| 1. |
- Amelina, Hanna, et al.
(författare)
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Quantitative subproteomic analysis of age-related changes in mouse liver peroxisomes by iTRAQ LC-MS/MS
- 2011
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 879:30, s. 3393-3400
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Tidskriftsartikel (refereegranskat)abstract
- Aging is a complex multifactorial phenomenon, which is believed to result from the accumulation of cellular damage to biological macromolecules. Peroxisomes recently emerged as another important source of reactive oxygen species (ROS) production in addition to mitochondria. However, the role of these organelles in the process of aging is still not clear. The aim of this study was to characterize the changes in protein expression profiles of young (10 weeks old) versus old (18 months old) mouse liver peroxisome-enriched fractions. We have applied shotgun proteomic approach based on liquid chromatography and tandem mass spectrometry (LC-MS/MS) combined with iTRAQ (isobaric tags for relative and absolute quantitation) labeling that allows comparative quantitative multiplex analysis. Our analysis led to identification and quantification of 150 proteins, 8 out of which were differentially expressed between two age groups at a statistically significant level (p < 0.05), with folds ranging from 1.2 to 4.1. These proteins involved in peroxisornal beta-oxidation, detoxification of xenobiotics and production of ROS. Noteworthy, differences in liver proteome have been observed between as well as within different age groups. In conclusion, our subproteomic quantitative study suggests that mouse liver proteome is sufficiently maintained until certain age.
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| 2. |
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| 3. |
- Cebula, Marcus, et al.
(författare)
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Catalytic Conversion of Lipophilic Substrates by Phase constrained Enzymes in the Aqueous or in the Membrane Phase
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Both soluble and membrane-bound enzymes can catalyze the conversion of lipophilic substrates. The precise substrate access path, with regard to phase, has however, until now relied on conjecture from enzyme structural data only (certainly giving credible and valuable hypotheses). Alternative methods have been missing. To obtain the first experimental evidence directly determining the access paths (of lipophilic substrates) to phase constrained enzymes we here describe the application of a BODIPY-derived substrate (PS1). Using this tool, which is not accessible to cytosolic enzymes in the presence of detergent and, by contrast, not accessible to membrane embedded enzymes in the absence of detergent, we demonstrate that cytosolic and microsomal glutathione transferases (GSTs), both catalyzing the activation of PS1, do so only within their respective phases. This approach can serve as a guideline to experimentally validate substrate access paths, a fundamental property of phase restricted enzymes. Examples of other enzyme classes with members in both phases are xenobiotic-metabolizing sulphotransferases/UDP-glucuronosyl transferases or epoxide hydrolases. Since specific GSTs have been suggested to contribute to tumor drug resistance, PS1 can also be utilized as a tool to discriminate between phase constrained members of these enzymes by analyzing samples in the absence and presence of Triton X-100.
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| 4. |
- Dahlin, Andreas P, et al.
(författare)
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Multiplexed quantification of proteins adsorbed to surface-modified and non-modified microdialysis membranes
- 2012
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 402:6, s. 2057-2067
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Tidskriftsartikel (refereegranskat)abstract
- A simple and straightforward method for discovery and quantification of proteins adsorbed onto delicate and sensitive membrane surfaces is presented. The adsorbed proteins were enzymatically cleaved while still adsorbed onto the membranes using an on-surface enzymatic digestion (oSED). This was followed by isobaric tagging, nanoliquid chromatography, and tandem mass spectrometry. Protein adsorption on tri-block copolymer Poloxamer 407 surface-modified microdialysis (MD) membranes were compared with protein adsorption on unmodified MD membranes. Ventricular cerebrospinal fluid (vCSF) kept at 37 °C was used as sample matrix. In total, 19 proteins were quantified in two biological replicates. The surface-modified membranes adsorbed 33% less proteins than control membranes and the most abundant proteins were subunits of hemoglobin and clusterin. The adsorption of clusterin on the modified membranes was on average 36% compared to control membranes. The most common protein in vCSF, Albumin, was not identified adsorbed to the surface at all. It was also experimentally verified that oSED, in conjunction with tandem mass spectrometry can be used to quantify femtomole amounts of proteins adsorbed on limited and delicate surfaces, such as MD membranes. The method has great potential and can be used to study much more complex protein adsorption systems than previously reported.
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| 5. |
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| 6. |
- Danielsson, Jakob
(författare)
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Automatic Characterization and Mitigation of Shared-resource Contention in Multi-core Systems
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multi-core computers are infamous for being hard to use in time-critical systems due to execution-time variations as an effect of shared resource contention. In this thesis, we study the problem of shared resource contention, which occurs when multiple applications executing on different cores do not have exclusive access to of a shared hardware resource. We investigate performance variations of parallel tasks in multi-core systems and present a method to pinpoint the source of the resource contention using hardware performance counters. We investigate mitigation methods for performance variations due to resource contention, including the Jailhouse hypervisor and the cache-partitioning tool PALLOC. We propose a benchmark strategy that quantifies the isolation gained from a specific isolation technique and exemplify this strategy using the Jailhouse hypervisor. We furthermore present and implement solutions for cache-partition allocation during application runtime. Our implementation aims to avoid over-provisioning of cache through pre-runtime estimations of an application's dependency towards the cache and continuous re-partitioning of the cache memory during application runtime.The primary goal of this thesis is to contribute to a process that automates some of the tedious manual testing needed to detect resource contention bottlenecks. The methods we present in this provide a holistic solution for automatic mitigating resource-contention in a multi-core system. First, we evaluate the risk for shared resource contention when several applications execute simultaneously. We then allocate partitions to mitigate resource contention for applications that risk severe performance degradations. We finally present methods that dynamically re-allocate partition space to meet the performance requirements of the running applications.
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| 7. |
- Danielsson, Jakob, et al.
(författare)
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Automatic Quality of Service Control in Multi-core Systems using Cache Partitioning
- 2021
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Konferensbidrag (refereegranskat)abstract
- In this paper, we present a last-level cache partitioning controller for multi-core systems. Our objective is to control the Quality of Service (QoS) of applications in multi-core systems by monitoring run-time performance and continuously re-sizing cache partition sizes according to the applications' needs. We discuss two different use-cases; one that promotes application fairness and another one that prioritizes applications according to the system engineers' desired execution behavior. We display the performance drawbacks of maintaining a fair schedule for all system tasks and its performance implications for system applications. We, therefore, implement a second control algorithm that enforces cache partition assignments according to user-defined priorities rather than system fairness. Our experiments reveal that it is possible, with non-instrusive (0.3-0.7\% CPU utilization) cache controlling measures, to increase performance according to setpoints and maintain the QoS for specific applications in an over-saturated system.
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| 8. |
- Danielsson, Jakob, et al.
(författare)
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LLM-shark -- A Tool for Automatic Resource-boundness Analysis and Cache Partitioning Setup
- 2021
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Ingår i: 45th IEEE Annual Computers, Software, and Applications Conference, COMPSAC 2021. - 9781665424639 ; , s. 49-58
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Konferensbidrag (refereegranskat)abstract
- We present LLM-shark, a tool for automatic hardware resource-boundness detection and cache-partitioning. Our tool has three primary objectives: First, it determines the hardware resource-boundness of a given application. Secondly, it estimates the initial cache partition size to ensure that the application performance is conserved and not affected by other processes competing for cache utilization. Thirdly, it continuously monitors that the application performance is maintained over time and, if necessary, change the cache partition size. We demonstrate LLM-shark's functionality through a series of tests using six different applications, including a set of feature detection algorithms and two synthetic applications. Our tests reveal that it is possible to determine an application's resource-boundness using a Pearson-correlation scheme implemented in LLM-shark. We propose a scheme to size cache partitions based on the correlation coefficient applications depending on their resource boundness.
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| 9. |
- Danielsson, Jakob, et al.
(författare)
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Measurement-based evaluation of data-parallelism for OpenCV feature-detection algorithms
- 2018
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Ingår i: Staying Smarter in a Smartening World COMPSAC'18. - 9781538626665 ; , s. 701-710
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Konferensbidrag (refereegranskat)abstract
- We investigate the effects on the execution time, shared cache usage and speed-up gains when using data-partitioned parallelism for the feature detection algorithms available in the OpenCV library. We use a data set of three different images which are scaled to six different sizes to exercise the different cache memories of our test architectures. Our measurements reveal that the algorithms using the default settings of OpenCV behave very differently when using data-partitioned parallelism. Our investigation shows that the executions of the algorithms SURF, Dense and MSER correlate to L3-cache usage and they are therefore not suitable for data-partitioned parallelism on multi-core CPUs. Other algorithms: BRISK, FAST, ORB, HARRIS, GFTT, SimpleBlob and SIFT, do not correlate to L3-cache in the same extent, and they are therefore more suitable for data-partitioned parallelism. Furthermore, the SIFT algorithm provides the most stable speed-up, resulting in an execution between 3 and 3.5 times faster than the original execution time for all image sizes. We also have evaluated the hardware resource usage by measuring the algorithm execution time simultaneously with the L3-cache usage. We have used our measurements to conclude which algorithms are suitable for parallelization on hardware with shared resources.
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| 10. |
- Danielsson, Jakob, et al.
(författare)
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Modelling Application Cache Behavior using Regression Models
- 2021
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Konferensbidrag (refereegranskat)abstract
- In this paper, we describe the creation of resource usage forecasts for applications with unknown execution characteristics, by evaluating different regression processes, including autoregressive, multivariate adaptive regression splines, exponential smoothing, etc. We utilize Performance Monitor Units (PMU) and generate hardware resource usage models for the L-2-cache and the L-3-cache using nine different regression processes. The measurement strategy and regression process methodology are general and applicable to any given hardware resource when performance counters are available. We use three benchmark applications: the SIFT feature detection algorithm, a standard matrix multiplication, and a version of Bubblesort. Our evaluation shows that Multi Adaptive Regressive Spline (MARS) models generate the best resource usage forecasts among the considered models, followed by Single Exponential Splines (SES) and Triple Exponential Splines (TES).
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| 11. |
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| 12. |
- Danielsson, Jakob, et al.
(författare)
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Testing Performance-Isolation in Multi-Core Systems
- 2019
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Konferensbidrag (refereegranskat)abstract
- In this paper we present a methodology to be used for quantifying the level of performance isolation for a multi-core system. We have devised a test that can be applied to breaches of isolation in different computing resources that may be shared between different cores. We use this test to determine the level of isolation gained by using the Jailhouse hypervisor compared to a regular Linux system in terms of CPU isolation, cache isolation and memory bus isolation. Our measurements show that the Jailhouse hypervisor provides performance isolation of local computing resources such as CPU. We have also evaluated if any isolation could be gained for shared computing resources such as the system wide cache and the memory bus controller. Our tests show no measurable difference in partitioning between a regular Linux system and a Jailhouse partitioned system for shared resources. Using the Jailhouse hypervisor provides only a small noticeable overhead when executing multiple shared-resource intensive tasks on multiple cores, which implies that running Jailhouse in a memory saturated system will not be harmful. However, contention still exist in the memory bus and in the system-wide cache.
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| 13. |
- Elhamili, Anisa, et al.
(författare)
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Analysis of peptides using N-methylpolyvinylpyridium as silica surface modifier for CE-ESI-MS
- 2010
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 31:7, s. 1151-1156
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the N-methylpolyvinylpyridinuim polymer has for the first time been used as a silica surface modifier for CE in combination with ESI MS (CE-ESI-MS). The compatibility for ESI-MS was demonstrated by the analysis of peptides and protein digests. The N-methylpolyvinylpyridium surface interacts electrostatically with the ionized silanol groups, giving a cationic surface with a reversed EOF. The surface modifier gave rapid and repeatable separations of peptides, proteins and protein digests at acidic pH for more than 4 h of continuous use. The CE separation yielded peak efficiencies of up to 4.3 x 10(5) plates/m. The surface coating is highly compatible with ESI and facilitates the separation and analysis of complex peptide mixtures as shown by the analysis of BSA digests.
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| 14. |
- Gebre-Medhin, Maria, et al.
(författare)
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ARTSCAN III : A randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer
- 2021
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 39:1, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE We performed an open-label randomized controlled phase III study comparing treatment outcome and toxicity between radiotherapy (RT) with concomitant cisplatin versus concomitant cetuximab in patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC; stage III-IV according to the Union for International Cancer Control TNM classification, 7th edition). MATERIALS AND METHODS Eligible patients were randomly assigned 1:1 to receive either intravenous cetuximab 400 mg/m2 1 week before start of RT followed by 250 mg/m2/wk, or weekly intravenous cisplatin 40 mg/m2, during RT. RT was conventionally fractionated. Patients with T3-T4 tumors underwent a second random assignment 1:1 between standard RT dose 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy. Primary end point was overall survival (OS) evaluated using adjusted Cox regression analysis. Secondary end points were locoregional control, local control with dose-escalated RT, pattern of failure, and adverse effects. RESULTS Study inclusion was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. At 3 years, OS was 88% (95% CI, 83% to 94%) and 78% (95% CI, 71% to 85%) in the cisplatin and cetuximab groups, respectively (adjusted hazard ratio, 1.63; 95% CI, 0.93 to 2.86; P 5 .086). The cumulative incidence of locoregional failures at 3 years was 23% (95% CI, 16% to 31%) compared with 9% (95% CI, 4% to 14%) in the cetuximab versus the cisplatin group (Gray’s test P 5 .0036). The cumulative incidence of distant failures did not differ between the treatment groups. Dose escalation in T3-T4 tumors did not increase local control. CONCLUSION Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with RT in patients with locoregionally advanced HNSCC. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.
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| 15. |
- Hao, J., et al.
(författare)
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Culture of human ovarian tissue in xeno-free conditions using laminin components of the human ovarian extracellular matrix
- 2020
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Ingår i: Journal of Assisted Reproduction and Genetics. - : Springer. - 1058-0468 .- 1573-7330. ; 37, s. 2137-2150
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Our purpose was to identify human ovarian extracellular matrix (ECM) components that would support in vitro culture of human ovarian tissue and be compatible with possible future clinical applications. We characterized ovarian expression of laminins and selected three laminin tripeptides for culture experiments to be compared with Matrigel, an undefined and animal-based mixture of ECM components. Methods: Expression of the 12 laminin genes was determined on transcript and protein levels using cortical tissue samples (n = 6), commercial ovary RNA (n = 1), follicular fluid granulosa cells (n = 20), and single-cell RNA-sequencing data. Laminin 221 (LN221), LN521, LN511, and their mixture were chosen for a 7-day culture experiment along with Matrigel using tissue from 17 patients. At the end of the culture, follicles were evaluated by scoring and counting from serial tissue sections, apoptosis measured using in situ TUNEL assay, proliferation by Ki67 staining, and endocrine function by quantifying steroids in culture media using UPLC-MS/MS. Results: Approximately half of the cells in ovarian cortex expressed at least one laminin gene. The overall most expressed laminin α-chains were LAMA2 and LAMA5, β-chains LAMB1 and LAMB2, and γ-chain LAMC1. In culture experiments, LN221 enhanced follicular survival compared with Matrigel (p < 0.001), whereas tissue cultured on LN521 had higher proportion of secondary follicles (p < 0.001). LN511 and mixture of laminins did not support the cultures leading to lower follicle densities and higher apoptosis. All cultures produced steroids and contained proliferating cells. Conclusions: LN221 and LN521 show promise in providing xeno-free growth substrates for human ovarian tissue cultures, which may help in further development of folliculogenesis in vitro for clinical practices. The system could also be used for identification of adverse effects of chemicals in ovaries.
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| 16. |
- Inam, Rafia, 1974-, et al.
(författare)
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Bandwidth Measurement using Performance Counters for Predictable Multicore Software
- 2012
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Ingår i: IEEE Symposium on Emerging Technologies and Factory Automation, ETFA 2012. ; , s. Article number: 6489714-
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Konferensbidrag (populärvet., debatt m.m.)abstract
- Memory contention is one of the largest sources of inter-core interference in statically partitioned multicore systems, and the contention reduces the overall performance of applications and causes unpredictable execution-times. A first step in achieving predictable execution is to accurately measure the amount of consumed memory bandwidth for each application. Such measurements can be used to track down bottlenecks, provide better partitioning among cores, and ultimately be used to arbitrate and police access to the memory bus. We propose to use hardware performance counters to continuously track the memory-bandwidth consumed by different applications executing in parallel. In this paper we describe ongoing efforts exploring suitable performance counters on core-level and on system-on-chip level for the 8-core Freescale P4080 processor. The aim is to accurately and efficiently track consumed memory bandwidth per application; with the final goal to use these measurements to improve predictability of multicore real-time software.
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| 17. |
- Lind, Anne-Li, et al.
(författare)
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Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients : A Proteomic Mass Spectrometric Analysis
- 2016
-
Ingår i: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 19:6, s. 549-562
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesElectrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. MethodsTwo different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. ResultsEighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). ConclusionPreviously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
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| 18. |
- Nordström, Erik, et al.
(författare)
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Field investigations on the risk for ASR when using potentially reactive aggregates and low alkali cements : Results after 50 years in Sweden
- 2013
-
Ingår i: ICOLD 2013 International Symposium — Seattle USA. - 9781884575631 ; , s. 393-402
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Konferensbidrag (refereegranskat)abstract
- The adverse effects from reactions of reactive aggregates in concrete dams are well known worldwide. The mechanisms ruling alkali silica reactions (ASR) are partly but not fully understood. A majority of the Swedish concrete dams are so far considered to be protected from ASR due to the common use during the 50:s, 60:s and 70:s of the Swedish low alkali cement Limhamn LH. Today there is a discussion if it still is possible to develop ASR after very long time in dams with reactive aggregates and use of low alkali cement. Via selection of seven facilities in the Swedish alpine area, where reactive aggregates are common, the current paper is aiming to compile experiences from almost 50 years of exposure. In the paper two examples on ASR in spite of use of low alkali cement are shown.
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| 19. |
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| 20. |
- Ranlund, Åsa, et al.
(författare)
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Metodbeskrivning : 2020 års inventeringar av gräsmarker och lövskogar
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- En generell stickprovsdesign, inom vilken det går att inventera både vanliga och ovanliga fenomen på såväl nationell som regional nivå, utvecklades under 2019 och 2020. Under 2020 har den nya stickprovsdesignen använts för inventeringar av gräsmarker och lövskogar med syfte att förbättra nationella data på naturtyper med höga naturvärden, dvs. naturtyper som uppfyller kriterierna för EU:s art- och habitatdirektivs annex 1, samtidigt som vanligare naturtyper följdes där behov funnits för att komplettera befintliga data. I den här rapporten redovisar vi metodiken vi utvecklat för flygbilds- och fältinventeringarna samt hur urval av trakter till stickprov och provytor för fältbesök gått till.För gräsmarks- och lövskogsinventeringarna gjordes först ett gemensamt så kallat balanserat urval för att slumpmässigt välja ut trakter ur urvalsramen till stickprov. Sedan klassades alla provytor inom de utvalda trakterna i en flygbildsinventering till både lövskogs- och gräsmarksklasser. Utifrån de flygbildsinventerade klasserna skapades urvalsklasser separat för gräsmarks- respektive lövskogsinventeringen. Urvalsklasserna användes sedan för att välja ut provytor för fältbesök, ett urval som gjordes för gräsmarks- respektive lövskogsinventeringen oberoende av varandra.Metodiken för flygbildsinventering utvecklades för att gräsmarks- och lövskogsinventeringarna skulle kunna använda stora stickprov, i linje med den nya stickprovsdesignen. En viktig princip vid flygbildsinveteringen var överklassning, dvs att provytor inkluderades där klassningen var osäker. Detta för att säkerställa att alla gräsmarker och lövskogar inom inventeringarnas respektive ramverk hade möjlighet att ingå så att det statistiska kravet för stickprovsdesignen var uppfyllda. Provytor som utifrån flygbildsinventeringen helt säkert inte innehöll eftersökta naturtyper behövde inte besökas i fält vilket gjorde att fältbesöken fokuserades till provytor av intresse för gräsmarks- eller lövskogsinventeringarna. Det minskade kostnaden för fältbesök och vi kunde använda större stickprov. Sammantaget flygbildsinventerades över 137 000 provytor fördelat på 701 trakter inför fältinventeringen 2020.För fältinventeringen inom gräsmarks- och lövskogsinventeringarna introducerades flera nyheter jämfört med tidigare inventeringar för att samla in mer data på bl.a. naturtypers kvalitet. Varje delyta klassades t.ex. till en naturtyp oavsett om den uppfyller kravet för att bli klassad som en annex 1-naturtyp. Utöver det registrerades ett antal kvalitetsvariabler som visar vilka kriterier för annex 1 som är uppfyllda eller inte. Det gör att det går att jämföra areal och statusvariabler för en annex 1-naturtyp) med areal och statusvariabler av motsvarande naturtyp med låga naturvärden (dvs. där annex 1-kriterierna inte är uppfyllda). 1763 provytor fördelat på 187 trakter slumpades ut för att inventeras i fält 2020. Av dem inventerades 64 provytor 2021 eftersom de inte hanns med säsongen 2020.Eftersom antalet trakter är den viktigaste faktorn i att bestämma precisionen i skattningarna så vill vi inte minska antalet trakter eftersom det ökar osäkerheten i skattningarna. För att effektivisera inventeringarna arbetar vi därför med två olika angreppssätt för en viss stickprovstäthet. Dels vill vi förbättra möjligheten att korrekt kunna utesluta provytor, och ibland hela trakter, från fältbesök genom att förbättra flygbildsinventeringen. Det kan t.ex. handla om att minska överklassningen, genom att göra kriterierna för klasserna snävare . Under det första inventeringsåret 2020 tog det lite längre tid att inventera en trakt i fält än vad som var önskvärt. För att minska fälttiden kan vi därför behöva minska antalet provytor som vi inventerar per trakt alternativt förenkla fältmetodiken per provyta. Fältinsatsen kan också bli effektivare genom att inventering av smala linjära objekt, som åker- och vägrenar, görs genom en linjekorsningsinventering istället för via gräsmarks- och lövskogsinventeringarnas provytor. För lövskogsinventeringen 2020 var ålderskriteriet >30 år . Ett sätt att fokusera denna inventering mot naturtyper av större intresse är att höja ålderskriteriet så att inventeringen riktas mer mot äldre lövskogar. Utöver färre provytor skulle det antagligen också leda till att vi behöver besöka färre trakter inom lövskogsinventeringen. Nackdelen blir förstås att inventeringen inte inkluderar yngre skogar, så det är ett beslut som bör tas utifrån vilka frågeställningar som ska besvaras och hur prioriteringen ser ut för vilka data som ska samlas in.För att kunna ta tillvara de möjligheter som den nya stickprovsdesignen ger har vi utvecklat ny metodik för flygbildsinventering av stora stickprov inom gräsmarks- och lövskogsinventeringarna. Det förbättrar våra möjligheter att möta kraven på tillfredställande data även för mer ovanliga naturtyper. För att möta de ökade kraven på data till artikel 17-rapporteringen har vi också utvecklat och omprioriterat fältinventeringen. 2020 var det första året för gräsmarks- och lövskogsinventeringarna. Redan då fanns allt på plats men många delar behöver utvecklas vidare för att ytterligare effektivisera dem.
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| 21. |
- Repouskou, Anastasia, et al.
(författare)
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Gestational exposure to an epidemiologically defined mixture of phthalates leads to gonadal dysfunction in mouse offspring of both sexes.
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- The increasing concern for the reproductive toxicity of abundantly used phthalates requires reliable tools for exposure risk assessment to mixtures of chemicals, based on real life human exposure and disorder-associated epidemiological evidence. We herein used a mixture of four phthalate monoesters (33% mono-butyl phthalate, 16% mono-benzyl phthalate, 21% mono-ethyl hexyl phthalate, and 30% mono-isononyl phthalate), detected in 1st trimester urine of 194 pregnant women and identified as bad actors for a shorter anogenita I distance (AGD) in their baby boys. Mice were treated with 0, 0.26, 2.6 and 13 mg/kg/d of the mixture, corresponding to 0x, 10x, 100x, 500x levels detected in the pregnant women. Adverse outcomes detected in the reproductive system of the offspring in pre-puberty and adulthood included reduced AGD index and gonadal weight, changes in gonadal histology and altered expression of key regulators of gonadal growth and steroidogenesis. Most aberrations were apparent in both sexes, though more pronounced in males, and exhibited a non-monotonic pattern. The phthalate mixture directly affected expression of steroidogenesis as demonstrated in a relevant in vitro model. The detected adversities at exposures close to the levels detected in pregnant women, raise concern on the existing safety limits for early-life human exposures and emphasizes the need for re-evaluation of the exposure risk.
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| 22. |
- Shahbazi, Sasha, et al.
(författare)
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A foresight study on future trends influencing material consumption and waste generation in production
- 2014
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Ingår i: Flexible Automation & Intelligent Manufacturing. - San Antonio, Texas, United States : DEStech Publications, Inc.. - 9781605951737
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Konferensbidrag (refereegranskat)abstract
- There are boundless upcoming factors that influence future of material waste in production. This broad range of factors needs to be scanned, categorized and analyzed in a structured way. This paper by a foresight study, aims to give an insight and increase awareness about external macro-level future trends concerning raw material consumption and waste generation in production. A limited pilot study indicated that technological forecasting and some reaction upon obvious trends are being taken, although in an ad hoc manner and without structured tools. However, political influences, economic visions and social-cultural shifts were seldom or never discussed. External macro trends and tendencies were examined through PEST analysis to identify potentials and opportunities influencing strategic decisions and innovation initiatives. It is vital to understand the whole picture of possible changes and not only considering the technological trends, but also other relevant development areas that might affect production in different ways.
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| 23. |
- Shepherd, Tyson R, et al.
(författare)
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De novo design and synthesis of a 30-cistron translation-factor module
- 2017
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Ingår i: Nucleic Acids Research. - : OXFORD UNIV PRESS. - 0305-1048 .- 1362-4962. ; 45:18, s. 10895-10905
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Tidskriftsartikel (refereegranskat)abstract
- Two of the many goals of synthetic biology are synthesizing large biochemical systems and simplifying their assembly. While several genes have been assembled together by modular idempotent cloning, it is unclear if such simplified strategies scale to very large constructs for expression and purification of whole pathways. Here we synthesize from oligodeoxyribonucleotides a completely de-novo-designed, 58-kb multigene DNA. This BioBrick plasmid insert encodes 30 of the 31 translation factors of the PURE translation system, each His-tagged and in separate transcription cistrons. Dividing the insert between three high-copy expression plasmids enables the bulk purification of the aminoacyl-tRNA synthetases and translation factors necessary for affordable, scalable reconstitution of an in vitro transcription and translation system, PURE 3.0.
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| 24. |
- Shevchenko, Ganna, et al.
(författare)
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Cloud-point extraction and delipidation of porcine brain proteins in combination with bottom-up mass spectrometry approaches for proteome analysis
- 2010
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Ingår i: Journal of Proteome Research. - : ACS. - 1535-3893 .- 1535-3907. ; 9:8, s. 3903-3911
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Tidskriftsartikel (refereegranskat)abstract
- In this study, temperature-induced phase fractionation also known as cloud-point extraction (CPE) with the nonionic surfactant Triton X-114 was used to simultaneously extract hydrophobic and hydrophilic proteins from porcine brain tissue. Various protein precipitation/delipidation procedures were investigated to efficiently remove lipids and detergents while retaining maximum protein recoveries. The best performing delipidation method was then used in combination with CPE to compare three different mass spectrometry (MS) based "bottom-up" proteomic approaches for protein analysis of the porcine brain. In the first approach, the intact proteins were initially separated by one-dimensional (1D) gel electrophoresis. The excised protein bands were digested with trypsin, and the peptides were separated by reversed phase nanoliquid chromatography (RP-nanoLC) followed by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis. The other bottom-up proteomic approaches were based on first enzymatical digestion of the proteins followed by RP-nanoLC separation in combination with matrix assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) or on the combination of in-solution isoelectric focusing (IEF) with ESI-nanoLC-MS/MS of the IEF separated peptides. In total, we found and unambiguously identified 331 unique proteins. The overlap between different techniques was about 10%, showing that the use of multiple proteomic approaches is beneficial to yield a better coverage of the proteome. Furthermore, the overlap between the CPE extracted hydrophilic and hydrophobic proteins was rather small (9-16%), indicating an efficient sample preparation technique to extract and separate hydrophilic and hydrophobic proteins from brain tissue. The percentage of identified membrane proteins was 27%, which is in accordance to the fact that about one-third of all genes in various organisms encode for this class of proteins. The results indicate that cloud point extraction is a promising sample preparation tool, which allows simultaneous in depth studies of brain derived membrane proteins as well as hydrophilic proteins. This technique can be very useful when studying human central nervous system (CNS) tissue or animal models of neurological diseases.
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| 25. |
- Sjödin, Marcus O.D. 1978-
(författare)
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Advances for Biomarker Discovery in Neuroproteomics using Mass Spectrometry : From Method Development to Clinical Application
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Proteins offer a prominent group of compounds which may be ubiquitously affected in disease and used as biomarkers for early diagnosis, assessing treatment or drug development. Clinical proteomics aim to screen for protein biomarkers by a comprehensive analysis of all proteins expressed in a biological matrix during a certain pathology. Characterization of thousands of proteins in a complex biological matrix is from an analytical point of view a challenging task. Hence, sophisticated methods that are sensitive, specific and robust in a high-throughput manner are required. Mass spectrometry (MS) is able to perform this to a wide extent is.A prominent source for finding protein biomarkers related to neurological diseases is the central nervous system (CNS) due to close proximity of the pathogenesis. Neuroproteomic analysis of CNS tissue samples is thus likely to reveal novel biomarkers. Cerebrospinal fluid (CSF) bathes the entire CNS and offers a good balance between clinical implementation and usefulness. Both matrices put further requirements on the methodology due to a high dynamic range, low protein concentration and limited sample amount.The central objective of this thesis was to develop, assess and utilize analytical methods to be used in combination with MS to enable protein biomarker discovery in the CNS. The use of hexapeptide ligand libraries was exemplified on CSF from patients with traumatic brain injury and demonstrated the ability to compress the dynamic range to enable protein profiling in the order of mg/mL to pg/mL. Further, a method based on cloud-point extraction was developed for simultaneous enrichment and fractionation of hydrophobic/hydrophilic proteins in brain tissue. Comparison between label and label-free MS based strategies were carried out, mimicking the true conditions with a few differentially expressed proteins and a bulk of proteins occurring in unchanged ratio. Finally, a clinical application was carried out to explore the molecular mechanism underlying the analgesic effect of spinal cord stimulation (SCS) in patients with neuropathic pain. The CSF concentration of Lynx1 was found to increase upon SCS. Lynx1, acting as a specific modulator of the cholinergic system in the CNS, may act as a potential important molecular explanation of SCS-induced analgesia.
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| 26. |
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| 27. |
- Sjödin, Marcus O.D. 1978-, et al.
(författare)
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Comparative study of label and label-free techniques using shotgun proteomics for relative protein quantification
- 2013
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 928, s. 83-92
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Tidskriftsartikel (refereegranskat)abstract
- The analytical performance of three different strategies, iTRAQ (isobaric tag for relative and absolute quantitation), dimethyl labeling (DML) and label free (LF) for relative protein quantification using shotgun proteomics have been evaluated. The methods have been explored using samples containing (i) Bovine proteins in known ratios and (ii) Bovine proteins in known ratios spiked into E.Coli. The latter case mimics the actual conditions in a typical biological sample with a few differentially expressed proteins and a bulk of proteins with unchanged ratios. Additionally, the evaluation was performed on both Q-TOF and LTQ-FTICR mass spectrometers. LF LTQ-FTICR was found to have the highest proteome coverage (94 %) while the highest accuracy based on the artificially regulated proteins was found for DML LTQ-FTICR (54%). A good linearity (r2: 0.61-0.96) was shown for all methods within selected dynamic ranges. All methods were found to consistently underestimate bovine protein ratios when matrix proteins were added. However LF LTQ-FTICR was more tolerant towards a compression effect. A single peptide was demonstrated to be sufficient for a reliable quantification using iTRAQ. A ranking system utilizing several parameters important for quantitative proteomics demonstrated that the overall performance of the five different methods were; DML LTQ-FTICR > iTRAQ QTOF > LF LTQ-FTICR > DML Q-TOF > LF Q-TOF.
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| 28. |
- Sjödin, Marcus O.D., et al.
(författare)
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Mining ventricular cerebrospinal fluid from patients with traumatic brain injury using hexapeptide ligand libraries to search for trauma biomarkers
- 2010
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Ingår i: Journal of chromatography. B. - : Elsevier. - 1570-0232 .- 1873-376X. ; 878:22, s. 2003-2012
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic brain injury (TBI) is an acute event resulting from external force to the brain and is a major cause of death and disability associated with high health care costs in the western world. Additional injuries, originating from the secondary molecular events after the initial intensive care, may be limited by the use of objective biomarkers to provide the best treatment and patient prediction outcome. In this study, hexapeptide ligand libraries (HLL) have been used for the enrichment of suggested protein biomarkers for TBI in cerebrospinal fluid (CSF). HLL have the potential to enrich low abundant proteins and simultaneously reduce the high abundant proteins, rendering a sample with significantly reduced dynamic range. The CSF proteome from two TBI inflicted patients have been extensively mapped using a large initial sample volume obtained by extraventricular drainage. Shotgun proteomics, in combination with isoelectric focusing (IEF) and nano-LC-MS/MS, identified 339 unique proteins (MudPIT scoring p ≤ 0.05) with a protein overlap of 130 between the patients. As much as 45% of the proteins reported in the literature to be associated with degenerative/regenerative processes occurring after a trauma to the head were identified. Out of the most prominent potential protein biomarkers, such as neuron specific enolase, glial fibrillary acidic protein, myelin basic protein, creatine kinase B-type and S-100β, all except myelin basic protein were detected in the study. This study shows the possibility of using HLL as a tool for screening of low abundant protein biomarkers in human CSF.
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| 29. |
- Sjödin, Marcus O.D. 1978-, et al.
(författare)
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Proteomic analysis of cerebrospinal fluid from neuropathic pain patients reveals proteins with potential role in spinal cord stimulation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral origin. Despite its well-established clinical use, the underlying physiological mechanisms behind the beneficial analgesic effects of SCS still remain only partially known. In this study, a proteomic approach was used to compare the protein concentration in cerebrospinal fluid (CSF) from responsive human patients (n=12). The comparison was made between samples taken during at two different timepoints. The first sample was taken when the stimulator had been off for 48 h, the second sample was taken after the stimulator had been used for three weeks. In total, 419 proteins could be identified (P<0.05) and relatively quantified using a shotgun proteomic approach based on immunoaffinity fractionation, multiplexed dimethyl labeling and reversed phase nanoliquid chromatography in combination with electrospray ionization high resolution tandem mass spectrometry. Statistical analysis (P<0.01) revealed two significantly down-regulated proteins; Co2 (P=0.0046), Ibp6 (P=0.0071) and five up-regulated proteins; Lynx1 (P=0.000048), Klk6 (P=0.00058), Angt (P=0.00057), A4 (P=0.0052) and Sap3 (P=0.0076) during the on state. Lynx1was the most significantly and consistently increased protein in all patients. Lynx1 is a modulator of the nicotinic acetylcholine receptor activity in the central nervous system previously described in mice. This study reports for the first time the possible involvement of Lynx1 in SCS-induced analgesia in humans.
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| 30. |
- Tsog, Nandinbaatar, et al.
(författare)
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Poster Abstract : Real-Time Capabilities of HSA Compliant COTS Platforms
- 2016
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Ingår i: PROCEEDINGS OF 2016 IEEE REAL-TIME SYSTEMS SYMPOSIUM (RTSS). - 9781509053032 ; , s. 364-364
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Konferensbidrag (refereegranskat)abstract
- During recent years, the interest in using heterogeneous computing architecture in industrial applications has increased dramatically. These architectures provide the computational power that makes them attractive for many industrial applications. However, most of these existing heterogeneous architectures suffer from the following limitations: difficulties of heterogeneous parallel programming and high communication cost between the computing units. To overcome these disadvantages, several leading hardware manufacturers have formed the HSA Foundation to develop a new hardware architecture: Heterogeneous System Architecture (HSA). In this paper, we investigate the suitability of using HSA for real-time embedded systems. A preliminary experimental study has been conducted to measure massive computing power and timing predictability of HSA.
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| 31. |
- Wetterhall, Magnus, et al.
(författare)
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Analysis of membrane and hydrophilic proteins simultaneously derived from the mouse brain using cloud-point extraction
- 2011
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 400:9, s. 2827-2836
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a temperature-induced phase fractionation known as cloud-point extraction (CPE) with the non-ionic surfactant Triton X-114 was used to simultaneously extract, concentrate, and fractionate hydrophobic and hydrophilic proteins from mouse brain tissue. Two bottom-up proteomic techniques were used to comprehensively identify the extracted proteins. The first "shotgun"-based approach included tryptic digestion of the proteins followed by reversed-phase nanoliquid chromatography (RP-nanoLC) in combination with electrospray ionization (ESI) tandem mass spectrometry (MS/MS). In the second approach, the extracted intact proteins were first separated by one-dimensional (1D) gel electrophoresis and then in-gel digested with trypsin and analyzed with nanoLC-MS/MS. In total, 1,825 proteins were unambiguously identified and the percentage of membrane proteins was 26% which is at the reported genome expression levels of 20-30%. The protein overlap between the two approaches was high. The majority (77%) of the identifications in the first approach was also found by the second method. The protein overlap between the CPE-extracted hydrophilic and hydrophobic fractions was rather small (16-23%) for both methods, which indicates a good phase separation. A quantitative evaluation of the CPE with iTRAQ labeling and nanoLC-ESI-MS/MS analysis gave iTRAQ ratios at the expected levels and an overall variation of the entire method at 17-31%. The results indicate very reproducible sample preparation and analysis methods that readily can be applied on large-scale sample sets.
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| 32. |
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