Моделирование лондонского текста в повести Е. И. Замятина "Островитяне"

Статья посвящена анализу лондонского текста русской культуры первой половины ХХ в. на материале повести Е. И. Замятина "Островитяне". Впервые образ города рассматривается сквозь призму модернистской поэтики. Лондон как центр научного, рационалистического метода познания становится воплощением идеологии модернизма. Это дает возможность говорить о многоуровневой структуре восприятия города в рамках русской ментальности. В статье показывается, как образ столицы западной цивилизации усваивается русским сознанием и включается в общерусский литературный и культурный контекст

Осуществление налогового планирования на различных этапах деятельности предприятия

Проанализированы основные условия реализации налогового планирования на разных стадиях жизненного цикла хозяйствующего субъекта. Показана возможность влияния налогов на принятие предпринимательских и управленческих решений внутри предприятия

A POWHEG generator for deep inelastic scattering

We present a new event generator for the simulation of both neutral- and charged-current deep inelastic scattering (DIS) at next-to-leading order in QCD matched to parton showers using the POWHEG method. Our implementation builds on the existing POWHEG BOX framework originally designed for hadron-hadron collisions, supplemented by considerable extensions to account for the genuinely different kinematics inherent to lepton-hadron collisions. In particular, we present new momentum mappings that conserve the special kinematics found in DIS, which we use to modify the POWHEG BOX implementation of the Frixione-Kunszt-Signer subtraction mechanism. We compare our predictions to fixed-order and resummed predictions, as well as to data from the HERA ep collider. Finally we study a few representative distributions for the upcoming Electron Ion Collider.Comment: 54 pages, 25 figures, code obtainable from svn://powhegbox.mib.infn.it/trunk/User-Processes-RES/DI

Economic implications in inflammatory bowel disease: results from a retrospective analysis in an Italian Centre

BACKGROUND: Inflammatory bowel disease (IBD) represents a group of chronic conditions characterized by elevated costs. Over the last years, also a considerable healthcare burden associated with IBD has emerged, due to an increasing use of biological drugs and hospitalization costs. Despite the creation of local or regional databases, data regarding healthcare expenditure are lacking in Italy.AIM: To evaluate the treatment cost (biological drugs and hospitalizations) for patients with ulcerative colitis (UC) or Crohn’s disease (CD) treated with biological drugs.METHODS: Disease severity was evaluated by clinical scores (partial Mayo score and Harvey Bradshaw Index). We analyzed retrospectively patients treated with biologics referred to our IBD Unit between May 2015-April 2016 who underwent at least six months of follow-up (last visit October 2016). We calculated a mean cost per month of treatment for each patient. We also investigated the presence of any correlation between the monthly cost of treatment and demographic or clinical variables.RESULTS: We enrolled 142 patients (52 UC, mean age 44.3 years, male 40.4%; 90 CD, mean age 38.8 years, male 56.7%). About half of CD patients (48.9%) underwent previous intestinal surgery. The disease severity was higher in UC group vs CD group. In UC group infliximab was the most prescribed biologic (51.9%), followed by golimumab (26.9%) and adalimumab (21.2%). While CD patients were treated with adalimumab in 54.4% and infliximab in 45.6%. The mean monthly cost of treatment was € 1,235.41 ± 358.38 for UC and € 1,148.92 ± 337.36 for CD (p = 0.16). In both groups expenditure due to biologics amounts for more than 80%. We found a correlation between costs and disease activity (UC: p < 0.01; CD: p < 0.01).CONCLUSION: The main cost is due to biological drugs, but patients enrolled were the most severe in comparison to the whole IBD population under conventional therapy. As no cost differences were found between biologic drugs and the way of administration (intravenous or subcutaneous), the therapeutic choice should be driven by clinical reasons and not only economic ones

Cost per NNT for upadacitinib in the treatment of patients with moderate-severe atopic dermatitis in Italy

Background: Targeted systemic therapies, including abrocitinib, baricitinib, dupilumab, tralokinumab and upadacitinib, are new treatments for moderate to severe atopic dermatitis (AD). We evaluated the efficacy and the costs of these targeted systemic therapies in the treatment of adult patients with moderate to severe AD. Methods: The clinical efficacy was assessed considering the results of a previous network meta-analysis (NMA). The analysis involved five therapies approved in Italy for the treatment of moderate to severe AD: abrocitinib (ABR), baricitinib (BAR), dupilumab (DUP), tralokinumab (TRA) and upadacitinib (UPA). According to the NMA, the cost of the treatment was based on the number of administrations dispensed at 16 weeks and the clinical efficacy was measured by the number needed to treat (NNT) compared to placebo using the improvement ≥ 75% (EASI-75) or ≥ 90 (EASI-90) from baseline of the eczema area and severity index (EASI). Only the ex-factory price of the targeted systemic therapies was considered. The cost per NNT was adopted as a cost-effectiveness indicator. Results: At 16 weeks, the cost per NNT based on EASI-75 was lower for UPA 15 mg (€ 6,384.00) compared to BAR 4 mg (€ 11,619.73) and 2 mg (€ 14,524.66), ABR 100 mg (€ 16,265.22), DUP 300 mg (€ 16,115.04) and TRA 300 mg (€ 31,710.24). UPA 15 (€ 8,512.00) also showed the lower cost per NNT based on EASI-90 at 16 weeks compared to BAR 4 mg (€ 14,788.75) and 2 mg (€ 20,862.70), ABR 100 mg (€ 25,922.69), DUP 300 mg (€ 25,992.00) and TRA 300 mg (€ 41,067.36). Conclusions: The findings show that upadacitinib is the most cost-effective option (cost per NNT) for the treatment of moderate to severe atopic dermatitis

Cell Swelling Stimulates Cytosol to Membrane Transposition of ICln

ICln is a multifunctional protein that is essential for cell volume regulation. It can be found in the cytosol and is associated with the cell membrane. Besides its role in the splicing process, ICln is critically involved in the generation of ion currents activated during regulatory volume decrease after cell swelling (RVDC). If reconstituted in artificial bilayers, ICln can form ion channels with biophysical properties related to RVDC. We investigated (i) the cytosol versus cell membrane distribution of ICln in rat kidney tubules, NIH 3T3 fibroblasts, Madin-Darby canine kidney (MDCK) cells, and LLC-PK1 epithelial cells, (ii) fluorescence resonance energy transfer (FRET) in living fibroblasts between fluorescently tagged ICln and fluorochromes in the cell membrane, and (iii) possible functional consequences of an enhanced ICln presence at the cell membrane. We demonstrate that ICln distribution in rat kidneys depends on the parenchymal localization and functional state of the tubules and that cell swelling causes ICln redistribution from the cytosol to the cell membrane in NIH 3T3 fibroblasts and LLC-PK1 cells. The addition of purified ICln protein to the extracellular solution or overexpression of farnesylated ICln leads to an increased anion permeability in NIH 3T3 fibroblasts. The swelling-induced redistribution of ICln correlates to altered kinetics of RVDC in NIH 3T3 fibroblasts, LLC-PK1 cells, and MDCK cells. In these cells, RVDC develops more rapidly, and in MDCK cells the rate of swelling-induced depolarization is accelerated if cells are swollen for a second time. This coincides with an enhanced ICln association with the cell membrane

Phase error estimation for synthetic aperture imagery.

The estimation of phase errors in synthetic aperture imagery is important for high quality images. Many methods of autofocus, or the estimation of phase errors from the measured data, are developed using certain assumptions about the imaged scene. This thesis develops improved methods of phase estimation which make full use of the information in the recorded signal. This results in both a more accurate estimate of the image phase error and improved imagery compared to using standard techniques. The standard phase estimation kernel used in echo-correlation techniques is shear-average. This technique averages the phase-difference between each ping over all range-bins, weighted by the signal strength. It is shown in this thesis that this is not the optimal method of weighting each phase estimate. In images where the signal to clutter ratio (SCR) is not proportional to the signal amplitude, shear-average does not meet the predicted error bound. This condition may be met by many image types, including those with shadows, distributed targets and varying surface structure. By measuring the average coherence between echos at each range-bin, it is possible to accurately estimate the variance of each phase estimate, and weight accordingly. A weighted phase-difference estimation (WPDE) using this coherence weighting meets the performance bound for all images tested. Thus an improved performance over shear-average is shown for many image types. The WPDE phase estimation method can be used within the framework of many echo-correlation techniques, such as phase-gradient autofocus (PGA), phase curvature estimation, redundant phase-centre or displaced phase-centre algorithms. In addition, a direct centre-shifting method is developed which reduces bias compared to the centre-shifting method used in PGA. For stripmap images, a weighted phase curvature estimator shows better performance than amplitude weighted shear-average for images with high SCR. A different method of phase estimation, known as sharpness maximisation, perturbs an estimate of the phase error to maximise the sharpness of the reconstructed image. Several improvements are made to the technique of sharpness maximisation. These include the reduction of over-sharpening using regularisation and an improvement in accuracy of the phase estimate using range-weighting based on the coherence measure. A cascaded parametric optimisation method is developed which converges significantly faster than standard optimisation methods for stripmap images. A number of novel insights into the method of sharpness maximisation are presented. A derivation of the phase that gives maximum intensity squared sharpness is extended from a noncoherent imaging system to a coherent spotlight system. A bound on the performance of sharpness-maximisation is presented. A method is developed which allows the direct calculation of the result of a sharpness maximisation for a single ping of a spotlight synthetic aperture image. The phase correction that maximises sharpness can be directly calculated from the signal in a manner similar to a high-order echo-correlation. This calculation can be made for all pings in a recursive manner. No optimisation is required, resulting in a significantly faster phase estimation. The techniques of sharpness maximisation and echo-correlation can be shown to be closely related. This is confirmed by direct comparisons of the results. However, the classical intensity-squared sharpness measure gives poorer results than WPDE and different sharpness measures tested for a distributed target. The standard methods of shear average and maximisation of the intensity-squared sharpness measure, both perform well below the theoretical performance bound. Two of the techniques developed, WPDE and direct entropy minimisation perform at the bound, showing improved performance over standard techniques. The contributions of this thesis add considerably to the body of knowledge on the technique of sharpness maximisation. This allows an improvement in the accuracy of some phase estimation methods, as well as an increase in the understanding of how these techniques work on coherent imagery in general

A bright megaelectronvolt emission line in γ\gamma-ray burst GRB 221009A

The highly variable and energetic pulsed emission of a long gamma-ray burst (GRB) is thought to originate from local, rapid dissipation of kinetic or magnetic energy within an ultra-relativistic jet launched by a newborn compact object, formed during the collapse of a massive star. The spectra of GRB pulses are best modelled by power-law segments, indicating the dominance of non-thermal radiation processes. Spectral lines in the X-ray and soft $\gamma$-ray regime for the afterglow have been searched for intensively, but never confirmed. No line features ever been identified in the high energy prompt emission. Here we report the discovery of a highly significant ($> 6 \sigma$) narrow emission feature at around $10$ MeV in the brightest ever GRB 221009A. By modelling its profile with a Gaussian, we find a roughly constant width $\sigma \sim 1$ MeV and temporal evolution both in energy ($\sim 12$ MeV to $\sim 6$ MeV) and luminosity ($\sim 10^{50}$ erg/s to $\sim 2 \times 10^{49}$ erg/s) over 80 seconds. We interpret this feature as a blue-shifted annihilation line of relatively cold ($k_\mathrm{B}T\ll m_\mathrm{e}c^2$) electron-positron pairs, which could have formed within the jet region where the brightest pulses of the GRB were produced. A detailed understanding of the conditions that can give rise to such a feature could shed light on the so far poorly understood GRB jet properties and energy dissipation mechanism.Comment: Submitte