Electropolishing of medical-grade stainless steel in preparation for surface nano-texturing

The purpose of this work is to investigate the electropolishing of medical grade 316L stainless steel to obtain a clean, smooth and defect free surface in preparation for surface nano-texturing. Electropolishing of steel was conducted under stationary conditions in four electrolyte mixtures: A) 4.5 M H2SO4 + 11 M H3PO4, B) 7.2 M H2SO4 + 6.5 M H3PO4, C) 6.4 M glycerol + 6.1 M H3PO4 and D) 6.1 M H3PO4. The influence of electrolyte composition and concentration, temperature and electropolishing time, in conjunction with linear sweep voltammetry and chronoamperometry, on the stainless steel surface was studied. The activation energies for dissolution of steel in the four electrolyte solutions were calculated. The resulting surfaces of unpolished and optimally-polished stainless steel were characterised in terms of contamination, defects, topography, roughness, hydrophilicity and chemical composition by optical and atomic force microscopies, contact angle goniometry and x-ray photoelectron spectroscopy. It was found that the optimally polished surfaces were obtained with the following parameters: electrolyte mixture A at 2.1 V applied potential, 80 °C for 10 minutes. This corresponded to the diffusion-limited dissolution of the surface. The root mean square surface roughness of the electropolished surface achieved was 0.4 nm over 2 x 2 μm2. Surface analysis showed that electropolishing led to ultraclean surfaces with reduced roughness and contamination thickness, and with Cr, P, S, Mo, Ni and O enrichment compared to untreated surfaces

Genomic variant sharing: a position statement.

Sharing de-identified genetic variant data is essential for the practice of genomic medicine and is demonstrably beneficial to patients. Robust genetic diagnoses that inform medical management cannot be made accurately without reference to genetic test results from other patients, as well as population controls. Errors in this process can result in delayed, missed or erroneous diagnoses, leading to inappropriate or missed medical interventions for the patient and their family. The benefits of sharing individual genetic variants, and the harms of not sharing them, are numerous and well-established. Databases and mechanisms already exist to facilitate deposition and sharing of pseudonomised genetic variants, but clarity and transparency around best practice is needed to encourage widespread use, prevent inconsistencies between different communities, maximise individual privacy and ensure public trust. We therefore recommend that widespread sharing of a small number of individual genetic variants associated with limited clinical information should become standard practice in genomic medicine. Information robustly linking genetic variants with specific conditions is fundamental biological knowledge, not personal information, and therefore should not require consent to share. For additional case-level detail about individual patients or more extensive genomic information, which is often essential for clinical interpretation, it may be more appropriate to use a controlled-access model for data sharing, with the ultimate aim of making as much information as open and de-identified as possible with appropriate consent

Correlative Microscopy Study of FIB Patterned Stainless Steel Surfaces as Novel Nano-Structured Stents for Cardiovascular Applications

Coronary artery disease is a major problem worldwide causing 7.2 million deaths worldwide annually, resulting from vascular occlusion, myocardial infarction and its complications. Stent implantation is a percutaneous interventional procedure that mitigates vessel stenosis, providing mechanical support within the artery. However, stenting causes physical damage to the arterial wall. It is well accepted that a valuable route to reduce in-stent re-stenosis can be based on promoting cell response to nano-structured stainless steel (SS) surfaces such as, for example, by patterning nano-pits in SS. In this regard patterning by Focussed Ion-Beam (FIB) milling offers several advantages for flexible prototyping (i) practically any substrate material that is able to withstand high vacuum conditions of the microscope chamber can be used, (ii) there is high flexibility in the obtainable shapes and geometries by modulating the ion beam current and the patterning conditions, (iii) reduced complexity of the pattering process e.g. it is a single-step process with a possibility of real-time monitoring of the milling progression. On the other hand FIB patterning of polycrystalline metals is greatly influenced by channelling effects and re-deposition. Correlative microscopy methods present an opportunity to study such effects comprehensively and derive structure-property understanding that is important for developing improved pattering.In this report we present a FIB patterning protocol for nano-structuring features (concaves) ordered in rectangular arrays on pre-polished 316L Stainless Steel (SS) surfaces. An investigation based on correlative microscopy approach of the size, shape and depth of the developed arrays in relation to the crystal orientation of the underlying SS domains, is presented. The correlative microscopy protocol is based on cross-correlation of top-view Scanning Electron Microscopy (SEM), Electron Backscattered Diffraction (EBSD), and Atomic Force Microscopy (AFM).Various dose tests were performed, aiming at improved productivity by preserving nano-size accuracy of the patterned process. The optimal FIB patterning conditions for achieving reasonably high throughput (patterned rate of about 0.03 mm2 per hour) and nano-size accuracy in dimensions and shapes of the features, are discussed as well

FIB patterning of stainless steel for the development of nano-structured stent surfaces for cardiovascular applications

Stent implantation is a percutaneous interventional procedure that mitigates vessel stenosis, providing mechanical support within the artery and as such a very valuable tool in the fight against coronary artery disease. However, stenting causes physical damage to the arterial wall. It is well accepted that a valuable route to reduce in-stent re-stenosis can be based on promoting cell response to nano-structured stainless steel (SS) surfaces such as by patterning nano-pits in SS. In this regard patterning by focused ion beam (FIB) milling offers several advantages for flexible prototyping. On the other hand FIB patterning of polycrystalline metals is greatly influenced by channelling effects and redeposition. Correlative microscopy methods present an opportunity to study such effects comprehensively and derive structure–property understanding that is important for developing improved patterning. In this chapter we present a FIB patterning protocol for nano-structuring features (concaves) ordered in rectangular arrays on pre-polished 316L stainless steel surfaces. An investigation based on correlative microscopy approach of the size, shape and depth of the developed arrays in relation to the crystal orientation of the underlying SS domains is presented. The correlative microscopy protocol is based on cross-correlation of top-view scanning electron microscopy, electron backscattering diffraction, atomic force microscopy and cross-sectional (serial) sectioning. Various FIB tests were performed, aiming at improved productivity by preserving nano-size accuracy of the patterned process. The optimal FIB patterning conditions for achieving reasonably high throughput (patterned rate of about 0.03 mm2/h) and nano-size accuracy in dimensions and shapes of the features are discussed as well

Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility

We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants repo

EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 96 (FGE.96): Consideration of 88 flavouring substances considered by EFSA for which EU production volumes / anticipated production volumes have been submitted on request by DG SANCO. Addendum to FGE. 51, 52, 53, 54, 56, 58, 61, 62, 63, 64, 68, 69, 70, 71, 73, 76, 77, 79, 80, 83, 84, 85 and 87

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism1. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia2, 3, 4. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancie

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are