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.     

Identification of the tyrosine nitration sites in human endothelial nitric oxide synthase by liquid chromatography-mass spectrometry

The formation of nitric oxide (NO) in biological systems has led to the discovery of a number of post- translational protein modifications that can affect biological conditions such as vasodilation. Studies both from our laboratory and others have shown that beside its effect on cGMP generation from soluble guanylate cylcase, NO can produce protein modifications through both S-nitrosylation of cysteine residues. Previously, we have identified the potential S-nitrosylation sites on endothelial NO synthase (eNOS). Thus, the goal of this study was to further increase our understanding of reactive nitrogen protein modifications of eNOS by identifing tyrosine residues within eNOS that are susceptible to nitration in vitro. To accomplish this, nitration was carried out using tetranitromethane followed by tryptic digest of the protein. The resulting tryptic peptides were analyzed by liquid chromatography/mass spectrometry (LC/MS) and the position of nitrated tyrosines in eNOS were identified. The eNOS sequence contains 30 tyrosine residues and our data indicate that multiple tyrosine residues are capable of being nitrated. We could identify 25 of the 30 residues in our tryptic digests and 19 of these were susceptible to nitration. Interstingly, our data identified four tyrosine residues that can be modified by nitration that are located in the region of eNOS responsible for the binding to heat shock protein 90 (Hsp90), which is responsible for ensuring efficient coupling of eNOS.     

Polydimethylsiloxane-LiNbO3 surface acoustic wave micropump devices for fluid control into microchannels

This paper presents prototypical microfluidic devices made by hybrid microchannels based on piezoelectric LiNbO(3) and polydimethylsiloxane. This system enables withdrawing micropumping by acoustic radiation in microchannels. The withdrawing configuration, integrated on chip, is here quantitatively investigated for the first time, and found to be related to the formation and coalescence dynamics of droplets within the microchannel, primed by surface acoustic waves. The growth dynamics of droplets is governed by the water diffusion on LiNbO(3), determining the advancement of the fluid front. Observed velocities are up to 2.6 mm s(-1) for 30 dBm signals applied to the interdigital transducer, corresponding to tens of nl s(-1), and the micropumping dynamics is described by a model taking into account an acoustic power exponentially decaying upon travelling along the microchannel. This straighforward and flexible micropumping approach is particularly promising for the withdrawing of liquids in lab-on-chip devices performing cycling transport of fluids and biochemical reactions.     

Ligand-mediated decarbonylation as an efficient synthetic method to Re(I) and Re(II) dicarbonyl complexes

A novel synthetic method based on a ligand-mediated decarbonylation reaction of complexes of the common fac-[Re(CO)3]+ core efficiently yields Re(I) and Re(II) dicarbonyl species.