Sub-pixel high-resolution imaging of high-energy x-rays inspired by sub-wavelength optical imaging.

We have developed and demonstrated an image super-resolution method-XR-UNLOC: X-Ray UNsupervised particle LOCalization-for hard x-rays measured with fast-frame-rate detectors that is an adaptation of the principle of photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM), which enabled biological fluorescence imaging at sub-optical-wavelength scales. We demonstrate the approach on experimental coherent Bragg diffraction data measured with 52 keV x-rays from a nanocrystalline sample. From this sample, we resolve the fine fringe detail of a high-energy x-ray Bragg coherent diffraction pattern to an upsampling factor of 16 of the native pixel pitch of 30 µm of a charge-integrating fastCCD detector. This was accomplished by analysis of individual photon locations in a series of "nearly-dark" instances of the diffraction pattern that each contain only a handful of photons. Central to our approach was the adaptation of the UNLOC photon fitting routine for PALM/STORM to the hard x-ray regime to handle much smaller point spread functions, which required a different statistical test for photon detection and for sub-pixel localization. A comparison to a photon-localization strategy used in the x-ray community ("droplet analysis") showed that XR-UNLOC provides significant improvement in super-resolution. We also developed a metric by which to estimate the limit of reliable upsampling with XR-UNLOC under a given set of experimental conditions in terms of the signal-to-noise ratio of a photon detection event and the size of the point spread function for guiding future x-ray experiments in many disciplines where detector pixelation limits must be overcome.

Post-traumatic stress disorder in Stevens-Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients.

BACKGROUND: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications. OBJECTIVES: To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation. METHODS: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale. RESULTS: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase. CONCLUSIONS: Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.

Revealing crystalline domains in a mollusc shell single-crystalline prism.

Biomineralization integrates complex processes leading to an extraordinary diversity of calcareous biomineral crystalline architectures, in intriguing contrast with the consistent presence of a sub-micrometric granular structure. Hence, gaining access to the crystalline architecture at the mesoscale, that is, over a few granules, is key to building realistic biomineralization scenarios. Here we provide the nanoscale spatial arrangement of the crystalline structure within the 'single-crystalline' prisms of the prismatic layer of a Pinctada margaritifera shell, exploiting three-dimensional X-ray Bragg ptychography microscopy. We reveal the details of the mesocrystalline organization, evidencing a crystalline coherence extending over a few granules. We additionally prove the existence of larger iso-oriented crystalline domains, slightly misoriented with respect to each other, around one unique rotation axis, and whose shapes are correlated with iso-strain domains. The highlighted mesocrystalline properties support recent biomineralization models involving partial fusion of oriented nanoparticle assembly and/or liquid droplet precursors.

High-resolution three-dimensional structural microscopy by single-angle Bragg ptychography.

Coherent X-ray microscopy by phase retrieval of Bragg diffraction intensities enables lattice distortions within a crystal to be imaged at nanometre-scale spatial resolutions in three dimensions. While this capability can be used to resolve structure-property relationships at the nanoscale under working conditions, strict data measurement requirements can limit the application of current approaches. Here, we introduce an efficient method of imaging three-dimensional (3D) nanoscale lattice behaviour and strain fields in crystalline materials with a methodology that we call 3D Bragg projection ptychography (3DBPP). This method enables 3D image reconstruction of a crystal volume from a series of two-dimensional X-ray Bragg coherent intensity diffraction patterns measured at a single incident beam angle. Structural information about the sample is encoded along two reciprocal-space directions normal to the Bragg diffracted exit beam, and along the third dimension in real space by the scanning beam. We present our approach with an analytical derivation, a numerical demonstration, and an experimental reconstruction of lattice distortions in a component of a nanoelectronic prototype device.

Three Dimensional Variable-Wavelength X-Ray Bragg Coherent Diffraction Imaging.

We present and demonstrate a formalism by which three-dimensional (3D) Bragg x-ray coherent diffraction imaging (BCDI) can be implemented without moving the sample by scanning the energy of the incident x-ray beam. This capability is made possible by introducing a 3D Fourier transform that accounts for x-ray wavelength variability. We demonstrate the approach by inverting coherent Bragg diffraction patterns from a gold nanocrystal measured with an x-ray energy scan. Variable-wavelength BCDI will expand the breadth of feasible in situ 3D strain imaging experiments towards more diverse materials environments, especially where sample manipulation is difficult.

Efficient modeling of Bragg coherent x-ray nanobeam diffraction.

X-ray Bragg diffraction experiments that utilize tightly focused coherent beams produce complicated Bragg diffraction patterns that depend on scattering geometry, characteristics of the sample, and properties of the x-ray focusing optic. Here, we use a Fourier-transform-based method of modeling the 2D intensity distribution of a Bragg peak and apply it to the case of thin films illuminated with a Fresnel zone plate in three different Bragg scattering geometries. The calculations agree well with experimental coherent diffraction patterns, demonstrating that nanodiffraction patterns can be modeled at nonsymmetric Bragg conditions with this approach--a capability critical for advancing nanofocused x-ray diffraction microscopy.

Texture tomography, a versatile framework to study crystalline texture in 3D.

Crystallographic texture is a key organization feature of many technical and biological materials. In these materials, especially hierarchically structured ones, the preferential alignment of the nano constituents heavily influences the macroscopic behavior of the material. To study local crystallographic texture with both high spatial and angular resolution, we developed Texture Tomography (TexTOM). This approach allows the user to model the diffraction data of polycrystalline materials using the full reciprocal space of the crystal ensemble and describe the texture in each voxel via an orientation distribution function, hence it provides 3D reconstructions of the local texture by measuring the probabilities of all crystal orientations. The TexTOM approach addresses limitations associated with existing models: it correlates the intensities from several Bragg reflections, thus reducing ambiguities resulting from symmetry. Further, it yields quantitative probability distributions of local real space crystal orientations without further assumptions about the sample structure. Finally, its efficient mathematical formulation enables reconstructions faster than the time scale of the experiment. This manuscript presents the mathematical model, the inversion strategy and its current experimental implementation. We show characterizations of simulated data as well as experimental data obtained from a synthetic, inorganic model sample: the silica-witherite biomorph. TexTOM provides a versatile framework to reconstruct 3D quantitative texture information for polycrystalline samples; it opens the door for unprecedented insights into the nanostructural makeup of natural and technical materials.

Impact and mitigation of angular uncertainties in Bragg coherent x-ray diffraction imaging.

Bragg coherent diffraction imaging (BCDI) is a powerful technique to explore the local strain state and morphology of microscale crystals. The method can potentially reach nanometer-scale spatial resolution thanks to the advances in synchrotron design that dramatically increase coherent flux. However, there are experimental bottlenecks that may limit the image reconstruction quality from future high signal-to-noise ratio measurements. In this work we show that angular uncertainty of the sample orientation with respect to a fixed incoming beam is one example of such a factor, and we present a method to mitigate the resulting artifacts. On the basis of an alternative formulation of the forward problem, we design a phase retrieval algorithm which enables the simultaneous reconstruction of the object and determination of the exact angular position corresponding to each diffraction pattern in the data set. We have tested the algorithm performance on simulated data for different degrees of angular uncertainty and signal-to-noise ratio.

A pyrene-functionalized foldamer: structural impact and recognition properties supported by donor-acceptor interactions.

An electroactive and luminescent foldamer based on an oligopyridine biscarboxamide skeleton was synthesized and characterised. Its conformation in the solid state proved to be strongly affected by the peripheral pyrene units. The latter also endow the target derivative with recognition abilities toward electron-withdrawing molecules, which allow tuning of the spectroscopic properties of the foldamer.

A robust viologen and Mn-based porous coordination polymer with two types of Lewis acid sites providing high affinity for H2O, CO2 and NH3.

A novel porous coordination polymer [Mn(pc3)(H2O)2]·xH2O (3 < x < 4) is synthesized in water at pH = 7 using the anionic viologen-carboxylate ligand 4,4'-bipyridinium,1,1'-bis-(2,4-dicarboxyphenyl) (pc32-). Dehydration of the material results in the formation of open pores containing two types of accessible Lewis acid sites: exposed Mn2+ cations and N+ atoms of viologen units. Due to this property the PCP shows high affinity and capacity in the adsorption of H2O, CO2 and NH3. Despite the presence of strong adsorption sites this material is stable in liquid water and in gaseous NH3.

Strain in a silicon-on-insulator nanostructure revealed by 3D x-ray Bragg ptychography.

Progresses in the design of well-defined electronic band structure and dedicated functionalities rely on the high control of complex architectural device nano-scaled structures. This includes the challenging accurate description of strain fields in crystalline structures, which requires non invasive and three-dimensional (3D) imaging methods. Here, we demonstrate in details how x-ray Bragg ptychography can be used to quantify in 3D a displacement field in a lithographically patterned silicon-on-insulator structure. The image of the crystalline properties, which results from the phase retrieval of a coherent intensity data set, is obtained from a well-controlled optimized process, for which all steps are detailed. These results confirm the promising perspectives of 3D Bragg ptychography for the investigation of complex nano-structured crystals in material science.

Synthesis, structure and biological activity of nickel(II) complexes of 5-methyl 2-furfural thiosemicarbazone.

5-Methyl 2-furfuraldehyde thiosemicarbazone (M5HFTSC) with nickel(II) leads to three types of complexes: [Ni(M5HFTSC)(2)X(2)], [Ni(M5FTSC)(2)] and [Ni(M5FTSC)(2)] x 2DMF. In the first type the ligand remains in thione form, while in the two other, the anionic thiolato form is involved. The species [Ni(M5HFTSC)(2)X(2)] has been characterized spectroscopically. The structures of [Ni(M5FTSC)(2)] x 2DMF and [Ni(M5FTSC)(2)] have been solved using X-ray diffraction. Biological studies of [Ni(M5HFTSC)(2)Cl(2)] have been carried out in vitro for antifungal activity on human pathogenic fungi, Aspergillus fumigatus and Candida albicans, and in vivo for toxicity on mice. The results are compared to those of the ligand, the metal salt and a similar copper complex [Cu(M5HFTSC)Cl(2)].

Cramer-Rao analysis of steady-state and time-domain fluorescence diffuse optical imaging.

Using a Cramer-Rao analysis, we study the theoretical performances of a time and spatially resolved fDOT imaging system for jointly estimating the position and the concentration of a point-wide fluorescent volume in a diffusive sample. We show that the fluorescence lifetime is a critical parameter for the precision of the technique. A time resolved fDOT system that does not use spatial information is also considered. In certain cases, a simple steady-state configuration may be as efficient as this time resolved fDOT system.

Three-dimensional high-resolution quantitative microscopy of extended crystals.

Hard X-ray lens-less microscopy raises hopes for a non-invasive quantitative imaging, capable of achieving the extreme resolving power demands of nanoscience. However, a limit imposed by the partial coherence of third generation synchrotron sources restricts the sample size to the micrometer range. Recently, X-ray ptychography has been demonstrated as a solution for arbitrarily extending the field of view without degrading the resolution. Here we show that ptychography, applied in the Bragg geometry, opens new perspectives for crystalline imaging. The spatial dependence of the three-dimensional Bragg peak intensity is mapped and the entire data subsequently inverted with a Bragg-adapted phase retrieval ptychographical algorithm. We report on the image obtained from an extended crystalline sample, nanostructured from a silicon-on-insulator substrate. The possibility to retrieve, without transverse size restriction, the highly resolved three-dimensional density and displacement field will allow for the unprecedented investigation of a wide variety of crystalline materials, ranging from life science to microelectronics.

Analysis of the depth resolution limit of luminescence diffuse optical imaging.

We introduce a methodology to determine quantitatively the depth resolution limit in luminescence diffuse optical imaging. The approach is based on a Cramer-Rao statistical analysis, a noise model, and calculations of photon transport in tissues. We illustrate the method in the case of luminescence imaging in a brain-skull model, showing its potential applications in molecular imaging on small animals.

A visual technique of chemotactic assessment for pharmacological studies.

A visual assay of chemotactic response was performed by measuring the extent of the migration of polymorphonuclear leukocytes (PMN) collected from the rat pleural cavity toward a dying cell. Various types of cells (erythrocytes, PMN, or monocytes) may be destroyed by means of an argon laser, and the process may be visualized under a phase-contrast microscope (necrotactic phenomenon). This experimental model may simulate pathological events that occur in damaged tissues, and it permits the study of cellular migration during inflammatory diseases. This method did not seem to involve chemokinetic effects, but instead represented a true measure of chemotaxis. A numeration of the migrating PMNs at t = 0 and t + 10 min after cell lysis allowed a statistical analysis and the use of this phenomenon for pharmacological studies. The modification of rat PMN chemotaxis by cholera toxin, substance P, and a synthetic muramyl dipeptide are presented as examples of the use of this technique.

S-position isomers of BEDT-TTF and EDT-TTF: synthesis and influence of outer sulfur atoms on the electrochemical properties and crystallographic network of related organic metals.

The synthesis and characterization of new modified tetrathiafulvalenes (TTF), the S-position isomers of BEDT-TTF and EDT-TTF, are described. The synthetic strategy presented in this work is based on an efficient and unprecedented two-step sequence for the conversion of a vicinal bis(hydroxymethyl) functionality into a disulfide ring. Different routes are discussed in terms of efficiency for the synthesis of the symmetric S-position isomer of BEDT-TTF and that of EDT-TTF. Their electrochemical properties are combined with data obtained from UV/Vis spectroscopy and orbital calculations, and the electronic influence of peripheral sulfur atoms on the neutral and oxidized species is discussed. The introduction of these outer sulfur atoms at the periphery of the TTF core gives rise to specific intermolecular S...S interactions in the corresponding organic materials. Crystallographic studies of radical cation salts synthesized upon electrocrystallization clearly showed that the network obtained is dictated by the outer sulfur atoms, which are responsible for a characteristic and unprecedented "windmill" array.