Економічне і правове регулювання міжнародного трансферу технологій

The article is devoted to the study of legal regulation of the most important branch of international economic and scientific and technical cooperation - international technology transfer. The article deals with specific legal forms and conditions for the transfer of technology, analyzes contractual relations of organizations of European countries among themselves, with firms and organizations of capitalist and developing countries. International technology transfer affects not only the interests of parties to treaties, but also important state interests in the field of economics. It has a significant impact on the level and pace of scientific, technical and socio-economic development of the countries of the world, largely defining the foreign economic relations between them. These factors, which are based on the intern ational transfer of technology, need to pay special attention to the fundamental transformation of the country's economy on the basis of the latest advances in world science and technology. The legal and economic regulation of the international transfer of technologies and objects of intellectual property is considered. Detailed analysis of the experience of different countries in the field of attraction of foreign technologies, as well as the problem of support of national technologically oriented industries at the present stage. Recommendations on the international transfer of innovative technologies in the conditions of the global financial crisis have been developed. In the article, the authors consider international transfer (transfer) of technologies in three aspects: as a mutually beneficial exchange of technologies, the international division of labor in the creation and practical study of intellectual property, as a decisive factor in the country's economic development, as a means of economic expansion, the technological dependence of one country on the other.Стаття присвячена вивченню правового регулювання найважливішої галузі міжнародної економічної та науково-технічної співпраці-міжнародного трансферу технологій. У статті розглядаються конкретні правові форми та умови передачі техніки, аналізуються договірні відносини організацій європейських країн між собою, з фірмами та організаціями капіталістичних і країн, що розвиваються. Міжнародна передача технології зачіпає не тільки інтереси сторін договорів, але і важливі державні інтереси в сфері економіки. Вона робить істотний вплив на рівень і темпи науково-технічного та соціально-економічного розвитку країн світу, багато в чому визначаючи зовнішньоекономічні зв'язки між ними. На ці фактори, в основі яких лежить міжнародна передача технології, необхідно звертати особливу увагу, домагаючись докорінної перебудови економіки країни на базі новітніх досягнень світової науки і техніки. Розглянуто правове та економічне регулювання міжнародного перенесення технологій та об'єктів інтелектуальної власності. Докладно аналізується досвід різних держав у сфері залучення зарубіжних технологій, а також проблема підтримки національних технологічно орієнтованих виробництв на сучасному етапі. Розроблено рекомендації щодо міжнародної передачі інноваційних технологій в умовах світової фінансової кризи. У статті автори розглядають міжнародну передачу (перенесення) технологій у три аспекти: як взаємовигідний обмін технологіями, міжнародний поділ праці у створенні та практичному дослідженні інтелектуальних цінностей, як вирішального фактора економічного розвитку країни, як засіб економічної експансії, технологічна залежність однієї країни від іншої

Визначення маркетингових характеристик місткості ринку електротехнічних засобів автоматизації

The problems of determining the marketing characteristics of the market products capacity do not have independent technological purposes. As the object of study selected electrical automation. It is proved that the most important characteristic of the market capacity of goods are the demand for them, which consists of several components. To determine the requirements for electrical automation and maintenance of technological equipment under operation, you need to know the industry Park. The technique of determining industry Park, products which do not have independent technological purpose and which are not maintained inventory records, for example, electrical automation of the basic steps of this methodology. The proposals of the authors based on the determination coefficients the applicability of certain types of electrical automation equipment per unit of basic technological equipment of machine-building industries.Розглянуто питання визначення маркетингових характеристик місткості ринку виробів, що не мають самостійного технологічного призначення. В якості об'єкта дослідження вибрано електротехнічні засоби автоматизації. Доведено, що найважливішою характеристикою ємності ринку виробів є потреба у них, яка складається з декількох складових. Для визначення потреби в електротехнічних засобах автоматизації на ремонт і експлуатацію технологічного обладнання, що знаходяться в експлуатації, необхідно знати його галузевої парк. Розроблена методика визначення галузевого парку виробів, що не мають самостійного технологічного призначення і за якими не ведеться інвентаризаційний облік. На прикладі електротехнічних засобів автоматизації розглянуто основні етапи даної методики. Пропозиції авторів побудовані на визначенні коефіцієнтів застосування окремих типів електротехнічних засобів автоматизації на одиницю основного технологічного обладнання в машинобудівних галузях

Фінансово–технологічний важіль в системі економічної оцінки інноваційних технологій

The article examines the conceptual, theoretical and methodological guidelines for economic evaluation of innovative technologies through financial and technological leverage. The concept of financial-technological linkage was developed with the aim of establishing a relationship between technological efficiency and effectiveness of operational and financial activities of the enterprise. The authors have developed measurement technology and the use of technological linkage as a tool for assessing commercial potential of new technologies, which allows establishing a link between technological efficiency and effectiveness of operational and financial activities of the engineering enterprise. It is proved that the concept of technological linkage explains how the creation of new technologies can raise the value of the business, exceeding significantly the value of the underlying technological innovations taken in isolation. In addition, there is a real possibility of effective monitoring of the economic impact (need, usage, efficiency) from the use of development, the exclusive rights which are at the disposal of the enterprise. Determined that the level of commercial potential of intellectual technology is not limited only to the influence of technological leverage. The potential power can be represented as a dependence of the level of commercial potential of several very important factors that act in parallel. They proposed to include the following, the most important components of the level of commercial potential of innovative technology: the lever of the early stages of the life cycle of an innovative product; the lever of the developer technological innovations; financial leverage. The effect of financial and technological leverage depends on innovation activity and innovation capacity of the enterprise–the developer of a technological product. Its value is usually higher for industries with higher technological level of production, which is very typical for innovative enterprises.В статті розглянуто концептуальні теоретико-методичні положення економічної оцінки інноваційних технологій на засадах фінансово-технологічного важеля. Обґрунтовано, що концепція технологічного важеля пояснює, яким чином створення нової технології може підняти вартість бізнесу, перевищуючи в рази цінність базової технологічної інновації, взятої ізольовано. Крім того, з'являється реальна можливість ефективного моніторингу економічної віддачі (потреби, використання, ефективності) від використання технологічної розробки, виключні права на яку знаходяться в розпорядженні даного підприємства

Engineering T Cells To Suppress Acute Gvhd and Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation

Acute graft-versus-host disease (aGVHD) limits the therapeutic benefit of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and requires immunosuppressive prophylaxis that compromises antitumor and antipathogen immunity. OX40 is a costimulatory receptor upregulated on circulating T cells in aGVHD and plays a central role in driving the expansion of alloreactive T cells. Here, we show that OX40 is also upregulated on T cells infiltrating GVHD target organs in a rhesus macaque model, supporting the hypothesis that targeted ablation of OX40+ T cells will mitigate GVHD pathogenesis. We thus created an OX40-specific cytotoxic receptor that, when expressed on human T cells, enables selective elimination of OX40+ T cells. Because OX40 is primarily upregulated on CD4+ T cells upon activation, engineered OX40-specific T cells mediated potent cytotoxicity against activated CD4+ T cells and suppressed alloreactive T-cell expansion in a mixed lymphocyte reaction model. OX40 targeting did not inhibit antiviral activity of memory T cells specific to Epstein-Barr virus, cytomegalovirus, and adenoviral antigens. Systemic administration of OX40-targeting T cells fully protected mice from fatal xenogeneic GVHD mediated by human peripheral blood mononuclear cells. Furthermore, combining OX40 targeting with a leukemia-specific chimeric antigen receptor in a single T cell product provides simultaneous protection against leukemia and aGVHD in a mouse xenograft model of residual disease posttransplant. These results underscore the central role of OX40+ T cells in mediating aGVHD pathogenesis and support the feasibility of a bifunctional engineered T-cell product derived from the stem cell donor to suppress both disease relapse and aGVHD following allo-HSCT

Pan-cancer experimental characteristic of human transcriptional patterns connected with telomerase reverse transcriptase (TERT) gene expression status

The TERT gene encodes the reverse transcriptase subunit of telomerase and is normally transcriptionally suppressed in differentiated human cells but reactivated in cancers where its expression is frequently associated with poor survival prognosis. Here we experimentally assessed the RNA sequencing expression patterns associated with TERT transcription in 1039 human cancer samples of 27 tumor types. We observed a bimodal distribution of TERT expression where ∼27% of cancer samples did not express TERT and the rest showed a bell-shaped distribution. Expression of TERT strongly correlated with 1443 human genes including 103 encoding transcriptional factor proteins. Comparison of TERT- positive and negative cancers showed the differential activation of 496 genes and 1975 molecular pathways. Therein, 32/38 (84%) of DNA repair pathways were hyperactivated in TERT+ cancers which was also connected with accelerated replication, transcription, translation, and cell cycle progression. In contrast, the level of 40 positive cell cycle regulator proteins and a set of epithelial-to-mesenchymal transition pathways was specific for the TERT- group suggesting different proliferation strategies for both groups of cancer. Our pilot study showed that the TERT+ group had ∼13% of cancers with C228T or C250T mutated TERT promoter. However, the presence of promoter mutations was not associated with greater TERT expression compared with other TERT+ cancers, suggesting parallel mechanisms of its transcriptional activation in cancers. In addition, we detected a decreased expression of L1 retrotransposons in the TERT+ group, and further decreased L1 expression in promoter mutated TERT+ cancers. TERT expression was correlated with 17 genes encoding molecular targets of cancer therapeutics and may relate to differential survival patterns of TERT- positive and negative cancers

Regularities of Microstructure Evolution in a Cu-Cr-Zr Alloy during Severe Plastic Deformation

The effect of severe plastic deformation by the conforming process of equal channel angular extrusion (ECAE-Conform) followed by cold rolling on the microstructures developed in a Cu-0.1Cr-0.1Zr alloy was investigated. Following the ECAE-Conform of 1 to 8 passes (corresponding strains were 0.8 to 6.4) cold rolling to a total strain of 4 was accompanied by substantial grain refinement and strengthening. An average grain size tended to approach 160 nm with an increase in the rolling reduction. An increase in the ECAE-Conform strain promoted the grain refinement during subsequent cold rolling. The fraction of the ultrafine grains with a size of 160 nm after cold rolling to a strain of 4 increased from 0.12 to 0.52 as the number of ECAE-Conform passes increased from 1 to 8. Correspondingly, the yield strength increased above 550 MPa. The strengthening could be expressed by a Hall–Petch type relationship with a grain size strengthening factor of 0.11 MPa m0.5

Визначення упущеної вигоди правовласників від контрафактної продукції

The processes of exclusive rights violation of the manufacturers of original (licensed) products on the technological market are investigated. It is proposed methodical approaches concerning economic valuation of the amount of lost profits of the rights holders (licensees) in violation of intellectual property rights, the amount of which is firstly connected by the authors with the degree of use the copyright of their manufacturing facilities. It is developed a block-structured approach to the definition of missed potential opportunities of right holders and it is proposed economic and mathematical models for their determination.Розглянуто процеси порушення виключних прав виробників оригінальної (ліцензійної) продукції на технологічному ринку. Запропоновано методичні підходи щодо економічної оцінки розміру упущеної вигоди правовласників (ліцензіатів) при порушенні прав інтелектуальної власності, розмір якої авторами вперше пов’язане з ступенем використання правовласником своїх виробничих потужностей. Розроблено блочно-структурний підхід до визначення упущених потенційних можливостей правовласників та запропоновано економіко-математичні моделі їх визначення

Distinct Traits of Structural and Regulatory Evolutional Conservation of Human Genes with Specific Focus on Major Cancer Molecular Pathways

The evolution of protein-coding genes has both structural and regulatory components. The first can be assessed by measuring the ratio of non-synonymous to synonymous nucleotide substitutions. The second component can be measured as the normalized proportion of transposable elements that are used as regulatory elements. For the first time, we characterized in parallel the regulatory and structural evolutionary profiles for 10,890 human genes and 2972 molecular pathways. We observed a ~0.1 correlation between the structural and regulatory metrics at the gene level, which appeared much higher (~0.4) at the pathway level. We deposited the data in the publicly available database RetroSpect. We also analyzed the evolutionary dynamics of six cancer pathways of two major axes: Notch/WNT/Hedgehog and AKT/mTOR/EGFR. The Hedgehog pathway had both components slower, whereas the Akt pathway had clearly accelerated structural evolution. In particular, the major hub nodes Akt and beta-catenin showed both components strongly decreased, whereas two major regulators of Akt TCL1 and CTMP had outstandingly high evolutionary rates. We also noticed structural conservation of serine/threonine kinases and the genes related to guanosine metabolism in cancer signaling: GPCRs, G proteins, and small regulatory GTPases (Src, Rac, Ras); however, this was compensated by the accelerated regulatory evolution

Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers.

Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived healthy normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min - 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact differential expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice

Large-scale assessment of pros and cons of autopsy-derived or tumor-matched tissues as the norms for gene expression analysis in cancers

Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived “healthy” normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min – 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact “differential” expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice