Let's Play the Arcade Machines

"Let's Play the Arcade Machines" showcases games made by children in schools in the Wester Hailes area of Edinburgh. The project aims to expose the children to a constructionist style of learning; supporting them to create and remix games about their local area using the Scratch programming environment, whilst encouraging them to engage with the idea that further study of computing could lead them to interesting and fulfilling careers.</p

Let's Play the Arcade Machines

"Let's Play the Arcade Machines" showcases games made by children in schools in the Wester Hailes area of Edinburgh. The project aims to expose the children to a constructionist style of learning; supporting them to create and remix games about their local area using the Scratch programming environment, whilst encouraging them to engage with the idea that further study of computing could lead them to interesting and fulfilling careers.</p

Navigation and Exploration in 3D-Game Automated Play Testing

To enable automated software testing, the ability to automatically navigate to a state of interest and to explore all, or at least sufficient number of, instances of such a state is fundamental. When testing a computer game the problem has an extra dimension, namely the virtual world where the game is played on. This world often plays a dominant role in constraining which logical states are reachable, and how to reach them. So, any automated testing algorithm for computer games will inevitably need a layer that deals with navigation on a virtual world. Unlike e.g. navigating through the GUI of a typical web-based application, navigating over a virtual world is much more challenging. This paper discusses how concepts from geometry and graph-based path finding can be applied in the context of game testing to solve the problem of automated navigation and exploration. As a proof of concept, the paper also briefly discusses the implementation of the proposed approach

Intervju: akademik Jakša Barbić

Over the past 20 years evidence has accumulated confirming the immunomodulatory role of the appendix in ulcerative colitis (UC). This led to the idea that appendectomy might alter the clinical course of established UC. The objective of this body of research is to evaluate the short-term and medium-term efficacy of appendectomy to maintain remission in patients with UC, and to establish the acceptability and cost-effectiveness of the intervention compared to standard treatment. These paired phase III multicenter prospective randomised studies will include patients over 18 years of age with an established diagnosis of ulcerative colitis and a disease relapse within 12 months prior to randomisation. Patients need to have been medically treated until complete clinical (Mayo score <3) and endoscopic (Mayo score 0 or 1) remission. Patients will then be randomised 1:1 to a control group (maintenance 5-ASA treatment, no appendectomy) or elective laparoscopic appendectomy plus maintenance treatment. The primary outcome measure is the one year cumulative UC relapse rate - defined both clinically and endoscopically as a total Mayo-score ≥5 with endoscopic subscore of 2 or 3. Secondary outcomes that will be assessed include the number of relapses per patient at 12 months, the time to first relapse, health related quality of life and treatment costs, and number of colectomies in each arm. The ACCURE and ACCURE-UK trials will provide evidence on the role and acceptability of appendectomy in the treatment of ulcerative colitis and the effects of appendectomy on the disease course. NTR2883 ; ISRCTN5652301

E-Cadherin-Deficient Epithelial Cells Are Sensitive to HDAC Inhibitors

Inactivating germline mutations in the CDH1 gene (encoding the E-cadherin protein) are the genetic hallmark of hereditary diffuse gastric cancer (HDGC), and somatic CDH1 mutations are an early event in the development of sporadic diffuse gastric cancer (DGC) and lobular breast cancer (LBC). In this study, histone deacetylase (HDAC) inhibitors were tested for their ability to preferentially inhibit the growth of human cell lines (MCF10A and NCI-N87) and murine organoids lacking CDH1 expression. CDH1−/− breast and gastric cells were more sensitive to the pan-HDAC inhibitors entinostat, pracinostat, mocetinostat and vorinostat than wild-type cells, with an elevated growth inhibition that was, in part, attributable to increased apoptosis. CDH1-null cells were also sensitive to more class-specific HDAC inhibitors, but compared to the pan-inhibitors, these effects were less robust to genetic background. Increased sensitivity to entinostat was also observed in gastric organoids with both Cdh1 and Tp53 deletions. However, the deletion of Tp53 largely abrogated the sensitivity of the Cdh1-null organoids to pracinostat and mocetinostat. Finally, entinostat enhanced Cdh1 expression in heterozygous Cdh1+/− murine organoids. In conclusion, entinostat is a promising drug for the chemoprevention and/or treatment of HDGC and may also be beneficial for the treatment of sporadic CDH1-deficient cancers

Loss of E-Cadherin Leads to Druggable Vulnerabilities in Sphingolipid Metabolism and Vesicle Trafficking

Germline inactivating variants of CDH1 are causative of hereditary diffuse gastric cancer (HDGC), a cancer syndrome characterized by an increased risk of both diffuse gastric cancer and lobular breast cancer. Because loss of function mutations are difficult to target therapeutically, we have taken a synthetic lethal approach to identify targetable vulnerabilities in CDH1-null cells. We have previously observed that CDH1-null MCF10A cells exhibit a reduced rate of endocytosis relative to wildtype MCF10A cells. To determine whether this deficiency is associated with wider vulnerabilities in vesicle trafficking, we screened isogenic MCF10A cell lines with known inhibitors of autophagy, endocytosis, and sphingolipid metabolism. Relative to wildtype MCF10A cells, CDH1−/− MCF10A cells showed significantly greater sensitivity to several drugs targeting these processes, including the autophagy inhibitor chloroquine, the endocytosis inhibitors chlorpromazine and PP1, and the sphingosine kinase 1 inhibitor PF-543. Synthetic lethality was confirmed in both gastric and mammary organoid models of CDH1 loss, derived from CD44-Cre/Cdh1fl/fl/tdTomato mice. Collectively, these results suggest that both sphingolipid metabolism and vesicle trafficking represent previously unrecognised druggable vulnerabilities in CDH1-null cells and may lead to the development of new therapies for HDGC

Navigation and exploration in 3D-game automated play testing

To enable automated software testing, the ability to automatically navigate to a state of interest and to explore all, or at least sufficient number of, instances of such a state is fundamental. When testing a computer game the problem has an extra dimension, namely the virtual world where the game is played on. This world often plays a dominant role in constraining which logical states are reachable, and how to reach them. So, any automated testing algorithm for computer games will inevitably need a layer that deals with navigation on a virtual world. Unlike e.g. navigating through the GUI of a typical web-based application, navigating over a virtual world is much more challenging. This paper discusses how concepts from geometry and graph-based path finding can be applied in the context of game testing to solve the problem of automated navigation and exploration. As a proof of concept, the paper also briefly discusses the implementation of the proposed approach