The role of β-titanium ligaments in the deformation of dual phase titanium alloys

Multiphase titanium alloys are critical materials in high value engineering components, for instance in aero engines. Microstructural complexity is exploited through interface engineering during mechanical processing to realise significant improvements in fatigue and fracture resistance and strength. In this work, we explore the role of select interfaces using in-situ micromechanical testing with concurrent observations from high angular resolution electron backscatter diffraction (HR-EBSD). Our results are supported with post mortem transmission electron microscopy (TEM). Using micro-pillar compression, we performed in-depth analysis of the role of select {\beta}-titanium (body centred cubic) ligaments which separate neighbouring {\alpha}-titanium (hexagonal close packed) regions and inhibit the dislocation motion and impact strength during mechanical deformation. These results shed light on the strengthening mechanisms and those that can lead to strain localisation during fatigue and failure

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

BACKGROUND: Retinitis pigmentosa (RP), a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP). Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. METHODS: Denaturing gradient gel electrophoresis (DGGE) analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. RESULTS: Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. CONCLUSION: Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations

Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells

Human CD8+ regulatory T cells, particularly the CD8+CD28− T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8+ T cells which results in significant expansions of donor-specific CD8+CD28− T suppressor cells in vitro. The expanded CD8+CD28− T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4+ T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8+CD28− T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation

The dynamic cilium in human diseases

Cilia are specialized organelles protruding from the cell surface of almost all mammalian cells. They consist of a basal body, composed of two centrioles, and a protruding body, named the axoneme. Although the basic structure of all cilia is the same, numerous differences emerge in different cell types, suggesting diverse functions. In recent years many studies have elucidated the function of 9+0 primary cilia. The primary cilium acts as an antenna for the cell, and several important pathways such as Hedgehog, Wnt and planar cell polarity (PCP) are transduced through it. Many studies on animal models have revealed that during embryogenesis the primary cilium has an essential role in defining the correct patterning of the body. Cilia are composed of hundreds of proteins and the impairment or dysfunction of one protein alone can cause complete loss of cilia or the formation of abnormal cilia. Mutations in ciliary proteins cause ciliopathies which can affect many organs at different levels of severity and are characterized by a wide spectrum of phenotypes. Ciliary proteins can be mutated in more than one ciliopathy, suggesting an interaction between proteins. To date, little is known about the role of primary cilia in adult life and it is tempting to speculate about their role in the maintenance of adult organs. The state of the art in primary cilia studies reveals a very intricate role. Analysis of cilia-related pathways and of the different clinical phenotypes of ciliopathies helps to shed light on the function of these sophisticated organelles. The aim of this review is to evaluate the recent advances in cilia function and the molecular mechanisms at the basis of their activity

Data bundle for "The role of beta-titanium ligaments in the deformation of dual phase titanium alloys"

Data bundle for "The role of ¥â-titanium ligaments in the deformation of dual phase titanium alloys" Tea-Sung Jun1,2, Xavier Maeder3, Ayan Bhowmik1,a, Gaylord Guillonneau3,4, Johann Michler3, Finn Giuliani1, T. Ben Britton1* 1 Department of Materials, Royal School of Mines, Imperial College London, London SW7 2AZ, UK 2 Department of Mechanical Engineering, Incheon National University, Incheon 22012, Republic of Korea 3 EMPA, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Mechanics of Materials and Nanostructures, Feuerwerkerstrasse 39, CH-3602 Thun, Switzerland 4 Universite de Lyon, Ecole Centrale de Lyon, LTDS UMR CNRS 5513, 36 Avenue Guy de Collongue, 69134 Ecully Cedex, France a now at Rolls-Royce@NTU Corporate Lab, Nanyang Technological University, Singapore For more information please contact: [email protected] (Ben Britton) --- This data bundle contains 1 file and 5 subfolders: Figures - all the images that were included in the paper Subfolder for Figure 4 - raw data for load vs. displacement Subfolder for Figure 7(A) - raw data for engineering stress vs. engineering strain Subfolder for Figure 7(B) - cross court data and images of beta vertical micropillar Subfolder for Figure 7(C) - cross court data and images of beta inclined micropillar Subfolder for Figure 10 - raw data for stress relaxation vs. timeData bundle for "The role of ¥â-titanium ligaments in the deformation of dual phase titanium alloys" Tea-Sung Jun1,2, Xavier Maeder3, Ayan Bhowmik1,a, Gaylord Guillonneau3,4, Johann Michler3, Finn Giuliani1, T. Ben Britton1* 1 Department of Materials, Royal School of Mines, Imperial College London, London SW7 2AZ, UK 2 Department of Mechanical Engineering, Incheon National University, Incheon 22012, Republic of Korea 3 EMPA, Swiss Federal Laboratories for Materials Science and Technology, Laboratory for Mechanics of Materials and Nanostructures, Feuerwerkerstrasse 39, CH-3602 Thun, Switzerland 4 Universite de Lyon, Ecole Centrale de Lyon, LTDS UMR CNRS 5513, 36 Avenue Guy de Collongue, 69134 Ecully Cedex, France a now at Rolls-Royce@NTU Corporate Lab, Nanyang Technological University, Singapore For more information please contact: [email protected] (Ben Britton) --- This data bundle contains 1 file and 5 subfolders: Figures - all the images that were included in the paper Subfolder for Figure 4 - raw data for load vs. displacement Subfolder for Figure 7(A) - raw data for engineering stress vs. engineering strain Subfolder for Figure 7(B) - cross court data and images of beta vertical micropillar Subfolder for Figure 7(C) - cross court data and images of beta inclined micropillar Subfolder for Figure 10 - raw data for stress relaxation vs. tim