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Voltage errors occur in whole cell voltage clamp. We make, to our knowledge, the first direct measurements of these errors and find that voltage errors are far smaller than standard calculations would predict. Since voltage errors were often minimal during the measurement of large ion channel currents, this technique may be applied to large neurons of adults to gain insight into ion channel function across the life span and progression of disease.

We investigate the spatiotemporal dynamics and control of an epidemic using a partial differential equation (PDE) based Susceptible-Latent-Infected-Recovered (SLIR) model. We first validate the model using empirical COVID-19 data corresponding to a period of 45 days from the state of Ohio, United States. Upon optimizing the model parameters in the learning phase of the analysis using actual infection data from a period of the first 30 days, we then find that the model output closely tracks the actual data for the next 15 days. Next, we introduce a control input into the model to represent the Non-Pharmaceutical Intervention of social distancing. Implementing the control using two distinct schemes, we find that in both cases the control input is able to significantly mitigate the infection spread. In addition to opening a novel pathway towards the characterization, analysis and implementation of Non-Pharmaceutical Interventions across multiple geographical scales using Control frameworks, our results highlight the importance of first-principles based PDE models in understanding the spatiotemporal dynamics of epidemics triggered by novel pathogens.

The pseudohypohalous acid hypothiocyanite / hypothiocyanous acid (OSCN(−) / HOSCN) has been known to play an antimicrobial role in mammalian immunity for decades. It is a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN(−)) and hydrogen peroxide (H(2)O(2)) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste. However, despite the well-recognized antibacterial role HOSCN plays in host-pathogen interactions, little is known about how bacteria sense and respond to this oxidant. In this work, we will summarize what is known and unknown about HOSCN in innate immunity and recent advances in understanding the responses that both pathogenic and nonpathogenic bacteria mount against this antimicrobial agent, highlighting studies done with three model organisms, Escherichia coli, Streptococcus spp., and Pseudomonas aeruginosa.

Hypothiocyanite and hypothiocyanous acid (OSCN − /HOSCN) are pseudohypohalous acids released by the innate immune system which are capable of rapidly oxidizing sulfur-containing amino acids, causing significant protein aggregation and damage to invading bacteria. HOSCN is abundant in saliva and airway secretions and has long been considered a highly specific antimicrobial that is nearly harmless to mammalian cells. However, certain bacteria, commensal and pathogenic, are able to escape damage by HOSCN and other harmful antimicrobials during inflammation, which allows them to continue to grow and, in some cases, cause severe disease. The exact genes or mechanisms by which bacteria respond to HOSCN have not yet been elucidated. We have found, in Escherichia coli , that the flavoprotein RclA, previously implicated in reactive chlorine resistance, reduces HOSCN to thiocyanate with near-perfect catalytic efficiency and strongly protects E. coli against HOSCN toxicity. This is notable in E. coli because this species thrives in the chronically inflamed environment found in patients with inflammatory bowel disease and is able to compete with and outgrow other important commensal organisms, suggesting that HOSCN may be a relevant antimicrobial in the gut, which has not previously been explored. RclA is conserved in a variety of epithelium-colonizing bacteria, implicating its HOSCN reductase activity in a variety of host–microbe interactions. We show that an rclA mutant of the probiotic Limosilactobacillus reuteri is sensitive to HOSCN and that RclA homologs from Staphylococcus aureus , Streptococcus pneumoniae , and Bacteroides thetaiotaomicron all have potent protective activity against HOSCN when expressed in E. coli .

Noise characterization of cavitation has use in biomedicine, sonochemistry, and waste degradation. Typically, spectral features of the cavitation noise signals obtained through Fourier analysis are specific to the experimental set-up and are analyzed to classify the signals in terms of presumed domains of bubble behaviors. The objective of this research was to develop the experimental capabilities and algorithm to monitor and classify cavitation a priori using machine learning (ML) in a precise, repeatable, and translatable fashion among various setups and applications. Initially, simultaneous high-speed videos and passive acoustics maps were acquired for a single oscillating bubble in a simple setup. Machine learning methods such as support vector machine and convolutional neural networks were used to classify the acoustic data and train a classification algorithm. The algorithm was then adapted for a novel sonochemical reactor that induces spontaneous cavitation nucleation and utilizes a passive cavitation detector to monitor cavitation noise. Further research will be done in correlating potassium iodide (KI) degradation with frequency spectra using ML classification in order to optimize the sonochemical efficiency.

As ultrasonic techniques rapidly evolve to provide a host of cavitation-mediated therapies, it is fair to ask: how can we reconcile thedata obtained across patients and hardware systems? This talk will describe progress made towards achieving system- and patient-independentcavitation localization and dosimetry. Methods and results will be presented for the characterization, quantification, and correction of biasing factors in the propagation path and receiver system. The talk will conclude with a discussion of limitations and ongoing efforts to demonstrate the full suite of proposed techniques.

There is a current pressing need to develop novel platform cancer therapeutics that are efficient, reduce side effects, and are minimally invasive. One of these platforms is photodynamic therapy where light is used as an external stimulus to activate drugs at a target location; however, clinical applications are limited due to poor light penetration. Previously, it has been shown that ultrasound with and without cavitation nuclei can be used to activate photodynamic drugs (sonodynamic therapy – SDT); however, the mechanism of this activation remains unclear. Recently, sonoluminescence has been detected in real time using a photomultiplier tube setup, up to millisecond temporal resolution; however, the spectra of light produced as well as the associated intensity has yet to be characterized. A proposed mechanism for SDT is that this light produced can activate photodynamic drugs at the target location resulting in reactive oxygen species (ROS) production (which leads to cell death). However, through temporal uncoupling of ultrasound application and compound administration in vitro and in vivo, this work shows that intracellular uptake of compound via cell permeabilization (sonoporation) plays an important role in SDT-induced cell death and potentially explains the high levels of cell death observed for comparatively low concentrations of ROS.

Since the development of the original passive acoustic mapping (PAM) algorithm for cavitation imaging in 2008, which employed a conventional beamformer adapted from seismology (time exposure acoustics), sequential algorithmic improvements have sought to enhance spatial resolution, reduce computation time and enable increasingly setup-independent reporting of cavitation activity. These enhancements have included the use of frequency-domain rather than time-domain implementations to improve computational efficiency, the introduction of the Robust Capon Beamformer to reduce artefacts, sub-aperture processing to further increase frame rate and the implementation of corrections for frequency-dependent attenuation and for array sensitivity and diffraction to account for probe- and depth-related variability. Once these corrections are taken into account, current PAM algorithms produce accurate estimates of cavitation source strength at a single location, but not in the surrounding region, leading to inaccurate estimates of the total cavitation energy over the treatment volume. We present an energy-preserving and computationally efficient PAM algorithm based on Lucy-Richardson deconvolution, that enables the calculation of a set-up independent Cavitational Radiated Energy Density (CRED) that ensures cavitation images accurately reflect the total energy of radiated acoustic emissions within the imaging domain.

Dalton-Barron, NE, McLaren, SJ, Black, CJ, Gray, M, Jones, B, and Roe, G. Identifying contextual influences on training load: an example in professional rugby union. J Strength Cond Res 35(2): 503-511, 2021-We aimed to investigate the contextual factors influencing training load (TL), as determined by session rating of perceived exertion (sRPE-TL), accumulated within a match-to-match microcycle in rugby union players. Session rating of perceived exertion-TL data were collected daily from 35 professional rugby union players from the same team in the English Championship over the course of an in-season period. Players were split by positional groups (backs and forwards) and sRPE-TL data were categorized as: field-based on-feet sRPE-TL (sRPEField-TL), gym-based sRPE-TL (sRPEGym-TL), and the total summation of both (sRPETotal-TL). Three 2-level linear mixed models were built for each dependent variable in each positional group, with magnitude-based inferences applied. Long between-match recovery cycles (≥7 days) resulted in very likely to almost certainly small to moderate increases in sRPE-TL for all modalities and positions (fixed effect [mean range] = 28.5%-42.0%), apart from sRPEField-TL for forwards. For backs, there was a very likely small decrease in sRPEField-TL as the season progressed (-16.7% per trimester). Losing the last league match was associated with very likely and almost certainly small decreases in sRPETotal-TL and sRPEGym-TL for backs (-20.7% and -36.4%, respectively). Losing the last match in any competition resulted in a very likely small increase in sRPEField-TL (21.2%) and a possibly small decrease sRPEGym-TL (-18.5%) for backs-with a likely smaller sRPEGym-TL for forwards (-33.4%). The strength of the upcoming opposition had no effect on sRPE-TL. Our findings highlight some of the multifactorial contextual factors that must be considered when planning and evaluating training microcycles.

Bacterial biofilms present a major challenge to achieving effective antibiotic therapy, as these sessile communities of microbes confer protection to bacteria by decreasing antibiotic efficacy. Focused ultrasound can mechanically disrupt biofilms, offering a new ‘drug-free’ antibiotic paradigm. The goal of this work is to validate, quantify, and optimize the role of acoustic cavitation in the biofilm disruption process through spatiotemporal monitoring of cavitation activity. A clinical isolate strain of Staphylococcus aureus from native valve endocarditis was cultured for 72 hours within a flow channel to form a biofilm. A 1.1 MHz spherically focused transducer was used to expose the biofilm from below at a 45° angle. The in situ acoustic field was characterized with a fibre-optic hydrophone. A calibrated 5–11 MHz linear array was placed 25 mm above the biofilm in order to record acoustic emissions during biofilm disruption from which passive acoustic maps of cavitation could be derived. Biofilms were exposed to 4.5 MPa peak rarefactional pressure (derated), 10,000 cycles, at a 1 Hz PRF. Qualitative reduction of biofilms was assessed by live/dead staining with Syto 9/propidium iodide, which was correlated with cavitation activity observed in the passive acoustic maps.

Inorganic polyphosphate (polyP) is synthesized by bacteria under stressful environmental conditions and acts by a variety of mechanisms to promote cell survival. While the kinase that synthesizes polyP (PPK, encoded by the ppk gene) is well known, ppk transcription is not activated by environmental stress and little is understood about how environmental stress signals lead to polyP accumulation. Previous work has shown that the transcriptional regulators DksA, RpoN (σ54) and RpoE (σ24) positively regulate polyP production, but not ppk transcription, in Escherichia coli . In this work, we examine the role of the alternative sigma factor RpoN and nitrogen starvation stress response pathways in controlling polyP synthesis. We show that the RpoN enhancer binding proteins GlnG and GlrR impact polyP production, and uncover a new role for the nitrogen phosphotransferase regulator PtsN (EIIANtr) as a positive regulator of polyP production, acting upstream of DksA, downstream of RpoN and apparently independently of RpoE. However, neither these regulatory proteins nor common nitrogen metabolites appear to act directly on PPK, and the precise mechanism(s) by which polyP production is modulated after stress remain(s) unclear. Unexpectedly, we also found that the genes that impact polyP production vary depending on the composition of the rich media in which the cells were grown before exposure to polyP-inducing stress. These results constitute progress towards deciphering the regulatory networks driving polyP production under stress, and highlight the remarkable complexity of this regulation and its connections to a broad range of stress-sensing pathways.

The aim of this research was to explore the interaction between ultrasound-activated microbubbles (MBs) and Pseudomonas aeruginosa biofilms, specifically the effects of MB concentration, ultrasound exposure and substrate properties on bactericidal efficacy. Biofilms were grown using a Centre for Disease Control (CDC) bioreactor on polypropylene or stainless-steel coupons as acoustic analogues for soft and hard tissue, respectively. Biofilms were treated with different concentrations of phospholipid-shelled MBs (107–108 MB/mL), a sub-inhibitory concentration of gentamicin (4 µg/mL) and 1-MHz ultrasound with a continuous or pulsed (100-kHz pulse repetition frequency, 25% duty cycle, 0.5-MPa peak-to-peak pressure) wave. The effect of repeated ultrasound exposure with intervals of either 15- or 60-min was also investigated. With polypropylene coupons, the greatest bactericidal effect was achieved with 2 × 5 min of pulsed ultrasound separated by 60 min and a microbubble concentration of 5 × 107 MBs/mL. A 0.76 log (83%) additional reduction in the number of bacteria was achieved compared with the use of an antibiotic alone. With stainless-steel coupons, a 67% (0.46 log) reduction was obtained under the same exposure conditions, possibly due to enhancement of a standing wave field which inhibited MB penetration in the biofilm. These findings demonstrate the importance of treatment parameter selection in antimicrobial applications of MBs and ultrasound in different tissue environments.

The software engineering community is facing challenges from quantum computers (QCs). In the era of quantum computing, Shor's algorithm running on QCs can break asymmetric encryption algorithms that classical computers practically cannot. Though the exact date when QCs will become "dangerous" for practical problems is unknown, the consensus is that this future is near. Thus, the software engineering community needs to start making software ready for quantum attacks and ensure quantum safety proactively. We argue that the problem of evolving existing software to quantum-safe software is very similar to the Y2K bug. Thus, we leverage some best practices from the Y2K bug and propose our roadmap, called 7E, which gives developers a structured way to prepare for quantum attacks. It is intended to help developers start planning for the creation of new software and the evolution of cryptography in existing software. In this paper, we use a case study to validate the viability of 7E. Our software under study is the IBM Db2 database system. We upgrade the current cryptographic schemes to post-quantum cryptographic ones (using Kyber and Dilithium schemes) and report our findings and lessons learned. We show that the 7E roadmap effectively plans the evolution of existing software security features towards quantum safety, but it does require minor revisions. We incorporate our experience with IBM Db2 into the revised 7E roadmap. The U.S. Department of Commerce's National Institute of Standards and Technology is finalizing the post-quantum cryptographic standard. The software engineering community needs to start getting prepared for the quantum advantage era. We hope that our experiential study with IBM Db2 and the 7E roadmap will help the community prepare existing software for quantum attacks in a structured manner., 25 pages, 4 figures

Coral reef soundscapes are increasingly studied for their ecological uses by invertebrates and fishes, their applications for monitoring habitat quality, and to investigate effects of anthropogenic noise pollution. Few examinations of aquatic soundscapes have reported particle motion levels and variability, despite their relevance to invertebrates and fishes. We quantified ambient particle acceleration from orthogonal hydrophone arrays over several months at four coral reef sites in the U.S. Virgin Islands, which varied in benthic habitat and fish communities. Temporal trends of particle acceleration were similar to those of sound pressure, and the strength of diel trends in both metrics significantly correlated with percent coral cover. Low frequency (

This paper focusses on the coin that, according to the Synoptics, was presented to Jesus over the question of paying tribute to Caesar, not so much which kind of coin it was (though the issue is mentioned) but whose head was on the coin.

Traditional antibody-drug conjugates (ADCs) selectively deliver cytotoxic payloads to tumor-associated antigen (TAA)-expressing tumor cells, thereby limiting healthy cell damage and toxicities associated with systemic administration. Analogously, a novel class of immune-stimulating antibody conjugates (ISACs) has recently emerged to achieve tumor-targeted activation of anti-tumor immune responses, avoiding dose-limiting immunotoxicities seen with the systemic immune agonist delivery. Most of the ADC or ISAC to date utilize random payload conjugation to native surface-exposed lysines or cysteines, and relatively labile linkage chemistries, leading to conjugation site and drug-to-antibody ratio (DAR) heterogeneity, and ADC/ISAC instability in systemic circulation. In particular, the presence of high-DAR species and linker instability can lead to off-tumor toxicity, thus limiting the therapeutic window. Here we describe the generation and preclinical characterization of a site-specific TLR7-agonist (TLR7a) ISAC targeting an undisclosed TAA1. To specify the conjugation site and DAR, a non-natural amino acid (nnAA), para-acetyl-L-phenylalanine (pAF) was genetically incorporated at defined sites within the anti-TAA1 antibody, providing an orthogonal chemical handle for covalent TLR7 agonist payload conjugation through a highly stable oxime bond. Using this site-specific, homogenous ISAC platform, we systematically screened different conjugate sites and TLR7 agonist payloads to obtain an optimized TAA1-TLR7a ISAC drug candidate. ISAC platform stability, homogeneity, and flexibility were critical, because conjugation site and payload structure dramatically influenced ISAC in vitro activity, PK profile and in vivo efficacy. Using in vitro co-culture assays with human immune cells and tumor cell lines, we showed that the optimized TAA1 ISAC can induce multiple anti-tumor immune mechanisms, including proinflammatory cytokine production, the myeloid cell activation markers induction and enhanced ADCC mediated tumor cell killing. The TAA1 ISAC is 100-fold more active than the free, unconjugated TLR7 agonist, and all activity is conditional on the presence of TAA1-expressing tumor cells. Finally, we demonstrated in vivo efficacy in both xenograft and syngeneic tumor models. In a syngeneic MC38-tumor model expressing human TAA1, ISAC treatment led to complete tumor regression and formation of immunologic memory. These results provide a strong rationale for site-specific TLR7 agonist ISAC as a next generation platform for tumor-targeted, innate immune agonist immunotherapy. Citation Format: Mingchao Kang, Sung-Ju Moon, Ji Young Kim, Andy Beck, Molly Allen, Jay Nelson, Keith Tatsukawa, Hon Tran, Manoj Pal, Michael Gray, Nick Knudsen, Lillian Skidmore, David Mills, Yingchun Lu, Ying Buechler, Sukumar Sakamuri, Shawn Zhang, Feng Tian. Tumor-targeted immune activation via a site-specific TLR7-agonist antibody-drug conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5616.

The biological effects of acoustic cavitation are mediated by a range of phenomena associated with different types of bubble activity, e.g., micro-streaming, micro-jetting, and shockwave generation. The acoustic emissions generated by cavitation are also correlated to bubble dynamics. Hence, monitoring these emissions during ultrasound therapy is desirable, to maximise treatment safety and efficacy. The precise relationship between the spectral content of acoustic emissions and bubble dynamics is, however, less well understood. The aim of this study was to use simultaneous ultra-high-speed optical imaging (1–10 MHz) and passive acoustic mapping to characterise the behaviour of individual and clusters of microbubbles over a range of ultrasound exposures. As expected from the literature and numerical modelling, both the number of discrete harmonic components and amplitude of broadband content in the emissions increased with increasing amplitude of bubble oscillation. This suggests that passive acoustic mapping provides a useful indicator of spherical bubble behaviour. Frequently, however, complex bubble behaviour, such as fragmentation and coalescence was observed, which could produce substantially different effects in tissue compared with spherical bubble collapse. Future work will focus on determining whether these differences can be adequately captured in defining a future cavitation “dose” based on acoustic emissions for different applications.

The immune response is governed by the dynamic spatiotemporal regulation of signalling proteins at the interface between immune cells and their targets. The broadened knowledge of immunology and antitumour immune responses has led to the development of a novel cancer therapy avenue: immunotherapy. Elucidating the underlying mechanisms of immunotherapy is, however, crucial as in some patients, and it is accompanied by a characteristic toxicity profile and severe side effects such as autoimmune endocrinopathies. This requires quantitative investigation of cell-cell interactions, including the cell membrane receptors and their molecular behaviour upon cellular contact. This work applies a novel strategy employing protein-loaded microbubbles and confocal fluorescence microscopy to investigate cavitation-induced microbubble-cell membrane interactions. To this end, microbubbles functionalised with a model protein were successfully produced and characterised using nickelated lipids and His-tagged proteins as an efficient tagging strategy. These microbubbles form a novel platform for studying the impact of changing ultrasound parameters on the non-invasive delivery of these proteins to target cells, by means of transfer and/or fusion. This knowledge will be applied to explore efficient targeting strategies for custom-made functionalised bubbles to increase their visibility to immune cells.

We investigate the spatiotemporal dynamics and control of an epidemic using a partial differential equation (PDE) based Susceptible-Latent-Infected-Recovered (SLIR) model. We first validate the model using empirical COVID-19 data corresponding to a period of 45 days from the state of Ohio, United States. Upon optimizing the model parameters in the learning phase of the analysis using actual infection data from a period of the first 30 days, we then find that the model output closely tracks the actual data for the next 15 days. Next, we introduce a control input into the model to represent the Non-Pharmaceutical Intervention of social distancing. Implementing the control using two distinct schemes, we find that in both cases the control input is able to significantly mitigate the infection spread. In addition to opening a novel pathway towards the characterization, analysis and implementation of Non-Pharmaceutical Interventions across multiple geographical scales using Control frameworks, our results highlight the importance of first-principles based PDE models in understanding the spatiotemporal dynamics of epidemics triggered by novel pathogens.

Vapor pressure osmometry presents a convenient method to measure chemical activity. The work presented here was carried out to provide confidence in using this technique for a VPO model that does not utilize the "hanging-drop" method. While validation studies are available for certain models of vapor pressure osmometers, none were located for the UIC Jupiter 833 osmometer. This study addresses that need by providing a comparison between original experimental data on sodium chloride, calcium chloride, and sodium sulfate solutions to values calculated using the Pitzer equations. A comparison is also made for experimental data on sucrose with a literature correlation. This study briefly reviews the assumptions going into the equation used to relate the osmometer signal to the diluent activity in order to identify potential sources of the error and the noise in the data. The experimental data shows that the UIC 833 osmometer yields diluent activity values accurate to an average of 0.02%, allowing calculation of osmotic coefficients and solute activity coefficients. Further studies need to be conducted on the accuracy at concentrations above 1.4 m. Qualitatively, however, comparison suggests the UIC Jupiter 833 osmometer yields more scatter in the experimental data than the Knauer instruments. Using more uniform mesh caps on the thermistors could possibly reduce that scatter. Finally, we show that replacing the glass thermistors with in-house made thermistors with Teflon incorporated in the structure give reproducible results and that certain modifications to the design are possible without losing accuracy in the measurements.

Purpose: To identify which combination metrics of external and internal training load (TL) capture similar or unique information for individual professional players during skills training in rugby union using principal-component (PC) analysis. Methods: TL data were collected from 21 male professional rugby union players across a competitive season. This included PlayerLoad™, total distance, and individualized high-speed distance (>61% maximal velocity; all external TL) obtained from a microtechnology device (OptimEye X4; Catapult Innovations, Melbourne, Australia) that was worn by each player and the session rating of perceived exertion (RPE) (internal TL). PC analysis was conducted on each individual to extract the underlying combinations of the 4 TL measures that best describe the total information (variance) provided by the measures. TL measures with PC loadings (PCL) above 0.7 were deemed to possess well-defined relationships with the extracted PC. Results: The findings show that from the 4 TL measures, the majority of an individual’s TL information (first PC: 55–70%) during skills training can be explained by session RPE (PCL: 0.72–0.95), total distance (PCL: 0.86–0.98), or PlayerLoad (PCL: 0.71–0.98). High-speed distance was the only variable to relate to the second PC (PCL: 0.72–1.00), which captured additional TL information (+19–28%). Conclusions: Findings suggest that practitioners could quantify the TL of rugby union skills training with one of PlayerLoad, total distance, or session RPE plus high-speed distance while limiting omitted information of the TL imposed during professional rugby union skills training.

In October 2013, five weathered specimens of botryoidal opal rough showing moderate green daylight luminescence were received from Ruben Avila (Gemimex), well-known El Paso-Juarez based importer of...

Tyro3, Axl, and Mertk (collectively TAM receptors) are three homologous receptor tyrosine kinases that bind vitamin K–dependent endogenous ligands, Protein S (ProS), and growth arrest–specific factor 6 (Gas6), and act as bridging molecules to promote phosphatidylserine (PS)-mediated clearance of apoptotic cells (efferocytosis). TAM receptors are overexpressed in a vast array of tumor types, whereby the level of expression correlates with the tumor grade and the emergence of chemo- and radioresistance to targeted therapeutics, but also have been implicated as inhibitory receptors on infiltrating myeloid-derived cells in the tumor microenvironment that can suppress host antitumor immunity. In the present study, we utilized TAM-IFNγR1 reporter lines and expressed TAM receptors in a variety of epithelial cell model systems to show that each TAM receptor has a unique pattern of activation by Gas6 or ProS, as well as unique dependency for PS on apoptotic cells and PS liposomes for activity. In addition, we leveraged this system to engineer epithelial cells that express wild-type TAM receptors and show that although each receptor can promote PS-mediated efferocytosis, AKT-mediated chemoresistance, as well as upregulate the immune checkpoint molecule PD-L1 on tumor cells, Mertk is most dominant in the aforementioned pathways. Functionally, TAM receptor–mediated efferocytosis could be partially blocked by PS-targeting antibody 11.31 and Annexin V, demonstrating the existence of a PS/PS receptor (i.e., TAM receptor)/PD-L1 axis that operates in epithelial cells to foster immune escape. These data provide a rationale that PS-targeting, anti–TAM receptor, and anti–PD-L1-based therapeutics will have merit as combinatorial checkpoint inhibitors. Implications: Many tumor cells are known to upregulate the immune checkpoint inhibitor PD-L1. This study demonstrates a role for PS and TAM receptors in the regulation of PD-L1 on cancer cells. Mol Cancer Res; 15(6); 753–64. ©2017 AACR.