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- Magnusson, Peter S., et al.
(författare)
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SimICS/sun4m : A virtual workstation
- 2019
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Ingår i: USENIX 1998 Annual Technical Conference. - New Orleans, LA, USA : USENIX Association.
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Konferensbidrag (refereegranskat)abstract
- System level simulators allow computer architects and system software designers to recreate an accurate and complete replica of the program behavior of a target system, regardless of the availability, existence, or instrumentation support of such a system. Applications include evaluation of architectural design alternatives as well as software engineering tasks such as traditional debugging and performance tuning. We present an implementation of a simulator acting as a virtual workstation fully compatible with the sun4m architecture from Sun Microsystems. Built using the system-level SPARC V8 simulator SimICS, SimICS/sun4m models one or more SPARC V8 processors, supports user-developed modules for data cache and instruction cache simulation and execution profiling of all code, and provides a symbolic and performance debugging environment for operating systems. SimICS/sun4m can boot unmodified operating systems, including Linux 2.0.30 and Solaris 2.6, directly from snapshots of disk partitions. To support essentially arbitrary code, we implemented binary-compatible simulators for several devices, including SCSI, console, interrupt, timers, EEPROM, and Ethernet. The Ethernet simulation hooks into the host and allows the virtual workstation to appear on the local network with full services available (NFS, NIS, rsh, etc). Ethernet and console traffic can be recorded for future playback. The performance of SimICS/sun4m is sufficient to run realistic workloads, such as the database benchmark TPC-D, scaling factor 1/100, or an interactive network application such as Mozilla. The slowdown in relation to native hardware is in the range of 25 to 75 (measured using SPECint95). We also demonstrate some applications, including modeling an 8-processor sun4m version (which does not exist), modeling future memory hierarchies, and debugging an operating system.
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- Sennefelt Nyman, Sofi, et al.
(författare)
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Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study : idarubicin dose selection, tissue response and survival
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31.
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- Arelakis, Angelos, 1984, et al.
(författare)
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HyComp: A Hybrid Cache Compression Method for Selection of Data-Type-Specific Compression Methods
- 2015
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Ingår i: 48th Annual IEEE/ACM International Symposium on Microarchitecture, MICRO 2015, Waikiki, United States, 5-9 December 2015. - New York, NY, USA : ACM. - 1072-4451. - 9781450340342 ; 05-09-December-2015, s. 38-49
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Konferensbidrag (refereegranskat)abstract
- Proposed cache compression schemes make design-time assumptions on value locality to reduce decompression latency. For example, some schemes assume that common values are spatially close whereas other schemes assume that null blocks are common. Most schemes, however, assume that value locality is best exploited by fixed-size data types (e.g., 32-bit integers). This assumption falls short when other data types, such as floating-point numbers, are common. This paper makes two contributions. First, HyComp - a hybrid cache compression scheme - selects the best-performing compression scheme, based on heuristics that predict data types. Data types considered are pointers, integers, floating-point numbers and the special (and trivial) case of null blocks. Second, this paper contributes with a compression method that exploits value locality in data types with predefined semantic value fields, e.g., as in the exponent and the mantissa in floating-point numbers. We show that HyComp, augmented with the proposed floating-point-number compression method, offers superior performance in comparison with prior art.
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- Balgoma, David, et al.
(författare)
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Orthogonality in Principal Component Analysis Allows the Discovery of Lipids in the Jejunum That Are Independent of Ad Libitum Feeding
- 2022
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Ingår i: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Ad libitum feeding of experimental animals is preferred because of medical relevance together with technical and practical considerations. In addition, ethical committees may require ad libitum feeding. However, feeding affects the metabolism so ad libitum feeding may mask the effects of drugs on tissues directly involved in the digestion process (e.g., jejunum and liver). Despite this effect, principal component analysis has the potential of identifying metabolic traits that are statistically independent (orthogonal) to ad libitum feeding. Consequently, we used principal component analysis to discover the metabolic effects of doxorubicin independent of ad libitum feeding. First, we analyzed the lipidome of the jejunum and the liver of rats treated with vehicle or doxorubicin. Subsequently, we performed principal component analysis. We could identify a principal component associated to the hydrolysis of lipids during digestion and a group of lipids that were orthogonal. These lipids in the jejunum increased with the treatment time and presented a polyunsaturated fatty acid as common structural trait. This characteristic suggests that doxorubicin increases polyunsaturated fatty acids. This behavior agrees with our previous in vitro results and suggests that doxorubicin sensitized the jejunum to ferroptosis, which may partially explain the toxicity of doxorubicin in the intestines.
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- Bergh Thorén, Fredrik, 1976, et al.
(författare)
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A hepatitis C virus-encoded, nonstructural protein (NS3) triggers dysfunction and apoptosis in lymphocytes: role of NADPH oxidase-derived oxygen radicals
- 2004
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Ingår i: Journal of leukocyte biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 76:6, s. 1180-6
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Tidskriftsartikel (refereegranskat)abstract
- The persistent infection caused by hepatitis C virus (HCV) is presumably explained by a deficient immune response to the infection, but the basis for the inefficiency of immune-mediated virus eradication is not known in detail. This study addresses mechanisms of relevance to dysfunction of cytotoxic lymphocytes in HCV infection, with a focus on the role of phagocyte-derived oxygen radicals. We show that NS3, a nonstructural, HCV-encoded protein, induces a prolonged release of oxygen radicals from mononuclear and polymorphnuclear phagocytes by activating a key enzyme in radical formation, the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The NS3-activated phagocytes, in turn, induced dysfunction and/or apoptosis in three major subsets of lymphocytes of relevance to defense against HCV infection: CD3+/56- T cells, CD3-/56+ natural killer (NK) cells, and CD3+/56+ NKT cells. Two inhibitors of the NADPH oxidase, histamine and diphenylene iodonium, suppressed the NS3-induced oxygen radical production and efficiently protected lymphocytes against NS3-induced apoptosis and dysfunction. In conclusion, we propose that NS3, by triggering oxygen radical formation in phagocytes, may contribute to the dysfunction of antiviral lymphocytes in HCV-infected liver tissue and that strategies to circumvent oxidative stress may be useful in preventing HCV-associated carcinogenesis and facilitating lymphocyte-mediated clearance of infected cells.
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