Italian Folk-Songs

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Thermodynamic properties of binary HCP solution phases from special quasirandom structures

Three different special quasirandom structures (SQS) of the substitutional hcp $A_{1-x}B_x$ binary random solutions ($x=0.25$, 0.5, and 0.75) are presented. These structures are able to mimic the most important pair and multi-site correlation functions corresponding to perfectly random hcp solutions at those compositions. Due to the relatively small size of the generated structures, they can be used to calculate the properties of random hcp alloys via first-principles methods. The structures are relaxed in order to find their lowest energy configurations at each composition. In some cases, it was found that full relaxation resulted in complete loss of their parental symmetry as hcp so geometry optimizations in which no local relaxations are allowed were also performed. In general, the first-principles results for the seven binary systems (Cd-Mg, Mg-Zr, Al-Mg, Mo-Ru, Hf-Ti, Hf-Zr, and Ti-Zr) show good agreement with both formation enthalpy and lattice parameters measurements from experiments. It is concluded that the SQS's presented in this work can be widely used to study the behavior of random hcp solutions.Comment: 15 pages, 8 figure

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers.</p> <p>Methods</p> <p>Mice carrying human (FaDu_dd) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared.</p> <p>Results</p> <p>In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu_dd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker.</p> <p>Conclusions</p> <p>The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among tested genes, our study identified CA9, GLUT1 and possibly LOX as highly specific biomarkers of tumor hypoxia in vivo.</p

In search of phylogenetic congruence between molecular and morphological data in bryozoans with extreme adult skeletal heteromorphy

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=tsab20© Crown Copyright 2015. This document is the author's final accepted/submitted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity.

Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice. A homozygous hypomorphic mutation in human OTULIN causes a potentially fatal autoinflammatory condition termed OTULIN-related autoinflammatory syndrome (ORAS). Four independent OTULIN mouse models reveal that OTULIN deficiency in immune cells results in cell-type-specific effects, ranging from over-production of inflammatory cytokines and autoimmunity due to accumulation of M1-linked polyubiquitin and spontaneous NF-κB activation in myeloid cells to downregulation of M1-polyubiquitin signaling by degradation of LUBAC in B and T cells. Remarkably, treatment with anti-TNF neutralizing antibodies ameliorates inflammation in ORAS patients and rescues mouse phenotypes. Hence, OTULIN is critical for restraining life-threatening spontaneous inflammation and maintaining immune homeostasis.This work was supported by the Medical Research Council (U105192732 and U105178805), the European Research Council (309756), the Lister Institute for Preventive Medicine, and the EMBO Young Investigator Program (to D.K.); a Marie-Sklodowska Curie Individual Fellowship from the European Commission (MC-IF-654019) and a Research Fellowship from Corpus Christi College Cambridge (to R.B.D.); and Wellcome Trust (to N.V.M., E.R.M., and A.N.J.M [100963/Z/13/Z]), WellChild (to N.V.M. and E.R.M.), and UCB (to H.L.T., D.M. and E.R.M.).This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.cell.2016.07.01