75 research outputs found

    Dissection of the amyloid formation pathway in AL amyloidosis

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    In antibody light chain (AL) amyloidosis, overproduced light chain (LC) fragments accumulate as fibrils in organs and tissues of patients. In vitro, AL fibril formation is a slow process, characterized by a pronounced lag phase. The events occurring during this lag phase are largely unknown. We have dissected the lag phase of a patient-derived LC truncation and identified structural transitions that precede fibril formation. The process starts with partial unfolding of the V-L domain and the formation of small amounts of dimers. This is a prerequisite for the formation of an ensemble of oligomers, which are the precursors of fibrils. During oligomerization, the hydrophobic core of the LC domain rearranges which leads to changes in solvent accessibility and rigidity. Structural transitions from an anti-parallel to a parallel beta-sheet secondary structure occur in the oligomers prior to amyloid formation. Together, our results reveal a rate-limiting multi-step mechanism of structural transitions prior to fibril formation in AL amyloidosis, which offers, in the long run, opportunities for therapeutic intervention. AL amyloidosis is caused by the accumulation of overproduced light chain (LC) fragments as fibrils in patient organs and it is the most prevalent systemic amyloidosis. Here, the authors combine biochemical and biophysical experiments to characterise the lag phase of a patient-derived truncated LC and they identify structural transitions that precede fibril formation

    Exploring initial challenges for green software engineering: summary of the first GREENS workshop, at ICSE 2012

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    The GREENS workshop provides a forum for practitioners and academics to share knowledge, ideas, practices and current results related to green and sustainable software engineering. This first workshop was held at ICSE 2012 in Zurich, Switzerland. It featured a keynote talk, twelve research position statements and two breakout sessions that discussed topics that ranged from bringing sustainability and energy efficiency into all software lifecycle stages, to green measures and estimations, practices, notations, and tools to both greening the software engineering process, and greening the resulting Information and Communication Technology systems. This report presents the themes of the workshop, summarizes the results of the discussions held in the breakout sessions, as well as the identified research challenge

    Microservice Transition and its Granularity Problem: A Systematic Mapping Study

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    Microservices have gained wide recognition and acceptance in software industries as an emerging architectural style for autonomic, scalable, and more reliable computing. The transition to microservices has been highly motivated by the need for better alignment of technical design decisions with improving value potentials of architectures. Despite microservices' popularity, research still lacks disciplined understanding of transition and consensus on the principles and activities underlying "micro-ing" architectures. In this paper, we report on a systematic mapping study that consolidates various views, approaches and activities that commonly assist in the transition to microservices. The study aims to provide a better understanding of the transition; it also contributes a working definition of the transition and technical activities underlying it. We term the transition and technical activities leading to microservice architectures as microservitization. We then shed light on a fundamental problem of microservitization: microservice granularity and reasoning about its adaptation as first-class entities. This study reviews state-of-the-art and -practice related to reasoning about microservice granularity; it reviews modelling approaches, aspects considered, guidelines and processes used to reason about microservice granularity. This study identifies opportunities for future research and development related to reasoning about microservice granularity.Comment: 36 pages including references, 6 figures, and 3 table

    Experiences from Scenario-Based Architecture Evaluations with ATAM

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    A Joint CS/ECE Undergraduate Option in Software Engineering

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    This paper describes a software engineering option which has been developed and is being taught jointly by two departments in two faculties: Computer Science (Faculty of Mathematics) and Electrical & Computer Engineering (Faculty of Engineering). The attempt to create a joint option has resulted in certain strengths and weaknesses. The strengths derive from the different approaches to software engineering in the two departments. The weaknesses derive from the constraints of having to deal with two sets of departmental, faculty, and accreditation board constraints, which leaves the option less flexibility. We describe the option, emphasizing three components: the course selection and, in particular the three new courses which were created specifically for the option; the CASE tools which accompany each of the new courses; and the project which spans all three of the new courses. The project is described in detail, emphasizing its bifurcated nature, with a real-time embedded ..

    Decision-making techniques for software architecture design: a comparative survey

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    The architecture of a software intensive system can be defined as the set of relevant design decisions that affect the qualities of the overall system functionality; therefore, architectural decisions are eventually crucial to the success of a software project. The software engineering literature describes several techniques to choose among architectural alternatives, but it gives no clear guidance on which technique is more suitable than another, and in which circumstances. As such, there is no systematic way for software engineers to choose among decision-making techniques for resolving tradeoffs in architecture design. In this paper, we provide a comparison of existing decision-making techniques, aimed to guide architects in their selection. Results show that there is no “best” decision-making technique; however, some techniques are more susceptible to specific difficulties. Hence, architects should choose a decision-making technique based on the difficulties that they wish to avoid. This paper represents a first attempt to reason on meta-decision-making, i.e., the issue of deciding how to decide

    Automated Scenario-Based Evaluation of Embedded Software and System Architectures

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    Architecture scenarios are widely used to systematize the elicitation of architecture significant requirements and to evaluate the appropriateness of architecture decisions. Due to the lack of tool support, architects perform this evaluation manually whenever an architecture changes. In this paper, we present a scenario modeling, and evaluation approach for embedded systems that enables automated evaluation of architecture concepts with respect to scenarios. Our approach utilizes function nets contained in candidate architectures to derive main event chains of the system under development. Architecture scenarios are executed on these function nets. A novel scenario modeling approach is used to enable execution on function nets that neither provides a detailed design nor an implementation for functions. We discuss the applicability of our approach in context of the design of a control system for an aluminum cold-rolling mill. This discussion covers both functional and non-functional requirements formulated as architecture scenarios
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