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Search Results: 1 - 10 of 6471 matches for " Anders Bj?rk "
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Monte Carlo Euler approximations of HJM term structure financial models
Thomas Bjrk,Anders Szepessy,Raul Tempone,Georgios E. Zouraris
Mathematics , 2012,
Abstract: We present Monte Carlo-Euler methods for a weak approximation problem related to the Heath-Jarrow-Morton (HJM) term structure model, based on \Ito stochastic differential equations in infinite dimensional spaces, and prove strong and weak error convergence estimates. The weak error estimates are based on stochastic flows and discrete dual backward problems, and they can be used to identify different error contributions arising from time and maturity discretization as well as the classical statistical error due to finite sampling. Explicit formulas for efficient computation of sharp error approximation are included. Due to the structure of the HJM models considered here, the computational effort devoted to the error estimates is low compared to the work to compute Monte Carlo solutions to the HJM model. Numerical examples with known exact solution are included in order to show the behavior of the estimates.
Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
Anders Olsson, Anders Bjrk, Johan Vallon-Christersson, John T Isaacs, Tomas Leanderson
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-107
Abstract: One of the most significant differentially expressed genes both in vitro and in vivo after exposure to tasquinimod, was thrombospondin-1 (TSP1). The up-regulation of TSP1 mRNA in LNCaP tumor cells both in vitro and in vivo correlated with an increased expression and extra cellular secretion of TSP1 protein. When nude mice bearing CWR-22RH human prostate tumors were treated with oral tasquinimod, there was a profound growth inhibition, associated with an up-regulation of TSP1 and a down- regulation of HIF-1 alpha protein, androgen receptor protein (AR) and glucose transporter-1 protein within the tumor tissue. Changes in TSP1 expression were paralleled by an anti-angiogenic response, as documented by decreased or unchanged tumor tissue levels of VEGF (a HIF-1 alpha down stream target) in the tumors from tasquinimod treated mice.We conclude that tasquinimod-induced up-regulation of TSP1 is part of a mechanism involving down-regulation of HIF1α and VEGF, which in turn leads to reduced angiogenesis via inhibition of the "angiogenic switch", that could explain tasquinimods therapeutic potential.During the last decades, development of new cancer treatments that are capable of inhibiting tumor growth by inhibition of the blood supply has received great attention [1,2]. The quinoline compound tasquinimod [ABR-215050; CAS number 254964-60-8; 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[(4-trifluoromethyl) phenyl]-1,2-dihydroquinoline-3-carboxamide] has emerged as a candidate [3], by virtue of its pharmacological profile with anti-angiogenic and anti-tumor potency in experimental human prostate cancer models [4,5]. Thrombospondin-1 (TSP1) is a 450 kDa glycoprotein initially found in platelets, but also synthesized and secreted by many normal and transformed cells. TSP1 has been shown to be a potent natural inhibitor of tumor progression and metastases via inhibition of angiogenesis and migration or by activation of TGFβ (for review see [6-8]). Several mechanisms have been propos
Identification of Human S100A9 as a Novel Target for Treatment of Autoimmune Disease via Binding to Quinoline-3-Carboxamides
Per Bjrk,Anders Bjrk,Thomas Vogl,Martin Stenstr?m,David Liberg,Anders Olsson,Johannes Roth,Fredrik Ivars,Tomas Leanderson
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000097
Abstract: Despite more than 25 years of research, the molecular targets of quinoline-3-carboxamides have been elusive although these compounds are currently in Phase II and III development for treatment of autoimmune/inflammatory diseases in humans. Using photoaffinity cross-linking of a radioactively labelled quinoline-3-carboxamide compound, we could determine a direct association between human S100A9 and quinoline-3-carboxamides. This interaction was strictly dependent on both Zn++ and Ca++. We also show that S100A9 in the presence of Zn++ and Ca++ is an efficient ligand of receptor for advanced glycation end products (RAGE) and also an endogenous Toll ligand in that it shows a highly specific interaction with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides. A clear structure-activity relationship (SAR) emerged with regard to the binding of quinoline-3-carboxamides to S100A9, as well as these compounds potency to inhibit interactions with RAGE or TLR4/MD2. The same SAR was observed when the compound's ability to inhibit acute experimental autoimmune encephalomyelitis in mice in vivo was analysed. Quinoline-3-carboxamides would also inhibit TNFα release in a S100A9-dependent model in vivo, as would antibodies raised against the quinoline-3-carboxamide–binding domain of S100A9. Thus, S100A9 appears to be a focal molecule in the control of autoimmune disease via its interactions with proinflammatory mediators. The specific binding of quinoline-3-carboxamides to S100A9 explains the immunomodulatory activity of this class of compounds and defines S100A9 as a novel target for treatment of human autoimmune diseases.
Identification of Human S100A9 as a Novel Target for Treatment of Autoimmune Disease via Binding to Quinoline-3-Carboxamides
Per Bjrk,Anders Bjrk,Thomas Vogl,Martin Stenstr?m,David Liberg,Anders Olsson,Johannes Roth,Fredrik Ivars,Tomas Leanderson
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000097
Abstract: Despite more than 25 years of research, the molecular targets of quinoline-3-carboxamides have been elusive although these compounds are currently in Phase II and III development for treatment of autoimmune/inflammatory diseases in humans. Using photoaffinity cross-linking of a radioactively labelled quinoline-3-carboxamide compound, we could determine a direct association between human S100A9 and quinoline-3-carboxamides. This interaction was strictly dependent on both Zn++ and Ca++. We also show that S100A9 in the presence of Zn++ and Ca++ is an efficient ligand of receptor for advanced glycation end products (RAGE) and also an endogenous Toll ligand in that it shows a highly specific interaction with TLR4/MD2. Both these interactions are inhibited by quinoline-3-carboxamides. A clear structure-activity relationship (SAR) emerged with regard to the binding of quinoline-3-carboxamides to S100A9, as well as these compounds potency to inhibit interactions with RAGE or TLR4/MD2. The same SAR was observed when the compound's ability to inhibit acute experimental autoimmune encephalomyelitis in mice in vivo was analysed. Quinoline-3-carboxamides would also inhibit TNFα release in a S100A9-dependent model in vivo, as would antibodies raised against the quinoline-3-carboxamide–binding domain of S100A9. Thus, S100A9 appears to be a focal molecule in the control of autoimmune disease via its interactions with proinflammatory mediators. The specific binding of quinoline-3-carboxamides to S100A9 explains the immunomodulatory activity of this class of compounds and defines S100A9 as a novel target for treatment of human autoimmune diseases.
Molecular Identification of Commercialized Medicinal Plants in Southern Morocco
Anneleen Kool, Hugo J. de Boer, ?sa Krüger, Anders Rydberg, Abdelaziz Abbad, Lars Bjrk, Gary Martin
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039459
Abstract: Background Medicinal plant trade is important for local livelihoods. However, many medicinal plants are difficult to identify when they are sold as roots, powders or bark. DNA barcoding involves using a short, agreed-upon region of a genome as a unique identifier for species– ideally, as a global standard. Research Question What is the functionality, efficacy and accuracy of the use of barcoding for identifying root material, using medicinal plant roots sold by herbalists in Marrakech, Morocco, as a test dataset. Methodology In total, 111 root samples were sequenced for four proposed barcode regions rpoC1, psbA-trnH, matK and ITS. Sequences were searched against a tailored reference database of Moroccan medicinal plants and their closest relatives using BLAST and Blastclust, and through inference of RAxML phylograms of the aligned market and reference samples. Principal Findings Sequencing success was high for rpoC1, psbA-trnH, and ITS, but low for matK. Searches using rpoC1 alone resulted in a number of ambiguous identifications, indicating insufficient DNA variation for accurate species-level identification. Combining rpoC1, psbA-trnH and ITS allowed the majority of the market samples to be identified to genus level. For a minority of the market samples, the barcoding identification differed significantly from previous hypotheses based on the vernacular names. Conclusions/Significance Endemic plant species are commercialized in Marrakech. Adulteration is common and this may indicate that the products are becoming locally endangered. Nevertheless the majority of the traded roots belong to species that are common and not known to be endangered. A significant conclusion from our results is that unknown samples are more difficult to identify than earlier suggested, especially if the reference sequences were obtained from different populations. A global barcoding database should therefore contain sequences from different populations of the same species to assure the reference sequences characterize the species throughout its distributional range.
S100A9 Interaction with TLR4 Promotes Tumor Growth
Eva K?llberg, Thomas Vogl, David Liberg, Anders Olsson, Per Bjrk, Pernilla Wikstr?m, Anders Bergh, Johannes Roth, Fredrik Ivars, Tomas Leanderson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034207
Abstract: By breeding TRAMP mice with S100A9 knock-out (S100A9?/?) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b+ S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68+ macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9?/? and TLR4?/?, but not in RAGE?/? animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGFβ expression in splenic CD11b+ cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.
Signatures of T Cells as Correlates of Immunity to Francisella tularensis
Kjell Enesl?tt, Monica Normark, Rafael Bjrk, Cecilia Rietz, Carl Zingmark, Lawrence A. Wolfraim, Svenja St?ven, Anders Sj?stedt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032367
Abstract: Tularemia or vaccination with the live vaccine strain (LVS) of Francisella tularensis confers long-lived cell-mediated immunity. We hypothesized that this immunity depends on polyfunctional memory T cells, i.e., CD4+ and/or CD8+ T cells with the capability to simultaneously express several functional markers. Multiparametric flow cytometry, measurement of secreted cytokines, and analysis of lymphocyte proliferation were used to characterize in vitro recall responses of peripheral blood mononuclear cells (PBMC) to killed F. tularensis antigens from the LVS or Schu S4 strains. PBMC responses were compared between individuals who had contracted tularemia, had been vaccinated, or had not been exposed to F. tularensis (na?ve). Significant differences were detected between either of the immune donor groups and na?ve individuals for secreted levels of IL-5, IL-6, IL-10, IL-12, IL-13, IFN-γ, MCP-1, and MIP-1β. Expression of IFN-γ, MIP-1β, and CD107a by CD4+CD45RO+ or CD8+CD45RO+ T cells correlated to antigen concentrations. In particular, IFN-γ and MIP-1β strongly discriminated between immune and na?ve individuals. Only one cytokine, IL-6, discriminated between the two groups of immune individuals. Notably, IL-2- or TNF-α-secretion was low. Our results identify functional signatures of T cells that may serve as correlates of immunity and protection against F. tularensis.
Common Interactions between S100A4 and S100A9 Defined by a Novel Chemical Probe
Per Bjrk, Eva K?llberg, Ulf Wellmar, Matteo Riva, Anders Olsson, Zhifei He, Marie T?rngren, David Liberg, Fredrik Ivars, Tomas Leanderson
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063012
Abstract: S100A4 and S100A9 proteins have been described as playing roles in the control of tumor growth and metastasis. We show here that a chemical probe, oxyclozanide (OX), selected for inhibiting the interaction between S100A9 and the receptor for advanced glycation end-products (RAGE) interacts with both S100A9 and S100A4. Furthermore, we show that S100A9 and S100A4 interact with RAGE and TLR4; interactions that can be inhibited by OX. Hence, S100A4 and S100A9 display similar functional elements despite their primary sequence diversity. This was further confirmed by showing that S100A4 and S100A9 dimerize both in vitro and in vivo. All of these interactions required levels of Zn++ that are found in the extracellular space but not intracellularly. Interestingly, S100A4 and S100A9 are expressed by distinct CD11b+ subpopulations both in healthy animals and in animals with either inflammatory disease or tumor burden. The functions of S100A9 and S100A4 described in this paper, including heterodimerization, may therefore reflect S100A9 and S100A4 that are released into the extra-cellular milieu.
In Situ Detection of Active Edge Sites in Single-Layer MoS$_2$ Catalysts
Albert Bruix,Henrik G. Füchtbauer,Anders K. Tuxen,Alex S. Walton,Mie Andersen,S?ren Porsgaard,Flemming Besenbacher,Bjrk Hammer,Jeppe V. Lauritsen
Physics , 2015, DOI: 10.1021/acsnano.5b03199
Abstract: MoS2 nanoparticles are proven catalysts for processes such as hydrodesulphurization and hydrogen evolution, but unravelling their atomic-scale structure under catalytic working conditions has remained significantly challenging. Ambient pressure X-ray Photoelectron Spectroscopy (AP-XPS) allows us to follow in-situ the formation of the catalytically relevant MoS2 edge sites in their active state. The XPS fingerprint is described by independent contributions to the Mo3d core level spectrum whose relative intensity is sensitive to the thermodynamic conditions. Density Functional Theory (DFT) is used to model the triangular MoS2 particles on Au(111) and identify the particular sulphidation state of the edge sites. A consistent picture emerges in which the core level shifts for the edge Mo atoms evolve counter-intuitively towards higher binding energies when the active edges are reduced. The shift is explained by a surprising alteration in the metallic character of the edge sites, which is a distinct spectroscopic signature of the MoS2 edges under working conditions.
The ideal dimensions of a Halbach cylinder of finite length
R. Bjrk
Physics , 2014, DOI: 10.1063/1.3525646
Abstract: In this paper the smallest or optimal dimensions of a Halbach cylinder of a finite length for a given sample volume and desired flux density are determined using numerical modeling and parameter variation. A sample volume that is centered in and shaped as the Halbach cylinder bore but with a possible shorter length is considered. The external radius and the length of the Halbach cylinder with the smallest possible dimensions are found as a function of a desired internal radius, length of the sample volume and mean flux density. It is shown that the optimal ratio between the outer and inner radius of the Halbach cylinder does not depend on the length of the sample volume. Finally, the efficiency of a finite length Halbach cylinder is considered and compared with the case of a cylinder of infinite length. The most efficient dimensions for a Halbach cylinder are found and it is shown that the efficiency increases slowly with the length of the cylinder.
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