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  • 1.
    Abergel, David
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Stockholm University, Sweden.
    Excitonic condensation in spatially separated one-dimensional systems2015In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 106, no 21, article id 213103Article in journal (Refereed)
    Abstract [en]

    We show theoretically that excitons can form from spatially separated one-dimensional ground state populations of electrons and holes, and that the resulting excitons can form a quasicondensate. We describe a mean-field Bardeen-Cooper-Schrieffer theory in the low carrier density regime and then focus on the core-shell nanowire giving estimates of the size of the excitonic gap for InAs/GaSb wires and as a function of all the experimentally relevant parameters. We find that optimal conditions for pairing include small overlap of the electron and hole bands, large effective mass of the carriers, and low dielectric constant of the surrounding media. Therefore, one-dimensional systems provide an attractive platform for the experimental detection of excitonic quasicondensation in zero magnetic field.

  • 2.
    Abergel, David
    et al.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Edge, Jonathan M.
    Balatsky, Alexander V.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    The role of spin-orbit coupling in topologically protected interface states in Dirac materials2014In: New Journal of Physics, ISSN 1367-2630, E-ISSN 1367-2630, Vol. 16, p. 065012-Article in journal (Refereed)
    Abstract [en]

    We highlight the fact that two-dimensional (2D) materials with Dirac-like low energy band structures and spin-orbit coupling (SOC) will produce linearly dispersing topologically protected Jackiw-Rebbi modes at interfaces where the Dirac mass changes sign. These modes may support persistent spin or valley currents parallel to the interface, and the exact arrangement of such topologically protected currents depends crucially on the details of the SOC in the material. As examples, we discuss buckled 2D hexagonal lattices such as silicene or germanene, and transition metal dichalcogenides such as MoS2.

  • 3.
    Abergel, David
    et al.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Mucha-Kruczynski, Marcin
    Infrared absorption of closely aligned heterostructures of monolayer and bilayer graphene with hexagonal boron nitride2015In: Physical Review B. Condensed Matter and Materials Physics, ISSN 1098-0121, E-ISSN 1550-235X, Vol. 92, no 11, article id 115430Article in journal (Refereed)
    Abstract [en]

    We model optical absorption of monolayer and bilayer graphene on hexagonal boron nitride for the case of closely aligned crystal lattices. We show that perturbations with different spatial symmetry can lead to similar absorption spectra. We suggest that a study of the absorption spectra as a function of the doping for an almost completely full first miniband is necessary to extract meaningful information about the moire characteristics from optical absorption measurements and to distinguish between various theoretical proposals for the physically realistic interaction. Also, for bilayer graphene, the ability to compare spectra for the opposite signs of electric-field-induced interlayer asymmetry might provide additional information about the moire parameters.

  • 4.
    Abergel, David S. L.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Center for Quantum Materials, Sweden.
    Robustness of topologically protected transport in graphene-boron nitride lateral heterostructures2017In: Journal of Physics: Condensed Matter, ISSN 0953-8984, E-ISSN 1361-648X, Vol. 29, no 7, article id 075303Article in journal (Refereed)
    Abstract [en]

    Previously, graphene nanoribbons set in lateral heterostructures with hexagonal boron nitride were predicted to support topologically protected states at low energy. We investigate how robust the transport properties of these states are against lattice disorder. We find that forms of disorder that do not couple the two valleys of the zigzag graphene nanoribbon do not impact the transport properties at low bias, indicating that these lateral heterostructures are very promising candidates for chip-scale conducting interconnects. Forms of disorder that do couple the two valleys, such as vacancies in the graphene ribbon, or substantial inclusions of armchair edges at the graphene-hexagonal boron nitride interface will negatively affect the transport. However, these forms of disorder are not commonly seen in current experiments.

  • 5. Abolmasov, Pavel
    et al.
    Poutanen, Juri
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Gamma-ray opacity of the anisotropic stratified broad-line regions in blazars2017In: Monthly notices of the Royal Astronomical Society, ISSN 0035-8711, E-ISSN 1365-2966, Vol. 464, no 1, p. 152-169Article in journal (Refereed)
    Abstract [en]

    The GeV-range spectra of blazars are shaped not only by non-thermal emission processes internal to the relativistic jet but also by external pair-production absorption on the thermal emission of the accretion disc and the broad-line region (BLR). For the first time, we compute here the pair-production opacities in the GeV range produced by a realistic BLR accounting for the radial stratification and radiation anisotropy. Using photoionization modelling with the CLOUDY code, we calculate a series of BLR models of different sizes, geometries, cloud densities, column densities and metallicities. The strongest emission features in the model BLR are Ly alpha and He II Ly alpha. Contribution of recombination continua is smaller, especially for hydrogen, because Ly continuum is efficiently trapped inside the large optical depth BLR clouds and converted to Lyman emission lines and higher order recombination continua. The largest effects on the gamma-ray opacity are produced by the BLR geometry and localization of the gamma-ray source. We show that when the gamma-ray source moves further from the central source, all the absorption details move to higher energies and the overall level of absorption drops because of decreasing incidence angles between the gamma-rays and BLR photons. The observed positions of the spectral breaks can be used to measure the geometry and the location of the gamma-ray emitting region relative to the BLR. Strong dependence on geometry means that the soft photons dominating the pair-production opacity may be actually produced by a different population of BLR clouds than the bulk of the observed broad line emission.

  • 6.
    Abraham, Mark James
    et al.
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Murtola, T.
    Schulz, R.
    Páll, Szilárd
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Smith, J. C.
    Hess, Berk
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindahl, Erik
    KTH, School of Engineering Sciences (SCI), Theoretical Physics, Theoretical & Computational Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gromacs: High performance molecular simulations through multi-level parallelism from laptops to supercomputers2015In: SoftwareX, ISSN 2352-7110, Vol. 1-2, p. 19-25Article in journal (Refereed)
    Abstract [en]

    GROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, preparation and analysis tools. Several advanced techniques for free-energy calculations are supported. In version 5, it reaches new performance heights, through several new and enhanced parallelization algorithms. These work on every level; SIMD registers inside cores, multithreading, heterogeneous CPU-GPU acceleration, state-of-the-art 3D domain decomposition, and ensemble-level parallelization through built-in replica exchange and the separate Copernicus framework. The latest best-in-class compressed trajectory storage format is supported.

  • 7. Abrahamsson, T. R.
    et al.
    Jakobsson, H. E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, B.
    Engstrand, Lars
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, M. C.
    Low gut microbiota diversity in early infancy precedes asthma at school age2014In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 44, no 6, p. 842-850Article in journal (Refereed)
    Abstract [en]

    Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.

  • 8. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Hedvig E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björksten, Bengt
    Engstrand, Lars
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jenmalm, Maria C.
    Gut microbiota diversity and atopic disease: Does breast-feeding play a role? Reply2013In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 131, no 1, p. 248-249Article in journal (Other academic)
  • 9. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Hedvig E.
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Björkstén, Bengt
    Engstrand, Lars
    Jenmalm, Maria C.
    Low diversity of the gut microbiota in infants with atopic eczema2012In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 129, no 2, p. 434-U244Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.

  • 10. Acero Sanchez, Josep Ll.
    et al.
    Joda, Hamdi
    Henry, Olivier Y. F.
    Solnestam, Beata W.
    Kvastad, Linda
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sahlén, Pelin
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Laddach, Nadja
    Ramakrishnan, Dheeraj
    Riley, Ian
    Schwind, Carmen
    Latta, Daniel
    O'Sullivan, Ciara K.
    Electrochemical Genetic Profiling of Single Cancer Cells2017In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 89, no 6, p. 3378-3385Article in journal (Refereed)
    Abstract [en]

    Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection. Cells were isolated using laser capture and lysed, and the mRNA was extracted and transcribed into DNA. Seven markers were amplified by MLPA, which allows for the simultaneous amplification of multiple targets with a single primer pair, using MLPA probes containing unique barcode sequences. Capture probes complementary to each of these barcode sequences were immobilized on a printed circuit board (PCB) manufactured electrode array and exposed to single-stranded MLPA products and subsequently to a single stranded DNA reporter probe bearing a HRP molecule, followed by substrate addition and fast electrochemical pulse amperometric detection. We present asimple, rapid, flexible, and inexpensive approach for the simultaneous quantification of multiple breast cancer related mRNA markers, with single tumor cell sensitivity.

  • 11. Adiels, Martin
    et al.
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Taskinen, Marja-Riitta
    Boren, Jan
    Kinetic Studies to Elucidate Impaired Metabolism of Triglyceride-rich Lipoproteins in Humans2015In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 6, article id 342Article, review/survey (Refereed)
    Abstract [en]

    To develop novel strategies for prevention and treatment of dyslipidemia, it is essential to understand the pathophysiology of dyslipoproteinemia in humans. Lipoprotein metabolism is a complex system in which abnormal concentrations of various lipoprotein particles can result from alterations in their rates of production, conversion, and/or catabolism. Traditional methods that measure plasma lipoprotein concentrations only provide static estimates of lipoprotein metabolism and hence limited mechanistic information. By contrast, the use of tracers labeled with stable isotopes and mathematical modeling, provides us with a powerful tool for probing lipid and lipoprotein kinetics in vivo and furthering our understanding of the pathogenesis of dyslipoproteinemia.

  • 12. Adori, Csaba
    et al.
    Barde, Swapnali
    Bogdanovic, Nenad
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Karolinska Institutet, Sweden.
    Reinscheid, Rainer R.
    Kovacs, Gabor G.
    Hokfelt, Tomas
    Neuropeptide S- and Neuropeptide S receptor-expressing neuron populations in the human pons2015In: Frontiers in Neuroanatomy, ISSN 1662-5129, E-ISSN 1662-5129, Vol. 9Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide with potent pharmacological effects. In rodents, NPS is expressed in a few pontine cell clusters. Its receptor (NPSR1) is, however, widely distributed in the brain. The anxiolytic and arousal promoting effects of NPS make the NPS NPSR1 system an interesting potential drug target in mood-related disorders. However, so far possible disease-related mechanisms involving NPS have only been studied in rodents. To validate the relevance of these animal studies for i.a. drug development, we have explored the distribution of NPS-expressing neurons in the human pons using in situ hybridization and stereological methods and we compared the distribution of NPS mRNA expressing neurons in the human and rat brain. The calculation revealed a total number of 22,317 +/- 2411 NPS mRNA-positive neurons in human, bilaterally. The majority of cells (84%) were located in the parabrachial area in human: in the extension of the medial and lateral parabrachial nuclei, in the Kolliker-Fuse nucleus and around the adjacent lateral lemniscus. In human, in sharp contrast to the rodents, only very few NPS-positive cells (5%) were found close to the locus coeruleus. In addition, we identified a smaller cell cluster (11% of all NPS cells) in the pontine central gray matter both in human and rat, which has not been described previously even in rodents. We also examined the distribution of NPSR1 mRNA-expressing neurons in the human pons. These cells were mainly located in the rostral laterodorsal tegmental nucleus, the cuneiform nucleus, the microcellular tegmental nucleus region and in the periaqueductal gray. Our results show that both NPS and NPSR1 in the human pons are preferentially localized in regions of importance for integration of visceral autonomic information and emotional behavior. The reported interspecies differences must, however, be considered when looking for targets for new pharmacotherapeutical interventions.

  • 13. Adori, Csaba
    et al.
    Barde, Swapnali
    Vas, Szilvia
    Ebner, Karl
    Su, Jie
    Svensson, Camilla
    Mathé, Aleksander A.
    Singewald, Nicolas
    Reinscheid, Rainer R.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Bagdy, Gyorgy
    Hökfelt, Tomas
    Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study2016In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, no 7, p. 3521-3546Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

  • 14. Adori, Csaba
    et al.
    Glueck, Laura
    Barde, Swapnali
    Yoshitake, Takashi
    Kovacs, Gabor G.
    Mulder, Jan
    Magloczky, Zsofia
    Havas, Laszlo
    Boelcskei, Kata
    Mitsios, Nicholas
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Szolcsanyi, Janos
    Kehr, Jan
    Ronnback, Annica
    Schwartz, Thue
    Rehfeld, Jens F.
    Harkany, Tibor
    Palkovits, Miklos
    Schulz, Stefan
    Hokfelt, Tomas
    Critical role of somatostatin receptor 2 in the vulnerability of the central noradrenergic system: new aspects on Alzheimer's disease2015In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 129, no 4, p. 541-563Article in journal (Refereed)
    Abstract [en]

    Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine beta-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2 (-/-) mice and, unlike in Sstr1 (-/-) or Sstr4 (-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (< 8 months) in Sstr2 (-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.

  • 15. Aebersold, Ruedi
    et al.
    Agar, Jeffrey N.
    Amster, I. Jonathan
    Baker, Mark S.
    Bertozzi, Carolyn R.
    Boja, Emily S.
    Costello, Catherine E.
    Cravatt, Benjamin F.
    Fenselau, Catherine
    Garcia, Benjamin A.
    Ge, Ying
    Gunawardena, Jeremy
    Hendrickson, Ronald C.
    Hergenrother, Paul J.
    Huber, Christian G.
    Ivanov, Alexander R.
    Jensen, Ole N.
    Jewett, Michael C.
    Kelleher, Neil L.
    Kiessling, Laura L.
    Krogan, Nevan J.
    Larsen, Martin R.
    Loo, Joseph A.
    Loo, Rachel R. Ogorzalek
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
    MacCoss, Michael J.
    Mallick, Parag
    Mootha, Vamsi K.
    Mrksich, Milan
    Muir, Tom W.
    Patrie, Steven M.
    Pesavento, James J.
    Pitteri, Sharon J.
    Rodriguez, Henry
    Saghatelian, Alan
    Sandoval, Wendy
    Schluter, Hartmut
    Sechi, Salvatore
    Slavoff, Sarah A.
    Smith, Lloyd M.
    Snyder, Michael P.
    Thomas, Paul M.
    Uhlen, Mathias
    Van Eyk, Jennifer E.
    Vidal, Marc
    Walt, David R.
    White, Forest M.
    Williams, Evan R.
    Wohlschlager, Therese
    Wysocki, Vicki H.
    Yates, Nathan A.
    Young, Nicolas L.
    Zhang, Bing
    How many human proteoforms are there?2018In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 14, no 3, p. 206-214Article in journal (Refereed)
    Abstract [en]

    Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.

  • 16.
    af Klinteberg, Ludvig
    et al.
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Numerical Analysis, NA. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Tornberg, Anna-Karin
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Numerical Analysis, NA. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    A fast integral equation method for solid particles in viscous flow using quadrature by expansion2016In: Journal of Computational Physics, ISSN 0021-9991, E-ISSN 1090-2716, Vol. 326, p. 420-445Article in journal (Refereed)
    Abstract [en]

    Boundary integral methods are advantageous when simulating viscous flow around rigid particles, due to the reduction in number of unknowns and straightforward handling of the geometry. In this work we present a fast and accurate framework for simulating spheroids in periodic Stokes flow, which is based on the completed double layer boundary integral formulation. The framework implements a new method known as quadrature by expansion (QBX), which uses surrogate local expansions of the layer potential to evaluate it to very high accuracy both on and off the particle surfaces. This quadrature method is accelerated through a newly developed precomputation scheme. The long range interactions are computed using the spectral Ewald (SE) fast summation method, which after integration with QBX allows the resulting system to be solved in M log M time, where M is the number of particles. This framework is suitable for simulations of large particle systems, and can be used for studying e.g. porous media models.

  • 17.
    Afkham, Heydar Maboudi
    et al.
    KTH, School of Computer Science and Communication (CSC).
    Qiu, Xuanbin
    KTH, School of Computer Science and Communication (CSC).
    The, Matthew
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Käll, Lukas
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uncertainty estimation of predictions of peptides' chromatographic retention times in shotgun proteomics2017In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 33, no 4, p. 508-513Article in journal (Refereed)
    Abstract [en]

    Motivation: Liquid chromatography is frequently used as a means to reduce the complexity of peptide-mixtures in shotgun proteomics. For such systems, the time when a peptide is released from a chromatography column and registered in the mass spectrometer is referred to as the peptide's retention time. Using heuristics or machine learning techniques, previous studies have demonstrated that it is possible to predict the retention time of a peptide from its amino acid sequence. In this paper, we are applying Gaussian Process Regression to the feature representation of a previously described predictor ELUDE. Using this framework, we demonstrate that it is possible to estimate the uncertainty of the prediction made by the model. Here we show how this uncertainty relates to the actual error of the prediction. Results: In our experiments, we observe a strong correlation between the estimated uncertainty provided by Gaussian Process Regression and the actual prediction error. This relation provides us with new means for assessment of the predictions. We demonstrate how a subset of the peptides can be selected with lower prediction error compared to the whole set. We also demonstrate how such predicted standard deviations can be used for designing adaptive windowing strategies.

  • 18. Agarwal, Abhishek
    et al.
    Lipstein, Arthur E.
    Young, Donovan
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Scattering amplitudes of massive N = 2 gauge theories in three dimensions2014In: Physical Review D, ISSN 1550-7998, E-ISSN 1550-2368, Vol. 89, no 4, p. 045020-Article in journal (Refereed)
    Abstract [en]

    We study the scattering amplitudes of mass-deformed Chern-Simons theories and Yang-Mills-Chern-Simons theories with N = 2 supersymmetry in three dimensions. In particular, we derive the on-shell supersymmetry algebras which underlie the scattering matrices of these theories. We then compute various 3 and 4-point on-shell tree-level amplitudes in these theories. For the mass-deformed Chern-Simons theory, odd-point amplitudes vanish and we find that all of the 4-point amplitudes can be encoded elegantly in superamplitudes. For the Yang-Mills-Chern-Simons theory, we obtain all of the 4-point tree-level amplitudes using a combination of perturbative techniques and algebraic constraints and we comment on difficulties related to computing amplitudes with external gauge fields using Feynman diagrams. Finally, we propose a Britto-Cachazo-Feng-Witten recursion relation for mass-deformed theories in three dimensions and discuss the applicability of this proposal to mass-deformed N = 2 theories.

  • 19. Agarwal, Akshat
    et al.
    Brandt, Luca
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, Centres, SeRC - Swedish e-Science Research Centre. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW.
    Zaki, Tamer A.
    Linear and nonlinear evolution of a localized disturbance in polymeric channel flow2014In: Journal of Fluid Mechanics, ISSN 0022-1120, E-ISSN 1469-7645, Vol. 760, p. 278-303Article in journal (Refereed)
    Abstract [en]

    The evolution of an initially localized disturbance in polymeric channel flow is investigated, with the FENE-P model used to characterize the viscoelastic behaviour of the flow. In the linear growth regime, the flow response is stabilized by viscoelasticity, and the maximum attainable disturbance energy amplification is reduced with increasing polymer concentration. The reduction in the energy growth rate is attributed to the polymer work, which plays a dual role. First, a spanwise polymer-work term develops, and is explained by the tilting action of the wall-normal voracity on the mean streamwise conformation tensor. This resistive term weakens the spanwise velocity perturbation thus reducing the energy of the localized disturbance. The second action of the polymer is analogous, with a wall-normal polymer work term that weakens the vertical velocity perturbation. Its indirect effect on energy growth is substantial since it reduces the production of Reynolds shear stress and in turn of the streamwise velocity perturbation, or streaks. During the early stages of nonlinear growth, the dominant effect of the polymer is to suppress the large-scale streaky structures which are strongly amplified in Newtonian flows. As a result, the process of transition to turbulence is prolonged and, after transition, a drag-reduced turbulent state is attained.

  • 20. Agarwal, S.
    et al.
    Wettlaufer, J. S.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Yale University, New Haven, CT, USA; Mathematical Institute, University of Oxford, Oxford, UK.
    Fluctuations in Arctic sea-ice extent: Comparing observations and climate models2018In: Philosophical Transactions. Series A: Mathematical, physical, and engineering science, ISSN 1364-503X, E-ISSN 1471-2962, Vol. 376, no 2129, article id 20170332Article in journal (Refereed)
    Abstract [en]

    The fluctuation statistics of the observed sea-ice extent during the satellite era are compared with model output from CMIP5 models using a multifractal time series method. The two robust features of the observations are that on annual to biannual time scales the ice extent exhibits white noise structure, and there is a decadal scale trend associated with the decay of the ice cover. It is shown that (i) there is a large inter-model variability in the time scales extracted from the models, (ii) none of the models exhibits the decadal time scales found in the satellite observations, (iii) five of the 21 models examined exhibit the observed white noise structure, and (iv) the multi-model ensemble mean exhibits neither the observed white noise structure nor the observed decadal trend. It is proposed that the observed fluctuation statistics produced by this method serve as an appropriate test bed for modelling studies. 

  • 21. Agarwal, Sahil
    et al.
    Del Sordo, Fabio
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Wettlaufer, John S.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    EXOPLANETARY DETECTION BY MULTIFRACTAL SPECTRAL ANALYSIS2017In: Astronomical Journal, ISSN 0004-6256, E-ISSN 1538-3881, Vol. 153, no 1, article id 12Article in journal (Refereed)
    Abstract [en]

    Owing to technological advances, the number of exoplanets discovered has risen dramatically in the last few years. However, when trying to observe Earth analogs, it is often difficult to test the veracity of detection. We have developed a new approach to the analysis of exoplanetary spectral observations based on temporal multifractality, which identifies timescales that characterize planetary orbital motion around the host star and those that arise from stellar features such as spots. Without fitting stellar models to spectral data, we show how the planetary signal can be robustly detected from noisy data using noise amplitude as a source of information. For observation of transiting planets, combining this method with simple geometry allows us to relate the timescales obtained to primary and secondary eclipse of the exoplanets. Making use of data obtained with ground-based and space-based observations we have tested our approach on HD 189733b. Moreover, we have investigated the use of this technique in measuring planetary orbital motion via Doppler shift detection. Finally, we have analyzed synthetic spectra obtained using the SOAP 2.0 tool, which simulates a stellar spectrum and the influence of the presence of a planet or a spot on that spectrum over one orbital period. We have demonstrated that, so long as the signal-to-noise-ratio >= 75, our approach reconstructs the planetary orbital period, as well as the rotation period of a spot on the stellar surface.

  • 22. Agarwal, Sahil
    et al.
    Wettlaufer, John S.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Maximal stochastic transport in the Lorenz equations2016In: Physics Letters A, ISSN 0375-9601, E-ISSN 1873-2429, Vol. 380, no 1-2, p. 142-146Article in journal (Refereed)
    Abstract [en]

    We calculate the stochastic upper bounds for the Lorenz equations using an extension of the background method. In analogy with Rayleigh-Benard convection the upper bounds are for heat transport versus Rayleigh number. As might be expected, the stochastic upper bounds are larger than the deterministic counterpart of Souza and Doering [1], but their variation with noise amplitude exhibits interesting behavior. Below the transition to chaotic dynamics the upper bounds increase monotonically with noise amplitude. However, in the chaotic regime this monotonicity depends on the number of realizations in the ensemble; at a particular Rayleigh number the bound may increase or decrease with noise amplitude. The origin of this behavior is the coupling between the noise and unstable periodic orbits, the degree of which depends on the degree to which the ensemble represents the ergodic set. This is confirmed by examining the close returns plots of the full solutions to the stochastic equations and the numerical convergence of the noise correlations. The numerical convergence of both the ensemble and time averages of the noise correlations is sufficiently slow that it is the limiting aspect of the realization of these bounds. Finally, we note that the full solutions of the stochastic equations demonstrate that the effect of noise is equivalent to the effect of chaos.

  • 23. Agarwal, Sahil
    et al.
    Wettlaufer, John S.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Yale University, United States; University of Oxford, United Kingdom.
    The Statistical Properties of Sea Ice Velocity Fields2017In: Journal of Climate, ISSN 0894-8755, E-ISSN 1520-0442, Vol. 30, no 13, p. 4873-4881Article in journal (Refereed)
    Abstract [en]

    By arguing that the surface pressure field over the Arctic Ocean can be treated as an isotropic, stationary, homogeneous, Gaussian random field, Thorndike estimated a number of covariance functions from two years of data (1979 and 1980). Given the active interest in changes of general circulation quantities and indices in the polar regions during the recent few decades, the spatial correlations in sea ice velocity fields are of particular interest. It is thus natural to ask, "How persistent are these correlations?'' To this end, a multifractal stochastic treatment is developed to analyze observed Arctic sea ice velocity fields from satellites and buoys for the period 1978-2015. Since it was previously found that the Arctic equivalent ice extent (EIE) has a white noise structure on annual to biannual time scales, the connection between EIE and ice motion is assessed. The long-term stationarity of the spatial correlation structure of the velocity fields and the robustness of their white noise structure on multiple time scales is demonstrated; these factors (i) combine to explain the white noise characteristics of the EIE on annual to biannual time scales and (ii) explain why the fluctuations in the ice velocity are proportional to fluctuations in the geostrophic winds on time scales of days to months. Moreover, it is shown that the statistical structure of these two quantities is commensurate from days to years, which may be related to the increasing prevalence of free drift in the ice pack.

  • 24. Agostinho, A.
    et al.
    Kouznetsova, A.
    Hernández-Hernández, A.
    Bernhem, Kristoffer
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höög, C.
    Sexual dimorphism in the width of the mouse synaptonemal complex2018In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 131, no 5, article id jcs212548Article in journal (Refereed)
    Abstract [en]

    Sexual dimorphism has been used to describe morphological differences between the sexes, but can be extended to any biologically related process that varies between males and females. The synaptonemal complex (SC) is a tripartite structure that connects homologous chromosomes in meiosis. Here, aided by superresolution microscopy techniques, we show that the SC is subject to sexual dimorphism, in mouse germ cells. We have identified a significantly narrower SC in oocytes and have established that this difference does not arise from a different organization of the lateral elements nor from a different isoform of transverse filament protein SYCP1. Instead, we provide evidence for the existence of a narrower central element and a different integration site for the C-termini of SYCP1, in females. In addition to these female-specific features, we speculate that post-translation modifications affecting the SYCP1 coiled-coil region could render a more compact conformation, thus contributing to the narrower SC observed in females.

  • 25. Agostinho, Ana
    et al.
    Manneberg, Otto
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van Schendel, Robin
    Hernandez-Hernandez, Abrahan
    Kouznetsova, Anna
    Blom, Hans
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Höög, Christer
    High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation2016In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 17, no 6, p. 901-913Article in journal (Refereed)
    Abstract [en]

    During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.

  • 26.
    Aguilar, Xavier
    et al.
    KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Fürlinger, K.
    Laure, Erwin
    KTH, Centres, SeRC - Swedish e-Science Research Centre. KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Online MPI trace compression using event flow graphs and wavelets2016In: Procedia Computer Science, Elsevier, 2016, p. 1497-1506Conference paper (Refereed)
    Abstract [en]

    Performance analysis of scientific parallel applications is essential to use High Performance Computing (HPC) infrastructures efficiently. Nevertheless, collecting detailed data of large-scale parallel programs and long-running applications is infeasible due to the huge amount of performance information generated. Even though there are no technological constraints in storing Terabytes of performance data, the constant flushing of such data to disk introduces a massive overhead into the application that makes the performance measurements worthless. This paper explores the use of Event flow graphs together with wavelet analysis and EZW-encoding to provide MPI event traces that are orders of magnitude smaller while preserving accurate information on timestamped events. Our mechanism compresses the performance data online while the application runs, thus, reducing the pressure put on the I/O system due to buffer flushing. As a result, we achieve lower application perturbation, reduced performance data output, and the possibility to monitor longer application runs. © The Authors. Published by Elsevier B.V.

  • 27.
    Aguilar, Xavier
    et al.
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Schliephake, Michael
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Gimenez, Judit
    Laure, Erwin
    KTH, School of Computer Science and Communication (CSC), High Performance Computing and Visualization (HPCViz). KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Scalability analysis of Dalton, a molecular structure program2013In: Future generations computer systems, ISSN 0167-739X, E-ISSN 1872-7115, Vol. 29, no 8, p. 2197-2204Article in journal (Refereed)
    Abstract [en]

    Dalton is a molecular electronic structure program featuring common methods of computational chemistry that are based on pure quantum mechanics (QM) as well as hybrid quantum mechanics/molecular mechanics (QM/MM). It is specialized and has a leading position in calculation of molecular properties with a large world-wide user community (over 2000 licenses issued). In this paper, we present a performance characterization and optimization of Dalton. We also propose a solution to avoid the master/worker design of Dalton to become a performance bottleneck for larger process numbers. With these improvements we obtain speedups of 4x, increasing the parallel efficiency of the code and being able to run in it in a much bigger number of cores.

  • 28. Ahmad, Yasmeen
    et al.
    Boisvert, Francois-Michel
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lamond, Angus I.
    Systematic Analysis of Protein Pools, Isoforms, and Modifications Affecting Turnover and Subcellular Localization2012In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 11, no 3Article in journal (Refereed)
    Abstract [en]

    In higher eukaryotes many genes encode protein isoforms whose properties and biological roles are often poorly characterized. Here we describe systematic approaches for detection of either distinct isoforms, or separate pools of the same isoform, with differential biological properties. Using information from ion intensities we have estimated protein abundance levels and using rates of change in stable isotope labeling with amino acids in cell culture isotope ratios we measured turnover rates and subcellular distribution for the HeLa cell proteome. Protein isoforms were detected using three data analysis strategies that evaluate differences between stable isotope labeling with amino acids in cell culture isotope ratios for specific groups of peptides within the total set of peptides assigned to a protein. The candidate approach compares stable isotope labeling with amino acids in cell culture isotope ratios for predicted isoform- specific peptides, with ratio values for peptides shared by all the isoforms. The rule of thirds approach compares the mean isotope ratio values for all peptides in each of three equal segments along the linear length of the protein, assessing differences between segment values. The three in a row approach compares mean isotope ratio values for each sequential group of three adjacent peptides, assessing differences with the mean value for all peptides assigned to the protein. Protein isoforms were also detected and their properties evaluated by fractionating cell extracts on one- dimensional SDS- PAGE prior to trypsin digestion and MS analysis and independently evaluating isotope ratio values for the same peptides isolated from different gel slices. The effect of protein phosphorylation on turnover rates was analyzed by comparing mean turnover values calculated for all peptides assigned to a protein, either including, or excluding, values for cognate phosphopeptides. Collectively, these experimental and analytical approaches provide a framework for expanding the func- tional annotation of the genome.

  • 29.
    Ahmadian, Afshin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    AnderssonSvahn, Helene
    KTH, School of Biotechnology (BIO), Nano Biotechnology (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Massively parallel sequencing platforms using lab on a chip technologies2011In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 11, no 16, p. 2653-2655Article in journal (Refereed)
  • 30. Ahmadinejad, F.
    et al.
    Møller, S. G.
    Hashemzadeh-Chaleshtori, M.
    Bidkhori, Gholamreza
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Jami, M. -S
    Molecular mechanisms behind free radical scavengers function against oxidative stress2017In: Antioxidants, ISSN 2076-3921, Vol. 6, no 3, article id 51Article in journal (Refereed)
    Abstract [en]

    Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimers disease, Parkinsons disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinsons disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS). Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA) used routinely in the treatment of Parkinsons disease (not as a free radical scavenger), and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone) that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1). Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein) with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

  • 31. Ahmed, Engy
    et al.
    Hugerth, Luisa W.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Logue, Jürg Brendan
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bruchert, Volker
    Andersson, Anders F.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Holmström, Sara J. M.
    Mineral Type Structures Soil Microbial Communities2017In: Geomicrobiology Journal, ISSN 0149-0451, E-ISSN 1521-0529, Vol. 34, no 6, p. 538-545Article in journal (Refereed)
    Abstract [en]

    Soil microorganisms living in close contact with minerals play key roles in the biogeochemical cycling of elements, soil formation, and plant nutrition. Yet, the composition of microbial communities inhabiting the mineralosphere (i.e., the soil surrounding minerals) is poorly understood. Here, we explored the composition of soil microbial communities associated with different types of minerals in various soil horizons. To this effect, a field experiment was set up in which mineral specimens of apatite, biotite, and oligoclase were buried in the organic, eluvial, and upper illuvial horizons of a podzol soil. After an incubation period of two years, the soil attached to the mineral surfaces was collected, and microbial communities were analyzed by means of Illumina MiSeq sequencing of the 16S (prokaryotic) and 18S (eukaryotic) ribosomal RNA genes. We found that both composition and diversity of bacterial, archaeal, and fungal communities varied across the different mineral surfaces, and that mineral type had a greater influence on structuring microbial assemblages than soil horizon. Thus, our findings emphasize the importance of mineral surfaces as ecological niches in soils.

  • 32. Ahmed, T.
    et al.
    Albers, R. C.
    Balatsky, Alexander V.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Friedrich, C.
    Zhu, J. -X
    G W quasiparticle calculations with spin-orbit coupling for the light actinides2014In: Physical Review B. Condensed Matter and Materials Physics, ISSN 1098-0121, E-ISSN 1550-235X, Vol. 89, no 3, p. 035104-Article in journal (Refereed)
    Abstract [en]

    We report on the importance of GW self-energy corrections for the electronic structure of light actinides in the weak-to-intermediate coupling regime. Our study is based on calculations of the band structure and total density of states of Np, U, and Pu using a one-shot GW approximation that includes spin-orbit coupling within a full potential LAPW framework. We also present RPA screened effective Coulomb interactions for the f-electron orbitals for different lattice constants, and show that there is an increased contribution from electron-electron correlation in these systems for expanded lattices. We find a significant amount of electronic correlation in these highly localized electronic systems.

  • 33. Ahmed, Towfiq
    et al.
    Haraldsen, Jason T.
    Rehr, John J.
    Di Ventra, Massimiliano
    Schuller, Ivan
    Balatsky, Alexander V.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases2014In: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 25, no 12, p. 125705-Article in journal (Refereed)
    Abstract [en]

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new 'multi-point cross-correlation' technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.

  • 34. Ahmed, Towfiq
    et al.
    Haraldsen, Jason T.
    Zhu, Jian-Xin
    Balatsky, Alexander V.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA. Institute for Materials Science, Los Alamos National Laboratory, United States.
    Next-Generation Epigenetic Detection Technique: Identifying Methylated Cytosine Using Graphene Nanopore2014In: Journal of Physical Chemistry Letters, ISSN 1948-7185, E-ISSN 1948-7185, Vol. 5, no 15, p. 2601-2607Article in journal (Refereed)
    Abstract [en]

    DNA methylation plays a pivotal role in the genetic evolution of both embryonic and adult cells. For adult somatic cells, the location and dynamics of methylation have been very precisely pinned down with the 5-cytosine markers on cytosine-phosphate-guanine (CpG) units. Unusual methylation on CpG islands is identified as one of the prime causes for silencing the tumor suppressant genes. Early detection of methylation changes can diagnose the potentially harmful oncogenic evolution of cells and provide promising guideline for cancer prevention. With this motivation, we propose a cytosine methylation detection technique. Our hypothesis is that electronic signatures of DNA acquired as a molecule translocates through a nanopore would be significantly different for methylated and nonmethylated bases. This difference in electronic fingerprints would allow for reliable real-time differentiation of methylated DNA. We calculate transport currents through a punctured graphene membrane while the cytosine and methylated cytosine translocate through the nanopore. We also calculate the transport properties for uracil and cyanocytosine for comparison. Our calculations of transmission, current, and tunneling conductance show distinct signatures in their spectrum for each molecular type. Thus, in this work, we provide a theoretical analysis that points to a viability of our hypothesis.

  • 35. Aidas, Kestutis
    et al.
    Angeli, Celestino
    Bak, Keld L.
    Bakken, Vebjorn
    Bast, Radovan
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Boman, Linus
    Christiansen, Ove
    Cimiraglia, Renzo
    Coriani, Sonia
    Dahle, Pal
    Dalskov, Erik K.
    Ekstrom, Ulf
    Enevoldsen, Thomas
    Eriksen, Janus J.
    Ettenhuber, Patrick
    Fernandez, Berta
    Ferrighi, Lara
    Fliegl, Heike
    Frediani, Luca
    Hald, Kasper
    Halkier, Asger
    Hattig, Christof
    Heiberg, Hanne
    Helgaker, Trygve
    Hennum, Alf Christian
    Hettema, Hinne
    Hjertenaes, Eirik
    Host, Stinne
    Hoyvik, Ida-Marie
    Iozzi, Maria Francesca
    Jansik, Branislav
    Jensen, Hans Jorgen Aa.
    Jonsson, Dan
    Jorgensen, Poul
    Kauczor, Joanna
    Kirpekar, Sheela
    Kjrgaard, Thomas
    Klopper, Wim
    Knecht, Stefan
    Kobayashi, Rika
    Koch, Henrik
    Kongsted, Jacob
    Krapp, Andreas
    Kristensen, Kasper
    Ligabue, Andrea
    Lutnaes, Ola B.
    Melo, Juan I.
    Mikkelsen, Kurt V.
    Myhre, Rolf H.
    Neiss, Christian
    Nielsen, Christian B.
    Norman, Patrick
    Olsen, Jeppe
    Olsen, Jogvan Magnus H.
    Osted, Anders
    Packer, Martin J.
    Pawlowski, Filip
    Pedersen, Thomas B.
    Provasi, Patricio F.
    Reine, Simen
    Rinkevicius, Zilvinas
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Ruden, Torgeir A.
    Ruud, Kenneth
    Rybkin, Vladimir V.
    Salek, Pawel
    Samson, Claire C. M.
    de Meras, Alfredo Sanchez
    Saue, Trond
    Sauer, Stephan P. A.
    Schimmelpfennig, Bernd
    Sneskov, Kristian
    Steindal, Arnfinn H.
    Sylvester-Hvid, Kristian O.
    Taylor, Peter R.
    Teale, Andrew M.
    Tellgren, Erik I.
    Tew, David P.
    Thorvaldsen, Andreas J.
    Thogersen, Lea
    Vahtras, Olav
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Watson, Mark A.
    Wilson, David J. D.
    Ziolkowski, Marcin
    Ågren, Hans
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    The Dalton quantum chemistry program system2014In: Wiley Interdisciplinary Reviews. Computational Molecular Science, ISSN 1759-0876, Vol. 4, no 3, p. 269-284Article in journal (Refereed)
    Abstract [en]

    Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.

  • 36. Ajello, M.
    et al.
    Atwood, W. B.
    Baldini, L.
    Ballet, J.
    Barbiellini, G.
    Bastieri, D.
    Bellazzini, R.
    Bissaldi, E.
    Blandford, R. D.
    Bloom, E. D.
    Bonino, R.
    Bregeon, J.
    Britto, R. J.
    Bruel, P.
    Buehler, R.
    Buson, S.
    Cameron, R. A.
    Caputo, R.
    Caragiulo, M.
    Caraveo, P. A.
    Cavazzuti, E.
    Cecchi, C.
    Charles, E.
    Chekhtman, A.
    Cheung, C. C.
    Chiaro, G.
    Ciprini, S.
    Cohen, J. M.
    Costantin, D.
    Costanza, F.
    Cuoco, A.
    Cutini, S.
    D'Ammando, F.
    de Palma, F.
    Desiante, R.
    Digel, S. W.
    Di Lalla, N.
    Di Mauro, M.
    Di Venere, L.
    Dominguez, A.
    Drell, P. S.
    Dumora, D.
    Favuzzi, C.
    Fegan, S. J.
    Ferrara, E. C.
    Fortin, P.
    Franckowiak, A.
    Fukazawa, Y.
    Funk, S.
    Fusco, P.
    Gargano, F.
    Gasparrini, D.
    Giglietto, N.
    Giommi, P.
    Giordano, F.
    Giroletti, M.
    Glanzman, T.
    Green, D.
    Grenier, I. A.
    Grondin, M. -H
    Grove, J. E.
    Guillemot, L.
    Guiriec, S.
    Harding, A. K.
    Hays, E.
    Hewitt, J. W.
    Horan, D.
    Jóhannesson, Gudlaugur
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Kensei, S.
    Kuss, M.
    La Mura, G.
    Larsson, Stefan
    KTH, School of Engineering Sciences (SCI), Physics, Particle and Astroparticle Physics.
    Latronico, L.
    Lemoine-Goumard, M.
    Li, J.
    Longo, F.
    Loparco, F.
    Lott, B.
    Lubrano, P.
    Magill, J. D.
    Maldera, S.
    Manfreda, A.
    Mazziotta, M. N.
    McEnery, J. E.
    Meyer, M.
    Michelson, P. F.
    Mirabal, N.
    Mitthumsiri, W.
    Mizuno, T.
    Moiseev, A. A.
    Monzani, M. E.
    Morselli, A.
    Moskalenko, I. V.
    Negro, M.
    Nuss, E.
    Ohsugi, T.
    Omodei, N.
    Orienti, M.
    Orlando, E.
    Palatiello, M.
    Paliya, V. S.
    Paneque, D.
    Perkins, J. S.
    Persic, M.
    Pesce-Rollins, M.
    Piron, F.
    Porter, T. A.
    Principe, G.
    Raino, S.
    Rando, R.
    Razzano, M.
    Razzaque, S.
    Reimer, A.
    Reimer, O.
    Reposeur, T.
    Parkinson, P. M. Saz
    Sgro, C.
    Simone, D.
    Siskind, E. J.
    Spada, F.
    Spandre, G.
    Spinelli, P.
    Stawarz, L.
    Suson, D. J.
    Takahashi, M.
    Tak, D.
    Thayer, J. G.
    Thayer, J. B.
    Thompson, D. J.
    Torres, D. F.
    Torresi, E.
    Troja, E.
    Vianello, G.
    Wood, K.
    Wood, M.
    3FHL: The Third Catalog of Hard Fermi-LAT Sources2017In: Astrophysical Journal Supplement Series, ISSN 0067-0049, E-ISSN 1538-4365, Vol. 232, no 2, article id 18Article in journal (Refereed)
  • 37.
    Akan, Pelin
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Alexeyenko, Andrey
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Costea, Paul Igor
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hedberg, Lilia
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Werne Solnestam, Beata
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundin, Sverker
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallman, Jimmie
    Lundberg, Emma
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Comprehensive analysis of the genome transcriptome and proteome landscapes of three tumor cell lines2012In: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 4, p. 86-Article in journal (Refereed)
    Abstract [en]

    We here present a comparative genome, transcriptome and functional network analysis of three human cancer cell lines (A431, U251MG and U2OS), and investigate their relation to protein expression. Gene copy numbers significantly influenced corresponding transcript levels; their effect on protein levels was less pronounced. We focused on genes with altered mRNA and/or protein levels to identify those active in tumor maintenance. We provide comprehensive information for the three genomes and demonstrate the advantage of integrative analysis for identifying tumor-related genes amidst numerous background mutations by relating genomic variation to expression/protein abundance data and use gene networks to reveal implicated pathways.

  • 38.
    Akan, Pelin
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Stranneheim, Henrik
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Lexow, Preben
    LingVitae, Oslo.
    Lundeberg, Joakim
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Design and assessment of binary DNA for nanopore sequencing2010In: Genome biology, ISSN 1474-760X, Vol. 11, p. P4-Article in journal (Other academic)
  • 39.
    Akhter, Shirin
    et al.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Kretzschmar, Warren W.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH Royal Inst Technol, Sch Engn Sci Biotechnol Chem & Hlth, Dept Gene Technol, Sci Life Lab, Solna, Sweden..
    Nordal, Veronika
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Delhomme, Nicolas
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Street, Nathaniel R.
    Umea Sweden, Dept Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Nilsson, Ove
    Swedish Univ Agr Sci, Dept Forest Genet & Plant Physiol, Umea Plant Sci Ctr, Umea, Sweden..
    Emanuelsson, Olof
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sundström, Jens F.
    Swedish Univ Agr Sci, Linnean Ctr Plant Biol, Uppsala Bioctr, Dept Plant Biol, Uppsala, Sweden..
    Integrative Analysis of Three RNA Sequencing Methods Identifies Mutually Exclusive Exons of MADS-Box Isoforms During Early Bud Development in Picea abies2018In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 9, article id 1625Article in journal (Refereed)
    Abstract [en]

    Recent efforts to sequence the genomes and transcriptomes of several gymnosperm species have revealed an increased complexity in certain gene families in gymnosperms as compared to angiosperms. One example of this is the gymnosperm sister Glade to angiosperm TM3-like MADS-box genes, which at least in the conifer lineage has expanded in number of genes. We have previously identified a member of this subclade, the conifer gene DEFICIENS AGAMOUS LIKE 19 (DAL19), as being specifically upregulated in cone-setting shoots. Here, we show through Sanger sequencing of mRNA-derived cDNA and mapping to assembled conifer genomic sequences that DAL19 produces six mature mRNA splice variants in Picea abies. These splice variants use alternate first and last exons, while their four central exons constitute a core region present in all six transcripts. Thus, they are likely to be transcript isoforms. Quantitative Real-Time PCR revealed that two mutually exclusive first DAL19 exons are differentially expressed across meristems that will form either male or female cones, or vegetative shoots. Furthermore, mRNA in situ hybridization revealed that two mutually exclusive last DAL19 exons were expressed in a cell-specific pattern within bud meristems. Based on these findings in DAL19, we developed a sensitive approach to transcript isoform assembly from short-read sequencing of mRNA. We applied this method to 42 putative MADS-box core regions in P abies, from which we assembled 1084 putative transcripts. We manually curated these transcripts to arrive at 933 assembled transcript isoforms of 38 putative MADS-box genes. 152 of these isoforms, which we assign to 28 putative MADS-box genes, were differentially expressed across eight female, male, and vegetative buds. We further provide evidence of the expression of 16 out of the 38 putative MADS-box genes by mapping PacBio Iso-Seq circular consensus reads derived from pooled sample sequencing to assembled transcripts. In summary, our analyses reveal the use of mutually exclusive exons of MADS-box gene isoforms during early bud development in P. abies, and we find that the large number of identified MADS-box transcripts in P. abies results not only from expansion of the gene family through gene duplication events but also from the generation of numerous splice variants.

  • 40.
    Akkuratov, Evgeny E.
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. KTH, Centres, Science for Life Laboratory, SciLifeLab. St Petersburg State Univ, Inst Translat Biomed, St Petersburg, Russia.
    Gelfand, Mikhail S.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia.;Natl Res Univ, Higher Sch Econ, Fac Comp Sci, Moscow, Russia.;MM Lomonosov Moscow State Univ, Dept Bioengn & Bioinformat, Moscow, Russia..
    Khrameeva, Ekaterina E.
    Skolkovo Inst Sci & Technol, Ctr Data Intens Biomed & Biotechnol, Moscow, Russia.;Russian Acad Sci, Inst Informat Transmiss Problems, Moscow, Russia..
    Neanderthal and Denisovan ancestry in Papuans: A functional study2018In: Journal of Bioinformatics and Computational Biology, ISSN 0219-7200, E-ISSN 1757-6334, Vol. 16, no 2, article id 1840011Article in journal (Refereed)
    Abstract [en]

    Sequencing of complete nuclear genomes of Neanderthal and Denisovan stimulated studies about their relationship with modern humans demonstrating, in particular, that DNA alleles from both Neanderthal and Denisovan genomes are present in genomes of modern humans. The Papuan genome is a unique object because it contains both Neanderthal and Denisovan alleles. Here, we have shown that the Papuan genomes contain different gene functional groups inherited from each of the ancient people. The Papuan genomes demonstrate a relative prevalence of Neanderthal alleles in genes responsible for the regulation of transcription and neurogenesis. The enrichment of specific functional groups with Denisovan alleles is less pronounced; these groups are responsible for bone and tissue remodeling. This analysis shows that introgression of alleles from Neanderthals and Denisovans to Papuans occurred independently and retention of these alleles may carry specific adaptive advantages.

  • 41. Akrami, Yashar
    et al.
    Koivisto, Tomi S.
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Solomon, Adam R.
    The nature of spacetime in bigravity: Two metrics or none?2015In: General Relativity and Gravitation, ISSN 0001-7701, E-ISSN 1572-9532, Vol. 47, no 1, p. 1838-Article in journal (Refereed)
    Abstract [en]

    The possibility of matter coupling to two metrics at once is considered. This appears natural in the most general ghost-free, bimetric theory of gravity, where it unlocks an additional symmetry with respect to the exchange of the metrics. This double coupling, however, raises the problem of identifying the observables of the theory. It is shown that if the two metrics couple minimally to matter, then there is no physical metric to which all matter would universally couple, and that moreover such an effective metric generically does not exist even for an individual matter species. By studying point particle dynamics, a resolution is suggested in the context of Finsler geometry.

  • 42.
    Akrami, Yashar
    et al.
    Leiden Univ, Lorentz Inst Theoret Phys, POB 9506, NL-2300 RA Leiden, Netherlands..
    Kuhnel, Florian
    Stockholm Univ, AlbaNova, Oskar Klein Ctr Cosmoparticle Phys, Dept Phys, SE-10691 Stockholm, Sweden..
    Sandstad, Marit
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Uncertainties in primordial black-hole constraints on the primordial power spectrum2018In: Physics of the Dark Universe, ISSN 0953-8585, E-ISSN 2212-6864, Vol. 19, p. 124-128Article in journal (Refereed)
    Abstract [en]

    The existence (and abundance) of primordial black holes (PBHs) is governed by the power spectrum of primordial perturbations generated during inflation. So far no PBHs have been observed, and instead, increasingly stringent bounds on their existence at different scales have been obtained. Up until recently, this has been exploited in attempts to constrain parts of the inflationary power spectrum that are unconstrained by cosmological observations. We first point out that the simple translation of the PBH non-observation bounds into constraints on the primordial power spectrum is inaccurate as it fails to include realistic aspects of PBH formation and evolution. We then demonstrate, by studying two examples of uncertainties from the effects of critical and non-spherical collapse, that even though they may seem small, they have important implications for the usefulness of the constraints. In particular, we point out that the uncertainty induced by non-spherical collapse may be much larger than the difference between particular bounds from PBH non-observations and the general maximum cap stemming from the condition Omega <= 1 on the dark-matter density in the form of PBHs. We therefore make the cautious suggestion of applying only the overall maximum dark-matter constraint to models of early Universe, as this requirement seems to currently provide a more reliable constraint, which better reflects our current lack of detailed knowledge of PBH formation. These, and other effects, such as merging, clustering and accretion, may also loosen constraints from non-observations of other primordial compact objects such as ultra-compact minihalos of dark matter. 

  • 43. Albornoz, N. L. Gonzalez
    et al.
    Schmidt-May, Angnis
    von Strauss, Mikael
    KTH, Centres, Nordic Institute for Theoretical Physics NORDITA.
    Dark matter scenarios with multiple spin-2 fields2018In: Journal of Cosmology and Astroparticle Physics, ISSN 1475-7516, E-ISSN 1475-7516, no 1, article id 014Article in journal (Refereed)
    Abstract [en]

    We study ghost-free multimetric theories for (N + 1) tensor fields with a coupling to matter and maximal global symmetry group S-N x (Z(2))(N). Their mass spectra contain a massless mode, the graviton, and N massive spin-2 modes. One of the massive modes is distinct by being the heaviest, the remaining (N - 1) massive modes are simply identical copies of each other. All relevant physics can therefore be understood from the case N = 2. Focussing on this case, we compute the full perturbative action up to cubic order and derive several features that hold to all orders in perturbation theory. The lighter massive mode does not couple to matter and neither of the massive modes decay into massless gravitons. We propose the lighter massive particle as a candidate for dark matter and investigate its phenomenology in the parameter region where the matter coupling is dominated by the massless graviton. The relic density of massive spin-2 can originate from a freeze-in mechanism or from gravitational particle production, giving rise to two different dark matter scenarios. The allowed parameter regions are very different from those in scenarios with only one massive spin-2 field and more accessible to experiments.

  • 44.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lee, Woojoo
    Pernemalm, Maria
    Guegan, Justin
    Dessen, Philippe
    Lazar, Vladimir
    Lehtio, Janne
    Pawitan, Yudi
    Network enrichment analysis: extension of gene-set enrichment analysis to gene networks2012In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 13, p. 226-Article in journal (Refereed)
    Abstract [en]

    Background: Gene-set enrichment analyses (GEA or GSEA) are commonly used for biological characterization of an experimental gene-set. This is done by finding known functional categories, such as pathways or Gene Ontology terms, that are over-represented in the experimental set; the assessment is based on an overlap statistic. Rich biological information in terms of gene interaction network is now widely available, but this topological information is not used by GEA, so there is a need for methods that exploit this type of information in high-throughput data analysis. Results: We developed a method of network enrichment analysis (NEA) that extends the overlap statistic in GEA to network links between genes in the experimental set and those in the functional categories. For the crucial step in statistical inference, we developed a fast network randomization algorithm in order to obtain the distribution of any network statistic under the null hypothesis of no association between an experimental gene-set and a functional category. We illustrate the NEA method using gene and protein expression data from a lung cancer study. Conclusions: The results indicate that the NEA method is more powerful than the traditional GEA, primarily because the relationships between gene sets were more strongly captured by network connectivity rather than by simple overlaps.

  • 45.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nystedt, Björn
    Vezzi, Francesco
    Sherwood, Ellen
    Ye, Rosa
    Knudsen, Bjarne
    Simonsen, Martin
    Turner, Benjamin
    de Jong, Pieter
    Wu, Cheng-Cang
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Efficient de novo assembly of large and complex genomes by massively parallel sequencing of Fosmid pools2014In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, no 1, p. 439-Article in journal (Refereed)
    Abstract [en]

    Background: Sampling genomes with Fosmid vectors and sequencing of pooled Fosmid libraries on the Illumina platform for massive parallel sequencing is a novel and promising approach to optimizing the trade-off between sequencing costs and assembly quality. Results: In order to sequence the genome of Norway spruce, which is of great size and complexity, we developed and applied a new technology based on the massive production, sequencing, and assembly of Fosmid pools (FP). The spruce chromosomes were sampled with similar to 40,000 bp Fosmid inserts to obtain around two-fold genome coverage, in parallel with traditional whole genome shotgun sequencing (WGS) of haploid and diploid genomes. Compared to the WGS results, the contiguity and quality of the FP assemblies were high, and they allowed us to fill WGS gaps resulting from repeats, low coverage, and allelic differences. The FP contig sets were further merged with WGS data using a novel software package GAM-NGS. Conclusions: By exploiting FP technology, the first published assembly of a conifer genome was sequenced entirely with massively parallel sequencing. Here we provide a comprehensive report on the different features of the approach and the optimization of the process. We have made public the input data (FASTQ format) for the set of pools used in this study: ftp://congenie.org/congenie/Nystedt_2013/Assembly/ProcessedData/FosmidPools/.(alternatively accessible via http://congenie.org/downloads).The software used for running the assembly process is available at http://research.scilifelab.se/andrej_alexeyenko/downloads/fpools/.

  • 46.
    Alexeyenko, Andrey
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Schmitt, Thomas
    Tjärnberg, Andreas
    Stockholm University, Science for Life Laboratory.
    Guala, Dmitri
    Stockholm University, Science for Life Laboratory.
    Frings, Oliver
    Stockholm University, Science for Life Laboratory.
    Sonnhammer, Erik L. L.
    Stockholm University, Science for Life Laboratory.
    Comparative interactomics with Funcoup 2.02012In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no D1, p. D821-D828Article in journal (Refereed)
    Abstract [en]

    FunCoup (http://FunCoup.sbc.su.se) is a database that maintains and visualizes global gene/protein networks of functional coupling that have been constructed by Bayesian integration of diverse high-throughput data. FunCoup achieves high coverage by orthology-based integration of data sources from different model organisms and from different platforms. We here present release 2.0 in which the data sources have been updated and the methodology has been refined. It contains a new data type Genetic Interaction, and three new species: chicken, dog and zebra fish. As FunCoup extensively transfers functional coupling information between species, the new input datasets have considerably improved both coverage and quality of the networks. The number of high-confidence network links has increased dramatically. For instance, the human network has more than eight times as many links above confidence 0.5 as the previous release. FunCoup provides facilities for analysing the conservation of subnetworks in multiple species. We here explain how to do comparative interactomics on the FunCoup website.

  • 47.
    Alghalibi, Dhiya
    et al.
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, Centres, SeRC - Swedish e-Science Research Centre. Kufa Univ, Coll Engn, Al Najaf, Iraq..
    Lashgari, Iman
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Brandt, L.uca
    KTH, School of Engineering Sciences (SCI), Mechanics. KTH, School of Engineering Sciences (SCI), Centres, Linné Flow Center, FLOW. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Hormozi, Sarah
    Ohio Univ, Dept Mech Engn, Athens, OH 45701 USA..
    Interface-resolved simulations of particle suspensions in Newtonian, shear thinning and shear thickening carrier fluids2018In: Journal of Fluid Mechanics, ISSN 0022-1120, E-ISSN 1469-7645, Vol. 852, p. 329-357Article in journal (Refereed)
    Abstract [en]

    We present a numerical study of non-colloidal spherical and rigid particles suspended in Newtonian, shear thinning and shear thickening fluids employing an immersed boundary method. We consider a linear Couette configuration to explore a wide range of solid volume fractions (0.1 <= Phi <= 0.4) and particle Reynolds numbers (0.1 <= Re<INF>p</INF><INF></INF> <= 10). We report the distribution of solid and fluid phase velocity and solid volume fraction and show that close to the boundaries inertial effects result in a significant slip velocity between the solid and fluid phase. The local solid volume fraction profiles indicate particle layering close to the walls, which increases with the nominal Phi. This feature is associated with the confinement effects. We calculate the probability density function of local strain rates and compare the latter's mean value with the values estimated from the homogenisation theory of Chateau et al. (J. Rheol., vol. 52, 2008, pp. 489-506), indicating a reasonable agreement in the Stokesian regime. Both the mean value and standard deviation of the local strain rates increase primarily with the solid volume fraction and secondarily with the Re<INF>p</INF>. The wide spectrum of the local shear rate and its dependency on Phi and Re<INF>p</INF> point to the deficiencies of the mean value of the local shear rates in estimating the rheology of these non-colloidal complex suspensions. Finally, we show that in the presence of inertia, the effective viscosity of these non-colloidal suspensions deviates from that of Stokesian suspensions. We discuss how inertia affects the microstructure and provide a scaling argument to give a closure for the suspension shear stress for both Newtonian and power-law suspending fluids. The stress closure is valid for moderate particle Reynolds numbers, O(Re<INF>p</INF>) similar to 10.

  • 48.
    Ali, Raja Hashim
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Bark, Mikael
    KTH, School of Information and Communication Technology (ICT).
    Miró, Jorge
    KTH, School of Information and Communication Technology (ICT).
    Muhammad, Sayyed Auwn
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, Centres, SeRC - Swedish e-Science Research Centre.
    Sjöstrand, J.
    Zubair, Syed M.
    KTH, School of Electrical Engineering (EES), Communication Networks. University of Balochistan, Pakistan.
    Abbas, R. M.
    Arvestad, L.
    VMCMC: A graphical and statistical analysis tool for Markov chain Monte Carlo traces2017In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 18, no 1, article id 97Article in journal (Refereed)
    Abstract [en]

    Background: MCMC-based methods are important for Bayesian inference of phylogeny and related parameters. Although being computationally expensive, MCMC yields estimates of posterior distributions that are useful for estimating parameter values and are easy to use in subsequent analysis. There are, however, sometimes practical difficulties with MCMC, relating to convergence assessment and determining burn-in, especially in large-scale analyses. Currently, multiple software are required to perform, e.g., convergence, mixing and interactive exploration of both continuous and tree parameters. Results: We have written a software called VMCMC to simplify post-processing of MCMC traces with, for example, automatic burn-in estimation. VMCMC can also be used both as a GUI-based application, supporting interactive exploration, and as a command-line tool suitable for automated pipelines. Conclusions: VMCMC is a free software available under the New BSD License. Executable jar files, tutorial manual and source code can be downloaded from https://bitbucket.org/rhali/visualmcmc/.

  • 49.
    Ali, Raja Hashim
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khan, Ammad Aslam
    Tracing the evolution of FERM domain of Kindlins2014In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 80, p. 193-204Article in journal (Refereed)
    Abstract [en]

    Kindlin proteins represent a novel family of evolutionarily conserved FERM domain containing proteins (FDCPs) and are members of B4.1 superfamily. Kindlins consist of three conserved protein homologs in vertebrates: Kindlin-1, Kindlin-2 and Kindlin-3. All three homologs are associated with focal adhesions and are involved in Integrin activation. FERM domain of each Kindlin is bipartite and plays a key role in Integrin activation. A single ancestral Kindlin protein can be traced back to earliest metazoans, e.g., to Parazoa. This protein underwent multiple rounds of duplication in vertebrates, leading to the present Kindlin family. In this study, we trace phylogenetic and evolutionary history of Kindlin FERM domain with respect to FERM domain of other FDCPs. We show that FERM domain in Kindlin homologs is conserved among Kindlins but amount of conservation is less in comparison with FERM domain of other members in B4.1 superfamily. Furthermore, insertion of Pleckstrin Homology like domain in Kindlin FERM domain has important evolutionary and functional consequences. Important residues in Kindlins are traced and ranked according to their evolutionary significance. The structural and functional significance of high ranked residues is highlighted and validated by their known involvement in Kindlin associated diseases. In light of these findings, we hypothesize that FERM domain originated from a proto-Talin protein in unicellular or proto-multicellular organism and advent of multi-cellularity was accompanied by burst of FDCPs, which supported multi-cellularity functions required for complex organisms. This study helps in developing a better understanding of evolutionary history of FERM domain of FDCPs and the role of FERM domain in metazoan evolution.

  • 50.
    Ali, Raja Hashim
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Muhammad, Sayyed Auwn
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Khan, Mehmodd Alam
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Arvestad, Lars
    Stockholms universitet.
    Quantitative synteny scoring improves homology inference and partitioning of gene families2013In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 14, p. S12-Article in journal (Refereed)
    Abstract [en]

    Background: Clustering sequences into families has long been an important step in characterization of genes and proteins. There are many algorithms developed for this purpose, most of which are based on either direct similarity between gene pairs or some sort of network structure, where weights on edges of constructed graphs are based on similarity. However, conserved synteny is an important signal that can help distinguish homology and it has not been utilized to its fullest potential. Results: Here, we present GenFamClust, a pipeline that combines the network properties of sequence similarity and synteny to assess homology relationship and merge known homologs into groups of gene families. GenFamClust identifies homologs in a more informed and accurate manner as compared to similarity based approaches. We tested our method against the Neighborhood Correlation method on two diverse datasets consisting of fully sequenced genomes of eukaryotes and synthetic data. Conclusions: The results obtained from both datasets confirm that synteny helps determine homology and GenFamClust improves on Neighborhood Correlation method. The accuracy as well as the definition of synteny scores is the most valuable contribution of GenFamClust.

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