Structure of 3-(3,5-Dimethylpiperidino)-\u3cem\u3eN\u3c/em\u3e-(\u3cem\u3ep\u3c/em\u3e-Chlorophenyl)Succinimide

In the title molecule, 3-(3,5-dimethylpiperidino )-1-(4-chlorophenyl)-2,5-pyrrolidinedione (1), the N-(p-chlorophenyl) substituent is rotated by 68.8° relative to the succinimide plane. The piperidinyl ring has a chair conformation with all substituents in equatorial positions; the conformation around the piperidino-succinimide C--N bond is staggered

N\u3csup\u3e1\u3c/sup\u3e-Acetyl-3\u27-methylandrosta-4,16-dieno[16,17-\u3cem\u3ed\u3c/em\u3e]pyrazole-3-one

In an attempt to find the structural features promoting the thermal isomerization of the N-acylated steroid [16,17-d]pyrazoles into [17,16-c]pyrazole derivatives,the X-ray structure analysis of the title compound, C23H30N2O3, (1), has been carried out. The steroid moiety of (I) has the usual conformation. The dihedral angle between the planar pyrazole ring and the N-acetyl group is very small [5.6 (2)°], but the amide C-N bond seems to be substantially elongated [1.404 (3) Å ]. The d-pyrazole ring junction via a double bond leads to deformations of some bond and torsion angles, which would be decreased in the case of a ring junction via a single bond in the [17, 16-c]pyrazole isomer

\u3cem\u3eβ\u3c/em\u3e-Homopipitzolone

The structure of β-homopipitzolone (one of the two isomers of an intermediate product in the homocedrole synthesis) has been unequivocally established as 1 O-hydroxy-2,6,9-trimetbyltricyclo[6.3.1.01,6] dodeca-9-ene-5, II, 12-trione with relative IR,2R,6R,8S configuration

Spectral analysis of Swift long GRBs with known redshift

We study the spectral and energetics properties of 47 long-duration gamma-ray bursts (GRBs) with known redshift, all of them detected by the Swift satellite. Due to the narrow energy range (15-150 keV) of the Swift-BAT detector, the spectral fitting is reliable only for fitting models with 2 or 3 parameters. As high uncertainty and correlation among the errors is expected, a careful analysis of the errors is necessary. We fit both the power law (PL, 2 parameters) and cut--off power law (CPL, 3 parameters) models to the time-integrated spectra of the 47 bursts, and present the corresponding parameters, their uncertainties, and the correlations among the uncertainties. The CPL model is reliable only for 29 bursts for which we estimate the nuf_nu peak energy Epk. For these GRBs, we calculate the energy fluence and the rest- frame isotropic-equivalent radiated energy, Eiso, as well as the propagated uncertainties and correlations among them. We explore the distribution of our homogeneous sample of GRBs on the rest-frame diagram E'pk vs Eiso. We confirm a significant correlation between these two quantities (the "Amati" relation) and we verify that, within the uncertainty limits, no outliers are present. We also fit the spectra to a Band model with the high energy power law index frozen to -2.3, obtaining a rather good agreement with the "Amati" relation of non-Swift GRBs.Comment: 16 pages. To appear in MNRAS. Minor changes were introduced in this last versio

Transcriptomic and ChIP-sequence interrogation of EGFR signaling in HER2+ breast cancer cells reveals a dynamic chromatin landscape and S100 genes as targets.

BACKGROUND:The Human Epidermal Growth Factor Receptor (EGFR/HER1) can be activated by several ligands including Transforming Growth Factor alpha (TGF-α) and Epidermal Growth Factor (EGF). Following ligand binding, EGFR heterodimerizes with other HER family members, such as HER2 (human epidermal growth factor receptor-2). Previously, we showed that the EGFR is upregulated in trastuzumab resistant HER2 positive (HER2+) breast cancer cells. This study is aimed to determine the downstream effects on transcription following EGFR upregulation in HER2+ breast cancer cells. METHODS:RNA-sequence and ChIP-sequence for H3K18ac and H3K27ac (Histone H3 lysine K18 and K27 acetylation) were conducted following an Epidermal Growth Factor (EGF) treatment time course in HER2+ breast cancer cells, SKBR3. The levels of several proteins of interest were confirmed by western blot analysis. The cellular localization of proteins of interest was examined using biochemically fractionated lysates followed by western blot analysis. RESULTS:Over the course of 24 h, EGFR stimulation resulted in the modulation of over 4000 transcripts. Moreover, our data demonstrates that EGFR/HER2 signaling regulates the epigenome, with global H3K18ac and H3K27ac oscillating as a function of time following EGF treatment. RNA-sequence data demonstrates the activation of immediate early genes (IEGs) and delayed early genes (DEGs) within 1 h of EGF treatment. More importantly, we have identified members of the S100 (S100 Calcium Binding Protein) gene family as likely direct targets of EGFR signaling as H3K18ac, H3K27ac and pol2 (RNA polymerase II) increase near the transcription start sites of some of these genes. CONCLUSIONS:Our data suggests that S100 proteins, which act as Ca2+ sensors, could play a role in EGF induced tumor cell growth and metastasis, contribute to trastuzumab resistance and cell migration and that they are likely drug targets in HER2+ breast cancer

Rate constant for the reaction of hydroxyl radical with formaldehyde over the temperature range 228-362 K

Absolute rate constants for the reaction OH ? H2CO measured over the temperature range 228-362 K using the flash photolysis-resonance fluorescence technique are given. The results are independent of variations in H2CO concentration, total pressure Ar concentration, and flash intensity (i.e., initial OH concentration). The rate constant is found to be invariant with temperature in this range, the best representation being k sub 1 = (1.05 ? or - 0.11) x 10 to the 11th power cu cm molecule(-1) s(-1) where the error is two standard deviations. This result is compared with previous absolute and relative determinations of k sub 1. The reaction is also discussed from a theoretical point of view

Frequency domain modelling of a coupled system of floating structure and mooring Lines: An application to a wave energy converter

Floating structures for single offshore renewable energy devices, i.e. wave energy converters, tend to be significantly smaller than those of the traditional offshore industry and the interaction between floater motions and mooring line dynamics become important. Installation sites are generally subject to powerful waves and currents experiencing more dynamically excited motions. Water depths are also lower, ranging generally from 50 m to 200 m and mooring systems are to be designed to assure the station keeping of them while not interfering with the power conversion. However, floater motions may induce large dynamic tensions on mooring lines, making quasistatic analyses inaccurate in terms of design tension while non-linear time domain simulations too time consuming. This paper introduces a numerical model of lumped mass for mooring lines and rigid body motions for the floating structure coupled by means of kinematic relations, and its subsequent linearization, which is solved in the frequency domain. The linearized model is applied to a two-body floating spar type oscillating water column, subject to the 36 most occurrent sea states at the BIMEP site. Its accuracy is verified through a comparison with the equivalent time domain simulation and a review of the results and its limitations are also pointed out

Diagnosis of the health status of mooring systems for floating offshore wind turbines using autoencoders

Floating offshore wind turbines (FOWTs) show promise in terms of energy production, availability, and sustainability, but remain unprofitable due to high maintenance costs. This work proposes a deep learning algorithm to detect mooring line degradation and failure by monitoring the dynamic response of the publicly available DeepCWind OC4 semi-submersible platform. This study implements an autoencoder capable of predicting multiple forms of damage occurring at once, with various levels of severity. Given the scarcity of real data, simulations performed in OpenFAST, recreating both healthy and damaged mooring systems, are used to train and validate the algorithm. The novelty of the proposed approach consists of using a set of key statistical metrics describing the platform’s displacements and rotations as input layer for the autoencoder. The statistics of the responses are calculated at 33-minute-long sea states under a broad spectrum of metocean and wind conditions. An autoencoder is trained using these parameters to discover that the proposed algorithm is capable of detecting mild anomalies caused by biofouling and anchor displacements, with correlation coefficients up to 98.51\% and 99.16\%, respectively. These results are encouraging for the continuous health monitoring of FOWT mooring systems using easily measurable quantities to plan preventive maintenance actions adequately

A comparison of numerical approaches for the design of mooring systems for wave energy converters

This paper analyses the numerical outcome of applying three different well-known mooring design approaches to a floating wave energy converter, moored by means of four catenary lines. The approaches include: a linearized frequency domain based on a quasistatic model of the mooring lines, a time domain approach coupled with an analytic catenary model of the mooring system, and a fully coupled non-linear time domain approach, considering lines' drag and inertia forces. Simulations have been carried out based on a set of realistic combinations of lines pretension and linear mass, subject to extreme environmental conditions. Obtained results provide realistic cost and performance indicators, presenting a comparison in terms of total mooring mass and required footprint, as well as the design line tension and structure offset. It has been found that lines' viscous forces influence significantly the performance of the structure with high pretensions, i.e., >1.2, while there is acceptable agreement between the modelling approaches with lower pretensions. Line tensions are significantly influenced by drag and inertia forces because of the occurrence of snap loads due to the heaving of the floater. However, the frequency domain approach provides an insight towards the optimal design of the mooring system for preliminary designs

Transpulmonary pressure to guide mechanical ventilation: Art or science?

open3noNo abstract availableSupported in part by Progetti di Ricerca di Interesse Nazionale (PRIN 2017, project J4BE7A) of the Italian Minister of Education, University, and Research.openRanieri V.M.; Tonetti T.; Nava S.Ranieri V.M.; Tonetti T.; Nava S