41 research outputs found
Wind power resources potential for energy supply of isolated regions of Kamchatska
The paper presents the potential of the wind resources for energy supply in the Kamchatka Territory. This region is isolated from the United Energy System of Russia and has a large number of remote settlements. The possibility of using wind energy resources in the region to replace diesel power plants and to reduce CO2 emissions are assessed. Estimates of the average power output values of the wind turbine Enercon E-53 810 kW, on the basis of hourly data on wind resources over a 10-year period (2011-2020) and the share of consumer load coverage for 11 settlements in the region are calculated. Territorial distribution of the specific power generation potential for this wind turbine model is presented with the use of GIS technologies. Daily and seasonal variations in productivity and share of load coverage, as well as the territorial distribution of these characteristics of the energy supply potential by the use of wind resources, are determined
An African-Specific Variant of TP53 Reveals PADI4 as a Regulator of p53-Mediated Tumor Suppression
TP53 is the most frequently mutated gene in cancer, yet key target genes for p53-mediated tumor suppression remain unidentified. Here, we characterize a rare, African-specific germline variant of TP53 in the DNA-binding domain Tyr107His (Y107H). Nuclear magnetic resonance and crystal structures reveal that Y107H is structurally similar to wild-type p53. Consistent with this, we find that Y107H can suppress tumor colony formation and is impaired for the transactivation of only a small subset of p53 target genes; this includes the epigenetic modifier PADI4, which deiminates arginine to the nonnatural amino acid citrulline. Surprisingly, we show that Y107H mice develop spontaneous cancers and metastases and that Y107H shows impaired tumor suppression in two other models. We show that PADI4 is itself tumor suppressive and that it requires an intact immune system for tumor suppression. We identify a p53–PADI4 gene signature that is predictive of survival and the efficacy of immune-checkpoint inhibitors.
Significance:
We analyze the African-centric Y107H hypomorphic variant and show that it confers increased cancer risk; we use Y107H in order to identify PADI4 as a key tumor-suppressive p53 target gene that contributes to an immune modulation signature and that is predictive of cancer survival and the success of immunotherapy
Lipid accumulation and dendritic cell dysfunction in cancer
Professional antigen presenting cells, dendritic cells (DC) are responsible for initiation and maintenance of immune responses. Here, we report that a substantial proportion of DCs in tumor-bearing mice and cancer patients have increased levels of triglycerides. Lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to up-regulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of MHC and co-stimulatory molecules. However, lipid-laden DCs had reduced capacity to process antigens. Pharmacological normalization of lipid levels in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of a cancer vaccine. These findings support the regulation of immune responses in cancer by manipulation of lipid levels in DCs
Light industry companies of Ukraine: overview and analysis of baseline conditions
The paper reviews and analyzes the baseline conditions of light industry companies: the nature and structure of the branch is covered, the economic downturn which is legacy of the economic complex of the Ukrainian Soviet Socialist Republic described, statistical key figures and other dynamic indicators of the current development of the industry reviewed, a complex of outstanding problems impeding its efficient development outlined. There are main constraints on the way to attraction of foreign and domestic investment in the branch identified.
It is indicated that since as long ago as the Soviet times the industry was structured in such a way that companies of the process chain "raw materials - products - sales" were located far from each other, in different republics of the USSR. After Ukraine had gained independence, there were companies of the final production cycle left in its territory. Since then the lack of raw materials and semi-finished products has become a chronic problem of the branch. The operational efficiency of companies gets also reduced due to the lack of manufacturers of specialized equipment and respective spare parts in Ukraine. As a result, today's production capacities of the branch are worn out by 70-80%.
Such a specific aspect of the investment environment of domestic light industry companies as the lack of their own capital gave rise to operation of most enterprises on a give-and-take basisс. On the one part, that allowed to retain the current key assets and personnel of the branch. On the other part, there are no more prospects for continued operation on the same basis as the global trend is to transfer a part of soft goods production to countries with cheaper labor. There is a tendency is observed to an increased production volume of soft goods worldwide owing to implementation of achievements of scientific and technological progress while the employment volume in this industry in highly developed countries is reduced; the share of states of the Asian region in the global production and export volume of soft goods is growing.
Extensive research and educational capabilities for training of skilled labor can not be considered today a competitive advantage of the branch because training programs for domestic specialists make no provisions for transfer of present knowledge regarding methods of procurement and merchandizing, approaches to research and details of designing competitive marketing strategies etc.
At present the state does not promote the development of the branch in any way, neither does it consider the branch a development priority. The author identifies the following major constraints for attraction of investment in the branch: the current taxation system and the state customs and tariff policy, though worn-out material and technical facilities also reduce its attractiveness to foreign and domestic investors, most light industry companies lacking raw materials and their own capital as well as great dependence on global economic processes and financial markets
Підприємства легкої промисловості України: огляд і аналіз сучасного стану
The paper reviews and analyzes the baseline conditions of light industry companies: the nature and structure of the branch is covered, the economic downturn which is legacy of the economic complex of the Ukrainian Soviet Socialist Republic described, statistical key figures and other dynamic indicators of the current development of the industry reviewed, a complex of outstanding problems impeding its efficient development outlined. There are main constraints on the way to attraction of foreign and domestic investment in the branch identified.It is indicated that since as long ago as the Soviet times the industry was structured in such a way that companies of the process chain "raw materials - products - sales" were located far from each other, in different republics of the USSR. After Ukraine had gained independence, there were companies of the final production cycle left in its territory. Since then the lack of raw materials and semi-finished products has become a chronic problem of the branch. The operational efficiency of companies gets also reduced due to the lack of manufacturers of specialized equipment and respective spare parts in Ukraine. As a result, today's production capacities of the branch are worn out by 70-80%.Such a specific aspect of the investment environment of domestic light industry companies as the lack of their own capital gave rise to operation of most enterprises on a give-and-take basisс. On the one part, that allowed to retain the current key assets and personnel of the branch. On the other part, there are no more prospects for continued operation on the same basis as the global trend is to transfer a part of soft goods production to countries with cheaper labor. There is a tendency is observed to an increased production volume of soft goods worldwide owing to implementation of achievements of scientific and technological progress while the employment volume in this industry in highly developed countries is reduced; the share of states of the Asian region in the global production and export volume of soft goods is growing.Extensive research and educational capabilities for training of skilled labor can not be considered today a competitive advantage of the branch because training programs for domestic specialists make no provisions for transfer of present knowledge regarding methods of procurement and merchandizing, approaches to research and details of designing competitive marketing strategies etc.At present the state does not promote the development of the branch in any way, neither does it consider the branch a development priority. The author identifies the following major constraints for attraction of investment in the branch: the current taxation system and the state customs and tariff policy, though worn-out material and technical facilities also reduce its attractiveness to foreign and domestic investors, most light industry companies lacking raw materials and their own capital as well as great dependence on global economic processes and financial markets.В статье выполнен обзор и анализ современного состояния предприятий легкой промышленности Украины: определена сущность и структура отрасли, охарактеризовано экономическое наследство, которое она получила от хозяйственного комплекса УССР, проанализированы статистические показатели и другие динамические параметры современного развития отрасли, обозначен комплекс нерешенных проблем, препятствующих ее эффективному развитию. Определены основные препятствия на пути привлечения внешних и внутренних инвестиций в отрасль.У статті виконано огляд й аналіз сучасного стану підприємств легкої промисловості України: визначено сутність та структуру галузі, охарактеризовано економічний спадок, який вона отримала від господарського комплексу УРСР, проаналізовано статистичні показники та інші динамічні параметри сучасного розвитку галузі, окреслено комплекс невирішених проблем, що перешкоджають її ефективному розвитку. Визначено основні першкоди на шляху залучення зовнішніх та внутрішніх інвестицій у галузь
Solar-optimum design principles for office buildings
New concept of passive cooling of buildings is presented in this article.. In order to achieve that, it is planned to define three basic elements of the building concept – shape of building, sun movement and sustainability of the building. These parameters will serve as corner stone’s also further in development of building concept. In addition not only passive cooling elements are considered during concept elaboration process but also passive building basic principles which include building location, window placement on facades, room alignment, building constructions and high comfort level. Dynamic simulation software was used in order to perform calculations, and to make conclusions on most optimal window/wall proportions and passive cooling potential. Paper presents study on multi apartment buildings renovation specifics in Latvia and its influence on total energy consumption. The necessary reconstruction goals are defined to reach European Regional Development Fund project “A New Concept for Sustainable and Nearly Zero-Energy Buildings” Nr. 1.1.1.1/16/A/007 main targets
Solar-optimum design principles for office buildings
New concept of passive cooling of buildings is presented in this article.. In order to achieve that, it is planned to define three basic elements of the building concept – shape of building, sun movement and sustainability of the building. These parameters will serve as corner stone’s also further in development of building concept. In addition not only passive cooling elements are considered during concept elaboration process but also passive building basic principles which include building location, window placement on facades, room alignment, building constructions and high comfort level. Dynamic simulation software was used in order to perform calculations, and to make conclusions on most optimal window/wall proportions and passive cooling potential. Paper presents study on multi apartment buildings renovation specifics in Latvia and its influence on total energy consumption. The necessary reconstruction goals are defined to reach European Regional Development Fund project “A New Concept for Sustainable and Nearly Zero-Energy Buildings” Nr. 1.1.1.1/16/A/007 main targets
Both ATM and DNA-PK Are the Main Regulators of HIV-1 Post-Integrational DNA Repair
The integration of a DNA copy of an HIV-1 RNA genome into the host genome, carried out by the viral enzyme integrase, results in the formation of single-stranded gaps in cellular DNA that must be repaired. Here, we have analyzed the involvement of the PI3K kinases, ATM, ATR, and DNA-PKcs, which are important players in the DNA damage response (DDR) in HIV-1 post-integrational DNA repair (PIR). The participation of the DNA-PK complex in HIV-1 PIR has been previously shown, and the formation of a complex between the viral integrase and the DNA-PK subunit, Ku70, has been found to be crucial for efficient PIR. Now, we have shown that the inhibition of both DNA-PKcs and ATM, but not ATR, significantly reduces PIR efficiency. The activation of both kinases is a sequential process, where one kinase, being activated, activates the other, and it occurs simultaneously with the integration of viral DNA. This fact suggests that the activation of both kinases triggers PIR. Most interestingly, the activation of not only DNA-PKcs, but also ATM depends on the complex formation between integrase and Ku70. The elucidation of the interactions between viruses and DDR is important both for understanding the modulation of host cell functions by these pathogens and for developing new approaches to combat viral infections