Testing the hypothesis that amphiphilic antineoplastic lipid analogues act through reduction of membrane curvature elastic stress

The alkyllysophospholipid (ALP) analogues Mitelfosine and Edelfosine are anticancer drugs whose mode of action is still the subject of debate. It is agreed that the primary interaction of these compounds is with cellular membranes. Furthermore, the membrane-associated protein CTP: phosphocholine cytidylyltransferase (CCT) has been proposed as the critical target. We present the evaluation of our hypothesis that ALP analogues disrupt membrane curvature elastic stress and inhibit membrane-associated protein activity (e.g. CCT), ultimately resulting in apoptosis. This hypothesis was tested by evaluating structure–activity relationships of ALPs from the literature. In addition we characterized the lipid typology, cytotoxicity and critical micelle concentration of novel ALP analogues that we synthesized. Overall we find the literature data and our experimental data provide excellent support for the hypothesis, which predicts that the most potent ALP analogues will be type I lipids.

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Cationic Type I Amphiphiles As Modulators of Membrane Curvature Elastic Stress in Vivo

Langmuir ◽

10.1021/la8017612 ◽

2008 ◽

Vol 24 (20) ◽

pp. 11743-11751 ◽

Cited By ~ 20

Author(s):

Marcus K. Dymond ◽

George S. Attard

Keyword(s):

Elastic Stress ◽

Membrane Curvature ◽

Type I

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Hybrid Imidazole-Pyridine Derivatives: An Approach to Novel Anticancer DNA Intercalators

Current Medicinal Chemistry ◽

10.2174/0929867326666181220094229 ◽

2020 ◽

Vol 27 (1) ◽

pp. 154-169 ◽

Cited By ~ 7

Author(s):

Claudiu N. Lungu ◽

Bogdan Ionel Bratanovici ◽

Maria Mirabela Grigore ◽

Vasilichia Antoci ◽

Ionel I. Mangalagiu

Keyword(s):

Experimental Data ◽

Antimicrobial Properties ◽

Qsar Model ◽

Therapeutic Effectiveness ◽

Computational Results ◽

Pyridine Derivatives ◽

Quadruplex Dna ◽

Dna Intercalators ◽

Structure Activity ◽

G Quadruplex

Lack of specificity and subsequent therapeutic effectiveness of antimicrobial and antitumoral drugs is a common difficulty in therapy. The aim of this study is to investigate, both by experimental and computational methods, the antitumoral and antimicrobial properties of a series of synthesized imidazole-pyridine derivatives. Interaction with three targets was discussed: Dickerson-Drew dodecamer (PDB id 2ADU), G-quadruplex DNA string (PDB id 2F8U) and DNA strain in complex with dioxygenase (PDB id 3S5A). Docking energies were computed and represented graphically. On them, a QSAR model was developed in order to further investigate the structure-activity relationship. Results showed that synthesized compounds have antitumoral and antimicrobial properties. Computational results agreed with the experimental data.

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Modulation of CTP:phosphocholine cytidylyltransferase by membrane curvature elastic stress

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.160260697 ◽

2000 ◽

Vol 97 (16) ◽

pp. 9032-9036 ◽

Cited By ~ 194

Author(s):

G. S. Attard ◽

R. H. Templer ◽

W. S. Smith ◽

A. N. Hunt ◽

S. Jackowski

Keyword(s):

Elastic Stress ◽

Membrane Curvature ◽

Ctp:Phosphocholine Cytidylyltransferase

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In Reply: Combinations of Antibiotics

PEDIATRICS ◽

10.1542/peds.26.3.499 ◽

1960 ◽

Vol 26 (3) ◽

pp. 499-499

Author(s):

Robert J. Haggerty

Keyword(s):

Experimental Data ◽

Clinical Data ◽

Experimental Work ◽

The Subject ◽

Antimicrobial Combinations

I am delighted to have Dr. Jawetz again bring to the attention of your readers his definitive work on the subject of antimicrobial combinations. We certainly have no quarrel with the points he reiterates. Our choice of words, "It is not clear why these results are at variance with the experimental data of Jawetz or the clinical data of Lepper and Dowling," was probably unfortunate, for Dr. Jawetz points out why the results did differ from his experimental work.

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Psychophysical interactions with a double-slit interference pattern: Exploratory evidence of a causal influence

Physics Essays ◽

10.4006/0836-1398-34.1.79 ◽

2021 ◽

Vol 34 (1) ◽

pp. 79-88

Author(s):

Dean Radin ◽

Helané Wahbeh ◽

Leena Michel ◽

Arnaud Delorme

Keyword(s):

Experimental Data ◽

Interference Pattern ◽

Type I Error ◽

Human Mind ◽

The Other ◽

Type I ◽

Fringe Visibility ◽

Future Studies ◽

Before And After ◽

Double Slit

An experiment we conducted from 2012 to 2013, which had not been previously reported, was designed to explore possible psychophysical effects resulting from the interaction of a human mind with a quantum system. Participants focused their attention toward or away from the slits in a double-slit optical system to see if the interference pattern would be affected. Data were collected from 25 people in individual half-hour sessions; each person repeated the test ten times for a total of 250 planned sessions. “Sham” sessions designed to mimic the experimental sessions without observers present were run immediately before and after as controls. Based on the planned analysis, no evidence for a psychophysical effect was found. Because this experiment differed in two essential ways from similar, previously reported double-slit experiments, two exploratory analyses were developed, one based on a simple spectral analysis of the interference pattern and the other based on fringe visibility. For the experimental data, the outcome supported a pattern of results predicted by a causal psychophysical effect, with the spectral metric resulting in a 3.4 sigma effect (p = 0.0003), and the fringe visibility metric resulting in 7 of 22 fringes tested above 2.3 sigma after adjustment for type I error inflation, with one of those fringes at 4.3 sigma above chance (p = 0.00001). The same analyses applied to the sham data showed uniformly null outcomes. Other analyses exploring the potential that these results were due to mundane artifacts, such as fluctuations in temperature or vibration, showed no evidence of such influences. Future studies using the same protocols and analytical methods will be required to determine if these exploratory results are idiosyncratic or reflect a genuine psychophysical influence.

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Modified methodology of computation of admissible continuous currents of plain conductors of overhead transmission lines and catenaries

Elektrichestvo ◽

10.24160/0013-5380-2021-2-36-43 ◽

2021 ◽

Vol 2 (2) ◽

pp. 36-43

Author(s):

Evgeniy P. FIGURNOV ◽

◽

Yury I. ZHARKOV ◽

Valeriy I. KHARCHEVNIKOV ◽

◽

...

Keyword(s):

Heat Transfer ◽

Experimental Data ◽

Transmission Lines ◽

Power Transmission ◽

Convection Heat Transfer ◽

Heating And Cooling ◽

Continuous Current ◽

The Subject ◽

The Common ◽

Overhead Power Transmission Line

Methodology provided summarizes published, original and foreign theoretic and experimental data on the subject of heating and cooling of standard and shaped conductors of overhead power transmission line and uses those of them which are most affected to fundamental heat-transfer laws. Computation surface area of standard and shaped wire formulas are given. The common formula of convection heat transfer coefficient is provided, based on wind speed and direction, concerning antiicing mode. Parameters of this formula do not coincide with those existing, as they are based on experimental data on standard and shaped conductors but not on round tubes. Formula of computation of heat transfer power under the influence of solar radiation is given. Summarized formula of admissible continuous current computation is given, all the components have detailed description in the article.

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Aggregation of Surfactants in Hydrocarbons. Incompatibility of the Critical Micelle Concentration Concept with Experimental Data

Micellization, Solubilization, and Microemulsions ◽

10.1007/978-1-4684-2346-4_23 ◽

1977 ◽

pp. 445-454 ◽

Cited By ~ 8

Author(s):

A. S. Kertes

Keyword(s):

Experimental Data ◽

Critical Micelle Concentration

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Application of descriptive statistics in analysis of experimental data

Veterinarski glasnik ◽

10.2298/vetgl0802085m ◽

2008 ◽

Vol 62 (1-2) ◽

pp. 85-95

Author(s):

Milorad Mirilovic ◽

Ivana Pejin

Keyword(s):

Experimental Data ◽

Statistical Analysis ◽

Standard Deviation ◽

Arithmetic Mean ◽

Descriptive Statistics ◽

Qualitative Investigation ◽

Scientific Methods ◽

The Subject ◽

Variation Interval ◽

Descriptive Statistical Analysis

Statistics today represent a group of scientific methods for the quantitative and qualitative investigation of variations in mass appearances. In fact, statistics present a group of methods that are used for the accumulation, analysis, presentation and interpretation of data necessary for reaching certain conclusions. Statistical analysis is divided into descriptive statistical analysis and inferential statistics. The values which represent the results of an experiment, and which are the subject of observation of a certain occurrence, are called parameters and they are divided into descriptive and numerical. All numerical parameters are divided into non-continuous and continuous. The graphic presentation of the distribution of frequencies can be by poligon or histogram. The most frequently applied descriptive statistical methods are: arithmetic mean, standard deviation, standard error of arithmetic mean, variation coefficient, and variation interval.

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Convolution and deconvolution: two mathematical tools to help performing tests in research and industry

International Journal of Metrology and Quality Engineering ◽

10.1051/ijmqe/2021004 ◽

2021 ◽

Vol 12 ◽

pp. 6

Author(s):

Jean-Pierre Fanton

Keyword(s):

Experimental Data ◽

Inverse Problem ◽

Electrical Energy ◽

Integral Transforms ◽

Physical Measurement ◽

Photographic Images ◽

Test Standards ◽

Energy Networks ◽

The Third ◽

The Subject

The concepts of convolution and deconvolution are well known in the field of physical measurement. In particular, they are of interest in the field of metrology, since they can positively influence the performance of the measurement. Numerous mathematical models and computer developments dedicated to convolution and deconvolution have emerged, enabling a more efficient use of experimental data; this in sectors as different as biology, astronomy, manufacturing and energy industries. The subject finds today a new topicality because it has been made accessible to a large public for applications such as processing photographic images. The purpose of this paper is to take into account some recent evolutions such as the introduction of convolution methods in international test standards. Thus, its first part delivers a few reminders of some associated definitions. They concern linear systems properties, and integral transforms. If convolution, in most cases, does not create major calculation problems, deconvolution on the contrary is an inverse problem, and as such needs more attention. The principles of some of the methods available today are exposed. In the third part, illustrations are given on recent examples of applications, belonging to the domain of electrical energy networks and photographic enhancement.

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