Microcompression experiments on glasses ‐ strain rate sensitive cracking behavior

Figure 11 – microcompression experiments on glasses showing stable crack growth (a) and reversible deformation (b) It is well known that the mechanical properties of glasses are closely related to their atomic structure. The exact structure-property-relationship, however, is only poorly understood even for fundamental mechanisms like shear and densification. Nanomechanical test methods like micropillar compression and nano indentation can help fill this gap. In this study a sodium-boro-silicate glass is quenched from different temperatures to induce changes in the atomic structure. Micropillar compression was used to introduce plastic deformation into these glasses at room temperature under a uniaxial stress state. By changing the strain rate it is shown that deformation shifts from completely reversible deformation, to stable crack growth, and finally brittle failure. It is shown that by changing the glass structure, the strain rates corresponding to these deformation regimes are shifted. Finally, the occurrence of shear and densification is discussed. These findings are analysed against the background of the glass structure. Please click Additional Files below to see the full abstract

Using impact‐nanoindentation to test glasses at high strain rates and room temperature

In many daily applications glasses are indispensable, and novel applications demanding improved strength and crack resistance are appearing continuously. Up to now, the fundamental mechanical processes in glasses subjected to high strain rates at room temperature are largely unknown and thus guidelines for one of the major failure conditions of glass components are non-existent. Here, we elucidate this important regime for the first time using glasses ranging from a dense metallic glass to open fused silica by impact as well as quasi-static nano-indentation. We show that towards high strain rates, shear deformation becomes the dominant mechanism in all glasses accompanied by Non-Newtonian behavior evident in a drop of viscosity with increasing rate covering eight orders of magnitude. All glasses converge to the same limit stress determined by the theoretical hardness, thus giving the first experimental and quantitative evidence that Non-Newtonian shear flow occurs at the theoretical strength at room temperature

Gene expression analysis in the pathogenesis of chronic immune thrombocytopenia in children

BackgroundA complex multifactorial dysregulation of immune system, including cytokines and autoantibodies production, and also proteins modification underlay the primary mechanism of immune thrombocytopenia (ITP). Specific genetic profile of ITP patients is presumed, especially those with a long and complex natural history of the disease.Aim of the studyGene expression analysis of VNN1 and PPARγ in children with immune thrombocytopenia.Materials and methodsCandidate genes were identified with microarray cDNA procedure. For the validation of VNN1 and PPARγ expression changes we used qRT-PCR performed comparatively in samples of newly diagnosed ITP (ndITP, n=16), chronic ITP (cITP, n=8) and patients without thrombocytopenia (n=5).ResultsWe analyzed the data of patients, followed for at least 12 months after ITP diagnosis. No significant differences of VNN1 expression profile were found in between groups (p>0.05). Lower signatures of mean PPARγ normalized expression values were noticed in chronic ITP patients in contrast to newly diagnosed ITP subjects (p=0.009). Differences between VNN1/PPARγ ratio values found in ndITP group comparing to subjects with progression to cITP were close to statistical significance (p=0.054).ConclusionsAnalysis of the VNN1 and PPARγ expression profiles utility in children diagnosed with ITP requires further investigation

Complete and Prolonged Response to Immune Checkpoint Blockade in POLE-Mutated Colorectal Cancer

Enid Robertson Logan Faculty Fellowship Fund6 month embargo; published online: 21 June 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Immunoglobulin and T Cell Receptor Gene High-Throughput Sequencing Quantifies Minimal Residual Disease in Acute Lymphoblastic Leukemia and Predicts Post-Transplantation Relapse and Survival

AbstractMinimal residual disease (MRD) quantification is an important predictor of outcome after treatment for acute lymphoblastic leukemia (ALL). Bone marrow ALL burden ≥ 10−4 after induction predicts subsequent relapse. Likewise, MRD ≥ 10−4 in bone marrow before initiation of conditioning for allogeneic (allo) hematopoietic cell transplantation (HCT) predicts transplantation failure. Current methods for MRD quantification in ALL are not sufficiently sensitive for use with peripheral blood specimens and have not been broadly implemented in the management of adults with ALL. Consensus-primed immunoglobulin (Ig), T cell receptor (TCR) amplification and high-throughput sequencing (HTS) permit use of a standardized algorithm for all patients and can detect leukemia at 10−6 or lower. We applied the LymphoSIGHT HTS platform (Sequenta Inc., South San Francisco, CA) to quantification of MRD in 237 samples from 29 adult B cell ALL patients before and after allo-HCT. Using primers for the IGH-VDJ, IGH-DJ, IGK, TCRB, TCRD, and TCRG loci, MRD could be quantified in 93% of patients. Leukemia-associated clonotypes at these loci were identified in 52%, 28%, 10%, 35%, 28%, and 41% of patients, respectively. MRD ≥ 10−4 before HCT conditioning predicted post-HCT relapse (hazard ratio [HR], 7.7; 95% confidence interval [CI], 2.0 to 30; P = .003). In post-HCT blood samples, MRD ≥10−6 had 100% positive predictive value for relapse with median lead time of 89 days (HR, 14; 95% CI, 4.7 to 44, P < .0001). The use of HTS-based MRD quantification in adults with ALL offers a standardized approach with sufficient sensitivity to quantify leukemia MRD in peripheral blood. Use of this approach may identify a window for clinical intervention before overt relapse

The role of CD8+ T cell clones in immune thrombocytopenia

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multi-dimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterised patients with ITP and compared them to age-matched controls using immunophenotyping, next-generation sequencing of T cell receptor (TCR) genes, single-cell RNA sequencing, and functional T cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon-g, tumour necrosis factor-a, and Granzyme B defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the T cell receptor showed expanded T cell clones in patients with ITP. T cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon-g and trigger platelet activation and apoptosis through TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries