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Invisible equivalence inside the operant demand platform: An overview and also look at multiple options for considering nonconsumption.
Cancer immunotherapy with 4-1BB agonists has limited further clinical development because of dose-limiting toxicity. Here, we developed a bispecific antibody (bsAb; B7-H3×4-1BB), targeting human B7-H3 (hB7-H3) and mouse or human 4-1BB, to restrict the 4-1BB stimulation in tumors. B7-H3×m4-1BB elicited a 4-1BB-dependent antitumor response in hB7-H3-overexpressing tumor models without systemic toxicity. BsAb primarily targets CD8 T cells in the tumor and increases their proliferation and cytokine production. Among the CD8 T cell population in the tumor, 4-1BB is solely expressed on PD-1+Tim-3+ "terminally differentiated" subset, and bsAb potentiates these cells for eliminating the tumor. Selleck MYCi975 Furthermore, the combination of bsAb and PD-1 blockade synergistically inhibits tumor growth accompanied by further increasing terminally differentiated CD8 T cells. B7-H3×h4-1BB also shows antitumor activity in h4-1BB-expressing mice. Our data suggest that B7-H3×4-1BB is an effective and safe therapeutic agent against B7-H3-positive cancers as monotherapy and combination therapy with PD-1 blockade.The ability to precisely control nanocrystal (NC) shape and composition is useful in many fields, including catalysis and plasmonics. Seed-mediated strategies have proven effective for preparing a wide variety of structures, but a poor understanding of how to selectively grow corners, edges, and facets has limited the development of a general strategy to control structure evolution. Here, we report a universal synthetic strategy for directing the site-specific growth of anisotropic seeds to prepare a library of designer nanostructures. This strategy leverages nucleation energy barrier profiles and the chemical potential of the growth solution to control the site-specific growth of NCs into exotic shapes and compositions. This strategy can be used to not only control where growth occurs on anisotropic seeds but also control the exposed facets of the newly grown regions. NCs of many shapes are synthesized, including over 10 here-to-fore never reported NCs and, in principle, many others are possible.On-surface synthesis has revealed remarkable potential in the fabrication of atomically precise nanographenes. However, surface-assisted synthesis often involves multiple-step cascade reactions with competing pathways, leading to a limited yield of target nanographene products. Here, we devise a strategy for the ultrahigh-yield synthesis of circumcoronene molecules on Cu(111) via surface-assisted intramolecular dehydrogenation of the rationally designed precursor, followed by methyl radical-radical coupling and aromatization. An elegant electrostatic interaction between circumcoronenes and metallic surface drives their self-organization into an extended superlattice, as revealed by bond-resolved scanning probe microscopy measurements. Density functional theory and tight-binding calculations reveal that unique hexagonal zigzag topology of circumcoronenes, along with their periodic electrostatic landscape, confines two-dimensional electron gas in Cu(111) into a chiral electronic Kagome-honeycomb lattice with two emergent electronic flat bands. Our findings open up a new route for the high-yield fabrication of elusive nanographenes with zigzag topologies and their superlattices with possible nontrivial electronic properties.Researchers have documented race and gender inequality in science, technology, engineering, and math (STEM) for decades. Do lesbian, gay, bisexual, transgender, and queer (LGBTQ) professionals face parallel experiences of disadvantage in STEM? Using representative survey data from 21 STEM professional societies (Nsample = 25,324; NLGBTQ = 1006), this paper presents multidimensional and methodologically robust documentation of 5 dimensions of LGBTQ inequality in STEM. Controlling for variation by demographic, discipline, and job factors, LGBTQ STEM professionals were more likely to experience career limitations, harassment, and professional devaluation than their non-LGBTQ peers. They also reported more frequent health difficulties and were more likely to intend to leave STEM. These trends were similar across STEM disciplines and employment sectors. We found no differences by LGBTQ status in education level, work effort, or job commitment. These findings reveal LGBTQ status as a clear axis of inequality in STEM and motivate further research into the mechanisms producing such outcomes.Timely restoration of blood supply following myocardial infarction is critical to save the infarcted myocardium, while reperfusion would cause additional damage. Strontium ions have been shown to promote angiogenesis, but it is unknown whether they can save the damaged myocardium. We report that myocardial ischemia/reperfusion (I/R)-induced functional deterioration and scar formation were notably attenuated by injection of strontium ion-containing composite hydrogels into murine infarcted myocardium at 20 minutes of reperfusion following 60 minutes of ischemia. These beneficial effects were accompanied by reduced cardiomyocyte apoptosis and increased angiogenesis. The effects of strontium ions were further confirmed by the enhanced viability of cardiomyocytes and stimulated angiogenesis in vitro. These findings are the first to reveal the cardioprotective effects of strontium ions against I/R injury, which may provide a new therapeutic approach to ischemic heart disease at a lower cost, with higher stability, and with potentially greater safety.Traditional imaging cytometry uses fluorescence markers to identify specific structures but is limited in throughput by the labeling process. We develop a label-free technique that alleviates the physical staining and provides multiplexed readouts via a deep learning-augmented digital labeling method. We leverage the rich structural information and superior sensitivity in reflectance microscopy and show that digital labeling predicts accurate subcellular features after training on immunofluorescence images. We demonstrate up to three times improvement in the prediction accuracy over the state of the art. Beyond fluorescence prediction, we demonstrate that single cell-level structural phenotypes of cell cycles are correctly reproduced by the digital multiplexed images, including Golgi twins, Golgi haze during mitosis, and DNA synthesis. We further show that the multiplexed readouts enable accurate multiparametric single-cell profiling across a large cell population. Our method can markedly improve the throughput for imaging cytometry toward applications for phenotyping, pathology, and high-content screening.
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