48 research outputs found

    The Dangers of Decoupling: Earth System Crisis and the 'Fourth Industrial Revolution'

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    The question of whether global capitalism can resolve the earth system crisis rests on the (im)possibility of ‘absolute decoupling’: whether or not economic growth can continue indefinitely as total environmental impacts shrink. Ecomodernists and other techno‐optimists argue for the feasibility of absolute decoupling, whereas degrowth advocates show that it is likely to be neither feasible in principle nor in the timeframe needed to ward off ecological tipping points. While primarily supporting the degrowth perspective, I will suggest that the ecomodernists have a wildcard in their pocket that hasn’t been systematically addressed by degrowth advocates. This is the ‘Fourth Industrial Revolution’, which refers to convergent innovations in biotechnology, nanotechnology, artificial intelligence, 3D printing, and other developments. However, I will argue that while these innovations may enable some degree of absolute decoupling, they will also intensify emerging risks in the domains of biosecurity, cybersecurity, and state securitization. Overall, these technologies will not only place unprecedented destructive power in the hands of non‐state actors but will also empower and incentivize states to create a global security regime with unprecedented surveillance and force mobilization capacities. This reinforces the conclusion that mainstream environmental policies based on decoupling should be reconsidered and supplanted by alternative policy trajectories based on material‐energetic degrowth, redistribution, and technological deceleration

    Adrenomedullin and tumour microenvironment

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    Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed

    Signal One and Two Blockade Are Both Critical for Non-Myeloablative Murine HSCT across a Major Histocompatibility Complex Barrier

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    Non-myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) is rarely achievable clinically, except where donor cells have selective advantages. Murine non-myeloablative conditioning regimens have limited clinical success, partly through use of clinically unachievable cell doses or strain combinations permitting allograft acceptance using immunosuppression alone. We found that reducing busulfan conditioning in murine syngeneic HSCT, increases bone marrow (BM):blood SDF-1 ratio and total donor cells homing to BM, but reduces the proportion of donor cells engrafting. Despite this, syngeneic engraftment is achievable with non-myeloablative busulfan (25 mg/kg) and higher cell doses induce increased chimerism. Therefore we investigated regimens promoting initial donor cell engraftment in the major histocompatibility complex barrier mismatched CBA to C57BL/6 allo-transplant model. This requires full myeloablation and immunosuppression with non-depleting anti-CD4/CD8 blocking antibodies to achieve engraftment of low cell doses, and rejects with reduced intensity conditioning (≀75 mg/kg busulfan). We compared increased antibody treatment, G-CSF, niche disruption and high cell dose, using reduced intensity busulfan and CD4/8 blockade in this model. Most treatments increased initial donor engraftment, but only addition of co-stimulatory blockade permitted long-term engraftment with reduced intensity or non-myeloablative conditioning, suggesting that signal 1 and 2 T-cell blockade is more important than early BM niche engraftment for transplant success

    Inflammatory Bowel Diseases

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