bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Inducible Nitric Oxide Synthase (iNOS) by Andrographolide and In Vitro Evaluation of Its Antiproliferative and Proapoptotic Effects on Cervical Cancer
Authors: Pasha Akbar , Kumbhakar Divya Vishambhar , Doneti Ravinder , Kumar Kiran , Dharmapuri Gangappa , Poleboyina Pavan Kumar , S. K. Heena , Basavaraju Preethi , Pasumarthi Deepthi , S. D. Annapurna , Soujanya Pavani , Arnold Emeson I. , Bodiga Vijayalaxmi , Pawar Smita C.
Published: March 2021

This work is aimed at investigating the expression levels of inducible nitric oxide synthase (iNOS) in cervical cancer and identifying a potential iNOS inhibitor. The data mining studies performed advocated iNOS to be a promising biomarker for cancer prognosis, as it is highly overexpressed in several malignant cancers. The elevated iNOS was found to be associated with poor survival and increased tumor aggressiveness in cervical cancer. Immunohistochemical and RT‐PCR investigations of iNOS showed significant upregulation of endogenous iNOS expression in the cervical tumor samples, thus making iNOS a potent target for decreasing tumor inflammation and aggressiveness. Andrographolide, a plant‐derived diterpenoid lactone, is widely reported to be effective against infections and inflammation, causing no adverse side effects on humans. In the current study, we investigated the effect of andrographolide on the prognostic value of iNOS expression in cervical cancer, which has not been reported previously. The binding efficacy of andrographolide was analyzed by performing molecular docking and molecular dynamic simulations. Multiple parameters were used to analyze the simulation trajectory, like root mean square deviation (RMSD), torsional degree of freedom, protein‐root mean square fluctuations (P‐RMSF), ligand RMSF, total number of intramolecular hydrogen bonds, secondary structure elements (SSE) of the protein, and protein complex with the time‐dependent functions of MDS. Ligand‐protein interactions revealed binding efficacy of andrographolide with tryptophan amino acid of iNOS protein. Cancer cell proliferation, cell migration, cell cycle analysis, and apoptosis‐mediated cell death were assessed in vitro, post iNOS inhibition induced by andrographolide treatment (demonstrated by Western blot). Results. Andrographolide exhibited cytotoxicity by inhibiting the in vitro proliferation of cervical cancer cells and also abrogated the cancer cell migration. A significant increase in apoptosis was observed with increasing andrographolide concentration, and it also induced cell cycle arrest at G1‐S phase transition. Our results substantiate that andrographolide significantly inhibits iNOS expression and exhibits antiproliferative and proapoptotic effects on cervical cancer cells.
Impact of Defending Strategy Decision on DDoS Attack
Authors: Zhang Chunming
Published: March 2021

Distributed denial‐of‐service (DDoS) attack is a serious threat to cybersecurity. Many strategies used to defend against DDoS attacks have been proposed recently. To study the impact of defense strategy selection on DDoS attack behavior, the current study uses logistic function as basis to propose a dynamic model of DDoS attacks with defending strategy decisions. Thereafter, the attacked threshold of this model is calculated. The existence and stability of attack‐free and attacked equilibria are proved. Lastly, some effective strategies to mitigate DDoS attacks are suggested through parameter analysis.
Safety of Polyethylene Glycol Solution plus Ascorbic Acid for Bowel Preparation for Colonoscopy in Patients with Chronic Kidney Disease
Authors: Ohmiya Naoki , Nakagawa Yoshihito , Horiguchi Noriyuki , Omori Takafumi , Kamano Toshiaki , Funasaka Kohei , Nagasaka Mitsuo , Shibata Tomoyuki
Published: March 2021

Introduction. Polyethylene glycol-electrolyte lavage solution plus ascorbic acid (PEG-ELS-Asc) has been recommended for colonoscopy, but little is known about the safety of PEG-ELS-Asc in patients with chronic kidney disease (CKD). The aim of this study was to determine its safety and efficacy in CKD patients. Methods. Blood and urine samples prospectively collected before and after same-day bowel preparation for colonoscopy with the conventional volume of PEG-ELS-Asc, vital signs before and after colonoscopy, and adverse events within 30 days postcolonoscopy were analyzed in consenting patients with CKD. The cleansing level was evaluated with the Boston bowel preparation score (BBPS) from colonoscopic findings. Results. Of 57 patients enrolled, 1 was excluded for refusal. Serum bicarbonate significantly dropped, and blood hemoglobin, serum total protein, albumin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, and uric acid significantly rose after bowel preparation, although these changes were not clinically important. Only in nondialysis patients did the platelet count and potassium significantly rise, although these changes were not clinically important either. Renal function, such as the urea, creatinine, and estimated glomerular filtration rate, was not significantly altered. An adequate bowel cleansing score,

BBPS
≥
6

, was achieved in 94% of patients. The blood pressure and heart rate were not significantly different between before and after colonoscopy in either nondialysis (

n
=
32

) or dialysis (

n
=
19

) patients. There were no adverse events associated with bowel preparation and colonoscopy within 30 days postcolonoscopy. Conclusions. The conventional volume of same-day bowel preparation with PEG-ELS-Asc may be safe and effective in CKD patients.
Experimental Study on Groutability of Sand Layer concerning Permeation Grouting
Authors: Guo Yan-Xu , Zhang Qing-Song , Zhang Lian-Zhen , Liu Ren-Tai , Chen Xin , Liu Yan-Kai
Published: March 2021

Permeation grouting is widely used in grouting engineering because of its low grouting pressure and minor disturbance to the stratum. However, influenced by the complex properties of sand layer and slurry, an accurate prediction of the groutability of the sand layer remains to be a hard work. In this paper, the permeability of sand layer is studied based on a self‐designed permeation grouting test device, which considers the different sand particle size, relative density of sand layer, slurry water‐cement ratio, and clay content. The influencing factors of sand layer groutability are analyzed, and the different parameters that affect the grouting of sand layer are evaluated, thus proposing a new approach to predict the groutability of sand layer. Results show that the sand particle size and slurry water‐cement ratio are positively related to the groutability of sand layer, and the relative density and clay content of sand layer are negatively correlated with the groutability of sand layer. The proposed alternative empirical formula to estimate the groutability of sand layer will help predict the groutability of sand layer with a higher degree of accuracy, which can provide a certain reference for engineering.
Mechanism and Optimized Process Conditions of Forming One-Dimensional ZnO Nanorods with Al-Doping by Electrodeposition Method
Authors: Chen Jianlin , Zhang Yu , Qiu Wei , Chen Shu , Liu Chang , Peng Zhuoyin , Chen Jian
Published: March 2021

Textured transparent conductive electrodes for thin-film solar cells have been considered as an effective route for enhancing sunlight harvest due to light trapping. Here, we report a self-assembling electrochemical approach for preparing Al-doped ZnO nanorod arrays (NRAs) as light-trapping electrodes from a mixed aqueous solution of zinc nitrate and aluminium nitrate. The mechanism and optimized process conditions of forming one-dimensional ZnO nanorods with Al-doping were systematically investigated. The results showed that Al atoms were successfully doped into ZnO crystal lattice, and the morphologies could be controlled by adjusting the Al3+/Zn2+ ratio in the precursors and deposition time. The Al-doped ZnO films grew into well-aligned hexagonal NRAs with c-axis perpendicular to the substrates and then transited into a mixture of nanosheets and nanorods with Al3+/Zn2+ ratio increasing. They exhibited good electrical conductivity with a sheet resistance of 68-167Ω/square and appropriate visible light transmittance of 61-82%. Taking into account of desired morphology and phase purity, as well as good electrical conductivity and optical transmittance, the optimal window of Al3+/Zn2+ ratio in the precursors was determined between 1 at% and 2 at% with applied potential of -1.5V, bath temperature of 80°C, and deposition time of about 30min. The electrodeposition method provides a facile and efficient route for obtaining large-area textured transparent electrodes at a low cost.
Antimalarial Effect of the Root of Silene macrosolen A. Rich (Caryophyllaceae) on Plasmodium-berghei-Infected Mice
Authors: Atsbha Gebru Hagos , Balasubramanian Rajkapoor , Gebre Abadi Kahsu
Published: March 2021

Background. Malaria remains a major public health problem globally. Poor access to antimalarial drugs compounded with rapidly evolving drug resistance encourages researchers to continuously look for new drugs. Of importance, traditionally used medicines of plant origin are the highest priority as the ethnobotanical claim can be used as an important clue for its safety and efficacy profiles. Silene macrosolen A. Rich (Caryophyllaceae) has been traditionally used for malaria treatment in Ethiopia. Therefore, this study was aimed to evaluate the in vivo antimalarial activity of the plant against Plasmodium-berghei-infected (ANKA strain) Swiss albino mice. Methods. The dried powdered root of Silene macrosolen was extracted using 80% methanol. The crude extract was fractionated using chloroform, ethyl acetate, and distilled water that have different affinities to plant phytoconstituents. The in vivo antimalarial activities of the crude extract were evaluated using 4-day suppressive, prophylactic, and curative tests. The antimalarial activity of the solvent fractions was evaluated in a 4-day suppressive test. The oral acute toxicity of the crude extract was also determined according to the OECD guidelines. Results. The percentage of parasite suppression on the crude extract was 31.02%, 35.82%, and 39.23% in prophylactic, curative, and 4-day suppressive tests, respectively, at the tested dose level of 400 mg/kg. The percentages of chemosuppression of the solvent fractions (400 mg/kg) were 43.07%, 42.61%, and 38.38% in aqueous, ethyl acetate, and chloroform fractions, respectively. Both the crude extract and solvent fractions also significantly prolonged survival time except in the prophylactic test. In addition, prevention of weight loss and reduction in temperature and packed cell volume (PCV) were observed in crude extract as well as solvent fractions. The acute toxicity test of the plant extract also exhibited no sign of toxicity. Conclusion. The result indicated that Silene macrosolen has a significant antimalarial activity, justifying the traditional use of the plant material for treatment of malaria.
HIF‐1, the Warburg Effect, and Macrophage/Microglia Polarization Potential Role in COVID‐19 Pathogenesis
Authors: Ferraro Elisabetta , Germanò Maria , Mollace Rocco , Mollace Vincenzo , Malara Natalia
Published: March 2021

Despite the international scientific community’s commitment to improve clinical knowledge about coronavirus disease 2019 (COVID‐19), knowledge regarding molecular details remains limited. In this review, we discuss hypoxia’s potential role in the pathogenesis of the maladaptive immune reaction against severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The state of infection, with serious respiratory dysfunction, causes tissues to become hypoxic due to a discrepancy between cellular O2 uptake and consumption similar to that seen within tumor tissue during the progression of numerous solid cancers. In this context, the heterogeneous clinical behavior and the multiorgan deterioration of COVID‐19 are discussed as a function of the upregulated expression of the hypoxia‐inducible factor‐1 (HIF‐1) and of the metabolic reprogramming associated with HIF‐1 and with a proinflammatory innate immune response activation, independent of the increase in the viral load of SARS‐CoV‐2. Possible pharmacological strategies targeting O2 aimed to improve prognosis are suggested.
Development of a Semiautomatic Parametric Method for Creation of an I-BIM Model of a Tunnel for Use in FEM Software
Authors: Klinc Robert , Gabršček Dani , Česnik Jure , Žibert Marko , Hostnik Martin , Logar Janko
Published: March 2021

This paper focuses on the design phase of I-BIM tunnelling projects using Sequential Excavation Method (SEM), in Europe, commonly referred to as the New Austrian Tunnelling Method (NATM), and addresses the problem of coupling geotechnical conditions and tunnelling Building Information Model (BIM) for the preparation of the computational model suitable for the finite element analysis method (FEM). The review of the literature led to the conclusion that an automatic merging of the tunnel model and ground model for use in the FEM software is currently not reliable due to the number of differences between various types of models as they serve contrasting needs. Consequently, modelling becomes a manual task, which is very time-consuming and error prone. In this paper, we present the development of a framework for the semiautomatic transformation of the various tunnelling models and respective ground models into the model suitable for further analysis. We conclude that the import and translation of the geometry into the FEM software are most successful and accurate when the initial I- BIM (tunnel) model is prepared at a level of detail appropriate for a computational model. The result is the I-BIM model, fit for use in the FEM software which speeds up the modelling process and reduces errors. We have shown that it is possible to prepare the geometry of a tunnel in the BIM software, transfer it, and use it in the software for geotechnical analysis. This makes the preparation of the tunnel geometry for FEM analysis much easier and faster. Due to the fast preparation of the geometry of the new model, the approach presented in this research is useful in practice. The applicability of the framework and the framework workflow are both presented through a practical case study.
Elevated Plasma Soluble Triggering Receptor Expressed on Myeloid Cells-1 Level in Patients with Acute Coronary Syndrome (ACS): A Biomarker of Disease Severity and Outcome
Authors: Shiber Shachaf , Kliminski Vitaly , Orvin Katia , Sagy Iftach , Vaturi Mordehay , Kornowski Ran , Drescher Michael , Molad Yair
Published: March 2021

Background and Aims. Plasma levels of soluble triggering receptor expressed on myeloid cells (sTREM-1) reflect innate immune cell activation. We sought to evaluate sTREM-1 levels in patients with acute coronary syndrome (ACS) and their predictive value for disease severity and outcome. Methods. Plasma sTREM-1 levels were prospectively measured by ELISA in 121 consecutive patients with new-onset (≤24 h) chest pain at arrival to the emergency department (ED) and 73 healthy controls. Secondary endpoints were the association of plasma levels of sTREM-1 with day 30 and month 6 major adverse cardiovascular events (MACE) defined as death, ACS, stroke, and need for coronary revascularization, as well as with CAD severity. The primary endpoint of the study was the association of plasma sTREM-1 level at the time of admission to the ED with a diagnosis of ACS at day 30. Results. Fifty-nine patients (48.7%) were diagnosed with ACS and 62 (51.3%) with nonspecific chest pain (NSCP). Median plasma sTREM-1 level at admission was significantly higher in the ACS group than the NSCP group and the control group (

539.4
±
330.3

 pg/ml vs.

432.5
±
196.4

 pg/ml vs.

230.1
±
85.5

 pg/ml, respectively;

P
<
0.001

) and positively correlated with the number of stenosed/occluded coronary arteries on angiography (

P
<
0.001

). On logistic regression analysis, higher sTREM-1 levels predicted definite ACS vs. NSCP determined on day 30 (OR 1.29, 95% CI 1.07-1.54,

P
=
0.01

) as well as with recurrent ACS (

P
=
0.04

) and stroke (

P
=
0.02

) at 6 months. Conclusions. Plasma sTREM-1 levels are significantly elevated in patients with ACS and might serve as a biomarker differentiating ACS from NSCP in the ED as well as an inflammatory biomarker for coronary artery disease severity and outcome.
Estimation of Soil Cohesion Using Machine Learning Method: A Random Forest Approach
Authors: Ly Hai-Bang , Nguyen Thuy-Anh , Pham Binh Thai
Published: March 2021

Soil cohesion (C) is one of the critical soil properties and is closely related to basic soil properties such as particle size distribution, pore size, and shear strength. Hence, it is mainly determined by experimental methods. However, the experimental methods are often time‐consuming and costly. Therefore, developing an alternative approach based on machine learning (ML) techniques to solve this problem is highly recommended. In this study, machine learning models, namely, support vector machine (SVM), Gaussian regression process (GPR), and random forest (RF), were built based on a data set of 145 soil samples collected from the Da Nang‐Quang Ngai expressway project, Vietnam. The database also includes six input parameters, that is, clay content, moisture content, liquid limit, plastic limit, specific gravity, and void ratio. The performance of the model was assessed by three statistical criteria, namely, the correlation coefficient (R), mean absolute error (MAE), and root mean square error (RMSE). The results demonstrated that the proposed RF model could accurately predict soil cohesion with high accuracy (R = 0.891) and low error (RMSE = 3.323 and MAE = 2.511), and its predictive capability is better than SVM and GPR. Therefore, the RF model can be used as a cost‐effective approach in predicting soil cohesion forces used in the design and inspection of constructions.
PERLEX: A Bilingual Persian-English Gold Dataset for Relation Extraction
Authors: Asgari-Bidhendi Majid , Nasser Mehrdad , Janfada Behrooz , Minaei-Bidgoli Behrouz
Published: March 2021

Relation extraction is the task of extracting semantic relations between entities in a sentence. It is an essential part of some natural language processing tasks such as information extraction, knowledge extraction, question answering, and knowledge base population. The main motivations of this research stem from a lack of a dataset for relation extraction in the Persian language as well as the necessity of extracting knowledge from the growing big data in the Persian language for different applications. In this paper, we present “PERLEX” as the first Persian dataset for relation extraction, which is an expert-translated version of the “SemEval-2010-Task-8” dataset. Moreover, this paper addresses Persian relation extraction utilizing state-of-the-art language-agnostic algorithms. We employ six different models for relation extraction on the proposed bilingual dataset, including a non-neural model (as the baseline), three neural models, and two deep learning models fed by multilingual BERT contextual word representations. The experiments result in the maximum F1-score of 77.66% (provided by BERTEM-MTB method) as the state of the art of relation extraction in the Persian language.
Perspectives on Care for Late-Stage Parkinson’s Disease
Authors: Rosqvist Kristina , Kylberg Marianne , Löfqvist Charlotte , Schrag Anette , Odin Per , Iwarsson Susanne
Published: March 2021

In the late stage of Parkinson’s disease (PD), there is an increasing disease burden not only for the patients but also for their informal caregivers and the health and social services systems. The aim of this study was to explore experiences of late-stage PD patients’ and their informal caregivers’ satisfaction with care and support, in order to better understand how they perceive the treatment and care they receive. This qualitative substudy was part of the longitudinal European multicentre Care of Late Stage Parkinsonism (CLaSP) project. Individual semistructured interviews were conducted with patients (n = 11) and informal caregivers (n = 9) in Sweden. Data were analysed through the content analysis technique. The final analyses generated one main category: “We are trying to get by both with and without the formal care” and five subcategories: “Availability of health care is important for managing symptoms and everyday life”; “Dependence on others and scheduled days form everyday life”; “There is a wish to get adequate help when it is needed”; “Mixed feelings on future housing and respite care”; and “Family responsibility and loyalty for a functioning everyday life”. Having regular contact with PD-specialised health care was perceived as important. Greater access to physiotherapy was wished for. Maintaining autonomy was perceived as important by patients, in both home health care and a future residential care setting. Responsibility and loyalty between spouses and support from children enabled everyday life to carry on at home, indicating a vulnerability for those without an informal caregiver. The results suggest that regular access to PD-specialised health care is important and that a specialised and multidisciplinary approach to the management of PD symptomatology is likely necessary. Non-PD-specialised staff in home health care and residential care facilities should regularly be given opportunities to obtain PD-specific education and information.
GPR15 Facilitates Recruitment of Regulatory T Cells to Promote Colorectal Cancer
Authors: Adamczyk Alexandra , Pastille Eva , Kehrmann Jan , Vu Vivian P. , Geffers Robert , Wasmer Marie-Hélène , Kasper Stefan , Schuler Martin , Lange Christian M. , Muggli Beat , Rau Tilman T. , Klein Diana , Hansen Wiebke , Krebs Philippe , Buer Jan , Westendorf Astrid M.
Published: March 2021

Colorectal cancer is one of the most frequent malignancies worldwide. Despite considerable progress in early detection and treatment, there is still an unmet need for novel antitumor therapies, particularly in advanced colorectal cancer. Regulatory T cells (Treg) are increased in the peripheral blood and tumor tissue of patients with colorectal cancer. Recently, transient ablation of tumor-associated Tregs was shown to foster CD8+ T-cell–mediated antitumoral immunity in murine colorectal cancer models. However, before considering therapies on targeting Tregs in patients with cancer, detailed knowledge of the phenotype and features of tumor-associated Tregs is indispensable. Here, we demonstrate in a murine model of inflammation-induced colorectal cancer that tumor-associated Tregs are mainly of thymic origin and equipped with a specific set of molecules strongly associated with enhanced migratory properties. Particularly, a dense infiltration of Tregs in mouse and human colorectal cancer lesions correlated with increased expression of the orphan chemoattractant receptor GPR15 on these cells. Comprehensive gene expression analysis revealed that tumor-associated GPR15+ Tregs have a Th17-like phenotype, thereby producing IL17 and TNFα. Gpr15 deficiency repressed Treg infiltration in colorectal cancer, which paved the way for enhanced antitumoral CD8+ T-cell immunity and reduced tumorigenesis. In conclusion, GPR15 represents a promising novel target for modifying T-cell–mediated antitumoral immunity in colorectal cancer.

Significance:

The G protein–coupled receptor 15, an unconventional chemokine receptor, directs Tregs into the colon, thereby modifying the tumor microenvironment and promoting intestinal tumorigenesis.

See related commentary by Chakraborty and Zappasodi, p. 2817
Phase II Clinical Trial of Everolimus in a Pan-Cancer Cohort of Patients with mTOR Pathway Alterations
Authors: Adib Elio , Klonowska Katarzyna , Giannikou Krinio , Do Khanh T. , Pruitt-Thompson Solida , Bhushan Ketki , Milstein Matthew I. , Hedglin Jennifer , Kargus Katherine E. , Sholl Lynette M. , Tsuji Junko , Hyman David M. , Sisk Anne , Shapiro Geoffrey I. , Vargas Hebert A. , Harding James J. , Voss Martin H. , Iyer Gopa , Kwiatkowski David J.
Published: March 2021

Purpose:

This was a multicenter, histology-agnostic, single-arm prospective phase II trial of therapeutic activity of everolimus, an oral mTORC1 inhibitor, in patients with advanced solid tumors that harbored TSC1/TSC2 or MTOR mutations.

Patients and Methods:

Patients with tumors with inactivating TSC1/TSC2 or activating MTOR mutations identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. Patients were treated with everolimus 10 mg once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Whole-exome sequencing was performed to identify co-occurring genomic alterations.

Results:

Between November 2015 and October 2018, 30 patients were enrolled at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. Tumors harbored TSC1 (13/30), TSC2 (15/30), concurrent TSC1 and TSC2 (1/30), or MTOR (1/30) mutations. The most common treatment-related adverse event of any grade was mucositis (8/30, 27%); 1 patient had fatal pneumonitis. Partial responses were seen in 2 patients [7%; 95% confidence interval (CI), 1%–22%]. Median progression-free survival was 2.3 months (95% CI, 1.8–3.7 months) and median overall survival (OS) was 7.3 months (95% CI, 4.5–12.7 months). There was no clear association between other genomic alterations and response. Of the 2 patients with objective response, 1 had upper tract urothelial carcinoma with biallelic inactivation of TSC1 and high tumor mutation burden, and the other had uterine carcinoma with biallelic TSC2-inactivating mutations and PEComa-like pathologic features.

Conclusions:

Everolimus therapy had a disappointing ORR (7%) in this pan-cancer, mutation-selected, basket study.

See related commentary by Kato and Cohen, p. 3807
Proteomic Analysis of Src Family Kinase Phosphorylation States in Cancer Cells Suggests Deregulation of the Unique Domain
Authors: Ruiz-Saenz Ana , Zahedi Farima , Peterson Elliott , Yoo Ashley , Dreyer Courtney A. , Spassov Danislav S. , Oses-Prieto Juan , Burlingame Alma , Moasser Mark M.
Published: March 2021

The Src family kinases (SFK) are homologs of retroviral oncogenes, earning them the label of proto-oncogenes. Their functions are influenced by positive and negative regulatory tyrosine phosphorylation events and inhibitory and activating intramolecular and extramolecular interactions. This regulation is disrupted in their viral oncogene counterparts. However, in contrast to most other proto-oncogenes, the genetic alteration of these genes does not seem to occur in human tumors and how and whether their functions are altered in human cancers remain to be determined. To look for proteomic-level alterations, we took a more granular look at the activation states of SFKs based on their two known regulatory tyrosine phosphorylations, but found no significant differences in their activity states when comparing immortalized epithelial cells with cancer cells. SFKs are known to have other less well-studied phosphorylations, particularly within their unstructured N-terminal unique domains (UD), although their role in cancers has not been explored. In comparing panels of epithelial cells with cancer cells, we found a decrease in S17 phosphorylation in the UD of Src in cancer cells. Dephosphorylated S17 favors the dimerization of Src that is mediated through the UD and suggests increased Src dimerization in cancers. These data highlight the important role of the UD of Src and suggest that a deeper understanding of proteomic-level alterations of the unstructured UD of SFKs may provide considerable insights into how SFKs are deregulated in cancers.

Implications:

This work highlights the role of the N-terminal UD of Src kinases in regulating their signaling functions and possibly in their deregulation in human cancers.
Surface Proteomics Reveals CD72 as a Target for In Vitro–Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL
Authors: Nix Matthew A. , Mandal Kamal , Geng Huimin , Paranjape Neha , Lin Yu-Hsiu T. , Rivera Jose M. , Marcoulis Makeba , White Kristie L. , Whitman Jeffrey D. , Bapat Sagar P. , Parker Kevin R. , Ramirez Jonathan , Deucher Anne , Phojanokong Paul , Steri Veronica , Fattahi Faranak , Hann Byron C. , Satpathy Ansuman T. , Manglik Aashish , Stieglitz Elliot , Wiita Arun P.
Published: March 2021

Alternative strategies are needed for patients with B-cell malignancy relapsing after CD19-targeted immunotherapy. Here, cell surface proteomics revealed CD72 as an optimal target for poor-prognosis KMT2A/MLL1-rearranged (MLLr) B-cell acute lymphoblastic leukemia (B-ALL), which we further found to be expressed in other B-cell malignancies. Using a recently described, fully in vitro system, we selected synthetic CD72-specific nanobodies, incorporated them into chimeric antigen receptors (CAR), and demonstrated robust activity against B-cell malignancy models, including CD19 loss. Taking advantage of the role of CD72 in inhibiting B-cell receptor signaling, we found that SHIP1 inhibition increased CD72 surface density. We establish that CD72-nanobody CAR-T cells are a promising therapy for MLLr B-ALL.

Significance:

Patients with MLLr B-ALL have poor prognoses despite recent immunotherapy advances. Here, surface proteomics identifies CD72 as being enriched on MLLr B-ALL but also widely expressed across B-cell cancers. We show that a recently described, fully in vitro nanobody platform generates binders highly active in CAR-T cells and demonstrate its broad applicability for immunotherapy development.

This article is highlighted in the In This Issue feature, p. 1861
Interference mitigation using antenna selection for the heterogeneous networks
Authors: Khaled Adel , Hassaneen Sally , ElAgooz Salah , Soliman Heba
Published: March 2021

A rapid increase in the wireless internet-based applications led to an enormous increase in wireless data rates. Intensification of future wireless networks faces a great challenge to meet such growing demand for payload data. A suggested solution that can be used to resolve this issue is to overlay small cell networks with macro cell networks to provide higher network capacity and better coverage. Small cell networks experience large interference from macro cell base stations (BSs) making data rates received by the small cell users not reliably. In this paper, an antenna selection scheme based on small cell user’s (SCU) channel gain is proposed. Whereas, the two tiers use the same network bandwidth resources; the macro BS selects a subset of antennas which has a minimum interfering effect to the SCU based on a pilot sent from SCU to macro cell. The proposed selection scheme has been compared with convex optimization antenna selection scheme. Simulation results show that the SCU data rates are significantly improved using proposed scheme. Execution time required for antenna selection is reduced significantly using the proposed scheme.
The first FOSD-tacotron-2-based text-to-speech application for Vietnamese
Authors: Tran Duc Chung
Published: March 2021

Recently, with the development and deployment of voicebots which help to minimize personnels at call centers, text-to-speech (TTS) systems supporting English and Chinese have attracted attentions of researchers and corporates worldwide. However, there is very limited published works in TTS developed for Vietnamese. Thus, this paper presents in detail the first Tacotron-2-based TTS application development for Vietnamese that utilizes the publicly available FPT open speech dataset (FOSD) containing approximately 30 hours of labeled audio files together with their transcripts. The dataset was made available by FPT Corporation with an open access license. A new cleaner was developed for supporting Vietnamese language rather than English which was provided by default in Mozilla TTS source code. After 225,000 training steps, the generated speeches have mean opinion score (MOS) well above the average value of 2.50 and center around 3.00 for both clearness and naturalness in a crowd-source survey.
The search for science and technology verses in Qur’an and hadith
Authors: Taufik Ichsan , Jaenudin Mohamad , Badriyah Fatimah Ulwiyatul , Subaeki Beki , Kurahman Opik Taupik
Published: March 2021

Currently, the Vector Space Model algorithm has been widely implemented for the document search feature because of its reliability in retrieving information. One of them in the search for verses of the Qur'an based on the translation. However, if the phrase or word used is different (even though it has one meaning) with the word in the document in the database, the system will not display the verse. As we know that the Qur'an has a very deep meaning, so an interpretation of the verse is needed. Therefore, this research focuses on implementing the Vector Space Model (VSM) algorithm for searching verses and hadiths in science and technology by using the discussion parameters of these verses or hadiths. The test results obtained with 20 keyword samples using metric recall were 81% with an average time of 2.24 seconds.
An intelligent digital low voltage power factor optimizer
Authors: Nayyef Mustafa Ahmed , Ahmed Yasir Abdulhafedh , Dahham Alazzawi Omar Kamil
Published: March 2021

In this paper, an intelligent digital low voltage power factor optimizer has been built. This power factor optimizer operates according to the measurement the value of phase shift angle between both of current and voltage, thus the power factor has been measured. It is simply that it will improve the power factor through connecting a set of shunt capacitors in order to reach to an optimal value of the power factor (close to unity). The proposed intelligent digital power factor optimizer for low voltage is built and simulated using the software which is called electronic work bench package (EWB) Multisim. Finally, this optimizer presents a good result when applied to different loads and variable currents. This optimizer is feasible, affordable and ready to be implemented especially in countries that suffer from higher prices of electrical power.
A new model for early diagnosis of alzheimer's disease based on BAT-SVM classifier
Authors: Taie Shereen A. , Ghonaim Wafaa
Published: March 2021

Magnetic Resonance Images (MRI) of the Brain is a significant tool to diagnosis Alzheimer's disease due to its ability to measure regional changes in the brain that reflect disease progression to detect early stages of the disease. In this paper, we propose a new model that adopts Bat for parameter optimization problem of Support vector machine (SVM) to diagnose Alzheimer’s disease via MRI biomedical image. The proposed model uses MRI for biomedical image classification to diagnose three classes; normal controls (NC), mild cognitive impairment (MCI) and Alzheimer’s disease (AD). The proposed model based on segmentation for the most involved areas in the disease hippocampus, the features of MRI brain images are extracted to build feature vector of the brain, then extracting the most significant features in neuroimaging to reduce the high dimensional space of MRI images to lower dimensional subspace, and submitted to machine learning classification technique. Moreover, the model is applied on different datasets to validate the efficiency which show that the new Bat-SVM model can yield promising acceptable level of accuracy reached to 95.36 % using maximum number of bats equal to 50 and number of generation equal to 10.
Rasefiberry: Secure and efficient Raspberry-Pi based gateway for smarthome IoT architecture
Authors: Simadiputra Vincent , Surantha Nico
Published: March 2021

Internet-of-Things or IoT technology becomes essential in everyday lives. The risk of security and privacy towards IoT devices, especially smarthomes IoT gateway device, becoming apparent as IoT technology progressed. The need for affordable, secure smarthome gateway device or router that smarthome user prefer. The problem of low-performance smarthome gateways was running security programs on top of smarthome gateway programs. This problem motivates the researcher designing a secure and efficient smarthome gateway using Raspberry Pi hardware as an affordable smarthome gateway device and able to run both smarthome gateways and security programs. In this research, researchers implemented snort as intrusion detection system (IDS), openHab as IoT gateway applications, and well-known encryption algorithms for file encryption in Raspberry PI 3B+ model. The researcher evaluated Snort capability on network attacks and compared each of the well-known encryption algorithm efficiency. From the result, we found Rasefiberry customized snort configuration for Raspberry pi 60 percent of the simulated network attacks. Twofish encryption algorithms were found to have best encryption time, throughput, and power consumption compared to other encryption algorithms in the research. Rasefiberry architecture successfully processes both lightweight security programs and Openhab smarthome gateway programs with a lowperformance computing device such as Raspberry Pi.
The COVID-19 fake news detection in Thai social texts
Authors: Mookdarsanit Pakpoom , Mookdarsanit Lawankorn
Published: March 2021

One important obstruction against Thai COVID-19 recovery is fake news shared on social media that is one of the “Artificial Intelligence Open Issues against COVID-19” reported by Montreal.AI. Misinformation spread is one of the main cyber-security threats that should be filtered out as the IDS for maintaining COVID-19 information quality. To detect fake news in Thai texts, Thai-NLP techniques are necessary. This paper proposes a state-of-the-art Thai COVID-19 fake news detection among word relations using transfer learning models. For pre-training from the global open COVID-19 datasets, the source dataset is constructed by English to Thai translating. The novel feature shifting is formulated to enlarge Thai text examples in target dataset. Machine translation can be used for constructing Thai source dataset to cope with the lack of local dataset for future Thai-NLP applications. To lead the knowledge in Thai text understanding forward, feature shifting is a promising accuracy improvement in fine-tuning stage.
An investigation on the application and challenges for wide area monitoring and control in smart grid
Authors: Ahmed Abdullah Sufyan Marwan , Zuhaib Mohd , Rihan Mohd
Published: March 2021

The complexity and dynamics of the modern power system are continuously changing due to the penetration of a large number of renewable energy sources and changing load patterns. These growing complexities have caused numerous outages around the world, primarily due to the lack of situational awareness about the grid operating states. Rectification of this problem requires advanced sensing technology to accurately capture the dynamics of the system for better monitoring and control. Measurement of synchrophasors is a potential solution to improve situational awareness in the grid. The synchrophasors technology is now widely accepted throughout the world and has the potential to replace the existing SCADA system in monitoring and control of the power system. Their installation enables efficient resolution to substantially improve transmission system planning, maintenance, operation, and energy trading. This paper reviews the state of the art potential applications that the PMU based WAMC offers to the power system. It also includes technical perspectives, challenges, and future possibilities.
A genetic algorithm for prediction of RNA-seq malaria vector gene expression data classification using SVM kernels
Authors: Adebiyi Marion O. , Arowolo Micheal O. , Olugbara Oludayo
Published: March 2021

Malaria larvae embrace unpredictable variable life periods as they spread across many stratospheres of the mosquito vectors. There are transcriptomes of a thousand distinct species. Ribonucleic acid sequencing (RNA-seq) is a ubiquitous gene expression strategy that contributes to the improvement of genetic survey recognition. RNA-seq measures gene expression transcripts data, including methodological enhancements to machine learning procedures. Scientists have suggested many addressed learning for the study of biological evidence. An enhanced optimized Genetic Algorithm feature selection technique is used in this analysis to obtain relevant information from a high-dimensional Anopheles gambiae dataset and test its classification using SVM-Kernel algorithms. The efficacy of this assay is tested, and the outcome of the experiment obtained an accuracy metric of 93% and 96% respectively.
Um panorama dos museus universitários mais visitados no Brasil, entre 2014 e 2018
Authors: Fernandes Ana Veronica Cook
Published: March 2021

A compreensão do papel atualmente desempenhado pelos museus universitários no Brasil passa pela identificação e caracterização dessas instituições, bem como pela análise dos resultados obtidos através das ações por elas empreendidas. Neste sentido, o presente trabalho apresenta um panorama quali-quantitativo dos museus universitários que estiveram presentes na lista dos 100 museus mais visitados no Brasil, conforme  levantamento do Formulário de Visitação Anual compilado pelo Instituto Brasileiro de Museus, referente aos anos de 2014 a 2018. Foram analisados  dados referentes à quantidade de museus universitários, a sua distribuição geográfica no país, ao seu vínculo institucional, às temáticas às quais se dedicam, ao ano de criação da instituição e à condição de preexistência e tombamento ou não de sua sede, realizando-se alguns cruzamentos dos dados para extrair informações adicionais. Não obstante seja um recorte numericamente restrito, ao contemplar as instituições que obtiveram melhor resultado de público nos cinco anos estudados, consideramos se tratar de uma amostragem qualitativamente significativa. Através desse panorama, podemos não apenas visualizar similaridades, mas também lacunas no cenário nacional, como a localização quase exclusiva nas regiões Sul e Sudeste do país; a maior incidência numérica e maior recorrência na lista dos museus vinculados a universidades públicas; e a predominância da temática científica. Esta é certamente uma abordagem parcial do tema dos museus universitários no país, que poderá complementar outras abordagens e apontar caminhos que poderão ser aprofundados em futuras investigações, de forma a possibilitar uma compreensão mais plena do papel que essas instituições desempenham no Brasil.
A formação de alunos bolsistas em museus de ciência: os museus universitários como espaço para a extensão
Authors: Lima Isabel Van Der Ley , Carvalho Cristina
Published: March 2021

O presente trabalho tem como objetivo discutir a formação de alunos de graduação bolsistas de extensão em museus e centros de ciência ligados a universidades. Para tanto, foram enviados questionários aos museus brasileiros cadastrados pela Associação Brasileira de Museus e Centros de Ciência para que fosse feito um levantamento dos museus que possuem alunos bolsistas de extensão. Além disso, foram entrevistados funcionários responsáveis pela formação desses alunos nos museus localizados na cidade do Rio de Janeiro. Na fala dos entrevistados, foi possível notar que a extensãotem seus objetivos ainda em disputa, sendo necessário superar a visão de extensão que se limite à transmissão do conhecimento. Entretanto, também são verificadas falas que indicam que, na formação dos alunos bolsistas, éconsiderada uma visão de extensão dialógica com a sociedade, interdisciplinar e que considera as três dimensões do tripé universitário – ensino, pesquisa e extensão. Desta forma, museus de ciência parecem ser espaços potentes para a formação de mediadores — considerando a produção do conhecimento científico como histórica e culturalmente situada — e para a construção de um ensino de ciências pautado no diálogo entre o conhecimento acadêmico e os saberes do público. Nestas perspectivas, o aluno bolsista de graduação terá, então, papel-chave no processo de mediação entre o conhecimento produzido pela academia e o trazido pelo público aos museus.
Arte moderna no campus da USP: o projeto de recepção do antigo MAM-SP na Universidade
Authors: Magalhães Ana Gonçalves , Brognara Gustavo
Published: March 2021

Durante a década de 1960, a Universidade de São Paulo (USP) tornou-se responsável por um conjunto de coleções histórico-artísticas de grande relevância com a recepção dos acervos que integram seus museus estatutários. No caso do Museu de Arte Contemporânea (MAC-USP), instituído em 1963 a partir da doação das chamadas Coleções Matarazzo, formadas por Francisco Matarazzo Sobrinho (1898-1977) e Yolanda Penteado (1903-1983), havia um projeto anterior ao implantado: o de receber o antigo Museu de Arte Moderna de São Paulo (MAM-SP) na Cidade Universitária. O presente artigo busca apresentar indícios desse projeto através da relação da Universidade com seus interlocutores, com especial atenção ao envolvimento de Mário Pedrosa (1900-1981). Entende-se aqui a criação do MAC-USP como resultante da tentativa de incorporação do MAM-SP e parte integrante de um processo de modernização do país de que a Universidade se firmava como expoente. O artigo é o primeiro resultado da pesquisa de Gustavo Brognara no PPGMus-USP sob orientação de Ana Gonçalves Magalhães. O tema central da dissertação é a história da recepção das obras que fundam o MAC-USP, buscando esclarecer os motivos e os  significados da destinação da coleção do antigo MAM-SP para a Universidade de São Paulo, bem como os projetos e os interesses desta ao recebê-la.
Poison pills e governança corporativa: um estudo no mercado acionário brasileiro
Authors: Azevedo Yuri Gomes Paiva , Gomes Hellen Bomfim , Nakao Sílvio Hiroshi
Published: March 2021

Este estudo tem por objetivo investigar se existe associação entre a adoção de poison pills e os níveis diferenciados de governança corporativa no mercado acionário brasileiro. A amostra é composta por 217 companhias abertas não-financeiras listadas na Brasil, Bolsa, Balcão (B3), com dados disponíveis ao longo do período 2010-2017. A análise de dados realizada por meio de regressões logit e probit evidencia que a adoção de poison pills está positivamente associada à listagem nos segmentos Novo Mercado e Nível 2 de governança corporativa. Assim, a adoção deste dispositivo anti-takeover por companhias que estão listadas nos níveis mais elevados de governança corporativa pode ser útil para atuais e potenciais investidores, ao passo que dado o aumento de companhias abertas com o capital predominantemente disperso no mercado acionário brasileiro, as tentativas de tomada de controle de forma hostil podem ser cada vez mais recorrentes. Além disso, os resultados contribuem teoricamente no sentido de uma possível convergência entre a Teoria da Sinalização e a adoção de poison pills, evidenciando que a adoção desse dispositivo anti-takeover como mecanismo complementar de governança corporativa pode representar um sinal de proteção emitido pelas empresas ao mercado visando a atração de novos investidores.
Abordagem integradora para implementação de um sistema de gestão de segurança e impactos de visitação em áreas naturais protegidas
Authors: Lopez-Richard Victor , Cassiano Andréia Márcia , Aguiar Rodrigo José Silva
Published: March 2021

A gestão de visitação em áreas protegidas age em duas frentes, em geral desconexas: a social e a biofísica. Na prática, a dicotomia entre gestão de segurança e de impactos da visitação transparece no uso de ferramentas díspares que inibe uma ou outra de acordo com a visão e capacitação das equipes envolvidas. Este trabalho propõe sistematizar uma visão integradora onde a qualidade da experiência da visitação, do ponto de vista da segurança da atividade, e as alterações ambientais diretas ou indiretas subsequentes possam ser ponderadas, avaliadas e geridas simultaneamente dentro de um Sistema de Gestão de Segurança e Impactos.