bluuebunny/crossref_metadata_2025 huggingface dataset:
Vacuum Preconsolidation Settlement Characteristics and Microstructural Evolution of Marine Dredger‐Filled Silt
Authors: Chen Keping , Ren Xinkai , He Yong , Gan Muyuan , Wu Danwei , Chen Lianwei
Published: June 2021

The method of vacuum preloading for foundation treatments is used in the construction of the Fangchenggang coastal area in Guangxi province, China. The thick marine dredger‐filled silt has a considerable impact on the treatment effort. In this study, the mineral composition and grain size distribution of these silts were analyzed to investigate their consolidation settlement property and microstructures. The scanning electron microscope and finite element method were adopted. The results reveal that the dredger‐filled silt in this area is composed mainly of sand with particle size mostly smaller than 0.075 mm. To replicate the construction process, the process of drainage by the vacuum preloading method was simulated by setting different water levels in the finite element analysis. The displacement and the dissipation of the pore water pressure obtained by simulations were reasonably consistent with the field monitoring data. In addition, the results obtained using the scanning electron microscope indicate that the equivalent diameter of the structural unit and that of the pore unit decrease with the silt depth. However, the value of the structural abundance approaches one, whereas the pore abundance is significantly different from one.
Feature-Level vs. Score-Level Fusion in the Human Identification System
Authors: Rasool Rabab A.
Published: June 2021

The design of a robust human identification system is in high demand in most modern applications such as internet banking and security, where the multifeature biometric system, also called feature fusion biometric system, is one of the common solutions that increases the system reliability and improves recognition accuracy. This paper implements a comprehensive comparison between two fusion methods, named the feature-level fusion and score-level fusion, to determine which method highly improves the overall system performance. The comparison takes into consideration the image quality for the six combination datasets as well as the type of the applied feature extraction method. The four feature extraction methods, local binary pattern (LBP), gray-level co-occurrence matrix (GLCM), principle component analysis (PCA), and Fourier descriptors (FDs), are applied separately to generate the face-iris machine vector dataset. The experimental results highlighted that the recognition accuracy has been significantly improved when the texture descriptor method, such as LBP, or the statistical method, such as PCA, is utilized with the score-level rather than feature-level fusion for all combination datasets. The maximum recognition accuracy is obtained at 97.53% with LBP and score-level fusion where the Euclidean distance (ED) is considered to measure the maximum accuracy rate at the minimum equal error rate (EER) value.
Hyperprogressive Disease Caused by PD-1 Inhibitors for the Treatment of Pan-Cancer
Authors: Chen Shiyun , Gou Miaomiao , Yan Huan , Fan Mengjiao , Pan Yuting , Fan Runjia , Qian Niansong , Dai Guanghai
Published: June 2021

Background. Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results. In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0–4.2) vs. 7.3 months (95% CI, 5.9–8.7);

P
<
0.01

). Factors related to HPD include more than 2 metastatic sites, ECOG performance

status
≥
2

, hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors’ analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions. HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.
Wild Bitter Melon Extract Regulates LPS-Induced Hepatic Stellate Cell Activation, Inflammation, Endoplasmic Reticulum Stress, and Ferroptosis
Authors: Ho Chang-Hsun , Huang Jen-Hsuan , Sun Maw-Sheng , Tzeng I-Shiang , Hsu Yi-Chiung , Kuo Chan-Yen
Published: June 2021

The activation of hepatic stellate cells (HSCs) is a key component of liver fibrosis. Two antifibrosis pathways have been identified, the reversion to quiescent-type HSCs and the clearance of HSCs through apoptosis. Lipopolysaccharide- (LPS-) induced HSCs activation and proliferation have been associated with the development of liver fibrosis. We determined the pharmacological effects of wild bitter melon (WM) on HSC activation following LPS treatment and investigated whether WM treatment affected cell death pathways under LPS-treated conditions, including ferroptosis. WM treatment caused cell death, both with and without LPS treatment. WM treatment caused reactive oxygen species (ROS) accumulation without LPS treatment and reversed the decrease in lipid ROS production in HSCs after LPS treatment. We examined the effects of WM treatment on fibrosis, endoplasmic reticulum (ER) stress, inflammation, and ferroptosis in LPS-activated HSCs. The western blotting analysis revealed that the WM treatment of LPS-activated HSCs induced the downregulation of the connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), integrin-β1, phospho-JNK (p-JNK), glutathione peroxidase 4 (GPX4), and cystine/glutamate transporter (SLC7A11) and the upregulation of CCAAT enhancer-binding protein homologous protein (CHOP). These results support WM as an antifibrotic agent that may represent a potential therapeutic solution for the management of liver fibrosis.
Identification of Permanent Faults and Disturbance Induced by Deicing Based on Permutation Entropy for the Large-Scale Clean Energy Transmission in Winter
Authors: Wang Yunlong , Tang Tiejun , Ju Xiang , Hong Dingding
Published: June 2021

Ice shedding may induce isolated ground wires’ temporary grounding, which can cause electric quantities of direct current (DC) deicing devices to fluctuate. Hence, the disturbance of ice shedding is able to trigger the protective relay frequently and unnecessarily, which adversely affects the deicing process. Due to the randomness of ice shedding, the grounding resistance varies quickly; thus, the disturbance in poles of deicing devices can be detected multiple times in a short time. Moreover, the permanent fault requires steady arc plasma because of the low output voltage and current of deicing devices, which cannot bring out multiple-time disturbances in the poles. This paper proposes the identification of permanent faults and disturbance induced by deicing based on the permutation entropy, which is verified by a large number of simulations.
Isolated ST-Elevation Myocardial Infarction Involving Leads I and aVL: Angiographic and Electrocardiographic Correlations from a Tertiary Care Center
Authors: Singh Abhishek , Dwivedi Sudhanshu , Pradhan Akshyaya , Narain Varun S , Sethi Rishi , Chandra Sharad , Vishwakarma Pravesh , Chaudhary Gaurav , Bhandari Monika , Sharma Akhil
Published: June 2021

Background. Determining the infarct-related artery in STEMI during a coronary angiogram can be challenging due to the affliction of multiple vessels. Isolated STEMI involving only EKG leads I and aVL is infrequent. Localization of infarct-related artery based on EKG findings has not been previously done in this subset. Methods. All consecutive de novo acute coronary syndrome (ACS) patients admitted to coronary care unit with ST elevations involving only leads I and aVL were screened for enrollment. Patients with ST elevation in any additional lead and those who refused a coronary angiogram were excluded. Subsequently, a coronary angiogram was done as part of primary PCI or a pharmacoinvasive approach to identify the infract-related artery (IRA). IRA was defined by characteristics of lesion, flow of blood through stenosis, and presence of intracoronary thrombus. Coronary angiogram was interpreted by two independent observers blinded to the EKG findings. ST changes in inferior and precordial leads were analyzed to find ECG predictors of the culprit artery. Results. A total of 54 eligible patients of ACS were included in the study. The first major diagonal (D1) was the most frequent IRA in 35.2% followed by left circumflex-obtuse marginal (LCX-OM11) in 29.6%, left anterior descending (LAD) in 20.4%, and ramus intermedius (RI) in 14.8%. Out of total patients with ST depression in lead V2, the LCX-OM11 group was IRA in 50% cases while the RI, D1, and LAD groups accounted for 31.8%, 13.6%, and 4.5%, respectively (

p
<
0.001

). Similarly, LCX-OM1 was the most frequent IRA subjects with ST depressions in leads V1 and V3 (44.4%;

p
=
0.010

and 46.2%;

p
=
0.003

, resp.). On the contrary, in patients with ST depression in lead III, LAD and D1 were the most frequent IRA as compared to LCX-OM1 and RI though statistical significance was not attained (

p
=
0.857

for lead III). ST-segment depression in lead V2 had a positive predictive value of 60% and a negative predictive value of 100% for LCX-OM1 as IRA. Similarly, ST-segment depression in lead V2 had a positive predictive value of 20% and a negative predictive value of 100% for the RI group. Conclusions. In patients presenting with isolated ST elevation in leads I and aVL, the most frequent IRA on angiogram was first diagonal. ST depressions in EKG leads V1–V3 were the most common predictor of LCX–OM1 while those in inferior leads indicated LAD-D1 as the IRA.
Data Analysis of Physical Fitness Monitoring Based on Mathematical Models
Authors: Guo Cuixiang , Suo Junwu , Xu Chunguang , Yang Xinhua , Zhang Liping
Published: June 2021

Physical monitoring and analysis are of great significance to improve national physical fitness. The main work of this paper is that the physical health level of college students is studied and analysed by using a statistical model and mathematical model. According to the characteristics of the collected data, different mathematical models are established. Firstly, the grey correlation model is used to analyse the correlation between pull-up and other physical fitness indexes. Then, based on the classification of college students and the influence and flow law of interclass crowd, a differential equation system is established based on the LMC model. By analysing the existence and stability of the equilibrium point of the system, as well as the possible folding bifurcation and backward bifurcation at the equilibrium point, this paper makes qualitative and quantitative research on the trend of college students’ physical exercise on campus.
Zn-Doped SnO2 Compact Layer for Enhancing Performance of Perovskite Solar Cells
Authors: Yang Chenjun , Chen Mengwei , Wang Jiaqi , Lu Haifei
Published: June 2021

Perovskite solar cells (PSCs) have been developing rapidly since they were discovered, and their excellent photoelectric properties have attracted wide attention from researchers. The compact layer is an important part of PSCs, which can transport electrons and block holes. SnO2 is an excellent and commonly used electron transport layer (ETL) material, and doping modification is an effective way to improve performance. Here, Zn with a similar radius to Sn has been introduced to the doping of the SnO2 compact layer to achieve the purposes of conductivity enhancement of the compact layer and followed photoelectric performance improvement of the device. Zn-SnO2 compact layers with different doping concentrations were prepared and applied to mesoporous architecture PSCs. When the doping content was 5%, the power conversion efficiency (PCE) of the device based on the Zn-SnO2 compact layer has increased from 9.08% to 10.21%, with an increase of 12.44%. The doping of SnO2 promotes its application in low-cost PSCs.
A Pilot Study of Whether the Cold-Heat Syndrome Type is Associated with Treatment Response and Immune Status in Patients with Non-Small Cell Lung Cancer
Authors: Choi Yujin , Kwon Ojin , Choi Chang-Min , Jeong Mi-Kyung
Published: June 2021

The cold-heat syndrome type (ZHENG) is one of the essential elements of syndrome differentiation in East Asian Medicine. This pilot study aimed to explore the characteristics of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) based on the cold-heat syndrome type. Twenty NSCLC patients treated with ICI monotherapy were included in the study and completed the cold-heat syndrome differentiation questionnaire. Demographic and clinical characteristics of the included patients were obtained through electronic medical records. Additionally, blood samples of 10 patients were analyzed with cytokine level and immune profiling. Patients were divided into two groups of cold type (n = 9) and non-cold type (n = 11), according to the cold symptoms questionnaire’s cutoff point. No significant difference between the two groups was observed in clinical response to ICIs (

p
=
0.668

). Progression-free survival (PFS) seemed to be longer in patients with non-cold type than cold type (

p
=
0.332

). In patients with adenocarcinoma, the non-cold type showed longer PFS than the cold type (

p
=
0.036

). Also, there were more patients with PD-L1 negative in the cold type compared to the non-cold type (

p
=
0.050

). In immune profiling, the proportion of effector memory CD8 T-cells was higher in patients with cold type than with non-cold type (

p
=
0.015

), and the proportion of terminal effector CD8 T-cells was lower in patients with cold type than with non-cold type (

p
=
0.005

). This pilot study has shown the potential for differences in prognosis and immune status between patients with cold and non-cold types. Hopefully, it provides essential information and insight into NSCLC patients’ characteristics from the perspective of syndrome differentiation. Further large-scale observational studies and intervention studies are required.
[Retracted] Algorithm of Classroom Teaching Quality Evaluation Based on Markov Chain
Authors: Yuan Tongqing
Published: June 2021

The Markov chain model teaching evaluation method is a quantitative analysis method based on probability theory and stochastic process theory, which establishes a stochastic mathematical model to analyse the quantitative relationship in the change and development process of real activities. Applying it to achieve a more comprehensive, reasonable, and effective evaluation of the classroom teaching quality of college teachers is of positive significance for promoting the continuous improvement of the teaching level of teachers and the teaching quality of schools. Therefore, after an in‐depth study of Markov chain algorithm theory, this research proposes an improved Markov chain hybrid teaching quality evaluation model and designs comparative experiments and applies it to the hybrid teaching quality evaluation system of universities, designs a corresponding hybrid teaching quality evaluation model, and finally verifies its effectiveness through experiments. The mathematical model of mixed classroom teaching quality evaluation given in this research focuses on the development and change of the teaching process. For the teaching process that is closely related to the causality of teaching quality, the model established in this paper is more objective and reasonable for evaluating the quality of teaching.
Improving the Tracking Performance under Nonlinear Time-Varying Constraints in Motion Control Applications: From Theoretical Servo Model to Experimental Validation
Authors: Nguyen Hung , Nguyen Thanh Phuong , Ngo Ha Quang Thinh
Published: June 2021

In the high-accuracy control of an AC machine, the knowledge of pure system parameters, with no deviation in drive coefficients and no disturbance or other nonlinear components, is a difficult issue for operators, even though it is occasionally nonviable. To overcome these troubles, this paper introduces a robust adaptation strategy based on pseudo fuzzy logic and sliding mode control (PFSMC) for an AC servo drive subject to uncertainties and/or external disturbance. Owing to the robustness of the SMC technique, the reduced sensitivity to uncertainties, and the enhanced resistance to disturbances from the pseudo fuzzy mechanism, this control algorithm can guarantee not only system stability but also the improvement of tracking errors in the steady state. To validate the design efficiency of PFSMC, both simulation and laboratory tests of the proposed scheme and a conventional PID scheme were performed to compare them as follows. In a computer environment, test cases with and without certainties were implemented with two controllers to visualize the comparative responses. Then, the two control methods were integrated into a real-world hardware platform to acquire practical outcomes. From these results, it can be noted that our successful approach showed a feasible, effective, and robust performance in AC drive.
Influence of Dental Pulp Harvesting Method on the Viability and Differentiation Capacity of Adult Dental Pulp-Derived Mesenchymal Stem Cells
Authors: Vendramini Victor Okada , Pouraghaei Sevda , Barbosa Rafael Maza , Aloise Antônio Carlos , Muniz José Ricardo Ferreira , Sperandio Marcelo , Moy Peter Karyen , Pelegrine André Antonio , Moshaverinia Alireza
Published: June 2021

Objective. To compare two pulp harvesting methods for stem cell expansion, namely, conservative pulpotomy and pulpectomy from exodontia. Method. Ten freshly extracted sound third molars from five patients were selected. Five were used in the control group, where pulp harvesting was performed by exodontia and the remaining teeth were used in the test group, where the pulp was harvested by conservative pulpotomy (preserving the tooth). This was a split-mouth design study, where a third molar from one side was randomly allocated into the test group and the contralateral tooth in the control group. After pulp harvesting, the following evaluations were performed: cell morphology, sterility test, immunophenotyping, differentiation assays, first pass live cell counts, time to cryopreservation, and total number of expanded cells at the end of the fourth pass. Results. Regarding morphology, the cells from both groups presented a fibroblastic phenotype. All samples were sterile. Immunophenotyping demonstrated a positive expression for CD105, CD90, and CD73 and negative expression for CD45 in both groups. Differentiation assays were positive for osteogenic and chondrogenic differentiation in both groups. Regarding live cell counts in the first passage, the control group had 95.8% live cells in the total count and the test group 91.2% (

p
<
0.05

). The time required for cryopreservation was equivalent in both groups 51.6 days and 52.6 days, respectively (

p
>
0.05

). The total number of cells at the end of the fourth passage was 5,286,782 and 5,736,862, respectively (

p
>
0.05

). Conclusion. These results suggest that adult stem cell harvesting from conservative pulpotomy is as effective as the traditional exodontia-based method.
Theory and Method of Data Collection for Mixed Traffic Flow Based on Image Processing Technology
Authors: Ge Dong-Yuan , Yao Xi-Fan , Xiang Wen-Jiang , Liu En-Chen , Xu Zhi-Bin
Published: June 2021

As a key element of ITS (intelligent traffic systems), traffic information collection facilities play a key role, with ITS being able to analyze the state of mixed traffic more appropriately and can provide effective technical support for the design, management, and the evaluation of constructions. Traffic Infrastructure. Focusing on image processing technology, this study takes pedestrians, electric motor, and vehicles in mixed traffic flow as the research object, and Gaussian mixed model, Kalman filtering, and Fisher linear discriminant are introduced in the recognition system. On this basis, the mixed motion flow data acquisition framework model is elaborated in detail, which includes attribute extraction, object recognition, and object tracking. Given the difficulty in capturing reliable images of objects in real traffic scenes, this study adopted a novel background and foreground classification method with region proposal network so as to decrease the number of regions proposal from 2000 to 300, which can detect objects fast and accurately. Experiments demonstrate that the designed programme can collect the flow data by detecting and tracking moving object in the surveillance video for mixed traffic. Further integration of various modules to achieve integrated collection is another important task for further research and development. In the future, research on dynamic calibration of monocular vision will be carried out for distance measurement and speed measurement of vehicles and pedestrians.
SOX11 Inhibitors Are Cytotoxic in Mantle Cell Lymphoma
Authors: Jatiani Shashidhar S. , Christie Stephanie , Leshchenko Violetta V. , Jain Rinku , Kapoor Abhijeet , Bisignano Paola , Lee Clement , Kaniskan H. Ümit , Edwards Donna , Meng Fanye , Laganà Alessandro , Youssef Youssef , Wiestner Adrian , Alinari Lapo , Jin Jian , Filizola Marta , Aggarwal Aneel K. , Parekh Samir
Published: June 2021

Purpose:

Mantle cell lymphoma (MCL) is a fatal subtype of non–Hodgkin lymphoma. SOX11 transcription factor is overexpressed in the majority of nodal MCL. We have previously reported that B cell–specific overexpression of SOX11 promotes MCL pathogenesis via critically increasing BCR signaling in vivo. SOX11 is an attractive target for MCL therapy; however, no small-molecule inhibitor of SOX11 has been identified to date. Although transcription factors are generally considered undruggable, the ability of SOX11 to bind to the minor groove of DNA led us to hypothesize that there may exist cavities at the protein–DNA interface that are amenable to targeting by small molecules.

Experimental Design:

Using a combination of in silico predictions and experimental validations, we report here the discovery of three structurally related compounds (SOX11i) that bind SOX11, perturb its interaction with DNA, and effect SOX11-specific anti-MCL cytotoxicity.

Results:

We find mechanistic validation of on-target activity of these SOX11i in the inhibition of BCR signaling and the transcriptional modulation of SOX11 target genes, specifically, in SOX11-expressing MCL cells. One of the three SOX11i exhibits relatively superior in vitro activity and displays cytotoxic synergy with ibrutinib in SOX11-expressing MCL cells. Importantly, this SOX11i induces cytotoxicity specifically in SOX11-positive ibrutinib-resistant MCL patient samples and inhibits Bruton tyrosine kinase phosphorylation in a xenograft mouse model derived from one of these subjects.

Conclusions:

Taken together, our results provide a foundation for therapeutically targeting SOX11 in MCL by a novel class of small molecules.
The Radiosensitizing Effect of AZD0530 in Glioblastoma and Glioblastoma Stem-Like Cells
Authors: Yun Hong Shik , Lee Jennifer , Kil Whoon Jong , Kramp Tamalee R. , Tofilon Philip J. , Camphausen Kevin
Published: June 2021

AZD0530, a potent small-molecule inhibitor of the Src kinase family, is an anticancer drug used in the treatment of various cancers. In the case of glioblastoma (GBM), where resistance to radiotherapy frequently occurs, Src kinase is known as one of the molecules responsible for imparting radioresistance to GBM. Thus, we evaluated the effect of AZD0530 on the radiosensitivity of human GBM cells and human glioblastoma stem-like cells (GSCs). We show that Src activity of GBM and GSC is increased by radiation and inhibited by AZD0530, and using clonogenic assays, AZD0530 enhances the radiosensitivity of GBM and GSCs. Also, AZD0530 induced a prolongation of radiation-induced γH2AX without specific cell cycle and mitotic index changes, suggesting that AZD0530-induced radiosensitization in GBM cells and GSCs results from the inhibition of DNA repair. In addition, AZD0530 was shown to inhibit the radiation-induced EGFR/PI3K/AKT pathway, which is known to promote and regulate radioresistance and survival of GBM cells by radiation. Finally, mice bearing orthotopic xenografts initiated from GBM cells were then used to evaluate the in vivo response to AZD0530 and radiation. The combination of AZD0530 and radiation showed the longest median survival compared with any single modality. Thus, these results show that AZD0530 enhances the radiosensitivity of GBM cells and GSCs and suggest the possibility of AZD0530 as a clinical radiosensitizer for treatment of GBM.
ATE1 Inhibits Liver Cancer Progression through RGS5-Mediated Suppression of Wnt/β-Catenin Signaling
Authors: Xu Cong , Li Yi-Ming , Sun Bo , Zhong Fang-Jing , Yang Lian-Yue
Published: June 2021

Arginyltransferase (ATE1) plays critical roles in many biological functions including cardiovascular development, angiogenesis, adipogenesis, muscle contraction, and metastasis of cancer. However, the role of ATE1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we find that ATE1 plays an essential role in growth and malignancy of liver cancer. ATE1 expression is significantly reduced in human HCC samples compared with normal liver tissue. In addition, low ATE1 expression is correlated with aggressive clinicopathologic features and is an independent poor prognostic factor for overall survival and disease-free survival of patients with HCC. Lentivirus-mediated ATE1 knockdown significantly promoted liver cancer growth, migration, and disease progression in vitro and in vivo. Opposing results were observed when ATE1 was upregulated. Mechanistically, ATE1 accelerated the degradation of β-catenin and inhibited Wnt signaling by regulating turnover of Regulator of G Protein Signaling 5 (RGS5). Loss- and gain-of-function assays confirmed that RGS5 was a key effector of ATE1-mediated regulation of Wnt signaling. Further studies indicated that RGS5 might be involved in regulating the activity of GSK3-β, a crucial component of the cytoplasmic destruction complex. Treatment with a GSK inhibitor (CHIR99021) cooperated with ablation of ATE1 or RGS5 overexpression to promote Wnt/β-catenin signaling, but overexpression of ATE1 or RGS5 knockdown did not reverse the effect of GSK inhibitor.

Implications:

ATE1 inhibits liver cancer progression by suppressing Wnt/β-catenin signaling and can serve as a potentially valuable prognostic biomarker for HCC.
Identification of Autophagy-Related Genes as Targets for Senescence Induction Using a Customizable CRISPR-Based Suicide Switch Screen
Authors: Schepers Arnout , Jochems Fleur , Lieftink Cor , Wang Liqin , Pogacar Ziva , Leite de Oliveira Rodrigo , De Conti Giulia , Beijersbergen Roderick L. , Bernards Rene
Published: June 2021

Pro-senescence therapies are increasingly being considered for the treatment of cancer. Identifying additional targets to induce senescence in cancer cells could further enable such therapies. However, screening for targets whose suppression induces senescence on a genome-wide scale is challenging, as senescent cells become growth arrested, and senescence-associated features can take 1 to 2 weeks to develop. For a screen with a whole-genome CRISPR library, this would result in billions of undesirable proliferating cells by the time the senescent features emerge in the growth arrested cells. Here, we present a suicide switch system that allows genome-wide CRISPR screening in growth-arrested subpopulations by eliminating the proliferating cells during the screen through activation of a suicide switch in proliferating cells. Using this system, we identify in a genome-scale CRISPR screen several autophagy-related proteins as targets for senescence induction. We show that inhibiting macroautophagy with a small molecule ULK1 inhibitor can induce senescence in cancer cell lines of different origin. Finally, we show that combining ULK1 inhibition with the senolytic drug ABT-263 leads to apoptosis in a panel of cancer cell lines.

Implications:

Our suicide switch approach allows for genome-scale identification of pro-senescence targets, and can be adapted to simplify other screens depending on the nature of the promoter used to drive the switch.
The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation
Authors: Chavkin Nicholas W. , Sano Soichi , Wang Ying , Oshima Kosei , Ogawa Hayato , Horitani Keita , Sano Miho , MacLauchlan Susan , Nelson Anders , Setia Karishma , Vippa Tanvi , Watanabe Yosuke , Saucerman Jeffrey J. , Hirschi Karen K. , Gokce Noyan , Walsh Kenneth
Published: June 2021

Background

A hallmark of heart failure is cardiac fibrosis, which results from the injury‐induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase–like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation.

Methods and Results

The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage.

Conclusions

Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.
Mitral Valve Prolapse and Its Motley Crew‐Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition
Authors: Morningstar Jordan E. , Nieman Annah , Wang Christina , Beck Tyler , Harvey Andrew , Norris Russell A.
Published: June 2021

Mitral valve prolapse (MVP) is a commonly occurring heart condition defined by enlargement and superior displacement of the mitral valve leaflet(s) during systole. Although commonly seen as a standalone disorder, MVP has also been described in case reports and small studies of patients with various genetic syndromes. In this review, we analyzed the prevalence of MVP within syndromes where an association to MVP has previously been reported. We further discussed the shared biological pathways that cause MVP in these syndromes, as well as how MVP in turn causes a diverse array of cardiac and noncardiac complications. We found 105 studies that identified patients with mitral valve anomalies within 18 different genetic, developmental, and connective tissue diseases. We show that some disorders previously believed to have an increased prevalence of MVP, including osteogenesis imperfecta, fragile X syndrome, Down syndrome, and Pseudoxanthoma elasticum, have few to no studies that use up‐to‐date diagnostic criteria for the disease and therefore may be overestimating the prevalence of MVP within the syndrome. Additionally, we highlight that in contrast to early studies describing MVP as a benign entity, the clinical course experienced by patients can be heterogeneous and may cause significant cardiovascular morbidity and mortality. Currently only surgical correction of MVP is curative, but it is reserved for severe cases in which irreversible complications of MVP may already be established; therefore, a review of clinical guidelines to allow for earlier surgical intervention may be warranted to lower cardiovascular risk in patients with MVP.
Perceiving Intersensory and Emotional Qualities of Everyday Objects: A Study on Smoothness or Sharpness Features with Line Drawings by Designers
Authors: Sinico Michele , Bertamini Marco , Soranzo Alessandro
Published: June 2021

A large number of studies have focused on the aesthetic value of smoothly curved objects. By contrast, angular shapes tend to be associated with tertiary qualities such as threat, hardness, loudness, nervousness, etc. The present study focuses on the effect of curvilinearity vs angularity on the aesthetic experience of design artefacts. We used the drawings of everyday objects with novel shapes created by 56 designers (IUAV image dataset). Each drawing had two versions: a smooth and an angular version. To test new tertiary associations, beyond aesthetic value, we obtained ratings for seven characteristics (‘soft/hard, sad/cheerful, male/female, bad/good, aggressive/peaceful, agitated/serene, useless/useful’) from 174 naïve observers. Importantly, each naïve rater saw only one of the two versions of an object. The results confirmed a significant relation between smoothness and hardness as well as other (tertiary) associations. The link between smoothness and usefulness confirms that perceptual utility is significantly influenced by the shape of the object. This finding suggests that tertiary qualities convey both static and functional information about design objects. The role of perceptual constraints in drawing design artefacts is also discussed.
Notes on Aphodius coenobita Gravenhorst, 1807, a forgotten name (Coleoptera: Scarabaeidae: Aphodiinae)
Authors: FERY HANS , DELLACASA GIOVANNI , DELLACASA MARCO
Published: June 2021

Aphodius coenobita Gravenhorst, 1807 is an almost forgotten name which has never been used as valid after its establishment. Studies of Gravenhorst’s life story and his relations with contemporary entomologists revealed that at least a part of the original syntype series of this taxon is stored in the “Museum für Naturkunde Berlin” (Germany). Furthermore, it is given evidence that Aphodius stercorosus F.E. Melsheimer, 1844 (currently placed in the genus Blackburneus Schmidt, 1913) is a junior synonym of Gravenhorst’s name. In order to stabilise the nomenclature the name A. coenobita is declared to be a nomen oblitum under Article 23.9 of the Code of Zoological Nomenclature. At the same time A. stercorosus is declared a nomen protectum and it is given precedence over the older name. Additionally, one and the same specimen of the syntype series is designated as lectotype for both taxa.
Effect of Liver Kinase B1 on Osteogenic/Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells in High Glucose Environment
Authors: Zhang Hao , Tian Yuan , Shi Xiaolin , Yuan Weidong , Liu Lei , Yang Yongming
Published: June 2021

Bone marrow mesenchymal stem cells (BMSCs) present reduced proliferation under high glucose condition. Liver kinase B1 (LKB1) can maintain the homeostasis of hematopoietic stem cells. However, whether LKB1 regulates BMSCs osteogenic/adipogenic differentiation under high glucose is unclear.
Rat BMSCs were isolated and separated into control group, high glucose group, and LKB1 group (BMSCs were transfected with pc-DNA 3.1-LKB1 plasmid under high glucose condition) followed by analysis of LKB1 expression by Real time PCR and Western blot, osteocalcin, type I collagen, RUNX2 and
OPN mRNA level by real-time PCR, FABP4 and PPARγ2 level by western blot. In high glucose group, LKB1 expression was significantly decreased, with reduced expression of osteocalcin, type I collagen, RUNX2 and OPN mRNA and elevated FABP4 and PPARγ2 level compared to control group
(P < 0.05). Transfection of LKB1 plasmid reduced LKB1 expression, upregulated osteocalcin, type I collagen, RUNX2 and OPN mRNA and downregulated FABP4 and PPARγ2. Compared with the high glucose group, there was a statistical difference (P <0.05). High glucose can
inhibit LKB1 expression and BMSCs osteogenic differentiation, and promote adipogenic differentiation. Upregulating LKB1 expression can promote BMSCs osteogenic differentiation.
The Mechanism of Rhein Ameliorating the Survival Rate of Transplanted Mesenchymal Stem Cells by Improving Myocardial Microenvironment in Acute Myocardial Infarction
Authors: Deng Xuejun , He Xiaojun , Huang Gang , Yu Dongmei , Lin Xiaozhen
Published: June 2021

Background: The paper investigated the mechanism of Rhein improving the ischemic myocardial microenvironment, promoting the survival rate of transplanted BMSCs and functional recovery of damaged myocardium by alleviating myocardial ERS-mediated hyperinflammation and apoptosis
after AMI. Material and Methods: A model of myocardial infarction was established. BLI was used to detect the survival rate of transplanted stem cells at 1, 7, 14, 21 and 28 days after surgery. TUNEL staining was used to assess apoptosis. ERS-related protein CHOP immunofluorescence
staining was used to assess ERS level. The expressions of ERS-related biomarkers ATF4, CHOP, GRP78 and GRP94 were detected by Western Blot. The inflammatory factors IL-6, TNF-α and IL- 10 of myocardial tissue were detected by ELISA. CD31 immunization was performed 28 days after surgery.
Fluorescence staining was used to assess tissue angiogenesis. Results: Rhein combined with BMSCs could improve cardiac function, decrease apoptosis and myocardial CHOP expression. WB showed that the expressions of ATF4, CHOP, GRP78 and GRP94 in myocardial tissue of MI rats were decreased.
ELISA showed that Rhein can inhibit the expressions of pro-inflammatory factors IL-6 and TNF-α, and promote anti-inflammatory factors IL-10 expression. CD31 immunofluorescence staining showed that Rhein can promote the formation of neovascularization in infarcted myocardium. Conclusion:
In AMI, myocardial ERS is activated. Rhein inhibits ERS and the mediated inflammation and oxidative stress after AMI, inhibits apoptosis, improves the survival rate of transplanted BMSCs, enhances BMSCs to promote neovascularization, inhibits myocardial fibers, and improves heart function.
Palmitic Acid Regulates miRNA-3148 via Insulin Receptor Substrate-1 and is Involved in Insulin Resistance
Authors: Xiang Xiaoxi , Zhang Changwei , Long Daying
Published: June 2021

Previous studies reported that saturated fatty acid palmitic acid (PA) is closely related to insulin resistance. miR-3148 regulates insulin receptor substrate-1 (IRS1) predicted by MiRDB analysis. However, whether PA regulates IRS1 via miR-3148 remains to be elucidated. Therefore, in
this work, we assessed whether PA regulates miRNA-3148 via IRS1 in insulin resistance. We cultured HepG2 cells in vitro and classified them into control group (NC group), miR-3148 Mimics group, and miR-3148 Mimics+ pFBD-IRS1 group. We used qRT-PCR to detect miR-3148 and IRS1 mRNA; used
Dual-Luciferase Reporter Assays to detect miR-3148 with 3′-UTR region of IRS1 mRNA; and utilized Western blot (WB) to detect IRS1, p-AKT, AKT and Tubulin. Our results showed that PA could increase miR-3148 and decrease IRS1 which is a target protein of miR-3148, as shown by Dual-Luciferase
Reporter assays. miR-3148 significantly inhibited the impact of insulin on p-AKT level (P < 0.01) and over-expression of IRS1 by pFBD-IRS1 can partially alleviate the inhibitory effect of miR-3148 mimics on p-AKT. In HepG2 cells, PA regulates miR-3148. Via targeting IRS1 mRNA, miR-3148
impairs insulin signaling pathway, leading to insulin resistance. Over-expression of IRS1 by pFBD-IRS1 alleviates miR-3148-induced insulin resistance.
Transforming Growth Factor Beta 1 Affects Gastric Cancer Cell Proliferation, Migration, and Invasion by Regulating Phosphatase and Tensin Homolog
Authors: Wang Yuchen , Huang Zhimin
Published: June 2021

Gastric cancer (GC) is a common tumor with high incidence and poor prognosis. So far, the pathogenesis of GC has not been fully elucidated, which has brought great difficulty to the treatment. TGF-β regulates cell growth and differentiation. As a key member, TGF-β1 is abnormally
expressed in various tumors, but its role on GC and related mechanisms have not been elucidated. Gastric cancer and adjacent tissues were collected to measure TGF-β1 level by real-time PCR. SGC-7901 cell was assigned into control group, mock group, and TGF-β1 siRNA group followed
by analysis of TGF-β1 level by ELISA, cell proliferation by MTT assay, apoptosis by flow cytometry, cell migration by cell scratch test, cell invasion by Transwell chamber assay, and Bcl-2, Bax, and PTEN level by Western blot. TGF-β1 was significantly upregulated in GC tissues (P
<0.05) and increased with TNM stage dependence. TGF-β1 siRNA transfection significantly decreased TGF-β1 mRNA level and secretion, inhibited cell proliferation, increased apoptosis rate, and attenuated cell migration and invasion along with downregulated Bcl-2 and elevated Bax
and PTEN expression (P <0.05). Downregulation of TGF-β1 can promote gastric cancer cell apoptosis, inhibit proliferation, migration, and invasion by regulating PTEN.
The impact of coupled data assimilation on Madden-Julian Oscillation predictability initialized from coupled satellite-era reanalysis
Authors: Yao Junchen , Vitart Frédéric , Balmaseda Magdalena Alonso , Wu Tongwen , Liu Xiangwen
Published: June 2021

This study investigates the impact of coupled initialization on the extended-range prediction of the Madden-Julian Oscillation (MJO). A set of reforecasts using combinations of the oceanic and atmospheric initial conditions produced with coupled and uncoupled data assimilation (DA) are conducted to evaluate the impact of coupling in the different domains, from the perspective of MJO forecasts. The coupled initial conditions are provided by CERA-SAT pilot coupled reanalysis for the satellite era recently produced by ECMWF. We focus on the prediction skill of the MJO using the Real-time Outgoing Long-wave Radiation (OLR) MJO index in a series of re-forecasts. The impact of atmospheric initial conditions produced by coupled DA shows slight benefit for the MJO prediction. However, compared with the operational ocean reanalysis, the ocean initial conditions created by CERA-SAT degrade the MJO prediction skill during the first 2-3 weeks of the re-forecast by 1.5% to 5.8%. A moist static energy budget analysis revealed that the underestimation of 0.2 K sea surface temperature, 1.4 W m-2 top of atmosphere downward longwave radiation, and 3.8 W m-2 latent heat flux over the Maritime Continent lead to small but statistically significant degradation of the MJO forecast skill. The results demonstrate that the MJO is sensitive to ocean initial conditions, and illustrate the value of the extended range MJO prediction for evaluating the quality of coupled data assimilation, and suggest that future efforts on coupled data assimilation pay special attention to the balance of air-sea interaction processes over the warm pool area, in terms of modeling, observational needs and system.
Communication in the Gig Economy: Buying and Selling in Online Freelance Marketplaces
Authors: Ludwig Stephan , Herhausen Dennis , Grewal Dhruv , Bove Liliana , Benoit Sabine , de Ruyter Ko , Urwin Peter
Published: June 2021

The proliferating gig economy relies on online freelance marketplaces, which support relatively anonymous interactions through text-based messages. Informational asymmetries thus arise that can lead to exchange uncertainties between buyers and freelancers. Conventional marketing thought recommends reducing such uncertainty. However, uncertainty reduction and uncertainty management theories indicate that buyers and freelancers might benefit more from balancing—rather than reducing—uncertainty, such as by strategically adhering to or deviating from common communication principles. With dyadic analyses of calls for bids and bids from a leading online freelance marketplace, this study reveals that buyers attract more bids from freelancers when they provide moderate degrees of task information and concreteness, avoid sharing personal information, and limit the affective intensity of their communication. Freelancers’ bid success and price premiums increase when they mimic the degree of task information and affective intensity exhibited by buyers. However, mimicking a lack of personal information and concreteness reduces freelancers’ success, so freelancers should always be more concrete and offer more personal information than buyers. These contingent perspectives offer insights into buyer–seller communication in two-sided online marketplaces. They clarify that despite, or sometimes due to, communication uncertainty, both sides can achieve success in the online gig economy.
The emperor’s herbarium: The German physician Leonhard Rauwolf (1535?–96) and his botanical field studies in the Middle East
Authors: Walter Tilmann , Ghorbani Abdolbaset , van Andel Tinde
Published: June 2021

This paper presents the results of the new interdisciplinary research done on Leonhard Rauwolf’s herbarium with plants from the Middle East, which was later owned by Emperor Rudolf II. Using various sources, it examines how the herbarium came into the imperial collections, Early Modern methods of botanical research as described by Rauwolf in his printed travelogue, and how the illustrations for the printed book were produced from the specimens in the herbarium. The appendix (available in the online version) presents the new corrected botanical identification of the c. 200 plants in the fourth volume of Rauwolf’s herbarium, and a correct transcription of the Early Modern Latin and vernacular names Rauwolf collected for these plants.
Tournament Incentives and Corporate Social Responsibility Performance
Authors: Zhao Xuezhou (Rachel) , Zhou Gaoguang (Stephen) , Rezaee Zabihollah
Published: June 2021

Management incentives for engaging and excelling in corporate social responsibility (CSR) performance is an important theme as business sustainability gains momentum. We examine the role of tournament incentives, which are created by competition among non-CEO (chief executive officer) senior executives (vice presidents [VPs]) for promotion to the CEO position, in firms’ CSR performance. Using a sample of U.S. Standard & Poor (S&P) 1500 firms from 1993 to 2014, we find that tournament incentives proxied by pay gaps between CEOs and VPs are negatively associated with CSR performance, suggesting that competition for promotion could be detrimental for CSR performance. We further show that such association is more pronounced when the perceived probability of promotion increases prior to CEO turnover. This article provides policy, practical, and education implications and contribute to the literature on the integration of CSR into the business culture and strategic management processes.