| 1. |
- Yang, Jun, 1979, et al.
(författare)
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A compact core-jet structure in the changing-look Seyfert NGC 2617
- 2021
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 3886-3895
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Tidskriftsartikel (refereegranskat)abstract
- The nearby face-on spiral galaxy NGC 2617 underwent an unambiguous 'inside-out' multiwavelength outburst in Spring 2013, and a dramatic Seyfert-type change probably between 2010 and 2012, with the emergence of broad optical emission lines. To search for the jet activity associated with this variable accretion activity, we carried out multiresolution and multiwavelength radio observations. Using the very long baseline interferometric (VLBI) observations with the European VLBI Network at 1.7 and 5.0 GHz, we find that NGC 2617 shows a partially synchrotron self-absorbed compact radio core with a significant core shift, and an optically thin steep-spectrum jet extending towards the north up to about 2 pc in projection. We also observed NGC 2617 with the electronic Multi-Element Remotely Linked Interferometer Network at 1.5 and 5.5 GHz, and revisited the archival data of the Very Large Array (VLA) and the Very Long Baseline Array (VLBA). The radio core had a stable flux density of similar to 1.4 mJy at 5.0 GHz between 2013 June and 2014 January, in agreement with the expectation of a supermassive black hole in the low accretion rate state. The northern jet component is unlikely to be associated with the 'inside-out' outburst of 2013. Moreover, we report that most optically selected changing-look active galactic nuclei (AGN) at z < 0.83 are sub-mJy radio sources in the existing VLA surveys at 1.4 GHz, and it is unlikely that they are more active than normal AGN at radio frequencies.
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| 2. |
- Jiang, Wenyu, et al.
(författare)
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Resolving Quantum Interference Black Box through Attosecond Photoionization Spectroscopy
- 2023
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Ingår i: Physical Review Letters. - 0031-9007. ; 131:20
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Tidskriftsartikel (refereegranskat)abstract
- Multiphoton light-matter interactions invoke a so-called "black box"in which the experimental observations contain the quantum interference between multiple pathways. Here, we employ polarization-controlled attosecond photoelectron metrology with a partial wave manipulator to deduce the pathway interference within this quantum 'black box"for the two-photon ionization of neon atoms. The angle-dependent and attosecond time-resolved photoelectron spectra are measured across a broad energy range. Two-photon phase shifts for each partial wave are reconstructed through the comprehensive analysis of these photoelectron spectra. We resolve the quantum interference between the degenerate p→d→p and p→s→p two-photon ionization pathways, in agreement with our theoretical simulations. Our approach thus provides an attosecond time-resolved microscope to look inside the "black box"of pathway interference in ultrafast dynamics of atoms, molecules, and condensed matter.
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| 3. |
- Marinaki, Maria Eleni, et al.
(författare)
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Implementation of process analytical technology (PAT) concepts in virus removal nanofiltration: A case study for a nanocellulose-based non-woven filter
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Annan publikation (populärvet., debatt m.m.)abstract
- Implementation of PAT is critical for reliable and predictable performance of virus removal filters in bioprocessing. The inspection of critical quality parameters of nanocellulose-based virus removal filters, such as filter thickness, basis weight, pore size and flux, was correlated to virus clearance capacity of filters produced on different heat presses, i.e. single-side heat press (SP) and double-side heat press (DP). The quality parameters of the filters were analyzed with statistical tools using ANOVA and Shewhart charts. It was found that SP and DP filters were essentially similar with critical quality parameters such as thickness, basis weight, and pore size distribution but not with flux, which was somewhat higher in the DP group (n=15; p>0.05). The latter statistically significant difference in flux resulted in 0.5-1.0 log10 lower virus clearance for DP group compared to SP (n=6; p=0.007). The results highlight the complexity of the size-exclusion virus removal filtration and necessitate continued studies involving not only macro-scale critical quality control descriptors but also attributes that treat the system on the level of local inhomogeneities.
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| 4. |
- Thorngren, Julia, et al.
(författare)
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Differentiation of human pluripotent stem cells into insulin-producing islet-like clusters using nanofiltered cell culture medium
- 2024
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Ingår i: Frontiers in Membrane Science and Technology. - : Frontiers Media S.A.. - 2813-1010. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The challenge of using patient-specific, autologous stem cell therapies in clinical settings is the need for advanced cell processing and expansion technologies. These include decentralized, small-scale manufacturing at the point of care in hospitals. The highest risk for contamination in cell-based therapy products comes from animal- and human-derived components such as serum, blood components, and growth factors. To mitigate the risk of adventitious microorganism contamination, preventive measures like size-exclusion virus removal filtration of cell media components can be employed. This article examines the impact of nanofiltration using nanocellulose-based virus clearance filter paper on the differentiation of human pluripotent stem cells into insulin-producing pancreatic islets (SC-islets). The cells were monitored for biomarkers using flow cytometry and immunohistochemistry along the 7-stage differentiation protocol. The produced SC-islets were evaluated functionally using low and high glucose stimulation under dynamic perifusion conditions. Pluripotent stem cells grown in culture media filtered through 20 nm cut-off nanocellulose filters showed similar expression of desired biomarkers at each stage compared to the control group. At the end of stage 7, SC-islets exhibited a rounded shape and strong expression of insulin, glucagon, and somatostatin in both the control and filtered media groups. The present study demonstrates that SC-islets differentiated with nanofiltered media were functional.
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| 5. |
- Wang, Faming, et al.
(författare)
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Coastal blue carbon in China as a nature-based solution toward carbon neutrality
- 2023
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Ingår i: INNOVATION. - 2666-6758. ; 4:5
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Forskningsöversikt (refereegranskat)abstract
- To achieve the Paris Agreement, China pledged to become "Carbon Neutral" by the 2060s. In addition to massive decarbonization, this would require significant changes in ecosystems toward negative CO2 emissions. The ability of coastal blue carbon ecosystems (BCEs), including mangrove, salt marsh, and seagrass meadows, to sequester large amounts of CO2 makes their conservation and restoration an important "nature-based solution (NbS)" for climate adaptation and mitigation. In this review, we examine how BCEs in China can contribute to climate mitigation. On the national scale, the BCEs in China store up to 118 Tg C across a total area of 1,440,377 ha, including over 75% as unvegetated tidal flats. The annual sedimental C burial of these BCEs reaches up to 2.06 Tg C year(-1) , of which most occurs in salt marshes and tidal flats. The lateral C flux of mangroves and salt marshes contributes to 1.17 Tg C year(-1) along the Chinese coastline. Conservation and restoration of BCEs benefit climate change mitigation and provide other ecological services with a value of $32,000 ha(-1) year(-1). The potential practices and technologies that can be implemented in China to improve BCE C sequestration, including their constraints and feasibility, are also outlined. Future directions are suggested to improve blue carbon estimates on aerial extent, carbon stocks, sequestration, and mitigation potential. Restoring and preserving BCEs would be a cost-effective step to achieve Carbon Neutral by 2060 in China despite various barriers that should be removed.
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| 6. |
- Wu, Lulu, et al.
(författare)
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Aggregate Removal Nanofiltration of Human Serum Albumin Solution Using Nanocellulose-Based Filter Paper
- 2020
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log10 reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65–3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m−2 and 63.6 ± 5.8 L m−2 at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment.
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| 7. |
- Wu, Lulu
(författare)
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Development of Nanocellulose Materials for Nano-filtration and Microfluidic Cell Culture
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nanocellulose, cellulose nanofibrils or nanocrystals, is an interesting material for a wide range of applications. It can be obtained from abundant sources (higher plants, bacteria and algae), and presents many advantages to be used in the biomedical field such as biological safety, high surface area, porosity, and tailorable rheological properties. This thesis selected two different areas to explore the use of nanocellulose materials in life sciences: bioprocessing of biological products and cell culture in microfluidic systems. The production of biopharmaceutical products (e.g. plasma-derived proteins) requires bioactive raw materials of animal or human origin, which present a viral risk. Virus contamination is one of the biggest challenges in the bioprocessing of such biological products, with size-exclusion virus filtration signalled as the preferred method. Commercial virus removal filters tend to have relatively low fluxes, which results in expensive industrial processes and the use of filters based on synthetic polymers is associated with environmental burden. When considering the application of microfluidic devices in cell research, the development of cheap and readily available nano- or micro-biomaterials that are easy to process and integrate is expected to advance the understanding of the relationship between cells and the microenvironment.The first part of the thesis focussed on Cladophora algae-derived cellulose nanofibrils virus removal filters (CCF-VFs) and investigated their application in the bioprocessing of plasma-derived proteins and stem cell differentiation medium. The second part explored the use of wood-derived cellulose nanofibrils (CNFs) as a cell culture substrate in microfluidics. Here, a concentric circular patterned CNF substrate was incorporated into a microfluidic chip to study the role of topography and shear stress in guiding the alignment of human umbilical vein endothelial cells (HUVECs). In conclusion, CCF-VFs show great potential to be integrated into the bioprocessing of plasma-derived products to remove viruses. The first evaluation of CCF-VFs in stem cell culture medium filtration showed promising results. Aligned CNFs were successfully integrated into microfluidic chips as a tool to study the role of mechanical cues on cell alignment.
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| 8. |
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| 9. |
- Wu, Lulu, et al.
(författare)
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Microfluidic system with integrated nanocellulose cell culture substrate to study alignment of human umbilical vein endothelial cells in relation to external physical cues
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this work, aligned cationic cellulose nanofibrils (c-CNF) were integrated into a microfluidic channel to guide cell attachment of human umbilical vein endothelial cells (HUVECs) and the effect of different mechanical cues on cell orientation was investigated. The on-chip cultured cells were exposed to external stimuli by the c-CNF topography and a fluid flow-induced shear stress, either separately or combined. Fluorescent images of the c-CNF pattern stained with calcofluor white and HUVECs stained for F-actin fibers and cell nuclei were obtained and used to quantify orientation of the CNFs, the F-actin fibers and the cell nuclei together with the eccentricity of the nuclei. Compared to the control, where the cells were cultured on a smooth surface in static conditions, cells cultured on the c-CNF pattern alone showed a clear alignment to the underlying microtopography. Cells cultured on a smooth surface responded slightly to the external mechanical stimuli indicating that the cell orientation was more strongly affected by c-CNF topography than the shear stress. With these results, we established a platform that can de-couple external mechanical stimuli originating from surface topography and shear stress to increase our understanding of how cells react to these factors when cultured in microfluidic in vitro systems.
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| 10. |
- Wu, Lulu, et al.
(författare)
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Nanocellulose-Based Nanoporous Filter Paper for Virus Removal Filtration of Human Intravenous Immunoglobulin
- 2019
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Ingår i: ACS APPLIED NANO MATERIALS. - : AMER CHEMICAL SOC. - 2574-0970. ; 2:10, s. 6352-6359
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Tidskriftsartikel (refereegranskat)abstract
- Human intravenous immunoglobulin (IVIG) is a highly valuable plasma-derived biotherapeutic with several important clinical indications in primary and acquired immunodeficiencies as well as autoimmune diseases, especially neuropathies. Ensuring the viral safety of plasma-derived products, such as human WIG, is mandatory. Viral filtration is commonly used to affect viral removal in the manufacture of plasma products. Viral filtration of large volumes of a IVIG feed solution can take significant time, the required filter area can be large, and the resultant total cost of filtration is considerable. Therefore, there is a need for a high-capacity filter, which can process large volumes of plasma-derived biotherapeutic products within a short time at reduced cost. Here, we describe for the first time the performance of a nanocellulose-based virus removal filter paper in the processing of human IVIG, which has the potential to address the above- stated issues. The filter exhibited 5-6 log virus clearance of Phi X174 (28 nm; pI 6.6) or MS2 (27 nm; pI 3.9) phages during the filtration of spiked IVIG solutions (11 mg/mL, pH 4.9). To simulate real-life production conditions, filtration at 288 L/m(2), corresponding to 3 kg of protein/m(2), at 3 bar was undertaken. No substantial filter fouling was evident, with the flux remaining stable throughout filtration at 20-30 L/m(2).h. The predicted volumetric capacity V-max was >= 1700 L/m(2), which corresponds to the processing of >= 19 kg/m(2) of immunoglobulins. A number of characterization tests encompassing size-exclusion high-pressure liquid chromatography, dynamic light scattering, and polyacrylamide gel electrophoresis confirmed immunoglobulin integrity before and after filtration. This study has shown that a mille-feuille filter paper manufacturing process offers the possibility of producing cost-efficient viral removal filters with the required performance capabilities suitable for the processing of plasma-derived immunoglobulins and recombinant monoclonal antibodies.
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| 11. |
- Wu, Lulu, et al.
(författare)
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Virus removal nanofiltration of intravenous immunoglobulin using nanocellulose-based filter paper
- 2019
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Replacement therapy using plasma-derived Factor IX products is a life-saving treatment for patients with hemophilia B. Ensuring viral safety of plasma-derived Factor IX products is a critical issue during their bioprocessing. Although nanofiltration is an attractive method for clearing viruses from plasma-derived Factor IX products, it is not easy to implement in practice. Various large molecular weight protein impurities and/or soluble aggregates, which are not retained on sterilizing grade 0.2 μm filters, may cause filter fouling and thereby interrupt the manufacturing. Here, for the first time, the nanofiltration of coagulation factor IX-rich prothrombin complex concentrate is shown using a nanocellulose-based virus removal filter paper, aka the mille-feuille filter paper. Furthermore, a new method of soluble aggregate removal is developed. As a result, high product recovery and high virus clearance capacity are demonstrated. The mille-feuille filter paper has a tailored pore size in the nm-range in the region most suitable for targeted removal of soluble protein aggregates and small-size viruses from biologics solutions. The filter paper is produced according to traditional paper making technology and consists of 100% cellulose nanofibers. The mille-feuille filter paper offers new possibilities in developing cost-efficient and robust bioprocesses for manufacturing plasma-derived hemophilia products.
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| 12. |
- Wu, Lulu
(författare)
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Virus retentive filter paper for processing of plasma-derived proteins
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The studies in the present thesis explored the feasibility of using nanocellulose-based filters in virus removal filtration of plasma-derived proteins. In Paper I, two-step nanofiltration of commercially available human serum albumin (HSA) product, which was diluted to 10 g L-1 by phosphate buffer saline (PBS) and adjusted pH to 7.4, was performed to remove soluble protein aggregates and reduce filter fouling. The two-step filtration of HSA employed nanocellulose-based filters of varying thickness, i.e. 11 μm and 22 μm filters. The removal of HSA aggregates during filtration through 11 μm pre-filters dramatically improves the flow properties of the 22 μm filter, enabling high protein throughput and high virus clearance. A distribution of pore sizes between 50 nm and 80 nm, which is present in the 11 μm filter and is absent in the 22 μm filter, plays a crucial part in removing the HSA aggregates. With respect to virus filtration, 1 bar constant trans-membrane pressure filtration shows poor removal ability of ΦX174 bacteriophage (28 nm), i.e., log10 reduction value (LRV) ≤ 3.75, while that at 3 bar and 5 bar achieves LRV[MOU1] [LW2] > 5 model virus clearance and overall rapid filtration. Removal of protein aggregates during bioprocessing of HSA products is key to improving the filtration flux, which makes it possible to apply virus removal filtration for HSA to ensure its virus safety. In Paper II, nanofiltration of human plasma-derived intravenous immuno-globulin (IVIG) intermediate (11.26 g L-1, pH 4.9) was carried out to demonstrate high product recovery and high model virus clearance. Virus removal filtration of industrial-grade human IVIG was achieved using 33μm filters at both low (60 Lm-2) and high (288 Lm-2) volumetric load. No changes in IVIG structure were detected and high product recovery was recorded. High virus clearance (LRV ≥ 5-6) was achieved for the small-size model viruses (ΦX174 and MS2 bacteriophages) during the load volume of 60 Lm-2. Side-by-side comparisons with commercial virus removal filters suggest that the nanocellulose-based filter paper presents great potential for industrial bioprocessing of plasma-derived IVIG. In Paper III, process analytical technology (PAT) approach was employed to identify the critical filter parameters, e.g. thickness, basis weight, pore size, and flux, affecting model virus removal efficiency using filters produced by different hot presses. The quality parameters were analyzed with ANOVA and Shewhart charts. Compared with other studied parameters, the hydraulic flux appears as the most relevant final product quality attribute of the nanocellulose-based filter paper to reflect the virus removal efficiency. In particular, a 15% higher flux may be associated with a 0.5-1.0 log10 reduced virus clearance (p=0.007). The results are highlight the importance of continued systematic studies in quality assurance using statistical process control tools [MOU1]Define LRV [LW2]Defined in the line above
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| 13. |
- Xiong, Yan, et al.
(författare)
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Small molecule Z363 co-regulates TAF10 and MYC via the E3 ligase TRIP12 to suppress tumour growth
- 2023
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Ingår i: CLINICAL AND TRANSLATIONAL MEDICINE. - : JOHN WILEY & SONS LTD. - 2001-1326. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe MYC oncoprotein, also known as the master regulator of genes, is a transcription factor that regulates numerous physiological processes, including cell cycle control, apoptosis, protein synthesis and cell adhesion, among others. MYC is overexpressed in approximately 70% of human cancers. Given its pervasive role in cancer biology, MYC down-regulation has become an attractive cancer treatment strategy. MethodsThe CRISPR/Cas9 method was used to produce KO cell models. Western blot was used to analyzed the expressions of MYC and TATA-binding proteinassociated factors 10 (TAF10) in cancer cells (MCF7, A549, HepG2 cells) Cell culture studies were performed to determine the mechanisms by which small molecules (Z363119456, Z363) affects MYC and TAF10 expressions and functions. Mouse studies were carried out to investigate the impact of Z363 regulation on tumor growth. ResultsZ363 activate Thyroid hormone Receptor-interacting Protein 12 (TRIP12), which phosphorylates MYC at Thr58, resulting in MYC ubiquitination and degradation and thereby regulating MYC target genes. Importantly, TRIP12 also induces TAF10 degradation, which reduces MYC protein levels. TRIP12, an E3 ligase, controls MYC levels both directly and indirectly by inhibiting MYC or TAF10 activity. ConclusionsIn summary,these results demonstrate the anti-cancer properties of Z363, a small molecule that is co-regulated by TAF10 and MYC.
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