Arup Group (United States)

Abstract The spatial organization of membrane proteins is an underexplored dimension of cell-surface biology. Spatial proximity shapes cellular function and therapeutic targetability, yet efforts to identify tumor-associated antigens (TAAs) have largely focused on expression alone. Here, we developed an industrialized surface-protein proximity mapping workflow to interrogate TAAs within their membrane microenvironments. In the process, we generated 248 proximity maps across 12 receptor tyrosine kinases (RTKs) and 28 tumor cell systems. This proximity atlas enabled two advances: first, MetaMap, a correlation-based analytical framework that defines spatial protein communities and infers non-targeted proximal proteins from reproducible proximity signatures; and second, tumor-associated proximity antigens (TAPAs), a conceptual class of co-targets defined by disease-specific spatial proximity to TAAs rather than expression alone. Applying these proximity-derived relationships within a multimodal prioritization framework, we identified and validated an EGFR×CDCP1 TAA-TAPA pair that enhanced tumor cell killing across therapeutic modalities. By integrating spatial organization with multimodal data, this work expands the design space for precision-guided therapeutic strategies.

Abstract Industry trends of using ever-larger wind turbine generators and developing farms in deeper waters with longer design lives have resulted in increased importance of optimisation of monopile foundation structures due to their favourability over more complex foundation types. Optimisation is crucial to adequately assess feasibility of monopiles, and to efficiently design the structures to minimise capital expenditure and levelised cost of energy. This paper presents a methodology for site-wide design space exploration and optimisation of monopiles to address these challenges, using OPTIF, Arup’s in-house tool for design and optimisation of offshore wind foundation structures. The methodology employs heuristic and numerical optimisation approaches to rapidly optimise many thousands of monopile geometries for given site conditions and design constraints under the governing load cases, providing both designs that minimise total mass, and valuable insights into site-specific effects. The methodology is applicable at both early-stage and later FEED/detailed design stages, employing highly-accurate, site-specific loads analysis fully integrated with the structural optimisation to enable accurate early stage foundation weight estimates, provide valuable insight to inform advanced clustering, and allow for position-specific optimised geometries at later stages. The methodology is applied to an early-stage design case study to identify optimum mudline diameters across a typical site, and this study is used to illustrate the possibility for more advanced clustering methods informed by rapid site-wide mass sensitivity studies using varied input parameters and clustering approaches.

Abstract Lithium‐ion battery (LIB) energy storage systems play a significant role in the current energy storage transition. Globally, codes and standards are quickly incorporating a framework for safe design, siting, installation, commissioning, and decommissioning of battery energy storage systems (BESS). Full‐scale fire testing provides essential understanding of thermal runaway, fire, and explosion hazards associated with LIBs and BESSs. Engineers must then interpret that data to inform the site‐specific design, but there are cell, module, unit, and installation‐level data to decipher. Understanding the testing data and their limitations is critical for the design and operation of BESSs. Real‐life examples of where engineers misunderstood or misapplied test data will be presented to help bridge the knowledge gaps between stakeholders, industry, and engineers.

<p>Ship collisions with bridges and other fixed infrastructure can be attributed to various types of ab- errancy, i.e. various causes for a vessel to deviate from its intended route and various resulting col- lision trajectories. Holistic approaches aim to create a simple model of aberrant behaviour, whereas. scenario-based approaches create an array of deviation trajectories. Regardless of the approach, it is both a philosophical and a practical challenge to calibrate the models, as observations of aberrant vessels are too rare and thus often insufficient for calibration. As a consequence, statistics from non- aberrant movements combined with engineering judgment are often used instead. This paper gives an overview of the different methodologies, their strengths and challenges.</p>

How does proximity to refugees affect citizens’ preferences towards citizenship inclusion orexclusion? In Africa, host to one-third of the world’s refugees, widespread protracted displacementhas led to calls for pathways to legal membership. Citizens living near refugees may be more supportive of inclusion because they are more likely to be coethnics and experience benefits from humanitarian aid. Conversely, they may fear negative spillovers and become more protective over membership. Using geo-referenced data of over 1,200 refugee communities and 43,000 Afrobarometer respondents across 28 countries, this study finds that citizens who live closer to refugees in their country are more likely to support restrictions on birthright citizenship and naturalization. Placebo tests using distance to future refugee sites assuage concerns around selection bias. Heterogeneous effects analyses show that citizens who are ethnic minorities, economically vulnerable, and live near older and smaller sites tendto be more exclusionary.

In the contemporary architectural and construction domain, a paradigm shift is evident through the adoption of Building Information Modeling (BIM) and sophisticated project review tools, notably Revit and Navisworks. This paper delves into this transformative journey from conventional 2D drafting methodologies to the intricate realm of 3D modeling, emphasizing its revolutionary impact on electrical design and the broader construction arena. Central to our exploration is a case study on electrical design of commercial aviation project located in California, USA meticulously developed using Revit software. This project serves as a testament to the enhanced precision, collaboration, and holistic insights afforded by these advanced tools, reshaping the trajectory of building design and construction. Through this paper, we aim to elucidate the multifaceted benefits, challenges, and the overarching implications of integrating BIM and associated technologies in modern construction endeavors.

Abstract From 2018, a significant amount of deck plate cracks have been discovered on the movable part of the Suurhoff bridge. These cracks reduce the strength of the bridge and might lead to unplanned hindrance and costly repairs. Renovation of the ortho‐tropic steel deck was chosen instead of frequent inspections and repairs or replacing the structure from a risk and cost perspective.The innovative strengthening scheme consists of the addition of a steel plate which is connected to the top of the existing deck plate by a combination of preloaded‐injection bolts and epoxy. The strengthening steel plate reduces the stress in the existing deck plate thereby improving the fatigue performance. The new and old steel work compositely due to the combined effect of bolts and epoxy resulting in a relatively light‐weight strengthening scheme. The design followed a risk‐based approach in which Arup closely collaborated with Rijkswaterstaat, contractors and research institutions to finish the full design and implementation in less than a year. The design objective is to provide at least 15 years additional fatigue life for the existing deck.The design was developed with the help of a combined numerical and experimental campaign. The novelty of the strengthening scheme and the use of different materials required experimental validation on small and large scale. The extensive validation resulted in sufficient confidence for the Rijkswaterstaat to implement this innovative scheme on an important bridge in The Netherlands. This scheme is especially beneficial from a weight and construction time perspective and therefore suitable for further implementation on other bridges.