Search Results
Improving Accuracy and Temporal Resolution of Learning Curve Estimation for within- and across-Session Analysis
2016, Deliano, Matthias, Tabelow, Karsten, König, Reinhard, Polzehl, Jörg
Estimation of learning curves is ubiquitously based on proportions of correct responses within moving trial windows. Thereby, it is tacitly assumed that learning performance is constant within the moving windows, which, however, is often not the case. In the present study we demonstrate that violations of this assumption lead to systematic errors in the analysis of learning curves, and we explored the dependency of these errors on window size, different statistical models, and learning phase. To reduce these errors in the analysis of single-subject data as well as on the population level, we propose adequate statistical methods for the estimation of learning curves and the construction of confidence intervals, trial by trial. Applied to data from an avoidance learning experiment with rodents, these methods revealed performance changes occurring at multiple time scales within and across training sessions which were otherwise obscured in the conventional analysis. Our work shows that the proper assessment of the behavioral dynamics of learning at high temporal resolution can shed new light on specific learning processes, and, thus, allows to refine existing learning concepts. It further disambiguates the interpretation of neurophysiological signal changes recorded during training in relation to learning.
State-of-the-art global models underestimate impacts from climate extremes
2019, Schewe, Jacob, Gosling, Simon N., Reyer, Christopher, Zhao, Fang, Ciais, Philippe, Elliott, Joshua, Francois, Louis, Huber, Veronika, Lotze, Heike K., Seneviratne, Sonia I., van Vliet, Michelle T. H., Vautard, Robert, Wada, Yoshihide, Breuer, Lutz, Büchner, Matthias, Carozza, David A., Chang, Jinfeng, Coll, Marta, Deryng, Delphine, de Wit, Allard, Eddy, Tyler D., Folberth, Christian, Frieler, Katja, Friend, Andrew D., Gerten, Dieter, Gudmundsson, Lukas, Hanasaki, Naota, Ito, Akihiko, Khabarov, Nikolay, Kim, Hyungjun, Lawrence, Peter, Morfopoulos, Catherine, Müller, Christoph, Müller Schmied, Hannes, Orth, René, Ostberg, Sebastian, Pokhrel, Yadu, Pugh, Thomas A. M., Sakurai, Gen, Satoh, Yusuke, Schmid, Erwin, Stacke, Tobias, Steenbeek, Jeroen, Steinkamp, Jörg, Tang, Qiuhong, Tian, Hanqin, Tittensor, Derek P., Volkholz, Jan, Wang, Xuhui, Warszawski, Lila
Global impact models represent process-level understanding of how natural and human systems may be affected by climate change. Their projections are used in integrated assessments of climate change. Here we test, for the first time, systematically across many important systems, how well such impact models capture the impacts of extreme climate conditions. Using the 2003 European heat wave and drought as a historical analogue for comparable events in the future, we find that a majority of models underestimate the extremeness of impacts in important sectors such as agriculture, terrestrial ecosystems, and heat-related human mortality, while impacts on water resources and hydropower are overestimated in some river basins; and the spread across models is often large. This has important implications for economic assessments of climate change impacts that rely on these models. It also means that societal risks from future extreme events may be greater than previously thought.
Guidance of mesenchymal stem cells on fibronectin structured hydrogel films
2014, Kasten, Annika, Naser, Tamara, Brüllhoff, Kristina, Fiedler, Jörg, Müller, Petra, Möller, Martin, Rychly, Joachim, Groll, Jürgen, Brenner, Rolf E., Engler, Adam J.
Designing of implant surfaces using a suitable ligand for cell adhesion to stimulate specific biological responses of stem cells will boost the application of regenerative implants. For example, materials that facilitate rapid and guided migration of stem cells would promote tissue regeneration. When seeded on fibronectin (FN) that was homogeneously immmobilized to NCO-sP(EO-stat-PO), which otherwise prevents protein binding and cell adhesion, human mesenchymal stem cells (MSC) revealed a faster migration, increased spreading and a more rapid organization of different cellular components for cell adhesion on fibronectin than on a glass surface. To further explore, how a structural organization of FN controls the behavior of MSC, adhesive lines of FN with varying width between 10 µm and 80 µm and spacings between 5 µm and 20 µm that did not allow cell adhesion were generated. In dependance on both line width and gaps, cells formed adjacent cell contacts, were individually organized in lines, or bridged the lines. With decreasing sizes of FN lines, speed and directionality of cell migration increased, which correlated with organization of the actin cytoskeleton, size and shape of the nuclei as well as of focal adhesions. Together, defined FN lines and gaps enabled a fine tuning of the structural organization of cellular components and migration. Microstructured adhesive substrates can mimic the extracellular matrix in vivo and stimulate cellular mechanisms which play a role in tissue regeneration.
A systematic review of non-productivity-related animal-based indicators of heat stress resilience in dairy cattle
2018-11-1, Galán, Elena, Llonch, Pol, Villagrá, Arantxa, Levit, Harel, Pinto, Severino, del Prado, AgustÃn
Introduction Projected temperature rise in the upcoming years due to climate change has increased interest in studying the effects of heat stress in dairy cows. Environmental indices are commonly used for detecting heat stress, but have been used mainly in studies focused on the productivity-related effects of heat stress. The welfare approach involves identifying physiological and behavioural measurements so as to start heat stress mitigation protocols before the appearance of impending severe health or production issues. Therefore, there is growing interest in studying the effects of heat stress on welfare. This systematic review seeks to summarise the animal-based responses to heat stress (physiological and behavioural, excluding productivity) that have been used in scientific literature. Methods Using systematic review guidelines set by PRISMA, research articles were identified, screened and summarised based on inclusion criteria for physiology and behaviour, excluding productivity, for animal-based resilience indicators. 129 published articles were reviewed to determine which animal-based indicators for heat stress were most frequently used in dairy cows. Results The articles considered report at least 212 different animal-based indicators that can be aggregated into body temperature, feeding, physiological response, resting, drinking, grazing and pasture-related behaviour, reactions to heat management and others. The most common physiological animal-based indicators are rectal temperature, respiration rate and dry matter intake, while the most common behavioural indicators are time spent lying, standing and feeding. Conclusion Although body temperature and respiration rate are the animal-based indicators most frequently used to assess heat stress in dairy cattle, when choosing an animal-based indicator for detecting heat stress using scientific literature to establish thresholds, characteristics that influence the scale of the response and the definition of heat stress must be taken into account, e.g. breed, lactation stage, milk yield, system type, climate region, bedding type, diet and cooling management strategies. © 2018 Galan∗E.∗Elena et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Monoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133)
2016, Thamm, Kristina, Graupner, Sylvi, Werner, Carsten, Huttner, Wieland B., Corbeil, Denis, Nabi, Ivan R
The pentaspan membrane glycoprotein prominin-1 (CD133) is widely used in medicine as a cell surface marker of stem and cancer stem cells. It has opened new avenues in stem cell-based regenerative therapy and oncology. This molecule is largely used with human samples or the mouse model, and consequently most biological tools including antibodies are directed against human and murine prominin-1. Although the general structure of prominin-1 including its membrane topology is conserved throughout the animal kingdom, its primary sequence is poorly conserved. Thus, it is unclear if anti-human and -mouse prominin-1 antibodies cross-react with their orthologs in other species, especially dog. Answering this issue is imperative in light of the growing number of studies using canine prominin-1 as an antigenic marker. Here, we address this issue by cloning the canine prominin-1 and use its overexpression as a green fluorescent protein fusion protein in Madin-Darby canine kidney cells to determine its immunoreactivity with antibodies against human or mouse prominin-1. We used immunocytochemistry, flow cytometry and immunoblotting techniques and surprisingly found no cross-species immunoreactivity. These results raise some caution in data interpretation when anti-prominin-1 antibodies are used in interspecies studies.
Environmental co-benefits and adverse side-effects of alternative power sector decarbonization strategies
2019, Luderer, Gunnar, Pehl, Michaja, Arvesen, Anders, Gibon, Thomas, Bodirsky, Benjamin L., de Boer, Harmen Sytze, Fricko, Oliver, Hejazi, Mohamad, Humpenöder, Florian, Iyer, Gokul, Mima, Silvana, Mouratiadou, Ioanna, Pietzcker, Robert C., Popp, Alexander, van den Berg, Maarten, van Vuuren, Detlef, Hertwich, Edgar G.
A rapid and deep decarbonization of power supply worldwide is required to limit global warming to well below 2 °C. Beyond greenhouse gas emissions, the power sector is also responsible for numerous other environmental impacts. Here we combine scenarios from integrated assessment models with a forward-looking life-cycle assessment to explore how alternative technology choices in power sector decarbonization pathways compare in terms of non-climate environmental impacts at the system level. While all decarbonization pathways yield major environmental co-benefits, we find that the scale of co-benefits as well as profiles of adverse side-effects depend strongly on technology choice. Mitigation scenarios focusing on wind and solar power are more effective in reducing human health impacts compared to those with low renewable energy, while inducing a more pronounced shift away from fossil and toward mineral resource depletion. Conversely, non-climate ecosystem damages are highly uncertain but tend to increase, chiefly due to land requirements for bioenergy.
ColiCoords: A Python package for the analysis of bacterial fluorescence microscopy data
2019, Smit, Jochem H., Li, Yichen, Warszawik, Eliza M., Herrmann, Andreas, Cordes, Thorben, Gilestro, Giorgio F
Single-molecule fluorescence microscopy studies of bacteria provide unique insights into the mechanisms of cellular processes and protein machineries in ways that are unrivalled by any other technique. With the cost of microscopes dropping and the availability of fully automated microscopes, the volume of microscopy data produced has increased tremendously. These developments have moved the bottleneck of throughput from image acquisition and sample preparation to data analysis. Furthermore, requirements for analysis procedures have become more stringent given the demand of various journals to make data and analysis procedures available. To address these issues we have developed a new data analysis package for analysis of fluorescence microscopy data from rod-like cells. Our software ColiCoords structures microscopy data at the single-cell level and implements a coordinate system describing each cell. This allows for the transformation of Cartesian coordinates from transmission light and fluorescence images and single-molecule localization microscopy (SMLM) data to cellular coordinates. Using this transformation, many cells can be combined to increase the statistical power of fluorescence microscopy datasets of any kind. ColiCoords is open source, implemented in the programming language Python, and is extensively documented. This allows for modifications for specific needs or to inspect and publish data analysis procedures. By providing a format that allows for easy sharing of code and associated data, we intend to promote open and reproducible research. The source code and documentation can be found via the project’s GitHub page.
Effect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study
2017, Walker, Jochen, Mertens, Ulf Kai, Schmidt, Carsten Oliver, Chenot, Jean-François
Spinal manual therapy (SMT) is a popular treatment option for low back pain (LBP). The aim of our analysis was to evaluate the effects of manual therapy delivered by general practitioners and ambulatory orthopedic surgeons in routine care on follow up consultations, sick leave, health service utilization and costs for acute LBP compared to matched patients not receiving manual therapy. This is a propensity score matched cohort study based on health claims data. We identified a total of 113.652 adult patients with acute LBP and no coded red flags of whom 21.021 (18%) received SMT by physicians. In the final analysis 17.965 patients in each group could be matched. Balance on patients' coded characteristics, comorbidity and prior health service utilization was achieved. The provision of SMT for acute LBP had no relevant impact on follow up visits and days of sick leave for LBP in the index billing period and the following year. SMT was associated with a higher proportion of imaging studies for LBP (30.6% vs. 23%, SMD: 0.164 [95% CI 0.143-0.185]). SMT did not lead to meaningful savings by replacing other health services for LBP. SMT for acute non-specific LBP in routine care was not clinically meaningful effective to reduce sick leave and reconsultation rates compared to no SMT and did not lead to meaningful savings by replacing other health services from the perspective of health insurance. This does not imply that SMT is ineffective but might reflect a problem with selection of suitable patients and the quality and quantity of SMT in routine care. National Manual Medicine societies should state clearly that imaging is not routinely needed prior to SMT in patients with low suspicion of presence of red flags and monitor the quality of provided services.
Key determinants of global land-use projections
2019, Stehfest, Elke, van Zeist, Willem-Jan, Valin, Hugo, Havlik, Petr, Popp, Alexander, Kyle, Page, Tabeau, Andrzej, Mason-D’Croz, Daniel, Hasegawa, Tomoko, Bodirsky, Benjamin L., Calvin, Katherine, Doelman, Jonathan C., Fujimori, Shinichiro, Humpenöder, Florian, Lotze-Campen, Hermann, van Meijl, Hans, Wiebe, Keith
Land use is at the core of various sustainable development goals. Long-term climate foresight studies have structured their recent analyses around five socio-economic pathways (SSPs), with consistent storylines of future macroeconomic and societal developments; however, model quantification of these scenarios shows substantial heterogeneity in land-use projections. Here we build on a recently developed sensitivity approach to identify how future land use depends on six distinct socio-economic drivers (population, wealth, consumption preferences, agricultural productivity, land-use regulation, and trade) and their interactions. Spread across models arises mostly from diverging sensitivities to long-term drivers and from various representations of land-use regulation and trade, calling for reconciliation efforts and more empirical research. Most influential determinants for future cropland and pasture extent are population and agricultural efficiency. Furthermore, land-use regulation and consumption changes can play a key role in reducing both land use and food-security risks, and need to be central elements in sustainable development strategies.
Simultaneous statistical inference for epigenetic data
2015, Schildknecht, Konstantin, Olek, Sven, Dickhaus, Thorsten
Epigenetic research leads to complex data structures. Since parametric model assumptions for the distribution of epigenetic data are hard to verify we introduce in the present work a nonparametric statistical framework for two-group comparisons. Furthermore, epigenetic analyses are often performed at various genetic loci simultaneously. Hence, in order to be able to draw valid conclusions for specific loci, an appropriate multiple testing correction is necessary. Finally, with technologies available for the simultaneous assessment of many interrelated biological parameters (such as gene arrays), statistical approaches also need to deal with a possibly unknown dependency structure in the data. Our statistical approach to the nonparametric comparison of two samples with independent multivariate observables is based on recently developed multivariate multiple permutation tests. We adapt their theory in order to cope with families of hypotheses regarding relative effects. Our results indicate that the multivariate multiple permutation test keeps the pre-assigned type I error level for the global null hypothesis. In combination with the closure principle, the family-wise error rate for the simultaneous test of the corresponding locus/parameter-specific null hypotheses can be controlled. In applications we demonstrate that group differences in epigenetic data can be detected reliably with our methodology.