Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Active target”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Production and purification of 43Sc and 47Sc from enriched [46Ti]TiO2 and [50Ti]TiO2 targets

Abstract The radioscandium isotopes, 43 Sc and 47 Sc, compose a promising elementally matched theranostic pair that can be used for the development of imaging and therapeutic radiopharmaceuticals with identical structures. This study aimed to investigate the production of high radionuclidic purity 43 Sc from enriched [ 46 Ti]TiO 2 targets and 47 Sc from enriched [ 50 Ti]TiO 2 targets and establish a target recycling technique. Enriched [ 46 Ti]TiO 2 targets were irradiated with 18 MeV protons, and enriched [ 50 Ti]TiO 2 targets were bombarded with 24 MeV protons. 43 Sc and 47 Sc were purified using ion chromatography attaining recovery yields of 91.7 ± 7.4% and 89.9 ± 3.9%, respectively. The average radionuclidic purity for 43 Sc was 98.8 ± 0.3% and for 47 Sc 91.5 ± 0.6%, while the average recovery of enriched titanium target material was 96 ± 4.0%. The highest apparent molar activity for [ 43 Sc]Sc-DOTA was 23.2 GBq/µmol and 3.39 GBq/µmol for [ 47 Sc]Sc-DOTA. This work demonstrates the feasibility of using enriched recycled [ 46 Ti]TiO 2 and [ 50 Ti]TiO 2 targets to produce high purity 43 Sc and 47 Sc as an elementally matched theranostic isotope pair.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2022

Systems for producing radionuclides using minimal target material

Among the various aspects of the present disclosure is the provision of systems for producing radioisotopes and improving the specific activity of radioisotopes (e.g., Cu-64 chloride). As described herein, the system includes a target material area or target material shape that matches the proton beam strike area or proton beam strike shape, resulting in optimal thickness with less target material required.

Gaehle, Gregory↗
DOE OSTI2025

Simulation and measurement of the dynamic strain response in a prototypical spallation target

The Second Target Station (STS) at the Spallation Neutron Source (SNS) will address emerging scientific challenges by providing a source of intense cold neutrons to instruments optimized for this source. The STS target will use rotating tungsten blocks and will receive 1.3 GeV proton beam pulses from the SNS accelerator at a repetition rate of 15 Hz. The facility life is planned for 40 years, and each target assembly life is expected to be approximately 10 years. An accurate strain prediction is then critical for fatigue life assessment of STS target blocks because they will be subject to approximately 10 8 beam pulses per lifetime. As an R&D activity, the Los Alamos Neutron Science Center (LANSCE) Weapons Neutron Research (WNR) Target 2 (Blue Room) facility was used to test the strain response of prototypical target blocks to the thermal shock of a proton pulse. The blue room was well suited for a pulsed proton beam impact test of subscale STS target blocks; the 800 MeV proton energy is approximately 60 % of the 1.3 GeV proton energy expected from the SNS accelerator to the STS. The LANSCE Proton Storage Ring (PSR) and SNS are both short-pulse proton beam sources with nominal pulse widths of 250 ns and 661 ns, respectively, so the energy deposition in the target occurs in <1 μs pulse duration. Strain measurements on the outer surface of three target blocks (bare tungsten, tantalum-clad tungsten, niobium-clad tungsten) were recorded for comparison against neutronics and structural simulations. In conclusion, this experiment and the supporting simulations satisfied the following primary research goals for the STS target.

Dynamic strain response↗
DOE OSTI2023

Ciliary localization of a light-activated neuronal GPCR shapes behavior

Many neurons in the central nervous system produce a single primary cilium that serves as a specialized signaling organelle. Several neuromodulatory G-protein-coupled receptors (GPCRs) localize to primary cilia in neurons, although it is not understood how GPCR signaling from the cilium impacts circuit function and behavior. We find that the vertebrate ancient long opsin A (VALopA), a Gi-coupled GPCR extraretinal opsin, targets to cilia of zebrafish spinal neurons. In the developing 1-d-old zebrafish, brief light activation of VALopA in neurons of the central pattern generator circuit for locomotion leads to sustained inhibition of coiling, the earliest form of locomotion. We find that a related extraretinal opsin, VALopB, is also Gi-coupled, but is not targeted to cilia. Light-induced activation of VALopB also suppresses coiling, but with faster kinetics. We identify the ciliary targeting domains of VALopA. Retargeting of both opsins shows that the locomotory response is prolonged and amplified when signaling occurs in the cilium. We propose that ciliary localization provides a mechanism for enhancing GPCR signaling in central neurons.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Current Status of Radiopharmaceutical Therapy

In radiopharmaceutical therapy (RPT), a radionuclide is systemically or locally delivered with the goal of targeting and delivering radiation to cancer cells while minimizing radiation exposure to untargeted cells. Examples of current RPTs include thyroid ablation with the administration of {sup 131}I, treatment of liver cancer with {sup 90}Y microspheres, the treatment of bony metastases with {sup 223}Ra, and the treatment of neuroendocrine tumors with {sup 177}Lu-DOTATATE. New RPTs are being developed where radionuclides are incorporated into systemic targeted therapies. To assure that RPT is appropriately implemented, advances in targeting need to be matched with advances in quantitative imaging and dosimetry methods. Currently, radiopharmaceutical therapy is administered by intravenous or locoregional injection, and the treatment planning has typically been implemented like chemotherapy, where the activity administered is either fixed or based on a patient’s body weight or body surface area. RPT pharmacokinetics are measurable by quantitative imaging and are known to vary across patients, both in tumors and normal tissues. Therefore, fixed or weight-based activity prescriptions are not currently optimized to deliver a cytotoxic dose to targets while remaining within the tolerance dose of organs at risk. Methods that provide dose estimates to individual patients rather than to reference geometries are needed to assess and adjust the injected RPT dose. Accurate doses to targets and organs at risk will benefit the individual patients and decrease uncertainties in clinical trials. Imaging can be used to measure activity distribution in vivo, and this information can be used to determine patient-specific treatment plans where the dose to the targets and organs at risk can be calculated. The development and adoption of imaging-based dosimetry methods is particularly beneficial in early clinical trials. In this work we discuss dosimetric accuracy needs in modern radiation oncology, uncertainties in the dosimetry in RPT, and best approaches for imaging and dosimetry of internal radionuclide therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

Senolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types

Cellular senescence is a driver of many age-related pathologies. There is an active search for pharmaceuticals termed senolytics that can mitigate or remove senescent cells in vivo by targeting genes that promote the survival of senescent cells. We utilized single-cell RNA sequencing to identify CRYAB as a robust senescence-induced gene and potential target for senolysis. Using chemical inhibitor screening for CRYAB disruption, we identified 25-hydroxycholesterol (25HC), an endogenous metabolite of cholesterol biosynthesis, as a potent senolytic. We then validated 25HC as a senolytic in mouse and human cells in culture and in vivo in mouse skeletal muscle. Thus, 25HC represents a potential class of senolytics, which may be useful in combating diseases or physiologies in which cellular senescence is a key driver.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation

The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function is the association of the p110γ catalytic subunit to either a p101 or p84 regulatory subunit, which mediates activation by G protein–coupled receptors. Here, we report the cryo–electron microscopy structure of a heterodimeric PI3Kγ complex, p110γ-p101. This structure reveals a unique assembly of catalytic and regulatory subunits that is distinct from other class I PI3K complexes. p101 mediates activation through its Gβγ-binding domain, recruiting the heterodimer to the membrane and allowing for engagement of a secondary Gβγ-binding site in p110γ. Mutations at the p110γ-p101 and p110γ–adaptor binding domain interfaces enhanced Gβγ activation. A nanobody that specifically binds to the p101-Gβγ interface blocks activation, providing a novel tool to study and target p110γ-p101–specific signaling events in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Self-Supervised Anomaly Detection via Neural Autoregressive Flows with Active Learning

Many self-supervised methods have been proposed with the target of image anomaly detection. These methods often rely on the paradigm of data augmentation with predefined transformations such as flipping, cropping, and rotations. However, it is not straightforward to apply these techniques for non-image data, such as time series or tabular data, while the performance of the existing deep approaches has been under our expectation on tasks beyond images. In this work, we propose a novel active learning (AL) scheme that relied on neural autoregressive flows (NAF) for self-supervised anomaly detection, specifically on small-scale data. Unlike other generative models such as GANs or VAEs, flow-based models allow to explicitly learn the probability density and thus can assign accurate likelihoods to normal data which makes it usable to detect anomalies. The proposed NAF-AL method is achieved by efficiently generating random samples from latent space and transforming them into feature space along with likelihoods via invertible mapping. The samples with lower likelihoods are selected and further checked by outlier detection using Mahalanobis distance. The augmented samples incorporating with normal samples are used for training a better detector so as to approach decision boundaries. Compared with random transformations, NAF-AL can be interpreted as a likelihood-oriented data augmentation that is more efficient and robust. Extensive experiments show that our approach outperforms existing baselines on multiple time series and tabular datasets, and a real-world application in advanced manufacturing, with significant improvement on anomaly detection accuracy and robustness over the state-of-the-art.

Zhang, Jiaxin↗
DOE OSTI2023

Biochemical Process Modeling and Simulation (BPMS)

The Biochemical Process Modeling and Simulation project aims to reduce the cost and time of research by applying theory, modeling, and simulation to the most relevant bottlenecks in the biochemical process. We use molecular modeling, quantum mechanics, metabolic modeling, fluid dynamics, and reaction-diffusion methods in close collaboration with pretreatment, hydrolysis, upgrading, and TEA. The project's outcomes are increased yields and efficiency of the biochemical process, added value to products, and reduced price of fuels by specifically targeting catalytic efficiency, reactor design, enzyme efficiency, and microbial design. We work closely with experimental projects to identify problems and iterate with experiments to find and refine solutions. By working with experimentalists, we decide on problems that can be solved with simulation that could otherwise not be solved or would take too long with experiment alone to reach BETO's targets. Over the years, we have produced solutions that have resulted in determining the most likely fatty-acid derivative for passive transport out of bacteria that upgrade biomass, and we have also designed enzyme mutations for enhanced lignin upgrading. Metabolic models have been developed to tune the activity of 2,3 butanediol production for the 2030 target. A computational method to deliver understanding of how complex omics data can be interpreted in the metabolic pathways of organisms used in the Agile Biofoundry. We have found methods to overcome specific barriers and continue to develop those methods. Our reactor studies have guided the design of both the microbes and reactors for aerobic and micro-aerobic production at all scales and have been instrumental in improving the accuracy of techno-economic analysis models. This project is essential in the process of selecting the final processes for 2030 SAF production targets. More specifically, recently, we have: 1) Predicted the strength of the basic structural interactions in commodity plastics to provide guidance for plastics upcycling strategies. 2) Developed computational tool to improve the characterization of lignin-derived compounds 3) Developed new methodologies to enable Machine Learning-based Directed Evolution for protein engineering. 4) Developed Machine Learning methods to predict protein promiscuity and mutations to further improve microbial and enzymatic driven processes and demonstrated the utility of ML approaches to engineering proteins from sparse experimental datasets. 5) Developed new methods to enable high-fidelity simulation of aerobic fermentation at industrial scale and resolving mismatch of time scales through subcycling/operator splitting 7) Identified the difficulty in preventing local high-oxygen conditions in industrial bubble columns, which leads to less-desirable acetoin production, suggesting future research directions in alternative reactor configurations (e.g loop reactors, shallow-channel reactors).

BIOMASS FUELS↗
DOE OSTI2020

Discovery of a Natural Product That Binds to the Mycobacterium tuberculosis Protein Rv1466 Using Native Mass Spectrometry

Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound’s cellular activity. A fraction derived from the plant Polyalthia sp. showed activity against Mycobacterium tuberculosis at 62.5 μge/μL. A known compound, altholactone, was identified from this fraction that showed activity towards M. tuberculosis at an minimum inhibitory concentration (MIC) of 64 μM. Retrospective analysis of a target-based screen against a TB proteome panel using native mass spectrometry established that the active fraction was bound to the mycobacterial protein Rv1466 with an estimated pseudo-Kd of 42.0 ± 6.1 µM. Our findings established Rv1466 as the potential molecular target of altholactone, which is responsible for the observed in vivo toxicity towards M. tuberculosis .

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Identification of 2-Hydroxyacyl-CoA Synthases with High Acyloin Condensation Activity for Orthogonal One-Carbon Bioconversion

One-carbon (C1) compounds are emerging as cost-effective and potentially carbon-negative feedstocks for biomanufacturing, which require efficient, versatile metabolic platforms for the synthesis of value-added products. Synthetic formyl-CoA elongation (FORCE) pathways allow diverse product synthesis from C1 compounds via iterative C1 elongation, operating independently from the host metabolism with reduced engineering complexity and improved theoretical yields. However, a major bottleneck was identified as the suboptimal kinetics of the core C1–C1 condensation enzyme, 2-hydroxyacyl-CoA synthase (HACS), catalyzing the acyloin condensation reaction between formaldehyde and formyl-CoA. Furthermore, we used a combinatorial approach of bioprospecting and rational protein engineering to identify multiple HACS variants with significantly improved activities toward C1 substrates. Sequence and structure alignment of the active variants elucidated the key regions for the catalytic function, which were targeted for mutagenesis, leading to improved catalytic efficiency. In parallel, a consecutive round of bioprospecting for homologs with high similarity with active variants revealed a highly active HACS variant exhibiting up to 7-fold improvement in catalytic efficiency (k cat /K M ) and 14-fold improvement in the FORCE pathway flux in vivo compared to the previous reports. Upon further optimization of the downstream pathway, the orthogonal C1-to-product bioconversion system showed a metabolic flux of up to 700 μM glycolate OD –1 h –1 (2.1 mmol gDCW –1 h –1 ) and an industrially relevant glycolate titer, rate, and yield of 5.2 g L –1 (67.8 mM), 0.22 g L –1 h –1 , and 94% carbon yield, respectively.

2-hydroxyacyl-CoA synthase↗
DOE OSTI2025

Radioisotope production at the Spallation Neutron Source: Design concept of isotope production target

Upon completion of the Second Target Station (STS) Project in the mid 2030s, the Spallation Neutron Source accelerator at Oak Ridge National Laboratory will deliver a 2.7 MW proton beam to the neutron production targets. In the post-STS phase, the accelerator will have a reserve beam power capacity of at least 100 kW beyond what the two neutron production targets will receive, which could potentially be ramped up to 300 kW. In this paper, a design concept for a radioisotope production target that could utilize 250 kW of the reserve beam power capacity is presented. The target consists of thorium discs encapsulated in 316L austenitic steel shells that are cooled by water. The estimated post-irradiation activity of Ac-225 and Ra-225, critical medical radioisotopes used in targeted alpha therapy cancer treatment, is calculated at the end of bombardment after a 14 day long irradiation time. Thermal and structural analyses are performed on the basis of calculated nuclear heating data. The technical feasibility of a high-power target under a 250-kW beam load with an extremely low duty factor of $3.5\cdot 10^{-6}$ is presented from thermal, structural and fatigue lifetime perspectives.

Lee, Yong Joong [ORNL] (ORCID:0000000298381723)↗
DOE OSTI2021

Targeted polyelectrolyte complex micelles treat vascular complications in vivo

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92a EC-TG /Apoe –/– ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe –/– mice. We tested the therapeutic effectiveness of the VCAM-1–targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1–targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti–miR-92a therapy in treating atherosclerosis and stenosis in Apoe –/– mice is markedly enhanced by the VCAM-1–targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Developing a Peptide That Inhibits DNA Repair by Blocking the Binding of Artemis and DNA Ligase IV to Enhance Tumor Radiosensitivity

Artemis and DNA Ligase IV are 2 critical elements in the nonhomologous end joining pathway of DNA repair, acting as the nuclease and DNA ligase, respectively. Enhanced cellular radiosensitivity by inhibition of either protein contributes to a promising approach to develop molecular targeted radiosensitizers. The interaction between Artemis and DNA Ligase IV is required for the activation of Artemis as nuclease at 3’overhang DNA; thus, we aim to generate an inhibitory peptide targeting the interaction between Artemis and DNA Ligase IV for novel radiosensitizer development.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2022

EstG is a novel esterase required for cell envelope integrity in Caulobacter

Proper regulation of the bacterial cell envelope is critical for cell survival. Identification and characterization of enzymes that maintain cell envelope homeostasis is crucial, as they can be targets for effective antibiotics. In this study, we have identified a novel enzyme, called EstG, whose activity protects cells from a variety of lethal assaults in the α-proteobacterium Caulobacter crescentus. Despite homology to transpeptidase family cell wall enzymes and an ability to protect against cell-wall-targeting antibiotics, EstG does not demonstrate biochemical activity toward cell wall substrates. Instead, EstG is genetically connected to the periplasmic enzymes OpgH and BglX, responsible for synthesis and hydrolysis of osmoregulated periplasmic glucans (OPGs), respectively. The crystal structure of EstG revealed similarities to esterases and transesterases, and we demonstrated esterase activity of EstG in vitro. Using biochemical fractionation, we identified a cyclic hexamer of glucose as a likely substrate of EstG. Further, this molecule is the first OPG described in Caulobacter and establishes a novel class of OPGs, the regulation and modification of which are important for stress survival and adaptation to fluctuating environments. Our data indicate that EstG, BglX, and OpgH comprise a previously unknown OPG pathway in Caulobacter. Ultimately, we propose that EstG is a novel enzyme that instead of acting on the cell wall, acts on cyclic OPGs to provide resistance to a variety of cellular stresses.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2025

Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel K Ca 3.1

The 1,4-dihydropyridines, drugs with well-established bioavailability and toxicity profiles, have proven efficacy in treating human hypertension, peripheral vascular disorders, and coronary artery disease. Every 1,4-dihydropyridine in clinical use blocks L-type voltage-gated calcium channels. We now report our development, using selective optimization of a side activity (SOSA), of a class of 1,4-dihydropyridines that selectively and potently inhibit the intermediate-conductance calcium-activated K + channel K Ca 3.1, a validated therapeutic target for diseases affecting many organ systems. One of these 1,4-dihydropyridines, DHP-103, blocked K Ca 3.1 with an IC 50 of 6 nM and exhibited exquisite selectivity over calcium channels and a panel of >100 additional molecular targets. Using high-resolution structure determination by cryogenic electron microscopy together with mutagenesis and electrophysiology, we delineated the drug binding pocket for DHP-103 within the water-filled central cavity of the K Ca 3.1 channel pore, where bound drug directly impedes ion permeation. DHP-103 inhibited gain-of-function mutant K Ca 3.1 channels that cause hereditary xerocytosis, suggesting its potential use as a therapeutic for this hemolytic anemia. In a rat model of acute ischemic stroke, the second leading cause of death worldwide, DHP-103 administered 12 h postischemic insult in proof-of-concept studies reduced infarct volume, improved balance beam performance (measure of proprioception) and decreased numbers of activated microglia in infarcted areas. K Ca 3.1-selective 1,4-dihydropyridines hold promise for the many diseases for which K Ca 3.1 has been experimentally confirmed as a therapeutic target.

Ong, Seow Theng [Lee Kong Chian School of Medicine↗
DOE OSTI2021

Click-Chemistry-Based Free Azide versus Azido Sugar Detection Enables Rapid In Vivo Screening of Glycosynthase Activity

Engineering of carbohydrate-active enzymes such as glycosynthases to enable chemoenzymatic synthesis of bespoke oligosaccharides has been limited by the lack of suitable ultrahigh-throughput screening methods capable of robustly detecting either starting substrates or end-products of the glycosidic bond formation reaction. Currently, there are limited screening methods available for rapid and highly sensitive single-cell-based screening of glycosynthase enzymes employing azido sugars as activated donor glycosyl substrates. Here, we report a fluorescence-based approach employing click-chemistry for the selective detection of glycosyl azides as substrates versus free inorganic azides as reaction products that facilitated an ultrahigh-throughput in vivo single-cell-based assay of glycosynthase activity. This assay was developed based on the distinct differences observed in relative fluorescence intensity of the triazole-containing fluorophore product formed during the click-chemistry reaction of organic glycosyl azides versus inorganic azides. This discovery formed the basis for proof of concept validation of a directed evolution methodology for screening and sorting glycosynthase mutants capable of synthesis of targeted fucosylated oligosaccharides. Our screening approach facilitated fluorescence-activated cell sorting of an error-prone polymerase chain reaction-based mutant library of fucosynthases expressed in Escherichia coli to identify several novel mutants that showed increased activity for ß-fucosyl azide-activated donor sugars toward desired acceptor sugars (e.g., pNP-xylose and lactose). Finally, we discuss avenues for improving this proof of concept in vivo assay method to identify better glycosynthase mutants and further demonstrate the broader applicability of this screening methodology for synthesis of bespoke glycans.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Correlating hot-electron preheat from the two-plasmon decay instability to $ρR$ degradation for direct-drive implosions on OMEGA

Focused experiments were performed with the goal of isolating the impact of hot-electron preheat on compression in deuterium–tritium (DT) layered, direct-drive implosions on OMEGA. Preheat from the hot-electrons generated by two-plasmon–decay (TPD) activity was varied through the incident laser intensity, with the total preheat energy deposited into unablated DT fuel being inferred using hard x-ray measurements. Results show a clear correlation between the inferred preheat levels and $ρR$ degradation that is consistent with a derived, 1D preheat model. A fit to the results also provides an estimated range of $ρR$ degradation from non-preheat sources for the adiabat ≈5 implosions used in this study. A follow-up study using targets containing Si-doped (5.5%) CH ablators (CHSi) demonstrated results consistent with mid-Z dopants mitigating TPD activity by showing these targets had almost no $ρR$ degradation as the laser intensity was increased up to levels previously considered damaging.

Doping↗