scholarly journals Holistic View on Cell Survival and DNA Damage: How Model-Based Data Analysis Supports Exploration of Dynamics in Biological Systems

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Mathias S. Weyland ◽  
Pauline Thumser-Henner ◽  
Katarzyna J. Nytko ◽  
Carla Rohrer Bley ◽  
Simone Ulzega ◽  
...  
Keyword(s):  
Dna Damage ◽  
Model Calibration ◽  
Biological Effects ◽  
Holistic Approach ◽  
Model Parameters ◽  
Calibration Model ◽  
Sources Of Information ◽  
Dna Damage And Repair ◽  
Holistic View ◽  
Successful Model

In this work, a method is established to calibrate a model that describes the basic dynamics of DNA damage and repair. The model can be used to extend planning for radiotherapy and hyperthermia in order to include the biological effects. In contrast to “syntactic” models (e.g., describing molecular kinetics), the model used here describes radiobiological semantics, resulting in a more powerful model but also in a far more challenging calibration. Model calibration is attempted from clonogenic assay data (doses of 0–6 Gy) and from time-resolved comet assay data obtained within 6 h after irradiation with 6 Gy. It is demonstrated that either of those two sources of information alone is insufficient for successful model calibration, and that both sources of information combined in a holistic approach are necessary to find viable model parameters. Approximate Bayesian computation (ABC) with simulated annealing is used for parameter search, revealing two aspects that are beneficial to resolving the calibration problem: (1) assessing posterior parameter distributions instead of point-estimates and (2) combining calibration runs from different assays by joining posterior distributions instead of running a single calibration run with a combined, computationally very expensive objective function.

Reconciling internal and external satisfaction through probabilistic graphical models

2017 ◽  
Vol 9 (3/4) ◽  
pp. 347-370 ◽  
Author(s):  
Flaminia Musella ◽  
Roberta Guglielmetti Mugion ◽  
Hendry Raharjo ◽  
Laura Di Pietro
Keyword(s):  
Customer Satisfaction ◽  
Bayesian Networks ◽  
Graphical Models ◽  
Object Oriented ◽  
Holistic Approach ◽  
Probabilistic Graphical Models ◽  
Model Parameters ◽  
Holistic View ◽  
Content Type ◽  
External Customer

Purpose This paper aims to holistically reconcile internal and external customer satisfaction using probabilistic graphical models. The models are useful not only in the identification of the most sensitive factors for the creation of both internal and external customer satisfaction but also in the generation of improvement scenarios in a probabilistic way. Design/methodology/approach Standard Bayesian networks and object-oriented Bayesian networks are used to build probabilistic graphical models for internal and external customers. For each ward, the model is used to evaluate satisfaction drivers by category, and scenarios for the improvement of overall satisfaction variables are developed. A global model that is based on an object-oriented network is modularly built to provide a holistic view of internal and external satisfaction. The linkage is created by building a global index of internal and external satisfaction based on a linear combination. The model parameters are derived from survey data from an Italian hospital. Findings The results that were achieved with the Bayesian networks are consistent with the results of previous research, and they were obtained by using a partial least squares path modelling tool. The variable ‘Experience’ is the most relevant internal factor for the improvement of overall patient satisfaction. To improve overall employee satisfaction, the variable ‘Product/service results’ is the most important. Finally, for a given target of overall internal and external satisfaction, external satisfaction is more sensitive to improvement than internal satisfaction. Originality/value The novelty of the paper lies in the efforts to link internal and external satisfaction based on a probabilistic expert system that can generate improvement scenarios. From an academic viewpoint, this study moves the service profit chain theory (Heskett et al., 1994) forward by delivering operational guidelines for jointly managing the factors that affect internal and external customer satisfaction in service organizations using a holistic approach.

scholarly journals Toxicity and Functional Tissue Responses of Two Freshwater Fish after Exposure to Polystyrene Microplastics

Toxics ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 289
Author(s):  
Martha Kaloyianni ◽  
Dimitra C. Bobori ◽  
Despoina Xanthopoulou ◽  
Glykeria Malioufa ◽  
Ioannis Sampsonidis ◽  
...  
Keyword(s):  
Dna Damage ◽  
Freshwater Fish ◽  
Fish Species ◽  
Biological Effects ◽  
Perca Fluviatilis ◽  
Aquatic Organisms ◽  
Gill Tissue ◽  
Holistic Approach ◽  
Protein Carbonyls ◽  
Chemical Additives

Microplastics (MPs)’ ingestion has been demonstrated in several aquatic organisms. This process may facilitate the hydrophobic waterborne pollutants or chemical additives transfer to biota. In the present study the suitability of a battery of biomarkers on oxidative stress, physiology, tissue function and metabolic profile was investigated for the early detection of adverse effects of 21-day exposure to polystyrene microplastics (PS-MPs, sized 5–12 μm) in the liver and gills of zebrafish Danio rerio and perch, Perca fluviatilis, both of which are freshwater fish species. An optical volume map representation of the zebrafish gill by Raman spectroscopy depicted 5 μm diameter PS-MP dispersed in the gill tissue. Concentrations of PS-MPs close to the EC50 of each fish affected fish physiology in all tissues studied. Increased levels of biomarkers of oxidative damage in exposed fish in relation to controls were observed, as well as activation of apoptosis and autophagy processes. Malondialdehyde (MDA), protein carbonyls and DNA damage responses differed with regard to the sensitivity of each tissue of each fish. In the toxicity cascade gills seemed to be more liable to respond to PS-MPs than liver for the majority of the parameters measured. DNA damage was the most susceptible biomarker exhibiting greater response in the liver of both species. The interaction between MPs and cellular components provoked metabolic alterations in the tissues studied, affecting mainly amino acids, nitrogen and energy metabolism. Toxicity was species and tissue specific, with specific biomarkers responding differently in gills and in liver. The fish species that seemed to be more susceptible to MPs at the conditions studied, was P. fluviatilis compared to D. rerio. The current findings add to a holistic approach for the identification of small sized PS-MPs’ biological effects in fish, thus aiming to provide evidence regarding PS-MPs’ environmental impact on wild fish populations and food safety and adequacy.

scholarly journals Role of DNA Damage and Repair in Detrimental Effects of Ionizing Radiation

Radiation ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 1-4
Author(s):  
Alexandros G. Georgakilas
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Biological Effects ◽  
Full Range ◽  
High Quality Research ◽  
Dna Damage And Repair ◽  
Biological Damage ◽  
Biological Responses ◽  
Technical Advances ◽  
Living Organisms

Ionizing radiation (IR) is considered a traditional mutagen and genotoxic agent. Exposure to IR affects in all cases biological systems and living organisms from plants to humans mostly in a pernicious way. At low (<0.1 Gy) and low-to-medium doses (0.1–1 Gy), one can find in the literature a variety of findings indicating sometimes a positive-like anti-inflammatory effect or detrimental-like toxicity. In this Special Issue and in general in the current research, we would like to acquire works and more knowledge on the role(s) of DNA damage and its repair induced by ionizing radiations as instigators of the full range of biological responses to radiation. Emphasis should be given to advances offering mechanistic insights into the ability of radiations with different qualities to severely impact cells or tissues. High-quality research or review studies on different species projected to humans are welcome. Technical advances reporting on the methodologies to accurately measure DNA or other types of biological damage must be highly considered for the near future in our research community, as well. Last but not least, clinical trials or protocols with improvements to radiation therapy and radiation protection are also included in our vision for the advancement of research regarding biological effects of IR.

scholarly journals Matching ERS scatterometer based soil moisture patterns with simulations of a conceptual dual layer hydrologic model over Austria

2009 ◽  
Vol 13 (2) ◽  
pp. 259-271 ◽  
Author(s):  
J. Parajka ◽  
V. Naeimi ◽  
G. Blöschl ◽  
J. Komma
Keyword(s):  
Soil Moisture ◽  
Model Calibration ◽  
Winter Season ◽  
Hydrologic Model ◽  
Model Parameters ◽  
Sources Of Information ◽  
Average Correlation ◽  
Robust Model ◽  
Spatial Coverage ◽  
Top Soil

Abstract. This study compares ERS scatterometer top soil moisture observations with simulations of a dual layer conceptual hydrologic model. The comparison is performed for 148 Austrian catchments in the period 1991–2000. On average, about 5 to 7 scatterometer images per month with a mean spatial coverage of about 37% are available. The results indicate that the agreement between the two top soil moisture estimates changes with the season and the weight given to the scatterometer in hydrologic model calibration. The hydrologic model generally simulates larger top soil moisture values than are observed by the scatterometer. The differences tend to be smaller for lower altitudes and the winter season. The average correlation between the two estimates is more than 0.5 in the period from July to October, and about 0.2 in the winter months, depending on the period and calibration setting. Using both ERS scatterometer based soil moisture and runoff for model calibration provides more robust model parameters than using either of these two sources of information.

scholarly journals Matching ERS scatterometer based soil moisture patterns with simulations of a conceptual dual layer hydrologic model over Austria

2008 ◽  
Vol 5 (6) ◽  
pp. 3313-3353 ◽  
Author(s):  
J. Parajka ◽  
V. Naeimi ◽  
G. Blöschl ◽  
J. Komma
Keyword(s):  
Soil Moisture ◽  
Model Calibration ◽  
Winter Season ◽  
Hydrologic Model ◽  
Model Parameters ◽  
Sources Of Information ◽  
Average Correlation ◽  
Robust Model ◽  
Spatial Coverage ◽  
Top Soil

Abstract. This study compares ERS scatterometer top soil moisture observations with simulations of a dual layer conceptual hydrologic model. The comparison is performed for 148 Austrian catchments in the period 1991–2000. On average, about 5 to 7 scatterometer images per month with a mean spatial coverage of about 37% are available. The results indicate that the agreement between the two top soil moisture estimates changes with the season and the weight given to the scatterometer in hydrologic model calibration. The hydrologic model generally simulates larger top soil moisture values than are observed by the scatterometer. The differences tend to be smaller for lower altitudes and the winter season. The average correlation between the two estimates is more than 0.5 in the period from July to October, and about 0.2 in the winter months, depending on the period and calibration setting. Using both ERS scatterometer based soil moisture and runoff for model calibration provides more robust model parameters than using either of these two sources of information.

DNA Damage and Repair in the Brain After Cerebral Ischemia

2001 ◽  
Vol 1 (6) ◽  
pp. 483-495 ◽  
Author(s):  
Bentham Science Publisher Philip K. Liu
Keyword(s):  
Dna Damage ◽  
Cerebral Ischemia ◽  
Dna Damage And Repair ◽  
The Brain

scholarly journals Transcriptome profiling of cells exposed to particular and intense electromagnetic radiation emitted by the "SG-III" prototype laser facility

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiangbin Wei ◽  
Qiwu Shi ◽  
Lidan Xiong ◽  
Guang Xin ◽  
Tao Yi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Pc12 Cells ◽  
Inertial Confinement Fusion ◽  
Biological Effects ◽  
Harmful Effect ◽  
Transcriptome Profiling ◽  
Target Chamber ◽  
Target Range ◽  
Inertial Confinement ◽  
Laser Facility

AbstractThe experiment of inertial confinement fusion by the “ShengGuang (SG)-III” prototype laser facility is a transient and extreme reaction process within several nanoseconds, which could form a very complicated and intense electromagnetic field around the target chamber of the facility and may lead to harmful effect on people around. In particular, the biological effects arising from such specific environment field could hardly be ignored and have never been investigated yet, and thus, we reported on the investigation of the biological effects of radiation on HaCat cells and PC12 cells to preliminarily assess the biological safety of the target range of the "SG-III" prototype laser facility. The viability revealed that the damage of cells was dose-dependent. Then we compared the transcriptomes of exposed and unexposed PC12 cells by RNA-Seq analysis based on Illumina Novaseq 6000 platform and found that most significantly differentially expressed genes with corresponding Gene Ontology terms and pathways were strongly involved in proliferation, transformation, necrosis, inflammation response, apoptosis and DNA damage. Furthermore, we find increase in the levels of several proteins responsible for cell-cycle regulation and tumor suppression, suggesting that pathways or mechanisms regarding DNA damage repair was are quickly activated. It was found that "SG-III" prototype radiation could induce DNA damage and promote apoptotic necrosis.

scholarly journals In Vivo and In Vitro Assays Evaluating the Biological Activity of Taurine, Glucose and Energetic Beverages

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2198
Author(s):  
Marcos Mateo-Fernández ◽  
Fernando Valenzuela-Gómez ◽  
Rafael Font ◽  
Mercedes Del Río-Celestino ◽  
Tania Merinas-Amo ◽  
...  
Keyword(s):  
Dna Damage ◽  
Drosophila Melanogaster ◽  
Biological Activity ◽  
Biological Effects ◽  
Methylation Status ◽  
Repetitive Sequences ◽  
Energy Drinks ◽  
Red Bull

Taurine is one of the main ingredients used in energy drinks which are highly consumed in adolescents for their sugary taste and stimulating effect. With energy drinks becoming a worldwide phenomenon, the biological effects of these beverages must be evaluated in order to fully comprehend the potential impact of these products on the health due to the fact nutrition is closely related to science since the population consumes food to prevent certain diseases. Therefore, the aim of this study was to evaluate the biological effects of taurine, glucose, classic Red Bull® and sugar-free Red Bull® in order to check the food safety and the nutraceutical potential of these compounds, characterising different endpoints: (i) Toxicology, antitoxicology, genotoxicology and life expectancy assays were performed in the Drosophila melanogaster model organism; (ii) The in vitro chemopreventive activity of testing compounds was determined by assessing their cytotoxicity, the proapoptotic DNA-damage capability to induce internucleosomal fragmentation, the strand breaks activity and the modulator role on the methylation status of genomic repetitive sequences of HL-60 promyelocytic cells. Whereas none tested compounds showed toxic or genotoxic effect, all tested compounds exerted antitoxic and antigenotoxic activity in Drosophila. Glucose, classic Red Bull® and sugar-free Red Bull® were cytotoxic in HL-60 cell line. Classic Red Bull® induced DNA internucleosomal fragmentation although none of them exhibited DNA damage on human leukaemia cells. In conclusion, the tested compounds are safe on Drosophila melanogaster and classic Red Bull® could overall possess nutraceutical potential in the in vivo and in vitro model used in this study. Besides, taurine could holistically be one of the bioactive compounds responsible for the biological activity of classic Red Bull®.

scholarly journals Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ding-fang Zhang ◽  
Zhi-chun Yang ◽  
Jian-qiang Chen ◽  
Xiang-xiang Jin ◽  
Yin-da Qiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Adhesion ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Dna Damage And Repair ◽  
Castration Resistant

Abstract Background Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer. Piperlongumine (PL) is a novel potential anticancer agent that has been demonstrated to exhibit anticancer efficacy against prostate cancer cells. However, the effects of PL on DNA damage and repair against CRPC have remained unclear. The aim of this study was to further explore the anticancer activity and mechanisms of action of PL against CRPC in terms of DNA damage and repair processes. Methods The effect of PL on CRPC was evaluated by MTT assay, long-term cell proliferation, reactive oxygen species assay, western blot assay, flow cytometry assay (annexin V/PI staining), β-gal staining assay and DAPI staining assay. The capacity of PL to inhibit the invasion and migration of CRPC cells was assessed by scratch-wound assay, cell adhesion assay, transwell assay and immunofluorescence (IF) assay. The effect of PL on DNA damage and repair was determined via IF assay and comet assay. Results The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells through affecting the expression and distribution of focal adhesion kinase (FAK), leading to concentration-dependent inhibition of CRPC cell proliferation and concomitantly increased cell death. Moreover, PL treatment triggered persistent DNA damage and provoked strong DNA damage responses in CRPC cells. Conclusion Collectively, our findings demonstrate that PL potently inhibited proliferation, migration, and invasion of CRPC cells and that these potent anticancer effects were potentially achieved via triggering persistent DNA damage in CRPC cells.

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