REVIEW | doi:10.20944/preprints202001.0332.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: transcriptomics; aquaculture; genetics; next generation sequencing
Online: 28 January 2020 (05:10:55 CET)
New challenges arise in the face of global climate change which impact every ecosystem on earth, including aquatic systems. This is evident in observations made in regard to the world’s oceans, which show trends of incremental changes in ocean surface temperatures, sea levels, and ocean acidity. These environmental shifts impact human resources such as fisheries and aquaculture. In addition, according to the World Bank, the increase in human population will also require more food and nutrient production, which include industries such as aquaculture. With this increasing demand in aquaculture and fisheries, we must develop efficient and productive methods to operate these industries. We can use genetic methods, specifically transcriptomic information to better understand the biology of our source of nutrition. With the advent of RNASeq techniques, we can provide a better understanding about growth and development, immune function and stress, and adaptations. The use of population genetics or (genomics) to detect Single Nucleotide Polymorphisms (SNPs) between populations or closely related species can provide greater insight from stock structure to fishery-induced evolution. In addition, candidate loci can be investigated further to better understanding evolutionary processes, which provide clues on physiological adaptations and gene expression patterns that can help elucidate how these organisms respond to their current environment. In addition, the use of transcriptomic analyses such as differential gene expression can be used to determine resilience in various environmental conditions such as pollution, hypoxic/anoxic conditions, fluctuations in salinity, and temperature extremes. There has been an increase in transcriptomic studies for many aquaculture species, which has aimed at improving our understanding of growth, development, and metabolism, providing vital information for fisheries and aquaculture industries to make adjustments to environmental conditions such as oxygen availability, nutrition, and salinity. All of these aspects provide insightful information for advancing our knowledge of aquaculture, fisheries and conservation management.
ARTICLE | doi:10.20944/preprints201908.0286.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: MicroRNAs; next generation sequencing; dog; melanoma
Online: 27 August 2019 (16:16:55 CEST)
MicroRNAs (miRNAs) dysregulation contribute the cancer pathogenesis. However, the miRNA profile of canine oral melanoma (COM), one of the frequent malignant melanoma in dog is still unrevealed. The aim of this study is to reveal the miRNA profile in canine oral melanoma. MicroRNAs profile of oral tissues from normal healthy dogs and COM patients were compared by next-generation sequencing. Along with tumour suppressor microRNAs (miRNAs), we report 30 oncogenic miRNAs in COM. Expression of miRNAs were further confirmed by quantitative real-time PCR (qPCR). Pathway analysis showed that deregulated miRNAs impact on cancer and signalling pathways. Three oncogenic miRNAs targets (miR-450b, 301a, and 223) from human study also were down-regulated in COM and had significant negative co-relation with their respective miRNA. Furthermore, we found that miR-450b expression is higher in metastatic cells and regulated MMP9 expression through a PAX9-BMP4-MMP9 axis. In silico analysis indicated that miR-126, miR-20b, and miR-106a regulated the highest numbers of differentially expressed transcription factors in respect to human melanoma. Chromosomal enrichment analysis revealed the X chromosome was enriched with oncogenic miRNAs. We comprehensively analyzed the miRNA’s profile in COM which will be a useful resource for developing therapeutic interventions in both species.
ARTICLE | doi:10.20944/preprints202002.0192.v1
Subject: Biology, Animal Sciences & Zoology Keywords: bacteria; fungi; livestock; microbiome; next generation sequencing
Online: 14 February 2020 (10:32:54 CET)
Ruminal microorganisms play a pivotal role in cattle nutrition. The discovery of the main microbes responsible for enhancing the gain of weight in beef cattle might be used in therapeutic approaches to increase animal performance and cause less environmental damages. Here, we examined differences in bacterial and fungal composition of rumen samples of Braford heifers raised in a natural grassland from Pampa Biome in Brazil. We aimed to detect microbial patterns in the rumen that could be correlated with the gain of weight. 16S and ITS1 genes were amplified from ruminal samples and sequenced to identify the closest microbial relatives within the microbial communities. A predictive model based on microbes responsible for the gain of weight was build and further tested using the entire dataset. The model detected a set of microorganisms associated with animals in the high gain of weight group, including the bacterial taxa RFN20, Prevotella, Anaeroplasma and RF16 and the fungal taxa Aureobasidium, Cryptococcus, Sarocladium, Pleosporales and Tremellales. Most of these organisms have been correlated to the production of substances that improve the ruminal digestion process. These findings provide new insights about cattle nutrition and suggest the use of these microbes to improve beef cattle breeding.
ARTICLE | doi:10.20944/preprints201811.0138.v2
Subject: Life Sciences, Microbiology Keywords: Acinetobacter; ANI; Bangladesh; next-generation sequencing; ATCC
Online: 21 November 2018 (07:07:54 CET)
In this study we announce the draft genome sequence of a newly identified Acinetobacter species cross-reacting with E. coli serotype 0157:H7. The advent of Next-Generation technology has paved to way to discover new species which could otherwise be misidentified using conventional cultural and serotyping methods. The whole genome sequence of this isolate will help to identify potential marker/s of intervention and further genomic analysis might also shed light onto the virulence properties of this newly identified Acinetobacter species which has been provided the new name of Acinetobacter maqsudiensis.
REVIEW | doi:10.20944/preprints201810.0708.v1
Subject: Life Sciences, Genetics Keywords: circular visualization; circos; genomics; next-generation sequencing
Online: 30 October 2018 (07:06:35 CET)
After human genome sequencing and rapid changes in genome sequencing methods, we have entered in the era of rapidly accumulating genome-sequencing data. This has poses development of several types of methods for representing results of genome sequencing data. Circular genome visualizations tools are also critical in this area as they provide rapid interpretation and simple visualization of overall data. In the last 15 years, we have seen rapid changes in circular visualization tools after the development of the circos tool with 1–2 tools published per year. Herein we have summarized and revisited all these tools until the third quarter of 2018.
ARTICLE | doi:10.20944/preprints202205.0225.v1
Subject: Life Sciences, Genetics Keywords: chloroplast; genome; sweet cucumber; Solanaceae; next-generation sequencing
Online: 17 May 2022 (08:38:03 CEST)
Sweet cucumber (Solanum muricatum) sect. Basarthrum, is a neglected horticultural crop native of the Andean region. It is naturally distributed very close to potatoes (Solanum sect. Petota) and tomatoes (Solanum sect. Lycopersicon), two groups of high economic importance. To date, molecular tools for this crop are still undetermined. We here obtained the first complete chloroplast (cp) genome of sweet cucumber and compared with seven Solanaceae species. Pair-end clean reads were obtained by PE 150 library and the Illumina HiSeq 2500 platform. The complete cp genome of S. muricatum had a 155,681 bp with typical quadripartite structure, containing a large single copy (LSC) region (86,182 bp) and a small single-copy (SSC) region (18,360 bp), separated by two inverted repeat (IR) regions (25,568 bp). The annotation of chloroplast genome predicted 88 protein-coding genes (CDS), 8 ribosomal RNA (rRNA) genes, 37 transfer RNA (tRNA) genes, and one pseudogene. A total of 48 perfect microsatellites were identified, divided in mononucleotide repeats (32), followed by tetranucleotide (6) and dinucleotides (5). SSRs with trinucleotides repeats (3), pentanucleotide (1) and hexanucleotide (1) repeats motifs in these genomes were identified in lower quantity. Most of these repeats were distributed in the noncoding regions. Whole chloroplast genome comparison with the other seven Solanaceae species revealed that the small and large single copy regions showed more divergence than inverted regions. Finally, phylogenetic analysis resolved that S. muricatum is a sister species to members of sections Petota + Lycopersicum + Etuberosum. This study reports for the first time the genome organization, gene content, and structural features of the cp genome of S. muricatum. Also, this study may provide the basis for evaluating genetic diversity within Solanum, and will be useful to examine the evolutionary processes in sweet cucumber landraces.
ARTICLE | doi:10.20944/preprints202103.0374.v1
Subject: Life Sciences, Biochemistry Keywords: cfDNA; next generation sequencing; full marathon; exercise; physiology
Online: 15 March 2021 (11:52:33 CET)
Plasma cell-free DNA (cfDNA) is frequently analyzed using liquid biopsy to investigate cancer markers. Accordingly, we hypothesized this concept could be applied to the field of exercise physiology. Here, we aimed to identify specific cfDNA (spcfDNA) sequences in the plasma of non-treated human participants using next generation sequencing (NGS) and to clearly define the dynamics regarding the amounts of spcfDNA-fragments upon extreme exercise, such as running a full marathon. NGS analysis was performed using cfDNA of pooled plasma collected from non-treated participants. We confirmed the TaqMan-qPCR assay had a high sensitivity and found the spcfDNA sequence abundance was 16,600-fold higher than a normal genomic region. We then used the TaqMan-qPCR assay to investigate the dynamics of the levels of spcfDNA-fragments upon running a full marathon. Quantities of the spcfDNA fragments were significantly increased post marathon. Furthermore, the amounts of spcfDNA fragments strongly correlated with the numbers of white blood cells and plasma myoglobin concentrations. These results suggest the spcfDNA fragments identified in this study were highly sensitive response markers to extreme physical stress. The findings of this study may provide new insights into exercise physiology and genome biology on the human.
CASE REPORT | doi:10.20944/preprints202103.0108.v1
Subject: Medicine & Pharmacology, Allergology Keywords: microcephalin gene, homozygous, next generation sequencing, microcephaly. MCPH1
Online: 2 March 2021 (16:22:48 CET)
MCPH1, otherwise known as the microcephalin gene (*607117) and protein, is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The Microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptide. There is a strong connection between mutations of the MCPH1 and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains which means smaller size, varying levels of mental retardation, delayed speech and poor language skills, individuals with mild microcephaly and normal intelligence notwithstanding. In this case, a fetus with novel homozygous mutation of the MCPH1 gene ((c.348del)), whose parents were recessive heterozygous for (c.348del), displayed severe microcephaly at 22 weeks of gestation. Due to the effect on splice sites in introns, this mutation causes forming of dysfunctional proteins which lack crucial domains of the C-terminus. Our findings portray an association between the new MCPH1 mutation ((c.348del)) and the clinical features of autosomal recessive primary microcephaly (MCPH) contributing to a broader spectrum related to these pathologies.
ARTICLE | doi:10.20944/preprints202002.0385.v1
Subject: Life Sciences, Virology Keywords: Coronavirus; SARS-CoV-2; enrichment; next-generation sequencing
Online: 26 February 2020 (02:27:21 CET)
SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.
BRIEF REPORT | doi:10.20944/preprints202208.0025.v1
Subject: Life Sciences, Other Keywords: glioblastoma; extracellular vesicles; Next Generation Sequencing; pathogenic mutations; NF1
Online: 1 August 2022 (15:07:04 CEST)
The biological heterogeneity of glioblastoma (GBM), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing the clinical progression over the time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of outmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EV) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors as well as glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next Generation Sequencing (NGS) in circulating EV of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare with the corresponding matched tissue samples, potential variants with pathogenic significance of the DNA contained in peripheral blood derived EV. The NGS analysis has revealed that patients with grade IV glioblastoma, exhibited lesser DNA content in EV than controls and that both in EV and matched cancer tissues, the NF1 gene was consistently mutated in all patients with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of the circulating EV in glioblastoma and as eligible tool for personalized medicine.
REVIEW | doi:10.20944/preprints202106.0526.v1
Subject: Life Sciences, Biochemistry Keywords: virome; microbiome; next generation sequencing; mycoviruses; plant pathogenic viruses
Online: 21 June 2021 (16:23:44 CEST)
Forest health is dependent on the variability of microorganisms interacting with the host tree/holobiont. Symbiotic microbiota and pathogens engage in a permanent interplay, which influences the host. Thanks to the development of NGS technologies, a vast amount of genetic information on the virosphere of temperate forests has been gained the last seven years. To estimate the qualitative/quantitative impact of NGS in forest virology, we have summarized viruses affecting major tree/shrub species and their fungal associates, including fungal plant pathogens, mutualists and saprotrophs. The contribution of NGS methods is extremely significant for forest virology. Reviewed data about viral presence in holobionts, allowed us to address the role of the virome in the holobionts. Genetic variation is a crucial aspect in hologenome, significantly reinforced by horizontal gene transfer among all interacting actors. Through virus-virus interplays synergistic or antagonistic relations may evolve, which may drastically affect the health of the holobiont. Novel insights of these interplays may allow practical applications for forest plant protection based on endophytes and mycovirus biocontrol agents. The current analysis is conceived in light of the prospect that novel viruses may initiate an emergent infectious disease and that measures for avoidance of future outbreaks in forests should be considered.
CASE REPORT | doi:10.20944/preprints202012.0704.v1
Subject: Medicine & Pharmacology, Allergology Keywords: left ventricular noncompaction; apical hypertrophic cardiomyopathy; next generation sequencing
Online: 28 December 2020 (13:19:41 CET)
Left ventricular noncompaction (LVNC) and hypertrophic cardiomyopathy (HCM) commonly occur as separate disorders with distinct clinical and pathoanatomical features. However, these cardiomyopathies may have a similar genetic origin with mutations encoding sarcomeric proteins. The described case demonstrates an example, in which phenotypic expression of both diseases occurs in the same patient.
ARTICLE | doi:10.20944/preprints202009.0483.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: next-generation sequencing; colorectal cancer; ATM mutation; FBXW7 mutation
Online: 20 September 2020 (15:20:52 CEST)
Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.
ARTICLE | doi:10.20944/preprints201911.0298.v2
Subject: Biology, Other Keywords: classification; prostate cancer; gleason score; machine learning; next-generation sequencing
Online: 26 November 2019 (04:01:21 CET)
1) Background: One of the most common cancer that affects men worldwide and North American men is prostate cancer. Gleason score is a pathological grading system to examine the potential aggressiveness of the disease in the prostate tissue. The advancement in computing and next-generation sequencing technology now allow us to study the genomic profiles of patients in association with their different Gleason score more accurately and effectively. 2) Methods: In this study, we used a novel machine learning method to analyze gene expression of prostate tumors with different Gleason scores, and identify potential genetic biomarkers for each Gleason group. We obtained a publicly-available RNA-Seq dataset of a cohort of 104 prostate cancer patients from the National Center for Biotechnology Information’s (NCBI) Gene Expression Omnibus (GEO) repository, and categorized patients based on their Gleason scores to create a hierarchy of disease progression. A hierarchical model with standard classifiers in different Gleason groups, also known as nodes, was developed to identify and predict nodes based on their mRNA or gene expression. In each node, patient samples were analyzed via class imbalance and hybrid feature selection techniques to build the prediction model. The outcome from analysis of each node is a set of genes that can differentiate each Gleason group from the remaining groups. To validate the proposed method, the set of identified genes are used to classify a second dataset of 499 prostate cancer patients collected from cBioportal . 3) Results: The overall accuracy of applying this novel method to the first dataset was 93.3%, and further validated to 87% accuracy using the second dataset. This method also identified genes that were not previously reported as potential biomarkers for specific Gleason groups. In particular, PIAS3 was identified as a potential biomarker for Gleason score 4+3=7, and UBE2V2 for Gleason score 6. 4) Insight: Previous reports show that the genes predicted by this newly proposed method strongly correlate with prostate cancer development and progression. Furthermore, pathway analysis shows that both PIAS3 and UBE2V2 share similar protein interaction pathways, the JAK/STAT signaling process.
REVIEW | doi:10.20944/preprints201811.0571.v2
Subject: Life Sciences, Genetics Keywords: prostate cancer; prostate-specific antigen; incidence; genomics; next generation sequencing
Online: 3 April 2019 (10:15:50 CEST)
In the recent past, there has been a rise in Prostate Cancer (PCa) in Asia, particularly India. Although systematic reviews on PCa have dealt on the genetics, genomics and the environmental influence in causal of PCa, no predictive analytics in comparing the PCa from Caucasian, American to Asian population was attempted. In this review article, we have attempted to elaborate this aspect of PCa and deliberated on challenges related to next generation sequencing methods of PCa’s manifestation when compared to the west.
ARTICLE | doi:10.20944/preprints201811.0110.v1
Subject: Life Sciences, Genetics Keywords: supernumerary chromosomes; B chromosomes; next-generation sequencing, coverage ratio analysis
Online: 5 November 2018 (11:33:17 CET)
B chromosomes (Bs) were discovered a century ago, and since then most studies have focused on describing their distribution and abundance using traditional cytogenetics. Only recently have attempts been made to understand their structure and evolution at the level of DNA sequence. Many questions regarding the origin, structure, function and evolution of B chromosomes remain unanswered. Here we identify B chromosome sequences from several species of cichlid fish from Lake Malawi by examining the ratios of DNA sequence coverage in individuals with and without B chromosomes. We examine the efficiency of this method, and compare results using both Illumina and PacBio sequence data. The B chromosome sequences detected in 13 individuals from 7 species were compared to assess the rates of sequence replacement. B-specific sequence common to at least 12 of the 13 datasets are identified as the “Core” B chromosome. The location of B sequence homologs throughout the genome provides further support for theories of B chromosome evolution. Finally, we identified candidate genes located on the B chromosome which may regulate the segregation and maintenance of the B chromosome.
Subject: Biology, Anatomy & Morphology Keywords: microbiomes; next generation sequencing, plant yield; rhizobacteria; rhizosphere; sustainable agriculture
Online: 25 January 2018 (17:41:19 CET)
Rhizosphere microbiomes which have been implicated to enhance plant growth and yield are modulated or influenced by a couple of environmental factors such as soil type, plant cultivar, climate change and anthropogenic activities. In particular, anthropogenic activity such as the use of nitrogen-based chemical fertilizers is associated with environmental destruction and this call for a more ecofriendly strategy to increase nitrogen level of agricultural land. This feat is attainable by harnessing nitrogen-fixing endophytic and free-living rhizobacteria. Rhizobium, Pseudomonas, Azospirillum and Bacillus have been found to have positive impacts on crops by enhancing both above and belowground biomass and could therefore play positive roles in achieving sustainable agriculture. Thus, it is needful to study these rhizosphere microbiomes with more sophisticated culture-independent technologies such as next generation sequencing (NGS) with the prospect of discovering novel bacteria with plant growth promoting traits. This review is therefore aimed at discussing factors that can modulate rhizosphere microbiomes with focus on the contributions of nitrogen fixing bacteria towards sustainable agricultural development and the techniques that can be used for their study.
ARTICLE | doi:10.20944/preprints202107.0068.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Angiosarcoma; biomarkers; tumor microenvironment; immunotherapy, next generation sequencing, whole transcriptome sequencing.
Online: 2 July 2021 (15:43:54 CEST)
We performed a comprehensive analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin. We aimed to describe the genomic landscape of AS in a cohort of 143 cases of AS profiled by Caris Life Sciences. Data of Next Generation Sequencing (NGS) with a 592 gene panel was available for the entire cohort. Fifty-three cases had data of Whole Exome Sequencing (WES) which we used to study the microenvironment phenotype. Immuno-therapy (IO) response biomarkers: Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and PD-L1 status were included. IO-response markers were present in 36.4% of the cohort and in 65% of head and neck AS (H/N-AS) (p<0.0001). H/N-AS cases had predominantly muta-tions in TP53 (50.0%, p=0.0004), POT1 (40.5%, p<0.0001) and ARID1A (33.3%, p=0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p<0.0001), HRAS (16.1%, p=0.0377), and PI3KCA (16.1%, p=0.2352). A microenvironment with a high immune signature, associated with better response to IO, was present in 13% of the cases. This signature was evenly distributed among different primary sites. We found that the molecular biology for AS varies significantly according to the primary site. Our findings can facilitate the design and optimiza-tion of therapeutic strategies for AS to overcome resistance to IO and targeted therapies.
REVIEW | doi:10.20944/preprints202103.0486.v1
Subject: Engineering, Automotive Engineering Keywords: Machine Learning; Next Generation; Contact Aware; Communication System; Machine-type Communications
Online: 18 March 2021 (13:20:00 CET)
Machine Learning (ML) and Artificial Intelligence(AI) have revolutionized almost all fields that are linked to the acquisition of intelligent behavior in the real world. It is an attractive alternative for a researcher of artificial intelligence. Contrary to rule-based programming, ML is an algorithmic approach in which learning comes from existing data. The more data we have these computer systems look at, we say we’re ‘training’ the computer system, and as the computers begin to identify patterns in the data, identify abnormalities in the data from these abnormalities we improve the system architect according to the requirement. This article introduces the use of comprehensive concepts of machine learning, in general, particular, and their potential applications in communications. Furthermore, the current state and futuristic potentials of enabling universal communication with implications of machine learning methods have been explained. In this review paper, we offer a comprehensive talk on distinctive methods/techniques of information analytics, artificial intelligence (AI), and machine learning (ML) moved forward the contact aware communication system.
ARTICLE | doi:10.20944/preprints202103.0103.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Next Generation Sequencing; Laboratory automation; Hereditary Cancer; Genetic Testing; Clinical Genomics.
Online: 2 March 2021 (16:00:24 CET)
(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.
REVIEW | doi:10.20944/preprints202012.0738.v1
Subject: Life Sciences, Biochemistry Keywords: Next generation sequencing; Genetic disorders; Genomic medicine; Genetic counseling; Rare diseases
Online: 29 December 2020 (16:47:01 CET)
Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.
REVIEW | doi:10.20944/preprints202006.0350.v1
Subject: Life Sciences, Biotechnology Keywords: Antibodies engineering; Computational approach; Novel drugs; Synthetic immunology; Next generation antibodies
Online: 28 June 2020 (20:24:49 CEST)
In the pre era of synthetic antibodies, pharmaceutical companies depend on finding novel drugs from medicinal plants and other traditional resources; while in present, technological advances in biology, computer and robotics give the researchers the ability to rewrite and edit DNA in order to synthesize very large sets of drug candidates; these novel and improved candidates serves the basis for creating another library of drug candidates and so on until we find the right biomolecule for the disease of interest. all these technologies combined together to synthesize therapeutic antibodies for many types of cancer, autoimmune diseases, and infectious diseases, that can address diseases much more readily to very rapidly get therapeutics into patients so that we can potentially have an impact on disease. The antibodies mechanism is recognize and bind to disease cells and pinpoint the immune system to attack those cells effectively. Now a days, they dependent on computational approach to guide and accelerate the process of antibodies engineering by combination of selection system and use of high-throughput data acquisition and analysis to build and construct populations of next generation antibodies that are thermo-stable, non-immunogenic as possible, and to be administered to many humans as possible. In this review, I will discuss the latest in silico methods for antibodies engineering.
REVIEW | doi:10.20944/preprints201807.0071.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: precision medicine; next generation sequencing; oncology, patient outcomes; health insurance coverage
Online: 4 July 2018 (11:06:43 CEST)
Precision medicine seeks to use genomic data to help provide the right treatment to the right patient at the right time. Next-generation sequencing technology allows for the rapid and accurate sequencing of many genes at once. This technology is becoming more common in oncology, though the clinical benefit of incorporating it into precision medicine strategies remains under significant debate. In this manuscript, we discuss the early findings of the impact of next-generation sequencing on cancer patient outcomes. We investigate why not all patients with genomic variants linked to a specific therapy receive that therapy and describe current barriers. Finally, we explore the current state of health insurance coverage for individual genome sequencing and targeted therapies for cancer. Based on our analysis, we recommend increased transparency around the determination of “actionable mutations” and a heightened focus on investigating the variations in health insurance coverage across patients receiving sequencing-matched therapies.
ARTICLE | doi:10.20944/preprints202012.0473.v1
Subject: Life Sciences, Biochemistry Keywords: transposable elements; mobile element insertion events; next generation sequencing (NGS); genome evolution
Online: 18 December 2020 (14:53:44 CET)
Transposable elements (TEs) are mobile genetic elements capable of rapidly altering the genome through their movements. The importance of TE activity has been documented in many biological processes, such as introducing genetic instability, altering patterns of gene expression, and accelerating genome evolution. Increasing appreciation of TEs results in the growing number of bioinformatics software to identify insertion events. However, the application of existing TE finding tools is limited by either narrow-focused design of the package, too many dependencies on other tools, or prior knowledge required as input files that may not be readily available to all users. Here, we report a simple pipeline, TEfinder, developed for the detection of new TE insertions with minimal software dependencies using four inputs that can be easily generated with popular variant calling pipelines. The external software requirements are BEDTools, SAMtools, and Picard. Necessary inputs include TEs present in the reference genome, binary paired-end alignment, reference genome index, and a list of TE names. We tested TEfinder pipeline among several evolving populations of Fusarium oxysporum generated through a short-term adaptation study. Our results demonstrate that this easy-to-use tool can effectively detect new TE insertion events, making it accessible and practical for TE analysis.
ARTICLE | doi:10.20944/preprints202012.0387.v1
Subject: Life Sciences, Biochemistry Keywords: next-generation sequencing; database; variant annotation; variant classification; data management; clinical genomics
Online: 15 December 2020 (13:14:21 CET)
The rapid evolution of Next Generation Sequencing in clinical settings and the resulting challenge of variants interpretation in the light of constantly updated information, requires robust data management systems and organized approaches to variant reinterpretation. In this paper, we present iVar: a freely available and highly customizable tool provided with a user-friendly web interface. It represents a platform for the unified management of variants identified by different sequencing technologies. iVar accepts, as input, VCF files and text annotation files and elaborates them, optimizing data organization and avoiding redundancies. Updated annotations can be periodically re-uploaded and associated to variants as historicize attributes. Data can be visualized through variant-centered and sample-centered interfaces. A customizable search functionality can be exploited to periodically check if pathogenicity related data of a variant are changed over time. Patient recontacting ensuing from variant reinterpretation is made easier by iVar through the effective identification of all patients present in the database and carrying a specific variant. We tested iVar by uploading 4171 VCF files and 1463 annotation files, obtaining a database of 4166 samples and 22569 unique variants. iVar has proven to be a useful tool with good performances for collecting and managing data from medium-throughput
COMMUNICATION | doi:10.20944/preprints201909.0346.v1
Subject: Life Sciences, Genetics Keywords: neurogenetics; dementia; next-generation sequencing; in silico analysis; genetic variant; phenotypic variability
Online: 30 September 2019 (11:05:36 CEST)
Background: Advancements in the next-generation sequencing (NGS) techniques have allowed for efficient genetic variant detection at reduced costs. Methods: We describe an ad hoc NGS-based custom designed resequencing gene panel to identify genetic variants in 8 patients with dementing disorders. Results: We found variants of TREM2 and APP genes in three patients; these have been previously identified as pathogenic or likely pathogenic and, therefore, considered as “Disease Causing”. In the remaining subjects, the pathogenicity was evaluated on the in silico analysis, according to the guidelines of the American College of Medical Genetics. In one patient, the p.R205W variant was causative of the disease, thus considered as “Possibly Disease Causing”. The variants found from the other four subjects in the CSF1R, SERPINI1, GRN, and APP genes revealed discordant in silico results and, therefore, it was not possible to assign a definitive pathogenicity. Conclusions: Notwithstanding the limitations of a customized panel, we detected some rare genetic variants with a probable disease association. The future application of NGS techniques and the further replication of these experimental data will replace the so-called “gene by gene” approach with a “panel of genes” strategy, that offers promising perspectives in the diagnosis and management of neurodegenerative disorders.
ARTICLE | doi:10.20944/preprints201703.0081.v1
Subject: Life Sciences, Molecular Biology Keywords: miRNAs; pre-miRNAs sequencing; Abelmoschus esculentus; Next generation sequencing; non-model plant
Online: 14 March 2017 (10:15:14 CET)
MicroRNAs (miRNAs) are crucial regulatory RNAs, originated from hairpin precursors. For the past decade, researchers are focusing extensively on miRNA profiles in various plants. However studies on precursor miRNAs (pre-miRNAs) global profiling stay static even in model plants. Here, for the first time in a non-model plant, Abelmoschus esculentus with negligible genome information, we are reporting the global profiling to characterize the miRNAs and their associated pre-miRNAs by applying next generation sequencing approach. Preliminarily we performed sRNA (small RNA) sequencing with five biological replicates of leaf samples to attain 207,285,863 reads and data analysis using miRPlant keyed out 128 known and 845 novel miRNA candidates. With the objective to seize their associated hairpin precursors, we accomplished pre-miRNA sequencing to attain 83,269,844 reads. The paired end reads are merged, adaptor trimmed and the resulting 40-241 nt (nucleotide) sequences were picked out for analysis by using perl scripts from miRGrep tool and in-house built shell script for Minimum Fold Energy Index (MFEI) calculation. Applying stringent criteria of dicer cleavage pattern and perfect stem loop structure revealed precursors for 57 known miRNAs of 15 families and 18 novel miRNAs. Quantitative Real Time (qRT) PCR was performed to determine the expression of selected miRNAs.
ARTICLE | doi:10.20944/preprints202101.0448.v1
Subject: Medicine & Pharmacology, Allergology Keywords: non-small-cell lung cancer; next-generation sequencing; bronchoscopy; Oncomine Dx target test
Online: 22 January 2021 (13:14:02 CET)
A sufficient amount of tissue sample is required to perform next-generation sequencing (NGS) with a high success rate, but the majority of patients with advanced non-small-cell lung cancer (NSCLC) are diagnosed with small biopsy specimens. Biopsy samples were collected from 184 patients with bronchoscopically diagnosed NSCLC. The tissue surface area, tumor cell count, and tumor content rate of each biopsy sample were evaluated. The impact of the cut-off criteria for the tissue surface area (≥ 1 mm2) and tumor content rate (≥ 30%) on the success rate of Oncomine Dx Target Test (ODxTT) was evaluated. The mean tissue surface area of the transbronchial biopsies was 1.23 ± 0.85 mm2 when small endobronchial ultrasonography with a guide sheath (EBUS-GS) was used, 2.16 ± 1.49 mm2 with large EBUS-GS, and 1.81 ± 0.75 mm2 with endobronchial biopsy (EBB). The proportion of samples with a tissue surface area of ≥ 1 mm2 was 48.8% for small EBUS-GS, 79.2% for large EBUS-GS, and 78.6% for EBB. Sixty-nine patients underwent ODxTT. The success rate of DNA sequencing was 84.1% and that of RNA sequencing was 92.7% over all patients. The success rate of DNA (RNA) sequencing was 57.1% (71.4%) for small EBUS-GS (n = 14), 93.4% (96.9%) for large EBUS-GS (n = 32), 62.5% (100%) for EBB (n = 8), and 100% (100%) for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 15). Regardless of the device used, a tissue surface area of ≥ 1 mm2 is adequate for samples to be tested with NGS.
ARTICLE | doi:10.20944/preprints201809.0428.v1
Subject: Biology, Other Keywords: inter- and intra-host nucleotide variations; Hepatitis A virus; next-generation sequencing; pyrosequencing
Online: 21 September 2018 (04:59:34 CEST)
The accurate virus detection, strain discrimination, and source attribution of contaminated food items remains a persistent challenge because of the high mutation rates anticipated to occur in foodborne RNA viruses, such as Hepatitis A virus (HAV). This has led to predictions of the existence of more than one sequence variant between the hosts (inter-host) or within an individual host (intra-host). However, there have been no reports of intra-host variants from an infected single individual, and little is known about the accuracy of the single nucleotide variations (SNVs) calling with various methods. In this study, the presence and identity of viral SNVs, either between HAV clinical specimens or among a series of samples derived from HAV clone1-infected FRhK4 cells, were determined following analyses of nucleotide sequences generated using next-generation sequencing (NGS) and pyrosequencing methods. The results demonstrate the co-existence of inter- and intra-host variants both in the clinical specimens and the cultured samples. The discovery and confirmation of multi-viral RNAs in an infected individual is dependent on the strain discrimination at the SNV level, and critical for successful outbreak traceback and source attribution investigations. The detection of SNVs in a time series of HAV infected FRhK4 cells improved our understanding on the mutation dynamics determined probably by different selective pressures. Additionally, it demonstrated that NGS could potentially provide a valuable investigative approach toward SNV detection and identification for other RNA viruses.
REVIEW | doi:10.20944/preprints202208.0502.v1
Subject: Life Sciences, Immunology Keywords: Trained immunity; innate immune memory; respiratory pathogens; BCG; next-generation vac-cines; COVID-19
Online: 30 August 2022 (03:55:12 CEST)
The COVID-19 pandemic exposed the vulnerability of current vaccine technologies characterized by a slow onset of action and antigen-specific immune response. Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against new vaccine variants. Moreover, growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. We further elaborate on the potential of trained immunity to leverage protection against emerging pathogens via recognition of diverse antigens by pathogen recognition receptors (PPRs) on innate immune cells. We also propose integrating trained- with adaptive- immunity to shape next-generation vaccines by coupling each one's unique characteristics.
CASE REPORT | doi:10.20944/preprints202202.0251.v1
Subject: Medicine & Pharmacology, Cardiology Keywords: Infective endocarditis; Granulicatela adiacens; Nutritionally variant streptococci (NVS); Next-generation sequencing (NGS); Aortic valve
Online: 21 February 2022 (10:45:14 CET)
In this report, we describe the course and successful treatment of complicated infective endocarditis (IE). A patient presented with a high-grade irregular fever with chills lasting at least 2 months, dyspnoea, chest pain, fatigue, weight loss, and night sweats during the previous 3 months. Above cardiac congenital disorders, he was found to have Granulicatella adiacens infective aortic valve endocarditis, presumably transmitted from the oral cavity niche. Validated metagenomic 16S rDNA next generation sequencing was used to perform taxonomic identification, allowing for specific adequate antibiotic therapy instead of empiric therapy. This paper highlights the critical role of rapid taxonomic identification of nutritionally variant streptococci crucial and the benefit of proper IE treatment to avoid relapses or fatal complications.
REVIEW | doi:10.20944/preprints201905.0130.v1
Subject: Biology, Plant Sciences Keywords: induced mutagenesis; fast neutron irradiation; mutation mapping; deletagene; next-generation sequencing technologies; reverse genetics
Online: 10 May 2019 (14:38:21 CEST)
Fast neutron (FN) radiation mediated mutagenesis is a unique approach among the several induced mutagenesis methods being used in plant science in terms of impacted mutations. The FN mutagenesis usually creates deletions from a few bases to several million bases (Mb). A library of random deletion generated using FN mutagenesis lines can provide indispensable resources for the reverse genetic approaches. In this review, information from several efforts made using FN mutagenesis has been compiled to understand the type of induced mutations, frequency, and genetic stability. Concerns regarding the utilization of FN mutagenesis technique for a plant with different level of ploidy and genome complexity are discussed. We have highlighted the utility of next-generation sequencing techniques which can be efficiently utilized for the characterization of mutant lines as well as for the mapping of causal mutations. Pros and cons of Mut-map, MutChromSeq, exon capture, whole genome sequencing, MutRen-Seq, and different tilling approaches can be used for the detection of FN-induced mutation has also been discussed. Genomic resources developed using the FN mutagenesis have been catalogued wooing to meaningful utilization of the available resources. The information provided here will be helpful for the efficient exploration for the crop improvement programs and for better understanding of genetic regulations.
REVIEW | doi:10.20944/preprints201709.0163.v1
Subject: Medicine & Pharmacology, Other Keywords: next-generation sequencing; whole-genome sequencing; hospital-acquired pneumonia; antibiotic resistance; prediction; clinical metagenomics
Online: 30 September 2017 (04:49:23 CEST)
Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.
REVIEW | doi:10.20944/preprints202106.0574.v1
Subject: Medicine & Pharmacology, Allergology Keywords: enterovirus; type 1 diabetes; virome; vaccine; antiviral; islet autoimmunity; coxsackievirus; next-generation sequencing; unbiased sequencing
Online: 23 June 2021 (11:19:33 CEST)
For over a century, viruses have left a long trail of evidence implicating them as frequent suspects in the development of type 1 diabetes. Through vigorous interrogation of viral infections in individuals with islet autoimmunity and type 1 diabetes using serological and molecular virus detection methods, and mechanistic studies of virus infected human pancreatic β-cells, the prime suspects have been narrowed down to predominantly human enteroviruses. Here we provide a comprehensive overview of evidence supporting the hypothesised role of enteroviruses in the development of islet autoimmunity and type 1 diabetes. We also discuss concerns over the historical focus and investigation bias toward enteroviruses, and summarise current unbiased efforts aimed at characterising the complete population of viruses (the “virome”) contributing early in life to the development of islet autoimmunity and type 1 diabetes. Finally, we review the range of vaccine and antiviral drug candidates currently being evaluated in clinical trials for the prevention and potential treatment of type 1 diabetes.
ARTICLE | doi:10.20944/preprints201912.0172.v1
Subject: Life Sciences, Virology Keywords: ticks; cattle, rna viruses; next-generation sequencing; phylogeny; microfluidic real-time pcr technology; Caribbean; lips
Online: 12 December 2019 (12:29:36 CET)
Ticks transmit a wide variety of pathogens including bacteria, parasites and viruses. Over the last decade, numerous novel viruses have been described in arthropods, including ticks, and their characterization has provided new insights into RNA virus diversity and evolution. However, little is known about their ability to infect vertebrates. As very few studies have described the diversity of viruses present in ticks from the Caribbean, we implemented an RNA-sequencing approach on Amblyomma variegatum and Rhipicephalus microplus ticks collected from cattle in Guadeloupe and Martinique. Among the viral communities infecting Caribbean ticks, we selected four viruses belonging to the Chuviridae, Phenuiviridae and Flaviviridae families for further characterization and designing antibody screening tests. While viral prevalence in individual tick samples revealed high infection rates, suggesting a high level of exposure of Caribbean cattle to these viruses, no seropositive animals were detected. These results suggest that the Chuviridae- and Phenuiviridae-related viruses identified in the present study are more likely tick endosymbionts, raising the question of the epidemiological significance of their occurrence in ticks, especially regarding their possible impact on tick biology and vector capacity. The characterization of these viruses might open the door to new ways of preventing and controlling tick-borne diseases.
ARTICLE | doi:10.20944/preprints201810.0017.v2
Subject: Engineering, Electrical & Electronic Engineering Keywords: Next Generation Wireless Networks; Cognitive Radios; Collaborative Intelligent Radio Networks; Spectrum Sharing; Coexistence; Experimental Evaluation
Online: 15 October 2018 (12:15:23 CEST)
The explosive emergence of wireless technologies and standards, covering licensed and unlicensed spectrum bands has triggered the appearance of a huge amount of wireless technologies, with many of them coexisting in the same band. Unfortunately, the wireless spectrum is a scarce resource, and the available frequency bands will not scale with the foreseen demand for new capacity. Certain parts of the spectrum, in particular the license-free ISM bands, are overcrowded, while other parts, mostly licensed bands, may be significantly underutilized. As such, there is a need to introduce more advanced techniques to access and share the wireless medium, either to improve the coordination within a given band, or to explore the possibilities of intelligently using unused spectrum in underutilized (e.g., licensed) bands. Therefore, in this paper, we present an open source SDR-based framework that can be employed to devise disruptive techniques to optimize the sub-optimal use of radio spectrum that exists today. Additionally, we describe three use cases where the proposed framework can be employed along with intelligent algorithms to achieve improved spectrum utilization.
REVIEW | doi:10.20944/preprints201803.0227.v1
Subject: Life Sciences, Biotechnology Keywords: Antivenom; snakebite; small molecule toxin inhibitors; oligonucleotides; antibodies; phage display; next generation antivenom; recombinant antivenom
Online: 27 March 2018 (13:41:46 CEST)
With the inclusion of snakebite envenoming on the World Health Organisation’s list of Neglected Tropical Diseases, an incentive has been established to promote research and development effort in novel snakebite antivenom therapies. Different technological approaches are being pursued by different research groups, including the use of small molecule inhibitors against enzymatic toxins, as well as peptide and oligonucleotide-based aptamers and antibody-based biotherapeutics against both enzymatic and non-enzymatic toxins. In this article, the most recent advances in these fields are presented, and the advantages, disadvantages, and feasibility of using different toxin-neutralizing molecules are reviewed. Particular focus within small molecules is directed towards the inhibitors, varespladib, batimastat, and marimastat, while in the field of antibody-based therapies, novel recombinant polyclonal plantivenom technology is discussed.
ARTICLE | doi:10.20944/preprints202108.0149.v1
Subject: Life Sciences, Biochemistry Keywords: Bioinformatics; Cervical cancer; Deep Sequencing; Human papillomavirus; HPV genotyping; Metagenome; Next generation sequencing; Taxonomic classification; Virome
Online: 6 August 2021 (08:00:00 CEST)
Next-generation sequencing (NGS) has actualized human papillomavirus (HPV) virome profiling for in-depth investigation of viral evolution and pathogenesis. However, viral computational analysis remains a bottleneck due to semantic discrepancies between computational tools and curated reference genomes. To address this, we developed and tested automated workflows for HPV taxonomic profiling and visualization using a customized Papillomavirus database in CLC Microbial Genomics Module. HPV genomes from Papilloma Virus Episteme were customized and incorporated into CLC “ready-to-use” workflows for stepwise data processing to include: 1) Taxonomic Analysis, 2) Estimate Alpha/Beta Diversities, and 3) Map Reads to Reference. Low-grade (n = 95) and high-grade (n = 60) Pap smears were tested with ensuing collective runtimes: Taxonomic Analysis (36 min); Alpha/Beta Diversities (5 sec); Map Reads (45 min). Tabular output conversion to visualizations entailed 1-2 keystrokes. Biodiversity analysis between low- (LSIL) and high-grade squamous intraepithelial lesions (HSIL) revealed loss of species richness and gain of dominance by HPV-16 in HSIL. Integrating clinically relevant, taxonomized HPV reference genomes within automated workflows proved to be an ultra-fast method of virome profiling. The entire process named “HPV DeepSeq” provides a simple, accurate and practical means of NGS data analysis for a broad range of applications in viral research.
CASE REPORT | doi:10.20944/preprints202012.0548.v1
Subject: Medicine & Pharmacology, Allergology Keywords: next-generation sequencing; hereditary breast cancer; Homologous Recombination Repair; hereditary cancer syndrome; Clinical genomics; Molecular diagnostics
Online: 22 December 2020 (10:17:48 CET)
Next Generation Sequencing based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. ATM germ-line heterozygosity has been described as able to increase tumor susceptibility. In particular, families that carry heterozygous germ-line variants of ATM gene show a 5- to 9-fold risk of developing breast cancer. Recent studies identified ATM as the second most mutated gene after CHEK2 in BRCA-negative patients. Nowadays, more than 170 potential missense variants and several truncating mutations have been identified in ATM gene. Here we present the molecular characterization a new ATM deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics’ Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed to identify a new inactivating deletion of exons 19-27 of ATM gene. DNA breakpoint was characterized both at DNA and RNA level
COMMUNICATION | doi:10.20944/preprints202006.0044.v1
Subject: Life Sciences, Microbiology Keywords: Epidemiology; COVID-19; coronavirus; bat; RaTG13; BtCoV/4991; SARS-CoV-2; Pangolin Coronavirus; next generation sequencing
Online: 5 June 2020 (06:17:26 CEST)
A recent manuscript (Zhou, P. et al. “A pneumonia outbreak associated with a new coronavirus of probable bat origin”, Nature 579, 270–273 (2020). https://doi.org/10.1038/s41586-020-2012-7) from Wuhan Institute of Virology claimed the identification of a bat coronavirus, RaTG13, which showed 96.2% genome homology with SARS-CoV-2. In this paper, we raise the puzzling observations surrounding the identification, characterization, unique genome features of this RaTG13 strain, as well as its 100% nucleotide identity in partial RdRp gene with another bat coronavirus strain BtCoV/4991. And the paper presented premature hypothesis of potential bat origin of SARS-CoV-2 while RaTG13 strain was not successfully isolated. We also present the concerns on the methodology, data quality and experiment procedures described in this paper. We call for the authors to provide additional data, to share related samples to be verified and further characterized by other scientists.
ARTICLE | doi:10.20944/preprints201808.0423.v1
Subject: Biology, Animal Sciences & Zoology Keywords: mitochondrial DNA; mitochondrial genome; genome assembly; genome annotation; next generation sequencing; animal genomics; partial genomics; bioinformatics
Online: 24 August 2018 (03:24:37 CEST)
Next-generation sequencing is now a mature technology, allowing partial animal genomes to be produced for many clades. Though many software exist for genome assembly and annotation, a simple pipeline that allows researchers to input raw sequencing reads in fastq format and allow the retrieval of a completely assembled and annotated mitochondrial genome is still missing. mitoMaker 1.0 is a pipeline developed in python that implements (i) recursive de novo assembly of mitochondrial genomes using a set of increasing k-mers; (ii) search for the best matching result to a target mitogenome and; (iii) performs iterative reference-based strategies to optimize the assembly. After (iv) checking for circularization and (v) positioning tRNA-Phe at the beginning, (vi) geneChecker.py module performs a complete annotation of the mitochondrial genome and provides a GenBank formatted file as output.
ARTICLE | doi:10.20944/preprints202208.0024.v1
Subject: Life Sciences, Virology Keywords: highly pathogenic avian influenza viruses; H5N8; H5N5; Clade 18.104.22.168; phylogenetic network analyses; next-generation sequencing; MinION; epidemiology
Online: 1 August 2022 (14:57:42 CEST)
During autumn/winter in 2016 – 2017 and 2020 – 2021, highly pathogenic avian influenza viruses (HPAIV) caused severe outbreaks in Germany and Europe. Multiple clade 22.214.171.124b H5 HPAI subtypes were responsible for increased mortality in wild birds and high mortality and massive losses in the poultry sector. To clarify putative entry sources and delineate interconnections between outbreaks in poultry holdings and wild birds, we applied whole-genome sequencing and phylodynamic analyses combined with the results of epidemiological outbreak investigations. Varying outbreak dynamics of the distinct reassortants allowed for the identification of individual, putatively wild bird-mediated entries into backyard holdings, several clusters comprising poultry holdings, local virus circulation for several weeks, direct farm-to-farm transmission and potential reassortment within a turkey holding with subsequent spill-over of the novel reassorted virus into the wild bird population. Whole-genome sequencing allowed for allowed for a unique high-resolution molecular epidemiology analysis of HPAIV H5Nx outbreaks, recommended to be used as a standard tool. The presented detailed account of the genetic, temporal and geographical characteristics of the recent German HPAI H5Nx situation emphasizes the role of poultry holdings as an important source of novel genetic variants and reassortants.
REVIEW | doi:10.20944/preprints202010.0437.v1
Subject: Life Sciences, Biochemistry Keywords: breast cancer; microbiota; bacteria; dysbiosis; pro-carcinogenic; anti-carcinogenic; genetics; next-generation sequencing; cancer treatments; cancer prevention
Online: 21 October 2020 (12:51:23 CEST)
One in eight women will be diagnosed with breast cancer (BC) in their lifetime, resulting in over 2 million cases annually. BC is the most common cancer among women. Unfortunately, the etiology of majority of cases remains unknown. Recently, evidence has shown that the human microbiota plays an important role in health and disease. Intriguingly, studies have revealed the presence of microorganisms in human breast tissue, which was previously presumed to be sterile. Next-generation sequencing technologies have paved way for the investigation of breast microbiota, uncovering bacterial signatures that are associated with BC. Some of the bacterial species were found to possess pro-carcinogenic and/or anti-carcinogenic properties, suggesting that the breast microbiota has potentially crucial roles in maintenance of breast health. In this review, we summarize the recent findings on breast tissue microbiota and its interplay with BC. Bacterial signatures identified via next-generation sequencing as well as their impact on breast carcinogenesis and cancer therapies are reviewed. Correlation of breast tissue microbiota and other factors, such as geographical and racial differences, in BC is discussed. Additionally, we discuss the future directions of research on breast microbiota as well as its potential role in prevention, diagnosis and treatment of BC.
REVIEW | doi:10.20944/preprints202108.0058.v1
Subject: Life Sciences, Molecular Biology Keywords: SARS-CoV-2; COVID-19; Phylogenetic analysis; Next generation sequence analysis; Virus-Host interaction; Immunology; Antiviral agents; Vaccine; Virus diagnosis
Online: 2 August 2021 (16:17:24 CEST)
The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.
ARTICLE | doi:10.20944/preprints201609.0080.v1
Subject: Life Sciences, Genetics Keywords: Anatolian Black; East Anatolian Red; South Anatolian Red; Turkish Grey; Holstein Friesian; Innate immunity; Next Generation Sequencing; TLR2; TLR4; TLR6
Online: 23 September 2016 (05:44:43 CEST)
In recent years, the focus of disease resistance and susceptibility studies in cattle have been on determining patterns in the innate immune response of key proteins, such as Toll-like receptors (TLR). In the bovine genome, there are 10 TLR family members and, of these, TLR2, TLR4 and TLR6 are specialized in recognition of bacterial ligands. Indigenous cattle breeds of Anatolia have been reported to show fewer signs of clinical bacterial infections, such as bovine tuberculosis and mastitis, and it is hypothesized that this might be due to a less stringent genetic selection during breeding. In contrast, Holstein-Friesian cattle have been under strong selection for milk production, which may have resulted in greater susceptibility to diseases. To test this hypothesis, we have compared the TLR2, TLR4 and TLR6 genes of Anatolian Black (AB), East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), and Holstein (HOL) cattle using Next Generation Sequencing. The SAR breed had the most variations overall, followed by EAR, AB, TG and HOL. TG had the most variations for TLR2 whereas SAR had the most variations in TLR4 and TLR6. We compared these variants with those associated with disease and susceptibility traits. We used exon variants to construct haplotypes, investigated shared haplotypes within breeds and determined candidate haplotypes for disease resistance phenotype in Anatolian cattle breeds.
COMMUNICATION | doi:10.20944/preprints202206.0374.v1
Subject: Life Sciences, Microbiology Keywords: antimicrobial resistance; CTX-M-1; Enterobactericeae,; Escherichia coli; extended-spectrum β-lactamase; food safety; IncI1; next-generation sequencing; One Health; virulence
Online: 28 June 2022 (04:18:22 CEST)
Studies have previously described the occurrence of multidrug-resistant (MDR) Escherichia coli in human and veterinary medical settings, livestock, and, to a lesser extent, in the environment and food. While they mostly analyzed foodborne E. coli regarding phenotypic and sometimes genotypic antibiotic resistance and basic phylogenetic classification, we have limited understanding of the in vitro and in vivo virulence characteristics and global phylogenetic contexts of these bacteria. Here, we investigated an E. coli strain (PBIO3502) isolated from a pork sausage in Germany in 2021 in-depth. Whole-genome sequence analysis revealed sequence type (ST)58, which is an emerging international high-risk clonal lineage. In addition to its MDR phenotype that mostly matched the genotype, PBIO3502 demonstrated pronounced virulence features, including in vitro biofilm formation, siderophore secretion, serum resilience, and in vivo mortality in Galleria mellonella larvae. Along with the genomic analysis indicating close phylogenetic relatedness of our strain with publicly available, clinically relevant representatives of the same ST, these results suggest the zoonotic and pathogenic character of PBIO3502 with the potential to cause infection in humans and animals. Also, our study highlights the necessity of the One Health approach while integrating human, animal, and environmental health, as well as the role of meat products and food chains in the putative transmission of MDR pathogens.
ARTICLE | doi:10.20944/preprints201803.0271.v1
Subject: Biology, Plant Sciences Keywords: Idaeovirus; Blackcurrant leaf chlorosis associated virus; next-generation sequencing (NGS); bridge reads; abutting primers; RNase R digestion; circular RNA; concatenated RNA
Online: 30 March 2018 (11:40:46 CEST)
Blackcurrant leaf chlorosis associated virus (BCLCaV) was detected recently by next-generation sequencing (NGS) and proposed as a new and distinct species in the genus Idaeovirus. Genomic components of BCLCaV that were detected and confirmed include: 1) RNA-1 that is monocistronic and encodes the replicase complex; 2) a bicistronic RNA-2 that encodes a movement protein (MP) and the coat protein (CP) of the virus, with open reading frames (ORF) that overlap by a single adenine (A) nucleotide (nt) representing the third position of an opal stop codon of the MP ORF2a and the first position of the start codon of the CP ORF2b; 3) a subgenomic form of RNA-2 (RNA-3) that contains ORF2b; and 4) a concatenated form of RNA-2 that consists of a complementary and inverted RNA-3 conjoined to the full-length RNA-2. Analysis of NGS-derived paired-end reads revealed the existence of bridge reads encompassing the 3’-terminus and 5’-terminus of RNA-2 or RNA-3 of BCLCaV. The full RNA-2 or RNA-3 could be amplified using outward facing or abutting primers; also RNA-2/RNA-3 could be detected even after three consecutive RNase R enzyme treatments with denaturation at 95 oC preceding each digestion. Evidence was obtained indicating that there are circular forms of BCLCaV RNA-2 and RNA-3.
ARTICLE | doi:10.20944/preprints202201.0390.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: non-small cell lung cancer (NSCLC); liquid biopsy; cell-free nucleic acid (cfNA); next generation sequencing (NGS); CNA (copy number amplifications); fusions, exon-skipping.
Online: 26 January 2022 (03:21:12 CET)
Liquid biopsies are an integral part of the diagnosis of cancer. Here, we have extended previous validation studies of a new targeted NGS panel to include the detection of copy number amplifications (CNAs), fusions, and exon skipping variants. Detection of these gene classes included specimens from clinical and healthy donors and cell lines (fusions: ROS1, EML4-ALK, NTRK1), (exon skipping: MET exon 14), and (CNAs: HER2, CDK6, EGFR, MYC and MET). The limit of detection (LOD) for fusion/skipping was 42 copies (QC threshold = 3 copies) and was verified using 3 additional fusion/skipping variants. LOD for CNAs was 1.40-fold-change (QC threshold = 1.15-fold change) and was verified with 3 additional CNAs. In precision studies, all fusion/skipping variants were detected in all runs and all days of testing (n=18/18; 100%); average CV for repeatability was 20.5% (range 8.7% - 34.8%), and for reproducibility was 20.8% (range 15.7% - 30.5%). For CNAs, 28/29 (96.6%) copy gains were detected. For CNAs, average CV of 1.85% (range 0% to 5.49%) for repeatability and 6.59% (range 1.65% to 9.22%) for reproducibility. The test panel meets the criteria for being highly sensitive and specific and extends its utility for the detection of clinically relevant variants in cancer.
REVIEW | doi:10.20944/preprints202201.0366.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: cell-free DNA; liquid biopsy; cancer; next-generation sequencing (NGS); minimal residual disease; measurable residual disease; molecular residual disease (MRD); leukemia; lymphoma; myeloma; myeloproliferative neoplasms; myelodysplastic syndrome
Online: 25 January 2022 (08:13:24 CET)
The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsy. Most of the studies about this topic have been focused on B cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for diagnosis and minimal residual monitoring in B cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real-time. However, there are limitations such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess minimal residual disease or the lack of standardization of the method and clinical studies to confirm its prognostic impact. This review focuses on clinical applications of cfDNA on minimal residual disease in hematological malignancies.
ARTICLE | doi:10.20944/preprints202209.0003.v1
Subject: Materials Science, Other Keywords: flame-retardant plywood; flammability; toxic gas generation; smoke generation
Online: 1 September 2022 (03:50:51 CEST)
Flammability was evaluated and the results showed the values of critical flux at extinguishment (CFE) as 49.5kW/㎡ on average, total heat release (Qt) as 0.21MJ on average, and peak heat release rate (Qp) as 0.66kW on average, which satisfied all of the thresholds presented by the IMO. Therefore, flame-retardant plywood, of which the flame-retardant performance was evaluated, was determined to be an applicable finishing material that satisfies fire safety standards.
ARTICLE | doi:10.20944/preprints202007.0735.v1
Subject: Life Sciences, Genetics Keywords: Variant of Unknown Significance (VUS); Single-Nucleotide Variant (SNV); Variant Effect Prediction (VEP); Stacked Ensemble of Supervised Deep Learners (SESDL); Next Generation Sequencing (NGS); Alternative Allele Frequency (AAF).
Online: 31 July 2020 (06:13:53 CEST)
Pathogenicity is unknown for the majority of human gene variants. For prioritization of sequenced somatic and germline mutation variants, in silico approaches can be utilized. In this study, 84 million non-synonymous Single Nucleotide Variants (SNVs) in the human coding genome were annotated using consensus Variant Effect Prediction (cVEP) method. An algorithm, implemented as a stacked ensemble of supervised learners, performed combination of the 39 functional, conservation mutation impact scores from dbNSFP4.0. Adding gene indispensability score, accounting for differences in the pathogenicities of the variants in the essential and the mutation-tolerant genes, improved the predictions. For each SNV the consensus combination gives either a continuous-value pathogenicity score, or a categorical score in five classes: pathogenic, likely pathogenic, uncertain significance, likely benign, benign. The provided class database is aimed for direct use in clinical practice. The trained prediction models were 5-fold cross-validated on the evidence-based categorical annotations from the ClinVar database. The rankings of the scores based on their ability to predict pathogenicity were obtained. A two-step strategy using the rankings, scores and class annotations is suggested for filtering and prioritization of the human exome mutations in clinical and biological applications of NGS technology.
ARTICLE | doi:10.20944/preprints202112.0515.v1
Online: 31 December 2021 (11:41:16 CET)
Background : The current corruption case in Indonesia are severely problematic since it is normalized by society. As a response, the current agenda of the Indonesian government to tackle it is by raising awareness of youth towards Indonesia’s corruption case. Aim : This study aims to knowing the importance of anti-corruption education and its applications among students. Method : The methodology of this study is the use of a qualitative survey on Faculty of Pharmacy students and interviews with representatives of students of the Faculty of Pharmacy. The population of this study is students of Airlangga University. The sample of this study is 52 students of class C the Faculty of Pharmacy Result : Students have awareness about corruption and even proposed that the current anti-corruption education is not enough to tackle corruption. Recommendation : The researcher suggests that students can be brave to campaign about the importance of anti-corruption education to the public. Limitation : The limitation of this study is that it is difficult to conduct research because in the online pandemic era, this results in delays in the research process.
ARTICLE | doi:10.20944/preprints202106.0321.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Pancasila; Young Generation; Globalization
Online: 11 June 2021 (14:15:25 CEST)
Pancasila is the identity of the Indonesian nation, which means that Pancasila is a national characteristic that cannot be found in any country. Pancasila points are taken from the noble values of the Indonesian state. These principles contain culture, customs, and national character known as manners, cooperation, and high nationalism. As the successor to Indonesian culture, the young generation must be able to preserve and develop Pancasila. In this era of globalization, there are many challenges for the younger generation in preserving Pancasila. This study aims to provide an overview of the decline of Pancasila identity among the younger generation due to the impact of globalization. The research question that has been determined is how the practice behaviour of the younger generation towards the implementation of Pancasila, the solutions and efforts that all Indonesian people can make regarding the crisis of Pancasila identity in the era of globalization. This research method uses a literature review. The research sources were conducted from the latest journals and books published in 2019 until 2021 related to the theme of Pancasila and the millennial generation. The results showed that globalization has greatly facilitated foreign cultures to enter Indonesia. The younger generations use this foreign culture as a lifestyle without filtering it, whether it contains Pancasila values or not. This causes Pancasila has been forgotten and no longer applied in their everyday life. Young people can make various efforts to preserve the national identity, namely Pancasila. Apart from the role of the young generation itself, Indonesian society can also play an essential role in supporting the younger generation to continue implementing Pancasila in their lives. By conducting this research, it is hoped that Indonesia's young generation can understand, select, and stay away from the negative impacts of globalization that enter Indonesia freely. The solution that can be given from this research is that the younger generation must love their own culture more and practice every principle in Pancasila. Parents, educational institutions, and the government must also support the younger generation to maintain national identity, Pancasila values. The limitation of this research is that the researcher did not conduct any primary data, which means the data were not directly from the source. This causes the accuracy of this study to be less guaranteed. The recommendation that the researchers can give for further research is to obtain primary data to ensure accuracy and explore research topics regarding the fading of Pancasila identity in the younger generation in this era of globalization.
ARTICLE | doi:10.20944/preprints202106.0287.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Pancasila; Millennial Generation; Globalization
Online: 10 June 2021 (10:44:19 CEST)
Technological developments, as a result of globalization, indirectly affect human lifestyles, one of which is the Indonesian people. In a situation of change towards the Industrial Revolution 4.0, Pancasila has a role as a guide for the Indonesian people to be what by the noble values of the nation. However, the role of the millennial generation in maintaining these noble values is important considering that they are the spearhead of the country's development. From this statement, this study aims to identify and formulate steps to maintain the noble values of Pancasila among the millennial generation so that it does not eliminate national identity and understand the urgency of implementing the Pancasila lifestyle in the era of globalization. By using the literature review method, it can be seen that "grounding" and strengthening the essence of Pancasila values can be a solution so that the existence of Pancasila continues to shine. The Pancasila lifestyle deserves to be implemented because it regulates all behaviors of speech, thought, behavior, action, and good manners so that it must be expressed in the life of the nation and state as well as our everyday life.
ARTICLE | doi:10.20944/preprints202104.0630.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: Paraphrase Identification; Paraphrase Generation; Natural Language Generation; Language Model; Encoder Decoder; Transformer
Online: 23 April 2021 (10:35:20 CEST)
Paraphrase Generation is one of the most important and challenging tasks in the field of Natural Language Generation. The paraphrasing techniques help to identify or to extract/generate phrases/sentences conveying the similar meaning. The paraphrasing task can be bifurcated into two sub-tasks namely, Paraphrase Identification (PI) and Paraphrase Generation (PG). Most of the existing proposed state-of-the-art systems have the potential to solve only one problem at a time. This paper proposes a light-weight unified model that can simultaneously classify whether given pair of sentences are paraphrases of each other and the model can also generate multiple paraphrases given an input sentence. Paraphrase Generation module aims to generate fluent and semantically similar paraphrases and the Paraphrase Identification systemaims to classify whether sentences pair are paraphrases of each other or not. The proposed approach uses an amalgamation of data sampling or data variety with a granular fine-tuned Text-To-Text Transfer Transformer (T5) model. This paper proposes a unified approach which aims to solve the problems of Paraphrase Identification and generation by using carefully selected data-points and a fine-tuned T5 model. The highlight of this study is that the same light-weight model trained by keeping the objective of Paraphrase Generation can also be used for solving the Paraphrase Identification task. Hence, the proposed system is light-weight in terms of the model’s size along with the data used to train the model which facilitates the quick learning of the model without having to compromise with the results. The proposed system is then evaluated against the popular evaluation metrics like BLEU (BiLingual Evaluation Understudy):, ROUGE (Recall-Oriented Understudy for Gisting Evaluation), METEOR, WER (Word Error Rate), and GLEU (Google-BLEU) for Paraphrase Generation and classification metrics like accuracy, precision, recall and F1-score for Paraphrase Identification system. The proposed model achieves state-of-the-art results on both the tasks of Paraphrase Identification and paraphrase Generation.
ARTICLE | doi:10.20944/preprints202106.0331.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Pancasila; Millennial Generation; Modern Era
Online: 14 June 2021 (07:57:40 CEST)
Introduction: Industrial revolution 4.0 in the current era of globalization plays an active role in the modern era in Indonesia. The influence of increasingly advanced technology affects the millennial generation as the nation's next generation to make Pancasila the basis of the State or the foundation of a State. In addition, the millennial generation has begun to shift the guidelines of life from Pancasila so that the appreciation of Pancasila values is starting to disappear along with the development of the times and in line with the progress of Science and Technology (IPTEK). If this continues, then the values of Pancasila will be replaced by a new ideology that will cause behavioural changes in society. Purpose: this study aims to provide the proper application to millennial life using Pancasila values, knowing the behaviour of the millennial generation towards the implementation of Pancasila values, and making Pancasila a way of life. Methods: the method used in this research is Literature Review and takes sources from journals published in 2019 to 2021 related to the Pancasila theme and the millennial generation. Results: the study results show that with the existence of Pancasila as the ideology and principle of the State, it is expected to strengthen the attitude and nature of the community in accepting things outside the norms that exist in Indonesia. In addition, the younger generation is expected to be able to apply Pancasila values along with the development of science and technology in the modern era and current globalization. The research question is how to make the millennial generation implement Pancasila in life in the contemporary period and what solutions can continue to instil Pancasila values in the 4.0 industrial revolution. Recommendation: the conclusion drawn is that Pancasila can become a unifying tool for the nation if the current generation or millennial generation still desires to maintain its values , even though they are in a modern era and many influences from its outside cultures. Limitation: the limitation of this research is not getting all the data directly from the source. The researcher recommends using primary data for the following study to ensure its truth and accuracy better because the researcher directly obtains it.
REVIEW | doi:10.20944/preprints202201.0436.v1
Subject: Chemistry, Electrochemistry Keywords: Methane Oxidation; reactor; generation energy; chemical
Online: 28 January 2022 (12:17:15 CET)
The conversion of methane into chemicals is of interest to achieve a decarbonized future. Fuel cells are electrochemical devices commonly used to obtain electrical energy, but can be utilized either for chemicals production or both energy and chemicals cogeneration. In this work, the partial oxidation of methane in fuel cells for electricity generation and valuable chemicals production at the same time is reviewed. For this purpose, different types of methane-fed fuel cells, both low temperature fuel cells, such as PEMFCs and AAEMFCs, and high temperature fuel cells, such as SOFCs, have been used. Also if few works have been devoted to this topic, the promising results drive the development of fuel cells using methane as the source for the cogeneration of power and valuable chemicals.
ARTICLE | doi:10.20944/preprints202106.0336.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Nationalism; The millennial generation; Covid-19
Online: 14 June 2021 (08:53:46 CEST)
Background: In the current era of globalization, the Indonesian government's problem today is the weakening of nationalism and patriotism among the millennial generation. The large number of foreign cultures that have entered Indonesia has caused a sense of nationalism and patriotism. In addition, Indonesia is also facing the problem of spreading the Covid-19 virus. During the pandemic, various policies set by the government received protests from some circles because they felt their freedom was restricted. Therefore, the awareness of millennial generation nationalism is needed, especially during the Covid-19 pandemic like today. This research aims to make millennials aware of nationalism sense, which mainly to prevent the spread of Covid-19. This research is used to answer the questions of what the problems that arise due to the waning of the spirit of nationalism during the pandemic are? and what efforts should be made to maintain the spirit of nationalism? Methods: This research is a qualitative study using the literature review method. The articles used are research published in 2019 to 2021 in Google Scholar, with keywords that match the topic of millennial generation nationalism in the Covid-19 pandemic. Results and Discussion: The results of the study found that the spirit of Indonesian nationalism during the Covid-19 pandemic was decreasing. The decline in the sense of nationalism is due to several government policies that impact the psychology of society and the Indonesian economy. As a result, society, particularly the millennial generation, must play a role in breaking the chain of the Covid-19 virus's propagation by following the government's health standards. Conclusion: The government and society need to work together to understand nationalism in the millennial generation, especially in dealing with problems caused by the Covid-19 pandemic. Based on this, various efforts need to be made to foster the spirit of nationalism and overcome the Covid-19 pandemic. So that later, it can produce a generation that upholds the value of nationalism in everyday life.
REVIEW | doi:10.20944/preprints202106.0300.v1
Subject: Keywords: multicultural education, morals, a young generation
Online: 10 June 2021 (15:16:01 CEST)
Introduction: Indonesia consists of a plural society with different ethnic, religious, racial, skin color, and other cultures. The difference must be understood by everyone, especially the younger generation in the digital age. If the younger generation does not have a sufficient understanding of multicultural education values, it will impact the moral crisis of the Indonesian nation. This research emphasizes the importance of multicultural education to the younger generation to understand the differences (pluralism) in society and respect them. Method: The method uses a qualitative method with the literature review method by collecting data on ten journals published in 2019, 2020, 2021. Results: The rise of socio-cultural conflicts in Indonesia is why applying multicultural values to the younger generation. Multiculturalism is needed to establish morals and sensitivity for a young person in the face of various social problems and symptoms at a growing age. Conclusion: Multicultural education is vital to the younger generation considering Indonesia has diverse nations and cultures. The efforts that can make to improve the morale of the nation's children, namely by learning citizenship education and religious education and utilizing information technology to spread things related to the values of multicultural education to the broader community
REVIEW | doi:10.20944/preprints202106.0216.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Pancasila, 21st Century Generation, 1945 Constitution
Online: 8 June 2021 (11:54:16 CEST)
Introduction: Pancasila was born as the ideology of the Indonesian nation, which reflects the values cultural values, ethics, morals, and the spirit of the nation. Pancasila was born as a form of national character, which reflects divinity, nationality, unity, togetherness, and justice. The purpose of this research is to know the practice of Pancasila values in the life of the nation and the state. Especially, the implementation of the life of the younger generation in the 21st century today. Methods: This study is literature research where data is collected using keywords in the database. Literature source search carried out with the help of Boolean operators and using the PICOS format. The results of selecting articles, using PRISMA Flow Diagrams. The search results found 125 articles that match the research theme. After checking for duplication, 82 articles were excluded because of the similarity in the results of the discussion. In the end, there were 43 articles used as a literature source. Results: Based on the analysis of research findings, which are supported by literature sources, it shows that the current values of Pancasila are worrying. This can be seen, where people's behavior has been contaminated by external cultures due to technological sophistication. At present, it can be said that the ethics and morals of society do not reflect the values of Pancasila. Conclusion: In order to re-install the values of Pancasila in people's lives, the participation of all parties is necessary. This is especially so, for today's younger generation. Therefore, it is necessary to develop a model for teaching Pancasila to be carried out by schools and colleges. So that later, it can produce a generation of ethics and morals who love the country.
ARTICLE | doi:10.20944/preprints202103.0715.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: closure; interior; network generation; community; eigenvector
Online: 30 March 2021 (09:31:31 CEST)
Three computer algorithms are presented. One reduces a network $\CALN$ to its interior, $\CALI$. Another counts all the triangles in the network, and the last randomly generates networks similar to $\CALN$ given just its interior $\CALI$. But these algorithms are not the usual numeric programs that manipulate a matrix representation of the network; they are set-based. Union and meet are essential binary operators; contained_in is the basic relational comparator. The interior $\CALI$ is shown to have desirable formal properties and to provide an effective way of revealing ``communities'' in social networks.
Subject: Engineering, Marine Engineering Keywords: Ferry design; wave generation; ship hydrodynamics
Online: 14 January 2021 (07:54:26 CET)
In this paper, we revisit the hydrodynamics supporting the design and development of the RiverCat class of catamaran ferries operating in Sydney Harbor since 1991. More advanced software is used here. This software accounts for the hydrodynamics of the transom demisterns which experience partial or full ventilation, depending on the vessel speed. This ventilation gives rise to the hydrostatic drag, which adds to the total drag of the vessel. The presence of the transom also creates a hollow in the water. This hollow causes an effective hydrodynamic lengthening of the vessel, which leads to a reduction in the wave resistance. Hence a detailed analysis is required in order to optimize the size of the transom. It is demonstrated that the drag of the vessel and the wave generation can be predicted with good accuracy. Finally, the software is also used to optimize the vessel further by means of affine transformations of the hull geometry.
ARTICLE | doi:10.20944/preprints202010.0080.v1
Subject: Medicine & Pharmacology, Allergology Keywords: bioflavonoids; superoxide generation; oxidative phosphorylation; translocation
Online: 5 October 2020 (12:13:08 CEST)
In present work, the effects of bioflavonoids (ginkgetin and sciadopitysin) on stimulus-induced superoxide generation, tyrosyl and serine/threonine phosphorylation of proteins in human neutrophils, and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane were studied, which were isolated from the needles of Taxus media var. Hicksii. Meanwhile, three normal flavonoids (apigenin, quercetin and isoquercetin) were involved as contrasts. The results indicated that ginkgetin and sciadopitysin were capable of concentration-dependently inhibitory effects on the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), arachidonic acid (AA) and phorbol-12-myristate 13-acetate (PMA). And they also suppressed fMLP- and AA- induced tyrosyl or PMA-induced serine/threonine phosphorylation and the translocation of cytosolic compounds (p47phox, p67phox and Rac) to cell membrane, which were in parallel with the suppression of the stimulus-induced superoxide generation. The effect of these compounds on the radical-scavenging was also investigated. Ginkgetin and sciadopitysin did not show remarkable effect on DPPH radical-scavenging activity, and they didn’t display the radical-scavenging activity on superoxide anion generated by phenagine methoxysulfate (PMS)-NADH system. Apparently, ginkgetin and sciadopitysin had great performance in pharmacological value and they are worthy of in-depth study.
ARTICLE | doi:10.20944/preprints202009.0265.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: Microgrid; Distribution System; Generation Transfer; Reliability
Online: 12 September 2020 (07:38:16 CEST)
When a microgrid is grid-tied to a distribution system, it can provide surplus power generation to the distribution system, if any abnormality or interruption occurs in the distribution system, the microgrid can operate in standalone mode to isolate the impact of the abnormality or interruption. However, if the microgrid can not collect enough information from the distribution system, it may cause the failure of generation transferring of distribution feeders, or even further influence the stability of the distribution system. In this paper, a strategy for the resilient control of a microgrid is proposed. It can solve the above-mentioned problem, reduce the duration of the outage of loads. This strategy is experimented in the microgrid in the Institute of Nuclear Energy Research (INER), the reliability is also analyzed to evaluate the unavailability of the microgrid in INER, and it is verified that the proposed strategy can reduce the duration of the outage of loads, and hence the reliability of a microgrid can be upgraded.
ARTICLE | doi:10.20944/preprints202205.0398.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: Generative Software Development; Code Generation; Complexty Space
Online: 30 May 2022 (11:32:07 CEST)
This survey proposed an evaluation model to analyze and examine different approaches to generativity. In addition to problem domain concepts, the following concepts were used to define this model: Complexity and complexity management, and Systematics view to achieve unified and integrated insight into disparate evaluation criteria. The research's approach to the said concepts is first introduced. Then, the evaluation model is presented.
ARTICLE | doi:10.20944/preprints202106.0348.v1
Online: 14 June 2021 (10:36:05 CEST)
Character education is essential for the current millennial generation and must be applied in everyday life in the surrounding community. The character of the millennial generation is different from the previous generation, which requires us to pay more attention to character education which is starting to erode along with the times. The Millennial generation is a generation that in everyday life can never be separated from science and technology. In this digital era, the millennial generation has a social function of strength in technology. In this study, there are research questions that will be discussed in this article, namely the first regarding what problems occur in the millennial generation who occupy the digital era?. Second, what is the important role and influence of the digital era on character education for the millennial generation in Indonesia?. Writing this article uses a qualitative research method, namely a literature review study, where researchers use or look for references from journals or books. Samples of respondents were taken randomly from each region, and there were ten respondents. From this research, it is found that the millennial generation in the digital era chooses to use social media to access the latest news and information rather than reading print media that contains education. This article aims to find out the importance of character education for the millennial generation, which is starting to erode with the times in the digital era. Many people underestimate character education, especially for the current millennial generation. Therefore, we must implement educational programs at any level, especially in Indonesia, because the character shows the national identity. This article will discuss the vital role and influence of character education for millennials who live in the digital era to be aware of the importance of character education in citizenship.
Subject: Engineering, Automotive Engineering Keywords: ADAS simulation; scenario generation; automated driving; Testing; innovation in mobility; self-driving cars; transportation
Online: 7 December 2020 (11:24:16 CET)
The increasingly used approach of combining different simulation software in testing of automated driving systems (ADS) increases the need for potential and convenient software designs. Recently developed co-simulation platforms (CSP) provide the possibility to cover the high demand on testing kilometers for ADS by combining vehicle simulation software (VSS) with traffic flow simulation software (TFSS) environments. The emphasis on the demand of testing kilometers is not enough to choose a suitable CSP. The complexity level of the used vehicle, object, sensors and environment models is essential for valid and representative simulation results. Choosing a suitable CSP raises the question of how the test procedures should be defined and constructed and what the relevant test scenarios are. Parameters of the ADS, the environments, objects, sensors in VSS as well as traffic parameters in TFSS can be used to define and generate test scenarios. In order to generate a large number of scenarios in a systematic and automated way, suitable and appropriate software designs are required. In this paper we present a software design for CSP based on the Model-View-Controller (MVC) design pattern and implementation of a complex CSP for virtual testing of ADS. Based on this design, an implementation of a CSP is presented using the VSS from IPG Automotive called CarMaker and the TFSS from PTV Group called Vissim. The results have shown that the presented CSP design and the implementation of the co-simulation can be used to generate relevant scenarios for testing of ADS.
ARTICLE | doi:10.20944/preprints201901.0048.v1
Subject: Earth Sciences, Atmospheric Science Keywords: precipitation; microphysics; convective precipitation; meteosat second generation
Online: 4 January 2019 (14:41:38 CET)
The Convective Rainfall Rate from Cloud Physical Properties (CRPh) for Meteosat Second Generation Satellites is a day-only precipitation algorithm developed at the Spanish Meteorological Agency (AEMET) for EUMETSAT’ Satellite Application Facility in support to Nowcasting and Very Short Range Forecasting (NWC SAF). It is therefore mainly intended to provide input for monitoring and near-real-time forecasts for the next few hours. This paper critically discusses the theoretical basis of the algorithm with special emphasis in the empirical values and assumptions in the microphysics of precipitation and compares the performances of the CRPh with its antecessor, the Convective Rainfall Rate algorithm (CRR), using an object-based method. The analyses show that AEMET’s CRPh is physically consistent and that outperforms the CRR. The applicability of the algorithm for nowcasting and the challenges to evolve the product to an all-day algorithm are also presented.
ARTICLE | doi:10.20944/preprints201806.0417.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: female, generation, hospital, intention to leave, nurse
Online: 26 June 2018 (12:34:58 CEST)
An understanding of the cultural conditions that determine the factors affecting nurses’ intention to leave is important for countries suffering from nurse shortage. Aim: to examine factors influencing intention to leave among female hospital nurses in a large Japanese sample, classified into four generations by age considering economic conditions. Methods: a cross-sectional survey with convenience sampling was conducted. Anonymous self-administered questionnaires were distributed to all nurses in 30 hospitals. To assess intention to leave, basic attributes, life conditions, work characteristics, and factors of psychosocial work environment were addressed. After classifying data into four generations based on age cohorts, we conducted multivariate logistic regression analysis using the completed data (N = 5,074, mean age = 36.24). Results: regardless of generational characteristics influenced by economic conditions, effort and monetary reward were generation-common factors. Over-commitment, social support, and the presence of a role model were generation-common factors in three generations. While having children increased intention to leave in the generation born 1965–1979, having family members in need of caregiving other than children decreased the risk in the generation born in the 1980s. Conclusion: generational countermeasures considering factors of psychosocial work environment and life conditions are needed to avert female nurse turnover.
ARTICLE | doi:10.20944/preprints202208.0016.v1
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: Security; Pseudorandom Number Generation; Parallel Computing; Cellular Automata
Online: 1 August 2022 (09:21:14 CEST)
Nowadays the practice of developing algorithms to maintain the confidentiality of data shows that there is a lack of some features, such as velocity, predictability, etc. Generating pseudorandom numbers is one such problem that lies in the basement of many algorithms, even in hardware microprograms. An unreliable generator can cause cyberattacks on it, despite the security in the upper layers. At the same time, the algorithm should be fast enough to provide uninterrupted circuit work for the entire system. The paper presents a new algorithm generating pseudorandom numbers on cellular automata, which is not only fast and easy-repeating, but unpredictable enough and can be used in cryptographic systems. Using the NIST statistical test suite for random and pseudorandom number generators (PRNG), it is shown that the presented algorithm is more than three times superior to the state-of-the-art methods and algorithms in terms of ? − ?????. A high level of the presented algorithm’s parallelization allows for implementation it effectively on calculators with parallel structure. CPU-based architecture, FPGA-based architecture, CUDA- based architecture of PRNG and different PRNG implementations are presented to confirm high performance of the proposed solution.
ARTICLE | doi:10.20944/preprints202203.0232.v1
Subject: Materials Science, Surfaces, Coatings & Films Keywords: Solar steam generation; Photothermal materials; Daikon; Polydopamine; Polypyrrole
Online: 16 March 2022 (10:16:34 CET)
Interface solar steam generation (ISSG) are charming for its applications in desalination and wastewater treatment. Biomass is an attractive substrate for utilizing solar vapor evaporators because of its natural pore structure and water transportability. Polymers like polydopamine (PDA) and polypyrrole (PPy) with broadband spectrum absorption are fascinating in photothermal materials (PTMs). Herein, PDA coated daikon-based (PDA-DK) and PPy coated daikon-based (PPy-DK) PTMs have been exploited for solar steam generation. When polyethylene foam (PEF) was used as an insulating layer to limit heat loss from the PTMs to bulk water, the evaporation rate of PDA-DK and PPy-DK was raised from 0.82 kg m–2 h–1 and 0.96 kg m–2 h–1 to 1.50 kg m–2 h–1 and 1.60 kg m–2 h–1, respectively. Meanwhile, the corresponding photothermal conversion efficiency was increased to 89.01% and 98.97%, which was increased by nearly 40% under 1-sun irradiation. In addition, PDA-DK and PPy-DK exhibited remarkable stability for the solar steam generation without significant change through 15 cycles. Furthermore, PDA-DK and PPy-DK could effectively desalt seawater and purify dyeing wastewater. All the results indicate that PDA-DK and PPy-DK have great potential in real-world applications for solar steam generation.
ARTICLE | doi:10.20944/preprints202106.0301.v1
Subject: Arts & Humanities, General Humanities Keywords: Character education, Pancasila, the millennial generation, digital era.
Online: 10 June 2021 (15:17:44 CEST)
Background: Currently, Indonesia is entering an era that is all digital and uses technology in all fields of activity. The internet has a lot to do with their behavior or character. Millennials are the nation's next generation. The emergence of the digital era caused by globalization has made the millennial generation less appreciative and practicing the values of Pancasila. In this case, character education is something that must be applied to the millennial generation. Purpose: This study aims to analyze the characteristics of the millennial generation, the role of character education in realizing the values of Pancasila in the daily life of the millennial generation, how to cultivate an attitude of patriotism and nationalism towards the nation by practicing Pancasila, and provide motivation for the millennial generation to realize these values. Pancasila values. Methods: This study uses a literature review method. The search for journals was carried out using the google scholar database with the keywords “Character Education”, “millenial generation”, and “Pancasila”. The journals selected are journals from 2019 to 2020. Results: By applying character education to the millennial generation, it will make it easier for them to practice the values of Pancasila. Pancasila should be the way of life of the millennial generation. Recommendation and limitation: As millennials, we must protect the country from values that are contrary to Pancasila. Character education must be applied following the nature of the millennial generation itself. Of course, the applied character education must prioritize and be based on the values of Pancasila as well.
REVIEW | doi:10.20944/preprints202106.0260.v1
Subject: Arts & Humanities, Anthropology & Ethnography Keywords: Pancasila; Millennial Generation; Industrial Revolution; human capital management
Online: 9 June 2021 (11:20:18 CEST)
Introduction: The imbalance between technological development and ideological strengthening has resulted in the fading of the Pancasila ideological values of millennials. Technology that accompanies everyday life seems to be the main character in human life. Yet if humans themselves do not use technology wisely, technology can be a threat to both individuals and the life of the nation and state. If technology is increasingly out of control, threats to the Pancasila ideology are very likely to occur, such as in the G 30S PKI incident. Therefore, it is necessary to take action both from the government and the community as individuals to safeguard the development of technology to be used wisely. That way, we can prevent the threat to the Pancasila ideology together. Writing this article aims to analyze how the role and influence of the Pancasila ideology on the millennial generation in the 4.0 industrial revolution and to find solutions so that the values of Pancasila remain attached to the next generation of the Indonesian nation. Method: Writing This article uses a qualitative method by using literature reviews from the results of related research journals that have been published online through websites and other online media. Results: Thirteen journals and one book have met the criteria for the inclusion of a predetermined review. Research is based on the stigma of society regarding technological developments in the Industrial revolution 4.0. Therefore, the government is expected to be more severe in implementing human capital management. Conclusion: By procuring human capital management, it will be possible that Human Resources (HR) in Indonesia will be able to carry out the ideals of a golden Indonesian generation with Pancasila values inherent in the hearts of the people and the nation's future generations.
ARTICLE | doi:10.20944/preprints202103.0290.v1
Subject: Engineering, Energy & Fuel Technology Keywords: Climate Change Scenario; Generation Potential; Hydropower; Renewable Energy
Online: 10 March 2021 (16:08:37 CET)
The interest in renewable energy to replace fossil fuel is increasing as the problem caused by climate change become more severe. Small hydropower (SHP) is evaluated as a resource with high development value because of its high energy density compared to other renewable energy sources. SHP may be an attractive and sustainable power generation environmental perspective because of its potential to be found in small rivers and streams. The power generation potential could be estimated based on the discharge in the river basin. Since the river discharge depends on the climate conditions, the hydropower generation potential changes sensitively according to climate variability. Therefore, it is necessary to analyze the SHP potential in consideration of future climate change. In this study, the future prospect of SHP potential is simulated for the period of 2021 to 2100 considering the climate change in three hydropower plants of Deoksong, Hanseok, and Socheon stations, Korea. As the results, SHP potential for the near future (2021 to 2040) shows a tendency to be increased and the highest increase is 23.4% at the Deoksong SPH plant. Through the result of future prospect, we have shown that hydroelectric power generation capacity or SHP potential will be increased in the future. Therefore, we believe that it is necessary to revitalize the development of SHP in order to expand the use of renewable energy. Also, a methodology presented in this study could be used for the future prospect of the small hydropower potential.
COMMUNICATION | doi:10.20944/preprints202009.0064.v1
Subject: Physical Sciences, Optics Keywords: Sum frequency generation; femtosecond pulses; noncollinear phase matching.
Online: 3 September 2020 (07:58:18 CEST)
We show broadband sum-frequency generation (SFG) in the Green-Yellow-Orange-Red spectral range using bismuth triborate, BiB3O6 crystal (BIBO) as nonlinear material. We perform a noncollinear phase-matching configuration within BIBO crystal using the remaining light behind the second harmonic generation stage and the infrared idler of an optical parametric amplifier (OPA). The obtained mixing radiation of ultrafast light sources to generate femtosecond pulses across 520.5 to 742.5 nm region is observed. SFG spectrum from single-pass cross-correlation intensity over such visible range is showed. The SFG wavelengths as a function of tunable wavelength idler OPA agrees with the expectations of parametric conversion condition and open the door to practical multi-beam or multi-color sum-frequency generators.
ARTICLE | doi:10.20944/preprints201808.0414.v1
Subject: Physical Sciences, Optics Keywords: Second harmonic generation, Mie resonances, all-dielectric nanoparticles
Online: 23 August 2018 (11:31:14 CEST)
We design an asymmetric nonlinear optical nanoantenna composed of a dielectric nanodisk and an adjacent nanobar. The proposed composite structure made of AlGaAs exhibits resonant response at both the fundamental and doubled frequencies. Being driven by the strong magnetic dipole resonance at the pump wavelength and a high-quality mode at the harmonic wavelength, the efficient second-harmonic radiation is generated predominantly along the vertical directions under the normally incident plane-wave excitation.
ARTICLE | doi:10.20944/preprints202110.0205.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: electricity distribution; microgrids; prosumers; phase generation management; metaheuristic optimization.
Online: 13 October 2021 (14:54:49 CEST)
Four-wire low voltage microgrids supply one-phase consumers with continuously changing electricity demand. For addressing climate change concerns, governments implemented incentive schemes for residential consumers, encouraging the installation of home PV panels for covering self-consumption needs. In the absence of sufficient storage capacities, the surplus is sold back by these entities, called prosumers, to the grid operator or in local markets, to other consumers. While these initiatives encourage the proliferation of green energy resources, and ample research is dedicated to local market designs for prosumer-consumer trading, the main concern of distribution network operators is the influence of power flows generated by prosumer surplus injection on the operating states of microgrids. The change in power flow amount and direction can greatly influence the economic and technical operating conditions of radial grids. This paper proposes a metaheuristic algorithm for prosumer surplus management that optimizes the power surplus injections using the automated control of three-phase inverters, with the aim of improving the active power losses and balancing the phase voltage profiles. A case study is performed on two real distribution networks with distinct layouts and load profiles and the algorithm shows its efficiency in both scenarios.
ARTICLE | doi:10.20944/preprints202012.0825.v1
Subject: Engineering, Automotive Engineering Keywords: Modular Climbing Robots; Vacuum Generation; Computer Fluid Dynamics; Optimization
Online: 31 December 2020 (16:01:52 CET)
Adhesion systems are very important in robots for infrastructure inspection (especially in vertical walls). They present the challenge of optimizing the ratio vacuum/power consumption in battery-powered robots. In this paper a CFD (Computer Fluid Dynamics) modelling and optimization process of a robot adhesion system is carried out to determine the best performing configuration in terms of vacuum and power consumption. Analytical and numerical models were developed to predict the behaviour of the system for different configurations. The models were validated, using test rig measurements, by calibrating an arbitrary defined inlet height that simulates the leakage flow. Then, different geometric parameters were varied to determine the best performing configuration based on the vacuum/power consumption ratio value. The model presented in the paper was capable of predicting the behaviour of the system for different configurations, with a margin of error of 15% for the vacuum prediction and a 25% for the motor power calculation. Finally, the model was used to optimize parameters of the system, like the number of blades of the impeller. The adhesion system was conceived for the modular autonomous climbing legged robot ROMERIN.
ARTICLE | doi:10.20944/preprints202011.0436.v1
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: Space-filling curves; Ergodic Theory; uniform random number generation.
Online: 16 November 2020 (16:51:07 CET)
In this paper the problem of sampling from uniform probability distributions is approached by means of space-filling curves (SFCs), a topological concept that has found a number of important applications in recent years. Departing from the theoretical fact that they are surjective but not necessarilly injective, the investigation focused upon the structure of the distributions obtained when their domain is swept in a uniform and discrete manner, and the corresponding values used to build histograms, that are approximations of their true PDFs. This work concentrates on the real interval [0,1], and the Sierpinski space-filling curve was chosen because of its favorable computational properties. In order to validate the results, the Kullback-Leibler distance is used when comparing the obtained distributions in several levels of granularity with other already established sampling methods. In truth, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. In this fashion, sequences resulting from this sort of process are not truly random.
Subject: Engineering, Automotive Engineering Keywords: microcombs; microwave photonics; micro-ring resonators; RF sideband generation
Online: 10 November 2020 (11:52:59 CET)
We review recent work on narrowband orthogonally polarized optical RF single sideband generators as well as dual-channel equalization, both based on high-Q integrated ring resonators. The devices operate in the optical telecommunications C-band and enable RF operation over a range of either fixed or thermally tuneable frequencies. They operate via TE/TM mode birefringence in the resonator. We achieve a very large dynamic tuning range of over 55 dB for both the optical carrier-to-sideband ratio and the dual-channel RF equalization for both the fixed and tunable devices.
ARTICLE | doi:10.20944/preprints202008.0051.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Variational autoencoder; Adversarial learning; Deep feature consistent; Data generation
Online: 2 August 2020 (18:11:27 CEST)
We present a method to improve the reconstruction and generation performance of variational autoencoder (VAE) by injecting an adversarial learning. On the other hand, instead of comparing the reconstructed with the original data to calculate the reconstruction loss, we use a consistency principle for deep features. The training process of the VAE is then divided into two steps, training the encoder and then training the decoder. By using this two-step learning process, our method can be more widely used in applications other than image processing. While training the encoder, the label information is integrated to better structure the latent space in a supervised way. The adversarial constraints allow the decoder to generate data with better authenticity and more realistic than the conventional VAE. We present experimental results to show that our method gives better performance than the original VAE.
Subject: Earth Sciences, Geophysics Keywords: solar radiation; meteosat second generation; validation; land surface modelling
Online: 27 October 2019 (04:25:31 CET)
High frequency knowledge of the spatio-temporal distribution of the Downwelling Surface Shortwave Flux (DSSF) and its diffuse fraction (fd) at the surface is nowadays essential for understanding climate processes at the surface-atmosphere interface, plant photosynthesis and carbon cycle, and for the solar energy sector. The EUMETSAT Satellite Application Facility for Land Surface Analysis operationally delivers estimation of the MDSSFTD (Downwelling Surface Short-wave radiation Fluxes – Total and Diffuse fraction) product with an operational status since the year 2019. The method for the retrieval was presented in the companion paper . The part 2 now focuses on the evaluation of the MDSSFTD algorithm and presents the comparison of the corresponding outputs, i.e. total DSSF and diffuse fraction (fd) components, against in-situ measurements acquired at four BSRN stations over a seven-month period. The validation is performed on an instantaneous basis. We show that the satellite estimates of DSSF and fd meet the target requirements defined by the user community for all-sky (clear and cloudy) conditions. For DSSF, the requirements are 20Wm-2 for DSSF<200Wm-2, and 10% for DSSF>=200Wm-2. The MBE and rMBE compared to the ground measurements are 3.618Wm-2 and 0.252%, respectively. For fd, the requirements are 0.1 for fd<0.5, and 20% for fd>=0.5. The MBE and rMBE compared to the ground measurements are -0.044 and -17.699%, respectively. The study also provides a separate analysis of the product performances for clear sky and cloudy sky conditions. The importance of representing the cloud-aerosol radiative coupling in the MDSSFTD method is discussed. Finally, it is concluded that the quality of the Aerosol Optical Depth (AOD) forecasts currently available is enough accurate to obtain reliable diffuse solar flux estimates. This quality of AOD forecasts was still a limitation a few years ago.
ARTICLE | doi:10.20944/preprints201909.0055.v1
Subject: Life Sciences, Biotechnology Keywords: P-MFCs; Cynodon dactylon; energy; bioelectric potential; electricity generation
Online: 5 September 2019 (09:55:54 CEST)
In these times electricity is big trouble of problem facing by the world. Therefore, there is necessitating for the property basis of energy that is employed for as bio-electricity. Many of the scientists and researchers are trying to find out the sustainable energy generates with the help of plant microbial fuel cell. Plant microbial fuel cell (P-MFCs) could be feasibility technology approach of bio-electricity generation which is mutualism interaction of the plants along with their rhizospheric bacteria. In the present study, Plant-microbial fuel cell was observed in grass e-table evaluated in term of bioelectricity generation from Cynodon dactylon (Dooba Ghas). This e-table was connected with electrode and different condition (physical and chemical) to detect the change in bioelectric potential. It was found that maximum voltage generated among all the conditions was 4.24 ±2V at 15 days by using Cynodon dactylon through P-MFCs. The potential difference generated through P-MFCs was measured using a multimeter. The generation of bioelectricity was observed under different conditions like exposure to light and shade condition measured for voltage was found to be significantly different parameters. The maximum recorded under light and shade conditions were 3.82 ±2 V and 4.25 ±2 V respectively at 15 days of incubation.
ARTICLE | doi:10.20944/preprints201901.0222.v1
Subject: Engineering, Marine Engineering Keywords: numerical wave tank; internal wavemaker; CFD; wave generation; OpenFOAM
Online: 22 January 2019 (12:09:25 CET)
Computational Fluid Dynamics (CFD) simulations, based on Reynolds Averaged Navier Stokes (RANS) models, are a useful tool for a wide range of coastal and offshore applications, providing a high fidelity representation of the underlying hydrodynamic processes. Generating input waves in the CFD simulation is performed by a numerical wavemaker (NWM), with a variety of different NWM methods existing for this task. While NWMs, based on impulse source methods, have been widely applied for wave generation in depth averaged, shallow water models, they have not seen the same level of adoption in the more general RANS based CFD simulations, due to difficulties in relating the required impulse source function to the resulting free surface elevation for non-shallow water cases. This paper presents an implementation of an impulse source wavemaker, which is able to self-calibrate the impulse source function to produce a desired wave series in deep or shallow water at a specific point in time and space. Example applications are presented, for a numerical wave tank (NWT), based on the opensource CFD software OpenFOAM, for wave packets in deep and shallow water, highlighting the correct calibration of phase and amplitude. Also, the suitability for cases requiring very low reflection from NWT boundaries is demonstrated. Possible issues in the use of the method are discussed and guidance for good application is given.
ARTICLE | doi:10.20944/preprints201901.0074.v1
Subject: Engineering, Mechanical Engineering Keywords: natural convection; entropy generation; square cavity; low pressure; nanofluid
Online: 8 January 2019 (15:29:16 CET)
Computational Fluid Dynamics (CFD) is utilized to study entropy generation for the rarefied steady state laminar 2-D flow of air-Al2O3 nanofluid in square cavity equipped with two solid fins at the hot wall. Such flows are of great importance in industrial applications, such cooling of the electronic equipment’s and nuclear reactors. In the current study, effects of Knudsen number (Kn), Rayleigh number (Ra) and the nano solid particles volume fraction (ϕ) on the entropy generation are investigated. The values of parameters considered in this work are as follows: 0≤Kn≤0.1, 〖10〗^3≤Ra≤〖10〗^6,0≤ϕ≤0.2. Length of the fins (LF) is considered to be fixed and equals to 0.5 m, whereas the location of the fins with respect to the lower wall (HF) is set to 0.25 and 0.75 m. Simulations demonstrate that there is an inverse direct effect of Kn on the entropy generation. Moreover, it is found that when Ra is less than 104, the entropy generation, due to the flow, increases as ϕ increases. In addition, the entropy generation due to the flow will decrease at Ra greater than 104 as ϕ increases. Moreover, the entropy generation due to heat will increase as both the ϕ and Ra increase. In addition, a correlation model of the total entropy generation as a function of all of the investigated parameters in this study is proposed. Finally, an optimization technique is adapted to find out the conditions at which the total entropy generation is minimized
ARTICLE | doi:10.20944/preprints202206.0339.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: Current Oscillator; Pyragas Model; Second-Generation Current Carrier; Bioimpedance Spectroscopy
Online: 24 June 2022 (13:45:47 CEST)
Current sources play an essential role in tissue excitation used in bioelectrical impedance spectroscopy. Most investigations use Howland current sources that, despite their practicality and simplified implementation, have operating frequency limitations and dependence on the load impedance due to theirs narrow output impedance, specially at higher frequencies. The objective of this work is to propose model for a robust current-controlled sinusoidal oscillator. The oscillator is based on fully analog electronics, which enables controlling oscillation phase and amplitude by using a voltage reference. The mathematical model is based on Pyragas control application to the classical harmonic oscillator. From the modelling process, it was build an oscillator topology based on second-generation current carriers and on transconductance amplifiers. The reference signal (Fsync) was a sinusoidal voltage source having a frequency of 1MHz and an amplitude of 1Vpp. The oscillator output current synchronized the oscillations’ phase and amplitude with Fsync, regardless of their magnitude before the control signal acted in the circuit at t≈13.5μs. SPICE simulations using ideal components have confirmed the successful operation of the proposed oscillator. This type of oscillator can be implemented in SOIC, then allowing oscillation control interface with logic circuits.
ARTICLE | doi:10.20944/preprints202112.0249.v4
Subject: Mathematics & Computer Science, Algebra & Number Theory Keywords: composite number; composite numbers distribution; composite numbers generation; prime number
Online: 24 December 2021 (07:36:30 CET)
Integer is either a composite number or a prime number. Therefore, detecting composite numbers is important for solving prime numbers. The study of prime numbers, apart from satisfying human curiosity, can be very important. In this article, the order of composite numbers has been detected. And explained with a simple method and a simple function. And, a method has been developed in which all composite numbers and therefore prime numbers can be determined by using the specified methods, functions and formulas.
ARTICLE | doi:10.20944/preprints202109.0493.v1
Subject: Physical Sciences, Optics Keywords: vortex propagation; difference frequency generation; nonlinear medium; vortex beams conversion
Online: 29 September 2021 (11:45:59 CEST)
The article is devoted to issues related to the propagation and transformation of vortexes in the optical range of frequency. Within the framework of the traditional and modified model of slowly varying envelope approximation (SVEA), the process of converting vortex beams of the optical domain into vortex beams of the terahertz radio range based on nonlinear generation of a difference frequency in a medium with a second-order susceptibility is considered. The modified SVEA splits a slowly varying amplitude into two factors, which makes it possible to more accurately describe the three-wave mixing process. The theoretical substantiation of the rule of vortex beams topological charges conversion is given – the topological charge of the output radio-vortex beam is equal to the difference between the topological charges of the input optical vortex beams. A numerical simulation model of the processes under consideration has been implemented and analyzed.
ARTICLE | doi:10.20944/preprints202109.0460.v1
Subject: Mathematics & Computer Science, Probability And Statistics Keywords: Space-filling curves; Ergodic Theory; random number generation; Gaussian distribution
Online: 28 September 2021 (09:56:55 CEST)
This work addresses the problem of sampling from Gaussian probability distributions by means of uniform samples obtained deterministically and directly from space-filling curves (SFCs), a purely topological concept. To that end, the well-known inverse cumulative distribution function method is used, with the help of the probit function,which is the inverse of the cumulative distribution function of the standard normal distribution. Mainly due to the central limit theorem, the Gaussian distribution plays a fundamental role in probability theory and related areas, and that is why it has been chosen to be studied in the present paper. Numerical distributions (histograms) obtained with the proposed method, and in several levels of granularity, are compared to the theoretical normal PDF, along with other already established sampling methods, all using the cited probit function. Final results are validated with the Kullback-Leibler and two other divergence measures, and it will be possible to draw conclusions about the adequacy of the presented paradigm. As is amply known, the generation of uniform random numbers is a deterministic simulation of randomness using numerical operations. That said, sequences resulting from this kind of procedure are not truly random. Even so, and to be coherent with the literature, the expression ”random number” will be used along the text to mean ”pseudo-random number”.
ARTICLE | doi:10.20944/preprints202009.0304.v2
Subject: Earth Sciences, Atmospheric Science Keywords: COVID-19; waste generation; waste collection; gap assessment; emergency plans
Online: 23 June 2021 (11:39:27 CEST)
The nationwide lockdown imposed to control the spread of novel coronavirus induced dramatic alterations in different sectors of the Nepalese governance, including Solid Waste Management (SWM) practices. The study identifies SW collection gaps in seven major cities of Nepal and highlights the municipal and public households on SW management practices before and during the lockdown to emphasize the linkage between COVID-19 and SWM. It includes information on solid waste status, collection frequency and coverage, workers safety practices, types of vehicles operated for collection and alternative methods adopted by households to manage SW during the lockdown. For this, 1329 households survey and key informant interviews were conducted in seven cities of Nepal during the lockdown. It was found that although the coverage of the collection service was similar during the pandemic, there was a drastic decrease in the collection frequency leading to a collection gap of around 570 tons/day. More than 50% of the surveyed households adopted no proper alternative measures as they claimed that they stored solid waste with proper management so that municipal authorities can take it. The study reveals poor occupational health and safety practices among the solid waste workers due to the unavailability of safety gears and equipment despite being aware of the modes of transmission of the virus. The pandemic exacerbated the challenges of smooth SWM as it is an essential and needy service. This study highlights the need for a timely strategic management framework to be developed by the government to continue the smooth SWM practices during the lockdown.
ARTICLE | doi:10.20944/preprints202106.0416.v1
Subject: Mathematics & Computer Science, Probability And Statistics Keywords: Prime Number; Prime Numbers Distribution; Prime Number Generation; Normal Distribution
Online: 15 June 2021 (15:58:34 CEST)
In this research first, a sequence of properties called delta is assigned to each prime number and then examined. Deltas are only dependent on the distribution of prime numbers, so the results obtained for the delta distribution can be considered as a proxy for the distribution of prime numbers. The first observation was that these properties are not unique and different prime numbers may have the same value of delta of a given order. It was found that a small number of deltas cover a large portion of prime numbers, so by recognizing repetitive deltas, the next prime numbers can be predicted with a certain probability, but the most important observation of this study is the normal distribution of deltas. This research has not tried to justify the obtained observations and instead of answering the questions, it seeks to ask the right question.
ARTICLE | doi:10.20944/preprints202103.0754.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: paraphrase generation; syntax information; Graph Convolutional Network; sequence-to-sequence
Online: 31 March 2021 (07:57:56 CEST)
Paraphrase generation is an important yet challenging task in NLP. Neural network-based approaches have achieved remarkable success in sequence-to-sequence(seq2seq) learning. Previous paraphrase generation work generally ignores syntactic information regardless of its availability, with the assumption that neural nets could learn such linguistic knowledge implicitly. In this work we make an endeavor to probe into the efficacy of explicit syntactic information for the task of paraphrase generation. Syntactic information can appear in the form of dependency trees which could be easily acquired from off-the-shelf syntactic parsers. Such tree structures could be conveniently encoded via graph convolutional networks(GCNs) to obtain more meaningful sentence representations, which could improve generated paraphrases. Through extensive experiments on four paraphrase datasets with different sizes and genres, we demonstrate the utility of syntactic information in neural paraphrase generation under the framework of seq2seq modeling. Specifically, our GCN-enhanced models consistently outperform their syntax-agnostic counterparts in multiple evaluation metrics.
ARTICLE | doi:10.20944/preprints202102.0283.v1
Subject: Medicine & Pharmacology, Allergology Keywords: aerosol generation; e-cigarette; coil resistance; e-liquid; manufacturing variation
Online: 11 February 2021 (11:50:14 CET)
This work investigated the effects of manufacturing variations including coil resistance, initial pod mass, and e-liquid color on coil lifetime and aerosol generation of Vuse ALTO pods. Random samples of pods were used until failure (where e-liquid was consumed, and coil resistance increased to high value indicating a coil break). Initial coil resistance, initial pod mass, and e-liquid net mass ranged between 0.89 to 1.14 , 6.48 to 6.61 [g], and 1.88 to 2.00 [g] respectively. Coil lifetime with light color e-liquid was (mean) = 149, (standard deviation) = 10.7 puffs while pods with dark color e-liquid was = 185, = 22.7 puffs with a difference of ~36 puffs (p <0.001). Total mass of e-liquid consumed until coil failure was = 1.93, = 0.035 [g]. TPM yield per puff of all test pods for the first session (brand new pods) was = 0.0123, = 0.0003 [g]. During usage, TPM yield per puff of pods with light color e-liquid was relatively steady while it was continuously decreasing for pods with dark e-liquid. Coil lifetime and TPM yield per puff were not correlated with either variation in initial coil resistance or variation in initial pod mass. The absence of e-liquid in the pod is an important factor in causing coil failure. Small bits of the degraded coil could be potentially introduced to the aerosol. There is a potential correlation of e-liquid color with both coil lifetime and TPM yield per puff. Change of e-liquid color might have been a result of oxidation which changed some nicotine into nicotyrine.
ARTICLE | doi:10.20944/preprints202101.0342.v1
Subject: Materials Science, Biomaterials Keywords: bismuth vanadium oxide; roots activity; reactive oxygen generation; gene expression
Online: 18 January 2021 (14:06:29 CET)
The excellent properties of nanomaterials have been confirmed in many fields, but the effects on plants are still unclear. In this study, we have found that bismuth vanadium promoted the growth of taproots and the development of lateral roots, increased the roots activity by regulating the expression of polyamine or hormone-related genes and reducing the accumulation of reactive oxygen species in Arabisdopsis thaliana. Meantime, BV had higher antimicrobial effect than that of graphene oxide (GO). These results showed us a new perspective possibility of nanomaterials assisting the development of plants and crops, which is expected to become one of the ways to solve the problem of controlling and promoting the development of plants and crops.
ARTICLE | doi:10.20944/preprints202101.0048.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: Artificial intelligence; Machine Learning; Reinforced Learning; Optimisation; Metaheuristic; Metaheuristic Generation
Online: 4 January 2021 (13:31:05 CET)
Machine learning research has been able to solve problems in multiple aspects. An open area of research is machine learning for solving optimisation problems. An optimisation problem can be solved using a metaheuristic algorithm, which is able to find a solution in a reasonable amount of time. However, there is a problem, the time required to find an appropriate metaheuristic algorithm, that would have the convenient configurations to solve a set of optimisation problems properly. A solution approach is shown here, using a proposal that automatically creates metaheuristic algorithms aided by a reinforced learning approach. Based on the experiments performed, the approach succeeded in creating a metaheuristic algorithm that managed to solve a large number of different continuous domain optimisation problems. This work's implications are immediate because they describe a basis for the generation of metaheuristic algorithms in real-time.
ARTICLE | doi:10.20944/preprints202011.0664.v1
Subject: Social Sciences, Accounting Keywords: Overlapping generation; Climate justice; Endogenous labor; OLG model; Intergenerational Sustainability
Online: 26 November 2020 (10:47:45 CET)
Climate justice as a commons is conceived as the intertemporal climate equity and equal- ity exchange amongst generations. Sustainability, intended as the interplay amongst the economy, the society, the environment, and the governance, is essential to forge the climate justice theoretical framework. On this base, the study attempts to model intertemporal choice amongst generations in these four domains, making use of an over- lapping generations (OLG) model. The proxies detected are GDP growth (economy), environmental quality (environment), and labor growth, and environmental investment (society) as assumptions. The governance dimension is captured by the di¤erence in wealth between young and old generations. The work aims at replying to the follow- ing research question: Which are the conditions for sustainable development such that climate justice holds? The intra-intergenerational exchange is de ned in two periods, while the individual provides their preferred economic and environmental choice mix as consumption-saving. This study shows that sustainable growth is achievable only with increased young e¤ort and less leisure and consumption.
ARTICLE | doi:10.20944/preprints202010.0516.v1
Subject: Keywords: Frequency response characteristic (FRC) curve; frequency response; renewable generation; governor
Online: 26 October 2020 (11:40:43 CET)
This letter introduces a frequency response characteristic (FRC) curve and its application in high renewable power systems. In addition, the letter presents a method for fast frequency response assessment and frequency nadir prediction without performing dynamic simulations using detailed models. The proposed FRC curve and fast frequency response assessment method are useful for operators to understand frequency response performance of high renewable systems in real time.
Subject: Mathematics & Computer Science, Applied Mathematics Keywords: entropy generation; heat and mass transfer; stretching sheet; variable viscosity
Online: 11 September 2020 (08:05:17 CEST)
This work probes the combined effects of magnetic field and viscous dissipation on heat field and examine the second law analysis (entropy generation) in an electrically conducting fluid under the effect of wall mass transfer over continuous stretched non-isothermal surface with variable viscosity. The viscosity of the fluid is assumed to be an inverse linear function of temperature. The governing equation for the problem are changed to dimensionless ordinary differential equations by using similarity transformation and solved numerically by using Rung Kutta and Shooting technique. Velocity, concentration and temperature distribution are obtained and used to compute the entropy generation and the Bejan number in the flow field. The effect of variable viscosity, Schmidt number, Hartman and Reynolds number on the velocity, concentration, temperature, entropy generation and Bejan number are studied and discussed.
ARTICLE | doi:10.20944/preprints202008.0304.v1
Subject: Physical Sciences, Optics Keywords: metasurfaces, second harmonic generation, phase control, finite difference time domain
Online: 13 August 2020 (11:32:52 CEST)
Metasurfaces of gold (Au) nanoparticles on a SiO2-Si substrate were fabricated for the enhancement of second harmonic generation (SHG) using electron beam lithography and lift-off. Triangular Au nanoprisms which are non-centro-symmetric and support the second- order non-linearity were examined for SHG. The thickness of the SiO2 spacer is shown to be an efficient parameter to spectrally tune to maximise SHG. Electrical field enhancement at the fundamental wavelength was shown to define the intensity of the second harmonics. Numerical modeling of light enhancement was verified by experimental measurements of SHG and reflectivity spectra at the normal incidence. At the plasmonic resonance, SHG is enhanced up to ∼3.5×103 times for the optimised conditions.
ARTICLE | doi:10.20944/preprints202002.0054.v1
Subject: Keywords: energy poverty; primary energy; renewable energy; distributed generation; energy storage
Online: 5 February 2020 (03:31:29 CET)
Following an updated outlook of global energy production and utilization, we show through selected examples from both developing and developed countries how distributed generation from renewable energy sources, and from solar energy in particular, is the key solution to ending energy poverty across the world. Guidelines aimed at policy makers suggest a systems view of energy that will be instrumental in guiding the transition from fossil fuels to combustion-free renewable energy for all energy end uses.