NK cells present an attractive alternative for immune cell therapy given their ability to kill multiple cells through non-MHC-restrictive effects and more favourable adverse event profiles compared ...to CAR-T cell therapies. Generation of clinical material is currently limited to patient or healthy donor-derived NK cells which are manipulated ex vivo to expand and genetically modify before administration and requires careful control of starting material through donor selection and screening. Truly allogeneic NK cell therapy can be attained through the differentiation of pluripotent stem cells to NK-like cells, thereby alleviating the need for selecting and maintaining donors and standardising starting material, as well as providing a near-unlimited source of cells through culture expansion.
Here we describe a process for generating pluripotent stem cell starting material in a scalable automated bioreactor system which is then used to produce NK-like cells demonstrating high purity and capable of killing multiple cancer cell types. Pluripotent stem cell expansion yielded >8E6 viable cells/mL expressing and NK productivity was 24-fold higher compared to the equivalent well plate process. Extensive process characterisation revealed critical process parameters linked to increased NK yield and function beyond the scope of traditionally utilised analytical methods. The developed process has the potential to meet expected clinical demand once scaled and further improves the manufacturability of pluripotent stem cell-derived cell therapies through automation and cost-reduction.
Typhuloid fungi are a very poorly known group of tiny clavarioid homobasidiomycetes. The phylogenetic position and family classification of the genera targeted here, Ceratellopsis, Macrotyphula, ...Pterula sensu lato and Typhula, are controversial and based on unresolved phylogenies. Our six-gene phylogeny with an expanded taxon sampling shows that typhuloid fungi evolved at least twice in the Agaricales (Pleurotineae, Clavariineae) and once in the Hymenochaetales. Macrotyphula, Pterulicium and Typhula are nested within the Pleurotineae. The type of Typhula (1818) and Sclerotium (1790), T. phacorrhiza and S. complanatum (synonym T. phacorrhiza), are encompassed in the Macrotyphula clade that is distantly related to a monophyletic group formed by species usually assigned to Typhula. Thus, the correct name for Macrotyphula (1972) and Typhula is Sclerotium and all Typhula species but those in the T. phacorrhiza group need to be transferred to Pistillaria (1821). To avoid undesirable nomenclatural changes, we suggest to conserve Typhula with T. incarnata as type. Clavariaceae is supported as a separate, early diverging lineage within Agaricales, with Hygrophoraceae as a successive sister taxon to the rest of the Agaricales. Ceratellopsis s. auct. is polyphyletic because C. acuminata nests in Clavariaceae and C. sagittiformis in the Hymenochaetales. Ceratellopsis is found to be an earlier name for Pterulicium, because the type, C. queletii, represents Pterulicium gracile (synonym Pterula gracilis), deeply nested in the Pterulicium clade. To avoid re-combining a large number of names in Ceratellopsis we suggest to conserve it with C. acuminata as type. The new genus Bryopistillaria is created to include C. sagittiformis. The families Sarcomyxaceae and Phyllotopsidaceae, and the suborder Clavariineae, are described as new. Six new combinations are proposed and 15 names typified.
The versatility of anaerobic digestion (AD) as an effective technology for solving central challenges met in applied biotechnological industry and society has been documented in numerous publications ...over the past many decades. Reduction of sludge volume generated from wastewater treatment processes, sanitation of industrial organic waste, and benefits from degassing of manure are a few of the most important applications. Especially, renewable energy production, integrated biorefining concepts, and advanced waste handling are delineated as the major market players for AD that likely will expand rapidly in the near future.
The complex, biologically mediated AD events are far from being understood in detail however. Despite decade-long serious academic and industrial research efforts, only a few general rules have been formulated with respect to assessing the state of the process from chemical measurements. Conservative reactor designs have dampened the motivation for employing new technologies, which also constitutes one of the main barriers for successful upgrade of the AD sector with modern process monitoring instrumentation.
Recent advances in Process Analytical Technologies (PAT) allow complex bioconversion processes to be monitored and deciphered using e.g. spectroscopic and electrochemical measurement principles. In combination with chemometric multivariate data analysis these emerging process monitoring modalities carry the potential to bring AD process monitoring and control to a new level of reliability and effectiveness. It is shown, how proper involvement of process sampling understanding, Theory of Sampling (TOS), constitutes a critical success factor.
We survey the more recent trends within the field of AD monitoring and the powerful PAT/TOS/chemometrics application potential is highlighted. The Danish co-digestion concept, which integrates utilisation of agricultural manure, biomass and industrial organic waste, is used as a case study. We present a first foray for the next research and development perspectives and directions for the AD bioconversion sector.
In the management of water distribution networks, large energy savings can be yielded by exploiting the head drop due to the network pressure control strategy, i.e., for leak reductions. Hydropower ...in small streams is already exploited, but technical solutions combining efficiency and economic convenience are still required. In water distribution networks, an additional design problem comes out from the necessity of ensuring a required head drop under variable operating conditions, i.e., head and discharge variations. Both a hydraulic regulation (HR)-via a series-parallel hydraulic circuit- and an electrical regulation (ER)-via inverter- are feasible solutions. A design procedure for the selection of a production device in a series-parallel hydraulic circuit has been recently proposed. The procedure, named VOS (Variable Operating Strategy), is based on the overall plant efficiency criteria and is applied to a water distribution network where a PAT (pump as a turbine) is used in order to produce energy. In the present paper the VOS design procedure has been extended to the electrical regulation and a comparison between HR and ER efficiency and flexibility within a water distribution network is shown: HR was found more flexible than ER and more efficient. Finally a preliminary economic study has been carried out in order to show the viability of both systems, and a shorter payback period of the electromechanical equipment was found for HR mode.
The phoma-like dilemma Hou, L.W.; Groenewald, J.Z.; Pfenning, L.H. ...
Studies in mycology,
06/2020, Letnik:
96, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Species of Didymellaceae have a cosmopolitan distribution and are geographically widespread, occurring in diverse ecosystems. The family includes several important plant pathogenic fungi associated ...with fruit, leaf, stem and root diseases on a wide variety of hosts, as well as endophytic, saprobic and clinically relevant species. The Didymellaceae was recently revised based on morphological and phylogenetic analyses of ex-type strains subjected to DNA sequencing of partial gene data of the LSU, ITS, rpb2 and tub2 loci. Several poly- and paraphyletic genera, including Ascochyta, Didymella and Phoma were redefined, along with the introduction of new genera. In the present study, a global collection of 1 124 Didymellaceae strains from 92 countries, 121 plant families and 55 other substrates, including air, coral, human tissues, house dust, fungi, insects, soil, and water were examined via multi-locus phylogenetic analyses and detailed morphological comparisons, representing the broadest sampling of Didymellaceae to date. Among these, 97 isolates representing seven new genera, 40 new species and 21 new combinations were newly introduced in Didymellaceae. In addition, six epitypes and six neotypes were designated to stabilise the taxonomy and use of older names. A robust, multi-locus reference phylogenetic tree of Didymellaceae was generated. In addition, rpb2 was revealed as the most effective locus for the identification of Didymellaceae at species level, and is proposed as a secondary DNA marker for the family.
Two-photon photoacoustic tomography (TP-PAT) is a noninvasive optical molecular imaging modality that aims at inferring the two-photon absorption property of heterogeneous media from photoacoustic ...measurements. In this work, we analyze an inverse problem in quantitative TP-PAT where we intend to reconstruct optical coefficients in a semilinear elliptic PDE, the mathematical model for the propagation of near infrared photons in tissue-like optical media with two-photon absorption, from the internal absorbed energy data. We derive uniqueness and stability results on the reconstructions of single and multiple optical coefficients, and present some numerical reconstruction results based on synthetic data to complement the theoretical analysis.
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