bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust Unsupervised Factory Activity Recognition with Body-worn Accelerometer Using Temporal Structure of Multiple Sensor Data Motifs
Authors: Xia Qingxin , Korpela Joseph , Namioka Yasuo , Maekawa Takuya
Published: September 2020

This paper presents a robust unsupervised method for recognizing factory work using sensor data from body-worn acceleration sensors. In line-production systems, each factory worker repetitively performs a predefined work process with each process consisting of a sequence of operations. Because of the difficulty in collecting labeled sensor data from each factory worker, unsupervised factory activity recognition has been attracting attention in the ubicomp community. However, prior unsupervised factory activity recognition methods can be adversely affected by any outlier activities performed by the workers. In this study, we propose a robust factory activity recognition method that tracks frequent sensor data motifs, which can correspond to particular actions performed by the workers, that appear in each iteration of the work processes. Specifically, this study proposes tracking two types of motifs: period motifs and action motifs, during the unsupervised recognition process. A period motif is a unique data segment that occurs only once in each work period (one iteration of an overall work process). An action motif is a data segment that occurs several times in each work period, corresponding to an action that is performed several times in each period. Tracking multiple period motifs enables us to roughly capture the temporal structure and duration of the work period even when outlier activities occur. Action motifs, which are spread throughout the work period, permit us to precisely detect the start time of each operation. We evaluated the proposed method using sensor data collected from workers in actual factories and achieved state-of-the-art performance.
Detecting deepfakes using crowd consensus
Authors: Tursman Eleanor
Published: September 2020

Deepfake videos are becoming more and more believable, outpacing fake detection methods. As a research community, we must embrace a wider variety of detection tactics to keep up and quell the spread of misinformation.
Checking Invariant Confluence, In Whole or In Parts
Authors: Whittaker Michael , Hellerstein Joseph M.
Published: September 2020

Strongly consistent distributed systems are easy to reason about but face fundamental limitations in availability and performance. Weakly consistent systems can be implemented with very high performance but place a burden on the application developer to reason about complex interleavings of execution. Invariant confluence provides a formal framework for understanding when we can get the best of both worlds. An invariant confluent object can be efficiently replicated with no coordination needed to preserve its invariants. However, actually determining whether or not an object is invariant confluent is challenging.

In this paper, we establish conditions under which a commonly used sufficient condition for invariant confluence is both necessary and sufficient, and we use this condition to design a general-purpose interactive invariant confluence decision procedure. We then take a step beyond invariant confluence and introduce a generalization of invariant confluence, called segmented invariant confluence, that allows us to replicate non-invariant confluent objects with a small amount of coordination. We implement these formalisms in a prototype called Lucy and find that our decision procedures efficiently handle common real-world workloads including foreign keys, escrow transactions, and more.
Linking Genes to Shape in Plants Using Morphometrics
Authors: Xu Hao , Bassel George W.
Published: September 2020

A transition from qualitative to quantitative descriptors of morphology has been facilitated through the growing field of morphometrics, representing the conversion of shapes and patterns into numbers. The analysis of plant form at the macromorphological scale using morphometric approaches quantifies what is commonly referred to as a phenotype. Quantitative phenotypic analysis of individuals with contrasting genotypes in turn provides a means to establish links between genes and shapes. The path from a gene to a morphological phenotype is, however, not direct, with instructive information progressing both across multiple scales of biological complexity and through nonintuitive feedback, such as mechanical signals. In this review, we explore morphometric approaches used to perform whole-plant phenotyping and quantitative approaches in capture processes in the mesoscales, which bridge the gaps between genes and shapes in plants. Quantitative frameworks involving both the computational simulation and the discretization of data into networks provide a putative path to predicting emergent shape from underlying genetic programs.
Socioeconomic Status and Intimate Relationships
Authors: Karney Benjamin R.
Published: September 2020

The ways that couples form and manage their intimate relationships at higher and lower levels of socioeconomic status (SES) have been diverging steadily over the past several decades. At higher SES levels, couples postpone marriage and childbirth to invest in education and careers, but they eventually marry at high rates and have relatively low risk for divorce. At lower SES levels, couples are more likely to cohabit and give birth prior to marriage and less likely to marry at all. This review examines how SES comes to be associated with the formation, development, and dissolution of intimate relationships. Overall, research has highlighted how a couple's socioeconomic context facilitates some choices and constrains others, resulting in different capacities for relationship maintenance and different adaptive mating strategies for more and less advantaged couples. A generalizable relationship science requires research that acknowledges these differences and one that recruits, describes, and attends to socioeconomic diversity across couples.
Life Change, Social Identity, and Health
Authors: Haslam Catherine , Haslam S. Alexander , Jetten Jolanda , Cruwys Tegan , Steffens Niklas K.
Published: September 2020

Life change affects health. Research aimed at understanding the consequences of life change has primarily focused on the important roles played by stress, social support, individual differences, and broader socioeconomic factors in shaping health outcomes, most notably mental health decline. In this review we extend these accounts by exploring social identity–based determinants of adjustment to life change. We do so by drawing on social identity theorizing and, in particular, the Social Identity Model of Identity Change (SIMIC). This points to the importance of multiple, maintained, new, and compatible group memberships as determinants of people's responses and adjustment to life change. We apply this model to understand the health consequences of adjustment to life change in four diverse areas: pursuit of higher education, migration, trauma and resilience, and recovery from illness and injury. Finally, we provide direction for future research on SIMIC and the health consequences of life change.
γ-ray Irradiation-Induced Chemical and Structural Changes in CVD Monolayer MoS2
Authors: Singh Aditya , Singh R.
Published: September 2020

Two dimensional (2D) materials are the ideal choice for highly efficient, lightweight, low power consumption nanoelectronics in space science applications. Therefore, investigation of radiation hardness of 2D-materials is of great interest. Herein, we report the effect of gamma irradiation on chemical vapor deposition (CVD) synthesized crystalline monolayer (1 L) molybdenum disulfide (MoS2) flakes on the sapphire substrate at various doses, viz., 1–1000 kGy. We estimated that the temperature of MoS2 increases by 1.3 °C per kGy of gamma-ray dose. It was observed that up to 130 kGy (∼195 °C), gamma exposure has no significant impact on the morphology and chemical properties of MoS2. However, X-ray photoelectron spectroscopy (XPS) shows that from 275 kGy (∼385 °C), MoS2 starts converting into MoOx. Raman spectroscopy shows that at low gamma doses, the crystallinity of MoS2 increases while at higher doses, a traceable amount of MoS2 starts converting into amorphous MoS3. Our findings show that both E1
2g and A1g Raman mode of MoS2 blue shift as gamma dose increases owing to the combined effect of sulfur vacancies creation and strain caused by thermal expansion of MoS2.
Prediction of hemodynamics after atrial septal defect closure using a framework of circulatory equilibrium in dogs
Authors: Uike Kiyoshi , Saku Keita , Nishikawa Takuya , Yamamura Kenichiro , Nagata Hazumu , Muraoka Mamoru , Ohga Shouichi , Tsutsui Hiroyuki , Sunagawa Kenji
Published: September 2020

We developed a framework to predict the impact of atrial septal defect (ASD) closure on hemodynamics by incorporating ASD shunt flow into the framework of circulatory equilibrium. The proposed framework accurately predicted hemodynamics after ASD closure. Patient-specific prediction of hemodynamics may be useful for safety management of ASD closure.
Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of nonreperfused myocardial infarction
Authors: Hanna Anis , Shinde Arti V. , Frangogiannis Nikolaos G.
Published: September 2020

We show that cardiac rupture accounts for 50% of deaths in C57BL/6J mice undergoing nonreperfused myocardial infarction protocols. Overestimation of rupture events in published studies likely reflects the low specificity of hemothorax as a criterion for documentation of rupture. In contrast, identification of a gross rupture site has high specificity and low sensitivity. We also show that mice dying of rupture have increased macrophage influx and attenuated myofibroblast infiltration in the infarct. These findings are consistent with a role for perturbations in the balance between inflammatory and reparative responses in the pathogenesis of postinfarction cardiac rupture. We also report that the male predilection for rupture in infarcted mice is not associated with increased inflammatory activation of myeloid cells.
Exercise heat acclimation has minimal effects on left ventricular volumes, function and systemic hemodynamics in euhydrated and dehydrated trained humans
Authors: Travers Gavin , González-Alonso José , Riding Nathan , Nichols David , Shaw Anthony , Périard Julien D.
Published: September 2020

This study demonstrates that 10 days of exercise heat acclimation has minimal effects on left ventricular volumes, intrinsic cardiac function, and systemic hemodynamics during prolonged, repeated semirecumbent exercise in moderate heat, where heart rate and blood volume are similar to preacclimation levels. However, progressive dehydration is consistently associated with similar degrees of hyperthermia and tachycardia and reductions in blood volume, diastolic filling of the left ventricle, stroke volume, and cardiac output, regardless of acclimation state.
Wild Edible Plant Nutritional Contribution and Consumer Perception in Ethiopia
Authors: Duguma Haile Tesfaye
Published: September 2020

The scarcity, high cost, and unreliable supply of healthy food in developing countries have resulted in the search for cheap and alternative sources of healthy and nutritious food. Wild edible plants (WEPs) are one of the alternative sources of healthy and nutritious food, and they are crucially important in supporting the global food basket in all parts of the world in general and in sub-Saharan Africa in particular. These wild edible plants have played a significant role in supplying food and nutritional requirements and increasing the health status of poor communities in many rural parts of the world. In Ethiopia, rural communities use wild edible plants as a means of survival especially during times of drought and famine and during other forms calamities and crises. Wild edible plants have high nutritional content, including proteins, vitamin B2, and vitamin C, which can be used as alternatives to conventional plant-based human diets. The available literature has revealed that some wild edible plants also have medicinal properties. Even though wild edible plants are important for food security, they are usually overlooked and perceived as food for poor families. This review indicates that fruits are the most commonly used WEPs, both for consumption and medicinal value, and most plant parts are eaten directly in raw forms. This review focuses on the commercial exploitation of wild edible plants as a source of dietary supplements and alternative medicines and as a means to generate income; it also focuses on consumer perception toward wild edible plants in Ethiopia. Despite easy accessibility and availability, the consumption of wild edible plants is challenged by numerous factors. This review suggests that nutrition policies have to promote the utilization of wild edible plants as one pillar of food and nutrition security. Bioactive compound contents and antinutritional factor contents of wild and medicinal plants need further investigation.
Excavation Sequence and Surrounding Rock Mass Stability of Large‐Scale Underground Engineering with 8 Tunnels
Authors: Zhang Zhiqiang , He Mingming , Chen Fangfang , Li Ning
Published: September 2020

In some large‐scale hydroelectric power projects, there are more than 3 tunnels that are too close to each other to eliminate the mutual influence during the excavation period, especially for large‐scale tunnel groups. In this paper, aimed at analyzing the Bukun hydropower station consisting of 8 tunnels in Malaysia, the displacement, stress, and plastic zone of the surrounding rock mass are analyzed to study the effect of the excavation sequence on the stability of the surrounding rock mass for large‐scale tunnel groups. On the one hand, the in situ monitoring of the surface displacement of the rock mass surrounding the tunnel using extensometers is performed to obtain the deformation characteristics on the excavation limit under the typical excavation sequence. On the other hand, a series of elastic‐plastic 3D numerical experiments are carried out to explore the displacement characteristics, stability of the large‐scale tunnel groups, and safety of the initial supporting system. The results show that the tendencies of the displacement increase corresponding to the tunnel face movement are similar for the three excavation sequences. The displacement under initial excavation sequence 2 (IES2) is the smallest among the three sequences; the area of the plastic zone under IES2 is the smallest among them; and the stresses in the shotcrete layer and axial forces in the rock bolt under the three excavation sequences are within the safety limitation. Initial excavation sequence 2 is an optimized excavation sequence, in which tunnels #1 and #5 are excavated first; after an advance of 3 times the diameter of the tunnel, tunnels #3 and #7 are excavated; tunnels #2 and #6 are excavated after an advance of 3 times diameters; and tunnels #4 and #8 are excavated after an advance of 3 times diameters.
Related Fixed Point Theorems via General Approach of Simulations Functions
Authors: Zoto Kastriot , Mlaiki Nabil , Aydi Hassen
Published: September 2020

In this work, we extend and complement some results in view of general and wider structures, such as

b
−

metric spaces. By considering existing classes of

Ζ
−

contractions and

Ψ
−

simulating functions with a solid impact in database results of fixed point theory, we introduce a new general class of simulating functions, called as

Ψ
−
s

simulation functions, and also types of

κ

ψ
−
s

−

contractions in a more general framework. This approach covers, extends, and unifies several published works in the early and late literature.
Overexpression of Spondin-2 Is Associated with Recurrence-Free Survival in Patients with Localized Clear Cell Renal Cell Carcinoma
Authors: Ma Hui-Min , Yu Meng , Wu Cong , Huang Hou-Bao , Li Ya-Wei , Zhang Peng , Huang Jian-Jun , Cheng Long , Feng Gang , Li Guo-Rong
Published: September 2020

Background. The spondin-2 (SPON2) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in clear cell renal cell carcinoma (ccRCC) are still unclear. Methods. SPON2 expression in ccRCC was evaluated using expression data from TCGA and GEO databases, then confirmed by local patient population (94 patients). The clinical significance of SPON2 expression was evaluated. Downregulation of SPON2 was performed using small-interfering RNA (siRNA). The effects of SPON2 silencing on cell proliferation, apoptosis, invasion, and migration in vitro were investigated. Results. SPON2 was overexpressed in the majority of the ccRCC at both mRNA and protein levels. SPON2 expression was significantly correlated with stage, grade, and recurrence (all P<0.05) in patients with localized ccRCC. The receiver operating characteristic (ROC) curve showed that SPON2 expression could serve as a predictor of recurrence. SPON2 expression was significantly associated with recurrence-free survival (RFS) in patients with localized ccRCC. Knocking down SPON2 resulted in suppressed cell invasion and migration in vitro. Conclusion. SPON2 expression might function as a prognostic biomarker in patients with localized ccRCC.
Correlation of Redox Status with Procalcitonin and C-reactive Protein in Septic Patients
Authors: Petrovic Jasna , Turnic Tamara Nikolic , Zivkovic Vladimir , Andjic Marijana , Draginic Nevena , Stojanovic Aleksandra , Milinkovic Ivan , Bolevich Sergey , Jevdjic Jasna , Jakovljevic Vladimir
Published: September 2020

Based on the role of oxidative stress in the pathophysiological mechanisms of sepsis and the importance of PCT as a clinically applicable biomarker for early detection of inflammatory response initiation, we aimed this study at examining the correlation between PCT levels and oxidative stress parameters (prooxidants and antioxidants) in patients with sepsis. This study was designed as a case-series prospective clinical study which involved 103 critically ill patients and 17 healthy participants with diagnosis of sepsis/septic shock (over 18 years of age, both gender) admitted to the Intensive Care Unit (ICU) of Valjevo General Hospital in Serbia. All subjects were divided into patients who were operated on/underwent surgery before sampling and have sepsis (n=24), patients who were operated on/underwent surgery before sampling and have septic shock (n=25), patients who were not operated on/did not undergo surgery before sampling and have sepsis (n=26), patients who were not operated on/did not undergo surgery before sampling and have septic shock (n=28), and participants who are healthy (n=17). PCT has confirmed a positive correlation with prooxidants and type of critical illness, and performing surgical intervention diminished oxidative stress in patients with septic shock. Prognosis in critically ill patients was strongly associated with PCT levels but not with nonspecifically C-reactive protein.
Use of Cesarean Birth among Robson Groups 2 and 4 at Mizan-Tepi University Hospital, Ethiopia
Authors: Harrison Margo S. , Liyew Tewodros , Kirub Ephrem , Teshome Biruk , Jimenez-Zambrano Andrea , Muldrow Margaret , Yarinbab Teklemariam
Published: September 2020

Background. Primary cesarean birth rates were high among women who were either nulliparous (Group 2) or multiparous (Group 4) with a single, cephalic, term fetus who were induced, augmented, or underwent cesarean birth before labor in our study cohort. Objectives. The objective of this analysis was to determine what risk factors were associated with cesarean birth among Robson Groups 2 and 4. Methods. This study was a prospective hospital-based cross-sectional analysis of a convenience sample of 1,000 women who delivered at Mizan-Tepi University Teaching Hospital in the summer and fall of 2019. Results. Women in Robson Groups 2 and 4 comprised 11.4% (n = 113) of the total population (n = 993). The cesarean birth rate in Robson Group 2 (n = 56) was 37.5% and in Robson Group 4 (n = 57) was 24.6%. In Robson Group 2, of all prelabor cesareans (n = 5), one birth was elective cesarean by maternal request; the intrapartum cesarean births (n = 16) mostly had a maternal or fetal indication (93.8%), with one birth (6.2%) indicated by “failed induction or augmentation,” which was a combined indication. In Robson Group 4, all 4 women delivered by prelabor cesarean had a maternal indication (one was missing data), and 3 of the intrapartum cesareans were indicated by “failed induction or augmentation.” In multivariable modeling of Robson Group 2, having a labor duration of “not applicable” increased the risk of cesarean delivery (RR 2.9, CI (1.5, 5.4)). The odds of requiring maternal antibiotics was the only notable outcome with increased risk (RR 11.1, CI (1.9, 64.9)). In multivariable modeling of Robson Group 4, having a labor longer than 24 hours trended towards a significant association with cesarean (RR 3.6, CI (0.9, 14.3)), and women had a more dilated cervix on admission trended toward having a lower odds of cesarean (RR 0.8, CI (0.6, 1.0)). Conclusion. Though rates of primary cesarean birth among women who have a term, single, cephalic fetus and are induced, augmented, or undergone prelabor cesarean birth are high, those that occur intrapartum seem to be associated with appropriate risk factors and indications, though we cannot say this definitely as we did not perform an audit. More research is needed on the prelabor subgroup as a separate entity.
Optimal Control and Simulation for Enterprise Financial Risk in Industry Environment
Authors: Liang Yanjun , Zhang Wei-hua , Lu Youjun , Wang Zhong-Sheng
Published: September 2020

A technique for enterprise financial risk optimal control with exponential decay rate and simulation is developed in industry environment. The factors of industry environment risks to enterprise financial activities are considered, based on the evaluation method taking into both subjectivity and objectivity, seven kinds of industry environment risks influencing enterprise financial activities are chosen as state variables, and the enterprise financial risk dynamical system model is established for the first time. In order to reduce the risk of enterprise financial activity subjected to industry environment, an average performance index with exponential decay rate is chosen for the systems. Using the optimal control approach, an optimal vibration controller with exponential decay rate is designed. Numerical simulation results illustrate the effectiveness of the proposed technique.
Schisandra Fruit Vinegar Lowers Lipid Profile in High‐Fat Diet Rats
Authors: Yuan Rui , Sun Guangren , Gao Jiaqi , Yu Zepeng , Yu Chunyan , Wang Chunmei , Sun Jinghui , Li He , Chen Jianguang
Published: September 2020

Hyperlipidemia and its associated obesity, hepatic steatosis, and NAFLD are worldwide problems. However, there is no ideal pharmacological treatment for these. Therefore, the complementary therapies that are both natural and safe have been focused. Healthy foods, such as fruit vinegar, may be one of the best choices. In this study, we made a special medicinal fruit vinegar, Schisandra fruit vinegar (SV), and examined its lipid‐lowering effects and the underlying mechanisms in a high‐fat diet rat model. The results showed that SV significantly reduced the body weight, liver weight, liver index, the serum triglyceride (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), free fatty acid (FFA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA), increased the content of high‐density lipoprotein cholesterol (HDL‐C) and the activity of superoxide dismutase (SOD), upregulated the expressions of peroxisome proliferative activated receptor (PPAR‐α), peroxisomal acyl‐coenzyme A oxidase 1 (ACOX1), and carnitine palmitoyltransferase 1 (CPT1) proteins, increased the contents of key component of antioxidant defense NF‐E2‐related factor 2 (NRF2) and its downstream heme oxygenase‐1 (HO‐1) protein, and downregulated the expression of Kelch‐like ECH‐associated protein 1 (KEAP1). These results suggest that SV has weight loss and lipid‐lowering effects in HFD rats, which may be related to its upregulation of the expressions of β‐oxidation ‐elated PPAR‐α, CPT1, and ACOX1 and the regulation of the expressions of antioxidant pathway‐related KEAP1‐NRF2‐HO‐1. Therefore, all these data provide an experimental basis for the development of SV as a functional beverage which is safe, effective, convenient, and inexpensive.
Herbicide Widespread: The Effects of Pethoxamid on Nonalcoholic Fatty Liver Steatosis In Vitro
Authors: Pirozzi Anna Virginia Adriana , Stellavato Antonietta , Schiraldi Chiara , Giuliano Mariateresa
Published: September 2020

Pethoxamid is a widespread herbicidal product, presenting itself as an extremely flexible active substance and with a high potential for use as an herbicide for preemergence. The emergence of multiple resistance in crops has been addressed using combinations of preemergence and postemergence herbicides in the same seeding-harvest cycle. A winning combination of pethoxamid and glyphosate mainly affected the acidobacteria population. Glyphosate scientific literature has demonstrated an observational link between herbicide exposure and liver disease in human subjects. Identifying and ranking the risk to the public that pethoxamid could exert on target organs has not been evaluated so far. Due to similarities to glyphosate, we did look at the effect of pethoxamid on impaired liver cells HepG2, using a nonalcoholic fatty liver disease (NAFLD) cell model in vitro. Pethoxamid was cytotoxic starting at 1 ppm. Fatty acid accumulation (FA) was enhanced while low doses of pethoxamid slightly decreased LDH protein expression compared to FA-treated HepG2. The same trend was observed for cytochrome c. Based on our data, we can argue that NAFLD hepatic cells react to pethoxamid trying detoxifying strategies, ready to undergo cell death to avoid further degeneration. Downregulation of cytochrome can lead to the hypothesis that pethoxamid should not induce herbicide resistance.
Vitamin D Auto-/Paracrine System Is Involved in Modulation of Glucocorticoid-Induced Changes in Angiogenesis/Bone Remodeling Coupling
Authors: Lisakovska Olha , Shymanskyi Ihor , Labudzynskyi Dmytro , Mazanova Anna , Veliky Mykola
Published: September 2020

Osteoporosis is a devastating side effect of chronic glucocorticoid (GC) treatment. Despite the crucial role of vitamin D (VD) in bone homeostasis, the precise molecular mechanisms of its action on GC-induced disturbances of bone remodeling remain undefined. The study was performed to elucidate the relation of VD status to GC-induced changes of the angiogenesis/osteogenesis/bone resorption coupling in bone tissue. Female Wistar rats received prednisolone (5 mg/kg of b.w.) with or without VD3 (1000 IU/kg of b.w., for 30 days). Biomechanical parameters of rat femurs were assessed by the three-point bending test. The levels of calcium, inorganic phosphate, activity of total alkaline phosphatase (ALP), and its isoenzymes were determined spectrophotometrically. Vascular endothelial growth factor-A (VEGF-A) and caspase-3 protein levels were detected by western blotting. Vdr and Cyp27b1 mRNAs were measured by qRT-PCR. Receptor activator of nuclear factor κB (RANK) expression in bone sections was visualized immunohistochemically. Serum 25(OH)D was assayed by ELISA. GC administration led to a decrease in maximal load (by 1.2-fold) and stiffness and toughness (by 1.3-fold), which was accompanied by a 3-fold reduction of 25(OH)D level, an elevation of the ALP bone isoenzyme activity in serum, hypocalcaemia, and hypophosphatemia. Along with prednisolone-induced VD deficiency, an impaired synthesis of Vdr (−30%) and Cyp27b1 (+71%) mRNA was observed, reflecting deregulation of bone tissue VD-auto-/paracrine system. GC caused an increase in caspase-3 content, suppressed the synthesis of the osteoclastic marker RANK, and altered angiogenesis/osteogenesis coupling by significantly reducing the level of VEGF-A.VD3 treatment restored serum 25(OH)D content and the expression of key components of the VD-auto-/paracrine system. VD3 supplementation diminished cell apoptosis and strongly improved angiogenesis/osteogenesis coupling as well as mineral metabolism and biomechanical parameters of femurs in GC-administered rats. Thus, VD3 can have a beneficial effect on the correction of GC-induced pathological changes in bone remodeling.
Effect of Temperature on the Chemical Composition and Physicochemical Properties of Diester Aviation Lubrication Oil
Authors: Yao Ting , Zhang Na , Hu Jianqiang , Liao Xiaoxiao , Shen Yongli , Gan Zhuoting
Published: September 2020

High temperature is the main factor responsible for degrading the lubrication and antiwear properties of aero-lubricating oils. Accordingly, this study assessed the effects of thermal treatment of diester aviation lubricating oil and the associated mechanism. Fourier-transform infrared spectroscopy and gas chromatography/mass spectrometry analyses showed that low-molecular-weight compounds, such as monoesters, diesters, alcohols, and olefins, were the primary degradation products. An assessment of the degradation mechanism of bis(2-ethylhexyl)decanedioate showed that pyrolysis, resulting in the cleavage of β-C–H and C–C bonds, was the main process involved. Additional investigation using advanced polymer chromatography showed that the molecular weights of oil samples changed slightly at high temperatures, while the viscosity and viscosity-temperature index values were relatively stable. High-pressure differential scanning calorimetry established that the thermal oxidation stability of these oils decreased above 250°C. Finally, variations in the chemical compositions of the oil samples were found to be highly correlated with changes in physicochemical properties during thermal processing, with the formation of low-molecular-weight polar compounds greatly increasing the acid numbers of the oils.
Research on the Source Mechanism and Source Prevention and Control System of Deep Rock Burst
Authors: Di Shuai
Published: September 2020

Deep rock burst accidents occur frequently and become increasingly serious. Further improving the effectiveness and accuracy of the prevention and control of rock burst, ensuring the safe and efficient production of mines, clarifying the basic causes of disasters, and refining the type of deep rock burst are the most important key links. Aiming at the problems such as unclear incentives and types and the lack of effective and targeted prevention measures of deep rock burst, taking Xin’an Mine as the research background, based on the energy theory, the coal and rock mass multisource energy unified equation was established to analyze coal and rock mass instability mechanism. According to the different degrees of participation of various factors, the types of deep rock burst are determined as three categories and four types, and the corresponding judgment criteria are proposed. The precise prevention and control system for the source of rock burst with Xin’an characteristics is proposed, successfully applied to the 8101 working face, which not only guarantees the safe production of the working face, but also achieves good economic benefits. The research results lay the foundation for improving the accuracy and precision of the prevention and control of deep rock burst and provide theoretical guidance for the safe and efficient mining of the mine.
Digital Twin‐based Safety Evaluation of Prestressed Steel Structure
Authors: Liu Zhansheng , Bai Wenyan , Du Xiuli , Zhang Anshan , Xing Zezhong , Jiang Antong
Published: September 2020

The safety of prestressed steel structures in service has been studied widely. However, traditional safety assessment methods for prestressed steel structures involve few sample points, do not provide accurate predictions, and consume substantial human and material resources. The digital twin technology can be used to monitor the structural behavior, state, and activity of a steel structure throughout its life cycle, which is equivalent to performing a safety assessment of the structure. The purpose of this study is to establish a digital twin multidimensional model of prestressed steel structures. Based on this model, the support vector machine and prediction model are trained using the relevant structural history data, and the safety risk level of the structure is then predicted based on the measured data. Finally, a proportional reduction model of the wheel‐spoke cable truss structure is used to verify the feasibility of the proposed method. The results show that digital twin technology can achieve real‐time monitoring of prestressed steel structures in use and can provide timely predictions of the safety level. This represents a new method for the safety risk assessment of prestressed steel structures.
PD1 Blockade Enhances ICAM1-Directed CAR T Therapeutic Efficacy in Advanced Thyroid Cancer
Authors: Gray Katherine D. , McCloskey Jaclyn E. , Vedvyas Yogindra , Kalloo Olivia R. , Eshaky Steve El , Yang Yanping , Shevlin Enda , Zaman Marjan , Ullmann Timothy M. , Liang Heng , Stefanova Dessislava , Christos Paul J. , Scognamiglio Theresa , Tassler Andrew B. , Zarnegar Rasa , Fahey Thomas J. , Jin Moonsoo M. , Min Irene M.
Published: September 2020

Purpose:

Advanced thyroid cancers, including poorly differentiated and anaplastic thyroid cancer (ATC), are lethal malignancies with limited treatment options. The majority of patients with ATC have responded poorly to programmed death 1 (PD1) blockade in early clinical trials. There is a need to explore new treatment options.

Experimental Design:

We examined the expression of PD-L1 (a ligand of PD1) and intercellular adhesion molecule 1 (ICAM1) in thyroid tumors and ATC cell lines, and investigated the PD1 expression level in peripheral T cells of patients with thyroid cancer. Next, we studied the tumor-targeting efficacy and T-cell dynamics of monotherapy and combination treatments of ICAM1-targeting chimeric antigen receptor (CAR) T cells and anti-PD1 antibody in a xenograft model of ATC.

Results:

Advanced thyroid cancers were associated with increased expression of both ICAM1 and PD-L1 in tumors, and elevated PD1 expression in CD8+ T cells of circulating blood. The expression of ICAM1 and PD-L1 in ATC lines was regulated by the IFNγ–JAK2 signaling pathway. ICAM1-targeted CAR T cells, produced from either healthy donor or patient T cells, in combination with PD1 blockade demonstrated an improved ability to eradicate ICAM1-expressing target tumor cells compared with CAR T treatment alone. PD1 blockade facilitated clearance of PD-L1 high tumor colonies and curtailed excessive CAR T expansion, resulting in rapid tumor clearance and prolonged survival in a mouse model.

Conclusions:

Targeting two IFNγ-inducible, tumor-associated antigens—ICAM1 and PD-L1—in a complementary manner might be an effective treatment strategy to control advanced thyroid cancers in vivo.
Statins as Anticancer Agents in the Era of Precision Medicine
Authors: Longo Joseph , van Leeuwen Jenna E. , Elbaz Mohamad , Branchard Emily , Penn Linda Z.
Published: September 2020

Statins are widely prescribed cholesterol-lowering drugs that inhibit HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate metabolic pathway. Multiple lines of evidence indicate that certain cancers depend on the mevalonate pathway for growth and survival, and, therefore, are vulnerable to statin therapy. However, these immediately available, well-tolerated, and inexpensive drugs have yet to be successfully repurposed and integrated into cancer patient care. In this review, we highlight recent advances and outline important considerations for advancing statins to clinical trials in oncology.
Abstract 1042: Preclinical pharmacokinetic and metabolic characterization of the next generation oral SERD AZD9833
Authors: Gangl Eric T. , Markandu Roshini , Sharma Pradeep , Sykes Andy , Pop-Damkov Petar , Gutierrez Pablo Morentin , Scott James S. , McGinnity Dermot F. , Fretland Adrian J. , Klinowska Teresa
Published: September 2020

AZD9833 is a potent, orally delivered, non-steroidal selective estrogen receptor degrader (SERD) that both antagonizes and degrades ERα. It is currently in clinical testing for the treatment of ER+ metastatic breast cancer (SERENA-1; NCT03616587). While ER is a clinically validated target, sustained inhibition of the target via oral delivery has proven an elusive goal. Despite intensive research, no oral SERD options are currently approved. Poor pharmacokinetic (PK) properties and/or short half-life (t ½) are often underlying features that limit oral SERD candidates from once or twice daily dose regimens. AZD9833 is a clinical stage next generation oral SERD that may overcome these challenges.

The pre-clinical PK properties of AZD9833 are consistent with once daily oral dosing in patients and are reported herein. AZD9833 is a low molecular weight (<500 Da), low lipophilicity (logD <3) base with good permeability characteristics. High volume of distribution (6-13 L/kg) and high bioavailability were observed in preclinical species. The in vitro hepatic metabolic clearance (CLint) for AZD9833 varied across species and were found to be nonlinear as a function of concentration. This nonlinear behaviour most strongly manifested in dog where in vivo bioavailability was <2 or 95 %F depending on dose. To explain these observations, detailed in vitro mechanistic studies were conducted and physiologically based PK (PBPK) models were created. Cytochrome P450 phenotyping studies suggest dog clearance is mediated by CYP2D15 whereas CYP3A is the dominant P450 isoform responsible for clearance in human. In vitro CLint vs. concentration studies exhibited a low Km in dog (0.2 μM) relative to human (2 μM) and other species. To further our understanding, we constructed PBPK models which demonstrated that the dose dependent exposures in dog were predictable. The human model suggests that nonlinear behaviour will manifest well above predicted efficacious doses. Modeling also allowed us to assess the potential for drug-drug interactions with likely co-medications such as CDK 4/6 inhibitors. The PBPK predictions of good human exposure and long t ½ are being explored in the ongoing clinical trial.

Citation Format: Eric T. Gangl, Roshini Markandu, Pradeep Sharma, Andy Sykes, Petar Pop-Damkov, Pablo Morentin Gutierrez, James S. Scott, Dermot F. McGinnity, Adrian J. Fretland, Teresa Klinowska. Preclinical pharmacokinetic and metabolic characterization of the next generation oral SERD AZD9833 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1042.
Abstract 1049: Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors
Authors: Wei Jia , Liu Qin , Qian Hanqing , Shao Jie , Zhu Lijing , Wang Lifeng , Yu Lixia , Sha Huizi , Liu Baorui
Published: September 2020

Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Nanotechnology has been reported to enhance immune responses of vaccines. Moreover, immunizing patients against such neoantigens, in combination with checkpoint inhibitor (CPI) and/or antiangiogenic drugs may elicit greater anti-tumor responses.

Methods: Patient-specific mutation-containing neoantigens were selected on the basis of tumour-specific mutations whole-exome sequencing (WES) and RNA sequencing. Cancer testis antigens were obtained according to immunohistochemical staining and HLA-binding affinity prediction. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) is an amphiphiles nanovaccine loaded with personalized vaccine encoding multiple neoantigens designed to induce neoantigen specific T cells responses. Patients will receive PVAC in combination with PD-1 monoclonal antibody and/or antiangiogenic drugs. Primary end points include safety and tolerability.

Results: 9 microsatellite stability (MSS) patients, which had relapsed from standard treatments, are enrolled in this study. 4 patients (1 gastric cancer, 1 liver cancer, 1 cervical carcinoma, 1 soft tissue sarcoma) received PVAC in combination with PD-1 mAb, and another 5 patients (2 gastric cancer, 1 colon cancer, 1 NSCLC, 1 renal carcinoma) received PVAC in combination with PD-1 mAb and antiangiogenic therapy. No DLTs were reported. Five patients developed grade 1 subcutaneous indurations in the injection sites,which collected with nanovaccine. One patient had grade 2 rash caused by antiangiogenic drug. No drug related SAEs have been observed. There are 1 CR, 4 PR, 3 SD and 1 PD. Neoantigen specific T cell responses have been detected by IFN-γ Elispot from PBMCs.

Conclusions: PVAC is safe and well tolerated. Clinical responses have been observed in combination with PD-1 mAb and antiangiogenic drugs and neoantigen-specific T cell response have been observed after vaccination. Clinical trial information: ChiCTR1900022986.

Citation Format: Jia Wei, Qin Liu, Hanqing Qian, Jie Shao, Lijing Zhu, Lifeng Wang, Lixia Yu, Huizi Sha, Baorui Liu. Personalized neoantigen/cancer testis antigen nanovaccine (PVAC) in combination with PD-1 monoclonal antibody and/or antiangiogenic treatment in patients with metastatic solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1049.
Abstract 118: FCHSD2 controls oncogenic ERK1/2 signaling by regulating endocytic trafficking in non-small-cell lung cancer
Authors: Xiao Guan-Yu , Schmid Sandra
Published: September 2020

Non-small-cell lung cancer (NSCLC) is the major cause of cancer deaths. The evolution of transformed NSCLC cells into metastatic tumors is, in part, driven by altered intracellular signaling downstream of receptor tyrosine kinases (RTKs). The surface levels and activity of RTKs are governed mainly through clathrin-mediated endocytosis (CME), endosomal recycling or degradation. We recently discovered that oncogenic signaling downstream of RTKs can reciprocally regulate CME and endocytic trafficking by creating feedback loops and that some of these mechanisms for crosstalk between signaling and endocytosis appear to be specific for, or co-opted by cancer cells to enhance tumor progression. We previously identified that FCHSD2 (FCH/F-BAR and double SH3 domain-containing protein) has a cancer-cell specific function in regulating CME downstream of ERK1/2 in NSCLC cells. It is now critical to further determine its role in RTK trafficking, signaling outcome and NSCLC progression. Here, we report that knockdown of FCHSD2 impacts recycling of the RTKs, EGFR and MET, and switches the RTK trafficking toward late endosome compartments and degradation. Notably, FCHSD2 loss results in active ERK1/2 signaling from late endosome and the nuclear translocation of ERK1/2 leading to upregulated EGFR and MET in NSCLC cells. We further identified the small GTPase, Rab7, as being essential for the FCHSD2 depletion-induced RTK upregulation. Loss of FCHSD2 activity in NSCLC cells leads to enhanced cell proliferation, survival and migration. Correspondingly, the expression level of FCHSD2 is negatively correlated with lung tumor grades and positively correlated with higher lung cancer patient survival rates, suggesting that FCHSD2 negatively affects cancer progression. Our study provides new insight into the molecular nexus for crosstalk between oncogenic signaling and RTK trafficking that can control cancer progression, opening the possibility of novel therapeutic strategies for lung cancer.

Citation Format: Guan-Yu Xiao, Sandra Schmid. FCHSD2 controls oncogenic ERK1/2 signaling by regulating endocytic trafficking in non-small-cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 118.
Abstract 176: The Evolution of NANOGP8 and its possible roles in tumorigenesis
Authors: Guo Yande
Published: September 2020

Human NANOG gene is located in Chromosome 12p13. It is a transcription factor in embryonic stem cells. There are 11 NANOG pseudogenes in human genome. NANOGP1 is an unprocessed pseudogene that arose through duplication of the chromosomal region containing NANOG before the human-chimpanzee (H/C) divergence and before insertion of the Alu element into the NANOG gene. NANOGP1 remained functional after duplication. NANOGP2 to NANOGP11 are ten processed pseudogenes in the human genome. NANOGP8 is theoretically unique since it has a complete open reading frame and an Alu element in the 3'-UTR which is homologous to that of Nanog. However, the human NANOGP8 is absent from the chimpanzee genome. Genome DNA sequence analysis revealed that NANOGP8 is the most recent of the NANOG pseudogenes and was inserted into chromosome 15 after the H/C divergence. Its transcription factor binding sites in SVA LTR may promote expression of NANOGP8 in cancer cells. This may be the partial reason of the higher genetic predisposition for cancer in humans compared with other primates.

Citation Format: Yande Guo. The Evolution of NANOGP8 and its possible roles in tumorigenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 176.