| 1. |
- Sandberg, Andreas, 1984-
(författare)
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Understanding Multicore Performance : Efficient Memory System Modeling and Simulation
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To increase performance, modern processors employ complex techniques such as out-of-order pipelines and deep cache hierarchies. While the increasing complexity has paid off in performance, it has become harder to accurately predict the effects of hardware/software optimizations in such systems. Traditional microarchitectural simulators typically execute code 10 000×–100 000× slower than native execution, which leads to three problems: First, high simulation overhead makes it hard to use microarchitectural simulators for tasks such as software optimizations where rapid turn-around is required. Second, when multiple cores share the memory system, the resulting performance is sensitive to how memory accesses from the different cores interleave. This requires that applications are simulated multiple times with different interleaving to estimate their performance distribution, which is rarely feasible with today's simulators. Third, the high overhead limits the size of the applications that can be studied. This is usually solved by only simulating a relatively small number of instructions near the start of an application, with the risk of reporting unrepresentative results.In this thesis we demonstrate three strategies to accurately model multicore processors without the overhead of traditional simulation. First, we show how microarchitecture-independent memory access profiles can be used to drive automatic cache optimizations and to qualitatively classify an application's last-level cache behavior. Second, we demonstrate how high-level performance profiles, that can be measured on existing hardware, can be used to model the behavior of a shared cache. Unlike previous models, we predict the effective amount of cache available to each application and the resulting performance distribution due to different interleaving without requiring a processor model. Third, in order to model future systems, we build an efficient sampling simulator. By using native execution to fast-forward between samples, we reach new samples much faster than a single sample can be simulated. This enables us to simulate multiple samples in parallel, resulting in almost linear scalability and a maximum simulation rate close to native execution.
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| 2. |
- Woll, Petter S, et al.
(författare)
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 25:6, s. 794-808
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Tidskriftsartikel (refereegranskat)abstract
- Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
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| 3. |
- Ahlström, Christer, et al.
(författare)
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Fit-for-duty test for estimation of drivers sleepiness level: Eye movements improve the sleep/wake predictor
- 2013
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Ingår i: Transportation Research Part C. - : Elsevier. - 0968-090X .- 1879-2359. ; 26, s. 20-32
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Tidskriftsartikel (refereegranskat)abstract
- Driver sleepiness contributes to a considerable proportion of road accidents, and a fit-for-duty test able to measure a drivers sleepiness level might improve traffic safety. The aim of this study was to develop a fit-for-duty test based on eye movement measurements and on the sleep/wake predictor model (SWP, which predicts the sleepiness level) and evaluate the ability to predict severe sleepiness during real road driving. Twenty-four drivers participated in an experimental study which took place partly in the laboratory, where the fit-for-duty data were acquired, and partly on the road, where the drivers sleepiness was assessed. A series of four measurements were conducted over a 24-h period during different stages of sleepiness. Two separate analyses were performed; a variance analysis and a feature selection followed by classification analysis. In the first analysis it was found that the SWP and several eye movement features involving anti-saccades, pro-saccades, smooth pursuit, pupillometry and fixation stability varied significantly with different stages of sleep deprivation. In the second analysis, a feature set was determined based on floating forward selection. The correlation coefficient between a linear combination of the acquired features and subjective sleepiness (Karolinska sleepiness scale, KSS) was found to be R = 0.73 and the correct classification rate of drivers who reached high levels of sleepiness (KSS andgt;= 8) in the subsequent driving session was 82.4% (sensitivity = 80.0%, specificity = 84.2% and AUC = 0.86). Future improvements of a fit-for-duty test should focus on how to account for individual differences and situational/contextual factors in the test, and whether it is possible to maintain high sensitive/specificity with a shorter test that can be used in a real-life environment, e.g. on professional drivers.
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| 4. |
- Ansari, David, et al.
(författare)
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Portal Venous System Thrombosis After Pancreatic Resection
- 2013
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 37:1, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- Portal venous system thrombosis (PVST) is a rare, potentially fatal complication after pancreatic resection. The aim of this study was to assess the incidence, presenting symptoms, management, and treatment of PVST in a large cohort of patients. Prospectively collected data on patients undergoing pancreatic resection between 1997 and 2009 were reviewed retrospectively. Preoperative and postoperative imaging were analyzed for the presence or absence of venous thrombi. All patients received standard thromboprophylaxis with low-molecular-weight heparin (LMWH). Of 516 pancreatic resections performed, 18 (3.5 %) were complicated by PVST. The most common clinical presentations were abdominal pain (n = 9) and ascites (n = 5) but never any alarm symptoms. Other symptoms were vague and nonspecific (e.g., weight loss, fatigue, fever). Total pancreatectomy was a risk factor compared to hemipancreatectomy (p < 0.01), whereas the underlying disease per se did not make any difference. The median interval between surgery and diagnosis of PVST was 105 days (range 1-1,440 days). PVST was at least a contributing factor in the postoperative deaths of two patients. LMWH therapy did not significantly affect survival. PVST remains a relatively infrequent complication after pancreatic resection. Because accurate diagnosis and timely intervention may reduce morbidity and mortality, the possibility of PVST should be considered in patients presenting with vague symptoms. Whether anticoagulant treatment is needed is still not clear; there were no obvious differences in outcome between treated and untreated patients.
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| 5. |
- Baliakas, Panagiotis, et al.
(författare)
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Clinical effect of stereotyped B-cell receptor immunoglobulins in chronic lymphocytic leukaemia: a retrospective multicentre study
- 2014
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Ingår i: The Lancet Haematology. - 2352-3026. ; 1:2, s. 74-84
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Tidskriftsartikel (refereegranskat)abstract
- Background About 30% of cases of chronic lymphocytic leukaemia (CLL) carry quasi-identical B-cell receptor immunoglobulins and can be assigned to distinct stereotyped subsets. Although preliminary evidence suggests that B-cell receptor immunoglobulin stereotypy is relevant from a clinical viewpoint, this aspect has never been explored in a systematic manner or in a cohort of adequate size that would enable clinical conclusions to be drawn. Methods For this retrospective, multicentre study, we analysed 8593 patients with CLL for whom immunogenetic data were available. These patients were followed up in 15 academic institutions throughout Europe (in Czech Republic, Denmark, France, Greece, Italy, Netherlands, Sweden, and the UK) and the USA, and data were collected between June 1, 2012, and June 7, 2013. We retrospectively assessed the clinical implications of CLL B-cell receptor immunoglobulin stereotypy, with a particular focus on 14 major stereotyped subsets comprising cases expressing unmutated (U-CLL) or mutated (M-CLL) immunoglobulin heavy chain variable genes. The primary outcome of our analysis was time to first treatment, defined as the time between diagnosis and date of first treatment. Findings 2878 patients were assigned to a stereotyped subset, of which 1122 patients belonged to one of 14 major subsets. Stereotyped subsets showed significant differences in terms of age, sex, disease burden at diagnosis, CD38 expression, and cytogenetic aberrations of prognostic significance. Patients within a specific subset generally followed the same clinical course, whereas patients in different stereotyped subsets-despite having the same immunoglobulin heavy variable gene and displaying similar immunoglobulin mutational status-showed substantially different times to first treatment. By integrating B-cell receptor immunoglobulin stereotypy (for subsets 1, 2, and 4) into the well established Dohner cytogenetic prognostic model, we showed these, which collectively account for around 7% of all cases of CLL and represent both U-CLL and M-CLL, constituted separate clinical entities, ranging from very indolent (subset 4) to aggressive disease (subsets 1 and 2). Interpretation The molecular classification of chronic lymphocytic leukaemia based on B-cell receptor immunoglobulin stereotypy improves the Dohner hierarchical model and refines prognostication beyond immunoglobulin mutational status, with potential implications for clinical decision making, especially within prospective clinical trials.
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| 6. |
- Bratt, Ola, et al.
(författare)
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The Study of Active Monitoring in Sweden (SAMS) : A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer
- 2013
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Ingår i: Scandinavian Journal of Urology. - : Medical Journals Sweden AB. - 2168-1805 .- 2168-1813. ; 47:5, s. 347-355
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Forskningsöversikt (refereegranskat)abstract
- Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.
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| 7. |
- Cuenot, Philippe, et al.
(författare)
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The EAST-ADL Architecture Description Language for Automotive Embedded Software
- 2010. - 1
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Ingår i: Model-Based Engineering of Embedded Real-Time Systems. - Berlin, Heidelberg : Springer Berlin/Heidelberg. - 9783642162770 ; , s. 297-207
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Bokkapitel (refereegranskat)abstract
- Current trends in automotive embedded systems focus on how to manage the increasing software content, with a strong emphasis on standardization of the embedded software structure. The management of engineering information remains a critical challenge in order to support development and other stages of the life-cycle. System modelling based on an Architecture Description Language (ADL) is a way to keep these assets within one information structure. This paper presents the EAST- ADL2 modelling language, developed in the ITEA EAST-EEA project and further enhanced in the ATESST project (www.atesst.org). EAST- ADL2 supports comprehensive model-based development of embedded systems and provides dedicated constructs to facilitate variability and product line management, requirements engineering, representation of functional as well as software/hardware solutions, and timing and safety analysis.
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| 8. |
- Fieblinger, Tim, et al.
(författare)
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Mechanisms of Dopamine D1 Receptor-Mediated ERK1/2 Activation in the Parkinsonian Striatum and Their Modulation by Metabotropic Glutamate Receptor Type 5
- 2014
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 34:13, s. 4728-4740
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Tidskriftsartikel (refereegranskat)abstract
- In animal models of Parkinsons disease, striatal overactivation of ERK1/2 via dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate the pathways involved in D1 receptor-dependent ERK1/2 activation using acute striatal slices from rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and downstream signaling in the DA-denervated but not the intact striatum. This response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate receptors but blocked by antagonists of L-type calcium channels. Coapplication of an antagonist of metabotropic glutamate receptor type 5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors) markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal mGluR5 in D1-dependent ERK1/2 activation was confirmed in vivo in 6-OHDA-lesioned animals treated systemically with SKF38393. In one experiment, local infusion of the mGluR5 antagonistMTEPin the DA-denervated rat striatum attenuated the activation of ERK1/2 signaling by SKF38393. In another experiment, 6-OHDA lesions were applied to transgenic mice with a cell-specific knockdown of mGluR5 in D1 receptor-expressing neurons. These mice showed a blunted striatal ERK1/2 activation in response to SFK38393 treatment. Our results reveal that D1-dependent ERK1/2 activation in the DA-denervated striatum depends on a complex interaction between PKA-and Ca2+ -dependent signaling pathways that is critically modulated by striatal mGluR5.
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| 9. |
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| 10. |
- Henkel, Werner, et al.
(författare)
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UEP concepts in modulation and coding
- 2010
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Ingår i: Advances in Multimedia. - : Hindawi Limited. - 1687-5680 .- 1687-5699. ; 2010
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Tidskriftsartikel (refereegranskat)abstract
- First unequal error protection (UEP) proposals date back to the 1960's (Masnick and Wolf; 1967), but now with the introduction of scalable video, UEP develops to a key concept for the transport of multimedia data. The paper presents an overview of some new approaches realizing UEP properties in physical transport, especially multicarrier modulation, or with LDPC and Turbo codes. For multicarrier modulation, UEP bit-loading together with hierarchical modulation is described allowing for an arbitrary number of classes, arbitrary SNR margins between the classes, and arbitrary number of bits per class. In Turbo coding, pruning, as a counterpart of puncturing is presented for flexible bit-rate adaptations, including tables with optimized pruning patterns. Bit- and/or check-irregular LDPC codes may be designed to provide UEP to its code bits. However, irregular degree distributions alone do not ensure UEP, and other necessary properties of the parity-check matrix for providing UEP are also pointed out. Pruning is also the means for constructing variable-rate LDPC codes for UEP, especially controlling the check-node profile.
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