Leptoquark mechanism of neutrino masses within the grand unification framework

We demonstrate the viability of the one-loop neutrino mass mechanism within the framework of grand unification when the loop particles comprise scalar leptoquarks (LQs) and quarks of the matching electric charge. This mechanism can be implemented in both supersymmetric and non-supersymmetric models and requires the presence of at least one LQ pair. The appropriate pairs for the neutrino mass generation via the up-type and down-type quark loops are \(S_3\)–\(R_2\) and \(S_{1,\,3}\)–\(\tilde{R}_2\), respectively. We consider two distinct regimes for the LQ masses in our analysis. The first regime calls for very heavy LQs in the loop. It can be naturally realized with the \(S_{1,\,3}\)–\(\tilde{R}_2\) scenarios when the LQ masses are roughly between \(10^{12}\) and \(5 \times 10^{13}\) GeV. These lower and upper bounds originate from experimental limits on partial proton decay lifetimes and perturbativity constraints, respectively. Second regime corresponds to the collider accessible LQs in the neutrino mass loop. That option is viable for the \(S_3\)–\(\tilde{R}_2\) scenario in the models of unification that we discuss. If one furthermore assumes the presence of the type II see-saw mechanism there is an additional contribution from the \(S_3\)–\(R_2\) scenario that needs to be taken into account beside the type II see-saw contribution itself. We provide a complete list of renormalizable operators that yield necessary mixing of all aforementioned LQ pairs using the language of SU(5). We furthermore discuss several possible embeddings of this mechanism in SU(5) and SO(10) gauge groups.     

Determination of ganglioside composition and structure in human brain hemangioma by chip-based nanoelectrospray ionization tandem mass spectrometry

We report here on a preliminary investigation of ganglioside composition and structure in human hemangioma, a benign tumor in the frontal cortex (HFC) in comparison to normal frontal cortex (NFC) tissue using for the first time advanced mass spectrometric methods based on fully automated chip-nanoelectrospray (nanoESI) high-capacity ion trap (HCT) and collision-induced dissociation (CID). The high ionization efficiency, sensitivity and reproducibility provided by the chip-nanoESI approach allowed for a reliable MS-based ganglioside comparative assay. Unlike NFC, ganglioside mixture extracted from HFC was found dominated by species of short glycan chains exhibiting lower overall sialic acid content. In HFC, only GT1 (d18:1/20:0), and GT3 (d18:1/25:1) polysialylated species were detected. Interestingly, none of these trisialylated forms was detected in NFC, suggesting that such components might selectively be associated with HFC. Unlike the case of previously investigated high malignancy gliosarcoma, in HFC one modified O-Ac-GD2 and one modified O-Ac-GM4 gangliosides were observed. This aspect suggests that these O-acetylated structures could be associated with cerebral tumors having reduced malignancy grade. Fragmentation analysis by CID in MS² mode using as precursors the ions corresponding to GT1 (d18:1/20:0) and GD1 (d18:1/20:0) provided data corroborating for the first time the presence of the common GT1a and GT1b isomers and the incidence of unusual GT1c and GT1d glycoforms in brain hemangioma tumor.      

Inorganic-inorganic nanocomposite: Surface and conductive properties

Our previous experiences with incorporation of polyoxometalates (POMs) in different substrates have been very successful, because new nanocomposites with better conductive, catalytical and biochemical characteristics have been obtained. The results of intercalation of different mass% of ammonium decavanadate (ADV) in Al-pillared interlayered clays (Al-PILCs) are presented.The Al-PILCs were prepared using natural raw material, bentonite, containing a high percentage of montmorillonite (MM). Synthesis of ADV has been described in a previous paper. The structure of ADV hexahydrate was determined at low temperature, 100 K. A kappa refinement was performed to estimate the atomic charges.A sol-gel procedure was applied to obtain Al-PILCs composite intercalated with ADV hexahydrate (from 2 to 5 mass% of ADV). Structure and morphological properties of the new material, a nanocomposite of Al-PILCs-ADV, were investigated by X-ray powder diffraction (XRPD) and atomic force microscopy (AFM). To understand better how ADV is incorporated in the MM substrate, specific surface areas, pore structures and pore distributions were determined.Electrical and dielectric properties of the new materials were investigated by thermally stimulated depolarization currents (TSDCs) and broadband dielectric relaxation spectroscopy (DRS). The electrical conductivity of the nanocomposite was found to increase, in relation to MM, by intercalating with a small amount of ADV.     

Determination of Racemic Ketorolac,Ketorolac Enantiomers and Their Metabolites in Human Plasma and Urine by LC–UV,Applied in Clinical Study During and After Pregnancy

In order to enhance the sensitivity and to develop a faster direct method for plasma and urine quantification of racemic ketorolac, its metabolites (p-hydroxy-ketorolac and ketorolac glucuronides) and ketorolac enantiomers, we developed an extraction procedure based on solid-phase extraction combined with specific and fast chromatographic separation. Extraction and chromatography resulted in cleaner chromatograms without interfering compounds. In both plasma and urine, linearity of the standard curves for racemic ketorolac and p-hydroxy-ketorolac was validated in the concentration range 0.025–10 mg L^?1, while for ketorolac enantiomers in the concentration range 0.025–5 mg L^?1. The lower limit of quantification was two times lower than in earlier described methods. The developed method was suitable for direct quantification of racemic ketorolac, p-hydroxy-ketorolac and ketorolac enantiomers in plasma and urine samples in women at delivery and in postpartum, enabling us to document significant intra-individual differences in pharmacokinetics between these physiological states.     

Direct photothermal techniques for rapid quantification of total anthocyanin content in sour cherry cultivars

The analytical performance of the newly proposed laser-based photoacoustic spectroscopy (PAS) and of optothermal window (OW) method for quantification of total anthocyanin concentration (TAC) in five sour cherry varieties is compared to that of the spectrophotometry (SP). High performance liquid chromatography (HPLC) was used to identify and quantify specific anthocyanins. Both, PAS and OW are direct methods that unlike SP and HPLC obviate the need for the extraction of analyte. The outcome of the study leads to the conclusion that PAS and OW are both suitable for quick screening of TAC in sour cherries. The correlation between the two methods and SP is linear with R² = 0.9887 for PAS and R² = 0.9918 for OW, respectively. Both methods are capable of the rapid determination of TAC in sour cherries without a need for a laborious sample pretreatment.     

Synthesis and structural studies of C-5 aryl- and C-6 alkyl-substituted pyrimidine derivatives

C-5 and C-6 disubstituted pyrimidine derivatives 2–7 were synthesized. Introduction of the aryl rings at C-5 of pyrimidine moiety in 5 and 6 was performed using palladium-catalyzed Stille cross-coupling reaction. The novel C-6 fluorophenylalkylated 5-phenylpyrimidine derivative (7) was prepared by lithiation of 5-phenylpyrimidine (6) and subsequent reaction of thus obtained organolithium intermediate with p-fluoroacetophenone. The structures of 3, 4 and 6 were determined by X-ray crystal structure analysis. Both methoxy groups in these structures adopt a synperiplanar conformation with respect to the N1 and N3 atoms of the pyrimidine ring. The molecules of 3 and 4 are linked through weak Br···Br interactions into zig-zag chains. The molecules of 6 are assembled into layers by one C–H···O hydrogen bond, C–H···π and aromatic π···π stacking interactions.     

Assessment of the Molecular Expression and Structure of Gangliosides in Brain Metastasis of Lung Adenocarcinoma by an Advanced Approach Based on Fully Automated Chip-Nanoelectrospray Mass Spectrometry

Gangliosides (GGs), sialic acid-containing glycosphingolipids, are known to be involved in the invasive/metastatic behavior of brain tumor cells. Development of modern methods for determination of the variations in GG expression and structure during neoplastic cell transformation is a priority in the field of biomedical analysis. In this context, we report here on the first optimization and application of chip-based nanoelectrospray (NanoMate robot) mass spectrometry (MS) for the investigation of gangliosides in a secondary brain tumor. In our work a native GG mixture extracted and purified from brain metastasis of lung adenocarcinoma was screened by NanoMate robot coupled to a quadrupole time-of-flight MS. A native GG mixture from an age-matched healthy brain tissue, sampled and analyzed under identical conditions, served as a control. Comparative MS analysis demonstrated an evident dissimilarity in GG expression in the two tissue types. Brain metastasis is characterized by many species having a reduced N-acetylneuraminic acid (Neu5Ac) content, however, modified by fucosylation or O-acetylation such as Fuc-GM4, Fuc-GM3, di-O-Ac-GM1, O-Ac-GM3. In contrast, healthy brain tissue is dominated by longer structures exhibiting from mono- to hexasialylated sugar chains. Also, significant differences in ceramide composition were discovered. By tandem MS using collision-induced dissociation at low energies, brain metastasis-associated GD3 (d18:1/18:0) species as well as an uncommon Fuc-GM1 (d18:1/18:0) detected in the normal brain tissue could be structurally characterized. The novel protocol was able to provide a reliable compositional and structural characterization with high analysis pace and at a sensitivity situated in the fmol range.     

Methoxymethyl (MOM) group nitrogen protection of pyrimidines bearing C-6 acyclic side-chains

Novel N-methoxymethylated (MOM) pyrimidine (4-13) and pyrimidine-2,4-diones (15-17) nucleoside mimetics in which an isobutyl side-chain is attached at the C-6 position of the pyrimidine moiety were synthesized. Synthetic methods via O-persilylated or N-anionic uracil derivatives have been evaluated for the synthesis of N-1- and/or N-3-MOM pyrimidine derivatives with C-6 acyclic side-chains. A synthetic approach using an activated N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed the predominant conformation of the compound to be one where the hydroxymethyl group in the C-6 side-chain is close to the N-1-MOM moiety, while the OMTr is in proximity to the CH(3)-5 group. Contrary to this no NOE enhancements between the N-1-MOM group and hydroxymethyl or fluoromethyl protons in 13 were observed, which suggested a nonrestricted rotation along the C-6 side-chain. Fluorinated N,N-1,3-diMOM pyrimidine 13 emerged as a model compound for development of tracer molecules for non-invasive imaging of gene expression using positron emission tomography (PET).     

Surface and capillary effects on detection limits of chromophoric analytical systems

Sorption and capillary effects of a solid supporter in microqualitative analysis can be studied using suitable chromophoric analytical systems. The identification limits (LI) of various analytical tests have been determined applying several types of microqualitative supporters of ion-exchange resin group and filter paper. The differences in LI values can be explained by the differences in phase volumes and areas in which the analytical reaction product (AR) accumulates. Accumulation of AR by sorption and division of AR by capillary spreading have the opposite effects on LI values. When AR is a colored complex the place of its formation in the identification test has also significant effect on LI values. However, it is difficult to correlate the sorption of AR on a supporter to the conditions of its formation in the solution and to the ionic character of the complex. Also, no relationship between simple physical properties of supporters and detection limits developed. The experimental techniques applied (spot test, resin spot test, ring test) affect the sensitivity of the microqualitative analysis significantly.     

Gangliosidome of a Human Hippocampus in Temporal Lobe Epilepsy Resolved by High-Resolution Tandem Mass Spectrometry

In this study, we developed a high-resolution tandem mass spectrometry (HR MS) approach to assess presumed changes in gangliosidome of a human hippocampus affected by temporal lobe epilepsy (TLE) in comparison with a normal hippocampus. Gangliosides, membrane glycolipids, are particularly diverse and abundant in the human brain, and participate in ion transport and modulation of neuronal excitability. Changes in structural ganglioside pattern potentially linked to TLE molecular pathogenesis have not been explored in detail. Aiming to characterize TLE-specific gangliosidome, we analyzed the native gangliosides purified from a human hippocampal tissue sample affected by TLE and a control hippocampus using HR MS. Marked differences of ganglioside expression were shown in TLE vs. control, particularly with respect to the sialylation degree of components, discovered as a characteristic feature of TLE. Another major finding is the occurrence of tetrasialofucogangliosides in TLE and species modified by either O-acetylation or CH₃COO⁻. Structural analysis by higher-energy collisional dissociation (HCD) MS/MS gave rise to fragmentation patterns implying that the GQ1b (d18:1/18:0) isomer is specifically associated with TLE. Further investigation in a larger sample is needed in order to confirm the discovery of ganglioside structures specifically expressed in human TLE and to provide information on the probable role of gangliosides in the molecular events underlying seizures.