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1.
Eur Phys J C Part Fields ; 81(4): 322, 2021.
Article in English | MEDLINE | ID: mdl-34720713

ABSTRACT

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE's sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

2.
Phys Rev Lett ; 77(16): 3299-3302, 1996 Oct 14.
Article in English | MEDLINE | ID: mdl-10062186
3.
Phys Rev C Nucl Phys ; 48(5): 2537-2540, 1993 Nov.
Article in English | MEDLINE | ID: mdl-9969116
4.
Biofizika ; 30(5): 833-6, 1985.
Article in Russian | MEDLINE | ID: mdl-3876849

ABSTRACT

Fluorescent probe-cation 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM) can be accumulated in mitochondria of rat thymus lymphocytes. A method is proposed for microfluorometric measuring of DSM concentrations ratio inside the thymocyte mitochondria and in the external medium. This method requires no knowledge about the cell and mitochondria volume, the number of accumulated probe and formation of ionic gradients in the cell by carriers. DSM concentration in energisized mitochondria of the thymocyte exceeds its concentration in the external medium by 10(4) times. This corresponds to the free energy accumulated by DSM equaling 5.2 +/- 0.2 kcal/mole. If such work on the probe accumulation is performed by the electrostatic fields on the plasma and mitochondrial cell membranes, the sum of the potentials of these two fields is 230 +/- 10 mV.


Subject(s)
Fluorescent Dyes , Mitochondria/metabolism , T-Lymphocytes/metabolism , Animals , Cations , Energy Metabolism , In Vitro Techniques , Pyridinium Compounds , Rats , Spectrometry, Fluorescence
5.
Bioorg Khim ; 11(1): 113-25, 1985 Jan.
Article in Russian | MEDLINE | ID: mdl-3986003

ABSTRACT

The conformational possibilities for sugar components of cardiac monoglycosides have been analyzed. A comparison of spatial disposition of oxygen atoms in the energetically allowed conformations of these residues permitted unambiguous determination of 1) monosaccharide bioactive conformations; 2) their functional groups involved in the receptor binding; 3) coordinates of the region wherein the oxygen atom should be accomodated in order to be bound to the receptor. It was shown that the conformational lability and the presence of several oxygen-containing groups in the first monosaccharide residue underlie the possibility for coexistance of several productive conformations. The rules for qualitative predictions of the carbohydrate contribution into biological activity of cardiac glycosides were formulated. A number of monosaccharide residues were distinguished that should have either favorable or unfavorable effects on the biological activity of cardenolides.


Subject(s)
Cardiac Glycosides/metabolism , Monosaccharides/metabolism , Receptors, Drug/metabolism , Sodium-Potassium-Exchanging ATPase , Humans , In Vitro Techniques , Models, Biological , Molecular Conformation , Myocardium/metabolism , Structure-Activity Relationship
6.
Mol Biol (Mosk) ; 18(6): 1606-16, 1984.
Article in Russian | MEDLINE | ID: mdl-6521738

ABSTRACT

The kinetics of interaction of antitumor glycoside antibiotic olivomycin with DNA has been investigated. The existence of two relaxation times in the experimental kinetics curves indicates that two types of antibiotic--DNA complex are formed. We have measured the rate constants of association and dissociation processes and determined their temperature dependences. It is suggested, that one of the complex form results from nonspecific interaction between glycoside residues of the antibiotic molecule and sugar-phosphate backbone of DNA whereas the other type of complex exhibits a pronounced specificity for GC-rich regions on DNA. The binding specificity probably results from formation of a H-bond between the antibiotic chromophore ring and guanine 2-amino group. A stereochemical model for olivomycin-DNA complex is proposed. According to this model the antibiotic chromophore and glycoside residues are located in the narrow groove of DNA.


Subject(s)
DNA/metabolism , Olivomycins/metabolism , In Vitro Techniques , Kinetics , Models, Molecular , Stereoisomerism , Temperature
7.
Antibiotiki ; 29(3): 208-14, 1984 Mar.
Article in Russian | MEDLINE | ID: mdl-6732207

ABSTRACT

The fluorescent characteristics of rubomycin as dependent on the environmental conditions (different solvents, acidity of the medium, ionic strength) were studied. A model explaining suppression of the rubomycin fluorescence on the antibiotic interaction with DNA is described. The model confirmed intercalation and preferable binding with purines as compared to pyrimidines. The constants of rubomycin and aglycone interaction with DNA were determined. The use of the antibiotic concentrations less than 10(-6) M allowed the determination of a higher constant characterizing "strong binding". The nonlinearity of the curve of DNA titration with the antibiotic plotted on the Scatchard coordinates indicates the heterogeneity of the binding sites. The constant of the aglycone binding to DNA was approximately 2 orders lower at the same number of the binding sites in one molecule. The decrease in the constant of rubomycin interaction with DNA of an increased ionic strength and the low constant of the aglycone interaction with DNA as compared to that of the antibiotic itself confirmed the suggestion that there formed a bond between the amino sugar and the phosphate groups.


Subject(s)
DNA/pharmacology , Daunorubicin/pharmacology , Naphthacenes/pharmacology , Animals , Binding Sites/drug effects , DNA/analysis , Daunorubicin/analysis , Dose-Response Relationship, Drug , Drug Interactions , Fluorescence , Free Radicals , Hydrogen-Ion Concentration , Male , Naphthacenes/analysis , Salmon , Solutions , Spectrometry, Fluorescence
8.
Bioorg Khim ; 9(8): 1112-27, 1983 Aug.
Article in Russian | MEDLINE | ID: mdl-6680307

ABSTRACT

The calculations have been performed to determine conformations and assess electronic structure of 44 compounds with known cardiotonic activity. Atoms O(3), C(13) and C(18) of all conformations were superimposed on the same atoms of digitoxigenin, and the relationship between the spatial disposition of the side chain carbonyl oxygen and biological activity of the respective compounds was examined. The most active cardiotonics are shown to share very similar topography. B- or A-conformations are active for cardenolides or bufadienolides, respectively. Some correlations between the structure and cardiotonic activity were disclosed. The principles for cardiotonic drug design are formulated and some formulas of new potentially active compounds are suggested.


Subject(s)
Cardiac Glycosides , Chemical Phenomena , Chemistry , Models, Molecular , Molecular Conformation , Structure-Activity Relationship
9.
Antibiotiki ; 28(5): 346-51, 1983 May.
Article in Russian | MEDLINE | ID: mdl-6881947

ABSTRACT

Olivomycin (I) is a fluorescent probe which is highly specific with respect to DNA. Its luminescence-absorption properties were studied at various pH values, in different solvents and in the presence of Mg2+ and DNA in the solutions. The presence of 2 tautomeric forms of I was suggested on the basis of the study (forms A and B having different characteristics with respect to the absorption spectra and fluorescence). Transition between forms A and B occurred in both the basic and the excited states. The quantitative ratio of the forms depended on the character of the environment. The presence of the 2 forms of I should be considered in analysis of the drug pharmacokinetics and pharmacodynamics.


Subject(s)
DNA/analysis , Olivomycins/analysis , Cations, Divalent/pharmacology , Drug Combinations , Hydrogen-Ion Concentration , Luminescent Measurements , Magnesium/pharmacology , Solvents/pharmacology , Spectrometry, Fluorescence
10.
Biofizika ; 27(2): 329-31, 1982.
Article in Russian | MEDLINE | ID: mdl-7074162

ABSTRACT

When staining intact erythrocytes with DSM no quenching of its fluorescence with hems in the membrane was observed. The positively charged fluorescent probe DSM is proposed for estimating a relative change of the charge in phospholipid membrane surface, in erythrocyte ghosts, and in the membranes of some non-hemolyzed erythrocytes. Charged ligands induced a change of the bound probe fluorescence corresponding to the changes in the value and symbol of the charge of the membrane surface. By means of DSM and negatively charged probe of ANS interaction between dimedrol and intact erythrocytes and their ghosts was studied. It has been stated that therewith the ANS binding with the erythrocyte membrane increases, while DSM binding decreases, which points to a decrease of efficient negative charge of the cell surface in the presence of dimedrol. On the basis of cytofluorometric data the binding constant of dimedrol with the membrane of intact erythrocytes was determined.


Subject(s)
Erythrocyte Membrane/physiology , Erythrocytes/physiology , Liposomes , Membrane Lipids/blood , Phospholipids/blood , Anilino Naphthalenesulfonates , Humans , Kinetics , Microscopy, Fluorescence
11.
Antibiotiki ; 26(12): 906-12, 1981 Dec.
Article in Russian | MEDLINE | ID: mdl-7325623

ABSTRACT

The study on the mechanisms of olivomycin and olivin interaction with the magnesium ions showed that formation of the olivomycin complexes with Mg2+ involved 2 stages. At the first (rapid) stage Mg2+ is attached to keto-oxygen of the aglycone polycyclic part. At the second (slow) stage the complex is relaxed into the stable state with a more compact configuration. the equilibrium constants (Ce) of the main processes of olivomycin and olivin interaction with Mg2+ were determined. In the first case Ce = 3 . 10(3) M+1 and in the second case Ce = 1.6 . 10(2) M-1. It was shown that the geometric and optic characteristics of the complexes were consistently related: formation of the stable complex was accompanied by a 10-time decrease in the fluorescence quantum efficiency.


Subject(s)
Magnesium/pharmacology , Olivomycins/pharmacology , Anthracenes/analysis , Anthracenes/pharmacology , Cations, Divalent/pharmacology , Drug Interactions , Kinetics , Olivomycins/analysis , Spectrometry, Fluorescence , Spectrophotometry, Atomic
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