136 research outputs found
Declarative testing and depolyment of distributed systems
No full textSystem administrators and developers who deploy distributed systems have to deal with a deployment process that is largely manual and hard to reproduce. This paper describes how networks of computer systems can be reproducibly and automatically deployed from declarative specifications. Reproducibility also ensures that users can easily instantiate a test environment, before deploying the specification to the production environment. Furthermore, from the same specifications we can instantiate virtual networks of virtual machines for both interactive and automated testing. This makes it easy to write automated regression tests that require external machines, need special privileges, or depend on the network topology. We instantiate machines from the specifications using NixOS, a Linux distribution built from a purely functional specification. We have applied our approach to a number of representative problems, including automatic regression testing of a Linux distribution and deployment of a continuous integration environment Preprint accepted for publication inSoftware TechnologyElectrical Engineering, Mathematics and Computer Scienc
Preventing Injection Attacks with Syntax Embeddings: A Host and Guest Language Independent Approach
No full textSoftware written in one language often needs to construct sentences in another language, such as SQL queries, XML output, or shell command invocations. This is almost always done using unhygienic string manipulation, the concatenation of constants and client-supplied strings. A client can then supply specially crafted input that causes the constructed sentence to be interpreted in an unintended way, leading to an injection attack. We describe a more natural style of programming that yields code that is impervious to injections by construction. Our approach embeds the grammars of the guest languages (e.g., SQL) into that of the host language (e.g., Java) and automatically generates code that maps the embedded language to constructs in the host language that reconstruct the embedded sentences, adding escaping functions where appropriate. This approach is generic, meaning that it can be applied with relative ease to any combination of host and guest languages. Preprint accepted for publiction in: Generative Programming and Component Engineering, 6th International Conference, GPCE 2007, Salzburg, Austria, October 1-3, 2007Software TechnologyElectrical Engineering, Mathematics and Computer Scienc
NixOS: A purely functional Linux distribution
No full textExisting package and system configuration management tools suffer from an imperative model, where system administration actions such as package upgrades or changes to system configuration files are stateful: they destructively update the state of the system. This leads to many problems, such as the inability to roll back changes easily, to deploy multiple versions of a package side-by-side, to reproduce a configuration deterministically on another machine, or to reliably upgrade a system. In this paper we show that we can overcome these problems by moving to a purely functional system configuration model. This means that all static parts of a system (such as software packages, configuration files and system startup scripts) are built by pure functions and are immutable, stored in a way analogous to a heap in a purely functional language. We have implemented this model in NixOS, a non-trivial Linux distribution that uses the Nix package manager to build the entire system configuration from a modular, purely functional specification.Software TechnologyElectrical Engineering, Mathematics and Computer Scienc
Current challenges in cell and gene therapy: a joint view from the European Committee of the International Society for Cell & Gene Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT)
No full textCell and gene therapy poses evolving challenges. The current article summarizes the discussions held by European Regional Committee of the International Society for Cell & Gene Therapy and the European Society for Blood and Marrow Transplantation (EBMT) on the current challenges in this field, focusing on the European setting. This article emphasizes the imperative assessment of real-world cell and gene therapy activity, advocating for expanded registries beyond hematopoietic transplantation and chimeric antigen receptor–T-cell therapy. Accreditation's role in ensuring standardized procedures, as exemplified by JACIE (The Joint Accreditation Committee of ISCT-Europe and EBMT), is crucial for safety. Access to commercial products and reimbursement variations among countries underscore the need for uniform access to advanced therapy medical products (ATMPs). Academic product development and point-of-care manufacturing face barriers to patient access. Hospital Exemption's potential, demonstrated by some initial experiences, may increase patient accessibility in individual situations. Regulatory challenges, including the ongoing European ATMPs legislation review, necessitate standardized criteria for Hospital Exemption and mandatory reporting within registries. Efforts to combat unproven therapies and fraud involve collaboration between scientific societies, regulatory bodies and patient groups. Finally, is important to highlight the vital role of education and workforce development in meeting the escalating demand for specialized professionals in the ATMP field. Collaboration among scientific societies, academic institutions, industry, regulatory bodies and patient groups is crucial for overcoming all these challenges to increase gene and cell therapy activity in Europe
Correction: The challenge of COVID-19 and hematopoietic cell transplantation: EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy (Bone Marrow Transplantation, (2020), 55, 11, (2071-2076), 10.1038/s41409-020-0919-0)
No full textThe original HTML and PDF versions of this article were updated shortly after publication to correct author Bregje Verhoeven’s name and affiliation. Bregje Verhoeven was incorrectly associated with Willem-Alexander Children’s Hospital, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. The correct affiliation is Foundation Hematon, Utrecht, The Netherlands. This has now been corrected in both the PDF and HTML versions of the article
Immune checkpoint molecules in acute myeloid leukaemia: managing the double-edged sword
No full textNew immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long-term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co-inhibitory signalling pathways have been shown to play a crucial role. Via up-regulation of inhibitory checkpoints, tumour-reactive T cell and Natural Killer cell responses can be strongly impeded. Accordingly, the introduction of checkpoint inhibitors targeting CTLA-4 (CTLA4) and PD-1 (PDCD1, CD279)/PD-L1 (CD274, PDCD1LG1) accomplished a breakthrough in cancer treatment, with impressive clinical responses. Numerous new co-inhibitory players and novel combination therapies are currently investigated for their potential to boost anti-tumour immunity and improve survival of cancer patients. Although the challenge here remains to avoid severe systemic toxicity. This review addresses the involvement of co-inhibitory signalling in AML immune evasion and discusses the opportunities for checkpoint blockers in AML treatment
Discovering Software License Constraints: Identifying a Binary’s Sources by Tracing Build Processes
No full textWith the current proliferation of open source software components, intellectual property in general, and copyright law in particular, has become a critical non-functional requirement for software systems. A key problem in license compliance engineering is that the legal constraints on a product depend on the licenses of all sources and other artifacts used to build it. The huge size of typical dependency graphs makes it infeasible to determine these constraints manually, while mistakes can expose software distributors to litigation. In this paper we show a generic method to reverse-engineer this information from the build processes of software products by tracing system calls (e.g., open) to determine the composition graph of sources and binaries involved in build processes. Results from an exploratory case study of seven open source systems, which allowed us to discover a licensing problem in a widely used open source package, suggest our method is highly effective.Software Computer TechnologyElectrical Engineering, Mathematics and Computer Scienc
Concurrent detection of circulating minor histocompatibility antigen-specific CD8+ T cells in SCT recipients by combinatorial encoding MHC multimers.
No full textAllogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematologic malignancies. Its therapeutic effect is largely dependent on recognition of minor histocompatibility antigens (MiHA) by donor-derived CD8⁺ T cells. Therefore, monitoring of multiple MiHA-specific CD8⁺ T cell responses may prove to be valuable for evaluating the efficacy of allogeneic SCT. In this study, we investigated the use of the combinatorial encoding MHC multimer technique to simultaneously detect MiHA-specific CD8⁺ T cells in peripheral blood of SCT recipients. Feasibility of this approach was demonstrated by applying dual-color encoding MHC multimers for a set of 10 known MiHA. Interestingly, single staining using a fluorochrome- and Qdot-based five-color combination showed comparable results to dual-color staining for most MiHA-specific CD8⁺ T cell responses. In addition, we determined the potential value of combinatorial encoding MHC multimers in MiHA identification. Therefore, a set of 75 candidate MiHA peptides was predicted from polymorphic genes with a hematopoietic expression profile and further selected for high and intermediate binding affinity for HLA-A2. Screening of a large cohort of SCT recipients resulted in the detection of dual-color encoded CD8⁺ T cells following MHC multimer-based T cell enrichment and short ex vivo expansion. Interestingly, candidate MiHA-specific CD8⁺ T cell responses for LAG3 and TLR10 derived polymorphic peptides could be confirmed by genotyping of the respective SNPs. These findings demonstrate the potency of the combinatorial MHC multimer approach in the monitoring of CD8⁺ T cell responses to known and potential MiHA in limited amounts of peripheral blood from allogeneic SCT recipients
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