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Abstract Background The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Results Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Conclusions Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.

Background/Objectives: Tendon structure is predominantly composed of the extracellular matrix (ECM), and genetic variants in non-collagenous ECM components may influence susceptibility to tendinopathy. We investigated the potential influence of single nucleotide polymorphisms (SNPs) in fibrillin-2 (FBN2), tenascin-C (TNC), and matrix metalloproteinase-3 (MMP3) on the tendon regeneration failure phenotype and impact on the susceptibility to tendinopathy in Brazilian high-performance athletes. Methods: This case–control study was conducted with 397 high-performance athletes from different sports modalities (197 tendinopathy cases and 200 controls), and they were analyzed by validated TaqManTM SNP genotyping assays of the SNPs FBN2 (rs331079), TNC (rs2104772), and MMP3 (rs591058). Results: Out of the 197 tendinopathy cases, 63% suffered from chronic tendon pain and 22% experienced more than three episodes of disease manifestation. The TNC-rs2104772-A allele was significantly associated with tendinopathy (OR: 1.4; 95% CI: 1.1–1.8), while athletes carrying the MMP3-rs591058-T allele were linked to an increased risk of more episodes of disease manifestation (OR: 1.7; 95% CI: 1.1–2.8). The TNC-MMP3 tendon regeneration failure phenotype (TNC-A/MMP3-T) was associated with an increased risk of tendinopathy (OR: 1.4; 95% CI: 1.1–2.0) and episodes of disease manifestation (OR: 2.0; 95% CI: 1.2–3.5). Athletes with tendinopathy who had the TNC-A/MMP3-T interaction were more prone to experiencing more than three disease exacerbations (OR: 4.3; 95% CI: 1.8–10.5) compared to TNC-A/TNC-C. Conclusions: This study suggests that rs2104772 and rs591058 SNPs could be involved in the tendon regeneration failure phenotype and may influence the molecular mechanism related to the regulation of the tendon ECM during training workload. [ABSTRACT FROM AUTHOR]

Background: The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge. Results: Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including Pclo in dental follicle cells, Wnt10a in pre-odontoblasts, Fst and Igfbp2 in periodontal ligament cells, and validated the expression of Igfbp3 in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes Ptn and Satb2, while dental follicle cell differentiation is associated with the genes Tnc, Vim, Slc26a7, and Fgfr1. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene TNC was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar. Conclusions: Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration. [ABSTRACT FROM AUTHOR]

Consolidation with autologous hematopoietic stem cell transplantation (HSCT) has improved survival for patients with central nervous system tumors (CNSTs). The impact of the autologous graft CD34+ dose on patient outcomes is unknown. We wanted to analyze the relationship between CD34+ dose, total nucleated cell (TNC) dose, and clinical outcomes, including overall survival (OS), progression-free survival (PFS), relapse, non-relapse mortality (NRM), endothelial-injury complications (EIC), and time to neutrophil engraftment in children undergoing autologous HSCT for CNSTs. A retrospective analysis of the CIBMTR database was performed. Children aged 3.6×106/kg CD34+ cells experienced superior PFS (p = .04) and OS (p = .04) compared to children receiving ≤3.6 × 106/kg. Relapse rates were lower in patients receiving >3.6 × 106/kg CD34+ cells (p = .05). Higher CD34+ doses were not associated with increased NRM (p = .59). Stratification of CD34+ dose by quartile did not reveal any statistically significant differences between quartiles for 3-year PFS (p = .66), OS (p = .29), risk of relapse (p = .57), or EIC (p = .87). There were no significant differences in patient outcomes based on TNC, and those receiving a TNC >4.4 × 108/kg did not experience superior PFS (p = .26), superior OS (p = .14), reduced risk of relapse (p = .37), or reduced NRM (p = .25). Children with medulloblastoma had superior PFS (p < .001), OS (p = .01), and relapse rates (p = .001) compared to those with other CNS tumor types. Median time to neutrophil engraftment was 10 days versus 12 days in the highest and lowest infused CD34+ quartiles, respectively. For children undergoing autologous HSCT for CNSTs, increasing CD34+ cell dose was associated with significantly improved OS and PFS, and lower relapse rates, without increased NRM or EICs.

Abstract Background Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

China’s hop market and its development have a significant impact on China’s beer market. As a world leader in beer production, China pays considerable attention to the production of hops of the appropriate quality and quantity, taking into account international requirements to increase exports in the future. The formation of the hop production infrastructure was carried out in several stages. The current stage is characterized by the presence of both Chinese companies, joint ventures and representative offices of major multinational companies that import hops into the territory of the People’s Republic of China. The number of farms and areas of hop production have been changing over the past 10 years, and the main hop growing areas are Gansu and Xinjiang Autonomous Region. The economic entities grow Chinese varieties of hops, and the main variety in terms of planting area is Tsingtao Flower. Hop cultivation is carried out under the influence of administrative decisions of local authorities of the People’s Republic of China as well as national and global trends in the hop and beer markets. Despite the functioning of world leaders in hop production on the territory of the People’s Republic of China, problematic issues do not allow to improve the quality of grown hops to ensure the domestic market, which requires the import of hops from Germany, the Czech Republic, and the USA.

Background: Chronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM. Methods: A mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated. Results: Repeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE. Conclusion: EE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM. [ABSTRACT FROM AUTHOR]

Nitrogen is one of the critical factors in water pollution and eutrophication, so applying the deep learning method in remote sensing inversion of nitrogen can provide basic information for environmental management. This paper proposes a two-step feature extraction method to solve the problem that the number of bands in water quality inversion is insufficient and the deep learning method cannot be fully exploited. Firstly, manual feature extraction is completed through the fusion between bands to obtain a set of high-latitude shallow factors, which make the features rich and diverse. Then, a one-dimensional convolutional residual network (ResNet-1D) is constructed, and the deep features are automatically extracted through convolution operations of the model, where the residual learning is used to reduce the training difficulty. The full connection is established through depth features. The comparison of models shows that the Mean Relative Error (MRE) is decreased by at least 10% in both test and validation datasets. Finally, the spatiotemporal distribution of total nitrogen concentration (TNC) in the coastal waters of Shandong is explored. In general, the spatial distribution is that the concentration near the coast is higher than the far. The temporal variation is that the monthly mean of the TNC is low in March, moderate in May and August, and high in October; the annual average value of TNC is 0.3mg/L, which has decreased slightly year by year since 2014. [ABSTRACT FROM AUTHOR]

The effects of meat pH on muscle fiber characteristics, cortisol level, and Tenascin C (TNC) gene expression were examined. The muscle samples (n=100) were randomly collected from the Longissimus thoracis et lumborum (LTL) to determine meat pH at 24 hours (meat pH24h) postmortem. Muscle samples (five samples per group) with divergent meat pH levels (low versus high) were selected to study muscle fiber characteristics and mRNA expression based on quantitative real-time polymerase chain reaction (qRT-PCR). Blood samples (five samples per group) of the two meat pH levels were taken for serum cortisol analysis. The results showed that there was no significant differences between the groups for the muscle fiber characteristics of total number of fibers, muscle fiber diameter, cross-section area, perimysium thickness, and endomysium thickness. Different meat pH24h values did not affect the cortisol level. The mRNA expression of the TNC gene was significantly (p<0.05) downregulated in the low meat pH24h group compared to the high meat pH24h group. In conclusion, meat pH24h was unrelated to the cortisol level and muscle fiber characteristics. However, the TNC gene might play a role in meat pH24h in pigs. [ABSTRACT FROM AUTHOR]

The article notes that in the context of globalization, multinational corporations exert an increasing influence on the economies of their home countries, host countries, and the overall state of international economic relations. The authors underline that tax planning is one of the TNC activities that grabs attention of the global public in terms of both its favorable and unfavorable effects. The article offers its own definition of the term «tax landscape», in which, unlike the existing ones, vertical, horizontal and temporal aspects are distinguished. The vertical aspect is presented as a synthesis of the supranational level of taxation and the national one; horizontal, as a system of tax rules and laws within a separate state; temporal, as a change in the main elements of taxation over time. It has been proven that at the current stage of formation of tax landscapes to characterize the supranational level, it is necessary to take into account the elements of taxation defined as part of the implementation of the international BEPS project: the global minimum tax, tax rates for surplus profits, and surplus profits as an object of taxation. The authors have been able to divide the studied countries into three groups depending on the level of direct taxation: high (United States, Canada and Australia), moderate (Great Britain, France, Italy, India, Germany and Switzerland), and low (China and Saudi Arabia). The first group (the United States) and the second group (the United Kingdom, Germany, France, Switzerland, and Italy) have been found to have the greatest tax losses as a result of «tax havens.» The level of direct taxation (profit and capital) in the countries of registration and countries of digital presence, the volatility of tax legislation, and compliance with the conditions of tax justice have been proposed as factors of the tax landscape to be taken into account by transnational corporations when developing tax planning strategies.

The article notes that in the context of globalization, multinational corporations exert an increasing influence on the economies of their home countries, host countries, and the overall state of international economic relations. The authors underline that tax planning is one of the TNC activities that grabs attention of the global public in terms of both its favorable and unfavorable effects. The article offers its own definition of the term «tax landscape», in which, unlike the existing ones, vertical, horizontal and temporal aspects are distinguished. The vertical aspect is presented as a synthesis of the supranational level of taxation and the national one; horizontal, as a system of tax rules and laws within a separate state; temporal, as a change in the main elements of taxation over time. It has been proven that at the current stage of formation of tax landscapes to characterize the supranational level, it is necessary to take into account the elements of taxation defined as part of the implementation of the international BEPS project: the global minimum tax, tax rates for surplus profits, and surplus profits as an object of taxation. The authors have been able to divide the studied countries into three groups depending on the level of direct taxation: high (United States, Canada and Australia), moderate (Great Britain, France, Italy, India, Germany and Switzerland), and low (China and Saudi Arabia). The first group (the United States) and the second group (the United Kingdom, Germany, France, Switzerland, and Italy) have been found to have the greatest tax losses as a result of «tax havens.» The level of direct taxation (profit and capital) in the countries of registration and countries of digital presence, the volatility of tax legislation, and compliance with the conditions of tax justice have been proposed as factors of the tax landscape to be taken into account by transnational corporations when developing tax planning strategies. [ABSTRACT FROM AUTHOR]

The Mobility on Demand (MOD) Sandbox Demonstration Program provides a venue through which integrated MOD concepts and strategies, supported through local partnerships, are demonstrated in real-world settings. For the 11 MOD Sandbox Demonstration projects, an independent evaluation was conducted that includes an analysis of project impacts from performance measures provided by the project partners and an assessment of the business models used. This document presents the results from the independent evaluation of the Dallas Area Rapid Transit (DART) First and Last Mile Solution MOD Sandbox Demonstration project. Evaluated were hypotheses that explored project impacts on travel behavior, user experiences, first and last mile to public transit accessibility, service quality for passengers with disabilities, and costs. The project improved first and last mile connectivity to DART transit, increased satisfaction among DART transit users, enhanced service for passengers with disabilities, and increased the geographic scope of DART transit service in the Plano area. In addition, wait and travel times for passengers with and without disabilities reflected similar distributions. The subsidy per rider of GoLink services was lower than the low-ridership fixed-route transit services that it replaced in Plano, but it was not lower than the subsidy for DART fixed-route transit in the overall Dallas region. DART project team members were interviewed to better understand challenges, barriers, successes, and broader lessons learned from the project, representing agency personnel from the offices of Innovation, Service Planning, Scheduling, Paratransit Operations, and Marketing. Lessons learned revealed the importance of having pre-planned, ready-to-go projects with committed partners, flexible contracting terms, metrics for adjusting spatial and temporal service coverage (including terminating service if appropriate), vehicle right-sizing, and understanding customer needs.

Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. Caveolin-1 (CAV1) is a protein that in breast cancer increases with disease progression. Extracellular vesicles (EVs) from breast cancer cells with CAV1 also contain Tenascin C (TNC) protein, but the importance of TNC remained to be defined. EVs were identified by size, microscopy and protein analysis. The effects of EVs on breast cancer cells were studied using cells and experiments in animals. CAV1 expression promotes TNC inclusion into EVs, which increased the aggressiveness of recipient breast cancer cells. In animals, only EVs with TNC increased features associated with cancer spread, while EVs lacking TNC reduced tumor growth. [ABSTRACT FROM AUTHOR]

Thirty years after the passage of the Americans with Disabilities Act, people with disabilities still face significant barriers to transportation access. Nearly one-third of disabled people describe inadequate transportation as a problem in their lives, and many major transportation systems have large accessibility gaps. In the San Francisco Bay Area, home to Silicon Valley and the 2010s tech boom, new mobility services are particularly widespread. TNCs, for example, make up approximately 25% of peak-hour traffic in Downtown San Francisco. San Francisco also has a well-established bike-share system and was among the first cities in the country to see hundreds of scooters on its streets and sidewalks. In light of the prevalence of these services and the significant transportation needs of the disability community, this project examines perceptions of new mobility among disabled people in San Francisco and makes recommendations for improving transportation access for people with disabilities.

Laccases are industrially relevant enzymes. However, their range of applications is limited by their functioning and stability. Most of the currently known laccases function in acidic conditions at temperatures below 60 °C, but two-domain laccases (2D) oxidize some substrates in alkaline conditions and above 70 °C. In this study, we aim to establish the structural factors affecting the alkaline activity of the 2D laccase from Streptomyces griseoflavus (SgfSL). The range of methods used allowed us to show that the alkaline activity of SgfSL is influenced by the polar residues located close to the trinuclear center (TNC). Structural and functional studies of the SgfSL mutants Met199Ala/Asp268Asn and Met199Gly/Asp268Asn revealed that the substitution Asp268Asn (11 Å from the TNC) affects the orientation of the Asn261 (the second coordination sphere of the TNC), resulting in hydrogen-bond-network reorganization, which leads to a change in the SgfSL-activity pH profile. The combination of the Met199Gly/Arg240His and Asp268Asn substitutions increased the efficiency (kcat/KM) of the 2,6-DMP oxidation by 34-fold compared with the SgfSL. Our results extend the knowledge about the structure and functioning of 2D laccases' TNC active sites and open up new possibilities for the directed engineering of laccases. [ABSTRACT FROM AUTHOR]

We evaluate the impact of three proposed regulations of transportation network companies (TNCs) like Uber, Lyft and Didi: (1) A minimum wage for drivers, (2) a cap on the number of drivers or vehicles, and (3) a per-trip congestion tax. The impact is assessed using a queuing theoretic equilibrium model which incorporates the stochastic dynamics of the app-based ride-hailing matching platform, the ride prices and driver wages established by the platform, and the incentives of passengers and drivers. We show that a floor placed under driver earnings can push the ride-hailing platform to hire more drivers and offer more rides, at the same time that passengers enjoy faster rides and lower total cost, while platform rents are reduced. Contrary to standard competitive labor market theory, enforcing a minimum wage for drivers benefits both drivers and passengers, and promotes the efficiency of the entire system. This surprising outcome holds for almost all model parameters, and it occurs because the wage floor curbs TNC labor market power. In contrast to a wage floor, imposing a cap on the number of vehicles hurts drivers, because the platform reaps all the benefits of limiting supply. The congestion tax has the expected impact: fares increase, wages and platform revenue decrease. We also construct variants of the model to briefly discuss platform subsidy, platform competition, and autonomous vehicles.

We evaluate the impact of three proposed regulations of transportation network companies (TNCs) like Uber, Lyft and Didi: (1) A minimum wage for drivers, (2) a cap on the number of drivers or vehicles, and (3) a per-trip congestion tax. The impact is assessed using a queuing theoretic equilibrium model which incorporates the stochastic dynamics of the app-based ride-hailing matching platform, the ride prices and driver wages established by the platform, and the incentives of passengers and drivers. We show that a floor placed under driver earnings can push the ride-hailing platform to hire more drivers and offer more rides, at the same time that passengers enjoy faster rides and lower total cost, while platform rents are reduced. Contrary to standard competitive labor market theory, enforcing a minimum wage for drivers benefits both drivers and passengers, and promotes the efficiency of the entire system. This surprising outcome holds for almost all model parameters, and it occurs because the wage floor curbs TNC labor market power. In contrast to a wage floor, imposing a cap on the number of vehicles hurts drivers, because the platform reaps all the benefits of limiting supply. The congestion tax has the expected impact: fares increase, wages and platform revenue decrease. We also construct variants of the model to briefly discuss platform subsidy, platform competition, and autonomous vehicles.

Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. Although recent studies have shed insights on the potential causes of male infertility, its underlining mechanisms still remain to be elucidated. We developed a Mrkn2 knockout mice model to study this gene and found that deletion of Mkrn2 in mice led to male infertility. Interestingly, the expression level of signal transducer and activator of the transcription (STAT)1 was significantly decreased in MKRN2 knockout testis and MEF cells. Co-IP assay showed an interaction between MKRN2 and STAT1. Moreover, our results further indicated that MKRN2 regulated the expression level of SIX4 and tenascin C (TNC) via the EBF transcription factor 2 (EBF2) in mice. The results of our study will provide insights into a new mechanism of male infertility. [ABSTRACT FROM AUTHOR]

Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site "A" to "T", and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI. [ABSTRACT FROM AUTHOR]

The purpose of the article is to analyze the specific modern features of the transformation of the knowledge component of TNC. The methodological basis of the articles can be described by the variety of methods, such as comparative and synthesis methods, methods of abstract logical evaluation, system approaches, methods of detailing, groupings and generalizations, logic analysis, paired and multiple correlation techniques. The scientific-theoretical principles of building up the intellectual capital of TNCs, which are expressed in the concentration of technological priorities, the development and implementation of innovations, technologies, business models, and the formation of a holistic knowledge management system, are analyzed. Levels of knowledge utilization of TNCs are determined. The strategic vision of the TNC in the paradigm of the knowledge economy has been developed. The substantiated role of the intellectual component in the process of forming the competitive potential of TNCs, which is based on the identification of the latest features of corporate knowledge, which serve as a determining factor of economic growth, being in various forms of its manifestation: as a resource embodied (materialized) in technologies and equipment; as a constituent element of human capital, which interacts with the subjects' existing skills, experience, ability to reproduce and update knowledge, use it in their activities; as newly created knowledge, which is the result of research, development and other types of scientific activity of a fundamental and applied nature; as new goods that further contribute to the formation of new markets. The main theoretical and methodological provisions of the development of the knowledge component are formulated, the determinants of the formation of a new knowledge paradigm of TNCs are determined, and recommendations are provided for the strategic development of TNCs in the knowledge economy can be used by scientists, teachers, students, and economists who deal with the issues of the influence of the knowledge component on the development of TNCs. [ABSTRACT FROM AUTHOR]

Abstract Background Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. Methods Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. Results Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie’s gender and birth weight have a positive correlation with CB TNC content. The babie’s birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie’s, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie’s, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B. Conclusion This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries.

The purpose of the article is to analyze the specific modern features of the transformation of the knowledge component of TNC. The methodological basis of the articles can be described by the variety of methods, such as comparative and synthesis methods, methods of abstract logical evaluation, system approaches, methods of detailing, groupings and generalizations, logic analysis, paired and multiple correlation techniques. The scientific-theoretical principles of building up the intellectual capital of TNCs, which are expressed in the concentration of technological priorities, the development and implementation of innovations, technologies, business models, and the formation of a holistic knowledge management system, are analyzed. Levels of knowledge utilization of TNCs are determined. The strategic vision of the TNC in the paradigm of the knowledge economy has been developed. The substantiated role of the intellectual component in the process of forming the competitive potential of TNCs, which is based on the identification of the latest features of corporate knowledge, which serve as a determining factor of economic growth, being in various forms of its manifestation: as a resource embodied (materialized) in technologies and equipment; as a constituent element of human capital, which interacts with the subjects' existing skills, experience, ability to reproduce and update knowledge, use it in their activities; as newly created knowledge, which is the result of research, development and other types of scientific activity of a fundamental and applied nature; as new goods that further contribute to the formation of new markets. The main theoretical and methodological provisions of the development of the knowledge component are formulated, the determinants of the formation of a new knowledge paradigm of TNCs are determined, and recommendations are provided for the strategic development of TNCs in the knowledge economy can be used by scientists, teachers, students, and economists who deal with the issues of the influence of the knowledge component on the development of TNCs.

Accumulating studies have demonstrated that hyperbaric oxygen (HBO) treatment alleviates spinal cord injury (SCI). However, the underlying mechanism by which HBO alleviates SCI remains to be elucidated. In this study, we performed genome-wide transcriptional profiling of the spinal cord between SCI mice and mice that received HBO treatment by high-throughput RNA sequencing at 1 week after SCI. We also compared genome-wide transcriptional profiles from SCI mice and sham-operated mice. We found 76 differentially co-expressed genes in sham-operated mice, SCI mice, and HBO-treated SCI mice. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, we identified the biological characteristics of these differentially expressed genes from the perspectives of cell component, biological process, and molecular function. We also found enriched functional pathways including ferroptosis, calcium signaling pathway, serotonergic synapse, hypoxia-inducible factor-1 signaling pathway, cholinergic synapse, and neuroactive ligand-receptor interaction. We performed quantitative reverse transcription-polymerase chain reaction and validated that HBO treatment decreased the expression of Hspb1 (heat shock protein beta 1), Hmox1 (heme oxygenase 1), Ftl1 (ferritin light polypeptide 1), Tnc (tenascin C) and Igfbp3 (insulin-like growth factor binding protein 3) and increased the expression of Slc5a7 (solute carrier family 5 choline transporter member 7) after SCI. These results revealed the genome-wide transcriptional profile of the injured spinal cord after HBO treatment. Our findings contribute to a better understanding of the mechanism by which HBO treats SCI and may provide new targets for SCI intervention.

The role of ridesourcing services on vehicle ownership is an important research area, especially in the context of the environmental implications and long term sustainability of these services. However, evidence from literature so far is mixed, with studies reporting both an increase and reduction in ownership, sometimes in the same country. This research adds to the current knowledge by econometrically estimating the impacts of ridesourcing services on vehicle ownership in a large emerging economy, India. Using a cross-sectional timeseries data on vehicle registrations in 18 large cities in India over 17 years, we find a statistically significant reduction in vehicle ownership (compared to baseline) since the introduction of these services. The growth in vehicle ownership has reduced by around 7.7% in the cities together since the introduction of ridesourcing services and this impact appears to grow over time; but the overall ownership is still increasing.

Abstract Background Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. Case presentation A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. Conclusions We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP.

Ride-hailing services have gained popularity in recent years due to attributes such as reduced travel costs, traffic congestion, and emissions. However, with the impact of COVID-19, the ride-hailing market is estimated to lose its fair share of an uprising as a transportation mode. During normal and critical circumstances, ride-hailing service users express their concerns, habits, and emotions through posting on social platforms such as Twitter. Hence, Twitter, as an emerging data source, is an effective and innovative digital platform to observe the rider’s behavior in ride-hailing services. This study hydrates large-scale Twitter reactions related to shared mobility to perform comparative sentiment and emotion analysis to understand the impact of COVID-19 on transportation network services in pre-pandemic and during pandemic conditions. Amid pandemic, negative tweets (34%) associated with ‘sad’ (15%) and ‘anger’ (15%) emotions were most prevalent in the dataset.

Background: Glioblastoma multiforme (GBM) is a common malignant brain tumor with high mortality. It is urgently necessary to develop a new treatment because traditional approaches have plateaued. Purpose: Here, we identified an immune-related gene (IRG)-based prognostic signature to comprehensively define the prognosis of GBM. Methods: Glioblastoma samples were selected from the Chinese Glioma Genome Atlas (CGGA). We retrieved IRGs from the ImmPort data resource. Univariate Cox regression and LASSO Cox regression analyses were used to develop our predictive model. In addition, we constructed a predictive nomogram integrating the independent predictive factors to determine the one-, two-, and 3-year overall survival (OS) probabilities of individuals with GBM. Additionally, the molecular and immune characteristics and benefits of ICI therapy were analyzed in subgroups defined based on our prognostic model. Finally, the proteins encoded by the selected genes were identified with liquid chromatography-tandemmass spectrometry and western blotting (WB). Results: Six IRGs were used to construct the predictive model. The GBM patients were categorized into a high-risk group and a low-risk group. High-risk group patients had worse survival than low-risk group patients, and stronger positive associations with multiple tumor-related pathways, such as angiogenesis and hypoxia pathways, were found in the high-risk group. The high-risk group also had a low IDH1 mutation rate, high PTEN mutation rate, low 1p19q co-deletion rate and low MGMT promoter methylation rate. In addition, patients in the high-risk group showed increased immune cell infiltration, more aggressive immune activity, higher expression of immune checkpoint genes, and less benefit from immunotherapy than those in the low-risk group. Finally, the expression levels of TNC and SSTR2 were confirmed to be significantly associated with patient prognosis by proteinmass spectrometry and WB. Conclusion: Herein, a robust predictive model based on IRGs was developed to predict the OS of GBM patients and to aid future clinical research. [ABSTRACT FROM AUTHOR]

Background: Cord blood plays a very important role in stem cell transplantation and therapy with an emerging implication also in regenerative medicine. The number of cells available in a single cord blood unit (CBU), in particular, the CD34+ and total nucleated cell (TNC) content influences the transplantation clinical outcome. We analysed a very large series of CBUs, collected for private banking without any specific volume restriction, to deeply investigate the best predictors of cord blood stem cells content. Methods: Maternal and neonatal clinic laboratory data of a total 2583 UCBs were obtained from the InScientiaFides cord blood bank based in Republic of San Marino. Univariate and multivariate analysis were conducted to better interpret the data and to build a predictive model to select, the CBU with high CD34+ content. Results: Our univariate analysis shows that seasonality and the geographical area affects the quality of umbilical cord blood. Gestational age, babie's gender and birth weight have a positive correlation with CB TNC content. The babie's birth weight affects positively also CD34+ content and CBU volume while the cesarean delivery affect the CB volume only. Our predictive model, based on multivariate analysis, shows that male babie's, gestational age lower to 39 weeks, cesarean delivery and CBUs with a content of TNC higher than 3.44 × 108 (group A) have a significant higher CD34+ content than group B (female babie's, gestational age higher than 39 weeks and vaginal delivery). The group A have a 37.5% of CBUs with a concentration of CD34+ > 2 × 106, while no CBUs with high concentration of CD34+ were detect in group B. Conclusion: This study, conducted on a very large series of CBUs without any specific volume constraint, highlighted the prenatal and maternal factors that significantly influence the quality of the CBU collected. Specifically, it highlights that volume is not the best predictor of CD34+ CBU content; for this reason it cannot be taken into consideration alone for the analysis of the collected samples. Our final aim is to identify relevant factors, immediately available, that help to choice UCB with high CD34+ cell content, especially in simultaneous deliveries. [ABSTRACT FROM AUTHOR]

Why does the Chinese economic modernization strategy include transnationalization of Chinese enterprises, the creation of numerous Small and Medium Foreign Affiliates (SMFAs)? The research hypothesis suggests that in the context of globalization, modernization requires influencing other participants in the global economy beyond national borders. SMFAs are able to transform the structure of the economy of the PRC and host countries to ensure demand for national innovations and highly skilled labor. The literature review highlights the challenges of modernizing the national economy in the context of globalization, as well as the advantages of TNCs and participation in global value chains (GVCs). However, the question of the connection between catchup development and transnationalization of local business, especially small and medium-sized ones, has been understudied. The novelty of the study is in the analysis of the sectoral and geographical structure of the foreign activities of Chinese TNCs and the analysis of the problems of the participation of Chinese TNCs in Western global value chains (GVCs). The main findings reveal that the creation of SMFAs is a response to the challenges of globalization, which impede the modernization of the Chinese economy. Powerful state support to SMFAs makes them dependent, and thus the government is able to direct the goals of private enterprises in accordance with the national interests. The major field of Chinese SMFAs is the promotion of products manufactured in the PRC in the American and European markets, and it contributes to the development of the national innovation system, redistributes the added value in favor of national manufacturers, and stimulates the development of hightech industries of the PRC. In developing countries SMFAs are represented by trade and manufacturing outlets within the “Belt and Road Initiative” They come after the infrastructural projects of large business, grouped in clusters, have strong coordination with other Chinese TNCs, and create Chinese GVCs. The main role of Chinese SMFAs in the modernization of the PRC economy is to ensure national interests, including industrial sovereignty and the growth of wellbeing of citizens as the basis of innovative demand. In the modern international labor division, this is achieved by a shift to high valueadded operations, accompanied by a struggle for the markets of developed countries and for sites for the low valueadded operations inside Chinese GVCs in developing countries.

Introduction: Osteoporosis is one of the main causes of bone fractures in old age. The examination of osteoporosis in the elderly is very complicated due to the heterogeneity of the aging process. This study aimed to investigate the correlation of the TNC gene in the patients with an inherited and very rare osteoporosis syndrome. The importance of this study was the identification of a specific biomarker for the osteoporosis process in a monogenic disease. Methods: In this case-control study, the patients with Osteogenesis Imperfecta were used as a simple and monogenic model to investigate the possibility of TNC gene role in osteoporosis. For this purpose, TNC protein network and its related biological pathways were firstly evaluated by bioinformatic analysis. Then, skin biopsies were taken from 3 patients with inherited osteoporosis syndrome called Osteogenesis Imperfecta and two healthy individuals. After culturing the biopsy, fibroblast cells were isolated from keratinocyte cells. Then, the total RNA of each sample was extracted from two different passages and cDNA was synthesized. Subsequently, the expression of TNC gene was measured by Real-time PCR in healthy and patient cells using various replicates. Results: TNC network proteins are significantly associated with the biological pathways involved in the ossification process. The expression of the TNC gene was assessed in wild type and patient cells. Finally, our results confirmed a significant increase in the expression of TNC in the patients’ compared to wild types’ cells by using technical and biological replicates (p:0.005, p:0.007) and Student t-test. In this study, Excel and GraphPad Prism 5.0 software (GraphPad Software, Inc., San Diego, CA) were used. Conclusion: Increased expression of TNC gene in a monogenic osteoporosis syndrome can indicate the potential role of this gene in the process of bone loss and introduce this gen as a new biomarker for osteoporosis. The study on rare Osteogenesis Imperfecta syndrome is a simple and monogenic model to investigate the heterogeneous osteoporosis. Therefore, the expression of the candidate gene needs to be evaluated and confirmed in an appropriate statistical population composed of patients with osteoporosis.

Review of the book:Graz, J.-C. The Power of Standards. Hybrid Authority and the Globalization of Services.CambridgeUniversityPress, 2019. 268 p.

The article is aimed at researching the peculiarities of development of Japan’s high-tech TNCs in the context of globalization and obtaining a coherent picture of the historical, organizational, innovation-technological features of the development of TNCs. The task of the research is analyzing and evaluating the historical, organizational, innovation-technological features of development of Japanese TNCs on the example of Toyota Motor Corporation. It is specified that for the rapid technological growth of transnational companies and the country as a whole, Japanese entrepreneurs have accumulated and reinvested profits exclusively in the sphere of scientific development and innovation. Continued development and research of the above mentioned spheres will provide leadership in a globalized society. The authors research one of the largest Japanese TNCs, Toyota Motor Corporation, successfully active in the automotive industry. The emphasis is placed on the fact that the main feature of the company is the huge costs of research and development, cooperating with startups, while this cooperation be called the exception rather than the rule. Innovations occur on the basis of continuous improvement through training. Improving quality, problem-solving comes at the expense of working groups. However, Toyota’s significant secrecy of organizational culture reduces the ability to be institutionally flexible when problems needs a quick solution. It is concluded that with a reliable public-private partnership Japanese companies, investing in research and development of foreigners, improved them and produced a new technological product, which allowed them to a rapid growth.

In 2015, Los Angeles increased the minimum wage to one of the highest in the country, leading the way to boost stagnating pay for workers and to ensure that workers are able to earn enough to support themselves and their families. Los Angeles needs to take the same care to ensure quality employment within the taxi industry, particularly in light of the rapid growth of transportation networking companies (TNCs) such as Uber and Lyft into Los Angeles.TNCs are on-demand ride services where unlicensed individuals use their personal vehicles as for-hire vehicles. These companies have constructed an app-based ridesharing model that is having a major impact on the taxi industry in regards to income for taxi drivers, revenue for cab companies, and the local economy. TNCs are receiving praise for their innovation and their rapid growth is changing the way we do work. Yet these changes inevitably signal a business model shift that has a widespread and dramatic impact on workers in Los Angeles and nationwide. It is important to further evaluate and research how this business model will impact Los Angeles workers and the future of quality jobs in the city.

Today the modern world is on the verge of a redistribution of transnational corporations, which compete with each other for new spheres of influence, markets of production and outlet, technology and maximum possible profits. Globalization and internationalization of production and capital, privatization, the creation of world political and economic associations, and the liberalization of trade have placed them at the center of modern economic development. The article reveals the issues of personnel management development in transnational corporations of the world economy. On the basis of the research theoretically and practically grounded theoretical and methodological approach to the organization of activities of transnational corporations in the globalization processes of the economy. The practical significance of ways and forms of organization of activities of transnational corporations in ensuring the development of international production, sales, trade and financial complex with a single decision-making center in the host country with its branches, representative offices and subsidiaries is analyzed. Research shows that transnational corporations have an important function in the development of the modern world economy. They directly affect the economies of recipient countries, accelerate the internationalization of economic life, as well as the scientific and technological process. Attracting foreign direct investment gives a country access to the financial resources of TNCs, as well as facilitates its integration into global economic processes and access to foreign markets. Transnational capital has created a new system of international relations, which has led to the formation of supranational institutions of governance. In addition, TNCs are actively influencing the processes of globalization. This article discusses the risks associated with the personnel of TNCs and the ways of economic and social protection of employees. In recent years, the international labour market has used the social package as a form of remuneration for work, which should be broadly understood as the employer's provision of material benefits in the form of fringe benefits, compensation, privileges and social guarantees. The social package can be implemented with the help of existing legislative mechanisms, such as contractual regulation of collective labour relations, normative regulation of labour in local legal acts of business entities, the written form of the employment contract.

Objective To construct human TNC expression plasmid for the investigation of the role of TNC in pancreatic cancer metastasis by using pancreatic cancer cell strain with stable over-expression of TNC. Methods TNC expression plasmid was constructed by unique primer design method, and then pancreatic cancer cell strain PANC1 with stable TNC expression were obtained by transfection and G418 screening. RT-qPCR and Western blot examined the expression of TNC. Transwell and Western blot were used to detecte the effects of TNC on cell migration, invasion and EMT-related molecules. Results TNC plasmid was successfully constructed. TNC promoted cell migration and invasion(P＜0.05), decreased epithelial marker E-cadherin expression and upregulated mesenchymal marker N-cadherin expression (P＜0.05). Conclusions The TNC expression plasmid and TNC stable expression pancreatic cancer cell strain may be used to explore the biological function of TNC and the pathogenesis of pancreatic cancer.

Stanislav Zakharovich Zhiznin is the founder of energy diplomacy in Russia and in the world, the author of the term “energy diplomacy”, a leading Russian expert on energy policy, diplomacy and international energy security. Prof. Zhiznin published first Russian textbook on energy diplomacy and many monographs on energy diplomacy, in Russian, English, and Chinese [Zhiznin 2005]. S.Z. Zhiznin graduated from the Kharkiv Aviation Institute in 1969 with a degree in electrical engineering, then - from the Diplomatic Academy of the USSR Ministry of Foreign Affairs in 1977 with a degree in international economic relations. In 1998 he defended his Candidate’s thesis on the issue “Energy diplomacy of Russia at the turn of the 20th - 21st centuries (foreign economic aspects)”, and in 2001 - his Doctor’s dissertation on “Strategic interests of Russia in world energy” and became a Doctor of Science (Economics). He has been working in the Ministry of Foreign Affairs of the Russian Federation since 1977. S. Zhiznin has a Diplomatic Rank of 1st Class Counsellor. Until the end of 2010, he was the chief adviser to the Department of Economic Cooperation of the Russian MFA. S. Zhiznin is currently a professor at the Department of International Dimension of Fuel and Energy Industry named after N.P. Laverov, MGIMO. He contributed to the development of the information materials for the Russian delegation for the meetings of G8 (now G7), OPEC, IEA, Gas Exporting Countries Forum, International Energy Forum, APEC, etc. S.Z. Zhiznin is the President of the Center for Energy Diplomacy and Geopolitics, established in 2003 with the participation of the Union of Oil & Gas Producers of Russia and support of the Russian MFA. In 2011, he became an OSCE expert on energy diplomacy and energy security. The interview presents the formation of energy diplomacy as a science, covers the evolution of the concept of “energy diplomacy”, discusses the energy factor influence on the policies of Russia and other countries, analyses the role of TNCs in shaping the state’s energy policy. Energy diplomacy, as S.Z. Zhiznin points out, is a complex symbiosis of economics, geopolitics, and technological sciences; so, research in energy diplomacy is inextricably linked with these sciences. At present, energy diplomacy is being heavily influenced by the technology development, which makes states take into account this factor while forming their energy strategies.

Background: Dermatofibrosarcoma protuberans (DFSP) is a superficial fibroblastic tumor characterized by high rate of local recurrence and low metastatic potential. Fibrosarcomatous transformation can rarely arise in DFSP either de novo or as recurrent, which represents a form of tumor progression and carries an increased risk of metastasis over classic DFSP. Cytogenetically, DFSP is characterized by a recurrent unbalanced chromosome translocation t (17;22)(q22;q13), leading to the formation of COL1A1-PDGFB fusion transcript that is present in more than 90% of cases. Alternative fusions involving the PDGFD with partners of COL6A3 or EMILIN2 have recently been documented in less than 2% of cases. Herein, we report a DFSP with fibrosarcomtous morphology harboring a novel TNC-PDGFD fusion. Case presentation: A 54-year-old female presented with a slowly growing mass in the right thigh. Excision demonstrated a 2-cm ovoid, well-circumscribed, gray-white, mass. Microscopic examination revealed a partially encapsulated subcutaneous nodule without dermal connection. The neoplasm was composed of cellular and fairly uniform spindle cells with brisk mitoses, arranged in elongated fascicles and herringbone patterns, with focal collagenized stroma. The neoplastic cells were positive for CD34 and smooth muscle actin. Fluorescence in-situ hybridization analyses showed negative for COL1A1-PDGFB fusion as well as NTRK1/2/3 rearrangements. A subsequent RNA sequencing detected an in-frame fusion between exon 15 of TNC and exon 6 of PDGFD. This fusion was further confirmed by nested reverse transcription polymerase chain reaction amplification followed by Sanger sequencing. A diagnosis of fibrosarcomatous DFSP was rendered and the patient was in good status at a follow-up of 12 months after the operation. Conclusions: We report a fibrosarcomatous DFSP with novel TNC-PDGFD fusion, which adds to the pathologic and genetic spectrum of PDGFD-rearranged DFSP. [ABSTRACT FROM AUTHOR]

RBM10 modulates transcriptome-wide cassette exon splicing. Loss-of-function RBM10 mutations are enriched in thyroid cancers with distant metastases. Analysis of transcriptomes and genes mis-spliced by RBM10 loss showed pro-migratory and RHO/RAC signaling signatures. RBM10 loss increases cell velocity. Cytoskeletal and ECM transcripts subject to exon-inclusion events included vinculin (VCL), tenascin C (TNC) and CD44. Knockdown of the VCL exon inclusion transcript in RBM10 -null cells reduced cell velocity, whereas knockdown of TNC and CD44 exon-inclusion isoforms reduced invasiveness. RAC1-GTP levels were increased in RBM10 -null cells. Mouse Hras thyrocytes develop metastases that are reversed by RBM10 or by combined knockdown of VCL, CD44 and TNC inclusion isoforms. Thus, G12V /Rbm1O KO thyrocytes develop metastases that are reversed by RBM10 or by combined knockdown of VCL, CD44 and TNC inclusion isoforms. Thus, RBM10 loss generates exon inclusions in transcripts regulating ECM-cytoskeletal interactions, leading to RAC1 activation and metastatic competency. Moreover, a CRISPR-Cas9 screen for synthetic lethality with RBM10 loss identified NFkB effectors as central to viability, providing a therapeutic target for these lethal thyroid cancers., Competing Interests: J.A.F. is a co-inventor of intellectual property focused on HRAS as a biomarker for treating cancer using tipifarnib which has been licensed by MSK to Kura Oncology. J.A.F. received prior research funding from Eisai and was a former consultant for LOXO Oncology, both unrelated to the current manuscript. B.R.U. and J.A.K are co-inventors of intellectual property (HRAS as a biomarker of tipifarnib efficacy) that has been licensed by MSK to Kura Oncology. O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc., Merck, Prelude Therapeutics, and Janssen, and is on the Scientific Advisory Board of Envisagenics Inc., AIChemy, Harmonic Discovery Inc., and Pfizer Boulder. O.A.-W. has received prior research funding from H3B Biomedicine, Nurix Therapeutics, Minovia Therapeutics, and LOXO Oncology unrelated to the current manuscript. R.K.B. is an inventor on patent applications filed by Fred Hutchinson Cancer Center related to modulating splicing for cancer therapy. R.K.B. and O.A.-W. are founders and scientific advisors of Codify Therapeutics, hold equity in this company and receive research support from this company unrelated to the current manuscript. R.K.B. is a founder and scientific advisor of Synthesize Bio and holds equity in this company. A.R.G is currently an Associate Professor of Surgery at the University of Sydney, Australia. M.S. is currently employed by Loxo Oncology.The remaining authors declare no competing interests.

The subject of consideration of this article is the mechanism for the formation of public administration of the United States. The US public administration system is characterized by continuity in domestic and foreign policy over the past 70 years as a minimum. Elite groups that can fight for power in the US and have the appropriate resource base and the necessary tools are traditionally formed from representatives of big business and financial circles. The authors of the article aim to identify and determine the role and place of big business as a source of recruiting American elites, which have a key influence on US policy in the form and scale in which we observe it today. In this study, the authors set themselves the following tasks: to analyze the mechanism for the formation of the US public administration system through the prism of the experience of the American corporation ExxonMobile. This analysis is carried out by the example of the incorporation of its representatives in the person of the head of the company Rex Tillerson in the US government system for the post of Secretary of State. This analysis is accompanied by the study of the ExxonMobile company as the largest and most influential transnational corporation. To achieve the objectives, the authors used the following research methods: structural, system, functional, comparative and historical methods. The authors also used the methodology of economic science: the method of scientific abstraction, the method of normative and functional analysis.

Abstract Background Neuropilin-1 (NRP-1), a non-tyrosine kinase glycoprotein receptor, is associated with poor prognosis breast cancer, however transcriptomic changes triggered by NRP-1 overexpression and its association with chemoresistance in breast cancer have not yet been explored. Methods BT-474 NRP-1 variant cells were generated by stable overexpression of NRP-1 in the BT-474 breast cancer cell line. RNA sequencing and qRT-PCR were conducted to identify differentially expressed genes. The role of an upregulated oncogene, Tenascin C (TNC) and its associated pathway was investigated by siRNA-mediated knockdown. Resistant variants of the control and BT-474 NRP-1 cells were generated by sequential treatment with four cycles of Adriamycin/Cyclophosphamide (4xAC) followed by four cycles of Paclitaxel (4xAC + 4xPAC). Results NRP-1 overexpression increased cellular tumorigenic behavior. RNA sequencing identified upregulation of an oncogene, Tenascin-C (TNC) and downregulation of several tumor suppressors in BT-474 NRP-1 cells. Additionally, protein analysis indicated activation of the TNC-associated integrin β3 (ITGB3) pathway via focal adhesion kinase (FAK), Akt (Ser473) and nuclear factor kappa B (NF-kB) p65. siRNA-mediated TNC knockdown ablated the migratory capacity of BT-474 NRP-1 cells and inactivated FAK/Akt473 signaling. NRP-1 overexpressing cells downregulated breast cancer resistance protein (BCRP/ABCG2). Consequently, sequential treatment with Adriamycin/Cyclophosphamide (AC) cytotoxic drugs to generate resistant cells indicated that BT-474 NRP-1 cells increased sensitivity to treatment by inactivating NRP-1/ITGB3/FAK/Akt/NF-kB p65 signaling compared to wild-type BT-474 resistant cells. Conclusions We thus report a novel mechanism correlating high baseline NRP-1 with upregulated TNC/ITGB3 signaling, but decreased ABCG2 expression, which sensitizes BT-474 NRP-1 cells to Adriamycin/Cyclophosphamide. The study emphasizes on the targetability of the NRP-1/ITGB3 axis and its potential as a predictive biomarker for chemotherapy response.

The article clarifies the contents of such phenomena as the development of “sustainable (green) industry”, “sustainable (green) energy”. Reveals their place in the unfolding processes of the fourth industrial revolution. Emphasized the main trends in “green” modernization in the production process of companies. Identified economic, environmental and social benefits as a result of carried out different scales of European and American industrial companies environmentally and socially responsible industrial policy on the principle of “Cradle to Cradle system”. Presented and analyzed examples of activities of specific companies engaged in a gradual transition to the principles of “green economy”. The article considers examples of international regulation, aimed at the development of sustainable development and the creation of conditions for the industrial revolution acceleration In this regard, significant to note the prospect of development of the corporate sector towards the wider application of renewable energy sources.

The tendency towards increasing digitalization, automation and robotics in numeral branches of the economy reflects on different aspects of the international business affairs. The paper examines the impact of the upcoming fourth industrial revolution on the foreign direct investment (FDI) attraction and realization processes. It studies the specific features of Industry 4.0, stressing their importance for the stakeholders in FDI. The main problem examined in the article is the shifting of the key FDI attraction factors that is expected due to the industrial revolution. The analysis of the FDI attraction factors amendment finds that we can expect changes in the behaviour and priorities of FDI stakeholders, but not a decrease in the international capital flows. [ABSTRACT FROM AUTHOR]

For developing countries, the textiles and clothing industries have traditionally been an important gateway to industrialization and increased exports. With the expiration of the Agreement on Textiles and Clothing, the quota system originally set up through the Multifibre Arrangement was phased out. This has important implications for the allocation of export-oriented production and is likely to affect in various ways a large number of developing countries that rely heavily on such exports.Drawing on a wide range of studies as well as on original research, this volume shows that transnational corporations (TNCs) are likely to play a critical role in determining the future global production structure in these industries. First, the sourcing strategies of a small number of very large retailing companies (based in the United States, Europe and Japan) place stringent requirements on the locations in which textiles and clothes will be produced. Second, the investment strategies of large transnational producers (mostly based in East Asia) will also affect the final outcome. Foreign affiliates of such developing-country TNCs already account for the bulk of exports from many developing economies. The growing role of TNC producers is still not well understood, and more research is needed on their strategies and the impact of their international investments. As TNCs become more important at the production stage, their bargaining power increases vis-à-vis retailers in developed economies.With the removal of quotas, sourcing and investment decisions are affected more by economic fundamentals. But low labour costs alone will not be sufficient to attract investment. There is likely to be more consolidation of production into larger factories in a smaller number of locations. China and India are likely to be in a particularly strong position in this new geography of production, but various factors may also work against too much consolidation. Proximity to markets continues to play an important role for some product categories, and some producers have signalled that they will retain several production bases in order not to become too dependent on a single source country. Moreover, various trade policy measures also influence sourcing and investment decisions. Data on foreign direct investment (FDI) projects in textiles and clothing manufacturing show that China, Bulgaria, the United States, Hungary, Brazil and India attracted the largest number of such projects in 2002–2004.The removal of quotas generally means intensified competition for FDI in textiles and clothing. To become or stay competitive as host locations, countries will need to develop their ability to move away from simple assembly to "full-package" production and eventually original brand manufacture. But replicating the success of East Asia will be difficult. Key policy areas in this regard include identification of specialized niches; skills training and technological upgrading; investment in information technology; improvement of infrastructure such as ports and export processing zones; and leveraging of existing tariff preferences in the global trading system. Moreover, investment promotion agencies may identify some of the major transnational producers as key addresses for future marketing activities.

In 1998 The Nature Conservancy (TNC) made the Rochester regional office of the New York State Department of Transportation aware of the need for improved habitat for birds along Lake Ontario. The lake shore is internationally recognized as an important migratory route, nesting and wintering area for many bird species, both songbirds and birds of prey. The Lake Ontario State Parkway, with more than 30 miles of expansive right-of-way along the shoreline, presented an ideal opportunity for the department to respond, while enhancing the aesthetics of the corridor for the traveling public and adjacent land owners. Planning and design began in 1999 with construction in the spring of 2000. The project included restoring and enhancing native vegetation (meadow, shrub and trees) for habitat and food, and adding nest boxes for wood ducks, kestrels and other native cavity dwellers. Nest boxes are monitored through the creation of an ‘adopt a nest box’ volunteer program which has successfully kept European Starling activity to a minimum. Boxes have been used by six different native bird species. Seven hundred native shrubs and 236 fruit or mast bearing trees were planted. Forty-four acres of non-native scrub shrub was removed, with three acres replanted with native woody plants and the rest left open as meadow. Since 2001, the 41-acre R.O.W. area is being managed so that mowing occurs once after September 1, which has improved nesting success for Savannah and Grasshopper Sparrows, Bobolink and Meadowlark. Upland Sandpiper nested there until 1999, and it is hoped they will return. The department is currently revising mowing management practices statewide, in part based on the success of this project. The NYSDOT partnered with TNC, NYS Department of Environmental Conservation, NYS Office of Parks, Recreation, and Historic Preservation, Cornell University, Braddock’s Bay Raptor Research Center, Braddock’s Bay Bird Observatory, Genesee Ornithological Society, Town of Greece, Otetiana Boy Scout Council and DOT staff volunteers through planning and implementation phases of this ongoing project. For a relatively small investment of time and money, the department has made a noticeable improvement in the environment and won accolades from our many partners.

Multinational enterprises (forward - MNE) from developing counties have intensified their foreign business recently, including activities in Africa (in terms of the past - transnational corporations, TNC). Methodology explanation of such expansion requires the increases of mainstream MNE theories adequacy level. These models are primarily applicable to MNEs from developed countries and should be upgraded by accounting specificities and conditions relevant to the operations of MNEs from the developing world. The current state of such MNEs’ internationalization in African economy has been analyzed and the factors of these companies’ competitiveness in external markets have been generalized (including the factors acquired during transformations in home country economies). The approach based upon assessing the congruency of corporate assets and external environment in developing host countries has been introduced.

Investigating emerging transportation services is critical to forecasting mode choice and providing appropriate infrastructure. One such infrastructure is parking, as parking demand may shift with the availability of ride-hailing services. This study uses ethnographic methods—complemented with passenger surveys collected when driving for Uber and Lyft in the Denver, Colorado, region—to gather quantitative and qualitative data on ride-hailing and analyze the impacts of ride-hailing on parking, including changes in parking demand and parking as a reason to deter driving. The study also examines relationships between parking time and cost. This includes building a classification tree-based model to predict the replaced driving trips as a function of car ownership, destination land type, parking stress, and demographics. The results suggest that: i) ride-hailing is replacing driving trips and could reduce parking demand, particularly at land uses such as airports, event venues, restaurants, and bars; ii) parking stress is a key reason respondents chose not to drive; and iii) respondents are generally willing to pay more for reduced parking time and distance. Conversely, parking supply, time, and cost can all influence travel behavior and ride-hailing use. This study provides insight into potential benefits and disadvantages of ride-hailing as related to parking.