9 research outputs found
Normative and economic foundations of high-rise construction in the city of Samara
Every year the number of free land plots for construction of buildings is steadily decreasing in cities. In this regard, the participants in the investment and construction process are increasingly seeking to maximize the use of land. A logical way for this is to use high-rise construction. However, until recently, builders encountered serious obstacles in the form of lack of special norms and rules for the design of high-rise buildings. It led to the need for individual coordination of each high-rise facility, the development and approval of special technical conditions, the passage of numerous administrative approvals. Thus, investment activity regarding the construction of high-rise buildings in the Russian Federation is reduced. In 2016, there were regulatory changes that substantially alleviated these difficulties. In this article, the authors analyze the features of the town-planning normative-legal field of high-rise construction and its development, track the interrelations between the regulatory regulation of the construction of similar facilities, with the real need, the technical feasibility and economic feasibility of their construction in the urban district of Samara. Conclusions and suggestions are also based on the analysis of the norms of urban zoning, the residential real estate market and the value of land plots
Normative and economic foundations of high-rise construction in the city of Samara
Every year the number of free land plots for construction of buildings is steadily decreasing in cities. In this regard, the participants in the investment and construction process are increasingly seeking to maximize the use of land. A logical way for this is to use high-rise construction. However, until recently, builders encountered serious obstacles in the form of lack of special norms and rules for the design of high-rise buildings. It led to the need for individual coordination of each high-rise facility, the development and approval of special technical conditions, the passage of numerous administrative approvals. Thus, investment activity regarding the construction of high-rise buildings in the Russian Federation is reduced. In 2016, there were regulatory changes that substantially alleviated these difficulties. In this article, the authors analyze the features of the town-planning normative-legal field of high-rise construction and its development, track the interrelations between the regulatory regulation of the construction of similar facilities, with the real need, the technical feasibility and economic feasibility of their construction in the urban district of Samara. Conclusions and suggestions are also based on the analysis of the norms of urban zoning, the residential real estate market and the value of land plots
Normative and economic foundations of high-rise construction in the city of Samara
Every year the number of free land plots for construction of buildings is steadily decreasing in cities. In this regard, the participants in the investment and construction process are increasingly seeking to maximize the use of land. A logical way for this is to use high-rise construction. However, until recently, builders encountered serious obstacles in the form of lack of special norms and rules for the design of high-rise buildings. It led to the need for individual coordination of each high-rise facility, the development and approval of special technical conditions, the passage of numerous administrative approvals. Thus, investment activity regarding the construction of high-rise buildings in the Russian Federation is reduced. In 2016, there were regulatory changes that substantially alleviated these difficulties. In this article, the authors analyze the features of the town-planning normative-legal field of high-rise construction and its development, track the interrelations between the regulatory regulation of the construction of similar facilities, with the real need, the technical feasibility and economic feasibility of their construction in the urban district of Samara. Conclusions and suggestions are also based on the analysis of the norms of urban zoning, the residential real estate market and the value of land plots
Novel Soloxolone Amides as Potent Anti-Glioblastoma Candidates: Design, Synthesis, In Silico Analysis and Biological Activities In Vitro and In Vivo
The modification of natural or semisynthetic triterpenoids with amines can be explored as a promising strategy for improving their pharmacological properties. Here, we report the design and synthesis of 11 novel amide derivatives of soloxolone methyl (SM), a cyano enone-bearing derivative of 18βH-glycyrrhetinic acid. Analysis of their bioactivities in vitro and in silico revealed their high toxicity against a panel of tumor cells (average IC50(24h) = 3.7 µM) and showed that the formation of amide moieties at the C-30 position of soloxolone did not enhance the cytotoxicity of derivatives toward tumor cells compared to SM, though it can impart an ability to pass across the blood–brain barrier. Further HPLC–MS/MS and mechanistic studies verified significant brain accumulation of hit compound 12 (soloxolone tryptamide) in a murine model and showed its high anti-glioblastoma potential. It was found that 12 induced ROS-dependent and autophagy-independent death of U87 and U118 glioblastoma cells via mitochondrial apoptosis and effectively blocked their clonogenicity, motility and capacity to form vessel-like structures. Further in vivo study demonstrated that intraperitoneal injection of 12 at a dosage of 20 mg/kg effectively inhibited the growth of U87 glioblastoma in a mouse xenograft model, reducing the proliferative potential of the tumor and leading to a depletion of collagen content and normalization of blood vessels in tumor tissue. The obtained results clearly demonstrate that 12 can be considered as a promising leading compound for drug development in glioblastoma treatment
Discovery of New Ginsenol-Like Compounds with High Antiviral Activity
A number of framework amides with a ginsenol backbone have been synthesized using the Ritter reaction. We named the acetamide as Ginsamide. A method was developed for the synthesis of the corresponding amine and thioacetamide. The new compounds revealed a high activity against H1N1 influenza, which was confirmed using an animal model. Biological experiments were performed to determine the mechanism of action of the new agents, a ginsamide-resistant strain of influenza virus was obtained, and the pathogenicity of the resistant strain and the control strain was studied. It was shown that the emergence of resistance to Ginsamide was accompanied by a reduction in the pathogenicity of the influenza virus
Discovery of New Ginsenol-Like Compounds with High Antiviral Activity
A number of framework amides with a ginsenol backbone have been synthesized using the Ritter reaction. We named the acetamide as Ginsamide. A method was developed for the synthesis of the corresponding amine and thioacetamide. The new compounds revealed a high activity against H1N1 influenza, which was confirmed using an animal model. Biological experiments were performed to determine the mechanism of action of the new agents, a ginsamide-resistant strain of influenza virus was obtained, and the pathogenicity of the resistant strain and the control strain was studied. It was shown that the emergence of resistance to Ginsamide was accompanied by a reduction in the pathogenicity of the influenza virus
Risk factors for fractures in patients with rheumatoid arthritis (preliminary results of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment»)
In patients with rheumatoid arthritis (RA), bone fractures occur 1.5-2 times more frequently than in the population. They often lead to reduced quality of life, to disability and death in the patients. It should be noted that risk factors (RFs) for fractures have not been studied on a sufficient sample in Russia; there are no recommendations on the prevention of fractures in this category of patients. Objective: to compare groups of RA patients with and without a history of fractures to further identify possible RFs for fractures. Subjects and methods. The trial included 254 patients aged 18 to 85 years, diagnosed with RA, from the database of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment», who had been followed up in 2010 to 2011. The patients were divided into two groups: 1) 101 (39.8%) patients with a history of low-trauma fractures and 2) 153 (60.2%) patients without a history of fractures. In Group 1, the patients were older than in Group 2 (mean age 59.8 and 56.1 years, respectively). Menopause was recorded in 88.1 and 77.8% of cases, respectively. The groups differed in the duration of RA an average of 15.5 and 11.5 years, respectively Results. The fractures in the history were associated with the use of glucocorticoids (GC), their higher cumulative dose and use duration. In Group 1 patients, the bone mineral density (BMD) was lower in all study skeleton portions and more frequently corresponded to osteoporosis. RA complications, such as amyloidosis and osteonecrosis, were more common in the patients with a history of fractures. Conclusion. In RA patients, the most likely RFs of fractures are age, the long-term intake of large-dose GC, low BMD, the severe course of RA, and the presence of its complications