Спектрометрия ионной подвижности N-метилимидазола и возможности его определения

Objectives. To determine the ion mobility of N-methylimidazole, establish the structure of ions corresponding to characteristic signals, and determine the detection limit of N-methylimidazole on the ion-drift detector Kerber.Methods. Ion mobility spectrometry was used to study the ionization processes. The enthalpies of the reactions of monomer and dimer ions were calculated in the ORCA 4.1.1 software by the B3LYP density functional method with a set of basic functions 6-31G (d, p).Results. The drift time and ion mobility values of N-methylimidazole were determined. A method for mathematical processing of spectra and a program for its implementation was developed. The changing peculiarities of the ion mobility spectrum during measurement at a given time were studied. According to the interpretation of the spectrum signals, the structure of the generated ions was proposed, and the enthalpies of ion formation were determined.Conclusions. The characteristic signal of the N-methylimidazole ion protonated at the nitrogen atom of the pyridine type was revealed. It was found that two signals in the ion mobility spectra of N-methylimidazole correspond to the presence of the monomer and dimer ions. The detection limit of N-methylimidazole on the ion-drift detector Kerber was determined, amounting to 3 pg.Цели. Определение значений ионной подвижности N-метилимидазола. Установление строения ионов, соответствующих характерным сигналам. Определение предела обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер.Методы. Метод спектрометрии ионной подвижности был использован для исследования процессов ионизации. Энтальпии реакций мономерных и димерных ионов расчитаны в программе ORCA 4.1.1 методом функционала плотности B3LYP с набором базисных функций 6-31G(d,p).Результаты. Определены значения времени дрейфа и ионной подвижности N-метилимидазола. Разработана методика математической обработки спектров и программа для ее реализации. Изучены особенности изменения характера спектра ионной подвижности в процессе измерения в данный момент времени. Предложено строение генерируемых ионов в соответствии с интерпретацией сигналов спектра. Определены энтальпии образования ионов.Выводы. Выявлен характеристический сигнал иона N-метилимидазола, протонированного по атому азота пиридинового типа. Установлено, что два сигнала в спектрах ионной подвижности N-метилимидазола соответствуют наличию мономерной и димерной формы ионов. Определен предел обнаружения N-метилимидазола на ионно-дрейфовом детекторе Кербер, составляющий 3 пг

Stable interference of EWS–FLI1 in an Ewing sarcoma cell line impairs IGF-1/IGF-1R signalling and reveals TOPK as a new target

BACKGROUND: Ewing sarcoma is a paradigm of solid tumour -bearing chromosomal translocations resulting in fusion proteins that act as deregulated transcription factors. Ewing sarcoma translocations fuse the EWS gene with an ETS transcription factor, mainly FLI1. Most of the EWS–FLI1 target genes still remain unknown and many have been identified in heterologous model systems

Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation γ rays

Neutrino- and antineutrino-oxygen neutral-current quasielastic-like interactions are measured at Super-Kamiokande using nuclear de-excitation $\gamma$-rays to identify signal-like interactions in data from a $14.94 \ (16.35)\times 10^{20}$protons-on-target exposure of the T2K neutrino (antineutrino) beam. The measured flux-averaged cross sections on oxygen nuclei are$\langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+ {\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$with a flux-averaged energy of 0.82 GeV and$\langle \sigma_{\bar{\nu} {\rm -NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are the most precise to date, and the antineutrino result is the first cross section measurement of this channel. They are compared with various theoretical predictions. The impact on evaluation of backgrounds to searches for supernova relic neutrinos at present and future water Cherenkov detectors is also discussed

Search for electron antineutrino appearance in a long-baseline muon antineutrino beam

Electron antineutrino appearance is measured by the T2K experiment in an accelerator-produced antineutrino beam, using additional neutrino beam operation to constrain parameters of the Pontecorvo-Maki-Nakagawa-Sakata (PMNS) mixing matrix. T2K observes 15 candidate electron antineutrino events with a background expectation of 9.3 events. Including information from the kinematic distribution of observed events, the hypothesis of no electron antineutrino appearance is disfavored with a significance of 2.40σ and no discrepancy between data and PMNS predictions is found. A complementary analysis that introduces an additional free parameter which allows non-PMNS values of electron neutrino and antineutrino appearance also finds no discrepancy between data and PMNS predictions

Resveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factor

Resveratrol (3, 4', 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer.Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1), and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity.These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer