bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Party Protocols, Information Complexity and Privacy
Authors: Kerenidis Iordanis , Rosén Adi , Urrutia Florent
Published: March 2019

We introduce a new information-theoretic measure, which we call
Public Information Complexity
(PIC), as a tool for the study of multi-party computation protocols, and of quantities such as their communication complexity, or the amount of randomness they require in the context of information-theoretic private computations. We are able to use this measure directly in the natural asynchronous message-passing
peer-to-peer
model and show a number of interesting properties and applications of our new notion: The Public Information Complexity is a lower bound on the Communication Complexity and an upper bound on the Information Complexity; the difference between the Public Information Complexity and the Information Complexity provides a lower bound on the amount of randomness used in a protocol; any communication protocol can be compressed to its Public Information Cost; and an explicit calculation of the zero-error Public Information Complexity of the
k
-party,
n
-bit Parity function, where a player outputs the bitwise parity of the inputs. The latter result also establishes that the amount of randomness needed by a private protocol that computes this function is Ω (
n
).
Effect of Radio Frequency Cold Plasma Treatment on Intermediate Wheatgrass (Thinopyrum intermedium) Flour and Dough Properties in Comparison to Hard and Soft Wheat (Triticum aestivum L.)
Authors: Held Sophie , Tyl Catrin E. , Annor George A.
Published: March 2019

Cold plasma is an emerging technology to improve microbiological safety as well as functionality of foods. This study compared the effect of radio frequency cold plasma on flour and dough properties of three members of the Triticeae tribe, soft as well as hard wheat (Triticum aestivum L.) and intermediate wheatgrass (Thinopyrum intermedium, IWG). These three flour types differ in their protein content and composition and were evaluated for their solubility, solvent retention capacity, starch damage, GlutoPeak and Farinograph profiles, and protein secondary structures. Plasma treatment resulted in dehydration of flours but did not change protein content or solubility. Farinograph water absorption increased for all flours after plasma treatment (from 56.5–61.1 before to 71.0–81.6%) and coincided with higher solvent retention capacity for water and sodium carbonate. Plasma treatment under our conditions was found to cause starch damage to the extent of 3.46–6.62% in all samples, explaining the higher solvent retention capacity for sodium carbonate. However, Farinograph properties were changed differently in each flour type: dough development time and stability time decreased for hard wheat and increased for soft wheat but remained unchanged in intermediate wheatgrass. GlutoPeak parameters were also affected differently: peak torque for intermediate wheatgrass increased from 32 to 39.5 GlutoPeak units but was not different for the other two flours. Soft wheat did not always aggregate after plasma treatment, i.e., did not aggregate within the measurement time. It was also the only flour where protein secondary structures were changed after plasma treatment, exhibiting an increase from 15.2 to 27.9% in β-turns and a decrease from 59.4 to 47.9% in β-sheets. While this could be indicative of a better hydrated gluten network, plasma-treated soft wheat was the only flour where viscoelastic properties were changed and extensibility decreased. Further research is warranted to elucidate molecular changes underlying these effects.
Functions of Macrophages in the Maintenance of Intestinal Homeostasis
Authors: Wang Shuai , Ye Qianhong , Zeng Xiangfang , Qiao Shiyan
Published: March 2019

Intestinal macrophages constitute the largest pool of macrophages in the body and have emerged as crucial sentinels for pathogen recognition and elimination. The source and development of intestinal macrophages, as well as their distinct properties have been well documented. Intestinal macrophages exert their functions in the maintenance of intestinal homeostasis by shaping host-microbiota symbiosis, managing gut inflammation, crosstalking with T cells, and facilitating wound repair. Recently, nutritional regulation of intestinal macrophages has attracted substantial attention and is becoming a promising approach to disease prevention and control. Understanding the mechanisms employed by intestinal macrophages in mediating intestinal immune homeostasis and inflammation, as well as the mode of action of dietary nutrients in the modulating functions of intestinal macrophages, represents an opportunity to prevent and control inflammatory bowel diseases.
Analytical Solution for One-Dimensional Transport of Particles considering Dispersion in Deposition Kinetics
Authors: Chen Xingxin , Zhang Xinran , Wu Zhonghan
Published: March 2019

The study of particle transport in porous media is of great significance for pollution mitigation, grouting reinforcement, municipal solid waste landfill management, and groundwater exploitation. We developed an analytical solution for a corrected convection-dispersion model that takes into account the effects of dispersion on deposition kinetics with regard to the particle concentration decay type. The rationality and correctness of the solution were verified using time, distance, deposition coefficient, diffusion coefficient, and decay coefficient. As the time increased, the particle concentration increased from zero to the peak value, then decreased to zero. However, as distance increased, the peak value of particle concentration gradually decreased. The deposition coefficient affected the magnitude of the peak value and the distance corresponding to the peak value. In addition, the greater the attenuation coefficient, the smaller the peak value. Overall, our method’s prediction results showed that considering the effect of dispersion on deposition kinetics produces better results than when this is not considered.
Smart Real-Time Video Surveillance Platform for Drowsiness Detection Based on Eyelid Closure
Authors: Tayab Khan Muhammad , Anwar Hafeez , Ullah Farman , Ur Rehman Ata , Ullah Rehmat , Iqbal Asif , Lee Bok-Hee , Kwak Kyung Sup
Published: March 2019

We propose drowsiness detection in real-time surveillance videos by determining if a person’s eyes are open or closed. As a first step, the face of the subject is detected in the image. In the detected face, the eyes are localized and filtered with an extended Sobel operator to detect the curvature of the eyelids. Once the curves are detected, concavity is used to tell whether the eyelids are closed or open. Consequently, a concave upward curve means the eyelid is closed whereas a concave downwards curve means the eye is open. The proposed method is also implemented on hardware in order to be used in real-time scenarios, such as driver drowsiness detection. The evaluation of the proposed method used three image datasets, where images in the first dataset have a uniform background. The proposed method achieved classification accuracy of up to 95% on this dataset. Another benchmark dataset used has significant variations based on face deformations. With this dataset, our method achieved classification accuracy of 70%. A real-time video dataset of people driving the car was also used, where the proposed method achieved 95% accuracy, thus showing its feasibility for use in real-time scenarios.
Comparative Evaluation of 68Ga-Citrate PET/CT and 18F-FDG PET/CT in the Diagnosis of Type II Collagen-Induced Arthritis in Rats
Authors: Wang Zi , Cai Liang , Xu Tingting , Tang Dan , Liu Lin , Chen Yue
Published: March 2019

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic, symmetrical, and erosive synovitis. RA is one of the most common disabling diseases in the clinic. The main clinical intervention strategies are early diagnosis and early treatment. This study aims to predict the diagnostic value of 68Ga-citrate and 18F-FDG PET/CT in RA by comparing and analyzing the value of 68Ga-citrate and 18F-FDG PET/CT for diagnosing type II collagen-induced arthritis (CIA) in rats. Some CIA models were established. Normal rats were selected as the control group, and 23 days and 40 days were selected as the early and late time points of arthritis, respectively. The semiquantitative analysis of CIA rats was carried out with 68Ga-citrate PET/CT and 18F-FDG PET/CT, and the ratio of the maximum standardized uptake (SUVmax) values in the regions of interest (ROIs) of the hind foot ankle joint and thigh muscle was calculated and statistically analyzed. The distribution of CIA rats in vivo at the 68Ga-citrate 90 min time point was studied, and the ankle tissues were evaluated with hematoxylin and eosin (HE) staining. 68Ga-citrate PET/CT is obviously superior to 18F-FDG PET/CT for CIA imaging, and the statistical results show that the difference between the two examination methods is statistically significant (P<0.001). The uptake of these two radiopharmaceuticals showed the same trend in arthritis rats with different scores. The distribution of 68Ga-citrate at 90 min is consistent with the trend shown by 68Ga-citrate PET/CT. 68Ga-citrate PET/CT can reflect the inflammatory activity of affected joints in CIA rats earlier and more sensitively than 18F-FDG PET/CT, and this imaging advantage continues until the later stage of inflammation. Therefore, 68Ga-citrate PET/CT is worthy of further promotion and application in the clinical diagnosis of RA.
A Joint Deep Recommendation Framework for Location‐Based Social Networks
Authors: Tal Omer , Liu Yang
Published: March 2019

Location‐based social networks, such as Yelp and Tripadvisor, which allow users to share experiences about visited locations with their friends, have gained increasing popularity in recent years. However, as more locations become available, the need for accurate systems able to present personalized suggestions arises. By providing such service, point‐of‐interest recommender systems have attracted much interest from different societies, leading to improved methods and techniques. Deep learning provides an exciting opportunity to further enhance these systems, by utilizing additional data to understand users’ preferences better. In this work we propose Textual and Contextual Embedding-based Neural Recommender (TCENR), a deep framework that employs contextual data, such as users’ social networks and locations’ geo‐spatial data, along with textual reviews. To make best use of these inputs, we utilize multiple types of deep neural networks that are best suited for each type of data. TCENR adopts the popular multilayer perceptrons to analyze historical activities in the system, while the learning of textual reviews is achieved using two variations of the suggested framework. One is based on convolutional neural networks to extract meaningful data from textual reviews, and the other employs recurrent neural networks. Our proposed network is evaluated over the Yelp dataset and found to outperform multiple state‐of‐the‐art baselines in terms of accuracy, mean squared error, precision, and recall. In addition, we provide further insight into the design selections and hyperparameters of our recommender system, hoping to shed light on the benefit of deep learning for location‐based social network recommendation.
Atorvastatin Inhibits Breast Cancer Cells by Downregulating PTEN/AKT Pathway via Promoting Ras Homolog Family Member B (RhoB)
Authors: Ma Qing , Gao Yang , Xu Pei , Li Kai , Xu Xiaolong , Gao Jingbo , Qi Yuwen , Xu Jingjing , Yang Yan , Song Wenjing , He Xin , Liu Shuting , Yuan Xiaoning , Yin Weinan , He Yanqi , Pan Wenting , Wei Lei , Zhang Jingwei
Published: March 2019

Background. Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. Methods. The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. Results. ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66–0.83], p =7e−8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. Conclusions. The exact mechanism of ATO’s carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer.
Horizontal Backward Launch Dynamics Modeling and Analysis
Authors: Zhao Liangyu , Jiang Yi , Wei Xinlin , Ma Liqi , Li Xiang
Published: March 2019

Fighters’ air strikes play a vital role in modern warfare. But, with the development of fighters, the amount of bombs will inevitably become a major disadvantage due to the limitations of the invisible design and other functions, so a combination of the old model bombers and the advanced fifth-generation fighters has been proposed. This paper takes the aircraft missile horizontal backward launch system as the research object; firstly, the finite element model of the missile’s off-track is established, and the simulation calculation under the fixed platform is tested to verify the correctness of the finite element model. Meanwhile, the simulation parameters of the initial trajectory are obtained. Then, by establishing the separation model of the machine under the open state of the aircraft’s rear launcher, the variation of the flow field during the separation process of the missile is analyzed, and the variation of the force and the attitude of the missile is studied. It is found that the pitching motion of the missile is greatly affected by the initial pitch angle, it is always in the heading state during the whole separation process, and the yaw motion is not obvious.
SSPSoC: A Secure SDN-Based Protocol over MPSoC
Authors: Ellinidou Soultana , Sharma Gaurav , Rigas Théo , Vanspouwen Tristan , Markowitch Olivier , Dricot Jean-Michel
Published: March 2019

In recent years, Multi-Processor System-on-Chips (MPSoCs) are widely deployed in safety-critical embedded systems. The Cloud-of-Chips (CoC) is a scalable MPSoC architecture comprised of a large number of interconnected Integrated Circuits (IC) and Processing Clusters (PC) destined for critical systems. While many researches have focused on addressing the hardware issues of MPSoCs, the communication over them has not been very well explored. Following the SDN concept, we propose a new protocol in order to secure the communication and efficiently manage the routing within the CoC. The SSPSoC includes a private key derivation phase, a group key agreement (GKA) phase, and a data exchange phase in order to ensure that basic security primitives are preserved and provide secure communication. Furthermore, a network of 1-30 nodes is set in order to validate the proposed protocol and measure the network performance and memory consumption of the proposed protocol.
Acupuncture Reversible Effects on Altered Default Mode Network of Chronic Migraine Accompanied with Clinical Symptom Relief
Authors: Zou Yan , Tang Weijun , Li Xiang , Xu Manwen , Li Ji
Published: March 2019

Objective. To determine whether and how longitudinal acupuncture modulates the impaired default mode network (DMN) in chronic migraine (CM) patients without aura. Methods. Resting-state functional magnetic resonance imaging (fMRI) data from 14 CM patients treated with longitudinal pre- and postacupuncture treatment (PPAT) and data of 18 age- and gender-matched healthy controls (HCs) were analyzed using independent component analysis (ICA) and seed-based correlation analysis (SCA) to investigate connectivity within the DMN. Correlation analyses were performed to identify associations between changes in functional connectivity (FC) and in clinical pain based on PPAT observations. The monthly mean visual analog scale (VAS) scores, monthly mean headache attacks, monthly headache days, monthly amount of acute headache medications, and immediate VAS scores were assessed for evaluation of pain. Results. The decreased FC within the DMN found in the left superior prefrontal gyrus (L_SPFG) and left precuneus (L_PRECUN) of CM patients was returned to the healthy control level after acupuncture treatments. Furthermore, the diminished pairwise FC strengths in some regions of interest (ROIs) within the DMN were also increased, mainly distributed between the right temporal lobe (R_TPL) and left anterior cingulate cortex, between the R_TPL and bilateral superior medial gyrus, and between the R_TPL and right precuneus. Increased z-scores within the DMN (L_SPFG and L_PRECUN) were associated with reduced immediate VAS scores, and increases in z-scores of the L_PRECUN were negatively correlated with reductions in the monthly amount of acute headache medications. However, no association existed between the increased DMN connectivity and reduced monthly mean VAS scores, monthly mean headache attacks, and monthly headache days. Conclusion. Altered DMN connectivity and its normalization postacupuncture can be employed to monitor CM and its modulating effects. The DMN is useful for understanding the therapeutic mechanisms of acupuncture in CM.
Deimplementing Untested Practices in Homecare Services: A Preobservational-Postobservational Design
Authors: Guay Manon , Ruest Mélanie , Contandriopoulos Damien
Published: March 2019

Introduction. With community-dwelling elders waiting to adapt their bathroom, Health and Social Services Centers in Quebec (Canada) combined human resources through cross-skilling within interdisciplinary teams. To this end, occupational therapists implemented in-house “tools” to support nonoccupational therapists in selecting bathing equipment. However, unknown psychometric properties of those in-house “tools” cast doubt on the quality of service provided to elders. Little is also known about the best processes to use to support the deimplementation of such nonevidence-based practices. This study presents the effect of a knowledge transfer and exchange intervention designed to deimplement in-house “tools” and replace them with an evidence-based tool (Algo). Methods. Censuses were conducted with the 94 Health and Social Services Centers of Quebec providing homecare services, before and after the knowledge transfer and exchange intervention (2009-2013). In 2013, the deimplementation of in-house “tools” and their replacement by Algo were measured with Knott and Wildavsky’s levels of utilization. Results. Cross-skilling within interdisciplinary teams increased between censuses (87% to 98%), as did use of in-house “tools” (67% to 81%). Algo’s uptake started during the knowledge transfer and exchange process as 25 Health and Social Services Centers achieved the first level of utilization. Nonetheless, no Health and Social Services Center deimplemented the in-house “tools” to use Algo. Conclusion. The knowledge transfer and exchange process led to the development of a scientifically sound clinical tool (Algo) and challenged the status quo in clinical settings regarding the use of nonevidence-based practices. However, the deimplementation of in-use practices has not yet been observed. This study highlights the need to act proactively on the deimplementation and implementation processes.
Pounding between Adjacent Frame Structures under Earthquake Excitation Based on Transfer Matrix Method of Multibody Systems
Authors: Zhang Yin , Ding Jianguo , Zhuang Hui , Chang Yu , Chen Peng , Zhang Xiangxiang , Xie Wenhao , Fan Jin
Published: March 2019

In this paper, the case of two adjacent frame structures is studied by establishing a mechanical model based on the transfer matrix method of multibody system (MS‐TMM). The transfer matrices of the related elements and total transfer equation are deduced, combining with the Hertz‐damp mode. The pounding process of two adjacent frame structures is calculated by compiling the relevant MATLAB program during severe ground motions. The results of the study indicate that the maximum error of the peak pounding forces and the peak displacements at the top of the frame structure obtained by the MS‐TMM and ANSYS are 6.22% and 9.86%, respectively. Comparing the calculation time by ANSYS and MS‐TMM, it shows that the computation efficiency increases obviously by using the MS‐TMM. The pounding mainly occurs at the top of the short structure; meanwhile, multiple pounding at the same time may occur when the separation gap is small. The parametric investigation has led to the conclusion that the pounding force, the number of poundings, the moment of pounding, and the structural displacement are sensitive to the change of the seismic peak acceleration and the separation gap size.
Accurate Method for Picking Up the First Arrival Time of Microseismic Signals Based on Entropy Theory
Authors: Jia Bao-xin , Sun Ao , Pan Yi-shan , Chen Hao , Liu Feng-pu
Published: March 2019

The entropy method describes the change in the signal state from a macroscopic angle and weakens the interference generated by random noise. From the angle of chaos, which describes the first arrival of microseismic signals, it predicts the trend of noise entropy based on the grey theory. The results indicate that the entropy method is sensitive to amplitude, frequency, and seismic phase changes. Compared with traditional methods, the entropy method has better noise immunity. In terms of the influence of the pickup parameter on the resulting error, the entropy method demonstrated the best result and produces the smallest error.
Association of Higher Circulating Insulin Antibody with Increased Mean Amplitude Glycemic Excursion in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional, Retrospective Case-Control Study
Authors: Zhu Jian , Yuan Lu , Ni Wen-ji , Luo Yong , Ma Jian-hua
Published: March 2019

Insulin antibody (IA) may potentially affect a patient’s glycemic control due to its variability in both binding and/or releasing insulin. However, the association between IA titer and daily glycemic variability (GV) is still unknown. We thus performed this cross-sectional, retrospective case-control study to assess the relationship between IA titer and mean amplitude glycemic excursion (MAGE) in type 2 diabetes mellitus (T2DM) patients using a continuous glucose monitoring (CGM) system. We recruited 100 eligible patients (IA>5%, IA positive) and divided them into two groups—a low (L) group and a high (H) group—based on their IA titer. The control (C) group consisted of 47 patients (IA≤5%, IA negative) matched for age, BMI, gender, and glycosylated hemoglobin A1c (HbA1c). The CGM determined the GV of enrolled patients. The primary outcome was the relationship between the IA titer and the MAGE, and the secondary outcome was the differences of GV among the three groups. We found that patients in the H group had higher levels of blood glucose fluctuation parameters than those in the L and C groups. The Ln(IA) was positively correlated with Ln(MAGE) even after adjusting for age, gender, BMI, HbA1c, and fasting and postprandial C-peptide(r=0.423, p<0.001). Multiple linear stepwise regression analysis revealed that Ln(IA) was an independent factor of Ln(MAGE) (beta=0.405, p<0.001). In conclusion, the higher circulating IA titer was associated with increased MAGE in T2DM patients, indicating that those patients with elevated IA titer should receive GV assessment and individualized treatment.
Suppression Method of Jump Points for Multipole Magnetic Encoder at Low Temperature Based on Single-Pole Angle Value Fitting
Authors: Wang L. , Ren Q. M. , Han J. C. , Zhang Y. D.
Published: March 2019

To eliminate the jump points of multipole angle values after subdivision at low temperature, the magnetic field and temperature field characteristics of a multipole magnetic encoder are analyzed in this study, and the effect of changes in magnetic field strength and temperature field on the precision of angle values is studied. To eliminate the jump point of multipole angle values caused by changes in the temperature field, the suppression method based on single-pole angle value fitting is proposed. The error between the single-pole and multipole angle values is tabulated by the oversampling linear interpolation method, and the precision of fitting single-pole to multipole angle values is effectively improved. The error of the angle value caused by changes in the temperature field is studied and analyzed, and the relationship between the jump angle values and the pole number of the multipole magnetic encoder is obtained. Furthermore, the jump point is compensated for by the jump range of the multipole angle values. Finally, the angle accuracy of the multipole magnetic encoder in a cryogenic chamber is experimentally verified. The experimental results show that the low-temperature jump point compensation method proposed for the multipole magnetic encoder in this paper can effectively suppress the jump of the angle values.
Channa striata (Ikan Gabus) Extract and the Acceleration of Tuberculosis Treatment: A True Experimental Study
Authors: Ma’rufi Isa , Ali Khaidar , Sedemen Ign Arya , Purwanto P. , Khoiri Abu
Published: March 2019

Tuberculosis is international health problem, which is classified in Global Emergency disease since 1992. The objective of the study is to determine the effect of Channa striata extract toward the acceleration of tuberculosis treatment. The study used true experiment, in which the intervention of the study was Channa striata supplementation to respondent. In addition, Chi-square was used to analyze the data with SPSS version 22. The result is the proportion of respondent classified in negative category in intervention group within week 0, week 1, week 2, week 3, and week 4 being 10.7%, 35.9%, 56.3%, 70.9%, and 90.3%, respectively. Besides, the proportion of respondent classified in negative category in control group within week 0, week 1, week 2, week 3, and week 4 was 13.4%, 23.7%, 37.1%, 49.5%, and 68%, respectively. Based on Chi-square test, the P value of Channa striata supplementation toward the acceleration of tuberculosis treatment week 1, week 3, and week 4 is 0.045, 0.019, and 0.005 (P< α; α=0.05), respectively. It means that there were differences between Channa striata supplementation and acceleration of tuberculosis treatment among respondent. Therefore, Channa striata treatment was significantly related to the acceleration of tuberculosis recovery.
Experimental Investigation of Steel Plate Shear Walls under Shear‐Compression Interaction
Authors: Lv Yang , Li Ling , Wu Di , Zhong Bo , Chen Yu , Chouw Nawawi
Published: March 2019

Four scaled one‐storey single‐bay steel plate shear wall (SPSW) specimens with unstiffened panels were tested to determine their behaviour under cyclic loadings. The shear walls had moment‐resisting beam‐to‐column connections. Four different vertical loads, i.e., 300 kN, 600 kN, 900 kN, and 1200 kN, representing the gravity load of the upper storeys were applied at the top of the boundary columns through a force distribution beam. A horizontal cyclic load was then applied at the top of the specimens. The specimen behaviour, envelope curves, axial stress distribution of the infill steel plate, and shear capacity were analyzed. The axial stress distribution and envelope curves were compared with the values predicted using an analytical model available in the literature.
Ground Settlements due to Construction of Triplet Tunnels with Different Construction Arrangements
Authors: Naseem Ahsan , Schotte Ken , De Pauw Bart , De Backer Hans
Published: March 2019

Combining two or three shield tunnels that are drilled consecutively at small intermediate distances into a single open cross section creates a larger useful tunnel area, while keeping the total construction area rather compact. However, the combination of several bored tunnel tubes into a singular cross section results in a complicated construction procedure. Current methodologies address the evaluation of the settlement trough for one single tunnel or two parallel tunnels only. This study aims at expanding the current methodologies to the multiple‐tunnel geometry. Various construction orders and intermediate distances between the tunnels are evaluated using finite element analyses. The grout pressure method is applied in combination with the hardening strain with the small strain stiffness (HS small) constitutive model to investigate the relative magnitude of the settlements due to shield tunneling. It is concluded that the configuration with a Top‐Left‐Right construction sequence is the optimal arrangement. It results in 22.4% and 36.9% lesser settlements when compared to the equivalent horizontal twin tunnels spaced at 3D and the Left‐Right‐Top sequence, respectively.
Stimulatory Effects of Boron Containing Bioactive Glass on Osteogenesis and Angiogenesis of Polycaprolactone: In Vitro Study
Authors: Xia Lunguo , Ma Wudi , Zhou Yuning , Gui Zhipeng , Yao Aihua , Wang Deping , Takemura Akimichi , Uemura Mamoru , Lin Kailin , Xu Yuanjin
Published: March 2019

Polycaprolactone (PCL) has attracted great attention for bone regeneration attributed to its cost-efficiency, high toughness, and good processability. However, the relatively low elastic modulus, hydrophobic nature, and insufficient bioactivity of pure PCL limited its wider application for bone regeneration. In the present study, the effects of the addition of boron containing bioactive glass (B-BG) materials on the mechanical properties and biological performance of PCL polymer were investigated with different B-BG contents (0, 10, 20, 30, and 40 wt.%), in order to evaluate the potential applications of B-BG/PCL composites for bone regeneration. The results showed that the B-BG/PCL composites possess better tensile strength, human neutral pH value, and fast degradation as compared to pure PCL polymers. Moreover, the incorporation of B-BG could enhance proliferation, osteogenic differentiation, and angiogenic factor expression for rat bone marrow stromal cells (rBMSCs) as compared to pure PCL polymers. Importantly, the B-BG also promoted the angiogenic differentiation for human umbilical vein endothelial cells (HUVECs). These enhanced effects had a concentration dependence of B-BG content, while 30 wt.% B-BG/PCL composites achieved the greatest stimulatory effect. Therefore the 30 wt.% B-BG/PCL composites have potential applications in bone reconstruction fields.
The Dosimetric Comparisons of CRT, IMRT, ARC, CRT+IMRT, and CRT+ARC of Postoperative Radiotherapy in IIIA-N2 Stage Non-Small-Cell Lung Cancer Patients
Authors: Zhang Yanqiu , Han A’meng , Fu Zhanzhao , Xu Shufeng , Zhang Zijian
Published: March 2019

Currently, studies about PORT in stage IIIA-N2 NSCLC patients in recent years have mostly adopted the conformal radiation therapy (CRT) technique, while other modern techniques such as intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT, hereinafter referred to as ARC), helical tomotherapy (HT), and so forth are also developing quickly. In this paper, we intended to compare the dosimetric characteristics of CRT, IMRT, ARC, CRT+IMRT, and CRT+ARC of PORT in stage IIIA-N2 NSCLC patients. Ten patients with stage IIIA-N2 completely resected NSCLC, whom were treated by PORT in the radiotherapy department of our hospital from January 1, 2017, to January 1, 2018, were randomly selected in this study. For each patient, the CRT plan, IMRT plan, ARC plan, CRT+IMRT plan, and CRT+ARC plan were designed separately on the same set of CT images. The isodose distribution and dose-volume histogram (DVH) of the five plans were compared to determine the dosimetric parameters of the targets, OAR (organs at risk), and the normal tissue (defined as body subtracted to PTV (planning target volume), B-P). No plan had absolute dosimetry advantages than any other plans. In clinical practice, the plans could be chosen according to their dosimetry characteristics.
Myc and Loss of p53 Cooperate to Drive Formation of Choroid Plexus Carcinoma
Authors: Wang Jun , Merino Diana M. , Light Nicholas , Murphy Brian L. , Wang Yong-Dong , Guo Xiaohui , Hodges Andrew P. , Chau Lianne Q. , Liu Kun-Wei , Dhall Girish , Asgharzadeh Shahab , Kiehna Erin N. , Shirey Ryan J. , Janda Kim D. , Taylor Michael D. , Malkin David , Ellison David W. , VandenBerg Scott R. , Eberhart Charles G. , Sears Rosalie C. , Roussel Martine F. , Gilbertson Richard J. , Wechsler-Reya Robert J.
Published: March 2019

Choroid plexus carcinoma (CPC) is a rare brain tumor that occurs most commonly in very young children and has a dismal prognosis despite intensive therapy. Improved outcomes for patients with CPC depend on a deeper understanding of the mechanisms underlying the disease. Here we developed transgenic models of CPCs by activating the Myc oncogene and deleting the Trp53 tumor suppressor gene in murine neural stem cells or progenitors. Murine CPC resembled their human counterparts at a histologic level, and like the hypodiploid subset of human CPC, exhibited multiple whole-chromosome losses, particularly of chromosomes 8, 12, and 19. Analysis of murine and human CPC gene expression profiles and copy number changes revealed altered expression of genes involved in cell cycle, DNA damage response, and cilium function. High-throughput drug screening identified small molecule inhibitors that decreased the viability of CPC. These models will be valuable tools for understanding the biology of choroid plexus tumors and for testing novel approaches to therapy.

Significance:

This study describes new mouse models of choroid plexus carcinoma and uses them to investigate the biology and therapeutic responsiveness of this highly malignant pediatric brain tumor.
CD317 Activates EGFR by Regulating Its Association with Lipid Rafts
Authors: Zhang Guizhong , Li Xin , Chen Qian , Li Junxin , Ruan Qingguo , Chen Youhai H. , Yang Xiaolu , Wan Xiaochun
Published: March 2019

EGFR regulates various fundamental cellular processes, and its constitutive activation is a common driver for cancer. Anti-EGFR therapies have shown benefit in cancer patients, yet drug resistance almost inevitably develops, emphasizing the need for a better understanding of the mechanisms that govern EGFR activation. Here we report that CD317, a surface molecule with a unique topology, activated EGFR in hepatocellular carcinoma (HCC) cells by regulating its localization on the plasma membrane. CD317 was upregulated in HCC cells, promoting cell-cycle progression and enhancing tumorigenic potential in a manner dependent on EGFR. Mechanistically, CD317 associated with lipid rafts and released EGFR from these ordered membrane domains, facilitating the activation of EGFR and the initiation of downstream signaling pathways, including the Ras–Raf–MEK–ERK and JAK–STAT pathways. Moreover, in HCC mouse models and patient samples, upregulation of CD317 correlated with EGFR activation. These results reveal a previously unrecognized mode of regulation for EGFR and suggest CD317 as an alternative target for treating EGFR-driven malignancies.

Significance:

Activation of EGFR by CD317 in hepatocellular carcinoma cells suggests CD317 as an alternative target for treating EGFR-dependent tumors.
PDLIM2 Is a Marker of Adhesion and β-Catenin Activity in Triple-Negative Breast Cancer
Authors: Cox Orla T. , Edmunds Shelley J. , Simon-Keller Katja , Li Bo , Moran Bruce , Buckley Niamh E. , Bustamante-Garrido Milan , Healy Nollaig , O'Flanagan Ciara H. , Gallagher William M. , Kennedy Richard D. , Bernards René , Caldas Carlos , Chin Suet-Feung , Marx Alexander , O'Connor Rosemary
Published: March 2019

The PDLIM2 protein regulates stability of transcription factors including NF-κB and STATs in epithelial and hemopoietic cells. PDLIM2 is strongly expressed in certain cancer cell lines that exhibit an epithelial-to-mesenchymal phenotype, and its suppression is sufficient to reverse this phenotype. PDLIM2 supports the epithelial polarity of nontransformed breast cells, suggesting distinct roles in tumor suppression and oncogenesis. To better understand its overall function, we investigated PDLIM2 expression and activity in breast cancer. PDLIM2 protein was present in 60% of tumors diagnosed as triple-negative breast cancer (TNBC), and only 20% of other breast cancer subtypes. High PDLIM2 expression in TNBC was positively correlated with adhesion signaling and β-catenin activity. Interestingly, PDLIM2 was restricted to the cytoplasm/membrane of TNBC cells and excluded from the nucleus. In breast cell lines, PDLIM2 retention in the cytoplasm was controlled by cell adhesion, and translocation to the nucleus was stimulated by insulin-like growth factor-1 or TGFβ. Cytoplasmic PDLIM2 was associated with active β-catenin and ectopic expression of PDLIM2 was sufficient to increase β-catenin levels and its transcriptional activity in reporter assays. Suppression of PDLIM2 inhibited tumor growth in vivo, whereas overexpression of PDLIM2 disrupted growth in 3D cultures. These results suggest that PDLIM2 may serve as a predictive biomarker for a large subset of TNBC whose phenotype depends on adhesion-regulated β-catenin activity and which may be amenable to therapies that target these pathways.

Significance:

This study shows that PDLIM2 expression defines a subset of triple-negative breast cancer that may benefit from targeting the β-catenin and adhesion signaling pathways.
Inhibition of NF-κB–Dependent Signaling Enhances Sensitivity and Overcomes Resistance to BET Inhibition in Uveal Melanoma
Authors: Ambrosini Grazia , Do Catherine , Tycko Benjamin , Realubit Ronald B. , Karan Charles , Musi Elgilda , Carvajal Richard D. , Chua Vivian , Aplin Andrew E. , Schwartz Gary K.
Published: March 2019

Bromodomain and extraterminal protein inhibitors (BETi) are epigenetic therapies aimed to target dysregulated gene expression in cancer cells. Despite early successes of BETi in a range of malignancies, the development of drug resistance may limit their clinical application. Here, we evaluated the mechanisms of BETi resistance in uveal melanoma, a disease with little treatment options, using two approaches: a high-throughput combinatorial drug screen with the clinical BET inhibitor PLX51107 and RNA sequencing of BETi-resistant cells. NF-κB inhibitors synergistically sensitized uveal melanoma cells to PLX51107 treatment. Furthermore, genes involved in NF-κB signaling were upregulated in BETi-resistant cells, and the transcription factor CEBPD contributed to the mechanism of resistance. These findings suggest that inhibitors of NF-κB signaling may improve the efficacy of BET inhibition in patients with advanced uveal melanoma.

Significance:

These findings provide evidence that inhibitors of NF-κB signaling synergize with BET inhibition in in vitro and in vivo models, suggesting a clinical utility of these targeted therapies in patients with uveal melanoma.
Long Noncoding RNA MPRL Promotes Mitochondrial Fission and Cisplatin Chemosensitivity via Disruption of Pre-miRNA Processing
Authors: Tian Tian , Lv Xiaobin , Pan Guokai , Lu Yingjuan , Chen Weixiong , He Wang , Lei Xinyuan , Zhang Hanqing , Liu Mo , Sun Sheng , Ou Zhanpeng , Lin Xinyu , Cai Lei , He Lile , Tu Zhiming , Wang Xinhui , Tannous Bakhos A. , Ferrone Soldano , Li Jinsong , Fan Song
Published: March 2019

Purpose:

The overall biological roles and clinical significance of most long noncoding RNAs (lncRNA) in chemosensitivity are not fully understood. We investigated the biological function, mechanism, and clinical significance of lncRNA NR_034085, which we termed miRNA processing–related lncRNA (MPRL), in tongue squamous cell carcinoma (TSCC).

Experimental Design:

LncRNA expression in TSCC cell lines with cisplatin treatment was measured by lncRNA microarray and confirmed in TSCC tissues. The functional roles of MPRL were demonstrated by a series of in vitro and in vivo experiments. The miRNA profiles, RNA pull-down, RNA immunoprecipitation, serial deletion analysis, and luciferase analyses were used to investigate the potential mechanisms of MPRL.

Results:

We found that MPRL expression was significantly upregulated in TSCC cell lines treated with cisplatin and transactivated by E2F1. MPRL controlled mitochondrial fission and cisplatin sensitivity through miR–483-5p. In exploring the underlying interaction between MPRL and miR–483-5p, we identified that cytoplasmic MPRL directly binds to pre–miR–483 within the loop region and blocks pre–miR–483 recognition and cleavage by TRBP–DICER-complex, thereby inhibiting miR–483-5p generation and upregulating miR–483-5p downstream target-FIS1 expression. Furthermore, overexpression or knockdown MPRL altered tumor apoptosis and growth in mouse xenografts. Importantly, we found that high expression of MPRL and pre–miR–483, and low expression of miR–483-5p were significantly associated with neoadjuvant chemosensitivity and better TSCC patients’ prognosis.

Conclusions:

We propose a model in which lncRNAs impair microprocessor recognition and are efficient of pre-miRNA cropping. In addition, our study reveals a novel regulatory network for mitochondrial fission and chemosensitivity and new biomarkers for prediction of neoadjuvant chemosensitivity in TSCC.

These findings uncover a novel mechanism by which lncRNA determines mitochondrial fission and cisplatin chemosensitivity by inhibition of pre-miRNA processing and provide for the first time the rationale for lncRNA and miRNA biogenesis for predicting chemosensitivity and patient clinical prognosis.
CD47-Targeted Near-Infrared Photoimmunotherapy for Human Bladder Cancer
Authors: Kiss Bernhard , van den Berg Nynke S. , Ertsey Robert , McKenna Kelly , Mach Kathleen E. , Zhang Chiyuan Amy , Volkmer Jens-Peter , Weissman Irving L. , Rosenthal Eben L. , Liao Joseph C.
Published: March 2019

Purpose:

Near-infrared photoimmunotherapy (NIR-PIT) is a localized molecular cancer therapy combining a photosensitizer-conjugated mAb and light energy. CD47 is an innate immune checkpoint widely expressed on bladder cancer cells, but absent from luminal normal urothelium. Targeting CD47 for NIR-PIT has the potential to selectively induce cancer cell death and minimize damage to normal urothelium.

Experimental Design:

The cytotoxic effect of NIR-PIT with anti-CD47-IR700 was investigated in human bladder cancer cell lines and primary human bladder cancer cells derived from fresh surgical samples. Phagocytosis assays were performed to evaluate macrophage activity after NIR-PIT. Anti-CD47-IR700 was administered to murine xenograft tumor models of human bladder cancer for in vivo molecular imaging and NIR-PIT.

Results:

Cytotoxicity in cell lines and primary bladder cancer cells significantly increased in a light-dose–dependent manner with CD47-targeted NIR-PIT. Phagocytosis of cancer cells significantly increased with NIR-PIT compared with antibody alone (P = 0.0002). In vivo fluorescence intensity of anti-CD47-IR700 in tumors reached a peak 24-hour postinjection and was detectable for at least 14 days. After a single round of CD47-targeted NIR-PIT, treated animals showed significantly slower tumor growth compared with controls (P < 0.0001). Repeated CD47-targeted NIR-PIT treatment further slowed tumor growth (P = 0.0104) and improved survival compared with controls.

Conclusions:

CD47-targeted NIR-PIT increased direct cancer cell death and phagocytosis resulting in inhibited tumor growth and improved survival in a murine xenograft model of human bladder cancer.
Sex Hormones and Anticancer Immunity
Authors: Özdemir Berna C. , Dotto Gian-Paolo
Published: March 2019

The impact of sex hormones on anticancer immunity deserves attention due to the importance of the immune system in cancer therapy and the recognition of sex differences in immunity. Cancer is ultimately the result of failed immune surveillance, and the diverging effects of male and female sex hormones on anticancer immunity could contribute to the higher cancer incidence and poorer outcome in men. Estrogens and androgens affect the number and function of immune cells, an effect that depends on cell type, tumor microenvironment, and the age and reproductive status of the individual. Despite the recent progress in immuno-oncology, our current understanding of the interplay between sex hormones and anticancer immune responses is in its infancy. In this review, we will focus on the impact of sex hormones on anticancer immunity and immunotherapy. We will discuss the potential role of the changing hormone levels in anticancer immunity during aging and in the context of menopausal hormone therapies and oral contraception. We will review emerging data on sex differences in PD-L1 expression and potential biomarkers predictive for the efficacy of immune checkpoint inhibitors such as the microbiome and consider ongoing clinical trials evaluating the potential impact of hormone deprivation therapies to increase response to immune checkpoint inhibitors in breast and prostate cancer. Finally, we will point to areas of future research.
Longitudinal Adherence to Immunochemical Fecal Occult Blood Testing vs Guaiac-based FOBT in an Organized Colorectal Cancer Screening Program
Authors: Benito Llucia , Travier Noemie , Binefa Gemma , Vidal Carmen , Espinosa Jose , Milà Núria , Garcia Montse
Published: March 2019

Longitudinal adherence is a critical component of the efficacy of stool-based screening programs because they should be repeated every 1–2 years. Few data have been published on the uptake in multiple rounds of fecal occult blood test-based (FOBT) colorectal cancer (CRC) screening. We calculated two measures of longitudinal adherence to biennial FOBT (guaiac fecal occult blood test:gFOBT or fecal immunochemical test:FIT) to better understand its impact on the programmatic effectiveness of a population-based CRC screening program (2000–2017). Ongoing population-based CRC program of men and women aged 50–69 years. Variables: Age at first CRC screening invitation, sex, number of screening invitations, number of screens, deprivation score, and uptake rate. Logistic regression models were used to assess the independent effect of sex, age at first invitation, deprivation, and the type of screening test offered on adherence. The uptake rate for guaiac fecal occult blood test (gFOBT) was 23.9%, and for the fecal immunochemical test (FIT), it was 37.4%. The overall rate of consistently screened invitees after seven rounds of screening was 14.2%, being 20.6% for those individuals who used FIT and 14.3% for those who used gFOBT. Factors associated with continued participation (consistent vs. inconsistent screenees) showed that the longitudinal adherence was associated with age, screening test used, and number of invitations. Continued participation was lower in individuals who were screened using FIT than among those screened using gFOBT [OR, 0.68; 95% confidence interval (CI), 0.57–0.81]. The overall rate of consistently screened invitees for colorectal cancer screening was higher with FIT than gFOBT. Studying the rate of individuals being current for screening may help to anticipate potential benefits before the long-term outcome data are available.