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  • 1
    Online Resource
    Online Resource
    Biophysical Characterization of Membrane Proteins Embedded in Nanodiscs Using Fluorescence Correlation Spectroscopy
    MDPI AG ; 2022
    In:  Membranes Vol. 12, No. 4 ( 2022-03-31), p. 392-
    Details
    In: Membranes, MDPI AG, Vol. 12, No. 4 ( 2022-03-31), p. 392-
    Abstract: Proteins embedded in biological membranes perform essential functions in all organisms, serving as receptors, transporters, channels, cell adhesion molecules, and other supporting cellular roles. These membrane proteins comprise ~30% of all human proteins and are the targets of ~60% of FDA-approved drugs, yet their extensive characterization using established biochemical and biophysical methods has continued to be elusive due to challenges associated with the purification of these insoluble proteins. In response, the development of nanodisc techniques, such as nanolipoprotein particles (NLPs) and styrene maleic acid polymers (SMALPs), allowed membrane proteins to be expressed and isolated in solution as part of lipid bilayer rafts with defined, consistent nanometer sizes and compositions, thus enabling solution-based measurements. Fluorescence correlation spectroscopy (FCS) is a relatively simple yet powerful optical microscopy-based technique that yields quantitative biophysical information, such as diffusion kinetics and concentrations, about individual or interacting species in solution. Here, we first summarize current nanodisc techniques and FCS fundamentals. We then provide a focused review of studies that employed FCS in combination with nanodisc technology to investigate a handful of membrane proteins, including bacteriorhodopsin, bacterial division protein ZipA, bacterial membrane insertases SecYEG and YidC, Yersinia pestis type III secretion protein YopB, yeast cell wall stress sensor Wsc1, epidermal growth factor receptor (EGFR), ABC transporters, and several G protein-coupled receptors (GPCRs).
    Type of Medium: Online Resource
    ISSN: 2077-0375
    URL: Article
    DOI: 10.3390/membranes12040392
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2614641-1
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  • 2
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    Online Resource
    Reproducible NiO/Ga2O3 Vertical Rectifiers with Breakdown Voltage 〉8 kV
    MDPI AG ; 2023
    In:  Crystals Vol. 13, No. 6 ( 2023-05-28), p. 886-
    Details
    In: Crystals, MDPI AG, Vol. 13, No. 6 ( 2023-05-28), p. 886-
    Abstract: Optimized vertical heterojunction rectifiers with a diameter of 100 µm, consisting of sputter-deposited p-type NiO forming a p–n junction with thick (10 µm) Ga2O3 drift layers grown by halide vapor phase epitaxy (HVPE) on (001) Sn-doped (1019 cm−3) β-Ga2O3 substrates, exhibited breakdown voltages 〉 8 kV over large areas ( 〉 1 cm2). The key requirements were low drift layer doping concentrations ( 〈 1016 cm3), low power during the NiO deposition to avoid interfacial damage at the heterointerface and formation of a guard ring using extension of the NiO beyond the cathode metal contact. Breakdown still occurred at the contact periphery, suggesting that further optimization of the edge termination could produce even larger breakdown voltages. On-state resistances without substrate thinning were 〈 10 mΩ.cm−2, leading to power figure-of-merits 〉 9 GW.cm−2. The devices showed an almost temperature-independent breakdown to 600 K. These results show the remarkable potential of NiO/Ga2O3 rectifiers for performance beyond the limits of both SiC and GaN. The important points to achieve the excellent performance were: (1) low drift doping concentration, (2) low power during the NiO deposition and (3) formation of a guard ring.
    Type of Medium: Online Resource
    ISSN: 2073-4352
    URL: Article
    DOI: 10.3390/cryst13060886
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661516-2
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  • 3
    Online Resource
    Online Resource
    Systems Analysis of Transcriptomic and Proteomic Profiles Identifies Novel Regulation of Fibrotic Programs by miRNAs in Pulmonary Fibrosis Fibroblasts
    MDPI AG ; 2018
    In:  Genes Vol. 9, No. 12 ( 2018-11-29), p. 588-
    Details
    In: Genes, MDPI AG, Vol. 9, No. 12 ( 2018-11-29), p. 588-
    Abstract: Fibroblasts/myofibroblasts are the key effector cells responsible for excessive extracellular matrix (ECM) deposition and fibrosis progression in both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) patient lungs, thus it is critical to understand the transcriptomic and proteomic programs underlying their fibrogenic activity. We conducted the first integrative analysis of the fibrotic programming in these cells at the levels of gene and microRNA (miRNA) expression, as well as deposited ECM protein to gain insights into how fibrotic transcriptional programs culminate in aberrant ECM protein production/deposition. We identified messenger RNA (mRNA), miRNA, and deposited matrisome protein signatures for IPF and SSc fibroblasts obtained from lung transplants using next-generation sequencing and mass spectrometry. SSc and IPF fibroblast transcriptional signatures were remarkably similar, with enrichment of WNT, TGF-β, and ECM genes. miRNA-seq identified differentially regulated miRNAs, including downregulation of miR-29b-3p, miR-138-5p and miR-146b-5p in disease fibroblasts and transfection of their mimics decreased expression of distinct sets of fibrotic signature genes as assessed using a Nanostring fibrosis panel. Finally, proteomic analyses uncovered a distinct “fibrotic” matrisome profile deposited by IPF and SSc fibroblasts compared to controls that highlights the dysregulated ECM production underlying their fibrogenic activities. Our comprehensive analyses of mRNA, miRNA, and matrisome proteomic profiles in IPF and SSc lung fibroblasts revealed robust fibrotic signatures at both the gene and protein expression levels and identified novel fibrogenesis-associated miRNAs whose aberrant downregulation in disease fibroblasts likely contributes to their fibrotic and ECM gene expression.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes9120588
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527218-4
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  • 4
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    Probing Differences in Mass-Transfer Coefficients in Beaker and Stirrer Digestion Systems and the USP Dissolution Apparatus 2 Using Benzoic Acid Tablets
    MDPI AG ; 2021
    In:  Processes Vol. 9, No. 12 ( 2021-12-02), p. 2168-
    Details
    In: Processes, MDPI AG, Vol. 9, No. 12 ( 2021-12-02), p. 2168-
    Abstract: Measurements of external mass-transfer coefficients for dissolution have been made with benzoic acid tablets with a diameter of 13 mm and approximately 3 mm thick, using two different dissolution systems. One system has been a beaker with a platform for the tablet and either 80 mL or 120 mL of water, with three different types of stirrers, and the other has been a USP dissolution apparatus 2 (paddle) with either 200 mL or 900 mL water. Various stirring speeds have also been used in the different pieces of equipment. The same mass-transfer coefficient may potentially be obtained from the same tablet by adjusting the operating conditions in the two different devices. The ranges of the external mass-transfer coefficients measured in both devices overlapped significantly, with the range being 0.193–4.48 × 10−5 m s−1 in the beaker and stirrer system and 0.222–3.45 × 10−5 m s−1 in the USP dissolution apparatus 2. Dimensional analysis of the results, using Sherwood and Reynolds numbers, shows that the Ranz–Marshall correlation provides a lower bound for estimates of the Sherwood numbers measured experimentally. Calculations of time constants for mass transfer suggest that mass transfer may be a rate-limiting step for dissolution and food digestion under some circumstances. The range of mass-transfer coefficients measured here is representative of other measurements from the literature, and the use of the Ranz–Marshall correlation supports the suggestion that this range of values should be generally expected in most situations.
    Type of Medium: Online Resource
    ISSN: 2227-9717
    URL: Article
    DOI: 10.3390/pr9122168
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720994-5
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  • 5
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    Online Resource
    The Role of Artificial Intelligence in Echocardiography
    MDPI AG ; 2023
    In:  Journal of Imaging Vol. 9, No. 2 ( 2023-02-20), p. 50-
    Details
    In: Journal of Imaging, MDPI AG, Vol. 9, No. 2 ( 2023-02-20), p. 50-
    Abstract: Echocardiography is an integral part of the diagnosis and management of cardiovascular disease. The use and application of artificial intelligence (AI) is a rapidly expanding field in medicine to improve consistency and reduce interobserver variability. AI can be successfully applied to echocardiography in addressing variance during image acquisition and interpretation. Furthermore, AI and machine learning can aid in the diagnosis and management of cardiovascular disease. In the realm of echocardiography, accurate interpretation is largely dependent on the subjective knowledge of the operator. Echocardiography is burdened by the high dependence on the level of experience of the operator, to a greater extent than other imaging modalities like computed tomography, nuclear imaging, and magnetic resonance imaging. AI technologies offer new opportunities for echocardiography to produce accurate, automated, and more consistent interpretations. This review discusses machine learning as a subfield within AI in relation to image interpretation and how machine learning can improve the diagnostic performance of echocardiography. This review also explores the published literature outlining the value of AI and its potential to improve patient care.
    Type of Medium: Online Resource
    ISSN: 2313-433X
    URL: Article
    DOI: 10.3390/jimaging9020050
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2824270-1
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  • 6
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    Online Resource
    Discovery and Optimization of Selective Inhibitors of Meprin α (Part II)
    MDPI AG ; 2021
    In:  Pharmaceuticals Vol. 14, No. 3 ( 2021-02-27), p. 197-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 14, No. 3 ( 2021-02-27), p. 197-
    Abstract: Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph14030197
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 7
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    Online Resource
    Transcatheter Aortic Valve Replacement Prognostication with Augmented Mean Arterial Pressure
    MDPI AG ; 2023
    In:  Journal of Cardiovascular Development and Disease Vol. 10, No. 5 ( 2023-04-26), p. 192-
    Details
    In: Journal of Cardiovascular Development and Disease, MDPI AG, Vol. 10, No. 5 ( 2023-04-26), p. 192-
    Abstract: Background: Post-transcatheter aortic valve replacement (TAVR) patient outcome is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure (AugMAP)) derived from blood pressure and aortic valve gradients. Methods: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between 1 January 2012 and 30 June 2017 were identified to retrieve baseline clinical, echocardiographic and mortality data. AugSBP, AugMAP and valvulo-arterial impedance (Zva) (Zva) were evaluated using Cox regression. Receiver operating characteristic curve analysis and the c-index were used to assess the model performance against the Society of Thoracic Surgeons (STS) risk score. Results: The final cohort contained 974 patients with a mean age of 81.4 ± 8.3 years old, and 56.6% were male. The mean STS risk score was 8.2 ± 5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Both univariate and multivariate Cox regression showed that AugSBP and AugMAP parameters were independent predictors for intermediate-term post-TAVR mortality (all p 〈 0.0001). AugMAP1 〈 102.5 mmHg was associated with a 3-fold-increased risk of all-cause mortality 1-year post-TAVR (hazard ratio 3.0, 95%confidence interval 2.0–4.5, p 〈 0.0001). A univariate model of AugMAP1 surpassed the STS score model in predicting intermediate-term post-TAVR mortality (area under the curve: 0.700 vs. 0.587, p = 0.005; c-index: 0.681 vs. 0.585, p = 0.001). Conclusions: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis.
    Type of Medium: Online Resource
    ISSN: 2308-3425
    URL: Article
    DOI: 10.3390/jcdd10050192
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2777082-5
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  • 8
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    Online Resource
    Using CFD Simulations to Guide the Development of a New Spray Dryer Design
    MDPI AG ; 2020
    In:  Processes Vol. 8, No. 8 ( 2020-08-02), p. 932-
    Details
    In: Processes, MDPI AG, Vol. 8, No. 8 ( 2020-08-02), p. 932-
    Abstract: A new spray-drying system has been designed to overcome the limitations caused by existing designs. A key feature of the approach has been the systematic use of Computational Fluid Dynamics (CFD) to guide innovation in the design process. An example of an innovation is the development of a box-shaped transitional feature between the bottom of the main drying chamber and the entrance to the secondary chamber. In physical experiments, the box design performed better in all three representative operating conditions, including the current conditions, a higher feed solids concentration (30% solids rather than 8.8%), and a higher inlet drying temperature (230 °C rather than 170 °C). The current conditions showed a 3% increase in yield (solids recovery) while the 30% feed condition improved the yield by 7.5%, and the higher temperature test increased the yield by 13.5%. Statistical analysis showed that there were significant reductions in the wall flux at the high solids feed concentration. The observed deposition in the box was primarily from the predicted particle impacts by an inertial deposition process on the base of the box, which underwent little degradation due to lower temperatures. There is therefore evidence that the box design is a better design alternative under all operating conditions compared with other traditional designs.
    Type of Medium: Online Resource
    ISSN: 2227-9717
    URL: Article
    DOI: 10.3390/pr8080932
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720994-5
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  • 9
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    Simulating Tablet Dissolution Using Computational Fluid Dynamics and Experimental Modeling
    MDPI AG ; 2023
    In:  Processes Vol. 11, No. 2 ( 2023-02-07), p. 505-
    Details
    In: Processes, MDPI AG, Vol. 11, No. 2 ( 2023-02-07), p. 505-
    Abstract: The study of mass transfer is essential in the food digestion process, especially when gastric acid interacts with food and nutrients dissolve in the gastric system. In this study, a computational fluid dynamics (CFD) model was built based on an in vitro study, which investigated the mass transfer in a tablet dissolution process in a beaker and stirrer system. The predicted mass transfer coefficients from the simulation aligned well with the experimental values. The effect of the type and rotation speed of the stirrers was also investigated. Mass transfer from the tablet was found to be closely related to the tablet Reynolds number of the fluid (ranging from 0 to 938) and the shear stress (0 to 0.167 Pa) acting on the tablet. The relationship between the power number (0.0061 to 0.196) and the Reynolds number for the impeller (719 to 5715) was also derived for different stirrers.
    Type of Medium: Online Resource
    ISSN: 2227-9717
    URL: Article
    DOI: 10.3390/pr11020505
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720994-5
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  • 10
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    Novel Image State Ensemble Decomposition Method for M87 Imaging
    MDPI AG ; 2020
    In:  Applied Sciences Vol. 10, No. 4 ( 2020-02-24), p. 1535-
    Details
    In: Applied Sciences, MDPI AG, Vol. 10, No. 4 ( 2020-02-24), p. 1535-
    Abstract: This paper proposes a new method of image decomposition with a filtering capability. The image state ensemble decomposition (ISED) method has generative capabilities that work by removing a discrete ensemble of quanta from an image to provide a range of filters and images for a single red, green, and blue (RGB) input image. This method provides an image enhancement because ISED is a spatial domain filter that transforms or eliminates image regions that may have detrimental effects, such as noise, glare, and image artifacts, and it also improves the aesthetics of the image. ISED was used to generate 126 images from two tagged image file (TIF) images of M87 taken by the Spitzer Space Telescope. Analysis of the images used various full and no-reference quality metrics as well as histograms and color clouds. In most instances, the no-reference quality metrics of the generated images were shown to be superior to those of the two original images. Select ISED images yielded previously unknown galactic structures, reduced glare, and enhanced contrast, with good overall performance.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app10041535
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704225-X
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