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1-Substituted 4-perylen-2(3)-yl-1,2,3-triazoles, easily accessible by ‘click’ reaction and combining in one molecule a polyaromatic unit and a nitrogen heterocycle, were found to strongly inhibit the reproduction of enveloped viruses. 5-[4-(Perylen-3-yl)-1,2,3-triazol-1-yl]-uridine and 2-[1-(2-hydroxyethyl)-1,2,3-triazol-4-yl]perylene show EC 50 of 0.031 and 0.023 μM, respectively, against tick-borne encephalitis virus (TBEV). Remarkably, the nucleoside unit appears to be not essential for antiviral activity. These results provide deeper understanding of structural basis of activity for this new class of antivirals. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that oxidative modifications of guanine (7,8-dihydro-8-oxoguanine, 8-oxoG) can affect cellular functions. 7,8-Dihydro-8-oxoadenine (8-oxoA) is another abundant paradigmatic ambiguous nucleobase but findings reported on the mutagenicity of 8-oxoA in bacterial and eukaryotic cells are incomplete and contradictory. Although several genotoxic studies have demonstrated the mutagenic potential of 8-oxoA in eukaryotic cells, very little biochemical and bioinformatics data about the mechanism of 8-oxoA-induced mutagenesis are available. In this review, we discuss dual coding properties of 8-oxoA, summarize historical and recent genotoxicity and biochemical studies, and address the main protective cellular mechanisms of response to 8-oxoA. We also discuss the available structural data for 8-oxoA bypass by different DNA polymerases as well as the mechanisms of 8-oxoA recognition by DNA repair enzymes. [ABSTRACT FROM AUTHOR]

Rose Bengal (RB) is an anionic xanthene dye with multiple useful biological features, including photosensitization properties. RB was studied extensively as a photosensitizer, mostly for antibacterial and antitumor photodynamic therapy (PDT). The application of RB to virus inactivation is rather understudied, and no RB derivatives have been developed as antivirals. In this work, we used a synthetic approach based on a successful design of photosensitizing antivirals to produce RB derivatives for virus photoinactivation. A series of n-alkyl-substituted RB derivatives was synthesized and evaluated as antiviral photosensitizers. The compounds exhibited similar 1O2 generation rate and efficiency, but drastically different activities against SARS-CoV-2, CHIKV, and HIV; with comparable cytotoxicity for different cell lines. Submicromolar-to-subnanomolar activities and high selectivity indices were detected for compounds with C4-6 alkyl (SARS-CoV-2) and C6-8 alkyl (CHIKV) chains. Spectrophotometric assessment demonstrates low aqueous solubility for C8-10 congeners and a significant aggregation tendency for the C12 derivative, possibly influencing its antiviral efficacy. Initial evaluation of the synthesized compounds makes them promising for further study as viral inactivators for vaccine preparations. [ABSTRACT FROM AUTHOR]

Perylene-based compounds are attracting significant attention due to their high broad-spectrum antiviral activity against enveloped viruses. Despite unambiguous results of in vitro studies and high selectivity index, the poor water solubility of these compounds prevented in vivo evaluation of their antiviral properties. In this work, we synthesized a series of compounds with a perylene pharmacophore bearing positively charged substituents to improve the aqueous solubility of this unique type of antivirals. Three types of charged groups were introduced: (1) quaternary morpholinium salts (3a–b); (2) a 2′-O-l-valinyl-uridine hydrochloride residue (8), and (3) a 3-methylbenzothiazolium cation (10). The synthesized compounds were evaluated based both on antiviral properties in vitro (CHIKV, SARS-CoV-2, and IAV) and on solubility in aqueous media. Compound 10 has the greatest aqueous solubility, making it preferable for pre-evaluation by intragastrical administration in a mouse model of lethal influenza pneumonia. The results indicate that the introduction of a positively charged group is a viable strategy for the design of drug candidates with a perylene scaffold for in vivo studies. [ABSTRACT FROM AUTHOR]

G4-stabilizing ligands are now being considered as anticancer, antiviral and antibacterial agents. Phenoxazine is a promising scaffold for the development of G4 ligands. Here, we profiled two known phenoxazine-based nucleoside analogs and five new nucleoside and non-nucleoside derivatives against G4 targets from telomere repeats and the KIT promoter region. Leading new derivatives exhibited remarkably high G4-stabilizing effects (comparable or superior to the effects of the commonly used selective G4 ligands PDS and NMM) and selectivity toward G4s over duplex (superior to BRACO-19). All phenoxazine-based ligands inhibited cellular metabolic activity. The phenoxazine derivatives were particularly toxic for lung adenocarcinoma cells A549' and human liver cancer cells HepG2 (CC 50 of the nucleoside analogues in the nanomolar range), but also affected breast cancer cells MCF7, as well as immortalized fibroblasts VA13 and embryonic kidney cells HEK293t (CC 50 in the micromolar range). Importantly, the CC 50 values varied mostly in accordance with G4-binding affinities and G4-stabilizing effects, and the phenoxazine derivatives localized in the cell nuclei, which corroborates G4-mediated mechanisms of action. • Phenoxazine-based derivatives were probed as G4 ligands. • Some derivatives exhibited remarkably high G4-stabilizing effects and selectivity. • All phenoxazine-based ligands inhibited cellular metabolic activity. • The ligands were particularly toxic for lung adenocarcinoma cells. • Localization in the cell nuclei corroborated G4-mediated mechanisms of action. [ABSTRACT FROM AUTHOR]

A benzothiazole-substituted derivative (X) of 1,3-diaza-2-oxophenoxazine was evaluated with respect to its ability to engage in Ag(I)-mediated homo base pair formation in two different DNA duplexes. The metal binding was determined by a combination of temperature-dependent UV spectroscopy, CD spectroscopy, and fluorescence spectroscopy, indicating the incorporation of two Ag(I) ions to generate a dinuclear X–Ag(I)2–X base pair. Interestingly, a luminescence increase was observed upon metal binding. Theoretical luminescence spectra were calculated using time-dependent density functional theory (TDDFT) for all possible Ag(I)-mediated X : X base pair geometries to identify the species responsible for the increase in luminescence. The study shows that even bulky non-planar artificial nucleobases can be applied to form stabilizing metal-mediated base pairs. [ABSTRACT FROM AUTHOR]

The lack of high throughput screening (HTS) techniques for small molecules that stabilize DNA iMs limits their development as perspective drug candidates. Here we showed that fluorescence monitoring for probing the effects of ligands on the iM stability using the FAM–BHQ1 pair provides incorrect results due to additional dye-related interactions. We developed an alternative system with fluorescent phenoxazine pseudonucleotides in loops that do not alter iM unfolding. At the same time, the fluorescence of phenoxazine residues is sensitive to iM unfolding that enables accurate evaluation of ligand-induced changes of iM stability. Our results provide the basis for new approaches for HTS of iM ligands. [ABSTRACT FROM AUTHOR]

1,3-Diaza-2-oxophenoxazine (X) has been introduced as a ligand in silver(I)-mediated base pairing in a parallel DNA duplex. This fluorescent cytosine analog is capable of forming stabilizing X–Ag(I)–X and X–Ag(I)–C base pairs in DNA duplexes, as confirmed by temperature-dependent UV spectroscopy and luminescence spectroscopy. DFT calculations of the silver(I)-mediated base pairs suggest the presence of a synergistic hydrogen bond. Molecular dynamics (MD) simulations of entire DNA duplexes nicely underline the geometrical flexibility of these base pairs, with the synergistic hydrogen bond facing either the major or the minor groove. Upon silver(I) binding to the X:X or X:C base pairs, the luminescence emission maximum experiences a red shift from 448 to 460 nm upon excitation at 370 nm. Importantly, the luminescence of the 1,3-diaza-2-oxophenoxazine ligand is not quenched significantly upon binding a silver(I) ion. In fact, the luminescence intensity even increases upon formation of a X–Ag(I)–C base pair, which is expected to be beneficial for the development of biosensors. As a consequence, the silver(I)-mediated phenoxazinone base pairs represent the first strongly fluorescent metal-mediated base pairs. [ABSTRACT FROM AUTHOR]

Analogs of benzothiazole orange (BO) with one, two or three methylbenzothiazolylmethylidene substituents in the 1-methylpyridinium ring were obtained from the respective picolinium, lutidinium or collidinium salts. Fluorescence parameters of the known and new dyes in complexes with various DNA structures, including G-quadruplexes (G4s) and i-motifs (IMs), were analyzed. All dyes efficiently distinguished G4s and ss-DNA. The bi- and tri-substituted derivatives had basically similar distributions of relative fluorescence intensities. The mono-substituted derivatives exhibited enhanced sensitivity to parallel G4s. All dyes were particularly sensitive to a G4 structure with an additional duplex module (the thrombin-binding aptamer TBA31), presumably due to a distinctive binding mode (interaction with the junction between the two modules). In particular, BO showed a strong (160-fold) enhancement in fluorescence quantum yield in complex with TBA31 compared to the free dye. The fluorescence quantum yields of the 2,4-bisubstituted derivative in complex with well-characterized G4s from oncogene promoters were in the range of 0.04–0.28, i.e. comparable to those of ThT. The mono/bi-substituted derivatives should be considered as possible light-up probes for G4 formation. • Analogs of benzothiazole orange with 1, 2 or 3 substituents in the pyridinium ring were obtained. • Mono/bi-substituted dyes have the potential for use as light-up probes for G4 formation. • 2,4-substituted analog could be used in FID assays for profiling of G4 ligands. • 2,4-substituted analog enhances melting temperatures of hybrid and parallel G4s in the presence of dsDNA. • All dyes were particularly sensitive to a TBA31 (G4 structure with an additional duplex module). [ABSTRACT FROM AUTHOR]

Abstract The phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism, etc. Here we present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human cytomegalovirus, enveloped RNA tick-borne encephalitis virus (TBEV), and non-enveloped RNA enteroviruses. Studied compounds were effective against DNA and RNA viruses reproduction in cell culture. 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication with superior activity against wild type than thymidine kinase deficient strains (EC 50 0.06 and 10 μM, respectively). This compound did not show cytotoxicity on all the studied cell lines. Several compounds showed promising activity against TBEV (EC 50 0.35–0.91 μM), but the activity was accompanied by pronounced cytotoxicity. These compounds may be considered as a good starting point for further structure optimization as antiherpesviral or antiflaviviral compounds. Highlights • 1,3-Diaza-2-oxophenoxazine nucleoside derivatives were synthesized. • These compounds were evaluated against DNA and RNA viruses in vitro. • 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication. • Several derivatives showed promising activity against TBEV, but the activity was accompanied with pronounced cytotoxicity. [ABSTRACT FROM AUTHOR]

A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C 1–4 -alkyl-1,2,3-triazol-1,4-diyl groups at 3′- O -position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds ( 4 , 6 , 8a , 8b ) showed EC 50  ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11 . [ABSTRACT FROM AUTHOR]

Most antivirals target viral proteins and are specific for only one virus, or viral type. Whereas viral proteins are encoded in the plastic viral genome, virion lipids are not and their rearrangements during fusion are conserved among otherwise unrelated enveloped viruses. Antivirals that inhibit these lipid rearrangements could thus pose a high barrier to resistance and have broad-spectrum activity. Fusion occurs through a hemifusion stalk in which only the outer leaflets are fused and thus curved with a smaller radius for the polar heads than for the hydrophobic tails (negative curvature). Outer leaflets enriched in phospholipids with head groups of larger cross sections than their lipid tails (“inverted cone”) disfavor negative curvature, inhibiting fusion. The rigid amphipathic fusion inhibitors (RAFIs) are synthetic compounds of inverted cone molecular geometry. They inhibit infectivity of otherwise unrelated enveloped viruses. The leading RAFI, aUY11, has an ethynyl-perylene hydrophobic and an uracil-arabinose polar moiety. aUY11 intercalates in viral envelopes and inhibits virion-to-cell fusion of a broad spectrum of otherwise unrelated enveloped viruses. Previous studies showed that amphipathicity, rigidity, and inverted cone molecular geometry were required. We propose that the inverted cone molecular geometry of the RAFIs increases the energy barrier for the hemifusion stalk, inhibiting fusion. Then, chemically distinct compounds with similar amphipathicity, rigidity, and inverted cone shape would have similar antiviral potencies, regardless of specific chemical groups. Alternatively, the perylene group exposed to visible light may induce viral lipid peroxidation. Then, the perylene group and absorbance at visible spectrum would be required. We now evaluated twenty-five chemically distinct RAFIs. The perylene moiety and absorption at visible spectrum were not required, but a minimum length of the hydrophobic moiety was, 10.3 Å. The arabino moiety could be modified or replaced by other groups. Cytidine was not tolerated. Bilayer intercalation was required but not sufficient. The vast majority of RAFIs had no overt cytotoxicity (CC 50 > 20 μM; TI > 250–1200). Carbonyl or butylamide substitutions for arabino, or cytidine replacement for uracil, increased cytotoxicity. Cytotoxicity was mainly determined by the polar moiety and there was no correlation between antiviral and cytostatic activities. The definition of the effects of shape and chemical groups of the RAFIs opens the possibility to the rational design of lipid-acting antivirals active against a broad spectrum of enveloped viruses. [ABSTRACT FROM AUTHOR]

Background: The initial stage of the biosynthesis of steroid hormones in animals occurs in the mitochondria of steroidogenic tissues, where cytochrome P450SCC (CYP11A1) encoded by the CYP11A1 gene catalyzes the conversion of cholesterol into pregnenolone – the general precursor of all the steroid hormones, starting with progesterone. This stage is missing in plants where mitochondrial cytochromes P450 (the mito CYP clan) have not been found. Generating transgenic plants with a mitochondrial type P450 from animals would offer an interesting option to verify whether plant mitochondria could serve as another site of P450 monooxygenase reaction for the steroid hormones biosynthesis. Results: For a more detailed comparison of steroidogenic systems of Plantae and Animalia, we have created and studied transgenic tobacco and tomato plants efficiently expressing mammalian CYP11A1 cDNA. The detailed phenotypic characterization of plants obtained has shown that through four generations studied, the transgenic tobacco plants have reduced a period of vegetative development (early flowering and maturation of bolls), enlarged biomass and increased productivity (quantity and quality of seeds) as compared to the only empty-vector containing or wild type plants. Moreover, the CYP11A1 transgenic plants show resistance to such fungal pathogen as Botrytis cinerea. Similar valuable phenotypes (the accelerated course of ontogenesis and/or stress resistance) are also visible in two clearly distinct transgenic tomato lines expressing CYP11A1 cDNA: one line (No. 4) has an accelerated rate of vegetative development, while the other (No. 7) has enhanced immunity to abiotic and biotic stresses. The progesterone level in transgenic tobacco and tomato leaves is 3-5 times higher than in the control plants of the wild type. Conclusions: For the first time, we could show the compatibility in vivo of even themost specific components of the systems of biosynthesis of steroid hormones in Plantae and Animalia. The hypothesis is proposed and substantiated that the formation of the above-noted special phenotypes of transgenic plants expressing mammalian CYP11A1 cDNA is due to the increased biosynthesis of progesterone that can be considered as a very ancient bioregulator of plant cells and the first real hormone common to plants and animals. [ABSTRACT FROM AUTHOR]

Nowadays modified oligonucleotides are widely used in diagnostics and as novel therapeutics. Introduction of modified or unnatural residues into oligonucleotides allows fine tuning of their binding properties to complementary nucleic acids and leads to improved stability both in vitro and in vivo . Previously it was demonstrated that insertion of phenoxazine nucleotides with various groups in C9-position into oligonucleotides leads to a significant increase of duplex stability with complementary DNA and RNA. Here the synthesis of a novel G-clamp nucleoside analogue (G 8AE -clamp) bearing 2-aminoethyl tether at C8-atom is presented. Introduction of such modified residues into oligonucleotides lead to enhanced specificity of duplex formation towards complementary DNA and RNA targets with increased thermal and 3′-exonuclease stability. According to CD-spectroscopy studies G 8AE -clamp does not substantially disrupt helix geometry. Primers containing G 8AE -clamp demonstrated superior sensitivity in qPCR detection of dsRNA of Kemerovo virus in comparison to native oligonucleotides. [ABSTRACT FROM AUTHOR]

Green fluorescent protein (GFP) chromophore and its congeners draw significant attention mostly for bioimaging purposes. In this work we probed these compounds as antiviral agents. We have chosen LTR-III DNA G4, the major G-quadruplex (G4) present in the long terminal repeat (LTR) promoter region of the human immunodeficiency virus-1 (HIV-1), as the target for primary screening and designing antiviral drug candidates. The stabilization of this G4 was previously shown to suppress viral gene expression and replication. FRET-based high-throughput screening (HTS) of 449 GFP chromophore-like compounds revealed a number of hits, sharing some general structural features. Structure-activity relationships (SAR) for the most effective stabilizers allowed us to establish structural fragments, important for G4 binding. Synthetic compounds, developed on the basis of SAR analysis, exhibited high LTR-III G4 stabilization level. NMR spectroscopy and molecular modeling revealed the possible formation of LTR-III G4-ligand complex with one of the lead selective derivative ZS260.1 positioned within the cavity, thus supporting the LTR-III G4 attractiveness for drug targeting. Selected compounds showed moderate activity against HIV-I (EC50 1.78–7.7 μM) in vitro, but the activity was accompanied by pronounced cytotoxicity. [ABSTRACT FROM AUTHOR]

Emerging and re-emerging viruses periodically cause outbreaks and epidemics all over the world, eventually leading to global events such as the current pandemic of the novel SARS-CoV-2 coronavirus infection COVID-19. Therefore, an urgent need for novel antivirals is crystal clear. Here we present the synthesis and evaluation of an antiviral activity of phenoxazine-based nucleoside analogs divided into three groups: (1) 8-alkoxy-substituted, (2) acyclic, and (3) carbocyclic. The antiviral activity was assessed against a structurally and phylogenetically diverse panel of RNA and DNA viruses from 25 species. Four compounds (11a-c , 12c) inhibited 4 DNA/RNA viruses with EC 50 ≤ 20 μM. Toxicity of the compounds for the cell lines used for virus cultivation was negligible in most cases. In addition, previously reported and newly synthesized phenoxazine derivatives were evaluated against SARS-CoV-2, and some of them showed promising inhibition of reproduction with EC 50 values in low micromolar range, although accompanied by commensurate cytotoxicity. [Display omitted] • 8-Alkoxy-substituted, acyclic and carbocyclic phenoxazine derivatives were synthesized. • The activity was assessed against a broad panel of RNA/DNA viruses from 25 species. • Four compounds (11a-c , 12c) inhibited 4 DNA/RNA viruses with EC 50 ≤ 20 μM. • Three of them exhibited submicromolar activity against VZV. • The compounds did not show pronounced cytotoxicity against all the studied cell lines. [ABSTRACT FROM AUTHOR]

The artificial nucleobase 7,8-dihydro-8-oxo-1, N 6-ethenoadenine (X) was investigated with respect to its ability to engage in Ag(I)-mediated base pairing in DNA. Spectroscopic data indicate the formation of dinuclear X –Ag(I) 2 – X homo base pairs and mononuclear X –Ag(I)– C base pairs (C , cytosine). Density functional theory calculations and molecular dynamics simulations indicate that the nucleobase changes from its lactam tautomeric form prior to the formation of the Ag(I)-mediated base pair to the lactim form after the incorporation of the Ag(I) ions. Fluorescence spectroscopy indicates that the two Ag(I) ions of the homo base pair are incorporated sequentially. Isothermal titration calorimetry confirms that the affinity of one of the Ag(I) ions is about tenfold higher than that of the other Ag(I) ion. The computational analysis by means of density functional theory confirms a much larger reaction energy for the incorporation of the first Ag(I) ion. The thermal stabilization upon the formation of the dinuclear Ag(I)-mediated homo base pair exceeds the one previously observed for the closely related nucleobase 1, N 6-ethenoadenine by far, despite very similar structures. This additional stabilization may stem from the presence of water molecules engaged in hydrogen bonding with the additional oxygen atom of the artificial nucleobase X. The highly stabilizing Ag(I)-mediated base pair is a valuable addition to established dinuclear metal-mediated base pairs. [Display omitted] • 7,8-Dihydro-8-oxo-1, N 6-ethenoadenine as a nucleobase for metal-mediated base pairs. • Formation of stable mono- and dinuclear Ag(I)-mediated base pairs. • Metal-mediated base pairs may contain synergistic hydrogen bonds. [ABSTRACT FROM AUTHOR]

We report the design of robust sensors for measuring intracellular pH, based on the native DNA i-motifs (iMs) found in neurodegeneration- or carcinogenesis-related genes. Those iMs appear to be genomic regulatory elements and might modulate transcription in response to pH stimuli. Given their intrinsic sensitivity to minor pH changes within the physiological range, such noncanonical DNA structures can be used as sensor core elements without additional modules other than fluorescent labels or quenchers. We focused on several iMs that exhibited fast folding/unfolding kinetics. Using stopped-flow techniques and FRET-melting/annealing assays, we confirmed that the rates of temperature-driven iM-ssDNA transitions correlate with the rates of the pH-driven transitions. Thus, we propose FRET-based hysteresis analysis as an express method for selecting sensors with desired kinetic characteristics. For the leading fast-response sensor, we optimized the labelling scheme and performed intracellular calibration. Unlike the commonly used small-molecule pH indicators, that sensor was transferred efficiently to cell nuclei. Considering its favourable kinetic characteristics, the sensor can be used for monitoring proton dynamics in the nucleus. These results argue that the 'genome-inspired' design is a productive approach to the development of biocompatible molecular tools. • A novel 'genome-inspired' approach for designing pH sensors was probed. • A robust method for selecting 'fast' sensors based on melting assays was proposed. • New sensors were obtained using selected genomic i-motifs and fluorescent labels. • The lead sensor detected rapid and slight pH changes within the physiological range. • The sensor is useable for pH imaging in living cells and localizes in cell nuclei. [ABSTRACT FROM AUTHOR]

Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophilic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxylic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM. [ABSTRACT FROM AUTHOR]

Aptasensors became popular instruments in bioanalytical chemistry and molecular biology. To increase specificity, perspective signaling elements in aptasensors can be separated into a G-quadruplex (G4) part and a free fluorescent dye that lights up upon binding to the G4 part. However, current systems are limited by relatively low enhancement of fluorescence upon dye binding. Here, we added duplex modules to G4 structures, which supposedly cause the formation of a dye-binding cavity between two modules. Screening of multiple synthetic GFP chromophore analogues and variation of the duplex module resulted in the selection of dyes that light up after complex formation with two-module structures and their RNA analogues by up to 20 times compared to parent G4s. We demonstrated that the short duplex part in TBA25 is preferable for fluorescence light up in comparison to parent TBA15 molecule as well as TBA31 and TBA63 stabilized by longer duplexes. Duplex part of TBA25 may be partially unfolded and has reduced rigidity, which might facilitate optimal dye positioning in the joint between G4 and the duplex. We demonstrated dye enhancement after binding to modified TBA, LTR-III, and Tel23a G4 structures and propose that such architecture of short duplex-G4 signaling elements will enforce the development of improved aptasensors. [ABSTRACT FROM AUTHOR]