Do Robots Dream of Virtual Sheep: Rediscovering the "Karel the Robot" Paradigm for the "Plug&Play Generation"

We introduce ”C-Sheep”, an educational system designed to teach students the fundamentals of computer programming in a novel and exciting way. Recent studies suggest that computer science education is fast approaching a crisis - application numbers for degree courses in the area of computer programming are down, and potential candidates are put off the subject which they do not fully understand. We address this problem with our system by providing the visually rich virtual environment of ”The Meadow”, where the user writes programs to control the behaviour of a sheep using our ”CSheep” programming language. This combination of the ”Karel the Robot” paradigm with modern 3D computer graphics techniques, more commonly found in computer games, aims to help students to realise that computer programming can be an enjoyable and rewarding experience and intends to help educators with the teaching of computer science fundamentals. Our mini-language-like system for computer science education uses a state of the art rendering engine offering features more commonly found in entertainment systems. The scope of the mini-language is designed to fit in with the curriculum for the first term of an introductory computer program ming course (using the C programming language)

C-Sheep: Controlling Entities in a 3D Virtual World as a Tool for Computer Science Education

One of the challenges in teaching computer science in general and computer programming in particular is to maintain the interest of students, who often perceive the subject as difficult and tedious. To this end, we introduce C-Sheep, a mini-language-like system for computer science education, using a state of the art rendering engine, usually found in entertainment systems. The intention is to motivate students to spend more time programming, which can be achieved by providing an enjoyable experience. Computer programming is an essential skill for software developers and as such is always an integral part of every computer science curriculum. However, even if students are pursuing a computer science related degree, it can be very difficult to interest them in the act of computer programming, the writing of software, itself. In the C-Sheep system this is addressed by using the visual gimmickry of modern computer games, which allows programs to provide instant visualisation of algorithms. This visual feedback is invaluable to the understanding of how the algorithm works, and - if there are unintended results - how errors in the program can be debugged. The C-Sheep programming language is a (100% compatible) subset of the ANSI C programming language. Apart from just being a tool for learning the basics of the C programming language, C-Sheep implements the C control structures that are required for teaching the basic computer science principles encountered in structured programming. Unlike other teaching languages which have minimal syntax and which are variable free to provide an environment with minimal complexity, C-Sheep allows the declaration and use of variables. C-Sheep also supports the definition of sub-routines (functions) which can be called recursively. "The Meadow" virtual environment is the virtual world in which entities (in our case sheep) controlled by C-Sheep programs exist. This micro world provides a graphical representation of the algorithms used in the programs controlling the virtual entities. Their position and orientation within the virtual world visualise the current state of the program. "The Meadow" is based on our proprietary "Crossbow" game engine which incorporates a virtual machine for executing CSheep programs. The Crossbow Engine is a compact game engine which is flexible in design and offers a number of features common to more complex engines. The Crossbow Virtual Machine used with C-Sheep in "The Meadow" - an improvement on the ZBL/0 virtual machine - is a module of the Crossbow Engine. The C-Sheep system also provides a counterpart library for C, mirroring the CSheep library functions of the virtual machine. This allows C-Sheep programs to be compiled into an executable using a normal off-the-shelf C/C++ compiler. This executable can then be run from within the native working environment of the operating system. The purpose of this library is to simplify the migration from the educational mini-language to real-world systems by allowing novice programmers to make an easy transition from using the C-Sheep system to using the C programming language

Critters in the Classroom: A 3D Computer-Game-Like Tool for Teaching Programming to Computer Animation Students

The brewing crisis threatening computer science education is a well documented fact. To counter this and to increase enrolment and retention in computer science related degrees, it has been suggested to make programming "more fun" and to offer "multidisciplinary and cross-disciplinary programs" [Carter 2006]. The Computer Visualisation and Animation undergraduate degree at the National Centre for Computer Animation (Bournemouth University) is such a programme. Computer programming forms an integral part of the curriculum of this technical arts degree, and as educators we constantly face the challenge of having to encourage our students to engage with the subject. We intend to address this with our C-Sheep system, a reimagination of the "Karel the Robot" teaching tool [Pattis 1981], using modern 3D computer game graphics that today's students are familiar with. This provides a game-like setting for writing computer programs, using a task-specific set of instructions which allow users to take control of virtual entities acting within a micro world, effectively providing a graphical representation of the algorithms used. Whereas two decades ago, students would be intrigued by a 2D top-down representation of the micro world, the lack of the visual gimmickry found in modern computer games for representing the virtual world now makes it extremely difficult to maintain the interest of students from today's "Plug&Play generation". It is therefore especially important to aim for a 3D game-like representation which is "attractive and highly motivating to today's generation of media-conscious students" [Moskal et al. 2004]. Our system uses a modern, platform independent games engine, capable of presenting a visually rich virtual environment using a state of the art rendering engine of a type usually found in entertainment systems. Our aim is to entice students to spend more time programming, by providing them with an enjoyable experience. This paper provides a discussion of the 3D computer game technology employed in our system and presents examples of how this can be exploited to provide engaging exercises to create a rewarding learning experience for our students

Triple positive breast cancer. A distinct subtype?

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets

HER2 and ESR1 mRNA expression levels and response to neoadjuvant trastuzumab plus chemotherapy in patients with primary breast cancer

Introduction: Recent data suggest that benefit from trastuzumab and chemotherapy might be related to expression of HER2 and estrogen receptor (ESR1). Therefore, we investigated HER2 and ESR1 mRNA levels in core biopsies of HER2-positive breast carcinomas from patients treated within the neoadjuvant GeparQuattro trial. Methods: HER2 levels were centrally analyzed by immunohistochemistry (IHC), silver in-situ hybridization (SISH) and qRT-PCR in 217 pretherapeutic formalin-fixed, paraffin-embedded (FFPE) core biopsies. All tumors had been HER2-positive by local pathology and had been treated with neoadjuvant trastuzumab/ chemotherapy in GeparQuattro. Results: Only 73% of the tumors (158 of 217) were centrally HER2-positive (cHER2-positive) by IHC/SISH, with cHER2-positive tumors showing a significantly higher pCR rate (46.8% vs. 20.3%, p<0.0005). HER2 status by qRT-PCR showed a concordance of 88.5% with the central IHC/SISH status, with a low pCR rate in those tumors that were HER2-negative by mRNA analysis (21.1% vs. 49.6%, p<0.0005). The level of HER2 mRNA expression was linked to response rate in ESR1-positive tumors, but not in ESR1-negative tumors. HER2 mRNA expression was significantly associated with pCR in the HER2-positive/ESR1-positive tumors (p=0.004), but not in HER2-positive/ESR1-negative tumors. Conclusions: Only patients with cHER2-positive tumors - irrespective of the method used - have an increased pCR rate with trastuzumab plus chemotherapy. In patients with cHER2-negative tumors the pCR rate is comparable to the pCR rate in the non-trastuzumab treated HER-negative population. Response to trastuzumab is correlated to HER2 mRNA levels only in ESR1-positive tumors. This study adds further evidence to the different biology of both subsets within the HER2-positive group

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

LittleDarwin: a Feature-Rich and Extensible Mutation Testing Framework for Large and Complex Java Systems

Mutation testing is a well-studied method for increasing the quality of a test suite. We designed LittleDarwin as a mutation testing framework able to cope with large and complex Java software systems, while still being easily extensible with new experimental components. LittleDarwin addresses two existing problems in the domain of mutation testing: having a tool able to work within an industrial setting, and yet, be open to extension for cutting edge techniques provided by academia. LittleDarwin already offers higher-order mutation, null type mutants, mutant sampling, manual mutation, and mutant subsumption analysis. There is no tool today available with all these features that is able to work with typical industrial software systems.Comment: Pre-proceedings of the 7th IPM International Conference on Fundamentals of Software Engineerin

The short-time Dynamics of the Critical Potts Model

The universal behaviour of the short-time dynamics of the three state Potts model in two dimensions at criticality is investigated with Monte Carlo methods. The initial increase of the order is observed. The new dynamic exponent $\theta$ as well as exponent $z$ and $\beta/\nu$ are determined. The measurements are carried out in the very beginning of the time evolution. The spatial correlation length is found to be very short compared with the lattice size.Comment: 6 pages, 3 figure