Publications by authors named "C Dietz"

308 Publications

Identification of Metal Stresses in Using Hyperspectral Reflectance Imaging.

Front Plant Sci 2021 16;12:624656. Epub 2021 Feb 16.

Department of Electrical and Computer Engineering, Sandia National Laboratories, Albuquerque, NM, United States.

Industrial accidents, such as the Fukushima and Chernobyl disasters, release harmful chemicals into the environment, covering large geographical areas. Natural flora may serve as biological sensors for detecting metal contamination, such as cesium. Spectral detection of plant stresses typically employs a few select wavelengths and often cannot distinguish between different stress phenotypes. In this study, we apply hyperspectral reflectance imaging in the visible and near-infrared along with multivariate curve resolution (MCR) analysis to identify unique spectral signatures of three stresses in : salt, copper, and cesium. While all stress conditions result in common stress physiology, hyperspectral reflectance imaging and MCR analysis produced unique spectral signatures that enabled classification of each stress. As the level of potassium was previously shown to affect cesium stress in plants, the response of to cesium stress under variable levels of potassium was also investigated. Increased levels of potassium reduced the spectral response of to cesium and prevented changes to chloroplast cellular organization. While metal stress mechanisms may vary under different environmental conditions, this study demonstrates that hyperspectral reflectance imaging with MCR analysis can distinguish metal stress phenotypes, providing the potential to detect metal contamination across large geographical areas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2021.624656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921809PMC
February 2021

Generative adversarial networks for the design of acoustic metamaterials.

J Acoust Soc Am 2021 Feb;149(2):1162

Chair of Vibroacoustics of Vehicles and Machines, Technical University of Munich, Garching 85748, Germany.

Metamaterials are attracting increasing interest in the field of acoustics due to their sound insulation effects. By periodically arranged structures, acoustic metamaterials can influence the way sound propagates in acoustic media. To date, the design of acoustic metamaterials relies primarily on the expertise of specialists since most effects are based on localized solutions and interference. This paper outlines a deep learning-based approach to extend current knowledge of metamaterial design in acoustics. We develop a design method by using conditional generative adversarial networks. The generative network proposes a cell candidate regarding a desired transmission behavior of the metamaterial. To validate our method, numerical simulations with the finite element method are performed. Our study reveals considerable insight into design strategies for sound insulation tasks. By providing design directives for acoustic metamaterials, cell candidates can be inspected and tailored to achieve desirable transmission characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1121/10.0003501DOI Listing
February 2021

Stakeholder Perspectives on Linking HIV Pre-Exposure Prophylaxis with Human Papillomavirus Vaccine.

AIDS Patient Care STDS 2021 Mar 23;35(3):65-68. Epub 2021 Feb 23.

Department of Population Health, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/apc.2020.0234DOI Listing
March 2021

Requirement of DNMT1 to orchestrate epigenomic reprogramming for NPM-ALK-driven lymphomagenesis.

Life Sci Alliance 2021 02 11;4(2). Epub 2020 Dec 11.

Department of Pathology, Medical University of Vienna, Vienna, Austria

Malignant transformation depends on genetic and epigenetic events that result in a burst of deregulated gene expression and chromatin changes. To dissect the sequence of events in this process, we used a T-cell-specific lymphoma model based on the human oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) translocation. We find that transformation of T cells shifts thymic cell populations to an undifferentiated immunophenotype, which occurs only after a period of latency, accompanied by induction of the MYC-NOTCH1 axis and deregulation of key epigenetic enzymes. We discover aberrant DNA methylation patterns, overlapping with regulatory regions, plus a high degree of epigenetic heterogeneity between individual tumors. In addition, ALK-positive tumors show a loss of associated methylation patterns of neighboring CpG sites. Notably, deletion of the maintenance DNA methyltransferase DNMT1 completely abrogates lymphomagenesis in this model, despite oncogenic signaling through NPM-ALK, suggesting that faithful maintenance of tumor-specific methylation through DNMT1 is essential for sustained proliferation and tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.26508/lsa.202000794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768196PMC
February 2021

Conceptual Framework for Dislocation-Modified Conductivity in Oxide Ceramics Deconvoluting Mesoscopic Structure, Core, and Space Charge Exemplified for SrTiO.

ACS Nano 2020 Nov 10. Epub 2020 Nov 10.

Department of Materials and Earth Science, Technical University of Darmstadt, Alarich-Weiss-Straße 2, 64287 Darmstadt, Germany.

The introduction of dislocations is a recently proposed strategy to tailor the functional and especially the electrical properties of ceramics. While several works confirm a clear impact of dislocations on electrical conductivity, some studies raise concern in particular when expanding to dislocation arrangements beyond a geometrically tractable bicrystal interface. Moreover, the lack of a complete classification on pertinent dislocation characteristics complicates a systematic discussion and hampers the design of dislocation-modified electrical conductivity. We proceed by mechanically introducing dislocations with three different mesoscopic structures into the model material single-crystal SrTiO and extensively characterizing them from both a mechanical as well as an electrical perspective. As a final result, a deconvolution of and enables us to obtain the complete picture of the effect of dislocations on functional properties, focusing here on electric properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c04491DOI Listing
November 2020

Vapor Pressure Assessment of Sulfolane-Based Eutectic Solvents: Experimental, PC-SAFT, and Molecular Dynamics.

J Phys Chem B 2020 11 9;124(46):10386-10397. Epub 2020 Nov 9.

Centro de Química Estrutural and Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal.

Since their discovery, deep eutectic solvents (DES) have been explored in multiple applications. However, the complete physicochemical characterization is still nonexistent for many of the proposed and used DES. In particular, vapor pressure, which is a crucial property for the application of DES as solvents, is very rarely available. In this work, the measurement of the total and partial pressures of two sulfolane-based DES, tetrabutylammonium bromide:sulfolane and tetrabutylphosphonium bromide:sulfolane, in several proportions, from 40 to 100 °C and atmospheric pressure, was performed using headspace gas chromatography mass spectrometry, HS-GC-MS. A large decrease on the total pressure was recorded which, together with the finding that total pressures showed negative deviations from Raoult's law, is indicative of the favorable, strong interactions between the two components within the DES. Additionally, the study of vapor pressure change with DES molar composition was carried out, and surprisingly, the existence of inflection points in the pressure curve was observed. Experimental results were modeled using the PC-SAFT equation of state, and in addition, MD simulations were performed to provide a molecular understanding of the pressure data. Considering the different results and insights obtained from the used strategies, it can be concluded that both DES systems have especially strong interactions between salt and sulfolane, at high sulfolane content, due to the different structural rearrangement of the liquid state.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jpcb.0c04837DOI Listing
November 2020

Integration of the ImageJ Ecosystem in the KNIME Analytics Platform.

Front Comput Sci 2020 Mar 17;2. Epub 2020 Mar 17.

Laboratory for Optical and Computational Instrumentation (LOCI), Laboratory of Cell and Molecular Biology, University of Wisconsin-Madison, Madison, WI, USA.

Open-source software tools are often used for analysis of scientific image data due to their flexibility and transparency in dealing with rapidly evolving imaging technologies. The complex nature of image analysis problems frequently requires many tools to be used in conjunction, including image processing and analysis, data processing, machine learning and deep learning, statistical analysis of the results, visualization, correlation to heterogeneous but related data, and more. However, the development, and therefore application, of these computational tools is impeded by a lack of integration across platforms. Integration of tools goes beyond convenience, as it is impractical for one tool to anticipate and accommodate the current and future needs of every user. This problem is emphasized in the field of bioimage analysis, where various rapidly emerging methods are quickly being adopted by researchers. ImageJ is a popular open-source image analysis platform, with contributions from a global community resulting in hundreds of specialized routines for a wide array of scientific tasks. ImageJ's strength lies in its accessibility and extensibility, allowing researchers to easily improve the software to solve their image analysis tasks. However, ImageJ is not designed for development of complex end-to-end image analysis workflows. Scientists are often forced to create highly specialized and hard-to-reproduce scripts to orchestrate individual software fragments and cover the entire life-cycle of an analysis of an image dataset. KNIME Analytics Platform, a user-friendly data integration, analysis, and exploration workflow system, was designed to handle huge amounts of heterogeneous data in a platform-agnostic, computing environment and has been successful in meeting complex end-to-end demands in several communities, such as cheminformatics and mass spectrometry. Similar needs within the bioimage analysis community led to the creation of the KNIME Image Processing extension which integrates ImageJ into KNIME Analytics Platform, enabling researchers to develop reproducible and scalable workflows, integrating a diverse range of analysis tools. Here we present how users and developers alike can leverage the ImageJ ecosystem via the KNIME Image Processing extension to provide robust and extensible image analysis within KNIME workflows. We illustrate the benefits of this integration with examples, as well as representative scientific use cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcomp.2020.00008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469687PMC
March 2020

Connecting High School Students With Nature - How Different Guided Tours in the Influence the Success of Extracurricular Educational Programs.

Front Psychol 2020 4;11:1804. Epub 2020 Aug 4.

Department of Biology, Bioscience Education and Zoo Biology, Goethe University Frankfurt, Frankfurt, Germany.

Zoos attract millions of visitors every year, many of whom are schoolchildren. For this reason, zoos are important institutions for the environmental education of future generations. Empirical studies on the educational impact of environmental education programs in zoos are still rare. To address this issue, we conducted two studies: In study 1, we investigated students' interests in different biological topics, including zoos ( = 1,587). Data analysis of individual topics revealed large differences of interest, with advanced students showing less interest in zoos. In study 2, we invited school classes of this age group to visit different guided tours at the zoo and tested connection to nature before and after each educational intervention ( = 608). The results showed that the guided tours are an effective tool to raise students' connection to nature. Add-on components have the potential to further promote connection to nature. The education programs are most effective with students with a low initial nature connection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2020.01804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417368PMC
August 2020

The Impact of an Intraoperative Clinical Decision Support Tool to Optimize Perioperative Glycemic Management.

J Med Syst 2020 Aug 21;44(10):175. Epub 2020 Aug 21.

Department of Anesthesiology, Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.

With the transition from Vanderbilt's Perioperative Information Management System (VPIMS) to Epic's Best Practice Advisory (BPA) framework, a replacement intraoperative glucose clinical decision support (CDS) system was designed. We examined changes in the frequency of intraoperative glucose monitoring, hyper- and hypoglycemia rates in the post-anesthesia care unit (PACU), to determine the impact of the changes on glucose management. Data were collected into three phases: 1) VPIMS CDS, 2) No CDS, and 3) BPA CDS. One-way ANOVA was conducted to test the significance of changes in the frequency of glucose monitoring and abnormal glucose across phases. Interrupted time series segmented analysis was performed to assess the autocorrelation and trend over times. A total of 3706 cases were analyzed. The monitoring rate fell from 84.5% in VPIMS CDS to 67.6% in No CDS (p < .001) and increased to 83.1% in BPA CDS (p < .001). The PACU hyperglycemia rate increased from VPIMS CDS to No CDS (5.2% to 10.4%, p < .001) and decreased from No CDS to BPA CDS (10.4% to 7.2%, p = 0.031). The segmented analysis demonstrated immediate changes in the intraoperative monitoring frequency (p < .001) and postoperative hyperglycemia rate (p = 0.002) with the replacement of CDS. The temporary removal of CDS was associated with a significant reduction in intraoperative glucose monitoring and increased hyperglycemia in the PACU. Implementation of the BPA CDS led to a significant improvement in the intraoperative glucose monitoring and glucose management in the PACU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10916-020-01643-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547403PMC
August 2020

Patterns of mtDNA introgression suggest population replacement in Palaearctic whiskered bat species.

R Soc Open Sci 2020 Jun 3;7(6):191805. Epub 2020 Jun 3.

Museum für Naturkunde, Leibniz-Institut für Evolutions- und Biodiversitätsforschung, Berlin 10115, Germany.

Secondary contacts can play a major role in the evolutionary histories of species. Various taxa diverge in allopatry and later on come into secondary contact during range expansions. When they meet, their interactions and the extent of gene flow depend on the level of their ecological differentiation and the strength of their reproductive isolation. In this study, we present the multilocus phylogeography of two cryptic whiskered bat species, and , with a particular focus on their putative sympatric zone. Our findings suggest that and evolved in allopatry and came into secondary contact during range expansions. Individuals in the area of secondary contact, in Anatolia and the Balkans, have discordant population assignments based on the mitochondrial and the nuclear datasets. These observed patterns suggest that the local populations hybridized with expanding populations, which resulted in mitochondrial introgression from the former. In the introgression area, individuals with concordant nuclear and mitochondrial genotypes were identified in relatively few locations, suggesting that the indigenous populations might have been largely replaced by invading . Changing environmental conditions coupled with ecological competition is the likely reason for this replacement. Our study presents one possible example of a historical population replacement that was captured in phylogeographic patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsos.191805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353987PMC
June 2020

Carcinomas with Occult Metastasis Potential: Diagnosis/Prognosis Accuracy Improvement by Means of Force Spectroscopy.

Adv Biosyst 2020 07 17;4(7):e2000042. Epub 2020 Jun 17.

Physics of Surfaces, Department of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 2, Darmstadt, 64287, Germany.

Accurate diagnosis of cancer stage is inevitable for the following prognosis in patients struggling with these lesions to promote their health and survival rate. Previous studies on survival rate statistics show, in some cases, failure in cancer stage surveys in which metastasis or recurrence of the disease was not accurately prognosed. Morphology study of cancer cells advances the understanding about cancer behavior and its progression, in which, in our previous study on invasive cancer cells, fewer formations of cytoskeleton components compared to their counterparts was observed. Here it is shown that carcinomas with an occult propensity of metastasis depict a number of poorly differentiated cells with decreased amounts of cytoskeleton components in a near-well differentiated population. Force spectroscopy in conjunction with fluorescence microscopy of lung cancer, liver hepatoma, and melanoma provides a general view of these cells' architecture, leading to the conclusion that the scarce abnormal-shaped cells with low formation of structural filaments convey the high risk of metastatic potential of the tumor. The results demonstrate that force spectroscopy complements conventional diagnostic approaches by an accurate cytoskeleton assessment and can improve the following prognosis in epithelial cancers with occult metastasis risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adbi.202000042DOI Listing
July 2020

Truck Platooning Under Real Traffic Conditions: First Insights on Behavioral Adaptations and Gap Preference of Professional Drivers.

Hum Factors 2020 Mar 9:18720820908481. Epub 2020 Mar 9.

52775 Hochschule Fresenius, Idstein, Hesse, Germany.

Objective: The aim of the study was to investigate (1) how different gap sizes are perceived by professional truck drivers under real traffic conditions and (2) whether semi-automated platoon driving leads to changes in driving behavior of subsequent manual driving.

Background: Platoon driving is a current branch in the development of automated driving in which two or more vehicles build a convoy. The lead vehicle is controlled manually while following vehicles are electronically coupled to it and drive semi-automated with small gaps in order to achieve a better traffic flow and potential fuel savings.

Method: In a real road experiment, 10 trained professional truck drivers completed a total of 33 test drives with a two-truck platoon on the German highway A9 with a gap size of either 15 or 21 m, in the leading and the following vehicle.

Results: (1) The drivers experienced both gap sizes as comfortable and preferred the smaller gap size of 15 m. (2) Both gap sizes led to significantly higher standard deviation of lane position in post- compared to pre-platoon driving. No significant difference in distance keepings in post- compared to pre-platoon driving occurred. Qualitative data give hints on difficulties, when switching back to regular truck driving.

Conclusion: The results implicate that small gap sizes are perceived as comfortable by drivers and that platoon driving has an influence on subsequent manual driving.

Application: Countermeasures to behavioral adaptations should be considered in order to ensure a safe conduction of platoon driving.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0018720820908481DOI Listing
March 2020

Stratification of Breast Cancer Risk in Terms of the Influence of Age and Mammographic density.

Rofo 2020 Jul 27;192(7):678-685. Epub 2020 Feb 27.

Institute of Epidemiology and Social Medicine, University of Münster, Germany.

Purpose:  Analysis of the influence of the singular risk factors age and breast density on the 2-year incidence of breast cancer among participants in the German mammography screening program.

Materials And Methods:  The multicenter study includes 111 456 subsequent round digital mammographic screening examinations from four screening units with prospective visual categorization of breast density. Based on detection in screening and during the 2-year interval after negative screening participation (interval cancers), 2-year breast cancer incidences (2 YBCI) (‰) were calculated in the 5-year age groups (5 YAG) of the target group 50-69 years and in the BI-RADS density categories ACR 1-4. Multivariate statistical evaluations were carried out using logistic regression models.

Results:  With an increase in the 5 YAG, the 2 YBCI increased by 5.0 ‰, 6.7 ‰, 8.5 ‰ to 9.7 ‰, and was significantly different among 55-59, 60-64 and 65-69-year-old women compared to the youngest reference group 50-54 years (odds ratio (OR): 1.34; 1.68; and 1.93; p-value < 0.0001). With an increase in density categories 1-4, the 2 YBCI increased from 2.6 ‰, to 5.8 ‰, 9.6 ‰, and 9.7 ‰. The 2 YBCI differed significantly in breast density categories 2, 3, 4 from reference group 1 (OR: 2.17; 3.65; and 3.76; p-value < 0.0001). Only within the two main breast density groups 2 (frequency 44.3 %) and 3 (44.7 %), a significant increase in the 2 YBCI was observed across the 5 YAG (category 2: 3.7-8.9 ‰; category 3: 5.8-11.7 ‰; p-value < 0.001 each). The 2 YBCI was above the median of 7.5 ‰ in women with breast density category 2 and aged 65-69 years, as well as in women with breast density categories 3 and 4 aged 55-69 years. A 2 YBCI below the median was seen in women between 50-54 years regardless of breast density, as well as women in category 1 in all age groups.

Conclusion:  Within the main breast density categories 2 and 3 (almost 90 % of participants), incidences increase with age to double. A consistently low incidence is found regardless of breast density at a young screening age and in women with the lowest breast density.

Key Points:   · The risk of breast cancer is modified by age in density categories.. · Women aged 50-54 years have a low risk in all density categories.. · Women in category ACR 1 of any age group have a low risk..

Citation Format: · Weigel S, Heindel W, Dietz C et al. Stratifizierung des Brustkrebsrisikos hinsichtlich der Einflüsse von Alter und mammografischer Dichte. Fortschr Röntgenstr 2020; 192: 678 - 685.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1100-0016DOI Listing
July 2020

TACAN Is an Ion Channel Involved in Sensing Mechanical Pain.

Cell 2020 03 20;180(5):956-967.e17. Epub 2020 Feb 20.

Department of Physiology and Cell Information Systems, McGill University, Montreal, QC, Canada; Alan Edwards Center for Research on Pain, McGill University, Montreal, QC, Canada. Electronic address:

Mechanotransduction, the conversion of mechanical stimuli into electrical signals, is a fundamental process underlying essential physiological functions such as touch and pain sensing, hearing, and proprioception. Although the mechanisms for some of these functions have been identified, the molecules essential to the sense of pain have remained elusive. Here we report identification of TACAN (Tmem120A), an ion channel involved in sensing mechanical pain. TACAN is expressed in a subset of nociceptors, and its heterologous expression increases mechanically evoked currents in cell lines. Purification and reconstitution of TACAN in synthetic lipids generates a functional ion channel. Finally, a nociceptor-specific inducible knockout of TACAN decreases the mechanosensitivity of nociceptors and reduces behavioral responses to painful mechanical stimuli but not to thermal or touch stimuli. We propose that TACAN is an ion channel that contributes to sensing mechanical pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2020.01.033DOI Listing
March 2020

Glycine Lipids of Porphyromonas gingivalis Are Agonists for Toll-Like Receptor 2.

Infect Immun 2020 03 23;88(4). Epub 2020 Mar 23.

Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA.

The serine-glycine dipeptide lipid classes, including lipid 430 and lipid 654, are produced by the periodontal pathogen and can be detected in lipid extracts of diseased periodontal tissues and teeth of humans. Both serine-glycine lipid classes were previously shown to engage human and mouse Toll-like receptor 2 (TLR2) and to inhibit mouse osteoblast differentiation and function through engagement of TLR2. It is not clear if other lipids related to serine-glycine lipids are also produced by The goal of this investigation was to determine whether produces additional lipid classes similar to the serine-glycine lipids that possess biological properties. (ATCC 33277) was grown in broth culture, and lipids were extracted and fractionated by high-performance liquid chromatography (HPLC). Lipids were separated using semipreparative HPLC, and specific lipid classes were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-multiple reaction monitoring (LC-MRM) mass spectrometric approaches. Two glycine lipid classes were identified, termed lipid 567 and lipid 342, and these lipid classes are structurally related to the serine-glycine dipeptide lipids. Both glycine lipid classes were shown to promote TLR2-dependent tumor necrosis factor alpha (TNF-α) release from bone marrow macrophages, and both were shown to activate human embryonic kidney (HEK) cells through TLR2 and TLR6 but not TLR1. These results demonstrate that synthesizes glycine lipids and that these lipids engage TLR2 similarly to the previously reported serine-glycine dipeptide lipids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/IAI.00877-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093120PMC
March 2020

Acceptance of truck platooning by professional drivers on German highways. A mixed methods approach.

Appl Ergon 2020 May 13;85:103042. Epub 2020 Jan 13.

Hochschule Fresenius, University of Applied Sciences, Idstein, Germany.

Truck platoon driving is a current branch of automated driving, which has the potential to radically change the work routine of professional drivers. In a platoon system, one truck (semi-)automatically follows a lead truck with a reduced distance, which produces significant savings in fuel and enables better traffic flow. In a current application of truck platoon driving, the following vehicle operates at level-2 automation. Thus, the driver of the following truck merely has to supervise the semi-automated system, which takes over steering and speed control when engaged. Level-2 truck platoon driving had not been tested with professional drivers in real traffic before. We hypothesized that user acceptance would improve after the experience of platoon driving. Quantitative questionnaires and qualitative interviews were conducted with 10 drivers before and after an extensive Autobahn experience. The results show a clear increase of acceptance after the experience. Platoon driving was evaluated to be more useful, easier to use, and safer after the experience. Besides perceived driving safety, the prestige of truck platooning, the perceived usefulness of the system, and general technology affinity co-determined user acceptance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.apergo.2019.103042DOI Listing
May 2020

Short-term effects of simulated microgravity on morphology and gene expression in human breast cancer cells.

Physiol Int 2019 Dec 3;106(4):311-322. Epub 2020 Jan 3.

Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Magdeburg, Germany.

Introduction: Microgravity has been shown to impose various effects on breast cancer cells. We exposed human breast cancer cells to simulated microgravity and studied morphology and alterations in gene expression.

Materials And Methods: Human breast cancer cells were exposed to simulated microgravity in a random positioning machine (RPM) for 24 h. Morphology was observed under light microscopy, and gene alteration was studied by qPCR.

Results: After 24 h, formation of three-dimensional structures (spheroids) occurred. BRCA1 expression was significantly increased (1.9×,  < 0.05) in the adherent cells under simulated microgravity compared to the control. Expression of KRAS was significantly decreased (0.6×,  < 0.05) in the adherent cells compared to the control. VCAM1 was significantly upregulated (6.6×, 2.0×,  < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. VIM expression was significantly downregulated (0.45×, 0.44×,  < 0.05 each) in the adherent cells under simulated microgravity and in the spheroids. There was no significant alteration in the expression of , , , and .

Conclusions: Simulated microgravity induces spheroid formation in human breast cancer cells within 24 h and alters gene expression toward modified adhesion properties, enhanced cell repair, and phenotype preservation. Further insights into the underlying mechanisms could open up the way toward new therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2019

The Role of C-X-C Chemokine Receptor Type 4 (CXCR4) in Cell Adherence and Spheroid Formation of Human Ewing's Sarcoma Cells under Simulated Microgravity.

Int J Mol Sci 2019 Dec 2;20(23). Epub 2019 Dec 2.

Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.

We studied the behavior of Ewing's Sarcoma cells of the line A673 under simulated microgravity (s-µg). These cells express two prominent markers-the oncogene EWS/FLI1 and the chemokine receptor CXCR4, which is used as a target of treatment in several types of cancer. The cells were exposed to s-µg in a random-positioning machine (RPM) for 24 h in the absence and presence of the CXCR4 inhibitor AMD3100. Then, their morphology and cytoskeleton were examined. The expression of selected mutually interacting genes was measured by qRT-PCR and protein accumulation was determined by western blotting. After 24 h incubation on the RPM, a splitting of the A673 cell population in adherent and spheroid cells was observed. Compared to 1 g control cells, was significantly upregulated in the adherent cells and in the spheroids, while and expression were significantly enhanced in spheroids only. Transcription of was upregulated and and were down-regulated in both, adherent in spheroid cells, respectively. Regarding, protein accumulation EWS/FLI1 was enhanced in adherent cells only, but CD44 decreased in spheroids and adherent cells. Inhibition of CXCR4 did not change spheroid count, or structure. Under s-µg, the tumor marker EWS/FLI1 is intensified, while targeting CXCR4, which influences adhesion proteins, did not affect spheroid formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20236073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929163PMC
December 2019

pH-depended protein shell dis- and reassembly of ferritin nanoparticles revealed by atomic force microscopy.

Sci Rep 2019 11 28;9(1):17755. Epub 2019 Nov 28.

Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 2, 64287, Darmstadt, Germany.

Ferritin, a protein that is present in the human body for a controlled iron storage and release, consists of a ferrihydrite core and a protein shell. Apoferritin, the empty shell of ferritin, can be modified to carry tailored properties exploitable for targeted and direct drug delivery. This protein shell has the ability to dis- and reassemble depending on the pH value of the liquid environment and can thus be filled with the desired substance. Here we observed the dis- and reassembly process of the protein shell of ferritin and apoferritin in situ and in real space using atomic force microscopy. Ferritin and apoferritin nanoparticles adsorbed on a mica substrate exhibited a change in their size by varying the pH value of the surrounding medium. Lowering the pH value of the solution led to a decrease in size of the nanoparticles whereas a successive increase of the pH value increased the particle size again. The pH dependent change in size could be related to the dis- and reassembling of the protein shell of ferritin and apoferritin. Supplementary imaging by bimodal magnetic force microscopy of ferritin molecules accomplished in air revealed a polygonal shape of the core and a three-fold symmetry of the protein shell providing valuable information about the substructure of the nanoparticles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-53943-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883049PMC
November 2019

Development of a neural rosette formation assay (RoFA) to identify neurodevelopmental toxicants and to characterize their transcriptome disturbances.

Arch Toxicol 2020 01 11;94(1):151-171. Epub 2019 Nov 11.

In Vitro Toxicology and Biomedicine, Department Inaugurated By the Doerenkamp-Zbinden Chair Foundation, University of Konstanz, Box 657, 78457, Konstanz, Germany.

The first in vitro tests for developmental toxicity made use of rodent cells. Newer teratology tests, e.g. developed during the ESNATS project, use human cells and measure mechanistic endpoints (such as transcriptome changes). However, the toxicological implications of mechanistic parameters are hard to judge, without functional/morphological endpoints. To address this issue, we developed a new version of the human stem cell-based test STOP-tox. For this purpose, the capacity of the cells to self-organize to neural rosettes was assessed as functional endpoint: pluripotent stem cells were allowed to differentiate into neuroepithelial cells for 6 days in the presence or absence of toxicants. Then, both transcriptome changes were measured (standard STOP-tox) and cells were allowed to form rosettes. After optimization of staining methods, an imaging algorithm for rosette quantification was implemented and used for an automated rosette formation assay (RoFA). Neural tube toxicants (like valproic acid), which are known to disturb human development at stages when rosette-forming cells are present, were used as positive controls. Established toxicants led to distinctly different tissue organization and differentiation stages. RoFA outcome and transcript changes largely correlated concerning (1) the concentration-dependence, (2) the time dependence, and (3) the set of positive hits identified amongst 24 potential toxicants. Using such comparative data, a prediction model for the RoFA was developed. The comparative analysis was also used to identify gene dysregulations that are particularly predictive for disturbed rosette formation. This 'RoFA predictor gene set' may be used for a simplified and less costly setup of the STOP-tox assay.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00204-019-02612-5DOI Listing
January 2020

Alteration of Cytoskeleton Morphology and Gene Expression in Human Breast Cancer Cells under Simulated Microgravity.

Cell J 2020 Apr 8;22(1):106-114. Epub 2019 Sep 8.

Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Magdeburg, Germany.Electronic

Objective: Weightlessness simulation due to the simulated microgravity has been shown to considerably affect behavior of tumor cells. It is aim of this study to evaluate characteristics of human breast cancer cells in this scaffoldfree 3D culture model.

Materials And Methods: In this experimental study, the cells were exposed to simulated microgravity in a randompositioning machine (RPM) for five days. Morphology was observed under phase-contrast and confocal microscopy. Cytofilament staining was performed and changes in expression level of cytofilament genes, proliferation/differentiation genes, oncogenes and tumor suppressor genes were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), followed by western blot confirmation.

Results: After five days, distinct spheroid formation was observed. Rearrangement of the cytoskeleton into spherical shape was visible. gene expression was significantly up-regulated for adherent cells and spheroids (3.3x and 3.6x respectively, P<0.05 each). also showed significant gene up-regulation for adherent cells and spheroids (3.2x and 3.9x respectively, P<0.05 each). showed significant gene up-regulation in adherent cells and spheroids (2.1x and 4.1x respectively, P<0.05 each). showed significant gene up-regulation (2.4x, P<0.05) in the spheroids, but not in the adherent cells. showed no significant alteration in gene expression. ) showed significant gene up-regulation in adherent cells and spheroids (3.2x, 3.0x, P<0.05 each). gene expression was down-regulated under simulated microgravity, without significance. Alterations of gene expressions could be confirmed on protein level for vimentin and MAPK1. Protein production was not increased for BRCA1, human epidermal growth factor receptor 2 (HER2) and VEGF. Contradictory changes were determined for and its related protein.

Conclusion: Microgravity provides an easy-to handle, scaffold-free 3D-culture model for human breast cancer cells. There were considerable changes in morphology, cytoskeleton shape and gene expressions. Identification of the underlying mechanisms could provide new therapeutic options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.22074/cellj.2020.6537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791064PMC
April 2020

Apoptosis Induction and Alteration of Cell Adherence in Human Lung Cancer Cells under Simulated Microgravity.

Int J Mol Sci 2019 Jul 23;20(14). Epub 2019 Jul 23.

Department of Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University, Leipziger Strasse 44, D-39120 Magdeburg, Germany.

Background: Lung cancer cells are known to change proliferation and migration under simulated microgravity. In this study, we sought to evaluate cell adherence, apoptosis, cytoskeleton arrangement, and gene expression under simulated microgravity.

Methods: Human lung cancer cells were exposed to simulated microgravity in a random-positioning machine (RPM). Cell morphology and adherence were observed under phase-contrast microscopy, cytoskeleton staining was performed, apoptosis rate was determined, and changes in gene and protein expression were detected by real-time PCR with western blot confirmation.

Results: Three-dimensional (3D)-spheroid formation was observed under simulated microgravity. Cell viability was not impaired. Actin filaments showed a shift in alignment from longitudinal to spherical. Apoptosis rate was significantly increased in the spheroids compared to the control. , , and gene expression was significantly upregulated in the adherent cells under simulated microgravity with an increase in corresponding protein production for p14 and RB1. expression was significantly upregulated in the adherent cells, but protein was not. Gene expressions of , and remained unaltered.

Conclusion: Simulated microgravity induces alteration in cell adherence, increases apoptosis rate, and leads to upregulation of tumor suppressor genes in human lung cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20143601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678991PMC
July 2019

Nanomechanical sub-surface mapping of living biological cells by force microscopy.

Nanoscale 2019 Jul 3;11(27):13089-13097. Epub 2019 Jul 3.

Physics of Surfaces, Institute of Materials Science, Technische Universität Darmstadt, Alarich-Weiss-Str. 2, 64287 Darmstadt, Germany.

Atomic force microscopy allows for the nanomechanical surface characterization of a multitude of types of materials with highest spatial precision in various relevant environments. In recent years, researchers have refined this methodology to analyze living biological materials in vitro. The atomic force microscope thus has become an essential instrument for the (in many cases) non-destructive, high-resolution imaging of cells and visualization of their dynamic mechanical processes. Mapping force versus distance curves and the local evaluation of soft samples allow the operator to "see" beneath the sample surface and to capture the local mechanical properties. In this work, we combine atomic force microscopy with fluorescence microscopy to investigate cancerous epithelial breast cells in culture medium. With unprecedented spatial resolution, we provide tomographic images for the local elasticity of confluent layers of cells. For these particular samples, a layer of higher elastic modulus located directly beneath the cell membrane in comparison with the average elastic properties was observed. Strikingly, this layer appears to be perforated at unique locations of the sample surface of weakest mechanical properties where distinct features were visible permitting the tip to indent farthest into the cell's volume. We interpret this layer as the cell membrane mechanically supported by the components of the cytoskeleton that is populated with sites of integral membrane proteins. These proteins act as breaking points for the indenter thus explaining the mechanical weakness at these locations. In contrast, the highest mechanical strength of the cell was found at locations of the cell cores as cross-checked by fluorescence microscopy images of staining experiments, in particular at nucleoli sites as the cumulative elastic modulus there comprises cytoskeletal features and the tight packing ribosomal DNA of the cell.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr03497hDOI Listing
July 2019

Treasure hunt for peptides with undefined chemical modifications: Proteomics identification of differential albumin adducts of 2-nitroimidazole-indocyanine green in hypoxic tumor.

J Mass Spectrom 2020 Feb 22;55(2):e4376. Epub 2019 Jul 22.

Department of Chemistry, University of Connecticut, Storrs, CT, 06269.

2-Nitroimidazole is a well-known chemical probe targeting hypoxic environments of solid tumors, and its derivatives are widely used as imaging agents to investigate tissue and tumor hypoxia. However, the underlying chemistry for the hypoxia-detection capability of 2-nitroimidazole is still unclear. In this study, we deployed a biotin conjugate of 2-nitroimidazole-indocyanine green (2-nitro-ICG) for the investigation of in vivo hypoxia-probing mechanism of 2-nitro-ICG compounds. By implementing mass spectrometry-based proteomics and exhaustive data mining, we report that 2-nitro-ICG and its fragments modify mouse serum albumin as the primary protein target but at two structurally distinct sites and possibly via two different mechanisms. The identification of probe-modified peptides not only contributes to the understanding of the in vivo metabolism of 2-nitroimidazole compounds but also demonstrates a competent analytical workflow that enables the search for peptides with undefined modifications in complex proteome digests.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jms.4376DOI Listing
February 2020

What is normal trauma healing and what is complex regional pain syndrome I? An analysis of clinical and experimental biomarkers.

Pain 2019 10;160(10):2278-2289

Department of Anesthesiology, University Hospital of Würzburg, Würzburg, Germany.

Complex regional pain syndrome (CRPS) typically develops after fracture or trauma. Many of the studies so far have analyzed clinical and molecular markers of CRPS in comparison with healthy or pain controls. This approach, however, neglects mechanisms occurring during physiological trauma recovery. Therefore, we compared the clinical phenotype, sensory profiles, patient-reported outcomes, and exosomal immunobarrier microRNAs (miRs) regulating barrier function and immune response between CRPS and fracture controls (FCs) not fulfilling the CRPS diagnostic criteria. We included upper-extremity FCs, acute CRPS I patients within 1 year after trauma, a second disease control group (painful diabetic polyneuropathy), and healthy controls. Fracture controls were not symptoms-free, but reported some pain, disability, anxiety, and cold pain hyperalgesia in quantitative sensory testing. Patients with CRPS had higher scores for pain, disability, and all patient-reported outcomes. In quantitative sensory testing, ipsilateral and contralateral sides differed significantly. However, on the affected side, patients with CRPS were more sensitive in only 3 parameters (pinprick pain and blunt pressure) when compared to FCs. Two principal components were identified in the cohort: pain and psychological parameters distinguishing FC and CPRS. Furthermore, the immunobarrier-protective hsa-miR-223-5p was increased in plasma exosomes in FCs with normal healing, but not in CRPS and healthy controls. Low hsa-miR-223-5p was particularly observed in subjects with edema pointing towards barrier breakdown. In summary, normal trauma healing includes some CRPS signs and symptoms. It is the combination of different factors that distinguish CRPS and FC. Fracture control as a control group can assist to discover resolution factors after trauma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000001617DOI Listing
October 2019

Aspergillus fumigatus induction of IL-33 expression in chronic rhinosinusitis is PAR2-dependent.

Laryngoscope 2019 10 11;129(10):2230-2235. Epub 2019 Apr 11.

Department of Otolaryngology-Head and Neck Surgery, McGovern Medical School at the University of Texas Health Science Center, Houston, Texas, U.S.A.

Objective: In the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP), Aspergillus fumigatus (A. fumigatus) can upregulate IL-33 from human sinonasal epithelial cells (SNECs), which then activates innate lymphoid cells causing release of IL-13, an important driver of allergic inflammation. However, the mechanism by which A. fumigatus mediates the induction of IL-33 expression remains to be elucidated. The objectives of this study were to determine the specific fungal component(s) and the receptor responsible for mediating the A. fumigatus induced increase in IL-33 expression in SNECs from patients with CRSwNP.

Methods: SNECs from CRSwNP patients were cultured and stimulated with various fungal components in the absence or presence of 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride, an irreversible serine protease inhibitor, or GB83, a reversible protease activated receptor 2 (PAR2) inhibitor. IL-33 expression was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). PAR2 expression was examined in inflamed mucosa from nonatopic control and CRSwNP patients.

Results: Elevation of IL-33 expression in primary SNECs was found in response to fungal protease but not fungal cell wall components. PAR2 expression was elevated in inflamed mucosa from CRSwNP patients in comparison to controls. The A. fumigatus fungal protease-mediated elevation in IL-33 expression by human SNECs was serine protease- and PAR2-dependent.

Conclusion: These data suggest that serine protease activity of A. fumigatus is capable of inducing IL-33 expression in CRSwNP SNECs via PAR2, a potential therapeutic target in the treatment of CRSwNP.

Level Of Evidence: NA Laryngoscope, 129:2230-2235, 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.28000DOI Listing
October 2019

Fluoropolymer-Containing Opals and Inverse Opals by Melt-Shear Organization.

Molecules 2019 Jan 17;24(2). Epub 2019 Jan 17.

Ernst-Berl Institute of Technical and Macromolecular Chemistry, Technische Universität Darmstadt, Alarich-Weiss-Straße 4, 64287 Darmstadt, Germany.

The preparation of highly ordered colloidal architectures has attracted significant attention and is a rapidly growing field for various applications, e.g., sensors, absorbers, and membranes. A promising technique for the preparation of elastomeric inverse opal films relies on tailored core/shell particle architectures and application of the so-called melt-shear organization technique. Within the present work, a convenient route for the preparation of core/shell particles featuring highly fluorinated shell materials as building blocks is described. As particle core materials, both organic or inorganic (SiO₂) particles can be used as a template, followed by a semi-continuous stepwise emulsion polymerization for the synthesis of the soft fluoropolymer shell material. The use of functional monomers as shell-material offers the possibility to create opal and inverse opal films with striking optical properties according to Bragg's law of diffraction. Due to the presence of fluorinated moieties, the chemical resistance of the final opals and inverse opals is increased. The herein developed fluorine-containing particle-based films feature a low surface energy for the matrix material leading to good hydrophobic properties. Moreover, the low refractive index of the fluoropolymer shell compared to the core (or voids) led to excellent optical properties based on structural colors. The herein described fluoropolymer opals and inverse opals are expected to pave the way toward novel functional materials for application in fields of coatings and optical sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24020333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359200PMC
January 2019

Phagosomal Copper-Promoted Oxidative Attack on Intracellular Mycobacterium tuberculosis.

ACS Infect Dis 2018 11 6;4(11):1623-1634. Epub 2018 Sep 6.

Department of Chemistry , University of Connecticut , 55 N. Eagleville Road , Storrs , Connecticut 06269 , United States.

Copper (Cu) ions are critical in controlling bacterial infections, and successful pathogens like Mycobacterium tuberculosis (Mtb) possess multiple Cu resistance mechanisms. We report, as proof of concept, that a novel Cu hypersensitivity phenotype can be generated in mycobacteria, including Mtb, through a peptide, DAB-10, that is able to form reactive oxygen species (ROS) following Cu-binding. DAB-10 induces intramycobacterial oxidative stress in a Cu-dependent manner in vitro and during infection. DAB-10 penetrates murine macrophages and encounters intracellular mycobacteria. Significant intracellular Cu-dependent protection was observed when Mtb-infected macrophages were treated with DAB-10 alongside a cell-permeable Cu chelator. Treatment with the Cu chelator reversed the intramycobacterial oxidative shift induced by DAB-10. We conclude that DAB-10 utilizes the pool of phagosomal Cu ions in the host-Mtb interface to augment the mycobactericidal activity of macrophages while simultaneously exploiting the susceptibility of Mtb to ROS. DAB-10 serves as a model with which to develop next-generation, multifunctional antimicrobials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsinfecdis.8b00171DOI Listing
November 2018

Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease.

Blood 2018 08 2;132(9):948-961. Epub 2018 Jul 2.

School of Medicine, Faculty of Health and Medical Sciences, and.

Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole-exome sequencing, copy-number variation, and/or RNA sequencing for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six patients with chronic-phase disease with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15 (56%) of 27 patients with subsequent BC or poor outcome and in 3 (16%) of 19 optimal responders ( = .007). Frequently mutated genes at diagnosis were , , and The methyltransferase was a novel recurrently mutated gene. A novel class of variant associated with the Philadelphia (Ph) translocation was detected at diagnosis in 11 (24%) of 46 patients comprising fusions and/or rearrangement of genes on the translocated chromosomes, with evidence of fragmentation, inversion, and imperfect sequence reassembly. These were more frequent at diagnosis in patients with poor outcome: 9 (33%) of 27 vs 2 (11%) of 19 optimal responders ( = .07). Thirty-nine patients were tested at BC, and all had cancer gene variants, including kinase domain mutations in 58%. However, mutations cooccurred with other mutated cancer genes in 89% of cases, and these predated mutations in 62% of evaluable patients. Gene fusions not associated with the Ph translocation occurred in 42% of patients at BC and commonly involved fusion partners that were known cancer genes (78%). Genomic analysis revealed numerous relevant variants at diagnosis in patients with poor outcome and all patients at BC. Future refined biomarker testing of specific variants will likely provide prognostic information to facilitate a risk-adapted therapeutic approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2018-02-832253DOI Listing
August 2018

Crystallization process of a three-dimensional complex plasma.

Phys Rev E 2018 May;97(5-1):053202

Institute of Experimental Physics I, Justus Liebig University Giessen, Heinrich-Buff-Ring 16, 35392 Giessen, Germany.

Characteristic timescales and length scales for phase transitions of real materials are in ranges where a direct visualization is unfeasible. Therefore, model systems can be useful. Here, the crystallization process of a three-dimensional complex plasma under gravity conditions is considered where the system ranges up to a large extent into the bulk plasma. Time-resolved measurements exhibit the process down to a single-particle level. Primary clusters, consisting of particles in the solid state, grow vertically and, secondarily, horizontally. The box-counting method shows a fractal dimension of d_{f}≈2.72 for the clusters. This value gives a hint that the formation process is a combination of local epitaxial and diffusion-limited growth. The particle density and the interparticle distance to the nearest neighbor remain constant within the clusters during crystallization. All results are in good agreement with former observations of a single-particle layer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevE.97.053202DOI Listing
May 2018