The World Health Organization has declared the rapid spread of COVID-19 around the world a global public health emergency. It is well-known that the spread of the disease is influenced by people's ...willingness to adopt preventative public health behaviors, which are often associated with public risk perception. In this study, we present the first assessment of public risk perception of COVID-19 around the world using national samples (total N = 6,991) in ten countries across Europe, America, and Asia. We find that although levels of concern are relatively high, they are highest in the UK compared to all other sampled countries. Pooled across countries, personal experience with the virus, individualistic and prosocial values, hearing about the virus from friends and family, trust in government, science, and medical professionals, personal knowledge of government strategy, and personal and collective efficacy were all significant predictors of risk perception. Although there was substantial variability across cultures, individualistic worldviews, personal experience, prosocial values, and social amplification through friends and family in particular were found to be significant determinants in more than half of the countries examined. Risk perception correlated significantly with reported adoption of preventative health behaviors in all ten countries. Implications for effective risk communication are discussed.
Uncertainty is inherent to our knowledge about the state of the world yet often not communicated alongside scientific facts and numbers. In the “posttruth” era where facts are increasingly contested, ...a common assumption is that communicating uncertainty will reduce public trust. However, a lack of systematic research makes it difficult to evaluate such claims. We conducted five experiments—including one preregistered replication with a national sample and one field experiment on the BBC News website (total n = 5,780)—to examine whether communicating epistemic uncertainty about facts across different topics (e.g., global warming, immigration), formats (verbal vs. numeric), and magnitudes (high vs. low) influences public trust. Results show that whereas people do perceive greater uncertainty when it is communicated, we observed only a small decrease in trust in numbers and trustworthiness of the source, and mostly for verbal uncertainty communication. These results could help reassure all communicators of facts and science that they can be more open and transparent about the limits of human knowledge.
Despite compelling rates of durable clinical responses to programmed cell death-1 (PD-1) blockade, advances are needed to extend these benefits to resistant tumors. We found that tumor-bearing mice ...deficient in the chemokine receptor CXCR3 responded poorly to anti-PD-1 treatment. CXCR3 and its ligand CXCL9 were critical for a productive CD8+ T cell response in tumor-bearing mice treated with anti-PD-1 but were not required for the infiltration of CD8+ T cells into tumors. The anti-PD-1-induced anti-tumor response was facilitated by CXCL9 production from intratumoral CD103+ dendritic cells, suggesting that CXCR3 facilitates dendritic cell-T cell interactions within the tumor microenvironment. CXCR3 ligands in murine tumors and in plasma of melanoma patients were an indicator of clinical response to anti-PD-1, and their induction in non-responsive murine tumors promoted responsiveness to anti-PD-1. Our data suggest that the CXCR3 chemokine system is a biomarker for sensitivity to PD-1 blockade and that augmenting the intratumoral function of this chemokine system could improve clinical outcomes.
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•Anti-PD-1 efficacy depends on intratumoral activity of the CXCR3 chemokine system•CD103+ dendritic-cell-derived CXCL9 and CXCR3 on CD8+ T cells are required•CXCR3 ligands are positive indicators of responsiveness to anti-PD-1 therapy•Inducing CXCR3 ligands in non-responsive tumors restores sensitivity to anti-PD-1
Chow et al. find the CXCR3 chemokine system is not required for CD8+ T cell migration into the tumor, but rather for the enhancement of the intratumoral CD8+ T cell response in the context of PD-1 blockade. The CXCR3 chemokine system might serve as a biomarker for sensitivity to PD-1 blockade and a target for improving clinical outcomes.
The Rashba effect is spin degeneracy lift originated from spin–orbit coupling under inversion symmetry breaking and has been intensively studied for spintronics applications. However, easily ...implementable methods and corresponding materials for directional controls of Rashba splitting are still lacking. Here, we propose organic–inorganic hybrid metal halide perovskites as 3D Rashba systems driven by bulk ferroelectricity. In these materials, it is shown that the helical direction of the angular momentum texture in the Rashba band can be controlled by external electric fields via ferroelectric switching. Our tight-binding analysis and first-principles calculations indicate that Formula and Formula Rashba bands directly coupled to ferroelectric polarization emerge at the valence and conduction band edges, respectively. The coexistence of two contrasting Rashba bands having different compositions of the spin and orbital angular momentum is a distinctive feature of these materials. With recent experimental evidence for the ferroelectric response, the halide perovskites will be, to our knowledge, the first practical realization of the ferroelectric-coupled Rashba effect, suggesting novel applications to spintronic devices.
Throughout the COVID-19 pandemic, social and traditional media have disseminated predictions from experts and nonexperts about its expected magnitude. How accurate were the predictions of ...'experts'-individuals holding occupations or roles in subject-relevant fields, such as epidemiologists and statisticians-compared with those of the public? We conducted a survey in April 2020 of 140 UK experts and 2,086 UK laypersons; all were asked to make four quantitative predictions about the impact of COVID-19 by 31 Dec 2020. In addition to soliciting point estimates, we asked participants for lower and higher bounds of a range that they felt had a 75% chance of containing the true answer. Experts exhibited greater accuracy and calibration than laypersons, even when restricting the comparison to a subset of laypersons who scored in the top quartile on a numeracy test. Even so, experts substantially underestimated the ultimate extent of the pandemic, and the mean number of predictions for which the expert intervals contained the actual outcome was only 1.8 (out of 4), suggesting that experts should consider broadening the range of scenarios they consider plausible. Predictions of the public were even more inaccurate and poorly calibrated, suggesting that an important role remains for expert predictions as long as experts acknowledge their uncertainty.
This, the second volume on quantum mechanics by Franz Schwabl, discusses nonrelativistic multi-particle systems, relativistic wave equations and relativistic quantum fields. Numerous exercises help ...the reader gain a thorough working knowledge of the subject.
Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical ...benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.
The physical sciences have alternated between revolutions driven by new ideas and explorations driven by new tools.
Thomas Kuhn was a theoretical physicist before he became a historian. He saw the ...history of science through the eyes of a theorist. He gave us an accurate view of events in the world of ideas. His favorite word, “paradigm,” means a system of ideas that dominate the science of a particular place and time. A scientific revolution is a discontinuous shift from one paradigm to another. The shift happens suddenly because new ideas explode with a barrage of new insights and new questions that push old ideas into oblivion. I remember the joy of reading Kuhn's book,
The Structure of Scientific Revolutions
, when it first appeared in 1962. It made sense of the relativity and quantum revolutions that had happened just before the theoretical physicists of my generation were born. Those were revolutions led by deep thinkers—Einstein and Heisenberg and Schrödinger and Dirac—who guessed nature's secrets by dreaming dreams of mathematical beauty. Their new paradigms were created out of abstract ideas. In those revolutionary years from 1900 to 1930, ideas led the way to understanding.
Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals that regulate the balance between T cell activation, tolerance, and immunopathology. Immune responses to foreign ...and self-antigens require specific and balanced responses to clear pathogens and tumors and yet maintain tolerance. Induction and maintenance of T cell tolerance requires PD-1, and its ligand PD-L1 on nonhematopoietic cells can limit effector T cell responses and protect tissues from immune-mediated tissue damage. The PD-1:PD-L pathway also has been usurped by microorganisms and tumors to attenuate antimicrobial or tumor immunity and facilitate chronic infection and tumor survival. The identification of B7-1 as an additional binding partner for PD-L1, together with the discovery of an inhibitory bidirectional interaction between PD-L1 and B7-1, reveals new ways the B7:CD28 family regulates T cell activation and tolerance. In this review, we discuss current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential.
Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A ...virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.
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