scholarly journals Intramolecular interactions dominate the autoregulation ofEscherichia colistringent factor RelA

2019 ◽  
Author(s):  
Kathryn Jane Turnbull ◽  
Ievgen Dzhygyr ◽  
Søren Lindemose ◽  
Vasili Hauryliuk ◽  
Mohammad Roghanian
Keyword(s):  
Enzymatic Activity ◽  
Ectopic Expression ◽  
Direct Interaction ◽  
Terminal Region ◽  
Intramolecular Interactions ◽  
Synthetic Activity ◽  
Rrm Domain ◽  
The Individual ◽  
High Level ◽  
A Site

AbstractAmino acid starvation inEscherichia coliactivates the enzymatic activity of the stringent factor RelA, leading to accumulation of the alarmone nucleotide (p)ppGpp. The alarmone acts as an intercellular messenger to regulate transcription, translation and metabolism to mediate bacterial stress adaptation. The enzymatic activity of RelA is subject to multi-layered allosteric control executed both by ligands – such as ‘starved’ ribosomal complexes, deacylated tRNA and pppGpp – and by individual RelA domains. The auto-regulation of RelA is proposed to act eitherin cis(inhibition of the enzymatic activity of the N-terminal region, NTD, by regulatory C-terminal region, CTD) orin trans(CTD-mediated dimerization leading to enzyme inhibition). In this report, we probed the regulatory roles of the individual domains ofE. coliRelA and our results are not indicative of RelA dimerization being the key regulatory mechanism. First, at growth-permitting levels, ectopic expression of RelA CTD does not interfere with activation of native RelA, indicating lack of regulationviainhibitory complex formation in the cell. Second, in our biochemical assays, increasing RelA concentration does not decrease the enzyme activity, as would be expected in the case of efficient auto-inhibitionviadimerization. Third, while high-level CTD expression efficiently inhibits the growth, the effect is independent of native RelA and is mediated by direct inhibition of protein synthesis, likelyviadirect interaction with the ribosomal A-site. Finally, deletion of the RRM domain of the CTD region leads to growth inhibition mediated by accumulation of (p)ppGpp, suggesting de-regulation of the synthetic activity in this mutant.

Territorial Distribution of Alcohol and Drug Addictions Mortality Concerning Regional Disparities in the Slovak Republic from Year 1996 to Year 2015

2020 ◽  
Keyword(s):  
Mortality Rate ◽  
Slovak Republic ◽  
Regional Disparities ◽  
Point Of View ◽  
Extreme Position ◽  
Data Set ◽  
Female Sex ◽  
Male Sex ◽  
The Individual ◽  
High Level

BACKGROUND: This paper deals with territorial distribution of the alcohol and drug addictions mortality at a level of the districts of the Slovak Republic. AIM: The aim of the paper is to explore the relations within the administrative territorial division of the Slovak Republic, that is, between the individual districts and hence, to reveal possibly hidden relation in alcohol and drug mortality. METHODS: The analysis is divided and executed into the two fragments – one belongs to the female sex, the other one belongs to the male sex. The standardised mortality rate is computed according to a sequence of the mathematical relations. The Euclidean distance is employed to compute the similarity within each pair of a whole data set. The cluster analysis examines is performed. The clusters are created by means of the mutual distances of the districts. The data is collected from the database of the Statistical Office of the Slovak Republic for all the districts of the Slovak Republic. The covered time span begins in the year 1996 and ends in the year 2015. RESULTS: The most substantial point is that the Slovak Republic possesses the regional disparities in a field of mortality expressed by the standardised mortality rate computed particularly for the diagnoses assigned to the alcohol and drug addictions at a considerably high level. However, the female sex and the male sex have the different outcome. The Bratislava III District keeps absolutely the most extreme position. It forms an own cluster for the both sexes too. The Topoľčany District bears a similar extreme position from a point of view of the male sex. All the Bratislava districts keep their mutual notable dissimilarity. Contrariwise, evaluation of a development of the regional disparities among the districts looks like notably heterogeneously. CONCLUSIONS: There are considerable regional discrepancies throughout the districts of the Slovak Republic. Hence, it is necessary to create a common platform how to proceed with the solution of this issue.

Quantitative indicators of air traffic controllers’ attitude to the danger of errors

2020 ◽  
pp. 68-78
Author(s):  
O. M. Reva ◽  
V. V. Kamyshin ◽  
S. P. Borsuk ◽  
V. A. Shulhin ◽  
A. V. Nevynitsyn
Keyword(s):  
Human Factor ◽  
Differential Method ◽  
Air Traffic ◽  
Professional Activity ◽  
Aviation Accidents ◽  
Air Traffic Controllers ◽  
The Difference ◽  
Level Of Significance ◽  
The Individual ◽  
High Level

The negative and persistent impact of the human factor on the statistics of aviation accidents and serious incidents makes proactive studies of the attitude of “front line” aviation operators (air traffic controllers, flight crewmembers) to dangerous actions or professional conditions as a key component of the current paradigm of ICAO safety concept. This “attitude” is determined through the indicators of the influence of the human factor on decision-making, which also include the systems of preferences of air traffic controllers on the indicators and characteristics of professional activity, illustrating both the individual perception of potential risks and dangers, and the peculiarities of generalized group thinking that have developed in a particular society. Preference systems are an ordered (ranked) series of n = 21 errors: from the most dangerous to the least dangerous and characterize only the danger preference of one error over another. The degree of this preference is determined only by the difference in the ranks of the errors and does not answer the question of how much time one error is more dangerous in relation to another. The differential method for identifying the comparative danger of errors, as well as the multistep technology for identifying and filtering out marginal opinions were applied. From the initial sample of m = 37 professional air traffic controllers, two subgroups mB=20 and mG=7 people were identified with statisti-cally significant at a high level of significance within the group consistency of opinions a = 1%. Nonpara-metric optimization of the corresponding group preference systems resulted in Kemeny’s medians, in which the related (middle) ranks were missing. Based on these medians, weighted coefficients of error hazards were determined by the mathematical prioritization method. It is substantiated that with the ac-cepted accuracy of calculations, the results obtained at the second iteration of this method are more ac-ceptable. The values of the error hazard coefficients, together with their ranks established in the preference systems, allow a more complete quantitative and qualitative analysis of the attitude of both individual air traffic controllers and their professional groups to hazardous actions or conditions.

scholarly journals Automatic Labeled Dialogue Generation for Nursing Record Systems

2020 ◽  
Vol 10 (3) ◽  
pp. 62
Author(s):  
Tittaya Mairittha ◽  
Nattaya Mairittha ◽  
Sozo Inoue
Keyword(s):  
Data Augmentation ◽  
Short Term Memory ◽  
Generative Models ◽  
Abstract Knowledge ◽  
Augmentation Techniques ◽  
Nursing Record ◽  
Long Short Term Memory ◽  
The Individual ◽  
High Level ◽  
Embedding Methods

The integration of digital voice assistants in nursing residences is becoming increasingly important to facilitate nursing productivity with documentation. A key idea behind this system is training natural language understanding (NLU) modules that enable the machine to classify the purpose of the user utterance (intent) and extract pieces of valuable information present in the utterance (entity). One of the main obstacles when creating robust NLU is the lack of sufficient labeled data, which generally relies on human labeling. This process is cost-intensive and time-consuming, particularly in the high-level nursing care domain, which requires abstract knowledge. In this paper, we propose an automatic dialogue labeling framework of NLU tasks, specifically for nursing record systems. First, we apply data augmentation techniques to create a collection of variant sample utterances. The individual evaluation result strongly shows a stratification rate, with regard to both fluency and accuracy in utterances. We also investigate the possibility of applying deep generative models for our augmented dataset. The preliminary character-based model based on long short-term memory (LSTM) obtains an accuracy of 90% and generates various reasonable texts with BLEU scores of 0.76. Secondly, we introduce an idea for intent and entity labeling by using feature embeddings and semantic similarity-based clustering. We also empirically evaluate different embedding methods for learning good representations that are most suitable to use with our data and clustering tasks. Experimental results show that fastText embeddings produce strong performances both for intent labeling and on entity labeling, which achieves an accuracy level of 0.79 and 0.78 f1-scores and 0.67 and 0.61 silhouette scores, respectively.

scholarly journals Opportunities and Challenges of Green-Lean: An Integrated System for Sustainable Construction

2020 ◽  
Vol 12 (11) ◽  
pp. 4460 ◽  
Author(s):  
Mohammadsoroush Tafazzoli ◽  
Ehsan Mousavi ◽  
Sharareh Kermanshachi
Keyword(s):  
Cost Savings ◽  
Integrated Approach ◽  
Integrated System ◽  
Waste Minimization ◽  
Sustainable Construction ◽  
Future Research ◽  
Safety Improvement ◽  
The Individual ◽  
High Level ◽  
Industry Professionals

Although the two concepts of lean and sustainable construction have been developed due to different incentives, and they do not pursue the same exact goals, there exists considerable commonality between them. This paper discusses the potentials for integrating the two approaches and their practices and how the resulting synergy from combining the two methods can potentially lead to higher levels of fulfilling the individual goals of each of them. Some limitations and challenges to implementing the integrated approach are also discussed. Based on a comprehensive review of existing papers related to sustainable and lean construction topics, the commonality between the two approaches is discussed and grouped in five categories of (1) cost savings, (2) waste minimization, (3) Jobsite safety improvement, (4) reduced energy consumption, and (5) customers’ satisfaction improvement. The challenges of this integration are similarly identified and discussed in the four main categories of (1) additional initial costs to the project, (2) difficulty of providing specialized expertise, (3) contractors’ unwillingness to adopt the additional requirements, and (4) challenges to establish a high level of teamwork. Industry professionals were then interviewed to rank the elements in each of the two categories of opportunities and challenges. The results of the study highlight how future research can pursue the development of a new Green-Lean approach by investing in the communalities and meeting the challenges of this integration.

scholarly journals Direct Interaction of Polar Scaffolding Protein Wag31 with Nucleoid-Associated Protein Rv3852 Regulates Its Polar Localization

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1558
Author(s):  
Rajni Garg ◽  
Chinmay Anand ◽  
Sohini Ganguly ◽  
Sandhya Rao ◽  
Rinkee Verma ◽  
...  
Keyword(s):  
Cell Wall ◽  
Cell Envelope ◽  
Transmembrane Helix ◽  
Ectopic Expression ◽  
Direct Interaction ◽  
Fine Tuning ◽  
Scaffolding Protein ◽  
Physical Interaction ◽  
Cell Wall Synthesis ◽  
Interaction Approach

Rv3852 is a unique nucleoid-associated protein (NAP) found exclusively in Mycobacterium tuberculosis (Mtb) and closely related species. Although annotated as H-NS, we showed previously that it is very different from H-NS in its properties and is distinct from other NAPs, anchoring to cell membrane by virtue of possessing a C-terminal transmembrane helix. Here, we investigated the role of Rv3852 in Mtb in organizing architecture or synthesis machinery of cell wall by protein–protein interaction approach. We demonstrated a direct physical interaction of Rv3852 with Wag31, an important cell shape and cell wall integrity determinant essential in Mtb. Wag31 localizes to the cell poles and possibly acts as a scaffold for cell wall synthesis proteins, resulting in polar cell growth in Mtb. Ectopic expression of Rv3852 in M. smegmatis resulted in its interaction with Wag31 orthologue DivIVAMsm. Binding of the NAP to Wag31 appears to be necessary for fine-tuning Wag31 localization to the cell poles, enabling complex cell wall synthesis in Mtb. In Rv3852 knockout background, Wag31 is mislocalized resulting in disturbed nascent peptidoglycan synthesis, suggesting that the NAP acts as a driver for localization of Wag31 to the cell poles. While this novel association between these two proteins presents one of the mechanisms to structure the elaborate multi-layered cell envelope of Mtb, it also exemplifies a new function for a NAP in mycobacteria.

scholarly journals Children’s Astronomy. Development of the Shape of the Earth Concept in Polish Children between 5 and 10 Years of Age

2021 ◽  
Vol 11 (2) ◽  
pp. 75
Author(s):  
Jan Amos Jelinek
Keyword(s):  
Mental Model ◽  
Cultural Influences ◽  
Test Results ◽  
The Earth ◽  
Spherical Earth ◽  
The Individual ◽  
High Level ◽  
Cognitive Problems ◽  
Teaching Situations ◽  
Model Approach

The Earth’s shape concept develops as consecutive cognitive problems (e.g., the location of people and trees on the spherical Earth) are gradually resolved. Establishing the order of problem solving may be important for the organisation of teaching situations. This study attempted to determine the sequence of problems to be resolved based on tasks included in the EARTH2 test. The study covered a group of 444 children between 5 and 10 years of age. It captured the order in which children solve cognitive problems on the way to constructing a science-like concept. The test results were compared with previous studies. The importance of cultural influences connected to significant differences (24%) in test results was emphasised. Attention was drawn to the problem of the consistency of the mental model approach highlighted in the literature. The analysis of the individual sets of answers provided a high level of consistency of indications referring to the same model (36%), emphasising the importance of the concept of mental models.

scholarly journals METTL3-dependent m6A modification programs T follicular helper cell differentiation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingpeng Yao ◽  
Ying Yang ◽  
Wenhui Guo ◽  
Lifan Xu ◽  
Menghao You ◽  
...  
Keyword(s):  
T Cells ◽  
Transcriptional Regulation ◽  
Cell Differentiation ◽  
Ectopic Expression ◽  
Signature Genes ◽  
Follicular Helper ◽  
Conditional Deletion ◽  
A Cell ◽  
A Site ◽  
Post Transcriptional Regulation

AbstractT follicular helper (TFH) cells are specialized effector CD4+ T cells critical to humoral immunity. Whether post-transcriptional regulation has a function in TFH cells is unknown. Here, we show conditional deletion of METTL3 (a methyltransferase catalyzing mRNA N6-methyladenosine (m6A) modification) in CD4+ T cells impairs TFH differentiation and germinal center responses in a cell-intrinsic manner in mice. METTL3 is necessary for expression of important TFH signature genes, including Tcf7, Bcl6, Icos and Cxcr5 and these effects depend on intact methyltransferase activity. m6A-miCLIP-seq shows the 3′ UTR of Tcf7 mRNA is subjected to METTL3-dependent m6A modification. Loss of METTL3 or mutation of the Tcf7 3′ UTR m6A site results in accelerated decay of Tcf7 transcripts. Importantly, ectopic expression of TCF-1 (encoded by Tcf7) rectifies TFH defects owing to METTL3 deficiency. Our findings indicate that METTL3 stabilizes Tcf7 transcripts via m6A modification to ensure activation of a TFH transcriptional program, indicating a pivotal function of post-transcriptional regulation in promoting TFH cell differentiation.

scholarly journals Specific Binding of Rubidium in Chlorella

1962 ◽  
Vol 45 (5) ◽  
pp. 959-977 ◽  
Author(s):  
Dan Cohen
Keyword(s):  
Active Transport ◽  
Binding Sites ◽  
Specific Binding ◽  
High Concentration ◽  
External Concentration ◽  
Specific Binding Sites ◽  
Dense Suspension ◽  
Concentration Of Ions ◽  
The Individual ◽  
A Site

Specific binding sites for potassium, which may be components of the carriers for active transport for K in Chlorella, were characterized by their capacity to bind rubidium. A dense suspension was allowed to take up Rb86 from a low concentration of Rb86 and a high concentration of ions which saturate non-specific sites. The amount bound was derived from the increase in the external concentration of Rb86 following addition of excess potassium. The sites were heterogeneous. The average affinity of Rb and various other ions for the sites was determined by plotting the degree of displacement of Rb86 against log molar concentration of the individual ions. Interpolation gave the concentration for 50 per cent displacement of Rb, which is inversely related to affinity. The order of affinity was not changed when the cells were frozen, or boiled either in water or in 70 per cent ethanol. The affinity is maximal for ions with a crystalline radius of 1.3 to 1.5 A and a high polarizability, and is not related to the hydrated radius or valency. It is suggested that binding groups in a site are rigidly arranged, the irregular space between them being 2.6 to 3.0 A across, so that affinity is high for ions of this diameter and high polarizability.

Migration of Solutes in Unsaturated, Fractured Rock at Yucca Mountain: Measurements, Mechanisms, and Models

1995 ◽  
Vol 412 ◽  
Author(s):  
A. V. Wolfsberg ◽  
B. A. Robinson ◽  
J. T. Fabryka-Martin
Keyword(s):  
Solute Transport ◽  
Transport Model ◽  
Alternative Hypothesis ◽  
Fractured Rock ◽  
Yucca Mountain ◽  
Nuclear Waste Repository ◽  
Transport Studies ◽  
And Performance ◽  
High Level ◽  
A Site

AbstractCharacterization and performance assessment (PA) studies for the potential high-level nuclear waste repository at Yucca Mountain require an understanding of migration mechanisms and pathways of radioactive solutes. Measurements of 36C1 in samples extracted from boreholes at the site are being used in conjunction with recent infiltration estimates to calibrate a site-scale flow and solute transport model. This exercise using the flow and solute transport model, FEHM, involves testing different model formulations and two different hypotheses to explain the occurrence of elevated 36Cl in the Calico Hills unit (CHn) which indicates younger water than in the overlying Topopah Spring unit (TSw). One hypothesis suggests fast vertical transport from the surface via fractures in the TSw to the CHn. An alternative hypothesis is that the elevated 36C1 concentrations reflect rapid horizontal flow in the CHn or at the interface between the CHn and the TSw with the source being vertical percolation under spatially isolated regions of high infiltration or at outcrops of those units. Arguments in favor of and against the hypotheses are described in conjunction with the site-scale transport studies.

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