MacroGenics (United States)

Abstract Solving the problem of hydrogen embrittlement is a critical goal for the energy industries. Research has traditionally focused on mechanisms while overlooking the causative aspects. Real-time measurement of hydrogen concentration in metals provides a direct pathway to mapping hydrogen embrittlement parameters as a function of deformation and fugacity. This approach enables the prediction of hydrogen embrittlement behavior in materials that have been systematically characterized, offering a quantitative framework to reconcile the contributions of hydrogen-enhanced localized plasticity (HELP) and hydrogen-enhanced decohesion (HED) mechanisms. The study also posits a newly recognized form of hydrogen embrittlement, where crack growth rate varies with stress intensity below the plateau region typically associated with constant velocity crack propagation. Practical implications emerge for cathodic protection design: by controlling applied potential, the degree of hydrogen trapping can be modified, revealing safe protection levels that mitigate failure within the design strain envelope. Specifically, it is shown that maintaining potentials around −900 mV provides effective mitigation against hydrogen embrittlement risks. This work highlights a transformative method for predicting and controlling hydrogen embrittlement in structural alloys.

Abstract Corrosion of galvanized steel transmission poles and lattice towers is a growing concern for electric utilities worldwide. This paper documents the design, implementation, and performance of system-wide impressed current cathodic protection (ICCP) programs successfully deployed at multiple utilities. Unlike localized retrofits, the system-wide approach distributes protective current along an entire corridor of structures by bonding through overhead ground wires and integrating copper substation grids with perimeter or deep-well anode beds. The results demonstrate effective polarization of galvanized structures, simultaneous protection of copper grounding systems, and significant extension of service life in corrosive soils. This paper presents background on galvanized steel corrosion, risk assessment methods, ICCP system design details, field performance observations, and lessons learned. The findings provide a framework for utilities considering similar system-wide corrosion mitigation strategies.

Abstract Coating degradation in galvanized steel transmission and distribution (T&D) structures is a gradual but critical process that affects the long-term reliability and integrity of utility assets. Unlike bare steel, galvanized steel benefits from a sacrificial zinc coating that deteriorates over time through electrochemical and environmental interactions. Understanding these mechanisms is essential for accurate condition assessment, proactive maintenance, and effective life-cycle management. This paper outlines the multi-stage degradation of zinc coatings, emphasizing the electrochemical corrosion of galvanizing intermetallic layers (gamma, delta, zeta, and eta) and the formation of oxides, hydroxides, and carbonates of zinc. Under chloride-rich or low-pH conditions, these layers weaken, exposing the steel substrate to corrosion. A high-confidence inspection approach is presented, integrating visual assessment, coating thickness, and electrochemical potential measurements to quantify corrosion risk more accurately. A case study demonstrates the use of real-time corrosion monitoring sensors for early detection and predictive modeling of coating lifespan. Integration with Geographic Information System (GIS)–based environmental mapping enables utilities to prioritize maintenance, extend asset life, and minimize unplanned outages.

Cancer remains one of the most significant global health challenges, characterized by an increasing incidence and mortality rate worldwide. In vitro models play a significant role in the initial investigations of cancer biology, drug screening, and therapeutic development. However, although widely used, conventional 2D cell cultures fail to replicate the complex tumor microenvironment, leading to discrepancies in drug response and therapeutic efficacy. This perspective explores the transition from 2D to 3D culture models, highlighting their advantages, limitations, and impact on cancer research. Various 3D culture approaches, including scaffold-based systems, hydrogels, 3D-printed models, microfluidics, and organ-on-a-chip technologies, are discussed in terms of their relevance to cancer modeling and drug testing. Additionally, the review also highlights the integration of theranostic nano- and microparticles in cancer treatment, focusing on their application in drug delivery and interactions with 3D tumor spheroids and organoids. A comparative analysis of uptake mechanisms and interactions between particles and 3D models is presented along with advanced techniques for probing nanoparticle behavior and drug screening in these models. By bridging the gap between in vitro assays and clinical outcomes, 3D culture systems integrated with nanotechnology offer promising tools for improving cancer therapeutics.

Cathodic protection (CP) is widely used to mitigate corrosion and protect the substrate. However, sacrificial anodes are often undersized or improperly positioned. This study systematically investigates how anode design factors affect the CP effectiveness through computational modelling and double-objective optimisation techniques around the optimum location and dimension of anodes. State-of-the-art algorithms including the Monte-Carlo, Nelder–Mead, co-ordinate search, constrained optimisation by linear approximation (COBYLA) and bound optimisation by quadratic approximation (BOBYQA) are employed to optimise anode locations and genetic algorithm is utilised for optimising anode dimension and the objective is maximising the current output and minimising the cost. In the current study, the BOBYQA technique proved efficient in reaching the optimal response at the appropriate time. The findings indicate that in double-objective (cost and potential) optimisation of 14.5 kg anode, minimising anode radius (from 6.5 cm to 5.4 cm) and optimising the position boosts the current output by up to 15.5%. Refined anode geometries increase the average structure potentials (806 → 822 mV) by over 15 mV, translating to extended service lifetimes. In the comparison of single (cost) and double (cost and potential)-objective optimisation, about 15% more current reaches the structure and causes about 2% less anode mass loss for the same anode dimensions. Also, the results show the 7.7 kg anode performs better than the 14.5 kg anode and so output current and the percentage of current that reaches the structure of the 7.7 kg and 14.5 kg are 0.66 A and 0.46 A and 66% and 60%, respectively.

Tebotelimab, a bispecific PD-1×LAG-3 DART molecule that blocks both PD-1 and LAG-3, was investigated for clinical safety and activity in a phase 1 dose-escalation and cohort-expansion clinical trial in patients with solid tumors or hematologic malignancies and disease progression on previous treatment. Primary endpoints were safety and maximum tolerated dose of tebotelimab when administered as a single agent (n = 269) or in combination with the anti-HER2 antibody margetuximab (n = 84). Secondary endpoints included anti-tumor activity. In patients with advanced cancer treated with tebotelimab monotherapy, 68% (184/269) experienced treatment-related adverse events (TRAEs; 22% were grade ≥3). No maximum tolerated dose was defined; the recommended phase 2 dose (RP2D) was 600 mg once every 2 weeks. There were tumor decreases in 34% (59/172) of response-evaluable patients in the dose-escalation cohorts, with objective responses in multiple solid tumor types, including PD-1-refractory disease, and in LAG-3+ non-Hodgkin lymphomas, including CAR-T refractory disease. To enhance potential anti-tumor responses, we tested margetuximab plus tebotelimab. In patients with HER2+ tumors treated with tebotelimab plus margetuximab, 74% (62/84) had TRAEs (17% were grade ≥3). The RP2D was 600 mg once every 3 weeks. The confirmed objective response rate in these patients was 19% (14/72), including responses in patients typically not responsive to anti-HER2/anti-PD-1 combination therapy. ClinicalTrials.gov identifier: NCT03219268.

Abstract Cathodic protection as a complementary method is one of the most effective ways to prevent corrosion, along with coating and choosing the suitable material. There are different ways to protect the storage tank bottom. Due to the presence of the geo membrane layer and its effective and pivotal role, the use of mixed metal oxide (MMO) anodes is highly recommended. In the current study, the protection process of the above-ground storage tank bottom is simulated using MMO backfilled wire (Concentric Rings) and ribbon anodes (Mesh Grid System). In this regard, several parameters must be considered in reaching the protection criteria. The simulation results show that the effect of the spacing between the anodes, the limiting oxygen current density and the anodic current have the greatest role. Anode depth and soil resistance are also critical factors. Due to the importance of the number of conductor bars and feeding cables, two configurations have been presented for ribbon anodes. These configurations have a direct impact on grid resistance, rectifier size, and related costs. Finally, an economic comparison has been made regarding the use of sacrificial and MMO anodes in the form of ribbon next to wire anodes. The results show that, in the use of ribbon anodes, MMO anodes have better performance than magnesium and zinc sacrificial anodes, and the cost required for MMO linear anodes is far lower than the method of sacrificial ribbon anodes. In the present study, the linear anode system has an estimated cost of approximately 20% less than the ribbon sacrificial anodes made of magnesium and zinc.

<p>Supplementary figures and tables Figure S1 PK/PD experimental design. This figure details the dose and sampling strategies for the PK/PD endpoints for all animal groups. Figure S2 Detailed structural PK/PD model of MGD006 administrated in cynomolgus monkeys. This figure supplements Fig. 1. Figure S3 Categorization of anti-drug antibody (ADA) development. This figure describes the method used to categorize the ADA effect in three different groups. Table S1 ADA development groups. This table summarizes the different identified groups and the number of animals in each group. Table S2 Parameter definitions of PK/ADA, total T-cell, and CD123+-cell models. Figure S4 /S5 /S6 Time-course of observed and model-fitted plasma MGD006 concentrations, total T-cell counts, and CD123+-cell counts following continuous 4-day infusion in cynomolgus monkeys. This figure supplements Fig. 3. Figure S7 Goodness-of-fit plots for PK, total T-cell, and CD123+-cell models: individual predictions vs. observations and individual weighted residuals vs. time. Figure S8 Prediction-corrected visual predictive checks (PC-VPC) of PK, total T-cell, and CD123+-cell models. Figure S9 /S10 /S11 External validation of the PK, total T-cell, and CD123+-cell models by VPC with data collected in animals following continous 7-day infusions. These figures supplement Fig. 4.</p>