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- Allalou, Amin, 1981-
(author)
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Methods for 2D and 3D Quantitative Microscopy of Biological Samples
- 2011
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Doctoral thesis (other academic/artistic)abstract
- New microscopy techniques are continuously developed, resulting in more rapid acquisition of large amounts of data. Manual analysis of such data is extremely time-consuming and many features are difficult to quantify without the aid of a computer. But with automated image analysis biologists can extract quantitative measurements and increases throughput significantly, which becomes particularly important in high-throughput screening (HTS). This thesis addresses automation of traditional analysis of cell data as well as automation of both image capture and analysis in zebrafish high-throughput screening. It is common in microscopy images to stain the nuclei in the cells, and to label the DNA and proteins in different ways. Padlock-probing and proximity ligation are highly specific detection methods that produce point-like signals within the cells. Accurate signal detection and segmentation is often a key step in analysis of these types of images. Cells in a sample will always show some degree of variation in DNA and protein expression and to quantify these variations each cell has to be analyzed individually. This thesis presents development and evaluation of single cell analysis on a range of different types of image data. In addition, we present a novel method for signal detection in three dimensions. HTS systems often use a combination of microscopy and image analysis to analyze cell-based samples. However, many diseases and biological pathways can be better studied in whole animals, particularly those that involve organ systems and multi-cellular interactions. The zebrafish is a widely-used vertebrate model of human organ function and development. Our collaborators have developed a high-throughput platform for cellular-resolution in vivo chemical and genetic screens on zebrafish larvae. This thesis presents improvements to the system, including accurate positioning of the fish which incorporates methods for detecting regions of interest, making the system fully automatic. Furthermore, the thesis describes a novel high-throughput tomography system for screening live zebrafish in both fluorescence and bright field microscopy. This 3D imaging approach combined with automatic quantification of morphological changes enables previously intractable high-throughput screening of vertebrate model organisms.
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| 3. |
- Bengtsson, Andreas, 1991, et al.
(author)
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Improved Success Probability with Greater Circuit Depth for the Quantum Approximate Optimization Algorithm
- 2020
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In: Physical Review Applied. - 2331-7019. ; 14:3
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Journal article (peer-reviewed)abstract
- Present-day, noisy, small or intermediate-scale quantum processors-although far from fault tolerant-support the execution of heuristic quantum algorithms, which might enable a quantum advantage, for example, when applied to combinatorial optimization problems. On small-scale quantum processors, validations of such algorithms serve as important technology demonstrators. We implement the quantum approximate optimization algorithm on our hardware platform, consisting of two superconducting transmon qubits and one parametrically modulated coupler. We solve small instances of the NP (nondeterministic polynomial time)-complete exact-cover problem, with 96.6% success probability, by iterating the algorithm up to level two.
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| 4. |
- Bengtsson, Andreas, 1991, et al.
(author)
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Nondegenerate parametric oscillations in a tunable superconducting resonator
- 2018
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In: Physical Review B. - 2469-9969 .- 2469-9950. ; 97:14
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Journal article (peer-reviewed)abstract
- We investigate nondegenerate parametric oscillations in a superconducting microwave multimode resonator that is terminated by a superconducting quantum interference device (SQUID). The parametric effect is achieved by modulating magnetic flux through the SQUID at a frequency close to the sum of two resonator-mode frequencies. For modulation amplitudes exceeding an instability threshold, self-sustained oscillations are observed in both modes. The amplitudes of these oscillations s how good quantitative agreement with a theoretical model. The oscillation phases are found to be correlated and exhibit strong fluctuations which broaden the oscillation spectral linewidths. These linewidths are significantly reduced by applying a weak on-resonant tone, which also suppresses the phase fluctuations. When the weak tone is detuned, we observe synchronization of the oscillation frequency with the frequency of the input. For the detuned input, we also observe an emergence of three idlers in the output. This observation is in agreement with theory indicating four-mode amplification and squeezing of a coherent input.
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- Bjurstöm, Helen, et al.
(author)
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GABA, a natural immunomodulator of T lymphocytes.
- 2008
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In: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 205:1-2, s. 44-50
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Journal article (peer-reviewed)abstract
- gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM-1 microM), physiological concentrations of GABA present around neurons in the brain. The cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 microM GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory.
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| 7. |
- Börgeson, Emma, et al.
(author)
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Lipoxin A(4) inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression
- 2011
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In: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 79:4, s. 1489-1497
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Journal article (peer-reviewed)abstract
- Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.
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| 8. |
- Envall, Ida, et al.
(author)
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What is the effect of giving the grazers access to additional nutrient sources on biodiversity in semi-natural pastures? A systematic review protocol
- 2021
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In: Environmental Evidence. - : Springer Science and Business Media LLC. - 2047-2382. ; 10:1
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Research review (peer-reviewed)abstract
- Background: Semi-natural pastures are unfertilized grasslands with a long history of traditional low-input grazing management. This kind of pastures are recognized for their high species richness. However, as a consequence of modernization of agriculture, many of the semi-natural pastures have been lost during the last century, leading to a serious threat to farmland biodiversity. Semi-natural pastures are relatively low in productivity. Hence, to increase profitability, farmers may want to give the grazing animals access to additional nutrient sources. This can be done either as supplementary feeding, or by fencing the semi-natural pastures into the same enclosure as improved, more nutrient-rich, pastures. These practices are, however, controversial. It is argued that since semi-natural pastures are species-rich partly because they are nutrient-poor, introducing additional nutrients into the system should be avoided. Accordingly, in Sweden, these interventions are often prohibited while receiving financial subsidies for management of semi-natural pastures. However, since many farmers are dependent on such support to maintain their pastures, these prohibitions often cause problems. The question has been raised whether giving the grazers access to additional nutrient sources really affect the biodiversity in semi-natural pastures, as is assumed. The primary aim of the proposed systematic review is to answer this question.Method: Peer-reviewed and grey literature will be searched for using bibliographic databases, search engines, specialist websites and stakeholder contacts. The references will be screened for relevance according to a predefined set of eligibility criteria. The criteria will be tested and clarified iteratively, until consistency in interpretations is achieved. Thereafter, the literature will be screened in two stages, first based upon title and abstract and then by examining full texts. Full text screening will be performed with blinded decisions by two independent reviewers. Each relevant study will then be critically appraised, based on a set of predefined validity criteria. A narrative synthesis will be provided, outlining the evidence base in terms of bibliographic information and study metadata. If possible, quantitative syntheses based on meta-analyses will be performed. Identified relevant knowledge gaps will be highlighted and discussed.
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| 9. |
- Gorgisyan, Jenny, et al.
(author)
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Evalutation of two commercial deep learning OAR segmentation models for prostate cancer treatment
- 2022
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Conference paper (peer-reviewed)abstract
- Purpose or ObjectiveTo evaluate two commercial, CE labeled deep learning-based models for automatic organs at risk segmentation on planning CT images for prostate cancer radiotherapy. Model evaluation was focused on assessing both geometrical metrics and evaluating a potential time saving.Material and MethodsThe evaluated models consisted of RayStation 10B Deep Learning Segmentation (RaySearch Laboratories AB, Stockholm, Sweden) and MVision AI Segmentation Service (MVision, Helsinki, Finland) and were applied to CT images for a dataset of 54 male pelvis patients. The RaySearch model was re-trained with 44 clinic specific patients (Skåne University Hospital, Lund, Sweden) for the femoral head structures to adjust the model to our specific delineation guidelines. The model was evaluated on 10 patients from the same clinic. Dice similarity coefficient (DSC) and Hausdorff distance (95th percentile) was computed for model evaluation, using an in-house developed Python script. The average time for manual and AI model delineations was recorded.ResultsAverage DSC scores and Hausdorff distances for all patients and both models are presented in Figure 1 and Table 1, respectively. The femoral head segmentations in the re-trained RaySearch model had increased overlap with our clinical data, with a DSC (mean±1 STD) for the right femoral head of 0.55±0.06 (n=53) increasing to 0.91±0.02 (n=10) and mean Hausdorff (mm) decreasing from 55±7 (n=53) to 4±1 (n=10) (similar results for the left femoral head). The deviation in femoral head compared to the RaySearch and MVision original models occurred due to a difference in the femoral head segmentation guideline in the clinic specific data, see Figure 2. Time recording of manual delineation was 13 minutes compared to 0.5 minutes (RaySearch) and 1.4 minutes (MVision) for the AI models, manual correction not included.ConclusionBoth AI models demonstrate good segmentation performance for bladder and rectum. Clinic specific training data (or data that complies to the clinic specific delineation guideline) might be necessary to achieve segmentation results in accordance to the clinical specific standard for some anatomical structures, such as the femoral heads in our case. The time saving was around 90%, not including manual correction.
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| 10. |
- Grdic Eliasson, Dubravka, et al.
(author)
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A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.
- 2011
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In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 29:23, s. 3951-61
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Journal article (peer-reviewed)abstract
- Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation.
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