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Our future hinges on a set of rare metals that few of us have even heard of. In this eye-opening book, a natural resource strategist reveals the critical importance of these transformative elements to our technological lifestyle and the consequences of our reliance upon them, including geopolitical instability and environmental degradation. To see our growing dependency, you need only look at your smartphone: cerium buffs the glass; indium allows your screen to respond to touch; terbium makes images more vibrant; and lithium helps it store energy. Abraham provides readers with a front-row seat to the life of these metals, tracing the paths of these high-tech elements through a dozen countries from the mine to our pockets. But it's not just smartphones that rely on these metals; they are the building blocks of modern society because they are critical for nearly all our electronic, military, and \"green\" technologies. Just as oil, iron, and bronze revolutionized previous eras, so too will these metals. The challenges this book reveals, and the plans it proposes, make it essential reading for our rare metal age.

A unique feature of systemic sclerosis (SSc) that distinguishes it from other fibrotic disorders is that autoimmunity and vasculopathy characteristically precede fibrosis. Moreover, fibrosis in SSc is not restricted to a single organ, but rather affects many organs and accounts for much of the morbidity and mortality associated with this disease. Although immunomodulatory drugs have been used extensively in the treatment of SSc, no therapy to date has been able to reverse or slow the progression of tissue fibrosis or substantially modify the natural progression of the disease. In this Review, we highlight recent studies that shed light on the cellular and molecular mechanisms underlying the fibrotic process in SSc and that identify cellular processes and intra- and extracellular proteins as potential novel targets for therapy in this prototypic multisystemic fibrotic disease.

An illuminating profile of one of today's most innovative and forward-looking architects, whose materials-based practice explores how space can provoke emotional response. Frida Escobedo's (b. 1979) designs for public spaces have received global accolades. In 2022 The Metropolitan Museum of Art announced that she would be the first woman to design a wing for the institution. This publication surveys her award-winning structures that treats space as a language--layered, responsive, and reflective of both a site's history and its present. Focusing on her full body of work in the context of her emerging and already vibrant career, this first consideration of Escobedo's two-decade multimedia practice includes an interview with the architect, alongside informed essays that discuss the bases of her work and her wide-reaching influences. This timely profile of a rising star explores Escobedo's attention to gender, accessibility, and the environment, as well as her diverse inspirations, ranging from concrete poetry to her hometown of Mexico City, which she describes as a \"modern metropolis with ancient roots . . . in other words, a living, breathing museum.\"-- Yale University Press

The human pathogenic nematode Strongyloides stercoralis infects approximately 30–100 million people worldwide. Analysis of the adaptive immune response to S. stercoralis beyond descriptive studies is challenging, as no murine model for the complete infection cycle is available. However, the combined employment of different models each capable of modelling some features of S. stercoralis life cycle and pathology has advanced our understanding of the immunological mechanisms involved in host defence. Here we review: (i) studies using S. stercoralis third stage larvae implanted in diffusion chambers in the subcutaneous tissue of mice that allow analysis of the immune response to the human pathogenic Strongyloides species; (ii) studies using Strongyloides ratti and Strongyloides venezuelensis that infect mice and rats to extend the analysis to the parasites intestinal life stage and (iii) studies using S. stercoralis infected gerbils to analyse the hyperinfection syndrome, a severe complication of human strongyloidiasis that is not induced by rodent specific Strongyloides spp. We provide an overview of the information accumulated so far showing that Strongyloides spp. elicits a classical Th2 response that culminates in different, site specific, effector functions leading to either entrapment and killing of larvae in the tissues or expulsion of parasitic adults from the intestine.

With favourable error thresholds and requiring only nearest-neighbour interactions on a lattice, the surface code is an error-correcting code that has garnered considerable attention. At the heart of this code is the ability to perform a low-weight parity measurement of local code qubits. Here we demonstrate high-fidelity parity detection of two code qubits via measurement of a third syndrome qubit. With high-fidelity gates, we generate entanglement distributed across three superconducting qubits in a lattice where each code qubit is coupled to two bus resonators. Via high-fidelity measurement of the syndrome qubit, we deterministically entangle the code qubits in either an even or odd parity Bell state, conditioned on the syndrome qubit state. Finally, to fully characterize this parity readout, we develop a measurement tomography protocol. The lattice presented naturally extends to larger networks of qubits, outlining a path towards fault-tolerant quantum computing. Quantum error correction protocols aim at protecting quantum information from corruption due to decoherence and imperfect control. Using three superconducting transmon qubits, Chow et al . demonstrate necessary elements for the implementation of the surface error correction code on a two-dimensional lattice.

IL-17 (IL-17A) is a pro-inflammatory cytokine produced by a sub-set of T helper cells termed Th17 cells primarily in response to cytokines like TGF-β and IL-23 and play an important role in host defense. IL-17 signals via the IL-17RA/RC heterodimer and the adaptor protein Act1 to activate both canonical and non-canonical pathways inducing transcriptional activation and stabilization of mRNAs. IL-17 appears to act not directly on immune cells but stimulates stromal cells such as endothelial and epithelial cells and fibroblasts to secrete other immunomodulatory factors. Fibroblast activated by IL-17 can support the growth and differentiation of immune cells. Studies have begun to uncover a dual role for IL-17; on one hand enhancing immune reactions and promoting inflammatory diseases and on the other decreasing responses and immune activity in established disease settings. The balance of double-edged sword effect of IL-17 and autoimmunity is illustrated in a variety of human diseases and experimental models of diseases. Specifically, the emerging interest in autoimmunity in systemic sclerosis (Scleroderma, SSc) has led to potential role of IL-17A as a target therapy in this disease.

CAPTCHAs (Completely Automated Public Turing test to tell Computers and Humans Apart) are widespread security measures on the World Wide Web that prevent automated programs from abusing online services. They do so by asking humans to perform a task that computers cannot yet perform, such as deciphering distorted characters. Our research explored whether such human effort can be channeled into a useful purpose: helping to digitize old printed material by asking users to decipher scanned words from books that computerized optical character recognition failed to recognize. We showed that this method can transcribe text with a word accuracy exceeding 99%, matching the guarantee of professional human transcribers. Our apparatus is deployed in more than 40,000 Web sites and has transcribed over 440 million words.

Oro-facial fibrosis in systemic sclerosis (Scleroderma;SSc) has a major impact on mouth function, facial appearance, and patient quality of life. Lipotransfer is a method of reconstruction that can be used in the treatment of oro-facial fibrosis. The effect of this treatment not only restores oro-facial volume but has also been found to reverse the effects of oro-facial fibrosis. Adipose derived stem cells (ADSCs) within the engrafted adipose tissue have been shown to be anti-fibrotic in SSc and are proposed as the mechanism of the anti-fibrotic effect of lipotransfer. A cohort of 62 SSc patients with oro-facial fibrosis were assessed before and after stem cell enriched lipotransfer treatment. Clinical evaluation included assessment of mouth function using a validated assessment tool (Mouth Handicap in Systemic Sclerosis Scale-MHISS), validated psychological measurements and pre and post-operative volumetric assessment. In addition, to understand the mechanism by which the anti-fibrotic effect of ADSCs occur, SSc derived fibroblasts and ADSCs from this cohort of patients were co-cultured in direct and indirect culture systems and compared to monoculture controls. Cell viability, DNA content, protein secretion of known fibrotic mediators including growth factor- β1 (TGF β-1) and connective tissue growth factor (CTGF) using ELISA analysis and fibrosis gene expression using a fibrosis pathway specific qPCR array were evaluated. Mouth function (MHISS) was significantly improved (6.85±5.07) (p<0.0001) after treatment. All psychological measures were significantly improved: DAS 24 (12.1±9.5) (p<0.0001); HADS-anxiety (2.8±3.2) (p<0.0001), HADS-depression (2.0±3.1) (p<0.0001); BFNE (2.9 ± 4.3) (p<0.0001); VAS (3.56±4.1) (p<0.0001). Multiple treatments further improved mouth function (p<0.05), DAS (p<0.0001) and VAS (p = 0.01) scores. SSc fibroblast viability and proliferation was significantly reduced in co-culture compared to monoculture via a paracrine effect over 14 days (p < 0.0001). Protein secretion of transforming growth factor (TGF-β1) and connective tissue growth factor (CTGF) was significantly reduced in co-culture compared to monoculture (p < 0.0001). Multiple fibrosis associated genes were down regulated in SSc co-culture compared to monoculture after 14 days including Matrix metalloproteinase-8 (MMMP-8), Platelet derived growth factor-β (PDGF-β) and Integrin Subunit Beta 6 (ITG-β6). Autologous stem cell enriched lipotransfer significantly improved the effects of oro-facial fibrosis in SSc in this open cohort study. Lipotransfer may reduce dermal fibrosis through the suppression of fibroblast proliferation and key regulators of fibrogenesis including TG-β1 and CTGF. Our findings warrant further investigation in a randomised controlled trial.

Background Conditions like fibrosis, rheumatoid arthritis or cancer, once seen as distinct diseases, are now recognized to share strikingly common pathogenic mechanisms. The key to this convergence lies in the fibroblast, a pivotal driver of disease progression, tissue injury and chronicity. Despite this central pathogenic role and growing recognition as a therapeutic target, effective treatments targeting fibroblasts remain elusive, leaving a critical gap in disease intervention. Methods Here we present a novel approach to target fibrosis using the melanocortin compound BMS-470539 to treat in vitro cultured human dermal fibroblasts obtained from healthy volunteers and systemic sclerosis patients and measuring various markers of senescence and fibroblast activation combining microscopy, DNA sequencing, cell migration and RNA sequencing and PCR techniques. We also used the in vivo bleomycin induced skin fibrosis in mice to determine pre-clinical efficacy of BMS-470539. Results BMS-470539 induced a ‘senescence-like’ state in human dermal fibroblasts from systemic sclerosis patients, characterised by proliferation arrest, lack of pro-inflammatory secretome and inability to induce secondary senescence. This senescence-like activity (accompanied by β-galactosidase activity, lipofuscin accumulation and other markers) resulted in the downregulation of fibrosis markers including ⍺-smooth muscle actin, migration, CCL2 and genes related to TGFβ and fibroblast activation. In vivo, the compound reduced skin thickness on the bleomycin-induced skin fibrosis murine model when administered intraperitoneally, and importantly, this senescence-like activity did not cause signs of fibrosis when administered intradermally. Conclusions Here, we introduce a novel strategy to disarm pathogenic fibroblasts in the context of skin fibrosis using a therapeutic pro-senescence-like approach using the unconventional melanocortin compound BMS-470539, to reset fibroblast behaviour and disrupt disease progression. This work also emphasizes the translational potential of how understanding shared pathogenic mechanisms across diseases may lead to new therapeutic opportunities to manage multiple diseases like arthritis and fibrosis.