| 1. |
- David, Jennifer, 1987-, et al.
(author)
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Design and Development of a Hexacopter for the Search and Rescue of a Lost Drone
- 2019
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Conference paper (peer-reviewed)abstract
- Search and rescue with an autonomous robot is an attractive and challenging task within the research community. This paper presents the development of an autonomous hexacopter that is designed for retrieving a lost object, like a drone, from a vast-open space, like a desert area. Navigating its path with a proposed coverage path planning strategy, the hexacopter can efficiently search for a lost target and locate it using an image-based object detection algorithm. Moreover, after the target is located, our hexacopter can grasp it with a customised gripper and transport it back to a destined location. It is also capable of avoiding static obstacles and dynamic objects. The proposed system was realised in simulations before implementing it in a real hardware setup, i.e. assembly of the drone, crafting of the gripper, software implementation and testing under real-world scenarios. The designed hexacopter won the best UAV design award at the CPS-VO 2018 Competition held in Arizona, USA.
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| 2. |
- Beyer, Sarah, 1982-, et al.
(author)
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Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells
- 2022
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In: Cancers. - : MDPI. - 2072-6694. ; 14:8
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Journal article (peer-reviewed)abstract
- Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3-and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.
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| 3. |
- Bonham, Euan, et al.
(author)
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Designing and Integrating a Digital Thread System for Customized Additive Manufacturing in Multi-Partner Kayak Production
- 2020
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In: Systems. - : MDPI AG. - 2079-8954. ; 8:4
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Journal article (peer-reviewed)abstract
- Additive manufacturing (AM) opens the vision of decentralised and individualised manufacturing, as a tailored product can be manufactured in proximity to the customers with minimal physical infrastructure required. Consequently, the digital infrastructure and systems solution becomes substantially more complex. There is always a need to design the entire digital system so that different partners (or stakeholders) access correct and relevant information and even support design iterations despite the heterogenous digital environments involved. This paper describes how the design and integration of a digital thread for AM can be approached. A system supporting a digital thread for AM kayak production has been designed and integrated in collaboration with a kayak manufacturer and a professional collaborative product lifecycle management (PLM) software and service provider. From the demonstrated system functionality, three key lessons learnt are clarified: (1) The need for developing a process model of the physical and digital flow in the early stages, (2) the separation between the data to be shared and the processing of data to perform each parties' task, and (3) the development of an ad-hoc digital application for the involvement of new stakeholders in the AM digital flow, such as final users. The application of the digital thread system was demonstrated through a test of the overall concept by manufacturing a functional and individually customised kayak, printed remotely using AM (composed of a biocomposite containing 20% wood-based fibre).
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| 4. |
- El-Schich, Zahra, et al.
(author)
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Sialic acid as a biomarker studied in breast cancer cell lines in vitro using fluorescent molecularly imprinted polymers
- 2021
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In: Applied Sciences. - : MDPI. - 2076-3417. ; 11:7
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Journal article (peer-reviewed)abstract
- Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation, and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors, correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or “plastic antibodies”, as nanoprobes. Because high expression of epithelial cell adhesion molecule (EpCAM) in primary tumors is often associated with proliferation and a more aggressive phenotype, the expression of EpCAM and CD44 was initially analyzed. The SA-MIPs were used for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the a-2,3 SA and a-2,6 SA variants were used for analysis of SA expression, with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the diagnostic analysis of breast cancer cells.
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| 5. |
- Johansson, Emil, 1985-, et al.
(author)
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Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction
- 2022
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In: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 12:4, s. 2319-2331
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Journal article (peer-reviewed)abstract
- Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC). Currently, neither prevention (vaccines) nor treatments (antivirals) are available for combating this disease. CVA24v attaches to cells by binding Neu5Ac-containing glycans on the surface of cells which facilitates entry. Previously, we have demonstrated that pentavalent Neu5Ac conjugates attenuate CVA24v infection of human corneal epithelial (HCE) cells. In this study, we report on the structure-based design of three classes of divalent Neu5Ac conjugates, with varying spacer lengths, and their effect on CVA24v transduction in HCE cells. In relative terms, the most efficient class of divalent Neu5Ac conjugates are more efficient than the pentavalent Neu5Ac conjugates previously reported.
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| 6. |
- Johansson, Emil, 1985-, et al.
(author)
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Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates
- 2021
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In: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 22:16
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Journal article (peer-reviewed)abstract
- Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.
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| 7. |
- Johansson, Emil, 1985-
(author)
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Tailored conjugates of N-acetylneuraminic acid and small molecules that block virus cell attachment and entry
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Viruses are obligate intracellular parasites, unable to replicate without exploiting machinery andmaterials from host cells. Pandemics of viral diseases have had large impacts on human socieities and are continued threats to global health. The most efficient means of controlling viral diseases are preventive measures such as immunization of the population, social distancing, and basic hygiene routines. Another mean is development of antiviral drugs that could be used as preventive measures and in treatment of infected individuals. Coxsackievirus A24 variant (CVA24v) is a highly contagious pathogen that cause large outbreaks and pandemics of the eye infection acute hemorrhagic conjunctivitis. Human adenovirus D species type 37 (HAdV-D37) causes epidemics of the severe eye infection epidemic keratoconjunctivitis, that can become life-threatening in immunocompromised individuals. Currently, no specific treatments (vaccine or antivirals) are available to combat the diseases caused by these two pathogens.CVA24v and HAdV-D37 bind to N-acetylneuraminic acid (Neu5Ac) glycans on host cells facilitating attachment and subsequent infection. In this thesis, we explored inhibition of this common recognition motif by development of pentavalent Neu5Ac containing molecules with radial topology to act as decoy receptors. This allowed us to study the potential of development of a general inhibitor targeting both these viruses. The developed compounds inhibited attachment of CVA24v and HAdVD37 to cells.Furthermore, we developed divalent Neu5Ac tools to validate if targeting the Neu5Acmediated attachment of CVA24v to cells were a potential target for antiviral drug discovery and development. The results from these studies indicate that development of a Neu5Ac-based antiviral targeting CVA24v looks bleak as the primary receptor utilized by this virus is ICAM-1. The work with developing Neu5Ac tools led to a side project with synthesis of 4-O-alkyl Neu5Ac analogs. In this project we provided a method to synthesize 4-O-alkyl analogs of Neu5Ac and gave insights into the scope of the reaction. This work could have have value in drug discovery.Targeting enterovirus uncoating is a well explored strategy for the inhibition of enterovirus infection. In this thesis, we synthezied novel branched probes of pleconaril (a well-known pocket binding molecule) to study if targeting the unique branched pocket of CVA24v could have potential as a target for antiviral drug discovery. Further experiments are needed to draw conclusions in regards to the future prospects of targeting this unique feature.At last, two novel classes of trivalent Neu5Ac conjugates were develop using a structure-based approach targeting HAdV-D37, -D36, and -D26. This led to a more potent compound towards HAdVD37 further validating that targeting the attachment of this virus to cells is a reasonable strategy for antiviral drug development. Towards HAdV-D26 the inhibitory effect was saturated at 50%, likely due to engagement of other receptors. Evaluation towards HAdV-D36 is currently ongoing. Structural biology studies, indicates the compounds bind to the viruses via chelation of their trimeric binding sites. Taken together, these compounds have potential to be used as chemical tools to study the biology of human adenoviruses and perhaps other Neu5Ac binding proteins.
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| 8. |
- Marklund, Emil, et al.
(author)
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DNA surface exploration and operator bypassing during target search
- 2020
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In: Nature. - : NATURE RESEARCH. - 0028-0836 .- 1476-4687. ; 583:7818, s. 858-
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Journal article (peer-reviewed)abstract
- Many proteins that bind specific DNA sequences search the genome by combining three-dimensional diffusion with one-dimensional sliding on nonspecific DNA(1-5). Here we combine resonance energy transfer and fluorescence correlation measurements to characterize how individual lac repressor (LacI) molecules explore the DNA surface during the one-dimensional phase of target search. To track the rotation of sliding LacI molecules on the microsecond timescale, we use real-time single-molecule confocal laser tracking combined with fluorescence correlation spectroscopy (SMCT-FCS). The fluctuations in fluorescence signal are accurately described by rotation-coupled sliding, in which LacI traverses about 40 base pairs (bp) per revolution. This distance substantially exceeds the 10.5-bp helical pitch of DNA; this suggests that the sliding protein frequently hops out of the DNA groove, which would result in the frequent bypassing of target sequences. We directly observe such bypassing using single-molecule fluorescence resonance energy transfer (smFRET). A combined analysis of the smFRET and SMCT-FCS data shows that LacI hops one or two grooves (10-20 bp) every 200-700 mu s. Our data suggest a trade-off between speed and accuracy during sliding: the weak nature of nonspecific protein-DNA interactions underlies operator bypassing, but also speeds up sliding. We anticipate that SMCT-FCS, which monitors rotational diffusion on the microsecond timescale while tracking individual molecules with millisecond resolution, will be applicable to the real-time investigation of many other biological interactions and will effectively extend the accessible time regime for observing these interactions by two orders of magnitude. Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.
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