EURAMET key comparison between INRiM and UME in Vickers hardness scales (HV1 - HV30) - EURAMET.M.H-K1.b and c

This report describes the method and results of a bilateral EURAMET Key Comparison in Vickers hardness scales of two National Metrology Institutes (NMIs) of Italy and Turkey, INRiM and UME, respectively. The Pilot Laboratory (PL) is INRiM in the comparison in which one set of hardness reference blocks with three hardness levels for the Vickers Hardness scales of both HV1 and HV30 was used. The comparison was realized as planned in the Technical Protocol with some delay. The aim of this comparison is to link the UME measurement results to the CCM.H-K1.b.c through the PL (INRiM) as a participant of the CCM key comparison. The measurement results and uncertainty assessments declared by INRiM and UME are in consistency with each other and UME results are also in consistency with the CCM.H-K1.b.c Key Comparison Reference Values (KCRVs). The CCM.H-K1.b.c was realized during 2001 to 2003 to investigate the metrological equivalence of national standards among national metrology institutes (NMIs) within the CCM

Result analysis of EURAMET Vickers comparison between INRiM and UME (EURAMET.M.H-K1.b.c)

A bilateral key comparison between INRiM (National Metrology Institute of Italy) and TUBITAK UME (National Metrology Institute of Turkey) had been decided to be organized in the field of Hardness Metrology to determine the consistency of the national hardness standards in both countries realizing Vickers Hardness measurements in accordance with ISO 6507–1:2018 [1] and ISO 6507–3:2018 [2] standards. Widely used Vickers Hardness scales such as HV1 and HV30 constitute the scope of the comparison which was piloted by INRiM. In this paper the procedure and measurement results of the bilateral EURAMET key comparison between the two laboratories are explained

Preliminary results of EURAMET Rockwell comparison between INRiM and UME (EURAMET.M.H-S1.A.B.C)

A bilateral supplementary comparison between INRiM (National Metrology Institute of Italy) and UME (National Metrology Institute of Turkey) had been decided to be organized in the field of Hardness Metrology to determine the consistency of the national hardness standards in both countries realizing Rockwell Hardness measurements in accordance with ISO 6508-1:2016 [1] and ISO 6508-3:2015 [2] standards. In this paper the procedure and preliminary measurement results of the bilateral EURAMET supplementary comparison between the two laboratories are explained

Result analysis of EURAMET Brinell comparison between INRiM, UME and PTB (EURAMET.M.H–S2.A.B)

A EURAMET supplementary comparison between INRiM (National Metrology Institute of Italy), UME (National Metrology Institute of Republic of Turkey) and PTB (National Metrology Institute of Germany) had been decided to be organized in the field of Hardness Metrology to determine the consistency of the national hardness standards in these three countries realizing Brinell Hardness measurements in accordance with ISO 6506–1:2014 [1] and ISO 6506–3:2014 [2] standards. Widely used Brinell Hardness scales such as HBW 1/30 and HBW 2.5/187.5 constitute the scope of the comparison. In this paper the procedure and comparison results are explained

The many faces of small B cell lymphomas with plasmacytic differentiation and the contribution of MYD88 testing

Plasmacytic differentiation may occur in almost all small B cell lymphomas (SBLs), although it varies from being uniformly present (as in lymphoplasmacytic lymphoma (LPL)) to very uncommon (as in mantle cell lymphomas (MCLs)). The discovery of MYD88 L265P mutations in the vast majority of LPLs has had a major impact on the study of these lymphomas. Review of the cases contributed to the 2014 European Association for Haematopathology/Society for Hematopathology slide workshop illustrated how mutational testing has helped refine the diagnostic criteria for LPL, emphasizing the importance of identifying a clonal monotonous lymphoplasmacytic population and highlighting how LPL can still be diagnosed with extensive nodal architectural effacement, very subtle plasmacytic differentiation, follicular colonization, or uncommon phenotypes such as CD5 or CD10 expression. MYD88 L265P mutations were found in 11/11 LPL cases versus only 2 of 28 other SBLs included in its differential diagnosis. Mutational testing also helped to exclude other cases that would have been considered LPL in the past. The workshop also highlighted how plasmacytic differentiation can occur in chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, SOX11 negative MCL, and particularly in marginal zone lymphomas, all of which can cause diagnostic confusion with LPL. The cases also highlighted the difficulty in distinguishing lymphomas with marked plasmacytic differentiation from plasma cell neoplasms. Some SBLs with plasmacytic differentiation can be associated with amyloid, other immunoglobulin deposition, or crystal-storing histiocytosis, which may obscure the underlying neoplasm. Finally, although generally indolent, LPL may transform, with the workshop cases suggesting a role for TP53 abnormalities

Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles

The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society

Vascular phenotypes in primary non-small cell lung carcinomas and matched brain metastases

BACKGROUND: Anti-angiogenic therapy with bevacizumab (an anti-vascular endothelial growth factor (VEGF) antibody) predominantly targets immature blood vessels. Bevacizumab has shown a survival benefit in non-small cell lung carcinoma (NSCLC) and has recently been demonstrated to be safe in patients with brain metastases. However, it is not known whether bevacizumab is effective against brain metastases or whether metastases are representative of their primary in terms of VEGF expression, hypoxia, proliferation and vascular phenotype. The aim of this study was to evaluate these factors in a series of matched primary NSCLCs and brain metastases. METHODS AND RESULTS: Immunohistochemistry showed strong correlation of carbonic anhydrase 9 expression (a marker of hypoxia) in primary and secondary cancers (P=0.0002). However, the proliferation index, VEGF expression, microvessel density and the proportion of mature vessels were discordant between primary and secondary cancers. The mean proportion of mature vessels was 63.2% higher in the brain metastases than the primary tumours (P=0.004). Moreover, the vascular pattern of the primary tumour was not representative of the metastasis. CONCLUSIONS: Brain metastases have a significantly higher proportion of mature vasculature, suggesting that they may be refractory to anti-VEGF therapy. These findings may have implications for clinical trials and biomarker studies evaluating anti-angiogenic agents in brain metastases