bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, hardware and software for heat mode control in testing machine for high temperature experiments
Authors: Mietielov Volodymyr , Breslavsky Dmytro , Lysenko Volodymyr , Tatarinova Oksana , Fesiukov Oleksii
Published: December 2023

A description of the design, control system, and software implementation of the thermal mode control of the experimental creep testing machine developed at the National Technical University "Kharkiv Polytechnic Institute" is given. As a result of testing the automated temperature control system, the main characteristics of the system were established. It was determined that the range of the temperature regulation task is from 0 to 999°С. The working range of heating is from 100 to 500°С. It was established that when the conditions for placing the specimen and ensuring the required thermal insulation of the heating chamber are met, the absolute value of the average temperature adjustment error has a value that does not exceed ±2°С. The root-mean-square value of the adjustment error is no more than ±1.6°С. It was determined that the stability of temperature maintenance depends on the location of the specimen: in the central zone of the chamber, the values of temperature fluctuations are smaller than when the specimen is placed at the bottom. The cycle time of measuring and adjusting the temperature regime is 1.0012 seconds. The power of the heaters is 2x1200 W (in phase switching) and 2x3500 W (in linear mode). The microcontroller used in the system has resources for connecting additional modules and primary converters, which enables expanding the functionality of the system by organizing additional measurement channels. The first results of testing in the study of creep of plane specimens made from aluminum alloys are presented. The character of the creep curve obtained from the strain measurements of the specimens fully corresponds to its classical forms with three sections. A view of a fragment of the destroyed specimen is provided. The modular design, versatility and high technical characteristics of the system and the testing machine as a whole allow its use in various experiments in research projects and in the educational process.
Software for processing of long-term strength data of materials by use of edwards curves
Authors: Breslavsky Dmytro , Khoroshun Andriy , Senko Alyona , Tatarinova Oksana
Published: December 2023

A description of the developed software for saving and analyzing data on high-temperature deformation and long-term strength of metallic materials is provided. The open source Laravel web framework was chosen to implement in the application. The Voyager solution is used together with it as a graphical interface for interacting with the database. A JavaScript programming language solution using Canvas technology is used to build plots. Basic classes and components are described. With the help of diagrams of use cases, the possibility of using the web application in the engineering practice of data processing of experimental high-temperature creep and fracture studies is shown. An approach and an algorithm for approximating long-term strength curves of general appearance, including different types of failure, using Edwards curves are proposed. With their use, an analytical nonlinear expression for the functional dependence between the time to failure and the failure stress was obtained. Approximations of various types of the long-term strength curve corresponding to the processes of accumulation of damage in the material by various types of physical mechanisms are discussed. The undesirable possibility of obtaining an overestimated value of the time to failure in the case of small and medium stress values without using information on the areas of intergranular failure, failure due to oxidation or corrosion, and overaging on the long-term strength curve is demonstrated. The use of the developed software, approach and method of analytical representation of the functional dependence of the values of failure stress on time in the evolution equation for the damage parameter allows you to carry out refined calculations of structural elements operating under high-temperature load conditions
STUDY OF PROBLEMS OF LEGAL PROTECTION OF INTELLECTUAL PROPERTY IN UKRAINE
Authors: Tkachоv Maxim
Published: December 2023

The article highlights the concept of "intellectual property", considers the types of intellectual property and their characteristics, reflects the essence of the concept of "protection of intellectual property", briefly reviews the system and forms of intellectual property at the international level, identifies the problems associated with this topic in Ukraine today moment. To analyze the social prerequisites for the fact that the organizational and legal aspects of improving the legal protection of intellectual property in modern Ukraine, identifying and eliminating significant problems in this area are an important factor in improving the country's economy, promoting scientific and technical progress, creating new inventions necessary for Ukraine and highly effective objects of intellectual property, as well as increasing the level of their legal protection. The research carried out by the authors confirmed the fact that currently in Ukraine the field of intellectual property protection has many gaps. The main problem identified by the authors is the problem of increasing the efficiency of the application of intellectual property legislation. The problem of a narrower nature is the lack of specific legislation regarding infringement of intellectual property rights. An important problem is the lack of an effectively functioning mechanism for the creation and distribution of all types of innovations. From it comes the problem of a not yet formed system of support for the development of science and its financing in market conditions. The authors also note the protracted process of creating and establishing a legislative mechanism for the use and distribution of innovations and the lack of strengthening of the country's scientific and technical potential. Today, there are special legal norms in Ukraine for the proper legal regulation of relations in the field of intellectual property, but mechanisms for protecting the interests of rights holders do not work or are completely absent. And the attempts made by the regulator are often of a formal or highly specialized nature. In fact, the results of intellectual activity begin to be implemented in commercial activities long before this result receives state registration. This situation allows for abuse in the open market, especially in the presence of marginalized participants and fierce competition in all areas.
FUNCTIONAL AND INFORMATIONAL UNDERSTANDING OF HR AND MOTIVATIONAL
Authors: Hutsan Oleksandr
Published: December 2023

In the presented article, on the basis of research, logical-analytical procedures and the author's point of view, a functional understanding of the need to implement a wide range of diagnostic procedures at the enterprise was formed. Taking into account the direction of the research, the functional relationship and the leading role of motivational and personnel studies on the adoption of appropriate quality decisions by managers and the important influence of these components on the effective operation of the enterprise are highlighted. A more detailed phasing of the diagnostic procedure, which was considered in previous works, is presented, which is more useful from a practical point of view for enterprises. Due attention is paid to the fact that the comprehensive information support of the management decision allows it to be implemented more qualitatively. The article provides a formalization of the information basis of the functional understanding of the components of diagnostic processes at the enterprise, from the author's point of view. The author's understanding is given that the application of HR and motivational diagnostics will allow to strengthen the information base in scientific, technical and economic aspects. A concise description of the functional-logical dependencies according to the cascade of the selected elements is considered and provided. It was found that one of the important roles, in view of the functional impact on the effectiveness of effective decision-making by managers (and employees of the administrative and management apparatus in general) in accordance with the hierarchy and direction of activity, is performed by HR and the motivational aspect of diagnostics, and, accordingly, the need their constant implementation in the daily activities of the enterprise.
MARKETING AUDIT OF ADVERTISING ACTIVITIES ON THE FOREIGN MARKET
Authors: Romanchik Tatiana , Vasyltsova Svitlana
Published: December 2023

The advertising activity of the enterprise affects the effectiveness of its communication and sales policy and has an impact on the economic results of its activity. Advertising involves significant financial resources, which requires constant control and regulation. This task allows you to solve the marketing audit of advertising activities. The work examines the features of advertising activity that affect the system of its evaluation. Taking into account that advertising has not only an economic, but also a communication impact, the main concept of conducting an audit of advertising activities in the domestic market is presented. Differences between consumers in different countries of the world are defined, which affect the perception of advertising materials and, ultimately, the effectiveness of advertising influence. Taking into account the peculiarities of the foreign audience, the main directions of the advertising audit in the foreign market and the stages of its implementation are formulated. It is emphasized that, in contrast to an advertising audit in the domestic market, in external advertising practice, the conformity of the content and design of the advertising message to the goals of the advertising campaign and the national characteristics of the target audience should be assessed, as well as a media audit should be conducted. The evaluation of the economic effectiveness of advertising campaigns in the international marketing system does not differ in principle from its determination in the conditions of the Ukrainian market. As for the criteria of communication effects from advertising, they are formed precisely on the maximum consideration of the peculiarities of the country in whose market the enterprise operates. The differences between evaluating the effectiveness of advertising campaigns and conducting an audit are given. It is emphasized that the evaluation of advertising effectiveness is a constituent element of its audit. The audit is aimed at identifying and eliminating weaknesses in advertising activities, optimizing the advertising budget and increasing the effectiveness of advertising.
A CONCEPTUAL FRAMEWORK FOR STRATEGIC CHANGE MANAGEMENT AT AN ENTERPRISE
Authors: Koptieva Hanna , Nashchekina Olga
Published: December 2023

The conceptualization of the modern vision of strategic change management at enterprises is one of the relevant scientific and practical tasks. Strategic changes are based on the concept of the development of an enterprise as an economic system operating in a certain business environment and adapting to the changes in that environment. Under conditions of uncertainty and dynamism, enterprises should build awareness of the need for changes and implement changes in a consistent, well-grounded, and coordinated way. Therefore, strategic change management becomes a key component of the entire strategic management system. The purpose of this research was to develop theoretical principles for strategic change management at an enterprise and, based on them, to create a conceptual framework for strategic change management. The tasks of the research included the analysis of the existing concepts, models and frameworks of strategic change management of the enterprise, their main elements, as well as the development of the authors’ own framework for strategic change management. Based on the performed analysis of the concepts and frameworks of strategic change management of the enterprise, it was established that the main idea of the creation of a framework is to ensure the effectiveness of management of changes at a strategically oriented enterprise. A framework for managing strategic changes of the enterprise that includes the theoretical-methodological, scientific-methodical and practical levels, was proposed and substantiated. The implementation of this framework would ensure the provision of reliable and relevant information for change management and the development of measures to improve the effectiveness of strategic changes. The proposed conceptual framework for managing strategic changes of the enterprise is based on modern management tools including the process and competence approaches as basic ones and systems, situational and adaptive approaches as supporting ones, and assumes the coherence of its components under conditions of uncertainty in a quickly changing environment. The combination of the elements of the developed framework for strategic change management makes it possible to systematically solve the task of ensuring the competitiveness of the enterprise in the long term, its stability and development.
ENTERPRISE PERSONNEL MANAGEMENT BASED ON THE CONCEPT OF SUSTAINABLE DEVELOPMENT IN THE CONTEXT OF INCLUSIVE EMPLOYMENT
Authors: Zamula Olena , Zamula Oleksii , Uhrimova Iryna
Published: December 2023

The paper proves the need to change approaches to personnel management in modern conditions, since there is a change in certain factors influencing the organizational behavior of employees of enterprises, namely: the number of people with disabilities is increasing in Ukraine, the labor potential of the social sphere is decreasing due to the mobilization and forced migration of specialists from various spheres of economic activity.

It has been proven that it is also necessary, among other work with the personnel of enterprises based on the concept of sustainable development, to highlight as a separate component the formation of sustainable tolerance for people with disabilities, as well as laying the foundations for inclusive employment when concluding employment contracts with them. Inclusive employment should be understood as the process of employment of persons with disabilities.

The executive and legislative power in Ukraine take care of employment of people with disabilities, but this initiative should be supported by business and the public. The objective of managers in this field is to develop staff development programs, which should include not only tools for employees to acquire professional and specialized competencies. Such programs should be aimed at forming a holistic view of both the technical and economic aspects of interaction in the process of realizing their knowledge and skills in order to achieve the goals of the organization, and about the social and environmental consequences of their behavior. Therefore, staff training and education should be carried out taking into account the latest scientific achievements in the field of sustainable development, in particular, in terms of encouraging ethical behavior of staff in relation to employees with disabilities.
MECHANISMS OF UKRAINIAN STATE SUPPORT OF INNOVATIONS BEFORE AND AFTER THE WAR
Authors: Novik Iryna , Zhurba Yevheniia
Published: December 2023

Today, the national economy is underinvested in the country's investment and innovation sector, which leads to a downturn in production and a reduction in the investment capacity of market participants and the state. Only a scientifically substantiated and highly functional investment policy of the state has the potential to improve the prevailing situation in Ukraine. This article is intended to analyze the analysis of the mechanisms of state support for innovations in the world and in Ukraine in the past, and to propose the development of possible methodological and scientific-practical recommendations for improving the mechanism of development of state support for innovations in the country in the former peaceful and post-war period. The issue of researching the mechanisms of state support for innovations has always been important and relevant for the country's economy as a whole, as well as for individual enterprises and research institutions. To assist in supporting innovation in the most effective way, the state can use the following mechanisms: providing financial support, creating incubators and accelerators, developing research institutions, creating regulatory incentives, attracting investment, training and supporting young entrepreneurs, funding research, creating technology parks, tax incentives, introducing legislative incentives, and developing international cooperation.
Surgery and the Aging Orthopaedic Surgeon
Authors: Bosco Joseph A. , Papalia Aidan , Zuckerman Joseph D.
Published: December 2023

➤ Aging is associated with well-documented neurocognitive and psychomotor changes.

➤ These changes can be expected to impact the skill with which orthopaedic surgeons continue to perform surgical procedures.

➤ Currently, there is no standardized approach for assessing the changes in surgical skills and clinical judgment that may occur with aging.

➤ Oversight by the U.S. Equal Employment Opportunity Commission, the impact of the Age Discrimination in Employment Act, and the current legal climate make it difficult to institute a mandatory assessment program.

➤ The regularly scheduled credentialing process that occurs at each institution can be the most effective time to assess for these changes because it utilizes an established process that occurs at regularly scheduled intervals.

➤ Each department of orthopaedic surgery and institution should determine an approach that can be utilized when there is concern that a surgeon’s surgical skills have shown signs of deterioration.
Relationship Between Residual Saturations and Wettability Using Pore-Network Modeling
Authors: Purswani Prakash , Johns Russell T. , Karpyn Zuleima T.
Published: December 2023

The relationship between residual saturation and wettability is critical for modeling multiphase processes like enhanced oil recovery, CO2 sequestration, and geologic storage of hydrogen. The wetting state of a core is often quantified through Amott indices, which are estimated from the ratio of the saturation fraction that flows spontaneously to the total saturation change that occurs due to spontaneous flow and forced injection. Observations from traditional coreflooding experiments show a minimum in the trends of residual oil saturation (Sor) around mixed-wet conditions. Amott indices, however, provide an average measure of wettability because of their intrinsic dependence on a variety of factors such as the initial oil saturation, aging conditions, rock heterogeneity, etc. Thus, the use of Amott indices could potentially cloud the observed trends of residual saturation with wettability.

Using pore-network modeling (PNM), we show that Sor varies monotonically with the contact angle, which is a direct measure of wettability. That is, for fixed initial oil saturation, the Sor decreases monotonically as the reservoir becomes more water-wet (decreasing contact angle). Further, the calculation of Amott indices for the PNM data sets shows that a plot of the Sor vs. Amott indices also shows this monotonic trend, but only if the initial oil saturation is kept fixed. Thus, for the cases presented here, we show that there is no minimum residual saturation at mixed-wet conditions as wettability changes.

In this research, we employ a numerical approach to quantify trends of Sor against the traditional definition of wettability. Through the analysis of our numerical work and literature experiments, we find that under isolated conditions (constant initial saturation), linear trends exist between Sor and wettability. This can have important implications for low salinity waterflooding, water-alternating-gas enhanced oil recovery, or CO2 sequestration where the effects of wettability are critical to understand phase trapping.
Bi-Objective Optimization of Subsurface CO2 Storage with Nonlinear Constraints Using Sequential Quadratic Programming with Stochastic Gradients
Authors: Nguyen Quang Minh , Onur Mustafa , Alpak Faruk Omer
Published: December 2023

This study focuses on carbon capture, utilization, and sequestration (CCUS) via the means of nonlinearly constrained production optimization workflow for a CO2-enhanced oil recovery (EOR) process, in which both the net present value (NPV) and the net present carbon tax credits (NPCTC) are bi-objectively maximized, with the emphasis on the consideration of injection bottomhole pressure (IBHP) constraints on the injectors, in addition to field liquid production rate (FLPR) and field water production rate (FWPR), to ensure the integrity of the formation and to prevent any potential damage during the life cycle injection/production process. The main optimization framework used in this work is a lexicographic method based on the line-search sequential quadratic programming (LS-SQP) coupled with stochastic simplex approximate gradients (StoSAG). We demonstrate the performance of the optimization algorithm and results in a field-scale realistic problem, simulated using a commercial compositional reservoir simulator. Results show that the workflow can solve the single-objective and bi-objective optimization problems computationally efficiently and effectively, especially in handling and honoring nonlinear state constraints imposed onto the problem. Various numerical settings have been experimented with to estimate the Pareto front for the bi-objective optimization problem, showing the trade-off between the two objectives of NPV and NPCTC. We also perform a single-objective optimization on the total life cycle cash flow, which is the aggregated quantity of NPV and NPCTC, and quantify the results to further emphasize the necessity of performing bi-objective production optimization, especially when used in conjunction with commercial flow simulators that lack the capability of computing adjoint-based gradients.
Single-cell CRISPR screening characterizes transcriptional deregulation in T-cell acute lymphoblastic leukemia
Authors: Meyers Sarah , Gielen Olga , Cools Jan , Demeyer Sofie
Published: December 2023

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of leukemia caused by accumulation of multiple genetic alterations in T-cell progenitors. However, for many genes it remains unknown how their mutation contributes to disease development. Therefore, we performed two single-cell CRISPR screens in primary pro-T cells ex vivo to study the transcriptional impact of such loss-of-function alterations and link this with effects on cell fitness. The various perturbations were clustered based on their effects on E2F/MYC or STAT/NOTCH signatures, which play a defining role in driving T-cell proliferation. Many of the perturbations resulted in positive effects on the STAT and NOTCH signatures, and were predicted to function as haploinsuffient tumor suppressors in T-ALL. Additionally, Spi1 was identified as an essential gene for pro-T cell survival, associated with deregulation of the MYC signature and epigenetic consequences. In contrast, Bcl11b was identified a strong tumor suppressor gene in immature T lymphocytes, associated with deregulation of NF-kB and JAK/STAT signaling. We found a correlation between BCL11B expression level and JAK/STAT pathway mutations in T-ALL patients, and demonstrated oncogenic cooperation between Bcl11binactivation and JAK3 hyperactivation in pro-T cells. Altogether, these single-cell CRISPR screens in pro-T cells provide insight in the mechanisms of transcriptional deregulation caused by genetic alterations in T-ALL.
Potential of mining waste and Hevea brasiliensis wood in the production of cement-wood panels
Authors: Ferreira Karine , Arantes Lorran de Sousa , Borges Ianca , Batista Felipe Gomes , de Medeiros Dayane Targino , Mendes Lourival Marin , Junior José Benedito Guimarães
Published: December 2023

The incorporation of residues in cement matrices is a viable alternative in obtaining new products for civil construction and a sustainable solution for the disposal of materials discarded by industries. In this context, the objective of the study was to evaluate the potential use of quartzite and particles of Hevea brasiliensis treated with aluminum sulfate [Al2(SO4)3] in the production of cement-wood panels. Quartzite residues and Hevea brasiliensis wood particles were obtained and characterized. The wood particles were mineralized with Al2(SO4)3 at a concentration of 9%. The panels were produced with CPV-ARI Portland cement, calcium chloride (CaCl2) as additive, treated wood particles and addition of quartzite in different proportions (0, 10, 20 and 40%), totaling four treatments. The physical-mechanical and microstructural properties of the panels were determined. The mineralization of the particles contributed to the adherence to the wood-cement. The incorporation of 20% quartzite contributed to the improvement in water absorption and thickness swelling of the panels and in the increase in the modulus of elasticity (MOE) and modulus of rupture (MOR) values. The cement-wood panels were suitable for non-structural and internal use, requiring further studies to evaluate alternative methods of replacing these residues.
Theoretical study on copper adsorption on ZnO surfaces for CO2 hydrogenation to methanol
Authors: Salmi Mustafa Al
Published: December 2023

The study of Cu on ZnO surfaces is a topic of ongoing research due to the importance of Cu as a promoter in the low-temperature synthesis of methanol, the water-gas shift process, and methanol steam reforming. The role of ZnO in supporting the stabilization of the Cu atoms and promoting the CO2 hydrogenation reaction is multifaceted and involves a range of physical and chemical factors. In this work, we used density functional theory (DFT) calculations to investigate the Cu adsorption on ZnO surfaces on different sites. Bader charge analysis, adsorption energy, and phonon inelastic neutron scattering (INS) associated with most stable systems were calculated and compared with previous theoretical and experimental results. We found that atomic Cu adsorption on hollow site of ZnO(111) is the most stable site and most favorable site for Cu adsorption comparing to other ZnO surfaces. This is due to the strong metal-oxygen interaction between Cu and the ZnO surface. The results suggest that the Cu/ZnO catalyst with Cu atoms at hollow site is most likely to be active for CO2 hydrogenation. We concluded that further studies are needed to investigate the catalytic activity of this catalyst under realistic reaction conditions with realistic models of Cu supported on ZnO.
On-surface synthesis and characterization of anti-aromatic cyclo[12]carbon and cyclo[20]carbon
Authors: Sun Luye , Zheng Wei , Kang Faming , Gao Wenze , Xu Wei
Published: December 2023

Cyclo[n]carbons (Cn) have recently attracted significant attentions owing to their geometric and electronic structures remaining largely unexplored in the condensed phase1-15. On-surface synthesis has demonstrated advantage for the generation of a series of cyclocarbons, for example, C1816,17, C1618, C1419, C1019 on the NaCl surface, and their geometric structures have been revealed in real space. However, endeavors to synthesize larger cyclocarbons (e.g., C20 or C24) have encountered difficulties owing to the unstability of precursor molecules18. Meanwhile, it has been extremely challenging to probe the electronic structures of cyclocarbons due to their high mobilities on the NaCl surface. In this study, we focus another two anti-aromatic cyclocarbons, the last and the next homologue of C16, that is, C12 and C20. By designing two fully halogenated molecular precursors both including 4-numbered rings, we further extend the on-surface retro-Bergman ring-opening reaction, and successfully produce the C12 and C20. Such a strategy is also very recently followed by Gross and Anderson's groups to produce C1320. The polyynic structures of C12 and C20 were unambiguously revealed by bond-resolved atomic force microscopy (AFM). More importantly, subtly positioning the C20 molecule into an “atomic fence” formed by Cl clusters allows to experimentally probe its frontier molecular orbitals, yielding a HOMO-LUMO bandgap of 3.8 eV measured from scanning tunneling spectroscopy. Our work may open up the field by easier synthesis of a series of cyclocarbons via on-surface retro-Bergman ring-opening strategy.
A foundation model for bioactivity prediction using pairwise meta-learning
Authors: Wang Sheng , Feng Bin , Liu Zequn , Huang Nanlan , Xiao Zhiping , Zhang Haomiao , Mirzoyan Srbuhi , Xu Hanwen , Hao Jiaran , Xu Yinghui , Zhang Ming
Published: December 2023

Compound bioactivity plays an important role in different stages of drug development and discovery. Existing machine learning approaches have poor generalization ability in compound bioactivity prediction due to the small number of compounds in each assay and incompatible measurements among assays. Here, we propose ActFound, a foundation model for bioactivity prediction trained on 1.6 million experimentally measured bioactivities and 35,644 assays from ChEMBL and BindingDB. The key idea of ActFound is to employ pairwise learning to learn the relative value differences between two compounds within the same assay to circumvent the incompatibility among assays. ActFound further exploits meta-learning to jointly optimize the model from all assays. On six real-world bioactivity datasets, ActFound demonstrates accurate in-domain prediction and strong generalization across datasets, assay types, and molecular scaffolds. We also demonstrated that ActFound can be used as an accurate alternative to the leading physics-based computational tool FEP+(OPLS4) by achieving comparable performance when only using a few data points for fine-tuning. The promising results of ActFound indicate that ActFound can be an effective foundation model for a wide range of tasks in compound bioactivity prediction, paving the path for machine learning-based drug development and discovery.
Visible-light-induced photocatalysis of copper phthalocyanines on cotton fibre
Authors: LUK Anson M.Y. , XIN John H.
Published: December 2023

There are various copper phthalocyanine (CuPc) dyes, which are the copper phthalocyanines (CuPcs) with different substituents, commonly available on the market. Several CuPc dyes were applied to cellulosic fibre for studying their photocatalytic activities by using stain decolourisation methods. Even though the molar quantity of each CuPc derivative on cotton fabric were controlled to be equivalent, there were great difference on their photocatalytic activities. Distinct extents of the CuPc molecules dissociated by the cellulosic medium, owing to different CuPc molecular structures, were observed via absorption spectroscopic analyses. Liquid chromatography-mass spectrometry (LC-MS) was employed to determine the molecular structures of the CuPcs. A novel elution profile, termed as “double-isocratic” method, was developed to separate the relatively complex mixtures of the CuPc compounds, to prevent interference against mass spectrometric detection by buffers and ion-pairing reagents. The stain decolourisation performance of CuPc dyes were also compared to one of the traditional photocatalysts, titanium dioxide (TiO2), under visible light. Stronger photocatalytic activity was exhibited by CuPc-functionalised cottons than the TiO2-coated cotton; convincing visible-light-catalytic effects were demonstrated by CuPcs on cotton under visible light. The outcomes of this study can make contributions to aggregation and photocatalytic studies of phthalocyanines in cellulosic medium; and the CuPcs defined with well-dissocated structures can be applied for functional cellulosic textiles triggered by visible light.
FOXP3 promote the progression of glioblastoma via inhibiting ferroptosis mediated by linc00857/miR-1290/GPX4 axis
Authors: Shan Lei , Cao Wenpeng , Chen Xiaozong , He Ya , Xiao Chaolun , Sun Baofei , Yun Wenfeng , Zeng Zhirui
Published: December 2023

The oncogenic properties of members belonging to the forkhead box (FOX) family have been extensively documented in different types of cancers. In this study, our objective was to investigate the impact of FOXP3 on glioblastoma multiforme (GBM) cells. By conducting a screen using a small hairpin RNA (shRNA) library, we discovered a significant association between FOXP3 and ferroptosis in GBM cells. Furthermore, we observed elevated levels of FOXP3 in both GBM tissues and cell lines, which correlated with a poorer prognosis. FOXP3 was found to promote the proliferation of GBM cells by inhibiting cell ferroptosis in vitro and in vivo. Mechanistically, FOXP3 not only directly upregulated the transcription of GPX4, but also attenuated the degradation of GPX4 mRNA through the linc00857/miR-1290 axis, thereby suppressing ferroptosis and promoting proliferation. Additionally, the FOXP3 inhibitor epirubicin exhibited the ability to impede proliferation and induce ferroptosis in GBM cells both in vitro and in vivo. In summary, our study provided evidences that FOXP3 facilitates the progression of glioblastoma by inhibiting ferroptosis via the linc00857/miR-1290/GPX4 axis, highlighting FOXP3 as a potential therapeutic target for GBM.
Influence of modified Halloysite Nanotube on the properties of Poly(ether etherketone)
Authors: Siraj Naved , Hashmi S. A. R. , Verma Sarika
Published: December 2023

The authors have requested that this preprint be removed from Research Square.
Enzyme-Assisted High Throughput Sequencing of an Expanded Genetic Alphabet at Single Base Resolution
Authors: Benner Steven , Wang Bang , Bradley Kevin , Kim Myong-Jung , Laos Roberto , Chen Cen , Gerloff Dietlind , Manfio Luran , Yang Zunyi
Published: December 2023

Many efforts have sought to apply laboratory in vitro evolution (LIVE) to natural nucleic acid (NA) scaffolds to directly evolve functional molecules. However, synthetic biology can move beyond natural NA scaffolds to create molecular systems whose libraries are far richer reservoirs of functionality than natural NAs. For example, "artificially expanded genetic information systems" (AEGIS) add up to eight nucleotides to the four found in standard NA. Even in its simplest 6-letter versions, AEGIS adds functional groups, information density, and folding motifs that natural NA libraries lack. To complete this vision, however, tools are needed to sequence molecules that are created by AEGIS LIVE. Previous sequencing approaches, including approaches from our laboratories, exhibited limited performance and lost many sequences in diverse library mixtures. Here, we present a new approach that enzymatically transforms the target AEGIS DNA. With higher transliteration efficiency and fidelity, this Enzyme-Assisted Sequencing of Expanded Genetic Alphabet (ESEGA) approach produces substantially better sequences of 6-letter (AGCTZP) DNA than previous transliteration approaches. Therefore, ESEGA facilitates precise analysis of libraries, allowing 'next-generation deep sequencing' to accurately quantify the sequences of 6-letter DNA molecules at single base resolution. We then applied ESEGA to three tasks: (a) defining optimal conditions to perform 6-nucleotide PCR (b) evaluating the fidelity of 6-nucleotide PCR with various DNA polymerases, and (c) extending that evaluation to AEGIS components functionalized with alkynyl and aromatic groups. No other approach at present has this scope, allowing this work to be the next step towards exploiting the potential of expanded DNA alphabets in biotechnology.
New tracers for the identification of the salinity contamination in a confined coastal aquifer; the use of the cesium and rubidium concentration to identify the salinization origin in the case of Llobregat Delta in Barcelona (Spain)
Authors: Diaz Alfredo , Pérez Isabel , Martin-Alonso Jordi
Published: December 2023

The Llobregat Aquifer located in the southern of the Barcelona’s Metropolitan Area (Spain) is the most important source of groundwater in Barcelona tap water distribution system, with a production of up to 70.000 m3 of tap water per day.
Since the year 2007, the salinity of this aquifer has been increased to a values higher than European directives for tap water (Na=200 mg/l), where sodium concentration achieved to 300 mg/l in most of groundwater samples analyzed from October 2008 to April 2009. The possible causes of the salinization could be the sea intrusion into the aquifer or otherwise, the breaking and subsequent contamination by the brine collector from salt mines landfills located in the upper course of the River.
All studies performed with ionic ratios of major elements such as Na, Cl, Br; K, Ca did not allow to obtain a definitive probe of the salinity’s source. However the determination of a minority elements such as cesium or rubidium at very low concentration levels showed that the main source of salinization was the Mediterranean Sea intrusion into the aquifer, probably due to the extensive use of the aquifer in the great period of dryness from 2005 to 2007.
The analytical technique for the determination of cesium, rubidium and other heavy metals at traces level (few ng/l) was optimized and validated with high salinity matrixes such as sea water and brines lixiviates by ICP-MS and good quality parameters were obtained (accuracy and variability <25%) with a limit of quantification of only 0.1 µg/l for cesium and rubidium in sea water. Thereby the cesium and rubidium usually present in saline samples at variable concentrations values has been confirmed as a good tracers to identify univocally the origin of the Aquifer salinization.
Estimates of Discrete Riesz Potentials on Discrete Weighted Lebesgue Spaces
Authors: Hao Xuebing , Li Baode , Yang Shuai
Published: December 2023

Let $0<\alpha<1$. We obtain the necessary and sufficient conditions for the boundedness of discrete fractional Hardy-Littlewood maximal operators ${\mathcal M}_\alpha$ on discrete weighted Lebesgue spaces. From this and a discrete variant of Whitney decomposition theorem, the necessary and sufficient conditions for the boundedness of the discrete Riesz potentials $I_\alpha$ on discrete weighted Lebesgue spaces are discussed. As applications, the boundedness of $I_\alpha$ on discrete weighted Morrey spaces is further obtained.
An Endogenous Promoter LpSUT2 Discovered in Duckweed: a Promising Transgenic Tool for Plants
Authors: Wei Cuicui , Hu Zhubin , Wang Songhu , Tan Xiao , Jin Yanling , Yi Zhuolin , He Kaize , Zhao Leyi , Chu Ziyue , Fang Yang , Chen Shuang , Liu Penghui , Zhao Hai
Published: December 2023

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35Spromoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher priming activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg/L G418 and 6.18 times at 500 mg/L G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFPwas weak, while the LpSUT2:eGFP only changed slightly. This is because under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This isa previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.
Effects of high temperature treatment on the stability and biological activity of catechins compounds
Authors: Wang Kui-Wu , Yang Chuang , Wu Si-Tong , Cao Xiao-Ji , He Shan , Wang Hong
Published: December 2023

The thermal stability and the transformation mechanism of five representative catechins compounds were studied using HPLC-QTOF-MS. The effects of high temperature treatment on the antioxidant, anti-glycation, and enzyme inhibitory activities of catechins compounds were evaluated in vitro. The thermal stability is as follows: ECG > EGCG > Cat > EC > EGC. The increase of hydroxyl groups in the B-ring is not conducive to the stability, while the substitution of Gallic acid is beneficial for the stability of catechins compounds. After heating treatment, the antioxidant activity decreased, while the anti-glycation activity and the inhibitory effects on three enzymes increased significantly. Molecular docking simulation analysis indicated that the degradation product Gallic acid had better binding effect with α-amylase, α-glucosidase, and tyrosinase than ECG, which was one of the reasons for the increased inhibitory activity on enzymes of catechins after heating treatment.
Effect of Heat Stress on physiological, behavioural, and production responses in lactating dairy cows
Authors: Sirtori Francesco , Parrini Silvia , Fabbri Maria Chiara , Crovetti Alessandro , Messeri Alessandro , Mancini Marco , Orlandini Simone , Pugliese Carolina , Grifoni Daniele , Bozzi Riccardo
Published: December 2023

Heat stress is one of the most significant issues occurred in the dairy systems during the last decades with adverse consequences on welfare and production. This study aims to evaluate the effect of heat stress on the main major physiological, behavioural and productive parameters considering two dairy herds located in hill/mountain area. Twenty Friesian cows were checked in two climatic condition periods: no stress, with average diurnal THI < 72 and heat stress with THI > 72. Physiological indices (respiration rate, panting score, skin udder temperature, heat evaporation loss, and heat stress index) as well as milk yield, were during 5 trial consecutive days for each period. Animal behaviours were recorded from 9 a.m. to 4 p.m., including feeding, dynamic and grooming activities. In the heat stress period, cows presented higher values relative to physiological parameters. In addition, the cows decreased the feeding frequency (from 25.18 to 14.74%) increasing their standing (from 9.73 to 22%) and drinking (from 1.77 to 3.60%) behaviour. Milk yield decreased (-3kg/day/cow), as the climatic conditions worsened. The results of this study confirmed the need of more effective strategies development to mitigate the heat load in dairy cattle also in hill/mountain area.
The Cerebellar Cognitive Affective / Schmahmann Syndrome Scale in Spinocerebellar Ataxias
Authors: Selvadurai Louisa P. , Perlman Susan L. , Ashizawa Tetsuo , Wilmot George R. , Onyike Chiadi U. , Rosenthal Liana S. , Shakkottai Vikram G. , Paulsen Henry L. , Subramony Sub H. , Bushara Khalaf O. , Kuo Sheng-Han , Dietiker Cameron , Geschwind Michael D. , Nelson Alexandra B. , Gomez Christopher M. , Opal Puneet , Zesiewicz Theresa A. , Hawkins Trevor , Yacoubian Talene A. , Nopoulos Peggy C. , Sha Sharon J. , Morrison Peter E. , Figueroa Karla P. , Pulst Stefan M. , Schmahmann Jeremy D.
Published: December 2023

The Cerebellar Cognitive Affective / Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS / Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation amongst Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate amongst Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. Use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.
Precision Pharmacotherapy With Zibotentan in Microvascular Angina: a randomized, placebo-controlled, cross-over trial.
Authors: Berry Colin , Morrow Andrew , Abraham George , Hoole Stephen , Greenwood John , Arnold Jayanth , Shanmuganathan Mayooran , Ferreira Vanessa , Rakhit Roby , Galasko Gavin , Sinha Aish , Perera Divaka , Al-lamee Rasha , Spyridopoulos Ioakim , Kotecha Ashish , Clesham Gerald , Ford Tom , Davenport Anthony , Jolly Lisa , Kellman Peter , Kaski Juan-Carlos , Weir Robin , Sattar Naveed , Welsh Paul , Kennedy Julie , Macfarlane Peter , McConnachie Alex , Shibly Mohamed El
Published: December 2023

Microvascular angina, linked to endothelin system dysregulation, was the focus of this double-blind, placebo-controlled, randomized, sequential crossover trial (NCT04097314). The trial compared zibotentan, an oral endothelin A receptor selective antagonist, with placebo in 118 patients with microvascular angina. Over 12 weeks, participants received either 10 mg daily zibotentan or placebo, with the primary outcome treadmill exercise duration. The study found no significant difference in exercise duration with zibotentan (-4.26 seconds; 95% CI: -19.60 to 11.06; P=0.5871). However, zibotentan increased plasma big endothelin-1, endothelin-1, and global myocardial blood flow, while reducing hemoglobin, diastolic, and systolic blood pressure (all p<0.001). Adverse events were more common during the zibotentan period (60.2%) compared to placebo (14.4%, p<0.001). In conclusion, daily administration of 10 mg zibotentan for 12 weeks did not enhance exercise duration and was commonly associated with adverse effects related to fluid retention. Further trials exploring lower zibotentan doses in combination with agents to mitigate fluid retention, and longer treatment durations, are warranted.