bluuebunny/crossref_metadata_2025 huggingface dataset:
The new small tyrosine kinase inhibitor ARQ531 targets acute myeloid leukemia cells by disrupting multiple tumor-addicted programs
Authors: Debora Soncini  , Stefania Orecchioni  , Samantha Ruberti  , Paola Minetto  , Claudia Martinuzzi  , Luca Agnelli  , Katia Todoerti  , Antonia Cagnetta  , Maurizio Miglino  , Marino Clavio  , Paola Contini  , Riccardo Varaldo  , Micaela Bergamaschi  , Fabio Guolo  , Mario Passalacqua  , Alessio Nencioni  , Fiammetta Monacelli  , Marco Gobbi  , Antonino Neri  , Giovanni Abbadessa  , Sudharshan Eathiraj  , Brian Schwartz  , Francesco Bertolini  , Roberto M. Lemoli  , Michele Cea
Published: October 2019

Tyrosine kinases have been implicated in promoting tumorigenesis of several human cancers. Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers. Here, we characterize a new multiple kinase inhibitor, ARQ531, and evaluate its mechanism of action in preclinical models of acute myeloid leukemia. Treatment with ARQ531, by producing global signaling pathway deregulation, resulted in impaired cell cycle progression and survival in a large panel of leukemia cell lines and patient-derived tumor cells, regardless of the specific genetic background and/or the presence of bone marrow stromal cells. RNA-seq analysis revealed that ARQ531 constrained tumor cell proliferation and survival through Bruton's tyrosine kinase and transcriptional program dysregulation, with proteasome-mediated MYB degradation and depletion of short-lived proteins that are crucial for tumor growth and survival, including ERK, MYC and MCL1. Finally, ARQ531 treatment was effective in a patient-derived leukemia mouse model with significant impairment of tumor progression and survival, at tolerated doses. These data justify the clinical development of ARQ531 as a promising targeted agent for the treatment of patients with acute myeloid leukemia.
Reconstruction of Acetabular Wall Using Autologous Bone Graft Following Resection of Pelvic Chondrosarcoma: Surgical Technique and Functional Outcome
Authors: Soetanto Rendy Cahya , Budi Muhammad Naseh , Ismono Darmadji
Published: October 2019

Background: Pelvic chondrosarcoma may be difficult to manage due to its proximities with vital structures. The study aimed to explain an alternative surgical technique for acetabular reconstruction.Case Presentation: We present a case of a 48-year-old female with large chondrosarcoma of the superior and inferior pubic rami with medial acetabular wall involvement. Pelvic type 3 resection was performed. There was a defect at medial acetabulum after resection. The defect was covered by autograft from iliac and fixation using screws. Rotational pelvic stability was maintained using a reconstruction plate. The functional outcome was assessed 6 months after operation using MSTS and the score was 30, which was painless, full weight bearing, normal gait, and no pain. Conclusions: Reconstruction of the pelvis after tumor resection requires a careful preoperative patient evaluation and extensive bone and soft tissue resection to achieve negative tumor margins and stable reconstruction of the osseous and soft tissue defects.
Between Social Utopia and Totalitarian Reality: “Children of Milky Way” by Dokiia Humenna
Authors: Vasylenko Vadym
Published: October 2019

The paper considers the novel “Children of Milky Way” by Dokiia Humenna in the context of the postwar Ukrainian diaspora’s literary process. The focus is on the issues of relations between fiction and documentary writing, the individual and collective experiences. The literary Kyiv, being one of the central images in Dokiia Humenna’s novel, appears not only as a page from individual or national histories, a sample of the Kyiv text in the Ukrainian diaspora’s prose, but also as a generalization based on such texts and made due to various forms of intertextuality, which absorb the history and atmosphere of the Kyiv 1920s. The problem of interrelations between the writer and government, art, politic, and ideology is one of the most essential in the novel: Dokia Humenna reveals various aspects of the writer’s life and work in conditions of the totalitarian state and culture – from suicide to madness, from resistance to adaptation and collaboration. A future person and society in “Children of Milky Way” are represented in a commune. The histories of the two characters-antipodes Taras Saragola and Seraphym Carmalita are connected to its progress and decline; in the world of totalitarian repressions and control they choose different life strategies and roles. The memory about Soviet terror and repressions, as well as the Holodomor-genocide, “killing the Ukrainian peasantry as a foundation of the nation and destructing intellectuals as a brain of the nation” is important in the novel. The history of collectivization is related to the traumatic memory of the serfdom times, which affects  the second and third generations and deepens the trauma caused by disintegration of a family, destruction of the patriarchal peasant world. This process was accompanied by desacralization of the Father’s figure as a personification of power, by infantilization of masculinity. The writer associates totalitarian reality with the metaphor of Night, which acquires different ambiguous meanings in the Ukrainian anti-totalitarian discourse.
Corneliu Irod – Ukrainian Writer from Romania (Creative Work Overview)
Authors: Nosenko Tamara
Published: October 2019

The essay surveys the works written by C. Irod, one of the leading contemporary Ukrainian writers of Romania. The main attention is paid to his trilogy of novels “The Feast” and stories that vary in thematic features and stylistics, some of them belonging to a particular type of short prose works – allegoric pieces called “blunder stories”. Considering main themes and ideas of C. Irod’s works and focusing on peculiarities of their literary interpretation, the researcher intends to represent the originality of the writer’s prose heritage, to determine his role in developing the genre of the modern novel and renovating flash fiction in Ukrainian literature of Romania. To achieve this aim, the researcher adds a comparative aspect and refers to the major development patterns of the world novel of the 1960s–1980s, in particular, focusing on such a remarkable feature as ‘new epics’. The themes and issues of the works by C. Irod have been compared to those in the works by Romanian writers, in particular D. R. Popescu. It is noted that C. Irode’s stories have the inherent connection with the flash fiction of the Ukrainian masters – H. Tiutiunnyk and Ye. Hutsalo. The essay follows correspondences in themes and literary technique that relate the Romanian writer to the mentioned Ukrainian authors. The essay also informs about C. Irod’s achievements in the Цeld of literary translation. In particular, he worked over translation of T. Shevchenko’s “Diary”, as well as the book “Taras Shevchenko’s life” by P. Zaitsev. The researcher also gives some details concerning C. Irod’s translations of the tales “When the animals could talk” and “Mykyta the Fox” by I. Franko, the stories written by H. Tiutiunnyk and some pieces in poetry and prose by junior Ukrainian authors.
Social Support and Modelling in Relation to Physical Activity Participation and Outdoor Play in Preschool Children
Authors: Reimers Anne Kerstin , Boxberger Karolina , Schmidt Steffen C. E. , Niessner Claudia , Demetriou Yolanda , Marzi Isabel , Woll Alexander
Published: October 2019

Physical activity during early childhood is a prerequisite for healthy development in many cases. The aim of this study was to assess the relationships of social modelling and support from parents, peers, and siblings and domain-specific physical activity participation in a nationwide sample of preschool boys and girls from Germany. 519 preschool children aged 4–6 and one of their parents participated in the ‘MoMo’ Wave 1 Study between 2009 and 2012. Participants and their parents provided self-reported data on social support modelling, and domain-specific physical activity participation (physical activity in sports clubs, physical activity outside of sports clubs, and outdoor play). Parental, peer, and sibling support and modelling were related to domain-specific physical activity: Parental support was particularly relevant for physical activity in sports clubs, and peer support for outdoor play. Parental modelling was only related to physical activity outside of sports clubs: Maternal modelling was a positive correlate in girls and paternal modelling in boys, respectively. Sibling and peer modelling were especially relevant for physical activity in sports clubs. The results were heterogeneous regarding types and providers of support and modelling. Thus, different providers and types of support should be targeted in physical activity promotion programs for preschool children.
Study on Emergency Load Shedding of Hybrid AC/DC Receiving-End Power Grid with Stochastic, Static Characteristics-Dependent Load Model
Authors: Jiang Yingying , Chen Xiaolin , Peng Sui , Du Xiao , Xu Dan , Tang Junjie , Li Wenyuan
Published: October 2019

When large-capacity HVDC (high voltage direct current) transmission line blocking occurs in a hybrid AC/DC (alternating current/direct current) power grid, the receiving-end system will encounter a huge power imbalance, which will lead to a frequency drop and redistribution of the power flow, and which may further lead to the overload of other transmission lines, cascading failures and a large-scale blackout. To resolve these problems, an emergency load-shedding strategy for the DC receiving-end system is proposed from the perspective of a quasi-steady state. The proposed method can accurately calculate the actual total power imbalance by modeling more detailed stochastic loads with static frequency/voltage characteristics and involving the inertia effect of the generator during the response delay period, which can effectively reduce the amount of load curtailment. In addition, several factors affecting the power imbalance estimation in stochastic scenarios and their mechanisms are analyzed in detail, and the key aspects relevant to the DC blocking fault analysis are identified as well. Finally, the influence of different load-shedding strategies on the receiving-end system security after a DC blocking fault is compared with the security indices, including those that are relevant to the frequency/load change proposed herein, and a uniform load-shedding coefficient is obtained via the proposed method, even for different power imbalances under a stochastic context, which makes the load-shedding strategy more practical.
A Hydraulic Model for Multiphase Flow Based on the Drift Flux Model in Managed Pressure Drilling
Authors: Fang Qiang , Meng Yingfeng , Wei Na , Xu Chaoyang , Li Gao
Published: October 2019

Managed pressure drilling (MPD) is a drilling technique used to address the narrow density window under complex geological environments. It has widespread applications in the exploration and exploitation of oil and gas, both onshore and offshore. In this study, to achieve effective control of the downhole pressure to ensure safety, a gas–liquid two-phase flow model based on the drift flux model is developed to describe the characteristics of transient multiphase flow in the wellbore. The advection upwind splitting method (AUSM) numerical scheme is used to assist with calculation and analysis, and the monotonic upwind scheme for conservation laws (MUSCLs) technique with second-order precision is adopted in combination with the Van Leer slope limiter to improve precision. Relevant data sourced from prior literature are used to validate the suggested model, the results of which reveal an excellent statistical consistency. Further, the influences of various parameters in a field application, including backpressure, density, and mass flow, are analyzed. Over the course of later-stage drilling, a combination of wellhead backpressure and displacement is recommended to exercise control.
A Risk Assessment Model of Coalbed Methane Development Based on the Matter-Element Extension Method
Authors: Wang Wanqing , Lyu Shuran , Zhang Yudong , Ma Shuqi
Published: October 2019

Coalbed methane development represents a complex system engineering operation that involves complex technology, many links, long cycles, and various risks. If risks are not controlled in a timely and effective manner, project operators may easily cause different levels of casualties, resource waste and property loss. To evaluate the risk status of coalbed methane development projects, this paper constructs a coalbed methane development risk assessment index system that consists of six first grade indexes and 45 second grade indexes. The weight of each index is calculated based on the structure entropy weight method. Then, a theoretical model for risk assessments of coalbed methane development is established based on the matter-element extension method. Finally, the model is applied to analyze a coalbed methane development project in the southern Qinshui Basin of China. The results show that the overall risk level of the coalbed methane development project is Grade II, indicating that the overall risk of the project is small, but the local risk of the project needs to be rectified in time. The assessment results are consistent with the actual operation of the project, indicating that the established risk assessment model has good applicability and effectiveness.
Real Time Energy Performance Control for Industrial Compressed Air Systems: Methodology and Applications
Authors: Benedetti Miriam , Bonfà Francesca , Introna Vito , Santolamazza Annalisa , Ubertini Stefano
Published: October 2019

Most manufacturing and process industries require compressed air to such an extent that in Europe, for instance, about 10% of the total electrical energy consumption of industries is due to compressed air systems (CAS). However, energy efficiency in compressed air production and handling is often ignored or underestimated, mainly because of the lack of awareness about its energy consumption, caused by the absence of proper measurements on CAS in most industrial plants. Therefore, any effective energy saving intervention on generation, distribution and transformation of compressed air requires proper energy information management. In this paper we demonstrate the importance of monitoring and controlling energy performance in compressed air generation and use, to enable energy saving practices, to enhance the outcomes of energy management projects, and to obtain additional benefits for non-energy-related activities, such as operations, maintenance management and energy accounting. In particular, we propose a novel methodology based on measured data, and baseline definition through statistical modelling and control charts. The proposed methodology is tested on a real compressed air system of a pharmaceutical manufacturing plant in order to verify its effectiveness and applicability.
Experimental Study of Performance Improvement of 3-Bed and 2-Evaporator Adsorption Chiller by Control Optimization
Authors: Chorowski Maciej , Pyrka Piotr , Rogala Zbigniew , Czupryński Piotr
Published: October 2019

The main challenge facing adsorption cooling technology is low Coefficient of Performance (COP), which becomes a key factor of the commercialization of this technology. This paper presents the results of modifications, aiming to increase COP, applied to the control software of a prototype three-bed two-evaporator adsorption chiller. Changes were mainly related to the sequence of the switching valves and had no influence on the hardware of the chiller. The sequence changes enabled the introduction of heat recovery and mass regeneration. Moreover, the precooling process was improved. The applied modifications not only resulted in significant improvement of the chiller’s COP, but also improved the cooperation adsorption unit heating source, which is of great importance in case of district heating supply. The improvement was also observed concerning such operational aspects as noise and vibrations. In the authors’ opinion, the presented modifications can be introduced to most exploited adsorption chillers and could potentially lead to similar improvements in performance.
Factors Related to the Number of Existing Teeth among Korean Adults Aged 55–79 Years
Authors: Lee Jung-Ha , Yi Seung-Kyoo , Kim Se-Yeon , Kim Ji-Soo , Kim Han-Na , Jeong Seung-Hwa , Kim Jin-Bom
Published: October 2019

This study aimed to determine the association between the number of existing teeth (NET) and socioeconomic status (SES), oral health-related behaviours, and metabolic syndrome in Korean adults aged 55–79 years. The study included 3255 adults who underwent oral health examinations and answered questionnaires regarding SES, oral health-related behaviours, and metabolic diseases in the Sixth Korea National Health and Nutrition Examination Survey (2013–2015). The dependent variable was the binary status based on the median NET in each age group. The independent variables were based on SES, oral health-related behaviours, and the presence of metabolic syndrome. The study findings showed that the factors associated with the NET were sex, household income, education level, region of residence, daily toothbrushing frequency, dental visit within 1 year, smoking, and metabolic syndrome. NET was lower in males (adjusted OR: 0.74), in low household income group (adjusted OR: 0.77), in primary school graduates (adjusted OR: 0.53) and in rural residents (adjusted OR: 0.78). The interventions aimed at preserving existing teeth in elderly population should consider their SES, oral health-related behaviours, and metabolic syndrome and overhauling current oral healthcare system and redefining the roles of oral health professionals.
Spatial-Temporal Characteristics of Agriculture Green Total Factor Productivity in China, 1998–2016: Based on More Sophisticated Calculations of Carbon Emissions
Authors: Xu Xiaocang , Huang Xiuquan , Huang Jun , Gao Xin , Chen Linhong
Published: October 2019

Environmental costs should be taken into account when measuring the achievements of China’s agricultural development, since the long-term extensive development of agriculture has caused huge environmental pollution. This study took agricultural carbon emissions as an undesired output to estimate the agricultural development efficiency in 31 provinces of China from 1998 to 2016, based on the green total factor productivity, as assessed by the slacks-based measure directional distance function and constructing the global Malmquist–Luenberger index. We measured agricultural carbon emissions in terms of five aspects: agricultural materials, rice planting, soil, livestock and poultry farming, and straw burning, and then compared the green total factor productivity index and the total factor productivity index. The study came to the following conclusions: (1) the green technology efficiency change was smaller than the technology efficiency change at first, but the gap between them is narrowing with time, such that the former is now larger than the latter; (2) the green technology efficiency was in a declining state and the green technology progress was increasing, promoting the green total factor productivity growth, from 1998 to 2016; and (3) China’s agricultural green total factor productivity increased by 4.2% annually in the east, 3.4% annually in the central region, and 2.5% annually in the west.
Predictors of E-Cigarette Use Susceptibility—A Study of Young People from a Socio-Economically Disadvantaged Rural Area in Poland
Authors: Kaleta Dorota , Niedzin Mirosław , Jankowska Agnieszka , Polańska Kinga
Published: October 2019

Identification of the youth at risk of e-cigarette use is crucial for development of effective prevention strategies. The current study aims at evaluation of predictors of susceptibility to e-cigarette initiation and experimentation among adolescents. This cross-sectional study included 1693 students (non-current users of e-cigarettes) attending 21 schools in Piotrkowski district (a socially disadvantaged rural area in central Poland). The regression models were applied so as to study factors linked to susceptibility to e-cigarette use among never users (n = 1054) and ever users (n = 639) of e-cigarettes, with susceptibility defined as the absence of a firm decision not to use these products. A high proportion of the youth was susceptible to e-cigarette use (68% of never and 78% of ever e-cigarette users). The adjusted model confirmed the following risk factors: smoking parents and friends (never users: OR = 3.0; p < 0.001; OR = 2.0; p < 0.05; ever users: OR = 2.2; OR = 2.2; p < 0.01), alcohol consumption (never users: moderate drinking OR = 2.9; p < 0.001; binge drinking OR = 2.2; p < 0.01; ever users: moderate drinking OR = 4.2; p < 0.001), cigarette smoking (never users: OR = 14.1; ever users: OR = 11.3; p < 0.001), and perception that e-cigarettes are less harmful than traditional cigarettes (never users: OR = 1.8; p < 0.001). The youth whose mothers had a medium and high educational level (never users: OR = 2.7; p < 0.01; OR = 2.7; p < 0.05; ever users: OR = 5.4; OR = 4.4; p < 0.001), those who perceived girls who use e-cigarettes as more attractive (never users: OR = 4.1; p < 0.001; ever users: OR = 2.9; p < 0.01), and secondary school students (ever users: OR = 5.6; p < 0.001) had higher odds of susceptibility to e-cigarette use. The youth who had more money per month were less susceptible to e-cigarette experimentation (OR = 0.4; p < 0.001). A multi-level intervention approach, considering vulnerable populations, is required to prevent the youth from e-cigarette initiation and experimentation.
Environmental Correlates of Health-Related Quality of Life among Women Living in Informal Settlements in Kenya
Authors: Winter Samantha C. , Obara Lena Moraa , Barchi Francis
Published: October 2019

Informal settlements (slums)—defined as residential areas lacking durable housing; sufficient living and public spaces; access to basic infrastructure, water, sanitation, and other services; and secure tenancy—are presumed to be poor health environments. Research in Kenya suggests that residents of these settlements have the worst health outcomes of any population, yet there is a paucity of research focused on the health and well-being of these residents. Even less attention is given to the role played by environment in health in these settings. The present study addresses these gaps by examining potential environmental correlates, specifically access to water and sanitation, of health-related quality of life (HRQOL) among 552 women in Mathare slum in Nairobi, Kenya. A Kiswahili version of the 36-Item Short Form Health Survey (SF-36) measured HRQOL. Results suggested that access to a toilet at all times was associated with every subscale of the mental health and general well-being domains of the SF-36. Primary water source was also associated with women’s HRQOL. Despite increasing efforts to expand sanitation and water access in informal settlements, more attention should be given to whether the interventions being introduced, which likely affect women’s psychosocial health, are appropriate for all residents, including women.
Reinforcement of Tobacco Control and Reduction in Medical Utilization for Asthma in Taiwan: A Population-Based Study
Authors: Liang Huang-Ju , Wu Ming-Jiuan , Jerng Jih-Shuin , Yang Chiang-Hsing
Published: October 2019

Environmental air quality can affect asthma control and the development of overt asthmatic manifestations. In this population-based study, we investigated the effect of reinforcing a smoking ban in Taiwan through the enactment of the Tobacco Hazards and Prevention Act (THPA) on healthcare utilization rate by asthmatics. Analysis was performed based on data relevant to non-hospitalized asthmatic patients with insurance claims between 2005 and 2013 from the National Health Insurance Research Database of Taiwan, reported data on Asian dust storms, and penalty rates for violations of the tobacco ban. Poisson regression showed that the risk for outpatient visits for asthma was lower after enactment of the THPA (RR = 0.98, 95% CI = 0.98–0.99), with a yearly trend of a reduced risk (RR = 0.99, 95% CI = 0.99–1.00), also lower in geographic regions with medium (RR = 0.79, 95% CI = 0.79–0.80) and high (RR = 0.91, 95% CI = 0.91–0.92) penalty rates. Subgroup analysis showed that asthma visit rates were reduced in both male and female groups after the enactment of the THPA. The risk of an asthma ER visit was increased after the enactment of the amended THPA (RR = 1.07, 95% CI = 1.05–1.09), although the yearly trend was not significant (RR = 1.00, 95% CI = 1.00–1.00). The risk of emergency room visits for asthma was significantly reduced in regions with medium (RR = 0.68, 95% CI = 0.68–0.69) and high (RR = 0.75, 95% CI = 0.74–0.76) penalty rates. Subgroup analysis showed that the visit rates were similar in both male and female groups. The effectiveness of reinforcing the smoking ban warrants further policies aimed at further reducing passive smoking.
Social Stability Risk Assessment of Land Expropriation: Lessons from the Chinese Case
Authors: Li Chenxi , Xi Zenglei
Published: October 2019

Scholars have paid much attention to the problems existing in the land expropriation risk assessment system and the sound countermeasures from a qualitative perspective. Empirical research on land expropriation social stability risk assessment from the micro-level perspective is limited. This study analyzed the Chinese social stability risk assessment system of land expropriation though a case study of a land expropriation project in China. The current social stability risk assessment system of land expropriation, which includes the assessment purposes, principles, contents, methods, and results, was analyzed. We concluded with lessons and deficiencies from the current social stability risk assessment system. The research findings show that: (1) the current land expropriation risk assessment system mostly takes the land administration department as the main body of responsibility, identifies the risks by means of seminars, visits, letters, and visits, and takes the opinion of the masses or experts as the risk assessment result. (2) The current land expropriation risk assessment system should be standardized in terms of defining the risk assessment of land expropriation, improving the land expropriation risk assessment system and optimizing land expropriation assessment procedures. This paper provides a reference for the sustainable development of land use in rural and urban areas in China.
Organised Physical Activity in the Forests of the Warsaw and Tricity Agglomerations, Poland
Authors: Janeczko Emilia , Wójcik Roman , Kędziora Wojciech , Janeczko Krzysztof , Woźnicka Małgorzata
Published: October 2019

Research Highlights: The achieved results indicate that in the period of 2010–2016, the number of sporting events (running, cycling and walking) as well as the number of participants has increased many times. Methods: A geostatistical method, i.e., kriging, was used to check the distance-based relationship between agglomerations proximity and sporting events. The questionnaire surveys were used to determine the reasons for physical activity in the forest. Results: The analysis of the impact of the scope of the urban agglomerations on the number of organised physical activities proved that, in both cases (Warsaw and Tricity), most events take place in forests located close to these cities. The larger the distance to Warsaw or Tricity, the lower the number of sporting events and the lower the number of participants. The reasons why people take up physical activity are mainly to improve their health and physical condition, reduce stress and improve wellbeing. Conclusions: The conducted research indicates a significant increase in the importance of non-productive functions of forests located in the vicinity of urban agglomerations, as well as the need for continuous monitoring of actions taken by foresters to promote active lifestyles.
Using Mosses as Bioindicators of Potentially Toxic Element Contamination in Ecologically Valuable Areas Located in the Vicinity of a Road: A Case Study
Authors: Radziemska Maja , Mazur Zbigniew , Bes Agnieszka , Majewski Grzegorz , Gusiatin Zygmunt M. , Brtnicky Martin
Published: October 2019

This study analyzed the impact of road transportation on the concentration of Zn, Ni, Pb, Co, and Cd in moss (Pleurozium schreberi). The study was carried out over five years near a national road running from the north to the east (Poland) in the area of Natura 2000 sites. Samples were collected at three significantly different locations: (1) near a sharp bend, (2) near a straight section of the road in a woodless area, and (3) in a slightly wooded area. At each location, moss samples were collected from sites situated 2, 4, 6, 8, 10, 12, and 14 m from the road edge. The highest Zn and Cd contents in the moss were recorded 6 m from the road edge near a sharp bend (where vehicles brake sharply and accelerate suddenly). At the same location, at a distance of 2 m, the highest Pb concentration was noted, and at a distance of 4 m from the road, the highest Ni concentration was noted. The Co concentration in the moss was the highest near the woodless straight section at a distance of 2 and 12 m from the road. The concentrations of Zn, Pb, Ni, Co (only at the woodless location), and Cd (at all locations) were significantly and negatively correlated with distance from the road.
Comprehensive Influences of Overexpression of a MYB Transcriptor Regulating Anthocyanin Biosynthesis on Transcriptome and Metabolome of Tobacco Leaves
Authors: Zong Yuan , Li Shiming , Xi Xinyuan , Cao Dong , Wang Zhong , Wang Ran , Liu Baolong
Published: October 2019

Overexpression of R2R3-MYB transcriptor can induce up-expression of anthocyanin biosynthesis structural genes, and improve the anthocyanin content in plant tissues, but it is not clear whether the MYB transcription factor overexpression does effect on other genes transcript and chemical compounds accumulation. In this manuscript, RNA-sequencing and the stepwise multiple ion monitoring-enhanced product ions (stepwise MIM-EPI) strategy were employed to evaluate the comprehensive effect of the MYB transcription factor LrAN2 in tobacco. Overexpression of LrAN2 could promote anthocyanin accumulation in a lot of tissues of tobacco cultivar Samsun. Only 185 unigenes express differently in a total of 160,965 unigenes in leaves, and 224 chemical compounds were differently accumulated. Three anthocyanins, apigeninidin chloride, pelargonidin 3-O-beta-D-glucoside and cyanidin 3,5-O-diglucoside, were detected only in transgenic lines, which could explain the phenotype of purple leaves. Except for anthocyanins, the phenylpropanoid, polyphenol (catechin), flavonoid, flavone and flavonol, belong to the same subgroups of flavonoids biosynthesis pathway with anthocyanin and were also up-accumulated. Overexpression of LrAN2 activated the bHLH (basic helix-loop-helix protein) transcription factor AN1b, relative to anthocyanin biosynthesis and the MYB transcription factor MYB3, relative to proanthocyanin biosynthesis. Then, the structural genes, relative to the phenylpropanoid pathway, were activated, which led to the up-accumulation of phenylpropanoid, polyphenol (catechin), flavonoid, flavone, flavonol and anthocyanin. The MYB transcription factor CPC, negative to anthocyanin biosynthesis, also induced up-expression in transgenic lines, which implied that a negative regulation mechanism existed in the anthocyanin biosynthesis pathway. The relative contents of all 19 differently accumulated amino and derivers were decreased in transgenic lines, which meant the phenylalanine biosynthesis pathway completed the same substrates with other amino acids. Interestingly, the acetylalkylglycerol acetylhydrolase was down-expressed in transgenic lines, which caused 19 lyso-phosphatidylcholine and derivatives of lipids to be up-accumulated, and 8 octodecane and derivatives were down-accumulated. This research will give more information about the function of MYB transcription factors on the anthocyanin biosynthesis and other chemical compounds and be of benefit to obtaining new plant cultivars with high anthocyanin content by biotechnology.
Programmed Death Ligand 1 Indicates Pre-Existing Adaptive Immune Response by Tumor-Infiltrating CD8+ T Cells in Non-Small Cell Lung Cancer
Authors: Li Yi-Ming , Yu Jing-Min , Liu Zhen-Yu , Yang Hai-Jiao , Tang Juan , Chen Zhi-Nan
Published: October 2019

Aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impedes antitumor immunity and instigates immune evasion. The remarkable efficacy of immune checkpoint blockade has been confirmed in various solid tumors. However, the correlation between PD-L1 expression and host immunological landscape remains of considerable controversy in non-small cell lung cancer (NSCLC). In the present study, PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) infiltration levels were determined by immunohistochemistry (IHC) in tumor sections of 138 NSCLC patients. The expression level of PD-L1 was positively correlated with the abundance of CD8 + TILs (p < 0.0001). Furthermore, no constitutive expression of PD-L1 was observed in the majority of six NSCLC cell lines detected by Western blot; but exposure to interferon-γ (IFN-γ), a primary cytokine secreted by activated CD8+ T cells, prominently increased PD-L1 expression. Notably, a significantly positive association was determined within PD-L1, CD8 and IFN-γ gene expression by qRT-PCR, which was corroborated by RNA-sequencing from TCGA lung cancer dataset. These findings demonstrate that PD-L1 expression indicates an adaptive immune resistance mechanism adopted by tumor cells in the aversion of immunogenic destruction by CD8+ TILs. Both higher expression of PD-L1 and infiltration of CD8+ TILs were correlated with superior prognosis (p = 0.044 for PD-L1; p = 0.002 for CD8). Moreover, Cox multivariate regression analysis showed that the combination of PD-L1 and CD8 were independent prognostic factors, which was more accurate in prediction of prognosis in NSCLC than individually. Finally, we found that IFN-γ induced the upregulation of PD-L1 in NSCLC cells, mainly through the JAK/STAT1 signaling pathway. In conclusion, PD-L1 expression is mainly induced by activated CD8+ TILs via IFN-γ in the immune milieu and indicates pre-existing adaptive immune response in NSCLC.
Laser-Driven Ultrashort Pulsed Electron Beam Radiation at Doses of 0.5 and 1.0 Gy Induces Apoptosis in Human Fibroblasts
Authors: Babayan Nelly , Grigoryan Bagrat , Khondkaryan Lusine , Tadevosyan Gohar , Sarkisyan Natalya , Grigoryan Ruzanna , Apresyan Lilit , Aroutiounian Rouben , Vorobyeva Natalia , Pustovalova Margarita , Grekhova Anna , Osipov Andreyan N.
Published: October 2019

Rapidly evolving laser technologies have led to the development of laser-generated particle accelerators as an alternative to conventional facilities. However, the radiobiological characteristics need to be determined to enhance their applications in biology and medicine. In this study, the radiobiological effects of ultrashort pulsed electron beam (UPEB) and X-ray radiation in human lung fibroblasts (MRC-5 cell line) exposed to doses of 0.1, 0.5, and 1 Gy are compared. The changes of γH2AX foci number as a marker of DNA double-strand breaks (DSBs) were analyzed. In addition, the micronuclei induction and cell death via apoptosis were studied. We found that the biological action of UPEB-radiation compared to X-rays was characterized by significantly slower γH2AX foci elimination (with a dose of 1 Gy) and strong apoptosis induction (with doses of 0.5 and 1.0 Gy), accompanied by a slight increase in micronuclei formation (dose of 1 Gy). Our data suggest that UPEB radiation produces more complex DNA damage than X-ray radiation, leading to cell death rather than cytogenetic disturbance.
Highly Selective Cleavage of TH2-Promoting Cytokines by the Human and the Mouse Mast Cell Tryptases, Indicating a Potent Negative Feedback Loop on TH2 Immunity
Authors: Fu Zhirong , Akula Srinivas , Thorpe Michael , Hellman Lars
Published: October 2019

Mast cells (MC) are resident tissue cells found primarily at the interphase between tissues and the environment. These evolutionary old cells store large amounts of proteases within cytoplasmic granules, and one of the most abundant of these proteases is tryptase. To look deeper into the question of their in vivo targets, we have analyzed the activity of the human MC tryptase on 69 different human cytokines and chemokines, and the activity of the mouse tryptase (mMCP-6) on 56 mouse cytokines and chemokines. These enzymes were found to be remarkably restrictive in their cleavage of these potential targets. Only five were efficiently cleaved by the human tryptase: TSLP, IL-21, MCP3, MIP-3b, and eotaxin. This strict specificity indicates a regulatory function of these proteases and not primarily as unspecific degrading enzymes. We recently showed that the human MC chymase also had a relatively strict specificity, indicating that both of these proteases have regulatory functions. One of the most interesting regulatory functions may involve controlling excessive TH2-mediated inflammation by cleaving several of the most important TH2-promoting inflammatory cytokines, including IL-18, IL-33, TSLP, IL-15, and IL-21, indicating a potent negative feedback loop on TH2 immunity.
Conjoint Analysis of Genome-Wide lncRNA and mRNA Expression of Heteromorphic Leavesin Response to Environmental Heterogeneityin Populus euphratica
Authors: Zeng Ming , He Shuhang , Hao Lin , Li Yujie , Zheng Caixia , Zhao Yuanyuan
Published: October 2019

Heterophylly is the phenomenon of leaf forms varying along the longitudinal axis within a single plant. Populus euphratica, a heterophyllous woody plant, develops lanceolate leaves and dentate broad-ovate leaves on the bottom and top of the canopy, respectively, which are faced with different intensities of ambient solar radiation. However, the mechanism of the heteromorphic leaf response to the microenvironment in P. euphratica remains elusive. Here, we show that the dentate broad-ovate leaves have advantages in tolerating high light intensity, while lanceolate leaves are excellent at capturing light. Compared with lanceolate leaves, more trichomes, higher stomatal density, thicker lamina, and higher specific leaf weight were observed in dentate broad-ovate leaves. Furthermore, high-throughput RNA sequencing analysis revealed that the expression patterns of genes and long noncoding RNAs (lncRNAs) are different between the two heteromorphic leaves. A total of 36,492 genes and 1725 lncRNAs were detected, among which 586 genes and 54 lncRNAs were differentially expressed. Based on targets prediction, lncRNAs and target genes involved in light adaption, protein repair, stress response, and growth and development pathways were differentially expressed in heteromorphic leaves, 10 pairs of which were confirmed by quantitative real-time PCR. Additionally, the analysis of interactions indicated that lncRNA–mRNA interactions were involved in the response to the microenvironment of heteromorphic leaves. Taken together, these results suggest that the morphological features and joint regulation of lncRNA–mRNA in heteromorphic leaves may serve as survival strategies for P. euphratica, which could lead to optimal utilization of environmental factors.
Bi-Material Negative Thermal Expansion Inverted Trapezoid Lattice based on A Composite Rod
Authors: Luo Weipeng , Xue Shuai , Zhang Meng , Zhao Cun , Li Guoxi
Published: October 2019

Negative thermal expansion (NTE) lattices are widely used in aerospace engineering where the structures experience large temperature variation. However, the available range of NTE of the current lattices is quite narrow, which severely limits their engineering application. In this paper, we report an inverted trapezoid lattice (ITL) with large NTE. The NTE of the ITL is 2.6 times that of a typical triangular lattice with the same height and hypotenuse angle. Theoretically, with a pin-jointed assumption, the ITL can improve the NTE by order of magnitude if the length ratio of the composite rod is changed. In the presented ITL, a composite rod is utilized as the base of the ITL. The composite rod has large inner NTE. The inverted trapezoid structure converts the inner NTE to the vertical direction contraction and obtains an extra NTE. Finite element simulations and experimental verification by interferometric measurement were conducted to verify the large thermal expansion of the ITL.
Investigation on Compression Mechanical Properties of Rigid Polyurethane Foam Treated under Random Vibration Condition: An Experimental and Numerical Simulation Study
Authors: Qiu Dacheng , He Yannan , Yu Zhiqiang
Published: October 2019

The mechanical failure properties of rigid polyurethane foam treated under random vibration were studied experimentally and by numerical simulation. The random vibration treatments were carried out in the frequency range of 5–500 Hz, 500–1000 Hz, and 1000–1500 Hz, respectively. The influence of the vibration frequency, mass block and acceleration on the mechanical performance of rigid polyurethane foam was further investigated by compression testing. The experimental results showed that the compression performance and energy absorption of foams decreased the least between 500–1000 Hz. In addition, in the 5–500 Hz range, the reduction rate of compression performance and energy absorption increased with the increase of the vibration mass block and acceleration. The resulting simulation indicated that the deformation degree of the sample was the most serious under the condition of 5–500 Hz. With the increase of deformation, the damage of the sample during the vibration process increased, which led to the decrease of compression property and energy absorption of rigid polyurethane foam. This further explained the variation mechanism of the compression test performance.
Preparation of Small-Particle and High-Density Cobalt Carbonate Using a Continuous Carbonate Precipitation Method and Evaluation of Its Growth Mechanism
Authors: Guo Miaomiao , Xi Xiaoli , Li Sen , Li Chenwei , Nie Zuoren , Xu Kaihua
Published: October 2019

Spherical CoCO3 powder with a small particle size and high density was successfully prepared using a continuous carbonate liquid precipitation method with a raw material of cobalt chloride solution, a precipitant of NH4HCO3, and without a template. The effects of the concentration of ammonium carbonate, process pH, and feeding rate on the tap density and apparent density of cobalt carbonate were investigated. It was found that the apparent and tap density values of 4.4 µm of cobalt carbonate were 1.27 g/cm3 and 1.86 g/cm3, respectively, when the initial concentration of NH4HCO3 solution was 60 g/L, the pH was 7.15–7.20, and the feeding rate of cobalt chloride was 2 L/h. The anisotropic growth process of the crystal lattice plane of CoCO3 under the aforementioned optimal conditions were studied. The results demonstrated that the crystal grew fastest along the (110) facet orientation, which was the dominant growth surface, determining the final morphology of the primary particles. The scanning electron microscopy (SEM) and high-resolution transmission electron microscopy (HR-TEM) results demonstrated that the primary particle morphology of the cobalt carbonate was a nanosheet. The unit cell of cobalt carbonate, of a hexagonal structure in the horizontal direction, grew horizontally along the (110) facet orientation, while 20–35 unit cells of the carbon carbonate were stacked along the c-axis in the thickness direction. Finally, the sheet-shaped particles were agglomerated into dense spherical secondary particles, as presented through the crystal re-crystallization model.
Sargassum Seaweed as a Source of Anti-Inflammatory Substances and the Potential Insight of the Tropical Species: A Review
Authors: Saraswati  , Giriwono Puspo Edi , Iskandriati Diah , Tan Chin Ping , Andarwulan Nuri
Published: October 2019

Sargassum is recognized both empirically and scientifically as a potential anti-inflammatory agent. Inflammation is an important response in the body that helps to overcome various challenges to body homeostasis such as microbial infections, tissue stress, and certain injuries. Excessive and uncontrolled inflammatory conditions can affect the pathogenesis of various diseases. This review aims to explore the potential of Sargassum’s anti-inflammatory activity, not only in crude extracts but also in sulfated polysaccharides and purified compounds. The tropical region has a promising availability of Sargassum biomass because its climate allows for the optimal growth of seaweed throughout the year. This is important for its commercial utilization as functional ingredients for both food and non-food applications. To the best of our knowledge, studies related to Sargassum’s anti-inflammatory activity are still dominated by subtropical species. Studies on tropical Sargassum are mainly focused on the polysaccharides group, though there are some other potentially bioactive compounds such as polyphenols, terpenoids, fucoxanthin, fatty acids and their derivatives, typical polar lipids, and other groups. Information on the modulation mechanism of Sargassum’s bioactive compounds on the inflammatory response is also discussed here, but specific mechanisms related to the interaction between bioactive compounds and targets in cells still need to be further studied.
The Origins of Enhanced and Retarded Crystallization in Nanocomposite Polymers
Authors: Jabbarzadeh Ahmad
Published: October 2019

Controlling the crystallinity of hybrid polymeric systems has an important impact on their properties and is essential for developing novel functional materials. The crystallization of nanocomposite polymers with gold nanoparticles is shown to be determined by free space between nanoparticles. Results of large-scale molecular dynamics simulations reveal while crystallinity is affected by the nanoparticle size and its volume fraction, their combined effects can only be measured by interparticle free space and characteristic size of the crystals. When interparticle free space becomes smaller than the characteristic extended length of the polymer molecule, nanoparticles impede the crystallization because of the confinement effects. Based on the findings from this work, equations for critical particle size or volume fraction that lead to this confinement-induced retardation of crystallization are proposed. The findings based on these equations are demonstrated to agree with the results reported in experiments for nanocomposite systems. The results of simulations also explain the origin of a two-tier crystallization regime observed in some of the hybrid polymeric systems with planar surfaces where the crystallization is initially enhanced and then retarded by the presence of nanoparticles.