ARTICLE | doi:10.20944/preprints201702.0061.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: multi-target tracking; multi-Bernoulli filter; sequential Monte-Carlo
Online: 16 February 2017 (09:39:29 CET)
We develop an interactive likelihood (ILH) for sequential Monte-Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, AFL, and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (OSPA and CLEAR MOT). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.
REVIEW | doi:10.20944/preprints202105.0364.v1
Subject: Engineering, Automotive Engineering Keywords: Poultry behaviour; target tracking; deep learning; precision livestock farming; poultry production systems.
Online: 16 May 2021 (22:43:58 CEST)
The world's growing population is highly dependent on animal agriculture. Animal products provide nutrient-packed meals that help to sustain individuals of all ages in communities across the globe. As the human demand for animal proteins grows, the agricultural industry must continue to advance its efficiency and quality of production. One of the most commonly farmed livestock is poultry and their significance is felt on a global scale. Current poultry farming practices result in the premature death and rejection of billions of chickens on an annual basis before they are processed for meat. This loss of life is concerning regarding animal welfare, agricultural efficiency, and economic impacts. The best way to prevent these losses is through the individualistic and/or group level assessment of animal on a continuous basis. On large-scale farms, such attention to detail was generally considered to be inaccurate and inefficient, but with the integration of Artificial Intelligence (AI) assisted technology individualized and per-herd assessments of livestock are possible and accurate. Various studies have shown cameras linked with specialized systems of AI can properly analyze flocks for health concerns, thus improving the survival rate and product quality of farmed poultry. Building on the recent advancements, this review explores the aspects of AI in the detection, counting and tracking of the poultry in commercial and research-based applications.
ARTICLE | doi:10.20944/preprints201704.0106.v1
Subject: Engineering, Control & Systems Engineering Keywords: maneuvering target tracking; interacting multiple model; fifth-degree spherical simplex-radial rule; Markov process
Online: 18 April 2017 (03:35:28 CEST)
For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named interacting multiple model fifth-degree spherical simplex-radial cubature filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and fifth-degree spherical simplex-radial cubature filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with IMMUKF, IMMCKF and IMM5thCKF.
Subject: Engineering, Control & Systems Engineering Keywords: Multi-Target Detection and Tracking; Multi-copter Drone; Aerial Imagery, Image Sensor, Deep Learning, GPU-based Embedded Module, Neural Computing Stick; Image Processing
Online: 18 July 2019 (10:09:05 CEST)
In recent years, demand has been increasing for target detection and tracking from aerial imagery via drones using onboard powered sensors and devices. We propose a very effective method for this application based on a deep learning framework. A state-of-art embedded hardware system empowers small flying robots to carry out the real-time onboard computation necessary for object tracking. Two types of embedded modules were developed: one is designed using a Jetson TX or AGX Xavier, and the other is based on an Intel Neural Compute Stick. These are suitable for real-time onboard computing power on small flying drones with limited space. A comparative analysis of current state-of-art deep-learning-based multi-object detection algorithms was carried out utilizing the designated GPU-based embedded computing modules to obtain detailed metric data about frame rates as well as the computation power. We also introduce an effective target tracking approach for moving objects. The algorithm for tracking moving objects is based on the extension of simple online and real-time tracking. It was developed by integrating a deep-learning-based association metric approach (Deep SORT), which uses a hypothesis tracking methodology with Kalman filtering and a deep-learning-based association metric. In addition, a guidance system that tracks the target position using a GPU-based algorithm is introduced. Finally, we demonstrate the effectiveness of the proposed algorithms by real-time experiments with a small multi-rotor drone.
ARTICLE | doi:10.20944/preprints202204.0254.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: multi-target tracking; DeepSORT; feature extraction; target detection
Online: 27 April 2022 (09:01:45 CEST)
Pedestrian multi-target tracking technology plays an important role in artificial intelligence, driverless, virtual reality and other fields. The pedestrian multi-target tracking algorithm DeepSORT based on detection is widely used in industry. It mainly tracks multiple pedestrian targets continuously and keeps their ID unchanged. In order to improve the applicability and tracking accuracy of DeepSORT algorithm, this paper improved the IOU distance measurement in the matching process. At the same time, ResNet50 is used as the feature extraction backbone network, and combined with FPN (Feature Pyramid Network), the appearance features of multi-layer pedestrians are fused to improve the tracking accuracy of DeepSORT algorithm. The proposed algorithm is verified on the public data set MOT-16 and it’s tracking accuracy is enhanced to 4.1%.
ARTICLE | doi:10.20944/preprints202207.0004.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: SARS-CoV-2; COVID-19; drug repurposing; artificial intelligence; target-target similarity network; drug-target interaction network
Online: 1 July 2022 (05:33:16 CEST)
The COVID-19 was described as a respiratory illness, however further studies recognize it as a complex heterogeneous multisystemic disorder. Global efforts have been proposed to combat COVID-19, emerging diverse therapeutic options, in which discovering new drug therapies, development of vaccines and drug repurposing have been considered the most promising approaches to fight the virus. This study aimed to repurpose known drugs for use against the COVID-19, finding better therapeutic options. Seventeen biological databases were used in this study. The genetic algorithm (GA) was performed for a set of drug target classes and COVID-19 proteins as input, whose drug candidates are obtained according to the target similarities found in the target-target similarity predictive network, resulting in a drug-target interaction network. Thus, recommended drugs correspond to the union of the drug subsets found during each GA execution. Twenty-eight drugs were indicated to be the best therapeutic targets for the virus, in special, the Cyclosporine drug was administered as adjuvant to steroid treatment for COVID-19 patients which showed positive outcomes, reducing mortality in moderate and severe cases. The drugs found have used to treat other diseases, evidencing that the COVID-19 is a multisystemic disorder and suggests that the viruses’ mechanism of action presents some comorbidity with other human diseases. Evidence shows that the drugs found in this research might act together to fight the virus in a broader fashion, however further studies including in vitro and in vivo experiments are needed to find the best combination of these drugs.
REVIEW | doi:10.20944/preprints202105.0471.v1
Online: 20 May 2021 (10:05:40 CEST)
Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.
Subject: Engineering, Marine Engineering Keywords: unmanned surface vehicles; optical visual perception; image stabilization; defogging; target detection; target tracking
Online: 24 November 2019 (16:54:46 CET)
Unmanned surface vehicles have the advantages of maneuverability, concealment, wide activity area and low cost of use. Therefore, they have broad application prospects. This makes unmanned surface vehicles a research hotspot at home and abroad, and the sensing technology is the basis for the unmanned surface vehicles to perform tasks. The perception technology based on optical vision has the advantages of convenient application, relatively low cost, easy data acquisition and large amount of information, and has been widely studied by scholars at home and abroad. This paper mainly discusses the research of optical vision in unmanned surface vehicles from five aspects: Firstly, the water surface image preprocessing based on unmanned surface vehicles, mainly including water surface image stabilization research and defogging enhancement research; two water boundary detection; It is the use of light vision target detection; the fourth is the surface target tracking method. Finally, the light vision research of unmanned surface vehicles is summarized and forecasted.
ARTICLE | doi:10.20944/preprints201805.0087.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: target detection; radar systems; K-distributed clutter; heavy-tailed; Swerling target; track-before-detect (TBD)
Online: 4 May 2018 (08:27:25 CEST)
This paper considers the detection of fluctuating target in heavy-tailed clutter through the use of dynamic programming based on track-before-detect (DP-TBD) in radar systems. The clutter is modeled in terms of K-distribution, which can be widely used to describe non-Gaussian clutter received from high-resolution radars and radars working at small grazing angle. Swerling type 1 is considered to describe the target fluctuation between scans. Conventional TBD techniques suffer from significant performance loss in heavy-tailed environments due to the more frequent occurrences of target-like outliers. In this paper, we resort to DP-TBD algorithm based on prior information, which can enhance the detection performance by using the environment and target fluctuating information during the integration process of TBD. Under non-Gaussian background, the expressions of the likelihood ratio merit function for Swerling type 1 target are derived first. However, the closed analytical form of the merit function is difficult to be obtained. In order to reduce the complexity of evaluating the merit function and the computational load, an efficient approximation method as well as a two-stage detection approach is proposed and used in the integration process. Finally, several numerical simulations of the new strategy and the comparisons are presented to verify that the proposed algorithm can improve the detection performance, especially for fluctuating target in heavy-tailed clutter.
ARTICLE | doi:10.20944/preprints202202.0113.v1
Online: 8 February 2022 (13:17:14 CET)
MicroRNAs act as the cardinal post-transcriptional monitors of gene regulatory networks sculpturing the developmental plasticity and stress responses in plants. Single miRNA target several genes and how the transcriptional regulation of miRNA impacts its pool of targets in different tissues and stress conditions is still elusive. The present study investigated the highly conserved and evolving MIR408 family comprehensively by redefining its evolutionary conservation and diversification in plants followed by detailed functional analysis in rice. MIR408 family comprises three dominant mature forms (21 nt) including a distinct monocot variant. Plant MIR408 family can be divided into six groups. miR408 majorly cleave genes belonging to blue copper protein in addition to several other species-specific targets in plants. Screening of 4726 rice accessions identified 22 sequence variants in 1 Kb upstream (15) and MIR408 region leading to the identification of 8 haplotypes (3: Japonica-specific and 5: Indica-specific). miR408-3p follows flag leaf preferential and drought upregulated expression profile in flag leaf and roots of N22 which seems to be regulated by differential fraction of mCs in the precursor region. The active pool of miR408 regulated targets under control and drought conditions is impacted by the tissue type. Comparative expression analysis of miR408/target module under different sets of conditions features 83 targets exhibiting antagonistic expression in rice. Twelve high confidence targets including 4 plantacyanins (OsUCL6, 7, 9 and 30), pirin, OsLPR1, OsCHUP1, OsDOF12, OsBGLU1, glycine rich cell wall, deoxyuridine 5-triphosphate nucleotidohydrolaseand OsERF7 with antagonistic expression under most conditions. Further, over-expression of osa-MIR408 in drought sensitive rice cultivar leads to the massive enhancement of vegetative growth in rice with improved ETR and Y(II) and enhanced the dehydration stress tolerance at seedling stage.
REVIEW | doi:10.20944/preprints202201.0271.v1
Online: 19 January 2022 (12:13:03 CET)
Mesothelin is a protein that is expressed in the mesothelial cell lining in the pleura, peritoneum and pericardium. The gene of mesothelin encodes a precursor protein that is processed to yield mesothelin, which is attached to the cell membrane by a glycophosphatidylinositol linkage and a shred fragment named the megakaryocytic-potentiating factor. The biological functions of this substance in normal cells are still unknown. Experimental studies on knockout mice suggest that this substance does not play an important role in development and reproduction. In contrast, it has been observed that mesothelin is produced in abnormal amounts in several malignant neoplasms such as mesotheliomas and pancreatic adenocarcinomas. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered a tumour marker or an antigenic target for many malignancies. Many molecular studies also have demonstrated that mesothelin is overexpressed in serous ovarian carcinomas and may bind to ovarian cancer antigen Ca-125, favouring the spread of the tumour in the abdominal cavity. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses as well as its impact on the prognosis in serous ovarian carcinomas. We also briefly discuss the latest progress of mesothelin-targeting therapies for this aggressive and lethal neoplasm.
REVIEW | doi:10.20944/preprints202003.0034.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Cancer; microRNA; miR-144; Therapeutic target
Online: 3 March 2020 (11:05:01 CET)
MicroRNAs (miRNAs) are small and non-coding RNAs displaying aberrant expression in the tissue and plasma of cancer patients in comparison to healthy individuals. In past decades, accumulating data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been identified that miRNAs can act either as oncogenes through silencing of tumor inhibitors or tumor suppressor via targeting oncoproteins. MiR-144 is located in chromosomal region 17q11.2 that was widely destroyed in many types of cancers. Several studies revealed that miR-144 has different target genes including rapamycin, zonula occludens1, SFRP1, and ANO1. MiR-144 acts as a tumor suppressor or oncogene by targeting specific genes. In this review, we define the role of miR‐144 and its targets in different cancers and provide understanding in tumor proliferation, migration, and apoptosis.
ARTICLE | doi:10.20944/preprints201809.0564.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Pritimerin; target fishing; druggability; network pharmacology
Online: 28 September 2018 (11:54:58 CEST)
Pristimerin (PM) is a naturally occurring quinonemethide triterpenoid compound that isolated from the Celastraceae and Hippocrateaceae families. Its anticancer effects have attracted a great deal of attention, but the mechanisms of action remain obscure. In this study, we screened for the active compounds of Pristimerin using a drug-likeness approach. Potential protein targets of Pristimerin were predicted by PharmMapper and Coremine database. Candidate protein targets were then uploaded to GeneMANIA and GO pathway analysis. Finally, compound-target, target-pathway, and compound-target-pathway networks were constructed using Cytoscape 3.3. The results showed that Pristimerin had good drug ability and identified 13 putative protein targets. Network analysis revealed that these targets are associated with cancer, inflammation and other physiological processes. In summary, Pristimerin is predicted to target a variety of proteins and pathways to form a network that exerts systemic pharmacological effects.
ARTICLE | doi:10.20944/preprints202002.0009.v1
Subject: Life Sciences, Biochemistry Keywords: target identification; drug affinity responsive target stability (DARTS); mass spectrometry imaging (MSI); voacangine; curcumin; natural products
Online: 3 February 2020 (04:36:54 CET)
Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.
REVIEW | doi:10.20944/preprints202110.0187.v1
Subject: Materials Science, Biomaterials Keywords: pancreatic cancer; molecular markers; target therapy; nanomedicine
Online: 12 October 2021 (20:45:44 CEST)
Pancreatic cancer leads the most common lethal tumor in America. This lethality is related to limited treatment options. Conventional treatments involve a non-specific use of chemotherapeutical agents like 5-FU, capecitabine, gemcitabine, cisplatine, oxaliplatine, or irinotecan, that produce several side effects. This review we focus on the use of targeted nanoparticles as an alternative to the standard treatment for the pancreatic cancer. The principal objective of the use of nanoparticles is the reduction in side effects that conventional treatments produce, mostly because of their nonspecificity. Currently, several molecular markets of pancreatic cancer cells have been studied to target nanoparticles and improve the actual treatment. Therefore, properly functionalizated nanoparticles with specific aptamers or antibodies can be used to recognize pancreatic cancer cells and once cancer is recognized, these nanoparticles can attack the tumor by drug delivery, hyperthermia, or gene therapy.
ARTICLE | doi:10.20944/preprints202110.0059.v1
Subject: Life Sciences, Genetics Keywords: Machine learning; ALS; Classification; Interpretation; Target Identification
Online: 4 October 2021 (12:50:04 CEST)
Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons to severely effect the functionality to control voluntary muscle movement. Most of the non additive genetic aberrations responsible for ALS make its molecular classification very challenging along with limited sample size, curse of dimensionality, class imbalance and noise in the data. Deep learning methods have been successful in many other related areas but have low minority class accuracy and suffer from the lack of explainailbilty when used directly with RNA expression features for ALS molecular classification. In this paper we propose a deep learning based molecular ALS classification and interpretation framework. Our framework is based on training a convolution neural network (CNN) on images obtained from converting RNA expression values into pixels based on DeepInsight similarity technique. Then we employed Shapley Additive Explanations (SHAP) to extract pixels with higher relevance to ALS classifications. These pixels were mapped back to the genes which made them up. This enabled us to classify ALS samples with high accuracy for a minority class along with identifying genes that might be playing an important role in ALS molecular classifications. Taken together with RNA expression images classified with CNN, our preliminary analysis of the genes identified by SHAP interpretation demonstrate the value of utilising Machine Learning to perform molecular classification of ALS and uncover disease-associated genes.
ARTICLE | doi:10.20944/preprints202105.0687.v1
Subject: Chemistry, Analytical Chemistry Keywords: nanobodies; gold nanoparticles; target imaging; nanoSIMS; SIMS
Online: 28 May 2021 (09:57:12 CEST)
Nanoscale imaging with the ability to identify cellular organelles and protein complexes has been a highly challenging subject in secondary ion mass spectrometry (SIMS) of biological samples. This is because only a few isotopic tags can be used successfully to target specific proteins or organelles. To address this, we have generated gold-nanoprobes, in which gold nanoparticles are conjugated to nanobodies. The nanoprobes were well suited for specific molecular imaging using NanoSIMS at subcellular resolution. They demonstrated to be highly selective to different proteins of interest, and sufficiently sensitive for SIMS detection. The nanoprobes offer the possibility of correlating the investigation of cellular isotopic turnover to the positions of specific proteins and organelles, thereby enabling an understanding of functional and structural relations that are currently obscure.
ARTICLE | doi:10.20944/preprints201907.0291.v1
Subject: Engineering, General Engineering Keywords: energy efficiency; clustering analysis; allocation target; Vietnam
Online: 25 July 2019 (11:48:43 CEST)
In order to meet the national energy saving goals set in the Vietnam National Energy Efficiency Program in the period of 2019 – 2030 (VNEEP), the Vietnamese government has adopted a series solutions and policies to improve energy efficiency. The Vietnam’s 63 provinces will be as main actor for the national achievement in energy efficiency. Thus, understanding the province’s potentiality of energy efficiency is useful for the harmonious and sustainable development between the economy and energy systems. In this study, provincial and national data from General Statistic Office are analyzed in terms of the energy efficiency levels. With the trends of economic development and energy consumption in both national and regional levels, the Lorenz curve between Vietnamese energy consumption and GDP is investigated. The Lorenz coefficient shows the energy allocation is nether reasonable nor balanced. By using clustering method, the 63 provinces of Vietnam clustered into 7 groups that the provinces in the cluster has the similar indexes of energy efficiency i.e. ability, responsibility, potential and difficulty. The energy consumption and GDP are predicted in the period of 2019 – 2025. Based on the difference of GDP development and energy consumption levels, the target of energy efficiency for each province through clustering is set. The results show that 33 provinces included in the cluster 1, 2, 3, 4 and 6 are heavy contribution. Among them, the provinces in the cluster 2 and 3 need to focus on the industry sector in their energy saving policy. The cluster 7 included the under-developed provinces can learn development’s experiences of the provinces in the cluster 1, 2, 3 and 4 to find the best way of their future development.
ARTICLE | doi:10.20944/preprints202002.0134.v1
Subject: Life Sciences, Biochemistry Keywords: autophagy; autophagonizer; target identification of label-free compound; target validation; autophagic flux; autophagy inhibition; lysosomal integrity function of Hsp70
Online: 11 February 2020 (09:03:51 CET)
Manipulating autophagy is a promising strategy for treating cancer as several autophagy inhibitors shown to induce autophagic cell death. One of these, autophagonizer (APZ), induces apoptosis-independent cell death by binding an unknown target via an unknown mechanism. To identify APZ targets we used a label-free drug affinity responsive target stability (DARTS) approach with a liquid chromatography/tandem mass spectrometry (LC-MS/MS) readout. Of 35 protein interactors, we identified Hsp70 as a key target protein of unmodified APZ in autophagy. Either APZ treatment or Hsp70 inhibition attenuates integrity of lysosomes, which leads to autophagic cell death exhibiting an excellent synergism with a clinical drug, temozolomide, in vitro, in vivo, and orthotropic glioma xenograft model. These findings demonstrate the potential of APZ to induce autophagic cell death and its development to combinational chemotherapeutic agent for glioma treatment. Collectively, our study demonstrated that APZ, a new autophagy inhibitor, can be used as a potent antitumor drug candidate to get over unassailable glioma and revealed a novel function of Hsp70 in lysosomal integrity regulation of autophagy.
ARTICLE | doi:10.20944/preprints202212.0350.v1
Subject: Life Sciences, Molecular Biology Keywords: miRNA target prediction; CLASH; deep learning; interpretation; visualization
Online: 20 December 2022 (03:28:52 CET)
MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in the post-transcriptional regulation of biological processes. miRNAs regulate transcripts by direct binding involving the Argonaute protein family. The exact rules of binding are not known, and several in silico miRNA target prediction methods have been developed to date. Deep Learning has recently revolutionized miRNA target prediction. However, the higher predictive power comes with decreased ability to interpret increasingly complex models. Here, we present a novel interpretation technique, called attribution sequence alignment, for miRNA target site prediction models that can interpret such Deep Learning models on a two-dimensional representation of miRNA and putative target sequence. Our method produces a human readable visual representation of miRNA:target interactions and can be used as a proxy for further interpretation of biological concepts learned by the neural network. We demonstrate applications of this method in clustering of experimental data into binding classes, as well as using the method to narrow down predicted miRNA binding sites on long transcript sequences. Importantly, the presented method works with any neural network model trained on a two-dimensional representation of interactions and can be easily extended to further domains such as protein-protein interactions.
REVIEW | doi:10.20944/preprints202210.0034.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: insect; genome; biopesticide; silencing; topical; gene target; validation
Online: 5 October 2022 (10:57:47 CEST)
Global crop yields are estimated to be reduced by 30–40% per year on account of plant pests and pathogens. Agricultural insect pests raise concerns about constraining global food security and climate changes contributing to the rise of infestation. The current management relies on plant breeding, associated or not with transgenes and chemical pesticides. Both approaches face serious technology obsolescence on the field due to resistance breakdown or development of insecticide resistance. The need for new Modes of Action (MoA) approaches in managing crop health grows each year, driven by market demands to reduce economic losses and phytosanitary requirements to meet the consumer perception. Disabling pest genes by sequence-specific expression silencing is considered a promising tool in the development of environment and health respectful biopesticides. The specificity conferred by long dsRNA-base solutions give support to minimizing effects on off-targeted genes in the insect pest genome and the target gene in non-target organisms (NTOs). In this review, we summarize the current status of gene silencing by RNA interference (RNAi) for agricultural control. More specifically, we focus on the engineering, development and application of gene silencing to control Lepidoptera by the employment of non-transforming dsRNA technologies. Despite some delivery and stability drawbacks of topical applications, we reviewed works showing convincing proof-of-concept results that point to imminent innovative solutions. Considerations about the regulamentation of the ongoing research on dsRNA-based pesticides to produce commercialized products for exogenous application are discussed. Academic and industry initiatives reveal a worthy effort to accomplish controlling Lepidoptera pests with this new mode of action to provide more sustainable and reliable technologies to field management. New data on genomics of this taxon encourage the increment of a customized target genes portfolio. As a case of study, we illustrate how dsRNA and associated methodologies could be applied to control an important Lepidopteran coffee pest.
ARTICLE | doi:10.20944/preprints202208.0331.v1
Subject: Mathematics & Computer Science, Information Technology & Data Management Keywords: Drug-Target Binding Affinity; Multi-Instance Learning; Transformer
Online: 18 August 2022 (03:58:34 CEST)
The prediction of drug-target interactions plays a fundamental role in facilitating drug discovery, where the goal is to find prospective drug candidates. With the increase in the number of drug-protein interactions, machine learning techniques, especially deep learning methods, have become applicable for drug-target interaction discovery because they significantly reduce the required experimental workload. In this paper, we present a spontaneous formulation of the drug-target interaction prediction problem as an instance of multi-instance learning. We address the problem in three stages, first organizing given drug and target sequences into instances via a private-public mechanism, then identifying the predicted scores of all instances in the same bag, and finally combining all the predicted scores as the output prediction. A comprehensive evaluation demonstrates that the proposed method outperforms other state-of-the-art methods on three benchmark datasets.
REVIEW | doi:10.20944/preprints202204.0013.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Organoids; IBD; Inflammation; Target therapy; microbiota; immune system
Online: 4 April 2022 (10:35:01 CEST)
Inflammatory bowel disease (IBD) is a chronic and relapsing disease caused by a dysregulated immune response to host intestinal microbiota that occurs in genetically predisposed individuals. IBD encompasses two major clinical entities: ulcerative colitis (UC), which is limited to the colonic mucosa, and Crohn disease (CD), which might affect any segment of the gastrointestinal tract. Despite the prevalence of IBD is increasing worldwide, therapy remains suboptimal, largely because the variability of causative mechanisms, raising the need to develop individualized therapeutic approaches targeted to each individual patient. In this context, patients-derived intestinal organoids represent an effective tool for advancing our understanding on IBD’ s pathogenesis. Organoid 3D culture systems offer a unique model for dissecting epithelial mechanisms involved IBDs and test individualized therapy, although the lack of a functional immune system and a microbiota, two driving components of the IBD pathogenesis, represent a major barrier for their exploitation in clinical medicine. In this review we have examined how to improve the translational utility of intestinal organoids in IBD and how co-coltures of 3D or 2D organoids and immune cells and/or intestinal microbiota might help to overcome these limitations.
REVIEW | doi:10.20944/preprints202110.0130.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: fusion protein; extracellular vesicles; target delivery; RNA sorting
Online: 8 October 2021 (09:21:36 CEST)
The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape from lysosomal destruction. Most of artificial nanocarriers suffer from intrinsic limitations that either prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and extracellular vesicles. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into extracellular vesicles.
ARTICLE | doi:10.20944/preprints202109.0362.v1
Online: 21 September 2021 (12:34:20 CEST)
Multiplex genome editing may induce genotoxicity and chromosomal rearrangements due to double-strand DNA breaks at multiple loci simultaneously induced by programmable nucleases, including CRISPR/Cas9. However, recently developed base-editing systems can directly substitute target sequences without double-strand breaks. Thus, the base-editing system is expected to be a safer method for multiplex genome-editing platforms for livestock. Target-AID is a base editing system composed of PmCDA1, a cytidine deaminase from sea lampreys, fused to Cas9 nickase. It can be used to substitute cytosine for thymine in 3-5 base editing windows, 18 bases upstream of the protospacer-adjacent motif site. In the current study, we demonstrated Target-AID-mediated base editing in porcine cells for the first time. We targeted multiple loci in the porcine genome using the Target-AID system and successfully induced target-specific base substitutions with up to 63.15% efficiency. This system can be used for the further production of various genome-engineered pigs.
ARTICLE | doi:10.20944/preprints202108.0498.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: CML; Disease progression; common biomarker; drug target; ANRD36.
Online: 25 August 2021 (16:03:46 CEST)
Background: Chronic Myeloid Leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(22;9) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKI) have changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find out novel biomarkers of CML progression by employing whole exome sequencing (WES).Materials and Methods: WES of accelerated phase (AP-) and blast crisis (BC-) CML patients was carried out, with chronic phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing was carried out using Illumina platforms. Statistical analysis was carried out using [SAS/STAT] software version 9.4 and R package employed to find mutations shared exclusively by all AP-/BC-CML. Confirmation of mutations was carried out using Sanger sequencing and protein structure modelling using I-Tasser followed by mutant generation and visualization using PyMOL. Results: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modelling studies showed that mutations induce structural changes in ANKRD36 protein. Conclusions: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in human. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in biology and progression of CML.
ARTICLE | doi:10.20944/preprints202106.0563.v1
Subject: Engineering, Automotive Engineering Keywords: Radar imaging; target detection; experimental measurements; Microwave imaging.
Online: 23 June 2021 (10:25:26 CEST)
In microwave imaging it is often of interest to inspect electrically large spatial regions. In these cases, data must be collected over a great deal of measurement points which entails long measurement time and/or costly, and often unfeasible, measurement configurations. In order to counteract such drawbacks, we have recently introduced a microwave imaging algorithm which looks for the scattering targets in terms of equivalent surface currents supported over a given reference plane. While this method is suited to detect shallowly buried targets, it allows to independently process each frequency data, hence the source and the receivers do not need to be synchronized. Moreover, spatial data can be reduced at large extent, without incurring in aliasing artefacts, by properly combining single-frequency reconstructions. In this paper, we validate such an approach by experimental measurements. In particular, the experimental test site consists of a sand box in open air where metallic plate targets are shallowly buried (few cm) under the air/soil interface. The investigated region is illuminated by a fixed transmitting horn antenna whereas the scattered field is collected over a planar measurement aperture at a fixed height from the air-sand interface. The transmitter and the receiver share only the working frequency information. Experimental results confirm the feasibility of the method.
ARTICLE | doi:10.20944/preprints202101.0494.v1
Subject: Engineering, Automotive Engineering Keywords: preparation; molybdenum target; sputtered film; microstructure; grain orientation
Online: 25 January 2021 (12:48:45 CET)
Abstract: Molybdenum (Mo) thin films were sputtered from two kinds of Mo targets with different microstructures under the same sputtering process, and the effect of microstructure of Mo target on morphology, deposition rate and resistance of sputtered film were studied and discussed. The results show that morphological differences between Mo thin films sputtered by Mo targets with different microstructures are very small. The more uniform and finer the grain structures of Mo target, the better the uniformity on thickness and resistance of Mo sputtered film. Moreover, during sputtering process, when Mo target’s grain size is finer and the surface area of grain boundary is higher, the thickness reduction of the target is more homogeneous and the sputtering film has faster deposition velocity. The difference in microstructure of the Mo target has not obvious influence on the grain orientation of sputtering film.
REVIEW | doi:10.20944/preprints202011.0603.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: genome editing, agriculture, crispr, talen, specificity, off-target
Online: 24 November 2020 (08:35:00 CET)
We are in a new chapter of crop and livestock improvement with the emergence of genome editing. This latest generation of molecular tools can be used to make targeted changes in a genome including insertions, deletions, and mutations. With new advances comes new risks for unintended changes and impacts, thus the need for appropriate risk assessment for product development and to inform regulatory measures. Though CRISPR/Cas has arisen as the predominant technology, there are multiple types of genome editing tools each with pros and cons depending on the organism and desired outcome. Furthermore, each editing tool differs in specificity as they may edit non-intended sites, referred to as off-target edits. The consensus of the agricultural editing community is to avoid off-target editing through design and detection, instead of determining whether off-target editing in each case is detrimental. The design of a targeting component, the tool chosen, and the identification of the edit(s) made are the critical factors in avoiding off-target edits and confirming intended edits in final products that are released commercially. The limited amount of head-to-head comparisons of genome editing tools in diverse crops and livestock make it difficult to develop broad conclusions and best practices, which is further compounded by the diversity of techniques, targets, and processes. Developers and breeders should consult the literature and test as needed to determine which editing technology will be the most effective for their purposes, especially as more tools with altered efficiency and specificity become available. Yet, the lack of off-target edits in studies that employed careful design of targeting components followed by wide testing for on- and off-target edits bodes well for the use of genome editing with proper precautions of target selection and screening.
ARTICLE | doi:10.20944/preprints202009.0446.v1
Subject: Medicine & Pharmacology, Other Keywords: Novel coronavirus diseases 2019; vaccination; target population; China
Online: 19 September 2020 (05:02:54 CEST)
All countries are facing decisions about which groups to prioritise for COVID-19 vaccination after the first vaccine product has been licensed, at which time supply shortages are inevitable. Here we define the key target populations and their size in China for a phased introduction of COVID-19 vaccination with evolving goals, accounting for the risk of illness and transmission. Essential workers (47.2 million) like healthcare workers could be prioritized for vaccination to maintain essential services. Subsequently, older adults, individuals with underlying health conditions and pregnant women (616.0 million) could be targeted to reduce severe COVID-19 outcomes. Then it could be further extended to target adults without underlying health conditions and children (738.7 million) to reduce symptomatic infections and/or to stop virus transmission. The proposed framework could assist Chinese policy-makers in the design of a vaccination program, and could be generalized to inform other national and regional COVID-19 vaccination strategies.
Subject: Social Sciences, Accounting Keywords: construction engineering; lean supply chain; target cost management
Online: 13 November 2019 (08:57:42 CET)
The lean supply chain of construction engineering projects is to achieve the maximum satisfaction of the owners' needs in order to effectively achieve the goal of supply chain management. This paper explores an effective method of lean supply chain cost management for construction engineering projects with target cost management, so that each participating unit on the supply chain node can fully utilizes its core competencies to minimize internal consumption and waste, and achieve the optimal overall efficiency of the supply chain. According to the requirements of the goal planning theory of the construction project company, establish a lean supply chain cost planning system for the construction project, realize the basic model of the lean supply chain cost management of the construction project, and set the target cost from the lean project of the construction project. The technical decomposition is established by the process of cost decomposition and cost pressure transmission and sub-target cost planning.
ARTICLE | doi:10.20944/preprints201905.0384.v2
Subject: Biology, Entomology Keywords: Arachnida; insect; phylogenomics methods; target enrichment; ultraconserved elements
Online: 4 August 2019 (16:54:42 CEST)
Targeted enrichment of ultraconserved elements (UCE) has emerged as a promising tool for inferring evolutionary history in many taxa, with utility ranging from phylogenetic and phylogeographic questions at deep time scales to population level studies at shallow time scales. However, the methodology can be daunting for beginners. Our goal is to introduce UCE phylogenomics to a wider audience by summarizing recent advances in arthropod research, and to familiarize readers with background theory and steps involved. We define terminology used in association with the UCE approach, evaluate current laboratory and bioinformatic methods and limitations, and, finally, provide a roadmap of steps in the UCE pipeline to assist phylogeneticists in making informed decisions as they employ this powerful tool. By facilitating increased adoption of UCE in phylogenomics studies that deepen our comprehension of the function of these markers across widely divergent taxa, we aim to ultimately improve understanding of the arthropod tree of life.
REVIEW | doi:10.20944/preprints201901.0158.v1
Subject: Medicine & Pharmacology, Dentistry Keywords: sialidase; sialic acid; sialoglycoprotease; pathogenicity; therapeutic target; siglec
Online: 16 January 2019 (08:49:16 CET)
Periodontitis is a chronic inflammatory disease affecting the tissues that surround and support the teeth. In the U. S., approximately 65 million people are affected by this condition. Its occurrence is also associated with many important systemic diseases such as cardiovascular disease, rheumatoid arthritis, and Alzheimer’s disease. Among the most important etiologies of periodontitis is Porphyromonas gingivalis, a keystone bacterial pathogen. Keystone pathogens can orchestrate inflammatory disease by remodeling a normally benign microbiota causing imbalance between normal and pathogenic microbiota (dysbiosis). The important characteristics of P. gingivalis causing dysbiosis are its virulence factors that cause effective subversion of host defenses to its advantage , allowing other pathogens to grow. However, the mechanisms involving these processes are poorly understood. However, various microbial strategies target host sialoglycoproteins for immune dysregulation. In addition, the enzymes that break down sialoglycoproteins/sialoglycans are the “sialoglycoproteases”, resulting in exposed terminal sialic acid. This process could lead to pathogen-toll like receptor (TLR) interactions mediated through sialic acid receptor–ligand mechanisms. By assessing the function of P. gingivalis sialoglycoproteases, could pave the way to designing carbohydrate analogues and sialic acid mimetics to serve as drug targets.
ARTICLE | doi:10.20944/preprints201811.0369.v1
Subject: Physical Sciences, Applied Physics Keywords: radionuclide production; target stations; targetry; 70 MeV cyclotron
Online: 16 November 2018 (04:01:41 CET)
The development of new target stations for radioisotope production based on a dedicated 70~MeV commercial cyclotron is described. Currently known as the South African Isotope Facility (SAIF), this initiative will free the existing separated-sector cyclotron (SSC) at iThemba LABS (near Cape Town) to mainly pursue research activities in nuclear physics and radiobiology. It is foreseen that the completed SAIF facility will realize a three-fold increase in radioisotope production capacity compared to the current programme based on the SSC.
ARTICLE | doi:10.20944/preprints201810.0316.v1
Subject: Social Sciences, Finance Keywords: estimation error; shrinkage; target matrix; risk-based portfolios
Online: 15 October 2018 (13:10:56 CEST)
Portfolio weights solely based on risk avoid estimation error from the sample mean, but they are still affected from the misspecification in the sample covariance matrix. To solve this problem, we shrink the covariance matrix towards the Identity, the Variance Identity, the Single-index model, the Common Covariance, the Constant Correlation and the Exponential Weighted Moving Average target matrices. By an extensive Monte Carlo simulation, we offer a comparative study of these target estimators, testing their ability in reproducing the true portfolio weights. We control for the dataset dimensionality and the shrinkage intensity in the Minimum Variance, Inverse Volatility, Equal-risk-contribution and Maximum Diversification portfolios. We find out that the Identity and Variance Identity have very good statistical properties, being well-conditioned also in high-dimensional dataset. In addition, the these two models are the best target towards to shrink: they minimise the misspecification in risk-based portfolio weights, generating estimates very close to the population values. Overall, shrinking the sample covariance matrix helps reducing weights misspecification, especially in the Minimum Variance and the Maximum Diversification portfolios. The Inverse Volatility and the Equal-Risk-Contribution portfolios are less sensitive to covariance misspecification, hence they benefit less from shrinkage.
REVIEW | doi:10.20944/preprints201805.0319.v1
Subject: Biology, Other Keywords: annexins; inflammation; wound healing; drug target; translational research
Online: 23 May 2018 (08:19:42 CEST)
The vertebrate annexin superfamily (AnxA) consists of 12 calcium (Ca2+) and phospholipid binding proteins which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+-controlled regulation of membrane events. In this review, we discuss several themes of potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, that repeatedly surface in the annexin action profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.
ARTICLE | doi:10.20944/preprints202209.0177.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: non-target action; soil microbiome; pesticide contamination; fungicide; soil quality
Online: 13 September 2022 (11:00:07 CEST)
Pesticides are widely used in agriculture as a pest control strategy. Despite the benefits of pesticides on crop yields, the persistence of chemical residues in soil have an unintended impact on non-targeted microorganisms. In this study, we evaluated the impact of the combined fungicide (difenoconazole, epoxiconazole, and kresoxim-methyl) on fungal and bacterial communities of Phaeozem. In the fungicide-treated soil, the Shannon index of both fungal and bacterial communities was decreased, while Chao1 index did not differ compared to the control soil. Among bacterial taxa, the relative abundance of Athrobacter, Sphingomicrobium, and Sphingomonas increased in fungicide-treated soil due to their ability to utilize fungicides and other toxic compounds. Rhizopus and plant-beneficial Chaetomium were the dominant fungal genera, which increased 2-4 times in the fungicide-treated soil, while the relative abundance of Mortierella and Talaromyces decreased. Fusarium acuminatum was the most abundant phytopathogenic fungus that causes root rot disease of wheat, but applied fungicide treatment decreased their diversity in the soil 2 times, which is consistent on the observed plants.
REVIEW | doi:10.20944/preprints202205.0068.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Chemotherapy-induced peripheral neuropathy; pain management; target therapy; immuno-therapy
Online: 6 May 2022 (09:14:17 CEST)
Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a dose reduction of chemo-therapy and its most common sensory symptoms are severe pain, tingling, and numbness in the hands and feet. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory abnormalities may occur for months, or even years after the termination of chemotherapy. This disease has complicated pathophysiology featured by underlying mechanisms not completely known. Although many pharmaco-logical and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized cure to prevent or treat CIPN. According to current guidelines, Duloxe-tine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective thera-pies for CIPN is mandatory. The purpose of this review is to dissect CIPN, the target and immunothera-py-based approaches to this disorder, as well as to offer new insights for novel therapeutic perspectives.
ARTICLE | doi:10.20944/preprints202011.0669.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: antenna; digital beamforming; reflection; frequency modulated continuous wave; target echo
Online: 26 November 2020 (11:20:08 CET)
In this paper, a high-performance antenna array system model is presented to analyze moving-object-skin-returns and track them in the presence of stationary objects using frequency modulated continuous wave (FMCW). The main features of the paper are bonding the aspects of antenna array and electromagnetic (EM) wave multi-skin-return modeling and simulation (M&S) with the aspects of algorithm and measurement/tracking system architecture. The M&S aspect models both phase and amplitude of the signal waveform from a transmitter to the signal processing in a receiver. In the algorithm aspect, a novel scheme for FMCW signal processing is introduced by combining time- and frequency-domain methods, including a vector moving target indication filter and a vector direct current canceller in time-domain, and a constant false alarm rate detector and a mono-pulse digital beamforming angle tracker in frequency-domain. In addition, unlike previous designs of using M×N fast Fourier transform (FFT) for an M×N array, only four FFTs are used, which tremendously saves time and space in hardware. With the presented model, the detection of the moving-target-skin-return in stationary objects under a noisy environment is feasible. Therefore, to track long range and high-speed objects, the proposed technique is promising. Using a scenario having 1) a target with 17 dBm2 radar cross section (RCS) at about 40 km range with 5.93 Mach speed and 11.6 dB post processing signal to noise ratio, and 2) a strong stationary clutter with 37 dBm2 RCS located at the proximity of the target, it demonstrates that the root-mean-square errors of range, angle and Doppler measurements are about 26 meters, 0.68 degree and 1100 Hz, respectively.
REVIEW | doi:10.20944/preprints202001.0325.v1
Subject: Life Sciences, Molecular Biology Keywords: QSAR evolution; Multi-target QSAR; Monte Carlo method; Fuzzy sets
Online: 27 January 2020 (09:29:19 CET)
Ability of quantitative structure – property / activity relationships (QSPRs/QSARs) to serve for epistemological processes in natural sciences is discussed. Some weirdness of QSPR/QSAR state-of-art are listed. There are some contradictions in the research results in this area. Sometimes, these should be classified as paradoxes or weirdness. These points often are ignored. Here these are listed and briefly commented. In addition, hypothesises on the future evolution of the QSPR/QSAR theory and practice are suggested.
ARTICLE | doi:10.20944/preprints201909.0128.v1
Subject: Life Sciences, Virology Keywords: virus; broad-spectrum antiviral; antiviral agent; drug target; systems biology
Online: 12 September 2019 (08:55:23 CEST)
Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.
ARTICLE | doi:10.20944/preprints201801.0160.v1
Subject: Mathematics & Computer Science, Artificial Intelligence & Robotics Keywords: target detection; dynamic background; information theory; feature matrix; computing resources
Online: 17 January 2018 (12:45:29 CET)
In recent years, many algorithms based on end-to-end deep networks have been proposed to deal with the target detection problem of videos. However, the deep network models usually consume a lot of computing resources during the procedure of analysis of videos with complex dynamic backgrounds. In this paper, a new method of object detection based on information theory is presented. Firstly, each frame in a video is converted into an effective information map by using the Harris corner detection method. Secondly, the sensitive areas in the frame are extracted by using the context information and the effective information maps of the consecutive video frames. The sensitive areas in the video frame are the candidate areas where the target objects would be appeared at high probabilities. Thirdly, the information entropy features of each sensitive area are extracted to form the feature matrix, based on which, an SVM model is trained for selecting the target areas from the sensitive areas. Finally, the locations of the objects are detected based on the target areas in the video with a complex dynamic background. As a lightweight video detection framework, the method presented in this paper can save a lot of computing resources. Experimental results show that this method can achieve good results in the benchmark of CDnet 2014.
ARTICLE | doi:10.20944/preprints202202.0232.v1
Subject: Biology, Entomology Keywords: Small RNA sequencing; miRNAs; Target prediction; Chemosensory-associated genes; Apolygus lucorum
Online: 18 February 2022 (10:01:58 CET)
MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.
REVIEW | doi:10.20944/preprints202202.0011.v1
Subject: Medicine & Pharmacology, Other Keywords: Rotavirus; off-target effects; neonatal; live attenuated; RV3-BB; epigenetic modulation
Online: 1 February 2022 (12:34:07 CET)
Following the introduction of live-attenuated rotavirus vaccines in many countries, a notable reduction in deaths and hospitalizations associated with diarrhoea in children <5 years of age has been reported. There is growing evidence to suggest that live-attenuated vaccines also provide protection against other infections beyond the vaccine-targeted pathogens. These so called off-target effects of vaccination have been associated with the tuberculosis vaccine Bacille Calmette Guérin (BCG), measles, oral polio and recently salmonella vaccines, and are thought to be mediated by modified innate and possibly adaptive immunity. Indeed, rotavirus vaccines have been reported to provide greater than expected reductions in acute gastroenteritis caused by other enteropathogens, that have mostly been attributed to herd protection and prior underestimation of rotavirus disease. Whether rotavirus vaccines also alter the immune system to reduce non targeted gastrointestinal infections has not been studied directly. Here we review the current understanding of the mechanisms underlying off-target effects of vaccines and propose a mechanism by which the live-attenuated neonatal rotavirus vaccine, RV3-BB, could promote protection beyond the targeted pathogen. Finally, we consider how vaccine developers may leverage these properties to improve health outcomes in children, particularly those in low-income countries where disease burden and mortality is disproportionately high relative to developed countries.
ARTICLE | doi:10.20944/preprints202107.0468.v1
Subject: Biology, Ecology Keywords: Hengduan mountains; Himalopsyche martynovi; gene flow; morphology; phylogeny; speciation; target enrichment
Online: 20 July 2021 (17:10:08 CEST)
Background: The Hengduan Mountains are one of the most species–rich mountainous areas in the world. The origin and evolution of such a remarkable biodiversity are likely to be associated with geological or climatic dynamics, as well as taxon-specific biotic processes (e.g., hybridization, polyploidization, etc.). Here, we investigate the mechanisms fostering the diversification of the endemic Himalopsyche martynovi complex, a poorly known group of aquatic insects. Methods: We used multiple allelic datasets generated from 691 AHE loci to reconstruct species and RaxML phylogenetic trees. We selected the most reliable phylogenetic tree to perform network and gene flow analyses. Results: Phylogenetic reconstructions and network analysis identified three clades, including H. epikur, H. martynovi sensu stricto and H. cf. martynovi. Himalopsyche martynovi sensu stricto and H. cf. martynovi present an intermediate morphology between H. epikur and H. viteceki, the closest known relative to the H. martynovi–complex. The gene flow analysis revealed extensive gene flow among these lineages. Conclusion: Our results suggest that H. viteceki and H. epikur are likely to have contributed to the evolution of H. martynovi sensu stricto and H. cf. martynovi via gene flow, and thus, our study provides insights in the diversification process of a lesser–known ecological group, and hints at the potential role of gene flow in the emergence of biological novelty in the Hengduan Mountains.
REVIEW | doi:10.20944/preprints202007.0478.v2
Subject: Life Sciences, Molecular Biology Keywords: Bioinformatics; Drug Design; Small Organic Molecule; Target identification; Web-based Server
Online: 25 July 2020 (17:50:30 CEST)
Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.
ARTICLE | doi:10.20944/preprints202007.0495.v1
Subject: Chemistry, Medicinal Chemistry Keywords: In silico target prediction; dihydrochalcones; SEA; SwissTargetPrediction; SuperPred; polyphamracology; virtual screening
Online: 21 July 2020 (13:43:40 CEST)
Natural products comprise a rich reservoir for innovative drug leads and are a constant source of bioactive compounds. To find pharmacological targets for new or already known natural products using modern computer-aided methods is a current endeavor in drug discovery. Nature’s treasures, however, could be used more effectively. Yet, reliable pipelines for large scale target prediction of natural products are still rare. We have developed an in silico workflow consisting of four independent, stand-alone target prediction tools and evaluated its performance on dihydrochalcones (DHCs) – a well-known class of natural products. Thereby, we revealed four previously unreported protein targets for DHCs, namely 5-lipoxygenase, cyclooxygenase-1, 17β- hydroxysteroid dehydrogenase 3, and aldo-keto reductase 1C3. Moreover, we provide a thorough strategy on how to perform computational target prediction and guidance on using the respective tools.
REVIEW | doi:10.20944/preprints202005.0010.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: bone metastasis; breast cancer; radiotherapy; diagnostic imaging; radiobiologic response; target therapy
Online: 2 May 2020 (12:48:23 CEST)
The standard of care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment in case of symptomatology onset. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive disease presentations are even more common, leading to a change of paradigm of focal treatments. In fact, acknowledgement of behaviour of disease in these setting of patients is carrying aim of radiotherapy towards modalities with radical intent. The aim of this literature review is to analyse available clinical data regarding disease behaviour, imaging, radiotherapy and chemo-radiotherapy integration outcomes for understanding bone metastasis from breast cancer and the potential impact of targeting it.
CONCEPT PAPER | doi:10.20944/preprints202004.0213.v1
Subject: Life Sciences, Biochemistry Keywords: covid-19; rlmE MTase; new drug target; corona diagnosis; corona pandemic
Online: 13 April 2020 (12:33:22 CEST)
Covid-19 infections are rapidly spreading worldwide with more than 100000 death and thus understanding the molecular mechanism of tropism of human cells is an urgent need for drug design. We have described here a bioinformatics approach to predict the functional aspects of non-structural nsp16 protein of Corona virus. The covid-19 7098 AA large polyprotein was degraded into sixteen proteins and last nsp16 protein was found an RlmE type rRNA methyltransferase. Nsp16 has no similarity to bacterial RlmABCD but has 25 percent similarity to the bacterial RlmE protein which methylates the U2551 2-hydroxy group of Ribose. The nsp16 proteins of different corona viruses like covid-19, bat-coronavirus, SARS and MERS have strong homology. Mrm2 and Dim1 like yeast and mammalian rRNA methyltransferases have 26-33 percent homologies but not with 2-O-capping MTase as reported previously. Rrp8 MTases also has no similarity to nsp16. We postulated that mitochondrial rRNA methylation of bronchial cells were mediated by the nsp16 protein causing inhibition of protein synthesis due to poor assembly of aminoacyl-tRNA or mRNA and peptidyl transferase at the PTC. This is one of the new molecular mechanism of corona virus cellular tropism and different than ACE-2 mediated blockage of cellular signalling to inhibit aldesterone biosynthesis with abnormal Na+ ions in cells. We also designed primers based on nsp16 cDNA sequence (nt 20659-21552, accession no MT121215) specific for Covid-19 diagnosis by RT-PCR.
ARTICLE | doi:10.20944/preprints202004.0027.v1
Subject: Engineering, Other Keywords: wildfire smoke detection; target-aware; depthwise separable; fixed convolution kernel; DSATA
Online: 3 April 2020 (04:43:58 CEST)
Since smoke usually occurs before a flame arises, fire smoke detection is especially significant for early warning systems. In this paper, a DSATA(Depthwise Separability And Target Awareness) algorithm based on depthwise separability and target awareness is proposed. Existing deep learning methods with convolutional neural networks pretrained by abundant and vast datasets are always used to realize generic object recognition tasks. In the area of smoke detection, collecting large quantities of smoke data is a challenging task for small sample smoke objects. The basis is that the objects of interest can be arbitrary object classes with arbitrary forms. Thus, deep feature maps acquired by target-aware pretrained networks are used in modelling these objects of arbitrary forms to distinguish them from unpredictable and complex environments. In this paper, this scheme is introduced to deal with smoke detection. The depthwise separable method with a fixed convolution kernel replacing the training iterations can improve the speed of the algorithm to meet the enhanced requirements of real-time fire spreading for detecting speed. The experimental results demonstrate that the proposed algorithm can detect early smoke, is superior to the state-of-the-art methods in accuracy and speed, and can also realize real-time smoke detection.
REVIEW | doi:10.20944/preprints202002.0098.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: Type 2 diabetes; insulin target tissues; iPSCs; genetic factors; disease modeling
Online: 7 February 2020 (11:45:04 CET)
In this review, we discuss the insulin resistance (IR) and its development in the insulin target tissues that leads to diabetes. Also, we highlight the use of induced pluripotent stem cells (iPSCs) to understand the mechanisms underlying the development of IR. IR is associated with several metabolic disorders, including type 2 diabetes (T2D). The development of IR in insulin target tissues involves genetic and acquired factors. Persons at genetic risk for T2D tend to develop IR several years before glucose intolerance. Although there are currently several mouse models for both IR and T2D that had provided a lot of information about the disease, these models cannot recapitulate all the aspects of this complex disease as seen in each individual. Patient-specific iPSCs can overcome the hurdles faced with the classical mouse models for studying IR. iPSC technology can generate cells genetically identical to IR individuals, which can help in distinguishing between genetic and acquired defects in insulin sensitivity. Combining the technologies of the genome editing and iPSCs may provide important information about the inherited factors underlying the development of different forms of IR. Further studies are required to fill the gaps in understanding the pathogenesis of IR and diabetes.
ARTICLE | doi:10.20944/preprints201811.0611.v1
Subject: Earth Sciences, Environmental Sciences Keywords: water resources; natural resources; resource security; SDGs; goal; target; benchmark; standard
Online: 28 November 2018 (14:03:52 CET)
The 2030 Agenda for Sustainable Development, the SDGs, are high on the agenda for most countries of the world. In its publication of the SDGs, the UN has provided the goals and target descriptions that, if implemented at a country level, would lead towards a sustainable future. The IAEG (InterAgency Expert Group of the SDGs) was tasked with disseminating indicators and methods to countries that can be used to gather data describing the global progress towards sustainability. However 2030 Agenda leaves it to countries to adopt the targets with each government setting its own national targets guided by the global level of ambition but taking into account national circumstances. At present, guidance on how to go about this is scant, but it is clear that the responsibility is with countries to implement and that it is actions at a country level that will determine the success of the SDGs. SDG reporting by countries takes on two forms 1) global reporting using prescribed indicator methods and data; 2) National Voluntary Reviews where a country reports on its own progress in more detail but is also able to present data that are more appropriate for the country. For the latter, countries need to be able to adapt the global indicators to fit national priorities and context, thus the global description of an indicator could be reduced to describe only what is relevant to the country. Countries may also, for the National Voluntary Review, use indicators that are unique to the country but nevertheless contribute to measurement of progress towards the global SDG target. Importantly, for those indicators that relate to the security of natural resources security (e.g. water) indicators, there are no prescribed numerical targets/standards or benchmarks. Rather countries will need to set their own benchmarks or standards against which performance can be evaluated. This paper presents a procedure that would enable a country to describe national targets with associated benchmarks that are appropriate for the country. The procedure focusses on those SDG targets that are natural resource-security focussed e.g. extent of water-related ecosystems (6.6), desertification (15.3) etc., because the selection of indicator methods and benchmarks is based on the location of natural resources, their use and present state and how they fit into national strategies.
REVIEW | doi:10.20944/preprints201805.0378.v1
Subject: Biology, Other Keywords: annexins; inflammation; wound healing; host-pathogen interplay; drug target; translational research
Online: 27 May 2018 (11:32:34 CEST)
The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca2+) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca2+-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically clinical point of view.
ARTICLE | doi:10.20944/preprints201805.0116.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: Target recognition, SAR, keypoint, local descriptor, sparse representation, feature quantization, classification
Online: 7 May 2018 (11:47:13 CEST)
This paper considers target characterization and recognition in radar images with keypoint-based local descriptor. Most of the preceding works rely on the global features or raw intensity values, and hence produce the limited recognition performance. Moreover, the global features are sensitive to the real-world sources of variability, such as aspect view, configu-ration, and incidence angle changes, clutter, articulation, and occlusion. Keypoint-based local descriptor was developed as a powerful strategy to address invariance to contrast change and geometric distortion. This property inspires us to investigate whether the family of local features are relevant for radar target recognition. Most of the preceding works typically devote to finding the correspondences between a collected image and a reference one. The representative applications include image register and change detection. Little work was pursued to target recognition in SAR images. This is because the huge number of local descriptors resulting from radar images make the computational cost and memory consumption unacceptable. To handle the problems, this paper develops two families of methods. The proposed methods are used to achieve target recognition by means of local descriptors. Our first solver refers to building multiple linear regression models, and addresses the problem by the theory of sparse representation. The second scheme rebuilds a new feature by the feature quantization skill, from which the inference can be drawn. Multiple comparative studies are pursued to verify the performance of detectors and descriptors popularly used. The source code was publicly released on https://ganggangdong.github.io/homepage/.
REVIEW | doi:10.20944/preprints202012.0684.v1
Subject: Life Sciences, Biochemistry Keywords: COVID-19; point-of-care diagnostic test; target product profile; clinical performance
Online: 28 December 2020 (11:14:55 CET)
COVID-19 pandemic will continue to pose a major public health threat until vaccination-mediated herd immunity is achieved. Most projections predict vaccine will reach a large subset of the population late in 2021 or early 2022. In the meantime, countries are exploring options to remove strict lockdown measures and allow for society and the economy to return to normal function. One possibility is to expand on existing COVID-19 testing strategies by including large-scale rapid point of care diagnostic tests (POCTs). Currently, there is significant variability in performance and features of available POCTs, making selection and procurement of appropriate test for specific use case difficult. In this review, we have used the World Health Organization’s (WHO) recently published Target Product Profiles (TPPs) for specific use cases of COVID-19 diagnostic tests to screen for top-performing POCTs on the market. Several top-performing POCTs, based on clinical sensitivity/specificity, the limit of detection, and time to results, that meet WHO TPP criteria for direct detection of SARS-CoV-2 (acute infection), or indirect diagnosis of past infection (host antibodies) are highlighted here.
ARTICLE | doi:10.20944/preprints202009.0095.v1
Subject: Engineering, Mechanical Engineering Keywords: fatigue; design fatigue factor; offshore wind turbine foundation; corrosion fatigue; target reliability
Online: 4 September 2020 (11:00:22 CEST)
The concept of Design Fatigue Factors (DFFs) was introduced for providing desired level of safety in structural fatigue design, often associated with damage calculated from S-N curves. Calculation of fatigue damage from S-N curves can be affected by multiple factors, e.g. types of weld class, corrosion condition, loading conditions, stress concentration on different geometries etc. Each of them can be subject to different level of uncertainties. This study intends to recalibrate the DFFs from a detailed reliability analysis by investigating the probabilistic models derived from the database of S-N curves that has been most frequently used in offshore wind industry. The results of such study indicate that the DFFs can be reduced substantially for the corrosive environmental fatigue models from current standards to the same level of target reliability.
ARTICLE | doi:10.20944/preprints201907.0018.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: atopic dermatitis; AD; dermatology; target identification; pathway identification; bioinformatics; protein-protein networks
Online: 1 July 2019 (12:47:49 CEST)
The exploration and identification of targets and pathways for Atopic dermatitis (AD) treatment and diagnosis are critical for AD control. The conventional target exploration approach such as the literature review is not satisfying in terms of efficiency and accuracy. Recently, the bioinformatic approach is drawing attention for its unique advantage of high-volume data analysis for target and pathway exploration; Open Targets Platform is the targets source for this study to extract top 200 high-rank proteins from 3122 AD associated proteins. STRING, Cytoscape, CytoHubba, ClueGo, and CluePedia function had been applied for data analysis. The KEGG Mapper search & colour pathway was the pathway map resource for identified pathways; 23 key hub genes (VDR, KIT, BCL2L11, NFKBIA, KRAS, IL13, JAK2, STAT3, IL21, IL4R, REL, PDGFRB, FOXP3, RARA, RELB, EGFR, IL21R, MYC, CREBBP, NR3C1, IL2, JAK1, and KITLG). Additionally, 8 correlated pathways and the biological process had been identified; Through this study, a viable approach for target and pathway exploration had been presented. The identified AD targets and pathways will be tested for upcoming research for traditional Chinese medicinal herb interactions
REVIEW | doi:10.20944/preprints201807.0606.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: protein-DNA interactions; facilitated diffusion; protein target search; discrete-state stochastic models
Online: 31 July 2018 (05:39:04 CEST)
Protein-DNA interactions are critical for the successful functioning of all natural systems. The key role in these interactions is played by processes of protein search for specific sites on DNA. Although it has been studied for many years, only recently microscopic aspects of these processes became more clear. In this work, we present a review on current theoretical understanding of the molecular mechanisms of the protein target search. A comprehensive discrete-state stochastic method to explain the dynamics of the protein search phenomena is introduced and explained. Our theoretical approach utilizes a first-passage analysis and it takes into account the most relevant physical-chemical processes. It is able to describe many fascinating features of the protein search, including unusually high effective association rates, high selectivity and specificity, and the robustness in the presence of crowders and sequence heterogeneity.
ARTICLE | doi:10.20944/preprints201709.0084.v1
Subject: Engineering, Control & Systems Engineering Keywords: Passive Sonar; Target Detection; Adaptive Threshold; Bayesian Classifier; K-Mean; Particle Filter
Online: 18 September 2017 (17:04:13 CEST)
This paper presents the results of an experimental investigation about target detecting with passive sonar in Persian Gulf. Detecting propagated sounds in the water is one of the basic challenges of the researchers in sonar field. This challenge will be complex in shallow water (like Persian Gulf) and noise less vessels. Generally, in passive sonar the targets are detected by sonar equation (with constant threshold) which increase the detection error in shallow water. Purpose of this study is proposed a new method for detecting targets in passive sonars using adaptive threshold. In this method, target signal (sound) is processed in time and frequency domain. For classifying, Bayesian classification is used and prior distribution is estimated by Maximum Likelihood algorithm. Finally, target was detected by combining the detection points in both domains using LMS adaptive filter. Results of this paper has showed that proposed method has improved true detection rate about 27% compare other the best detection method.
ARTICLE | doi:10.20944/preprints201702.0054.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: human antibody; invasion; lung cancer; therapeutic target; VCAM-1; VCAM-1-D6
Online: 15 February 2017 (10:45:16 CET)
Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.
ARTICLE | doi:10.20944/preprints202212.0186.v1
Subject: Engineering, Automotive Engineering Keywords: remote sensing image (RSI); target detection; convolution neural networks (CNN); FESSD; feature enhancement
Online: 12 December 2022 (02:52:16 CET)
Automatic target detection of remote sensing images (RSI) plays an important role in military reconnaissance, disaster monitoring, and target rescue. The core task of remote sensing target detection is to judge the target categories and complete precise location. However, the existing target detection algorithms have limited accuracy and weak generalization capability for remote sensing images with complex backgrounds. To achieve accurate detection of different categories targets in remote sensing images, this study presents a novel feature enhancement single shot multibox detector (FESSD) algorithm for remote sensing target detection. The FESSD introduces feature enhancement module and attention mechanism into the convolution neural networks (CNN) model, which can effectively enhance the feature extraction ability and nonlinear relationship between different convolution features. Specifically, the feature enhancement module is used to extract the multi-scale feature information, and enhance the model nonlinear learning ability; the self-learning attention mechanism (SAM) is used to expand the convolution kernel local receptive field, which makes the model extract more valuable features. In addition, the nonlinear relationship between different convolution features is enhanced using the feature pyramid attention mechanism (PAM). The advantage of FESSD over other state-of-the-art target detection methods is validated by experiments on the presented seven-class target detection dataset (SD-RSI) and the public DIOR dataset.
ARTICLE | doi:10.20944/preprints202109.0257.v1
Subject: Life Sciences, Biochemistry Keywords: protein-protein interactions; PDZ domains; choanoflagellates; evolution; target selectivity; protein-peptide interactions; signaling
Online: 15 September 2021 (12:25:01 CEST)
Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.
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/preprints202007.0627.v1
Subject: Medicine & Pharmacology, Pediatrics Keywords: Erythrocytapheresis; red blood cell exchange; sickle cell disease; target HbS level; heparin locking
Online: 26 July 2020 (02:22:35 CEST)
The aim of our study was to describe our experience using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated red blood cell exchange (RCE) to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7-13]. We analysed 649 exchange sessions. Peripheral venous access was limited in a number of the children, thus requiring a femoral central double‐lumen venous catheter (CVC). We recommend the use of heparin locking, with 500 units in each lumen of a CVC. This method was well tolerated, with few complications during the procedures. For preoperative prevention, all of the patients had achieved a post-RCE HbS level of <30% since this is a mandatory condition imposed by the anaesthesiologist. With a post-RCE Hb level of approximately 10-11 g/dL, a blood exchange volume of ≥32 mL/kg, and an interval between each RCE procedure of ≤30 days, it was able to maintain the residual HbS level below 30%. Despite a target pre‐exchange HbS level of 47%, we did not encounter a single stroke recurrence. Erythrocytapheresis is useful and safe for children with SCD.
Subject: Biology, Other Keywords: nucleoid-associated proteins (NAPs); moonlighting proteins; drug target; biofilm; specificity determination; phylogenetic analysis
Online: 7 June 2020 (09:07:56 CEST)
Nucleoid-associated proteins (NAPs) play an architectural role by bending, bridging, and wrapping the DNA along with a regulatory role of controlling various transcriptional units in the cell. Previews reviews have highlighted the role of HU and its paralog IHF plays in intracellular function as a transcriptional regulator, nucleoid bending protein and sometimes also moonlights in other functions. This review highlights along with the canonical functions of HU and IHF which affects genes responsible for translational machineries, cell wall biosynthesis, aerobic respiration and virulence ; other non-canonical roles which HU plays outside the cellular milieu, notably in acting as an adhesin and playing role in host-cell adhesion, its role in biofilm architecture and its association with cationic low complexity region, resembling histone like H1 proteins. HU and IHF thus has evolved as a hub protein performing a vast type of functions which makes it a important drug target for antibacterial therapy.
ARTICLE | doi:10.20944/preprints201912.0136.v1
Subject: Earth Sciences, Environmental Sciences Keywords: Bioconcentration Factor; Estimated Daily Intake; Nyabarongo river; Protopterus annectens; Rwanda; Target Hazard Quotient.
Online: 10 December 2019 (15:07:13 CET)
Water is an indispensable natural resource that is often prodigiously threatened by anthropomorphic activities. This study evaluated the physicochemical properties of water and selected heavy metals in edible muscles of a piscivorous fish (Protopterus annectens) from Nyabarongo and Nyabugogo rivers of Rwanda. Edibility health risk was evaluated using the target hazard quotient method. Water samples were taken in triplicate from Ruliba station and Kirinda bridge on Nyabarongo river and Giticyinyoni on Nyabugogo river. Fish samples were obtained from the sampling stations on Nyabarongo river. All samples were analyzed following standard methods and analytical results indicated that the average temperature, pH, total dissolved solids and electrolytic conductivity of water from the rivers were within WHO acceptable limits. The statistical mean concentrations of the ionic components of the water samples were 1.61 ± 0.03, 0.53 ± 0.002, 0.24 ± 0.02 and 0.051 ± 0.01 mg/L for Fe, Mn, Cu and Pb respectively at Ruliba station and 0.63 ± 0.02, 0.02 ± 0.002, 0.09 ± 0.01, 0.06 ± 0.002 and 0.75 ± 0.02 mg/L for Fe, Mn, Zn, Cr and Pb respectively at Kirinda bridge. Water from Giticyinyoni had 1.57 ± 0.02, 0.49 ± 0.03, 0.29 ± 0.058, 0.43 ± 0.058, 0.15 ± 0.00 and 0.59 ± 0.058 mg/L of Fe, Mn, Cu, Zn, Cr and Pb respectively. Zinc, Cu, Cr and Cd were below detection limits in samples from Ruliba station and Kirinda bridge (Nyabarongo river). Edible muscles of P. annectens from Nyabarongo river contained 272.8 ± 0.36, 292.2 ± 0.25, 8.8 ± 0.36, 135.2 ± 0.15, 148.0 ± 0.21 and 432. 0 ± 0.50 mgkg-1 for Fe, Mn, Cu, Zn, Cr and Pb at Ruliba station and 336.0 ± 0.70, 302.6 ± 1.22, 6.4 ± 0.26, 44.7 ± 0.20, 138.2 ± 0.17 and 302.4 ± 1.50 mgkg-1 for Fe, Mn, Cu, Zn, Cr and Pb respectively at Kirinda bridge. Health risk assessment indicated that consumption of the edible muscles of P. annectens may lead to deleterious health effects as reflected by values of target hazard quotients being greater than one. Therefore, the Rwandese government should lay strategies to reduce pollution of the rivers. Further research should evaluate the heavy metal content of metabolically active organs of P. annectens from Nyabarongo river as well as the microbiological profile of water from the rivers.
REVIEW | doi:10.20944/preprints201812.0066.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: renal cell carcinoma; circulating DNA; CTC; diagnosis; follow-up; genetic alteration; target therapy
Online: 5 December 2018 (08:01:30 CET)
Liquid biopsy, based on the circulating tumor cells (CTCs) and cell-free nucleic acids has potential applications at multiple points throughout the natural course of cancer, from diagnosis to follow-up. The advantages of doing ctDNA assessment vs. tissue-based genomic profile are the minimal procedural risk, the possibility to serial testing in order to monitor disease-relapse and response to therapy over time and to reduce hospitalization costs during the entire process. However some critical issues related to ctDNA assays should be taken in consideration. The sensitivity of ctDNA assays depends on the assessment technique and genetic platforms used, on tumor-organ, stage, tumor heterogeneity, tumor clonality. The specificity is usually very high, whereas the concordance with tumor-based biopsy is generally low. In patients with renal cell carcinoma (RCC) qualitative analyses of ctDNA have been performed with interesting results regarding selective pressure from therapy, therapeutic resistance, exceptional treatment response to everolimus and mutations associated with aggressive behavior. Quantitative analyses showed variations of cfDNA levels at different tumor stage. Compared to CTC assay, ctDNA is more stable than cells and easier to isolate. Splice variants, information at single-cell level and functional assays along with proteomics, transcriptomics and metabolomics studies can be performed only in CTCs.
ARTICLE | doi:10.20944/preprints201810.0116.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: head and neck cancer; induction chemotherapy; 18F-FDG PET/CT; target volume delineation
Online: 7 October 2018 (09:48:55 CEST)
Background and objectives: Induction chemotherapy (ICT) before definitive chemoradiation (CRT) gives high response rates in LA-SCCHN. However, pre-ICT gross tumour volume (GTV) for radiotherapy (RT) planning is still recommended. As 18F-FDG PET/CT has an advantage of biological tumour information comparing to standard imaging methods, we aimed to evaluate the feasibility of 18F-FDG PET/CT-based post-ICT GTV delineation for RT planning in LA-SCCHN and to assess the prognostic value of PET parameters: maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Methods: 47 LA-SCCHN patients were treated with 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil) followed by CRT (70 Gy in 35 fractions with weekly cisplatin). Pre- and post-ICT PET/CT examinations were acquired. Planning CT was co-registered with post-ICT PET/CT and RT target volumes were contoured according to post-ICT PET. Post-ICT percentage decrease of SUVmax, MTV and TLG in primary tumour and metastatic regional lymphnodes (LN) was counted. Loco-regional failure patterns, 3-year progression free (PFS) and overall survival (OS) were evaluated. Results: 3-year PFS and OS rates for study population were 67% and 61% respectively. 31.9% of patients progressed loco-regionally. All progresses were localised in high-to-intermediate dose (60–70 Gy) RT volumes and none in low dose (50 Gy) volumes. Decrease of SUVmax ≥74% (p = 0.03), MTV ≥ 68% (p = 0.04), TLG ≥ 76% (p = 0.02) in primary tumour, and LN TLG decrease ≥74% (p = 0.03) were associated with PFS. Decrease of primary tumour SUVmax ≥ 74% (p = 0.04), MTV ≥ 69% (p = 0.04), TLG ≥ 74% (p = 0.02) and LN TLG ≥ 73% (p = 0.02) were prognostic factors for OS. Conclusions: According to our results, 18F-FDG PET/CT-based post-ICT GTV delineation is feasible strategy without negative impact on loco-regional control and survival. Percentage decrease of metabolic PET parameters SUVmax, MTV and TLG has a prognostic value in LA-SCCHN.
ARTICLE | doi:10.20944/preprints201809.0520.v1
Subject: Behavioral Sciences, Other Keywords: Energy consumption, Energy savings, Home Energy Management System (HEMS), Homeowners, Target group segmentation
Online: 26 September 2018 (15:39:15 CEST)
In contrast to physical sustainable measures carried out in homes, such as insulation, the installation of a Home Energy Management System (HEMS) has no direct and immediate energy-saving effect. A HEMS gives insight into resident behaviour regarding energy use. When this is linked to the appropriate feedback, the resident is in a position to change his or her behaviour. This should result in reduced gas and/or electricity consumption. The aim of our study is to contribute towards the effective use of home energy management systems (HEMS) by identifying types of homeowners in relation to the use of HEMS. The research methods used were a literature review and the Q-method. A survey using the Q-method was conducted among 39 owners of single-family homes in various Rotterdam neighbourhoods. In order to find shared views among respondents, a principal component analysis (PCA) was performed. Five different types of homeowner could be distinguished: the optimists, the privacy-conscious, the technicians, the sceptics, and the indifferent. Their opinions vary as regards the added value of a HEMS, what characteristics a HEMS should have, how much confidence they have in the energy-saving effect of such systems, and their views on the privacy and safety of HEMS. The target group classification can be used as input for a way in which local stakeholders, e.g. a municipality, can offer HEMS that is in line with the wishes of the homeowner.
REVIEW | doi:10.20944/preprints202110.0450.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Fibrosis; Integrin; TGFβ; Therapeutic target; Drug; Inhibitor; Monoclonal antibody; α8β1; α11β1; Hepatic stellate cell
Online: 29 October 2021 (10:16:13 CEST)
Huge effort has been devoted to developing drugs targeting integrins over 30 years, because of the primary roles of integrins in the cell-matrix milieu. Five αv-containing integrins, in the 24 family members, have been a central target of fibrosis. Currently, a small molecule against αvβ1 is undergoing a clinical trial for NASH-associated fibrosis as a rare reagent aiming at fibrogenesis. Latent TGFβ activation, a distinct talent of αv-integrins, has been intriguing as therapeutic target. None of the αv-integrin inhibitors, however, has been in the clinical market. αv-integrins commonly recognize an Arg-Gly-Asp (RGD) sequence, and thus the pharmacophore of inhibitors for the 5-integrins is based on the same RGD structure. The RGD preference of the integrins, at the same time, dilutes ligand specificity, as the 5-integrins share ligands containing RGD sequence such as fibronectin. With the inherent little specificity in both drugs and targets, “disease specificity” has become less important for the inhibitors than blocking as many αv-integrins. In fact, an almighty inhibitor for αv-integrins, pan-αv, was in a clinical trial. On the contrary, approved integrin inhibitors are all specific to target integrins, which are expressed in cell-type specific manner: αIIbβ3 on platelets, α4β1, α4β7 and αLβ2 on leukocytes. Herein, “disease specific” integrins would serve as attractive targets. α8β1 and α11β1 are selectively expressed in hepatic stellate cells (HSCs) and distinctively induced upon culture activation. The exceptional specificity to activated HSCs reflects rather “pathology specific” nature of these new integrins. The monoclonal antibodies against α8β1 and α11β1 in preclinical examinations may illuminate the road to the first medical reagents.
ARTICLE | doi:10.20944/preprints201808.0521.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: Target difference, clinically important difference, sample size, guidance, randomised trial, effect size, realistic difference
Online: 30 August 2018 (10:33:40 CEST)
The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.
REVIEW | doi:10.20944/preprints201807.0518.v1
Subject: Life Sciences, Virology Keywords: virus; antiviral agent; drug target; drug side effect; innate immunity; precision medicine; systems biology
Online: 26 July 2018 (15:33:03 CEST)
There are dozens of approved, investigational and experimental antiviral agents. Many of these agents cause serious side effects, which can be revealed only after drug administration. Identification of the side effects prior to drug administration is challenging. Here we describe an ex vivo approach for studying immuno- and neuro-modulatory properties of antiviral agents, which could be associated with potential side effects of these therapeutics. The approach combines drug toxicity/efficacy tests and transcriptomics, which is followed by cytokine and metabolite profiling. We demonstrated the utility of this approach with several examples of antiviral agents. We also showed that the approach can utilize different immune stimuli and cell types. It can also include other omics techniques, such as genomics and epigenomics, to allow identification of individual markers associated with adverse reactions to antivirals with immuno- and neuro-modulatory properties.
ARTICLE | doi:10.20944/preprints201804.0374.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: STAT3 as a drug target; cyclic STAT3 decoy; oligodeoxynucleotide inhibitor; head and neck cancer
Online: 29 April 2018 (10:10:00 CEST)
Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.
ARTICLE | doi:10.20944/preprints201705.0117.v1
Subject: Engineering, Control & Systems Engineering Keywords: autonomous aerial refueling; computer vision; probe and drogue; target detection and tracking; ellipse fitting
Online: 16 May 2017 (05:56:11 CEST)
Autonomous aerial refueling technology is an effective solution to extend flight duration of unmanned aerial vehicles, and also a great challenge due to its high risk. For autonomous probe-and-drogue refueling tasks, relative navigation to provide relative position between the receiver aircraft and the refueling drogue is the first and essential step, and vision-based method is the most frequently used. A new monocular vision navigation sensor with image processing strategy consisting of the drogue detection method and the tracking method is developed for autonomous aerial refueling in this paper. In the drogue detection method, thresholding and mathematical morphology method are adopted to eliminate image interference, and contours extraction method is applied to obtain all contours, which are then subsequently checked to achieve target contour of drogue. In the tracking method, a rectangle of interest (ROI) of current frame image is determined by positioning results of last frame, and then processed by the previous drogue detection method. Finally, the proposed image processing strategy in monocular vision navigation sensor is validated using real flight images, which are captured from an autonomous aerial refueling testbed using a micro six-rotor aircraft as receiver aircraft.
ARTICLE | doi:10.20944/preprints201612.0029.v1
Subject: Engineering, Automotive Engineering Keywords: electric vehicle; battery heat generation; battery degradation; vehicle operation cost; preheating target temperature; heating system
Online: 6 December 2016 (07:46:46 CET)
This paper presents an optimized energy management strategy for Li-ion power batteries used on electric vehicles (EVs) at low temperatures. Under low-temperature environments, EVs suffer a sharp driving range loss resulted from the energy and power capability reduction of the battery. Simultaneously, because of Li plating, battery degradation becomes an increasing concern as temperature drops. All these factors could greatly increase the total vehicle operation cost. Prior to battery charging and vehicle operating, preheating battery to a battery-friendly temperature is an approach to promote energy utilization and reduce total cost. Based on the proposed LiFePO4 battery model, the total vehicle operation cost under certain driving cycles is quantified in the present paper. Then given a certain ambient temperature, a target temperature of preheating is optimized under the principle of minimizing total cost. As for the preheating method, a liquid heating system is also implemented on an electric bus. Simulation results show that the preheating process becomes increasingly necessary with a decreasing ambient temperature; however, the preheating demand declines as driving range grows. Vehicle tests verify that the preheating management strategy proposed in this paper is able to save total vehicle operation cost.
ARTICLE | doi:10.20944/preprints202205.0392.v1
Subject: Life Sciences, Biophysics Keywords: atrial-fibrillation; multi-target; drug promiscuity; druggable binding site; flecainide; Nav1.5; Kv1.5; binding site comparison; polypharmacology
Online: 30 May 2022 (10:10:41 CEST)
Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that combined blockade of Nav1.5 (and its current INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without effect on ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD), as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We presented a computational workflow for flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the inner cavity and consist of a hydrophobic patch and a polar region, involving residues from S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.
ARTICLE | doi:10.20944/preprints202109.0240.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Gene Silencing; Host–Virus Interaction; RNA Interference; Saccharum officinarum; Sugarcane Yellow Leaf Virus and Target Prediction
Online: 14 September 2021 (12:43:22 CEST)
The Sugarcane yellow leaf virus (SCYLV) is associated with sugarcane yellow leaf disease (SCYLD) and is considered to be the most economically deleterious emerging pathogen that represents a potential threat and danger to sugarcane cultivation in China. Over the last two decades, high genetic diversity in the SCYLV genotypes was observed worldwide, with a greater chance of YLD incidence for sugarcane injury. SCYLV infection has significantly damaged its economic traits and is responsible for substantial losses in biomass production in sugarcane cultivars. This study aims to identify and comprehensively analyze sugarcane microRNAs (miRNAs) as therapeutic targets against SCYLV using plant miRNA prediction tools. Mature sugarcane miRNAs are retrieved and are used for hybridization of the SCYLV. A total of seven common sugarcane miRNAs were selected based on consensus genomic positions. The biologically significant, top ranked ssp-miR528 was consensually predicted to have a potentially unique hybridization site at nucleotide position 4162 for targeting the ORF5 of the SCYLV genome; this was predicted by all the algorithms used in this study. Then, the miRNA–mRNA regulatory network was generated using the Circos algorithm, which was used to predict novel targets. There are no acceptable commercial SCYLV-resistant sugarcane varieties available at present. Therefore, the predicted biological data offer valuable evidence for the generation of SCYLV-resistant sugarcane plants.
REVIEW | doi:10.20944/preprints202012.0288.v1
Subject: Medicine & Pharmacology, Allergology Keywords: desmoplastic small round cell tumor; treatment; prognosis; surgery; radiotherapy; chemotherapy; tyrosine kinase receptor; target therapy; rare disease
Online: 11 December 2020 (15:53:20 CET)
Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.
ARTICLE | doi:10.20944/preprints202012.0164.v1
Subject: Engineering, Automotive Engineering Keywords: variational Bayesian; multiple-fading factors; time-varying noise covariance matrices; inaccurate noise; target tracking; update monitoring strategy
Online: 7 December 2020 (14:54:14 CET)
Aiming at the problem that the performance of Adaptive Kalman filter estimation will be affected when the statistical characteristics of the process and measurement noise matrix are inaccurate and time-varying in the linear Gaussian state-space model, an algorithm of Multi-fading factor and update monitoring strategy adaptive Kalman filter based variational Bayesian is proposed. Inverse Wishart distribution is selected as the measurement noise model, the system state vector and measurement noise covariance matrix are estimated with the variational Bayesian method. The process noise covariance matrix is estimated by the maximum a posteriori principle, and the update monitoring strategy with adjustment factors is used to maintain the positive semi-definite of the updated matrix. The above optimal estimation results are introduced as time-varying parameters into the multiple fading factors to improve the estimation accuracy of the one-step state predicted covariance matrix. The application of the proposed algorithm in target tracking is simulated. The results show that compared with the current filters, the proposed filtering algorithm has better accuracy and convergence performance, and realizes the simultaneous estimation of inaccurate time-varying process and measurement noise covariance matrices.
ARTICLE | doi:10.20944/preprints202004.0068.v2
Subject: Life Sciences, Biotechnology Keywords: coronavirus; COVID-19; hACE-2; MPro; multi-target-directed ligand; protease inhibito; RdRp; SARS-CoV-2 virus
Online: 9 April 2020 (05:13:05 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in the current COVID-19 pandemic. Worldwide this disease has infected around 1.5 million individuals with a mortality rate ranging from 5 to 10%. It has also imposed extreme challenges on global health, economy, and social behavior. Due to the unavailability of therapeutics, several efforts are going on in the drug discovery to control the SARS-CoV-2 viral infection. The main protease (MPro) plays a critical role in viral replication and maturation, thus can serve as the primary drug target. To understand the structural evolution of MPro, we have performed phylogenetic and SSN analysis, that depicted divergence of Coronaviridae MPro in five clusters specific to viral hosts. This clustering was also corroborated with the comparison of MPro structures. Furthermore, it has been observed that backbone and binding site conformations are conserved despite variation in some of the residues. This conservation can be exploited to repurpose available viral protease inhibitors against SARS-CoV-2 MPro. In agreement with this, we performed screening of the custom-made library of ~7100 molecules including active ingredients present in the Ayurvedic anti-tussive medicines, anti-viral phytochemicals and synthetic anti-virals against SARS-CoV-2 MPro as the primary target. We identified several natural molecules that strongly binds to SARS-CoV-2 MPro among which top seven molecules are d-Viniferin, Myricitrin, Taiwanhomoflavone A, Lactucopicrin 15-oxalate, Nympholide A, Biorobin and Phyllaemblicin B. Most of the predicted lead molecules are from Vitis vinifera, also reported for anti-tussive and/or antiviral activities. These molecules also showed strong binding with other main targets RdRp and hACE-2. We anticipate that our approach for identification of multi-target-directed ligand will provide new avenues for drug discovery against SARS-CoV-2 infection.
ARTICLE | doi:10.20944/preprints201909.0160.v1
Subject: Engineering, Mechanical Engineering Keywords: geometric errors; rigid body kinematics; lateral stage errors; Imaging Confocal Microscope; MCM uncertainty evaluation; dot grid target
Online: 16 September 2019 (10:43:59 CEST)
This paper presents the experimental implementations of the mathematical models and algorithms developed in Part I. Two experiments are carried out. The first experiment aims at the determinations of the correction coefficients of the mathematical model. The dot grid target is measured and the measurement data are processed by our developed and validated algorithms introduced in Part I. The values of the coefficients are indicated and analysed. Uncertainties are evaluated with implementation of the Monte Carlo method. The second experiment measures a different area of the dot grid target. The measurement results are corrected according to the coefficients determined in the first experiment. The mean residual between the measured points and their corresponding certified values reduced 29.6% after the correction. The sum of squared errors reduced 47.7%. The methods and the algorithms for raw data processing, such as data partition, fittings of dots’ centres, K-means clustering, etc., are the same for both two experiments. The experimental results demonstrate that our method for the correction of the errors produced by the movement of lateral stage of confocal microscope is meaningful and practicable.
ARTICLE | doi:10.20944/preprints201801.0122.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: hot spot temperature; transformer oil-paper insulating system; reliability assessment; dynamic correction; dissolved gas analysis; grey target theory
Online: 15 January 2018 (09:09:34 CET)
This paper develops a novel dynamic correction method for the reliability assessment of large oil-immersed power transformers. First, with the transformer oil-paper insulation system (TOPIS) as the target of evaluation and the winding hot spot temperature (HST) as the core point, an HST-based static ageing failure model is built according to the Weibull distribution and Arrhenius reaction law, in order to describe the transformer ageing process and calculate the winding HST for obtaining the failure rate and life expectancy of TOPIS. A grey target theory based dynamic correction model is then developed, combined with the data of Dissolved Gas Analysis (DGA) in power transformer oil, in order to dynamically modify the life expectancy calculated by the built static model, such that the corresponding relationship between the state grade and life expectancy correction coefficient of TOPIS can be built. Furthermore, the life expectancy loss recovery factor is introduced to correct the life expectancy of TOPIS again. Lastly, a practical case study of an operating transformer has been undertaken, in which the failure rate curve after introducing dynamic corrections can be obtained for the reliability assessment of this transformer. The curve shows a better ability of tracking the actual reliability level of transformer, thus verifying the validity of the proposed method and providing a new way for transformer reliability assessment. This contribution presents a novel model for the reliability assessment of TOPIS, in which the DGA data, as a source of information for the dynamic correction, is processed based on the grey target theory, thus the internal faults of power transformer can be diagnosed accurately as well as its life expectancy updated in time, ensuring that the dynamic assessment values can commendably track and reflect the actual operation state of the power transformers.
ARTICLE | doi:10.20944/preprints202112.0281.v1
Subject: Engineering, Control & Systems Engineering Keywords: microturbine; turbojet; component maps; map scaling; off-design; transient simulation; aerial target; unmanned aerial vehicle; flight data; digital twin
Online: 16 December 2021 (16:10:05 CET)
Microturbines can be used not only in models and education but also to propel UAVs. However, their wider adoption is limited by their relatively low efficiency and durability. Validated simulation models are required to monitor their performance, improve their lifetime, and design engine control systems. This study aims at developing a numerical model of a micro gas turbine for prediction and prognostics of engine performance. To build a reliable zero-dimensional model, the available compressor and turbine maps were scaled to the available test bench data with the least squares method, to meet the performance of the engine achieved during bench and flight tests. A steady-state aeroengine model was implemented in GSP and compared with experimental operating points. The selected flight data was then used as input for the transient engine model. The exhaust gas temperature (EGT) and fuel flow were chosen as the two key parameters to validate the model, comparing the numerical predicted values with the experimental ones. The observed difference between the model and the flight data was lower than 3% for both EGT and fuel flow.
ARTICLE | doi:10.20944/preprints202110.0145.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: immune checkpoint inhibitors; PD-1; PD-L1; CTLA-4; immunotherapy; target therapy; BRAF; MET; melanoma; [18F]FDG PET/CT
Online: 8 October 2021 (14:14:14 CEST)
Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: 44 melanoma patients who underwent [18F]FDG-PET/CT before first-line target therapy (28/50) or immunotherapy (16/50) were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared with Mann-Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan-Meier analysis. Results: Median(IQR) MTVwb and TLGwb were 13.1 mL and 72.4 respectively. Non-responders patients were 38/44, 26/28 and 12/16 at early evaluation, and in 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target and immunotherapy subgroup respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p<0.037) in the whole-cohort and target subgroup and also MTVwb and TLGwb (all p<0.022) in target subgroup. No significant differences were found for immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversy, MTVlfn, TLGlfn, MTVsoft+lfn, TLG-soft+lfn, MTVwb and TLGwb were significantly associated (all p<0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusion: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS.
ARTICLE | doi:10.20944/preprints202011.0303.v1
Subject: Engineering, Automotive Engineering Keywords: turbofan; unmanned aerial vehicles; cruise missile; aerial target; axial compressor; blade; titanium alloy; aluminium alloy; titanium aluminide; safety factor
Online: 10 November 2020 (11:20:07 CET)
BACKGROUND: Manufacturing costs, along with operational performance, are among the major factors determining the selection of the propulsion system for unmanned aerial vehicles (UAVs), especially for aerial targets and cruise missiles. OBJECTIVES: In this paper, the design requirements and operating parameters of small turbofan engines for single-use and reusable UAVs are analysed to introduce alternative materials and technologies for manufacturing their compressor blades, such as sintered titanium, a new generation of aluminium and an alloy based on titanium aluminides. METHODS: To assess the influence of severe plastic deformation (SPD) on the hardening efficiency of the proposed materials, the alloys in the coarse-grained and submicrocrystalline states were studied. Changes in physical and mechanical properties of materials were taken into account. The thermodynamic analysis of the compressor was performed in a finite element analysis system (ANSYS) to determine the impact of gas pressure and temperature on the aerodynamic surfaces of compressor blades of all stages. RESULTS: Based on thermal and structural analysis, the stress and temperature maps on compressor blades and vanes were obtained, taking into account the physical and mechanical properties of advanced materials and technologies of their processing. The safety factors of the components were established based on the assessment of their stress-strength reliability. Thanks to nomograms, the possibility of using the new materials and the technologies was confirmed in view of the permissible operating temperature and safety factors of blades. CONCLUSIONS: The proposed alternative materials and production technologies for the compressor blades and vanes meet the design requirements of the turbofan at lower manufacturing costs.
ARTICLE | doi:10.20944/preprints201712.0074.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: radar; transmit signal waveform design; doubly spread; extended target; fluctuation; Kullback-Leibler divergence; locally most powerful detector; colored noise
Online: 12 December 2017 (08:48:57 CET)
Radar transmit signal design is a critical factor for the radar performance. In this paper, we investigate the problem of radar signal waveform design under the small signal power conditions for detecting a doubly spread target, whose impulse response can be modeled as a random process, in a colored noise environment. The doubly spread target spans multiple range bins (range-spread) and its impulse response is time-varying due to fluctuation (hence also Doppler-spread), such that the target impulse response is both time-selective and frequency-selective. Instead of adopting the conventional assumption that the target is wide-sense stationary uncorrelated scattering,we assume that the target impulse response is both wide-sense stationary in range and in time to account for the possible correlation between the impulse responses corresponding to close range intervals. The locally most powerful detector, which is asymptotically optimal for small signal cases, is then derived for detecting such targets. The signal waveform is optimized to maximizing the detection performance of the detector or equivalently maximizing the Kullback-Leibler divergence. Numerical simulations validate the effectiveness of the proposed waveform design for the small signal power conditions and performance of optimum waveform design are shown in comparison to the frequency modulated waveform.
ARTICLE | doi:10.20944/preprints202208.0213.v1
Subject: Life Sciences, Biophysics Keywords: intermolecular binding affinity; drug target binding affinity; computer-aided drug design (CADD); artificial intelligence-integrated drug discovery (AIDD); machine learning
Online: 11 August 2022 (08:40:37 CEST)
Thanks to the continued development of experimental structural biology and the half-a-century old Protein Data Bank, 2021 saw a big step forward in the development of protein structure prediction with deep learning algorithms. Recently, DeepMinds AlphaFold has determined the structures of ∼ 200 million proteins from 1 million species. The speed of this progress raise the question of what becomes possible for computational drug discovery and design when we have a systems-wide account of the structures and motions of most proteins. Therefore, this article puts forward the concept of a general intermolecular binding affinity calculator (GIBAC): Kd = f(molA, molB, envPara), towards the acceleration of traditional computer-aided drug design (CADD) and artificial intelligence-integrated drug discovery (AIDD), for both small molecules and biologics such as therapeutic proteins.
ARTICLE | doi:10.20944/preprints202301.0371.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Network pharmacology; GO enrichment analysis; Key target validation; Hyperlipidemia; Hepatic steatosis; herbal combination; combinational effect; Arum ternata; Poria cocos; Zingiber officinale
Online: 20 January 2023 (06:41:44 CET)
The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The KEGG pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, a combinational effect of the mixture of three herbs was found. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFAs-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.
ARTICLE | doi:10.20944/preprints201907.0144.v1
Subject: Life Sciences, Biochemistry Keywords: longevity; life expectancy; CODAS syndrome; Perrault syndrome; protease target substrates; respiratory complex assembly; oxidative stress; glutathione pathway; lysosomal degradation; fidelity protein synthesis
Online: 10 July 2019 (10:18:22 CEST)
Research on healthy ageing shows that lifespan reductions are often caused by mitochondrial dysfunction. Thus, it is very interesting that the deletion of mitochondrial matrix peptidase LonP1 was observed to abolish embryogenesis, while deletion of the mitochondrial matrix peptidase ClpP prolonged survival. To unveil the targets of each enzyme, we documented the global proteome of LonP1+/- mouse embryonal fibroblasts (MEF), for comparison with ClpP-/- depletion. Proteomic profiles of LonP1+/- MEF generated by label-free mass spectrometry were further processed with the STRING webserver Heidelberg for protein interactions. ClpP was previously reported to degrade Eral1 as a chaperone involved in mitoribosome assembly, so ClpP deficiency triggers accumulation of mitoribosomal subunits and inefficient translation. LonP1+/- MEF also showed Eral1 accumulation, but no systematic effect on mitoribosomal subunits. In contrast to ClpP-/- profiles, several components of the respiratory complex I membrane arm were accumulated, whereas the upregulation of numerous innate immune defense components was similar. Overall, LonP1 as opposed to ClpP appears to have no effect on translational machinery, instead it shows enhanced respiratory dysfunction; this agrees with reports on the human CODAS syndrome caused by LonP1 mutations.
ARTICLE | doi:10.20944/preprints202212.0073.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: SARS-COV-2; respiratory tests; Xpert® Xpress COV-2 plus; Xpert(2) Xpress COV-2/Flu/RSV plus; diagnostic evaluation; novel target
Online: 5 December 2022 (10:17:58 CET)
The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.
CONCEPT PAPER | doi:10.20944/preprints202204.0104.v1
Subject: Life Sciences, Other Keywords: Method validation; droplet digital PCR; orthogonal factorial design; variance components; Poisson assumption; cloglog model; target DNA copies per droplet; Monte Carlo; prediction interval
Online: 12 April 2022 (08:46:49 CEST)
For the in-house validation of a droplet digital PCR method, a factorial experimental design was implemented. This design serves different purposes. On the one hand, it is an efficient design in relation to the workload involved in achieving a desirable level of reliability of variance estimates. On the other hand, it allows a partitioning of total variance into different components, thus providing information regarding the dominant sources of random variation. The statistical modelling reflects the actual measurement mechanism, establishing relationships between nominal target DNA copies per well, the range of variation of copy numbers per droplet, probability of detection values, and estimated numbers of copies.
ARTICLE | doi:10.20944/preprints202012.0637.v1
Subject: Medicine & Pharmacology, Allergology Keywords: miRNA; gene targets; intronic miRNA; miRNA prediction; human miRNAs; PHEX miRNAs; chimpanzee homologues; experimentally-validated miRNA targets; miRNA computational survey; miRNA target multiplicity
Online: 24 December 2020 (15:30:33 CET)
The knowledge of what separates us genetically from our less-evolved relatives is crucial for gaining new biomedical insights about the human-chimpanzee relatedness for the use of appropriate stand-in towards the development of new treatments and diagnostic aids for various ailments. Although the genomes of humans and chimpanzees share 99% similarity, significant differences exist between the two species in their non-coding intronic regions. However, no work has been carried out in the aspects of target prediction concerning the ‘predicted homology’ in their microRNA sequences. Non-coding miRNAs which are post-transcriptional regulators of development, differentiation, growth, and metabolism, harboring the intronic regions may be crucial for expanding the horizons of our understanding. In this study, we proposed to perform the target prediction for the human-chimp miRNA homologs in the PHEX gene of the human X chromosome using various computational tools and databases. We identified a total of 1296 human miRNAs, 46, 957 gene targets, and 30, 563 targets of human and homologous chimp miRNAs respectively. Furthermore, we analysed gene interacting networks to identify the top interacting targets in both the species. Finally, we interpreted the biological importance of top-interacting miRNAs and their targets. The results demonstrated varying levels of multiplicity and cooperativity between the predicted miRNAs and target genes in the two genera. Such miRNAs may be responsible for the dysregulation of gene expression in several signaling pathways.
ARTICLE | doi:10.20944/preprints201903.0094.v1
Subject: Engineering, Control & Systems Engineering Keywords: Internet of Things; Cyber Physical Systems; Digital Economy; Industrial Internet of Things; Industry 4.0; empirical analysis; cyber risk assessment; cyber risk target state
Online: 7 March 2019 (12:25:15 CET)
The world is currently experiencing the fourth industrial revolution driven by the newest wave of digitisation in the manufacturing sector. The term Industry 4.0 (I4.0) represents at the same time: a paradigm shift in industrial production, a generic designation for sets of strategic initiatives to boost national industries, a technical term to relate to new emerging business assets, processes and services, and a brand to mark a very particular historical and social period. I4.0 is also referred to as Industrie 4.0 the New Industrial France, the Industrial Internet, the Fourth Industrial Revolution and the digital economy. These terms are used interchangeably in this text. The aim of this article is to discuss major developments in this space in relation to the integration of new developments of IoT and cyber physical systems in the digital economy, to better understand cyber risks and economic value and risk impact. The objective of the paper is to map the current evolution and its associated cyber risks for the digital economy sector and to discuss the future developments in the Industrial Internet of Things and Industry 4.0.
ARTICLE | doi:10.20944/preprints201903.0080.v1
Subject: Engineering, Control & Systems Engineering Keywords: Internet of Things; Micro Mart model; Goal-Oriented Approach; transformation roadmap; Cyber risk regulations; empirical analysis; cyber risk self-assessment; cyber risk target state
Online: 6 March 2019 (11:47:04 CET)
The Internet-of-Things (IoT) enables enterprises to obtain profits from data but triggers data protection questions and new types of cyber risk. Cyber risk regulations for the IoT however do not exist. The IoT risk is not included in the cyber security assessment standards, hence, often not visible to cyber security experts. This is concerning, because companies integrating IoT devices and services need to perform a self-assessment of its IoT cyber security posture. The outcome of such self-assessment needs to define a current and target state, prior to creating a transformation roadmap outlining tasks to achieve the stated target state. In this article, a comparative empirical analysis is performed of multiple cyber risk assessment approaches, to define a high-level potential target state for company integrating IoT devices and/or services. Defining a high-level potential target state represent is followed by a high-level transformation roadmap, describing how company can achieve their target state, based on their current state. The transformation roadmap is used to adapt IoT risk impact assessment with a Goal-Oriented Approach and the Internet of Things Micro Mart model.
ARTICLE | doi:10.20944/preprints202211.0243.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: deep neural network (DNN); synthetic aperture radar automatic target recognition (SAR-ATR); universal adversarial perturbation (UAP); U-Net; attention heatmap; layer-wise relevance propagation (LRP)
Online: 14 November 2022 (06:37:35 CET)
Recent studies have proven that synthetic aperture radar (SAR) automatic target recognition (ATR) models based on deep neural networks (DNN) are vulnerable to adversarial examples. However, existing attacks are easily failed in the case where adversarial perturbations cannot be fully fed to victim models. We call this situation perturbation offset. Moreover, since background clutter takes up most of the areas in SAR images and has low relevance to recognition results, fooling models with global perturbations is quite inefficient. This paper proposes a semi-whitebox attack network, called Universal Local Adversarial Network (ULAN), to generate universal adversarial perturbations (UAP) for the target regions of SAR images. In the proposed network, we calculate the model’s attention heatmaps through layer-wise relevance propagation (LRP), which is used to locate the target regions of SAR images that have high relevance to recognition results. In particular, we utilize a generator based on the U-Net to learn the mapping from noise to UAPs and craft adversarial examples by adding the generated local perturbations to target regions. Experiments indicate that the proposed method fundamentally prevents perturbation offset and achieves comparable attack performance to conventional global UAPs by perturbing only a quarter or less of SAR image areas.
Subject: Earth Sciences, Environmental Sciences Keywords: Food waste index; Household food waste; Waste characterisation; Waste sorting analysis; Avoidable food waste; Preparation residues; SDG Target 12.3; Methodology development; Assessment of current situation
Online: 15 July 2021 (15:38:01 CEST)
Target 12.3 of the United Nations Sustainable Development Goals (SDGs) calls for halving per capita global food waste at the retail and consumer levels, by 2030. The Food Waste Index is suggested as a methodology for grasping the situation. This paper focuses on the consumer level (household food waste). We argue that in order for generating useful information for devising and implementing effective measures for reducing food waste, it should be measured at Level 3 of the Food Waste Index, based on sorting analysis of generated waste, making a distinction between avoidable and non-avoidable food waste. Furthermore, a breakdown by sub-categories that reflect the flow of food in the household could help identify target behaviours. We have developed a categorisation scheme that is internationally agreeable and adoptable, and 1) generates useful information for policy-making and for tackling with reduction of food waste, 2) makes clear the concept of avoidable food waste, and 3) is practical and does not overcomplicate the work of grasping the situation of food wastage. Results of workshops regarding this scheme suggest that the scheme satisfies the criteria. This scheme has been applied to a few sorting analyses of household food waste in Japan, and their results are compared.
ARTICLE | doi:10.20944/preprints202301.0340.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: alternative food; resilient food; distributed production; edible plants; existential risk; food security; global catastrophic risk; leaf concentrate; leaf protein; non-target screening; resilience; sustainable food systems; toxins
Online: 19 January 2023 (01:57:51 CET)
In the event of an abrupt sunlight reduction scenario there is a time window that occurs between when food stores would likely run out for many countries (~6 months or less) and ~1 year when resilient foods are scaled up. A promising temporary resilient food is leaf protein concentrate (LPC). Although it is possible to extract LPC from tree biomass (e.g. leaves and needles), neither the yields nor the toxicity of the protein concentrates for humans from the most common tree species has been widely investigated. To help fill this knowledge gap, this study uses high-resolution mass spectrometry and an open source toolchain for non-targeted screening of toxins on five common North American coniferous species: Western Cedar, Douglas Fir, Ponderosa Pine, Western Hemlock, and Lodgepole Pine. The yields for LPC extraction from the conifers ranged from 1% to 7.5%. The toxicity screenings confirm that these trees may contain toxins that can be consumed in small amounts and additional studies including measuring the quantity of each toxin are needed. The results indicate that LPC is a promising candidate to be used as resilient food, but future work is needed before LPCs from conifers can be used as a wide-scale human food.
ARTICLE | doi:10.20944/preprints202104.0788.v1
Subject: Life Sciences, Biochemistry Keywords: SARS-CoV-2; COVID-19; Flux Balance Analysis (FBA); Genome-Scale Metabolic Models; Target Identification; Reaction Knock-Out; Structural Proteins; Purine Metabolism; Pyrimidine Metabolism; B.1.1.7; B.1.351
Online: 30 April 2021 (15:14:06 CEST)
The current SARS-CoV-2 pandemic is still threatening humankind. Despite first successes in vaccine development and approval, no antiviral treatment is available for COVID-19 patients. The success is further tarnished by the emergence and spreading of mutation variants of SARS-CoV-2, for which some vaccines are not effective anymore. This highlights the urgent need for antiviral therapies even more. This article describes how the Genome-Scale Metabolic Model (GEM) of the host-virus interaction of human alveolar macrophages and SARS-CoV-2 was refined by incorporating the latest information about the virus’s structural proteins and the mutant variants B.1.1.7 and B.1.351. We confirmed the initially identified guanylate kinase as a potential antiviral target with this refined model and identified further potential targets from the purine and pyrimidine metabolism. The model was further extended by incorporating the virus’ lipid requirements. This opened new perspectives for potential antiviral targets in the altered lipid metabolism. Especially the phosphatidylcholine biosynthesis seems to play a pivotal role in viral replication. The guanylate kinase is even a robust target in all investigated mutation variants currently spreading worldwide. These new insights can guide laboratory experiments for the validation of identified potential antiviral targets. Only the combination of vaccines and antiviral therapies will effectively defeat this ongoing pandemic.
Subject: Engineering, Automotive Engineering Keywords: functional dependency; network-based linear dependency modelling; internet of things; micro mort model; goal-oriented approach; transformation roadmap; cyber risk regulations; empirical analysis; cyber risk self-assessment; cyber risk target state.
Online: 25 December 2020 (11:35:48 CET)
The Internet-of-Things (IoT) triggers new types of cyber risks. Therefore, the integration of new IoT devices and services requires a self-assessment of IoT cyber security posture. By security posture this article refers to the cybersecurity strength of an organisation to predict, prevent and respond to cyberthreats. At present, there is a gap in the state-of-the-art, because there are no self-assessment methods for quantifying IoT cyber risk posture. To address this gap, an empirical analysis is performed of 12 cyber risk assessment approaches. The results and the main findings from the analysis is presented as the current and a target risk state for IoT systems, followed by conclusions and recommendations on a transformation roadmap, describing how IoT systems can achieve the target state with a new goal-oriented dependency model. By target state, we refer to the cyber security target that matches the generic security requirements of an organisation. The research paper studies and adapts four alternatives for IoT risk assessment and identifies the goal-oriented dependency modelling as a dominant approach among the risk assessment models studied. The new goal-oriented dependency model in this article enables the assessment of uncontrollable risk states in complex IoT systems and can be used for a quantitative self-assessment of IoT cyber risk posture.
ARTICLE | doi:10.20944/preprints202207.0361.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: PSPS; FBSS; SCS; surgical lead; SCS implantation; MAST (for Minimal Access Spine Technologies); TCIVA (for Target Controlled Intra-Veinous Anesthesia); composite score; pain mapping; neuropathic pain; chronic pain; quality of life; anesthesia; hypnosis
Online: 25 July 2022 (08:34:26 CEST)
Spinal Cord Stimulation (SCS) is an effective and validated treatment to address chronic refractory neuropathic pain in Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients. Surgical SCS lead placement is traditionally performed under general anesthesia due to its invasiveness. In parallel, recent works have suggested that Awake Anesthesia (AA), consisting in Target Controlled Intra-Veinous Anesthesia (TCIVA), could be an interesting tool to optimize lead anatomical placement using patient intra-operative feedback. We hypothesized that combining AA with Minimal Invasive Surgery (MIS) could improve SCS outcomes. The goal of this study was to evaluate SCS lead performance (defined by the area of pain adequately covered by paraesthesia generated via SCS), using an intraoperative objective quantitative mapping tool, and secondarily to assess pain relief, functional improvement and change in quality of life with a composite score. We analyzed data from a prospective multicenter study (ESTIMET) to compare the outcomes of 115 patients implanted with MIS under AA (MISAA group) or General Anesthesia (MISGA group), or by Laminectomy under General Anesthesia (LGA group). All in all, MISAA appears to show significantly better performance in terms of patient pain coverage, as well as improved secondary outcomes. One step further, our results suggest that MISAA combined with intra-operative hypnosis could potentialize patient intraoperative cooperation and could be proposed as a personalized package offered to PSPS-T2 patients eligible for SCS implantation in highly dedicated neuromodulation centers.