scholarly journals Enhancement of Carrimycin Production Via Traditional Mutagenesis with Metabolic Engineering in Streptomyces Spiramyceticus 54IA

2022 ◽  
Author(s):  
Kemeng Li ◽  
Jianlu Dai ◽  
Juanjuan Liu ◽  
Tianyi Hao ◽  
Weiqing He
Keyword(s):  
Metabolic Engineering ◽  
Large Scale ◽  
Regulatory Gene ◽  
The Novel ◽  
Mutant Selection ◽  
Polyketide Biosynthesis ◽  
Primary Metabolites ◽  
Synthetic Genes ◽  
Differential Expression Genes ◽  
Selection Of

Abstract Background: Carrimycin is a new approved class I antibiotic in China. The novel carrimycin producing strain, Streptomyces spiramyceticus 54IA, was constructed by CRISPR-Cas9 editing system without insertion of antibiotics resistant gene. The problem of low yield limits this strain in large scale fermentation. In this study, the carrimycin production was significantly improved by strain mutagenesis coupled metabolic engineering. Results: The sspD gene is responsible for degradation of triacylglycerol to provide precursors of the polyketide biosynthesis. The extra sspD gene controlled by the promoters of pks and bsm42 genes could moderately enhance carrimycin production. The Bsm42 was identified to play a pathway-specific positive regulator for carrimycin biosynthesis. Due to production of carrimycin significantly enhanced by bsm42 overexpression, the two different length promoters of bsm42 individually ligated with two reporter genes were used to monitor bsm42 expression for screening the higher carrimycin production mutants treated by plasma and ultraviolet. 47% of the 608 selected mutants had higher fermentation titer than the starting strain. The shorter promoter of bsm42 displayed more appropriate for selection of the carrimycin production improved mutants. The F2R-15 mutant had highest titer (1010±30 μg/mL), which was about 9 times higher than that of 54IA strain. Comparative analysis of transcriptome profiles of F2R-15 mutant and 54IA strains found 158 differential expression genes with more than 2 fold-changes. The up-regulated genes were associated with macrolide precursor biosynthesis, macrolide-inactivation, antibiotics transporter, oxidative phosphorylation; while the most down-regulated genes were referring to the primary metabolites synthetic genes and biosynthetic genes of other secondary metabolites. Conclusion: These results suggested that manipulation of the positive regulatory gene bsm42 and traditional mutagenesis coupled with reporter-guided mutant selection method facilitated selection of carrimycin high-yielding mutants.

Platelet Anti-Aggregating Activity and Tolerance of Clopidogrel in Atherosclerotic Patients

1996 ◽  
Vol 76 (06) ◽  
pp. 0939-0943 ◽  
Author(s):  
B Boneu ◽  
G Destelle ◽  
Keyword(s):  
Platelet Aggregation ◽  
Large Scale ◽  
Bleeding Time ◽  
Antithrombotic Activity ◽  
Ambulatory Patients ◽  
Patients At Risk ◽  
Set Up ◽  
Ischemic Events ◽  
Large Scale Clinical Trial ◽  
Selection Of

SummaryThe anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trial of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50,75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 \lM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.

Covalent Atomic Bridges Enable Unidirectional Enhancement of Electronic Transport in Aligned Carbon Nanotubes

2019 ◽  
Author(s):  
Mingguang Chen ◽  
Wangxiang Li ◽  
Anshuman Kumar ◽  
Guanghui Li ◽  
Mikhail Itkis ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Electrical Transport ◽  
Large Scale ◽  
The Novel ◽  
Electrical Measurements ◽  
Metal Atoms ◽  
Aligned Carbon Nanotubes ◽  
Transport Channels ◽  
Walled Carbon Nanotubes ◽  
Bulk Structures

<p>Interconnecting the surfaces of nanomaterials without compromising their outstanding mechanical, thermal, and electronic properties is critical in the design of advanced bulk structures that still preserve the novel properties of their nanoscale constituents. As such, bridging the p-conjugated carbon surfaces of single-walled carbon nanotubes (SWNTs) has special implications in next-generation electronics. This study presents a rational path towards improvement of the electrical transport in aligned semiconducting SWNT films by deposition of metal atoms. The formation of conducting Cr-mediated pathways between the parallel SWNTs increases the transverse (intertube) conductance, while having negligible effect on the parallel (intratube) transport. In contrast, doping with Li has a predominant effect on the intratube electrical transport of aligned SWNT films. Large-scale first-principles calculations of electrical transport on aligned SWNTs show good agreement with the experimental electrical measurements and provide insight into the changes that different metal atoms exert on the density of states near the Fermi level of the SWNTs and the formation of transport channels. </p>

scholarly journals Methodology for Determining the Location of River Ports on a Modernized Waterway Based on Non-Cost Criteria: A Case Study of the Odra River Waterway

2021 ◽  
Vol 13 (6) ◽  
pp. 3571
Author(s):  
Bogusz Wiśnicki ◽  
Dorota Dybkowska-Stefek ◽  
Justyna Relisko-Rybak ◽  
Łukasz Kolanda
Keyword(s):  
Large Scale ◽  
Multicriteria Decision Making ◽  
Research Process ◽  
Optimal Selection ◽  
Investment Projects ◽  
Odra River ◽  
Research Problems ◽  
Selection Of ◽  
Construction Works

The paper responds to research problems related to the implementation of large-scale investment projects in waterways in Europe. As part of design and construction works, it is necessary to indicate river ports that play a major role within the European transport network as intermodal nodes. This entails a number of challenges, the cardinal one being the optimal selection of port locations, taking into account the new transport, economic, and geopolitical situation that will be brought about by modernized waterways. The aim of the paper was to present an original methodology for determining port locations for modernized waterways based on non-cost criteria, as an extended multicriteria decision-making method (MCDM) and employing GIS (Geographic Information System)-based tools for spatial analysis. The methodology was designed to be applicable to the varying conditions of a river’s hydroengineering structures (free-flowing river, canalized river, and canals) and adjustable to the requirements posed by intermodal supply chains. The method was applied to study the Odra River Waterway, which allowed the formulation of recommendations regarding the application of the method in the case of different river sections at every stage of the research process.

scholarly journals IoT Traffic: Modeling and Measurement Experiments

IoT ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 140-162
Author(s):  
Hung Nguyen-An ◽  
Thomas Silverston ◽  
Taku Yamazaki ◽  
Takumi Miyoshi
Keyword(s):  
Smart Home ◽  
Large Scale ◽  
Traffic Modeling ◽  
The Novel ◽  
Network Behavior ◽  
Performance Accuracy ◽  
Traffic Generator ◽  
Multiple Devices ◽  
Iot Devices ◽  
The Internet Of Things

We now use the Internet of things (IoT) in our everyday lives. The novel IoT devices collect cyber–physical data and provide information on the environment. Hence, IoT traffic will count for a major part of Internet traffic; however, its impact on the network is still widely unknown. IoT devices are prone to cyberattacks because of constrained resources or misconfigurations. It is essential to characterize IoT traffic and identify each device to monitor the IoT network and discriminate among legitimate and anomalous IoT traffic. In this study, we deployed a smart-home testbed comprising several IoT devices to study IoT traffic. We performed extensive measurement experiments using a novel IoT traffic generator tool called IoTTGen. This tool can generate traffic from multiple devices, emulating large-scale scenarios with different devices under different network conditions. We analyzed the IoT traffic properties by computing the entropy value of traffic parameters and visually observing the traffic on behavior shape graphs. We propose a new method for identifying traffic entropy-based devices, computing the entropy values of traffic features. The method relies on machine learning to classify the traffic. The proposed method succeeded in identifying devices with a performance accuracy up to 94% and is robust with unpredictable network behavior with traffic anomalies spreading in the network.

scholarly journals BonMOLière: Small-Sized Libraries of Readily Purchasable Compounds, Optimized to Produce Genuine Hits in Biological Screens across the Protein Space

2021 ◽  
Vol 22 (15) ◽  
pp. 7773
Author(s):  
Neann Mathai ◽  
Conrad Stork ◽  
Johannes Kirchmair
Keyword(s):  
Large Scale ◽  
Computational Approach ◽  
Large Sets ◽  
Compound Libraries ◽  
Wide Range ◽  
Protein Space ◽  
High Chance ◽  
Large Scale Screening ◽  
Early Drug ◽  
Selection Of

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).

scholarly journals Multi-Objective Optimization of Integrated Civilian-Military Scheduling of Medical Supplies for Epidemic Prevention and Control

Healthcare ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 126
Author(s):  
Hai-Feng Ling ◽  
Zheng-Lian Su ◽  
Xun-Lin Jiang ◽  
Yu-Jun Zheng
Keyword(s):  
Prevention And Control ◽  
Large Scale ◽  
Medical Services ◽  
The Novel ◽  
Multi Objective ◽  
Medical Supplies ◽  
Problem Instances ◽  
Novel Coronavirus ◽  
And Control ◽  
Minimum Ratio

In a large-scale epidemic, such as the novel coronavirus pneumonia (COVID-19), there is huge demand for a variety of medical supplies, such as medical masks, ventilators, and sickbeds. Resources from civilian medical services are often not sufficient for fully satisfying all of these demands. Resources from military medical services, which are normally reserved for military use, can be an effective supplement to these demands. In this paper, we formulate a problem of integrated civilian-military scheduling of medical supplies for epidemic prevention and control, the aim of which is to simultaneously maximize the overall satisfaction rate of the medical supplies and minimize the total scheduling cost, while keeping a minimum ratio of medical supplies reservation for military use. We propose a multi-objective water wave optimization (WWO) algorithm in order to efficiently solve this problem. Computational results on a set of problem instances constructed based on real COVID-19 data demonstrate the effectiveness of the proposed method.

scholarly journals Comparative genomics suggests a taxonomic revision of the Staphylococcus cohnii species complex

2021 ◽  
Author(s):  
Anna Lavecchia ◽  
Matteo Chiara ◽  
Caterina De Virgilio ◽  
Caterina Manzari ◽  
Carlo Pazzani ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
Species Complex ◽  
Large Scale ◽  
Genomic Sequence ◽  
Bacterial Species ◽  
Taxonomic Revision ◽  
Distinct Species ◽  
The Novel ◽  
Staphylococcus Cohnii ◽  
Taxonomic Assignments

Abstract Staphylococcus cohnii (SC), a coagulase-negative bacterium, was first isolated in 1975 from human skin. Early phenotypic analyses led to the delineation of two subspecies (subsp.), Staphylococcus cohnii subsp. cohnii (SCC) and Staphylococcus cohnii subsp. urealyticus (SCU). SCC was considered to be specific to humans whereas SCU apparently demonstrated a wider host range, from lower primates to humans. The type strains ATCC 29974 and ATCC 49330 have been designated for SCC and SCU, respectively. Comparative analysis of 66 complete genome sequences—including a novel SC isolate—revealed unexpected patterns within the SC complex, both in terms of genomic sequence identity and gene content, highlighting the presence of 3 phylogenetically distinct groups. Based on our observations, and on the current guidelines for taxonomic classification for bacterial species, we propose a revision of the SC species complex. We suggest that SCC and SCU should be regarded as two distinct species: SC and SU (Staphylococcus urealyticus), and that two distinct subspecies, SCC and SCB (SC subsp. barensis, represented by the novel strain isolated in Bari) should be recognized within SC. Furthermore, since large scale comparative genomics studies recurrently suggest inconsistencies or conflicts in taxonomic assignments of bacterial species, we believe that the approach proposed here might be considered for more general application.

scholarly journals Predicting Shifts in Land Suitability for Maize Cultivation Worldwide Due to Climate Change: A Modeling Approach

Land ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 295
Author(s):  
Yuan Gao ◽  
Anyu Zhang ◽  
Yaojie Yue ◽  
Jing’ai Wang ◽  
Peng Su
Keyword(s):  
Climate Change ◽  
Crop Production ◽  
Large Scale ◽  
Land Suitability ◽  
Large Scale Assessment ◽  
Scale Assessment ◽  
Maize Cultivation ◽  
Large Scale Screening ◽  
Selection Of

Suitable land is an important prerequisite for crop cultivation and, given the prospect of climate change, it is essential to assess such suitability to minimize crop production risks and to ensure food security. Although a variety of methods to assess the suitability are available, a comprehensive, objective, and large-scale screening of environmental variables that influence the results—and therefore their accuracy—of these methods has rarely been explored. An approach to the selection of such variables is proposed and the criteria established for large-scale assessment of land, based on big data, for its suitability to maize (Zea mays L.) cultivation as a case study. The predicted suitability matched the past distribution of maize with an overall accuracy of 79% and a Kappa coefficient of 0.72. The land suitability for maize is likely to decrease markedly at low latitudes and even at mid latitudes. The total area suitable for maize globally and in most major maize-producing countries will decrease, the decrease being particularly steep in those regions optimally suited for maize at present. Compared with earlier research, the method proposed in the present paper is simple yet objective, comprehensive, and reliable for large-scale assessment. The findings of the study highlight the necessity of adopting relevant strategies to cope with the adverse impacts of climate change.

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