scholarly journals Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 579 ◽  
Author(s):  
Weronika Wanat ◽  
Michał Talma ◽  
Błażej Dziuk ◽  
Jean-Luc Pirat ◽  
Paweł Kafarski
Keyword(s):  
Molecular Modeling ◽  
Aromatic Ring ◽  
Phosphonic Acid ◽  
Inhibitory Activity ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Active Compounds ◽  
The Difference ◽  
The Individual

A library of phosphonic acid analogs of phenylalanine substituted with fluorine, chlorine and trifluoromethyl moieties on the aromatic ring was synthesized and evaluated for inhibitory activity against human (hAPN) and porcine (pAPN) aminopeptidases. Fluorogenic screening indicated that these analogs are micromolar or submicromolar inhibitors, both enzymes being more active against hAPN. In order to better understand the mode of the action of the most active compounds, molecular modeling was used. It confirmed that aminophosphonic portion of the enzyme is bound nearly identically in the case of all the studied compounds, whereas the difference in activity results from the placement of aromatic side chain of an inhibitor. Interestingly, both enantiomers of the individual compounds are usually bound quite similarly.

scholarly journals An Aromatic Side Chain Is Required at Residue 8 of SU for Fusion of Ecotropic Murine Leukemia Virus

2004 ◽  
Vol 78 (1) ◽  
pp. 508-512 ◽  
Author(s):  
Zhaohui Qian ◽  
Lorraine M. Albritton
Keyword(s):  
Membrane Fusion ◽  
Aromatic Ring ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Surface Glycoprotein ◽  
Side Chain ◽  
Complete Fusion ◽  
Aromatic Side Chain ◽  
Fusion Pores ◽  
Murine Leukemia

ABSTRACT The surface glycoprotein (SU) of most gammaretroviruses contains a conserved histidine at its amino terminus. In ecotropic murine leukemia virus SU, replacement of histidine 8 with arginine (H8R) or deletion of H8 (H8del) abolishes infection and cell-cell fusion but has no effect on binding to the cellular receptor. We report here that an aromatic ring side chain is essential to the function of residue 8. The size of the aromatic ring appears to be important, as does its ability to form a hydrogen bond. In addition, infection by all of the nonaromatic amino acid substitutions could be partially rescued by the addition of two suppressor mutations (glutamine 227 to arginine [Q227R] and aspartate 243 to tyrosine [D243Y]) or by exposure to chlorpromazine, an agent that induces fusion pores in hemifusion intermediates to complete fusion, suggesting that, like the previously described H8R mutant, the mutants reported here also arrest membrane fusion at the hemifusion state. We propose that H8 is a key switch-point residue in the conformation changes that lead to membrane fusion and present a possible mechanism for how its substitution arrests fusion at the hemifusion state.

scholarly journals Phosphonic Acid Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase, Tomato Acidic Leucine Aminopeptidase and Aminopeptidase from Barley Seeds

2019 ◽  
Vol 12 (3) ◽  
pp. 139 ◽  
Author(s):  
Weronika Wanat ◽  
Michał Talma ◽  
Małgorzata Pawełczak ◽  
Paweł Kafarski
Keyword(s):  
Phosphonic Acid ◽  
Inhibitory Activity ◽  
Leucine Aminopeptidase ◽  
Aminopeptidase N ◽  
Binding Modes ◽  
Aromatic Rings ◽  
Phenyl Rings ◽  
The Difference ◽  
Uniform Manner ◽  
Highly Uniform

The inhibitory activity of 14 racemic phosphonic acid analogs of phenylglycine, substituted in aromatic rings, towards porcine aminopeptidase N (pAPN) and barley seed aminopeptidase was determined experimentally. The obtained patterns of the inhibitory activity against the two enzymes were similar. The obtained data served as a basis for studying the binding modes of these inhibitors by pAPN using molecular modeling. It was found that their aminophosphonate fragments were bound in a highly uniform manner and that the difference in their affinities most likely resulted from the mode of substitution of their phenyl rings. The obtained binding modes towards pAPN were compared, with these predicted for bovine lens leucine aminopeptidase (blLAP) and tomato acidic leucine aminopeptidase (tLAPA). The performed studies indicated that the binding manner of the phenylglycine analogs to biLAP and tLAPA are significantly similar and differ slightly from that predicted for pAPN.

Empirical Study On Attributes Leading To Satisfaction Among Bank Customer

2019 ◽  
Vol 118 (7) ◽  
pp. 101-110
Author(s):  
Ms.U.Sakthi Veeralakshmi ◽  
Dr.G. Venkatesan
Keyword(s):  
Service Quality ◽  
Behavioral Intention ◽  
Banking Sector ◽  
Positive Impact ◽  
Quality Performance ◽  
Public And Private ◽  
The Difference ◽  
The Individual ◽  
Private Banking ◽  
Service Gap

This research aims at measuring the service quality in public and private banking sector and identifying its relationship to customer satisfaction and behavioral intention. The study was conducted among 500 bank customers by using revised SERVQUAL instrument with 26 items. Behavioral intention of the customers was measured by using the behavioral intention battery. The researcher has used a seven point likert scaling to measure the expected and perceived service quality (performance) and the behavioral intention of the customer. The instrument was selected as the most reliable device to measure the difference-score conceptualization. It is used to evaluate service gap between expectation and perception of service quality. Modifications are made on the SERVQUAL instrument to make it specific to the Banking sector. Questions were added to the instrument like Seating space for waiting (Tangibility), Parking space in the Bank (Tangibility), Variety of products / schemes available (Tangibility), Banks sincere steps to handling Grievances of the customers (Responsiveness). The findings of the study revealed that the customer’s perception (performance) is lower than expectation of the service quality rendered by banks. Responsiveness and Assurance SQ dimensions were the most important dimensions in service quality scored less SQ gap. The study concluded that the individual service quality dimensions have a positive impact on Overall Satisfaction.

THE SUBJECT FIELD OF INSTITUTIONAL EDUCATION: THE SENSE AND PROSPECTS OF DEVELOPMENT IN UKRAINE

2020 ◽  
pp. 25-38
Author(s):  
Irina Mordous
Keyword(s):  
Decisive Role ◽  
Subject Field ◽  
National Education ◽  
Progressive Development ◽  
Separate Area ◽  
Economic Transformations ◽  
The Difference ◽  
The Individual ◽  
Political Economic

The development of modern civilization attests to its decisive role in the progressive development of institutions. They identified the difference between Western civilization and the rest of the world. Confirmation of the institutional advantages of the West was its early industrialization. The genesis and formation of institutionalism in its ideological and conceptualmethodological orientation occurs as a process alternative to neoclassic in the context of world heterodoxia, which quickly spread in social science. Highlighting institutional education as a separate area of sociocultural activity is determined by the factor of differentiation of institutional theory as a whole. A feature of institutional education is its orientation toward the individual and his/her transformation into a personality. The content of institutional education is revealed through the analysis of the institution, which includes a set of established customs, traditions, ways of thinking, behavioral stereotypes of individuals and social groups. The dynamics of socio-political, economic transformations in Ukraine requires a review of the foundations of national education and determination of the prospects for its development in the 21st century in the context of institutionalism.

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.

Quality-of-Life Measurement in Advanced Cancer: Assessing the Individual

1999 ◽  
Vol 17 (11) ◽  
pp. 3603-3611 ◽  
Author(s):  
Dympna Waldron ◽  
Ciaran A. O'Boyle ◽  
Michael Kearney ◽  
Michael Moriarty ◽  
Desmond Carney
Keyword(s):  
Quality Of Life ◽  
Advanced Cancer ◽  
Internal Validity ◽  
Semistructured Interview ◽  
Incurable Cancer ◽  
Life Measurement ◽  
The Difference ◽  
The Individual ◽  
Very High

PURPOSE: Despite the increasing importance of assessing quality of life (QoL) in patients with advanced cancer, relatively little is known about individual patient's perceptions of the issues contributing to their QoL. The Schedule for the Evaluation of Individual Quality of Life (SEIQoL) and the shorter SEIQoL–Direct Weighting (SEIQoL-DW) assess individualized QoL using a semistructured interview technique. Here we report findings from the first administration of the SEIQoL and SEIQoL-DW to patients with advanced incurable cancer. PATIENTS AND METHODS: QoL was assessed on a single occasion using the SEIQoL and SEIQoL-DW in 80 patients with advanced incurable cancer. RESULTS: All patients were able to complete the SEIQoL-DW, and 78% completed the SEIQoL. Of a possible score of 100, the median QoL global score was as follows: SEIQoL, 61 (range, 24 to 94); SEIQoL-DW, 60.5 (range, 6 to 95). Psychometric data for SEIQoL indicated very high levels of internal consistency (median r = .90) and internal validity (median R2 = 0.88). Patients' judgments of their QoL were unique to the individual. Family concerns were almost universally rated as more important than health, the difference being significant when measured using the SEIQoL-DW (P = .002). CONCLUSION: Patients with advanced incurable cancer were very good judges of their QoL, and many patients rated their QoL as good. Judgments were highly individual, with very high levels of consistency and validity. The primacy given to health in many QoL questionnaires may be questioned in this population. The implications of these findings are discussed with regard to clinical assessment and advance directives.

scholarly journals Effects of Amino Acid Side-Chain Length and Chemical Structure on Anionic Polyglutamic and Polyaspartic Acid Cellulose-Based Polyelectrolyte Brushes

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1789
Author(s):  
Dmitry Tolmachev ◽  
George Mamistvalov ◽  
Natalia Lukasheva ◽  
Sergey Larin ◽  
Mikko Karttunen
Keyword(s):  
Glutamic Acid ◽  
Chain Length ◽  
Chemical Structure ◽  
Side Chain ◽  
Side Chains ◽  
Side Chain Length ◽  
Polyelectrolyte Brushes ◽  
Grafting Density ◽  
The Difference ◽  
Cellulose Surface

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α,L-glutamic acid and α,L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is to search for ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side-chain length, the chemical structure and their interplay are required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side-chain rotation, enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side-chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main-chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

scholarly journals Nondestructive Detection of the Gel State of Preserved Eggs Based on Dielectric Impedance

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 394
Author(s):  
Cheng-Han Li ◽  
Chun-Hung Hsieh ◽  
Cheng-Chu Hung ◽  
Ching-Wei Cheng
Keyword(s):  
Decay Rate ◽  
Mechanical Vibration ◽  
Scientific Basis ◽  
Nondestructive Method ◽  
Inspection System ◽  
Nyquist Diagram ◽  
Detection Technology ◽  
The Difference ◽  
The Individual

After completing the production of preserved eggs, traditionally, the degree of gelling is judged by allowing workers to tap the preserved eggs with their fingers and sense the resulting oscillations. The amount of oscillation is used for the quality classification. This traditional method produces varying results owing to the differences in the sensitivity of the individual workers, who are not objective. In this study, dielectric detection technology was used to classify the preserved eggs nondestructively. The impedance in the frequency range of 2–300 kHz was resolved into resistance and reactance, and was plotted on a Nyquist diagram. Next, the diagram curve was fitted in order to obtain the equivalent circuit, and the difference in the compositions of the equivalent circuits corresponding to gelled and non-gelled preserved eggs was analyzed. A preserved egg can be considered an RLC series circuit, and its decay rate is consistent with the decay rate given by mechanical vibration theory. The Nyquist diagrams for the resistance and reactance of preserved eggs clearly showed that the resistance and reactance of gelled and non-gelled eggs were quite different, and the classification of the eggs was performed using Bayesian network (BN). The results showed that a BN classifier with two variables, i.e., resistance and reactance, can be used to classify preserved eggs as gelled or non-gelled, with an accuracy of 81.0% and a kappa value of 0.62. Thus, a BN classifier based on resistance and reactance demonstrates the ability to classify the quality of preserved egg gel. This research provides a nondestructive method for the inspection of the quality of preserved egg gel, and provides a theoretical basis for the development of an automated preserved egg inspection system that can be used as the scientific basis for the determination of the quality of preserved eggs.

scholarly journals The Physical Adsorption of Gelatinized Starch with Tannic Acid Decreases the Inhibitory Activity of the Polyphenol against α-Amylase

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1233
Author(s):  
Yueyi Wang ◽  
Shuangshuang Li ◽  
Fangting Bai ◽  
Junwei Cao ◽  
Lijun Sun
Keyword(s):  
Enzyme Inhibition ◽  
Tannic Acid ◽  
Inhibitory Activity ◽  
Adsorption Property ◽  
Physical Adsorption ◽  
Enzyme Active Site ◽  
Opposite Trend ◽  
Gelatinized Starch ◽  
The Difference

The effects of mixing orders of tannic acid (TA), starch, and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with the opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Moreover, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol has an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

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