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  • 151.
    Aghaee Ghaleshahi, Nima
    et al.
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, The Institute of Technology.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, The Institute of Technology.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, The Institute of Technology.
    Process-Variation and Temperature Aware SoC Test Scheduling Using Particle Swarm Optimization2011In: The 6th IEEE International Design and Test Workshop (IDT'11), Beirut, Lebanon, December 11–14, 2011., IEEE , 2011Conference paper (Refereed)
    Abstract [en]

    High working temperature and process variation are undesirable effects for modern systems-on-chip. It is well recognized that the high temperature should be taken care of during the test process. Since large process variations induce rapid and large temperature deviations, traditional static test schedules are suboptimal in terms of speed and/or thermalsafety. A solution to this problem is to use an adaptive test schedule which addresses the temperature deviations by reacting to them. We propose an adaptive method that consists of a computationally intense offline-phase and a very simple onlinephase. In the offline-phase, a near optimal schedule tree is constructed and in the online-phase, based on the temperature sensor readings, an appropriate path in the schedule tree is traversed. In this paper, particle swarm optimization is introduced into the offline-phase and the implications are studied. Experimental results demonstrate the advantage of the proposed method.

  • 152.
    Aghaee Ghaleshahi, Nima
    et al.
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Process-Variation Aware Multi-temperature Test Scheduling2014In: 27th International Conference on VLSI Design and 13th International Conference on Embedded Systems, IEEE conference proceedings, 2014, p. 32-37Conference paper (Refereed)
    Abstract [en]

    Chips manufactured with deep sub micron technologies are prone to large process variation and temperature-dependent defects. In order to provide high test efficiency, the tests for temperature-dependent defects should be applied at appropriate temperature ranges. Existing static scheduling techniques achieve these specified temperatures by scheduling the tests, specially developed heating sequences, and cooling intervals together. Because of the temperature uncertainty induced by process variation, a static test schedule is not capable of applying the tests at intended temperatures in an efficient manner. As a result the test cost will be very high. In this paper, an adaptive test scheduling method is introduced that utilizes on-chip temperature sensors in order to adapt the test schedule to the actual temperatures. The proposed method generates a low cost schedule tree based on the variation statistics and thermal simulations in the design phase. During the test, a chip selects an appropriate schedule dynamically based on temperature sensor readings. A 23% decrease in the likelihood that tests are not applied at the intended temperatures is observed in the experimental studies in addition to 20% reduction in test application time.

  • 153.
    Aghaee Ghaleshahi, Nima
    et al.
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Temperature-Gradient Based Burn-In for 3D Stacked ICs2013In: The 12th Swedish System-on-Chip Conference (SSoCC 2013), Ystad, Sweden, May 6-7, 2013 (not reviewed, not printed)., 2013Conference paper (Other academic)
    Abstract [en]

    3D Stacked IC fabrication, using Through-Silicon-Vias, is a promising technology for future integrated circuits. However, large temperature gradients may exacerbate early-life-failures to the extent that the commercialization of 3D Stacked ICs is challenged. The effective detection of these early-life-failures requires that burn-in is performed when the IC’s temperatures comply with the thermal maps that properly specify the temperature gradients. In this paper, two methods that efficiently generate and maintain the specified thermal maps are proposed. The thermal maps are achieved by applying heating and cooling intervals to the chips under test through test access mechanisms. Therefore, no external heating system is required. The scheduling of the heating and cooling intervals is based on thermal simulations. The schedule generation is guided by functions that are derived from the temperature equations. Experimental results demonstrate the efficiency of the proposed method.

  • 154.
    Aghaee Ghaleshahi, Nima
    et al.
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Temperature-Gradient Based Test Scheduling for 3D Stacked ICs2013In: 2013 IEEE International Conference on Electronics, Circuits, and Systems, IEEE conference proceedings, 2013, p. 405-408Conference paper (Refereed)
    Abstract [en]

    Defects that are dependent on temperature-gradients (e.g., delay-faults) introduce a challenge for achieving an effective test process, in particular for 3D ICs. Testing for such defects must be performed when the proper temperature gradients are enforced on the IC, otherwise these defects may escape the test. In this paper, a technique that efficiently heats up the IC during test so that it complies with the specified temperature gradients is proposed. The specified temperature gradients are achieved by applying heating sequences to the cores of the IC under test trough test access mechanism; thus no external heating mechanism is required. The scheduling of the test and heating sequences is based on thermal simulations. The schedule generation is guided by functions derived from the IC's temperature equation. Experimental results demonstrate that the proposed technique offers considerable test time savings.

  • 155.
    Aghaee, Nima
    et al.
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Faculty of Science & Engineering.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Faculty of Science & Engineering.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, ESLAB - Embedded Systems Laboratory. Linköping University, Faculty of Science & Engineering.
    A Test-Ordering Based Temperature-Cycling Acceleration Technique for 3D Stacked ICs2015In: Journal of electronic testing, ISSN 0923-8174, E-ISSN 1573-0727, ISSN 0923-8174, Vol. 31, no 5, p. 503-523Article in journal (Refereed)
    Abstract [en]

    n a modern three-dimensional integrated circuit (3D IC), vertically stacked dies are interconnected using through silicon vias. 3D ICs are subject to undesirable temperature-cycling phenomena such as through silicon via protrusion as well as void formation and growth. These cycling effects that occur during early life result in opens, resistive opens, and stress induced carrier mobility reduction. Consequently these early-life failures lead to products that fail shortly after the start of their use. Artificially-accelerated temperature cycling, before the manufacturing test, helps to detect such early-life failures that are otherwise undetectable. A test-ordering based temperature-cycling acceleration technique is introduced in this paper that integrates a temperature-cycling acceleration procedure with pre-, mid-, and post-bond tests for 3D ICs. Moreover, it reduces the need for costly temperature chamber based temperature-cycling acceleration methods. All these result in a reduction in the overall test costs. The proposed method is a test-ordering and schedule based solution that enforces the required temperature cycling effect and simultaneously performs the tests whenever appropriate. Experimental results demonstrate the efficiency of the proposed technique.

  • 156.
    Aghaee, Nima
    et al.
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Peng, Zebo
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Eles, Petru
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Temperature-Gradient-Based Burn-In and Test Scheduling for 3-D Stacked ICs2015In: IEEE Transactions on Very Large Scale Integration (vlsi) Systems, ISSN 1063-8210, E-ISSN 1557-9999, Vol. 23, no 12, p. 2992-3005Article in journal (Refereed)
    Abstract [en]

    Large temperature gradients exacerbate various types of defects including early-life failures and delay faults. Efficient detection of these defects requires that burn-in and test for delay faults, respectively, are performed when temperature gradients with proper magnitudes are enforced on an Integrated Circuit (IC). This issue is much more important for 3-D stacked ICs (3-D SICs) compared with 2-D ICs because of the larger temperature gradients in 3-D SICs. In this paper, two methods to efficiently enforce the specified temperature gradients on the IC, for burn-in and delay-fault test, are proposed. The specified temperature gradients are enforced by applying high-power stimuli to the cores of the IC under test through the test access mechanism. Therefore, no external heating mechanism is required. The tests, high power stimuli, and cooling intervals are scheduled together based on temperature simulations so that the desired temperature gradients are rapidly enforced. The schedule generation is guided by functions derived from a set of thermal equations. The experimental results demonstrate the efficiency of the proposed methods.

  • 157.
    Aghapournahr, M
    et al.
    Arak University.
    Melkersson, Leif
    Linköping University, Department of Mathematics, Applied Mathematics. Linköping University, The Institute of Technology.
    Finiteness properties of minimax and coatomic local cohomology modules2010In: ARCHIV DER MATHEMATIK, ISSN 0003-889X, Vol. 94, no 6, p. 519-528Article in journal (Refereed)
    Abstract [en]

    Let R be a noetherian ring, alpha an ideal of R, and M an R-module. We prove that for a finite module M, if H-alpha(i)(M) is minimax for all i andgt;= r andgt;= 1, then H-alpha(i)(M) is artinian for i andgt;= r. A local-global principle for minimax local cohomology modules is shown. If H-alpha(i)(M) is coatomic for i andlt;= r (M finite) then H-alpha(i)(M) is finite for i andlt;= r. We give conditions for a module which is locally minimax to be a minimax module. A non-vanishing theorem and some vanishing theorems are proved for local cohomology modules.

  • 158.
    Aghapournahr, Moharram
    et al.
    Arak University.
    Melkersson, Leif
    Linköping University, Department of Mathematics, Applied Mathematics. Linköping University, The Institute of Technology.
    A natural map in local cohomology2010In: ARKIV FOR MATEMATIK, ISSN 0004-2080, Vol. 48, no 2, p. 243-251Article in journal (Refereed)
    Abstract [en]

    Let R be a Noetherian ring, a an ideal of R, M an R-module and n a non-negative integer. In this paper we first study the finiteness properties of the kernel and the cokernel of the natural map f: Ext(R)(n) (R/alpha, M) -andgt; Hom(R)(R/alpha, H-alpha(n) (M)), under some conditions on the previous local cohomology modules. Then we get some corollaries about the associated primes and Artinianness of local cohomology modules. Finally we will study the asymptotic behavior of the kernel and the cokernel of the natural map in the graded case.

  • 159.
    Aghapournahr, Moharram
    et al.
    Arak University, Iran .
    Melkersson, Leif
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, The Institute of Technology.
    Artinianness of local cohomology modules2014In: Arkiv för matematik, ISSN 0004-2080, E-ISSN 1871-2487, Vol. 52, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    Some uniform theorems on the artinianness of certain local cohomology modules are proven in a general situation. They generalize and imply previous results about the artinianness of some special local cohomology modules in the graded case.

  • 160.
    Aghapournahr, Moharram
    et al.
    Arak Univ, Arak, Iran.
    Melkersson, Leif
    Linköping University, Department of Mathematics, Applied Mathematics. Linköping University, The Institute of Technology.
    COFINITENESS AND COASSOCIATED PRIMES OF LOCAL COHOMOLOGY MODULES2009In: Mathematica Scandinavica, ISSN 0025-5521, E-ISSN 1903-1807, Vol. 105, no 2, p. 161-170Article in journal (Refereed)
    Abstract [en]

    Let R be a noetherian ring, alpha an ideal of R such that dim R/alpha = 1 and M a finite R-module. We will study cofiniteness and some other properties of the local cohomology modules H-alpha(i)(M). For an arbitrary ideal alpha and an R-module M (not necessarily finite), we will characterize alpha-cofinite artinian local cohomology modules. Certain sets of coassociated primes of top local cohomology modules over local rings are characterized.

  • 161.
    Aghighi, Meysam
    et al.
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Bäckström, Christer
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Jonsson, Peter
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Ståhlberg, Simon
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Analysing Approximability and Heuristics in Planning Using the Exponential-Time Hypothesis2016In: ECAI 2016: 22ND EUROPEAN CONFERENCE ON ARTIFICIAL INTELLIGENCE, IOS Press, 2016, Vol. 285, p. 184-192Conference paper (Refereed)
    Abstract [en]

    Cost-optimal planning has become a very well-studied topic within planning. Needless to say, cost-optimal planning has proven to be computationally hard both theoretically and in practice. Since cost-optimal planning is an optimisation problem, it is natural to analyse it from an approximation point of view. Even though such studies may be valuable in themselves, additional motivation is provided by the fact that there is a very close link between approximability and the performance of heuristics used in heuristic search. The aim of this paper is to analyse approximability (and indirectly the performance of heuristics) with respect to lower time bounds. That is, we are not content by merely classifying problems into complexity classes - we also study their time complexity. This is achieved by replacing standard complexity-theoretic assumptions (such as P not equal NP) with the exponential time hypothesis (ETH). This enables us to analyse, for instance, the performance of the h(+) heuristic and obtain general trade-off results that correlate approximability bounds with bounds on time complexity.

  • 162.
    Aghighi, Meysam
    et al.
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Bäckström, Christer
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Jonsson, Peter
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Ståhlberg, Simon
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, Faculty of Science & Engineering.
    Refining complexity analyses in planning by exploiting the exponential time hypothesis2016In: Annals of Mathematics and Artificial Intelligence, ISSN 1012-2443, E-ISSN 1573-7470, Vol. 78, no 2, p. 157-175Article in journal (Refereed)
    Abstract [en]

    The use of computational complexity in planning, and in AI in general, has always been a disputed topic. A major problem with ordinary worst-case analyses is that they do not provide any quantitative information: they do not tell us much about the running time of concrete algorithms, nor do they tell us much about the running time of optimal algorithms. We address problems like this by presenting results based on the exponential time hypothesis (ETH), which is a widely accepted hypothesis concerning the time complexity of 3-SAT. By using this approach, we provide, for instance, almost matching upper and lower bounds onthe time complexity of propositional planning.

  • 163.
    Aghighi, Meysam
    et al.
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Jonsson, Peter
    Linköping University, Department of Computer and Information Science, Software and Systems. Linköping University, The Institute of Technology.
    Oversubscription planning: Complexity and compilability2014In: Proceedings of the Twenty-Eighth AAAI Conference on Artificial Intelligence, AI Access Foundation , 2014, Vol. 3, p. 2221-2227Conference paper (Refereed)
    Abstract [en]

    Many real-world planning problems are oversubscription problems where all goals are not simultaneously achievable and the planner needs to find a feasible subset. We present complexity results for the so-called partial satisfaction and net benefit problems under various restrictions; this extends previous work by van den Briel et al. Our results reveal strong connections between these problems and with classical planning. We also present a method for efficiently compiling oversubscription problems into the ordinary plan existence problem; this can be viewed as a continuation of earlier work by Keyder and Geffner.

  • 164.
    Aghili, Mohammed
    Linköping University, Department of Computer and Information Science.
    Jämförelse av aggregeringswebbdelar i MOSS 20072010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    En typisk funktion på startsidan till många webbportaler är den webbdel som presenterar exempelvis desenaste blogginläggen, nyheterna eller händelserna som har lagts till på webbplatsen. Dessa funktioner ärkända som aggreggeringswebbdelar. Eftersom startsidan är den sida som besöks mest jämfört med alla andrawebbsidor i portalen innebär det i sin tur att denna funktion utnyttjas väldigt ofta.Detta arbete syftar till att finna ett antal olika metoder som kan användas för att uppnå denna funktion ochatt ta reda på hur väl dessa webbdelar presterar.Denna rapport presenterar både de olika metoder som fanns och resultaten på en systematisk testning avdessa. Resultaten av testerna presenteras på ett överskådligt sätt.Slutligen dras slutsatser angående resultaten. Resultaten förespråkar inte en specifik metod, den metod somlämpar sig bäst för varje enskild sammanhang avgörs till största del av andra faktorer såsom frekvens avbesökare eller ändringar på innehållet som metoden söker igenom.

  • 165.
    Agnvall, Beatrix
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Early domestication?: Phenotypic alterations of Red Junglefowl selected for divergent fear of humans2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Domestication is the process through which animals adapt to conditions provided by humans. The domesticated phenotype differs from wild ancestors in a number of traits relating to physiology, morphology and behaviour. One of the most striking differences is the animals’ fear response towards humans, and reduced fear of humans is assumed to have been an early prerequisite for the success of domestication. The early alterations seen in the domesticated phenotype may be traits developed as a correlated selection response due to tameness rather than selected upon one by one.

    This thesis summarizes a project where Red Junglefowl were selected for divergent fear of humans during six generations. In every generation, fear response to human was assessed in a standardized test and, according to fear score, the animals were bred for either high fear of humans (H) or low fear of humans (L). The animals were, above that of the standardized selection test, behaviourally phenotyped in different tests in each generation mainly focusing on fear, exploration and social behaviour. In addition to behaviour, the animals were phenotyped for body weight, egg weight, metabolism, feed intake, plumage condition, blood plasma corticosterone and peripheral serotonin. After culling, vital organs and brains were harvested and weighed.

    In paper I, we demonstrated that the selection trait has a significant genetic heritability and is genetically correlated with other behavioural responses associated with fearfulness and exploration. In paper II, we concluded that animals from the L strain had better plumage condition, higher weight, laid larger eggs and also generated larger offspring. Furthermore, when tested in a social dominance test with a limited resource, they received less and performed more aggression regardless of whether the restricted source was edible or not. In paper III, we revealed that animals from the L strain had higher basal metabolic rate as chicks, gained more weight in relation to feed intake and were bolder in a Novel Object test. Furthermore, the L males had higher plasma levels of peripheral serotonin, but the corticosterone after a restraint stress test did not differ. In paper IV and V, we concluded the project by comparing brain and organ weights as well as behaviour of the parental generation (P0) with the fifth selected generation (S5). The absolute brain weight as well as the weight specific brain weight were larger in the animals selected on H than in the L-animals. The relative weight of telencephalon was significantly higher in H whereas relative weight of cerebellum was significantly lower. Heart, liver, spleen and testes were all relatively heavier in H animals than in L. Interestingly, the behaviours assessed in P0 and S5 seemed to be rather resilient to the selection with only small differences in S5.

    To summarize, the selection on divergent tameness in Red Junglefowl has affected several phenotypic traits associated with the domesticated phenotype. The results of this project indicate that tameness in Red Junglefowl could be an underlying factor driving trait modifications towards the domesticated phenotype.

    List of papers
    1. Heritability and Genetic Correlations of Fear-Related Behaviour in Red Jungelfowl -Possible Implications for Early Domestication
    Open this publication in new window or tab >>Heritability and Genetic Correlations of Fear-Related Behaviour in Red Jungelfowl -Possible Implications for Early Domestication
    2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e35162-Article in journal (Refereed) Published
    Abstract [en]

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-76833 (URN)10.1371/journal.pone.0035162 (DOI)000305336200026 ()
    Available from: 2012-04-20 Created: 2012-04-20 Last updated: 2017-12-07
    2. Red Junglefowl (Gallus gallus) selected for low fear of humans are larger, more dominant and produce larger offspring
    Open this publication in new window or tab >>Red Junglefowl (Gallus gallus) selected for low fear of humans are larger, more dominant and produce larger offspring
    2014 (English)In: animal, ISSN 1751-7311, Vol. 8, no 9, p. 1498-1505Article in journal (Refereed) Published
    Abstract [en]

    Many traits associated with domestication are suggested to have developed as correlated responses to reduced fear of humans. Tameness may have reduced the stress of living in human proximity and improved welfare in captivity. We selected Red Junglefowl (ancestors of all domestic chickens) for four generations on high or low fear towards humans, mimicking an important aspect of the earliest period of domestication, and tested birds from the third and fourth generation in three different social tests. Growth and plumage condition, as well as size of eggs and offspring were also recorded, as indicators of some aspects of welfare. Birds selected for low fear had higher weight, laid larger eggs and generated larger offspring, and had a better plumage condition. In a social dominance test they also performed more aggressive behaviour and received less of the same, regardless of whether the restricted resource was feed or not. Hence, dominance appeared to increase as a consequence of reduced fear of humans. Furthermore, egg size and the weight of the offspring were larger in the less fearful birds, and plumage condition better, which could be interpreted as the less fearful animals being better adapted to the environment in which they were selected.

    Place, publisher, year, edition, pages
    Cambridge University Press, 2014
    Keywords
    Red Junglefowl, domestication, fearfulness, selection, social behaviour
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:liu:diva-109499 (URN)10.1017/S1751731114001426 (DOI)000342219000013 ()24910136 (PubMedID)
    Available from: 2014-08-20 Created: 2014-08-20 Last updated: 2016-11-17
    3. Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus)
    Open this publication in new window or tab >>Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus)
    2015 (English)In: Biology Letters, ISSN 1744-9561, E-ISSN 1744-957X, Vol. 11, no 9, article id 20150509Article in journal (Refereed) Published
    Abstract [en]

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication.

    Place, publisher, year, edition, pages
    ROYAL SOC, 2015
    Keywords
    genetics; domestication; stress
    National Category
    Zoology Evolutionary Biology
    Identifiers
    urn:nbn:se:liu:diva-123162 (URN)10.1098/rsbl.2015.0509 (DOI)000364772300009 ()26382075 (PubMedID)
    Note

    Funding Agencies|research council Formas; ERC [322206]

    Available from: 2015-12-07 Created: 2015-12-04 Last updated: 2019-10-07Bibliographically approved
    4. Effects of Divergent Selection for Fear of Humans on Behaviour in Red Junglefowl
    Open this publication in new window or tab >>Effects of Divergent Selection for Fear of Humans on Behaviour in Red Junglefowl
    2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, p. 1-12Article in journal (Refereed) Published
    Abstract [en]

    Domestication has caused a range of similar phenotypic changes across taxa, relating to physiology, morphology and behaviour. It has been suggested that this recurring domesticated phenotype may be a result of correlated responses to a central trait, namely increased tameness. We selected Red Junglefowl, the ancestors of domesticated chickens, during five generations for reduced fear of humans. This caused a marked and significant response in tameness, and previous studies have found correlated effects on growth, metabolism, reproduction, and some behaviour not directly selected for. Here, we report the results from a series of behavioural tests carried out on the initial parental generation (P0) and the fifth selected generation (S5), focusing on behaviour not functionally related to tameness, in order to study any correlated effects. Birds were tested for fear of humans, social reinstatement tendency, open field behaviour at two different ages, foraging/exploration, response to a simulated aerial predator attack and tonic immobility. In S5, there were no effects of selection on foraging/exploration or tonic immobility, while in the social reinstatement and open field tests there were significant interactions between selection and sex. In the aerial predator test, there were significant main effects of selection, indicating that fear of humans may represent a general wariness towards predators. In conclusion, we found only small correlated effects on behaviours not related to the tameness trait selected for, in spite of them showing high genetic correlations to fear of humans in a previous study on the same population. This suggests that species-specific behaviour is generally resilient to changes during domestication.

    Place, publisher, year, edition, pages
    PLOS, 2016
    National Category
    Developmental Biology Genetics
    Identifiers
    urn:nbn:se:liu:diva-132742 (URN)10.1371/journal.pone.0166075 (DOI)000387909300035 ()27851792 (PubMedID)
    Note

    European Research Council [322206]; FORMAS [221-2007-838]; Vetenskapsradet [621-2008-5437]

    Available from: 2016-11-22 Created: 2016-11-22 Last updated: 2017-11-29Bibliographically approved
  • 166.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Ali, A.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Olby, S.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Red Junglefowl (Gallus gallus) selected for low fear of humans are larger, more dominant and produce larger offspring2014In: animal, ISSN 1751-7311, Vol. 8, no 9, p. 1498-1505Article in journal (Refereed)
    Abstract [en]

    Many traits associated with domestication are suggested to have developed as correlated responses to reduced fear of humans. Tameness may have reduced the stress of living in human proximity and improved welfare in captivity. We selected Red Junglefowl (ancestors of all domestic chickens) for four generations on high or low fear towards humans, mimicking an important aspect of the earliest period of domestication, and tested birds from the third and fourth generation in three different social tests. Growth and plumage condition, as well as size of eggs and offspring were also recorded, as indicators of some aspects of welfare. Birds selected for low fear had higher weight, laid larger eggs and generated larger offspring, and had a better plumage condition. In a social dominance test they also performed more aggressive behaviour and received less of the same, regardless of whether the restricted resource was feed or not. Hence, dominance appeared to increase as a consequence of reduced fear of humans. Furthermore, egg size and the weight of the offspring were larger in the less fearful birds, and plumage condition better, which could be interpreted as the less fearful animals being better adapted to the environment in which they were selected.

  • 167.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Brain size is reduced by selectionfor tameness in Red Junglefowl–correlated effects in vital organs2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 3306Article in journal (Refereed)
    Abstract [en]

    During domestication animals have undergone changes in size of brain and other vital organs. We hypothesize that this could be a correlated effect to increased tameness. Red Junglefowl (ancestors of domestic chickens) were selected for divergent levels of fear of humans for five generations. The parental (P0) and the fifth selected generation (S5) were culled when 48–54 weeks old and the brains were weighed before being divided into telencephalon, cerebellum, mid brain and optic lobes. Each single brain part as well as the liver, spleen, heart and testicles were also weighed. Brains of S5 birds with high fear scores (S5 high) were heavier both in absolute terms and when corrected for body weight. The relative weight of telencephalon (% of brain weight) was significantly higher in S5 high and relative weight of cerebellum was lower. Heart, liver, testes and spleen were all relatively heavier (% of body weight) in S5 high. Hence, selection for tameness has changed the size of the brain and other vital organs in this population and may have driven the domesticated phenotype as a correlated response.

  • 168.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Bélteky, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Katajamaa, Rebecca
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Is evolution of domestication driven by tameness? A selective review with focus on chickens2018In: Applied Animal Behaviour Science, ISSN 0168-1591, E-ISSN 1872-9045, Vol. 205, p. 227-233Article in journal (Refereed)
    Abstract [en]

    Domestication of animals offers unique possibilities to study evolutionary changes caused by similar selection pressures across a range of species. Animals from separate genera tend to develop a suite of phenotypic alterations referred to as "the domesticated phenotype". This involves changes in appearance, including loss of pigmentation, and alterations in body size and proportions. Furthermore, effects on reproduction and behaviour are typical. It is hypothesized that this recurring phenotype may be secondary effects of the increased tameness that is an inevitable first step in the domestication of any species. We first provide a general overview of observations and experiments from different species and then review in more detail a project attempting to recreate the initial domestication of chickens. Starting from an outbred population of Red Junglefowl, ancestors of all modem chickens, divergent lines were selected based on scores in a standardized fear-of-human test applied to all birds at 12 weeks of age. Up to the eighth selected generation, observations have been made on correlated effects of this selection on various phenotypes. The fear score had a significant heritability and was genetically correlated to several other behavioural traits. Furthermore, low-fear birds were larger at hatch, grew faster, laid larger eggs, had a modified metabolism and increased feed efficiency, had modified social behaviour and reduced brain size. Selection affected gene expression and DNA-methylation in the brains, but the genetic and epigenetic effects were not specifically associated with stress pathways. Further research should be focused on unraveling the genetic and epigenetic mechanisms underlying the correlated side-effects of reduced fear of humans.

  • 169.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Effects of Divergent Selection for Fear of Humans on Behaviour in Red Junglefowl2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Domestication has caused a range of similar phenotypic changes across taxa, relating to physiology, morphology and behaviour. It has been suggested that this recurring domesticated phenotype may be a result of correlated responses to a central trait, namely increased tameness. We selected Red Junglefowl, the ancestors of domesticated chickens, during five generations for reduced fear of humans. This caused a marked and significant response in tameness, and previous studies have found correlated effects on growth, metabolism, reproduction, and some behaviour not directly selected for. Here, we report the results from a series of behavioural tests carried out on the initial parental generation (P0) and the fifth selected generation (S5), focusing on behaviour not functionally related to tameness, in order to study any correlated effects. Birds were tested for fear of humans, social reinstatement tendency, open field behaviour at two different ages, foraging/exploration, response to a simulated aerial predator attack and tonic immobility. In S5, there were no effects of selection on foraging/exploration or tonic immobility, while in the social reinstatement and open field tests there were significant interactions between selection and sex. In the aerial predator test, there were significant main effects of selection, indicating that fear of humans may represent a general wariness towards predators. In conclusion, we found only small correlated effects on behaviours not related to the tameness trait selected for, in spite of them showing high genetic correlations to fear of humans in a previous study on the same population. This suggests that species-specific behaviour is generally resilient to changes during domestication.

  • 170.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jöngren, Markus
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Strandberg, Erling
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Heritability and Genetic Correlations of Fear-Related Behaviour in Red Jungelfowl -Possible Implications for Early Domestication2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e35162-Article in journal (Refereed)
    Abstract [en]

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness.

  • 171.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Katajamaa, Rebecca
    Linköping University, Department of Physics, Chemistry and Biology, Biology.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Is domestication driven by reduced fear of humans? Boldness, metabolism and serotonin levels in divergently selected red junglefowl (Gallus gallus)2015In: Biology Letters, ISSN 1744-9561, E-ISSN 1744-957X, Vol. 11, no 9, article id 20150509Article in journal (Refereed)
    Abstract [en]

    Domesticated animals tend to develop a coherent set of phenotypic traits. Tameness could be a central underlying factor driving this, and we therefore selected red junglefowl, ancestors of all domestic chickens, for high or low fear of humans during six generations. We measured basal metabolic rate (BMR), feed efficiency, boldness in a novel object (NO) test, corticosterone reactivity and basal serotonin levels (related to fearfulness) in birds from the fifth and sixth generation of the high- and low-fear lines, respectively (44-48 individuals). Corticosterone response to physical restraint did not differ between selection lines. However, BMR was higher in low-fear birds, as was feed efficiency. Low-fear males had higher plasma levels of serotonin and both low-fear males and females were bolder in an NO test. The results show that many aspects of the domesticated phenotype may have developed as correlated responses to reduced fear of humans, an essential trait for successful domestication.

  • 172.
    Agren, H
    et al.
    Linkoping Univ, Inst Phys & Measurement Technol, S-58183 Linkoping, Sweden.
    Gel'mukhanov, F
    Linkoping Univ, Inst Phys & Measurement Technol, S-58183 Linkoping, Sweden.
    Kramers-Heisenberg and Weisskopf-Wigner descriptions of resonant X-ray Raman scattering2000In: Journal of Electron Spectroscopy and Related Phenomena, ISSN 0368-2048, E-ISSN 1873-2526, Vol. 110, no 1-3, p. 153-178Article in journal (Refereed)
    Abstract [en]

    An overview is presented of the theory of X-ray Raman scattering as originally formulated by Kramers and Heisenberg and by Weisskopf and Wigner. Two particular aspects of the theory are described in some detail, the formation of band profiles and the role of symmetry, These aspects are discussed in connection with recent results for atomic and molecular scatterers obtained in radiative and nonradiative scattering experiments conducted with 2nd and 3rd generation synchrotron radiation sources. (C) 2000 Elsevier Science B.V. All rights reserved.

  • 173.
    Aguilar, Edgar A.
    et al.
    Univ Gdansk, Poland.
    Farkas, Mate
    Univ Gdansk, Poland.
    Martinez, Daniel
    Univ Concepcion, Chile.
    Alvarado, Matias
    Univ Concepcion, Chile.
    Carine, Jaime
    Univ Concepcion, Chile.
    Xavier, Guilherme B
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, Faculty of Science & Engineering. Univ Concepcion, Chile.
    Barra, Johanna F.
    Univ Concepcion, Chile.
    Canas, Gustavo
    Univ Bio Bio, Chile.
    Pawlowski, Marcin
    Univ Gdansk, Poland.
    Lima, Gustavo
    Univ Concepcion, Chile.
    Certifying an Irreducible 1024-Dimensional Photonic State Using Refined Dimension Witnesses2018In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 120, no 23, article id 230503Article in journal (Refereed)
    Abstract [en]

    We report on a new class of dimension witnesses, based on quantum random access codes, which are a function of the recorded statistics and that have different bounds for all possible decompositions of a high-dimensional physical system. Thus, it certifies the dimension of the system and has the new distinct feature of identifying whether the high-dimensional system is decomposable in terms of lower dimensional subsystems. To demonstrate the practicability of this technique, we used it to experimentally certify the generation of an irreducible 1024-dimensional photonic quantum state. Therefore, certifying that the state is not multipartite or encoded using noncoupled different degrees of freedom of a single photon. Our protocol should find applications in a broad class of modern quantum information experiments addressing the generation of high-dimensional quantum systems, where quantum tomography may become intractable.

  • 174. Aguilar, V
    et al.
    Staver, C
    Milberg, Per
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Ecology .
    Weed vegetation response to chemical and manual selective ground cover management in a shaded coffee plantation2003In: Weed research (Print), ISSN 0043-1737, E-ISSN 1365-3180, Vol. 43, p. 68-75Article in journal (Refereed)
  • 175.
    Aguilar-Calvo, Patricia
    et al.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA.
    Xiao, Xiangzhu
    Case Western Reserve University, OH 44116 USA.
    Bett, Cyrus
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; US FDA, MD USA.
    Erana, Hasier
    CIC bioGUNE, Spain.
    Soldau, Katrin
    University of Calif San Diego, CA 92093 USA.
    Castilla, Joaquin
    University of Calif San Diego, CA 92093 USA; CIC bioGUNE, Spain; Ikerbasque, Spain.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Surewicz, Witold K.
    Case Western Reserve University, OH 44116 USA.
    Sigurdson, Christina J.
    University of Calif San Diego, CA 92093 USA; University of Calif San Diego, CA 92093 USA; University of Calif Davis, CA 95616 USA.
    Post-translational modifications in PrP expand the conformational diversity of prions in vivo2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43295Article in journal (Refereed)
    Abstract [en]

    Misfolded prion protein aggregates (PrPSc) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-beta, tau, alpha-synuclein, and serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)anchorless prion protein, PrPC, together with hydrogen-deuterium exchange coupled with mass spectrometry (HXMS) and a battery of biochemical and biophysical tools to investigate how posttranslational modifications impact the aggregated prion protein properties and disease phenotype. Four GPI-anchorless prion strains caused a nearly identical clinical and pathological disease phenotype, yet maintained their structural diversity in the anchorless state. HXMS studies revealed that GPIanchorless PrPSc is characterized by substantially higher protection against hydrogen/deuterium exchange in the C-terminal region near the N-glycan sites, suggesting this region had become more ordered in the anchorless state. For one strain, passage of GPI-anchorless prions into wild type mice led to the emergence of a novel strain with a unique biochemical and phenotypic signature. For the new strain, histidine hydrogen-deuterium mass spectrometry revealed altered packing arrangements of beta-sheets that encompass residues 139 and 186 of PrPSc. These findings show how variation in posttranslational modifications may explain the emergence of new protein conformations in vivo and also provide a basis for understanding how the misfolded protein structure impacts the disease.

  • 176.
    Agwa, Mohamed
    et al.
    Department of Mechanical Design and Production Engineering, Faculty of Engineering, Zagazig Egypt.
    Andersson, Lars-Erik
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, The Institute of Technology.
    Pinto da Costa, Ant´onio
    Departamento de Engenharia Civil, Instituto Superior T´ecnico and ICIST, Universidade T´ecnica de Lisboa, Avenida Rovisco Pais, 1049 􀀀 001 Lisboa, Portugal.
    Critical bounds for discrete frictional incremental problems, rateproblems and wedging problems2012Conference paper (Other academic)
    Abstract [en]

    Summary. Questions of existence and uniqueness for discrete frictional quasi-static incremental problems, rate problems and wedging problems are discussed. Various methods to compute critical bounds for the coefficient of friction which guarantee existence and uniqueness are described, as well as the sharpness of the bounds and their interdependence.

  • 177.
    Ahl, Ing-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Protein Engineering of Extracellular Superoxide Dismutase: Characterization of Binding to Heparin and Cellular Surfaces2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Accumulating evidence indicates that oxygen free radicals are involved in many diseases and pathological conditions, such as aging, inflammation, reperfusion damage of ischemic tissue and various cardiovascular diseases. Extracellular superoxide dismutase (ECSOD) thus plays a major role in the maintenance of cells by providing protection against these toxic substances in the extracellular space. Various animal studies have shown that ECSOD has the ability to protect against many of these disorders, and interest has therefore evolved in the potential therapeutic use of the enzyme.

    However, despite strenuous efforts, large-scale production of the enzyme has not been achieved. To overcome this problem, a mimic of the enzyme, PseudoECSOD, has previously

    been constructed. This chimera is easy to produce in large amounts and has all the structural, enzymatic and heparin-binding characteristics of ECSOD, making it a potential substitute for ECSOD in therapeutic situations. However, the copper content of PseudoECSOD has been shown to be rather low, and since the copper ion is very important for the catalytic function of the enzyme, a production system that utilizes a copper chaperone for proper insertion of copper into the active site of the enzyme was constructed. The results show that the copper content of PseudoECSOD produced by this system is close to 100 %.

    In order to use PseudoECSOD therapeutically, further investigations of its binding capability and protective properties are needed. Therefore, the binding of ECSOD and PseudoECSOD to heparin was investigated using isothermal titration calorimetry. The results show that although some purely ionic interactions are important for the binding between ECSOD and heparin, there is also a substantial contribution from non-ionic interactions. The investigation also showed that the C-terminal domain is the only part of ECSOD that contributes to productive binding, and that the binding of PseudoECSOD and ECSOD to heparin is similar.

    In addition, analysis of mutant proteins strongly indicated that the amino acids R210, K211 and R214 are important for optimal binding of ECSOD to heparin, accounting for about 30 % of the total binding energy. The structural placement of these amino acids in an α-helix also confirms the hypothesis postulated by Margalit et al., that a common structural motif for heparin-binding proteins may be two positively charged amino acids at a distance of approximately 20 Å in the 3D-structure, facing opposite directions of a α-helix. The importance of these residues was also confirmed by analysis of a phage display library of the C-terminal domain of ECSOD.

    The binding of PseudoECSOD to heparan sulfate on cell surfaces of two different cell types, HepG2 and endothelial cells, was also investigated. The results clearly show that PseudoECSOD binds to these cells in a very similar manner to ECSOD. To investigate the protective properties of PseudoECSOD against ischemia-reperfusion injuries, an isolated rabbit heart model was used. The results indicate that the enzyme has a protective effect. However, more experiments using the rabbit heart and other animal models are needed to identify the optimal dose for protective purposes. The protective properties of PseudoECSOD in human tissue should also be thoroughly investigated.

    In summary, the findings in these studies, together with earlier results showing the close resemblance of PseudoECSOD to ECSOD in structural, enzymatic and heparin-binding properties, further support the proposition that PseudoECSOD may be a good substitute for ECSOD to use in therapeutic interventions.

    List of papers
    1. Thermodynamic Characterization of the Interaction between the C-Terminal Domain of Extracellular Superoxide Dismutase and Heparin by Isothermal Titration Calorimetry
    Open this publication in new window or tab >>Thermodynamic Characterization of the Interaction between the C-Terminal Domain of Extracellular Superoxide Dismutase and Heparin by Isothermal Titration Calorimetry
    2009 (English)In: BIOCHEMISTRY, ISSN 0006-2960, Vol. 48, no 41, p. 9932-9940Article in journal (Refereed) Published
    Abstract [en]

    Extracellular superoxide dismutase (ECSOD) interacts with heparin through its C-terminal domain. In this study we used isothermal titration calorimetry (ITC) to get detailed thermodynamic information about the interaction. We have shown that the interaction between ECSOD and intestinal mucosal heparin (M-w 6000-30000 Da) is exothermic and driven by enthalpy at physiological salt concentration. However, the contribution from entropy is favorable for binding or small isolated heparin fragments. By studying different size-defined heparin fragments, we also concluded that it hexasaccharide moiety is sufficient for strong binding to ECSOD. The binding involves proton transfer from the buffer to the ECSOD-heparin complex, and the results indicate that the number of ionic interactions made between ECSOD and heparin upon binding varies from three to five for heparin and an octasaccharide fragment, respectively. Surprisingly and despite the many charges found oil both the protein and the polysaccharide, our results indicate that the nonionic contribution to the binding is large. From the temperature dependence we have calculated the constant pressure heat capacity change (Delta C-p) of the interaction to -644 J K-1 mol(-1) and -306 J K-1 mol(-1) for heparin and all octasaccharide, respectively

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-51398 (URN)10.1021/bi900981k (DOI)
    Available from: 2009-10-30 Created: 2009-10-30 Last updated: 2016-05-04
    2. Analysis of Effects of Mutations in the C-Terminal Domain of Extracellular Superoxide Dismutase by Isothermal Titration Calorimetry and Phage Display
    Open this publication in new window or tab >>Analysis of Effects of Mutations in the C-Terminal Domain of Extracellular Superoxide Dismutase by Isothermal Titration Calorimetry and Phage Display
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    n/a

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-52450 (URN)
    Available from: 2009-12-21 Created: 2009-12-21 Last updated: 2016-05-04
    3. Coexpression of yeast copper chaperone (yCCS) and CuZn-superoxide dismutases in Escherichia coli yields protein with high copper contents
    Open this publication in new window or tab >>Coexpression of yeast copper chaperone (yCCS) and CuZn-superoxide dismutases in Escherichia coli yields protein with high copper contents
    2004 (English)In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 37, no 2, p. 311-319Article in journal (Refereed) Published
    Abstract [en]

    To fully understand the function of the Cu- and Zn-containing superoxide dismutases in normal and disordered cells, it is essential to study protein variants with full metal contents. We describe the use of an Escherichia coli-based expression system for the overproduction of human intracellular wild type CuZn-superoxide dismutase (SOD), the CuZnSOD variant F50E/G51E (monomeric), two amyotrophic lateral sclerosis-related mutant CuZnSOD variants (D90A and G93A), and PseudoEC-SOD, all with high Cu contents. This system is based on coexpression of the SOD variants with the yeast copper chaperone yCCS during growth in a medium supplemented with Cu2+ and Zn2+. The recombinant SOD enzymes were all found in the cytosol and represented 30-50% of the total bacterial protein. The enzymes were purified to homogeneity and active enzymes were obtained in high yield. The resulting proteins were characterized through immunochemical reactivity and specific activity analyses, in conjunction with mass-, photo-, and atomic absorption-spectroscopy. © 2004 Elsevier Inc. All rights reserved.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-22221 (URN)10.1016/j.pep.2004.06.006 (DOI)1379 (Local ID)1379 (Archive number)1379 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13
    4. Cell Association and Protective Effects of PseudoECSOD: a progress report
    Open this publication in new window or tab >>Cell Association and Protective Effects of PseudoECSOD: a progress report
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    n/a

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-52451 (URN)
    Available from: 2009-12-21 Created: 2009-12-21 Last updated: 2016-05-04
  • 178.
    Ahl, Ing-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Jonsson, Bengt-Harald
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology . Linköping University, The Institute of Technology.
    Tibell, Lena A. E.
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Analysis of Effects of Mutations in the C-Terminal Domain of Extracellular Superoxide Dismutase by Isothermal Titration Calorimetry and Phage DisplayManuscript (preprint) (Other academic)
    Abstract [en]

    n/a

  • 179.
    Ahl, Ing-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Nelson, Sally K
    Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, CO-800 45, Aurora, USA.
    Enström, Camilla
    Department of Medical Sciences, Uppsala University, SE-751 85, Uppsala, Sweden.
    Ericson, Ann-Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Tibell, Lena A. E.
    Linköping University, Department of Science and Technology, Visual Information Technology and Applications (VITA). Linköping University, The Institute of Technology.
    Cell Association and Protective Effects of PseudoECSOD: a progress reportManuscript (preprint) (Other academic)
    Abstract [en]

    n/a

  • 180.
    Ahl, Linda
    Linköping University, Department of Computer and Information Science.
    Hur fungerar datorer?: En fallstudie av att utveckla pedagogisk multimedia för ett datorhistoriskt museum.2004Independent thesis Basic level (professional degree)Student thesis
    Abstract [sv]

    Få människor vet hur datorer fungerar, vilka komponenter de är uppbyggda av och hur dessa samverkar. I detta examensarbete har en prototyp till en multimediepresentation utvecklats. Presentationen kommer att placeras på ett datorhistoriskt museum och dess syfte kommer där att vara att hjälpa människor förstå hur datorer fungerar. Prototypen är baserad på bilder och enklare animationer som förklarar samverkan och funktion hos de olika datorkomponenterna, bland annat genom att visa scenarier som många människor troligtvis känner igen från sin vardag.

    Målet med arbetet har varit att inskaffa kunskap kring hur multimedia kan användas för att illustrera tekniska processer, samt kunskap kring hur multimediepresentationer skall utveck-las. Därför har en systemutvecklingsmetod tagits fram som är anpassad till denna typ av system och som använts vid utvecklingen av prototypen.

    Systemutvecklingsmetoden är av iterativ modell, eftersom det visat sig att ett iterativt arbetssätt är att föredra framför ett linjärt vid multimedieutveckling. Detta beror på att det i denna typ av arbete där det till en början oftast är oklart vilka krav och önskemål som finns på slutprodukten är svårt att gå enkelriktat genom utvecklingsprocessen, d v s att göra ett steg helt färdigt innan nästa påbörjas.

    När det gäller multimedia är en slutsats att det med fördel kan användas för att visa och förklara tekniska förlopp och att det verkar vara ett användbart hjälpmedel inom utbildning och museiverksamhet.

  • 181.
    Ahlberg, Gustav
    Linköping University, Department of Computer and Information Science, Database and information techniques. Linköping University, The Institute of Technology.
    Generating web applications containing XSS and CSRF vulnerabilities2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Most of the people in the industrial world are using several web applications every day. Many of those web applications contain vulnerabilities that can allow attackers to steal sensitive data from the web application's users. One way to detect these vulnerabilities is to have a penetration tester examine the web application. A common way to train penetration testers to find vulnerabilities is to challenge them with realistic web applications that contain vulnerabilities. The penetration tester's assignment is to try to locate and exploit the vulnerabilities in the web application. Training on the same web application twice will not provide any new challenges to the penetration tester, because the penetration tester already knows how to exploit all the vulnerabilities in the web application. Therefore, a vast number of web applications and variants of web applications are needed to train on.

    This thesis describes a tool designed and developed to automatically generate vulnerable web applications. First a web application is prepared, so that the tool can generate a vulnerable version of the web application. The tool injects Cross Site Scripting (XSS) and Cross Site Request Forgery (CSRF) vulnerabilities in prepared web applications. Different variations of the same vulnerability can also be injected, so that different methods are needed to exploit the vulnerability depending on the variation. A purpose of the tool is that it should generate web applications which shall be used to train penetration testers, and some of the vulnerabilities the tool can inject, cannot be detected by current free web application vulnerability scanners, and would thus need to be detected by a penetration tester.

    To inject the vulnerabilities, the tool uses abstract syntax trees and taint analysis to detect where vulnerabilities can be injected in the prepared web applications.

    Tests confirm that web application vulnerability scanners cannot find all the vulnerabilities on the web applications which have been generated by the tool.

  • 182.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering.
    Arsic, Dejan
    Munich University of Technology, Germany.
    Ganchev, Todor
    University of Patras, Greece.
    Linderhed, Anna
    FOI Swedish Defence Research Agency.
    Menezes, Paolo
    University of Coimbra, Portugal.
    Ntalampiras, Stavros
    University of Patras, Greece.
    Olma, Tadeusz
    MARAC S.A., Greece.
    Potamitis, Ilyas
    Technological Educational Institute of Crete, Greece.
    Ros, Julien
    Probayes SAS, France.
    Prometheus: Prediction and interpretation of human behaviour based on probabilistic structures and heterogeneous sensors2008Conference paper (Refereed)
    Abstract [en]

    The on-going EU funded project Prometheus (FP7-214901) aims at establishing a general framework which links fundamental sensing tasks to automated cognition processes enabling interpretation and short-term prediction of individual and collective human behaviours in unrestricted environments as well as complex human interactions. To achieve the aforementioned goals, the Prometheus consortium works on the following core scientific and technological objectives:

    1. sensor modeling and information fusion from multiple, heterogeneous perceptual modalities;

    2. modeling, localization, and tracking of multiple people;

    3. modeling, recognition, and short-term prediction of continuous complex human behavior.

  • 183.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering. Termisk Systemteknik AB, Linköping, Sweden.
    Berg, Amanda
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering. Termisk Systemteknik AB, Linköping, Sweden.
    Evaluating Template Rescaling in Short-Term Single-Object Tracking2015Conference paper (Refereed)
    Abstract [en]

    In recent years, short-term single-object tracking has emerged has a popular research topic, as it constitutes the core of more general tracking systems. Many such tracking methods are based on matching a part of the image with a template that is learnt online and represented by, for example, a correlation filter or a distribution field. In order for such a tracker to be able to not only find the position, but also the scale, of the tracked object in the next frame, some kind of scale estimation step is needed. This step is sometimes separate from the position estimation step, but is nevertheless jointly evaluated in de facto benchmarks. However, for practical as well as scientific reasons, the scale estimation step should be evaluated separately – for example,theremightincertainsituationsbeothermethodsmore suitable for the task. In this paper, we describe an evaluation method for scale estimation in template-based short-term single-object tracking, and evaluate two state-of-the-art tracking methods where estimation of scale and position are separable.

  • 184.
    Ahlberg, Jörgen
    et al.
    Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Dornaika, Fadi
    Linköping University, Department of Electrical Engineering, Image Coding. Linköping University, The Institute of Technology.
    Efficient active appearance model for real-time head and facial feature tracking2003In: Analysis and Modeling of Faces and Gestures, 2003. AMFG 2003. IEEE International Workshop on, IEEE conference proceedings, 2003, p. 173-180Conference paper (Refereed)
    Abstract [en]

    We address the 3D tracking of pose and animation of the human face in monocular image sequences using active appearance models. The classical appearance-based tracking suffers from two disadvantages: (i) the estimated out-of-plane motions are not very accurate, and (ii) the convergence of the optimization process to desired minima is not guaranteed. We aim at designing an efficient active appearance model, which is able to cope with the above disadvantages by retaining the strengths of feature-based and featureless tracking methodologies. For each frame, the adaptation is split into two consecutive stages. In the first stage, the 3D head pose is recovered using robust statistics and a measure of consistency with a statistical model of a face texture. In the second stage, the local motion associated with some facial features is recovered using the concept of the active appearance model search. Tracking experiments and method comparison demonstrate the robustness and out-performance of the developed framework.

  • 185.
    Ahlberg, Jörgen
    et al.
    Dept. of IR Systems, Div. of Sensor Technology, Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Dornaika, Fadi
    Computer Vision Center, Universitat Autonoma de Barcelona, Bellaterra, Spain.
    Parametric Face Modeling and Tracking2005In: Handbook of Face Recognition / [ed] Stan Z. Li, Anil K. Jain, Springer-Verlag New York, 2005, p. 65-87Chapter in book (Other academic)
  • 186.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Image Coding. Linköping University, The Institute of Technology. Div. of Sensor Technology, Swedish Defence Research Agency, Linköping, Sweden.
    Forchheimer, Robert
    Linköping University, Department of Electrical Engineering, Image Coding. Linköping University, The Institute of Technology.
    Face tracking for model-based coding and face animation2003In: International journal of imaging systems and technology (Print), ISSN 0899-9457, E-ISSN 1098-1098, Vol. 13, no 1, p. 8-22Article in journal (Refereed)
    Abstract [en]

    We present a face and facial feature tracking system able to extract animation parameters describing the motion and articulation of a human face in real-time on consumer hardware. The system is based on a statistical model of face appearance and a search algorithm for adapting the model to an image. Speed and robustness is discussed, and the system evaluated in terms of accuracy.

  • 187.
    Ahlberg, Jörgen
    et al.
    Div. of Sensor Technology, Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Klasén, Lena
    Div. of Sensor Technology, Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Surveillance Systems for Urban Crisis Management2005Conference paper (Other academic)
    Abstract [en]

    We present a concept for combing 3D models and multiple heterogeneous sensors into a surveillance system enabling superior situation awareness. The concept has many military as well as civilian applications. A key issue is the use of a 3D environment model of the area to be surveyed, typically an urban area. In addition to the 3D model, the area of interest is monitored over time using multiple heterogeneous sensors, such as optical, acoustic, and/or seismic sensors. Data and analysis results from the sensors are visualized in the 3D model, thus putting them in a common reference frame and making their spatial and temporal relations obvious. The result is highlighted by an example where data from different sensor systems is integrated in a 3D model of a Swedish urban area.

  • 188.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, The Institute of Technology.
    Li, Haibo
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, The Institute of Technology.
    Representing and Compressing MPEG-4 Facial Animation Parameters using Facial Action Basis Functions1999In: IEEE Transactions on Circuits and Systems, ISSN 0098-4094, E-ISSN 1558-1276, Vol. 9, no 3, p. 405-410Article in journal (Refereed)
    Abstract [en]

    In model-based, or semantic, coding, parameters describing the nonrigid motion of objects, e.g., the mimics of a face, are of crucial interest. The facial animation parameters (FAPs) specified in MPEG-4 compose a very rich set of such parameters, allowing a wide range of facial motion. However, the FAPs are typically correlated and also constrained in their motion due to the physiology of the human face. We seek here to utilize this spatial correlation to achieve efficient compression. As it does not introduce any interframe delay, the method is suitable for interactive applications, e.g., videophone and interactive video, where low delay is a vital issue.

  • 189.
    Ahlberg, Jörgen
    et al.
    Termisk Systemteknik AB Linköping, Sweden; Visage Technologies AB Linköping, Sweden.
    Markuš, Nenad
    Human-Oriented Technologies Laboratory, Faculty of Electrical Engineering and Computing, University of Zagreb, Croatia.
    Berg, Amanda
    Termisk Systemteknik AB, Linköping, Sweden.
    Multi-person fever screening using a thermal and a visual camera2015Conference paper (Other academic)
    Abstract [en]

    We propose a system to automatically measure the body temperature of persons as they pass. In contrast to exisitng systems, the persons do not need to stop and look into a camera one-by-one. Instead, their eye corners are automatically detected and the temperatures therein measured using a thermal camera. The system handles multiple simultaneous persons and can thus be used where a flow of people pass, such as at airport gates.

  • 190.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering. Glana Sensors AB, Sweden.
    Renhorn, Ingmar
    Glana Sensors AB, Sweden.
    Chevalier, Tomas
    Scienvisic AB, Sweden.
    Rydell, Joakim
    FOI, Swedish Defence Research Agency, Sweden.
    Bergström, David
    FOI, Swedish Defence Research Agency, Sweden.
    Three-dimensional hyperspectral imaging technique2017In: ALGORITHMS AND TECHNOLOGIES FOR MULTISPECTRAL, HYPERSPECTRAL, AND ULTRASPECTRAL IMAGERY XXIII / [ed] Miguel Velez-Reyes; David W. Messinger, SPIE - International Society for Optical Engineering, 2017, Vol. 10198, article id 1019805Conference paper (Refereed)
    Abstract [en]

    Hyperspectral remote sensing based on unmanned airborne vehicles is a field increasing in importance. The combined functionality of simultaneous hyperspectral and geometric modeling is less developed. A configuration has been developed that enables the reconstruction of the hyperspectral three-dimensional (3D) environment. The hyperspectral camera is based on a linear variable filter and a high frame rate, high resolution camera enabling point-to-point matching and 3D reconstruction. This allows the information to be combined into a single and complete 3D hyperspectral model. In this paper, we describe the camera and illustrate capabilities and difficulties through real-world experiments.

  • 191.
    Ahlberg, Jörgen
    et al.
    Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Renhorn, Ingmar G.
    Swedish Defence Research Agency (FOI), Linköping, Sweden.
    Wadströmer, Niclas
    Swedish Defence Research Agency (FOI), Linköping, Sweden.
    An information measure of sensor performance and its relation to the ROC curve2010In: Proc. SPIE 7695, Algorithms and Technologies for Multispectral, Hyperspectral, and Ultraspectral Imagery XVI / [ed] Sylvia S. Shen; Paul E. Lewis, SPIE - International Society for Optical Engineering, 2010, p. Art.nr. 7695-72-Conference paper (Refereed)
    Abstract [en]

    The ROC curve is the most frequently used performance measure for detection methods and the underlying sensor configuration. Common problems are that the ROC curve does not present a single number that can be compared to other systems and that no discrimination between sensor performance and algorithm performance is done. To address the first problem, a number of measures are used in practice, like detection rate at a specific false alarm rate, or area-under-curve. For the second problem, we proposed in a previous paper1 an information theoretic method for measuring sensor performance. We now relate the method to the ROC curve, show that it is equivalent to selecting a certain point on the ROC curve, and that this point is easily determined. Our scope is hyperspectral data, studying discrimination between single pixels.

  • 192.
    Ahlberg, Jörgen
    et al.
    Linköping University, Department of Electrical Engineering, Computer Vision. Linköping University, Faculty of Science & Engineering.
    Åstrom, Anders
    Swedish Natl Forens Ctr NFC, Linkoping, Sweden.
    Forchheimer, Robert
    Linköping University, Department of Electrical Engineering, Information Coding. Linköping University, Faculty of Science & Engineering.
    Simultaneous sensing, readout, and classification on an intensity-ranking image sensor2018In: International journal of circuit theory and applications, ISSN 0098-9886, E-ISSN 1097-007X, Vol. 46, no 9, p. 1606-1619Article in journal (Refereed)
    Abstract [en]

    We combine the near-sensor image processing concept with address-event representation leading to an intensity-ranking image sensor (IRIS) and show the benefits of using this type of sensor for image classification. The functionality of IRIS is to output pixel coordinates (X and Y values) continuously as each pixel has collected a certain number of photons. Thus, the pixel outputs will be automatically intensity ranked. By keeping track of the timing of these events, it is possible to record the full dynamic range of the image. However, in many cases, this is not necessary-the intensity ranking in itself gives the needed information for the task at hand. This paper describes techniques for classification and proposes a particular variant (groves) that fits the IRIS architecture well as it can work on the intensity rankings only. Simulation results using the CIFAR-10 dataset compare the results of the proposed method with the more conventional ferns technique. It is concluded that the simultaneous sensing and classification obtainable with the IRIS sensor yields both fast (shorter than full exposure time) and processing-efficient classification.

  • 193.
    Ahlgren, Anna
    Linköping University, Department of Computer and Information Science.
    MobiAnn: androidapplikationen som underlättar lärares arbetsuppgifter2011Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [sv]

    Examensarbetet diskuterar behovet av ett stödsystem för lärare vid undervisning och tar upp olika aspekter utifrån lärarnas arbetssituation. Som en del av denna diskussion finns en implementation av ett system i form av en Androidapplikation.

    Applikationen ger lärarna möjlighet till ett stödsystem med olika användningsområde som närvarokontroll, anmärkningsmöjligheter om förseningar och stök under lektionstid, verktyg för att anteckna elevarbete och motivera betyg direkt på plats.

    Stor vikt har lagts på att göra applikationen lättanvänd och användarvänlig och därför har tester med användare varit en stor del under utvecklingen.

  • 194.
    Ahlinder, Jon
    et al.
    Totalförsvarets Forskningsinstitut, FOI, Stockholm, Sweden.
    Nordgaard, Anders
    Swedish National Forensic Centre (NFC), Linköping, Sweden.
    Wiklund Lindström, Susanne
    Totalförsvarets Forskningsinstitut, FOI, Stockholm, Sweden.
    Chemometrics comes to court: evidence evaluation of chem–bio threat agent attacks2015In: Journal of Chemometrics, ISSN 0886-9383, E-ISSN 1099-128X, Vol. 29, no 5, p. 267-276Article in journal (Refereed)
    Abstract [en]

    Forensic statistics is a well-established scientific field whose purpose is to statistically analyze evidence in order to support legal decisions. It traditionally relies on methods that assume small numbers of independent variables and multiple samples. Unfortunately, such methods are less applicable when dealing with highly correlated multivariate data sets such as those generated by emerging high throughput analytical technologies. Chemometrics is a field that has a wealth of methods for the analysis of such complex data sets, so it would be desirable to combine the two fields in order to identify best practices for forensic statistics in the future. This paper provides a brief introduction to forensic statistics and describes how chemometrics could be integrated with its established methods to improve the evaluation of evidence in court.

    The paper describes how statistics and chemometrics can be integrated, by analyzing a previous know forensic data set composed of bacterial communities from fingerprints. The presented strategy can be applied in cases where chemical and biological threat agents have been illegally disposed.

  • 195.
    Ahlman, Gustav
    Linköping University, Department of Electrical Engineering, Computer Vision.
    Improved Temporal Resolution Using Parallel Imaging in Radial-Cartesian 3D functional MRI2011Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    MRI (Magnetic Resonance Imaging) is a medical imaging method that uses magnetic fields in order to retrieve images of the human body. This thesis revolves around a novel acquisition method of 3D fMRI (functional Magnetic Resonance Imaging) called PRESTO-CAN that uses a radial pattern in order to sample the (kx,kz)-plane of k-space (the frequency domain), and a Cartesian sample pattern in the ky-direction. The radial sample pattern allows for a denser sampling of the central parts of k-space, which contain the most basic frequency information about the structure of the recorded object. This allows for higher temporal resolution to be achieved compared with other sampling methods since a fewer amount of total samples are needed in order to retrieve enough information about how the object has changed over time. Since fMRI is mainly used for monitoring blood flow in the brain, increased temporal resolution means that we can be able to track fast changes in brain activity more efficiently.The temporal resolution can be further improved by reducing the time needed for scanning, which in turn can be achieved by applying parallel imaging. One such parallel imaging method is SENSE (SENSitivity Encoding). The scan time is reduced by decreasing the sampling density, which causes aliasing in the recorded images. The aliasing is removed by the SENSE method by utilizing the extra information provided by the fact that multiple receiver coils with differing sensitivities are used during the acquisition. By measuring the sensitivities of the respective receiver coils and solving an equation system with the aliased images, it is possible to calculate how they would have looked like without aliasing.In this master thesis, SENSE has been successfully implemented in PRESTO-CAN. By using normalized convolution in order to refine the sensitivity maps of the receiver coils, images with satisfying quality was able to be reconstructed when reducing the k-space sample rate by a factor of 2, and images of relatively good quality also when the sample rate was reduced by a factor of 4. In this way, this thesis has been able to contribute to the improvement of the temporal resolution of the PRESTO-CAN method.

  • 196.
    Ahlner, Alexandra
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Improved Methods for Characterization of Protein Dynamics by NMR spectroscopy and Studies of the EphB2 Kinase Domain2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Proteins are essential for all known forms of life and in many lethal diseases protein failure is the cause of the disease. To understand proteins and the processes they are involved in, it is valuable to know their structures as well as their dynamics and interactions. The structures may not be directly inspected because proteins are too small to be visible in a light microscope, which is why indirect methods such as nuclear magnetic resonance (NMR) spectroscopy have to be utilized. This method provides atomic information about the protein and, in contrast to other methods with similar resolution, the measurements are performed in solution resulting in more physiological conditions, enabling analysis of dynamics. Important dynamical processes are the ones on the millisecond timeframe, which may contribute to interactions of proteins and their catalysis of chemical reactions, both of significant value for the function of the proteins.

    To better understand proteins, not only do we need to study them, but also develop the methods we are using. This thesis presents four papers about improved NMR techniques as well as a fifth where the kinase domain of ephrinB receptor 2 (EphB2) has been studied regarding the importance of millisecond dynamics and interactions for the activation process. The first paper presents the software COMPASS, which combines statistics and the calculation power of a computer with the flexibility and experience of the user to facilitate and speed up the process of assigning NMR signals to the atoms in the protein. The computer program PINT has been developed for easier and faster evaluation of NMR experiments, such as those that evaluate protein dynamics. It is especially helpful for NMR signals that are difficult to distinguish, so called overlapped peaks, and the soft- ware also converts the detected signals to the indirectly measured physical quantities, such as relaxation rate constants, principal for dynamics. Next are two new versions of the Carr-Purcell-Maiboom-Gill (CPMG) dispersion pulse sequences, designed to measure millisecond dynamics in a way so that the signals are more separated than in standard experiments, to reduce problems with overlaps. To speed up the collection time of the data set, a subset is collected and the entire data set is then reconstructed, by multi-dimensional decomposition co-processing. Described in the thesis is also a way to produce suitably labeled proteins, to detect millisecond dynamics at Cα positions in proteins, using the CPMG dispersion relaxation experiment at lower protein concentrations. Lastly, the kinase domain of EphB2 is shown to be more dynamic on the millisecond time scale as well as more prone to interact with itself in the active form than in the inactive one. This is important for the receptor function of the protein, when and how it mediates signals.

    To conclude, this work has extended the possibilities to study protein dynamics by NMR spectroscopy and contributed to increased understanding of the activation process of EphB2 and its signaling mechanism. 

    List of papers
    1. Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches
    Open this publication in new window or tab >>Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches
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    2015 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 1, p. e1004022-Article in journal (Refereed) Published
    Abstract [en]

    The process of resonance assignment is fundamental to most NMR studies of protein structure and dynamics. Unfortunately, the manual assignment of residues is tedious and time-consuming, and can represent a significant bottleneck for further characterization. Furthermore, while automated approaches have been developed, they are often limited in their accuracy, particularly for larger proteins. Here, we address this by introducing the software COMPASS, which, by combining automated resonance assignment with manual intervention, is able to achieve accuracy approaching that from manual assignments at greatly accelerated speeds. Moreover, by including the option to compensate for isotope shift effects in deuterated proteins, COMPASS is far more accurate for larger proteins than existing automated methods. COMPASS is an open-source project licensed under GNU General Public License and is available for download from http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en. Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.

    Place, publisher, year, edition, pages
    Public Library of Science, 2015
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-115010 (URN)10.1371/journal.pcbi.1004022 (DOI)000349309400013 ()25569628 (PubMedID)
    Note

    Funding Agencies|Swedish Research Council [Dnr. 2012-5136]

    Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-12-04
    2. PINT: a software for integration of peak volumes and extraction of relaxation rates
    Open this publication in new window or tab >>PINT: a software for integration of peak volumes and extraction of relaxation rates
    2013 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 56, no 3, p. 191-202Article in journal (Refereed) Published
    Abstract [en]

    We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2013
    Keywords
    Peak integration, Overlapped peaks, Relaxation rates, Protein dynamics
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-95951 (URN)10.1007/s10858-013-9737-7 (DOI)000321544600001 ()
    Note

    Funding Agencies|Swedish Research Council||

    Available from: 2013-08-19 Created: 2013-08-12 Last updated: 2018-01-11Bibliographically approved
    3. Measurement of Protein Backbone 13CO and 15N Relaxation Dispersion at High Resolution
    Open this publication in new window or tab >>Measurement of Protein Backbone 13CO and 15N Relaxation Dispersion at High Resolution
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Three-dimensional pulse sequences for the measurement of Carr-Purcell-Meiboom-Gill relaxation dispersions and new methods for co-processing non-uniformly sampled data are presented. The new methodology was validated for the disordered protein IgA and for an SH3 domain from Abp1p in exchange between its free form and bound to a peptide from the protein Ark1p. We show that the results are similar to ones obtained using traditional experiments and that accurate excited state chemical shifts can be determined. Furthermore, we show that jackknife analysis of down sampled spectra yields robust estimates of peak intensities errors, eliminating the need for recording duplicate data points. The methodology should be useful for characterization of millisecond dynamics in small to medium-sized proteins with poorly dispersed spectra.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-117070 (URN)
    Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2015-04-15Bibliographically approved
    4. Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity
    Open this publication in new window or tab >>Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity
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    2015 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 62, no 3, p. 341-351Article in journal (Refereed) Published
    Abstract [en]

    A selective isotope labeling scheme based on the utilization of [2-13C]-glycerol as the carbon source during protein overexpression has been evaluated for the measurement of excited state 13Cα chemical shifts using Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion (RD) experiments. As expected, the fractional incorporation of label at the Cα positions is increased two-fold relative to labeling schemes based on [2-13C]-glucose, effectively doubling the sensitivity of NMR experiments. Applications to a binding reaction involving an SH3 domain from the protein Abp1p and a peptide from the protein Ark1p establish that accurate excited state 13Cα chemical shifts can be obtained from RD experiments, with errors on the order of 0.06 ppm for exchange rates ranging from 100 to 1000 s−1, despite the small fraction of 13Cα–13Cβ spin-pairs that are present for many residue types. The labeling approach described here should thus be attractive for studies of exchanging systems using 13Cα spin probes.

    Place, publisher, year, edition, pages
    Springer Netherlands, 2015
    Keywords
    CPMG, 13Cα labeling, [2-13C]-Glycerol, Excited states
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-117073 (URN)10.1007/s10858-015-9948-1 (DOI)000357489200010 ()
    Note

    At the time for thesis presentation publication was in status: Manuscript

    At the time for thesis presentation name of publication was: Fractional enrichment using [2-13C]-glycerol as the carbon source facilitates measurements of excited state 13Cα chemical shifts with improved sensitivity

    Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2017-12-04Bibliographically approved
    5. Conformational Dynamics and Multimerization of Active Forms of the EphrinB Receptor 2 Kinase Domain
    Open this publication in new window or tab >>Conformational Dynamics and Multimerization of Active Forms of the EphrinB Receptor 2 Kinase Domain
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Active and autoinhibited forms of the ephrinB receptor 2 (EphB2) kinase domain have been studied using NMR spectroscopy. The project was initiated because of the finding that the crystal structures of active forms of the kinase domain and previous NMR studies suggested that a change in inter-lobe flexibility and the sampling of catalytically competent excited states conformations are responsible for activity. Using Carr-Purcell-Meiboom-Gill relaxation dispersion experiments, we have measured millisecond dynamics to identify such states. We have also performed concentration dependent relaxation experiments and analytical ultracentrifugation experiments that report on the effective protein size to look for possible differences in self-association for active and autoinhibited forms of the EphB2 kinase domain. We show that the active but not autoinhibited forms exchange between a ground state and an excited state at a rate of 1900 s-1. Similar results were found for the S677/680A mutant of the protein. The nature and importance of the excited state is still unknown. Our most important finding is that active forms of the kinase domain self-associate in a concentration dependent manner and form tetramers and possibly larger oligomers. Multimerization of the kinase domain may enable the assembly of complexes of downstream proteins and could be important for Eph signaling.

    Keywords
    Kinase activation | Eph receptors | chemical exchange | nmr spectroscopy | protein dynamics | self-association
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:liu:diva-117071 (URN)
    Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2015-04-15Bibliographically approved
  • 197.
    Ahlner, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Andresen, Cecilia
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Khan, Shahid N.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Kay, Lewis E.
    Departments of Medical Genetics, Biochemistry and Chemistry, The University of Toronto, Canada.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity2015In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 62, no 3, p. 341-351Article in journal (Refereed)
    Abstract [en]

    A selective isotope labeling scheme based on the utilization of [2-13C]-glycerol as the carbon source during protein overexpression has been evaluated for the measurement of excited state 13Cα chemical shifts using Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion (RD) experiments. As expected, the fractional incorporation of label at the Cα positions is increased two-fold relative to labeling schemes based on [2-13C]-glucose, effectively doubling the sensitivity of NMR experiments. Applications to a binding reaction involving an SH3 domain from the protein Abp1p and a peptide from the protein Ark1p establish that accurate excited state 13Cα chemical shifts can be obtained from RD experiments, with errors on the order of 0.06 ppm for exchange rates ranging from 100 to 1000 s−1, despite the small fraction of 13Cα–13Cβ spin-pairs that are present for many residue types. The labeling approach described here should thus be attractive for studies of exchanging systems using 13Cα spin probes.

  • 198.
    Ahlner, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Khan, Shahid N.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Forman-Kay, Julie D.
    Molecular Structure and Function Program, Hospital for Sick Children; Department and Biochemistry, University of Toronto, Canada.
    Sicheri, Frank
    cDepartment and Biochemistry, University of Toronto; Department of Molecular Genetics, University of Toronto; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Canada.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Conformational Dynamics and Multimerization of Active Forms of the EphrinB Receptor 2 Kinase DomainManuscript (preprint) (Other academic)
    Abstract [en]

    Active and autoinhibited forms of the ephrinB receptor 2 (EphB2) kinase domain have been studied using NMR spectroscopy. The project was initiated because of the finding that the crystal structures of active forms of the kinase domain and previous NMR studies suggested that a change in inter-lobe flexibility and the sampling of catalytically competent excited states conformations are responsible for activity. Using Carr-Purcell-Meiboom-Gill relaxation dispersion experiments, we have measured millisecond dynamics to identify such states. We have also performed concentration dependent relaxation experiments and analytical ultracentrifugation experiments that report on the effective protein size to look for possible differences in self-association for active and autoinhibited forms of the EphB2 kinase domain. We show that the active but not autoinhibited forms exchange between a ground state and an excited state at a rate of 1900 s-1. Similar results were found for the S677/680A mutant of the protein. The nature and importance of the excited state is still unknown. Our most important finding is that active forms of the kinase domain self-associate in a concentration dependent manner and form tetramers and possibly larger oligomers. Multimerization of the kinase domain may enable the assembly of complexes of downstream proteins and could be important for Eph signaling.

  • 199.
    Ahlner, Alexandra
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Mayzel, Maxim
    The Swedish NMR Centre, University of Gothenburg, Sweden.
    Lundström, Patrik
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Orekhov, Vladislav Y.
    The Swedish NMR Centre, University of Gothenburg, Sweden.
    Measurement of Protein Backbone 13CO and 15N Relaxation Dispersion at High ResolutionManuscript (preprint) (Other academic)
    Abstract [en]

    Three-dimensional pulse sequences for the measurement of Carr-Purcell-Meiboom-Gill relaxation dispersions and new methods for co-processing non-uniformly sampled data are presented. The new methodology was validated for the disordered protein IgA and for an SH3 domain from Abp1p in exchange between its free form and bound to a peptide from the protein Ark1p. We show that the results are similar to ones obtained using traditional experiments and that accurate excited state chemical shifts can be determined. Furthermore, we show that jackknife analysis of down sampled spectra yields robust estimates of peak intensities errors, eliminating the need for recording duplicate data points. The methodology should be useful for characterization of millisecond dynamics in small to medium-sized proteins with poorly dispersed spectra.

  • 200.
    Ahlquist, Mari
    Linköping University, Department of Mathematics. Linköping University, Faculty of Science & Engineering.
    On Knots and DNA2017Independent thesis Basic level (degree of Bachelor), 10,5 credits / 16 HE creditsStudent thesis
    Abstract [en]

    Knot theory is the mathematical study of knots. In this thesis we study knots and one of its applications in DNA. Knot theory sits in the mathematical field of topology and naturally this is where the work begins. Topological concepts such as topological spaces, homeomorphisms, and homology are considered. Thereafter knot theory, and in particular, knot theoretical invariants are examined, aiming to provide insights into why it is difficult to answer the question "How can we tell knots appart?". In knot theory invariants such as the bracket polynomial, the Jones polynomial and tricolorability are considered as well as other helpful results like Seifert surfaces. Lastly knot theory is applied to DNA, where it will shed light on how certain enzymes interact with the genome.

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