scholarly journals Integrated Autolysis, DNA Hydrolysis and Precipitation Enables an Improved Bioprocess for Q-Griffithsin, a Broad-Spectrum Antiviral and Clinical-Stage anti-COVID-19 Candidate

2022 ◽  
Author(s):  
John S Decker ◽  
Romel Menacho-Melgar ◽  
Michael D Lynch
Keyword(s):  
Host Cell ◽  
Broad Spectrum ◽  
High Titer ◽  
Low Cost ◽  
Clinical Stage ◽  
Production Capacity ◽  
Complete Removal ◽  
Unit Operation ◽  
E Coli ◽  
The Face

Across the biomanufacturing industry, innovations are needed to improve efficiency and flexibility, especially in the face of challenges such as the COVID-19 pandemic. Here we report an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral currently in clinical trials for COVID-19. Q-Griffithsin is produced at high titer in E. coli and purified to anticipated clinical grade without conventional chromatography or the need for any fixed downstream equipment. The process is thus both low-cost and highly flexible, facilitating low sales prices and agile modifications of production capacity, two key features for pandemic response. The simplicity of this process is enabled by a novel unit operation that integrates cellular autolysis, autohydrolysis of nucleic acids, and contaminant precipitation, giving essentially complete removal of host cell DNA as well as reducing host cell proteins and endotoxin by 3.6 and 2.4 log10 units, respectively. This unit operation can be performed rapidly and in the fermentation vessel, such that Q-GRFT is obtained with 100% yield and >99.9% purity immediately after fermentation and requires only a flow-through membrane chromatography step for further contaminant removal. Using this operation or variations of it may enable improved bioprocesses for a range of other high-value proteins in E. coli.

Acetate Kinase (AcK) is Essential for Microbial Growth and Betel-derived Compounds Potentially Target AcK, PhoP and MDR Proteins in M. tuberculosis, V. cholerae and Pathogenic E. coli: An in silico and in vitro Study

2019 ◽  
Vol 18 (31) ◽  
pp. 2731-2740 ◽  
Author(s):  
Sandeep Tiwari ◽  
Debmalya Barh ◽  
M. Imchen ◽  
Eswar Rao ◽  
Ranjith K. Kumavath ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
In Silico ◽  
Pathogenic Bacteria ◽  
In Vitro Study ◽  
Docking Studies ◽  
Acetate Kinase ◽  
E Coli ◽  
Pathogenic Escherichia Coli ◽  
Novel Target

Background: Mycobacterium tuberculosis, Vibrio cholerae, and pathogenic Escherichia coli are global concerns for public health. The emergence of multi-drug resistant (MDR) strains of these pathogens is creating additional challenges in controlling infections caused by these deadly bacteria. Recently, we reported that Acetate kinase (AcK) could be a broad-spectrum novel target in several bacteria including these pathogens. Methods: Here, using in silico and in vitro approaches we show that (i) AcK is an essential protein in pathogenic bacteria; (ii) natural compounds Chlorogenic acid and Pinoresinol from Piper betel and Piperidine derivative compound 6-oxopiperidine-3-carboxylic acid inhibit the growth of pathogenic E. coli and M. tuberculosis by targeting AcK with equal or higher efficacy than the currently used antibiotics; (iii) molecular modeling and docking studies show interactions between inhibitors and AcK that correlate with the experimental results; (iv) these compounds are highly effective even on MDR strains of these pathogens; (v) further, the compounds may also target bacterial two-component system proteins that help bacteria in expressing the genes related to drug resistance and virulence; and (vi) finally, all the tested compounds are predicted to have drug-like properties. Results and Conclusion: Suggesting that, these Piper betel derived compounds may be further tested for developing a novel class of broad-spectrum drugs against various common and MDR pathogens.

Understanding the Role of Chlorine and Ozone to Control Postharvest Diseases in Fruit and Vegetables: A Review

2020 ◽  
Vol 16 (4) ◽  
pp. 455-461
Author(s):  
Gabriela M. Baia ◽  
Otniel Freitas-Silva ◽  
Murillo F. Junior
Keyword(s):  
Chlorine Dioxide ◽  
Broad Spectrum ◽  
Fruits And Vegetables ◽  
Low Cost ◽  
Residual Effects ◽  
Pathogenic Microorganisms ◽  
Postharvest Diseases ◽  
Post Harvest ◽  
By Products

Fruits and vegetables are foods that come into contact with various types of microorganisms from planting to their consumption. A lack or poor sanitation of these products after harvest can cause high losses due to deterioration and/ or pathogenic microorganisms. There are practically no post-harvest fungicides or bactericides with a broad spectrum of action that have no toxic residual effects and are safe. However, to minimize such problems, the use of sanitizers is an efficient device against these microorganisms. Chlorine is the most prevalent sanitizing agent because of its broad spectrum, low cost and well-established practices. However, the inevitable formation of disinfection by-products, such as trihalomethanes (THMs) and haloacetic acids (HAAs), is considered one of the main threats to food safety. Alternative sanitizers, such as chlorine dioxide (ClO2) and ozone, are becoming popular as a substitute for traditional post-harvest treatments. Thus, this review addresses the use of chlorine, chlorine dioxide and ozone emphasizing aspects, such as usage, safe application, spectrum of action and legislation. In order to ensure the quality and safety of final products, the adoption of well-prepared sanitation and sanitation programs for post-harvest fruits and vegetables is essential.

scholarly journals Exploiting RNA thermometer-driven molecular bioprocess control as a concept for heterologous rhamnolipid production

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Philipp Noll ◽  
Chantal Treinen ◽  
Sven Müller ◽  
Lars Lilge ◽  
Rudolf Hausmann ◽  
...  
Keyword(s):  
High Titer ◽  
Production Capacity ◽  
Batch Process ◽  
Product Formation ◽  
Effect Of Temperature ◽  
Industrial Biotechnology ◽  
Temperature Sensitive ◽  
Translation Control ◽  
Rhamnolipid Production ◽  
Rna Thermometer

AbstractA key challenge to advance the efficiency of bioprocesses is the uncoupling of biomass from product formation, as biomass represents a by-product that is in most cases difficult to recycle efficiently. Using the example of rhamnolipid biosurfactants, a temperature-sensitive heterologous production system under translation control of a fourU RNA thermometer from Salmonella was established to allow separating phases of preferred growth from product formation. Rhamnolipids as bulk chemicals represent a model system for future processes of industrial biotechnology and are therefore tied to the efficiency requirements in competition with the chemical industry. Experimental data confirms function of the RNA thermometer and suggests a major effect of temperature on specific rhamnolipid production rates with an increase of the average production rate by a factor of 11 between 25 and 38 °C, while the major part of this increase is attributable to the regulatory effect of the RNA thermometer rather than an unspecific overall increase in bacterial metabolism. The production capacity of the developed temperature sensitive-system was evaluated in a simple batch process driven by a temperature switch. Product formation was evaluated by efficiency parameters and yields, confirming increased product formation rates and product-per-biomass yields compared to a high titer heterologous rhamnolipid production process from literature.

Face recognition in an intelligent door lock with ResNet model based on deep learning

2021 ◽  
pp. 1-11
Author(s):  
Suphawimon Phawinee ◽  
Jing-Fang Cai ◽  
Zhe-Yu Guo ◽  
Hao-Ze Zheng ◽  
Guan-Chen Chen
Keyword(s):  
Face Recognition ◽  
Detection System ◽  
Low Cost ◽  
Ease Of Use ◽  
Raspberry Pi ◽  
Training Methods ◽  
Graphics Recognition ◽  
Face Images ◽  
The Face ◽  
Door Lock

Internet of Things is considerably increasing the levels of convenience at homes. The smart door lock is an entry product for smart homes. This work used Raspberry Pi, because of its low cost, as the main control board to apply face recognition technology to a door lock. The installation of the control sensing module with the GPIO expansion function of Raspberry Pi also improved the antitheft mechanism of the door lock. For ease of use, a mobile application (hereafter, app) was developed for users to upload their face images for processing. The app sends the images to Firebase and then the program downloads the images and captures the face as a training set. The face detection system was designed on the basis of machine learning and equipped with a Haar built-in OpenCV graphics recognition program. The system used four training methods: convolutional neural network, VGG-16, VGG-19, and ResNet50. After the training process, the program could recognize the user’s face to open the door lock. A prototype was constructed that could control the door lock and the antitheft system and stream real-time images from the camera to the app.

A Low-Cost Biomimetic Heterostructured Multilayer Membrane with Geopolymer Microparticles for Broad-Spectrum Water Purification

2020 ◽  
Vol 12 (10) ◽  
pp. 12133-12142 ◽  
Author(s):  
Ying Song ◽  
Zhili Li ◽  
Jiubing Zhang ◽  
Ying Tang ◽  
Yuanyuan Ge ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Water Purification ◽  
Low Cost ◽  
Multilayer Membrane

scholarly journals IoT and Deep Learning Based Approach for Rapid Screening and Face Mask Detection for Infection Spread Control of COVID-19

2021 ◽  
Vol 11 (8) ◽  
pp. 3495
Author(s):  
Shabir Hussain ◽  
Yang Yu ◽  
Muhammad Ayoub ◽  
Akmal Khan ◽  
Rukhshanda Rehman ◽  
...  
Keyword(s):  
Deep Learning ◽  
Low Cost ◽  
Face Mask ◽  
World Health ◽  
Rapid Screening ◽  
Screening System ◽  
Source Of Infection ◽  
The Face ◽  
Health Organization ◽  
Vaccine Distribution

The spread of COVID-19 has been taken on pandemic magnitudes and has already spread over 200 countries in a few months. In this time of emergency of COVID-19, especially when there is still a need to follow the precautions and developed vaccines are not available to all the developing countries in the first phase of vaccine distribution, the virus is spreading rapidly through direct and indirect contacts. The World Health Organization (WHO) provides the standard recommendations on preventing the spread of COVID-19 and the importance of face masks for protection from the virus. The excessive use of manual disinfection systems has also become a source of infection. That is why this research aims to design and develop a low-cost, rapid, scalable, and effective virus spread control and screening system to minimize the chances and risk of spread of COVID-19. We proposed an IoT-based Smart Screening and Disinfection Walkthrough Gate (SSDWG) for all public places entrance. The SSDWG is designed to do rapid screening, including temperature measuring using a contact-free sensor and storing the record of the suspected individual for further control and monitoring. Our proposed IoT-based screening system also implemented real-time deep learning models for face mask detection and classification. This module classified individuals who wear the face mask properly, improperly, and without a face mask using VGG-16, MobileNetV2, Inception v3, ResNet-50, and CNN using a transfer learning approach. We achieved the highest accuracy of 99.81% while using VGG-16 and the second highest accuracy of 99.6% using MobileNetV2 in the mask detection and classification module. We also implemented classification to classify the types of face masks worn by the individuals, either N-95 or surgical masks. We also compared the results of our proposed system with state-of-the-art methods, and we highly suggested that our system could be used to prevent the spread of local transmission and reduce the chances of human carriers of COVID-19.

scholarly journals The effectiveness of antiviral agents with broad-spectrum activity against chikungunya virus varies between host cell lines

2018 ◽  
Vol 26 ◽  
pp. 204020661880758 ◽  
Author(s):  
Evelyn J Franco ◽  
Jaime L Rodriquez ◽  
Justin J Pomeroy ◽  
Kaley C Hanrahan ◽  
Ashley N Brown
Keyword(s):  
Antiviral Activity ◽  
Host Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Broad Spectrum ◽  
Chikungunya Virus ◽  
Plaque Assay ◽  
A549 Cells ◽  
Western Hemisphere ◽  
Viral Burden

Chikungunya virus (CHIKV) is a mosquito-borne virus that has recently emerged in the Western Hemisphere. Approved antiviral therapies or vaccines for the treatment or prevention of CHIKV infections are not available. This study aims to evaluate the antiviral activity of commercially available broad-spectrum antivirals against CHIKV. Due to host cell-specific variability in uptake and intracellular processing of drug, we evaluated the antiviral effects of each agent in three cell lines. Antiviral activities of ribavirin (RBV), interferon-alfa (IFN-α) and favipiravir (FAV) were assessed in CHIKV-infected Vero, HUH-7, and A549 cells. CHIKV-infected cells were treated with increasing concentrations of each agent for three days and viral burden was quantified by plaque assay on Vero cells. Cytotoxic effects of RBV, FAV and IFN-α were also evaluated. Antiviral activity differed depending on the cell line used for evaluation. RBV had the greatest antiviral effect in HUH-7 cells (EC50 = 2.575 µg/mL); IFN-α was most effective in A549 cells (EC50 = 4.235 IU/mL); and FAV in HUH-7 cells (EC50 = 20.00 μg/mL). The results of our study show FAV and IFN-α are the most promising candidates, as their use led to substantial reductions in viral burden at clinically achievable concentrations in two human-derived cell lines. FAV is an especially attractive candidate for further investigation due to its oral bioavailability. These findings also highlight the importance of cell line selection for preclinical drug trials.

Giving when it costs

2017 ◽  
Vol 35 (5) ◽  
pp. 722-742 ◽  
Author(s):  
Lisa C. Day ◽  
Emily A. Impett
Keyword(s):  
Romantic Relationships ◽  
Low Cost ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Daily Experience ◽  
Self Construal ◽  
Interdependent Self ◽  
The Face ◽  
Willingness To Sacrifice

Do some people exhibit a greater willingness to sacrifice in romantic relationships and derive more satisfaction from doing so, even in the face of high costs? In a cross-sectional study and a daily experience study, we show that people low in interdependent self-construal were less willing to sacrifice when the costs were relatively high, whereas people high in interdependent self-construal were equally willing to make high- and low-cost sacrifices. Further, when people low in interdependent self-construal chose to sacrifice, they felt less authentic when the costs were high, which in turn, detracted from their satisfaction with sacrifice. In contrast, people high in interdependent self-construal did not feel less authentic and were buffered against feeling less satisfied when making more costly sacrifices. The findings identify a set of individuals who are more willing to sacrifice, even in the face of high costs, and who feel more satisfied and authentic when doing so.

scholarly journals Analysis of the Fee-to-Tax Reform on Water Resources in China

2021 ◽  
Vol 9 ◽  
Author(s):  
Zi-Rui Chen ◽  
Yuan Yuan ◽  
Xu Xiao
Keyword(s):  
Water Resources ◽  
Water Resource ◽  
Water Consumption ◽  
Tax Reform ◽  
Low Cost ◽  
Production Capacity ◽  
Cost Difference ◽  
Tax Rate ◽  
Leading Position ◽  
The Cost

The Resource Tax Law was officially implemented on September 1, 2020, in China. This law presents the “Fee-to-Tax” reform of water resources. This article compares the effects of the “Fee-to-Tax” reform under asymmetric duopoly conditions with perfect information. The mechanisms of the two policies are different when all firms simultaneously respond to water resources: the water resource fee affects output by reducing market size, while the water resource tax reduces output by amplifying the weighted cost difference effects between companies. Water resource taxes work better than fees for eliminating backward production capacity. A comparison of the situation when companies respond sequentially is also carried out. When a low-cost firm is in the leading position, the collection of fees actually reduces the output difference, whereas the tax improves it. When a high-cost firm acts as a leader, the effects depend on the cost difference. When the cost difference between firms is small, the first-move advantage of high-cost firms dominates the cost advantages of low-cost firms. Therefore, a higher tax rate yields a smaller output difference. When cost differences are relatively larger, the cost advantage of low-cost firms dominates the first-move advantage of high-cost firms. As the operational cost for reducing water consumption increases, the reduced water consumption first increases and then decreases.

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