bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6312: Use of differential sensing-based biosensors to quantify ERK kinase activity in complex biological samples
Authors: Zamora-Olivares Diana , Pridgen Jacey R. , Zeng Lingyu , Kaoud Tamer S. , Anslyn Eric V. , Dalby Kevin N.
Published: September 2020

The expeditious quantification of signalling in complex biological system by novel technologies will aid in the development of biological models, help to identify targets for treatment, and assess treatment plans. The biochemical process of protein phosphorylation, which underlies almost all aspects of cell signaling, is typically evaluated by immunoblotting procedures like western blot. More recently, proteomics procedures, which provide qualitative estimates of the concentration of proteins and their modifications in cells have also been used. However, enzyme activity can be difficult to correlate to protein modifications.vRecently we reported a differential sensing-based approach to differentiate nine MAPKs from each other. From this we developed a cabilbration regression model to measure ERK activation and inhibition while both JNK and p38 MAPKs were present. Our previous studies were carried out using purified MAPKs, which do not necessarily reflect endogenous activity. Here, we report a similar approach to rapidly quantify unknown levels of endogenous ERK activity in biological samples. To do so, a library of cross-reactive SOX-peptide-based biosensors along with chemometric analysis, was used to quantify nanograms of active ERK in micrograms of unfractionated cell lysates and tumor extracts. This approach can be used to measure multiple samples quickly, allowing for faster analysis of the response of actual ERK activity in treatments in cell lines or animal models than other methods. This approach might also provide an alternative to assessing ERK activity in human tumor biopsies, which would be valuable for evaluating treatments and inhibitor resistance.

Citation Format: Diana Zamora-Olivares, Jacey R. Pridgen, Lingyu Zeng, Tamer S. Kaoud, Eric V. Anslyn, Kevin N. Dalby. Use of differential sensing-based biosensors to quantify ERK kinase activity in complex biological samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6312.
Abstract 6415: RAF dimer inhibitor lifirafenib enhances the antitumor activity of MEK inhibitor mirdametinib in RAS mutant tumors
Authors: Yuan Xi , Zhang Xinwen , Du Rong , Cheung Shing-Hu , Wei Min , Zhou Changyou , Wang Lai , Shearer Todd , Edris Badreddin , Smith Mary , Yao Zhan , Thant Claire N. , Rosen Neal , Luo Lusong
Published: September 2020

K-RAS mutation represents one of the most frequent genetic alterations in cancers. Monotherapy approaches targeting RAS downstream effectors such as MEK and ERK have had limited clinical success in patients with K-RAS-mutated cancers. The reduced sensitivity of K-RAS-mutated cells to certain MEK inhibitors is associated with feedback phosphorylation of MEK and reactivation of mitogen-activated protein kinase (MAPK) signaling. Herein, we report that RAF dimer inhibitor lifirafenib (BGB-283) shows strong synergistic effect with MEK inhibitor mirdametinib (PD-0325901) in suppressing proliferation of K-RAS-mutated cancer cell lines. This synergistic effect was not observed using vemurafenib, a first-generation B-RAFV600E selective inhibitor. Mechanistic analysis revealed that RAF dimer inhibition could suppress RAF-dependent MEK reactivation and led to sustained inhibition of MAPK signaling in K-RAS-mutated cells. Furthermore, combination synergy was observed in K-RAS mutant xenograft models. Pharmacodynamic analysis supported the role of synergistic phospho-ERK blockade in enhancing the antitumor activity in the K-RAS mutant models. These findings support the rationale to combine a RAF dimer inhibitor and a MEK inhibitor to treat K-RAS-mutated cancers and led to the ongoing a Phase Ib/II clinical trial of lifirafenib and mirdametinib in patients with K-RAS mutations or other MAPK pathway aberrations (Clinical Trial ID: NCT03905148).

Citation Format: Xi Yuan, Xinwen Zhang, Rong Du, Shing-Hu Cheung, Min Wei, Changyou Zhou, Lai Wang, Todd Shearer, Badreddin Edris, Mary Smith, Zhan Yao, Claire N. Thant, Neal Rosen, Lusong Luo. RAF dimer inhibitor lifirafenib enhances the antitumor activity of MEK inhibitor mirdametinib in RAS mutant tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6415.
Abstract 6527: Targeting glycosylated PD-1 induces potent anti-tumor immunity
Authors: Wang Yuhan , Sun Linlin , Yang Riyao , Liu Jielin , Qiu Yufan , Hsu Jennifer L. , Cha Jong-ho , Chan Li-Chuan , Hsu Jung-Mao , Lee Heng-Huan , Lai Yun-Ju , Khoo Kay-Hooi , Chung Ezra M , Li Chia-Wei , Kim Yong-Soo , Park Andrew H , Yang Yi , Yoo Stephen S. , Hung Mien-Chie
Published: September 2020

Immunotherapy targeting programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) immune checkpoints represents a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T cells that dampens T-cell receptor (TCR)/CD28 signaling by engaging with its ligand PD-L1 expressed on cancer cells. Despite the clinical success of PD-1 blockade using monoclonal antibodies, most patients do not show promising results, and the underlying regulatory mechanisms of PD-1 remain incompletely defined. Here, we showed that PD-1 is extensively N-glycosylated in T cells, and the intensities of its specific glycoforms are altered upon TCR activation. Glycosylation is critical for maintaining PD-1 protein stability and cell surface localization. Importantly, the glycosylation of PD-1, especially at the N58 site, is essential for mediating the interaction with PD-L1. A monoclonal antibody that specifically targets glycosylated PD-1, STM418, exhibits higher binding affinity to PD-1 than FDA-approved PD-1 antibodies, potently inhibits PD-L1/PD-1 binding, and enhances anti-tumor immunity. Our findings provide novel insights into the functional significance of PD-1 glycosylation and offer a rationale for targeting glycosylated PD-1 as a potential strategy for immunotherapy.

Citation Format: Yuhan Wang, Linlin Sun, Riyao Yang, Jielin Liu, Yufan Qiu, Jennifer L. Hsu, Jong-ho Cha, Li-Chuan Chan, Jung-Mao Hsu, Heng-Huan Lee, Yun-Ju Lai, Kay-Hooi Khoo, Ezra M Chung, Chia-Wei Li, Yong-Soo Kim, Andrew H Park, Yi Yang, Stephen S. Yoo, Mien-Chie Hung. Targeting glycosylated PD-1 induces potent anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6527.
Abstract 6528: Anti-PD-1 induces the endocytosis of the co-receptor from the surface of T-cells: Nivolumab is more effective than Pembrolizumab
Authors: Saad Elham Ben , Oroya Andres , Rudd Christopher E.
Published: September 2020

Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer. Present models show that anti-PD-1 operates simply by blocking co-receptor binding to its ligand PD-L1. Surprisingly, no previous studies have assessed whether ICB also induces the internalization or endocytosis of PD-1 from the cell surface. Many, but not all receptors, undergo endocytosis upon antibody or ligand binding. In this study, PD-1 internalization was assessed on activated human T cells by flow cytometry and fluorescence microscopy. Immunoprecipitation and western blotting were performed to assess the destiny of PD-1 after internalization. Our results report that anti-PD-1 induces the rapid internalization of PD-1 from the surface of T-cells in a manner comparable to CD28. A substantial minority of receptors were also resistant to antibody-induced endocytosis. Further, Nivolumab was considerably more effective than Pembrolizumab in inducing the endocytosis of PD-1 in primary human T-cells. This difference was the result of several factors where Nivolumab bound to a greater number of PD-1 molecules on the surface of T-cells than Pembrolizumab, indicating that the co-receptor might exist with different conformations on activated cells. Moreover, Nivolumab induced more rapid endocytosis (5.5 versus 3.6% per minute) and a greater percentage of PD-1 molecules than Pembrolizumab (70% versus 50%). The relative effect of anti-PD-1 molecules on internalization was seen equally on activated CD4 helper and CD8+ effector/memory T-cells. The internalization and the degradation of PD-1 were partially blocked by the inhibition of clathrin-mediated endocytosis and proteasome activity. Our studies show for the first time that ICB involves a second level of modulation involving the internalization of PD-1 from the surface of T-cells, an event which will contribute to the efficacy of ICB.

Citation Format: Elham Ben Saad, Andres Oroya, Christopher E. Rudd. Anti-PD-1 induces the endocytosis of the co-receptor from the surface of T-cells: Nivolumab is more effective than Pembrolizumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6528.
Abstract 661: Synergistic antitumor activity of futibatinib, an FGFR1-4 inhibitor, and TAS-117, a selective AKT inhibitor, in FGFR-deregulated cancer models
Authors: Iwasaki Junya , Kuramoto Takuya , Komori Toshiharu , Saito Hitoshi , Hirai Hiroshi
Published: September 2020

Background: TAS-117 is a potent oral allosteric non-ATP inhibitor selective for AKT. A phase 1 study with TAS-117 is ongoing in patients with endometrial cancer and ovarian clear cell carcinoma. Futibatinib (TAS-120) is a selective, irreversible small-molecule fibroblast growth factor receptor (FGFR) 1-4 inhibitor, with potent antiproliferative activity in preclinical models with FGFR aberrations. Phase 2 studies are ongoing in patients with various FGFR-deregulated cancers. We evaluated the antitumor activity of futibatinib plus TAS-117 in FGFR-aberrant cancer models.

Methods: Effects of futibatinib plus TAS-117 were investigated in human endometrial FGFR2-N549K-mutated AN3CA cancer cells and small-cell lung cancer FGFR1-amplified DMS114 cells. Activation of RAS and PI3K pathways was assessed by detecting phosphorylation of ERK1/2, AKT, and S6. Antitumor combination indices (CI) for cell viability over time were determined with the Chou-Talalay median-effect method and CalcuSyn software; a CI<0.9 indicates synergy. Antitumor effects of futibatinib (15 mg/kg/d) plus TAS-117 (4 or 8 mg/kg/d) or monotherapy were also evaluated in a mouse AN3CA xenograft model. FGFR signaling, apoptosis (via caspase activity and PARP cleavage), and relative tumor volume (RTV; compared with Day 0) were assessed.

Results: Futibatinib and TAS-117 synergistically increased cell death and decreased cell growth in AN3CA (CI<0.40) and DMS114 (CI<0.40) cells, respectively. Apoptosis induction was readily detected with futibatinib plus TAS-117 in AN3CA cells, but low activity was observed with monotherapy. In both AN3CA and DMS114 cells, futibatinib suppressed ERK1/2, but not AKT phosphorylation; the futibatinib plus TAS-117 combination suppressed phosphorylation of both ERK1/2 and AKT. In AN3CA xenografts, combination therapy inhibited the FGFR, PI3K, and MEK pathways. Futibatinib plus TAS-117 increased PARP cleavage more than monotherapy. Compared with Day 0, RTV on Day 15 was 60.71 in the control, 13.40 with futibatinib monotherapy, and 33.63 with TAS-117 (8 mg/kg/d) monotherapy. Treatment with 3 different futibatinib plus TAS-117 combination dosing regimens resulted in marked reductions in RTVs on Day 15 (2.16, 0.53, and 0.22).

Conclusions: Our findings suggest that futibatinib plus TAS-117 has synergistic antitumor effects in FGFR-aberrant tumors. A phase 1/2 study of this combination in advanced solid tumors (JapicCTI-194864) is ongoing.

Citation Format: Junya Iwasaki, Takuya Kuramoto, Toshiharu Komori, Hitoshi Saito, Hiroshi Hirai. Synergistic antitumor activity of futibatinib, an FGFR1-4 inhibitor, and TAS-117, a selective AKT inhibitor, in FGFR-deregulated cancer models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 661.
Abstract 664: BGB-10188, a highly selective PI3Kδ inhibitor with improved safety profile and superior anti-tumor activities in vivo
Authors: Yang Xiao , Yang Xiaolong , Cui Xinxin , Su Dan , Wu Yue , Sun Xuebing , Wang Jingyuan , Bai Huichen , Wei Wei , Li Jing , Yuan Xi , Liu Ye , Wang Fan , Wang Zhiwei , Wang Lai , Liu Xuesong , Song Xiaomin
Published: September 2020

Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes capable of phosphorylating phosphatidylinositol to phosphoinositides, which are important secondary messengers involved in various cell signaling and functions. PI3Kδ is one of four isoforms (PI3Kα, β, δ and γ) of the PI3K class I family. It is restrictively expressed in leukocytes. PI3Kδ is a key signal transduction component for normal and malignant B cells and also important for the homeostasis and function of T-regulatory cells (Treg), making it a promising target for treatment of both hematologic malignancies and solid tumors.

BGB-10188 is a highly selective inhibitor of PI3Kδ, showing no significant inhibition over 376 protein kinases and 17 lipid kinases, and more than three-thousand folds selectivity over PI3Kα, PI3Kβ, and PI3Kγ. BGB-10188 potently inhibited PI3Kδ in biochemical, cellular and human whole blood assays with IC50s ranging from 1.7-16 nM. It also showed a long-lasting and strong target inhibition activity in mouse pharmacodynamics (PD) studies at doses as low as 10mg/kg. The elimination half-life (t1/2) of BGB-10188 in plasma was 12.6 hours and 10.4 hours in rats and dogs, respectively.

BGB-10188 showed significant antitumor effects in different types of B cell Lymphoma xenograft models. The liver toxicities of BGB-10188 were evaluated in mice and significantly improved safety margin was observed for BGB-10188 in comparison with other PI3Kδ inhibitors.

In summary, BGB-10188 is a novel PI3Kδ inhibitor with high selectivity, potency and improved safety profile shown in preclinical studies, which is promising and warrants the testing of the compound in human.

Citation Format: Xiao Yang, Xiaolong Yang, Xinxin Cui, Dan Su, Yue Wu, Xuebing Sun, Jingyuan Wang, Huichen Bai, Wei Wei, Jing Li, Xi Yuan, Ye Liu, Fan Wang, Zhiwei Wang, Lai Wang, Xuesong Liu, Xiaomin Song. BGB-10188, a highly selective PI3Kδ inhibitor with improved safety profile and superior anti-tumor activities in vivo [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 664.
Abstract 6710: AVID200, a first-in-class selective TGF-beta 1 and -beta 3 inhibitor, sensitizes tumors to immune checkpoint blockade therapies
Authors: Tremblay Gilles , Gruosso Tina , Denis Jean-François , Figueredo Rene , Koropatnick Jim , O'Connor-McCourt Maureen
Published: September 2020

AVID200 is a first-in-class rationally designed receptor ectodomain trap that selectively neutralizes TGF-beta 1 and -beta 3 with pM potency while sparing TGF-beta 2, thereby reducing the potential for toxicities associated with neutralization of this isoform. A Phase 1 dose-escalation clinical study of AVID200 monotherapy has recently been completed and established that the agent was well tolerated and exhibited target engagement at all dose levels tested without reaching a maximally tolerated dose.

To explore the potential of AVID200 as a combination agent with immunotherapy, expression analysis of TGF-beta isoforms across various solid tumors has been carried out and the ability of AVID200 to increase anti-tumor immunity as a single agent and in combination has been explored in vivo.

Analysis of >10,000 tumor samples from TCGA revealed that TGF-beta1 and -beta3 are the predominant isoforms expressed in solid tumors, with TGF-beta2 showing only minimal expression. This corroborates the attractiveness of TGF-beta1 and -beta3 as promising anti-cancer targets and emphasizes the need to target both isoforms simultaneously. Furthermore, AVID200 increased T-cell-mediated cytotoxicity as a single agent as well as potentiating the efficacy of immune checkpoint inhibitors (ICI) in syngeneic mouse tumor models. In line with these observations, we have found that AVID200 increases the infiltration of T-cells in the tumor microenvironment.

In conclusion, AVID200, a first-in-class, potent and selective TGF-beta trap, enhances the activity of ICI agents in vivo and holds promise as a potential novel immunotherapy combination regimen which warrants exploration in patients with solid tumor malignancies. Phase 1 clinical trials are underway in various indications.

Citation Format: Gilles Tremblay, Tina Gruosso, Jean-François Denis, Rene Figueredo, Jim Koropatnick, Maureen O'Connor-McCourt. AVID200, a first-in-class selective TGF-beta 1 and -beta 3 inhibitor, sensitizes tumors to immune checkpoint blockade therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6710.
Abstract 971: Effects of tumor cryo-ablation on cGAS-STING pathway and antitumor immunity in syngeneic murine rhabdomyosarcoma
Authors: Alshebremi Mohammad Abdulaziz , Myers Jay T. , Kingsley Daniel T. , Huang Alex Y.
Published: September 2020

Even with current improvement in cancer therapy, tumor immunosuppressive microenvironment and metastatic tumors are important factors which have shown to be a challenge for cancer treatment. Thus, targeting the tumor microenvironment (TME) locally are required to modify the activation of innate immunity, which can provoke subsequent global adaptive anti-tumor immunity. Tumor cryo-ablation, a medical procedure that utilizes ultra-cold temperatures to destroy in situ local tumor tissues, has the capability to induce the release of immune danger signals that activate antigen-presenting cells to initiate the anti-tumor immunity. To understand the mechanism of immune activation by cryo-ablation, we performed comprehensive analyses on the effects of tumor cryo-ablation on mononuclear phagocytic lineage cells and the antitumor immunity. Here, we show that cryo-ablation of syngeneic Rhabdomyosarcoma (RMS) tumor, an aggressive sarcoma affecting children and young adults, was able to induce both the regression of tumor and the upregulation of the critical immune cytokines and chemokines profile. Moreover, cryo-ablation of RMS tumor initiates cGAS-STING signaling activation and type I interferon production in dendritic cells, which are consequential in pro-inflammatory TME. We also report that antitumor effects of cryo-ablation was more inhibitive, but not completely abrogated, in STING-deficient mice comparing with wild-type mice, demonstrating that both host-derived and tumor-intrinsic cGAS-STING signaling plays an important role in antitumor effects of tumor cryo-ablation. Ongoing experiments will address the efficacy of RMS tumor cryo-ablation on systemic anti-tumor immune activation leading to an abscopal effect on tumor regression at metastatic tumor. Taken together, our results demonstrate that tumor cryo-ablation affects antitumor immunity and cGAS-STING signaling in RMS tumor, and this approach may help guide future immunotherapy to improve cancer treatment outcomes.

Citation Format: Mohammad Abdulaziz Alshebremi, Jay T. Myers, Daniel T. Kingsley, Alex Y. Huang. Effects of tumor cryo-ablation on cGAS-STING pathway and antitumor immunity in syngeneic murine rhabdomyosarcoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 971.
CRISPR-GEMM Pooled Mutagenic Screening Identifies KMT2D as a Major Modulator of Immune Checkpoint Blockade
Authors: Wang Guangchuan , Chow Ryan D. , Zhu Lvyun , Bai Zhigang , Ye Lupeng , Zhang Feifei , Renauer Paul A. , Dong Matthew B. , Dai Xiaoyun , Zhang Xiaoya , Du Yaying , Cheng Yujing , Niu Leilei , Chu Zhiyuan , Kim Kristin , Liao Cun , Clark Paul , Errami Youssef , Chen Sidi
Published: September 2020

Immune checkpoint blockade (ICB) has shown remarkable clinical efficacy in several cancer types. However, only a fraction of patients will respond to ICB. Here, we performed pooled mutagenic screening with CRISPR-mediated genetically engineered mouse models (CRISPR-GEMM) in ICB settings, and identified KMT2D as a major modulator of ICB response across multiple cancer types. KMT2D encodes a histone H3K4 methyltransferase and is among the most frequently mutated genes in patients with cancer. Kmt2d loss led to increased DNA damage and mutation burden, chromatin remodeling, intron retention, and activation of transposable elements. In addition, Kmt2d-mutant cells exhibited increased protein turnover and IFNγ-stimulated antigen presentation. In turn, Kmt2d-mutant tumors in both mouse and human were characterized by increased immune infiltration. These data demonstrate that Kmt2d deficiency sensitizes tumors to ICB by augmenting tumor immunogenicity, and also highlight the power of CRISPR-GEMMs for interrogating complex molecular landscapes in immunotherapeutic contexts that preserve the native tumor microenvironment.

Significance:

ICB is ineffective in the majority of patients. Through direct in vivo CRISPR mutagenesis screening in GEMMs of cancer, we find Kmt2d deficiency sensitizes tumors to ICB. Considering the prevalence of KMT2D mutations, this finding potentially has broad implications for patient stratification and clinical decision-making.

This article is highlighted in the In This Issue feature, p. 1775
Integrate for car brake failure and engine overheat system
Authors: Subhashini G. , Aiman Albanna Anas , Abdullah Raed
Published: September 2020

One of the most important features in a car is its braking system and engine. The braking system enables the driver to control the speed of the vehicle when the need arises in order to protect the car, driver and other road users from accidents which might be fatal. The performance of the entire car also relies largely on the effective delivery and operation of the car engine whose ability to deliver the required performance is hinged on its temperature. In recent years a variety of IOT based monitoring and control systems have been explored in various areas of modern technology. This Final Year research project proposes the design and development of an IOT based vehicle brake failure and engine overheating system. The proposed system utilizes a network of sensors to monitor the temperature of the car engine, obstacles along the path of the car and the speed of the vehicle. The sensor data retrieved from the monitoring system is used by the control system consisting of a microcontroller to make decisive automatic decisions for the vehicle brake and failure system. A warning system consisting of LCD, Buzzer and LED has also been added into the system to warn the driver regarding the operation of the braking and engine overheating system. Two microcontrollers have been utilized for this research i.e. Arduino Uno for sensor data acquisition and processing and a Raspberry Pi microcontroller for purposes of sending the data wirelessly to a web platform. The web platform developed enables the user to remotely access real-time and past data from the system vehicle brake failure and engine overheating system. A variety of tests were conducted on the system to evaluate its performance whereby 95.4% accuracy was achieved in in terms of the ability of the car to effectively and automatically brake in the presence of obstacles and in terms of speed control. Testing done on the ability of the system to accurately monitor the engine temperature shows that its able to achieve 97.5% accuracy. The IOT system is able to transmit the sensor data retrieved from the system using both WIFI and mobile data whereby an average transmission time of 2.32 s and 4.33 s was recorded for each system respectively.
Investigation on the BER performance of downlink JT-CoMP-NOMA with different modulation schemes
Authors: Katiran Norshidah , Mohd Shah Shaharil , Abdullah Noorsaliza , Abdul Ghaffar Aimi Syamimi , Saparudin Faiz Asraf
Published: September 2020

The principle of joint transmission coordinated multipoint with non-orthogonal multiple access (JT-CoMP-NOMA) is to allow multiple cells in the network to cooperatively transmit data to users using the same network resources in frequency and time domains. The approach would be beneficial in enhancing the system performance in the context of spectral efficiency. This paper presents the performance comparison of JT-CoMP-NOMA for several modulation schemes including QPSK, 16-QAM and 64 QAM in downlink transmission in the context of bit error rate. We conduct an investigation to compare the error performance of JT-CoMP-NOMA with NOMA system. Our simulation results demonstrate that the JT-CoMP-NOMA provides lower bit error rate compared to NOMA system.
1 Slash 100%: gamification of mathematics with hybrid QR-based card game
Authors: Yung Ong C , Junaini Syahrul Nizam , Kamal Ahmad A , Md Ibrahim Laili F
Published: September 2020

Mathematics is important in our life and society. However, gamification of mathematics is rare for the topics such as fractions and decimals. This paper presents the development of an educational mathematics game called One Slash One Hundred Percent (1 Slash 100%). It is the hybridization of conventional card game and Quick Response (QR). This research aims to study how the respondents explore the card game to master decimal, fraction and percentage. The testing was conducted among secondary school students in Kuching, Sarawak, Malaysia (n=12; age=14). The respondents were asked to answer a set of questions in pre-test and post-test question. The results were promising where the analysis showed a significant difference between pre (M=14.3, SD=2.103) and post-test scores (M=17.6, SD=2.234). Thus, gamification of mathematics using hybrid card game increases their mastery of decimal, fraction and percentage.
A lightweight secure CoAP for IoT-cloud paradigm using Elliptic-curve cryptography
Authors: Ayoub Amrani , Najat Rafalia , Jaafar Abouchabaka
Published: September 2020

Cloud Computing and the Internet of Things (IoT), two different technologies, are already part of our lives. Their impressive adoption increasing more and more, which makes them the future of the future internet. The tsunami of interconnectivity between objects and data collection is increasingly based on Cloud Computing, where data analysis and intelligence really reside. A new paradigm where the Cloud and the IoT are merged will create a new air in the world of technology, which can offer many services and applications useful to humanity. However, despite the great benefits that can bring this technology in term of new services, elasticity and flexibility, the security aspect still remains a serious constraint which hampers the expansion of this technology. This paper proposes a lightweight Mutual authentication protocol based on Constrained Application Protocol (CoAP); that is suitable for IoT devices than HTTP and using elliptic curve cryptography to secure data transmission between the Cloud and devices. We used the AVISPA tool to verify our proposed scheme.
Face recognition using viola-jones depending on python
Authors: Dheyaa Ismael Khansaa , Irina Stanciu
Published: September 2020

In this paper, the proposed software system based on face recognition the proposed system can be implemented in the smart building or any VIP building need security interring in general, The human face will be recognized from a stream of pictures or video feed, this technology recognizes the person according to the specific algorithm, the algorithm that employed in this paper is the Viola–Jones object detection framework by using Python. The task of the proposed facial recognition system consists of two steps, the first one was detected the human face from live video using the webcamera in the computer, and the second step recognizes if this face allowed to enter the building or not by comparing it with the existing database, the two steps depending on the OpenCV python by importing cv2 method for detecting the human face, the frames can be read or written to file with the cv2.imread and cv2.imwrite functions respectively Finally, this proposed software system can be used to control access in smart buildings as a rule and the advancement of techniques connected around there, Providing a security system is one of the most important features must be achieved in the smart buildings, this proposed system can be used as an application in a smart building as a security system. Face recognition is one of the most important applications using today for practical facial recognition, The proposed software system, depending on using OpenCV (Open Source Computer Vision) is a popular computer vision library, in 1999 this library started by Intel. The platform library sets its focus on real-time image processing and includes patent-free implementations of the latest computer vision algorithms. OpenCV 2.3.1 now comes with a programming interface to C, C++, Python, and Android. OpenCV library of python, the three algorithms that will be used in this proposed system. The currently available algorithms are:

Eigenfaces → createEigenFaceRecognizer()

Fisherfaces → createFisherFaceRecognizer()

Local Binary Patterns Histograms → createLBPHFaceRecognizer()
Finally the proposed system provide entering to the building just for the authorized person according to face recognition algorithem.
 
Optimized formation control of multi-agent system using PSO algorithm
Authors: Hasan Ahmed Mudheher , Raafat Safanah Mudheher
Published: September 2020

Formation Control (FC) is an important application for Multi-agent Systems (MASs) in coordinated control and especially for Unmanned Aerial Vehicle (UAV) which are widely used nowadays in military and civil sections. FC is mostly applied in conjunction with consensus algorithm. In this paper, a framework for an implementation of consensus FC that involves the decentralized type of network control is considered in order to achieve formation keeping, where the control of each vehicle is calculated dependent upon locally existed facts. The dynamic behavior of each vehicle agent is governed by its second-order dynamic model, and the networked mobile vehicle system is modeled by a directed graph. Then, Particle Swarm Optimization (PSO) is implemented for speeding up the convergence to the desired geometrical shape. Acceleration of the network while approaching the coveted shape is achieved and omissions of undesired swing that transpires through the acceleration is examined. The merits and effectiveness of the applied approach are demonstrated using two different examples.
Internet of things (IoT): a technology review, security issues, threats, and open challenges
Authors: Ahmed Abbood Alaa , Makki Shallal Qahtan , A. Fadhel Mohammed
Published: September 2020

Internet of Things (IoT) devices are spread in different areas such as e-tracking, e-commerce, e-home, and e-health, etc. Thus, during the last ten years, the internet of things technology (IoT) has been a research focus. Both privacy and security are the key concerns for the applications of IoT, and still face a huge number of challenges. There are many elements used to run the IoT technology which include hardware and software such as sensors, GPS, cameras, applications, and so forth. In this paper, we have analyzed and explain the technology of IoT along with its elements, security features, security issues, and threats that attached to each layer of IoT to guide the consideration of researchers into solve and understand the most serious problems in IoT environment.
Las infancias y el currículo del capital: el caso Divercity
Authors: Cuervo-Montoya Edisson Cuervo-Montoya , Giraldo-Urrego Laura María
Published: September 2020

(analítico) En Colombia, un modelo de negocio educativo centra su interés en la infancia como nicho de clientes, asegurándose rentabilidad por dos vías: desde el ofrecimiento de servicios de entretenimiento infantil y procesos de formación, y desde la fidelización de marcas comerciales a través de juegos de rol, los cuales pretenden educarles para el «mundo real». El artículo presenta reflexiones teórico-críticas sobre Divercity bajo la estrategia de análisis documental, develando sus intencionalidades y prácticas formativas, así como identificando componentes curriculares que le constituyen desde el punto de vista ideológico-económico. Los resultados apuntan a un creciente ejercicio de consumo instructivo de los infantes en los centros comerciales. Se concluye que existe una consolidación de procesos iniciales de mímesis del consumo adulto y una fidelización de las grandes marcas presentadas por Divercity.
Modos de habitar y creación fotográfica con jóvenes del Kilómetro 41
Authors: Pérez-Vallejo Andrés Uriel , Arroyave-Montoya Luz Amparo
Published: September 2020

(analítico) En este artículo de investigación cualitativa, la tecnología fotográfica y la memoria visual se convierten en plataformas para producir expresiones artísticas de reconciliación. En tal sentido, la creación fotográfica se usó como medio para exteriorizar significados e interpretaciones visuales sobre un territorio. Estudiantes de una institución educativa rural participaron en talleres de creación fotográfica y laboratorios de fundamentación sobre memoria y reconciliación. Este trabajo empírico permitió aplicar instrumentos de observación participante, explorando el acto creativo a través de una guía de elementos que potenciaron posturas críticas de los jóvenes hacia el territorio. Los resultados de un modelo de acciones creativas, aplicado a procesos de pensamiento crítico, permitieron comprobar que el autorretrato fotográfico se convierte en un artefacto comunicativo autorreferenciado socialmente.
Reformas que se parecen a sí mismas en el sistema penal juvenil uruguayo
Authors: González-Laurino Carolina
Published: September 2020

(analítico) Se estudia el funcionamiento del sistema penal juvenil uruguayo a través de reiteradas modificaciones en la institucionalidad existente. Se trata de una investigación cualitativa de caso único, empírica y contextualizada, sustentada en el análisis de discurso de entrevistas a los agentes legislativos, judiciales y ejecutivos del sistema penal juvenil y de los documentos que figuran en una muestra de expedientes judiciales. Los resultados señalan la justificación de la utilización del encierro en el ordenamiento de la cotidianidad adolescente, así como las consecuencias que la privación de libertad deja impresa en los jóvenes, analizadas mediante prácticas profesionales en medio abierto. Las conclusiones plantean la tensión aun existente entre castigo y protección social en discursos divergentes acerca de las medidas reguladoras de la transgresión normativa.
Desmitificando la violencia escolar: un análisis crítico de las representaciones
Authors: Patierno Nicolás , Southwell Myriam
Published: September 2020

(analítico) El artículo se desprende de una investigación dedicada al análisis crítico de lo que suele ser referenciado como violencia escolar. La misma fue realizada en tres escuelas secundarias de la ciudad de La Plata, Argentina, entre los años 2011 y 2018 y pretende evidenciar, entre otras cuestiones, la influencia de los imaginarios sociales negativos sobre el modo en que los educadores suelen intervenir en la resolución de conflictos considerados (por ellos mismos) como violentos. Para llevar adelante esta tarea, se optó por una metodología de tipo cualitativa nutrida por el análisis de testimonios y el relevamiento de bibliografía especializada. La conclusión invita a repensar el lugar de la educación secundaria en la contención y el redireccionamiento de la violencia hacia una convivencia pacífica y democrática.
Fibrinolytic Strategy for ST-Segment–Elevation Myocardial Infarction
Authors: Engel Gonzalez Pedro , Omar Wally , Patel Kunal V. , de Lemos James A. , Bavry Anthony A. , Koshy Thomas P. , Mullasari Ajit S. , Alexander Thomas , Banerjee Subhash , Kumbhani Dharam J.
Published: September 2020

The ongoing coronavirus disease 2019 pandemic has resulted in additional challenges for systems designed to perform expeditious primary percutaneous coronary intervention for patients presenting with ST-segment–elevation myocardial infarction. There are 2 important considerations: the guideline-recommended time goals were difficult to achieve for many patients in high-income countries even before the pandemic, and there is a steep increase in mortality when primary percutaneous coronary intervention cannot be delivered in a timely fashion. Although the use of fibrinolytic therapy has progressively decreased over the last several decades in high-income countries, in circumstances when delays in timely delivery of primary percutaneous coronary intervention are expected, a modern fibrinolytic-based pharmacoinvasive strategy may need to be considered. The purpose of this review is to systematically discuss the contemporary role of an evidence-based fibrinolytic reperfusion strategy as part of a pharmacoinvasive approach, in the context of the emerging coronavirus disease 2019 pandemic.
Prevalence of Abnormal Heart Weight After Sudden Death in People Younger than 40 Years of Age
Authors: Schoppen Zachary J. , Balmert Lauren C. , White Steven , Olson Rachael , Arunkumar Ponni , Dellefave‐Castillo Lisa M. , Puckelwartz Megan J. , George Alfred L. , McNally Elizabeth M. , Webster Gregory
Published: September 2020

Background

After sudden cardiac death in people aged <40 years, heart weight is a surrogate for cardiomegaly and a marker for cardiomyopathy. However, thresholds for cardiomegaly based on heart weight have not been validated in a cohort of cases of sudden cardiac death in young people.

Methods and Results

We surveyed medical examiner offices to determine which tools were used to assess heart weight norms. The survey determined that there was no gold standard for cardiomegaly (52 centers reported 22 different methods). We used a collection of heart weight data from sudden deaths in the Northwestern Sudden Death Collaboration (NSDC) to test the 22 methods. We found that the methods reported in our survey had little consistency: they classified between 18% and 81% of NSDC hearts with cardiomegaly. Therefore, we obtained biometric and postmortem data from a reference population of 3398 decedents aged <40 years. The reference population was ethnically diverse and had no known cardiac pathology on autopsy or histology. We derived and validated a multivariable regression model to predict normal heart weights and a threshold for cardiomegaly (upper 95% CI limit) in the young reference population (the Chicago model). Using the new model, the prevalence of cardiomegaly in hearts from the NSDC was 19%.

Conclusions

Medical examiner offices use a variety of tools to classify cardiomegaly. These approaches produce inconsistent results, and many overinterpret cardiomegaly. We recommend the model proposed to classify postmortem cardiomegaly in cases of sudden cardiac death in young people.
Breton Masculine Human Plurals, Locality, and Impoverishment
Authors: Mondon Jean-François
Published: September 2020

This article presents an apparent locality condition violation observed in Standard Breton masculine human plurals ending in -où. It proposes a unique impoverishment rule deleting a syntacticosemantic feature conditioned by a specified phonological exponent. Adopting a specific architectural view of lenition, it forces a rethinking of the precise timing of various postsyntactic processes, including certain types of impoverishment rules as well as Agree-Copy in dissociated Agr nodes. It also lends support to the independent claims that syntacticosemantic features are not overridden during Spell-Out and that Vocabulary Insertion applies to a linearized structure, not a hierarchical one.
The Role of Speech-Language Pathologists in Otolaryngology Resident Education
Authors: Abdel-Aty Yassmeen , Charney Sara , Lott David G.
Published: September 2020

Objectives/Introduction:

Laryngology is an expanding field that has been increasingly incorporated into otolaryngology resident training programs nationwide. The exposure to the field is variable across training programs, despite the fact that laryngological complaints comprise a large proportion of consultations to otolaryngologists. Laryngology education is vital for the care of patients with voice, swallowing, and airway complaints as well as for the appropriate referral of patients to the laryngology team for specialized care. Speech-language pathologists (SLPs) specialized in voice and swallowing disorders are well-trained in the assessment and treatment for these populations. This team recently published a paper regarding the experience of laryngology education in residency. During analysis of the results, an interesting beneficial trend developed regarding the positive impact of exposure to SLPs. This appeared to be distinct and deserved further analysis and discussion. We propose that involving SLPs in resident education may greatly enhance their training in laryngology.

Methods:

As per our previous paper, a cross sectional, multi-institutional study was designed to assess the exposure of residents to laryngology. Descriptive statistics were obtained for questions involving exposure to SLPs. Fisher’s exact test was used to compare differences between groups.

Results:

Most respondents (135/151, 89.4%) indicated having SLPs specializing in voice and swallowing disorders in their departments, although only half (77/151, 51.0%) stated that they spent formal time with them during training. Results show that residents with formal training with SLPs were more comfortable interpreting videofluoroscopic swallow studies (VFSS) ( P = .0032). Residents with SLPs in their departments were also more likely to feel confident in terminology to describe different dysphonic voices ( P = .0213).

Conclusion:

Formal time with SLPs within otolaryngology residency programs varies across the country. Speech-language pathologists are a useful resource for laryngology resident training and should be included in their education.
A peer-led non-diet behaviour change intervention: FitU
Authors: Lee Sae-Mi , Li Shuang , Newland Aubrey , Leedeman Juliana , Clifford Dawn E , Keeler Linda A
Published: September 2020

Objective:

Despite the popularity of weight loss interventions, research indicates these methods are ineffective for promoting long-term health. College age is a developmentally important age for developing lifelong health habits. FitU is a peer-led non-diet nutrition and physical activity (PA) mentoring intervention developed to promote lifelong health habits for college students. The purpose of this study was to examine the nutrition and PA outcomes of FitU participants.

Design:

Pre-experimental single group repeated-measures field study design with qualitative programme evaluation feedback at post-test.

Setting:

FitU participants met with both a nutrition and PA peer mentor four times each for a total of eight sessions.

Method:

Participants ( N = 125) completed pre- and post-surveys about their nutrition and PA attitudes and behaviours.

Results:

FitU participants increased their eating competence from pre-to-post assessment and decreased their perceived barriers to healthy eating. Participants also increased their readiness to exercise and reported being more physically active.

Conclusion:

Findings demonstrate the effectiveness of a peer-led, non-diet mentoring intervention in promoting health-supporting habits among college students.
Exploring the Influence of Job Satisfaction Upon the Retention of Bahamian Special Educators
Authors: Newton Norrisa , Hunter-Johnson Yvonne , Niu Yuanlu
Published: September 2020

Attrition has affected special education for decades. Understanding the influence of job satisfaction upon employee retention is vital in developing a country’s work force. This qualitative study consisted of 12 participants and explored the influencing factors of Bahamian special educators’ withdrawal from public education. Job Satisfaction and Social Cognitive Career Theory grounded this study, emphasizing the influence of experiences upon career decisions. Data were collected using semi-structured interviews and analyzed via open coding. Findings revealed that Bahamian special educators left special education because of (a) lack of support, (b) inadequate training, and (c) burnout, resulting in poor job satisfaction.
Politicising the debate on urban sprawl: The case of the Lyon metropolitan region
Authors: Charmes Eric , Rousseau Max , Amarouche Maryame
Published: September 2020

The fight against urban sprawl has become an international motto for planners. However, recent urban policies promoting ‘smart growth’ and ‘new urbanism’ are the subject of growing criticism from various scientific disciplines. This paper goes beyond the debate for or against sprawl to examine the political and social issues behind anti-sprawl policies. We show how and why urban compaction can be perceived as a burden or a resource, depending on the different sub-metropolitan territories concerned. These issues are discussed in the case of the second largest metropolitan area in France, the region of Lyon. The paper analyses how the national legislation on urban sprawl and the ‘compact city’ is implemented in the very diverse territories within Lyon’s metropolis and how some of those territories use it to their advantage. It reveals that the resulting compromises are deceptive and raise spatial justice issues. It also shows how compaction or densification are negotiated in the suburbs to preserve the status quo in wealthy municipalities.
A Manager’s Guide to Free Speech and Social Media in the Public Workplace: An Analysis of the Lower Courts’ Recent Application of Pickering
Authors: Brewer Adam M.
Published: September 2020

Public organizations are experiencing a burgeoning of workplace challenges involving employee use of social media. Comments, images, or videos ranging from racist remarks, to calls to violence, simple criticism of one’s organization, to full on whistle blowing significantly challenge public organizations’ policies for addressing speech that creates discord in the workplace. With the blurring of lines between personal and professional lives, these challenges create uncertainty for public organizations regarding how to maintain the efficient operation of the workplace, deal with the social and political fallout of such instances, and manage organizational liability. This article performs content analysis on 33 federal lower court opinions involving speech/social media workplace issues. The study analyzes the manner in which the lower courts apply free speech precedent on contemporary workplace speech cases. The findings suggest that patterns emerge from the opinions providing key insights for public managers regarding how to better manage these complex issues.