scholarly journals QSAR-modeling of desoxyuridine triphosphatase inhibitors in a series of some derivatives of uracil

2019 ◽  
Vol 65 (2) ◽  
pp. 103-113
Author(s):  
Yu.Z. Martynova ◽  
V.R. Khairullina ◽  
A.R. Gimadieva ◽  
A.G. Mustafin
Keyword(s):  
Practical Application ◽  
Qsar Modeling ◽  
Dna Biosynthesis ◽  
Promising Target ◽  
Wide Range ◽  
Consensus Models ◽  
Qsar Models ◽  
Selection Stage ◽  
The Relationship ◽  
Derivatives Of

Due to the widespread prevalence, deoxyuridine triphosphatase (UTPase) is considered by modern biochemists and physicians as a promising target for the development of drugs with a wide range of activities. The therapeutic effect of these drugs will be due to suppression of DNA biosynthesis in various viruses, bacteria and protozoa. In order to rationalize the search for new dUTPase inhibitors, domestic and foreign researchers are actively using the QSAR methodology at the selection stage of hit compounds. However, the practical application of this methodology is impossible without existence of valid QSAR models. With the use of the GUSAR 2013 program, a quantitative analysis of the relationship between the structure and efficacy of 135 dUTPase inhibitors based on uracil derivatives was performed in the IC50 range of 30¸185000 nmol/L. Six statistically significant valid consensus models, characterized by high descriptive ability and moderate prognostic ability on the structures of training and test samples, are constructed. To build valid QSAR models for dUTPase inhibitors can use QNA or MNA descriptors and their combinations in a consensus approach.

Metal-detecting in archaeological excavation

Antiquity ◽  
1984 ◽  
Vol 58 (224) ◽  
pp. 179-184 ◽  
Author(s):  
T. Gregory ◽  
A. J. G. Rogerson
Keyword(s):  
Free Will ◽  
Human Action ◽  
Electronic Instrument ◽  
Practical Application ◽  
Archaeological Excavation ◽  
Metal Detector ◽  
Wide Range ◽  
Considerable Length ◽  
Good And Evil ◽  
The Relationship

The metal-detector is an electronic instrument; it is incapable of any independent act of free will. It is outside the reference of a system of good and evil : it is neither benign nor malign, ethical nor unethical, as neutral in such matters as a stone. It is capable merely of indicating the presence of certain objects on or below the soil. It bears no responsibility for human action consequent upon such indications. If this appears to be superfluous comment, it must be borne in mind that the very mention of the words ‘metal-detector’, with no reference at all to the machine's user, is guaranteed to raise the hackles of many archaeologists. Readers of this journal are surely aware of the wide range of archaeological opinion on metaldetecting; the issue of the relationship between orthodox archaeology and nietal-detecting has been aired at considerable length over the last few years and does not directly concern us here. Rather we intend to examine the practical application of the instrument to archaeological procedures.

Use of QSAR Modeling to Predict the Carcinogenicity of Color Additives

2013 ◽  
Author(s):  
Ronald Brown ◽  
Shannon White ◽  
Jennifer Goode ◽  
Prachi Pradeep ◽  
Stephen Merrill
Keyword(s):  
Medical Devices ◽  
Safety Evaluation ◽  
Toxicity Testing ◽  
Quantitative Structure Activity Relationship ◽  
Draft Guidance ◽  
Qsar Modeling ◽  
Wide Range ◽  
Qsar Models ◽  
Us Fda ◽  
Radiological Health

Patients may be exposed to potentially carcinogenic color additives released from polymers used to manufacture medical devices; therefore, the need exists to adequately assess the safety of these compounds. The US FDA Center for Devices and Radiological Health (CDRH) recently issued draft guidance that, when final, will include FDA’s recommendations for the safety evaluation of color additives and other potentially toxic chemical entities that may be released from device materials. Specifically, the draft guidance outlines an approach that calls for evaluating the potential for the color additive to be released from the device in concert with available toxicity information about the additive to determine what types of toxicity information, if any, are necessary. However, when toxicity data are not available from the literature for the compounds of interest, a scientific rationale can sometimes be provided for omission of these tests. Although the FDA has issued draft guidance on this topic, the Agency continues to explore alternative approaches to understand when additional toxicity testing is needed to assure the safety of medical devices that contain color additives. An emerging approach that may be useful for determining the need for further testing of compounds released from device materials is Quantitative Structure Activity Relationship (QSAR) modeling. In this paper, we have shown how three publically available QSAR models (OpenTox/Lazar, Toxtree, and the OECD Toolbox) are able to successfully predict the carcinogenic potential of a set of color additives with a wide range of structures. As a result, this computational modeling approach may serve as a useful tool for determining the need to conduct carcinogenicity testing of color additives intended for use in medical devices.

The Problem of Identifying and Modeling the Relationship between Monetary Factor and Inflation in the Russian Economy

2008 ◽  
pp. 61-76
Author(s):  
A. Porshakov ◽  
A. Ponomarenko
Keyword(s):  
Money Supply ◽  
Money Demand ◽  
Russian Economy ◽  
Long Run ◽  
Complex Approach ◽  
Wide Range ◽  
Long Time ◽  
The Relationship ◽  
Supply Side Factors

The role of monetary factor in generating inflationary processes in Russia has stimulated various debates in social and scientific circles for a relatively long time. The authors show that identification of the specificity of relationship between money and inflation requires a complex approach based on statistical modeling and involving a wide range of indicators relevant for the price changes in the economy. As a result a model of inflation for Russia implying the decomposition of inflation dynamics into demand-side and supply-side factors is suggested. The main conclusion drawn is that during the recent years the volume of inflationary pressures in the Russian economy has been determined by the deviation of money supply from money demand, rather than by money supply alone. At the same time, monetary factor has a long-run spread over time impact on inflation.

Modern prevention and active longevity programs on the basis of disruptive domestic technologies: positive experience and prospects for application

2020 ◽  
pp. 66-73
Author(s):  
A. Simonova ◽  
S. Chudakov ◽  
R. Gorenkov ◽  
V. Egorov ◽  
A. Gostry ◽  
...  
Keyword(s):  
Personalized Medicine ◽  
Early Detection ◽  
Laboratory Diagnostics ◽  
Positive Experience ◽  
Practical Application ◽  
Wide Range ◽  
Integrated Program ◽  
Long Term Experience ◽  
Early Detection And Prevention

The article summarizes the long-term experience of practical application of domestic breakthrough technologies of preventive personalized medicine for laboratory diagnostics of a wide range of socially significant non-infectious diseases. Conceptual approaches to the formation of an integrated program for early detection and prevention of civilization diseases based on these technologies are given. A vision of the prospects for the development of this area in domestic and foreign medicine has been formed.

QSAR Analysis of Selected Antimicrobial Structures Belonging to Nitro-derivatives of Heterocyclic Compounds

2020 ◽  
Vol 17 (2) ◽  
pp. 214-225 ◽  
Author(s):  
Piotr Kawczak ◽  
Leszek Bober ◽  
Tomasz Bączek
Keyword(s):  
Antimicrobial Activity ◽  
Heterocyclic Compounds ◽  
Molecular Descriptors ◽  
Microbiological Activity ◽  
Activity Data ◽  
Qsar Analysis ◽  
Qsar Models ◽  
Nitro Derivatives ◽  
Semi Empirical ◽  
Derivatives Of

Background: Nitro-derivatives of heterocyclic compounds were used as active agents against pathogenic microorganisms. A set of 4- and 5-nitroimidazole derivatives exhibiting antimicrobial activity was analyzed with the use of Quantitative Structure-Activity Relationships (QSAR) method. The study included compounds used both in documented treatment and those described as experimental. Objective: The purpose of this study was to demonstrate the common and differentiating characteristics of the above-mentioned chemical compounds alike physicochemically as well as pharmacologically based on the quantum chemical calculations and microbiological activity data. Methods: During the study PCA and MLR analysis were performed, as the types of proposed chemometric approach. The semi-empirical and ab initio level of in silico molecular modeling was performed for calculations of molecular descriptors. Results: QSAR models were proposed based on chosen descriptors. The relationship between the nitro-derivatives structure and microbiological activity data was able to class and describe the antimicrobial activity with the use of statistically significant molecular descriptors. Conclusion: The applied chemometric approaches revealed the influential features of the tested structures responsible for the antimicrobial activity of studied nitro-derivatives.

Elaboration of Novel TTK1 Inhibitory Leads via QSAR-Guided Selection of Crystallographic Pharmacophores Followed By In vitro Assay

2020 ◽  
Vol 16 ◽  
Author(s):  
Mahmoud A. Al-Sha'er ◽  
Mutasem O. Taha
Keyword(s):  
Standard Error ◽  
Qsar Model ◽  
Qsar Modeling ◽  
Vitro Assay ◽  
Physicochemical Descriptors ◽  
Qsar Models ◽  
Ic50 Values ◽  
Pharmacophore Hypotheses ◽  
Selection Of

Introduction: Tyrosine threonine kinase (TTK1) is a key regulator of chromosome segregation. TTK targeting received recent concern for the enhancement of possible anticancer therapies. Objective: In this regard we employed our well-known method of QSAR-guided selection of best crystallographic pharmacophore(s) to discover considerable binding interactions that anchore inhibitors into TTK1 binding site. Method:Sixtyone TTK1 crystallographic complexes were used to extract 315 pharmacophore hypotheses. QSAR modeling was subsequently used to choose a single crystallographic pharmacophore that when combined with other physicochemical descriptors elucidates bioactivity discrepancy within a list of 55 miscellaneous inhibitors. Results: The best QSAR model was robust and predictive (r2(55) = 0.75, r2LOO = 0.72 , r2press against external testing list of 12 compounds = 0.67), Standard error of estimate (training set) (S)= 0.63 , Standard error of estimate (testing set)(Stest) = 0.62. The resulting pharmacophore and QSAR models were used to scan the National Cancer Institute (NCI) database for new TTK1 inhibitors. Conclusion: Five hits confirmed significant TTK1 inhibitory profiles with IC50 values ranging between 11.7 and 76.6 micM.

Infrared spectra and substituent effects in 2-(3-, and 4-substituted phenylmethylene)-1,3-cycloheptanediones

1983 ◽  
Vol 48 (2) ◽  
pp. 586-595 ◽  
Author(s):  
Alexander Perjéssy ◽  
Pavol Hrnčiar ◽  
Ján Šraga
Keyword(s):  
Substituent Effects ◽  
Phenyl Group ◽  
Wave Number ◽  
Vibrational Coupling ◽  
Wave Numbers ◽  
Stretching Vibration ◽  
Stretching Vibrations ◽  
The Relationship ◽  
Derivatives Of ◽  
Effect Of Structure

The wave numbers of the fundamental C=O and C=C stretching vibrations, as well as that of the first overtone of C=O stretching vibration of 2-(3-, and 4-substituted phenylmethylene)-1,3-cycloheptanediones and 1,3-cycloheptanedione were measured in tetrachloromethane and chloroform. The spectral data were correlated with σ+ constants of substituents attached to phenyl group and with wave number shifts of the C=O stretching vibration of substituted acetophenones. The slope of the linear dependence ν vs ν+ of the C=C stretching vibration of the ethylenic group was found to be more than two times higher than that of the analogous correlation of the C=O stretching vibration. Positive values of anharmonicity for asymmetric C=O stretching vibration can be considered as an evidence of the vibrational coupling in a cyclic 1,3-dicarbonyl system similarly, as with derivatives of 1,3-indanedione. The relationship between the wave numbers of the symmetric and asymmetric C=O stretching vibrations indicates that the effect of structure upon both vibrations is symmetric. The vibrational coupling in 1,3-cycloheptanediones and the application of Seth-Paul-Van-Duyse equation is discussed in relation to analogous results obtained for other cyclic 1,3-dicarbonyl compounds.

Private and Public Law

2020 ◽  
pp. 574-592
Author(s):  
Thomas W. Merrill
Keyword(s):  
Law And Economics ◽  
Public Law ◽  
Private Law ◽  
General Criterion ◽  
The Public ◽  
Private Ordering ◽  
Public Rights ◽  
Private And Public ◽  
The Relationship ◽  
Derivatives Of

This chapter explores the relationship between private and public law. In civil law countries, the public-private distinction serves as an organizing principle of the entire legal system. In common law jurisdictions, the distinction is at best an implicit design principle and is used primarily as an informal device for categorizing different fields of law. Even if not explicitly recognized as an organizing principle, however, it is plausible that private and public law perform distinct functions. Private law supplies the tools that make private ordering possible—the discretionary decisions that individuals make in structuring their lives. Public law is concerned with providing public goods—broadly defined—that cannot be adequately supplied by private ordering. In the twentieth and twenty-first centuries, various schools of thought derived from utilitarianism have assimilated both private and public rights to the same general criterion of aggregate welfare analysis. This has left judges with no clear conception of the distinction between private and public law. Another problematic feature of modern legal thought is a curious inversion in which scholars who focus on fields of private law have turned increasingly to law and economics, one of the derivatives of utilitarianism, whereas scholars who concern themselves with public law are increasingly drawn to new versions of natural rights thinking, in the form of universal human rights.

scholarly journals Polymorphic Iterable Sequential Effect Systems

2021 ◽  
Vol 43 (1) ◽  
pp. 1-79
Author(s):  
Colin S. Gordon
Keyword(s):  
Algebraic Structure ◽  
Position Effect ◽  
Type Systems ◽  
Sequential Effect ◽  
Prior Work ◽  
Sequential Effects ◽  
Wide Range ◽  
The Relationship ◽  
Categorical Semantics

Effect systems are lightweight extensions to type systems that can verify a wide range of important properties with modest developer burden. But our general understanding of effect systems is limited primarily to systems where the order of effects is irrelevant. Understanding such systems in terms of a semilattice of effects grounds understanding of the essential issues and provides guidance when designing new effect systems. By contrast, sequential effect systems—where the order of effects is important—lack an established algebraic structure on effects. We present an abstract polymorphic effect system parameterized by an effect quantale—an algebraic structure with well-defined properties that can model the effects of a range of existing sequential effect systems. We define effect quantales, derive useful properties, and show how they cleanly model a variety of known sequential effect systems. We show that for most effect quantales, there is an induced notion of iterating a sequential effect; that for systems we consider the derived iteration agrees with the manually designed iteration operators in prior work; and that this induced notion of iteration is as precise as possible when defined. We also position effect quantales with respect to work on categorical semantics for sequential effect systems, clarifying the distinctions between these systems and our own in the course of giving a thorough survey of these frameworks. Our derived iteration construct should generalize to these semantic structures, addressing limitations of that work. Finally, we consider the relationship between sequential effects and Kleene Algebras, where the latter may be used as instances of the former.

Age-Dependency of Total Tau in the Cerebrospinal Fluid Is Corrected by Amyloid-β 1–40: A Correlational Study in Healthy Adults

2021 ◽  
pp. 1-8
Author(s):  
Paul Theo Zebhauser ◽  
Achim Berthele ◽  
Marie-Sophie Franz ◽  
Oliver Goldhardt ◽  
Janine Diehl-Schmid ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Healthy Adults ◽  
Tau Proteins ◽  
Clinical Settings ◽  
Inclusion Criteria ◽  
Total Tau ◽  
Potential Marker ◽  
Wide Range ◽  
The Relationship

Background: Tau proteins are established biomarkers of neuroaxonal damage in a wide range of neurodegenerative conditions. Although measurement of total-Tau in the cerebrospinal fluid is widely used in research and clinical settings, the relationship between age and total-Tau in the cerebrospinal fluid is yet to be fully understood. While past studies reported a correlation between age and total-Tau in the cerebrospinal fluid of healthy adults, in clinical practice the same cut-off value is used independently of patient’s age. Objective: To further explore the relationship between age and total-Tau and to disentangle neurodegenerative from drainage-dependent effects. Methods: We analyzed cerebrospinal fluid samples of 76 carefully selected cognitively healthy adults and included amyloid-β 1–40 as a potential marker of drainage from the brain’s interstitial system. Results: We found a significant correlation of total-Tau and age, which was no longer present when correcting total-Tau for amyloid-β 1–40 concentrations. These findings were replicated under varied inclusion criteria. Conclusion: Results call into question the association of age and total-Tau in the cerebrospinal fluid. Furthermore, they suggest diagnostic utility of amyloid-β 1–40 as a possible proxy for drainage-mechanisms into the cerebrospinal fluid when interpreting biomarker concentrations for neurodegenerative diseases.

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