert problem. Their method can be used to evaluate c (with more efforts), but does not allow for the evaluation of C. In this work, we obtain expressions for the constants c and C by employing a differential identity in θ. When θ is rational, we find that C can be expressed in terms of Barnes’ G-function. We also show that the asymptotic formula can be extended to all orders in s.
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