The Hide-and-Seek of Grain Boundaries from Moire Pattern Fringe of Two-Dimensional Graphene

Grain boundaries (GBs) commonly exist in crystalline materials and affect various properties of materials. The facile identification of GBs is one of the significant requirements for systematical study of polycrystalline materials including recently emerging two-dimensional materials. Previous observations of GBs have been performed by various tools including high resolution transmission electron microscopy. However, a method to easily identify GBs, especially in the case of low-angle GBs, has not yet been well established. In this paper, we choose graphene bilayers with a GB as a model system and investigate the effects of interlayer rotations to the identification of GBs. We provide a critical condition between adjacent moire fringe spacings, which determines the possibility of GB recognition. In addition, for monolayer graphene with a grain boundary, we demonstrate that low-angle GBs can be distinguished easily by inducing moire patterns deliberately with an artificial reference overlayopen0

Regulation of Cathepsin G Reduces the Activation of Proinsulin-Reactive T Cells from Type 1 Diabetes Patients

Autoantigenic peptides resulting from self-proteins such as proinsulin are important players in the development of type 1 diabetes mellitus (T1D). Self-proteins can be processed by cathepsins (Cats) within endocytic compartments and loaded to major histocompatibility complex (MHC) class II molecules for CD4+ T cell inspection. However, the processing and presentation of proinsulin by antigen-presenting cells (APC) in humans is only partially understood. Here we demonstrate that the processing of proinsulin by B cell or myeloid dendritic cell (mDC1)-derived lysosomal cathepsins resulted in several proinsulin-derived intermediates. These intermediates were similar to those obtained using purified CatG and, to a lesser extent, CatD, S, and V in vitro. Some of these intermediates polarized T cell activation in peripheral blood mononuclear cells (PBMC) from T1D patients indicative for naturally processed T cell epitopes. Furthermore, CatG activity was found to be elevated in PBMC from T1D patients and abrogation of CatG activity resulted in functional inhibition of proinsulin-reactive T cells. Our data suggested the notion that CatG plays a critical role in proinsulin processing and is important in the activation process of diabetogenic T cells

Systemic inhibition of tumour angiogenesis by endothelial cell-based gene therapy

Angiogenesis and post-natal vasculogenesis are two processes involved in the formation of new vessels, and both are essential for tumour growth and metastases. We isolated endothelial cells from human blood mononuclear cells by selective culture. These blood outgrowth cells expressed endothelial cell markers and responded correctly to functional assays. To evaluate the potential of blood outgrowth endothelial cells (BOECs) to construct functional vessels in vivo, NOD-SCID mice were implanted with Lewis lung carcinoma cells subcutaneously (s.c.). Blood outgrowth endothelial cells were then injected through the tail vein. Initial distribution of these cells occurred throughout the lung, liver, spleen, and tumour vessels, but they were only found in the spleen, liver, and tumour tissue 48 h after injection. By day 24, they were mainly found in the tumour vasculature. Tumour vessel counts were also increased in mice receiving BOEC injections as compared to saline injections. We engineered BOECs to deliver an angiogenic inhibitor directly to tumour endothelium by transducing them with the gene for human endostatin. These cells maintained an endothelial phenotype and decreased tumour vascularisation and tumour volume in mice. We conclude that BOECs have the potential for tumour-specific delivery of cancer gene therapy

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Evaluation of a domestic violence intervention in the maternity and sexual health services of a UK hospital.

This paper reports on an evaluation of a domestic violence intervention in the maternity and sexual health services of a UK hospital. The intervention encompassed guidelines, staff training, inclusion of routine enquiry for domestic violence with all patients, and referral of women disclosing violence to an on-site advocacy service. An "assumption querying" approach was applied to evaluate the intervention. Programmatic assumptions were identified and tested using interviews with service providers and patients, review of patient records, and pre- and post-training questionnaires. Domestic violence training resulted in changes in health professionals' knowledge and practice in the short-term, but universal routine enquiry was not achieved even in a context of organisational support, guidelines, training and advocacy. Potential and actual harm occurred, including breaches of confidentiality and failure to document evidence, limiting women's ability to access civil and legal remedies. Advocacy support led to positive outcomes for many women, as long as support to maintain positive changes, whether women stayed with or left the violent partner, continued to be given. Maternity and sexual health services were found to be opportune points of intervention for domestic violence services that combine routine enquiry by clinicians, support after disclosure and attention to harm reduction