Browsing by Subject "LOCALIZATION"

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  • Kia, Ghazaleh; Ruotsalainen, Laura; Talvitie, Jukka (IEEE, 2022)
    International Conference on Localization and GNSS
    The advent of Artificial Intelligence (AI) has impacted all aspects of human life. One of the concrete examples of AI impact is visible in radio positioning. In this article, for the first time we utilize the power of AI by training a Convolutional Neural Network (CNN) using 5G New Radio (NR) fingerprints consisting of beamformed Channel State Information (CSI). By observing CSI, it is possible to characterize the multipath channel between the transmitter and the receiver, and thus provide a good source of spatiotemporal data to find the position of a User Equipment (UE). We collect ray-tracing-based 5G NR CSI from an urban area. The CSI data of the signals from one Base Station (BS) is collected at the reference points with known positions to train a CNN. We evaluate our work by testing: a) the robustness of the trained network for estimating the positions for the new measurements on the same reference points and b) the accuracy of the CNN-based position estimation while the UE is on points other than the reference points. The results prove that our trained network for a specific urban environment can estimate the UE position with a minimum mean error of 0.98 m.
  • Motazacker, Mahdi M.; Pirhonen, Juho; van Capelleveen, Julian C.; Weber-Boyvat, Marion; Kuivenhoven, Jan Albert; Shah, Saundarya; Hovingh, G. Kees; Metso, Jari; Li, Shiqian; Ikonen, Elina; Jauhiainen, Matti; Dallinga-Thie, Geesje M.; Olkkonen, Vesa M. (2016)
    Background and aims: Among subjects with high-density-lipoprotein cholesterol (HDL-C) below the 1st percentile in the general population, we identified a heterozygous variant OSBPL1A p.C39X encoding a short truncated protein fragment that co-segregated with low plasma HDL-C. Methods: We investigated the composition and function of HDL from the carriers and non-carriers and studied the properties of the mutant protein in cultured hepatocytes. Results: Plasma HDL-C and apolipoprotein (apo) A-I were lower in carriers versus non-carriers, whereas the other analyzed plasma components or HDL parameters did not differ. Sera of the carriers displayed a reduced capacity to act as cholesterol efflux acceptors (p <0.01), whereas the cholesterol acceptor capacity of their isolated HDL was normal. Fibroblasts from a p.C39X carrier showed reduced cholesterol efflux to lipid-free apoA-I but not to mature HDL particles, suggesting a specific defect in ABCA1-mediated efflux pathway. In hepatic cells, GFP-OSBPL1A partially co-localized in endosomes containing fluorescent apoA-I, suggesting that OSBPL1A may regulate the intracellular handling of apoA-I. The GFP-OSBPL1A-39X mutant protein remained in the cytosol and failed to interact with Rab7, which normally recruits OSBPL1A to late endosomes/lysosomes, suggesting that this mutation represents a loss-of-function. Conclusions: The present work represents the first characterization of a human OSBPL1A mutation. Our observations provide evidence that a familial loss-of-function mutation in OSBPL1A affects the first step of the reverse cholesterol transport process and associates with a low HDL-C phenotype. This suggests that rare mutations in OSBPL genes may contribute to dyslipidemias. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Vidilaseris, Keni; Kiriazis, Alexandros; Turku, Ainoleena; Khattab, Ayman Abdelnaby Shaaban; Johansson, Niklas G; Leino, Teppo Olavi; Kiuru, Paula Sinikka; Boije af Gennäs, Per Gustav; Meri, Seppo Kalevi; Yli-Kauhaluoma, Jari Tapani; Xhaard, Henri Guillaume Michel; Goldman, Adrian (2019)
    Membrane-bound pyrophosphatases are homodimeric integral membrane proteins that hydrolyze pyrophosphate into orthophosphates, coupled to the active transport of protons or sodium ions across membranes. They are important in the life cycle of bacteria, archaea, plants, and parasitic protists, but no homologous proteins exist in vertebrates, making them a promising drug target. Here, we report the first nonphosphorus allosteric inhibitor of the thermophilic bacterium Thermotoga maritima membrane-bound pyrophosphatase and its bound structure together with the substrate analog imidodiphosphate. The unit cell contains two protein homodimers, each binding a single inhibitor dimer near the exit channel, creating a hydrophobic clamp that inhibits the movement of beta-strand 1-2 during pumping, and thus prevents the hydrophobic gate from opening. This asymmetry of inhibitor binding with respect to each homodimer provides the first clear structural demonstration of asymmetry in the catalytic cycle of membrane-bound pyrophosphatases.
  • Martin, Isabel M.; Nava, Michele M.; Wickström, Sara A.; Graeter, Frauke (2022)
    Focal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component integrin-linked kinase (ILK) dynamically responds to mechanical force and what role adenosine triphosphate (ATP) bound to this pseudokinase plays remain elusive. Here, we apply force-probe molecular-dynamics simulations of human ILK:alpha-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. We identify two key salt-bridge-forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Our study proposes a role of ATP as an obligatory binding partner for structural and mechanical integrity of the pseudokinase ILK, ensuring efficient cellular force generation and migration.
  • Arnulfo, Gabriele; Narizzano, Massimo; Cardinale, Francesco; Fato, Marco Massimo; Palva, Jaakko Matias (2015)
    Background: Invasive monitoring of brain activity by means of intracerebral electrodes is widely practiced to improve pre-surgical seizure onset zone localization in patients with medically refractory seizures. Stereo-Electroencephalography (SEEG) is mainly used to localize the epileptogenic zone and a precise knowledge of the location of the electrodes is expected to facilitate the recordings interpretation and the planning of resective surgery. However, the localization of intracerebral electrodes on post-implant acquisitions is usually time-consuming (i.e., manual segmentation), it requires advanced 3D visualization tools, and it needs the supervision of trained medical doctors in order to minimize the errors. In this paper we propose an automated segmentation algorithm specifically designed to segment SEEG contacts from a thresholded post-implant Cone-Beam CT volume (0.4 mm, 0.4 mm, 0.8 mm). The algorithm relies on the planned position of target and entry points for each electrode as a first estimation of electrode axis. We implemented the proposed algorithm into DEETO, an open source C++ prototype based on ITK library. Results: We tested our implementation on a cohort of 28 subjects in total. The experimental analysis, carried out over a subset of 12 subjects (35 multilead electrodes; 200 contacts) manually segmented by experts, show that the algorithm: (i) is faster than manual segmentation (i.e., less than 1s/subject versus a few hours) (ii) is reliable, with an error of 0.5 mm +/- 0.06 mm, and (iii) it accurately maps SEEG implants to their anatomical regions improving the interpretability of electrophysiological traces for both clinical and research studies. Moreover, using the 28-subject cohort we show here that the algorithm is also robust (error <0.005 mm) against deep-brain displacements (<12 mm) of the implanted electrode shaft from those planned before surgery. Conclusions: Our method represents, to the best of our knowledge, the first automatic algorithm for the segmentation of SEEG electrodes. The method can be used to accurately identify the neuroanatomical loci of SEEG electrode contacts by a non-expert in a fast and reliable manner.
  • Koskenvuo, Juha W.; Saarinen, Inka; Ahonen, Saija; Tommiska, Johanna; Weckström, Sini; Seppala, Eija H.; Tuupanen, Sari; Kangas-Kontio, Tiia; Schleit, Jennifer; Helio, Krista; Hathaway, Julie; Gummesson, Anders; Dahlberg, Pia; Ojala, Tiina H.; Vepsäläinen, Ville; Kytola, Ville; Muona, Mikko; Sistonen, Johanna; Salmenpera, Pertteli; Gentile, Massimiliano; Paananen, Jussi; Myllykangas, Samuel; Alastalo, Tero-Pekka; Heliö, Tiina (2021)
    Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.
  • Koskenvuo, Juha W.; Saarinen, Inka; Ahonen, Saija; Tommiska, Johanna; Weckström, Sini; Seppala, Eija H.; Tuupanen, Sari; Kangas-Kontio, Tiia; Schleit, Jennifer; Helio, Krista; Hathaway, Julie; Gummesson, Anders; Dahlberg, Pia; Ojala, Tiina H.; Vepsäläinen, Ville; Kytola, Ville; Muona, Mikko; Sistonen, Johanna; Salmenpera, Pertteli; Gentile, Massimiliano; Paananen, Jussi; Myllykangas, Samuel; Alastalo, Tero-Pekka; Heliö, Tiina (2021)
    Background Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. Methods and results We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p Conclusion Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.
  • Saarinen, Jukka Kalle Samuel; Gütter, Friederike; Lindman, Mervi M; Agopov, Mikael; Fraser-Miller, Sara J.; Scherließ, Regina; Jokitalo, Eija; Almeida Santos, Helder; Peltonen, Leena; Isomäki, Antti; Strachan, Clare J. (2019)
    A wide variety of nanoparticles are playing an increasingly important role in drug delivery. Label-free imaging techniques are especially desirable to follow the cellular uptake and intracellular fate of nanoparticles. The combined correlative use of different techniques, each with unique advantages, facilitates more detailed investigation about such interactions. The synergistic use of correlative coherent anti-Stokes Raman scattering and electron microscopy (C-CARS-EM) imaging offers label-free, chemically-specific, and (sub)-nanometer spatial resolution for studying nanoparticle uptake into cells as demonstrated in the current study. Coherent anti-Stokes Raman scattering (CARS) microscopy offers chemically-specific (sub)micron spatial resolution imaging without fluorescent labels while transmission electron microscopy (TEM) offers (sub)-nanometer scale spatial resolution and thus visualization of precise nanoparticle localization at the sub-cellular level. This proof-of-concept imaging platform with unlabeled drug nanocrystals and macrophage cells revealed good colocalization between the CARS signal and electron dense nanocrystals in TEM images. The correlative TEM images revealed subcellular localization of nanocrystals inside membrane bound vesicles, showing multivesicular body (MVB)-like morphology typical for late endosomes (LEs), endolysosomes, and phagolysosomes. C-CARS-EM imaging has much potential to study the interactions between a wide range of nanoparticles and cells with high precision and confidence.
  • Orosz, Zsuzsanna Z.; Bardos, Helga; Shemirani, Amir H.; Debreceni, Ildiko Beke; Lassila, Riitta; Riikonen, Antti S.; Hovinga, Johanna A. Kremer; Seiler, Theo G.; van Dorland, Hendrika A.; Schroeder, Verena; Boda, Zoltan; Nemes, Laszlo; Frueh Eppstein, Beatrice; Nagy, Bence; Facsko, Andrea; Kappelmayer, Janos; Muszbek, Laszlo (2019)
    Cellular factor XIII (cFXIII, FXIII-A(2)), a transglutaminase, has been demonstrated in a few cell types. Its main function is to cross-link proteins by isopeptide bonds. Here, we investigated the presence of cFXIII in cells of human cornea. Tissue sections of the cornea were immunostained for FXIII-A in combination with staining for CD34 antigen or isopeptide cross-links. Isolated corneal keratocytes were also evaluated by immunofluorescent microscopy and flow cytometry. FXIII-A in the corneal stroma was quantified by Western blotting. FXIII-A mRNA was detected by RT-qPCR. The cornea of FXIII-A-deficient patients was evaluated by cornea topography. FXIII-A was detected in 68 +/- 13% of CD34+ keratocytes. Their distribution in the corneal stroma was unequal; they were most abundant in the subepithelial tertile. cFXIII was of cytoplasmic localization. In the stroma, 3.64 ng cFXIII/mg protein was measured. The synthesis of cFXIII by keratocytes was confirmed by RT-qPCR. Isopeptide cross-links were detected above, but not within the corneal stroma. Slight abnormality of the cornea was detected in six out of nine FXIII-A-deficient patients. The presence of cFXIII in human keratocytes was established for the first time. cFXIII might be involved in maintaining the stability of the cornea and in the corneal wound healing process.
  • Hlushchenko, Iryna; Hotulainen, Pirta (2019)
    Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin's response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest - but relatively long-lasting - elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.
  • Boggavarapu, Nageswara Rao; Lalitkumar, Sujata; Joshua, Vijay; Kasvandik, Sergo; Salumets, Andres; Lalitkumar, Parameswaran Grace; Gemzell-Danielsson, Kristina (2016)
    The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity.
  • Ruskamo, Salla; Krokengen, Oda C.; Kowal, Julia; Nieminen, Tuomo; Lehtimäki, Mari; Raasakka, Arne; Dandey, Venkata P.; Vattulainen, Ilpo; Stahlberg, Henning; Kursula, Petri (2020)
    Myelin protein P2 is a peripheral membrane protein of the fatty acid?binding protein family that functions in the formation and maintenance of the peripheral nerve myelin sheath. Several P2 gene mutations cause human Charcot-Marie-Tooth neuropathy, but the mature myelin sheath assembly mechanism is unclear. Here, cryo-EM of myelin-like proteolipid multilayers revealed an ordered three-dimensional (3D) lattice of P2 molecules between stacked lipid bilayers, visualizing supramolecular assembly at the myelin major dense line. The data disclosed that a single P2 layer is inserted between two bilayers in a tight intermembrane space of ?3 nm, implying direct interactions between P2 and two membrane surfaces. X-ray diffraction from P2-stacked bicelle multilayers revealed lateral protein organization, and surface mutagenesis of P2 coupled with structure-function experiments revealed a role for both the portal region of P2 and its opposite face in membrane interactions. Atomistic molecular dynamics simulations of P2 on model membrane surfaces suggested that Arg-88 is critical for P2-membrane interactions, in addition to the helical lid domain. Negatively charged lipid headgroups stably anchored P2 on the myelin-like bilayer surface. Membrane binding may be accompanied by opening of the P2 ?-barrel structure and ligand exchange with the apposing bilayer. Our results provide an unprecedented view into an ordered, multilayered biomolecular membrane system induced by the presence of a peripheral membrane protein from human myelin. This is an important step toward deciphering the 3D assembly of a mature myelin sheath at the molecular level.
  • Al-Tahmeesschi, Ahmed; Talvitie, Jukka; Lopez-Benitez, Miguel; Ruotsalainen, Laura (IEEE, 2022)
    International Conference on Localization and GNSS
    Outdoor user equipment (UE) localisation has attracted a significant amount of attention due to its importance in many location-based services. Typically, in rural and open areas, global navigation satellite systems (GNSS) can provide an accurate and reliable localisation performance. However, in urban areas GNSS localisation accuracy is significantly reduced due to shadowing, scattering and signal blockages. In this work, the UE positioning assisted by deep learning in 5G and beyond networks is investigated in an urban area environment. We study the impact of utilising the spatial correlation in the received signal strengths (RSSs) on the UE positioning accuracy and how to utilise such correlation with deep learning algorithms to improve the localisation accuracy. Numerical results showed the importance of utilising the spatial correlation in the RSS to improve the prediction accuracy for all of the considered models. In addition, the impact of varying the number of access points (APs) transmitters on the localisation accuracy is also investigated. Numerical results showed that a lower number of APs may be sufficient when not considering uncertainties in RSS measurements. Moreover, we study how much the degrading effect of RSS uncertainty can be compensated for by increasing the number of APs.
  • Herranen, Anni; Ikäheimo, Kuu; Lankinen, Tuuli; Pakarinen, Emmi; Fritzsch, Bernd; Saarma, Mart; Lindahl, Maria; Pirvola, Ulla (2020)
    The non-conventional neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-resident protein that promotes ER homeostasis. MANF has a cytoprotective function, shown in the central nervous system neurons and pancreatic beta cells. Here, we report that MANF is expressed in the hair cells and neurons and in selected non-sensory cells of the cochlea and that Manf inactivation triggers upregulation of the ER chaperones in these cells. However, Manf inactivation resulted in the death of only outer hair cells (OHCs), the cells responsible for sound amplification in the cochlea. All OHCs were formed in Manf-inactivated mice, but progressive OHC death started soon after the onset of hearing function. The robust OHC loss was accompanied by strongly elevated hearing thresholds. Conditional Manf inactivation demonstrated that MANF has a local function in the cochlea. Immunostainings revealed the upregulation of CHOP, the pro-apoptotic component of the unfolded protein response (UPR), in Manf-inactivated OHCs, linking the UPR to the loss of these cells. The phenotype of Manf-inactivated OHCs was distinctly dependent on the mouse strain, such that the strains characterized by early-onset age-related hearing loss (C57BL/6J and CD-1) were affected. These results suggest that Manf deficiency becomes detrimental when accompanied by gene mutations that predispose to hearing loss, by intensifying ER dyshomeostasis. Together, MANF is the first growth factor shown to antagonize ER stress-mediated OHC death. MANF might serve as a therapeutic candidate for protection against hearing loss induced by the ER-machinery-targeting stressors.
  • Egashira, Yuka; Kaga, Yoshimi; Gunji, Atsuko; Kita, Yosuke; Kimura, Motohiro; Hironaga, Naruhito; Takeichi, Hiroshige; Hayashi, Sayuri; Kaneko, Yuu; Takahashi, Hidetoshi; Hanakawa, Takashi; Okada, Takashi; Inagaki, Masumi (2022)
    Reading fluency is based on the automatic visual recognition of words. As a manifestation of the automatic processing of words, an automatic deviance detection of visual word stimuli can be observed in the early stages of visual recognition. To clarify whether this phenomenon occurs with Japanese kanji compounds-since their lexicality is related to semantic association-we investigated the brain response by utilizing three types of deviants: differences in font type, lexically correct or incorrect Japanese kanji compound words and pseudo-kanji characters modified from correct and incorrect compounds. We employed magnetoencephalography (MEG) to evaluate the spatiotemporal profiles of the related brain regions. The study included 22 adult native Japanese speakers (16 females). The abovementioned three kinds of stimuli containing 20% deviants were presented during the MEG measurement. Activity in the occipital pole region of the brain was observed upon the detection of font-type deviance within 250 ms of stimulus onset. Although no significant activity upon detecting lexically correct/incorrect kanji compounds or pseudo-kanji character deviations was observed, the activity in the posterior transverse region of the collateral sulcus (pCoS)-which is a fusiform neighboring area-was larger when detecting lexically correct kanji compounds than when detecting pseudo-kanji characters. Taken together, these results support the notion that the automatic detection of deviance in kanji compounds may be limited to a low-level feature, such as the stimulus stroke thickness.
  • Hernandez-Pavon, Julio C.; Makela, Niko; Lehtinen, Henri; Lioumis, Pantelis; Makela, Jyrki P. (2014)
  • Johansson, Niklas G; Dreano, Loic; Vidilaseris, Keni; Khattab, Ayman; Liu, Jianing; Lasbleiz, Arthur; de Castro Ribeiro, Orquidea Marilia; Kiriazis, Alexandros; Boije af Gennäs, Gustav; Meri, Seppo; Goldman, Adrian; Yli-Kauhaluoma, Jari; Xhaard, Henri (2021)
    Inhibition of membrane-bound pyrophosphatase (mPPase) with small molecules offer a new approach in the fight against pathogenic protozoan parasites. mPPases are absent in humans, but essential for many protists as they couple pyrophosphate hydrolysis to the active transport of protons or sodium ions across acidocalcisomal membranes. So far, only few nonphosphorus inhibitors have been reported. Here, we explore the chemical space around previous hits using a combination of screening and synthetic medicinal chemistry, identifying compounds with low micromolar inhibitory activities in the Thermotoga maritima mPPase test system. We furthermore provide early structure-activity relationships around a new scaffold having a pyrazolo[1,5-a]pyrimidine core. The most promising pyrazolo[1,5-a]pyrimidine congener was further investigated and found to inhibit Plasmodium falciparum mPPase in membranes as well as the growth of P. falciparum in an ex vivo survival assay.
  • Jheon, Andrew H.; Li, Chun-Ying; Wen, Timothy; Michon, Frederic; Klein, Ophir D. (2011)