bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB-204: Oncogenic Ras signaling requires serine protease hepsin to induce invasive breast cancer phenotype
Authors: Pant Shishir Mani , Tervonen Topi , Belitskin Denis , Englund Johanna , Verschuren Emmy , Kovanen Panu , Klefstrom Juha
Published: September 2020

Invasive cancer growth occurs when epithelial tumor cells individually or collectively detach from the primary tumor and migrate into the adjacent healthy tissue. This process starts a gradual tumor progression that may lead to life-threatening metastatic disease. Hepsin is a type II transmembrane serine protease that is frequently overexpressed in breast, prostate, and other epithelial cancers. It promotes tumor progression through activating growth factors and disrupting cell-cell and cell-basement membrane (BM) junctions. Although hepsin participates in pericellular cancer degradome, the oncogenic upstream mechanisms that activate hepsin in cancer are not well known. We found that oncogenic Ras proteins by activating MAPK pathway signaling alter the ratio of hepsin and HAI-1 to increase the proteolytic activity of hepsin. In 3D epithelial culture models of Ras-driven cancer, depletion of hepsin by shRNA restored desmosomes, BM defects, and glandular morphology but not the apical polarity. Mechanistically, Ras-MAPK pathway affected hepsin/HAI-1 via two distinct downstream pathways: Hepsin protein was stabilized via Ras-induced and heat shock transcription factor-1-mediated stress pathway, whereas HAI-1 was down-regulated by Ras via tumor suppressor LKB1 and PI3K-dependent pathways. Altogether, the results suggest that abnormal activation of Ras-MAPK pathway elevates hepsin activity to execute early steps of breast cancer invasion.

Citation Format: Shishir Mani Pant, Topi Tervonen, Denis Belitskin, Johanna Englund, Emmy Verschuren, Panu Kovanen, Juha Klefstrom. Oncogenic Ras signaling requires serine protease hepsin to induce invasive breast cancer phenotype [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 LB-204.
Abstract LB-209: Integrative analysis of recurrent-metastatic progression in high-risk human papillomavirus cervical carcinomas
Authors: Choi Youn Jin , Jung Yu Yeon
Published: September 2020

Purpose: The acquisition of recurrent/metastatic potential by a tumor cell defines a critical step of malignant progression. However, the understanding of metastatic progression at the molecular level is scarce for cervical carcinomas (CES).

Materials and Methods: In this study, we performed comprehensive genomic, transcriptomic and viral profiling of five pairs of primary (CES-P) and matched recurrent/metastatic tumors (CES-R/M) with high risk human papillomavirus.

Results: Whole exome sequencing revealed mutation features of CES-R/M such as elevated mutation burdens and prevalent copy number alterations compared to their matched CES-P. A relative deficit of APOBEC-related mutation signatures accompanying the transcriptional down-regulation of APOBEC3A was also observed for CES-R/M. Mutations on genes encoding epigenetic regulators were also commonly observed as CES-R/M-specific alterations. Immunoprofiling and gene set analysis further revealed that CES-P were enriched with transcripts representing activated anticancer immunity such as cytolytic scores and interferon-gamma pathway but CES-R/M showed the up-regulation of genes involved in epithelial-mesenchymal transition and angiogenesis. Viral capture sequencing also revealed the hotspots of viral integration such as 12q13. Moreover, we found that the transcriptional upregulation of POSTN and downregulation of APOBEC3A were associated with unfavorable clinical outcomes in CES.

Conclusions: The comprehensive genomic and transcriptomic profiling of a rare cohort including CES-R/M identified metastases-specific features to advance the molecular understanding into the CES metastatic progression with potential clinical implication.

Citation Format: Youn Jin Choi, Yu Yeon Jung. Integrative analysis of recurrent-metastatic progression in high-risk human papillomavirus cervical carcinomas [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 LB-209.
Abstract LB-234: Development of HER2 targeted HSP90 inhibitors delivery system
Authors: Lim Kwangsuk , Hong Yudong , Won Young-Wook
Published: September 2020

Heat shock protein 90 (HSP90) plays a crucial role in the survival and growth of cancer cells by improvement of the stability and activity of many signaling proteins such as Akt, Raf-1 and HER2/neu. HSP90 inhibitors (HSP90i) such as geldamanycin (GM), AUY922 and STA-9090 have been developed for inhibition of multiple signaling pathways that are initiated by HSP90. Although geldanamycin derivatives (GM) which is the first class of HSP90 inhibitors were disappointing in the initial clinical trials, these studies have shown promise in patients with HER2 positive cancers. To improve anticancer efficacy of HSP90i, HER2 targeted HSP90i delivery system (HER2-HBD) was constructed because of difficulty in chemical modification of HSP90i. HER2-HBD consist of HER2 scFv and HSP90i binding domain, was expressed from 293 cells. This system could incorporate HSP90i into recombinant antibody fusion protein based on biological binding affinity. HER2-HBD and HSP90i was spontaneously formed HER2-HBD/HSP90i complex. HER2-HBD/HSP90i complex specifically delivered HSP90i into HER2 positive cancer cell and reduced cancer cell growth in vitro and in vivo test. HER2-HBD recombinant system based on biological affinity between HSP90i and HBD was not required chemical reaction to conjugate antibody and drug. This system might be useful targeted delivery systems for HSP90i without tailored conjugation method to develop antibody-drug conjugate (ADC) and also applied to develop targeted delivery systems for biological inhibitor drugs.

Citation Format: Kwangsuk Lim, Yudong Hong, Young-Wook Won. Development of HER2 targeted HSP90 inhibitors delivery system [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 LB-234.
Abstract LB-244: A proteomics validated pipeline for detection of differential and tumor-specific splice events
Authors: Halperin Rebecca F. , Hegde Apurva , Lang Jessica , Raupach Elizabeth , Pirrotte Patrick , Schork Nicholas
Published: September 2020

Splicing dysregulation is a common feature of cancer, and may produce tumor specific proteins that have altered function or antigenicity. While many tools are available to detect splicing in RNAseq data, robust methods for translating the effects of alternative splicing to altered protein sequences are lacking. In addition, statistical approaches for detecting splicing defects in a tumor compared to normal tissues are only now being considered by bioinformaticians. We have developed a protein sequence generation method and splicing outlier detection strategy and validated this pipeline using a dataset with matched RNAseq and mass spectrometry data from normal tissues. Splice events were detected using SplAdder and our protein sequence generation and annotation tools were implemented in python. We developed a novel approach to outlier detection using a beta binomial model, where splice isoform read counts are modeled with a binomial distribution, and the expected proportion of each splice isoform (‘percent spliced in' or ‘PSI') is modeled as the beta distribution based on the PSI observed in a reference dataset. In a normal tissue validation dataset, we detected isoform-specific peptides for 77,369 splice events, including 2,171 that encode novel protein sequences. Both isoforms were detected for 1,476 of these events, and 271 events showed tissue exclusive detection patterns. To evaluate our proposed outlier detection method, we used a set of gastrointestinal (GI) tissues as a reference set and looked for outlier splice events in normal brain, tonsil, and ovarian tissues. We identified examples of peptides where one isoform was exclusively detected in the GI tissues and the other isoform was detected in one of the other tissues. Our outlier detection method was able to predict these events from the RNAseq data with better specificity compared to thresholds set using the distribution of PSIs. We also implemented a differential splicing test using the beta binomial model and benchmarked it against the more commonly used negative binomial model using the normal tissue dataset, and found our proposed method improved sensitivity and specificity. We then applied our splicing outlier detection pipeline to tumor data from TCGA using GTEx as a reference set, and were able to identify tumor specific splice events that generated novel protein sequences. Our splicing pipeline enables the identification of tumor-specific isoforms which may be candidate targets for immunotherapies.

Citation Format: Rebecca F. Halperin, Apurva Hegde, Jessica Lang, Elizabeth Raupach, Patrick Pirrotte, Nicholas Schork. A proteomics validated pipeline for detection of differential and tumor-specific splice events [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 LB-244.
Abstract LB-246: Venice: A new algorithm for finding marker genes of single-cell populations in tumor microenvironment
Authors: Pham Son , Vuong Hy , Truong Thao
Published: September 2020

Most widely used tools for finding marker genes insingle-cell data(SeuratT/NegBinom/Poisson, CellRanger, EdgeR, limmatrend) rely on a conventional definition of differentially expressed genes from bulk RNA-seq: genes with different means of expression values . However, in single-cell data (e.g., cell populations in tumor microenvironments), a cell population can be a mixture of many cell types/cell states, hence the mean expression of genes cannot represent the whole population. In addition, these tools assume that the gene expression of a population belongs to a specific family of distribution. This assumption is often violated in single-cell data. In this work, we define marker genes of a cell population as genes that can be used to distinguish cells in the population from cells in other populations. Besides log-fold change, we devise anew metric to classify genes into up-regulated, down-regulated, and transitional states. In a benchmark for finding up-regulated and down-regulated genes, our tool outperforms all compared methods, including Seurat, ROTS, scDD, edgeR, MAST, limma, normal t-test, Wilcoxonand Kolmogorov-Smirnov test. Our method is much faster than all compared methods, therefore, it enables interactive analysis for large single-cell data sets in BioTuring Browser (https://bioturing.com/bbrowser).

Citation Format: Son Pham, Hy Vuong, Thao Truong. Venice: A new algorithm for finding marker genes of single-cell populations in tumor microenvironment [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 LB-246.
Abstract LB-254: The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life
Authors: Morales Joanna , Bryant Monica
Published: September 2020

A cancer diagnosis may carry with it a variety of legal issues, including insurance coverage, government benefits, and consumer rights. These legal issues can cause people unnecessary worry, confusion, and stress, and can be overwhelming. The Insurance and Finance Intensive is focused on providing healthcare professionals tools to proactively identify the presence of cancer-related legal, health insurance, and financial issues facing their patients. Additionally, the training helps health care professionals to offer referrals to appropriate legal and related resources, once those issues are identified. Oncology healthcare professionals participated in an eight-hour comprehensive training. Attendees were provided with substantive information about cancer-related legal issues, such as identifying health insurance options, navigating disability insurance and appeals, and managing finances. A follow-up survey was sent to all past intensive attendees to measure the effectiveness of the training and to address any lingering questions and difficult case studies. Ninety-four percent of survey respondents strongly agreed or agreed that the information provided by the training helped them reduce the stress and anxiety of their patients and their families. Ninety-two percent of survey respondents strongly agreed or agreed that the information provided by the training improved the quality of life of their patients and their families. The Insurance & Finance Intensive successfully provided health care professionals with valuable information on the practical and legal issues that impact individuals diagnosed with cancer. It is recommended that more healthcare professionals participate in this training to improve the quality of life of their patients beyond diagnosis.

Citation Format: Joanna Morales, Monica Bryant. The effectiveness of healthcare professional training on the legal issues impacting individuals diagnosed with cancer to improve patient quality of life [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 LB-254.
Abstract LB-264: Biodynamic chemotherapy selection in breast cancer patients
Authors: An Ran , Turek John , Nolte David , Loesch David , Morgan Travis
Published: September 2020

Purpose: Biodynamic signatures (temporal patterns of microscopic motion within a three-dimensional tumor explant) offer a phenomic biomarker that is highly predictive for therapeutic response. The purpose of this study is to evaluate predictive accuracy of a biodynamic drug response classifier in breast cancer patients receiving neoadjuvant chemotherapy (NAC). Methods: Consecutive breast cancer patients from 4 institutions were screened for enrollment in a prospective observational study (NCT03164863). Treatment-naïve needle biopsies were delivered to a central laboratory where biodynamic signatures were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received NAC per institutional guidelines and were followed through surgical intervention. A four-point classifier was trained to predict pathologic complete response (CR) then prospectively validated. Results: Among patients completing neoadjuvant treatment and surgical intervention, 33% (24 of 72) achieved CR. The biodynamic classifier predicted CR with 96% sensitivity and 97% negative predictive value. Biodynamically “favored” (scoring ≥ 3) and “strongly favored” (scoring 4) regimens produced CR at rates of 56% (23 of 41) and 73% (19 of 26), respectively. Only 3% of patients (1 of 31) achieved CR from regimens scoring 1 or 2. Area under the receiver operating curve (AUC) was 87% (95% CI: 75% to 93%, p <.0001), with similar performance across all subtypes and therapy cohorts (range: 84% to 89%). Performance of the classifier on training and validation patients was statistically equivalent. Conclusion: Biodynamic scoring accurately predicts response in breast cancer patients receiving NAC and holds promise to substantially improve management of these patients.

Chemotherapy response distribution by biodynamic scoreBiodynamic ScoreNo ResponsePartial ResponseComplete ResponseTotal111 (58%)7 (37%)1 (5%)1922 (17%)10 (83%)0 (0%)1231 (7%)10 (67%)4 (27%)1540 (0%)7 (27%)19 (73%)26Totals14 (19%)34 (47%)24 (33%)72

Citation Format: Ran An, John Turek, David Nolte, David Loesch, Travis Morgan. Biodynamic chemotherapy selection in breast cancer patients [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 LB-264.
Abstract LB-272: T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation
Authors: Gittelman Rachel M. , Leick Mark , DeFilipp Zachariah , Ritz Jerome , Yusko Erik , Sanders Catherine , Robins Harlan
Published: September 2020

Delayed reconstitution of the immune system after allogeneic hematopoietic cell transplantation (HCT) is a long-recognized complication. Specifically, loss of T-cell diversity has been implicated in infectious complications, graft-versus-host disease (GVHD), and disease relapse. We performed serial high-resolution next generation sequencing using the immunoSEQ® Assay (Adaptive Biotechnologies, Seattle, WA) to characterize the TCRβ locus in 99 HCT recipients in the first 3 months after transplant. Transplant donor type included unrelated (n=57) and related (n=42) donors. Conditioning regimen intensity included reduced intensity (n=55) and myeloablative (n=44). We measured T-cell fraction, clonality, and richness in the donor and at days +15, +30, +50 and +100 post-transplant in the recipient, and correlated metrics to clinical variables. In agreement with prior studies, we found that although absolute T-cell numbers recover relatively quickly after transplant, repertoire diversity remains diminished. Restricted diversity was associated with conditioning intensity, use of ATG, and donor type. Increased T-cell clonal expansion at Day +30 compared to the donor sample was associated with the incidence of acute GVHD (HR=1.11, p=5x10-5). Even after exclusion of the twelve patients who had experienced acute GVHD by day +30, the association between acute GVHD and clonal expansion persisted (HR=1.098, p=0.041), indicating that clonal expansion preceded the development of acute GVHD. Our results indicate the importance of early post-transplant sampling and highlight T-cell clonal expansion as a potential novel biomarker for GVHD which warrants further study.

Citation Format: Rachel M. Gittelman, Mark Leick, Zachariah DeFilipp, Jerome Ritz, Erik Yusko, Catherine Sanders, Harlan Robins. T-cell clonal dynamics determined by high resolution TCR-β sequencing in recipients of allogeneic hematopoietic cell transplantation [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 LB-272.
Abstract LB-354: Immune phenotyping of diverse syngeneic brain tumors identifies critical tumor micro-environmental differences
Authors: Khalsa Jasneet K. , Keegan Joshua W. , Cheng Nina , Driver Joseph , Chaudry Ameen , Bi Wenya Linda , Lederer James A. , Shah Khalid
Published: September 2020

Immunotherapy has emerged as a promising approach to treat cancer, however, its efficacy in highly malignant brain-tumors, glioblastomas (GBM), is limited. Pre-clinical syngeneic mouse models are at the forefront of testing and understanding emerging novel immune based therapies prior to their translation in patients. We generated distinct imageable syngeneic GBM-tumor models and assessed tumor infiltrating immune cells from end-stage tumors by utilizing RNA sequencing, CyTOF (mass Cytometry by Time of Flight) and correlative immunohistochemistry. CyTOF facilitates multiparametric analysis of up to 40 different markers which is useful especially in the case of GBM where number of TILs is limiting. We identified immunologically-inert and active syngeneic tumor types and show that inert tumors have an immune-suppressive phenotype with numerous MDSCs (Ly6C+ CD11b+), exhausted CD8 T cells and fewer eosinophils. To mimic the clinical settings of first line of GBM treatment, we performed tumor resection in an immunologically inert tumor model. We show that tumor-resection invigorates an anti-tumor response via significant increase in CD8+ T cells, monocyte/macrophages and decrease in Ly6G+ myeloid cells. A comparative CyTOF analysis of resected-tumor samples from GBM patients and mouse GBM tumors showed stark similarities in one of the mouse GBM tumors tested. These findings guide informed choices for use of GBM models for immunotherapeutic interventions and offer a potential to facilitate immune-therapies in GBM patients.

Citation Format: Jasneet K. Khalsa, Joshua W. Keegan, Nina Cheng, Joseph Driver, Ameen Chaudry, Wenya Linda Bi, James A. Lederer, Khalid Shah. Immune phenotyping of diverse syngeneic brain tumors identifies critical tumor micro-environmental differences [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 LB-354.
Abstract LB-360: Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells
Authors: Wang Jing , Hall Matthew , Bushnell Grace , Decker Joseph , Orbach Sophia , Raghani Ravi , Zhang Yining , Morris Aaron , Ma Jeffery , Kandagatla Pridvi , Jeruss Jacqueline , Shea Lonnie
Published: September 2020

Immune signaling within a metastatic niche drives recruitment and colonization, and the subsequent tumor cell fate within the niche. We employed a biomaterial scaffold as a synthetic metastatic niche to dissect the signals driving the responses within the niche relative to the native metastatic niche, which was the lung in these models. For both the natural and the synthetic niche, Gr-1+ cells secreting S100A8/A9 were the major factors contributing to tumor cell recruitment. Interestingly, upon recruitment, tumor cells in the synthetic niche were observed to undergo senescence and were cleared whereas cells within the native niche accumulated and ultimately proliferated to form macrometastases. The synthetic niche has underlying inflammation due to the foreign body responses (FBR) consisting of N1-polarized Gr1+ myeloid cells, M1-polarizedmacrophage, mature dendritic cells and highly cytotoxic CTLs and NK cells, which were not observed in the lung. Furthermore, we found two proteins (osteopontin and decorin) that are associated with developing FBR greatly improve the cytotoxicity of CTLs and NK cells in the lung from stage 3 breast cancers by increasing their production of Perforin/Granzyme, Fas/TRAIL and IFNr/TNFa. Our results highlight the potential of FBR-associated biomolecules to be used as immune-editing anticancer drugs and also inspire the development of therapeutic implants to actively catch and eradicate metastatic cells.

Citation Format: Jing Wang, Matthew Hall, Grace Bushnell, Joseph Decker, Sophia Orbach, Ravi Raghani, Yining Zhang, Aaron Morris, Jeffery Ma, Pridvi Kandagatla, Jacqueline Jeruss, Lonnie Shea. Foreign body responses create a highly active anti-tumor environment to recruit and eradicate metastatic cells [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 LB-360.
Prognostic Roles of Neutrophil-to-Lymphocyte Ratio and Stromal Tumor-Infiltrating Lymphocytes and Their Relationship in Locally Advanced Triple-Negative Breast Cancer Treated with Neoadjuvant Chemotherapy
Authors: Dong Xue , Liu Congfang , Yuan Jiaqi , Wang Shouman , Ding Nianhua , Li Yong , Wu Yuhui , Xiao Zhi
Published: September 2020

Introduction: The neutrophil-to-lymphocyte ratio (NLR) and stromal tumor-infiltrating lymphocytes (sTILs) are associated with immunogenicity and prognosis of patients with triple-negative breast cancer (TNBC). Objective: To investigated the prognostic roles of NLR and sTILs and their rela­tionship of TNBC patients treated with neoadjuvant chemotherapy (NAC). Methods: The clinical data of 170 patients with locally advanced TNBC who received NAC from January 2010 to December 2014 were collected. The difference among variables was calculated by χ2 test. The association between essential clinicopathological characteristics, pathological complete response (pCR), NLR, and sTILs with disease-free survival (DFS) was analyzed. Kaplan-Meier and Cox analysis were performed to address the effects of clinical parameters on prognosis. Results: There was a trend that TNBC patients with lower baseline NLR (NLR1) or higher sTILs scoring would obtain a better pCR rate. NLR1 and sTILs were not associated (p > 0.05). Patients with low NLR1 or high sTILs scoring had a significantly improved DFS compared to those with high NLR1 or low sTILs scoring (p = 0.002 and p = 0.001, respectively). The increased lymphocyte count in peripheral blood after NAC was associated with the improved DFS outcome in both high and low NLR1 groups. Cox analysis revealed that NLR1 and sTILs were independent prognostic predictors of DFS outcome (p < 0.001). Conclusion: Low NLR1 and high sTILs were associated with better DFS outcome in locally advanced TNBC patients treated with NAC. Further studies are needed to explore the connection between systemic and local inflammatory/immune markers.
The Genetic and Clinical Significance of Fetal Hemoglobin Expression in Sickle Cell Disease
Authors: Adekile Adekunle
Published: September 2020

Sickle cell disease (SCD) is phenotypically heterogeneous. One major genetic modifying factor is the patient’s fetal hemoglobin (HbF) level. The latter is determined by the patient’s β-globin gene cluster haplotype and cis- and trans-acting single nucleotide polymorphisms (SNPs) at other distant quantitative trait loci (QTL). The Arab/India haplotype is associated with persistently high HbF levels and also a relatively mild phenotype. This haplotype carries the Xmn1 (C/T) SNP, rs7482144, in the HBG2 locus. The major identified trans-acting QTL contain SNPs residing in the BCL11A on chromosome 2 and the HMIP locus on chromosome 6. These collectively account for 15–30% of HbF expression in different world populations and in patients with SCD or β-thalassemia. Patients with SCD in Kuwait and Eastern Saudi Arabia uniformly carry the Arab/India haplotype, but despite this, the HbF and clinical phenotypes show considerable heterogeneity. Pain episodes and avascular necrosis of the femoral head are particularly common, but severe bacterial infections, stroke, priapism, and leg ulcers are uncommon. Moreover, the HbF modifiers appear to be different; the reported BCL11A and HMIP SNPs appear to play insignificant roles. There are probably novel modifiers to be discovered in this population. This review examines the common clinical phenotypes in Kuwaiti patients with elevated HbF and the available information on HbF modifiers. The response of the patients to hydroxyurea is discussed. The presentation of patients with other sickle compound heterozygotes (Sβthal and HbSD), vis-à-vis their HbF levels, is also addressed critically.
Design of experiments approach for modeling the electrical response of a photovoltaic module
Authors: Zohra Kessaissia Fatma , Zegaoui Abdallah , Taleb Rachid , Fares Chahinez , Aillerie Michel
Published: September 2020

In the current paper, modeling and evaluation of the significant effect of
independent variables on the behavior of the electrical response of a multi-
crystalline photovoltaic (PV) module using design of experiments (DoE)
approach is simulated. The main purpose of this contribution is to evaluate
the maximum power response dependence within the indoor conditions of
both variations of solar irradiation and surface temperature and checking the
pertinent one on the defined response. The DoE approach is used for
estimating both main and combined effect of the two independents
considered variables. Multiple linear regression was been introduced to
justify the relationship between the independent input variables and
dependent output variable, also to determine which input factor is the most
significant on the output variable. The DoE model can be used for predicting
the response variable at different operating condition in a considered domain
study. In addition, DoE approach based on statistical tool for analyzing the
accuracy of the predictive model, then the significance of coefficients in the
predictive model using statistical and graphical analysis. Therefore, an
ANOVA Table can summarize the results, detect the parameters influences
on responses variations and determine the best predictive model then
reproduce the most possible the experimental data.
New improved hybrid MPPT based on neural network-model predictive control-kalman filter for photovoltaic system
Authors: Kacimi Nora , Grouni Said , Idir Abdelhakim , Seghir Boucherit Mohamed
Published: September 2020

In this paper, new hybrid Maximum Power Point Tracking strategy for
Photovoltaic Systems has been proposed. The proposed technique for
control based on a novel combination of an Artificial Neural Network with
an improved Model Predictive Control using Kalman Filter . In this paper the
Kalman Filter is used to estimate the converter state vector for minimized the
cost function then predict the future value to track the Maximum Power
Point with fast changing weather parameters. The proposed control
technique can track the in fast changing irradiance conditions and a small
overshoot. Finally, the system is simulated in the MATLAB/Simulink
environment. Several tests under stable and variable environmental
conditions are made for the four algorithms, and results show a better
performance of the proposed compared to conventional Perturb and
Observation Neural Network based Proprtional Integral Control and Neural
Network based Model Predictive Control in terms of response time,
efficiency and steady-state oscillations.
Biometric authenticator algorithm based on multiresolution analysis
Authors: Kerrache Soumia , Mohammed Beladgham , Aymen Hamza , Ibrahim Kadri
Published: September 2020

Features extraction is an essential process in identifying person biometrics because the effectiveness of the system depends on it. Multiresolution Analysis success can be used in the system of a person’s identification and pattern recognition. In this paper, we present a feature extraction method for two-dimensional face and iris authentication.  Our approach is a combination of principal component analysis (PCA) and curvelet transform as an improved fusion approach for feature extraction. The proposed fusion approach involves image denoising using 2D-Curvelet transform to achieve compact representations of curves singularities. This is followed by the application of PCA as a fusion rule to improve upon the spatial resolution. The limitations of the only PCA algorithm are a poor recognition speed and complex mathematical calculating load, to reduce these limitations, we are applying the curvelet transform.
 To assess the performance of the presented method, we have employed three classification techniques: Neural networks (NN), K-Nearest Neighbor (KNN) and Support Vector machines (SVM).
The results reveal that the extraction of image features is more efficient using Curvelet/PCA.
Performance analysis of flow-based attacks detection on CSE-CIC-IDS2018 dataset using deep learning
Authors: Farhan Rawaa Ismael , Maolood Abeer Tariq , Hassan Nidaa Flaih
Published: September 2020

The emergence of the Internet of Things (IOT) as a result of the development of the communications system has made the study of cyber security more important. Day after day, attacks evolve and new attacks are emerged. Hence, network anomaly-based intrusion detection system is become very important, which plays an important role in protecting the network through early detection of attacks. Because of the development in  machine learning and the emergence of deep learning field,  and its ability to extract high-level features with high accuracy, made these systems involved to be worked with  real network traffic CSE-CIC-IDS2018 with a wide range of intrusions and normal behavior is an ideal way for testing and evaluation . In this paper , we  test and evaluate our  deep model (DNN) which achieved good detection accuracy about  90% .
A hybrid control system for investigating a high level of decision in IoT
Authors: Al-Obaidi Mohanad Ali Meteab , Ali Basim Jamil , H.Ssaud Jamila , Sutikno Tole
Published: September 2020

In the modern world, the search  started  for cheap and efficient operating system sources has begun can converted to civilian ends. Internet of Things (IoT) is one of the most realistic applications for remote control and remote management using a wide network.In this paper, a control system is designed and built to manage and control traffic lights and street lighting systems, as well as turning on/off generators in a small virtual environment. This was implemented by designing and building a hybrid electronic circuit that combines the closed-circuit control system and the open circuit system. The closed circuit regulates the system according to the desired condition without operator interaction; while the open circuit operates on demand. This type of a hybrid control system demonstrated its high flexibility by controlling devices and its high efficiency compared to the closed circuit and the open circuit system independently. It also helps reduce the number of maintenance guys and energy consumption as well as the cost.
Design and implementation DVB-S & DVB-S2 systems
Authors: Jasim Mohammed Samir , Saadi Hussein Zaid
Published: September 2020

Digital video broadcasting plays an important role in most digital communication systems. Digital broadcasting systems are designed with great accuracy and delicate design which has a major role in our lives today especially digital video broadcasting. It is these systems that are considered to be the most advanced in transmission, reception and reliability. From these systems they develop through the digital video broadcasting project group.The most important are digital video broadcasting of terrestrial, digital video broadcasting of cable and digital video broadcasting of satellite because of that many user's desires to use communications and entertainment in their lives there are new and demanding situations that the standards of these systems can only meet for their own applications .In this paper, it will design and implement the digital video broadcasting of satellite first generation and digital video broadcasting of satellite second generation of binary data,image and audio using Matlab-Simulink environment.In addition,  will calculate the bit error rate of the signal. This system is designed with precision to improve performance errors and increase transmission capacity as well as provide a safe environment for information.
Calculating algorithm of service quality statistical parameters for asynchronous network subscribers
Authors: Zhanar Satibaldievna Kemelbekova , O.Z Sembiyev , Zh.R Umarova
Published: September 2020

It is often necessary to determine statistical parameters that characterize the quality of service on the network by managing when designing computer networks using the concept of virtual connections with bypass directions.  In many ways, the attainable level of quality of the services provided is determined at the stage of network design, when decisions was made regarding the subscriber capacity of stations, the capacity of bundles of trunk lines, the composition and volume of telecommunication services provided. Despite constant progress in the field of network technologies, the problem of determining the necessary amount of network resources and ensuring the quality of user service remains relevant. In this regard, this article discusses a broadband digital network with service integration, based on an asynchronous network in which an iterative method implemented. Here the flow distribution is determined by the route matrix, and the load distribution between the nodes of each pair of nodes made through the path tree obtained on the matrix of routes when calculating this pair. At the same time, an algorithm has been built for allow optimal allocation of channel resources between circuit switching and packet switching subnets within an asynchronous network.
Best neural simultaneous approximation
Authors: Almurieb Hawraa Abbas , Bhaya Eman S.
Published: September 2020

For many years, approximation concepts has been investigated in view of neural networks for the several applications of the two topics. Researchers studied simultaneous approximation in the 2-normed space and proved essential theorems concern with existence, uniqueness and degree of best approximation. Here, we define a new 2-norm in -space, with  so we call it  quasi 2- normed space ( ). The set of approximations is a space of feedforward neural networks that is constructed in this paper. Existence and uniqueness of best neural approximation for a function from  is proved, describing the rate of best approximation in terms of modulus of smoothness.
Transición hacia la vida adulta en mujeres de sectores populares (Córdoba, Argentina)
Authors: Cardozo Griselda , González Ana Silvia
Published: September 2020

(analítico): La transición hacia la adultez de los y las jóvenes de sectores populares en Argentina se tornó más prolongada y compleja. Introducir la perspectiva de género al problema obliga a interrogarse si, además, el ser mujer no constituye una dificultad adicional. Este trabajo analiza los modos en los que se produce la transición hacia la vida adulta en mujeres de sectores populares de Córdoba. Es un estudio cualitativo que utiliza como instrumento de recolección de datos el relato biográfico. Se trabajó con 12 mujeres entre 19 y 26 años que concurren a dos centros socioeducativos y laborales. Se concluye que la inserción al mundo adulto no se presenta del mismo modo. Se expresa en recorridos individuales —laborales y educativos— con problemáticas y tensiones que darían lugar a transiciones más o menos favorables.
Evaluación de la Escala de Identidad Étnica en adolescentes mapuche de Chile
Authors: Briceño-Olivera Claudio , Tereucán-Angulo Julio , Galván-Cabello Miguel , Miranda-Vargas Horacio
Published: September 2020

(analítico) Los estudios evidencian que la identidad étnica es un factor protector para sociedades con relaciones interétnicas e interculturales desiguales. Sin embargo, los instrumentos para su medición presentan escasas validaciones psicométricas en contextos indígenas chilenos y latinoamericanos. El estudio evaluó las propiedades psicométricas de la Escala de Identidad Étnica en una muestra de 501 adolescentes indígenas mapuche con una edad promedio de 15.63 años. Los análisis factoriales exploratorios y confirmatorios evidenciaron una estructura factorial coincidente con la propuesta teórica de tres factores (exploración, resolución y afirmación), la cual explicó el 76 % de la varianza. El análisis de fiabilidad indicó un alfa ordinal de .90 para la escala total y el análisis correlacional demostró validez externa. Se concluyó que la escala presenta evidencia psicométrica para su uso en población adolescente mapuche.
An Important Role for DNMT3A-Mediated DNA Methylation in Cardiomyocyte Metabolism and Contractility
Authors: Madsen Alexandra , Höppner Grit , Krause Julia , Hirt Marc N. , Laufer Sandra D. , Schweizer Michaela , Tan Wilson Lek Wen , Mosqueira Diogo , Anene-Nzelu Chukwuemeka George , Lim Ives , Foo Roger S.Y. , Eschenhagen Thomas , Stenzig Justus
Published: September 2020

Background:

DNA methylation acts as a mechanism of gene transcription regulation. It has recently gained attention as a possible therapeutic target in cardiac hypertrophy and heart failure. However, its exact role in cardiomyocytes remains controversial. Thus, we knocked out the main de novo DNA methyltransferase in cardiomyocytes, DNMT3A, in human induced pluripotent stem cells. Functional consequences of DNA methylation-deficiency under control and stress conditions were then assessed in human engineered heart tissue from knockout human induced pluripotent stem cell–derived cardiomyocytes.

Methods:

DNMT3A
was knocked out in human induced pluripotent stem cells by CRISPR/Cas9gene editing. Fibrin-based engineered heart tissue was generated from knockout and control human induced pluripotent stem cell–derived cardiomyocytes. Development and baseline contractility were analyzed by video-optical recording. Engineered heart tissue was subjected to different stress protocols, including serum starvation, serum variation, and restrictive feeding. Molecular, histological, and ultrastructural analyses were performed afterward.

Results:

Knockout of
DNMT3A
in human cardiomyocytes had three main consequences for cardiomyocyte morphology and function: (1) Gene expression changes of contractile proteins such as higher atrial gene expression and lower MYH7/MYH6 ratio correlated with different contraction kinetics in knockout versus wild-type; (2) Aberrant activation of the glucose/lipid metabolism regulator peroxisome proliferator-activated receptor gamma was associated with accumulation of lipid vacuoles within knockout cardiomyocytes; (3) Hypoxia-inducible factor 1α protein instability was associated with impaired glucose metabolism and lower glycolytic enzyme expression, rendering knockout-engineered heart tissue sensitive to metabolic stress such as serum withdrawal and restrictive feeding.

Conclusion:

The results suggest an important role of DNA methylation in the normal homeostasis of cardiomyocytes and during cardiac stress, which could make it an interesting target for cardiac therapy.
Lifelong Aspirin for All in the Secondary Prevention of Chronic Coronary Syndrome
Authors: Jacobsen Alan P. , Raber Inbar , McCarthy Cian P. , Blumenthal Roger S. , Bhatt Deepak L. , Cusack Ronan W. , Serruys Patrick W.J.C. , Wijns William , McEvoy John W.
Published: September 2020

Four decades have passed since the first trial suggesting the efficacy of aspirin in the secondary prevention of myocardial infarction. Further trials, collectively summarized by the Antithrombotic Trialists’ Collaboration, solidified the historical role of aspirin in secondary prevention. Although the benefit of aspirin in the immediate phase after a myocardial infarction remains incontrovertible, a number of emerging lines of evidence, discussed in this narrative review, raise some uncertainty as to the primacy of aspirin for the lifelong management of all patients with chronic coronary syndrome (CCS). For example, data challenging the previously unquestioned role of aspirin in CCS have come from recent trials where aspirin was discontinued in specific clinical scenarios, including early discontinuation of the aspirin component of dual antiplatelet therapy after percutaneous coronary intervention and the withholding of aspirin among patients with both CCS and atrial fibrillation who require anticoagulation. Recent primary prevention trials have also failed to consistently demonstrate net benefit for aspirin in patients treated to optimal contemporary cardiovascular risk factor targets, indicating that the efficacy of aspirin for secondary prevention of CCS may similarly have changed with the addition of more modern secondary prevention therapies. The totality of recent evidence supports further study of the universal need for lifelong aspirin in secondary prevention for all adults with CCS, particularly in stable older patients who are at highest risk for aspirin-induced bleeding.
Possible Dependence of Climate on Atmospheric Mass: A Convection–Circulation–Cloud Coupled Feedback
Authors: Xiong Junyan , Yang Jun , Nie Ji
Published: September 2020

The total mass of the atmosphere [or equivalently, the background surface pressure (SP)] may have varied significantly over the evolutionary histories of Earth and other planets. Atmospheric mass can affect climate by modifying physical processes, including shortwave scattering, the emissivity of greenhouse gases, the atmospheric heat capacity, and surface fluxes. We apply a three-dimensional global climate model to explore the dependence of climate on SP over the range of 0.5–2.5 bar. Our simulations show an intriguing, nonmonotonic dependence of climate on SP. Over the SP range of 0.5–0.9 and 1.5–2.5 bar, the surface temperature increases with SP; however, over the SP range of 0.9–1.5 bar, the surface temperature decreases with SP. The negative correlation is due to a convection–circulation–cloud coupled feedback. As SP increases, the moist adiabatic lapse rate increases, leading to upper-troposphere cold anomalies in the tropics and middle latitudes that increase the midlatitude baroclinicity and eddy activity. In association with these changes, the eddy-driven jet is strengthened and shifts equatorward, and two separate westerly jets merge into a single jet. These abrupt circulation changes result in an equatorward shift of the midlatitude cloud belt and reduction of polar clouds, which induce strong negative cloud radiative forcing that cools the climate. Our results demonstrate that the regime transition of flow state (e.g., the merge of jets here) may induce large anomalies in clouds and radiative forcing, resulting in nonlinear climate responses.
Boundary Layer and Surface Verification of the High-Resolution Rapid Refresh, Version 3
Authors: Fovell Robert G. , Gallagher Alex
Published: September 2020

While numerical weather prediction models have made considerable progress regarding forecast skill, less attention has been paid to the planetary boundary layer. This study leverages High-Resolution Rapid Refresh (HRRR) forecasts on native levels, 1-s radiosonde data, and (primarily airport) surface observations across the conterminous United States. We construct temporally and spatially averaged composites of wind speed and potential temperature in the lowest 1 km for selected months to identify systematic errors in both forecasts and observations in this critical layer. We find near-surface temperature and wind speed predictions to be skillful, although wind biases were negatively correlated with observed speed and temperature biases revealed a robust relationship with station elevation. Above ≈250 m above ground level, below which radiosonde wind data were apparently contaminated by processing, biases were small for wind speed and potential temperature at the analysis time (which incorporates sonde data) but became substantial by the 24-h forecast. Wind biases were positive through the layer for both 0000 and 1200 UTC, and morning potential temperature profiles were marked by excessively steep lapse rates that persisted across seasons and (again) exaggerated at higher elevation sites. While the source or cause of these systematic errors are not fully understood, this analysis highlights areas for potential model improvement and the need for a continued and accessible archive of the data that make analyses like this possible.