Experience in the use of steroid hormones in the complex treatment of rheumatism and some other diseases in children

Of 33 patients with active rheumatism in 1958-60. 20 received cortisone and 13 received ACTH. Myocarditis was observed in 5 people, endomyocarditis with mitral valve insufficiency - in 1, endomyocarditis with combined defects - in 23, pancarditis with combined defects - in 4. Articular manifestations (polyarthritis, polyarthralgia) were noted in 16 children. Only 5 children fell ill with rheumatism for the first time.

RECOGNITION OF DISCHARGES THAT ARE ACCOMPANIED BY LOW-TEMPERATURE OVERHEATING BASED ON THE ANALYSIS OF GASES DISSOLVED IN THE OIL OF HIGH-VOLTAGE TRANSFORMERS

Based on the analysis of test results for 135 high-voltage transformers, ranges of gas percentage, gas ratio values were obtained and nomograms for 10 types of combined defects were made, representing discharges with different intensity which are accompanied by overheating with temperature of 150-300°C. It has been established that in transformers with discharges accompanied by low-temperature overheating the values of CH4/H2, C2H2/CH4, C2H2/C2H6 and C2H2/C2H4 ratios determine the discharge energy, in accordance with the norms regulated by the most known standards, the C2H4/C2H6 ratio varies slightly depending on the hot spot temperature and the C2H6/CH4>1 ratio value. Dynamics of defects nomograms changing in the process of their development is analyzed. It is stated by the analysis results that in majority of cases the primary defect is discharges with different intensity, which are accompanied by low-temperature overheating. Overheating occurs in the process of discharge development. The analysis of recognition reliability of discharges with different intensity which are accompanied by 150-300°C overheating was made, using norms and criteria regulated by the most known standards and methods. The results of the analysis show that the most reliable recognition of the defects analyzed is provided to a large extent by the graphical methods, namely the ETRA square and the Duval triangle. The results obtained will significantly increase the recognition reliability of combined defects based on the results of the dissolved gas analysis in the oil.

Numerical Study on Strength and Failure Behavior of Rock with Composite Defects under Uniaxial Compression

The cracks and holes in underground engineering are the critical factors that cause the instability of the surrounding rock. It is helpful to control the stability of surrounding rock to study the samples with combined defects of cracks and holes. In this study, PFC 2D is used to analyze the numerical models. Seven combined models of single circular hole and double cracks with different angles are established, and the fracture angle varies from 0° to 90° with an interval of 15°. First, uniaxial compression experiments and numerical simulations are carried out in the 0° defect combination model, and the microscopic parameters of PFC 2D are determined. Then, the numerical simulations of seven defect models under uniaxial compression are carried out, and the crack development law and acoustic emission characteristics of different defect combination models are studied. The failure modes, mechanical behavior, and stress states are studied. The displacement vector distributions of different defect combination models are analyzed; it is found that there are three main types of macro cracks in the defect combination samples. The results show that the combined defects reduce the strength of the model. Meanwhile, the distributions of the stress and displacement are changed by the cracks with different angles in the defective models.

BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

Human bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and early elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

BET family members Bdf1/2 modulate global transcription initiation and elongation in Saccharomyces cerevisiae

Human bromodomain-containing BET family members are promising targets for therapy of cancer and immunoinflammatory diseases, but their mechanisms of action and functional redundancies are poorly understood. Bdf1/2, yeast homologues of the human BET factors, were previously proposed to target transcription factor TFIID to acetylated histone H4, analogous to bromodomains that are present within the largest subunit of metazoan TFIID. We investigated the genome-wide roles of Bdf1/2 and found that their important contributions to transcription extend beyond TFIID function, as transcription of many genes is more sensitive to Bdf1/2 than to TFIID depletion. Bdf1/2 co-occupy the majority of yeast promoters and affect preinitiation complex formation through recruitment of TFIID, Mediator and basal transcription factors to chromatin. Surprisingly, we discovered that hypersensitivity of genes to Bdf1/2 depletion results from combined defects in transcription initiation and processive elongation, a striking functional similarity to human BET proteins, most notably Brd4. Our results establish Bdf1/2 as critical for yeast transcription and provide important mechanistic insights into the function of BET proteins in all eukaryotes.

Detection and Severity Evaluation of Combined Rail Defects Using Deep Learning

Various techniques have been developed to detect railway defects. One of the popular techniques is machine learning. This unprecedented study applies deep learning, which is a branch of machine learning techniques, to detect and evaluate the severity of rail combined defects. The combined defects in the study are settlement and dipped joint. Features used to detect and evaluate the severity of combined defects are axle box accelerations simulated using a verified rolling stock dynamic behavior simulation called D-Track. A total of 1650 simulations are run to generate numerical data. Deep learning techniques used in the study are deep neural network (DNN), convolutional neural network (CNN), and recurrent neural network (RNN). Simulated data are used in two ways: simplified data and raw data. Simplified data are used to develop the DNN model, while raw data are used to develop the CNN and RNN model. For simplified data, features are extracted from raw data, which are the weight of rolling stock, the speed of rolling stock, and three peak and bottom accelerations from two wheels of rolling stock. In total, there are 14 features used as simplified data for developing the DNN model. For raw data, time-domain accelerations are used directly to develop the CNN and RNN models without processing and data extraction. Hyperparameter tuning is performed to ensure that the performance of each model is optimized. Grid search is used for performing hyperparameter tuning. To detect the combined defects, the study proposes two approaches. The first approach uses one model to detect settlement and dipped joint, and the second approach uses two models to detect settlement and dipped joint separately. The results show that the CNN models of both approaches provide the same accuracy of 99%, so one model is good enough to detect settlement and dipped joint. To evaluate the severity of the combined defects, the study applies classification and regression concepts. Classification is used to evaluate the severity by categorizing defects into light, medium, and severe classes, and regression is used to estimate the size of defects. From the study, the CNN model is suitable for evaluating dipped joint severity with an accuracy of 84% and mean absolute error (MAE) of 1.25 mm, and the RNN model is suitable for evaluating settlement severity with an accuracy of 99% and mean absolute error (MAE) of 1.58 mm.

Novel Mutations of TYK2 Leading to Divergent Clinical Phenotypes

TYK2 deficiency is a rare Primary immunodeficiency disease caused by loss of function mutations of TYK2 gene, which is initially proposed as a subset of Hyper IgE syndrome (HIES). However, accumulating evidence suggest TYK2 deficient patients do not necessarily present with HIES characteristics, indicating a vacuum of knowledge on the exact roles of TYK2 in human immune system. Here we describe five more TYK2 deficient cases presenting with or without hyper IgE levels, atopy and distinct pathogen infection profile, which are caused by novel TYK2 mutations. These mutations were all found by high throughout sequencing and confirmed by Sanger sequencing. Pathogenic effects were confirmed by qRT-PCR and western blot. Peripheral blood mononulear cells (PBMCs) from these patients showed heterogenous responses to various cytokines treatment, including IFN-a/b/g, IL-6, IL-10, IL12 and IL-23. The homeostasis of lymphocytes is also disrupted. Based on our findings, we propose that TYK2 works as a multi-tasker in orchestrating various cytokines signaling pathways, differentially combined defects of which account for the expressed clinical manifestations.

Digital Customized Titanium Mesh for Bone Regeneration of Vertical, Horizontal and Combined Defects: A Case Series

Background and Objective: Guided bone regeneration allows new bone formation in anatomical sites showing defects preventing implant rehabilitation. Material and Methods: The present case series reported the outcomes of five patients treated with customized titanium meshes manufactured with a digital workflow for achieving bone regeneration at future implant sites. A significant gain in both width and thickness was achieved for all patients. Results: From a radiographic point of view (CBTC), satisfactory results were reached both in horizontal and vertical defects. An average horizontal gain of 3.6 ± 0.8 mm and a vertical gain of 5.2 ± 1.1 mm. Conclusions: The findings from this study suggest that customized titanium meshes represent a valid method to pursue guided bone regeneration in horizontal, vertical or combined defects. Particular attention must be paid by the surgeon in the packaging of the flap according to a correct method called the “poncho” technique in order to reduce the most frequent complication that is the exposure of the mesh even if a partial exposure of one mesh does not compromise the final outcome of both the reconstruction and the healing of the implants.