6 research outputs found
A pragmatic continuum level model for the prediction of the onset of keyholing in laser powder bed fusion
Laser powder bed fusion (L-PBF) is a complex process involving a range of multi-scale and multi-physical phenomena. There has been much research involved in creating numerical models of this process using both high and low fidelity modelling approaches where various approximations are made. Generally, to model single lines within the process to predict melt pool geometry and mode, high fidelity computationally intensive models are used which, for industrial purposes, may not be suitable. The model proposed in this work uses a pragmatic continuum level methodology with an ablation limiting approach at the mesoscale coupled with measured thermophysical properties. This model is compared with single line experiments over a range of input parameters using a modulated yttrium fibre laser with varying power and line speeds for a fixed powder layer thickness. A good trend is found between the predicted and measured width and depth of the tracks for 316L stainless steel where the transition into keyhole mode welds was predicted within 13% of experiments. The work presented highlights that pragmatic reduced physics-based modelling can accurately capture weld geometry which could be applied to more practical based uses in the L-PBF process
Site-Specifically Labeled Immunoconjugates for Molecular Imaging—Part 1: Cysteine Residues and Glycans
Due to their remarkable selectivity and specificity for cancer biomarkers, immunoconjugates have emerged as extremely promising vectors for the delivery of diagnostic radioisotopes and fluorophores to malignant tissues. Paradoxically, however, these tools for precision medicine are synthesized in a remarkably imprecise way. Indeed, the vast majority of immunoconjugates are created via the random conjugation of bifunctional probes (e.g., DOTA-NCS) to amino acids within the antibody (e.g., lysines). Yet antibodies have multiple copies of these residues throughout their macromolecular structure, making control over the location of the conjugation reaction impossible. This lack of site specificity can lead to the formation of poorly defined, heterogeneous immunoconjugates with suboptimal in vivo behavior. Over the past decade, interest in the synthesis and development of site-specifically labeled immunoconjugates—both antibody-drug conjugates as well as constructs for in vivo imaging—has increased dramatically, and a number of reports have suggested that these better defined, more homogeneous constructs exhibit improved performance in vivo compared to their randomly modified cousins. In this two-part review, we seek to provide an overview of the various methods that have been developed to create site-specifically modified immunoconjugates for positron emission tomography, single photon emission computed tomography, and fluorescence imaging. We will begin with an introduction to the structure of antibodies and antibody fragments. This is followed by the core of the work: sections detailing the four different approaches to site-specific modification strategies based on cysteine residues, glycans, peptide tags, and unnatural amino acids. These discussions will be divided into two installments: cysteine residues and glycans will be detailed in Part 1 of the review, while peptide tags and unnatural amino acids will be addressed in Part 2. Ultimately, we sincerely hope that this review fosters interest and enthusiasm for site-specific immunoconjugates within the nuclear medicine and molecular imaging communities