Development Of System Research Articles

Advances and Challenges in Automated Drowning Detection and Prevention Systems

Drowning is among the most common reasons for children’s death aged one to fourteen around the globe, ranking as the third leading cause of unintentional injury death. With rising populations and the growing popularity of swimming pools in hotels and villas, the incidence of drowning has accelerated. Accordingly, the development of systems for detecting and preventing drowning has become increasingly critical to provide safe swimming settings. In this paper, we propose a comprehensive review of recent existing advancements in automated drowning detection and prevention systems. The existing approaches can be broadly categorized according to their objectives into two main groups: detection-based systems, which alert lifeguards or parents to perform manual rescues, and detection and rescue-based systems, which integrate detection with automatic rescue mechanisms. Automatic drowning detection approaches could be further categorized into computer vision-based approaches, where camera-captured images are analyzed by machine learning algorithms to detect instances of drowning, and sensing-based approaches, where sensing instruments are attached to swimmers to monitor their physical parameters. We explore the advantages and limitations of each approach. Additionally, we highlight technical challenges and unresolved issues related to this domain, such as data imbalance, accuracy, privacy concerns, and integration with rescue systems. We also identify future research opportunities, emphasizing the need for more advanced AI models, uniform datasets, and better integration of detection with autonomous rescue mechanisms. This study aims to provide a critical resource for researchers and practitioners, facilitating the development of more effective systems to enhance water safety and minimize drowning incidents.

Constitutionalization in the context of modern constitutionalism: theoretical and methodological analysis

The article examines constitutionalization as an important category of constitutional law. The author explores various approaches to understanding this concept, its historical development, and modern interpretations. The views of domestic and foreign scholars on the essence, characteristics, and forms of manifestation of constitutionalization are analyzed. Special attention is paid to the relationship between the concepts of “constitutional order”, “constitutionalism”, and “constitutionalization”. The author emphasizes that constitutionalization is a dynamic process that reflects the practical aspect of constitutionalism and has a global character. The article examines various aspects of constitutionalization, including its impact on the legal system, the expansion of constitutional regulation, and the subordination of government activities to constitutional principles. The author analyzes the role of constitutionalization in ensuring the unity of the legal system and guaranteeing constitutional rights and freedoms. Special attention is paid to the process of constitutionalization in the context of developing a democratic state governed by the rule of law. Based on the analysis of scientific sources, the author formulates their own definition of constitutionalization as a multifaceted process that includes the formal establishment of rights in the constitution, subordination of government activities to constitutional principles, expansion of constitutional regulation of various spheres of public life, and the influence of constitutional norms on the development of the legal system. The conclusions emphasize the importance of further research on constitutionalization for improving constitutional and legal regulation and ensuring the effective operation of constitutional norms in modern society.

INTEGRATION OF DIGITAL TECHNOLOGIES INTO THE PERSONNEL DEVELOPMENT MANAGEMENT MECHANISM IN HEALTHCARE INSTITUTIONS

This article explores the integration of digital technologies into the personnel management mechanisms of healthcare institutions in Ukraine. In an era marked by rapid digital transformation, the healthcare sector is increasingly recognizing the importance of utilizing modern technological tools to enhance operational efficiency, improve patient care, and streamline administrative processes. The study begins by examining the current state of personnel management in Ukrainian healthcare institutions, identifying key challenges such as workforce shortages, inefficient communication channels, and inadequate training programs. The research further delves into the various digital solutions available, including human resource management systems (HRMS), telemedicine platforms, and data analytics tools. These technologies are evaluated for their potential to optimize recruitment processes, enhance employee performance tracking, and facilitate continuous professional development. The article also highlights case studies from healthcare institutions that have successfully implemented digital technologies, showcasing tangible improvements in staff engagement, patient outcomes, and overall institutional effectiveness. Additionally, the paper discusses the critical role of digital literacy among healthcare professionals, emphasizing the need for targeted training initiatives to ensure that staff can effectively utilize new technologies. It concludes by proposing a strategic framework for integrating digital tools into personnel management practices, advocating for a holistic approach that encompasses technological adoption, staff training, and organizational culture change. Ultimately, the article aims to provide valuable insights and practical recommendations for healthcare leaders seeking to navigate the complexities of digital integration in personnel management. It has been determined that further research can significantly contribute to the development of effective personnel management strategies in healthcare institutions, which will not only enhance the quality of medical services but also promote the sustainable development of the healthcare system in Ukraine.

PROBLEMS AND PROSPECTS OF THE DEVELOPMENT OF BANKING REGULATION AND SUPERVISION IN UKRAINE

Effective banking regulation and supervision are key factors for ensuring the stability of the national banking system of Ukraine. The purpose of this article is to analyze the peculiarities of banking regulation and supervision in Ukraine in order to identify problems and possible ways of development, including in the context of world experience. The article examines the theoretical aspects of the essence of the concepts of banking regulation and banking supervision. The main indicators of the banking system of Ukraine for 2020-2024 and the mechanism for identifying risks in the activities of banking institutions are also considered. The global trends in banking regulation at the current stage are its centralization, the concept of risk-oriented supervision, the introduction of new financial technologies, the development of the principles of proportional banking regulation. The main positive and negative methods of supervision in the banking sector are singled out. It has been proven that the conditions of a full-scale military conflict significantly undermined the development of the banking system of Ukraine. The destruction of infrastructure, loss of customer confidence, risks to the bank's loan portfolio and capitalization have become major problems. In addition, the decrease in liquidity and the growth of inflation risks create serious challenges for the banking system. The degree of suitability of world models in terms of the priority tasks of the state regarding the regulation of the banking sector is analyzed. Directions for improving banking supervision through improvement of banking activity licensing procedures are proposed; introduction of permanent monitoring of the activities of domestic commercial banks, in particular their financial condition; implementation of constant monitoring of compliance with banking regulations and current legislation; introduction of permanent inspections of banking activities; implementation by commercial banks of ongoing internal control and external audit control; developing and sending supervisory instructions for banking institutions regarding the implementation of Basel III standards.

Development of a Novel Microphysiological System for Peripheral Neurotoxicity Prediction Using Human iPSC-Derived Neurons with Morphological Deep Learning

A microphysiological system (MPS) is an in vitro culture technology that reproduces the physiological microenvironment and functionality of humans and is expected to be applied for drug screening. In this study, we developed an MPS for the structured culture of human iPSC-derived sensory neurons and then predicted drug-induced neurotoxicity by morphological deep learning. Using human iPSC-derived sensory neurons, after the administration of representative anti-cancer drugs, the toxic effects on soma and axons were evaluated by an AI model with neurite images. Significant toxicity was detected in positive drugs and could be classified by different effects on soma or axons, suggesting that the current method provides an effective evaluation of chemotherapy-induced peripheral neuropathy. The results of neurofilament light chain expression changes in the MPS device also agreed with clinical reports. Therefore, the present MPS combined with morphological deep learning is a useful platform for in vitro peripheral neurotoxicity assessment.

Instruction Teaching Support System and Teaching Competency in Applied Colleges, China

The research investigates the effectiveness of the Instruction Teaching Support System and Teaching Competency in Applied Colleges in China, surveying 303 teachers and 381 students using a quantitative research design. The results demonstrate that the school's initiatives in providing teaching support have successfully met teachers' needs for capacity enhancement and professional development, contributing positively to their daily teaching and career growth. Teachers generally expressed satisfaction with the school's teaching support system, particularly highlighting its positive impact on their teaching practices. The management system in place was seen as stable and well-organized, providing clear development paths and solid institutional backing for overall teaching quality improvement. Additionally, the school's performance incentives, including merit-based pay, title promotions, and welfare benefits, were widely appreciated, effectively motivating teachers and supporting the enhancement of teaching quality across the school. In terms of teaching skills training, teachers acknowledged the school's diversified initiatives aimed at improving their skills. This support has been crucial in helping teachers not only transmit knowledge but also adapt to the evolving demands of modern education, which requires a blend of diverse skills and innovative thinking. The training opportunities provided by the school were recognized as a significant means to equip teachers with the tools needed to face educational challenges. Professional development remains central to improving education quality. The school's comprehensive support system has helped teachers advance in their careers, boosting their sense of achievement and establishing a strong foundation for the overall enhancement of teaching standards at the institution. Students also responded positively to their teachers' competencies, with high ratings reflecting the professionalism and ethical conduct of the educators. Teacher ethics, including care for students, fairness in evaluations, and respect, were seen as key factors in creating a trusting and stimulating learning environment. Students believed that teachers with strong professional ethics could foster a more engaging and motivating educational experience. The students' favorable feedback on teachers' assessment abilities also highlights the latter's comprehensive skills in assigning and grading homework, conducting evaluations, and implementing teaching reforms. These competencies were linked to the robust support system that teachers received from the school, showing that the development of the teaching support system directly influences the enhancement of teachers' teaching competency. In conclusion, the findings suggest that a well-structured teaching support system is instrumental in promoting teachers' professional growth and, in turn, improving their teaching competency.

Coupling Rotary Motion to Helicene Inversion within a Molecular Motor

Towards complex coupled molecular motions, the remote handedness inversion of a helicene moiety was achieved by a rotary molecular motor. The use of a specifically engineered dynamic helicene stator in a novel overcrowded‐alkene second‐generation molecular motor based on a fluorinated dibenzofluorene fragment allows for an unprecedented control over helicity inversion. This is achieved by the mechanical coupling of the rotation of the rotor to the helicene inversion of the stator half via a remote chirality transmission process. Thus, the unidirectional rotary motion generated upon irradiation is used to invert the dynamic stereochemistry of a helicene, leading to a 6‐steps cycle with eight intermediates. In this cycle, both alternation between P and M configurations of the helicene stator and dynamic thermal interconversion (paddling motion) can be achieved. In‐depth computational and spectroscopic studies were performed to support the associated mechanism. The control over coupled motion and dynamic helicity offers prospects for the development of complex responsive systems.

MANAGEMENT OF THE FINANCIAL FLOWS OF LOGISTICS SYSTEMS

In the context of globalization and integration of the world economy, the main task of every business entity is to ensure financial stability and security of its operations. The logistics industry is no exception. In such a context, there is a necessity of fundamentally new approaches to the development of an effective system for managing financial flows of logistics systems. The insufficiency of the theoretical and practical study of the problems of managing financial flows of logistics systems, the difficult current economic conditions of management, outlined by the impact of the financial crisis and economic instability, the necessity to manage and control the level of financial stability of logistics enterprises in order to prevent bankruptcy, are the key reasons for the relevance of the study. In article considers issues of management of financial flows of logistics systems. The analysis of management processes in the system of financial activity of the logistics industry has been conducted. It is noted that the relevant aspects of managing the financial flows of logistics systems should include measures to improve the efficiency of using borrowed capital and investment resources. The study theoretically substantiates and solves a set of issues related to the development of an effective concept for managing financial flows of logistics systems under conditions of uncertainty. The analysis of the status and trends in the development of the logistics sector, as well as topical aspects of financial management of logistics enterprises, has allowed to develop a set of measures to improve the system of management of financial flows of logistics systems, which should be implemented on the principles of financial management. The concept of management of financial flows of logistics systems is proposed. A scheme for ensuring the financial security of logistics systems has been developed. The key principles of management of financial flows of logistics systems under conditions of uncertainty are determined. The study made it possible to state that the conceptual approach to managing the financial flows of logistics systems will help to prevent the crisis, increase the efficiency of activities and the successful development of the industry as a whole.

Development and Assessment of a Batch Type Ohmic Heating System for Milk Processing

This study aims to develop and assess the performance of a batch-type ohmic heating system for the thermal processing of cow and buffalo milk, particularly investigating whether the ohmic system affects the nutritional and microbial quality of the milk. An experimental setup was fabricated with a 7-liter capacity, utilizing an agitator as one electrode and the vessel surface as the other. The system was tested for heating milk from 32°C to target temperatures of 75°C and 92°C. Key processing parameters, including agitator speed and applied voltage, were optimized for both milk types. The physicochemical and microbial properties of the ohmically heated milk were evaluated, along with performance metrics such as heating rates, power consumption, and system efficiency. The developed ohmic heating system achieved heating rates of 4.29°C/min for cow milk and 2.85°C/min for buffalo milk. Cow milk demonstrated lower energy consumption, requiring less time and voltage compared to buffalo milk, with system performance coefficients of 58% for cow milk and 50% for buffalo milk. However, fouling on the agitator surface was identified as a challenge for industrial applications. Importantly, the ohmic heating process preserved the nutritional content while effectively reducing microbial load, confirming its potential for dairy processing. In conclusion, the batch-type ohmic heating system exhibited high efficiency and rapid heating capabilities for both cow and buffalo milk, indicating its viability for commercial use. Future research should focus on addressing fouling issues and further optimizing the system, enhancing the overall potential of ohmic heating technology in the dairy industry.

Coupling Rotary Motion to Helicene Inversion within a Molecular Motor

Towards complex coupled molecular motions, the remote handedness inversion of a helicene moiety was achieved by a rotary molecular motor. The use of a specifically engineered dynamic helicene stator in a novel overcrowded‐alkene second‐generation molecular motor based on a fluorinated dibenzofluorene fragment allows for an unprecedented control over helicity inversion. This is achieved by the mechanical coupling of the rotation of the rotor to the helicene inversion of the stator half via a remote chirality transmission process. Thus, the unidirectional rotary motion generated upon irradiation is used to invert the dynamic stereochemistry of a helicene, leading to a 6‐steps cycle with eight intermediates. In this cycle, both alternation between P and M configurations of the helicene stator and dynamic thermal interconversion (paddling motion) can be achieved. In‐depth computational and spectroscopic studies were performed to support the associated mechanism. The control over coupled motion and dynamic helicity offers prospects for the development of complex responsive systems.

Pathways to a sustainable electricity sector in Kenya: Challenges and transformational factors

Which factors may enable a secure, affordable, and sustainable development of the Kenyan energy system? The present study aims to understand how the country's energy system could be structured in 2050, to unravel the main challenges, and to identify critical leverage points for policy action. To this end, we designed energy scenarios for Kenya using cross-impact balance and succession analysis, drawing extensively from expert judgments. The results highlight the importance of improving the quality of the grid, further reforming the electricity market structure, encouraging more competition, and promoting decentralization as the main leverage points for ensuring a secure and sustainable energy future.

Expanding Applications and Future of Robotic Microsurgery

Robotic-assisted microsurgery has emerged as a transformative technology, offering enhanced precision for complex procedures across various fields, including lymphatic surgery, breast reconstruction, trauma, and neurosurgery. This paper reviews current advancements, applications, and potential future directions for robotic-assisted microsurgery. In lymphatic surgery, robotic systems such as Symani have improved precision in thoracic duct reconstruction and lymphatic vessel anastomoses, reducing morbidity despite longer surgery times. In breast reconstruction, robotic systems are being used to refine techniques like the miraDIEP approach, minimizing tissue damage and enhancing precision in individualized treatments. Trauma reconstruction, particularly for extremities, has also benefited from robotic assistance, enabling successful sutures in small vessels and nerves. Emerging applications in meningeal lymphatics show potential for treating neurodegenerative diseases through improved drainage. In neurosurgery, robots enhance precision in deep and narrow anatomic spaces, although advancements in specialized instruments are needed for full implementation. Future development of robotic microsurgery systems will focus on improved maneuverability, miniaturization, and integration of tools like augmented reality and haptic feedback. The goal is to combine robotic precision, data storage, and processing with human skills such as judgment and flexibility. Although robots are unlikely to replace surgeons, they are poised to play an increasingly significant role in enhancing surgical outcomes. As the technology evolves, further research and clinical trials are needed to refine robotic systems and validate their expanding applications in clinical practice.

Development of a Smart Lock System using QR Code Technology

A smart lock system refers to a modern security solution that enables users to remotely control access to their homes or businesses using a smart device such as smartphone, tablet, or computer. This paper presents the development of a smart lock system using Quick Response (QR) code technology to address the problem of insecurity, inconvenience, and inflexibility in access control. The proposed system eliminates the need for physical keys or complex authentication and verification methods. The system integrates an ESP8266 microcontroller, barcode scanner, 16x2 liquid-crystal display (LCD), solenoid lock, relay, and a 12V power supply. The system allows authorised users to generate unique QR codes representing their access credentials through a user-friendly interface. These QR codes are scanned by the system, which processes the codes, verifies access permissions via a central server and provides real-time feedback through the LCD. Upon successful verification, the system triggers a relay to control the solenoid lock, to grant or deny access. The implementation and testing of the smart lock system demonstrated successful operation. The performance indices include authentication speed, system reliability, accuracy and response time, which were evaluated and found to be satisfactory. The obtained results showed that the proposed system outperformed traditional methods such as keys, and fingerprint authentication, with an access speed of 2.00 seconds, which is significantly faster than the alternatives. Comparative analysis with existing access control techniques demonstrated the developed system's enhanced security features and user-friendly operation, making it applicable for residential, commercial, and industrial use. Additionally, the system's scalability and adaptability allow it to be customised for various environments, offering a versatile solution to diverse security challenges. This work contributes to the field of security technology by providing an efficient and scalable smart lock system with novel algorithms, which enhances the convenience, robustness of access control and seamless user experience.

ORGANIZATION OF METHODOLOGICAL PRINCIPLES OF THE STATE INNOVATION POLICY IN THE SPHERE OF INFORMATIZATION OF THE HEALTH PROTECTION SYSTEM OF UKRAINE

The article highlights the key issues related to the need to modernize the health care system, globalization and integration into international structures, health care reform. In Ukraine, the process of health care reform is underway, which involves increasing the efficiency of the medical services system, their availability and quality. Innovations can accelerate these processes, in particular through the introduction of digital technologies (e-health, telemedicine), automation of management of medical facilities, development of remote diagnosis and treatment. The state innovation policy will allow to more effectively prepare for similar challenges in the future through the development of new vaccines, diagnostic methods, monitoring systems and management of medical resources. Support from the state (for example, through preferential taxation) to the development of the private medical services sector will reduce the burden on the state budget. In addition, it contributes to the attraction of investments in this area. Therefore, the state innovation policy in the field of health care is a relevant tool for ensuring the sustainable development of the health care system of Ukraine, increasing its efficiency and competitiveness, which meets the modern challenges and needs of society. The authors analyze the key aspects of the state policy aimed at the informatization of medical institutions, in particular, the digitalization of medical services, the introduction of electronic medicine, the creation of unified information platforms and patient databases. The article examines the importance of developing a clear methodology for the implementation of innovative solutions, as well as the role of the state in creating favorable conditions for the informatization of the health care system. The authors also analyze the international experience and the possibilities of its adaptation for Ukrainian realities, emphasizing the need to establish effective cooperation between state bodies, medical institutions and technological companies. The article concludes about the importance of an integrated approach to the informatization of the health care sector in order to improve the quality of medical services and increase the efficiency of medical resource management.

THE ROLE AND SIGNIFICANCE OF INTERNATIONAL TRANSFER OF TECHNOLOGY IN THE CONDITIONS OF DEVELOPING THE NATIONAL ECONOMY OF THE COUNTRY

The purpose of the article is to study the theoretical and practical aspects of the development of international technology transfer. It has been established that today the latest technologies and innovations affect all spheres of the national economy. Participation in the international transfer of technologies becomes a necessary and imperative condition for the existence of any production, not only at the state level, but also at the global level. That is why state support for innovative activities, namely the promotion of research and development, affects the socio-economic development of modern society. The functioning and development of the world economic system takes place under the influence of the processes of integration and globalization, which leads to the acceleration of the movement of capital, financial and labor resources, goods and the growth of the intensity of information exchange. Due to the accumulation of scientific and technical potential in a number of economically developed countries, it is knowledge, intelligence and innovation that become the main driving force behind the success of individual companies in these countries in the global economy. Today, modern companies enter into a competitive struggle not so much for the level of development of the production structure and its volumes, as for the level of available innovations on the global technology market. Today, domestic science is on the brink of disaster, this state is explained by the economic crisis that occurred against the background of the military aggression of our northeastern "neighbor". In Ukraine until 2022, there were negative processes associated with the development of scientific and technological developments, as evidenced by numerous studies of the dynamics of the share of R&D expenditures in GDP, it is obvious that in today's conditions this is an unacceptable trend and the state should make maximum efforts for practical and rapid accumulation of such a sector of the national economy as science. It has been proven that Ukraine should focus on the specifics of the development of international legal regulation and guarantees in the field of technology transfer, from the point of view of international obligations. Since even those norms of international regulations implemented in domestic legislation do not provide full guarantees for the formation and development of a transparent and fair international technology transfer.

Isotopic heterogeneity in U.S. Urban water supply systems reflects climatic, environmental, and sociodemographic factors: Implications for forensic identification

The forensic application of stable oxygen isotope data from human tissues depends on naturally occurring isotopic variation in drinking water across geographic areas. One factor which complicates interpretation of forensic data is local variability: if a wide range of drinking water values is in a small geographic region it may be difficult to identify or rule out that region as a location of origin. We examine data from community collection programs documenting tap water isotope variation within 30 cities\developed areas throughout the United States. Isotopic variation within individual developed areas ranged widely, from essentially nil to greater than 9‰ (δ18O interdecile range). Many (14/30) of the study areas exhibited multi-modal isotope distributions, even in cases where the isotopic range was very small (e.g., <2.0‰), suggesting that the use of multiple, isotopically different sources was common. Most variation was attributed to differences in the source-region altitude or degree of evaporation for different water sources, and we observe limited variation in areas where contrasts in these variables are small. Variation tended to be largest in cities across the western USA. We explored correlations between the magnitude of local isotopic variation and climatic, environmental, and socioeconomic variables. We found that higher levels of variation occurred at sites where local water resources were likely to be more isotopically heterogeneous and in lower supply, consistent with the development of supply systems in these areas that access diverse and isotopically heterogeneous water resources. We also found that variation was positively correlated with larger developed areas, suggesting that pressures related to city growth may affect the degree to which infrastructure tapping diverse water resources is developed. Collectively, our results suggest that the influence of local tap water isotope heterogeneity on the precision of forensic geolocation is systematic and somewhat predictable, information to be factored into future applications.

Sustainable intensification of livestock systems using forage legumes in the Anthropocene

AbstractSustainable intensification of livestock systems implies greater efficiency in resource utilization resulting in greater output of products and other ecosystem services per unit of resource input. Integrating forage legumes into livestock systems is a viable way to reduce the input of industrial N fertilizer, reducing the use of fossil fuels and helping to mitigate global warming, a major problem during the Anthropocene. Some forage legumes have greater concentrations of secondary compounds, such as condensed tannins, that might reduce the emission of greenhouse gases (GHG) from ruminant eructation and excreta. Furthermore, forage legumes might enhance cattle performance because of greater nutritive value, resulting in greater production per unit of GHG released. Shortening the production cycle and improving cattle reproductive efficiency could have a major impact on reducing the overall carbon footprint of the system. Grazing systems with more diversified plant species are typically more resistant and resilient, adapting to current climate changes during the Anthropocene. Novel technologies might accelerate the development of future grazing systems using forage legumes as a key component. Breeding efforts for the next‐generation legumes must focus on adaptation and potential use for mitigation of negative environmental impacts. There are examples of successful integration of forage legumes into livestock systems in different regions of the world, with a major reduction in off‐farm inputs and maintaining the system productive. These successful examples could be used to increase adoption and improve the efficiency of current livestock systems.

Ontogenetic and evolutionary trends on cephalopod digestive systems

AbstractMeropelagic octopuses hatch as planktonic paralarvae, being the subject of progressive morphological and behavioural changes ending with settlement on the seafloor as juveniles. The comparative morphological study of digestive systems can help to understand the adaptation to particular niches during this challenging plankton-benthos transition. Here, the morphometric development of the digestive system of the common octopus (Octopus vulgaris) is described through 3D microscopy techniques over the first two months of life. This morphological development is compared with those of adults and the holobenthic cuttlefish Sepia officinalis, as well as with the holopelagic squids Loligo vulgaris and Illex coindetii. Based on present and published results, we suggest four stages for the early development of O. vulgaris: (1) post embryonic, (2) early paralarval, (3) advanced paralarval and (4) early juvenile. The digestive system development was variable over time, with faster growth during the first days of planktonic life and after settlement. All the paralarvae-bearing species showed very proportionally enlarged posterior salivary glands at hatching compared both to more developed conspecifics and to the cuttlefish hatchling. This could reflect a potential common feeding mechanism through external digestion and probably a compensatory mechanism for an early digestive gland underperformance. The proportionally smallest digestive system has been found in L. vulgaris, mainly because of their remarkably smaller digestive glands. All species showed major changes in digestive organs between hatchlings and developed phases, indicating how different ecological contexts over ontogeny are reflected in their digestive structures. Graphical abstract

Identification of plasmids from thermophilic Streptomyces strains and development of a gene cloning system for thermophilic Streptomyces species

Abstract To develop a host-vector system for use in thermophilic Streptomyces, multi-copy plasmids were screened for thermophilic Streptomyces species using data from public bioresource centers (JCM and NBRC). Of 27 thermophilic Streptomyces strains, three harbored plasmids. One plasmid (pSTVU1), derived from S. thermovulgaris NBRC 16615 (= JCM 4520, ATCC 19284, DSM 40444, ISP 5444, NRRL B-12375, NCIMB 10078), was multi-copy and relatively small in size. Analysis of the sequence of this multi-copy plasmid revealed that it was 7 838 bp and contained at least 10 predicted open reading frames (ORFs). The plasmid was introduced into 14 thermophilic Streptomyces strains (of 18 strains examined) and several mesophilic Streptomyces strains (S. lividans, S. parvulus, and S. avermitilis). pSTVU1 can be transferred by mixed culture because the plasmid encodes the ORF that regulates the transfer function. Plasmid transfer was observed not only between strains within the same species but also between mesophilic Streptomyces and thermophilic Streptomyces (and vice versa); however, the efficiency of this transfer was extremely low. We also confirmed that a derivative of pSTVU1 can be used as a multi-copy vector in the gene expression system that is expected to exhibit gene-dosage effects, establishing a method for efficient production of thermophilic α-amylase.

EPCO-32. PROSPECTIVE GERMLINE SEQUENCING OF PATIENTS WITH GLIOMAS, GLIONEURONAL OR NEURONAL TUMORS

Abstract BACKGROUND Several genetic syndromes have been linked to the development of central nervous system (CNS) tumors; however, the prevalence and clinical significance of germline pathogenic variants in this population remain unclear. METHODS 2,367 patients with a glioma, glioneuronal, or neuronal tumor (WHO grade 1-4) ages 0.2-93.8 years underwent tumor and matched normal sequencing with MSK-IMPACT. Germline variants and copy-number variants affecting 90 well-established cancer predisposing genes were analyzed; the presence of biallelic inactivation was determined using FACETS. RESULTS Eleven percent harbored germline pathogenic mutations in high-, moderate-, and low-penetrance genes. High- and moderate-penetrance genes included CHEK2 (n=32, 1.3%), BRCA2 (n=10; 0.4%), TP53 (n=9; 0.4%), NF1 (n=6; 0.2%), and mismatch repair (MMR) genes (n=20, 0.9%). Low-penetrance genes included monoallelic MUTYH (n=42; 1.8%) and the APC I1307K variant (n=28, 1.2%). Biallelic inactivation was found in all tumors from patients with germline TP53 and NF1 mutations, with lower rates in tumors from patients with a germline MMR alteration (53%). Biallelic inactivation was rare among patients with a germline mutation in homologous recombination pathway (HRD) genes (27%), and in the aforementioned low-penetrance APC (15.3%) and MUTYH (10.2%) variants. All patients with biallelic inactivation of an MMR gene were hypermutated. Biallelic inactivation of MMR genes and TP53 were observed in IDH-mutant astrocytoma and IDH-WT gliomas, while biallelic inactivation of NF1 and somatic IDH1/2 mutation were mutually exclusive. When examining the age at diagnosis among patients with germline alterations, tumors with biallelic inactivation were diagnosed at a younger age compared to tumors with monoallelic alterations (37.7 vs 51.6 years, p=0.002). CONCLUSION Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.