Showing papers by "Thomas A. Wynn published in 2022"

Identification of a Broadly Fibrogenic Macrophage Subset Induced by Type 3 Inflammation in Human and Murine Liver and Lung Fibrosis

Abstract: Macrophages are central orchestrators of the tissue response to injury, with distinct macrophage activation states playing key roles in the progression and resolution of fibrosis. Identifying the unique fibrogenic macrophages that are found in human fibrotic tissues could lead to new and more effective treatments for fibrosis. Here we used human liver and lung single cell RNA sequencing datasets to identify a unique subset of CD9+ TREM2+ macrophages expressing SPP1, GPNMB, FABP5, and CD63 with strong pro-fibrotic activity. This population was validated across orthogonal techniques, species and tissues. These macrophages were enriched at the outside edges of scarring adjacent to activated mesenchymal cells, and in the fibrotic niche across species and organs. Neutrophils producing the type 3 cytokines GM-CSF and IL-17A, and expressing MMP9, which participates in the activation of TGF-β1, clustered with these scar-associated macrophages. Using in vitro primary human cell assays, we determined that GM-CSF, IL-17A and TGF-β1 drive the differentiation of these scar-associated macrophages, and that co-culture of monocyte-derived macrophages with hepatic stellate cells and TGF-β1 augmented type 1 collagen deposition. In vivo blockade of GM-CSF, IL-17A or TGF-β1 with small or large molecules reduced scar-associated macrophage expansion and fibrosis in multiple models of hepatic and pulmonary fibrosis. Our work demonstrates that a specific scar-associated macrophage population is linked with fibrosis across species and tissues. It further provides a strategy for unbiased discovery, triage and preclinical validation of therapeutic targets within this fibrogenic macrophage population.

Enhanced oxygen evolution over dual corner-shared cobalt tetrahedra

Abstract: Developing efficient catalysts is of paramount importance to oxygen evolution, a sluggish anodic reaction that provides essential electrons and protons for various electrochemical processes, such as hydrogen generation. Here, we report that the oxygen evolution reaction (OER) can be efficiently catalyzed by cobalt tetrahedra, which are stabilized over the surface of a Swedenborgite-type YBCo4O7 material. We reveal that the surface of YBaCo4O7 possesses strong resilience towards structural amorphization during OER, which originates from its distinctive structural evolution toward electrochemical oxidation. The bulk of YBaCo4O7 composes of corner-sharing only CoO4 tetrahedra, which can flexibly alter their positions to accommodate the insertion of interstitial oxygen ions and mediate the stress during the electrochemical oxidation. The density functional theory calculations demonstrate that the OER is efficiently catalyzed by a binuclear active site of dual corner-shared cobalt tetrahedra, which have a coordination number switching between 3 and 4 during the reaction. We expect that the reported active structural motif of dual corner-shared cobalt tetrahedra in this study could enable further development of compounds for catalyzing the OER.

Freestanding LiPON: from Fundamental Study to Uniformly Dense Li Metal Deposition Under Zero External Pressure

Abstract: Lithium phosphorus oxynitride (LiPON) is a well-known amorphous thin film solid electrolyte that has been extensively studied in the last three decades. Despite the promises to pair with Li metal anode and various cathode materials, the presence of rigid substrate and LiPONs unique amorphous, air-sensitive nature set limitations to comprehensively understand its intrinsic properties for future development and applications. This work demonstrates a methodology to synthesize LiPON in a freestanding form that exhibits remarkable flexibility and a Young s modulus of ~33 GPa. Solid-state nuclear magnetic resonance (ss-NMR) and differential scanning calorimetry (DSC) results with unprecedented high signal-to-noise ratio could be obtained with such freestanding LiPON (FS-LiPON), revealing the Li-LiPON interface bonding environments quantitatively and a well-defined glass transition temperature for LiPON. Combining interfacial stress and a seeding layer, FS-LiPON demonstrates a uniform and fully dense Li metal deposition without the aid of external pressure. Such a FS-LiPON film offers new opportunities for fundamental study of LiPON material and associated interfaces, and provides perspectives for interface engineering in bulk solid-state battery.

Suite libertine: vies du xviiie siècle. Par Pierre Saint-Amand

Abstract: A stylist of the highest order, Pierre Saint-Amand is that rare dix-huitiémiste, a writer whose elegant and captivating prose rivals that of his subjects. Yet style is no mere affectation for Saint-Amand; it is the very matter of his excellent new book, and comprises the aestheticization of existence, the thrusting forth of the self, and the propensity to exuberant forms of life. A few of the chapters in this volume have previously appeared as articles, though in no way does this diminish its overall cohesion and quality. At the heart of this study lies the battle of the sexes which Saint-Amand approaches not head on, but by detours, displacements, and sequels. Desire here connotes caprice and liberty rather than cruelty and violence. One of Saint-Amand’s great talents is to take a word or phrase that other readers would miss; as if looking through a jeweller’s eyeglass, he discovers all sorts of colours and tones which are the basis for riveting interpretations of celebrated and lesser-known texts. The first chapter compares economy in Manon Lescaut and Margot la ravaudeuse: playing with the terms ‘ménager’, ‘ménage’, and ‘déménager’, Saint-Amand demonstrates that Prévost’s heroine refuses intimacy and prefers instead an aristocratic display of wealth outside the home; Fougeret de Monbron’s Margot, however, adopts a bourgeois system of exchange, ending her story as a well-to-do lady of the house. In addition to illuminating chapters on Godard d’Aucour’s Thémidore and Thérèse philosophe (here attributed to Boyer d’Argens), the volume features a superb examination of Pidansat de Mairobert’s Confession d’une jeune fille which includes the famous La Secte des anandrynes; this short text innovates with its emphasis on the psychological (not anatomical) aspects of lesbianism (‘tribadisme’) and its depiction of female protagonists united by a similar culture and ‘style de vie’ (p. 87). Turning to men, Saint-Amand offers a brilliant analysis of disorder, masculinity, and incarceration in Manon Lescaut, and a fascinating account of unorthodox family arrangements as recounted by Casanova who, on arrival in Paris, encounters a new kind of paternity, one shared between men and freed from its parental functions. The figure of the petit-maître is the starting point for a suggestive chapter on the confusion of the sexes, virility, and antimatter. The highlight of this volume is the chapter on the place of religion in libertine fiction. It reminds us that the culture of seduction remains thoroughly embedded in discourses of myth and faith from which its protagonists might seem liberated, as Valmont’s demonic possession of Mme de Tourvel in Laclos’s Les Liaisons dangereuses demonstrates. Similarly, Versac in Crébillon fils’s Les Égarements du cœur et de l’esprit is recognized as a magician of metamorphosis, disruption, and contradiction. The magnificent final paragraphs of this chapter remind us that something irreducibly archaic continues to haunt the Enlightenment.

An Introduction to Evolutionary Cognitive Archaeology

Abstract: An Introduction to Evolutionary Cognitive Archaeology is the first concise introduction that lays out the epistemological foundations of evolutionary cognitive archaeology in a way that is accessible to students. The volume is divided into three sections. The first section situates cognitive archaeology in the pantheon of archaeological approaches and distinguishes between ideational cognitive archaeology and evolutionary cognitive archaeology. This is followed by a close look at the nature of cognitive archaeological inferences and concludes with brief summaries of the major methods of evolutionary cognitive archaeology. The second section of the book introduces the reader to a variety of cognitive phenomena that are accessible using the methods of cognitive archaeology: memory, technical cognition, spatial cognition, social cognition, art and aesthetics, and symbolism and language. The third section presents a brief outline of hominin cognitive evolution from the perspective of evolutionary cognitive archaeology. The authors divide the archaeological record into three major phases: The Bipedal Apes—3.3 million-1.7 million years ago; The Axe Age—1.7 million-300,000 years ago; and The Emergence of Modern Thinking—300,000–12,000 years ago. An Introduction to Evolutionary Cognitive Archaeology is an essential text for undergraduate students, graduate students, and scholars across the behavioral and social sciences interested in learning about cognitive archaeology, including psychologists, philosophers, anthropologists, and archaeologists.