91 research outputs found
Contract Aware Components, 10 years after
The notion of contract aware components has been published roughly ten years
ago and is now becoming mainstream in several fields where the usage of
software components is seen as critical. The goal of this paper is to survey
domains such as Embedded Systems or Service Oriented Architecture where the
notion of contract aware components has been influential. For each of these
domains we briefly describe what has been done with this idea and we discuss
the remaining challenges.Comment: In Proceedings WCSI 2010, arXiv:1010.233
From bulletins to bullets to blogs and beyond: The Karenâs ongoing communication war
Geff Green focuses on the communication approaches taken by the Karen communities displaced from Burma and who live in diaspora. Apparent control and empowerment provided by new technologies may be illusive. When using media for warfare or perhaps for more innocuous public relations purposes, activists may actually create âammunitionâ for opponents. Targeted attacks on specific communities or âaudiencesâ have a high impact by reifying discourse in a devastating way by connecting to lived experience in the victim
Neutrophil dysfunction triggers inflammatory bowel disease in G6PC3 deficiency
From Wiley via Jisc Publications RouterHistory: received 2019-12-09, rev-recd 2020-08-28, accepted 2020-08-29, pub-electronic 2020-09-15, pub-print 2021-06Article version: VoRPublication status: PublishedFunder: Medical Research Council Clinical Research Training Fellowship; Grant(s): MR/N001427/1Funder: European Society of Paediatric Infectious Diseases FellowshipFunder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269; Grant(s): 202865/Z/16/ZAbstract: The glucoseâ6âphosphatase catalytic subunit 3 (G6PC3) encodes a ubiquitously expressed enzyme that regulates cytoplasmic glucose availability. Lossâofâfunction biallelic G6PC3 mutations cause severe congenital neutropenia and a diverse spectrum of extraâhematological manifestations, among which inflammatory bowel disease (IBD) has been anecdotally reported. Neutrophil function and clinical response to granulocyte colonyâstimulating factor (GâCSF) and hematopoietic stem cell transplantation (HSCT) were investigated in 4 children with G6PC3 deficiencyâassociated IBD. G6PC3 deficiency was associated with earlyâonset IBD refractory to treatment with steroids and infliximab. The symptoms of IBD progressed despite GâCSF treatment. In vitro studies on the patientsâ blood showed that neutrophils displayed higher levels of activation markers (CD11b, CD66b, and CD14), excessive ILâ8 and reactive oxygen species, and increased apoptosis and secondary necrosis. Secondary necrosis was exaggerated after stimulation with Escherichia coli and could be partially rescued with supplemental exogenous glucose. HSCT led to normalization of neutrophil function and remission of gastrointestinal symptoms. We conclude that neutrophils in G6PC3 deficiency release proâinflammatory mediators when exposed to gut bacteria, associated with intestinal inflammation, despite treatment with GâCSF. HSCT is an effective therapeutic option in patients with G6PC3 deficiencyâassociated IBD refractory to immune suppressants
Unravelling the genetic causes of mosaic islet morphology in congenital hyperinsulinism
Congenital hyperinsulinism (CHI) causes dysregulated insulin secretion which can lead to life-threatening hypoglycaemia if not effectively managed. CHI can be sub-classified into three distinct groups: diffuse, focal and mosaic pancreatic disease. Whilst the underlying causes of diffuse and focal disease have been widely characterised, the genetic basis of mosaic pancreatic disease is not known. To gain new insights into the underlying disease processes of mosaic-CHI we studied the islet tissue histopathology derived from limited surgical resection from the tail of the pancreas in a patient with CHI. The underlying genetic aetiology was investigated using a combination of high depth next-generation sequencing, microsatellite analysis and p57kip2 immunostaining. Histopathology of the pancreatic tissue confirmed the presence of a defined area associated with marked islet hypertrophy and a cytoarchitecture distinct from focal CHI but compatible with mosaic CHI localised to a discrete region within the pancreas. Analysis of DNA extracted from the lesion identified a de novo mosaic ABCC8 mutation and mosaic paternal uniparental disomy which were not present in leukocyte DNA or the surrounding unaffected pancreatic tissue. This study provides the first description of two independent disease-causing somatic genetic events occurring within the pancreas of an individual with localised mosaic CHI. Our findings increase knowledge of the genetic causes of islet disease and provide further insights into the underlying developmental changes associated with ÎČ-cell expansion in CHI
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