Time-resolved relaxation and fragmentation of polycyclic aromatic hydrocarbons investigated in the ultrafast XUV-IR regime.

Polycyclic aromatic hydrocarbons (PAHs) play an important role in interstellar chemistry and are subject to high energy photons that can induce excitation, ionization, and fragmentation. Previous studies have demonstrated electronic relaxation of parent PAH monocations over 10-100 femtoseconds as a result of beyond-Born-Oppenheimer coupling between the electronic and nuclear dynamics. Here, we investigate three PAH molecules: fluorene, phenanthrene, and pyrene, using ultrafast XUV and IR laser pulses. Simultaneous measurements of the ion yields, ion momenta, and electron momenta as a function of laser pulse delay allow a detailed insight into the various molecular processes. We report relaxation times for the electronically excited PAH*, PAH+* and PAH2+* states, and show the time-dependent conversion between fragmentation pathways. Additionally, using recoil-frame covariance analysis between ion images, we demonstrate that the dissociation of the PAH2+ ions favors reaction pathways involving two-body breakup and/or loss of neutral fragments totaling an even number of carbon atoms.

Structures and internal dynamics of diphenylether and its aggregates with water.

We report on a detailed multi-spectroscopic analysis of the structures and internal dynamics of diphenylether and its aggregates with up to three water molecules by employing molecular beam experiments. The application of stimulated Raman/UV and IR/UV double resonance methods as well as chirped-pulse Fourier transform microwave spectroscopy in combination with quantum-chemical computations yield the energetically preferred monomer and cluster geometries. Furthermore, the complex internal dynamics of the diphenylether monomer and the one-water clusters are analysed. In the cluster with three water molecules, water forms a cyclic structure similar to the isolated water trimer. The interactions ruling the structures of the higher-order water clusters are a combination of the ones identified for the two monohydrate isomers, with dispersion being a decisive contribution for systems that have a delicate energetic balance between different hydrogen-bonded arrangements of similar energy.

Dispersion-controlled docking preference: multi-spectroscopic study on complexes of dibenzofuran with alcohols and water.

The structural preferences within a series of dibenzofuran-solvent complexes have been investigated by electronic, vibrational, and rotational spectroscopic methods probing supersonic jet expansions. The experimental study is accompanied by a detailed theoretical analysis including dispersion-corrected density functional theory, symmetry adapted perturbation theory, as well as coupled cluster approaches. The complementary, multi-spectroscopic results reveal a preferred OHO structure for the smallest complex of dibenzofuran-water, whereas for the methanol complex an OHπ isomer is simultaneously observed. For the largest complex, dibenzofuran-tert-butyl alcohol, only a π-bound structure is found. These comprehensive investigations show that a completely inverse trend regarding the docking preference is observed by comparing the present results with the ones for analogous diphenyl ether complexes. This can be rationalized on the basis of the planarity/non-planarity and rigidity/flexibility of the different systems, providing valuable insight into the interplay between different non-covalent interactions. This analysis is a further step towards a quantitative description of very delicate energetic balances with the overall goal of yielding reliable structural predictions for non-covalently bound systems.

Microsolvated complexes of ibuprofen as revealed by high-resolution rotational spectroscopy.

Hydrogen-bonded complexes between ibuprofen and water generated in a supersonic expansion were characterized using chirped-pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency range. Four spectra were observed allowing the determination of their rotational parameters. Comparison with quantum-chemical calculations led to their identification as the lowest energy 1 : 1 ibuprofen-water complexes. These correspond to the complexes between water and the four different conformers of ibuprofen previously detected in the gas phase, owing to their similar stabilization energies and abundances. Water seems to not change the conformational distribution of ibuprofen.

New developments in rabies vaccination.

Current rabies vaccines are safe and, when administered properly, they are highly effective. In addition, they elicit long-lasting immunity, with virus-neutralising antibody titres persisting for years after vaccination. However, current regimens require multiple doses to achieve high neutralising titres and they are costly, which means that it is difficult for developing countries, where rabies deaths are highest, to implement widespread vaccination. New innovations are the only way to reduce rabies disease to acceptable rates. Numerous preclinical and clinical studies are under way, testing novel vaccines, adjuvants and injection methods. Research into the use of live vaccines and alternative vaccine vectors is ongoing, while attempts to develop DNA vaccines have so far failed to match the immunogenicity and neutralising capability of traditional vaccines. The development of molecular adjuvants that induce faster, stronger immune responses with less antigen has yielded exciting preclinical results and appears to edge us closer to a better rabies vaccine. However, steep challenges remain: molecular adjuvants require administration with live vaccines, and differences in species specificity of immune molecules complicate development. Over all, the array of research undertaken over the past decade is impressive and encouraging, but most new vaccines have yet to be tested in clinical trials, and the viability of such experimental vaccines in the global market remains to be seen. Only a vaccine that outperforms currently available vaccines in every area will have a chance at widespread adoption. Nevertheless, the authors are confident that some vaccine candidates will meet these criteria.

Les vaccins actuels contre la rage sont sûrs et très efficaces lorsqu'ils sont administrés correctement. En outre, ils confèrent une immunité durable, avec le maintien de titres neutralisants d'anticorps plusieurs années après la vaccination. Néanmoins, les régimes actuels nécessitent l'administration de plusieurs doses pour obtenir des titres élevés d'anticorps neutralisants et ils sont onéreux, de sorte que la vaccination à grande échelle est difficile à mettre en oeuvre dans les pays en développement, pourtant les plus touchés par la mortalité par rage. Seule l'adoption de solutions innovantes permettra de ramener l'incidence de la rage à un niveau acceptable. De nombreuses études précliniques et cliniques sont en cours, visant à tester les innovations en matière de vaccins, de modes d'injection et d'adjuvants. La recherche sur l'utilisation de vaccins à virus vivant et sur de nouveaux vecteurs vaccinaux se poursuit, alors que les tentatives de développement de vaccins à ADN n'ont pas réussi jusqu'à présent à obtenir un effet immunogène ou des capacités de neutralisation virale équivalents à ceux des vaccins traditionnels. Les résultats d'essais précliniques sur de nouveaux adjuvants moléculaires induisant une réponse immune plus rapide et plus puissante avec moins d'antigène sont extrêmement prometteurs et semblent annoncer l'imminence de meilleurs vaccins contre la rage. Il subsiste toutefois d'importantes difficultés : les adjuvants moléculaires ne peuvent être administrés qu'avec des vaccins vivants et les différences de spécificité d'espèce des molécules immunes rendent le développement plus complexe. Globalement, les efforts déployés depuis une décennie par la recherche sont impressionnants et encourageants mais la plupart des nouveaux vaccins doivent encore être soumis à des essais cliniques ; d'autre part la viabilité de ces vaccins expérimentaux dans le marché mondial reste à démontrer. Seul un vaccin capable de surpasser les performances des vaccins actuels dans chaque domaine aura une chance d'être largement adopté. Les auteurs estiment cependant que certains vaccins candidats pourront satisfaire à ces exigences.

Las actuales vacunas antirrábicas son seguras y, si se administran debidamente, muy eficaces. Además, inducen inmunidad duradera, con títulos de anticuerpos neutralizantes que subsisten años después de la vacunación. Sin embargo, los regímenes actuales resultan costosos y exigen dosis múltiples para lograr títulos de neutralización elevados, lo que dificulta a los países en desarrollo, que son los más golpeados por la rabia, la implantación generalizada de la vacunación. El único camino para reducir la rabia a niveles aceptables pasa por la innovación. Están en marcha numerosos estudios preclínicos y clínicos en los que se ensayan vacunas, adyuvantes y métodos de inyección novedosos. También sigue adelante la investigación sobre el uso de vacunas vivas y vectores vacunales alternativos, mientras que ninguna de las tentativas realizadas hasta la fecha con vacunas de ADN ha deparado niveles de inmunogenicidad y capacidad de neutralización equiparables a los de las vacunas tradicionales. La obtención de adyuvantes moleculares que inducen una respuesta inmunitaria más rápida y vigorosa en presencia de menos cantidad de antígeno ha dado resultados preclínicos muy interesantes y poco a poco parece acercarnos al logro de una mejor vacuna antirrábica. Subsisten, empero, arduas dificultades: los adyuvantes moleculares solo funcionan si se administran con vacunas vivas, y las diferencias existentes entre las especies en cuanto a la especificidad de las moléculas inmunitarias complican las labores de desarrollo. Globalmente, el conjunto de investigaciones emprendidas en el último decenio es impresionante y alentador, pero la mayoría de las nuevas vacunas aún deben pasar por la fase de ensayo clínico, y está por ver qué viabilidad tienen estas vacunas experimentales en el mercado mundial. Solo una vacuna que supere a las actuales en todos los aspectos tiene posibilidades de ser adoptada a gran escala. Pese a todo, los autores expresan su confianza en que algunas de las vacunas candidatas cumplan estos criterios.

Experimental demonstration of the microscopic origin of circular dichroism in two-dimensional metamaterials.

Optical activity and circular dichroism are fascinating physical phenomena originating from the interaction of light with chiral molecules or other nano objects lacking mirror symmetries in three-dimensional (3D) space. While chiral optical properties are weak in most of naturally occurring materials, they can be engineered and significantly enhanced in synthetic optical media known as chiral metamaterials, where the spatial symmetry of their building blocks is broken on a nanoscale. Although originally discovered in 3D structures, circular dichroism can also emerge in a two-dimensional (2D) metasurface. The origin of the resulting circular dichroism is rather subtle, and is related to non-radiative (Ohmic) dissipation of the constituent metamolecules. Because such dissipation occurs on a nanoscale, this effect has never been experimentally probed and visualized. Using a suite of recently developed nanoscale-measurement tools, we establish that the circular dichroism in a nanostructured metasurface occurs due to handedness-dependent Ohmic heating.

Real-Space Mapping of the Chiral Near-Field Distributions in Spiral Antennas and Planar Metasurfaces.

Chiral antennas and metasurfaces can be designed to react differently to left- and right-handed circularly polarized light, which enables novel optical properties such as giant optical activity and negative refraction. Here, we demonstrate that the underlying chiral near-field distributions can be directly mapped with scattering-type scanning near-field optical microscopy employing circularly polarized illumination. We apply our technique to visualize, for the first time, the circular-polarization selective nanofocusing of infrared light in Archimedean spiral antennas, and explain this chiral optical effect by directional launching of traveling waves in analogy to antenna theory. Moreover, we near-field image single-layer rosette and asymmetric dipole-monopole metasurfaces and find negligible and strong chiral optical near-field contrast, respectively. Our technique paves the way for near-field characterization of optical chirality in metal nanostructures, which will be essential for the future development of chiral antennas and metasurfaces and their applications.

Direct Observation of the Injection Dynamics of a Laser Wakefield Accelerator Using Few-Femtosecond Shadowgraphy.

We present few-femtosecond shadowgraphic snapshots taken during the nonlinear evolution of the plasma wave in a laser wakefield accelerator with transverse synchronized few-cycle probe pulses. These snapshots can be directly associated with the electron density distribution within the plasma wave and give quantitative information about its size and shape. Our results show that self-injection of electrons into the first plasma-wave period is induced by a lengthening of the first plasma period. Three-dimensional particle-in-cell simulations support our observations.

Quantitative confocal phase imaging by synthetic optical holography.

We demonstrate quantitative phase mapping in confocal optical microscopy by applying synthetic optical holography (SOH), a recently introduced method for technically simple and fast phase imaging in scanning optical microscopy. SOH is implemented in a confocal microscope by simply adding a linearly moving reference mirror to the microscope setup, which generates a synthetic reference wave analogous to the plane reference wave of wide-field off-axis holography. We demonstrate that SOH confocal microscopy allows for non-contact surface profiling with sub-nanometer depth resolution. As an application for biological imaging, we apply SOH confocal microscopy to map the surface profile of an onion cell, revealing nanoscale-height features on the cell surface.

The broadband microwave spectra of the monoterpenoids thymol and carvacrol: conformational landscape and internal dynamics.

The rotational spectra of the monoterpenoids thymol and carvacrol are reported in the frequency range 2-8.5 GHz, obtained with broadband Fourier-transform microwave spectroscopy. For carvacrol four different conformations were identified in the cold conditions of the molecular jet, whereas only three conformations were observed for thymol. The rotational constants and other molecular parameters are reported and compared with quantum chemical calculations. For both molecules, line splittings due to methyl group internal rotation were observed and the resulting barrier heights could be determined. The experimental barrier heights, 4.0863(25) kJ/mol for trans-carvacrol-A, 4.4024(16) kJ/mol for trans-carvacrol-B, and 0.3699(11) kJ/mol for trans-thymol-A, are compared with similar molecules.

Synthetic optical holography for rapid nanoimaging.

Holography has paved the way for phase imaging in a variety of wide-field techniques, including electron, X-ray and optical microscopy. In scanning optical microscopy, however, the serial fashion of image acquisition seems to challenge a direct implementation of traditional holography. Here we introduce synthetic optical holography (SOH) for quantitative phase-resolved imaging in scanning optical microscopy. It uniquely combines fast phase imaging, technical simplicity and simultaneous operation at visible and infrared frequencies with a single reference arm. We demonstrate SOH with a scattering-type scanning near-field optical microscope (s-SNOM) where it enables reliable quantitative phase-resolved near-field imaging with unprecedented speed. We apply these capabilities to nanoscale, non-invasive and rapid screening of grain boundaries in CVD-grown graphene, by recording 65 kilopixel near-field images in 26 s and 2.3 megapixel images in 13 min. Beyond s-SNOM, the SOH concept could boost the implementation of holography in other scanning imaging applications such as confocal microscopy.

[Research with participants suffering from dementia. Ethical and legal considerations in research involving human subjects]. / Forschung mit demenzkranken Probanden. Zum forschungsethischen und rechtlichen Umgang mit diesen Personen.

Using case reports from the health services research project Action Alliance Pain-Free City Muenster, fundamental issues of research ethics, data protection and legal guardianship are shown and explained. A plan of important aspects to be considered while planning, conducting and recruiting for research with nursing home inhabitants suffering from dementia in a legally correct and safe manner is presented.

Resolving the electromagnetic mechanism of surface-enhanced light scattering at single hot spots.

Light scattering at nanoparticles and molecules can be dramatically enhanced in the 'hot spots' of optical antennas, where the incident light is highly concentrated. Although this effect is widely applied in surface-enhanced optical sensing, spectroscopy and microscopy, the underlying electromagnetic mechanism of the signal enhancement is challenging to trace experimentally. Here we study elastically scattered light from an individual object located in the well-defined hot spot of single antennas, as a new approach to resolve the role of the antenna in the scattering process. We provide experimental evidence that the intensity elastically scattered off the object scales with the fourth power of the local field enhancement provided by the antenna, and that the underlying electromagnetic mechanism is identical to the one commonly accepted in surface-enhanced Raman scattering. We also measure the phase shift of the scattered light, which provides a novel and unambiguous fingerprint of surface-enhanced light scattering.

Infrared-spectroscopic nanoimaging with a thermal source.

Fourier-transform infrared (FTIR) spectroscopy is a widely used analytical tool for chemical identification of inorganic, organic and biomedical materials, as well as for exploring conduction phenomena. Because of the diffraction limit, however, conventional FTIR cannot be applied for nanoscale imaging. Here we demonstrate a novel FTIR system that allows for infrared-spectroscopic nanoimaging of dielectric properties (nano-FTIR). Based on superfocusing of thermal radiation with an infrared antenna, detection of the scattered light, and strong signal enhancement employing an asymmetric FTIR spectrometer, we improve the spatial resolution of conventional infrared spectroscopy by more than two orders of magnitude. By mapping a semiconductor device, we demonstrate spectroscopic identification of silicon oxides and quantification of the free-carrier concentration in doped Si regions with a spatial resolution better than 100 nm. We envisage nano-FTIR becoming a powerful tool for chemical identification of nanomaterials, as well as for quantitative and contact-free measurement of the local free-carrier concentration and mobility in doped nanostructures.

[The wisdom of the elderly]. / Weisheit des alten Menschen.

Old age is nowadays defined as very old and people are characterized by illness, degeneration and health costs. Ethics in this case have to be healthcare ethics, which accept the challenge to lead people in old age through the healthcare point of view and demonstrate how to integrate their wisdom into culture and society.

Phase-resolved mapping of the near-field vector and polarization state in nanoscale antenna gaps.

We demonstrate that the local near-field vector and polarization state on planar antenna structures and in nanoscale antenna gaps can be determined by scattering-type near-field optical microscopy (s-SNOM). The near-field vector is reconstructed from the amplitude and phase images of the in- and out-of-plane near-field components obtained by polarization-resolved interferometric detection. Experiments with a mid-infrared inverse bowtie antenna yield a vectorial near-field distribution with unprecedented resolution of about 10 nm and in excellent agreement with numerical simulations. Furthermore, we provide first direct experimental evidence that the nanoscale confined and strongly enhanced fields at the antenna gap are linearly polarized. s-SNOM vector-field mapping paves the way to a full near-field characterization of nanophotonic structures in the broad spectral range between visible and terahertz frequencies, which is essential for future development and quality control of metamaterials, optical sensors, and waveguides.

A novel merged beams apparatus to study anion-neutral reactions.

We have developed a novel laboratory instrument for studying gas phase, anion-neutral chemistry. To the best of our knowledge, this is the first such apparatus which uses fast merged beams to investigate anion-neutral chemical reactions. As proof-of-principle we have detected the associative detachment reaction H(-)+H-->H(2)+e(-). Here we describe the apparatus in detail and discuss related technical and experimental issues.

Role of virus-induced neuropeptides in the brain in the pathogenesis of rabies.

Rabies virus (RABV) infection is characterized by the rapid neuronal spread of RABV into the CNS before a protective immune response is raised. Therefore, a typical feature of RABV infection is the paucity of inflammatory reactions in the brain. Here we examined whether the induction of immunosuppressive neuropeptides, in particular CGRP, may contribute to the ability of RABV to evade immune responses. RABV infection of mice caused a strong induction of calcitonin gene-related peptide (CGRP) in neurons and fibres in the neocortex as well as in the dentate gyrus and CA1 region of the hippocampus although RABV did not infect neurons in which CGRP expression was upregulated. Neuropeptide Y (NPY) or vasoactive intestinal peptide (VIP) expressing neurons also were not infected by RABV. In contrast, somatostatin neurons were infected by RABV. There was evidence for an RABV-induced increase of VIP and somatostatin but not of NPY. To test how CGRP expression is related to TNFalpha-induced enhancement of CNS innate and adaptive immunity during RABV infection, we used recombinant RABVs that contained either an active (SPBN-TNFalpha(+)) or an inactive (SPBN-TNFalpha(-)) TNFalpha gene. As compared to SPBN-TNFalpha(-), infection with SPBN-TNFalpha(+) attenuated the induction of CGRP but simultaneously enhanced induction of the invariant chain of MHC II, microglial activation and T cell infiltration. In conclusion, distinct neuropeptidergic neurons in the brain are remarkably spared from RABV infection suggesting a pivotal role of neuropeptides during CNS virus infection. Given the inhibitory effect of CGRP on antigen presentation, we propose that the strong RABV-induced upregulation of CGRP in the brain may contribute to the mechanism by which RABV escapes immune detection. Targeting the expression of neuropeptides, in particular CGRP, that are induced during RABV infection may open a new avenue for therapeutic intervention in human rabies.