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  • 1
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    Online Resource
    Sexual Differentiation Is Coordinately Regulated by Cryptococcus neoformans CRK1 and GAT1
    MDPI AG ; 2020
    In:  Genes Vol. 11, No. 6 ( 2020-06-19), p. 669-
    Details
    In: Genes, MDPI AG, Vol. 11, No. 6 ( 2020-06-19), p. 669-
    Abstract: The heterothallic basidiomycetous fungus Cryptococcus neoformans has two mating types, MATa and MATα. Morphological progression of bisexual reproduction in C. neoformans is as follows: yeast to hyphal transition, filament extension, basidium formation, meiosis, and sporulation. C. neoformans Cdk-related kinase 1 (CRK1) is a negative regulator of bisexual mating. In this study, we characterized the morphological features of mating structures in the crk1 mutant and determined the genetic interaction of CRK1 in the regulatory networks of sexual differentiation. In the bilateral crk1 mutant cross, despite shorter length of filaments than in the wild-type cross, dikaryotic filaments and other structures still remained intact during bisexual mating, but the timing of basidium formation was approximately 18 h earlier than in the cross between wild type strains. Furthermore, gene expression analyses revealed that CRK1 modulated the expression of genes involved in the progression of hyphal elongation, basidium formation, karyogamy and meiosis. Phenotypic results showed that, although deletion of C. neoformans CRK1 gene increased the efficiency of bisexual mating, filamentation in the crk1 mutant was blocked by MAT2 or ZNF2 mutation. A bioinformatics survey predicted the C. neoformans GATA transcriptional factor Gat1 as a potential substrate of Crk1 kinase. Our genetic and phenotypic findings revealed that C. neoformans GAT1 and CRK1 formed a regulatory circuit to negatively regulate MAT2 to control filamentation progression and transition during bisexual mating.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes11060669
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527218-4
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  • 2
    Online Resource
    Online Resource
    Discovery of an Orally Effective Factor IX-Transferrin Fusion Protein for Hemophilia B
    MDPI AG ; 2019
    In:  International Journal of Molecular Sciences Vol. 21, No. 1 ( 2019-12-18), p. 21-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 1 ( 2019-12-18), p. 21-
    Abstract: Hemophilia B is a severe blood clotting disorder caused by the deficiency of factor IX (FIX). FIX is not bioavailable when given orally due to poor stability and permeability in the gastrointestinal tract. The feasibility of fusing FIX with transferrin (Tf) to enhance the oral bioavailability of FIX is explored. Seven recombinant fusion proteins (rFIX-Tf) with different linkers were constructed and expressed in HEK293 cells and characterized by in vitro transcytosis and transferrin receptor (TfR) binding assay in Caco-2 cells and a one-stage clotting assay. The in vivo efficacy study was performed using a tail-bleeding model in hemophilia B mice. Fusion proteins rFIX-Tf/G2 and rFIX-Tf/SVSQ were most permeable and showed a specific binding ability to TfR in Caco-2 cells. Both proteins retained FIX activity in clotting generation. The in vivo efficacy study showed that both proteins by intravenous injection significantly reduced blood loss. Most significantly, rFIX-Tf/G2 demonstrated anti-bleeding activity when administered orally. Our results showed that the fusion protein technique with Tf could be potentially used for oral delivery of FIX and the linker between FIX and Tf in the fusion protein is crucial. rFIX-Tf/G2 appears to be the most promising fusion protein as potential oral therapeutics for hemophilia B.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21010021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 2 ( 2018-01-26), p. 378-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 2 ( 2018-01-26), p. 378-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19020378
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
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    Online Resource
    Characterization of Polyelectrolyte Complex Formation Between Anionic and Cationic Poly(amino acids) and Their Potential Applications in pH-Dependent Drug Delivery
    MDPI AG ; 2017
    In:  Molecules Vol. 22, No. 7 ( 2017-06-30), p. 1089-
    Details
    In: Molecules, MDPI AG, Vol. 22, No. 7 ( 2017-06-30), p. 1089-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules22071089
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2008644-1
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  • 5
    Online Resource
    Online Resource
    Electric Load Forecasting Based on a Least Squares Support Vector Machine with Fuzzy Time Series and Global Harmony Search Algorithm
    MDPI AG ; 2016
    In:  Energies Vol. 9, No. 2 ( 2016-01-26), p. 70-
    Details
    In: Energies, MDPI AG, Vol. 9, No. 2 ( 2016-01-26), p. 70-
    Type of Medium: Online Resource
    ISSN: 1996-1073
    URL: Article
    DOI: 10.3390/en9020070
    Language: English
    Publisher: MDPI AG
    Publication Date: 2016
    detail.hit.zdb_id: 2437446-5
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  • 6
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    Online Resource
    Tooth Position Determination by Automatic Cutting and Marking of Dental Panoramic X-ray Film in Medical Image Processing
    MDPI AG ; 2021
    In:  Applied Sciences Vol. 11, No. 24 ( 2021-12-14), p. 11904-
    Details
    In: Applied Sciences, MDPI AG, Vol. 11, No. 24 ( 2021-12-14), p. 11904-
    Abstract: This paper presents a novel method for automatic segmentation of dental X-ray images into single tooth sections and for placing every segmented tooth onto a precise corresponding position table. Moreover, the proposed method automatically determines the tooth’s position in a panoramic X-ray film. The image-processing step incorporates a variety of image-enhancement techniques, including sharpening, histogram equalization, and flat-field correction. Moreover, image processing was implemented iteratively to achieve higher pixel value contrast between the teeth and cavity. The next image-enhancement step is aimed at detecting the teeth cavity and involves determining the segment and points separating the upper and lower jaw, using the difference in pixel values to cut the image into several equal sections and then connecting each cavity feature point to extend a curve that completes the description of the separated jaw. The curve is shifted up and down to look for the gap between the teeth, to identify and address missing teeth and overlapping. Under FDI World Dental Federation notation, the left and right sides receive eight-code sequences to mark each tooth, which provides improved convenience in clinical use. According to the literature, X-ray film cannot be marked correctly when a tooth is missing. This paper utilizes artificial center positioning and sets the teeth gap feature points to have the same count. Then, the gap feature points are connected as a curve with the curve of the jaw to illustrate the dental segmentation. In addition, we incorporate different image-processing methods to sequentially strengthen the X-ray film. The proposed procedure had an 89.95% accuracy rate for tooth positioning. As for the tooth cutting, where the edge of the cutting box is used to determine the position of each tooth number, the accuracy of the tooth positioning method in this proposed study is 92.78%.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app112411904
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704225-X
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  • 7
    Online Resource
    Online Resource
    Detection of Dental Apical Lesions Using CNNs on Periapical Radiograph
    MDPI AG ; 2021
    In:  Sensors Vol. 21, No. 21 ( 2021-10-24), p. 7049-
    Details
    In: Sensors, MDPI AG, Vol. 21, No. 21 ( 2021-10-24), p. 7049-
    Abstract: Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s21217049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2052857-7
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  • 8
    Online Resource
    Online Resource
    Design and Fabrication of the Reliable GaN Based Vertical-Cavity Surface-Emitting Laser via Tunnel Junction
    MDPI AG ; 2019
    In:  Crystals Vol. 9, No. 4 ( 2019-04-01), p. 187-
    Details
    In: Crystals, MDPI AG, Vol. 9, No. 4 ( 2019-04-01), p. 187-
    Abstract: In this study, we theoretically designed and experimentally fabricated an InGaN vertical-cavity surface-emitting laser (VCSEL) with a tunnel junction (TJ) structure. From numerical simulation results, the optical loss of the device can be reduced by a TJ structure. Additionally, the leakage current of the VCSEL with TJ structure was much smaller than that of the VCSEL with an Indium-Tin-Oxide (ITO) layer. We have been demonstrated that laser output performance is improved by using the TJ structure when compared to the typical VCSEL structure of the ITO layer. The output power obtained at 2.1 mW was enhanced by a factor of 3.5 by the successful reduction of threshold current density (Jth) from 12 to 8.5 kA/cm2, and the enlarged slope efficiency was due to less absorption in VCSEL with a TJ structure. Finally, the samples passed the high temperature (70 °C) and high operation current (1.5 × Jth) test for over 500 h.
    Type of Medium: Online Resource
    ISSN: 2073-4352
    URL: Article
    DOI: 10.3390/cryst9040187
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2661516-2
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  • 9
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    Online Resource
    Computer-Aided Detection (CADe) System with Optical Coherent Tomography for Melanin Morphology Quantification in Melasma Patients
    MDPI AG ; 2021
    In:  Diagnostics Vol. 11, No. 8 ( 2021-08-19), p. 1498-
    Details
    In: Diagnostics, MDPI AG, Vol. 11, No. 8 ( 2021-08-19), p. 1498-
    Abstract: Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and bias. We used a cellular resolution full-field optical coherence tomography (FF-OCT) to assess melanin features of melasma lesions and perilesional skin on the cheeks of eight Asian patients. A computer-aided detection (CADe) system is proposed to mark and quantify melanin. This system combines spatial compounding-based denoising convolutional neural networks (SC-DnCNN), and through image processing techniques, various types of melanin features, including area, distribution, intensity, and shape, can be extracted. Through evaluations of the image differences between the lesion and perilesional skin, a distribution-based feature of confetti melanin without layering, two distribution-based features of confetti melanin in stratum spinosum, and a distribution-based feature of grain melanin at the dermal–epidermal junction, statistically significant findings were achieved (p-values = 0.0402, 0.0032, 0.0312, and 0.0426, respectively). FF-OCT enables the real-time observation of melanin features, and the CADe system with SC-DnCNN was a precise and objective tool with which to interpret the area, distribution, intensity, and shape of melanin on FF-OCT images.
    Type of Medium: Online Resource
    ISSN: 2075-4418
    URL: Article
    DOI: 10.3390/diagnostics11081498
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662336-5
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  • 10
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    Online Resource
    Longitudinal Metabolomic Analysis Reveals Gut Microbial-Derived Metabolites Related to Formula Feeding and Milk Sensitization Development in Infancy
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 2 ( 2022-01-28), p. 127-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 2 ( 2022-01-28), p. 127-
    Abstract: Early exposure to formula milk increases the likelihood of cow’s milk sensitization and food allergies in the later childhood. However, the underlying mechanisms are multifactorial and unclear. Fifty-five children from a follow-up birth cohort study were grouped into exclusive breastfeeding (EBF, n = 33) and formula feeding (EFF, n = 22) in the first six months of life. Urinary metabolites were longitudinally assessed and analyzed at 6 months, 1, and 2 years of age using 1H-nuclear magnetic resonance (NMR) spectroscopy. Integrated analysis of metabolic profiling associated with formula feeding and milk sensitization related to IgE reactions was also investigated. Twenty-two metabolites were significantly obtained in the EFF set at age 0.5, whereas nine metabolites were predominantly obtained in the milk sensitization set at age 1. A subsequent analysis of metabolic change from 6 months to age 1 identified eight metabolites, including 3-methyl-2-oxovaleric acid, glutarate, lysine, N-phenylacetylglycine, N,N-dimethylglycine, 3-indoxysulfate, 2-oxoglutaric acid, and pantothenate associated with formula feeding and milk sensitization with same trend variation. Among them, 3-indoxysulfate, N-phenylacetylglycine, and N,N-dimethylglycine were gut microbial-derived without IgE association. By contrast, 3-methyl-2-oxovaleric acid, glutarate, and lysine were IgE related associated with formula feeding contributing to milk sensitization (p 〈 0.05). Longitudinal urinary metabolomic analysis provides molecular insight into the mechanism of formula feeding associated with milk sensitization. Gut microbial-derived metabolites associated with formula feeding and IgE associated metabolites related to branched-chain amino acid metabolism play roles in developing sensitization and allergic symptoms in response to formula feeding.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12020127
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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