On one-relator products induced by generalized triangle groups II

This is the second of two papers in which we study a group which is the quotient of a free product of groups by the normal closure of a single word that is contained in a subgroup which has the form of a free product of two cyclic groups. We use known properties of generalized triangle groups, together with detailed analysis of pictures and of words in free monoids, to prove a number of results such as a Freiheitssatz and the existence of Mayer-Vietoris sequences for such groups under suitable hypotheses. The results generalize those in an earlier article of the second author and Shwartz.     

Overcoming Selectivity and Sensitivity Issues of Direct Inject Electrospray Mass Spectrometry via DAPNe-NSI-MS

Direct inject electrospray mass spectrometry offers minimal sample preparation and a “shotgun” approach to analyzing samples. However, complex matrix effects often make direct inject an undesirable sample introduction technique, particularly for trace level analytes. Highlighted here is our solution to the pitfalls of direct inject mass spectrometry and other ambient ionization methods with a focus on trace explosives. Direct analyte-probed nanoextraction coupled to nanospray ionization mass spectrometry solves selectivity issues and reduces matrix effects while maintaining minimal sample preparation requirements. With appropriate solvent conditions, most explosive residues can be analyzed with this technique regardless of the nature of the substance (i.e., nitroaromatic, oxidizing salt, or peroxide).

Polystyrene Microspheres in Tissue-Simulating Phantoms Can Collisionally Quench Fluorescence

Tissue-simulating phantoms that replicate intrinsic optical properties in a controlled manner are useful for quantitative studies of photon transport in turbid biological media. In such phantoms, polystyrene microspheres are often used to simulate tissue optical scattering. Here, we report that using polystyrene microspheres in fluorescent tissue-simulating phantoms can reduce fluorophore quantum yield via collisional quenching. Fluorescence lifetime spectroscopy was employed to characterize quenching in phantoms consisting of a fluorescein dye and polystyrene microspheres (scattering coefficients _s 100-600cm^–1). For this range of tissue-simulating phantoms, analysis using the Stern-Volmer equation revealed that collisional quenching by polystyrene microspheres accounted for a decrease in fluorescence intensity of 6-17% relative to the intrinsic intensity value when no microspheres (quenchers) were present. The intensity decrease from quenching is independent of additional, anticipated losses arising from optical scattering associated with the microspheres. These results suggest that quantitative fluorescence measurements in studies employing such phantoms may be influenced by collisional quenching.     

On one-relator products induced by generalized triangle groups I

In this paper and a sequel, we study a group which is the quotient of a free product of groups by the normal closure of a single word that is contained in a subgroup which has the form of a free product of two cyclic groups. We use known properties of generalized triangle groups, together with detailed analysis of pictures and of words in free monoids, to prove a number of results such as a Freiheitssatz and the existence of Mayer-Vietoris sequences for such groups under suitable hypotheses. The results generalize those in an earlier article of the second author and Shwartz.     

Role of host layer flexibility in DNA guest intercalation revealed by computer simulation of layered nanomaterials

Layered double hydroxides (LDHs) have been shown to form staged intermediate structures in experimental studies of intercalation. However, the mechanism by which staged structures are produced remains undetermined. Using molecular dynamics simulations, we show that LDHs are flexible enough to deform around bulky intercalants such as deoxyribonucleic acid (DNA). The flexibility of layered materials has previously been shown to affect the pathway by which staging occurs. We explore three possible intermediate structures which may form during intercalation of DNA into Mg2Al LDHs and study how the models differ energetically. When DNA strands are stacked directly on top of each other, the LDH system has a higher potential energy than when they are stacked in a staggered or interstratified structure. It is generally thought that staged intercalation occurs through a Daumas-Herold or a Rudorff model. We find, on average, greater diffusion coefficients for DNA strands in a Daumas-Herold configuration compared to a Rudorff model and a stage-1 structure. Our simulations provide evidence for the presence of peristaltic modes of motion within Daumas-Herold configurations. This is confirmed by spectral analysis of the thickness variation of the basal spacing. Peristaltic modes are more prominent in the Daumas-Herold structure compared to the Rudorff and stage-1 structures and support a mechanism by means of which bulky intercalated molecules such as DNA rapidly diffuse within an LDH interlayer.     

Do fluorescence decays remitted from tissues accurately reflect intrinsic fluorophore lifetimes?

Fluorescence spectroscopy and imaging methods, including fluorescence lifetime sensing, are being developed for noninvasive tissue diagnostics. The purpose of this study was to identify and quantify those factors affecting the accurate recovery of fluorophore lifetimes from inhomogeneous tissues in vivo. A Monte Carlo code was developed to numerically simulate time-resolved fluorescence measurements on layered epithelial tissues. Simulations were run with experimental parameters matching previously reported clinical studies in the gastrointestinal tract. The results demonstrate that variations in fluorescence decay time as large as those detected clinically between normal and premalignant tissues (approximately 2 ns) could be simulated by variations in tissue morphology or biochemistry, even when intrinsic fluorophore lifetimes were held constant.     

Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling,Auto-QSAR,and Molecular Docking Approaches

Neurodegenerative diseases, for example Alzheimer’s, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds’ pIC₅₀ values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R² = 0.86 and Q² = 0.73), pls_38 (R² = 0.77 and Q² = 0.72), kpls_desc_44 (R² = 0.81 and Q² = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of −9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of −9.60 and −9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (−6.30 kcal/mol). The docking scores of our standards were −10.40 and −7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.     

Computer simulation study of the structural stability and materials properties of DNA-intercalated layered double hydroxides

The intercalation of DNA into layered double hydroxides (LDHs) has various applications, including drug delivery for gene therapy and origins of life studies. The nanoscale dimensions of the interlayer region make the exact conformation of the intercalated DNA difficult to elucidate experimentally. We use molecular dynamics techniques, performed on high performance supercomputing grids, to carry out large-scale simulations of double stranded, linear and plasmid DNA up to 480 base pairs in length intercalated within a magnesium-aluminum LDH. Currently only limited experimental data have been reported for these systems. Our models are found to be in agreement with experimental observations, according to which hydration is a crucial factor in determining the structural stability of DNA. Phosphate backbone groups are found to align with aluminum lattice positions. At elevated temperatures and pressures, relevant to origins of life studies which maintain that the earliest life forms originated around deep ocean hydrothermal vents, the structural stability of LDH-intercalated DNA is substantially enhanced as compared to DNA in bulk water. We also discuss how the materials properties of the LDH are modified due to DNA intercalation.