bluuebunny/crossref_metadata_2025 huggingface dataset:
D2Park
Authors: Zhao Dong , Cao Zijian , Ju Chen , Zhang Desheng , Ma Huadong
Published: December 2020

To address the increasingly serious parking pain, numerous mobile Apps have emerged to help drivers to find a convenient parking spot with various auxiliary information. However, the phenomenon of "multiple cars chasing the same spot" still exists, especially for on-street parking. Existing reservation-based resource allocation solutions could address the parking competition issue to some extent, but it is impractical to treat all spots as reservable resources. This paper first conducts a qualitative investigation based on the online survey data, which identifies diversified parking requirements involving i) reserved users, who request guaranteed spots with a reservation fee, ii) normal users, who request non-guaranteed spots with a "best-effort" service, and iii) external users, who do not use any guidance service. To this end, we design the D2Park system for diversified demand-aware parking guidance services. We formulate the problem as a novel Heterogeneous-Agent Dynamic Resource Allocation (HADRA) problem, which considers both current and future parking demands, and different constraints for diversified requirements. Two main modules are used in the system: 1) multi-step parking prediction, which makes multi-step parking inflow and occupancy rate predictions given the current parking events data and external factors; and 2) diversified parking guidance, which integrates the cooperation-based and competition-based resource allocation mechanisms based on a model predictive control framework to achieve a better performance balance among different user groups. Extensive experiments with a four-month real-world on-street parking dataset from the Chinese city Shenzhen demonstrate the effectiveness and efficiency of D2Park.
Evaluating the Gradual Delivery of Knowledge-focused and Mindset-focused Messages for Facilitating the Acceptance of COPD
Authors: Zeng Steven Y. , Wu Robert , Truong Khai N. , Chevalier Fanny
Published: December 2020

Chronic Obstructive Pulmonary Disease (COPD) is a terminal, progressive lung condition which mainly affects older adults. The onset of symptoms, obstacles, and impairments brought about by COPD often necessitates a grieving process for patients. Acceptance is the stage of the grieving process in which the patient has healthily integrated the condition into his or her lifestyle and identity. Because of the progressive nature of COPD, the process of acceptance is a perpetual journey in which patients must continuously shift their mindsets and lifestyles to adapt to the increasing severity of the condition. Using the health belief model as a theoretical foundation, we explore the usage of daily automated SMS messages as an engaging and accessible means of facilitating and maintaining a patient's acceptance of COPD. The results of our investigation show that SMS messages serve as an effective tool for improving patients' acceptance of COPD while also reducing patients' proclivities to the nonacceptance stages of the grieving process.
3D Point Cloud Generation with Millimeter-Wave Radar
Authors: Qian Kun , He Zhaoyuan , Zhang Xinyu
Published: December 2020

Emerging autonomous driving systems require reliable perception of 3D surroundings. Unfortunately, current mainstream perception modalities, i.e., camera and Lidar, are vulnerable under challenging lighting and weather conditions. On the other hand, despite their all-weather operations, today's vehicle Radars are limited to location and speed detection. In this paper, we introduce MILLIPOINT, a practical system that advances the Radar sensing capability to generate 3D point clouds. The key design principle of MILLIPOINT lies in enabling synthetic aperture radar (SAR) imaging on low-cost commodity vehicle Radars. To this end, MILLIPOINT models the relation between signal variations and Radar movement, and enables self-tracking of Radar at wavelength-scale precision, thus realize coherent spatial sampling. Furthermore, MILLIPOINT solves the unique problem of specular reflection, by properly focusing on the targets with post-imaging processing. It also exploits the Radar's built-in antenna array to estimate the height of reflecting points, and eventually generate 3D point clouds. We have implemented MILLIPOINT on a commodity vehicle Radar. Our evaluation results show that MILLIPOINT effectively combats motion errors and specular reflections, and can construct 3D point clouds with much higher density and resolution compared with the existing vehicle Radar solutions.
MIMU
Authors: Qin Zhou , Xian Yikun , Zhang Fan , Zhang Desheng
Published: December 2020

Mobile WiFi is a newly emerging service in recent years, which provides convenience for users to access online resources and increases revenues for operators via services such as advertisements and application promotions. However, in practice, the prohibitively high system implementation and operational costs, especially the costs of perpetual data traffic, hinder the further deployment of mobile WiFi services. In this paper, we present MIMU, a usage inference system for data traffic saving suitable for ubiquitous mobile WiFi services. We demonstrate the performance of the system via an example from the real-world nationwide edge computing mobile WiFi infrastructure. To address the impact of diverse user behaviors, we investigate the WiFi network usage from the perspective of users and devices, focusing on two unique features of mobile WiFi: user mobility regularity and access irregularity. In particular, we first design a deep learning-based two-dimension usage predictor to infer the future mobile WiFi usage with 1) a user dimension model with temporal attention addressing dominant users with heavy bus WiFi usage, and 2) a device dimension model with spatial attention addressing diverse WiFi usage and connection. Based on the results of the predictor, an application of content caching is implemented in an iterative fashion to save the data traffic. We evaluate MIMU by real-world bus WiFi system data sets of three major cities with 6,643 bus WiFi devices and 150k daily active users in total. Our results show that MIMU outperforms state-of-the-art methods in terms of usage inference. Moreover, we summarize the lessons learned from our large-scale bus WiFi system investigation.
BitLight
Authors: Liu Song , He Tian
Published: December 2020

This paper presents BitLight, a novel paradigm that uses the rapid flashing of a digital light processing (DLP) projector to encode an imperceptible mask temporally that, when sensed by a photodiode, uniquely specifies where the photodiode is located on the projected image. BitLight is inspired by the psychophysical phenomenon that the human visual system (HVS) cannot resolve rapid temporal changes in optical signals, so redundant optical signals could be inserted for tracking with some or little compromise on the original human perceived visual content. BitLight is the first to devise a bit-level temporal encoding to display RGB colors while also embedding tracking signals in a digital fashion. Compared to traditional visible-light-communication (VLC) systems that use frame-level encoding techniques such as luminance changes [10, 25, 26, 32] and alpha channel [16], the bit-level encoding of BitLight makes better use of the ultra-fine temporal division capabilities of DLP projectors to embed a much higher tracking data throughput and thus achieve faster localization speed. With our current prototype hardwares of a low-end microcontroller, cheap photodiodes, and a commercial off-the-shelfDLP projector, evaluation results have demonstrated an average of only 9.5ms to localize the sensor, versus 200ms by a comparison testbed that uses simple frame-level encodings.
Uncovering Practical Security and Privacy Threats for Connected Glasses with Embedded Video Cameras
Authors: Opaschi Octav , Vatavu Radu-Daniel
Published: December 2020

We address in this work security and privacy threats for connected camera glasses, for which very few investigations have been conducted so far, despite the considerable attention to understanding security concerns for other wearables, such as smartwatches and fitness trackers. To raise awareness about such threats, we present the results of a case study involving a low-cost spy camera glasses device, readily available on the market, that can be used to record and stream live video, for which we demonstrate infringement of several privacy requirements (regarding the camera glasses device itself, the data collected by the embedded video camera, the wearer of the device, and for bystanders as well) that lead to corresponding security threats (e.g., data confidentiality, integrity, availability, and access control). To foster replicability and reproducibility of our empirical results, investigation method, and implementation of attacks, we describe our case study in the form of a detailed activity log and release full C++ code implementing our approach. Furthermore, we present our findings to three IT security experts and summarize their recommendations for designing more secure connected camera glasses.
GAME
Authors: Miura Takahiro , Matsuo Masaki , Yabu Ken-ichiro , Katagiri Atsushi , Sakajiri Masatsugu , Onishi Junji , Kurata Takeshi , Ifukube Tohru
Published: December 2020

Although many computer games have become diversified in recent years, much effort and ingenuity are needed to produce games that persons with visual impairments can enjoy. However, game developers face difficulties in adjusting the parameters of these games, including difficulty and interface features, because the control skills and disability conditions of gamers vary. Thus, it is essential to establish a scheme to evaluate game interfaces and stages with individuals trials with a short time. In this study, our purpose is to propose and establish the concept of GAME (Game As a Measurement Environment) that can evaluate game interfaces and stages. This concept aims to divide a game stage into substages and then randomly allocate them to the stage. Then, the generated stage records the play logs and play conditions and then analyzes them logs based on test theories, including classical test theory (CTT) and item response theory (IRT). Based on the analysis of the gathered play logs of side-scroller action games, our concept could clarify the relationship between the stage contents, interface effects, and players skills and disabilities.
Looking at Patent Law: Patenting a Methane Conversion Process – A Case Study
Authors: Jennings Taylor E. , Inman Maria
Published: December 2020

In this installment of the “Looking at Patent Law” articles, we present a case study of an elevated temperature methane conversion process. We have chosen this invention to align with the focus of this issue of Interface on the High-Temperature Energy, Materials, & Processes (H-TEMP) Division of The Electrochemical Society.
Advanced Manufacturing for High-Temperature Materials
Authors: Bishop Sean , Tong Jianhua (Joshua)
Published: December 2020

Advances in manufacturing are largely driven by reducing cost and energy use and taking advantage of materials and designs to unlock new device properties. Energy conversion and storage is a key electrochemistry application in the high-temperature energy, materials, and processes (H-TEMP) Division.
Aerosol Jet Deposition for Structured Materials
Authors: Tsui Lok-Kun , Garzon Fernando , Plumley John
Published: December 2020

The roots of Aerosol Jet Printing (AJP) materials trace back to the development of digital inkjet printing. Pressure driven, continuous flow methods for inkjet printing were first developed at Stanford University by R. Sweet in the 1960s and led to a number of continuous flow printing technologies by the 1970s. Electrostatic control was used to guide the trajectory of continuously flowing ink drops. The drops were either directed to the print media or deflected into a gutter. These systems required the recirculation of the unused ink, adding considerable system complexity.
Advanced Manufacturing of Intermediate-Temperature Protonic Ceramic Electrochemical Cells
Authors: Mu Shenglong , Zhao Zeyu , Huang Hua , Lei Jincheng , Peng Fei , Xiao Hai , Brinkman Kyle S. , Tong Jianhua (Joshua)
Published: December 2020

Proton conducting oxide (i.e., protonic ceramic) has been thought of as an ideal solid electrolyte for energy conversion and storage applications since Iwahara et al. reported the perovskite-type protonic ceramics represented by doped barium/strontium cerates and zirconates in the 1980s. Proton, as the charge carrier in protonic ceramics, possesses a much lower transport activation energy than oxide-ion, which has rendered protonic ceramics for extensive intermediate-temperature (IT, 400-700°C) electrochemical devices such as protonic ceramic fuel cells (PCFCs), reversible protonic ceramic fuel cells, and protonic ceramic membrane reactors.
Towards Using Macro-homogeneous Models to Study Electrode Wetting in CO2 Electrolyzers
Authors: Leonard McLain E.
Published: December 2020

2020 Joseph W. Richards Summer Research Fellowship – Summary Report
Exercise-mitigated sex-based differences in aging: from genetic alterations to heart performance
Authors: Börzsei Denise , Priksz Dániel , Szabó Renáta , Bombicz Mariann , Karácsonyi Zoltán , Puskás László G. , Fehér Liliána Z. , Radák Zsolt , Kupai Krisztina , Berkó Anikó Magyariné , Varga Csaba , Juhász Béla , Pósa Anikó
Published: December 2020

Voluntary exercise has proved to be an effective therapeutic tool to improve cardiac function in aged rats with clearly visible sex differences. Long-term exercise is associated with decreased Ogn and Comt expression and enhanced presence of Pcp4 and Esm1 genes. Sex-dependent changes were also observed in the expression of the cardiovascular key proteins. Fundamental alterations in gene and protein expression may contribute to the improvement of cardiac performance.
A new implantable tool for repeated assessment of supraventricular electrophysiology and atrial fibrillation susceptibility in freely moving rats
Authors: Murninkas Michael , Gillis Roni , Lee Danielle I. , Elyagon Sigal , Bhandarkar Nikhil S. , Levi Or , Polak Rotem , Klapper-Goldstein Hadar , Mulla Wesam , Etzion Yoram
Published: December 2020

Rodents are increasingly used in AF research. However, technical challenges restrict long-term supraventricular electrophysiology studies in these species. Here, we developed an implantable electrode adapted for such studies in the rat. Our findings indicate that this new tool is effective for long-term follow-up of critical parameters such as atrial refractoriness. Obtained data shed light on the normal electrophysiology and on the increased AF susceptibility that develops in rats with implanted atrial electrodes over time.
Improved Chaos-Based Cryptosystem for Medical Image Encryption and Decryption
Authors: Gafsi Mohamed , Abbassi Nessrine , Hajjaji Mohamed Ali , Malek Jihene , Mtibaa Abdellatif
Published: December 2020

In the medical sector, the digital image is multimedia data that contain secret information. However, designing an efficient secure cryptosystem to protect the confidential images in sharing is a challenge. In this work, we propose an improved chaos-based cryptosystem to encrypt and decrypt rapidly secret medical images. A complex chaos-based PRNG is suggested to generate a high-quality key that presents high randomness behaviour, high entropy, and high complexity. An improved architecture is proposed to encrypt the secret image that is based on permutation, substitution, and diffusion properties. In the first step, the image’s pixels are randomly permuted through a matrix generated using the PRNG. Next, pixel’s bits are permuted using an internal condition. After that, the pixels are substituted using two different S-boxes with an internal condition. In the final step, the image is diffused by XORing pixels with the key stream generated by the PRNG in order to acquire an encrypted image. R rounds of encryption can be performed in a loop to increase the complexity. The cryptosystem is evaluated in depth by his application on several medical images with different types, contents, and sizes. The obtained simulation results demonstrate that the system enables high-level security and performance. The information entropy of the encrypted image has achieved an average of 7.9998 which is the most important feature of randomness. The algorithm can take full advantage of parallelism and pipeline execution in hardware implementation to meet real-time requirements. The PRNG was tested by NIST 800-22 test suit, which indicates that it is suitable for secure image encryption. It provides a large key space of 2192 which resists the brute-force attack. However, the cryptosystem is appropriate for medical image securing.
Fund Network Centrality, Hard-to-Value Portfolio, and Investment Performance
Authors: Hu Xiao , Cang Yimeng , Ren Long , Liu Jun
Published: December 2020

Based on the quarterly data of mutual funds in China from the fourth quarter of 2004 to the fourth quarter of 2019, this paper constructs a series of complex bipartite networks based on the overlapped portfolios of mutual funds and then explores the influences of fund network position on mutual fund’s investment behavior and performance. This paper finds that a mutual fund with shorter information transmission path to other entities in the fund network (i.e., having higher closeness centrality) or with stronger ties with those entities in important information positions (i.e., having higher eigenvector centrality) will achieve better investment performance. However, a stronger mediating role over the potential information flow of the fund network (i.e., having higher betweenness centrality) cannot help a mutual fund increase performance. The empirical results also indicate that a mutual fund holding stock portfolios with high valuation difficulties caused by the market or fundamental information uncertainty will achieve better investment performance, while holding hard-to-value portfolios caused by limited public information will reduce the performance of the fund. Furthermore, high closeness centrality or eigenvector centrality can help mutual funds deal with the disclose problems of public information, thus reducing the likelihood of a mutual fund holding hard-to-value portfolios caused by limited public information to achieve worse performance. Eigenvector centrality brings information advantages about company fundamentals, so it is easier for a mutual fund with high eigenvector centrality to profit from holding hard-to-value portfolios caused by the fundamental information uncertainty. The conclusions of this paper can enhance our understanding of the fund network and its information mechanism and shed new light on mutual fund’s information advantages and related asset allocation strategies.
Learning Curve and Clinical Outcome of Biportal Endoscopic‐Assisted Lumbar Interbody Fusion
Authors: Kim Ju-Eun , Yoo Hyun-Seung , Choi Dae-Jung , Hwang Jin-Ho , Park Eugene J. , Chung Seungho
Published: December 2020

Interbody fusion is a common surgical technique for diseases of the lumbar spine. Biportal endoscopic‐assisted lumbar interbody fusion (BE‐LIF) is a novel minimally invasive technique that has a long learning curve, which can be a barrier for surgeons. Therefore, we analyzed the learning curve in terms of operative time and evaluated the outcomes of BE‐LIF. A retrospective study of fifty‐seven consecutive patients who underwent BE‐LIF for degenerative lumbar disease by a single surgeon from January 2017 to December 2018 was performed. Fifty patients underwent a single‐level procedure, and 7 underwent surgery at two levels. The mean follow‐up period was 24 months (range, 14–38). Total operative time, postoperative drainage volume, time to ambulation, and complications were analyzed. Clinical outcome was measured using the Oswestry Disability Index (ODI), Visual Analog Scale (VAS) score for back and leg pain, and modified Macnab criteria. The learning curve was evaluated by a nonparametric regression locally weighted scatterplot smoothing curve. Cases before the stable point on the curve were designated as group A, and those after the stable point were designated group B. Operative time decreased as the number of cases increased. A stable point was noticed on the 400th day and the 34th case after the first BE‐LIF was performed. All cases showed improved ODI and VAS scores at the final follow‐up. Overall mean operative time was 171.74 ± 35.1 min. Mean operative time was significantly lower in group B (139.7 ± 11.6 min) compared to group A (193.4 ± 28.3 min). Time to ambulation was significantly lower in group B compared to group A. VAS and ODI scores did not differ between the two groups. BE‐LIF is an effective minimally invasive technique for lumbar degenerative disease. In our case series, this technique required approximately 34 cases to reach an adequate performance level.
Application of Improved Dynamic Substructure Finite Element Model-Based State-Space Techniques in Mistuned Blisks
Authors: Bai Bin , Zhang Chuan hui , Zhu Guangwei , Wu Qi liang
Published: December 2020

Aeroengine is a complex mechanical equipment, and it works at high temperature, pressure, rotational-speed, and severe loads. One of the core problems is that the vibration and mistuning of bladed disk lead to failure and affect the safety and reliability of aeroengine. Previously, one sector taken as the research object is not suitable; the integrally mistuned bladed disk (blisk) is taken as the research object is very necessary; however, the computational efficiency of mistuned blisk is very low. Therefore, a reduced-order model approach, i.e., an improved dynamic substructure finite element model-based state-space technique (IDSFEM-SST), is proposed to investigate the mistuned blisk. Firstly, the reduced-order substructure finite element model is established by this method, and then, the modal frequencies and modal strain energy amplitudes are investigated. Secondly, the maximum displacement responses are analyzed. Finally, the computational efficiency and accuracy of mistuned blisk via IDSFEM-SST is compared with that of the classical dynamic substructure finite element model and the high-fidelity finite element model to verify the effectiveness of this approach. This study has significance to the dynamic research and engineering practices for complex mechanical structures.
SK-FMYOLOV3: A Novel Detection Method for Urine Test Strips
Authors: Yang Rui , Zhang Yonglin , Deng Zhenrong , Huang Wenming , Lan Rushi , Luo Xiaonan
Published: December 2020

To accurately detect small defects in urine test strips, the SK-FMYOLOV3 defect detection algorithm is proposed. First, the prediction box clustering algorithm of YOLOV3 is improved. The fuzzy C-means clustering algorithm is used to generate the initial clustering centers, and then, the clustering center is passed to the K-means algorithm to cluster the prediction boxes. To better detect smaller defects, the YOLOV3 feature map fusion is increased from the original three-scale prediction to a four-scale prediction. At the same time, 23 convolutional layers of size

3
×
3

in the YOLOV3 network are replaced with SkNet structures, so that different feature maps can independently select different convolution kernels for training, improving the accuracy of defect classification. We collected and enhanced urine test strip images in industrial production and labeled the small defects in the images. A total of 11634 image sets were used for training and testing. The experimental results show that the algorithm can obtain an anchor frame with an average cross ratio of 86.57, while the accuracy rate and recall rate of nonconforming products are 96.8 and 94.5, respectively. The algorithm can also accurately identify the category of defects in nonconforming products.
Examining the Impact of Adverse Weather on Travel Time Reliability of Urban Corridors in Shanghai
Authors: Zou Yajie , Zhu Ting , Xie Yifan , Li Linbo , Chen Ying
Published: December 2020

Travel time reliability (TTR) is widely used to evaluate transportation system performance. Adverse weather condition is an important factor for affecting TTR, which can cause traffic congestions and crashes. Considering the traffic characteristics under different traffic conditions, it is necessary to explore the impact of adverse weather on TTR under different conditions. This study conducted an empirical travel time analysis using traffic data and weather data collected on Yanan corridor in Shanghai. The travel time distributions were analysed under different roadway types, weather, and time of day. Four typical scenarios (i.e., peak hours and off-peak hours on elevated expressway, peak hours and off-peak hours on arterial road) were considered in the TTR analysis. Four measures were calculated to evaluate the impact of adverse weather on TTR. The results indicated that the lognormal distribution is preferred for describing the travel time data. Compared with off-peak hours, the impact of adverse weather is more significant for peak hours. The travel time variability, buffer time index, misery index, and frequency of congestion increased by an average of 29%, 19%, 22%, and 63%, respectively, under the adverse weather condition. The findings in this study are useful for transportation management agencies to design traffic control strategies when adverse weather occurs.
Exploring Risk Factors with Crash Severity on China Two-Lane Rural Roads Using a Random-Parameter Ordered Probit Model
Authors: Xie Shikun , Ji Xiaofeng , Yang Wenchen , Fang Rui , Hao Jingjing
Published: December 2020

Understanding the factors that contribute to traffic crashes can help provide a fundamental basis to plan and develop appropriate countermeasures for road safety issues emerging in particular on two-lane rural roads. However, most of the studies have focused on urban roadways and freeway systems, and few studies have investigated the issue of heterogeneity on two-lane rural roads. The purpose of this study is to uncover the risk factors influencing crash severity on two-lane rural roads in China. A sample of 1490 traffic crashes occurring on two-lane rural roads between 2012 and 2017 was collected from the Mouding County Highway Bureau in Yunnan, China. A random-parameter ordered probit model was estimated using these data to capture underlying unobserved characteristics in personal traits, vehicle attributes, roadway conditions, environmental factors, and crash attribute. To better understand the effect of critical factors on crash severity outcome probability, an elasticity analysis was then introduced. The results show that six factors such as driver’s attribution, illegal driving behaviour, access segment, day of week, vehicle type, and crash form have a significant impact on the injury severity, and the impacts of driving behaviours, access segment, and vehicle-fixed object crashes had significant variation across observations. Besides, the correlations between critical factors and the probability of serious injury sustained in traffic crashes are identified and discussed. The local driver indicator has more positive impact on the crash severity than nonlocal driver, and nonaccess segment appears a higher probability of serious or vicious collisions. It is worth mentioning that motorcycle-involved crashes do show an obvious correlation with crash injury severity. As for crash forms, vehicle-vehicle crashes are more likely to lead to severe crash injury. Besides, high-risk driving behaviour (e.g., fatigue driving, speeding, and converse driving), weekends, and holidays are found to have significant contribution to increasing the probability of traffic crash injuries and fatalities on two-lane rural roads.
Tool Wear Assessment Approach Based on the Neighborhood Rough Set Model and Nearest Neighbor Model
Authors: Sheng Ren , Zhu Xiaoran
Published: December 2020

In order to assess the degree of wear of tool for milling process quantitatively, a new assessment approach is proposed. Firstly, making full use of the neighbor information, two sensitive features are selected by using the neighborhood rough set model, and then, boundary curves are established by using the nearest neighbor model with noncounter data in two dimension spaces. Secondly, the intersection area or expanding area is used to describe the difference between two boundary models because the intersection area or expanding area can consider the effect of distance and angle simultaneously in two dimension spaces. Thirdly, after determining a baseline state, a new quantitative assessment indicator (QAI) can be calculated based on the intersection area or expanding area. The QAI can directly measure the difference between the model of baseline state and the model of unknown state and indirectly measure the degree of wear of tool. Finally, the effectiveness of the assessment approach is proven by using the Milling Dataset which was provided by the NASA Ames Research Center.
Abstract A25: Activating alterations of p110 subunits determine PI3K isoform selectivity in prostate cancer
Authors: Zhang Zeda , Mao Ninghui , Lee Young Sun , Li Dan , Rosen Neal , Sawyers Charles , Carver Brett
Published: December 2020

Oncogenic activity of PI3K mutated tumors is often dependent on different PI3K isoforms. In breast cancer PI3Kα activating mutations are dominant drivers, whereas in PTEN-deficient prostate cancer such activity is thought to be driven by PI3Kβ. In particular, loss of PTEN function is seen in 40% of metastatic prostate cancer patients, which remains a challenging clinical problem. Recent success of selectively targeting PI3Kα or PI3Kβ to treat disease caused by hyperactivation of PI3K pathway sheds light on further developing such agents to a boarder disease spectrum. Yet relatively little is known about how different PI3K isoforms are selected as dominant drivers in different genetic and pathologic contexts. Here we use multiple prostate cancer cell lines and organoid models to study the mechanisms of PI3K isoform dependency in prostate cancer. We found PI3K isoform dependency is not always correlated with PTEN status across a panel of prostate cancer models in which different levels of PI3K signaling are observed. However, such dependency can be shifted towards either PI3Kα or PI3Kβ in the presence of its corresponding activating alteration, regardless of its original isoform dependency. Interestingly, such PI3K isoform activating alteration is able to further enhance PI3K signal in the setting of PTEN loss. PI3Kα mutant models are more sensitive to the α selective inhibitor BYL719 while PI3Kβ mutant models are more sensitive to the β selective inhibitor AZD8186. Besides, we found that PI3Kα mutant prostate tumors are sensitive to PI3Ksy inhibition by AZD8186 at a high dosage both in vitro and in vivo. High dose of AZD8186 also inhibits PI3K signaling in PI3Kα mutant breast cancer models. These data raise the possibility that the PI3Kβ selective inhibitor AZD8186 can also target PI3Kα at a high dose. In an ongoing clinical trial at MSK, a prostate cancer patient with PI3Kα mutation also responded to PI3Kβ inhibition. This finding reveals a new mechanism of how PI3K activating mutations determine PI3K isoform selectivity regardless of PTEN status. Results from this study also present new opportunities to treat cancer patients with PI3Kα or PI3Kβ inhibition.

Citation Format: Zeda Zhang, Ninghui Mao, Young Sun Lee, Dan Li, Neal Rosen, Charles Sawyers, Brett Carver. Activating alterations of p110 subunits determine PI3K isoform selectivity in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr A25.
Abstract B29: Targeting EZH2 and PI3K/mTOR for a novel combination therapeutic strategy in aggressive variant prostate cancer
Authors: Morel Katherine L. , Sweeney Christopher J. , Ellis Leigh
Published: December 2020

Androgen-deprivation therapy (ADT) is the current standard of care for metastatic prostate cancer; however, ADT fails to provide a durable response in 90% of patients due to acquired resistance and progression to castration-resistance prostate cancer. Aggressive-variant prostate cancer (AVPC) is a lethal phenotype that arises upon treatment with ADT, resulting in a lineage switch to a neuroendocrine morphology and the acquisition of molecular alterations that enable the cells to survive independent of AR signaling. Our work, and the work of others, has established that combinatorial loss/mutation of tumor suppressor genes—PTEN, TP53 and RB1—drive lineage plasticity and therapeutic resistance to ADT. Further, epigenetic regulators, including EZH2, are indicated as driver effectors of lineage plasticity downstream of these key combinatorial genetic events. With the known activation PI3K/AKT/mTOR signaling due to PTEN loss and the data supporting epigenetic targeting of EZH2, it remains to be determined if co-inhibition of PI3K/AKT/mTOR and EZH2 will provide a significant response in AVPC patients. GEMMs and GEMM-derived 3D organoid models representing either prostate-specific PTEN and RB1 loss (PbCre4:Ptenfl/fl:Rb1fl/fl), or PTEN and P53 loss (PbCre4:Ptenfl/fl:p53fl/fl), were used to determine if inhibition of PI3K/AKT/mTOR and EZH2 provides lineage reversal and novel therapeutic directions to treat AVPC phenotypes. Tumor organoids were treated in vitro and in vivo with PI3K/AKT/mTOR and EZH2 inhibitors as 1) a monotherapy, 2) each in combination with ADT, and 3) both in combination with ADT. Tumors were interrogated in either androgen-sensitive or androgen-resistant conditions to identify if the combination-therapy approach is more beneficial to prevent progression to AVPC and ADT-resistance or to reverse the AVPC phenotype and restore hormone sensitivity. Quantitative determination of therapeutic response was carried out in vitro in 3D using fluorescent cytotoxicity and proliferation assays. In vivo, tumor response will be assessed by histologic analysis and RNA sequencing. Protein and mRNA expression was measured by qPCR, IHC and Western blot. Despite recent progress in the field, men with AVPC still face a terminal prognosis, and no current therapy provides durable response. The results of this research will help pave the way for early-phase clinical trials testing the efficacy of EZH2 inhibitors in combination with enzalutamide and/or PI3K/AKT/mTOR inhibitors.

Citation Format: Katherine L. Morel, Christopher J. Sweeney, Leigh Ellis. Targeting EZH2 and PI3K/mTOR for a novel combination therapeutic strategy in aggressive variant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr B29.
Palliative Sedation at the End of Life: A Comparative Study of Chronic Obstructive Pulmonary Disease and Lung Cancer Patients
Authors: Tejero Elena , Pardo Paloma , Sánchez-Sánchez Sonia , Galera Raúl , Casitas Raquel , Martínez-Cerón Elisabet , García-Rio Francisco
Published: December 2020

Background: Although patients with chronic obstructive pulmonary disease (COPD) receive poor-quality palliative care, information about the use of palliative sedation (PS) in the last days of life is very scarce. Objectives: To compare the use of PS in hospitalized patients who died from COPD or lung cancer and identify factors correlating with PS application. Methods: In a retrospective observational cohort study, from 1,675 patients died at a teaching hospital between 2013 and 2015, 109 patients who died from COPD and 85 from lung cancer were compared. Sociodemographic data, clinical characteristics, health care resource utilization, application of PS and prescribed drugs were recorded. Results: In the last 6 months of life, patients who died from COPD had more hospital admissions due to respiratory causes and less frequent support by a palliative home care team (PHCT). Meanwhile, during their last hospitalization, patients who died from COPD had fewer do-not-resuscitate orders and were subjected to more intensive care unit admissions and cardiopulmonary resuscitation maneuvers. PS was applied less frequently in patients who died from COPD than in those who died from lung cancer (31 vs. 53%, p = 0.002). Overall, previous use of opioid drugs, support by a PHCT, and a diagnosis of COPD (adjusted odds ratio 0.48, 95% CI: 0.26–0.89, p = 0.020) were retained as factors independently related to PS. In COPD patients, only previous use of opioid drugs was identified as a PS-related factor. Conclusion: During their last days of life, hospitalized COPD patients receive PS less frequently than patients with lung cancer.
Acute Alcohol Intake Deteriorates Hearing Thresholds and Speech Perception in Noise
Authors: Choi Hyo Geun , Hong Sung Kwang , Lee Hyo-Jeong , Chang Jiwon
Published: December 2020

Objectives: The hearing process involves complex peripheral and central auditory pathways and could be influenced by various situations or medications. To date, there is very little known about the effects of alcohol on the auditory performances. The purpose of the present study was to evaluate how acute alcohol administration affects various aspects of hearing performance in human subjects, from the auditory perceptive threshold to the speech-in-noise task, which is cognitively demanding. Methods: A total of 43 healthy volunteers were recruited, and each of the participants received calculated amounts of alcohol according to their body weight and sex with a targeted blood alcohol content level of 0.05% using the Widmark formula. Hearing was tested in alcohol-free conditions (no alcohol intake within the previous 24 h) and acute alcohol conditions. A test battery composed of pure-tone audiometry, speech reception threshold (SRT), word recognition score (WRS), distortion product otoacoustic emission (DPOAE), gaps-in-noise (GIN) test, and Korean matrix sentence test (testing speech perception in noise) was performed in the 2 conditions. Results: Acute alcohol intake elevated pure-tone hearing thresholds and SRT but did not affect WRS. Both otoacoustic emissions recorded with DPOAE and the temporal resolution measured with the GIN test were not influenced by alcohol intake. The hearing performance in a noisy environment in both easy (−2 dB signal-to-noise ratio [SNR]) and difficult (−8 dB SNR) conditions was decreased by alcohol. Conclusions: Acute alcohol elevated auditory perceptive thresholds and affected performance in complex and difficult auditory tasks rather than simple tasks.
Colorful Semantics in Cypriot-Greek-Speaking Children with Autism Spectrum Disorder
Authors: Christopoulou Maria , Voniati Louiza , Drosos Konstantinos , Armostis Spyros
Published: December 2020

Objectives: The aims of this study were: (1) to investigate the effect of colorful semantics (CS) on the morphosyntactic and semantic development of Cypriot-Greek (CG)-speaking children with autism spectrum disorder (ASD) to obtain a better understanding of its role in an augmentative communication (AC) intervention program; (2) to address the paucity of intervention tools geared for CG-speaking children with ASD. Participants and Methods: The study included 24 boys and 16 girls with ASD, all preschool-aged 4–6 years. All were verbal but with limited production and minimal mean length of utterance. The study followed a randomized control trial design with equally sized experimental and control groups. The experimental group followed a therapeutic program using the AC with a CS protocol, while the control group’s AC intervention did not include the CS protocol. Results: The use of CS significantly improved the children’s semantic and morphosyntactic development. Conclusions: The intervention results illustrate the effectiveness of CS in this study; however, generalizability of effectiveness to other similar CG-speaking children with ASD requires further evidence.
Effect of Originator Infliximab Treatment on Disease-Related Hospitalizations, Work Productivity and Activity Impairment, and Health Resource Utilization in Patients with Crohn’s Disease in a Real-Life Setting: Results of a Prospective Multicenter Study in Germany
Authors: Teich Niels , Bläker Michael , Holtkamp-Endemann Frank , Jörgensen Eric , Stallmach Andreas , Hohenberger Susanne
Published: December 2020

Introduction: Infliximab (IFX) therapy is efficacious for inducing and maintaining symptomatic remission in patients with Crohn’s disease (CD), but whether this benefit results in reduced hospitalization rates and therefore may improve patients’ quality of life in an economically sensible way is conflicting so far. Methods: We conducted a noninterventional, multicenter, open-label, prospective study to evaluate the effect of originator IFX treatment on patient-reported outcomes and disease-related hospitalizations in adult CD patients in Germany treated for the first time with IFX according to label. Results: Two hundred and ninety-four patients were included in the study. We observed a statistically significant reduction in the number of CD-related hospitalizations from the year before baseline (mean 1.00 per patient, SD ± 0.93) to the mean value of the 1st (0.62, SD ± 0.95) and 2nd year (0.32, SD ± 0.75) of the observation period (p < 0.0001). After 3 months of IFX therapy, work productivity and activity increased by an average of 12.6 and 17.1%, respectively. Patient’s clinical outcome was markedly improved as the total CD activity index (CDAI) sum score continuously decreased from baseline to month 24 and the mean score of the total inflammatory bowel disease questionnaire (IBDQ) changed substantially from 141 at baseline to 172 after 24 months of IFX treatment. Additionally, the number of work incapacity days declined. Recently, no new safety issues of IFX have been identified. Conclusion: In this large, prospective, multicenter study on disease-related hospitalization rates, work productivity, capacity for daily activities, and HRQoL in patients with CD, IFX significantly reduces their hospitalization rates and improves work productivity, daily activity, and quality of life over 24 months.
Long-Term Decreases in the Expression of Calcineurin and GABAA Receptors Induced by Early Maternal Separation Are Associated with Increased Anxiety-Like Behavior in Adult Male Rats
Authors: Mahmoodkhani Maryam , Ghasemi Maedeh , Derafshpour Leila , Amini Mohammad , Mehranfard Nasrin
Published: December 2020

Introduction: Early life stress is a well-described risk factor of anxiety disorders in adulthood. Dysfunction in GABA/glutamate receptors and their functional regulator, calcineurin, is linked to anxiety disorders. Here, we investigated the effect of early life stress, such as repeated maternal separation (MS; 3 h per day from postnatal day [P] 2 to 11), on changes in the expression of calcineurin as well as the ionotropic glutamatergic and GABAergic receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and GABAA receptors in the hippocampus and prefrontal cortex (PFC) of adolescent (P35) and adult (P62) male Wistar rats and their correlations with anxiety-like behavior in adulthood. Methods: The protein levels were assessed by Western blot analysis. Anxiety-like behavior was measured in the elevated plus maze (EPM) and open field (OF) tests. Results: MS induced a regional transient decrease of glutamate receptors expression at P35, with decreased NMDA and AMPA receptor levels, respectively, in the hippocampus and PFC, suggesting a possible decrease in excitatory synaptic strength. In contrast to glutamate receptors, MS had long-lasting influence on GABAA receptor and calcineurin levels, with reduced expression of GABAA receptor and calcineurin in both brain regions at P35 that continued into adulthood. These results were accompanied by increased anxiety behavior in adulthood, shown by lower percentage of number of total entries and time spent in the open arms of the EPM, and by lower time spent and number of entries in the OF central area. Conclusions: Together, our study suggests that GABAA receptors via calcineurin-dependent signaling pathways may play an important role in the expression of stress-induced anxiety-like behavior.
Apontamentos sobre a literatura italiana dos anos 2000
Authors: Benvenuti Giuliana
Published: December 2020

A literatura italiana dos anos 2000 parece ser caracterizada por um contato cada vez mais próximo com outras mídias, no interior daquela que é definida como so- ciedade pós-mídiática. Com base nas mudanças que ocorreram já a partir dos anos 1980, a contribuição indaga em um dos percursos menos investigados: o que se origina da co- laboração entre romancistas e cartunistas e que, com frequência, se inscreve sob o signo do noir. As experiências do grupo Valvoline assim como a dos Cannibali parecem ser seminais de um emaranhado de linguagens destinado a continuar nas décadas seguintes, dentro de uma experimentação que, mesmo pouco estudada na crítica literária, segue até o presente global dos anos 2000.
insegnamento dell’italiano e l’educazione interculturale in Slovenia
Authors: Antonič Nives , Cerkvenik Mojca
Published: December 2020

L’articolo si propone di presentare una panoramica delle principali caratteristiche che riguardano l’insegnamento/apprendimento dell’italiano in Slovenia e una riflessione sull’importanza dell’educazione interculturale al fine di contribuire all’inclusione del singolo nella società che lo circonda. Dopo una sintetica illustrazione del quadro giuridico nel quale si inserisce la tutela delle lingue minoritarie in Slovenia, si presenta il percorso scolastico e le caratteristiche dell’insegnamento/apprendimento della lingua italiana come lingua materna (L1) e lingua seconda (L2) nel territorio bilingue nonché come lingua straniera (LS) nel resto della Slovenia. In particolare, vengono delineate le peculiarità del modello di educazione bilingue del Litorale sloveno, territorio di confine e area di contatto di culture prevalentemente romanze e slave. Infine, si evidenzia la necessità di applicare un approccio interculturale all’insegnamento in quanto il buon funzionamento della società multiculturale contemporanea dipende dalla consapevolezza della propria cultura congiuntamente all’esistenza di altre culture dell’ambiente. In questo modo sia insegnanti che studenti saranno coscienti del bisogno costante di accrescere le proprie competenze sia linguistiche che interculturali.
rastro dos emigrati na Argentina: Da Garibaldi a Che Guevara e Quando Dio ballava il tango
Authors: Marcolini Adriana
Published: December 2020

O texto apresenta os livros Da Garibaldi a Che Guevara. Storie della mia famiglia (2015), de Beatrice Mortillaro, e Quando Dio ballava il tango (2002), de Laura Pariani, e traça uma análise comparativa entre eles. As famílias das duas autoras são marcadas pela emigração para a Argentina. As obras situam-se no contexto da “redescoberta” da emigração italiana por parte dos escritores contemporâneos da Península. Inserem-se no âmbito da proliferação de obras literárias sobre a emigração para a Argentina, a maioria escritas por mulheres. Tais obras trazem à tona o olhar feminino sobre a emigração.