Main Members Research Articles

DISP-15. DISPARITIES IN THE AVAILABILITY OF NEURO-ONCOLOGY CLINICAL TRIAL SUPPORTING INFRASTRUCTURE IN THE UNITED STATES

Abstract BACKGROUND Barriers to clinical trial access have significant implications for patient care and disproportionally impact rural and socioeconomically disadvantaged populations. Expanding on reported disparities in neuro-oncology trial availability, we assessed whether existing networks of clinical providers and collaboratives, including NCI’s National Clinical Trials Network (NCTN) and Community Oncology Research Program (NCORP), can effectively bridge these disparities. METHODS Locations of adult neuro-oncology trial sites, UCNS-certified neuro-oncologists, NCTN Main Members, NCORP Community Affiliates, and general oncologists reporting to Centers for Medicare/Medicaid Services were obtained, mapped to zip code tabulation areas (ZCTAs), and annotated with US Census population and geography data and the Neighborhood Atlas Area Deprivation Index (ADI). Regression and spatial analyses were conducted assessing the role of geography, socioeconomic disadvantage, and population on infrastructure accessibility. RESULTS We identified 1976 neuro-oncology trials, 586 NCTN institutions, 962 NCORP sites, 306 neuro-oncologists, and 863 general oncologists located in just 8% of all ZCTAs, inhabited by 19% of the US population. All trial-supporting infrastructure components were more likely to exist in more populated, geographically neighboring regions (OR >1, p< 0.00001). Trial sites, NCTN institutions, and neuro-oncologists served ZCTAs with less disadvantage (OR=0.99, p=0.03958; OR=0.99, p< 0.00001; OR=0.98, p< 0.00001), while NCORP served more disadvantaged areas (OR=1.01, p=0.00102) and general oncologists were distributed similarly across ADI (OR=1.00, p=0.94317). Investigating potentially underutilized infrastructure, 2 neuro-oncologists, 8 NCTN institutions, 10 NCORP sites, and 107 general oncologists were located more than 25 miles from utilized trial sites. CONCLUSION The identified disparities in neuro-oncologists and trial-supporting institutions reflect disparities in trial-site access and point to broader disparities in neuro-oncology care access. NCORP sites reach more socioeconomically disadvantaged populations, but the overall sparsity of trial-supporting networks indicates that the existing infrastructure cannot effectively bridge trial-access barriers and novel approaches including telehealth and decentralized trial designs may be necessary to promote equity.

Study on wind-induced fatigue performance of large-span transmission tower-line system considering the combined distribution probability of wind direction and speed

To accurately evaluate the fatigue life of transmission line structures under wind loads, this study proposes a multivariate member fatigue damage analysis method for investigating the wind-induced fatigue performance of a large-span transmission tower-line with full consideration of the combined distribution effects of wind direction and speed in the actual wind field. With the background of in-service transmission line project, a refined finite element model of the large-span transmission tower-line system is established, and the wind load is simulated and generated based on the linear filtering method. According to the meteorological statistics of the project site in the past 50 years, the wind-induced fatigue sensitivity analysis of the tower-line system is performed through considering the combined distribution probability of wind direction and speed. The wind-induced fatigue damage of the tower-line system is calculated based on the rain-fall counting method and Miner's fatigue cumulative damage theory, and its wind-induced fatigue life is further analyzed. The analysis results show that the sensitive members of the tower-line system are mainly distributed in the 2nd, 6th, 8th and 9th segments by combining the effects of wind attack angle and wind speed. The fatigue damage of the sensitive members decreases gradually with the increase of wind attack angle (0° wind attack angle damage is the largest), and the effect of wind speed on the vertical main member is larger than that of the crossarm upper chord member. Moreover, the fatigue damage at the end of the member is significantly larger than that in the center, and even at small wind speeds, the member's end can produce a stress amplitude larger than the fatigue cut-off limit. The fatigue life of crossarm upper chord members is 72.89 years, and that of the vertical main member is 77.60 years. In particular, the vertical main member should be employed as the control member for the structural fatigue life when considering extreme wind loads.

Genus <i>Betula</i> L.: Species-Specific Population-Genetic Features and Taxonomy Problems

The article summarizes and systematizes the results of studies by Russian and foreign authors related to the population-genetic features of the main members (silver birch Betula pendula Roth, downy birch Betula pubescens Ehrh, curly (or Karelian) birch Betula pendula Roth var. carelica (Mercklin) Hämet-Ahti) of the birch genus (Betula L.) growing in the forest zone of Europe. Information is provided about forming of birch populations in the region and about its migration pathways when recolonizing the territory after the Ice Age. We demonstrate that due to certain geographic and climatic affiliations there appeared zones of hybridization between different birch species, which had an effect on the subsequent evolution of this genus. Attention is given to the role of hybridization in shaping the genetic structure of the birch population in the north-western part of continental Europe, where introgression has generated unusual genotypes and haplotypes, among which curly birch has probably become differentiated. We argue that the introgressive hybridization of species observed now and then in the birch genus may be of the main reasons for the problems with definite taxonomic identification of silver birch and downy birch. It is also remarked that curly birch, although meeting the conventional biological criteria of a species, is still regarded a variety of silver birch. Having analyzed the population-genetic features of members of the genus Betula L., the authors conclude that the species status of silver birch and downy birch should be retained in spite of the identification difficulties and that instating curly birch as a separate biological species is advisable. We emphasize the importance and relevance of studying the population-genetic features of both common and rare members of the Betula genus to enable the development of efficient methods and practices of their selective breeding and reproduction of the most valuable genotypes as a solid scientific foundation for sustainable forest management.

Numerical Investigation of the Effect of Aluminum Yielding Damper for the Retrofitting of Semi-rigid Steel Frames

During an earthquake, yielding dampers yield before the main members of the structure and with their plastic deformations, they dissipate part of the earthquake energy. Therefore, ductile materials are a suitable option for this type of dampers. In this research, numerical studies were conducted to investigate the effect of aluminum yielding damper (AYD) on semi-rigid steel frame. First, the steel frame and the AYD were verified based on experimental samples and analytical equations. An approximate equation for estimating the elastic stiffness of the damper was also presented. Parametric studies were conducted in order to investigate the effect of the number of dampers and the axial force of the column on the stiffness, ultimate strength, ductility and energy dissipation parameters of the frame. The additional forces applied to the connections, beams and columns of the frame due to the addition of dampers were also calculated, which is important in the design of the frame. The results showed that the addition of the damper increased the frame's stiffness, energy dissipation, ultimate strength, and ductility, and also reduced the negative effect of the column's axial force on energy dissipation of the frame.

Effect of an educational video about ERAS on reducing preoperative anxiety and promoting recovery

Video propaganda is reported effectively improving patients' understanding of operation. However, whether a video introducing patients' most concerns can reduce preoperative anxiety and promote recovery stays unsealed. In this study, we investigated the effects of complementary therapy of educational video during preoperative visit. The results showed that thirty-five (23.2%) parents in Group Control were diagnosed as anxiety according to SAS, and nineteen (12.3%) patients were diagnosed after video intervention. The APAIs anxiety score and APAIs information score in Group Video were lower than those in Group Control. Compared with Group Control, video visit helped to increase the first-attempt pass rate of the knowledge retention exam and solve the patient's most worried concerns, and decrease incidence of emergence agitation, total cost of hospitalization and length of hospital stay. Moreover, video visit improved satisfaction degrees of patients and their main family members. Briefly, our study demonstrated video visit can improve patients' knowledge of anesthesia and decrease their preoperative anxiety, which may represent an important complementary therapy to routine preoperative visits.

Mass Media Role in Spreading the Sports for All Culture among Female University Students in the Sultanate of Oman in the Light of Oman Vision 2040

The research aims to identify the mass media role in spreading sports culture among women in the Sultanate of Oman in the light of Oman Vision 2040. The descriptive method using the survey way was used. The survey was conducted on a pilot sample of (25) examinees during the period from 2-15 December 2020, and it was conducted on the (84) research main sample members, between December 20/2020 to February 1/ 2021. The results indicated that the mass media focused on the importance of practicing all aspects of sports for all activities in terms of the positive effects on their physical, psychological and social health. The study recommends that sports media should rely on academic experiences to convey their ideas about the importance of women exercising.

Failure mechanism of a Q690 steel tubular transmission Tower: Full-Scale experiment and numerical simulation

The failure mechanism of a Q690 steel tubular transmission tower is investigated through full-scale experiment. The tower is mainly subject to the influence of the wind and the loads from the transmission lines. The displacements and the strains of the key positions as well as the ultimate bearing capacity of the tower are thus obtained. The final collapse is induced by the buckling instability of the compressed main member of a tower leg. A finite element model is established, whose validity is verified by the experimental data. Then, the numerical model is used for further analysis on the structural responses of the tower. It is found that once plasticity occurs at a certain point on the main member, its lateral displacement would be much accelerated, thus amplifying the second-order effect thereof. The horizontal auxiliary members, connected to the bottom of the compressed main member, are initially under tension. While the deformation of the main member is aggravated, they gradually undergo the transition from tension to compression, constituting a lateral support to the main member. This support then enforces the plasticity to develop towards the middle section of the main member, resulting in the final failure at the same location as observed in the full-scale experiment. These findings are crucial for a progressive understanding of the failure mechanism of this type of high-strength steel tubular towers, and they have contributed to the optimization of the design method to prevent the collapse of transmission tower under similar circumstances.

Making, Living and Remaking the Myth: Plath and Her Mythical World of Poetry

Sylvia Plath is a very well-known figure in American and English literature. She is the back of modern literature and the face of postmodern literature, as her works reflect the characteristics of both ages. She is one of the four main members of the Confessional School of Poetry, and most of her works depict the theme of self-obsession. Her poetry is the poetry of “I”, but what makes her poetry different from others is her use of myth in her craft. As she was very fond of dying and death, she has used various myths related to death or can, say, in an altered way. She has done it so artfully that with her subtle usage of myth in her poetry, she has become a myth. The central theme of her poetry, as well as her myth, is, as it is obvious, death and rebirth. As a confessional poet, she has never been interested in the life and death of other people but in her own. Each anthology of hers, chiefly Colossus, and Ariel, discusses the very theme. Many of her poems depict her desperate desire to die. Lady Lazarus, Ariel, Fever 103, and The Manor Garden are chief among them. These poems also depict this theme of morbidity through the subtle use of mythology. In this paper, the researcher is willing to discuss the Sylvian myth in the poem, Lady Lazarus, along with the original myth.

The effectiveness of blended learning technologies in higher education: Assessment methodology

Introduction. The modern system of higher education has undergone a serious digital transformation in recent years. Electronic, blended, mobile learning is being actively introduced. However, the most significant innovative trend in modern education in recent years is blended learning, which is characterised using both traditional and digital learning technologies, which together contribute to the preservation of university traditions and the active use of modern information and communication tools in solving educational problems. The use of new models of blended learning makes higher education more accessible to all categories of not only Russian but also foreign students, stimulating their independence and increasing motivation for education based on the rich experience of their digital communication. In this regard, scientists and practitioners show increasing interest to the problem of the effective use of blended learning technologies, approaches and methods in higher education.Aim. The present research aims to theoretically substantiate the methodology for studying the blended learning technologies effectiveness, to develop and approbate appropriate methodological tools, followed by its verification for reliability and validity.Methodology and research methods. The problem research of the effectiveness of the blended learning technologies applied in higher education provides for the analysis of foreign and Russian science literature; systematisation and generalisation of the applied approaches; the use of modelling methods and mathematical statistics. The studying methodology of blended learning technologies effectiveness is represented by the integration of procedural, activity-based and environmental approaches in the selection and justification of three criteria for evaluation (effective, didactic, resource) and a system of their indicators in higher educational practice, which served as the theoretical basis of the developed methodology and selected methodological tools.Results. In the course of the research, the authors formulated conceptual foundations and developed a methodology to study the effectiveness of blended learning technologies used in modern higher education. Procedural stages were defined, and evaluation tools were described. The methodology was approbated and verified for reliability and validity.Scientific novelty. The concept and methodology of studying the blended learning technologies effectiveness is a component of quality management concept of higher education in the context of its digital transformation and its resource-didactic provision. The authors’ methodology not only reflects current trends in improving the objectivity of pedagogical assessment, but also replenishes its scientific and methodological arsenal with the addition of a multi-level system of goals, criteria and methods for determining the effectiveness of blended learning technologies in higher education.Practical significance. A new methodology to study the blended learning technologies effectiveness in the higher education system is proposed. Based on the obtained valid data and the results of the approbation, it is concluded that the authors’ methodology has functional certainty, providing controllability in the didactic and resource support for the effective use of different models of blended learning. The practical application of the methodology will contribute to improving the quality of blended learning in higher education and the involvement of the main members of higher education (teachers and students) in the process of designing and selecting traditional and digital technologies to ensure its effectiveness.

Enhancing the cyclic performance of shear links using longitudinal stiffeners

Shear links constitute the most crucial part of eccentrically braced frames. Their main responsibility is to dissipate the earthquake input energy away from the main structural members; therefore, keeping them responding within the elastic stage. However, the rotation capacity of vertical shear links directly influences the allowable interstorey drift of the eccentrically braced frame and the energy dissipation capacity. To enhance their rotation capacity and performance, transverse stiffeners in vertical shear links are proposed to be replaced with longitudinal stiffeners in this research. A numerical study is conducted, using Ansys Workbench, on fourteen shear links with different parameters to investigate their cyclic behaviour. The considered parameters are the stiffener configuration (transverse or longitudinal), web thickness, stiffeners number, stiffeners thickness, flanges width, and web aspect ratio. The influence of these parameters on the failure mode, hysteretic response, mechanical parameters (strength, rotation capacity, etc.), ductility, cyclic web shear buckling, and energy dissipation is analysed and discussed. The results demonstrate that longitudinally stiffened shear links surpass conventional transversely stiffened ones in terms of strength, overstrength, rotation capacity, ductility, web shear buckling resistance, and energy dissipation. Additionally, it is found that the current design provisions of EN 1998–1 cannot accurately predict the yield shear strength of longitudinally stiffened shear links. Moreover, numerous remarks involved with the influence of different parameters on the cyclic performance of longitudinally stiffened shear links are presented and discussed.

Identification of influencing factors on bridge damages using Bayesian network

AbstractIn Japan, bridge inspections are compulsorily performed in 5‐year cycles. With the institutionalization of the inspection cycle, essential data have been continuously accumulated. However, effective data utilization requires trend analysis and causal analysis for a group of bridges. In this study, a method for determining factors affecting deterioration is established. The analysis is performed for concrete and steel bridges with Bayesian networks by utilizing data on bridge inspection and repair, and open data such as traffic census and rainfall. For concrete and steel bridges, the target members are the deck slab and main structural members, whereas the damage type is “Delamination/rebar exposure” and “corrosion,” respectively. The validity of the selected explanatory variables is verified by crossvalidation using separately prepared test data; evidently, the maximum damage rating prediction accuracy is 86%. Furthermore, the influencing factors extracted in this study are reasonable for the two damages, thus indicating the possibility of probabilistically extracting influencing factors for specific damages by Bayesian networks.

Catch-22: A patient’s right to informational determination and the rendering of accounts by medical schemes

Many people who have reached the age of majority still qualify as financial dependents of their parents, and may be registered as dependents on their parents’ medical schemes. This poses a practical conundrum, because major persons enjoy complete autonomy over their bodies to choose healthcare services as they please, including informational determination. However, their sensitive health information may end up being disclosed in the accounts rendered to their parents, as main members of medical schemes, thereby breaching their informational privacy, medical confidentiality and possibly also damaging personal relationships. On the other hand, medical schemes must ensure that they strictly manage the business of their hospitalisation to ensure that they can adhere to their contractual and legal medical insurance obligations. Both major but financially dependent patients and medical schemes have good legal grounds to defend their respective positions. In this article, we will analyse and clarify the applicable legal and ethical grounds by considering medical confidentiality, the Protection of Personal Information Act, the Consumer Protection Act and the Medical Schemes Act and rules. We shall conclude with recommendations to accommodate the interests of both parties.

Corroborating the autoptic identification of archeological glyptics in museum collections: The contribution of portable Raman spectroscopy

AbstractA collection of Hellenistic–Roman glyptics, kept at the Regional Archaeological Museum “Paolo Orsi” (Syracuse, Italy), was investigated in situ with portable Raman spectroscopy with the aim of assessing the viability of this approach, not only for the immediate identification of the gemstones but also for a more in‐depth successive data treatment. At the same time, a corroboration of the autoptic identification of the materials, both archeological and belonging to historical collections, was looked for in order to verify and potentially correct what reported in the museum catalogue. Actually, most of the identifications could be confirmed, the glyptics being mainly made of chalcedony. Other materials found were garnet, glass, and amber. The larger group of chalcedony Raman spectra was subjected to principal components analysis treatment that, after appropriate pretreatment, resulted successful in separating spectra with higher or lower contribution of the band due to the presence of moganite and SiOH bonds. The garnet spectra were instead subjected to quantitative study to identify the main end member. Both the quick identifications and the more detailed studies on chalcedonies and garnets were achieved thanks to the nondestructive and noninvasive investigation, directly in situ, with no sample preparation and minimal interference with the museum's activities.

Performance of single-bolted laminated flattened-bamboo connection with steel plate under compression parallel to grain – An experimental and numerical study

This paper investigated the mechanical performance of the bolted steel-laminated-flattened-bamboo (LFB)-steel connection under compression parallel to grain using experimental and finite element (FEM) methods, focusing on the bolt diameter and the thickness of the main member. Results showed that increasing the bolt diameter significantly enhanced the connection’s bearing capacity and initial stiffness. However, the strength of the connection no longer increased when the main member’s thickness exceeded 75 mm. Two ductile failure types were identified for the bolted steel-LFB-steel connection: bearing failure of the main member beneath the bolt and bending yield failure of the bolt. Based on Johansen’s yield theory, a theoretical calculation equation for the connection’s bearing capacity was proposed considering the transition of connection behaviour and the development of friction force between the main member and steel plate surface. A theoretical calculation equation for the load-slip curve of the bolted connection was proposed, assuming the strain of the LFB material beneath the bolt was linearly distributed, which could predict the behaviour in the elastic and yielding stage of the load-slip curve. Finally, another multilinear model for the load-slip curve was proposed based on the proposed theoretical equation and test results, which could better demonstrate the strengthening stage of the load-slip behaviour.

Fragility Analysis of Transmission Towers Subjected to Downburst Winds

A downburst is a typical local highly intensive wind all over the world, which is attributed to be the main cause of wind damage to transmission lines in inland areas worldwide. The collapse accidents of transmission towers under the downburst still occur every year. Therefore, it is of great significance to assess the safety of the transmission towers under downbursts. The motivation of the present study is to propose a fragility assessment method for transmission towers under the action of a downburst considering the uncertainty of wind-resistance capacity and the stochastic wind load effect. First, the downburst wind field of the transmission tower with different wind attack angles and different radial distances is simulated according to the mixed stochastic model. Then, random material characteristic samples are generated by the Latin hypercube sampling technique and applied to establish uncertain finite element models for transmission towers. Next, the static nonlinear buckling analysis is carried out by numerical methods to determine the ultimate capacity under the downburst wind load. The parameter analysis of different wind attack angles and radial distances between the downburst and the tower is conducted to determine the most unfavorable location of the maximum response. The failure mode of the transmission tower and the probabilities of the initial failure main members are summarized. Finally, the fragility curves of the transmission tower under the downburst and the atmospheric boundary layer (ABL) wind are compared. The results show that the maximum response is located at R = 1.6D. Most of the initial buckling members are located close to the first section of the tower. The fragility curves of the tower under the downburst are more dangerous than the ABL wind with the attack angle increasing from 0° to 90°. Furthermore, considering the probability model of intensity and direction of the downburst and based on the previous fragility analysis, the collapse probability of the transmission tower caused by the downburst is obtained. By probability analysis of the parameters, including layout conditions, different directions, and different wind speeds, it is found that the most favorable arrangement is 157.5°, and the most unfavorable arrangement is 112.5°.

Stiffened Hollow Structural Section Joints in Fire

This research examines the ability of stiffened Hollow Structural joints to withstand elevated temperatures when subjected to axial compressive loads on the brace. Extensive numerical simulations were conducted to assess the impact of geometrical factors in the main members and reinforcing plate on the fire resistance of SHS T-joints. The accuracy of the numerical models was verified by comparing them to existing test results. The findings demonstrate that the use of stiffener significantly enhances the ability of SHS T-joints to withstand elevated temperatures. The fire resistance of the reinforced joints primarily relied on the brace-to-chord width ratio and the reinforcing plate thickness to chord wall thickness ratio. However, increasing the reinforcing plate thickness beyond 1.5 times the chord wall thickness did not yield any beneficial effects on fire resistance. Additionally, factors such as half-width to thickness ratio of the chord, reinforcing length, and reinforcing type had negligible effects as long as they adhered to the required limit values based on Eurocode 3 EN 1993-1-8.

Effects of early postnatal hyperoxia exposure combined with early ovalbumin sensitization on lung inflammation and bacterial flora in a juvenile mouse model of asthma.

The aim of this study is to explore the effects of early postnatal hyperoxia exposure combined with early ovalbumin (OVA) sensitization on lung inflammation and bacterial flora in neonatal mice on a juvenile mouse model of asthma. Thirty-two newborn female C57BL/6 J mice were randomly divided into four groups, which including room air+phosphate-buffered saline (PBS) group, hyperoxia+PBS group, room air+OVA group, and hyperoxia+OVA group, according to the hyperoxia exposure and/or OVA induction. Mice were exposed to either 95% O2 or room air for 7 days after birth; after 7 days, they were exposed to air and received an intraperitoneal injection of OVA suspension or PBS solution on postnatal days 21 (P21) and 28 (P28). From P36 to P42, the mice were allowed to inhale of 1% OVA or 0.9% NaCl solution. The mice were observed after the last excitation. HE staining was performed to observe the pathological changes in lung tissues. Wright-Giemsa staining was used to perform bronchoalveolar lavage fluid (BALF) leukocyte sorting. Enzyme-linked immunosorbent assay was used to determined the cytokines levels of interleukin (IL)-2, IL-5, IL-13, IL-17A, and IL-10 and serum IgE levels in BALF. Additionally, 16S rRNA sequencing was used to analyze the characteristics of lung microbiota. Mice in the hyperoxia+OVA group showed asthma-like symptoms. HE staining results revealed a significant thickening of the airway wall and airway inflammation. BALF analysis of cellular components showed significant increases in total leukocyte and eosinophil counts and the levels of cytokines related to Th2 (IL-5 and IL-13) and Th17 (IL-17A); 16S rRNA sequencing revealed that the main members of the pulmonary microflora were Actinobacteriota, Proteobacteria, Firmicutes, and Bacteroidota at the phylum level. In addition, the bacteria with a major role were Acinetobacter and Moraxellaceae in the O2 + OVA group. The mouse suffering from postnatal hyperoxia exposure and early OVA sensitization, changes in symptoms, pathology, leukocyte and eosinophil counts, and levels of different T-cell cytokines in BALF and lung microbiota, which may provide a basis for the establishment of a juvenile mouse model of asthma.

Discontinuity of Three-Component Verbal Phrasal Units

Key words: one-word, polyword, classification by quantity, classification by syntactic ratio, proportionate and disproportionate, participial structure Discontinuity has become material of study in recent years. Before now interjections and introductory words, phrases and sentences have been largely studied, but the discontinuity of phrasal units hasn’t been studied yet. The constant dependence of components is the most common type of dependence among substantive phraseological units. The complete constancy of the components is by no means a mandatory feature of phraseological units. If a variant appears, the constant dependence can turn into a constant-variant one. Phraseological variants are identical in quality and quantity of meanings, as well as in stylistic and syntactic functions. If phraseological units with partially substituted components have the same number of meanings, but they do not completely coincide, differing in shade, figurativeness, stylistic orientation, the structural synonyms are formed. If the number of meanings does not match, with a partially different lexical composition, with a different figurative basis, even if there is a common meaning, it is not possible to talk about phraseological variation or structural synonymy. Such turns should be considered as independent phraseological units. In this article, we will consider discontinuity of three-component verbal phrasal units in two main ways: according to the principle of quantitative attribute and syntactic relation. Discontinuity of three-component verbal phrasal units often occurs with one interval. These may be one-word or polyword, which may or may not be members of the sentence. Discontinuity can perform the role of main and secondary members in the sentence. Phrasal units are rare with two intervals. In this case, intervals can be one-word or polyword, doing or not doing the position of a sentence member.

Cardioprotective effect of ultrasound-targeted destruction of Sirt3-loaded cationic microbubbles in a large animal model of pathological cardiac hypertrophy.

Pathological cardiac hypertrophy occurs in response to numerous increased afterload stimuli and precedes irreversible heart failure (HF). Therefore, therapies that ameliorate pathological cardiac hypertrophy are urgently required. Sirtuin 3 (Sirt3) is a main member of histone deacetylase class III and is a crucial anti-oxidative stress agent. Therapeutically enhancing the Sirt3 transfection efficiency in the heart would broaden the potential clinical application of Sirt3. Ultrasound-targeted microbubble destruction (UTMD) is a prospective, noninvasive, repeatable, and targeted gene delivery technique. In the present study, we explored the potential and safety of UTMD as a delivery tool for Sirt3 in hypertrophic heart tissues using adult male Bama miniature pigs. Pigs were subjected to ear vein delivery of human Sirt3 together with UTMD of cationic microbubbles (CMBs). Fluorescence imaging, western blotting, and quantitative real-time PCR revealed that the targeted destruction of ultrasonic CMBs in cardiac tissues greatly boosted Sirt3 delivery. Overexpression of Sirt3 ameliorated oxidative stress and partially improved the diastolic function and prevented the apoptosis and profibrotic response. Lastly, our data revealed that Sirt3 may regulate the potential transcription of catalase and MnSOD through Foxo3a. Combining the advantages of ultrasound CMBs with preclinical hypertrophy large animal models for gene delivery, we established a classical hypertrophy model as well as a strategy for the targeted delivery of genes to hypertrophic heart tissues. Since oxidative stress, fibrosis and apoptosis are indispensable in the evolution of cardiac hypertrophy and heart failure, our findings suggest that Sirt3 is a promising therapeutic option for these diseases. STATEMENT OF SIGNIFICANCE: Pathological cardiac hypertrophy is a central prepathology of heart failure and is seen to eventually precede it. Feasible targets that may prevent or reverse disease progression are scarce and urgently needed. In this study, we developed surface-filled lipid octafluoropropane gas core cationic microbubbles that could target the release of human Sirt3 reactivating the endogenous Sirt3 in hypertrophic hearts and protect against oxidative stress in a pig model of cardiac hypertrophy induced by aortic banding. Sirt3-CMBs may enhance cardiac diastolic function and ameliorate fibrosis and apoptosis. Our work provides a classical cationic lipid-based, UTMD-mediated Sirt3 delivery system for the treatment of Sirt3 in patients with established cardiac hypertrophy, as well as a promising therapeutic target to combat pathological cardiac hypertrophy.

Синтаксические функции инфинитива в современном эрзянском языке

The aim of the study is to identify the syntactic functions of the infinitive using the material of one of the Mordovian languages, Erzya. The paper presents the polyfunctionality of this indefinite verb form conditioned by the synthesis of verbal and substantive semes. The study is novel in that it is the first in Mordovian linguistics to describe in detail the syntactic role of the infinitive. As a result, it has been revealed that in the sentence, the infinitive, just like the noun, can perform the functions of all the members of the sentence that are, except for the predicate, unmorphologized. A number of syntactic functions of the infinitive have been commented on. It has been indicated that taking into account the syntactic use, the infinitive is divided into the independent type (the subject of a two-member sentence or the main member of a one-member verbal sentence) and the dependent type (a component of a compound verbal predicate, attribute, object, adverbial modifiers of various categories). It has been determined that the infinitive subordinate to a finite verb form can be a subject infinitive (denotes an action whose subject coincides with the subject of the finite verb form), an object infinitive (indicates an action (state) as the object of activity of someone or something that is not the subject) or a subject-object infinitive (indicates the subject that is the producer of an action that should not be carried out). It has been noted that the infinitive can occupy important communicative positions in the text, bringing emotional coloring to its content.