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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.

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At least 757 records · Page 42

Optimum Design of a Compound Helicopter

A design and aeromechanics investigation was conducted for a 100,000-lb compound helicopter with a single main rotor, which is to cruise at 250 knots at 4000 ft/95 deg F condition. Performance, stability, and control analyses were conducted with the comprehensive rotorcraft analysis CAMRAD II. Wind tunnel test measurements of the performance of the H-34 and UH-1D rotors at high advance ratio were compared with calculations to assess the accuracy of the analysis for the design of a high speed helicopter. In general, good correlation was obtained when an increase of drag coefficients in the reverse flow region was implemented. An assessment of various design parameters (disk loading, blade loading, wing loading) on the performance of the compound helicopter was conducted. Lower wing loading (larger wing area) and higher blade loading (smaller blade chord) increased aircraft lift-to-drag ratio. However, disk loading has a small influence on aircraft lift-to-drag ratio. A rotor parametric study showed that most of the benefit of slowing the rotor occurred at the initial 20 to 30% reduction of the advancing blade tip Mach number. No stability issues were observed with the current design. Control derivatives did not change significantly with speed, but the did exhibit significant coupling.

Yeo, Hyeonsoo↗

A spin-filter made of quantum anomalous Hall insulator nanowires

Topological end states (TES) in quantum anomalous Hall insulator nanowires can induce tunneling within the gap. Such TES are spin polarized, thus the induced current is spin polarized as well, which can be used to construct a spin-filter applied in spintronics. An interferometry device is designed to control the polarized current as well. The advantage and finite size effect on this system are discussed.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Dynamic, Adaptive, Systems and Materials: Complex, Simple and Emergent Behaviors

This program has been funded by DoE/BES for twenty years. It has moved into and out of various subjects as it has developed, but it has retained its focus on complexity and complex systems. The project has evolved in the following way: Self-Assembly and Biomimetic Self-Assembly: All self-assembling systems depend upon a minimum of two types of interaction: a repulsion and an attraction. For the familiar molecular systems, attractive interactions are typically hydrogen bonds and electrostatic interactions. Repulsive interactions include steric effects, hydrophobic effects (in biological systems), and charge-charge repulsion. We have expanded this repertoire to include surface interactions, magnetic interactions, and others. I list these systems in the order in which we have explored them: i) A key emphasis in current work is in understanding how the movement of ions in a magnetic field (the Lorentz effect) interacts with catalytic systems. We have demonstrated that an acceleration in rate of reduction of CO 2 to CO can be accomplished by applying an external magnetic field. This acceleration is largely due to the application of the Lorentz effect on mass transport at the catalyst’s surface. ii) We have also extensively explored the influence of electrostatics, as exhibited in self-assembling systems, by tribocharging. iii) Another key system involves surface tension effects; examples include interactions between heavy particles floating at a liquid-air interface, and interacting by changes in surface area; interactions of bubbles and bubble rafts, behaviors of bubble trains in microfluidic networks, and behaviors of microorganisms in constraining environments. iv) This work has intentionally de-emphasized biological systems; but it does include some work on protein-ligand interactions and interactions among microorganisms. v) We have also explored applications of some of these effects, these explorations include bubble rafts as diffraction gratings, exploration of the structures that can be obtained by tribocharging and uses of these structures in exploring nucleation and melting of crystals. vi) Although not a major focus of this work, several other topics have emerged and offer opportunities for future work. These include the behavior of bubble trains and bubble rafts in microfluidic systems. A particularly interesting example is the formation of bubble trains that repeat in the alteration of large and small bubbles according to rules we do not presently understand, but are uniquely large-period oscillating systems. These systems offer a new route into understanding the instabilities of the type represented by oscillations. vii) We have also begun exploratory projects on magnetic levitation (especially to determine molecular density), and information storage (in molecules). Magnetic Levitation: Self-assembling and biomimetic systems require both attraction and repulsion. We have used electrostatics (tribocharging), interfacial free-energies (surface tension and related forces) and others. Potential uses include reconfigurable diffraction gratings and liquid lenses; exploration of mechanisms in tribocharging; tunneling in EGaIn junctions; and bubble trains (especially in micro-fluidic systems). Examples of systems representing these topics is included in the following papers: Complexity: Disks rotating at a water-air interface; Benard-Marangoni effects; Vortex-Crystals from spinning magnetic disks (Marangoni effects); EGaIn Electrode to study quantum tunneling; Self-Assembly of electrostatically-charged metallic spheres (electrets); Dynamically reconfigurable lens; Using computational designs of ligands for enzymes; Electrostatic self-assembly by tribocharging; Monodisperse bubble trains in microchannel systems; Inverted dripping faucet; Flames; Printing of micro-organisms to regenerate the “ink” of printing device; Using micro-organisms to move loads (“microoxen”); Motion of bacterial swarms near surfaces; Making monodisperse particles in microfluidic systems; Coding/decoding of information stored in droplet trains in microfluidic networks; Magnetic levitation; and Information storage. i) Tribocharging. The change in focus of this work on electrets from the fundamentals of charging to applications of these materials in studying self-assembly using electrostatic interactions. ii) Bubbles in Microchannels. The realization that systems of bubbles in microchannels represented a major opportunity to study complexity in a very tractable system, and the development of a semi-quantitative theory of this subject. iii) Flames. The growth of “flames” remains an exploratory subject for the research, although their currently relatively little active work involving it ongoing. iv) Systems with Microorganisms. The removal of work in biological systems from this project. Based on work supported in this program, we now have a significant project on the development of microfluidic tools for studying C. elegans (a nematode), but this work was not appropriate for a program focused on complexity, and we developed separate support for it. (It is, however, an example of successful seeding of a new area by BES.) The work on electrets has gone through a period in which a part of the program was the subject of a MURI; the focus of this work was to develop materials that did not charge electrostatically on friction or contact. The MURI is now over, and the work on dynamic self-assembly (supported by BES) is the major focus. “Flames” has also enjoyed synergistic support, in terms of a project supported by DARPA on flame suppression (in the absence of extinguishing agents, using acoustic and electrostatic interactions). This work was helpful in understanding some of the basics of flames, but is entirely distinct from the BES focus in complexity. A growing interest is in the Lorentz effect. The Lorentz effect is the force exerted on charged particles (electrons, ions, charged molecules) when they move through a perpendicular magnetic field. The Lorentz effect is almost ubiquitous in modern technology: examples of applications include electric motors, dynamos, cathode ray tubes, many batteries, and most systems that control electrical currents with magnetic forces. We have begun to explore the Lorentz effect in electrochemical systems and heterogeneous catalytic systems involving charged organic species and inorganic ions. This work is still at an early stage, but initial studies that Lorentz effects can be large when ions move through magnetic fields, or magnetic fields move in the presence of ions.

36 MATERIALS SCIENCE↗

Collaborative Arrival Planning: Data Sharing and User Preference Tools

Air traffic growth and air carrier economic pressures have motivated efforts to increase the flexibility of the air traffic management process and change the relationship between the air traffic control service provider and the system user. One of the most visible of these efforts is the U.S. government/industry "free flight" initiative, in which the service provider concentrates on safety and cross-airline fairness, and the user on their business objectives and operating preferences, including selecting their own path and speed in real-time. In the terminal arrival phase of flight, severe restrictions and rigid control are currently placed on system users, typically without regard for individual user operational preferences. Airborne delays applied to arriving aircraft into capacity constrained airports are imposed on a first-come, first-serve basis, and thus do not allow the system user to plan for or prioritize late arrivals, or to economically optimize their arrival sequence. A central tenant of the free-flight operating paradigm is collaboration between service providers and users in reaching air traffic management decisions. Such collaboration would be particularly beneficial to an airline's "hub" operation, where off-schedule arrival aircraft are a consistent problem, as they cause serious air-port ramp difficulties, rippling airline scheduling effects, and result in large economic inefficiencies. Greater collaboration can also lead to increased airport capacity and decrease the severity of over-capacity rush periods. In the NASA Collaborative Arrival Planning (CAP) project, both independent exchange of real-time data between the service provider and system user and collaborative decision support tools are addressed. Data exchange of real-time arrival scheduling, airspace management, and air carrier fleet data between the FAA service provider and an air carrier is being conducted and evaluated. Collaborative arrival decision support tools to allow intra-airline arrival preferences are being developed and simulated. The CAP project is part of and leveraged from the NASA/FAA Center TRACON Automation System (CTAS), a fielded set of decision support tools that provide computer generated advisories for both enroute and terminal area controllers to manage and control arrival traffic more efficiently. In this paper, the NASA Collaborative Arrival Planning project is outlined and recent results detailed, including the real-time use of CTAS arrival scheduling data by a major air carrier and simulations of tactical and strategic user preference decision support tools.

Zelenka, Richard E.↗

Stochastic Guidance of Buoyancy Controlled Vehicles under Ice Shelves using Ocean Currents

We propose a novel technique for guidance ofbuoyancy-controlled vehicles in uncertain under-ice ocean flows.In-situ melt rate measurements collected at the grounding zoneof Antarctic ice shelves, where the ice shelf meets the underlyingbedrock, are essential to constrain models of future sea levelrise. Buoyancy-controlled vehicles, which control their verticalposition in the water column but have no means of horizontalpropulsion, offer an affordable and reliable platform for suchin-situ data collection. However, reaching the grounding zonerequires vehicles to traverse tens of kilometers under the iceshelf, with approximate position knowledge and no meansof communication, in highly variable and uncertain oceancurrents. To address this challenge, we propose a partiallyobservable MDP approach that exploits model-based knowledgeof the under-ice currents and, critically, of their uncertainty,to synthesize effective guidance policies. The approach usesapproximate dynamic programming to model uncertainty inthe currents, and QMDP to address localization uncertainty.Numerical experiments show that the policy can deliver upto 88.8% of underwater vehicles to the grounding zone – a33% improvement compared to state-of-the-art guidance techniques, and a 262% improvement over uncontrolled drifters.Collectively, these results show that model-based under-iceguidance is a highly promising technique for exploration ofunder-ice cavities, and has the potential to enable cost-effectiveand scalable access to these challenging and rarely observed environments.

Clark, Evan B.↗

Including the temporal change in PM{sub 2.5} concentration in the assessment of human health impact: Illustration with renewable energy scenarios to 2050

This article proposes a new method to assess the health impact of populations exposed to fine particles (PM{sub 2.5}) during their whole lifetime, which is suitable for comparative analysis of energy scenarios. The method takes into account the variation of particle concentrations over time as well as the evolution of population cohorts. Its capabilities are demonstrated for two pathways of European energy system development up to 2050: the Baseline (BL) and the Low Carbon, Maximum Renewable Power (LC-MRP). These pathways were combined with three sets of assumptions about emission control measures: Current Legislation (CLE), Fixed Emission Factors (FEFs), and the Maximum Technically Feasible Reductions (MTFRs). Analysis was carried out for 45 European countries. Average PM{sub 2.5} concentration over Europe in the LC-MRP/CLE scenario is reduced by 58% compared with the BL/FEF case. Health impacts (expressed in days of loss of life expectancy) decrease by 21%. For the LC-MRP/MTFR scenario the average PM{sub 2.5} concentration is reduced by 85% and the health impact by 34%. The methodology was developed within the framework of the EU's FP7 EnerGEO project and was implemented in the Platform of Integrated Assessment (PIA). The Platform enables performing health impact assessments for various energy scenarios. - Highlights: • A new method to assess health impact of PM{sub 2.5} for energy scenarios is proposed. • An algorithm to compute Loss of Life Expectancy attributable to exposure to PM{sub 2.5} is depicted. • Its capabilities are demonstrated for two pathways of European energy system development up to 2050. • Integrating the temporal evolution of PM{sub 2.5} is of great interest for assessing the potential impacts of energy scenarios.

54 ENVIRONMENTAL SCIENCES↗

Low drift type N thermocouples in out-of-pile advanced gas reactor mock-up test: metallurgical analysis

Thermocouples are the most commonly used sensors for temperature measurement in nuclear reactors. They are crucial for the control of current nuclear reactors and for the development of GEN IV reactors. In nuclear applications thermocouples are strongly affected by intense neutron fluxes. As a result of the interaction with neutrons, the thermoelements of the thermocouples undergo transmutation, which produces a time dependent change in composition and, as a consequence, a time dependent drift of the thermocouple signal. Thermocouple drift can be very significant for in-pile temperature measurements and may render the temperature sensors unreliable after exposure to nuclear radiation for relatively short times compared to the life required for temperature sensors in nuclear applications. Previous experiences with type K thermocouples in nuclear reactors have shown that they are affected by neutron irradiation only to a limited extent. Similarly type N thermocouples are expected to be only slightly affected by neutron fluxes. Currently the use of Nickel based thermocouples is limited to temperatures lower than 1000 deg. C due to drift related to phenomena other than nuclear irradiation. As part of a collaboration between Idaho National Laboratory (INL) and the University of Cambridge a variety of Type N thermocouples have been exposed at INL in an Advanced Gas Reactor mock-up test at 1150 deg. C for 2000 h, 1200 deg. C for 2000 h, 125 deg. C for 200 h and 1300 deg. C for 200 h, and later analysed metallurgically at the University of Cambridge. The use of electron microscopy allows to identify the metallurgical changes occurring in the thermocouples during high temperature exposure and correlate the time dependent thermocouple drift with the microscopic changes experienced by the thermoelements of different thermocouple designs. In this paper conventional Inconel 600 sheathed type N thermocouples and a type N using a customized sheath developed at the University of Cambridge have been investigated. The rationale for the superior performance of the type N using a customized sheath developed at the University of Cambridge is explained in comparison with the behavior of conventional type N Inconel 600 sheathed thermocouples. (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Synthetic Reference-based Transition Optimal Control of Inverter for Surge-Current-Free Rapid Interface to Grid

This article addresses the problem of the transition between objective functions in optimal control for power inverters when switching between standalone and grid-connected modes. The work proposes the use of a synthetic reference during the transition between the corresponding objective functions. Moreover, the authors aim to show that a transition function can be imposed and controlled externally from the main optimal control routine. In the end, the simulation results demonstrate the importance of properly applying the proposed strategy for a smooth transition between the operating modes with minimal surge current. These results contrast with the strategies found in the literature where the smooth transition comes with the price of a few grid cycles to sync.

Roig Greidanus, Mateo D.↗

An Improved Distributed Secondary Control Method for DC Microgrids With Enhanced Dynamic Current Sharing Performance

This paper proposes an improved distributed secondary control scheme for dc microgrids (MGs), aiming at overcoming the drawbacks of conventional droop control method. The proposed secondary control scheme can remove the dc voltage deviation and improve the current sharing accuracy by using voltage-shifting and slope-adjusting approaches simultaneously. Meanwhile, the average value of droop coefficients is calculated, and then it is controlled by an additional controller included in the distributed secondary control layer to ensure that each droop coefficient converges at a reasonable value. Hence, by adjusting the droop coefficient, each participating converter has equal output impedance, and the accurate proportional load current sharing can be achieved with different line resistances. Furthermore, the current sharing performance in steady and transient states can be enhanced by using the proposed method. The effectiveness of the proposed method is verified by detailed experimental tests based on a 3 × 1 kW prototype with three interface converters.

30 DIRECT ENERGY CONVERSION↗

Large–Scale Syntheses of 2D Materials: Flash Joule Heating and Other Methods

In the past 17 years, the larger-scale production of graphene and graphene family materials has proven difficult and costly, thus slowing wider-scale commercial applications. Here, the quality of the graphene that is prepared on larger scales has often been poor, demonstrating a need for improved quality controls. Here, current industrial graphene synthetic and analytical methods, as well as recent academic advancements in larger-scale or sustainable synthesis of graphene, defined here as weights more than 200 mg or films larger than 200 cm 2 , are compiled and reviewed. There is a specific emphasis on recent research in the use of flash Joule heating as a rapid, efficient, and scalable method to produce graphene and other 2D nanomaterials. Reactor design, synthetic strategies, safety considerations, feedstock selection, Raman spectroscopy, and future outlooks for flash Joule heating syntheses are presented. To conclude, the remaining challenges and opportunities in the larger-scale synthesis of graphene and a perspective on the broader use of flash Joule heating for larger-scale 2D materials synthesis are discussed.

01 COAL, LIGNITE, AND PEAT↗

Adaptive changes in sexual behavior in the high–risk population in response to human monkeypox transmission in Canada can help control the outbreak: Insights from a two–group, two–route epidemic model

Monkeypox, a zoonotic disease, is emerging as a potential sexually transmitted infection/disease, with underlying transmission mechanisms still unclear. We devised a risk-structured, compartmental model, incorporating sexual behavior dynamics. We compared different strategies targeting the high-risk population: a scenario of control policies geared toward the use of condoms and/or sexual abstinence (robust control strategy) with risk compensation behavior change, and a scenario of control strategies with behavior change in response to the doubling rate (adaptive control strategy). Monkeypox's basic reproduction number is 1.464, 0.0066, and 1.461 in the high-risk, low-risk, and total populations, respectively, with the high-risk group being the major driver of monkeypox spread. Policies imposing condom use or sexual abstinence need to achieve a 35% minimum compliance rate to stop further transmission, while a combination of both can curb the spread with 10% compliance to abstinence and 25% to condom use. With risk compensation, the only option is to impose sexual abstinence by at least 35%. Adaptive control is more effective than robust control where the daily sexual contact number is reduced proportionally and remains constant thereafter, shortening the time to epidemic peak, lowering its size, facilitating disease attenuation, and playing a key role in controlling the current outbreak.

60 APPLIED LIFE SCIENCES↗

Impact of Lubricant Oil Additives on the Performance of Pd-Based Three-Way Catalysts

As alternative lubricant anti-wear additives are sought to reduce friction and improve overall fuel economy, it is important that these additives are also compatible with current emissions control catalysts. In the present work, a second-generation oil-miscible phosphorous-containing ionic liquid (IL), is evaluated for its impact on Pd-based three-way catalyst (TWC) reactivity and benchmarked against the industry standard zinc dialkyl-dithio-phosphate (ZDDP). The TWCs are exposed to the lubricant additives in an engine bench under four different scenarios: base case with no additive (NA), ZDDP-only, IL-only, and IL + ZDDP. The engine-aged TWC samples, along with the as-received TWC, are characterized through various analytical techniques including catalyst reactivity evaluation in a bench-flow reactor. The temperature of 50% conversion (T 50 ) for the ZDDP-aged TWC increases by 11, 21, and 36 °C for CO, C 3 H 6 , and C 3 H 8 , respectively, as compared with the no-additive case. Similarly, the T50 for IL-only and IL + ZDDP-aged TWCs also increase as compared with the no-additive case. Even though the water-gas-shift (WGS) reactivity is similar for all engine-aged samples, the IL-aged TWC had higher oxygen storage capacity than the ZDDP-aged TWC. EPMA analysis reveals penetration of phosphorus deep into the washcoat for all engine-aged TWCs. Results from XRD indicate the presence of CePO 4 and AlPO 4 on the washcoat of IL, ZDDP, and IL + ZDDP-aged TWC samples but not on the fresh and NA TWC samples. Additionally, ICP-OES results show a large amount of phosphorus in the washcoat of IL, ZDDP and IL + ZDDP-aged TWC samples and a lesser amount in NA TWC samples.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma

Highlights: Black-Right-Pointing-Pointer IL-33 is considered a new therapeutic target for reducing inflammation in asthma. Black-Right-Pointing-Pointer This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. Black-Right-Pointing-Pointer IL-33 also promotes fibrocyte proliferation without reducing collagen production. Black-Right-Pointing-Pointer The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.

60 APPLIED LIFE SCIENCES↗

Radiation-hard miniature optical engine with high bandwidth

Future silicon trackers will be operated in an intense radiation environment and require large volumes of data to be transmitted off detector. In addition, the optical modules must be of low mass in order to limit multiple scattering and nuclear interactions that would degrade the overall performance of the detector. Here, we present a miniature optical engine that satisfies these constraints. The optical engine consists of an ASIC driving a VCSEL (Vertical Cavity Surface Emitting Laser) array in an optical package. Two ASICs are designed to operate a 12-channel VCSEL array at 1.28 or 5.12 Gb/s per channel, which yields a total data rate of up to 60 Gb/s. The core transistors are fabricated in a 65 nm CMOS process which enhance the radiation-hardness. Each channel contains equalizer (CTLE) and clock-data recovery circuits (CDR) so that the ASIC can restore the highly distorted electrical signal after propagating through several meters of cables of small diameter. The equalizer, CDR, and VCSEL driver are configured via a digital I 2 C chip interface with triple redundant memory to mitigate single event upset (SEU) effects. The bias and modulation currents are controlled by a digital-to-analog converter (DAC). We present the design of the circuit together with the results of the simulations and preliminary measurements.

47 OTHER INSTRUMENTATION↗

Discovery of a magnetic conductive interface in PbZr 0.2 Ti 0.8 O 3 /SrTiO 3 heterostructures

Here, emergent physical properties often arise at interfaces of complex oxide heterostructures due to the interplay between various degrees of freedom, especially those with polar discontinuities. It is desirable to explore if these structures may generate pure and controllable spin currents, which are needed to attain unmatched performance and energy efficiency in the next-generation spintronic devices. Here we report the emergence of a spin-polarized two-dimensional electron gas (SP-2DEG) at the interface of two insulators, SrTiO 3 and PbZr 0.2 Ti 0.8 O 3 . This SP-2DEG is strongly localized at the interfacial Ti atoms, due to the interplay between Coulomb interaction and band bending, and can be tuned by the ferroelectric polarization. Our findings open a door for engineering ferroelectric/insulator interfaces to create tunable ferroic orders for magnetoelectric device applications and provide opportunities for designing multiferroic materials in heterostructures.

36 MATERIALS SCIENCE↗

Vanishing carrier-envelope-phase-sensitive response in optical-field photoemission from plasmonic nanoantennas

At the surfaces of nanostructures, enhanced electric fields can drive optical-field photoemission and thereby generate and control electrical currents at frequencies exceeding 100 THz. A hallmark of such optical-field photoemission is the sensitivity of the total emitted current to the carrier-envelope phase (CEP). In this work, we examine CEP-sensitive photoemission from plasmonic gold nanoantennas excited with few-cycle optical pulses. At a critical pulse energy, which we call a vanishing point, we observe a pronounced dip in the magnitude of the CEP-sensitive photocurrent accompanied by a sudden shift of π radians in the photocurrent phase. Analysis shows that this vanishing behaviour arises due to competition between sub-optical-cycle electron emission events from neighbouring optical half-cycles and that both the dip and phase shift are highly sensitive to the precise shape of the driving optical waveform at the surface of the emitter. As the mechanisms underlying the dip and phase shift are a general consequence of nonlinear, field-driven photoemission, they may be used to probe sub-optical-cycle emission processes from solid-state emitters, atoms and molecules. Improved understanding of these CEP-sensitive photocurrent features will be critical to the development of optical-field-driven photocathodes for time-domain metrology and microscopy applications demanding attosecond temporal and nanometre spatial resolution.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Structural basis for the activity and specificity of the immune checkpoint inhibitor lirilumab

The clinical success of immune checkpoint inhibitors has underscored the key role of the immune system in controlling cancer. Current FDA-approved immune checkpoint inhibitors target the regulatory receptor pathways of cytotoxic T-cells to enhance their anticancer responses. Despite an abundance of evidence that natural killer (NK) cells can also mediate potent anticancer activities, there are no FDA-approved inhibitors targeting NK cell specific checkpoint pathways. Lirilumab, the most clinically advanced NK cell checkpoint inhibitor, targets inhibitory killer immunoglobulin-like receptors (KIRs), however it has yet to conclusively demonstrate clinical efficacy. Here we describe the crystal structure of lirilumab in complex with the inhibitory KIR2DL3, revealing the precise epitope of lirilumab and the molecular mechanisms underlying KIR checkpoint blockade. Notably, the epitope includes several key amino acids that vary across the human population, and binding studies demonstrate the importance of these amino acids for lirilumab binding. These studies reveal how KIR variations in patients could influence the clinical efficacy of lirilumab and reveal general concepts for the development of immune checkpoint inhibitors targeting NK cells.

60 APPLIED LIFE SCIENCES↗