Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer

The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Technology of organization of network design in educational process

New forms, methods and facilities, allowing to useeffectively possibilities of information and communication technologies, are actively inculcated in a modern teaching and upbringing process. The organization of network design in education process supposes the use of the virtual education environment with application of services, allows to provide updating of content of education and to create conditions for satisfaction of various information and cognitive needs of pupils

Evaluation of the ecological efficiency of soil cultivation machines with innovative dynamic working bodies

The research results are related to the problem of enhancing the environmental safety of technical means in crop production. A research object is a tillage machine with standard and innovative dynamic working bodies. The research is aimed to a comparative ecological assessment of the efficiency of using typical and dynamic working bodies for surface tillage. The scientific novelty is represented by the regularities of changes in resistivity per unit of active frontal area of the investigated working bodies, inertia force and total kinetic energy, per hectare fuel consumption, fuel economy and reduction of emissions of toxic components at different speed modes of operation of the tillage unit. During the research, the methods of experimental research in the field, analysis and generalization of experimental data were used. It has been established that the resistivity per unit of active frontal area of a dynamic tillage working body with an energy-storage transmission mechanism within the range of speed variation from 2.22 to 3.33 m/s decreases by 33-41% in comparison with a typical working body. With an increase in the speed of the tillage unit with standard working bodies from 2.22 to 3.33 m/s, the fuel consumption increases from 5.12 to 9.21 kg/ha. Within these limits of the speed of the tillage unit with dynamic tillage working bodies and energy-accumulating transmission mechanisms, the per hectare fuel consumption increases from 4.81 to 8.30 kg. The use of dynamic working bodies on the tillage machine allows to save from 0.310 to 0.910 kg of fuel per 1 ha. Herewith, the decrease in the level of emissions of toxic components is 6-10%, which ensures a decrease in the environmental load of soil-cultivating units during the cultivation of crop products

Ecologically responsible entrepreneurship and its contribution to the green economy's sustainable development: Financial risk management prospects

This paper's goal is to develop a scientific methodology of financial risk management of ecologically responsible entrepreneurship for the sustainable development of the green economy. The originality of this paper is due to the fact that, for the first time, the financial risks of the green economy are considered through the prism of its sustainability. The paper's novelty is due to the modelling and quantitative measuring of the impact of the COVID-19 pandemic and the financial and economic crisis on the financial risks to the green economy's sustainability, in addition to the development of precise quantitative recommendations for financial risk management of the green economy. This enables an increase in its sustainability and reduces ecological disproportion in regions of the world (reducing the differences in the green economy's sustainability among regions of the world through the management of green investments). The paper's contribution to the literature consists of specifying the theory of financial risks to the green economy. According to the specified fundamental provisions of this theory, the essence of the process of green economy development is clarified (the "black box" is opened) as the increase in its contribution to sustainable development. As the indicator of achieving this development, an increase in the green economy's sustainability is offered. A new source of achieving the goal is proposed, consisting of a financial risk management of ecologically responsible entrepreneurship based on (private) green investments

The Analysis of Efficiency on the Base Discount System in the Pharmaceutical Organizations Depending on their Category and Level of the Competition on the Basis of Statistical Processing of Results Of Questionnaire

Authors set the task on the basis of questionnaire of pharmaceutical workers to analyse interrelation between efficiency use of discount system and such characteristics of the pharmaceutical organizations as category, location, competition level, and also lasting uses of discount system. Accurately expressed tendency of increase of conviction of staff of the pharmaceutical organizations in efficiency of use of discount programs at their long use is shown, interrelation of level of the competition in the developed pharmaceutical market, locations of the pharmaceutical organization and efficiency of use of discount systems. The used criteria of an assessment of efficiency of discount systems (increase in number of buyers, increase in the sum of the average check, etc.) by the pharmaceutical organizations depending on a site, competition level are considered

Ecologically Responsible Entrepreneurship and Its Contribution to the Green Economy&rsquo;s Sustainable Development: Financial Risk Management Prospects

This paper&rsquo;s goal is to develop a scientific methodology of financial risk management of ecologically responsible entrepreneurship for the sustainable development of the green economy. The originality of this paper is due to the fact that, for the first time, the financial risks of the green economy are considered through the prism of its sustainability. The paper&rsquo;s novelty is due to the modelling and quantitative measuring of the impact of the COVID-19 pandemic and the financial and economic crisis on the financial risks to the green economy&rsquo;s sustainability, in addition to the development of precise quantitative recommendations for financial risk management of the green economy. This enables an increase in its sustainability and reduces ecological disproportion in regions of the world (reducing the differences in the green economy&rsquo;s sustainability among regions of the world through the management of green investments). The paper&rsquo;s contribution to the literature consists of specifying the theory of financial risks to the green economy. According to the specified fundamental provisions of this theory, the essence of the process of green economy development is clarified (the &ldquo;black box&rdquo; is opened) as the increase in its contribution to sustainable development. As the indicator of achieving this development, an increase in the green economy&rsquo;s sustainability is offered. A new source of achieving the goal is proposed, consisting of a financial risk management of ecologically responsible entrepreneurship based on (private) green investments

Studying the Factors Influencing a Choice of Devices for Carrying Out Inhalations on the Basis of Statistical Processing of Results Of Questionnaire

Authors set the object, to study the factors influencing a choice of buyers of devices for carrying out inhalation on the basis of statistical processing of results of questionnaire of buyers, to analyze interrelation between the factors influencing a choice and purchase of the device and gender and age characteristics of potential buyers. The role of the doctor, worker of a drugstore, the Internet sites in the course of a choice, opinion of consumers of different age categories on the most preferable sources of information on devices for carrying out inhalation is revealed, preferences of buyers at a choice of a place of commission of purchase of devices for carrying out inhalation are defined. Feature of respondents of sources of information and making decision on purchase, female and male concerning use is shown