167 research outputs found

    A molecular map of mesenchymal tumors

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    Background Bone and soft tissue tumors represent a diverse group of neoplasms thought to derive from cells of the mesenchyme or neural crest. Histological diagnosis is challenging due to the poor or heterogenous differentiation of many tumors, resulting in uncertainty over prognosis and appropriate therapy. Results We have undertaken a broad and comprehensive study of the gene expression profile of 96 tumors with representatives of all mesenchymal tissues, including several problem diagnostic groups. Using machine learning methods adapted to this problem we identify molecular fingerprints for most tumors, which are pathognomonic (decisive) and biologically revealing. Conclusion We demonstrate the utility of gene expression profiles and machine learning for a complex clinical problem, and identify putative origins for certain mesenchymal tumor

    Radiation-grafted anion-exchange membranes for CO2 electroreduction cells: an unexpected effect of using a lower excess of N-methylpiperidine in their fabrication

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    Giron Rodriguez et al. [ACS Sustainable Chem. Eng., 2023, 11, 1508] previously showed that radiation-grafted anion-exchange membranes containing N-benzyl-N-methylpiperidinium headgroups (MPIP-RG-AEM) are promising for use in CO2 electrolysis (cf. commercial and other RG-AEM types). For a more sustainable synthesis, MPIP-RG-AEMs have now been fabricated using a reduced 1.1 times excess of amine reagent (historically made using >5 times excess). A resulting RG-AEM promisingly had a bulk amination level that was comparable to those made with the traditional large excess. Unexpectedly, however, it had a significantly reduced water content, with two further batches showing that this observation was repeatable (and reproducible via measurements collected on a single batch using different techniques in different labs). The ionic conductivities of the RG-AEM made with a controlled 1.1 excess of amine were also lower, with higher activation energies. Terahertz time-domain spectroscopy measurements showed that the lower water uptake RG-AEMs, made with the 1.1 amine excess, contained smaller amounts of bulk water relative to bound water (a repeatable observation with different counter-anions). This lack of bulk water, yielding reduced water diffusion coefficients, led to a change in the water management when such RG-AEMs were tested in CO2 electrolysis cells, with significantly affected in situ performances. Small angle scattering data (X-ray and neutron) indicated that MPIP-RG-AEM fabrication with the 1.1 excess of amine reduced the size of the amorphous lamella domains on hydration, and this change is suspected to be the cause of the lower water uptakes and swelling. The finding that chemically similar AEMs can have significantly different hydration properties is potentially important to all ion-exchange membrane users and developers (beyond the CO2 electrolysis scope of this study)

    Parkour, Counter-Conducts and the Government of Difference in Post-industrial Turin

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    The following paper aims to offer a critical discussion of the unfolding politics of belonging and exclusion taking place in Turin's regenerating cityscape as a way to illuminate the paradoxes, tensions and daily negotiations of emerging forms of social and spatial restructuring in the post-industrial city. In developing this analysis, we engage with an integrated methodological approach that privileges the voices and experiences of about 30 young men, mostly of migrant origins and aged 16-21, practicing parkour in the city's public spaces. In addressing these issues, we focus on the participants' engagement with one of the symbols of Turin's (multi)cultural, community-oriented and creative renewal, the post-industrial urban park of Parco Dora in order to unpack the processes of inclusion/exclusion and the conduct of conduct (Rose 2000) enacted in the creation, management and use of the city's regenerating areas. Our discussion of the participants' ambivalent and contested practices in Turin's cityscape enabled us to address how these young men re-inscribe tensions, instabilities and fault-lines relational to the “selective story-telling” (Vanolo 2015, 2) characterizing Turin's narratives of consensual transformation, post-industrial renaissance and (multi)cultural vitality. In particular, by engaging with the participants' bodily and spatial negotiations in Turin's public spaces through the lens of counter-conduct (Foucault 2007[1978]), we highlight the significance of recognising and examining partial, but productive forms of urban contestation within contemporary, pacified scenarios of urban regeneration

    Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

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    GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem
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