scholarly journals High-throughput Mutational Surveillance of the SARS-CoV-2 Spike Gene

2021 ◽  
Author(s):  
Ezgi Özkan ◽  
Marcus Martin Strobl ◽  
Maria Novatchkova ◽  
Ramesh Yelagandula ◽  
Tanino Giuseppe Albanese ◽  
...  
Keyword(s):  
Immune Escape ◽  
Viral Evolution ◽  
Cost Effective ◽  
Spike Protein ◽  
Successful Implementation ◽  
Close Monitoring ◽  
Gene Encoding ◽  
Spike Gene ◽  
S Gene ◽  
Specific Pcr

SARS-CoV-2 has evolved rapidly towards higher infectivity and partial immune escape over the course of the pandemic. This evolution is driven by the enormous virus population, that has infected close to 200 million people by now. Therefore, cost effective and scalable methods are needed to monitor viral evolution globally. Mutation-specific PCR approaches have become inadequate to distinguish the variety of circulating SARS-CoV-2 variants and are unable to detect novel ones. Conversely, whole genome sequencing protocols remain too labor- and cost-intensive to monitor SARS-CoV-2 at the required density. By adapting SARSeq we present a simple, fast, and scalable S-gene tiling pipeline for focused sequencing of the S-gene encoding for the spike protein. This method reports on all sequence positions with known importance for infectivity and immunity, yet scales to >20K samples per run. S-gene tiling is used for nationwide surveillance of SARS-CoV-2 at a density of 10% to 50% of all cases of infection in Austria. SARSeq S-tiling uncovered several infection clusters with variants of concern such as the biggest known cluster of Beta/B.1.351 outside Africa and successfully informed public health measures in a timely manner, allowing their successful implementation. Our close monitoring of mutations further highlighted evolutionary constraints and freedom of the spike protein ectodomain and sheds light on foreseeable evolutionary trajectories.

scholarly journals HiSpike Method for High-Throughput Cost Effective Sequencing of the SARS-CoV-2 Spike Gene

2022 ◽  
Vol 8 ◽  
Author(s):  
Ephraim Fass ◽  
Gal Zizelski Valenci ◽  
Mor Rubinstein ◽  
Paul J. Freidlin ◽  
Shira Rosencwaig ◽  
...  
Keyword(s):  
Real Time ◽  
High Throughput ◽  
Cost Effective ◽  
Developed Countries ◽  
Spike Protein ◽  
Medical Community ◽  
Effective Vaccine ◽  
Gene Variants ◽  
Spike Gene ◽  
Field Samples

The changing nature of the SARS-CoV-2 pandemic poses unprecedented challenges to the world's health systems. Emerging spike gene variants jeopardize global efforts to produce immunity and reduce morbidity and mortality. These challenges require effective real-time genomic surveillance solutions that the medical community can quickly adopt. The SARS-CoV-2 spike protein mediates host receptor recognition and entry into the cell and is susceptible to generation of variants with increased transmissibility and pathogenicity. The spike protein is the primary target of neutralizing antibodies in COVID-19 patients and the most common antigen for induction of effective vaccine immunity. Tight monitoring of spike protein gene variants is key to mitigating COVID-19 spread and generation of vaccine escape mutants. Currently, SARS-CoV-2 sequencing methods are labor intensive and expensive. When sequence demands are high sequencing resources are quickly exhausted. Consequently, most SARS-CoV-2 strains are sequenced in only a few developed countries and rarely in developing regions. This poses the risk that undetected, dangerous variants will emerge. In this work, we present HiSpike, a method for high-throughput cost effective targeted next generation sequencing of the spike gene. This simple three-step method can be completed in < 30 h, can sequence 10-fold more samples compared to conventional methods and at a fraction of their cost. HiSpike has been validated in Israel, and has identified multiple spike variants from real-time field samples including Alpha, Beta, Delta and the emerging Omicron variants. HiSpike provides affordable sequencing options to help laboratories conserve resources for widespread high-throughput, near real-time monitoring of spike gene variants.

scholarly journals Efficient Design of Energy Disaggregation Model with BERT-NILM Trained by AdaX Optimization Method for Smart Grid

Energies ◽  
2021 ◽  
Vol 14 (15) ◽  
pp. 4649
Author(s):  
İsmail Hakkı ÇAVDAR ◽  
Vahit FERYAD
Keyword(s):  
Smart Grids ◽  
Energy Demand ◽  
Optimization Technique ◽  
Cost Effective ◽  
Optimization Method ◽  
Long Term Memory ◽  
Successful Implementation ◽  
Efficient Design ◽  
Energy Disaggregation ◽  
Load Monitoring

One of the basic conditions for the successful implementation of energy demand-side management (EDM) in smart grids is the monitoring of different loads with an electrical load monitoring system. Energy and sustainability concerns present a multitude of issues that can be addressed using approaches of data mining and machine learning. However, resolving such problems due to the lack of publicly available datasets is cumbersome. In this study, we first designed an efficient energy disaggregation (ED) model and evaluated it on the basis of publicly available benchmark data from the Residential Energy Disaggregation Dataset (REDD), and then we aimed to advance ED research in smart grids using the Turkey Electrical Appliances Dataset (TEAD) containing household electricity usage data. In addition, the TEAD was evaluated using the proposed ED model tested with benchmark REDD data. The Internet of things (IoT) architecture with sensors and Node-Red software installations were established to collect data in the research. In the context of smart metering, a nonintrusive load monitoring (NILM) model was designed to classify household appliances according to TEAD data. A highly accurate supervised ED is introduced, which was designed to raise awareness to customers and generate feedback by demand without the need for smart sensors. It is also cost-effective, maintainable, and easy to install, it does not require much space, and it can be trained to monitor multiple devices. We propose an efficient BERT-NILM tuned by new adaptive gradient descent with exponential long-term memory (Adax), using a deep learning (DL) architecture based on bidirectional encoder representations from transformers (BERT). In this paper, an improved training function was designed specifically for tuning of NILM neural networks. We adapted the Adax optimization technique to the ED field and learned the sequence-to-sequence patterns. With the updated training function, BERT-NILM outperformed state-of-the-art adaptive moment estimation (Adam) optimization across various metrics on REDD datasets; lastly, we evaluated the TEAD dataset using BERT-NILM training.

scholarly journals Real-time SARS-CoV-2 diagnostic and variants tracking over multiple candidates using nanopore DNA sequencing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
François Stüder ◽  
Jean-Louis Petit ◽  
Stefan Engelen ◽  
Marco Antonio Mendoza-Parra
Keyword(s):  
Real Time ◽  
Optimal Solution ◽  
Proof Of Concept ◽  
Gene Encoding ◽  
Spike Gene ◽  
Long Period ◽  
The World ◽  
Receptor Recognition ◽  
Nanopore Dna Sequencing ◽  
Novel Coronavirus

AbstractSince December 2019, a novel coronavirus responsible for a severe acute respiratory syndrome (SARS-CoV-2) is accountable for a major pandemic situation. The emergence of the B.1.1.7 strain, as a highly transmissible variant has accelerated the world-wide interest in tracking SARS-CoV-2 variants’ occurrence. Similarly, other extremely infectious variants, were described and further others are expected to be discovered due to the long period of time on which the pandemic situation is lasting. All described SARS-CoV-2 variants present several mutations within the gene encoding the Spike protein, involved in host receptor recognition and entry into the cell. Hence, instead of sequencing the whole viral genome for variants’ tracking, herein we propose to focus on the SPIKE region to increase the number of candidate samples to screen at once; an essential aspect to accelerate diagnostics, but also variants’ emergence/progression surveillance. This proof of concept study accomplishes both at once, population-scale diagnostics and variants' tracking. This strategy relies on (1) the use of the portable MinION DNA sequencer; (2) a DNA barcoding and a SPIKE gene-centered variant’s tracking, increasing the number of candidates per assay; and (3) a real-time diagnostics and variant’s tracking monitoring thanks to our software RETIVAD. This strategy represents an optimal solution for addressing the current needs on SARS-CoV-2 progression surveillance, notably due to its affordable implementation, allowing its implantation even in remote places over the world.

scholarly journals Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 326
Author(s):  
Dona Sinha ◽  
Sraddhya Roy ◽  
Priyanka Saha ◽  
Nabanita Chatterjee ◽  
Anupam Bishayee
Keyword(s):  
Cancer Progression ◽  
Targeted Delivery ◽  
Cancer Biology ◽  
Vaccine Development ◽  
Immune Escape ◽  
Immune Therapy ◽  
Bioactive Molecules ◽  
Successful Implementation ◽  
Scale Production ◽  
Exosome Biogenesis

Exosomes, the endosome-derived bilayered extracellular nanovesicles with their contribution in many aspects of cancer biology, have become one of the prime foci of research. Exosomes derived from various cells carry cargoes similar to their originator cells and their mode of generation is different compared to other extracellular vesicles. This review has tried to cover all aspects of exosome biogenesis, including cargo, Rab-dependent and Rab-independent secretion of endosomes and exosomal internalization. The bioactive molecules of the tumor-derived exosomes, by virtue of their ubiquitous presence and small size, can migrate to distal parts and propagate oncogenic signaling and epigenetic regulation, modulate tumor microenvironment and facilitate immune escape, tumor progression and drug resistance responsible for cancer progression. Strategies improvised against tumor-derived exosomes include suppression of exosome uptake, modulation of exosomal cargo and removal of exosomes. Apart from the protumorigenic role, exosomal cargoes have been selectively manipulated for diagnosis, immune therapy, vaccine development, RNA therapy, stem cell therapy, drug delivery and reversal of chemoresistance against cancer. However, several challenges, including in-depth knowledge of exosome biogenesis and protein sorting, perfect and pure isolation of exosomes, large-scale production, better loading efficiency, and targeted delivery of exosomes, have to be confronted before the successful implementation of exosomes becomes possible for the diagnosis and therapy of cancer.

scholarly journals Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1192
Author(s):  
Ivana Lazarevic ◽  
Vera Pravica ◽  
Danijela Miljanovic ◽  
Maja Cupic
Keyword(s):  
Immune Evasion ◽  
Human Population ◽  
Evolutionary Rate ◽  
Spike Protein ◽  
Close Monitoring ◽  
Global Level ◽  
Therapeutic Application ◽  
Neutralization Capacity ◽  
Rapid Transmission ◽  
Potential Impact

Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled “variants of concern” (VOC), due to their potential impact on transmission, morbidity/mortality, and the evasion of neutralization by antibodies elicited by infection, vaccination, or therapeutic application. The potential to evade neutralization is the result of diversity of the target epitopes generated by the accumulation of mutations in the spike protein. While three globally recognized VOCs (Alpha or B.1.1.7, Beta or B.1.351, and Gamma or P.1) remain sensitive to neutralization albeit at reduced levels by the sera of convalescent individuals and recipients of several anti-COVID19 vaccines, the effect of spike variability is much more evident on the neutralization capacity of monoclonal antibodies. The newly recognized VOC Delta or lineage B.1.617.2, as well as locally accepted VOCs (Epsilon or B.1.427/29-US and B1.1.7 with the E484K-UK) are indicating the necessity of close monitoring of new variants on a global level. The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.

Telemedicine During A Crisis: Challenges, Opportunities & Way Forward At A Tertiary Care Hospital (Preprint)

2021 ◽  
Author(s):  
Sadia Masood ◽  
Zanaib Samad ◽  
Sarah Nadeem ◽  
Unzela Ghulam
Keyword(s):  
Health Care ◽  
Health Care Services ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Cost Effective ◽  
Successful Implementation ◽  
Care Hospital ◽  
Quality Health Care ◽  
Cross Sectional ◽  
Innovative Strategy

BACKGROUND Telemedicine is utilized to deliver health care services remotely. Recently, it is well established due to pandemics because it can help the patients get required supportive care while minimizing their hospital exposure. In the future, it will continue to be used as a convenient, cost-effective patient care modality. OBJECTIVE The objectives were to identify physicians' challenges during teleconsultations and recognize the opportunities and strengths of this modality during the pandemic in a lower-income country. METHODS This cross-sectional study was conducted in a tertiary care hospital. The self-made questionnaire was filled through an online medium and responses were recorded on a five-point Likert scale. RESULTS A total of 83 participants were enrolled in this study. Most of them were Associate professors (29.8%), Assistant professors (26.2%), the ratio of the females was (52.4%) greater than males (,47.6%). 46 (54.8%) have laid between the age group 30-40 years. Pediatricians and senior instructors faced more difficulty in using telemedicine. The ones having clinical experience of fewer than 15 years or categorized in the age of 50-60 years faced challenges while using this modality. CONCLUSIONS During the current pandemic, situation telemedicine is the only glimmer of light to provide better quality health care. Telemedicine is an innovative strategy and it is important to understand the perception of physicians about it. Incomplete and inadequate infrastructure and attitude of the physicians is the main obstacle toward successful implementation of telemedicine. Successful installation and deployment of this technology require a complete grasp of the process among physicians.

scholarly journals Energy Sustainability Study of a Rural ICT Telecenter at the Bario Highland

2007 ◽  
Author(s):  
Mohammad Omar Abdullah ◽  
Voon Chun Yung ◽  
Audra Anak Jom ◽  
Alvin Yeo Wee ◽  
Martin Anyi ◽  
...  
Keyword(s):  
Renewable Energy ◽  
Fuel Cell ◽  
Power Systems ◽  
Alternative Energy ◽  
Cost Effective ◽  
Energy Resources ◽  
Successful Implementation ◽  
Combined System ◽  
Pv System ◽  
Simple Method

The eBario project has won the eAsia Award and the Mondialogo Engineering Award in 2004 and 2005 respectively for it’s successful implementation of an Information and Telecommunications Technology Center (ICT) and solar renewable energy-incentive rural community project at the Bario Highland of Sarawak, East Malaysia, Borneo (http://www.unimas.my/ebario/). Although solar photovoltaic (PV) energy has been opted for power generation at the ICT Telecenter for the past five years, there is still a need to investigate the cost-effectiveness of the current energy setup as well as to conduct sustainability study taking into account factors such as system efficiency, weather, costs of fuel, operating costs, as well as to explore the feasibility of implementing alternative energy resources for the rural ICT Telecenter. Recent theoretical study conducted has shown that renewable combined power systems are more sustainable in terms of supplying electricity to the ICT Telecenter, and in a more cost-effective way compared to a standalone PV system which is subject to the cloud and the recent dense haze problems. For that purpose, two combined power systems are being put into consideration namely PV-Hydro and PV-Hydro-Fuel Cell, where the total simulated annualized cost for these two system configurations are US$10,847 and US$76,010 respectively as far as the present location is concerned. The PVHydro-Fuel Cell produces electrical energy at the amount of 3,577 kWh/yr while the annual energy consumption is 3,203 kWhr/yr. On the other hand, PV-Hydro produces 3,789 kWhr/yr of electricity annually load which consumes energy at 3,209 kWhr/yr. Results thus obtained has shown that the PVHydro scheme is expected to have advantages over the existing PV standalone system. Firstly, it is more cost-effective. Secondly, it provides the best outcomes for the local indigenous community and the natural highland environments both for now and the future. Thirdly, it also able to relate the continuity of both economic and social aspects of the local society as a whole. As the combined PV-Hydro system had been chosen, plus for completeness purposes, the present paper also discussed the custom design and construction of a small waterwheel breast-shot hydro-generator, suited to the local location and existing water energy resources. Energy saving design calculations and Sankey diagram showing the energy flows for the new combined system are also given herein. Finally, the energy system performance equations and the performance curves introduced in this study provide a new simple method of evaluating renewable energy systems.

scholarly journals The polymorphism of ETR1 gene in autochthonous apple cultivars

Genetika ◽  
2007 ◽  
Vol 39 (3) ◽  
pp. 387-394 ◽  
Author(s):  
Sladjana Maric ◽  
Radovan Boskovic ◽  
Milan Lukic
Keyword(s):  
Plant Hormone ◽  
Allelic Polymorphism ◽  
Ethylene Receptor ◽  
Gene Encoding ◽  
Fruit Storage ◽  
Specific Pcr ◽  
Pcr Product ◽  
Apple Cultivars ◽  
Storage Ability

Ethylene is a plant hormone, which plays an important role in the ripening of climacteric fruits such as the apple. We studied allelic polymorphism of the ETR1 gene, encoding ethylene receptor, in 23 autochthonous apple cultivars. The polymorphism was revealed by combining the gene specific PCR and restriction of PCR product. Four alleles of the ETR1 gene (a, b, c and d) were detected, and their possible association with the fruit storage ability examined.

scholarly journals ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19.

2021 ◽  
Author(s):  
Daniele Focosi ◽  
Fabrizio Maggi ◽  
Massimo Franchini ◽  
Scott McConnell ◽  
Arturo Casadevall
Keyword(s):  
Public Health ◽  
Monoclonal Antibodies ◽  
Immune Evasion ◽  
Immune Escape ◽  
Selective Pressure ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Amino Acid Mutations

Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), the few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of Spike protein (e.g, delHV69-70, delLGVY141-144 and delAL243-244). Continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and fitness of emerging variants.

scholarly journals How to Implement Safe, Efficient and Cost-Effective SARS-CoV-2 Testing in Urban and Rural Schools within One Month

COVID ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 717-727
Author(s):  
Parastoo Kheiroddin ◽  
Magdalena Gründl ◽  
Michael Althammer ◽  
Patricia Schöberl ◽  
Linda Plail ◽  
...  
Keyword(s):  
Data Transfer ◽  
Cost Effective ◽  
Testing System ◽  
Successful Implementation ◽  
Rural And Urban ◽  
Local Involvement ◽  
Working Day ◽  
Set Up ◽  
The Individual ◽  
Time Required

(1) Background: With vaccination and new variants of SARS-CoV-2 on the horizon, efficient testing in schools may enable prevention of mass infection outbreaks, keeping schools safe places and buying time until decisions on feasibility and the necessity of vaccination in children and youth are made. We established, in the course of the WICOVIR (Where Is the COrona VIRus) study, that gargle-based pool-PCR testing offers a feasible, efficient, and safe testing system for schools in Germany when applied by central university laboratories. (2) Objectives: We evaluated whether this approach can be implemented in different rural and urban settings. (3) Methods: We assessed the arrangements required for successful implementation of the WICOVIR approach in a variety of settings in terms of transport logistics, data transfer and pre-existing laboratory set-up, as well as the time required to establish the set-up. (4) Results: We found that once regulatory issues have been overcome, all challenges pertaining to logistics, data transfer, and laboratory testing on different platforms can be solved within one month. Pooling and depooling of samples down to the individual test result were achievable within one working day in all settings. Local involvement of the community and decentralized set-ups were keys for success. (5) Conclusion: The WICOVIR gargle-based pool-PCR system is so robust and simple that it can be implemented within one month in all settings now or in future pandemics.

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