Drivers and implications of alternative routes to fuels decarbonization in net-zero energy systems.

Energy transition scenarios are characterized by increasing electrification and improving efficiency of energy end uses, rapid decarbonization of the electric power sector, and deployment of carbon dioxide removal (CDR) technologies to offset remaining emissions. Although hydrocarbon fuels typically decline in such scenarios, significant volumes remain in many scenarios even at the time of net-zero emissions. While scenarios rely on different approaches for decarbonizing remaining fuels, the underlying drivers for these differences are unclear. Here we develop several illustrative net-zero systems in a simple structural energy model and show that, for a given set of final energy demands, assumptions about the use of biomass and CO2 sequestration drive key differences in how emissions from remaining fuels are mitigated. Limiting one resource may increase reliance on another, implying that decisions about using or restricting resources in pursuit of net-zero objectives could have significant tradeoffs that will need to be evaluated and managed.

Concurrent Middle Cerebral Artery and Basilar Artery Occlusions Treated With Mechanical Thrombectomy in a Patient With Active COVID-19 Infection.

We report a rare case of acute ischemic stroke from concurrent large vessel occlusions (LVOs) and subsequent successful mechanical thrombectomy revascularization in a patient with active coronavirus disease 2019 (COVID-19) pneumonia. A 59-year-old woman presented to the emergency department after one week of intermittent chest pain, dyspnea, and diarrhea found to have COVID-19 pneumonia. On hospital day three, the patient developed acute altered mental status and hemiparesis with a National Institutes of Health Stroke Scale (NIHSS) of 22. CT with angiography demonstrated concurrent occlusions of the basilar artery and the M1 segment of the right middle cerebral artery (MCA) without intracranial hemorrhage. The patient was taken for urgent mechanical thrombectomy of the basilar artery, followed by the MCA, both of which were successful (thrombolysis in cerebral infarction (TICI) 3 and 2B) and timely. Despite early revascularization, the patient did not improve clinically with absent brainstem reflexes and a full MCA territorial infarct on imaging. This case describes a rare stroke syndrome of concurrent LVOs with rapid infarct progression despite timely revascularization. This example illustrates a severe cerebrovascular complication of active COVID-19 infection and the importance of vigilance regarding stroke prevention and neurological examination monitoring.

Nested non-covalent interactions expand the functions of supramolecular polymer networks.

Supramolecular polymer networks contain non-covalent cross-links that enable access to broadly tunable mechanical properties and stimuli-responsive behaviors; the incorporation of multiple unique non-covalent cross-links within such materials further expands their mechanical responses and functionality. To date, however, the design of such materials has been accomplished through discrete combinations of distinct interaction types in series, limiting materials design logic. Here we introduce the concept of leveraging "nested" supramolecular crosslinks, wherein two distinct types of non-covalent interactions exist in parallel, to control bulk material functions. To demonstrate this concept, we use polymer-linked Pd2L4 metal-organic cage (polyMOC) gels that form hollow metal-organic cage junctions through metal-ligand coordination and can exhibit well-defined host-guest binding within their cavity. In these "nested" supramolecular network junctions, the thermodynamics of host-guest interactions within the junctions affect the metal-ligand interactions that form those junctions, ultimately translating to substantial guest-dependent changes in bulk material properties that could not be achieved in traditional supramolecular networks with multiple interactions in series.

Caspase-3-Responsive, Fluorogenic Bivalent Bottlebrush Polymers.

Controlling the access of proteases to cleavable peptides placed at specific locations within macromolecular architectures represents a powerful strategy for biologically responsive materials design. Here, we report the synthesis of peptide-containing bivalent bottlebrush (co)polymers (BBPs) featuring polyethylene glycol (PEG) and 7-amino-4-methylcoumarin (AMC) pendants on each backbone repeat unit. The AMCs are linked via caspase-3-cleavable peptides which, upon enzymatic cleavage, provide a "turn-on" fluorescence signal due to the release of free AMC. Time-dependent fluorscence measurements demonstrate that the caspase-3-induced peptide cleavage and AMC release from BBPs is strongly dependent on the BBP backbone length and the AMC-peptide linker location within the BBP architecture, revealing fundamental insights into the interactions of enzymes with BBPs.

Defining Reactivity-Deconstructability Relationships for Copolymerizations Involving Cleavable Comonomer Additives.

The incorporation of cleavable comonomers as additives into polymers can imbue traditional polymers with controlled deconstructability and expanded end-of-life options. The efficiency with which cleavable comonomer additives (CCAs) can enable deconstruction is sensitive to their local distribution within a copolymer backbone, which is dictated by their copolymerization behavior. While qualitative heuristics exist that describe deconstructability, comprehensive quantitative connections between CCA loadings, reactivity ratios, polymerization mechanisms, and deconstruction reactions on the deconstruction efficiency of copolymers containing CCAs have not been established. Here, we broadly define these relationships using stochastic simulations characterizing various polymerization mechanisms (e.g., coltrolled/living, free-radical, and reversible ring-opening polymerizations), reactivity ratio pairs (spanning 2 orders of magnitude between 0.01 and 100), CCA loadings (2.5% to 20%), and deconstruction reactions (e.g., comonomer sequence-dependent deconstruction behavior). We show general agreement between simulated and experimentally observed deconstruction fragment sizes from the literature, demonstrating the predictive power of the methods used herein. These results will guide the development of more efficient CCAs and inform the formulation of deconstructable materials.

Mechanism-Guided Discovery of Cleavable Comonomers for Backbone Deconstructable Poly(methyl methacrylate).

The development of cleavable comonomers (CCs) with suitable copolymerization reactivity paves the way for the introduction of backbone deconstructability into polymers. Recent advancements in thionolactone-based CCs, exemplified by dibenzo[c,e]-oxepine-5(7H)-thione (DOT), have opened promising avenues for the selective deconstruction of multiple classes of vinyl polymers, including polyacrylates, polyacrylamides, and polystyrenics. To date, however, no thionolactone CC has been shown to copolymerize with methacrylates to an appreciable extent to enable polymer deconstruction. Here, we overcome this challenge through the design of a new class of benzyl-functionalized thionolactones (bDOTs). Guided by detailed mechanistic analyses, we find that the introduction of radical-stabilizing substituents to bDOTs enables markedly increased and tunable copolymerization reactivity with methyl methacrylate (MMA). Through iterative optimizations of the molecular structure, a specific bDOT, F-p-CF3PhDOT, is discovered to copolymerize efficiently with MMA. High molar mass deconstructable PMMA-based copolymers (dPMMA, Mn > 120 kDa) with low percentages of F-p-CF3PhDOT (1.8 and 3.8 mol%) are prepared using industrially relevant bulk free radical copolymerization conditions. The thermomechanical properties of dPMMA are similar to PMMA; however, the former is shown to degrade into low molar mass fragments (<6.5 kDa) under mild aminolysis conditions. This work presents the first example of a radical ring-opening CC capable of nearly random copolymerization with MMA without the possibility of cross-linking and provides a workflow for the mechanism-guided design of deconstructable copolymers in the future.

An organometallic swap strategy for bottlebrush polymer-protein conjugate synthesis.

Polymer-protein bioconjugation offers a powerful strategy to alter the physical properties of proteins, and various synthetic polymer compositions and architectures have been investigated for this purpose. Nevertheless, conjugation of molecular bottlebrush polymers (BPs) to proteins remains an unsolved challenge due to the large size of BPs and a general lack of methods to transform the chain ends of BPs into functional groups suitable for bioconjugation. Here, we present a strategy to address this challenge in the context of BPs prepared by "graft-through" ring-opening metathesis polymerization (ROMP), one of the most powerful methods for BP synthesis. Quenching ROMP of PEGylated norbornene macromonomers with an activated enyne terminator facilitates the transformation of the BP Ru alkylidene chain ends into Pd oxidative addition complexes (OACs) for facile bioconjugation. This strategy is shown to be effective for the synthesis of two BP-protein conjugates (albumin and ERG), setting the stage for a new class of BP-protein conjugates for future therapeutic and imaging applications.

Self-Amplified HF Release and Polymer Deconstruction Cascades Triggered by Mechanical Force.

Hydrogen fluoride (HF) is a versatile reagent for material transformation, with applications in self-immolative polymers, remodeled siloxanes, and degradable polymers. The responsive in situ generation of HF in materials therefore holds promise for new classes of adaptive material systems. Here, we report the mechanochemically coupled generation of HF from alkoxy-gem-difluorocyclopropane (gDFC) mechanophores derived from the addition of difluorocarbene to enol ethers. Production of HF involves an initial mechanochemically assisted rearrangement of gDFC mechanophore to α-fluoro allyl ether whose regiochemistry involves preferential migration of fluoride to the alkoxy-substituted carbon, and ab initio steered molecular dynamics simulations reproduce the observed selectivity and offer insights into the mechanism. When the alkoxy gDFC mechanophore is derived from poly(dihydrofuran), the α-fluoro allyl ether undergoes subsequent hydrolysis to generate 1 equiv of HF and cleave the polymer chain. The hydrolysis is accelerated via acid catalysis, leading to self-amplifying HF generation and concomitant polymer degradation. The mechanically generated HF can be used in combination with fluoride indicators to generate an optical response and to degrade polybutadiene with embedded HF-cleavable silyl ethers (11 mol %). The alkoxy-gDFC mechanophore thus provides a mechanically coupled mechanism of releasing HF for polymer remodeling pathways that complements previous thermally driven mechanisms.

Glycan-costumed virus-like particles promote type 1 anti-tumor immunity.

Cancer vaccine development is inhibited by a lack of strategies for directing dendritic cell (DC) induction of effective tumor-specific cellular immunity. Pathogen engagement of DC lectins and toll-like receptors (TLRs) shapes immunity by directing T cell function. Strategies to activate specific DC signaling pathways via targeted receptor engagement are crucial to unlocking type 1 cellular immunity. Here, we engineered a glycan-costumed virus-like particle (VLP) vaccine that delivers programmable peptide antigens to induce tumor-specific cellular immunity in vivo. VLPs encapsulating TLR7 agonists and decorated with a selective mannose-derived ligand for the lectin DC-SIGN induced robust DC activation and type 1 cellular immunity, whereas VLPs lacking this key DC-SIGN ligand failed to promote DC-mediated immunity. Vaccination with glycan-costumed VLPs generated tumor antigen-specific Th1 CD4+ and CD8+ T cells that infiltrated solid tumors, inhibiting tumor growth in a murine melanoma model. Thus, VLPs employing lectin-driven immune reprogramming provide a framework for advancing cancer immunotherapies.

Gut metabolite L-lactate supports Campylobacter jejuni population expansion during acute infection.

How the microaerobic pathogen Campylobacter jejuni establishes its niche and expands in the gut lumen during infection is poorly understood. Using 6-wk-old ferrets as a natural disease model, we examined this aspect of C. jejuni pathogenicity. Unlike mice, which require significant genetic or physiological manipulation to become colonized with C. jejuni, ferrets are readily infected without the need to disarm the immune system or alter the gut microbiota. Disease after C. jejuni infection in ferrets reflects closely how human C. jejuni infection proceeds. Rapid growth of C. jejuni and associated intestinal inflammation was observed within 2 to 3 d of infection. We observed pathophysiological changes that were noted by cryptic hyperplasia through the induction of tissue repair systems, accumulation of undifferentiated amplifying cells on the colon surface, and instability of HIF-1α in colonocytes, which indicated increased epithelial oxygenation. Metabolomic analysis demonstrated that lactate levels in colon content were elevated in infected animals. A C. jejuni mutant lacking lctP, which encodes an L-lactate transporter, was significantly decreased for colonization during infection. Lactate also influences adhesion and invasion by C. jejuni to a colon carcinoma cell line (HCT116). The oxygenation required for expression of lactate transporter (lctP) led to identification of a putative thiol-based redox switch regulator (LctR) that may repress lctP transcription under anaerobic conditions. Our work provides better insights into the pathogenicity of C. jejuni.

The neurosurgery research & education foundation-young neurosurgeons committee webinar series: Providing education and inspiration during the COVID-19 pandemic.

OBJECTIVE: During the COVID-19 pandemic, the American Association of Neurological Surgeons (AANS) Young Neurosurgeons Committee (YNC) and Neurosurgery Research & Education Foundation (NREF) launched the YNC-NREF Webinar Series to provide young and aspiring neurosurgeons with timely information, education, and inspiration in the absence of in-person programming. DESIGN: Five 90-minute Zoom webinars were evaluated, each including 1-2 keynote speakers, a panel discussion, and an audience question-and-answer section. Topics included overviews of neurosurgery, the match, subspecialties, and inspirational career stories. Optional pre- and post-webinar surveys with 11-point Likert-type scores were distributed to attendees. We compared groups using chi-squared and Kruskal-Willis tests, and perceptions pre- and post-webinar using Mann-Whitney tests. SETTING: The webinars were live using Zoom, and the recordings were published on NREF's YouTube channel. PARTICIPANTS: The webinar series targeted young neurosurgeons. The first five episodes had a particular focus on medical students and undergraduates. RESULTS: A total of 673 unique participants attended the webinar series; 257 (38%) and 78 (11%) attendees completed the pre- and post-webinar survey, respectively. Respondents had high baseline interest in neurosurgery and were motivated to learn about the match and training in the US, understand neurosurgeons' day-to-day lives, and ask questions. There were significant differences in perceptions between USMSs, IMSs, and undergraduate students. The webinar improved attendees' knowledge about neurosurgical specialties, the match, and US neurosurgery training. CONCLUSIONS: The YNC and NREF effectively engaged a large, diverse audience through an online webinar series, building a foundation for future virtual programming by organized neurosurgery. ACGME competencies.

Life Cycle Greenhouse Gas Emissions of CO2-Enabled Sedimentary Basin Geothermal.

The expansion of renewable energy and the large-scale deployment of carbon dioxide (CO2) capture and storage (CCS) can decarbonize the power sector. The use of CO2 to extract geothermal heat from naturally porous and permeable sedimentary basins to generate electricity (CO2-plume geothermal (CPG) system) presents an opportunity to simultaneously generate renewable energy and geologically store CO2. In this study, we estimate the life cycle greenhouse gas (GHG) impacts of CPG systems through 12 scenarios in which CPG systems are combined with one of six CO2 sources (e.g., bioenergy with carbon capture and storage (BECCS) and iron and steel facilities) and operate in two geological settings. We find the life cycle GHG emissions of CPG systems ranging from -0.25 to -6.18 kg CO2eq/kWh. CPG systems can achieve the highest emissions reductions when utilizing the CO2 captured from BECCS. We evaluate uncertainty through a Monte Carlo simulation, demonstrating consistent net reductions in life cycle emissions and a local, one-parameter-at-a-time sensitivity analysis that identifies the CO2 capture capacity as the high-impact parameter of the results. Through the production of electricity, CPG systems can provide additional environmental benefits to the deployment of large-scale CCS.

Development of a rabbit human glioblastoma model for testing of endovascular selective intra-arterial infusion (ESIA) of novel stem cell-based therapeutics.

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24). METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on magnetic resonance imaging, histologic, and immunohistochemistry analysis. Selective microcatheter infusion of MSC-D24 was performed via the ipsilateral internal carotid artery to assess model utility and the efficacy and safety of this approach. RESULTS: Twenty-five rabbits were implanted (18 with U87, 2 MDA-GSC-17, and 5 MDA-GSC-8-11). Tumors formed in 68% of rabbits (77.8% for U87, 50.0% for MDA-GSC-17, and 40.0% for MDA-GSC-8-11). On MRI, the tumors were hyperintense on T2-weighted image with variable enhancement (evidence of blood brain barrier breakdown). Histologically, tumors showed phenotypic traits of human GBM including varying levels of vascularity. ESIA infusion into the distal internal carotid artery of 2 ml of MSCs-D24 (107 cells) was safe in the model. Examination of post infusion specimens documented that MSCs-D24 homed to the implanted tumor at 24 hours. CONCLUSIONS: The intracranial immunosuppressed rabbit human GBM model allows testing of ESIA infusion of novel therapeutics (eg, MSC-D24) in a clinically relevant fashion.

Viscosity-dependent determinants of Campylobacter jejuni impacting the velocity of flagellar motility.

IMPORTANCE: Bacteria can adapt flagellar motor output in response to the load that the extracellular milieu imparts on the flagellar filament to enable propulsion. Bacteria can adapt flagellar motor output in response to the load that the extracellular milieu imparts on the flagellar filament to enable propulsion through diverse environments. These changes may involve increasing power and torque in high-viscosity environments or reducing power and flagellar rotation upon contact with a surface. C. jejuni swimming velocity in low-viscosity environments is comparable to other bacterial flagellates and increases significantly as external viscosity increases. In this work, we provide evidence that the mechanics of the C. jejuni flagellar motor has evolved to naturally promote high swimming velocity in high-viscosity environments. We found that C. jejuni produces VidA and VidB as auxiliary proteins to specifically affect flagellar motor activity in low viscosity to reduce swimming velocity. Our findings provide some of the first insights into different mechanisms that exist in bacteria to alter the mechanics of a flagellar motor, depending on the viscosity of extracellular environments.

Safe and Scalable Syntheses of N,N-Dimethyltrifluoromethanesulfonamide (DMTMSA) and Other Trifluoromethanesulfonamide Solvents for High Energy Density Battery Applications.

A simple, scalable synthetic methodology for the synthesis of N,N-dimethyltrifluoromethanesulfonamide (DMTMSA) and other trifluoromethanesulfonamide solvents is described. No specialized glassware is required, water is the solvent, and an ice bath is used for cooling. Up to 155 g of DMTMSA is synthesized in a single batch in 92% yield. The optimized process is highly mass efficient (PMI = 9.1), and excess dimethylamine may be recovered (93% recovery, 51% decrease in waste) and recycled via a simple short-path distillation.

A Model Ensemble Approach Enables Data-Driven Property Prediction for Chemically Deconstructable Thermosets in the Low-Data Regime.

Thermosets present sustainability challenges that could potentially be addressed through the design of deconstructable variants with tunable properties; however, the combinatorial space of possible thermoset molecular building blocks (e.g., monomers, cross-linkers, and additives) and manufacturing conditions is vast, and predictive knowledge for how combinations of these molecular components translate to bulk thermoset properties is lacking. Data science could overcome these problems, but computational methods are difficult to apply to multicomponent, amorphous, statistical copolymer materials for which little data exist. Here, leveraging a data set with 101 examples, we introduce a closed-loop experimental, machine learning (ML), and virtual screening strategy to enable predictions of the glass transition temperature (Tg) of polydicyclopentadiene (pDCPD) thermosets containing cleavable bifunctional silyl ether (BSE) comonomers and/or cross-linkers with varied compositions and loadings. Molecular features and formulation variables are used as model inputs, and uncertainty is quantified through model ensembling, which together with heavy regularization helps to avoid overfitting and ultimately achieves predictions within <15 °C for thermosets with compositionally diverse BSEs. This work offers a path to predicting the properties of thermosets based on their molecular building blocks, which may accelerate the discovery of promising plastics, rubbers, and composites with improved functionality and controlled deconstructability.

Thermally Robust yet Deconstructable and Chemically Recyclable High-Density Polyethylene (HDPE)-Like Materials Based on Si-O Bonds.

Polyethylene (PE) is the most widely produced synthetic polymer. By installing chemically cleavable bonds into the backbone of PE, it is possible to produce chemically deconstructable PE derivatives; to date, however, such designs have primarily relied on carbonyl- and olefin-related functional groups. Bifunctional silyl ethers (BSEs; SiR2 (OR'2 )) could expand the functional scope of PE mimics as they possess strong Si-O bonds and facile chemical tunability. Here, we report BSE-containing high-density polyethylene (HDPE)-like materials synthesized through a one-pot catalytic ring-opening metathesis polymerization (ROMP) and hydrogenation sequence. The crystallinity of these materials can be adjusted by varying the BSE concentration or the steric bulk of the Si-substituents, providing handles to control thermomechanical properties. Two methods for chemical recycling of HDPE mimics are introduced, including a circular approach that leverages acid-catalyzed Si-O bond exchange with 1-propanol. Additionally, despite the fact that the starting HDPE mimics were synthesized by chain-growth polymerization (ROMP), we show that it is possible to recover the molar mass and dispersity of recycled HDPE products using step-growth Si-O bond formation or exchange, generating high molecular weight recycled HDPE products with mechanical properties similar to commercial HDPE.

Gut metabolite L-lactate supports Campylobacter jejuni population expansion during acute infection.

How the microaerobic pathogen Campylobacter jejuni establishes its niche and expands in the gut lumen during infection is poorly understood. Using six-week-old ferrets as a natural disease model, we examined this aspect of C. jejuni pathogenicity. Unlike mice, which require significant genetic or physiological manipulation to become colonized with C. jejuni , ferrets are readily infected without the need to disarm the immune system or alter the gut microbiota. Disease after C. jejuni infection in ferrets reflects closely how human C. jejuni infection proceeds. Rapid growth of C. jejuni and associated intestinal inflammation was observed within two-three days of infection. We observed pathophysiological changes that were noted by cryptic hyperplasia through the induction of tissue repair systems, accumulation of undifferentiated amplifying cells on the colon surface, and instability of HIF-1α in colonocytes, which indicated increased epithelial oxygenation. Metabolomic analysis demonstrated that lactate levels in colon content were elevated in infected animals. A C. jejuni mutant lacking lctP , which encodes an L-lactate transporter, was significantly decreased for colonization during infection. Lactate also influences adhesion and invasion by C. jejuni to a colon carcinoma cell line (HCT116). The oxygenation required for expression of lactate transporter ( lctP ) led to discovery of a putative thiol based redox switch regulator (LctR) that may repress lctP transcription under anaerobic conditions. Our work provides new insights into the pathogenicity of C. jejuni . Significance: There is a gap in knowledge about the mechanisms by which C. jejuni populations expand during infection. Using an animal model which accurately reflects human infection without the need to alter the host microbiome or the immune system prior to infection, we explored pathophysiological alterations of the gut after C. jejuni infection. Our study identified the gut metabolite L-lactate as playing an important role as a growth substrate for C. jejuni during acute infection. We identified a DNA binding protein, LctR, that binds to the lctP promoter and may repress lctP expression, resulting in decreased lactate transport under low oxygen levels. This work provides new insights about C. jejuni pathogenicity.

Contour subregion error detection methodology using deep learning auto-segmentation.

BACKGROUND: Inaccurate manual organ delineation is one of the high-risk failure modes in radiation treatment. Numerous automated contour quality assurance (QA) systems have been developed to assess contour acceptability; however, manual inspection of flagged cases is a time-consuming and challenging process, and can lead to users overlooking the exact error location. PURPOSE: Our aim is to develop and validate a contour QA system that can effectively detect and visualize subregional contour errors, both qualitatively and quantitatively. METHODS/MATERIALS: A novel contour subregion error detection (CSED) system was developed using subregional surface distance discrepancies between manual and deep learning auto-segmentation (DLAS) contours. A validation study was conducted using a head and neck public dataset containing 339 cases and evaluated according to knowledge-based pass criteria derived from a clinical training dataset of 60 cases. A blind qualitative evaluation was conducted, comparing the results from the CSED system with manual labels. Subsequently, the CSED-flagged cases were re-examined by a radiation oncologist. RESULTS: The CSED system could visualize the diverse types of subregional contour errors qualitatively and quantitatively. In the validation dataset, the CSED system resulted in true positive rates (TPR) of 0.814, 0.800, and 0.771; false positive rates (FPR) of 0.310, 0.267, and 0.298; and accuracies of 0.735, 0.759, and 0.730, for brainstem and left and right parotid contours, respectively. The CSED-assisted manual review caught 13 brainstem, 19 left parotid, and 21 right parotid contour errors missed by conventional human review. The TPR/FPR/accuracy of the CSED-assisted manual review improved to 0.836/0.253/0.784, 0.831/0.171/0.830, and 0.808/0.193/0.807 for each structure, respectively. Further, the time savings achieved through CSED-assisted review improved by 75%, with the time for review taking 24.81 ± 12.84, 26.75 ± 10.41, and 28.71 ± 13.72 s for each structure, respectively. CONCLUSIONS: The CSED system enables qualitative and quantitative detection, localization, and visualization of manual segmentation subregional errors utilizing DLAS contours as references. The use of this system has been shown to help reduce the risk of high-risk failure modes resulting from inaccurate organ segmentation.

Polymer Networks with Cubic, Mixed Pd(II) and Pt(II) M6L12 Metal-Organic Cage Junctions: Synthesis and Stress Relaxation Behavior.

Metal-organic cages/polyhedra (MOCs) are versatile building blocks for advanced polymer networks with properties that synergistically blend those of traditional polymers and crystalline frameworks. Nevertheless, constructing polyMOCs from very stable Pt(II)-based MOCs or mixtures of metal ions such as Pd(II) and Pt(II) has not, to our knowledge, been demonstrated, nor has exploration of how the dynamics of metal-ligand exchange at the MOC level may impact bulk polyMOC energy dissipation. Here, we introduce a new class of polymer metal-organic cage (polyMOC) gels featuring polyethylene glycol (PEG) strands of varied length cross-linked through bis-pyridyl-carbazole-based M6L12 cubes, where M is Pd(II), Pt(II), or mixtures thereof. We show that, while polyMOCs with varied Pd(II) content have similar network structures, their average stress-relaxation rates are tunable over 3 orders of magnitude due to differences in Pd(II)- and Pt(II)-ligand exchange rates at the M6L12 junction level. Moreover, mixed-metal polyMOCs display relaxation times indicative of intrajunction cooperative interactions, which stands in contrast to previous materials based on point metal junctions. Altogether, this work (1) introduces a novel MOC architecture for polyMOC design, (2) shows that polyMOCs can be prepared from mixtures of Pd(II)/Pt(II), and (3) demonstrates that polyMOCs display unique relaxation behavior due to their multivalent junctions, offering a strategy for controlling polyMOC properties independently of their polymer components.