Browsing by Subject "MODEL"

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  • Fernandez-Prieto, D.; Kesselmeier, J.; Ellis, M.; Marconcini, M.; Reissell, A.; Suni, T. (2013)
  • Beauchamp, Philippe; Jackson, Christopher B.; Ozhathil, Lijo Cherian; Agarkova, Irina; Galindo, Cristi L.; Sawyer, Douglas B.; Suter, Thomas M.; Zuppinger, Christian (2020)
    Purpose: Both cardiomyocytes and cardiac fibroblasts (CF) play essential roles in cardiac development, function, and remodeling. Properties of 3D co-cultures are incompletely understood. Hence, 3D co-culture of cardiomyocytes and CF was characterized, and selected features compared with single-type and 2D culture conditions.Methods: Human cardiomyocytes derived from induced-pluripotent stem cells (hiPSC-CMs) were obtained from Cellular Dynamics or Ncardia, and primary human cardiac fibroblasts from ScienCell. Cardiac spheroids were investigated using cryosections and whole-mount confocal microscopy, video motion analysis, scanning-, and transmission-electron microscopy (SEM, TEM), action potential recording, and quantitative PCR (qPCR).Results: Spheroids formed in hanging drops or in non-adhesive wells showed spontaneous contractions for at least 1 month with frequent media changes. SEM of mechanically opened spheroids revealed a dense inner structure and no signs of blebbing. TEM of co-culture spheroids at 1 month showed myofibrils, intercalated disc-like structures and mitochondria. Ultrastructural features were comparable to fetal human myocardium. We then assessed immunostained 2D cultures, cryosections of spheroids, and whole-mount preparations by confocal microscopy. CF in co-culture spheroids assumed a small size and shape similar to the situation in ventricular tissue. Spheroids made only of CF and cultured for 3 weeks showed no stress fibers and strongly reduced amounts of alpha smooth muscle actin compared to early spheroids and 2D cultures as shown by confocal microscopy, western blotting, and qPCR. The addition of CF to cardiac spheroids did not lead to arrhythmogenic effects as measured by sharp-electrode electrophysiology. Video motion analysis showed a faster spontaneous contraction rate in co-culture spheroids compared to pure hiPSC-CMs, but similar contraction amplitudes and kinetics. Spontaneous contraction rates were not dependent on spheroid size. Applying increasing pacing frequencies resulted in decreasing contraction amplitudes without positive staircase effect. Gene expression analysis of selected cytoskeleton and myofibrillar proteins showed more tissue-like expression patterns in co-culture spheroids than with cardiomyocytes alone or in 2D culture.Conclusion: We demonstrate that the use of 3D co-culture of hiPSC-CMs and CF is superior over 2D culture conditions for co-culture models and more closely mimicking the native state of the myocardium with relevance to drug development as well as for personalized medicine.
  • Laurila-Pant, Mirka; Mäntyniemi, Samu; Östman, Örjan; Olsson, Jens; Uusitalo, Laura; Lehikoinen, Annukka (2021)
    Ecological indicator approaches typically compare the prevailing state of an ecosystem component to a reference state reflecting good environmental conditions, i.e. the desirable state. However, defining the reference state is challenging due to a wide range of uncertainties related to natural variability and measurement error in data, as well as ecological understanding. This study propose a novel probabilistic approach combining historical monitoring data and ecological understanding to estimate the uncertainty associated with the boundary value of an ecological indicator between good and poor environmental states. Bayesian inference is used to estimate the epistemic uncertainty about the true state of an indicator variable during an historical reference period. This approach replaces the traditional boundary value with probability distribution, indicating the uncertainty about the boundary between environmental states providing a transparent safety margin associated with the risk of misclassification of the indicator's state. The approach is demonstrated by applying it to a time-series of an ecological status indicator, 'Abundance of coastal key fish species', included in HELCOM's Baltic Sea regional status assessment. We suggest that acknowledgement of the uncertainty behind the final classification leads to more transparent and better-informed decision-making processes.
  • Crispino, Marta; Arjas, Elja; Vitelli, Valeria; Barrett, Natasha; Frigessi, Arnoldo (2019)
    We are interested in learning how listeners perceive sounds as having human origins. An experiment was performed with a series of electronically synthesized sounds, and listeners were asked to compare them in pairs. We propose a Bayesian probabilistic method to learn individual preferences from nontransitive pairwise comparison data, as happens when one (or more) individual preferences in the data contradicts what is implied by the others. We build a Bayesian Mallows model in order to handle nontransitive data, with a latent layer of uncertainty which captures the generation of preference misreporting. We then develop a mixture extension of the Mallows model, able to learn individual preferences in a heterogeneous population. The results of our analysis of the musicology experiment are of interest to electroacoustic composers and sound designers, and to the audio industry in general, whose aim is to understand how computer generated sounds can be produced in order to sound more human.
  • Leinonen, Jussi; Moisseev, Dmitri; Leskinen, Matti; Petersen, Walter A. (2012)
    To improve the understanding of high-latitude rain microphysics and its implications for the remote sensing of rainfall by ground-based and spaceborne radars, raindrop size measurements have been analyzed that were collected over five years with a Joss–Waldvogel disdrometer located in Järvenpää, Finland. The analysis shows that the regional climate is characterized by light rain and small drop size with narrow size distributions and that the mutual relations of drop size distribution parameters differ from those reported at lower latitudes. Radar parameters computed from the distributions demonstrate that the high latitudes are a challenging target for weather radar observations, particularly those employing polarimetric and dual-frequency techniques. Nevertheless, the findings imply that polarimetric ground radars can produce reliable “ground truth” estimates for space observations and identify dual-frequency radars utilizing a W-band channel as promising tools for observing rainfall in the high-latitude climate.
  • Chew, Tracy; Haase, Bianca; Bathgate, Roslyn; Willet, Cali E.; Kaukonen, Maria K.; Mascord, Lisa J.; Lohi, Hannes T.; Wade, Claire M. (2017)
    Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (P-CHISQ = 3.425e(-14), n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet-Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and
  • Radhakrishnan, Dhanya; Shanmukhan, Anju Pallipurath; Kareem, Abdul; Aiyaz, Mohammed; Varapparambathu, Vijina; Toms, Ashna; Kerstens, Merijn; Valsakumar, Devisree; Landge, Amit N.; Shaji, Anil; Mathew, Mathew K.; Sawchuk, Megan G.; Scarpella, Enrico; Krizek, Beth A.; Efroni, Idan; Mähönen, Ari Pekka; Willemsen, Viola; Scheres, Ben; Prasad, Kalika (2020)
    Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.
  • Funderud, Tonje; Mononen, Riikka; Radišić, Jelena; Laine, Anu (2019)
    The study aimed to investigate variations in addition and subtraction fluency by observing grade three students in Norway (n = 253, M-age = 8.38 y.) and Finland (n = 209, M-age = 9.35 y.) while controlling for their age and non-verbal reasoning. Gender differences were also examined. The focus of the study was on the performance of the low-achieving (LA) students in comparison to the typically achieving (TA) group, not neglecting differences in how early educational support was organised across the two countries. Two-minute speed tests in both addition and subtraction within the 1-20 number range were used to assess fluency. The Finnish students outperformed students in the Norwegian sample both in addition and subtraction fluency. There were more Norwegian students in the LA group (i.e. performance at or below the 25th percentile) in both addition (37.9% vs. 20.1%) and subtraction (39.1% vs. 15.8%). In comparison to the TA students, the LA students made more errors and skipped over more arithmetic tasks in an attempt to solve them. Observed differences are discussed in relation to both country characteristics concerning early mathematics education and early educational support.
  • Reckling, Moritz; Hecker, Jens-Martin; Bergkvist, Goeran; Watson, Christine A.; Zander, Peter; Schlaefke, Nicole; Stoddard, Frederick L.; Eory, Vera; Topp, Cairistiona F. E.; Maire, Juliette; Bachinger, Johann (2016)
    Methods are needed for the design and evaluation of cropping systems, in order to test the effects of introducing or reintroducing crops into rotations. The interaction of legumes with other crops (rotational effects) requires an assessment at the cropping system scale. The objective of this work is to introduce a cropping system framework to assess the impacts of changes in cropping systems in a participatory approach with experts, i.e., the integration of legumes into crop rotations and to demonstrate its application in two case studies. The framework consists of a rule-based rotation generator and a set of algorithms to calculate impact indicators. It follows a three-step approach: (i) generate rotations, (ii) evaluate crop production activities using environmental, economic and phytosanitary indicators, and (iii) design cropping systems and assess their impacts. Experienced agronomists and environmental scientists were involved at several stages of the framework development and testing in order to ensure the practicability of designed cropping systems. The framework was tested in Vastra Gotaland (Sweden) and Brandenburg (Germany) by comparing cropping systems with and without legumes. In both case studies, cropping systems with legumes reduced nitrous oxide emissions with comparable or slightly lower nitrate-N leaching, and had positive phytosanitary effects. In arable systems with grain legumes, gross margins were lower than in cropping systems without legumes despite taking pre-crop effects into account. Forage cropping systems with legumes had higher or equivalent gross margins and at the same time higher environmental benefits than cropping systems without legumes. The framework supports agronomists to design sustainable legume-supported cropping systems and to assess their impacts. (C) 2015 The Authors. Published by Elsevier B.V.
  • Grubman, Alexandra; Vandekolk, Teresa H.; Schröder, Jan; Sun, Guizhi; Hatwell-Humble, Jessica; Chan, Jonathan; Oksanen, Minna; Lehtonen, Sarka; Hunt, Cameron; Koistinaho, Jan E.; Nilsson, Susan K.; Haynes, John M.; Pouton, Colin W.; Polo, Jose M. (2020)
    Multiple protocols have been published for generation of iMGLs from hESCs/iPSCs. To date, there are no guides to assist researchers to determine the most appropriate methodology for microglial studies. To establish a framework to facilitate future microglial studies, we first performed a comparative transcriptional analysis between iMGLs derived using three published datasets, which allowed us to establish the baseline protocol that is most representative of bona fide human microglia. Secondly, using CRISPR to tag the classic microglial marker CX3CR1 with nanoluciferase and tdTomato, we generated and functionally validated a reporter ESC line. Finally, using this cell line, we demonstrated that co-culture of iMGL precursors with human glia and neurons enhanced transcriptional resemblance of iMGLs to ex vivo microglia. Together, our comprehensive molecular analysis and reporter cell line are a useful resource for neurobiologists seeking to use iMGLs for disease modeling and drug screening studies.
  • Silva, Sofia Marques; Townsend Peterson, A.; Carneiro, Lincoln; Tortola Burlamaqui, Tiberio Cesar; Ribas, Camila C.; Sousa-Neves, Tiago; Miranda, Leonardo S.; Fernandes, Alexandre M.; d'Horta, Fernando M.; Araujo-Silva, Lucas Eduardo; Batista, Romina; Bandeira, Cinthia H. M. M.; Dantas, Sidnei M.; Ferreira, Mateus; Martins, Denise M.; Oliveira, Joiciane; Rocha, Taina C.; Sardelli, Carla H.; Thom, Gregory; Rego, Pericles Sena; Santos, Marcos Persio; Sequeira, Fernando; Vallinoto, Marcelo; Aleixo, Alexandre (2019)
    The Amazon is the primary source of Neotropical diversity and a nexus for discussions on processes that drive biotic diversification. Biogeographers have focused on the roles of rivers and Pleistocene climate change in explaining high rates of speciation. We combine phylogeographic and niche-based paleodistributional projections for 23 upland terra firme forest bird lineages from across the Amazon to derive a new model of regional biological diversification. We found that climate-driven refugial dynamics interact with dynamic riverine barriers to produce a dominant pattern: Older lineages in the wetter western and northern parts of the Amazon gave rise to lineages in the drier southern and eastern parts. This climate/drainage basin evolution interaction links landscape dynamics with biotic diversification and explains the east-west diversity gradients across the Amazon.
  • Hytönen, Marjo Kristiina; Arumilli, Meharji; Lappalainen, Anu K.; Kallio, Heli; Snellman, Marjatta; Sainio, Kirsi; Lohi, Hannes (2012)
  • Salo, Tuula; Sutinen, Meeri; Apu, Ehsanul Hoque; Sundquist, Elias; Cervigne, Nilva K.; de Oliveira, Carine Ervolino; Akram, Saad Ullah; Ohlmeier, Steffen; Suomi, Fumi; Eklund, Lauri; Juusela, Pirjo; Astrom, Pirjo; Bitu, Carolina Cavalcante; Santala, Markku; Savolainen, Kalle; Korvala, Johanna; Paes Leme, Adriana Franco; Coletta, Ricardo D. (2015)
    Background: The composition of the matrix molecules is important in in vitro cell culture experiments of e.g. human cancer invasion and vessel formation. Currently, the mouse Engelbreth-Holm-Swarm (EHS) sarcoma -derived products, such as Matrigel (R), are the most commonly used tumor microenvironment (TME) mimicking matrices for experimental studies. However, since Matrigel (R) is non-human in origin, its molecular composition does not accurately simulate human TME. We have previously described a solid 3D organotypic myoma disc invasion assay, which is derived from human uterus benign leiomyoma tumor. Here, we describe the preparation and analyses of a processed, gelatinous leiomyoma matrix, named Myogel. Methods: A total protein extract, Myogel, was formulated from myoma. The protein contents of Myogel were characterized and its composition and properties compared with a commercial mouse Matrigel (R). Myogel was tested and compared to Matrigel (R) in human cell adhesion, migration, invasion, colony formation, spheroid culture and vessel formation experiments, as well as in a 3D hanging drop video image analysis. Results: We demonstrated that only 34 % of Myogel's molecular content was similar to Matrigel (R). All test results showed that Myogel was comparable with Matrigel (R), and when mixed with low-melting agarose (Myogel-LMA) it was superior to Matrigel (R) in in vitro Transwell (R) invasion and capillary formation assays. Conclusions: In conclusion, we have developed a novel Myogel TME matrix, which is recommended for in vitro human cell culture experiments since it closely mimics the human tumor microenvironment of solid cancers.
  • Fritsch, Coralie; Campillo, Fabien; Ovaskainen, Otso (2017)
    We propose a numerical approach to study the invasion fitness of a mutant and to determine evolutionary singular strategies in evolutionary structured models in which the competitive exclusion principle holds. Our approach is based on a dual representation, which consists of the modeling of the small size mutant population by a stochastic model and the computation of its corresponding deterministic model. The use of the deterministic model greatly facilitates the numerical determination of the feasibility of invasion as well as the convergence-stability of the evolutionary singular strategy. Our approach combines standard adaptive dynamics with the link between the mutant survival criterion in the stochastic model and the sign of the eigenvalue in the corresponding deterministic model. We present our method in the context of a mass-structured individual-based chemostat model. We exploit a previously derived mathematical relationship between stochastic and deterministic representations of the mutant population in the chemostat model to derive a general numerical method for analyzing the invasion fitness in the stochastic models. Our method can be applied to the broad class of evolutionary models for which a link between the stochastic and deterministic invasion fitnesses can be established. (C) 2017 Elsevier Inc. All rights reserved.
  • Siiki, Antti; Rinta-Kiikka, Irina; Sand, Juhani; Laukkarinen, Johanna (2018)
    Background and Aims: Self-expanding biodegradable biliary stents (BDBSs) have recently become available for use in endoscopic retrograde cholangiography (ERC). The aim was to evaluate the effectiveness and safety of novel BDBSs in iatrogenic cystic duct leaks and benign biliary strictures (BBSs). Methods: Patients providing informed consent were recruited for the prospective study. Braided self-expanding poly-dioxanone BDBSs were inserted using ERC during from 2014 to 2016. Repeated liver function tests and magnetic resonance imaging were performed during follow-up. The main outcomes were treatment success and adverse events. Results: Thirteen patients, 5 women, median age 67 years (range, 43-79) underwent BDBS insertion for iatrogenic cystic duct leak (n = 7) or BBS (n = 6). Stent insertion using ERC was successful in all cases. All bile leaks were treated uneventfully with BDBSs. In BBSs, the clinical success rate of BDBS therapy was 83% in a median of 21 months of follow-up (range, 14-25). Early ERC-related adverse events included 1 cholangitis (8%) and 1 pancreatitis (8%), both in the stricture group. During the first 90 days, 23% of patients were readmitted for mild cholangitis. Conclusions: The short-and long-term safety of endoscopically inserted poly-dioxanone BDBSs was satisfactory. The management of cystic duct leaks and benign distal common bile duct strictures was highly successful. Episodes of mild cholangitis during stent indwelling seemed to be typical of BDBSs. The advantage of BDBSs is the avoidance of repeated endoscopy for stent removal. (Clinical trial registration number: NCT02353286.)
  • Schnitzbauer, Andreas A.; Zuelke, Carl; Graeb, Christian; Rochon, Justine; Bilbao, Itxarone; Burra, Patrizia; de Jong, Koert P.; Duvoux, Christophe; Kneteman, Norman M.; Adam, Rene; Bechstein, Wolf O.; Becker, Thomas; Beckebaum, Susanne; Chazouilleres, Olivier; Cillo, Umberto; Colledan, Michele; Faendrich, Fred; Gugenheim, Jean; Hauss, Johann P.; Heise, Michael; Hidalgo, Ernest; Jamieson, Neville; Koenigsrainer, Alfred; Lamby, Philipp E.; Lerut, Jan P.; Mäkisalo, Heikki; Margreiter, Raimund; Mazzaferro, Vincenzo; Mutzbauer, Ingrid; Otto, Gerd; Pageaux, Georges-Philippe; Pinna, Antonio D.; Pirenne, Jacques; Rizell, Magnus; Rossi, Giorgio; Rostaing, Lionel; Roy, Andre; Sanchez Turrion, Victor; Schmidt, Jan; Troisi, Roberto I.; van Hoek, Bart; Valente, Umberto; Wolf, Philippe; Wolters, Heiner; Mirza, Darius F.; Scholz, Tim; Steininger, Rudolf; Soderdahl, Gunnar; Strasser, Simone I.; Jauch, Karl-Walter; Neuhaus, Peter; Schlitt, Hans J.; Geissler, Edward K. (2010)
  • Lappalainen, Hanna K.; Sevanto, Sanna; Dal Maso, Miikka; Taipale, Risto; Kajos, Maija; Kolari, Pasi; Back, Jaana (2013)
  • Stegmann, Roelant A.; Zliobaite, Indre; Tolvanen, Tuukka; Hollmén, Jaakko; Read, Jesse (2018)
    Personal mobility data can nowadays be easily collected by personal mobile phones and used for analytical modeling. To assist in such an analysis, a variety of computational approaches have been developed. The goal is to extract mobility patterns in order to provide traveling assistance, information, recommendations or on-demand services. While various computational techniques are being developed, research literature on destination and route prediction lacks consistency in evaluation methods for such approaches. This study presents a review and categorization of evaluation criteria and terminology used in assessing the performance of such methods. The review is complemented by experimental analysis of selected evaluation criteria, to highlight the nuances existing between the evaluation measures. The experimental study uses previously unpublished mobility data of 15 users collected over a period of 6 months in Helsinki metropolitan area in Finland. The article is primarily intended for researchers developing approaches for personalized mobility analysis, as well as a guideline for practitioners to select criteria when assessing and selecting between computational approaches. Our main recommendation is to consider user-specific accuracy measures in addition to averaged aggregates, as well as to take into consideration that for many users accuracy does not saturate fast and the performance keeps evolving over time. Therefore, we recommend using time-weighted measures. (c) 2017 Wiley Periodicals, Inc.
  • Chawade, Aakash; Armoniene, Rita; Berg, Gunilla; Brazauskas, Gintaras; Frostgard, Gunilla; Geleta, Mulatu; Gorash, Andrii; Henriksson, Tina; Himanen, Kristiina; Ingver, Anne; Johansson, Eva; Jorgensen, Lise Nistrup; Koppel, Mati; Koppel, Reine; Makela, Pirjo; Ortiz, Rodomiro; Podyma, Wieslaw; Roitsch, Thomas; Ronis, Antanas; Svensson, Jan T.; Vallenback, Pernilla; Weih, Martin (2018)
    The Baltic Sea is one of the largest brackish water bodies in the world. Eutrophication is a major concern in the Baltic Sea due to the leakage of nutrients to the sea with agriculture being the primary source. Wheat (Triticum aestivum L.) is the most widely grown crop in the countries surrounding the Baltic Sea and thus promoting sustainable agriculture practices for wheat cultivation will have a major impact on reducing pollution in the Baltic Sea. This approach requires identifying and addressing key challenges for sustainable wheat production in the region. Implementing new technologies for climate-friendly breeding and digital farming across all surrounding countries should promote sustainable intensification of agriculture in the region. In this review, we highlight major challenges for wheat cultivation in the Baltic Sea region and discuss various solutions integrating transnational collaboration for pre-breeding and technology sharing to accelerate development of low input wheat cultivars with improved host plant resistance to pathogen and enhanced adaptability to the changing climate.