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Open AccessArticle
Comparison of Cellular Death Pathways after mTHPC-mediated Photodynamic Therapy (PDT) in Five Human Cancer Cell Lines
Cancers 2019, 11(5), 702; https://doi.org/10.3390/cancers11050702 (registering DOI) -
Abstract
One of the most promising photosensitizers (PS) used in photodynamic therapy (PDT) is the porphyrin derivative 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, temoporfin), marketed in Europe under the trade name Foscan®. A set of five human cancer cell lines from head and neck [...] Read more.
One of the most promising photosensitizers (PS) used in photodynamic therapy (PDT) is the porphyrin derivative 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, temoporfin), marketed in Europe under the trade name Foscan®. A set of five human cancer cell lines from head and neck and other PDT-relevant tissues was used to investigate oxidative stress and underlying cell death mechanisms of mTHPC-mediated PDT in vitro. Cells were treated with mTHPC in equitoxic concentrations and illuminated with light doses of 1.8–7.0 J/cm2 and harvested immediately, 6, 24, or 48 h post illumination for analyses. Our results confirm the induction of oxidative stress after mTHPC-based PDT by detecting a total loss of mitochondrial membrane potential (Δψm) and increased formation of ROS. However, lipid peroxidation (LPO) and loss of cell membrane integrity play only a minor role in cell death in most cell lines. Based on our results, apoptosis is the predominant death mechanism following mTHPC-mediated PDT. Autophagy can occur in parallel to apoptosis or the former can be dominant first, yet ultimately leading to autophagy-associated apoptosis. The death of the cells is in some cases accompanied by DNA fragmentation and a G2/M phase arrest. In general, the overall phototoxic effects and the concentrations as well as the time to establish these effects varies between cell lines, suggesting that the cancer cells are not all dying by one defined mechanism, but rather succumb to an individual interplay of different cell death mechanisms. Besides the evaluation of the underlying cell death mechanisms, we focused on the comparison of results in a set of five identically treated cell lines in this study. Although cells were treated under equitoxic conditions and PDT acts via a rather unspecific ROS formation, very heterogeneous results were obtained with different cell lines. This study shows that general conclusions after PDT in vitro require testing on several cell lines to be reliable, which has too often been ignored in the past. Full article
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Open AccessArticle
Numerical and Experimental Study of the Solo Duck Wave Energy Converter
Energies 2019, 12(10), 1941; https://doi.org/10.3390/en12101941 (registering DOI) -
Abstract
The Edinburgh Duck is one of the highly-efficient wave energy converters (WECs). Compared to the spine-connected Duck configuration, the solo Duck will be able to use the point absorber effect to enhance its power capture performance. In this paper, a 3D computational fluid [...] Read more.
The Edinburgh Duck is one of the highly-efficient wave energy converters (WECs). Compared to the spine-connected Duck configuration, the solo Duck will be able to use the point absorber effect to enhance its power capture performance. In this paper, a 3D computational fluid dynamic (CFD) model is developed to predict the hydrodynamic performance of the solo Duck WEC in regular waveswithin a wide range ofwave steepness until the Duck capsizes. A set of experiments was designed to validate the accuracy of the CFD model. Boundary element method (BEM) simulations are also performed for comparison. CFD results agree well with experimental results and the main difference comes from the friction in the mechanical transmission system. CFD results also agree well with BEM results and differences appear at large wave steepness as a result of two hydrodynamic nonlinear factors: the nonlinear waveform and the vortex generation process. The influence of both two nonlinear factors iscombined to be quantitatively represented by the drag torque coefficient.The vortex generation process is found to cause a rapid drop ofthe pressure force due to the vortexes taking away the kinetic energy from the fluid. Full article
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Open AccessArticle
Nature-Based Designs to Mitigate Urban Heat: The Efficacy of Green Infrastructure Treatments in Portland, Oregon
Atmosphere 2019, 10(5), 282; https://doi.org/10.3390/atmos10050282 (registering DOI) -
Abstract
Urban heat is a growing environmental concern in cities around the world. The urban heat island effect, combined with warming effects of climate change, is likely to cause an increase in the frequency and intensity of extreme heat events. Alterations to the physical, [...] Read more.
Urban heat is a growing environmental concern in cities around the world. The urban heat island effect, combined with warming effects of climate change, is likely to cause an increase in the frequency and intensity of extreme heat events. Alterations to the physical, built environment are a viable option for mitigating urban heat, yet few studies provide systematic guidance to practitioners for adapting diverse land uses. In this study, we examine the use of green infrastructure treatments to evaluate changes in ambient temperatures across diverse land uses in the city of Portland, Oregon. We apply ENVI-met® microclimate modeling at the city-block scale specifically to determine what built environment characteristics are most associated with high temperatures, and the extent to which different physical designs reduce ambient temperature. The analysis included six green infrastructure interventions modeled across six different land-use types, and indicated the varying degrees to which approaches are effective. Results were inconsistent across landscapes, and showed that one mitigation solution alone would not significantly reduce extreme heat. These results can be used to develop targeted, climate- and landscape-specific cooling interventions for different land uses, which can help to inform and refine current guidance to achieve urban climate adaptation goals. Full article
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Open AccessFeature PaperArticle
Predicting Host Immune Cell Dynamics and Key Disease-Associated Genes Using Tissue Transcriptional Profiles
Processes 2019, 7(5), 301; https://doi.org/10.3390/pr7050301 (registering DOI) -
Abstract
Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using [...] Read more.
Motivation: Immune cell dynamics is a critical factor of disease-associated pathology (immunopathology) that also impacts the levels of mRNAs in diseased tissue. Deconvolution algorithms attempt to infer cell quantities in a tissue/organ sample based on gene expression profiles and are often evaluated using artificial, non-complex samples. Their accuracy on estimating cell counts given temporal tissue gene expression data remains not well characterized and has never been characterized when using diseased lung. Further, how to remove the effects of cell migration on transcript counts to improve discovery of disease factors is an open question. Results: Four cell count inference (i.e., deconvolution) tools are evaluated using microarray data from influenza-infected lung sampled at several time points post-infection. The analysis finds that inferred cell quantities are accurate only for select cell types and there is a tendency for algorithms to have a good relative fit (R2) but a poor absolute fit (normalized mean squared error; NMSE), which suggests systemic biases exist. Nonetheless, using cell fraction estimates to adjust gene expression data, we show that genes associated with influenza virus replication and increased infection pathology are more likely to be identified as significant than when applying traditional statistical tests. Full article
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Open AccessArticle
Effect of Pre-Stretching on Microstructures and Mechanical Behaviors of Creep-Aged 7055 Al Alloy and Its Constitutive Modeling
Metals 2019, 9(5), 584; https://doi.org/10.3390/met9050584 (registering DOI) -
Abstract
The rational pre-stretching can contribute to obtaining better mechanical properties. This paper studies the effect of creep stain, mechanical properties, and microstructures of 7055 alloy under different pre-stretching conditions. The results show that compared with solid-quenched alloy, the 7055-T6 alloy is the optimal [...] Read more.
The rational pre-stretching can contribute to obtaining better mechanical properties. This paper studies the effect of creep stain, mechanical properties, and microstructures of 7055 alloy under different pre-stretching conditions. The results show that compared with solid-quenched alloy, the 7055-T6 alloy is the optimal scheme to attain more creep strain, and the range of pre-stretching from 1.6% to 3.3% is suitable for creep-aged 7055-T6 alloy to obtain better mechanical properties. Further examination by TEM test shows that pre-stretching promotes the formation of dislocations, which provides superior nucleation regions for ή phase resulting in a higher strength alloy. Meanwhile, a unified creep-aging constitutive model for 7055-T6 alloy is established which can be used to accurately predict its creep behavior under the different pre-stretching. Full article
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Open AccessArticle
Promoting Contemplative Culture through Media Arts
Multimodal Technologies Interact. 2019, 3(2), 35; https://doi.org/10.3390/mti3020035 (registering DOI) -
Abstract
This paper presents the practice of designing mediation technologies as artistic tools to expand the creative repertoire to promote contemplative cultural practice. Three art–science collaborations—Mandala, Imagining the Universe, and Resonance of the Heart—are elaborated on as proof-of-concept case studies. Scientifically, the empirical research [...] Read more.
This paper presents the practice of designing mediation technologies as artistic tools to expand the creative repertoire to promote contemplative cultural practice. Three art–science collaborations—Mandala, Imagining the Universe, and Resonance of the Heart—are elaborated on as proof-of-concept case studies. Scientifically, the empirical research examines the mappings from (bodily) action to (sound/visual) perception in technology-mediated performing art. Theoretically, the author synthesizes media arts practices on a level of defining general design principles and post-human artistic identities. Technically, the author implements machine learning techniques, digital audio/visual signal processing, and sensing technology to explore post-human artistic identities and give voice to underrepresented groups. Realized by a group of multinational media artists, computer engineers, audio engineers, and cognitive neuroscientists, this work preserves, promotes, and further explores contemplative culture with emerging technologies. Full article
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Open AccessArticle
Effect of Triblock Copolymer on Carbon-Based Boron Nitride Whiskers for Efficient CO2 Adsorption
Polymers 2019, 11(5), 913; https://doi.org/10.3390/polym11050913 (registering DOI) -
Abstract
Herein, we investigated novel carbon-containing P123 copolymer-activated boron nitride whiskers (P123-CBNW) fabricated via a structure directing approach followed by a single-step heat treatment under N2. The resulting materials were found to be highly micro- and mesoporous. The influence of the activating [...] Read more.
Herein, we investigated novel carbon-containing P123 copolymer-activated boron nitride whiskers (P123-CBNW) fabricated via a structure directing approach followed by a single-step heat treatment under N2. The resulting materials were found to be highly micro- and mesoporous. The influence of the activating agent (P123 copolymer) on the CO2 adsorption efficiency was determined. The prepared samples possessed high specific surface areas (594–1732 m2/g) and micropore volumes (0.258–0.672 cm3/g). The maximum CO2 uptakes of the prepared adsorbents were in the range 136–308 mg/g (3.09–7.01 mmol/g) at 273 K and 1 bar and 97–114 mg/g (2.22–4.62 mmol/g) in the following order: CBNW < P123-CBNW3 < P123-CBNW2 < P123-CBNW1 < P123-CBNW0.5. The isosteric heat of adsorption values (∆Qst) were found to be 33.7–43.7 kJ/mol, demonstrating the physisorption nature of the CO2 adsorption. Extensive analysis revealed that the presence of carbon, the high specific surface area, the high microporosity, and the chemical structural defects within the adsorbents are responsible for raising the CO2 adsorption ability and the selectivity over N2 gas. The fabricated adsorbents show excellent regeneration ability after several repeated adsorption cycles, making the prepared adsorbents promising candidates for gas storage applications. Full article
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Open AccessArticle
Replacing Fish Meal with Defatted Insect Meal (Yellow Mealworm Tenebrio molitor) Improves the Growth and Immunity of Pacific White Shrimp (Litopenaeus vannamei)
Animals 2019, 9(5), 258; https://doi.org/10.3390/ani9050258 (registering DOI) -
Abstract
Recently, ecological and economic issues have affected fish meal (FM) supply, the main source of protein for shrimp. This triggered a search for alternative dietary protein sources for shrimp production. We studied the consequences of replacing FM with a defatted insect meal, ŸnMeal [...] Read more.
Recently, ecological and economic issues have affected fish meal (FM) supply, the main source of protein for shrimp. This triggered a search for alternative dietary protein sources for shrimp production. We studied the consequences of replacing FM with a defatted insect meal, ŸnMealTM (YM), comprised of yellow mealworm (Tenebrio molitor). Growth and immune parameters of juvenile Pacific white shrimp (Litopenaeus vannanmei) were compared after an eight-week feeding trial. Shrimp were kept in aquaria with densities of 60 and 40 shrimp/m2 and fed one of five diets in which a proportion of FM was replaced by YM. All diets were isoproteic, isoenergetic, and balanced in lysine and methionine. After the feeding trial, shrimp were challenged with pathogenic bacteria (Vibrio parahaemolyticus). Growth and feed conversion parameters improved when YM was included in shrimp diets; with the highest weight gain and best food conversion ratio (FCR) achieved when 50% of FM was replaced by YM versus the control diet that contained no YM (initial weight: 1.60 g/shrimp; growth: 5.27 vs. 3.94 g/shrimp; FCR 1.20 vs. 1.59). In challenged shrimp, mortality rates were significantly less among groups that received YM, with a 76.9% lower mortality rate in the 50% FM replacement group versus the control. Full article
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Open AccessArticle
Transglutaminase-2 Mediates the Biomechanical Properties of the Colorectal Cancer Tissue Microenvironment that Contribute to Disease Progression
Cancers 2019, 11(5), 701; https://doi.org/10.3390/cancers11050701 (registering DOI) -
Abstract
Colorectal cancer is the third most common cancer worldwide, and the fourth leading cause of malignancy-related mortality. This highlights the need to understand the processes driving this disease in order to develop new treatments and improve patient outcomes. A potential therapeutic target is [...] Read more.
Colorectal cancer is the third most common cancer worldwide, and the fourth leading cause of malignancy-related mortality. This highlights the need to understand the processes driving this disease in order to develop new treatments and improve patient outcomes. A potential therapeutic target is the increased stiffness of the tumour microenvironment, which is linked to aggressive cancer cell behaviour by enhancing biomechanical signalling. In this study, we used an siRNA-based approach to investigate the contribution of the protein cross-linking enzyme transglutaminase-2 (TG2) to matrix remodelling and biomechanical properties of the tumour microenvironment. TG2 inhibited cancer cell growth in organotypic 3D fibroblast/SW480 co-culture models, and biomechanical analysis demonstrated that colorectal cancer cells induced fibroblast-mediated stiffness which was inhibited by silencing TG2. These biomechanical changes were associated with observed alterations to collagen fibre structure, notably fibre thickness. Our in vitro findings of collagen composition changes were also seen with imaging biopsied tissues from patients with colorectal cancer, with TG2 correlating positively with thicker collagen fibres, and associating with poor outcome as determined by disease recurrence post-surgery and overall survival. In conclusion, this study demonstrates a role for TG2 in the stromal response to invading tumour, leading to tissue stiffening and poor outcome in patients. Full article
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Open AccessArticle
Pitfalls of Two-Step Testing for Changes in the Error Variance and Coefficients of a Linear Regression Model
Econometrics 2019, 7(2), 22; https://doi.org/10.3390/econometrics7020022 (registering DOI) -
Abstract
In empirical applications based on linear regression models, structural changes often occur in both the error variance and regression coefficients, possibly at different dates. A commonly applied method is to first test for changes in the coefficients (or in the error variance) and, [...] Read more.
In empirical applications based on linear regression models, structural changes often occur in both the error variance and regression coefficients, possibly at different dates. A commonly applied method is to first test for changes in the coefficients (or in the error variance) and, conditional on the break dates found, test for changes in the variance (or in the coefficients). In this note, we provide evidence that such procedures have poor finite sample properties when the changes in the first step are not correctly accounted for. In doing so, we show that testing for changes in the coefficients (or in the variance) ignoring changes in the variance (or in the coefficients) induces size distortions and loss of power. Our results illustrate a need for a joint approach to test for structural changes in both the coefficients and the variance of the errors. We provide some evidence that the procedures suggested by Perron et al. (2019) provide tests with good size and power. Full article
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Open AccessArticle
Antifungal Resistance in Clinical Isolates of Aspergillus spp.: When Local Epidemiology Breaks the Norm
J. Fungi 2019, 5(2), 41; https://doi.org/10.3390/jof5020041 (registering DOI) -
Abstract
Aspergillosis is a set of very frequent and widely distributed opportunistic diseases. Azoles are the first choice for most clinical forms. However, the distribution of azole-resistant strains is not well known around the world, especially in developing countries. The aim of our study [...] Read more.
Aspergillosis is a set of very frequent and widely distributed opportunistic diseases. Azoles are the first choice for most clinical forms. However, the distribution of azole-resistant strains is not well known around the world, especially in developing countries. The aim of our study was to determine the proportion of non-wild type strains among the clinical isolates of Aspergillus spp. To this end, the minimum inhibitory concentration of three azoles and amphotericin B (used occasionally in severe forms) was studied by broth microdilution. Unexpectedly, it was found that 8.1% of the isolates studied have a diminished susceptibility to itraconazole. This value turned out to be similar to the highest azole resistance rate reported in different countries across the world. Full article
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