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Abstract: One of the most challenging aspects of developing advanced cell therapy products (CTPs) is defining the mechanism of action (MOA), potency and efficacy of the product. This perspective examines these concepts and presents helpful ways to think about them through the lens of metrology. A logical framework for thinking about MOA, potency and efficacy is presented that is consistent with the existing regulatory guidelines, but also accommodates what has been learned from the 27 US FDA-approved CTPs. Available information regarding MOA, potency and efficacy for the 27 FDA-approved CTPs is reviewed to provide background and perspective. Potency process and efficacy process charts are introduced to clarify and illustrate the relationships between six key concepts: MOA, potency, potency test, efficacy, efficacy endpoint and efficacy endpoint test. Careful consideration of the meaning of these terms makes it easier to discuss the challenges of correlating potency test results with clinical outcomes and to understand how the relationships between the concepts can be misunderstood during development and clinical trials. Examples of how a product can be “potent but not efficacious” or “not potent but efficacious” are presented. Two example applications of the framework compare how MOA is assessed in cell cultures, animal models and human clinical trials and reveals the challenge of establishing MOA in humans. Lastly, important considerations for the development of potency tests for a CTP are discussed. These perspectives can help product developers set appropriate expectations for understanding a product’s MOA and potency, avoid unrealistic assumptions and improve communication among team members during the development of CTPs.
Keywords: cell therapy product, efficacy endpoint test, mechanism of action, potency test, metrology
Published in DiRROS: 27.05.2024; Views: 36; Downloads: 22
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Abstract: Direct-co-direct product $G\circledast H$ of graphs $G$ and $H$ is a graph on the vertex set $V(G)\times V(H)$. Two vertices $(g,h)$ and $(g',h')$ are adjacent if $gg'\in E(G)$ and $hh'\in E(H)$ or $gg'\notin E(G)$ and $hh'\notin E(H)$. We show that if at most one factor of $G\circledast H$ is connected, then the distance between two vertices of $G\circledast H$ is bounded by three unless some small number of exceptions. All the exceptions are completely described which yields the distance formula.
Keywords: direct-co-direct product, distance, eccentricity, disconnected graphs
Published in DiRROS: 19.03.2024; Views: 150; Downloads: 74
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Abstract: To foster sustainable development, the environmental impacts of the construction sector need to be reduced substantially. Life cycle assessment (LCA) is the established methodology for the quantification of environmental impacts, and therefore has been increasingly applied to assess the environmental performance of buildings. By coupling LCAs with digital design tools, e.g., building information modeling (BIM), the identification of environmental hotspots and their mitigation is possible during the design process. The objective of the study is to identify the current integration approaches, and determine the pros and cons of the integration process from different viewpoints, namely, technical, informational, organizational and functional issues. Therefore, a comprehensive systematic literature review (SLR) was performed. We identified 60 relevant BIM-LCA case studies and analyzed the applied BIM-LCA workflows in detail. A total of 16 of the reviewed studies applied LCA during the early design stage. These studies used a manual or semiautomatic data exchange between the BIM models and LCA tools. In most cases, contemporary BIM-LCA workflows utilized conventional spreadsheets (e.g., Excel sheets in 16 cases). However, the analysis shows that an automated link between LCA and BIM can be achieved when overcoming the technical, organizational and informational issues discussed in the paper. This could enable the streamlining of LCA applications in design practice, and thus support the necessary improvements in the environmental performance of buildings.
Keywords: building information modeling (BIM), life cycle assessment (LCA), systematic literaturereview (SLR), environmental product declarations (EPD), workflow, bill of quantities (BoQ)
Published in DiRROS: 05.03.2024; Views: 231; Downloads: 76
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Abstract: A set of vertices $X$ of a graph $G$ is a strong edge geodetic set if to any pair of vertices from $X$ we can assign one (or zero) shortest path between them such that every edge of $G$ is contained in at least one on these paths. The cardinality of a smallest strong edge geodetic set of $G$ is the strong edge geodetic number ${\rm sg_e}(G)$ of $G$. In this paper, the strong edge geodetic number of complete multipartite graphs is determined. Graphs $G$ with ${\rm sg_e}(G) = n(G)$ are characterized and ${\rm sg_e}$ is determined for Cartesian products $P_n\,\square\, K_m$. The latter result in particular corrects an error from the literature.
Keywords: strong edge geodetic problem, complete multipartite graph, edge-coloring, Cartesian product of graphs
Published in DiRROS: 19.02.2024; Views: 200; Downloads: 80
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Abstract: To increase the sustainability of prefabricated timber buildings and constructions, composite timber beams with “box” cross-sections were developed in collaboration with an industry partner. They were constructed from a solid timber frame and from webs made of residual waste wood- particle boards from prefabricated timber buildings production. The developed beams’ design concepts presented in this paper were governed by architectural features of prefabricated timber buildings, geometrical limitations, available production technology, and structural demand related to various possible applications. The paper presents the results of experimental bending tests of six variations of the developed composite timber beams constructed by mechanical fasteners only. The developed design concept of composite timber beams without adhesives is beneficial compared to glued beams in terms of design for deconstruction and lower VOC emissions. The tests were conducted to study the influence of the following parameters on the beams’ mechanical behavior: (i) web material (oriented strand boards (OSBs) vs. cement-particle boards); (ii) the influence of beam timber frame design (flanges and web stiffeners vs. flanges, web stiffeners, and compressive diagonals), and (iii) the influence of stiffener–flange joint design. Besides the beams’ load-bearing capacities, their linear and non-linear stiffness characteristics were the main research interest. While adding compressive timber diagonals did not prove to significantly increase the stiffness of the beams in the case of cement-particle board webs, it increased their load-bearing capacity by enabling the failure of flanges instead of prior webs and stiffener–flange joints failure. For beams with OSB webs, failure of the bottom flange was achieved already with the “basic” timber frame design, but timber diagonals proved beneficial to increase the stiffness characteristics. Finally, mechanical characteristics of the developed beams needed in structural design for their application are provided together with further development guidelines.
Keywords: composite timber beam, box beam, OSB, cement-particle boards, innovative engineered wood product, experimental tests, flexural performance, mechanical fasteners, open access
Published in DiRROS: 29.05.2023; Views: 300; Downloads: 175
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