Martensitic transformation of individual grains in low-alloyed TRIP steels

We have performed in situ synchrotron X-ray diffraction experiments on low-alloyed multiphase TRIP steels during cooling, to monitor the martensitic transformation of individual austenite grains within the bulk material. Direct experimental evidence is presented that the stability of the austenite grains is controlled not only by the local carbon level but also by the grain size. This new quantitative information on the martensitic transformation in complex microstructures is of great importance for the design of martensite-based metallic materials.</p

Characterization of individual retained austenite grains and their stability in low-alloyed TRIP steels

In situ three-dimensional (3-D) X-ray diffraction experiments have been performed at a synchrotron source on low-alloyed multiphase TRIP steels containing 0.25 wt.% Si and 0.44 wt.% Al and produced with different bainitic holding times, in order to assess the influence of the bainitic transformation on the thermal stability of individual austenite grains with respect to their martensitic transformation. A detailed characterization of the austenite grain volume distribution at room temperature was performed as a function of the prior bainitic holding time. In addition, the martensitic transformation behaviour of individual metastable grains was studied in situ during cooling to a temperature of 100 K. Both the carbon content and the grain volume play a key role in the stability of the austenite grains below 15 μm3, while the carbon content exerts the dominant effect in the stability of the bigger grains. Measurements also suggest that the tetragonality of the thermally formed martensite is suppressed.</p

Structural tale of two novel (Cr, Mn)C carbides in steel

Chromium (Cr), manganese (Mn) and carbon (C) are well known alloying elements used in technologically important alloy steels and advanced high strength steels. It is known that binary CrCx and MnCx carbides can be formed in steels, but in this study we reveal for the first time that Cr and Mn were found combined in novel ternary cementite type (Cr, Mn)C carbides. Electron diffraction experiments showed that Cr, Mn and C formed two distinct carbide phases possessing orthorhombic and monoclinic crystal structures. Density functional theory calculations were performed on these phases and excellent agreement was found between calculations and experiments on the lattice parameters and relative atomic positions. The calculations showed that the combination of Mn and Cr resulted in a very high thermodynamic stability of the (Cr, Mn)C carbides, and that local structural relaxations are associated with carbon additions. Possible implications of these ternary carbides for novel applications in steel design and manufacturing are discussed

The PKC, HOG and Ca2+ signalling pathways co-ordinately regulate chitin synthesis in Candida albicans

Open Access via PMC2649417Peer reviewedPublisher PD

Therapeutic prospects of exon skipping for epidermolysis bullosa

Epidermolysis bullosa is a group of genetic skin conditions characterized by abnormal skin (and mucosal) fragility caused by pathogenic variants in various genes. The disease severity ranges from early childhood mortality in the most severe types to occasional acral blistering in the mildest types. The subtype and severity of EB is linked to the gene involved and the specific variants in that gene, which also determine its mode of inheritance. Current treatment is mainly focused on symptomatic relief such as wound care and blister prevention, because truly curative treatment options are still at the preclinical stage. Given the current level of understanding, the broad spectrum of genes and variants underlying EB makes it impossible to develop a single treatment strategy for all patients. It is likely that many different variant-specific treatment strategies will be needed to ultimately treat all patients. Antisense-oligonucleotide (ASO)-mediated exon skipping aims to counteract pathogenic sequence variants by restoring the open reading frame through the removal of the mutant exon from the pre-messenger RNA. This should lead to the restored production of the protein absent in the affected skin and, consequently, improvement of the phenotype. Several preclinical studies have demonstrated that exon skipping can restore protein production in vitro, in skin equivalents, and in skin grafts derived from EB-patient skin cells, indicating that ASO-mediated exon skipping could be a viable strategy as a topical or systemic treatment. The potential value of exon skipping for EB is supported by a study showing reduced phenotypic severity in patients who carry variants that result in natural exon skipping. In this article, we review the substantial progress made on exon skipping for EB in the past 15 years and highlight the opportunities and current challenges of this RNA-based therapy approach. In addition, we present a prioritization strategy for the development of exon skipping based on genomic information of all EB-involved genes

Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective stud

Monocyte Gene Expression Signature of Patients with Early Onset Coronary Artery Disease

The burden of cardiovascular disease (CVD) cannot be fully addressed by therapy targeting known pathophysiological pathways. Even with stringent control of all risk factors CVD events are only diminished by half. A number of additional pathways probably play a role in the development of CVD and might serve as novel therapeutic targets. Genome wide expression studies represent a powerful tool to identify such novel pathways. We compared the expression profiles in monocytes from twenty two young male patients with premature familial CAD with those from controls matched for age, sex and smoking status, without a family history of CVD. Since all patients were on statins and aspirin treatment, potentially affecting the expression of genes in monocytes, twelve controls were subsequently treated with simvastatin and aspirin for 6 and 2 weeks, respectively

The influence of different culture microenvironments on the generation of dendritic cells from non-small-cell lung cancer patients

This study extends the model developed in Williams and Seaman’s [Williams, J. J. and Seaman, A. E. (2010). Corporate Governance and Mindfulness: The Impact of Management Accounting Systems Change, The Journal of Applied Business Research, Vol. 26, No. 5, pp. 1-17] exploratory paper examining the moderating effects of management accounting systems (MAS) change on the corporate governance/mindfulness relationship for a Canadian sample of 124 top-level accounting professionals. Canonical correlation analysis was applied to the linkage of multiple cognitive processes of mindfulness (Weick and Sutcliffe, 2001; 2007) and the governance dimensions of performance and conformance specified by the International Federation of Accountants (2009), underpinned by the moderating effects of five different components of MAS change, which yielded 13 significant relationships. The latter were subsequently analyzed for important gestalts (i.e., patterns) in the overall relationship, and assessed within the context of aligning professional accounting practices involving systems changes to the IFAC (2009) governance framework. These findings appear to have implications for improved governance structures in practice as well as offering a rich foundation for future research

Suboptimal blood pressure control in chronic kidney disease stage 3: baseline data from a cohort study in primary care

BACKGROUND: Poorly controlled hypertension is independently associated with mortality, cardiovascular risk and disease progression in chronic kidney disease (CKD). In the UK, CKD stage 3 is principally managed in primary care, including blood pressure (BP) management. Controlling BP is key to improving outcomes in CKD. This study aimed to investigate associations of BP control in people with CKD stage 3. METHODS: 1,741 patients with CKD 3 recruited from 32 general practices for the Renal Risk in Derby Study underwent medical history, clinical assessment and biochemistry testing. BP control was assessed by three standards: National Institute for Health and Clinical Excellence (NICE), National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Descriptive statistics were used to compare characteristics of people achieving and not achieving BP control. Univariate and multivariate logistic regression was used to identify factors associated with BP control. RESULTS: The prevalence of hypertension was 88%. Among people with hypertension, 829/1426 (58.1%) achieved NICE BP targets, 512/1426 (35.9%) KDOQI targets and 859/1426 (60.2%) KDIGO targets. Smaller proportions of people with diabetes and/or albuminuria achieved hypertension targets. 615/1426 (43.1%) were only taking one antihypertensive agent. On multivariable analysis, BP control (NICE and KDIGO) was negatively associated with age (NICE odds ratio (OR) 0.27; 95% confidence interval (95% CI) 0.17-0.43) 70–79 compared to <60), diabetes (OR 0.32; 95% CI 0.25-0.43)), and albuminuria (OR 0.56; 95% CI 0.42-0.74)). For the KDOQI target, there was also association with males (OR 0.76; 95% CI 0.60-0.96)) but not diabetes (target not diabetes specific). Older people were less likely to achieve systolic targets (NICE target OR 0.17 (95% CI 0.09,0.32) p < 0.001) and more likely to achieve diastolic targets (OR 2.35 (95% CI 1.11,4.96) p < 0.001) for people >80 compared to < 60). CONCLUSIONS: Suboptimal BP control was common in CKD patients with hypertension in this study, particularly those at highest risk of adverse outcomes due to diabetes and or albuminuria. This study suggests there is scope for improving BP control in people with CKD by using more antihypertensive agents in combination while considering issues of adherence and potential side effects