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- ItemCell stimulation versus cell death induced by sequential treatments with pulsed electric fields and cold atmospheric pressure plasma(San Francisco, California, US : PLOS, 2018) Steuer, Anna; Wolff, Christina M.; von Woedtke, Thomas; Weltmann, Klaus-Dieter; Kolb, Juergen F.Pulsed electric fields (PEFs) and cold atmospheric pressure plasma (CAP) are currently both investigated for medical applications. The exposure of cells to PEFs can induce the formation of pores in cell membranes and consequently facilitate the uptake of molecules. In contrast, CAP mainly acts through reactive species that are generated in the liquid environment. The objective of this study was to determine, if PEFs combined with plasma-treated cell culture medium can mutually reinforce effects on viability of mammalian cells. Experiments were conducted with rat liver epithelial WB-F344 cells and their tumorigenic counterpart WB-ras for a direct comparison of non-tumorigenic and tumorigenic cells from the same origin. Viability after treatments strongly depended on cell type and applied field strength. Notably, tumorigenic WB-ras cells responded more sensitive to the respective treatments than non-tumorigenic WB-F344 cells. More cells were killed when plasma-treated medium was applied first in combination with treatments with 100-μs PEFs. For the reversed treatment order, i.e. application of PEFs first, the combination with 100-ns PEFs resulted in a stimulating effect for non-tumorigenic but not for tumorigenic cells. The results suggest that other mechanisms, besides simple pore formation, contributed to the mutually reinforcing effects of the two methods.
- ItemImproving Accuracy and Temporal Resolution of Learning Curve Estimation for within- and across-Session Analysis(San Francisco, California, US : PLOS, 2016) Deliano, Matthias; Tabelow, Karsten; König, Reinhard; Polzehl, JörgEstimation 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.
- ItemMonoclonal Antibodies 13A4 and AC133 Do Not Recognize the Canine Ortholog of Mouse and Human Stem Cell Antigen Prominin-1 (CD133)(San Francisco, California, US : PLOS, 2016) Thamm, Kristina; Graupner, Sylvi; Werner, Carsten; Huttner, Wieland B.; Corbeil, Denis; Nabi, Ivan RThe 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.
- ItemProximal Soil Sensing - A Contribution for Species Habitat Distribution Modelling of Earthworms in Agricultural Soils?(San Francisco, California, US : PLOS, 2016) Schirrmann, Michael; Joschko, Monika; Gebbers, Robin; Kramer, Eckart; Zörner, Mirjam; Barkusky, Dietmar; Timmer, JensBackground: Earthworms are important for maintaining soil ecosystem functioning and serve as indicators of soil fertility. However, detection of earthworms is time-consuming, which hinders the assessment of earthworm abundances with high sampling density over entire fields. Recent developments of mobile terrestrial sensor platforms for proximal soil sensing (PSS) provided new tools for collecting dense spatial information of soils using various sensing principles. Yet, the potential of PSS for assessing earthworm habitats is largely unexplored. This study investigates whether PSS data contribute to the spatial prediction of earthworm abundances in species distribution models of agricultural soils. Methodology/Principal Findings: Proximal soil sensing data, e.g., soil electrical conductivity (EC), pH, and near infrared absorbance (NIR), were collected in real-time in a field with two management strategies (reduced tillage / conventional tillage) and sandy to loam soils. PSS was related to observations from a long-term (11 years) earthworm observation study conducted at 42 plots. Earthworms were sampled from 0.5 x 0.5 x 0.2 m³ soil blocks and identified to species level. Sensor data were highly correlated with earthworm abundances observed in reduced tillage but less correlated with earthworm abundances observed in conventional tillage. This may indicate that management influences the sensor-earthworm relationship. Generalized additive models and state-space models showed that modelling based on data fusion from EC, pH, and NIR sensors produced better results than modelling without sensor data or data from just a single sensor. Regarding the individual earthworm species, particular sensor combinations were more appropriate than others due to the different habitat requirements of the earthworms. Earthworm species with soil-specific habitat preferences were spatially predicted with higher accuracy by PSS than more ubiquitous species. Conclusions/Significance: Our findings suggest that PSS contributes to the spatial modelling of earthworm abundances at field scale and that it will support species distribution modelling in the attempt to understand the soil-earthworm relationships in agroecosystems.
- ItemAssessing agreement between preclinical magnetic resonance imaging and histology: An evaluation of their image qualities and quantitative results(San Francisco, California, US : PLOS, 2017) Elschner, Cindy; Korn, Paula; Hauptstock, Maria; Schulz, Matthias C.; Range, Ursula; Jünger, Diana; Scheler, UlrichOne consequence of demographic change is the increasing demand for biocompatible materials for use in implants and prostheses. This is accompanied by a growing number of experimental animals because the interactions between new biomaterials and its host tissue have to be investigated. To evaluate novel materials and engineered tissues the use of nondestructive imaging modalities have been identified as a strategic priority. This provides the opportunity for studying interactions repeatedly with individual animals, along with the advantages of reduced biological variability and decreased number of laboratory animals. However, histological techniques are still the golden standard in preclinical biomaterial research. The present article demonstrates a detailed method comparison between histology and magnetic resonance imaging. This includes the presentation of their image qualities as well as the detailed statistical analysis for assessing agreement between quantitative measures. Exemplarily, the bony ingrowth of tissue engineered bone substitutes for treatment of a cleft-like maxillary bone defect has been evaluated. By using a graphical concordance analysis the mean difference between MRI results and histomorphometrical measures has been examined. The analysis revealed a slightly but significant bias in the case of the bone volume ðbiasHisto MRI: Bonevolume = 2: 40 %, p < 0: 005) and a clearly significant deviation for the remaining defect width ðbiasHisto MRI: Defectwidth = 6: 73 %, p 0: 005Þ: But the study although showed a considerable effect of the analyzed section position to the quantitative result. It could be proven, that the bias of the data sets was less originated due to the imaging modalities, but mainly on the evaluation of different slice positions. The article demonstrated that method comparisons not always need the use of an independent animal study, additionally.
- ItemInvestigating the Mutagenicity of a Cold Argon-Plasma Jet in an HET-MN Model(San Francisco, California, US : PLOS, 2016) Kluge, Susanne; Bekeschus, Sander; Bender, Claudia; Benkhai, Hicham; Sckell, Axel; Below, Harald; Stope, Matthias B.; Kramer, Axel; Yousfi, MohammedObjective: So-called cold physical plasmas for biomedical applications generate reactive oxygen and nitrogen species and the latter can trigger DNA damage at high concentrations. Therefore, the mutagenic risks of a certified atmospheric pressure argon plasma jet (kINPen MED) and its predecessor model (kINPen 09) were assessed. Methods: Inner egg membranes of fertilized chicken eggs received a single treatment with either the kINPen 09 (1.5, 2.0, or 2.5 min) or the kINPen MED (3, 4, 5, or 10 min). After three days of incubation, blood smears (panoptic May-Grünwald-Giemsa stain) were performed, and 1000 erythrocytes per egg were evaluated for the presence of polychromatic and normochromic nuclear staining as well as nuclear aberrations and binucleated cells (hen’s egg test for micronuclei induction, HET-MN). At the same time, the embryo mortality was documented. For each experiment, positive controls (cyclophosphamide and methotrexate) and negative controls (NaCl-solution, argon gas) were included. Additionally, the antioxidant potential of the blood plasma was assessed by ascorbic acid oxidation assay after treatment. Results: For both plasma sources, there was no evidence of genotoxicity, although at the longest plasma exposure time of 10 min the mortality of the embryos exceeded 40%. The antioxidant potential in the egg’s blood plasma was not significantly reduced immediately (p = 0.32) or 1 h (p = 0.19) post exposure to cold plasma. Conclusion: The longest plasma treatment time with the kINPen MED was 5–10 fold above the recommended limit for treatment of chronic wounds in clinics. We did not find mutagenic effects for any plasma treatment time using the either kINPen 09 or kINPen MED. The data provided with the current study seem to confirm the lack of a genotoxic potential suggesting that a veterinary or clinical application of these argon plasma jets does not pose mutagenic risks.
- ItemEffect on healthcare utilization and costs of spinal manual therapy for acute low back pain in routine care: A propensity score matched cohort study(San Francisco, California, US : PLOS, 2017) Walker, Jochen; Mertens, Ulf Kai; Schmidt, Carsten Oliver; Chenot, Jean-FrançoisSpinal 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.
- ItemThe stability of memristive multidirectional associative memory neural networks with time-varying delays in the leakage terms via sampled-data control(San Francisco, California, US : PLOS, 2018) Wang, Weiping; Yu, Xin; Luo, Xiong; Wang, Long; Li, Lixiang; Kurths, Jürgen; Zhao, Wenbing; Xiao, JiuhongIn this paper, we propose a new model of memristive multidirectional associative memory neural networks, which concludes the time-varying delays in leakage terms via sampled-data control. We use the input delay method to turn the sampling system into a continuous time-delaying system. Then we analyze the exponential stability and asymptotic stability of the equilibrium points for this model. By constructing a suitable Lyapunov function, using the Lyapunov stability theorem and some inequality techniques, some sufficient criteria for ensuring the stability of equilibrium points are obtained. Finally, numerical examples are given to demonstrate the effectiveness of our results.
- ItemDiscovery of chitin in skeletons of non-verongiid Red Sea demosponges(San Francisco, California, US : PLOS, 2018) Ehrlich, Hermann; Shaala, Lamiaa A.; Youssef, Diaa T. A.; Żółtowska- Aksamitowska, Sonia; Tsurkan, Mikhail; Galli, Roberta; Meissner, Heike; Wysokowski, Marcin; Petrenko, Iaroslav; Tabachnick, Konstantin R.; Ivanenko, Viatcheslav N.; Bechmann, Nicole; Joseph, Yvonne; Jesionowski, TeofilMarine demosponges (Porifera: Demospongiae) are recognized as first metazoans which have developed over millions of years of evolution effective survival strategies based on unique metabolic pathways to produce both biologically active secondary metabolites and biopolymer-based stiff skeletons with 3D architecture. Up to date, among marine demosponges, only representatives of the Verongiida order have been known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. This work, to our knowledge, demonstrates for the first time that chitin is an important structural component within skeletons of non-verongiid demosponges Acarnus wolffgangi and Echinoclathria gibbosa collected in the Red Sea. Calcofluor white staining, FTIR and Raman analysis, ESI-MS, SEM, and fluorescence microscopy as well as a chitinase digestion assay were applied in order to confirm, with strong evidence, the finding of α-chitin in the skeleton of both species. We suggest that, the finding of chitin within these representatives of Poecilosclerida order is a promising step in the evaluation of these sponges as novel renewable sources for both biologically active metabolites and chitin, which are of prospective application for pharmacology and biomedicine.
- ItemBiogas residue parameterization for soil organic matter modeling(San Francisco, California, US : PLOS, 2018-10-12) Prays, Nadia; Dominik, Peter; Sänger, Anja; Franko, UweA variety of biogas residues (BGRs) have been used as organic fertilizer in agriculture. The use of these residues affects the storage of soil organic matter (SOM). In most cases, SOM changes can only be determined in long-term observations. Therefore, predictive modeling can be an efficient alternative, provided that the parameters required by the model are known for the considered BGRs. This study was conducted as a first approach to estimating the organic matter (OM) turnover parameters of BGRs for process modeling. We used carbon mineralization data from six BGRs from an incubation experiment, representing a range of substrate inputs, to calculate a turnover coefficient k controlling the velocity of fresh organic matter (FOM) decay and a synthesis coefficient describing the SOM creation from FOM. An SOM turnover model was applied in inverse mode to identify both parameters. In a second step, we related the parameters k and to chemical properties of the corresponding BGRs using a linear regression model and applied them to a long-term scenario simulation. According to the results of the incubation experiment, the k values ranged between 0.28 and 0.58 d-1 depending on the chemical composition of the FOM. The estimated values ranged between 0.8 and 0.89. The best linear relationship of k was found to occur with pH (R2 = 0.863). Parameter is related to the Ct/Norg ratio (R2 = 0.696). Long-term scenario simulations emphasized the necessity of specific k and values related to the chemical properties for each BGR. However, further research is needed to validate and improve these preliminary results. © 2018 Prays 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.