Product Changes Research Articles

Digital twin-driven parameter change propagation path optimization for production line variant design

ABSTRACT Current mass individualization requires that production lines for processing products be able to quickly vary to adapt to product changes. The variation and propagation of parameters have a central role in the variation process of a flexible production line, which increases the complexity of the design due to the non-unique propagation path of the variation. Obtaining the optimal variant design scheme has become a major challenge for designers. This paper aims to develop a method to determine optimal paths of change propagation. The digital twin-driven framework of parameter correlation path instantiation is presented. The high-fidelity simulation capability of digital twinning will contribute to the fast variant design of flexible production lines at low cost of trial and error. Then, a parameter variation search algorithm based on multi-fork tree has been proposed. The optimal variation design scheme has been achieved for the optimal propagation path of parameter variation from the perspectives of cost, time and complexity. A prototype verification system of production line design based on digital twin is developed to support the instantiation design of parameter change propagation path. An example of mobile phone welding assembly lines was taken to verify the effectiveness of the method.

THE ROLE OF TOURISM AS THE FACTOR ENSURING ECONOMIC GROWTH IN THE REPUBLIC OF ARMENIA: CHALLENGES AND PROSPECTS

The tourist arrivals were growing from 2012 to 2019, and 1.8 million people visited Armenia in 2019. That number was not surpassed in subsequent years, and the expenditures by international inbound visitors amounted to about 2.44 billion US dollars in 2022 (accounting for 12.5% of GDP). The article attempts to identify the role of expenditures by international inbound visitors in Armenia in explaining the statistically significant changes in the real gross domestic product (GDP), and the role of tourist arrivals and exchange rate in explaining statistically significant changes in tourism receipts in the short run utilizing the least squares estimation techniques and using quarterly data (2012q1-2023q2); and how vulnerable the Armenian economy is to external shocks to propose respective recommendations on priorities to address the challenges faced under various scenarios we built. We find evidence of the «multiplier effect» with respect to tourism receipts and conclude that the Armenian economy is vulnerable to changes in tourist arrivals (especially visitors from Russia). The slight reduction in tourist arrivals from Russia or if their number remains unchanged could be accompanied by a decrease in expenditures by Russian visitors in Armenia in the period 2024-2026. We conclude that the overvalued Armenian dram against the US dollar in the short run and medium term would negatively affect the price competitiveness of Armenia as an attractive travel destination for foreign visitors unless Armenia succeeds in offering specific tourism products by taking into account the price-perceived quality ratio to attract foreigners. We emphasize the importance of the availability of 2-star hotels or affordable accommodation in the medium term to prevent a drop in tourist arrivals if the Armenian dram remains overvalued.

Ethical and Medicolegal Issues: When Obstetric Patients Who Refuse Blood Products Change Their Minds.

Ethical and Medicolegal Issues: When Obstetric Patients Who Refuse Blood Products Change Their Minds.

Blessed be intelligent assistance systems at high task rotation? The effect on motivational work design in assembly

AbstractWe aimed to provide causal evidence on the contradictory effects of projection‐based intelligent assistance systems (IASs) for nine motivational work characteristics (MWCs). IASs are increasingly implemented in assembly to counteract rising cognitive workload due to individualized manufacturing processes. However, how IASs enhance or restrict MWCs is largely unknown. We conducted two studies with experimental vignette methodology. In Study 1 (N1 = 169 German employees), we manipulated an assembly workplace (with IAS vs. without IAS) and tested whether findings indicating only positive effects of IASs in the support of a simple assembly process can be transferred to more complex assembly processes. In Study 2 (N2 = 176 German employees), we manipulated again the assembly workplace (with IAS vs. without IAS) and in addition the dynamic of product changes (task rotation after 1 h vs. no task rotation). Analyzing the data with SPSS 27, we found increased feedback from job and information processing and decreased work scheduling, decision‐making, and work methods autonomy when working with IAS. In Study 2, we did not find the main or interaction effects of task rotation on MWCs. Our experimental evidence suggests that working with IASs represents a double‐edged sword regarding MWCs and that the effect of task rotation is limited. Hence, our results provide vital theoretical implications for a much‐needed work design theory that delineates how new technologies shape work design and practical implications for modern assembly.

Future climate impacts of sodium-ion batteries

Sodium-ion batteries (SIBs) have emerged as an alternative to lithium-ion batteries (LIBs) due to their promising performance in terms of battery cycle lifetime, safety, operating in wider temperature range, as well as the abundant and low-cost of sodium resources. This study evaluated the climate impacts of three SIBs, and compared to two LIBs under four scenarios with considering potential changes in battery performance and background productions between 2020 and 2050. To ensure a fair comparison, all batteries were modeled in the 21,700 form, and a battery dimensioning model was developed to calculate the required amount of components for each battery. We found that equal to lower GHG emissions result from the use of SIBs compared to LIBs under optimal performance scenarios. From 2020 to 2050, the climate impacts of SIBs decreased by 43–57 %. The relative contribution of the battery manufacturing process decreases from 18–32 % to 2–4 % due to the increasingly share of clean energy in the electricity grid, while the relative contribution of key battery component materials increases over time, especially for cathode active materials. These results emphasize the significance of decarbonizing the electric grid, and suggest that future investment in SIBs is promising from an environmental point of view.

The effect of cumulative lipid accumulation product and related long-term change on incident stroke: The Kailuan Study

Background and aimsA single measurement lipid accumulation product (LAP) level has been shown to increase cardiovascular disease, but cumulative LAP on stroke effects is uncertain. Methods and resultsThis study included 43,089 participants, free of any cardiovascular diseases at baseline, from the Kailuan Study. The cumulative LAP was determined by multiplying the average LAP index and the time interval between two consecutive examinations, resulting in their categorization into four quartile groups. The higher LAP exposure was defined as participants with LAP values exceeding 90% of this population during each health survey. The association between cumulative LAP and stroke was assessed using multivariable Cox proportional hazard models. During a median follow-up period of 11.0 (10.6–11.3) years, 2461 participants developed stroke (of which 2220 were ischemic stroke, 320 were hemorrhagic stroke, and 79 were concurrent). After adjusting for potential confounders, the risk of stroke gradually increased in Groups Q2 to Q4 compared to Q1, with hazard ratios (HRs) ranging from 1.19 (95% CI: 1.05–1.36) to 1.50 (95% CI: 1.30–1.70). Specifically, the risk of ischemic stroke showed an increase from 1.21 (1.06–1.39) to 1.56 (1.36–1.79), while no statistically significant effect was observed for hemorrhagic stroke. The longer duration of higher LAP index exposure was also associated with increased stroke risk. Similar results were obtained in the stratification and sensitivity analyses. ConclusionCumulative LAP was positively and significantly associated with incident stroke, especially ischemic stroke, and a longer duration of exposure to higher LAP may increase the risk of stroke.

Forced Degradation Studies of Stigmasterol: Development of Stability Indicating Hptlc Method and I’ts Validation as Per Ich Guidelines

Background - Forced degradation is a method for determining the stability of pharmaceuticals so that stable formulations can be developed & the shelf life of pharmaceuticals can be predicted. During force degradation studies in pharmaceuticals, this research describes the characterization of generated contaminants and mechanism of formation. Forced degradation studies are used in the early stages of pharmaceutical development to ensure that the final products are stable. The goal of herbal drug stability testing is to give data on how much quality of the herbal products changes over time as a result of environmental variables like temperature, oxygen, and humidity, and to determine suggested storage settings, retest intervals, and shelf life. Objective - The current research focuses on the degradation profile of Stigmasterol, an active medicinal component in Chlorophytum borivilianum (Safed Musli), under several ICH mandated stress conditions. Material and Method - The stationary phase was TLC plates precoated with silica gel 60F-254.The solvent system is made up of toluene and ethyl acetate (8:2). This system produced well-separated Stigmasterol spots at Rf (0.40 ± 0.02). After derivatization by anisaldehyde sulphuric acid, stigmasterol was analysed at a wavelength of 550 nm. The Q1AR (parent drug stability testing guidelines) issued by the International ICH (Conference on Harmonization) were strictly followed. Conclusion - The current research establishes the degradation of stigmasterol under ICH-mandated stress conditions (i.e., Acid, Base, and Oxidative hydrolysis) using HPTLC. The drug breaks down in acidic and oxidative environments, but not in bases. The standard stigmasterol has an Rf value of 0.40± 0.02, in acidic conditions, the degradant is found on 1st day, 2nd day, 3rd day, 4th day and 5th day having an Rf value of 0.58 ± 0.02 and in the oxidative medium also, the degradant is found on 1st day ,2ndday ,3rdday ,4th day and 5th day having an Rf value of 0.17 ± 0.02. The method can be utilized as a stability indicator because it effectively separates the drug by its degradation products in acidic and oxidative conditions. Identification of degradants and impurities below the 0.1 percent limit is not required, as stated by ICH recommendations on impurities in new herbal drug products, unless possible impurities and degradants are predicted to be exceptionally powerful or dangerous and the highest daily dosage qualification threshold to be generally considered is < 2g per day 0.1 percent or 1 mg per day consumption (whichever is less) >2g per day 0.05 percent. Degradants obtained in the present study can be used as lead compounds for the novel drug discovery process and the biological activity of these compounds can also be established as ICH guidelines.

ВЛИЯНИЕ СВЕТЛОЗЕРНОЙ РЖИ И ПОРОШКА САХАРНОЙ СВЕКЛЫ НА КАЧЕСТВО БИСКВИТНОГО ПОЛУФАБРИКАТА

In order to expand the range of flour confectionery products for a healthy diet, the possibilities of using cheap and affordable plant raw materials rich in nutrients have been studied. The main raw material is flour from light-grain rye of the Pamyati Bambysheva variety of the FASC of the South-East breeding. As a substitute for white sugar, powder from sugar beet root crops grown in the Balakovo district of the Saratov region was used. The evaluation of organoleptic indicators of the quality of products was determined according to GOST 14621-78, and a tasting assessment of the quality of finished products was carried out, quality indicators were evaluated on a 9-point scale. Physico-chemical parameters were determined according to generally accepted methods: the mass fraction of sugar – according to GOST 5903-89, the mass fraction of fat – according to GOST 31902-2012, ash content – according to GOST 5901-2014, humidity of products – according to GOST 5900-2014. The foaming ability, density and stability of the whipped mass were determined in the work. As a result of research, it can be concluded that when wheat flour is replaced with flour from light-grain rye of the Pamyati Bambysheva variety, a pleasant smell and taste are noted in the finished biscuit semi-finished product, according to physico-chemical indicators, the mass fraction of sugar and fat decreases, which gives the products dietary properties. The nutritional and energy value of the biscuit semi-finished product changes in a positive direction, as the carbohydrate content decreases, and the content of polyunsaturated omega-3 and omega-6 fatty acids, vitamins, macro- and microelements, many of which are antioxidants, increases markedly. Therefore, the results of these studies make it possible to position the finished product as a product with functional and dietary properties.

Improving Products Considering Customer Expectations and Life Cycle Assessment (LCA)

Abstract Dynamically identifying key product changes is a challenge for enterprises. It is even more complicated if companies strive for the sustainable development of their activities. Therefore, the aim of the article was to develop a method to help predict the direction of product improvement, taking into account its quality level and environmental impact during the life cycle (LCA). The method was based on the design phase of LCA and the process of obtaining and processing customer expectations. Techniques supporting the developed method were: a questionnaire, a seven-point Likert scale, a standardised list of criteria for assessing the product life cycle, the WSM method, and a scale of relative states. The product analysis was carried out according to modified criteria states, which were evaluated according to: i) customer satisfaction (quality criteria), ii) environmental impact of LCA (environmental criteria), and iii) importance of quality and environmental criteria for customers. The originality of the method is to support the product improvement process to make it environmentally friendly within LCA and, at the same time, satisfactory to customers in terms of quality. The method will be used mainly by SMEs that want to initially predict the environmental impact of a product, including taking into account customer expectations.

“To Be or Not to Be” of a Polymer Nanogel—Unravelling the Relationship of Product Properties vs. Synthesis Conditions Governing the Radiation Crosslinking of Poly(acrylic acid) Using GPC/SEC—MALLS

In this paper, a state-of-the-art multi-detection gel permeation chromatography/size exclusion chromatography (GPC/SEC) system including multi-angle laser light scattering (MALLS) is applied to monitor radiation-induced synthesis of internally crosslinked nanostructures from poly(acrylic acid) (PAA). The aim is to demonstrate that this modern tool yields a more detailed picture of reaction mechanism and product structure than the techniques used to date. The prevailing intramolecular crosslinking narrows the molecular weight distribution from Mw/Mn = 3.0 to 1.6 for internally crosslinked structures. A clear trend from over 0.7 to 0.5 in the Mark–Houwink exponent and a decrease in Rg/Rh from 1.7 to 1.0 point to the formation of nanogels, more rigid and less permeable than the starting coils. Changes in the coil contraction factor (g′ = [η]irradiated/[η]linear) as a function of the radical density revealed the existence of two modes in intramolecular crosslinking, the initial one (up to 0.075 radicals per monomer unit) where the compactness of products changes strongly with progressing crosslinking and a second one where further compacting is suppressed by the lower flexibility of the partially crosslinked chain segments. This indicates a transition from soft, still internally crosslinkable nanogels to more rigid structures, less prone to further intramolecular loop formation. Our findings provide means for the tailored design of new PAA nanomaterials.

Effect of pickling on pyrolysis characteristics and adsorption properties of biomass

ABSTRACT In order to explore the influence of pickling on the pyrolysis characteristics and adsorption performance of biomass, this paper used pickled rice husk as raw material, and used TG-FTIR coupling instrument to explore the pyrolysis characteristics and product changes of rice husk; The Coats-Redfern (C-R) method was used to analyze the pyrolysis kinetics, and the adsorption performance of pyrolysis biochar on heavy metal Cu was investigated. The results show that pickling can effectively reduce AAEMs, change the pyrolysis path, increase the release of volatiles, and increase the calorific value of raw materials by about 17.10%. The surface of rice husk retains abundant functional groups, and the vibration of characteristic peaks is more intense. The C-R kinetic analysis showed that the pyrolysis process was consistent with the reaction order n = 1, and the influence on the activation energy of rice husk was sulfuric acid > phosphoric acid > nitric acid. The pickling pyrolysis biochar can promote the adsorption of heavy metal Cu2+ in the aqueous phase, the adsorption capacity is up to 41.4 mg·g−1, and the adsorption efficiency is up to 82.8%.

Transformed through the CARTA experience: changes reported by CARTA fellows about their PhD journey

ABSTRACT Transformative learning occurs when a person, group, or larger social unit encounters ideas that are at odds with their prevailing perspective. This discrepant perspective can lead to an examination of previously held beliefs, values, and assumptions. The Consortium for Advanced Research Training in Africa (CARTA) has since 2011 been training and supporting faculty from different African universities, to become more reflective and productive researchers, research leaders, educators, and change agents who will drive institutional changes in their institutions. As part of a mid-term evaluation of CARTA, an open-ended question was posed to the CARTA fellows asking them to describe any changes they had experienced in their professional lives as a result of the CARTA Programme. The 135 responses were inductively coded and analysed using qualitative thematic analysis. These themes were subsequently mapped onto Hoggan’s typology of transformative learning outcomes. CARTA fellows reported shifts in their sense of self; worldviews; beliefs about the definition of knowledge, how it is constructed and evaluated; and changes in behaviour/practices and capacities. This paper argues that the changes described by the CARTA fellows reflect transformative learning that is embedded in CARTA’s Theory of Change. The reported transformation was enabled by a curriculum intentionally designed to facilitate critical reflection, further exploration, and questioning, both formally and informally during the fellows’ PhD journey with the support of CARTA facilitators. Documenting and disseminating these lessons provide a guide for future practice, and educators wishing to revitalise their PhD training may find it useful to review the CARTA PhD curriculum.

New insights on the environmental Kuznets curve (EKC) for Central Asia

We estimate the environmental Kuznets curve (EKC) for Central Asia by allowing for the possibility of linear, U-shaped and N-shaped forms, and considering the impact of ecological footprint, climate change adaptation and energy consumption. We employ a fully modified ordinary least squares framework for cointegrating polynomial regressions, and include obtained long-run relations in a panel Vector Error Correction model. The findings suggest that the linear EKC form is more coherent for Central Asia compared to the N-shaped EKC form. We link this to the fact that the Central Asian countries are in the first stage of the EKC. We observe that Gross domestic product, ecological footprint, energy consumption and climate change adaptation positively impact carbon dioxide emissions in the long-run. Moreover, there is bidirectional causality from GDP\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$GDP$$\\end{document} and climate change adaptation to CO2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${CO}_{2}$$\\end{document} emissions, while causality is unidirectional between emissions and energy consumption.

Treasures & Baggage: A New Way to Navigate Change

All around us, from large corporations to universities, from design consultancies to small businesses, we are all, as individuals and organizations, facing a massive cultural upheaval.It's no surprise that we're living in the midst of incredible change. As tempting as it is to race to embrace the new, maybe a closer examination of what to keep and what to get rid of will ultimately lead to real, more productive change.

Investigating the Dynamic Relationship Between Greenhouse Gas Emissions and Gross Domestic Product in Türkiye

This study aims to investigate the causal relationship between Gross Domestic Product and greenhouse gas emissions in Türkiye from 1951 to 2018, using the Causal Decomposition Method that integrates Ensemble Empirical Mode Decomposition, Hilbert-Huang Transform, and Phase Coherence Methods. The primary focus is on identifying the key sectors contributing significantly to greenhouse gas emissions, particularly those connected to industrial production. The analysis reveals a one-way, short-term causal relationship from Gross Domestic Product to greenhouse gas emissions, spanning approximately 3 years. This finding suggests that changes in Gross Domestic Product have short-term effects on emissions, but not vice versa. Special emphasis is placed on the gases Cardon Dioxide, Methane and Nitrous Oxide, as they demonstrate a strong, consistent causal connection with Gross Domestic Product. The significance of this study lies in its utilization of the Ensemble Empirical Mode Decomposition approach to investigate this dynamic causality and address a notable gap in the existing literature. Empirical results indicate a complex yet observable association between Gross Domestic Product growth and greenhouse gas emissions in Türkiye, and that this relationship becomes more important, especially in the short and long term, with periodic fluctuations.

Examining the Impact of Hysteresis on the Projected Adoption of Autonomous Vehicles

This study explores the potential impact of per capita gross domestic product (GDP) changes on the adoption of autonomous vehicles (AVs). The level of adoption of AVs is anticipated to influence the benefits of future mobility, prompting numerous studies that forecast the market share of AVs using various methods. The influence of changes in the per capita GDP on vehicle ownership is crucial in assessing the challenges associated with reducing dependence on AVs in the future. This phenomenon, known as the hysteresis effect, implies that AV adoption estimates may differ when the GDP is rising as opposed to when it is falling. This research examines the effect of rising and falling GDP per capita on the anticipated AV diffusion in Hungary, utilising a scenario-based method to account for the variation in adoption rates in the literature. The study findings indicate that declines in GDP in the past will impact AV ownership, leading to a shift in future adoption patterns. The AV market is projected to reach saturation in the 2070s and the 2090s in favourable and moderate scenarios, respectively, while a pessimistic state would delay this outcome until after the year 2100.

Configuration design of reconfigurable single-product robotic assembly line for capacity scalability

Rapid product changes and fierce global competition force companies to react quickly to market changes associated with dynamic capacity. This paper investigates how to design and reconfigure configurations of the single-product scalable reconfigurable robotic assembly line (RAL) over multiple demand periods (DPs) with fluctuating demands. A two-phase approach is proposed, in phase 1, the configuration of RAL is designed to minimize the capital cost following the initial demand. In phase 2, the reconfiguration for each DP is performed according to demand fluctuations to minimize the sum of capital costs and reconfiguration costs between consecutive DPs. Mathematical models for the two phases are established. Then a hybrid particle swarm algorithm combined with simulated annealing (PSOSA) is proposed for practical-sized problems, and PSO and SA are chosen for comparison. Two other different approaches are selected for comparison. In approach 1 (robust strategy), each DP of the product lifecycle is calculated separately, and then a fixed configuration that can satisfy the maximal capacity of all DPs is obtained. In approach 2 (changeable strategy), the minimal-cost configuration for each DP is calculated separately first, and then the reconfiguration cost between adjacent DPs is counted. Furthermore, a set of instances is designed and the computational results of three approaches accompanied by PSOSA, PSO and SA versus the devised instances demonstrate the superiority and robustness of the proposed approach and PSOSA.

Intercomparison of recent microwave satellite soil moisture products on European ecoregions

Several satellite microwave-based soil moisture (SM) products have become available in recent years, making possible to produce different datasets at continental and/or a global scale. Numerous variables, including geographic heterogeneity, weather and climate, and land cover, have an impact on these products' accuracy. In this study, we account for all these variables by using the ecoregions as the scale of analysis and conducting a thorough comparison of satellite products with ground-based SM measurements. The whole Europe has been selected as study area, considering it as the aggregation of several ecoregions, each of them classified as an homogeneous zones, in terms of climate, vegetation and potentially investigable soil cover. Selected SM satellite data includes: i) the National Aeronautics and Space Administration (NASA) SMAP L4 V5; ii) the European Space Agency (ESA) SMOS-IC V2.0; iii) the H115 and H116 SM products in time-series format generated by analyzing data collected by the Advanced Scatterometer (ASCAT) aboard MetOp satellites; iv) the CGLS SSM 1 km obtained by the radar onboard ESA’s SENTINEL-1 platforms; and v) the European Space Agency’s Climate Change Initiative for Soil Moisture (ESA CCI SM) “COMBINED” ESA CCI SM v06.1 product, created by merging satellite-based passive/active microwave measurements. Such a variety, in terms of technologies and main features, of publicly available online SM products (in their up-to-date version), allowed for a comprehensive intercomparison against in situ measurements of the International Soil Moisture Network (ISMN), that spreads across all of Europe within the above-mentioned terrestrial ecoregion, using four different metrics, i.e., r, bias, ubRMSE and r/rANOM.Overall the intercomparison has underlined how SMAP L4 and ESA CCI show the best performance regardless of the considered metric. ASCAT has achieved best performances among non-modeled/blended products, while SMOS-IC has showed slightly better performance than the CGLS SSM 1 km. Using ecoregions allowed to further characterize the differences of each satellite products and identify the areas where all these products are more reliable (e.g., group (1) made by ecoregions as the Cantabrian Mixed forests or the Balkan Mixed forests; or group 2 made by ecoregions which belong to Mediterranean area) or less performing (e.g., the Central European mixed forests and the Pontic steppe). Hence, these classes have been further analyzed exploiting the ERA5-Land data, in terms of the SM, air temperature, precipitation, evaporation and Leaf area index. The research has provided helpful insights into how the performance of particular SM satellite products changes based on both the characteristics of the product under consideration and the area under investigation (i.e., one ecoregion compared to another).

Do the Outcomes of Clinical Efficacy Trials Matter in Regulatory Decision-Making for Biosimilars?

There is an increasing body of evidence supporting a more flexible approach in clinical data requirements for the approval of more complex biosimilar substances such as monoclonal antibodies (mAbs). The aim of this paper is to further analyse the role of quality/chemistry, manufacturing and controls (CMC) and clinical data for the conclusion on biosimilarity and the decision on marketing authorisation (MA). In the present study, we analysed the MA applications (MAAs) of all 33 mAbs and three fusion proteins evaluated by the European Medicines Agency (EMA) between July 2012 and November 2022 with special emphasis on all submitted rituximab (four products) and trastuzumab (seven products) biosimilar candidates, including withdrawn applications. For the two withdrawn applications, the comparative efficacy trials suggested biosimilarity, but the quality/CMC package was not accepted by EMA. We therefore investigated whether a negative MAA outcome could have been predicted based on the evidence generated in the quality/CMC packages, regardless of clinical trial data. For this purpose, we reviewed the respective European Public Assessment Reports (EPARs) or withdrawal assessment reports, and the first regulatory assessments for all these 36 MAAs (i.e. day 120 of the centralized procedure), which are not publicly available. During EMA review, where significant issues are identified which would preclude a marketing authorisation, these issues are raised as questions to the applicant and are classified as major objections (MO). In 67% of cases, the outcome of the quality and clinical assessment was the same, i.e. both the quality and clinical assessments either supported approval or did not support approval. In 11% of cases, MO were identified in the quality part of the submission but not in the clinical data. In 22% of cases, MO were raised on the clinical data package but not on the quality data. However, we found no instance where seemingly negative clinical data, including failed efficacy trials, led to a negative overall decision. In each instance, the failure to confirm similar clinical performance in all investigated aspects was eventually viewed as not being related to the biosimilar per se but as being due to imbalances in the trial arms, immaturity of secondary endpoint results, change in the reference product, or even chance findings. Furthermore, when performing an in-depth analysis of the quality and clinical packages of trastuzumab and rituximab biosimilars, we found that in no case were clinical trial data necessary to resolve residual uncertainties regarding the quality part. The results further support the argument that sufficient evidence for biosimilarity can be obtained from a combination of analytical and functional testing and pharmacokinetic studies which may also generate immunogenicity data. This calls into question the usefulness of comparative efficacy studies for the purposes of regulatory decision-making when approving biosimilar mAbs and fusion proteins.

Метод створення і впровадження FPGA проєктів стійких до змін вимог і середовищ розроблення для хмарних інфраструктур

The subject of study in this article is the modern technologies of programmable logic devices, the history of product changes of leading manufacturers, including development environments, and project optimization processes. The goal is to improve modern methods, technologies, and software tools for the development and integration of FPGA-as-a-Service in the form of services in cloud infrastructures, data centers, and on-board high-performance systems, with taking into account the ever-changing conditions and requirements, and the constraints of platforms. Task: to analyze the history of product changes of the leading vendors and manufacturers of programmable logic devices; analyze the dynamics of changes in the functionality of project development environments for FPGA-based systems, with taking into account the existing requirements and restrictions from vendors of software and hardware platforms and components; perform a comparative analysis of modern development boards and accelerator cards for the prototyping and testing of projects based on the chips of programmable logic; analyze the use of an existing services and solutions based on FPGA technologies as part of cloud services from modern cloud providers; propose practical steps for the development of systems based on FPGA resistant to project requirements change; propose the sequence for the development and optimization of high-performance systems with their implementation based on FPGA; and to provide practical example of the use of the proposed method. According to the tasks, the following results were obtained. The history of changes in the leading companies of programmable logic manufacturers, as well as changes in versions of the development environments and the products of one of the largest companies, is analyzed. The use of existing FPGA-based solutions as part of cloud services is analyzed in detail. Two sequences for optimizing projects and increasing their productivity with reducing of the prototyping efforts during their creation and porting to new versions of software and hardware platforms are provided. Based on the results of the research, a prototype was developed and tested, which allowed the application of the proposed method in practice for adapting and porting the FPGA as a service project during the transfer to another version of the accelerator card. Conclusions. The main contribution and scientific novelty of the obtained results is that an experimental study of the paradigm of runtime reprogramming of programmable logic was performed, which made it possible to formulate the elements of a new method of creation projects as a service for cloud infrastructures, data centers, and artificial intelligence systems. A set of practical steps for the development of systems that are tolerant to changes in conditions and requirements is proposed. The application of the proposed method allows to avoid costs of project support in the case of changes in requirements.