Scanning Probe Instruments and Synchrotron Light at the ESRF

In 2004, the aim of the X-Tip European Project was to pursue the integration of scanning probe microscopy techniques into synchrotron radiation beamlines to provide new opportunities to both fields of microscopy and spectroscopy. Given the limited X-ray focusing capabilities at that time and the difficulty of alignment, the first emphasis was given to the possibility of exploring the morphology of the sample surface within the area illuminated by the X-rays, selecting an area of interest and, using the scanning tip, aligning it into the X-ray beam and extract by total electron yield spectroscopic information, with lateral resolutions ideally defined by tip dimensions.     

Characterization of crude oil biomarkers using comprehensive two‐dimensional gas chromatography coupled to tandem mass spectrometry

Oil samples from Recôncavo basin (NE Brazil), previously analyzed by traditional techniques such as gas chromatography coupled to tandem mass spectrometry, were evaluated using comprehensive two‐dimensional gas chromatography coupled to quadrupole mass spectrometry and comprehensive two‐dimensional gas chromatography coupled to tandem mass spectrometry along with simplified methods of samples preparation to evaluate the differences and advantages of these analytical techniques to better understand the development of the organic matter in this basin without altering the normal distribution of the compounds in the samples. As a result, the geochemical parameters calculated by comprehensive two‐dimensional gas chromatography coupled to tandem mass spectrometry described better the origin, maturity, and biodegradation of both samples probably by increased selectivity, resolution, and sensitivity inherent of the multidimensional technique. Additionally, the detection of the compounds such as, the C(14α‐) homo‐26‐nor‐17α‐hopane series, diamoretanes, nor‐spergulanes, C₁₉–C₂₆ A‐nor‐steranes and 4α‐methylsteranes resolved and detected by comprehensive two‐dimensional gas chromatography coupled to tandem mass spectrometry were key to classify and differentiate these lacustrine samples according to their maturity and deposition conditions.     

Bankruptcy problems with non-integer claims: definition and characterizations of the ICEA Solution

In Fragnelli et al. (TOP 22:892–933, 2014), we considered a bankruptcy problem with the additional constraint that the estate has to be assigned in integer unities, allowing for non-integer claims. We dealt with the question of existence and uniqueness of a solution and proposed the “box method” that is strongly oriented towards the constrained equal losses solution; uniqueness may be guaranteed by introducing a ranking on the claimants. Here, we introduce a solution oriented towards the constrained equal awards solution and give three characterizations and a simple method for determining the solution.     

A Categorical Interpretation of the Intuitionistic,Typed, First Order Logic with Hilbert’s $${\varepsilon}$$-Terms

We introduce a typed version of the intuitionistic epsilon calculus. We give a categorical semantics of it introducing a class of categories which we call \({\varepsilon}\)-categories. We compare our results with earlier ones of Bell (Math Logic Quart 39(3):323–337, 1993).     

Inelastic electron interaction with chloroform clusters embedded in helium droplets

The inelastic electron interaction (ionization/attachment) with chloroform embedded in helium droplets has been studied utilizing a two-sector field mass spectrometer. Positive mass spectra have been recorded at the electron energy of 70 eV and are compared with previous results in the gas phase and with other systems embedded in helium droplets. Moreover, the negative ion mass spectrum has been recorded at the electron energy of 1.5 eV. Both negative and positive mass spectra show that chloroform clusters are easily formed by embedding single molecules in the helium droplets. Moreover, for anions appearing in the mass spectrum, the ion yield has been determined as function of the electron energy. While no parent anion of chloroform can be observed in the gas phase, the present cluster environment allows the stabilization of the transient negative ion. The influence of the helium droplet upon the ionization or attachment process of the embedded chloroform is discussed.     

Three-Photon Infrared Stimulation of Endogenous Neuroreceptors in Vivo

To interrogate neural circuits and crack their codes, in vivo brain activity imaging must be combined with spatiotemporally precise stimulation in three dimensions using genetic or pharmacological specificity. This challenge requires deep penetration and focusing as provided by infrared light and multiphoton excitation, and has promoted two-photon photopharmacology and optogenetics. However, three-photon brain stimulation in vivo remains to be demonstrated. We report the regulation of neuronal activity in zebrafish larvae by three-photon excitation of a photoswitchable muscarinic agonist at 50 pM, a billion-fold lower concentration than used for uncaging, and with mid-infrared light of 1560 nm, the longest reported photoswitch wavelength. Robust, physiologically relevant photoresponses allow modulating brain activity in wild-type animals with spatiotemporal and pharmacological precision. Computational calculations predict that azobenzene-based ligands have high three-photon absorption cross-section and can be used directly with pulsed infrared light. The expansion of three-photon pharmacology will deeply impact basic neurobiology and neuromodulation phototherapies.     

Nitric Oxide Disproportionation Mediated by a Rh Complex with an Asymmetric Pincer Ligand: Spectroscopic Detection of a Dinitrosyl Intermediate

The disproportionation of nitric oxide was studied by FTIR with two different Rh(I)PCN complexes as mediators (PCN 1-((diethylamino)methyl)-3-((di-tertbutylphosphino)methyl)-benzene). As had already been reported for a PCP analogue, reaction yielded a Rh(PCN)(NO)(NO₂) complex along with gaseous N₂O in both cases. However, when [Rh(PCN)(NO)]⋅ was used as a reactant, FTIR monitoring allowed for the detection of signals of a reaction intermediate, coherent with the expected but seldom reported dinitrosyl species Rh(PCN)(NO)(NO). DFT studies on this species revealed that pincer hemilability of the amino arm is involved in its stabilization, therefore accounting for the differences observed in reactivity between PCN and PCP.     

High-content analysis of kinase activity in cells

High-content analysis (HCA) is a term used to describe techniques involving multiplexed analysis of fluorescent markers to measure multiple cellular responses to biological stimuli or drug treatment. HCA is usually based on automated microscopy or related technologies, and its value lies in providing multiparametric information on single cells within a population. During the last decade, several HCA approaches have been developed and applied to assess cellular mechanism of action of pharmacologically relevant compounds identified through biochemical screening or similar in vitro methods. With automation and instrument development, these approaches have evolved to the extent that the technique is now routinely used in screening applications, including primary HTS on compound collections. Here, we review the field and discuss in particular the application of HCA to the discovery of small molecule inhibitors targeting kinases which are implicated in Oncology.     

Metastable Dissociation of Anions Formed by Electron Attachment

A comprehensive analysis of metastable dissociation of 2,4‐dinitrotoluene (DNT) parent anions formed by attachment of electrons of controlled energy is presented. We characterize the energy dependence and kinetic energy release of the reaction which competes with autodetachment. A surprising finding is a highly exothermic metastable reaction triggered by the attachment of thermal electrons which we relate to the well‐known electrostatic ignition hazards of DNT and other explosives. Quantum chemical calculations are performed for dinitrobenzene in order to elucidate the process of NO abstraction.