Additional Signal Research Articles

PPARα agonist ameliorates cholestatic liver injury by regulating hepatic macrophage homeostasis.

Inflammatory response plays an essential role in the pathogenesis of cholestatic liver injury. PPARα agonists have been shown to regulate bile acid homeostasis and hepatic inflammation. However, the immunoregulatory mechanisms through which PPARα agonists ameliorate cholestatic liver injury remain unclear. In this study, surgical bile duct ligation was performed to establish a mouse model of cholestasis. Our study revealed that PPARα agonist alleviated cholestatic liver injury in mice by suppressing inflammatory response, reducing neutrophil infiltration, and promoting M2-like macrophage polarization. CyTOF analysis showed that PPARα agonist increased the proportion of anti-inflammatory F4/80hiCD44+MHCII- M2-like macrophages while decreasing the proportion of pro-inflammatory CD64+CX3CR1+CCR2hiVISTAhiCD172a+CD44hi M1-like MoMFs. Additionally, scRNA-seq indicated that PPARα agonist regulated the developmental trajectory and homeostasis of hepatic macrophages. Mechanistically, PPARα agonist may influence the expression of immune regulators in heterogeneous macrophages to exert protective effects against cholestasis. In addition, the CCL and MIF signaling pathways may participate in the communication among hepatic immune cells, including macrophages, neutrophils, natural killer cells, and dendritic cells, in response to the PPARα agonist. In conclusions, PPARα agonist alleviated cholestatic liver injury by attenuating the inflammatory response and restoring hepatic macrophage homeostasis. This study might enhance the understanding of the immunoregulatory mechanisms of PPARα agonists, providing promising therapeutic targets for cholestatic liver diseases.

Lightning and radar measures of mixed phase updraft variability in tracked storms during the TRACER field campaign in Houston, Texas

Abstract Properties of 7488 thunderstorms are summarized for June-September 2022 during the TRACER field campaign Houston, Texas using polarimetric weather radar and VHF 3D lightning mapping array data. Automated tracking of storms linked each instrument’s measurements to a data-defined, time-evolving storm footprint. Within each storm, the depth and magnitude of episodic columns of radar differential reflectivity and specific differential phase quantified the prevalence of updrafts that activated mixed-phase precipitation pathways. Lightning measurements further distinguished the degree of rimed precipitation formation: the fraction of tracks with lightning varied from day to day, and cells with lightning had stronger polarimetric columns. Track-level correlation of lightning flash rate with radar polarimetric measures had substantial spread, showing that lightning provides an additional signal of mixed-phase precipitation processes that can complement future studies of thermodynamic and aerosol controls on cloud microphysics in the Houston region.

Enhancement of cyclic spectral coherence map by statistical testing approach—application to bearing faults diagnosis in electric motors

Abstract Efficiency of fault detection in rolling element bearings is heavily influenced by the quality of data. In controlled environments, such as test rigs designed for bearing diagnostics, data quality is relatively good. Similarly, diagnosing bearings that support shafts in industrial machinery is relatively straightforward. However, diagnosing bearings in electric motors presents greater complexity due to the influence of additional cyclic components on vibration signals. These extra components, originating from mechanical or electrical sources, complicate frequency-based analysis.
This paper proposes a novel approach for diagnosing bearings in electric motors, utilizing statistical analysis within the bi-frequency domain through a cyclostationary framework. The method involves applying a statistical testing procedure to individual pixels on the Cyclic Spectral Coherence (CSC) map. The statistical significance of these pixels is assessed based on quantiles of CSC maps obtained from a dataset representing a healthy bearing. This process results in an enhanced or cleaned CSC map, facilitating the identification of fault-related components. Consequently, this approach enables the detection of defects in electric motor bearings, even when additional signal components unrelated to the defect, but characteristic of a healthy bearing, are present.

More than stridulation: signal interaction and constraint in the complex vibroacoustic courtship of a cricket

Field crickets (Gryllidae) produce sounds by tegminal stridulation, well-studied for its role in female attraction and choice. However, understanding female preferences for their courtship song remains elusive, despite considering additional chemical, visual, and thermal signals. Beyond stridulation, crickets also display vibrational courtship behaviours that remain largely unexplored. Using Acheta domesticus as a model, we conduct the first comprehensive analysis of the entirety of vibroacoustic courtship signals in crickets, including their interaction. Employing audio recording, laser vibrometry, and videorecording, we unveil a complex signal involving simultaneous wing stridulation, body tremulation, and leg drumming against the substrate in a prolonged display, unique among insects. We identify robust correlations, coupling, and coordination between these signal components. We show the tightest coupling between the two types of stridulation pulses, and between tremulation and drumming signals, while drumming-stridulation coupling is less consistent, revealing a constraint on drumming performance. This constraint in the expression of one signal component, without a trade-off, represents a specific case within complex dynamic signalling. In addition, we find no correlation between drumming rate and its accuracy relative to stridulation, challenging common expectations. Our findings indicate that the information conveyed by the complex courtship display in A. domesticus is not simply proportional to that in the song, shedding light on previous ambiguities surrounding its function. Spectral-intensity analysis indicates the closest perceptual connection between stridulation and drumming signals, likely commonly influencing female choice, while proposing another function for tremulation. Further research should delve deeper into the function of this intricate signal.

A memristor‐sourced key for encrypted power and data synchronous transmission in switched mode power supplies

AbstractIn power and data synchronous transmission (PDST), it is crucial to modulate additional signals onto the voltage bus of the converters. This reduces the cost of monitoring and control of the power grid. There is thus the need to ensure that the data transmitted is well secured. This study, designs an electronic system that uses the common coupling point for PDST. Then Chua's memristive circuit is introduced as an entropy source for generating a random bit sequence for encrypted PDST in a switched mode power supply. The encrypted data signal is modulated using phase shift key modulation. Thereafter, the carrier signal is pulse width modulation modulated to control the switching operation of the power switch. The use of Chua's memristive circuit for generating a random number is not new; however, there is little study directly adopting its use in PDST. This allows for resource sharing since multiple signal sources can share the same bus without interference or security risk. The generated random bits are tested for randomness using National Institute of Standards and Technology test suite and autocorrelation test. MATLAB/Simulink and experimental results both confirm the effectiveness of the proposed data encryption method.

Sodium-dependent glucose co-transport proteins (SGLTs) are not involved in human glucose taste detection

The sweet taste of saccharides, such as sucrose and glucose, and other sweeteners is known to result from activation of the TAS1R2/R3 receptor expressed in taste receptor cells (TRCs) of the taste bud. Recent reports have suggested the existence of an additional sweet taste signaling pathway for metabolizable saccharides that is dependent on the activity of glucose transporters, especially SGLT1, also expressed in TRCs. We have investigated the potential contribution of SGLT1 to glucose taste signaling in humans. Concentration-response analysis of glucose mediated changes in membrane potential measured in Chinese hamster ovary (CHO) cells transiently expressing the human SGLT1 (hSGLT1) yielded an EC50 value of 452 μM. The SGLT inhibitor phlorizin inhibited the membrane potential response to 10 mM glucose with an IC50 of 3.5 μM. In contrast, EC50 values of 127 and 132 mM were obtained from concentration-response analysis of glucose taste in vehicles of water or 20 mM NaCl, respectively, by rapid throughput taste discrimination with human subjects. Lactisole, an antagonist of TAS1R2/R3, at a concentration of 1 mM completely inhibited taste responses to glucose concentrations of 250 mM and below. Phlorizin (0.2 mM) and the high potency SGLT1-selective inhibitor mizagliflozin (10 μM) failed to inhibit glucose taste detection measured at peri-threshold concentrations in the rapid throughput taste discrimination assay. A Yes/No experiment using the taste discrimination assay revealed that 0.2 mM phlorizin was discriminable from water for some subjects. Taken together the results indicate that agonist activation of TAS1R2/R3 is sufficient to account for all glucose taste without contribution by an alternative SGLT-mediated signaling pathway. Furthermore, the taste of phlorizin could be a confounding variable for studies evaluating a role for SGLTs in taste.

Dynamics of convolutional recurrent neural networks near their critical point

We examine the dynamical properties of a single-layer convolutional recurrent network with a smooth sigmoidal activation function, for small values of the inputs and when the convolution kernel is unitary, so all eigenvalues lie exactly at the unit circle. Such networks have a variety of hallmark properties: the outputs depend on the inputs via compressive nonlinearities such as cubic roots and both the and the depend sensitively on the inputs as power laws, both diverging as the input →0. The basic dynamical mechanism is that inputs to the network generate ongoing activity, which in turn controls how additional inputs or signals propagate spatially or attenuate in time. We present analytical solutions for the steady states when the network is forced with a single oscillation and when a background value creates a steady state of “ongoing activity” and derive the relationships shaping the value of the temporal decay and spatial propagation length as a function of this background value. Published by the American Physical Society 2024

CAUSALdb2: an updated database for causal variants of complex traits.

Unraveling the causal variants from genome wide association studies (GWASs) is pivotal for understanding genetic underpinnings of complex traits and diseases. Despite continuous efforts, tools to refine and prioritize GWAS signals need enhancement to address the direct causal implications of genetic variations. To overcome challenges related to statistical fine-mapping in identifying causal variants, CAUSALdb has been updated with novel features and comprehensive datasets, morphing into CAUSALdb2. This expanded repository integrates 15057 updated GWAS summary statistics across 10839 unique traits and implements both LD-based and LD-free fine-mapping approaches, including innovative applications of approximate Bayes Factor and SuSiE. Additionally, by incorporating larger LD reference panels such as TOPMED and UK Biobank, and integrating functional annotations via PolyFun, CAUSALdb2 enhances the accuracy and context of fine-mapping results. The database now supports interrogation of additional causal signals and offers sophisticated visualizations to aid researchers in deciphering complex genetic architectures. By facilitating a deeper and more precise characterisation of causal variants, CAUSALdb2 serves as a crucial tool for advancing the genetic analysis of complex diseases. Available freely, CAUSALdb2 continues to set benchmarks in the post-GWAS era, fostering the development of targeted diagnostics and therapeutics derived from responsible genetic research. Explore these advancements at http://mulinlab.org/causaldb.

Abstract PR017: Anti-metastatic immunotherapy discovery using ex vivo lung tissue cultures and high-throughput single-cell chemical transcriptomics

Abstract Introduction: Tumors systemically remodel the immune system during metastasis. Developing anti-metastatic immunotherapies that target these tumor-immune interactions to make the metastatic niche hostile colonization would represent a paradigm shift in cancer treatment. However, traditional high-throughput screening (HTS) platforms that use simple read-outs and contrived in vitro systems are ill-suited to identify such therapies. In contrast, HTS platforms that accurately model the metastatic niche and use high-dimensional read-outs such as multiplexed single-cell RNA-sequencing (scRNA-seq) can accurately profile nuanced perturbation responses in individual immune cell types and therefore have the potential to discover anti-metastatic immunotherapies. In this study, we describe the development of an ex vivo lung tissue culture HTS platform that preserves immune gene expression signatures observed in the in vivo metastatic niche and is amenable to single-cell chemical transcriptomic analysis using MULTI- seq (McGinnis et al., Nature Methods, 2019). Inspired by our recent description of myeloid cell TLR-NFκB inflammation during breast cancer lung metastasis (McGinnis et al., Cancer Cell, 2024), we then performed the first anti-metastatic immunotherapy drug screen and identified TLR-NFκB inhibitors that effectively operate on all desired myeloid cell types in the lung metastatic niche. Methods and Results: Building upon existing techniques for culturing precision-cut lung slices (Wu et al., Journal of Experimental Medicine, 2024) and patient- derived tumor fragments (Voabil et al., Nature Medicine, 2021), we established and optimized an ex vivo lung tissue culture system that enables 48-hour culturing of lung slices isolated from 4T1 tumor-bearing mice. scRNA-seq profiling revealed successful capture of all relevant immune cell types and retention of metastasis-associated gene expression programs (e.g., myeloid TLR-NFκB inflammation and neutrophil degranulation) following culture. We then scaled our platform to address how myeloid cells in the lung metastatic niche respond to perturbations targeting every component of the canonical TLR-NFκB signaling cascade. Cell-type-specific perturbation modeling and quantification of TLR-NFκB signaling inhibition identified compounds that optimally perturb all intended myeloid cell types (e.g., tissue-resident macrophages, neutrophils, and monocytes) and represent prioritized candidates for future in vivo validation studies to assess impact on metastatic disease progression. Conclusions: In this study, we describe the development and application of a novel HTS platform that couples ex vivo lung tissue cultures with single-cell chemical transcriptomics to identify anti-metastatic immunotherapy candidates. We demonstrate how our platform can identify TLR-NFκB signaling inhibitors that optimally operate in the lung metastatic niche, paving the way for future interrogation of additional metastasis-associated immune cell signaling pathways in different disease and tissue backgrounds. Citation Format: Chris McGinnis, Winnie Yao, Ansuman Satpathy. Anti-metastatic immunotherapy discovery using ex vivo lung tissue cultures and high-throughput single-cell chemical transcriptomics [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR017.

A PSMA-targeted Tri-specific Killer Engager enhances NK cell cytotoxicity against prostate cancer.

Natural killer (NK) cell tumor infiltration is associated with good prognosis in patients with metastatic castration-resistant prostate cancer (mCRPC). NK cells recognize and kill targets by a process called natural cytotoxicity. We hypothesized that promoting an antigen-specific synapse with co-activation may enhance NK cell function in mCRPC. We describe a Tri-specific Killer Engager (TriKE) construct that engages with the activating receptor CD16 on NK cells, prostate-specific membrane antigen (PSMA) on mCRPC cells, and has an interleukin (IL)-15 moiety that is essential for NK cell survival, proliferation, and priming. We show that the PSMA TriKE specifically binds to PSMA-expressing cells and significantly enhances expansion, degranulation and cytokine production of NK cells derived from healthy donors or prostate cancer patients. Bystander killing of PSMA-negative was also achieved with PSMA TriKE treatment when co-cultured with PSMA-positive cells, suggesting potential PSMA TriKE benefit in controlling tumor antigen escape. When tested under physiologic conditions recapitulating the mCRPC tumor microenvironment (TME), NK cells treated with PSMA TriKE and prolonged exposure to hypoxia or MDSCs maintained their potent function while IL-15 treated NK cells showed greatly impaired cytotoxicity. Finally, in vivo testing of PSMA TriKE showed improved tumor control and survival of mice as compared to IL-15 and untreated control groups. In conclusion, PSMA TriKE demonstrates potential as a new therapy for advanced prostate cancer by providing additional signals to NK cells to maximize their anti-tumor potential in prostate cancer, especially in the setting of a hostile TME.

Spatiotemporal Proximity-Enhanced Biocatalytic Cascades Within Metal-Organic Frameworks for Wearable and Theranostic Applications.

Enzymatic catalysis, particularly multi-enzyme cascade catalytic, is often limited by the spatial and temporal separation of enzymes and their signal substrates. Herein, a facile method for producing a spatiotemporal proximity-enhanced biocatalytic cascade system is introduced by encasing enzymes within metal-organic frameworks (MOFs) that are modulated with sulfonic acid-functionalized signal substrates. The modulated behavior relies on the sulfonic acid groups coordinated with Zn2+. As a proof of concept, by utilizing 2,2'-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS), a widely-used signal substrate for horseradish peroxidase, two-enzyme/substrate, and three-enzyme/substrate MOFs, which demonstrated a 7.4- and 10.2-fold increase in biocatalytic efficiency over free systems are successfully synthesized. Incorporating the synthesized MOFs into homemade wearable patches and in vivo settings, noninvasive sweat glucose colorimetric detection and photoacoustic imaging-guided photothermal tumor therapy are enabled, respectively. This advancement stems from the newly established coordinative bonds between Zn2+ centers and substrates' sulfonic acid groups, which negates the need for additional signal substrates, thereby not only enhancing but also streamlining bioapplication processes.

The danger theory of immunity revisited.

The danger theory of immunity, introduced by Polly Matzinger in 1994, posits that tissue stress, damage or infection has a decisive role in determining immune responses. Since then, a growing body of evidence has supported the idea that the capacity to elicit cognate immune responses (immunogenicity) relies on the combination of antigenicity (the ability to be recognized by T cell receptors or antibodies) and adjuvanticity (additional signals arising owing to tissue damage). Here, we discuss the molecular foundations of the danger theory while focusing on immunologically relevant damage-associated molecular patterns, microorganism-associated molecular patterns, andneuroendocrine stress-associated immunomodulatory molecules, as well as on their receptors. We critically evaluate patient-relevant evidence, examining how cancer cells and pathogenic viruses suppress damage-associated molecular patterns to evade immune recognition, how intestinal dysbiosis can reduce immunostimulatory microorganism-associated molecular patterns and compromise immune responses, and which hereditary immune defects support the validity of the danger theory. Furthermore, we incorporate the danger hypothesis into a close-to-fail-safe hierarchy of immunological tolerance mechanisms that also involve the clonal deletion and inactivation of immune cells.

Adaptive frequency driving scan driver based on a‐InGaZnO TFTs for extremely low‐power displays

AbstractIn this paper, we propose a novel scan driver combined with a logic circuit using amorphous indium‐gallium‐zinc‐oxide (a‐InGaZnO) thin‐film transistors (TFTs) in order to enhance the electrical stability and reduce power consumption in display panels. The latest mobile displays with high resolution and refresh rates consume more battery power, which inevitably limits portability and usability. The proposed scan driver can mask the signal by combining the output stage with a logic circuit, thereby blocking the output pulse for static images. This allows the display panel to operate in a partial driving mode depending on the display content. Due to the masking of the scan driver's output pulses, the connected pixel circuits are consistently maintained in the same state as the previous frame, leading to a lower refresh rate and reduced power consumption. Furthermore, by constructing additional control signals, the proposed scan driver can operate stably in depletion mode under a ∆VTH = −3 V.

High performance SERS boosting by Fabry- Pérot cavities of silica-gold-silicon multilayers

Surface-enhanced Raman scattering (SERS), an advanced technique for molecular spectroscopy, relies heavily on the preparation of SERS active materials that can significantly enhance the Raman scattering signals for highly sensitive detection of trace molecules. Traditionally, SERS measurements are performed on silicon or silica substrates, the SERS performance is determined by the structure of SERS materials. Here, we show that the SERS signal can be amplified and modulated using Fabry-Pérot (F-P) cavities made of silica-silicon (SiO2-Si) or silica-gold-silicon (SiO2-Au-Si) multilayers as substrates. Periodic SERS signal variations as SiO2 thickness increases are observed, exhibiting optimal enhancement with the SiO2 thickness of 250 nm due to the optical interference in the cavity. Although the signal enhancement by optical interference is weaker than that by plasmonic resonance, additional signal amplification is essential for highly sensitive SERS materials. Moreover, we applied this strategy to detect thiram in bean sprout extracts, demonstrating that the detection sensitivity is two orders of magnitude higher than that using Si substrates. The utilization of the pseudo-internal standard intensity calibration method facilitates the quantitative analysis of thiram concentrations. Our results provide a promising approach for further amplification of SERS signals with great potential for practical applications.

Behavior of leadless atrioventricular synchronous pacing during exercise

BackgroundThe leadless Micra AV pacemaker is designed to provide atrioventricular (AV) synchronous tracking by detecting atrial contraction. Detection of the mechanical atrial signals can become challenging at a fast sinus rate. ObjectiveThe purpose of the study was to evaluate the AV synchronous performance at exercise in outpatients implanted with a Micra AV pacemaker. MethodsPatients were enrolled at least 1 month after Micra AV implantation and underwent a cycle test protocol. Serial device interrogations (each minute) and continuous electrocardiograms were collected to measure AV synchrony and determine maximum achieved sinus and ventricular rates for each patient. In addition, the A1, A2, A3, and A4 accelerometer signal amplitudes were measured at the start and peak of exercise. ResultsThirty-five patients (mean age 75.6 ± 13.4 years; 80% male) were enrolled in the study; 22 (64%) were predominantly ventricular paced (>90%) during exercise. Average AV synchrony was 90.4% in the entire cohort and 84.7% in patients with high-degree AV block. The mean amplitude of the accelerometer signals increased significantly from the start to the peak of exercise: A1, 4.1–6.3 m/s2; A2, 2.4–3.8 m/s2; and A4, 4.5–7.6 m/s2 (P < .01 for all). The time from the VP-A2 decreased 25 ms for each 100 ms of the R-R interval decrease. ConclusionMaintaining AV synchrony during maximal exercise in elderly patients is achievable by adequate detection of atrial contraction at high sinus rates by the leadless Micra AV pacemaker. All components of the accelerometer signal increased, likely because of increased contractility related to exercise.

A CRISPR-Cas9 knockout screening identifies IRF2 as a key driver of OAS3/RNase L-mediated RNA decay during viral infection

OAS-RNase L is a double-stranded RNA-induced antiviral pathway triggered in response to diverse viral infections. Upon activation, OAS-RNase L suppresses virus replication by promoting the decay of host and viral RNAs and inducing translational shutdown. However, whether OASs and RNase L are the only factors involved in this pathway remains unclear. Here, we develop CRISPR-Translate, a FACS-based genome-wide CRISPR-Cas9 knockout screening method that uses translation levels as a readout and identifies IRF2 as a key regulator of OAS3. Mechanistically, we demonstrate that IRF2 promotes basal expression of OAS3 in unstressed cells, allowing a rapid activation of RNase L following viral infection. Furthermore, IRF2 works in concert with the interferon response through STAT2 to further enhance OAS3 expression. We propose that IRF2-induced RNase L is critical in enabling cells to mount a rapid antiviral response immediately after viral infection, serving as the initial line of defense. This rapid response provides host cells the necessary time to activate additional antiviral signaling pathways, forming secondary defense waves.

Dynamic range extension method for sinusoidal phase modulating interferometer based on in-phase component signal reconstruction

Abstract The continuous increase of the amplitude of the measured vibration will cause spectrum aliasing in the interference signal of the sinusoidal phase modulating interferometer (SPMI), thereby constraining its measurement dynamic range (DR). To address this issue, a DR extension method of SPMI based on the reconstruction of in-phase component signal is proposed. On the basis of conventional SPMI, an additional reference signal is introduced for estimating the phase modulation depth (PMD) and the major to minor axis ratio R e of the Lissajous ellipse formed by orthogonal interference signal pair and a phase demodulation algorithm named as phase generated carrier (PGC)- in-phase component signal reconstruction (ICR)- differential-and-cross-multiplying algorithm (DCM) which integrates PGC-DCM algorithm and the ICR is proposed. Initially, the PMD is regulated to approximately 1.8412 rad, ensuring that the quadrature component signal can be accurately extracted from the mixed signal of the interference and carrier signals, even in the presence of spectrum aliasing in the original interference signal. Then, the undistorted quadrature component signal is used to reconstruct an in-phase component signal with the estimated value of R e. Finally, the reconstructed in-phase component signal and quadrature component signal are normalized, and a DCM approach is applied to obtain the measured vibration. A SPMI measurement system based on Michelson interferometer structure is constructed to experimentally validate the proposed method. The experimental results demonstrate that the proposed method can effectively extend the DR of the SPMI system in the presence of spectrum aliasing. The DR of the system is increased from 97.52 dB @ 55 Hz to 102.6 dB @ 55 Hz, with the maximum measurable amplitude increasing from 7728.75 nm @ 55 Hz to 13 705.16 nm @ 55 Hz.

Preclinical development of SGN-CD47M: Protease-activated antibody technology enables selective tumor targeting of the innate immune checkpoint receptor CD47.

CD47 is a cell surface glycoprotein that is expressed on normal human tissues and has a key role as a marker of self. Tumor cells have coopted CD47 overexpression to evade immune surveillance and thus blockade of CD47 is a highly active area of clinical exploration in oncology. However, clinical development of CD47-targeted agents has been complicated by its robust expression in normal tissues and the toxicities that arise from blocking this inhibitory signal. Further, pro-phagocytic signals are not uniformly expressed in tumors and antibody blockade alone is often not sufficient to drive antitumor activity. The inclusion of an IgG1 antibody backbone into therapeutic design has been shown to serve as an additional pro-phagocytic signal but also exacerbates toxicities in normal tissues. Therefore, a need persists for more selective therapeutic modalities targeting CD47. To address these challenges, we developed SGN-CD47M, a humanized anti-CD47 IgG1 monoclonal antibody linked to novel masking peptides through linkers designed to be cleaved by active proteases enriched in the tumor microenvironment. Masking technology has the potential to increase the amount of drug that reaches the tumor microenvironment, while concomitantly reducing systemic toxicities. We demonstrate that SGN-CD47M is well tolerated in cynomolgus monkeys and displays a 20-fold improvement in tolerability to hematologic toxicities when compared to the unmasked antibody. SGN-CD47M also displays preferential activation in the tumor microenvironment that leads to robust single-agent antitumor activity. For these reasons, SGN-CD47M may have enhanced antitumor activity and improved tolerability relative to existing therapies that target the CD47-SIRPα interaction.

Pair formation in Enchenopa treehoppers (Hemiptera: Membracidae) involves complex male–female duetting, and three stages of female mate choice

Abstract We explore the complexity of the signal repertoire and sequences of behavioural interactions involved in pair formation in Enchenopa binotata treehoppers, which communicate via plant-borne vibrational signals, and whose pair formation involves prolonged male-female duetting interactions. We recorded these interactions using laser vibrometry and video assays. In males, we report two phases of signalling: a searching phase in which males use a basic repertoire to solicit engagement from females; and a more complex phase incorporating additional signal types and elements males used once engaged by females. In females, we report a novel three-stage process of selective cooperation with males, as well as a novel signal type that was necessary but not sufficient for copulation to occur. These three stages include active duetting with a male that was necessary for him to locate and mount females; the novel signal that females produce after continued mounted duetting that prompts the male to attempt genital coupling; and the female actively allowing coupling. We discuss implications of our observations for these insects’ cognitive abilities in terms of the memory and selective attention required to sustain signalling interactions and proceed along the decision-making stages of mate choice. Using attention to detail as an aid to discovery, we aim to promote research on how such animals express such capabilities.

A 23–29 GHz GaN Low-Noise Amplifier with Drain-to-Source Coupling Feedback

In this paper, a four-stage gallium nitride (GaN) low noise amplifier (LNA) using coupled-line (CL) feedback in a 0.15-μm GaN-on-SiC process is proposed. The electromagnetic coupling feedback between the drain and source of each transistor is employed to generate an additional signal path for neutralization, which enhances gain and improves stability performance. A series transmission line-capacitor-transmission line (TL-C-TL) network is introduced between stages of the LNA for wider band interstage matching. The measured results show that the designed LNA achieves a 3-dB bandwidth of 23.6 to 29.8 GHz, a peak gain of 23.7 dB at 25.8 GHz, and a minimum noise figure (NF) of 2.2 dB at 27.8 GHz. The output-referred 1-dB compression point (OP1dB) is 13 dBm. The total power consumption of the LNA is 200 mW.