Aim To assess the influence of artefacts generated by metal posts on the detection of simulated internal root resorption (IRR) in adjacent teeth using cone-beam computed tomography (CBCT), as well as to verify the impact of metal artefact reduction (MAR) on these cases. Methodology CBCT images of 14 premolar teeth were acquired before and after IRR simulation using chemical and mechanical procedures, in an OP300 Maxio unit, with and without MAR. Each tooth was placed in the socket of a human mandible and scanned under three different conditions 1, without adjacent teeth - control group; 2, distal adjacent tooth restored with metal post; and 3, with both adjacent teeth restored with metal post. Five oral radiologists scored the IRR detection using a 5-point scale. Diagnostic values were obtained for the tested groups and compared using two-way analysis of variance (α=0.05). Results The presence of a single adjacent tooth restored with metal post did not significantly influence the diagnostic values for IRR detection (p>0.05). The presence of both adjacent teeth with metal posts, without MAR application, were associated with a significantly lower area under the ROC curve (Az) compared to the control (p=0.0182). In this case, the application of MAR increased Az, leading to non-significant differences from the control group and the group with one adjacent restored tooth (p>0.05). Sensitivity decreased significantly when two adjacent restored teeth were present, regardless of MAR application (p=0.0379). Specificity was not affected by the conditions tested (p>0.05). Conclusion CBCT detection of internal root resorption was impaired by artefacts only when both adjacent teeth restored with metal posts were present. In such cases, activation of MAR improved the performance on this diagnostic task.Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to nerve elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga ****. https://www.selleckchem.com/products/ITF2357(Givinostat).html Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.Urinary β2 microglobulin (β2-m) is a marker of renal tubule dysfunction; however, β2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of β2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of β2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). β2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of β2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that post-translational modifications of β2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.Intrinsically disordered regions (IDR) play an important role in key biological processes and are closely related to human diseases. IDRs have great potential to serve as targets for drug discovery, most notably in disordered binding regions. Accurate prediction of IDRs is challenging because their genome wide occurrence and a low ratio of disordered residues make them difficult targets for traditional classification techniques. Existing computational methods mostly rely on sequence profiles to improve accuracy which is time consuming and computationally expensive. This article describes an ab initio sequence-only prediction method - which tries to overcome the challenge of accurate prediction posed by IDRs - based on reduced amino acid alphabets and convolutional neural networks (CNNs). We experiment with six different 3-letter reduced alphabets. We argue that the dimensional reduction in the input alphabet facilitates the detection of complex patterns within the sequence by the convolutional step. Experimental results show that our proposed IDR predictor performs at the same level or outperforms other state-of-the-art methods in the same class, achieving accuracy levels of 0.76 and AUC of 0.85 on the publicly available Critical Assessment of protein Structure Prediction dataset (CASP10). Therefore, our method is suitable for proteome-wide disorder prediction yielding similar or better accuracy than existing approaches at a faster speed. This article is protected by copyright. All rights reserved.Chemical herbicides, which are commonly used to kill weeds in the field, have been extensively applied and transformed the way of weed management in modern agriculture due to its efficiency, ease of use and relatively low cost. In last decades, a large number of transgenic herbicide-tolerant crops (i.e. corn, soybean, cotton, rice etc.) have been developed and commercialized, reshaping the global seed market (Schutte et al., 2017). However, the use of chemical herbicides (i.e. ALS inhibitors, EPSPS inhibitors, ACCase inhibitors etc.) has also drastically increased, resulting in the occurrence of weed species resistant to these herbicides.
Aim To assess the influence of artefacts generated by metal posts on the detection of simulated internal root resorption (IRR) in adjacent teeth using cone-beam computed tomography (CBCT), as well as to verify the impact of metal artefact reduction (MAR) on these cases. Methodology CBCT images of 14 premolar teeth were acquired before and after IRR simulation using chemical and mechanical procedures, in an OP300 Maxio unit, with and without MAR. Each tooth was placed in the socket of a human mandible and scanned under three different conditions 1, without adjacent teeth - control group; 2, distal adjacent tooth restored with metal post; and 3, with both adjacent teeth restored with metal post. Five oral radiologists scored the IRR detection using a 5-point scale. Diagnostic values were obtained for the tested groups and compared using two-way analysis of variance (α=0.05). Results The presence of a single adjacent tooth restored with metal post did not significantly influence the diagnostic values for IRR detection (p>0.05). The presence of both adjacent teeth with metal posts, without MAR application, were associated with a significantly lower area under the ROC curve (Az) compared to the control (p=0.0182). In this case, the application of MAR increased Az, leading to non-significant differences from the control group and the group with one adjacent restored tooth (p>0.05). Sensitivity decreased significantly when two adjacent restored teeth were present, regardless of MAR application (p=0.0379). Specificity was not affected by the conditions tested (p>0.05). Conclusion CBCT detection of internal root resorption was impaired by artefacts only when both adjacent teeth restored with metal posts were present. In such cases, activation of MAR improved the performance on this diagnostic task.Background Endothelin-1 (EDN1) can evoke histamine-independent pruritus in mammals and is upregulated in the lesional epidermis of atopic dermatitis (AD). EDN1 increases the production of interleukin 25 (IL-25) from keratinocytes to accelerate T helper type 2 immune deviation. Plasma EDN1 levels are positively correlated with the clinical severity and itch intensity of AD. Therefore, we hypothesized that the inhibition of EDN1 might be useful for treating atopic inflammation and itch and investigated the effects of the topical application of the EDN1 receptor antagonist bosentan on the skin inflammation and itch in a murine AD model. Methods We analyzed the mite-induced AD-like NC/Nga murine model, which was topically applied with bosentan or ethanol control every day for 3 weeks. We also subjected in vitro primary sensory neuron culture systems to nerve elongation and branching assays after EDN1 stimulation. Results Topical application of bosentan significantly attenuated the development of mite-induced AD-like skin inflammation, dermatitis scores, ear thickness, scratching bouts, and serum level of thymus and activation-regulated chemokine in NC/Nga mice. https://www.selleckchem.com/products/ITF2357(Givinostat).html Bosentan application also significantly reduced the gene expression of Il13, Il17, and Ifng in the treated lesions. Histologically, the number of infiltrated dermal cells, the epidermal EDN1 expression, and the number of intraepidermal nerve fibers were significantly inhibited upon bosentan application. While EDN1 significantly elongated the neurites of dorsal root ganglion cells in a dose- and time-dependent manner, bosentan treatment attenuated this. Conclusions EDN1 plays a significant role in mite-induced inflammation and itch. Topical bosentan is a potential protective candidate for AD.Urinary β2 microglobulin (β2-m) is a marker of renal tubule dysfunction; however, β2-m might become degraded under acidic conditions. To confirm the degradation and consequent deactivation of β2-m under acidic conditions, we used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) to detect the levels and forms of β2-m in the urine samples of patients with high proteinuria (n = 21) and healthy subjects (n = 6). β2-m was purified in crude form using immunoprecipitation. A signal of 11.74 kDa, corresponding to the molecular weight of β2-m, was detected in all samples. In addition, several high-molecular-weight proteins were detected in a patient as integrals of the intensity at 11.74 kDa. These results indicate that post-translational modifications of β2-m might be involved in the pathological process of proteinuria. Therefore, MS can be used for monitoring proteinuria and predicting the risk of progression.Intrinsically disordered regions (IDR) play an important role in key biological processes and are closely related to human diseases. IDRs have great potential to serve as targets for drug discovery, most notably in disordered binding regions. Accurate prediction of IDRs is challenging because their genome wide occurrence and a low ratio of disordered residues make them difficult targets for traditional classification techniques. Existing computational methods mostly rely on sequence profiles to improve accuracy which is time consuming and computationally expensive. This article describes an ab initio sequence-only prediction method - which tries to overcome the challenge of accurate prediction posed by IDRs - based on reduced amino acid alphabets and convolutional neural networks (CNNs). We experiment with six different 3-letter reduced alphabets. We argue that the dimensional reduction in the input alphabet facilitates the detection of complex patterns within the sequence by the convolutional step. Experimental results show that our proposed IDR predictor performs at the same level or outperforms other state-of-the-art methods in the same class, achieving accuracy levels of 0.76 and AUC of 0.85 on the publicly available Critical Assessment of protein Structure Prediction dataset (CASP10). Therefore, our method is suitable for proteome-wide disorder prediction yielding similar or better accuracy than existing approaches at a faster speed. This article is protected by copyright. All rights reserved.Chemical herbicides, which are commonly used to kill weeds in the field, have been extensively applied and transformed the way of weed management in modern agriculture due to its efficiency, ease of use and relatively low cost. In last decades, a large number of transgenic herbicide-tolerant crops (i.e. corn, soybean, cotton, rice etc.) have been developed and commercialized, reshaping the global seed market (Schutte et al., 2017). However, the use of chemical herbicides (i.e. ALS inhibitors, EPSPS inhibitors, ACCase inhibitors etc.) has also drastically increased, resulting in the occurrence of weed species resistant to these herbicides.
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