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Sökning: WFRF:(Kunc Martin)

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1.
  • Petropoulos, Fotios, et al. (författare)
  • Operational Research : methods and applications
  • 2024
  • Ingår i: Journal of the Operational Research Society. - : Taylor & Francis Group. - 0160-5682 .- 1476-9360. ; 75:3, s. 423-617
  • Forskningsöversikt (refereegranskat)abstract
    • Throughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes.
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  • Arefin, Badrul, et al. (författare)
  • The Immune Phenotype of Three Drosophila Leukemia Models
  • 2017
  • Ingår i: G3. - : Oxford University Press (OUP). - 2160-1836. ; 7:7, s. 2139-2149
  • Tidskriftsartikel (refereegranskat)abstract
    • Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene (Ras(V12)) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll-dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia.
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4.
  • Heredia Pérez, Jorge A., et al. (författare)
  • Impact of competition from unregistered firms on R&D investment by industrial sectors in emerging economies
  • 2018
  • Ingår i: Technological forecasting & social change. - : Elsevier. - 0040-1625 .- 1873-5509. ; 133, s. 179-189
  • Tidskriftsartikel (refereegranskat)abstract
    • This research evaluates the impact of competition from unregistered firms on R&D investment by formal firms in emerging economies by considering their industrial sector and institutional factors, such as intellectual property rights. We performed a study using the propensity score matching approach and the World Bank Enterprise Survey of 16 Latin American emerging economies. We observed that the R&D investment response of formal firms varies according to the typology of industrial sectors. Supplier-dominated industries reduce investments in R&D when confronted with the informal sector. However, science-based, specialized suppliers and scale-intensive industries do not alter their investments. In addition, the level of intellectual property (e.g., IPRI) modifies the effect of the informal sector on R&D investment. Formal firms reduce their investments in R&D when the IPRI environment is underdeveloped. This reduction does not occur in highly developed IPRI environments. We also discuss the finding's theoretical and practical implications and suggest avenues for future research.
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5.
  • Khalili, Dilan, 1988-, et al. (författare)
  • Chitinase-like proteins promoting tumorigenesis through disruption of cell polarity via enlarged endosomal vesicles
  • 2023
  • Ingår i: Frontiers in Oncology. - 2234-943X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Chitinase-like proteins (CLPs) are associated with tissue-remodeling and inflammation but also with several disorders, including fibrosis, atherosclerosis, allergies, and cancer. However, CLP’s role in tumors is far from clear.Methods: Here, we utilize Drosophila melanogaster and molecular genetics to investigate the function of CLPs (imaginal disc growth factors; Idgf’s) in RasV12 dysplastic salivary glands.Results and discussion: We find one of the Idgf’s members, Idgf3, is transcriptionally induced in a JNK-dependent manner via a positive feedback loop mediated by reactive oxygen species (ROS). Moreover, Idgf3 accumulates in enlarged endosomal vesicles (EnVs) that promote tumor progression by disrupting cytoskeletal organization. The process is mediated via the downstream component, aSpectrin, which localizes to the EnVs. Our data provide new insight into CLP function in tumors and identifies specific targets for tumor control.
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6.
  • Khalili, Dilan, 1988-, et al. (författare)
  • Single-cell sequencing of tumor-associated macrophages in a Drosophila model
  • 2023
  • Ingår i: Frontiers in Immunology. - 1664-3224. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Tumor-associated macrophages may act to either limit or promote tumor growth, yet the molecular basis for either path is poorly characterized.Methods: We use a larval Drosophila model that expresses a dominant-active version of the Ras-oncogene (RasV12) to study dysplastic growth during early tumor progression. We performed single-cell RNA-sequencing of macrophage-like hemocytes to characterize these cells in tumor- compared to wild-type larvae. Hemocytes included manually extracted tumor-associated- and circulating cells.Results and discussion: We identified five distinct hemocyte clusters. In addition to RasV12 larvae, we included a tumor model where the activation of effector caspases was inhibited, mimicking an apoptosis-resistant setting. Circulating hemocytes from both tumor models differ qualitatively from control wild-type cells—they display an enrichment for genes involved in cell division, which was confirmed using proliferation assays. Split analysis of the tumor models further reveals that proliferation is strongest in the caspase-deficient setting. Similarly, depending on the tumor model, hemocytes that attach to tumors activate different sets of immune effectors—antimicrobial peptides dominate the response against the tumor alone, while caspase inhibition induces a shift toward members of proteolytic cascades. Finally, we provide evidence for transcript transfer between hemocytes and possibly other tissues. Taken together, our data support the usefulness of Drosophila to study the response against tumors at the organismic level.
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7.
  • Kunc, Martin, et al. (författare)
  • Monitoring the effect of pathogenic nematodes on locomotion of Drosophila larvae
  • 2017
  • Ingår i: fly. - : Informa UK Limited. - 1933-6934 .- 1933-6942. ; 11:3, s. 208-217
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the key factors that determine the interaction between hosts and their parasites is the frequency of their interactions, which depends on the locomotory behavior of both parts. To address host behavior we used natural infections involving insect pathogenic nematodes and Drosophila melanogaster larvae as hosts. Using a modified version of a recently described method (FIMTrack) to assess several parameters in larger sets of animals, we initially detected specific differences in larval food searching when comparing Drosophila strains. These differences were further influenced by the presence of nematodes. Given a choice, Drosophila larvae clearly avoided nematodes irrespective of their genetic background. Our newly developed methods will be useful to test candidate genes and pathways involved in host/pathogen interactions in general and to assess specific parameters of their interaction.
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