Nitration of primary amines to form primary nitramines (Review)

Poster presentation at 19th Seminar on New Trends in Research of Energetic Materials; Pardubice, Czech Republic; 20/04/2016-22/04/2016The nitration of primary amines to form primary nitramines is a rarely reported synthetic procedure which proceeds through a minimum of two steps. This is in stark contrast to the nitration of alcohols and secondary amines which is readily achievable by a number of methods in a single step. In general the primary amine must initially be activated to nitration as direct exposure to nitrating media tends to result in the formation of an ionic nitrate salt. This activation may be achieved through the use of a multitude of protecting groups that are stable to the nitrating conditions used thereafter. The review presented here is an attempt to bring together the published literature on this often overlooked synthetic procedure in energetic materials chemistry

An Automated Algorithm to Distinguish and Characterize Solar Flares and Associated Sequential Chromospheric Brightenings

We present a new automated algorithm to identify, track, and characterize small-scale brightening associated with solar eruptive phenomena observed in H{\alpha}. The temporal spatially-localized changes in chromospheric intensities can be separated into two categories: flare ribbons and sequential chromospheric brightenings (SCBs). Within each category of brightening we determine the smallest resolvable locus of pixels, a kernel, and track the temporal evolution of the position and intensity of each kernel. This tracking is accomplished by isolating the eruptive features, identifying kernels, and linking detections between frames into trajectories of kernels. We fully characterize the evolving intensity and morphology of the flare ribbons by observing the tracked flare kernels in aggregate. With the location of SCB and flare kernels identified, they can easily be overlaid on top of complementary data sets to extract Doppler velocities and magnetic field intensities underlying the kernels. This algorithm is adaptable to any dataset to identify and track solar features.Comment: 22 pages, 9 figure

Improved methods for determining the kinematics of coronal mass ejections and coronal waves

The study of solar eruptive events and associated phenomena is of great importance in the context of solar and heliophysics. Coronal mass ejections (CMEs) and coronal waves are energetic manifestations of the restructuring of the solar magnetic field and mass motion of the plasma. Characterising this motion is vital for deriving the dynamics of these events and thus understanding the physics driving their initiation and propagation. The development and use of appropriate methods for measuring event kinematics is therefore imperative. Traditional approaches to the study of CME and coronal wave kinematics do not return wholly accurate nor robust estimates of the true event kinematics and associated uncertainties. We highlight the drawbacks of these approaches, and demonstrate improved methods for accurate and reliable determination of the kinematics. The Savitzky-Golay filter is demonstrated as a more appropriate fitting technique for CME and coronal wave studies, and a residual resampling bootstrap technique is demonstrated as a statistically rigorous method for the determination of kinematic error estimates and goodness-of-fit tests. It is shown that the scatter on distance-time measurements of small sample size can significantly limit the ability to derive accurate and reliable kinematics. This may be overcome by (i) increasing measurement precision and sampling cadence, and (ii) applying robust methods for deriving the kinematics and reliably determining their associated uncertainties. If a priori knowledge exists and a pre-determined model form for the kinematics is available (or indeed any justified fitting-form to be tested against the data), then its precision can be examined using a bootstrapping technique to determine the confidence interval associated with the model/fitting parameters.Comment: 12 pages, 12 figure

Tissue multifractality and Born approximation in analysis of light scattering: a novel approach for precancers detection

Multifractal, a special class of complex self-affine processes, are under recent intensive investigations because of their fundamental nature and potential applications in diverse physical systems. Here, we report on a novel light scattering-based inverse method for extraction/quantification of multifractality in the spatial distribution of refractive index of biological tissues. The method is based on Fourier domain pre-processing via the Born approximation, followed by the Multifractal Detrended Fluctuation Analysis. The approach is experimentally validated in synthetic multifractal scattering phantoms, and tested on biopsy tissue slices. The derived multifractal properties appear sensitive in detecting cervical precancerous alterations through an increase of multifractality with pathology progression, demonstrating the potential of the developed methodology for novel precancer biomarker identification and tissue diagnostic tool. The novel ability to delineate the multifractal optical properties from light scattering signals may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin

Horizontal supergranule-scale motions inferred from TRACE ultraviolet observations of the chromosphere

We study horizontal supergranule-scale motions revealed by TRACE observation of the chromospheric emission, and investigate the coupling between the chromosphere and the underlying photosphere. A highly efficient feature-tracking technique called balltracking has been applied for the first time to the image sequences obtained by TRACE (Transition Region and Coronal Explorer) in the passband of white light and the three ultraviolet passbands centered at 1700 {\AA}, 1600 {\AA}, and 1550 {\AA}. The resulting velocity fields have been spatially smoothed and temporally averaged in order to reveal horizontal supergranule-scale motions that may exist at the emission heights of these passbands. We find indeed a high correlation between the horizontal velocities derived in the white-light and ultraviolet passbands. The horizontal velocities derived from the chromospheric and photospheric emission are comparable in magnitude. The horizontal motions derived in the UV passbands might indicate the existence of a supergranule-scale magnetoconvection in the chromosphere, which may shed new light on the study of mass and energy supply to the corona and solar wind at the height of the chromosphere. However, it is also possible that the apparent motions reflect the chromospheric brightness evolution as produced by acoustic shocks which might be modulated by the photospheric granular motions in their excitation process, or advected partly by the supergranule-scale flow towards the network while propagating upward from the photosphere. To reach a firm conclusion, it is necessary to investigate the role of granular motions in the excitation of shocks through numerical modeling, and future high-cadence chromospheric magnetograms must be scrutinized.Comment: 5 figures, accepted by Astronomy & Astrophysic

Genetically encoded sender-receiver system in 3D mammalian cell culture

Engineering spatial patterning in mammalian cells, employing entirely genetically encoded components, requires solving several problems. These include how to code secreted activator or inhibitor molecules and how to send concentration-dependent signals to neighboring cells, to control gene expression. The Madin-Darby Canine Kidney (MDCK) cell line is a potential engineering scaffold as it forms hollow spheres (cysts) in 3D culture and tubulates in response to extracellular hepatocyte growth factor (HGF). We first aimed to graft a synthetic patterning system onto single developing MDCK cysts. We therefore developed a new localized transfection method to engineer distinct sender and receiver regions. A stable reporter line enabled reversible EGFP activation by HGF and modulation by a secreted repressor (a truncated HGF variant, NK4). By expanding the scale to wide fields of cysts, we generated morphogen diffusion gradients, controlling reporter gene expression. Together, these components provide a toolkit for engineering cell-cell communication networks in 3D cell culture.Facultad de Ciencias Exacta

A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial

BACKGROUND: Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis. METHODS/DESIGN: We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2. DISCUSSION: We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis. TRIAL REGISTRATION: ISRCTN13127147 . Registered on 1st August 2016. EudraCT, 2015-003600-23 . Registered on 1st April 2016

A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial

Background Palmoplantar pustulosis is a rare but painful and debilitating disease. It consistently ranks the highest of all psoriasis phenotypic variants in terms of symptoms and functional impairment. Management of plaque-type psoriasis has been revolutionised in the last 10 years with the advent of biologic therapies, but treatment options for pustular psoriasis remain profoundly limited. On the basis of mechanistic findings which suggest a key pathogenic role for interleukin (IL)-1 in pustular psoriasis, we hypothesise that anakinra (IL-1 blockade) will be an efficacious treatment for pustular psoriasis. Methods/design We will conduct a two-stage, adaptive, double-blind, randomised, placebo-controlled trial to test the hypothesis that anakinra, self-administered daily by subcutaneous injection over 8 weeks, will deliver therapeutic benefit in palmoplantar pustular psoriasis, a localised form of pustular psoriasis typically involving the palms and/or soles. Safety outcomes will be collected for 20 weeks. A total of 64 participants will be randomised to anakinra or placebo in a 1:1 ratio. At the end of stage 1, a decision to progress to stage 2 will be made. This decision will take place after 24 participants have been randomised and followed for 8 weeks and will be based on the ordering of the observed mean outcome values in both treatment arms. At the end of stage 1, the reliability of outcome measurements and method to collect the data will also be assessed, and the primary outcome will be confirmed for stage 2. Discussion We have undertaken an adaptive approach in which we will gain proof-of-concept data prior to completing a powered efficacy trial because pustular psoriasis is a rare disease, no validated outcome measures to detect change exist, and limited safety data for anakinra exist in this population. To our knowledge, this will be the first randomised controlled trial that will provide valuable evidence for the efficacy and safety of IL-1 blockade for treatment in pustular psoriasis