bluuebunny/crossref_metadata_2025 huggingface dataset:
Video Retrieval with Similarity-Preserving Deep Temporal Hashing
Authors: Shen Ling , Hong Richang , Zhang Haoran , Tian Xinmei , Wang Meng
Published: December 2019

Despite the fact that remarkable progress has been made in recent years, Content-based Video Retrieval (CBVR) is still an appealing research topic due to increasing search demands in the Internet era of big data. This article aims to explore an efficient CBVR system by discriminately hashing videos into short binary codes. Existing video hashing methods usually encounter two weaknesses originating from the following sources: (1) Most works adopt the separated stages method or the frame-pooling based end-to-end architecture. However, the spatial-temporal properties of videos cannot be fully explored or kept well in the follow-up hashing step. (2) Discriminative learning based on pairwise or triplet constraints often suffers from slow convergence and poor local optimization, mainly because of the limited samples for each update. To alleviate these problems, we propose an end-to-end video retrieval framework called the Similarity-Preserving Deep Temporal Hashing (SPDTH) network. Specifically, we equip the model with the ability to capture spatial-temporal properties of videos and to generate binary codes by stacked Gated Recurrent Units (GRUs). It unifies video temporal modeling and learning to hash into one step to allow for maximum retention of information. We also introduce a deep metric learning objective called ℓ
2
All
_
loss
for network training by preserving intra-class similarity and inter-class separability, and a quantization loss between the real-valued outputs and the binary codes is minimized. Extensive experiments on several challenging datasets demonstrate that SPDTH can consistently outperform state-of-the-art methods.
AB-LSTM
Authors: Liu Zhandong , Zhou Wengang , Li Houqiang
Published: December 2019

Detection of scene text in arbitrary shapes is a challenging task in the field of computer vision. Most existing scene text detection methods exploit the rectangle/quadrangular bounding box to denote the detected text, which fails to accurately fit text with arbitrary shapes, such as curved text. In addition, recent progress on scene text detection has benefited from Fully Convolutional Network. Text cues contained in multi-level convolutional features are complementary for detecting scene text objects. How to explore these multi-level features is still an open problem. To tackle the above issues, we propose an Attention-based Bidirectional Long Short-Term Memory (AB-LSTM) model for scene text detection. First, word stroke regions (WSRs) and text center blocks (TCBs) are extracted by two AB-LSTM models, respectively. Then, the union of WSRs and TCBs are used to represent text objects. To verify the effectiveness of the proposed method, we perform experiments on four public benchmarks: CTW1500, Total-text, ICDAR2013, and MSRA-TD500, and compare it with existing state-of-the-art methods. Experiment results demonstrate that the proposed method can achieve competitive results, and well handle scene text objects with arbitrary shapes (i.e., curved, oriented, and horizontal forms).
Dissecting the Performance of VR Video Streaming through the VR-EXP Experimentation Platform
Authors: Filho Roberto Iraja Tavares Da Costa , Luizelli Marcelo Caggiani , Petrangeli Stefano , Vega Maria Torres , Hooft Jeroen Van der , Wauters Tim , Turck Filip De , Gaspary Luciano Paschoal
Published: December 2019

To cope with the massive bandwidth demands of Virtual Reality (VR) video streaming, both the scientific community and the industry have been proposing optimization techniques such as viewport-aware streaming and tile-based adaptive bitrate heuristics. As most of the VR video traffic is expected to be delivered through mobile networks, a major problem arises: both the network performance and VR video optimization techniques have the potential to influence the video playout performance and the Quality of Experience (QoE). However, the interplay between them is neither trivial nor has it been properly investigated. To bridge this gap, in this article, we introduce VR-EXP, an open-source platform for carrying out VR video streaming performance evaluation. Furthermore, we consolidate a set of relevant VR video streaming techniques and evaluate them under variable network conditions, contributing to an in-depth understanding of what to expect when different combinations are employed. To the best of our knowledge, this is the first work to propose a systematic approach, accompanied by a software toolkit, which allows one to compare different optimization techniques under the same circumstances. Extensive evaluations carried out using realistic datasets demonstrate that VR-EXP is instrumental in providing valuable insights regarding the interplay between network performance and VR video streaming optimization techniques.
An Image Cues Coding Approach for 3D Human Pose Estimation
Authors: Xing Meng , Feng Zhiyong , Su Yong , Zhang Jianhai
Published: December 2019

Although Deep Convolutional Neural Networks (DCNNs) facilitate the evolution of 3D human pose estimation, ambiguity remains the most challenging problem in such tasks. Inspired by the Human Perception Mechanism (HPM), we propose an image-to-pose coding method to fill the gap between image cues and 3D poses, thereby alleviating the ambiguity of 3D human pose estimation. First, in 3D pose space, we divide the whole 3D pose space into multiple subregions named
pose codes
, turning a disambiguation problem into a classification problem. The proposed coding mechanism covers multiple camera views and provides a complete description for 3D pose space. Second, it is noteworthy that the articulated structure of the human body lies on a sophisticated product manifold and the error accumulation in the chain structure will undoubtedly affect the coding performance. Therefore, in image space, we extract the image cues from independent local image patches rather than the whole image. The mapping relationship between image cues and 3D pose codes is established by a set of DCNNs. The image-to-pose coding method transforms the implicit image cues into explicit constraints. Finally, the image-to-pose coding method is integrated into a linear matching mechanism to construct a 3D pose estimation method that effectively alleviates the ambiguity. We conduct extensive experiments on widely used public benchmarks. The experimental results show that our method effectively alleviates the ambiguity in 3D pose recovery and is robust to the variations of view.
An End-to-End Attention-Based Neural Model for Complementary Clothing Matching
Authors: Liu Jinhuan , Song Xuemeng , Nie Liqiang , Gan Tian , Ma Jun
Published: December 2019

In modern society, people tend to prefer fashionable and decent outfits that can meet more than basic physiological needs. In fact, a proper outfit usually relies on good matching among complementary fashion items (e.g., the top, bottom, and shoes) that compose it, which thus propels us to investigate the automatic complementary clothing matching scheme. However, this is non-trivial due to the following challenges. First, the main challenge lies in how to accurately model the compatibility between complementary fashion items (e.g., the top and bottom) that come from the heterogeneous spaces with multi-modalities (e.g., the visual modality and textual modality). Second, since different features (e.g., the color, style, and pattern) of fashion items may contribute differently to compatibility modeling, how to encode the confidence of different pairwise features presents a tough challenge. Third, how to jointly learn the latent representation of multi-modal data and the compatibility between complementary fashion items contributes to the last challenge. Toward this end, in this work, we present an end-to-end attention-based neural framework for the compatibility modeling, where we introduce a feature-level attention model to adaptively learn the confidence for different pairwise features. Extensive experiments on a public available real-world dataset show the superiority of our model over state-of-the-art methods.
Pregnancy and diet-related changes in the maternal gut microbiota following exposure to an elevated linoleic acid diet
Authors: Shrestha Nirajan , Sleep Simone L. , Cuffe James S. M. , Holland Olivia J. , McAinch Andrew J. , Dekker Nitert Marloes , Hryciw Deanne H.
Published: December 2019

Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome diversity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal samples before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta-diversity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera Akkermansia, Peptococcus, Sutterella, and Xo2d06 but higher abundance of Butyricimonas and Coprococcus. Over gestation, in LLA but not HLA rats, there was a reduction in alpha-diversity and an increase in beta-diversity. In the LLA group, the abundance of Akkermansia, Blautia, rc4.4, and Streptococcus decreased over gestation, whereas Coprococcus increased. In the HLA group; only the abundance of Butyricimonas decreased. At E20, there were no differences in alpha- and beta-diversity, and the abundance of Roseburia was significantly increased in the HLA group. In conclusion, consumption of a HLA diet alters gut microbiota composition, as does pregnancy in rats consuming a LLA diet. In pregnancy, consumption of a HLA diet does not alter gut microbiota composition.
An AMPK/Axin1-Rac1 signaling pathway mediates contraction-regulated glucose uptake in skeletal muscle cells
Authors: Yue Yingying , Zhang Chang , Zhang Xuejiao , Zhang Shitian , Liu Qian , Hu Fang , Lv Xiaoting , Li Hanqi , Yang Jianming , Wang Xinli , Chen Liming , Yao Zhi , Duan Hongquan , Niu Wenyan
Published: December 2019

Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMP-activated protein kinase (AMPK) and Rac1. However, the molecular details of how contraction activates these signaling proteins are not clear. Recently, Axin1 has been shown to form a complex with AMPK and liver kinase B1 during glucose starvation-dependent activation of AMPK. Here, we demonstrate that electrical pulse-stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal coimmunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with compound C or siRNA-mediated knockdown of AMPK or Axin1 blocked contraction-induced GTP loading of Rac1, p21-activated kinase phosphorylation, and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling pathway mediates contraction-stimulated skeletal muscle glucose uptake.
Acidosis induces antimicrobial peptide expression and resistance to uropathogenic E. coli infection in kidney collecting duct cells via HIF-1α
Authors: Peng Hu , Purkerson Jeffrey M. , Freeman Robert S. , Schwaderer Andrew L. , Schwartz George J.
Published: December 2019

Acute pyelonephritis is frequently associated with metabolic acidosis. We previously reported that metabolic acidosis stimulates expression of hypoxia-inducible factor (HIF)-1α-induced target genes such as stromal derived factor-1 and cathelicidin, an antimicrobial peptide. Since the collecting duct (CD) plays a pivotal role in regulating acid-base homeostasis and is the first nephron segment encountered by an ascending microbial infection, we examined the contribution of HIF-1α to innate immune responses elicited by acid loading of an M-1 immortalized mouse CD cell line. Acid loading of confluent M-1 cells was achieved by culture in pH 6.8 medium supplemented with 5-( N-ethyl- N-isopropyl)-amiloride to block Na+/H+ exchange activity for 24 h. Acid loading induced antimicrobial peptide [cathelicidin and β-defensin (Defb2 and Defb26)] mRNA expression and M-1 cell resistance to uropathogenic Escherichia coli infection to an extent similar to that obtained by inhibition of HIF prolyl hydroxylases, which promote HIF-1α protein degradation. The effect of acid loading on M-1 cell resistance to uropathogenic E. coli infection was reduced by inhibition of HIF-1α (PX-478), and, in combination with prolyl hydroxylase inhibitors, acidosis did not confer additional resistance. Thus, metabolic stress of acidosis triggers HIF-1α-dependent innate immune responses in CD (M-1) cells. Whether pharmacological stabilization of HIF prevents or ameliorates pyelonephritis in vivo warrants further investigation.
Glucagon-like peptide-1 receptors in the kidney: impact on renal autoregulation
Authors: Hviid Aleksander Vauvert R. , Sørensen Charlotte M.
Published: December 2019

Glucagon-like peptide-1 (GLP-1) and strategies based on this blood sugar-reducing and appetite-suppressing hormone are used to treat obesity and type 2 diabetes. However, the GLP-1 receptor (GLP-1R) is also present in the kidney, where it influences renal function. The effect of GLP-1 on the kidney varies between humans and rodents. The effect of GLP-1 on kidney function also seems to vary depending on its concentration and the physiological or pathological state of the kidney. In studies with rodents or humans, acute infusion of pharmacological doses of GLP-1 stimulates natriuresis and diuresis. However, the effect on the renal vasculature is less clear. In rodents, GLP-1 infusion increases renal plasma flow and glomerular filtration rate, suggesting renal vasodilation. In humans, only a subset of the study participants exhibits increased renal plasma flow and glomerular filtration rate. Differential status of kidney function and changes in renal vascular resistance of the preglomerular arterioles may account for the different responses of the human study participants. Because renal function in patients with type 2 diabetes is already at risk or compromised, understanding the effects of GLP-1R activation on kidney function in these patients is particularly important. This review examines the distribution of GLP-1R in the kidney and the effects elicited by GLP-1 or GLP-1R agonists. By integrating results from acute and chronic studies in healthy individuals and patients with type 2 diabetes along with those from rodent studies, we provide insight into how GLP-1R activation affects renal function and autoregulation.
Effects of a prolyl hydroxylase inhibitor on kidney and cardiovascular complications in a rat model of chronic kidney disease
Authors: Uchida Lisa , Tanaka Tetsuhiro , Saito Hisako , Sugahara Mai , Wakashima Takeshi , Fukui Kenji , Nangaku Masaomi
Published: December 2019

Cardiovascular disease (CVD) is the main cause of death in patients with kidney disease. Hypoxia plays a crucial role in the progression of chronic kidney disease (CKD) and cardiovascular disease, which is associated with fibrosis, inflammation, and oxidative injury. Previous studies have indicated that prolyl hydroxylase (PHD) inhibitors, stabilizers of hypoxia-inducible factors (HIFs), can be used to treat acute organ injuries such as renal ischemia-reperfusion, myocardial infarction, and, in some contexts, CKD. However, the effects of PHD inhibitors on cardiovascular complications in CKD remain unknown. In the present study, we investigated whether HIF activation has a beneficial effect on kidney and cardiovascular outcomes in the remnant kidney model. We used the 5/6 nephrectomy model with the nitric oxide synthase inhibitor Nω-nitro-l-arginine (20 mg/L in the drinking water). Rats received diet with 0.005% enarodustat (PHD inhibitor) or vehicle for 8 wk starting 2 wk before 5/6 nephrectomy. Activation of HIF by the PHD inhibitor reduced cardiac hypertrophy and ameliorated myocardial fibrosis in association with restored capillary density and improvement in mitochondrial morphology. With regard to kidneys, enarodustat ameliorated fibrosis in association with reduced proinflammatory cytokine expression, reduced apoptosis, and restored capillary density, even though renal endpoints such as proteinuria and serum creatinine levels were not significantly affected by enarodustat, except for blood urea nitrogen levels at 4 wk. In addition, cardiac hypertrophy marker genes, including atrial natriuretic peptide, were suppressed in P19CL6 cells treated with enarodustat. These findings suggest that PHD inhibitors might show beneficial effects in cardiovascular complications caused by CKD.
Expression, localization, and functional properties of inwardly rectifying K+channels in the kidney
Authors: Manis Anna D. , Hodges Matthew R. , Staruschenko Alexander , Palygin Oleg
Published: December 2019

Inwardly rectifying K+(Kir) channels are expressed in multiple organs and cell types and play critical roles in cellular function. Most notably, Kirchannels are major determinants of the resting membrane potential and K+homeostasis. The renal outer medullary K+channel (Kir1.1) was the first renal Kirchannel identified and cloned in the kidney over two decades ago. Since then, several additional members, including classical and ATP-regulated Kirfamily classes, have been identified to be expressed in the kidney and to contribute to renal ion transport. Although the ATP-regulated Kirchannel class remains the most well known due to severe pathological phenotypes associated with their mutations, progress is being made in defining the properties, localization, and physiological functions of other renal Kirchannels, including those localized to the basolateral epithelium. This review is primarily focused on the current knowledge of the expression and localization of renal Kirchannels but will also briefly describe their proposed functions in the kidney.
Experimental Investigation on the Release Rule of the Gas Expansion Potential of Loaded Water‐Filled Soft Coal
Authors: Qin Hengjie , Wei Jianping , Li Donghao , Li Sen
Published: December 2019

The aim of this study was to explore the evolution and release rule of internal energy storage in the process of coal and gas outburst and to further reveal the mechanism of coal and gas outburst from the perspective of energy. In this paper, the experiment of gas expansion energy release of coal samples under different adsorption pressures and with different moisture contents was carried out with the self‐developed experimental device for release of gas‐bearing coal expansion energy under load, and the energy of the whole outburst process was divided into three parts: the total expansion energy of gas, the energy consumed by destroying and throwing out coal body and the energy released inefficiently. On the basis of reasonable assumption, the energy evolution calculation model of each part was constructed with mathematical method. By analyzing the changes and distribution rules of three parts of energy under different experimental conditions, this paper explored the controlling effects of gas pressure, water content, and other variables on the energy evolution rules in the process of coal and gas outburst. Experimental and theoretical studies showed that in the gas‐dominated coal and gas outburst process, the destruction of coal body was in the form of stratification; under each experimental condition, there existed a critical gas pressure value for the occurrence of coal and gas outburst, and there was a sudden change of energy evolution near this value; the existence of water made the critical pressure and the minimum energy consumption of coal and gas outburst increase obviously; under the experimental conditions, there was a linear relationship between the critical gas pressure and water content and a positive exponential relationship between the minimum energy consumption and water content.
Numerical and Experimental Investigations on Dynamic Response of Hydraulic Cylinder with 3D Spatial Joints considering Radial and Axial Clearances
Authors: Chen Ke , Zhang Guojun , Wang Haishuo , Wu Rui , Zheng Hongmei , Chen Shunhua
Published: December 2019

Radial clearance, particularly the axial clearance in the 3D joint of a mechanism owing to the assemblage, manufacturing tolerances, wear, and other conditions, has become a research focus in the field of multibody dynamics in recent years. In this study, a hydraulic cylinder model with 3D clearance joints was constructed by combining various potential contact scenarios. The novelty of this study is that potential contact points between the bearing wall and journal were calculated when the bearing wall circle was projected to an ellipse owing to misalignment of axes. Moreover, the simulation model considered the effective bulk modulus of the hydraulic oil and applied the Lagrange multiplier method. Subsequently, an experiment was conducted to verify the simulation results. The simulation and experimental results indicated that the dynamic responses of the hydraulic cylinder with 3D clearance joints can be classified as free, rebound, slide, and contact. The effects of input force, frequency, and clearance size on the dynamic behavior of the hydraulic cylinder were also investigated. Increasing the input force and clearance size will degrade the hydraulic cylinder dynamic response; however, the input force frequency can reduce the deterioration of the dynamic response. This study aids in providing improved understanding of the hydraulic cylinder with 3D clearances in the theoretical field and for practical engineering applications.
Plastic Dynamical Model for Bulk Metallic Glasses
Authors: Yao Shaowen , Cheng Zhibo
Published: December 2019

Based on previous experimental results of the plastic dynamic analysis of metallic glasses upon compressive loading, a dynamical model is proposed. This model includes the sliding speed of shear bands in the plastically strained metallic glasses, the shear resistance of shear bands, the internal friction resulting from plastic deformation, and the influences from the testing machine. This model analysis quantitatively predicts that the loading rate can influence the transition of the plastic dynamics in metallic glasses from chaotic (low loading rate range) to stable behavior (high loading rate range), which is consistent with the previous experimental results on the compression tests of a Cu50Zr45Ti5 metallic glass. Moreover, we investigate the existence of a nonconstant periodic solution for plastic dynamical model of bulk metallic glasses by using Manásevich–Mawhin continuation theorem.
Antimicrobial Activity of Lactic Acid Bacteria Starters against Acid Tolerant, Antibiotic Resistant, and Potentially VirulentE. coliIsolated from a Fermented Sorghum-Millet Beverage
Authors: Byakika Stellah , Mukisa Ivan Muzira , Mugabi Robert , Muyanja Charles
Published: December 2019

Bacterial contamination of fermented foods is a serious global food safety challenge that requires effective control strategies. This study characterized presumptiveE. coliisolated fromObushera, a traditional fermented cereal beverage from Uganda. Thereafter, the antimicrobial effect of lactic acid bacteria (LAB) previously isolated fromObushera,against theE. coli, was examined. The presumptiveE. coliwas incubated in brain heart infusion broth (pH = 3.6) at 25°C for 48 h. The most acid-stable strains were clustered using (GTG)5rep-PCR fingerprinting and identified using 16S rRNA sequencing.E. coliwas screened forShigatoxins (Stx 1andStx 2) andIntimin(eae) virulence genes as well as antibiotic resistance. The spot-on-the-lawn method was used to evaluate antimicrobial activity. Eighteen isolates were acid stable and are identified asE. coli,Shigella, andLysinibacillus.TheStx2 gene and antibiotic resistance were detected in someE.coliisolates. The LAB were antagonistic against theE. coli. Lactic acid bacteria from traditional fermented foods can be applied in food processing to inhibit pathogens.Obusheralactic acid bacteria could be used to improve the safety of fermented foods.
Identification of Mitochondrial Ligands with Hepatoprotective Activity from Notopterygii Rhizoma et Radix Using Affinity Ultrafiltration/Liquid Chromatography/Mass Spectrometry
Authors: Liang Li , Li Feng-Jiao , Liu Xin , Mu Jian-Kang , Wang Xi , Dong Jin-Cai , Zeng Lin-Xi , Gu Wen , Li Jing-Ping , Yang Xing-Xin , Yu Jie
Published: December 2019

In recent years, the incidence of diseases associated with hepatic injury has increased in prevalence. Targeting the mitochondria to protect liver function has gained momentum due to their central role in energy production, apoptotic cell death, oxidative stress, calcium homeostasis, and lipid metabolism. In this study, we employed a hepatic mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method (CM-HMC) to identify hepatic mitochondria ligands from medicinal herbs (MHs) including Notopterygii Rhizoma et Radix (NRR) that possess hepatic-protective effects. A total of 4 newly identified mitochondrial ligands were successfully identified by CM-HMC. The mitochondria-regulating activities of 3 of the 4 hits were confirmed using isolated mitochondria. The hepatic-protective effects of one of these hits were validated in carbon tetrachloride-damaged human liver L02 cell models. We have thus identified new natural hepatic-protectants that enhance our understanding of the hepatic-protective mechanisms of MHs. CM-HMC was proven to efficiently screen for mitochondrial ligands from MHs.
Lactobacillus Endocarditis-Associated Glomerulonephritis Complicated by anti-Coagulant Nephropathy and Renal Amyloidosis
Authors: Moosavi Mitchell , Zuckerman Jonathan E.
Published: December 2019

Kidney injury is a well-known sequelae of infectious endocarditis. Various types of kidney injury can be seen, including endocarditis-associated glomerulonephritis, and may affect nearly half of the patients with infectious endocarditis. Lactobacillus species are an infrequently documented cause of endocarditis. We present a case of Lactobacillus endocarditis-associated glomerulonephritis in a patient with a complex medical history including Lactobacillus infection of an artificial heart valve. To our knowledge, this is the first reported case of development of endocarditis-associated glomerulonephritis secondary to Lactobacillus species organisms. Furthermore, the patient’s renal biopsy revealed several frequently overlooked concomitant findings including anti-coagulant nephropathy and renal amyloidosis.
Evaluating the Effects of One-Way Traffic Management on Different Vehicle Exhaust Emissions Using an Integrated Approach
Authors: Fan Jieyu , Gao Kun , Xing Yingying , Lu Jian
Published: December 2019

One-way traffic management is a recognized traffic organization to improve traffic efficiency and safety, but its effects on different traffic emissions remains unclear. This paper aims to investigate the impacts of one-way traffic management on three typical vehicle exhaust emissions including Carbonic Oxide (CO), Hydrocarbon Compounds (HC), and Nitrogen Oxides (NOx) in a traffic system using an integrated approach. Field experiment was conducted to collect the vehicular emission data under different traffic conditions using the onboard portable emission measurement system. An instantaneous emission model (i.e., Vehicle Specific Power) is calibrated using the collected field emission data and is incorporated into the microscopic traffic simulation tool VISSIM for quantifying the emissions before and after one-way traffic management through simulation. Two scenarios based on real networks and traffic demands of peak hours in part areas of Shanghai are developed for simulation and evaluation. The results show that in the intersections, the emission rates of COHC, NOx after one-way traffic management is significantly reduced by 20.46%, 21.29% and 21.06%, respectively. In the road sections, the emission rates of CO, HC, NOx in the road sections decrease by 23.38% and 26.29%. The overall CO, HC, NOx emissions in the studied network reduce by 21.34%, 22.29% and 23.77% separately due to one-way traffic management. The results provide insights into the derivative effects of one-way traffic management on traffic emissions in the intersections, road sections and network levels, and thus support scientific traffic management for promoting the sustainability of transport system.
A New Slip Length Model for Enhanced Water Flow Coupling Molecular Interaction, Pore Dimension, Wall Roughness, and Temperature
Authors: Li Lei , Su Yuliang , Wang Han , Sheng Guanglong , Wang Wendong
Published: December 2019

In this paper, a slip length model is proposed to analyze the enhanced flow based on the Hagen–Poiseuille equation. The model considers the multimechanisms including wall-water molecular interactions, pore dimensions, fractal roughness, and temperature. The increasing wall-water interactions result in the greater slip length and flow enhancement factor. The increased temperature enhances the kinetic energy of water molecules that leads to great surface diffusion coefficient and small work of adhesion. The wall roughness can decrease the slip length and flow enhancement factor in hydrophilic nanopores. This work studies the effects of multimechanisms on slip length and flow enhancement factor theoretically, which can accurately describe the liquid flow in nanopores.
Exploring the Performance of Different On-Demand Transit Services Provided by a Fleet of Shared Automated Vehicles: An Agent-Based Model
Authors: Wang Senlei , Correia Goncalo Homem de Almeida , Lin Hai Xiang
Published: December 2019

Automated vehicles used as public transport show a great promise of revolutionizing current transportation systems. Still, there are many questions as to how these systems should be organized and operated in cities to bring the best out of future services. In this study, an agent-based model (ABM) is developed to simulate the on-demand operations of shared automated vehicles (SAVs) in a parallel transit service (PTS) and a tailored time-varying transit service (TVTS). The proposed TVTS system can switch service schemes between a door-to-door service (DDS) and a station-to-station service (SSS) according to what is best for the service providers and the travelers. In addition, the proposed PTS system that allows DDS and SSS to operate simultaneously is simulated. To test the conceptual design of the proposed SAV system, simulation experiments are performed in a hypothetical urban area to show the potential of different SAV schemes. Simulation results suggest that SAV systems together with dynamic ridesharing can significantly reduce average waiting time, the vehicle kilometres travelled and empty SAV trips. Moreover, the proposed optimal vehicle assignment algorithm can significantly reduce the empty vehicle kilometres travelled (VKT) for the pickups for all tested SAV systems up to about 40% and improve the system capacity for transporting the passengers. Comparing the TVTS system, which has inconvenient access in peak hours, with the PTS systems, which always makes available door-to-door transport, we conclude that the latter could achieve a similar system performance as the former in terms of average waiting time, service time and system capacity.
Effects of Different Positions and Angles of Implants in Maxillary Edentulous Jaw on Surrounding Bone Stress under Dynamic Loading: A Three-Dimensional Finite Element Analysis
Authors: Liu Xiaqing , Pang Fang , Li Ying , Jia Hui , Cui Xiaohua , Yue Yuan , Yang Xuelian , Yang Qi
Published: December 2019

Purpose. To evaluate the effects of different placements of mesial implants and different angles of distant implants in maxillary edentulous jaws on the stress on the implant and the surrounding bone tissue under dynamic loading. Materials and Methods. Cone beam computed tomography was used to acquire images of maxillary edentulous jaws. Using Mimics 17.0, Geomagic, and Unigraphics NX8.5 software, three-dimensional models were established: two mesial implants were placed vertically in the anterior region of the maxilla (bilateral central incisor, lateral incisor, and canine), and two distant implants were placed obliquely in the bilateral second premolar area at different inclined angles (15°, 30°, and 45°). The established models were designated I–IX. The models were subjected to dynamic load using Abaqus 6.12, with the working side posterior teeth loading of 150 N and simulation cycle of 0.875 s. Results. During the second to fourth phases of the mastication cycle, the stress was mainly concentrated on the neck of the distal implant. The stress of the distal implants was greater than that of mesial implants. Stress levels peaked in the third stage of the cycle. The stress of the distal cortical bone of distal implant of Model I reached the maximum of 183.437 MPa. The stress of the distal cortical bone and cancellous bone of distal implant of Model VIII represented the minima (62.989 MPa and 17.186 MPa, respectively). Conclusions. Our models showed optimal stress reductions when the mesial implants were located in the canine region and the distal implants tilted 30°.
Effect of Cellulose Nanocrystals on the Properties of Cement Paste
Authors: Liu Qiaoling , Peng Yujiao , Liang Long , Dong Xiaobin , Li Hancai
Published: December 2019

The effect of the addition of cellulose nanocrystals (CNCs) on the properties of cement pastes is studied herein. The compressive strength of CNC/cement paste was investigated under the curing conditions defined in this study. Two-dimensional micrographs and pore size distributions were obtained by scanning electron microscopy, X-ray computed tomography (XCT), and nitrogen adsorption. The addition of CNCs was found to significantly enhance the mechanical properties of cement pastes with a rapid decrease in temperature and humidity. XCT and nitrogen adsorption analyses show that the addition of CNCs leads to a refinement of the pore structure in the cement matrix. Almost no hydration products, including C-S-H, are formed in the cement matrix without CNCs under extreme conditions. This is in contrast with the results for the cement paste with 0.5% CNCs.
Urotensin-II-Targeted Liposomes as a New Drug Delivery System towards Prostate and Colon Cancer Cells
Authors: Zappavigna Silvia , Abate Marianna , Cossu Alessia Maria , Lusa Sara , Campani Virginia , Scotti Lorena , Luce Amalia , Yousif Ali Munaim , Merlino Francesco , Grieco Paolo , De Rosa Giuseppe , Caraglia Michele
Published: December 2019

Urotensin-II (UT-II) and its receptor (UTR) are involved in the occurrence of different epithelial cancers. In particular, UTR was found overexpressed on colon, bladder, and prostate cancer cells. The conjugation of ligands, able to specifically bind receptors that are overexpressed on cancer cells, to liposome surface represents an efficient active targeting strategy to enhance selectivity and efficiency of drug delivery systems. The aim of this study was to develop liposomes conjugated with UT-II (LipoUT) for efficient targeting of cancer cells that overexpress UTR. The liposomes had a mean diameter between 150 nm and 160 nm with a narrow size distribution (PI≤0.1) and a doxo encapsulation efficiency of 96%. Moreover, the conjugation of UT-II to liposomes weakly reduced the zeta potential. We evaluated UTR expression on prostate (DU145, PC3, and LNCaP) and colon (WIDR and LoVo) cancer cells by FACS and western blotting analysis. UTR protein was expressed in all the tested cell lines; the level of expression was higher in WIDR, PC3, and LNCaP cells compared with LoVo and DU145. MTT cell viability assay showed that LipoUT-doxo was more active than Lipo-doxo on the growth inhibition of cells that overexpressed UTR (PC3, LNCaP, and WIDR) while in LoVo and DU145 cell lines, the activity was similar to or lower than that one of Lipo-doxo, respectively. Moreover, we found that cell uptake of Bodipy-labeled liposomes in PC3 and DU145 was higher for LipoUT than the not-armed counterparts but at higher extent in UTR overexpressing PC3 cells (about 2-fold higher), as evaluated by both confocal and FACS. In conclusion, the encapsulation of doxo in UT-II-targeted liposomes potentiated its delivery in UTR-overexpressing cells and could represent a new tool for the targeting of prostate and colon cancer.
HPV16 E5 Mediates Resistance to PD-L1 Blockade and Can Be Targeted with Rimantadine in Head and Neck Cancer
Authors: Miyauchi Sayuri , Sanders P. Dominick , Guram Kripa , Kim Sangwoo S. , Paolini Francesca , Venuti Aldo , Cohen Ezra E.W. , Gutkind J. Silvio , Califano Joseph A. , Sharabi Andrew B.
Published: December 2019

There is a critical need to understand mechanisms of resistance and to develop combinatorial strategies to improve responses to checkpoint blockade immunotherapy (CBI). Here, we uncover a novel mechanism by which the human papillomavirus (HPV) inhibits the activity of CBI in head and neck squamous cell carcinoma (HNSCC). Using orthotopic HNSCC models, we show that radiation combined with anti–PD-L1 immunotherapy significantly enhanced local control, CD8+ memory T cells, and induced preferential T-cell homing via modulation of vascular endothelial cells. However, the HPV E5 oncoprotein suppressed immune responses by downregulating expression of major histocompatibility complex and interfering with antigen presentation in murine models and patient tumors. Furthermore, tumors expressing HPV E5 were rendered entirely resistant to anti–PD-L1 immunotherapy, and patients with high expression of HPV16 E5 had worse survival. The antiviral E5 inhibitor rimantadine demonstrated remarkable single-agent antitumor activity. This is the first report that describes HPV E5 as a mediator of resistance to anti–PD-1/PD-L1 immunotherapy and demonstrates the antitumor activity of rimantadine. These results have broad clinical relevance beyond HNSCC to other HPV-associated malignancies and reveal a powerful mechanism of HPV-mediated immunosuppression, which can be exploited to improve response rates to checkpoint blockade.

Significance:

This study identifies a novel mechanism of resistance to anti–PD-1/PD-L1 immunotherapy mediated by HPV E5, which can be exploited using the HPV E5 inhibitor rimantadine to improve outcomes for head and neck cancer patients.
Tim-3 Hampers Tumor Surveillance of Liver-Resident and Conventional NK Cells by Disrupting PI3K Signaling
Authors: Tan Siyu , Xu Yong , Wang Zehua , Wang Tixiao , Du Xianhong , Song Xiaojia , Guo Xiaowei , Peng Jiali , Zhang Jie , Liang Yan , Lu Jinghui , Peng Jun , Gao Chengjiang , Wu Zhuanchang , Li Chunyang , Li Nailin , Gao Lifen , Liang Xiaohong , Ma Chunhong
Published: December 2019

Natural killer (NK) cells are enriched within the liver. Apart from conventional NK (cNK) cells, recent studies identified a liver-resident NK (LrNK) subset, which constitutes about half of hepatic NK cells and exhibits distinct developmental, phenotypic, and functional features. However, it remains unclear whether and how LrNK cells, as well as cNK cells, participate in the development of hepatocellular carcinoma (HCC) individually. Here, we report that both LrNK and cNK cells are significantly decreased in HCC. The T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was significantly upregulated in both tumor-infiltrating LrNK and cNK cells and suppressed their cytokine secretion and cytotoxic activity. Mechanistically, phosphatidylserine (PtdSer) engagement promoted phosphorylation of Tim-3, which then competed with PI3K p110 to bind p85, inhibiting downstream Akt/mTORC1 signaling and resulting in malfunctioning of both NK-cell subsets. Tim-3 blockade retarded HCC growth in a NK-cell–dependent manner. These studies for the first time report the presence and dysfunction of LrNK cells in HCC and show that Tim-3–mediated PI3K/mTORC1 interference is responsible for the dysfunction of both tumor-infiltrating cNK and LrNK cells, providing a new strategy for immune checkpoint-based targeting.

Significance:

Tim-3 enhances hepatocellular carcinoma growth by blocking natural killer cell function.
Primary Preclinical and Clinical Evaluation of 68Ga-DOTA-TMVP1 as a Novel VEGFR-3 PET Imaging Radiotracer in Gynecological Cancer
Authors: Li Fei , Zhang Zhenzhong , Cai Jiong , Chen Xi , Zhou Ying , Ma Xiangyi , Dong Qingjian , Li Fang , Xi Ling
Published: December 2019

Purpose:

Tumor periphery and lymph nodes of tumor-induced lymphangiogenesis often abundantly express VEGFR-3. In our previous study, we identified a 5-amino acid peptide named TMVP1, which binds specifically to VEGFR-3. The objective of this study was to develop a novel 68Ga-labeled TMVP1 for VEGFR-3 PET imaging and to investigate its safety, biodistribution, and tumor-localizing efficacy in xenograft tumor models and a small cohort of patients with recurrent ovarian and cervical cancer.

Experimental Design:

The DOTA-conjugated TMVP1 peptide was labeled with radionuclide 68Ga. SPR and saturation binding assays were used for the receptor-binding studies. Gynecologic xenograft tumors were employed for small-animal PET imaging and biodistribution of 68Ga-DOTA-TMVP1 in vivo. In the clinical study, 5 healthy volunteers and 8 patients with gynecologic cancer underwent whole-body PET/CT after being injected with 68Ga-DOTA-TMVP1.

Results:

DOTA-TMVP1 was successfully labeled with 68Ga. LECs showed higher binding capacity with 68Ga-DOTA-TMVP1 than LEC(shVEGFR-3) and human umbilical vein endothelial cells. In mice with subcutaneous C33-A and SKOV-3 xenografts, the tracer was rapidly eliminated through the kidney to the bladder, and the small-animal PET/CT helped to clearly visualize the tumors. In patients with recurrent ovarian cancer and cervical cancer, tracer accumulation well above the background level was demonstrated in most identified sites of disease; especially with recurrent endodermal sinus tumors, the diagnostic value of 68Ga-DOTA-TMVP1 was comparable with that of 18F-FDG PET/CT.

Conclusions:

68Ga-DOTA-TMVP1 is a potential PET tracer for imaging VEGFR-3 with favorable pharmacokinetics.
A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors
Authors: Varga Andrea , Soria Jean-Charles , Hollebecque Antoine , LoRusso Patricia , Bendell Johanna , Huang Shih-Min A. , Wagle Marie-Claire , Okrah Kwame , Liu Lichuan , Murray Elaine , Sanabria-Bohorquez Sandra M. , Tagen Michael , Dokainish Hatem , Mueller Lars , Burris Howard
Published: December 2019

Purpose:

ERK1/2 signaling can be dysregulated in cancer. GDC-0994 is an oral inhibitor of ERK1/2. A first-in-human, phase I dose escalation study of GDC-0994 was conducted in patients with locally advanced or metastatic solid tumors.

Patients and Methods:

GDC-0994 was administered once daily on a 21-day on/7-day off schedule to evaluate safety, pharmacokinetics, and preliminary signs of efficacy. Patients with pancreatic adenocarcinoma and BRAF-mutant colorectal cancer were enrolled in the expansion stage.

Results:

Forty-seven patients were enrolled in six successive cohorts (50–800 mg). A single DLT of grade 3 rash occurred at 600 mg. The most common drug-related adverse events (AE) were diarrhea, rash, nausea, fatigue, and vomiting. Pharmacokinetic data showed dose-proportional increases in exposure, with a mean half-life of 23 hours, supportive of once daily dosing. In evaluable paired biopsies, MAPK pathway inhibition ranged from 19% to 51%. Partial metabolic responses by FDG-PET were observed in 11 of 20 patients across dose levels in multiple tumor types. Overall, 15 of 45 (33%) patients had a best overall response of stable disease and 2 patients with BRAF-mutant colorectal cancer had a confirmed partial response.

Conclusions:

GDC-0994 had an acceptable safety profile and pharmacodynamic effects were observed by FDG-PET and in serial tumor biopsies. Single-agent activity was observed in 2 patients with BRAF-mutant colorectal cancer.
Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas
Authors: Chang Long-Sheng , Oblinger Janet L. , Burns Sarah S. , Huang Jie , Anderson Larry W. , Hollingshead Melinda G. , Shen Rulong , Pan Li , Agarwal Garima , Ren Yulin , Roberts Ryan D. , O'Keefe Barry R. , Kinghorn A. Douglas , Collins Jerry M.
Published: December 2019

Malignant peripheral nerve sheath tumors (MPNST) frequently overexpress eukaryotic initiation factor 4F components, and the eIF4A inhibitor silvestrol potently suppresses MPNST growth. However, silvestrol has suboptimal drug-like properties, including a bulky structure, poor oral bioavailability (<2%), sensitivity to MDR1 efflux, and pulmonary toxicity in dogs. We compared ten silvestrol-related rocaglates lacking the dioxanyl ring and found that didesmethylrocaglamide (DDR) and rocaglamide (Roc) had growth-inhibitory activity comparable with silvestrol. Structure–activity relationship analysis revealed that the dioxanyl ring present in silvestrol was dispensable for, but may enhance, cytotoxicity. Both DDR and Roc arrested MPNST cells at G2–M, increased the sub-G1 population, induced cleavage of caspases and PARP, and elevated the levels of the DNA-damage response marker γH2A.X, while decreasing the expression of AKT and ERK1/2, consistent with translation inhibition. Unlike silvestrol, DDR and Roc were not sensitive to MDR1 inhibition. Pharmacokinetic analysis confirmed that Roc had 50% oral bioavailability. Importantly, Roc, when administered intraperitoneally or orally, showed potent antitumor effects in an orthotopic MPNST mouse model and did not induce pulmonary toxicity in dogs as found with silvestrol. Treated tumors displayed degenerative changes and had more cleaved caspase-3–positive cells, indicative of increased apoptosis. Furthermore, Roc effectively suppressed the growth of osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma cells and patient-derived xenografts. Both Roc- and DDR-treated sarcoma cells showed decreased levels of multiple oncogenic kinases, including insulin-like growth factor-1 receptor. The more favorable drug-like properties of DDR and Roc and the potent antitumor activity of Roc suggest that these rocaglamides could become viable treatments for MPNST and other sarcomas.