Mathematical and fuzzy logic models in prediction of geological and geomechanical properties of rock mass by excavation data on underground works /

In underground works, the continual consciousness of geological and geomechanical properties of rock mass during drilling, is of major importance to optimize the works and the equipment used. In this paper, the mathematical relationship obtained from tunnel excavations, considering percussion drilling for blasting by a drilling machine and by a tunnel boring machine (TBM) are exposed. These mathematical relationships are useful in the percussion drilling case, to adjust the drilling parameter recorder (DPR) tools, and in the case of TBM to predict the rock mass geomechanical index (RMR). Taking into account the complexity of these mathematical models obtained, as a consequence of the affected variables and their relations, a fuzzy logic model based on parameters accessible to the drilling machine has been used in tricone bit drilling. Santrauka Atliekant požeminius uolienų gręžimo darbus ir optimizuojant darbus bei jiems naudojamą įrangą, labai svarbu prognozuoti geologines ir geomechanines uolienos savybes. Šiame darbe pateikiamos gautos matematinės išraiškos, taikant tunelių kasimo duomenis, gautus naudojant smūginio gręžimo ir tunelių gręžimo (TBM) įrangą. Šios matematinės išraiškos yra naudingos smūginio gręžimo metu koreguojant gręžimo parametro fiksavimo (DPR) duomenis, o naudojant TBM įrangą – nustatant uolienos geomechaninį indeksą (RMR). Atsižvelgiant į gautų matematinių modelių kompleksiškumą, t. y. į gautus parametrus ir jų sąryšius, naudotinas neraiškiosios logikos modelis, jungiantis parametrus, tinkamus trigalvio grąžto gręžimo įrangai. Reikšminiai žodžiai: neraiškioji logika, tunelių gręžimo įranga, gręžimo parametro fiksavimas, trigalvis grąžta

Развитие инвестиционного кредитования в Украине

Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS2 and LC-MS3 were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization

In-line sample trap columns with diatomite for large-volume injection in CZE–IM–MS

The analysis of low-abundant compounds with capillary zone electrophoresis–drift-tube ion mobility spectrometry–mass spectrometry (CZE–DTIMS–MS) is compromised due to the low injectable sample volumes in CZE and low duty cycle in DTIMS. Fritless packed in-line trap columns, using solid-phase extraction sorbent particles, have been used to increase injection volumes in CZE, but these columns are difficult to prepare and exhibit rapidly increasing back pressures. To provide smooth and complete filling of trap columns as well as to ensure higher and sustained flow rates though the columns, blends of cation and anion exchange particles with diatomite were used. The application of diatomite blends ensured the use of trap columns for at least 100 injections, with maximum injection volumes over 10 µl, which corresponds to an enrichment factor of more than 1000 over conventional injections in CZE–MS, enabling the detection of low nM concentrations of N-glycans with CZE–IMS–MS

Dosimetry characterization of 32^{32}P intravascular brachytherapy source wires using Monte Carlo codes PENELOPE and GEANT4

Monte Carlo calculations using the codes PENELOPE and GEANT4 have been performed to characterize the dosimetric parameters of the new 20 mm long catheter based $^{32}$P beta source manufactured by Guidant Corporation. The dose distribution along the transverse axis and the two dimensional dose rate table have been calculated. Also, the dose rate at the reference point, the radial dose function and the anisotropy function were evaluated according to the adapted TG-60 formalism for cylindrical sources. PENELOPE and GEANT4 codes were first verified against previous results corresponding to the old 27 mm Guidant $^{32}$P beta source. The dose rate at the reference point for the unsheathed 27 mm source in water was calculated to be $0.215 \pm 0.001$ cGy s$^{-1}$ mCi$^{-1}$, for PENELOPE, and $0.2312 \pm 0.0008$ cGy s$^{-1}$ mCi$^{-1}$, for GEANT4. For the unsheathed 20 mm source these values were $0.2908 \pm 0.0009$ cGy s$^{-1}$ mCi$^{-1}$ and $0.311 \pm 0.001$ cGy s$^{-1}$ mCi$^{-1}$, respectively. Also, a comparison with the limited data available on this new source is shown. We found non negligible differences between the results obtained with PENELOPE and GEANT4.Comment: 13 pages, 7 figures, 7 tables (accepted for publication in Medical Physics

Oxidative Release of O-Glycans under Neutral Conditions for Analysis of Glycoconjugates Having Base-Sensitive Substituents

Protein O-glycosylation is one of the most diverse post-translational modifications. A critical step in the analysis of O-glycomes is the release of glycans from glycoconjugates. Current release methods rely mainly on β-elimination, which can result in peeling reactions and loss of base-sensitive functionalities leading to misidentification of glycans. To address this challenge, well-defined synthetic glycopeptides were used to establish a robust workflow for the oxidative release of O-glycans suitable for glycomics. Treatment of O-glycopeptides with neutralized hypochlorite resulted in the selective formation of lactic/glycolic acid glycosides, thereby retaining unique information of the parent amino acid (serine/threonine) that is lost by β-elimination. It locks the glycan in a closed ring configuration, thereby preventing peeling, and furthermore, the carboxylate of the anomeric tag promotes ionization in negative ion mode mass spectrometry, thereby increasing signal intensities. Labile modifications such as sialic acids, sulfates, and acetyl esters are maintained during the release procedure. The promise of the approach was demonstrated by the analysis of O-glycans from bovine submaxillary mucin, which identified mono- and di- O-acetylated sialoglycans as well as previously undetected tri- O-acetylated and sulfated glycans. The use of well-defined glycopeptide standards made it also possible to identify reaction intermediates, which in turn allowed us to postulate a reaction mechanism for oxidative O-glycan release under neutral conditions

Sialic acid O-acetylation patterns and glycosidic linkage type determination by ion mobility-mass spectrometry

O-acetylation is a common modification of sialic acids that has been implicated in a multitude of biological and disease processes. A lack of analytical methods that can determine exact structures of sialic acid variants is a hurdle to determine roles of distinct O-acetylated sialosides. Here, we describe a drift tube ion mobility-mass spectrometry approach that can elucidate exact O-acetylation patterns as well as glycosidic linkage types of sialosides isolated from complex biological samples. It is based on the use of a library of synthetic O-acetylated sialosides to establish intrinsic collision cross section (CCS) values of diagnostic fragment ions. The CCS values were used to characterize O-acetylated sialosides from mucins and N-linked glycans from biologicals as well as equine tracheal and nasal tissues. It uncovered contrasting sialic acid linkage types of acetylated and non-acetylated sialic acids and provided a rationale for sialic acid binding preferences of equine H7 influenza A viruses

Inhibitors of nicotinamide:N -methyltransferase designed to mimic the methylation reaction transition state

Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyses the methylation of nicotinamide to form N'-methylnicotinamide. Both NNMT and its methylated product have recently been linked to a variety of diseases, suggesting a role for the enzyme as a therapeutic target beyond its previously ascribed metabolic function in detoxification. We here describe the systematic development of NNMT inhibitors derived from the structures of the substrates involved in the methylation reaction. By covalently linking fragments of the NNMT substrates a diverse library of bisubstrate-like compounds was prepared. The ability of these compounds to inhibit NNMT was evaluated providing valuable insights into the structural tolerances of the enzyme active site. These studies led to the identification of new NNMT inhibitors that mimic the transition state of the methylation reaction and inhibit the enzyme with activity on par with established methyltransferase inhibitors

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors

H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells

In differentiated cells, aging is associated with hypermethylation of DNA regions enriched in repressive histone post-translational modifications. However, the chromatin marks associated with changes in DNA methylation in adult stem cells during lifetime are still largely unknown. Here, DNA methylation profiling of mesenchymal stem cells (MSCs) obtained from individuals aged 2 to 92 yr identified 18,735 hypermethylated and 45,407 hypomethylated CpG sites associated with aging. As in differentiated cells, hypermethylated sequences were enriched in chromatin repressive marks. Most importantly, hypomethylated CpG sites were strongly enriched in the active chromatin mark H3K4me1 in stem and differentiated cells, suggesting this is a cell type-independent chromatin signature of DNA hypomethylation during aging. Analysis of scedasticity showed that interindividual variability of DNA methylation increased during aging in MSCs and differentiated cells, providing a new avenue for the identification of DNA methylation changes over time. DNA methylation profiling of genetically identical individuals showed that both the tendency of DNA methylation changes and scedasticity depended on nongenetic as well as genetic factors. Our results indicate that the dynamics of DNA methylation during aging depend on a complex mixture of factors that include the DNA sequence, cell type, and chromatin context involved and that, depending on the locus, the changes can be modulated by genetic and/or external factors