Ändra sökning
Avgränsa sökresultatet
891011 501 - 533 av 533
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 501.
    Vogginger, Bernhard
    et al.
    Technical University Dresden.
    Schüffny, Rene
    Technical University Dresden.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm University, Sweden.
    Cederström, Love
    Technical University Dresden.
    Parzsch, Johannes
    Technical University Dresden.
    Höppner, Sebastian
    Technical University Dresden.
    Reducing the computational footprint for real-time BCPNN learning2015Ingår i: Frontiers in Neuroengineering, ISSN 1662-6443, Vol. 9, nr 2, artikel-id 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The implementation of synaptic plasticity in neural simulation or neuromorphic hardware is usually very resource-intensive, often requiring a compromise between efficiency and flexibility. A versatile, but computationally-expensive plasticity mechanism is provided by the Bayesian Confidence Propagation Neural Network (BCPNN) paradigm. Building upon Bayesian statistics, and having clear links to biological plasticity processes, the BCPNN learning rule has been applied in many fields, ranging from data classification, associative memory, reward-based learning, probabilistic inference to cortical attractor memory networks. In the spike-based version of this learning rule the pre-, postsynaptic and coincident activity is traced in three low-pass-filtering stages, requiring a total of eight state variables, whose dynamics are typically simulated with the fixed step size Euler method. We derive analytic solutions allowing an efficient event-driven implementation of this learning rule. Further speedup is achieved by first rewriting the model which reduces the number of basic arithmetic operations per update to one half, and second by using look-up tables for the frequently calculated exponential decay. Ultimately, in a typical use case, the simulation using our approach is more than one order of magnitude faster than with the fixed step size Euler method. Aiming for a small memory footprint per BCPNN synapse, we also evaluate the use of fixed-point numbers for the state variables, and assess the number of bits required to achieve same or better accuracy than with the conventional explicit Euler method. All of this will allow a real-time simulation of a reduced cortex model based on BCPNN in high performance computing. More important, with the analytic solution at hand and due to the reduced memory bandwidth, the learning rule can be efficiently implemented in dedicated or existing digital neuromorphic hardware.

  • 502. Volkovsky, A.R
    et al.
    Kozlov, Alexander
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Shalfeev, V.D
    Synchronous chaotic response and transmission of information in experiments with the tunnel diod generator1995Ingår i: Radiofizika, Vol. 38, nr 1-2, s. 159-162Artikel i tidskrift (Refereegranskat)
  • 503. Wadden, T
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, A
    Grillner, S
    Intersegmental coordination in the lamprey: Simulations using a continuous network model1996Konferensbidrag (Refereegranskat)
  • 504. Wadden, T
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, A
    Grillner, S
    Simulations of the intersegmental coordination during swimming in the lamprey using a continuous network model1995Konferensbidrag (Refereegranskat)
  • 505. Wang, B.
    et al.
    Aihara, K.
    Kim, Beom Jun
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Sungkyunkwan University, South Korea .
    Immunization of geographical networks2009Ingår i: Complex Sciences: First International Conference, Complex 2009, Shanghai, China, February 23-25, 2009, Revised Papers, Part 2, Springer Berlin/Heidelberg, 2009, nr PART 2, s. 2388-2395Konferensbidrag (Refereegranskat)
    Abstract [en]

    We numerically investigate the epidemic spread phenomena and efficient immunization strategies on complex networks embedded in geometry. It is assumed that there exists an unavoidable time delay (we call it the detection time) between the actual infection and the beginning of immunization, and we implement two different immunization strategies: one is based on topological connection neighbors (CN) of the infected vertex and the other on geographical spatial neighbors (SN). It is found that the decrease of the detection time is very important for a successful immunization. Our results suggest that within the limitation of the network models considered here, in which the infection probability is assumed to decrease with the geographic distance, the simple SN strategy works almost equally or better than the CN strategy, especially when the detection time is longer.

  • 506. Wang, Bing
    et al.
    Aihara, Kazuyuki
    Kim, Beom Jun
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Comparison of immunization strategies in geographical networks2009Ingår i: Physics Letters A, ISSN 0375-9601, E-ISSN 1873-2429, Vol. 373, nr 42, s. 3877-3882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time. for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy. especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy. which may have potential applications for preventing the real epidemic spread.

  • 507.
    Werner, Maria
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Studies of Cellular Regulatory Mechanisms: from Genetic Switches to Cell Migration2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Cellular behaviour depends ultimately on the transcription of genes. If we know how transcription is controlled we have a better chance of understanding cellular processes. This thesis presents six studies, all concerning cellular regulatory mechanisms. One study is purely experimental and five are computational studies.

    A large part of the research concerns the Epstein-Barr virus (EBV). We investigate the latency programme switching of EBV, with an equilibrium statistical mechanics model that describes the transcription activities of two central viral promoters. We demonstrate that this system is bistable and predict promoter activities that correlate well with experimental data. Further we study the switching efficiency of one of the promoters, highlighting how competitive binding of transcription factors generates a more efficient geneticswitch.

    The EBV protein EBNA1 is known to affect cellular gene expression. With a dinucleotide position weight matrix we search the complete human genome for regions with multiple EBNA1 binding sites. 40 potential binding regions are identified, with several of particular interest in relation to EBV infections. The final study on EBV is purely experimental, in which we demonstrate an interaction between the Syk kinase and integrin β4. Moreover, we show how reduced levels of these proteins affect migration of epithelial LMP2a positive cells, and hypothesise that these effects are due to the Syk-β4 interaction.

    The two remaining studies presented in this thesis concern other cellular systems. Dynamic properties of two different regulatory feedback mechanisms for transport and metabolism of small molecules are investigated. The synergetic effect of adding a regulatory loop is exemplified with the iron metabolism in bacteria. The final project concerns the λ phage. With the equilibrium statistical mechanics method for describing promoter activities we characterise the equilibrium properties of λ mutants and compare with experimental findings. We argue that the observed differences between model and experiment are due to a larger perturbation of the genetic circuit than presumed.

    The research presented in this thesis shed light on the properties of several regulatory mechanisms. As computational studies they add perspective to the experimental research in this field and provide new hypothesis for further research.

  • 508.
    Werner, Maria
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    A computational study of lambda-lac mutants2009Ingår i: PHYS BIOL, ISSN 1478-3967, Vol. 6, nr 4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a comprehensive, computational study of the properties of bacteriophage lambda mutants designed by Atsumi and Little (2006 Proc. Natl. Acad. Sci. 103 4558-63). These phages underwent a genetic reconstruction where Cro was replaced by a dimeric form of the Lac repressor. To clarify the theoretical characteristics of these mutants, we built a detailed thermodynamic model. The mutants all have a different genetic wiring than the wild-type. lambda One group lacks regulation of P-RM by the lytic protein. These mutants only exhibit the lysogenic equilibrium, with no transiently active P-R. The other group lacks the negative feedback from CI. In this group, we identify a handful of bi-stable mutants, although the majority only exhibit the lysogenic equilibrium. The experimental identification of functional phages differs from our predictions. From a theoretical perspective, there is no reason why only 4 out of 900 mutants should be functional. The differences between theory and experiment can be explained in two ways. Either, the view of the lambda phage as a bi-stable system needs to be revised, or the mutants have in fact not undergone a modular replacement, as intended by Atsumi and Little, but constitute instead a wider systemic change.

  • 509.
    Werner, Maria
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    A computational systems biology study of the lambda-lac mutants2007Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    We present a comprehensive computational study of some 900 possible “λ-lac” mutants of thelysogeny maintenance switch in phage λ, of which up to date 19 have been studied experimentally(Atsumi & Little, PNAS 103: 4558-4563, (2006)). We clarify that these mutants realise regulatoryschemes quite different from wild-type λ, and can therefore be expected to behave differently, withinthe conventional mechanistic setting in which this problem has often been framed. We verify thatindeed, within this framework, across this wide selection of mutants the λ-lac mutants for the mostpart either have no stable lytic states, or should only be inducible with difficulty. In particular, thecomputational results contradicts the experimental finding that four λ-lac mutants both show stablelysogeny and are inducible. This work hence suggests either that the four out of 900 mutants are special,or that λ lysogeny and inducibility are holistic effects involving other molecular players or othermechanisms, or both. The approach illustrates the power and versatility of computational systemsbiology to systematically and quickly test a wide variety of examples and alternative hypotheses for future closer experimental studies.

  • 510.
    Werner, Maria
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ernberg, Ingemar
    Zou, JieZhi
    Almqvist, Jenny
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Epstein-Barr virus latency switch in human B-cells: a physico-chemical model2007Ingår i: BMC SYST BIOL, ISSN 1752-0509, Vol. 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Epstein-Barr virus is widespread in all human populations and is strongly associated with human disease, ranging from infectious mononucleosis to cancer. In infected cells the virus can adopt several different latency programs, affecting the cells' behaviour. Experimental results indicate that a specific genetic switch between viral latency programs, reprograms human B-cells between proliferative and resting states. Each of these two latency programs makes use of a different viral promoter, C-P and Q(P), respectively. The hypothesis tested in this study is that this genetic switch is controlled by both human and viral transcription factors; Oct-2 and EBNA-1. We build a physico-chemical model to investigate quantitatively the dynamical properties of the promoter regulation and experimentally examine protein level variations between the two latency programs. Results: Our experimental results display significant differences in EBNA-1 and Oct-2 levels between resting and proliferating programs. With the model we identify two stable latency programs, corresponding to a resting and proliferating cell. The two programs differ in robustness and transcriptional activity. The proliferating state is markedly more stable, with a very high transcriptional activity from its viral promoter. We predict the promoter activities to be mutually exclusive in the two different programs, and our relative promoter activities correlate well with experimental data. Transitions between programs can be induced, by affecting the protein levels of our transcription factors. Simulated time scales are in line with experimental results. Conclusion: We show that fundamental properties of the Epstein-Barr virus involvement in latent infection, with implications for tumor biology, can be modelled and understood mathematically. We conclude that EBNA-1 and Oct-2 regulation of C-P and Q(P) is sufficient to establish mutually exclusive expression patterns. Moreover, the modelled genetic control predict both mono-and bistable behavior and a considerable difference in transition dynamics, based on program stability and promoter activities. Both these phenomena we hope can be further investigated experimentally, to increase the understanding of this important switch. Our results also stress the importance of the little known regulation of human transcription factor Oct-2.

  • 511.
    Werner, Maria
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Semsey, Szabolcs
    Sneppen, Kim
    Krishna, Sandeep
    Dynamics of Uptake and Metabolism of Small Molecules in Cellular Response Systems2009Ingår i: PLOS ONE, ISSN 1932-6203, Vol. 4, nr 3Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Proper cellular function requires uptake of small molecules from the environment. In response to changes in extracellular conditions cells alter the import and utilization of small molecules. For a wide variety of small molecules the cellular response is regulated by a network motif that combines two feedback loops, one which regulates the transport and the other which regulates the subsequent metabolism.

    Results: We analyze the dynamic behavior of two widespread but logically distinct two-loop motifs. These motifs differ in the logic of the feedback loop regulating the uptake of the small molecule. Our aim is to examine the qualitative features of the dynamics of these two classes of feedback motifs. We find that the negative feedback to transport is accompanied by overshoot in the intracellular amount of small molecules, whereas a positive feedback to transport removes overshoot by boosting the final steady state level. On the other hand, the negative feedback allows for a rapid initial response, whereas the positive feedback is slower. We also illustrate how the dynamical deficiencies of one feedback motif can be mitigated by an additional loop, while maintaining the original steady-state properties.

    Conclusions: Our analysis emphasizes the core of the regulation found in many motifs at the interface between the metabolic network and the environment of the cell. By simplifying the regulation into uptake and the first metabolic step, we provide a basis for elaborate studies of more realistic network structures. Particularly, this theoretical analysis predicts that FeS cluster formation plays an important role in the dynamics of iron homeostasis.

  • 512.
    Werner, Maria
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Zhu, Lizhe
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Cooperative action in eukaryotic gene regulation: Physical properties of a viral example2007Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics, ISSN 1063-651X, E-ISSN 1095-3787, Vol. 76, nr 6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Epstein-Barr virus (EBV) infects more than 90% of the human population, and causes glandular fever as well as several more serious diseases. It is a tumor virus, and has been widely studied as a model system for cell transformation in humans. A central feature of the EBV life cycle is its ability to persist in human B cells in different latency states, denoted latency I, II, and III. In latency III the host cell is driven to cell proliferation and hence expansion of the viral population without entering the lytic pathway, while the latency I state is almost completely dormant. We here study the effective cooperativity of the viral C promoter, active in latency III EBV cell lines. We show that the unusually large number of binding sites of two competing transcription factors, one viral and one from the host, serves to make the switch sharper (higher Hill coefficient), either by cooperative binding between molecules of the same species when they bind, or by competition between the two species if there is sufficient steric hindrance.

  • 513.
    Westermark, Pål
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA. KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Björklund, Anneli
    Grill, Valdemar
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    A mathematical model of the mitochondrial NADH shuttles and anaplerosis in the pancreatic beta-cell2007Ingår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 292, nr 2, s. E373-E393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The pancreatic beta-cells respond to an increased glycolytic flux by secreting insulin. The signal propagation goes via mitochondrial metabolism, which relays the signal to different routes. One route is an increased ATP production that, via ATP-sensitive K+ (K-ATP) channels, modulates the cell membrane potential to allow calcium influx, which triggers insulin secretion. There is also at least one other "amplifying" route whose nature is debated; possible candidates are cytosolic NADPH production or malonyl-CoA production. We have used mathematical modeling to analyze this relay system. The model comprises the mitochondrial NADH shuttles and the mitochondrial metabolism. We found robust signaling toward ATP, malonyl-CoA, and NADPH production. The signal toward NADPH production was particularly strong. Furthermore, the model reproduced the experimental findings that blocking the NADH shuttles attenuates the signaling to ATP production while retaining the rate of glucose oxidation (Eto K, Tsubamoto Y, Terauchi Y, Sugiyama T, Kishimoto T, Takahashi N, Yamauchi N, Kubota N, Murayama S, Aizawa T, Akanuma Y, Aizawa S, Kasai H, Yazaki Y, Kadowaki T. Science 283: 981 - 985, 1999) and provides an explanation for this apparent paradox. The model also predicts that the mitochondrial malate dehydrogenase reaction may proceed backward, toward malate production, if the activity of malic enzyme is sufficiently high. An increased fatty acid oxidation rate was found to attenuate the signaling strengths. This theoretical study has implications for our understanding of both the healthy and the diabetic beta-cell.

  • 514.
    Widing, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tailoring biomechanical model meshes for aero-acoustic simulations2015Ingår i: Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization, ISSN 2168-1171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To simulate the airflow and acoustic wave propagation associated with voice production, a closed surface mesh representing the vocal tract is needed. Biomechanically, the vocal tract is composed of surfaces from several different anatomical structures. We present a method for assembling a dynamic vocal tract mesh by trimming and stitching surface meshes tracking biomechanical models of relevant structures. Two algorithms, one for trimming and one for stitching, are used to first isolate surface mesh patches that are in contact with the airway and then merge them into a closed surface. The algorithms rely on manually selected boundaries and are able to cover gaps between mesh patches. Test cases are used to illustrate how the algorithms behave in various situations. The algorithms are implemented in the toolkit ArtiSynth where many relevant biomechanical models are already available.

  • 515. WIkström, M
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hill, R.H
    Grillner, S
     5-HT1A like receptors modulates network output pattern for locomotion1994Konferensbidrag (Refereegranskat)
  • 516. Wikström, M
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hill, R.H.
    Grillner, S
    A 5-HT1A like receptor modulates fictive locomotion and the slow AHP in the lamprey1994Konferensbidrag (Refereegranskat)
  • 517. Wikström, M
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hill, R.H.
    Grillner, S
    Classification of the receptor responsible for the 5-HT effect on Ca-dependent K-channels in the lamprey1993Konferensbidrag (Refereegranskat)
  • 518. Wikström, M
    et al.
    Hill, R.H.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Grillner, S
    The action of 5-HT on calcium-dependent potassium channels and on the spinal locomotor network in lamprey is mediated by 5-HT1A-like receptors.1995Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 678, s. 191-199Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    5-HT has a powerful modulatory action on the firing properties of single neurons as well as on locomotor activity. In lamprey, 5-HT increases the neuronal firing frequency in spinal neurons by reducing the conductance in Ca(2+)-dependent K+ channels (KCa) underlying the slow afterhyperpolarization (sAHP), and it also lowers the burst frequency of the spinal locomotor network. To elucidate which type of 5-HT receptor mediates these effects, different specific receptor agonists and antagonists were applied during intracellular current clamp recordings and during NMDA-induced fictive locomotion in the lamprey spinal cord in vitro preparation. The 5-HT1A receptor agonist 8-OH-DPAT ((+/-)-8-hydroxy-dipropylaminotetralin hydrobromide), the 5-HT1 receptor agonist 5-CT (5-carboxyamidotryptamine maleate) and the 5-HT2 receptor agonist alpha-CH3-5-HT (alpha-methylserotonin maleate) all reproduced the actions of 5-HT at both the cellular and the network levels. The effects of all agonists were completely or partially blocked by the 5-HT1A and 5-HT2 receptor antagonist spiperone (spiroperidol hydrochloride) while selective 5-HT2 receptor antagonists were ineffective. The selective 5-HT1A receptor antagonist S(-)-UH301 (S(-)-5-fluoro-8-hydroxy-dipropylaminotetralin hydrochloride) also counteracted the effect of 5-HT on the sAHP. 5-HT3 and 5-HT4 receptor agonists and antagonists were without effects. The intracellular coupling mechanism was not sensitive to pertussis toxin nor to the cAMP dependent protein kinase blocker (Rp)-cAMPS.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 519. Wu, Lu-Lu
    et al.
    Zhou, Hai-Jun
    Alava, Mikko
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. KTH, Skolan för elektro- och systemteknik (EES), Centra, ACCESS Linnaeus Centre.
    Orponen, Pekka
    Witness of unsatisfiability for a random 3-satisfiability formula2013Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics, ISSN 1539-3755, E-ISSN 1550-2376, Vol. 87, nr 5, s. 052807-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The random 3-satisfiability (3-SAT) problem is in the unsatisfiable (UNSAT) phase when the clause density alpha exceeds a critical value alpha(s) approximate to 4.267. Rigorously proving the unsatisfiability of a given large 3-SAT instance is, however, extremely difficult. In this paper we apply the mean-field theory of statistical physics to the unsatisfiability problem, and show that a reduction to 3-XORSAT, which permits the construction of a specific type of UNSAT witnesses (Feige-Kim-Ofek witnesses), is possible when the clause density alpha > 19. We then construct Feige-Kim-Ofek witnesses for single 3-SAT instances through a simple random sampling algorithm and a focused local search algorithm. The random sampling algorithm works only when a scales at least linearly with the variable number N, but the focused local search algorithm works for clause density alpha > cN(b) with b approximate to 0.59 and prefactor c approximate to 8. The exponent b can be further decreased by enlarging the single parameter S of the focused local search algorithm.

  • 520.
    Wärnberg, Emil
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST). KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Modelling Low Dimensional Neural Activity2016Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Ett antal nyligen publicerade studier has visat att dimensionaliten för neural aktivitet är låg. Dock är det inte klarlagt vilka nätverksstrukturer som kan uppbringa denna typ av aktivitet. I denna uppsats diskuterar jag möjliga lösningsförslag, och demonstrerar att ett nätverk med en flerdimensionell attraktor ger upphov till lågdimensionell aktivitet. Nätverket skapas med hjälp av the Neural Engineering Framework, och uppvisar ett flertal biologiskt trovärdiga egenskaper. I synnerhet är fördelningen av synapsvikter log-normalt fördelad.

  • 521. Ya. I., Molkov
    et al.
    Sushchik, M.M
    Kuznetsov, A.S.
    Kozlov, Alexander
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Zakharov, D.G
    Dynamical model of locomotor-like movements of human evoked by muscle vibration1999Ingår i: Applied Nonlinear Dynamic, Vol. 7, nr 2-3, s. 107-121Artikel i tidskrift (Refereegranskat)
  • 522. Yang, K-H
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Blackwell, K.T.
    The role of protein kinase C in the temporal specificity of Purkinje cells2000Konferensbidrag (Refereegranskat)
  • 523. Yoshida, Motoharu
    et al.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hasselmo, Michael E.
    mGluR-dependent persistent firing in entorhinal cortex layer III neurons2008Ingår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 28, nr 6, s. 1116-1126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Persistent firing is believed to be a crucial mechanism for memory function including working memory. Recent in vivo and in vitro findings suggest an involvement of metabotropic glutamate receptors (mGluRs) in persistent firing. Using whole-cell patch-recording techniques in a rat entorhinal cortex (EC) slice preparation, we tested whether EC layer III neurons display persistent firing due to mGluR activation, independently of cholinergic activation. Stimulation of the angular bundle drove persistent firing in 90% of the cells in the absence of a cholinergic agonist. The persistent firing was typically stable for > 4.5 min at which point persistent firing was terminated by the experimenter. The average frequency of the persistent firing was 2.1 Hz, ranging from 0.4 to 5.5 Hz. This persistent firing was observed even in the presence of atropine (2 mu M), suggesting that the persistent firing can occur independent of cholinergic activation. Furthermore, ionotropic glutamate and GABAergic synaptic blockers (2 mm kynurenic acid, 100 mu M picrotoxin and 1 mu M CGP55845) did not block the persistent firing. On the other hand, blockers of group I mGluRs (100 mu M LY367385 and 20 mu M MPEP) completely blocked or suppressed the persistent firing. An agonist of group I mGluRs (20 mu M DHPG) greatly enhanced the persistent firing induced by current injection. These results indicate that persistent firing can be driven through group I mGluRs in entorhinal layer III neurons, suggesting that glutamatergic synaptic input alone could enable postsynaptic neurons to hold input signals in the form of persistent firing.

  • 524. Yuste, R.
    et al.
    MacLean, J. N.
    Smith, J.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    The cortex as a central pattern generator2005Ingår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 6, nr 6, s. 477-483Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits.

  • 525. Zeng, Hong-Li
    et al.
    Alava, Mikko
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. KTH, Skolan för elektro- och systemteknik (EES), Centra, ACCESS Linnaeus Centre.
    Hertz, John
    KTH, Centra, Nordic Institute for Theoretical Physics NORDITA.
    Roudi, Yasser
    KTH, Centra, Nordic Institute for Theoretical Physics NORDITA.
    Maximum Likelihood Reconstruction for Ising Models with Asynchronous Updates2013Ingår i: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 110, nr 21, s. 210601-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe how the couplings in an asynchronous kinetic Ising model can be inferred. We consider two cases: one in which we know both the spin history and the update times and one in which we know only the spin history. For the first case, we show that one can average over all possible choices of update times to obtain a learning rule that depends only on spin correlations and can also be derived from the equations of motion for the correlations. For the second case, the same rule can be derived within a further decoupling approximation. We study all methods numerically for fully asymmetric Sherrington-Kirkpatrick models, varying the data length, system size, temperature, and external field. Good convergence is observed in accordance with the theoretical expectations.

  • 526. Zeng, Hong-Li
    et al.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Alava, Mikko
    Mahmoudi, Hamed
    Network inference using asynchronously updated kinetic Ising model2011Ingår i: Physical Review E, ISSN 1539-3755, Vol. 83, nr 4, s. 041135-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Network structures are reconstructed from dynamical data by respectively naive mean field (nMF) and Thouless-Anderson-Palmer (TAP) approximations. TAP approximation adds simple corrections to the nMF approximation, taking into account the effect of the focused spin on itself via its influence on other neighboring spins. For TAP approximation, we use two methods to reconstruct the network: (a) iterative method; (b) casting the inference formula to a set of cubic equations and solving it directly. We investigate inference of the asymmetric Sherrington-Kirkpatrick (aS-K) model using asynchronous update. The solutions of the set of cubic equations depend on temperature T in the aS-K model, and a critical temperature T-c approximate to 2.1 is found. The two methods for TAP approximation produce the same results when the iterative method is convergent. Compared to nMF, TAP is somewhat better at low temperatures, but approaches the same performance as temperature increases. Both nMF and TAP approximation reconstruct better for longer data length L, but for the degree of improvement, TAP performs better than nMF.

  • 527.
    Zhao, Jing
    et al.
    Logist Engn Univ, Dept Math, Chongqing 400016, Peoples R China.;Second Mil Med Univ, Dept Nat Med Chem, Coll Pharm, Shanghai, Peoples R China..
    Holme, Petter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Three Faces of Metabolites: Pathways, Localizations and Network Positions2010Ingår i: COMPUTATIONAL SYSTEMS BIOLOGY / [ed] Chen, L Zhang, XS Shen, B Wu, LY Wang, Y, WORLD PUBLISHING CORPORATION , 2010, Vol. 13, s. 13-+Konferensbidrag (Refereegranskat)
    Abstract [en]

    In this study, we investigate the relative organization of three (not independent) categorizations of metabolites pathways, subcellular localizations and network clusters both qualitatively and quantitatively and further characterize the categories from topological point of view. The picture of the metabolism we obtain is that of peripheral modules, characterized both by being dense network clusters and localized to organelles, connected by a central, highly connected core. Pathways typically run through several network clusters and localizations, connecting them-laterally. The significant overlap between organelles, pathways and network clusters suggest that, to some extent, the topology of metabolic networks could spell out the spatial isolations of cellular architectures and functional coherence of metabolic systems. Such systems level analysis of the correlation between different categorizations is helpful for understanding the influence of intracellular organization on the regulation of metabolic processes.

  • 528. Zhou, Joseph Xu
    et al.
    Aliyu, M. D. S.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Huang, Sui
    Quasi-potential landscape in complex multi-stable systems2012Ingår i: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 9, nr 77, s. 3539-3553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The developmental dynamics of multicellular organisms is a process that takes place in a multi-stable system in which each attractor state represents a cell type, and attractor transitions correspond to cell differentiation paths. This new understanding has revived the idea of a quasi-potential landscape, first proposed by Waddington as a metaphor. To describe development, one is interested in the 'relative stabilities' of N attractors (N > 2). Existing theories of state transition between local minima on some potential landscape deal with the exit part in the transition between two attractors in pair-attractor systems but do not offer the notion of a global potential function that relates more than two attractors to each other. Several ad hoc methods have been used in systems biology to compute a landscape in non-gradient systems, such as gene regulatory networks. Here we present an overview of currently available methods, discuss their limitations and propose a new decomposition of vector fields that permits the computation of a quasi-potential function that is equivalent to the Freidlin-Wentzell potential but is not limited to two attractors. Several examples of decomposition are given, and the significance of such a quasi-potential function is discussed.

  • 529. Zhou, T.
    et al.
    Kiet, H. A. T.
    Kim, Beom Jun
    Wang, B. H.
    Holme, Petter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Role of activity in human dynamics2008Ingår i: Europhysics letters, ISSN 0295-5075, E-ISSN 1286-4854, Vol. 82, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The human society is a very complex system; still, there are several non-trivial, features. One type of them is the presence of power-law-distributed quantities in temporal statistics. In this letter, we focus on the origin of power laws in rating of movies. We present a systematic empirical exploration of the time between two consecutive ratings of movies ( the interevent time). At an aggregate level, we find a monotonous relation between the activity of individuals and the power law exponent of the interevent time distribution. At an individual level, we observe a heavy-tailed distribution for each user, as well as a negative correlation between the activity and the width of the distribution. We support these findings by a similar data set from mobile phone text-message communication. Our results demonstrate a significant role of the activity of individuals on the society-level patterns of human behavior. We believe this is a common character in the interest-driven human dynamics, corresponding to (but different from) the universality classes of task-driven dynamics.

  • 530.
    Åkerborg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Taking advantage of phylogenetic trees in comparative genomics2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Phylogenomics can be regarded as evolution and genomics in co-operation. Various kinds of evolutionary studies, gene family analysis among them, demand access to genome-scale datasets. But it is also clear that many genomics studies, such as assignment of gene function, are much improved by evolutionary analysis. The work leading to this thesis is a contribution to the phylogenomics field. We have used phylogenetic relationships between species in genome-scale searches for two intriguing genomic features, namely and A-to-I RNA editing. In the first case we used pairwise species comparisons, specifically human-mouse and human-chimpanzee, to infer existence of functional mammalian pseudogenes. In the second case we profited upon later years' rapid growth of the number of sequenced genomes, and used 17-species multiple sequence alignments. In both these studies we have used non-genomic data, gene expression data and synteny relations among these, to verify predictions. In the A-to-I editing project we used 454 sequencing for experimental verification.

    We have further contributed a maximum a posteriori (MAP) method for fast and accurate dating analysis of speciations and other evolutionary events. This work follows recent years' trend of leaving the strict molecular clock when performing phylogenetic inference. We discretised the time interval from the leaves to the root in the tree, and used a dynamic programming (DP) algorithm to optimally factorise branch lengths into substitution rates and divergence times. We analysed two biological datasets and compared our results with recent MCMC-based methodologies. The dating point estimates that our method delivers were found to be of high quality while the gain in speed was dramatic.

    Finally we applied the DP strategy in a new setting. This time we used a grid laid out on a species tree instead of on an interval. The discretisation gives together with speciation times a common timeframe for a gene tree and the corresponding species tree. This is the key to integration of the sequence evolution process and the gene evolution process. Out of several potential application areas we chose gene tree reconstruction. We performed genome-wide analysis of yeast gene families and found that our methodology performs very well.

  • 531.
    Åkerborg, Örjan
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Sennblad, Bengt
    Arvestad, Lars
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lagergren, Jens
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Simultaneous Bayesian gene tree reconstruction and reconciliation analysis2009Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, s. 5714-5719Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present GSR, a probabilistic model integrating gene duplication, sequence evolution, and a relaxed molecular clock for substitution rates, that enables genomewide analysis of gene families. The gene duplication and loss process is a major cause for incongruence between gene and species tree, and deterministic methods have been developed to explain such differences through tree reconciliations. Although probabilistic methods for phylogenetic inference have been around for decades, probabilistic reconciliation methods are far less established. Based on our model, we have implemented a Bayesian analysis tool, PrIME-GSR, for gene tree inference that takes a known species tree into account. Our implementation is sound and we demonstrate its utility for genomewide gene-family analysis by applying it to recently presented yeast data. We validate PrIME-GSR by comparing with previous analyses of these data that take advantage of gene order information. In a case study we apply our method to the ADH gene family and are able to draw biologically relevant conclusions concerning gene duplications creating key yeast phenotypes. On a higher level this shows the biological relevance of our method. The obtained results demonstrate the value of a relaxed molecular clock. Our good performance will extend to species where gene order conservation is insufficient.

  • 532.
    Åkerborg, Örjan
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Sennblad, Bengt
    Lagergren, Jens
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Birth-death prior on phylogeny and speed dating2008Ingår i: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 8, nr 1, s. 77-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In recent years there has been a trend of leaving the strict molecular clock in order to infer dating of speciations and other evolutionary events. Explicit modeling of substitution rates and divergence times makes formulation of informative prior distributions for branch lengths possible. Models with birth-death priors on tree branching and auto-correlated or iid substitution rates among lineages have been proposed, enabling simultaneous inference of substitution rates and divergence times. This problem has, however, mainly been analysed in the Markov chain Monte Carlo (MCMC) framework, an approach requiring computation times of hours or days when applied to large phylogenies.

    Results: We demonstrate that a hill-climbing maximum a posteriori (MAP) adaptation of the MCMC scheme results in considerable gain in computational efficiency. We demonstrate also that a novel dynamic programming (DP) algorithm for branch length factorization, useful both in the hill-climbing and in the MCMC setting, further reduces computation time. For the problem of inferring rates and times parameters on a fixed tree, we perform simulations, comparisons between hill-climbing and MCMC on a plant rbcL gene dataset, and dating analysis on an animal mtDNA dataset, showing that our methodology enables efficient, highly accurate analysis of very large trees. Datasets requiring a computation time of several days with MCMC can with our MAP algorithm be accurately analysed in less than a minute. From the results of our example analyses, we conclude that our methodology generally avoids getting trapped early in local optima. For the cases where this nevertheless can be a problem, for instance when we in addition to the parameters also infer the tree topology, we show that the problem can be evaded by using a simulated-annealing like (SAL) method in which we favour tree swaps early in the inference while biasing our focus towards rate and time parameter changes later on.

    Conclusion: Our contribution leaves the field open for fast and accurate dating analysis of nucleotide sequence data. Modeling branch substitutions rates and divergence times separately allows us to include birth-death priors on the times without the assumption of a molecular clock. The methodology is easily adapted to take data from fossil records into account and it can be used together with a broad range of rate and substitution models.

  • 533. Åkerman, S.
    et al.
    Lindeberg, Tony
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Roland, P.
    Surface Model Generation and Segmentation of the Human Celebral Cortex for the Construction of Unfolded Cortical Maps1996Ingår i: Proc. 2nd International Conference on Functional Mapping of the Human Brain: HBM'96, published in Neuroimage, volume 3, number 3, 1996, s. S126-S126Konferensbidrag (Refereegranskat)
    Abstract [en]

    Representing the shape of the human cerebral cortex arises as a basic subproblem in several areas of brain science, such as when describing the anatomy of the cortex and when relating functional measurements to cortical regions. 

    Most current methods for building such representions of the cortical surface are either based on contours from two-dimensional cross sections or landmarks that have been obtained manually.

    In this article, we outline a methodology for semi-automatic contruction of a solely surface based representation of the human cerebral cortex in vivo for subsequent generation of  (unfolded) two-dimensional brain maps.

    The method is based on input data in the form of three-dimensional NMR images, and comprises the following main steps:

    • suppression of disturbing fine-scale structures by linear and non-linear scale-space techniques,
    • generation of a triangulated surface representation based on either iso-surfaces or three-dimensional edge detection,
    • division of the surface model into smaller segments based on differential invariants computed from the image data.

    When constructing an unfolded (flattened) surface representation, the instrinsic curvature of the cortex means that such a unfolding cannot be done without introducing distortions. To reduce this problem, we propose to cut the surface into smaller parts, where a ridge detector acts as guideline, and then unfold each patch individually, so as to obtain low distortions.

    Having a solely surface based representation of the cortex and expressing the image operations using multi-scale differential invariants in terms of scale-space derivatives as done in this work is a natural choice both in terms of conceptual and algorithmic simplicity. Moreover, explicitly handling the multi-scale nature of the data is necessary to obtain robust results.

891011 501 - 533 av 533
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf