automatic-laser-based-geometry-capture-for-finite-element-analysis

Automatic Laser-based Geometry Capture for Finite Element Analysis of Weld Beads

Fusion welding for high-value manufacturing requires strict process controls on component distortion and ascertaining levels of residual stress imparted ...

University of Manchester

A novel fluoride-centered triangular-bridged carboxylate complex, [Ni2Cr(μ3-F)(O2C(t)Bu)6(HO2C(t)Bu)3] (1), is reported. Simple postsynthetic substitution of the terminal pivalic acids in 1 with pyridine and 4-methylpyridine led to the isolation of [Ni2Cr(μ3-F)(O2C(t)Bu)6(C5H5N)3] (2) and [Ni2Cr(μ3-F)(O2C(t)Bu)6((4-CH3)C5H4N)3] (3). Structural and magnetic characterizations carried out on the series reveal a dominating antiferromagnetic interaction between the nickel and chromium centers leading to an S = (1)/2 ground state with a very unusual value of geff = 2.48.

Electronic Structure of a Mixed-Metal Fluoride-Centered Triangle Complex: A Potential Qubit Component.

Definition, aims, and implementation of GA LEN/HAEi Angioedema Centers of Reference and Excellence.

Throughout their evolutionary history, bacteria have faced diverse threats from other microorganisms, including competing bacteria, bacteriophages and predators. In response to these threats, they have evolved sophisticated defence mechanisms that today also protect bacteria against antibiotics and other therapies. In this Review, we explore the protective strategies of bacteria, including the mechanisms, evolution and clinical implications of these ancient defences. We also review the countermeasures that attackers have evolved to overcome bacterial defences. We argue that understanding how bacteria defend themselves in nature is important for the development of new therapies and for minimizing resistance evolution.

Bacterial defences: mechanisms, evolution and antimicrobial resistance.

Bacteria commonly face attacks from other strains using the type VI secretion system (T6SS), which acts like a molecular speargun to stab and intoxicate competitors. Here we show how bacteria can work together to collectively defend themselves against these attacks. This project began with an outreach activity: while developing an online computer game of bacterial warfare, we noticed that one strategist ("Slimy") that made extracellular polymeric substances (EPS) was able to resist attacks from another strategist that employed the T6SS ("Stabby"). This observation motivated us to model this scenario more formally, using dedicated agent-based simulations. The model predicts that EPS production can serve as a collective defence mechanism, which protects both producing cells and neighbouring cells that do not make EPS. We then tested our model with a synthetic community that contains a T6SS-wielding attacker (Acinetobacter baylyi), and two T6SS-sensitive target strains (Escherichia coli) that either secrete EPS, or not. As predicted by our modelling, we find that the production of EPS leads to collective protection against T6SS attacks, where EPS producers protect each other and nearby non-producers. We identify two processes that explain this protection: EPS sharing between cells and a second general mechanism whereby groups of resistant cells shield susceptible cells, which we call "flank protection". Our work shows how EPS-producing bacteria can work together to defend themselves from the type VI secretion system.

Collective protection against the type VI secretion system in bacteria.

Predicting nanoparticle aggregation and attachment phenomena requires a rigorous understanding of the interplay among crystal structure, particle morphology, surface chemistry, solution conditions, and interparticle forces, yet no comprehensive picture exists. We used an integrated suite of experimental, theoretical, and simulation methods to resolve the effect of solution pH on the aggregation of boehmite nanoplatelets, a case study with important implications for the environmental management of legacy nuclear waste. Real-time observations showed that the particles attach preferentially along the (010) planes at pH 8.5 and the (101) planes at pH 11. To rationalize these results, we established the connection between key physicochemical phenomena across the relevant length scales. Starting from  simulations of surface hydroxyl reactivity, we developed an  model of the corresponding electrostatic potentials, with subsequent  calculations of the resulting driving forces allowing successful prediction of the attachment modes. Finally, we scaled these phenomena to understand the collective structure at the . Our results indicate that facet-specific differences in surface chemistry produce heterogeneous surface charge distributions that are coupled to particle anisotropy and shape-dependent hydrodynamic forces, to play a key role in controlling aggregation behavior.

Predicting Outcomes of Nanoparticle Attachment by Connecting Atomistic, Interfacial, Particle, and Aggregate Scales.

Bacteria possess a diverse range of mechanisms for inhibiting competitors, including bacteriocins, tailocins, type VI secretion systems and contact-dependent inhibition (CDI). Why bacteria have evolved such a wide array of weapon systems remains a mystery. Here we develop an agent-based model to compare short-range weapons that require cell-cell contact, with long-range weapons that rely on diffusion. Our model predicts that contact weapons are useful when an attacking strain is outnumbered, facilitating invasion and establishment. By contrast, ranged weapons tend to be effective only when attackers are abundant. We test our predictions with the opportunistic pathogen Pseudomonas aeruginosa, which naturally carries multiple weapons, including CDI and diffusing tailocins. As predicted, short-range CDI can function at low and high frequencies, while long-range tailocins require high frequency and cell density to function effectively. Head-to-head competition experiments with the two weapon types further support our predictions: a tailocin attacker defeats CDI only when it is numerically dominant, but then we find it can be devastating. Finally, we show that the two weapons work well together when one strain employs both. We conclude that short- and long-range weapons serve different functions and allow bacteria to fight both as individuals and as a group.

The evolution of short- and long-range weapons for bacterial competition.

The bacterial type 6 secretion system (T6SS) is a toxin-injecting nanoweapon that mediates competition in plant- and animal-associated microbial communities. Bacteria can evolve de novo resistance against T6SS attacks, but resistance is far from universal in natural communities, suggesting key features of T6SS weaponry may act to limit its evolution. Here, we combine ecoevolutionary modeling and experimental evolution to examine how toxin type and multiplicity in  attackers shape resistance evolution in susceptible  competitors. In both our models and experiments, we find that combinations of multiple distinct toxins limit resistance evolution by creating genetic bottlenecks, driving resistant lineages extinct before they can reach high frequency. We also show that, paradoxically, single-toxin attackers can drive the evolution of cross-resistance, protecting bacteria against unfamiliar toxin combinations, even though such evolutionary pathways were inaccessible against multitoxin attackers. Our findings indicate that, comparable to antimicrobial and anticancer combination therapies, multitoxin T6SS arsenals function to limit resistance evolution in competing microbes. This helps us to understand why T6SSs remain widespread and effective weapons in microbial communities, and why many T6SS-armed bacteria encode functionally diverse anticompetitor toxins.

Multiplicity of type 6 secretion system toxins limits the evolution of resistance.

Chinese hamster ovary (CHO) cells are the industrial workhorse for manufacturing biopharmaceuticals, including monoclonal antibodies. CHO cell line development requires a more data-driven approach for the accelerated identification of hyperproductive cell lines. Traditional methods, which rely on time-consuming hierarchical screening, often fail to elucidate the underlying cellular mechanisms driving optimal bioreactor performance. Big data analytics, coupled with advancements in "omics" technologies, are revolutionizing the study of industrial cell lines. Translating this knowledge into practical methods widely utilized in industrial biomanufacturing remains a significant challenge. This study leverages discovery proteomics to characterize dynamic changes within the CHO cell proteome during a 14-day fed-batch bioreactor cultivation. Utilizing a global untargeted proteomics workflow on both a ZenoTOF 7600 and a Cyclic IMS QToF, we identify 3358 proteins and present a comprehensive data set that describes the molecular changes that occur within a well-characterized host chassis. By mapping relative abundances to key cellular processes, eight protein targets were selected as potential biomarkers. The abundance of these proteins through the production run is quantified using a 15-min targeted triple quadrupole (MRM) assay, which provides a molecular-level QC for cell viability. This discovery to target workflow has the potential to assist engineering of new chassis and provide simple readouts of successful bioreactor batches.

Article	Year
Electronic Structure of a Mixed-Metal Fluoride-Centered Triangle Complex: A Potential Qubit Component. Inorganic chemistry\| PubMed ID: 26636473	2015
Definition, aims, and implementation of GA LEN/HAEi Angioedema Centers of Reference and Excellence. Allergy\| PubMed ID: 32248571	2020
Bacterial defences: mechanisms, evolution and antimicrobial resistance. Nature reviews. Microbiology\| PubMed ID: 37095190	2023
Collective protection against the type VI secretion system in bacteria. The ISME journal\| PubMed ID: 37095301	2023
Predicting Outcomes of Nanoparticle Attachment by Connecting Atomistic, Interfacial, Particle, and Aggregate Scales. ACS nano\| PubMed ID: 37556761	2023
The evolution of short- and long-range weapons for bacterial competition. Nature ecology & evolution\| PubMed ID: 38036633	2023
Multiplicity of type 6 secretion system toxins limits the evolution of resistance. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 39786933	2025
From Discovery to Delivery: A Rapid and Targeted Proteomics Workflow for Monitoring Chinese Hamster Ovary Biomanufacturing. Molecular & cellular proteomics : MCP\| PubMed ID: 40480342	2025

William Smith

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