Cavity-dumping a single infrared pulse from a free-electron laser for two-color pump-probe experiments.

Electromagnetic radiation in the mid- to far-infrared spectral range represents an indispensable tool for the study of numerous types of collective excitations in solids and molecules. Short and intense pulses in this terahertz spectral range are, however, difficult to obtain. While wide wavelength-tunability is easily provided by free-electron lasers, the energies of individual pulses are relatively moderate, on the order of microjoules. Here, we demonstrate a setup that uses cavity-dumping of a free-electron laser to provide single, picosecond-long pulses in the mid- to far-infrared frequency range. The duration of the Fourier-limited pulses can be varied by cavity detuning, and their energy was shown to exceed 100 µJ. Using the aforementioned infrared pulse as a pump, we have realized a two-color pump-probe setup facilitating single-shot time-resolved imaging of magnetization dynamics. We demonstrate the capabilities of the setup first on thermally induced demagnetization and magnetic switching of a GdFeCo thin film and second by showing a single-shot time-resolved detection of resonant phononic switching of the magnetization in a magnetic garnet.

Structural determination of neutral Co n clusters (n = 4-10,13) through IR-UV two-color vibrational spectroscopy and DFT calculations.

We recorded IR spectra for neutral cobalt clusters via two-color IR-UV ionization, using the Free Electron Laser for intracavity experiments (FELICE). Well-resolved IR spectra are presented for [Formula: see text] (n = 4-10, 13) and analyzed with the help of Density Functional Theory calculations using two different correlation exchange functionals: the revisited Tao-Perdew-Staroverov-Scuseria (revTPSS) and the frequently used Perdew-Burke-Ernzerhof (PBE) approaches. Although we have not performed an extensive structure search, we tentatively assign the spectra for all cluster sizes except for n = 7, and n = 10. We find that neither of the two functionals chosen clearly outperforms the other in predicting IR spectra, and that relatively low scaling factors of 0.82 (PBE) and 0.8 (revTPSS) are required. In contrast to the magnetic moments, the calculated electric dipole moments fluctuate strongly as a function of cluster size and could therefore be used as an indirect probe to the cluster structure.

Mechano-electric coupling, heterogeneity in repolarization and the electrocardiographic T-wave.

Stretch influences repolarization by mechano-electric coupling (MEC) and contributes to arrhythmogenesis. Although there is an abundance of research on electrophysiological effects of MEC, it is still unclear how MEC translates to the ECG. We aim to provide an overview of the MEC research focused on the ECG and the underlying changes in electrophysiology. In addition, we present new data on the effect of left ventricular pressure on the electrocardiographic T-wave. We show that an increase in left ventricular pressure leads to prolonged QT-intervals with increased amplitudes of the STT-segment. This corresponds to a prolongation in repolarization and an increased interventricular dispersion of repolarization. MEC is dependent on timing, intensity and modality of stretch and these three factors should be taken into account to analyse the effects of MEC on the heart and on the ECG. In addition, the deformation of the heart itself should be considered, since it influences the amplitude of the STT-segment. Because the electrocardiographic T-wave represents heterogeneity in repolarization, left ventricular pressure increases may have significant influence on the inducibility of (re-entrant) arrhythmias.

Determination of the geometric structure of neutral niobium carbide clusters via infrared spectroscopy.

We report experimental vibrational spectra of small neutral niobium carbide clusters in the 350-850 cm-1 spectral range. Clusters were first irradiated by IR light and subsequently probed using UV light with photon energies just below the ionization threshold. Upon resonance with an IR vibrational mode, the number of cluster ions increases, allowing to record a vibrational spectrum. In complementary density functional theory calculations, we have simulated the IR spectra for several low-energy isomers. We were able to assign the spectra experimentally obtained for each cluster size to a specific geometric structure based on the match with the computed spectra. The number of the cluster sizes investigated here allows to follow the evolution of the geometric structure of the niobium and carbon components of clusters separately. For Nb6Cm (m = 4, 5, 6), we observe the emergence of the cubic crystal structures similar to the bulk.

The repopulation of electronic states upon vibrational excitation of niobium carbide clusters.

We study the infrared (IR) resonant heating of neutral niobium carbide clusters probed through ultraviolet photoionization spectroscopy. The IR excitation not only changes the photoionization spectra for the photon energies above the ionization threshold, but also modulates ion yield for energies significantly below it. An attempt to describe the experimental spectra using either Fowler's theory or thermally populated vibrational states was not successful. However, the data can be fully modeled by vibrationally and rotationally broadened discrete electronic levels obtained from Density Functional Theory (DFT) calculations. The application of this method to spectra with different IR pulse energies not only yields information about the excited electronic states in the vicinity of the HOMO level, populated by manipulation of the vibrational coordinates of a cluster, but also can serve as an extra indicator for the cluster isomeric structure and corresponding DFT-calculated electronic levels.

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the µ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Single-size thermometric measurements on a size distribution of neutral fullerenes.

We present measurements of the velocity distribution of electrons emitted from mass-selected neutral fullerenes, performed at the intracavity free electron laser FELICE. We make use of mass-specific vibrational resonances in the infrared domain to selectively heat up one out of a distribution of several fullerene species. Efficient energy redistribution leads to decay via thermionic emission. Time-resolved electron kinetic energy distributions measured give information on the decay rate of the selected fullerene. This method is generally applicable to all neutral species that exhibit thermionic emission and provides a unique tool to study the stability of mass-selected neutral clusters and molecules that are only available as part of a size distribution.

Structures of the dehydrogenation products of methane activation by 5d transition metal cations.

The activation of methane by gas-phase transition metal cations (M(+)) has been studied extensively, both experimentally and using density functional theory (DFT). Methane is exothermically dehydrogenated by several 5d metal ions to form [M,C,2H](+) and H2. However, the structure of the dehydrogenation product has not been established unambiguously. Two types of structures have been considered: a carbene structure where an intact CH2 fragment is bound to the metal (M(+)-CH2) and a carbyne (hydrido-methylidyne) structure with both a CH and a hydrogen bound to the metal separately (H-M(+)-CH). For metal ions with empty d-orbitals, an agostic interaction can occur that could influence the competition between carbene and carbyne structures. In this work, the gas phase [M,C,2H](+) (M = Ta, W, Ir, Pt) products are investigated by infrared multiple-photon dissociation (IR-MPD) spectroscopy using the Free-Electron Laser for IntraCavity Experiments (FELICE). Metal cations are formed in a laser ablation source and react with methane pulsed into a reaction channel downstream. IR-MPD spectra of the [M,C,2H](+) species are measured in the 300-3500 cm(-1) spectral range by monitoring the loss of H (2H in the case of [Ir,C,2H](+)). For each system, the experimental spectrum closely resembles the calculated spectrum of the lowest energy structure calculated using DFT: for Pt, a classic C(2v) carbene structure; for Ta and W, carbene structures that are distorted by agostic interactions; and a carbyne structure for the Ir complex. The Ir carbyne structure was not considered previously. To obtain this agreement, the calculated harmonic frequencies are scaled with a scaling factor of 0.939, which is fairly low and can be attributed to the strong redshift induced by the IR multiple-photon excitation process of these small molecules. These four-atomic species are among the smallest systems studied by IR-FEL based IR-MPD spectroscopy, and their spectra demonstrate the power of IR spectroscopy in resolving long-standing chemical questions.

Scaling laws for photoelectron holography in the midinfrared wavelength regime.

Midinfrared strong-field laser ionization offers the promise of measuring holograms of atoms and molecules, which contain both spatial and temporal information of the ion and the photoelectron with subfemtosecond temporal and angstrom spatial resolution. We report on the scaling of photoelectron holographic interference patterns with the laser pulse duration, wavelength, and intensity. High-resolution holograms for the ionization of metastable xenon atoms by 7-16 µm light from the FELICE free electron laser are presented and compared to semiclassical calculations that provide analytical insight.

Monitoring cardiac fibrosis: a technical challenge.

The heart contains a collagen network that contributes to the contractility of the heart and provides cardiac strength. In cardiac diseases, an increase in collagen deposition is often observed. This fibrosis formation causes systolic and diastolic dysfunction, and plays a major role in the arrythmogenic substrate. Therefore, accurate detection of cardiac fibrosis and its progression is of clinical importance with regard to diagnostics and therapy for patients with cardiac disease. To evaluate cardiac collagen deposition, both invasive and non-invasive techniques are used. In this review the different techniques that are currently used in clinical and experimental setting are summarised, and the advantages and disadvantages of these techniques are discussed.

Noninvasive detection of epicardial and endocardial activity of the heart.

Determining electrical activation of the heart in a noninvasive way is one of the challenges in cardiac electrophysiology. The ECG provides some, but limited information about the electrical status of the heart. This article describes a method to determine both endocardial and epicardial activation of the heart of an individual patient from 64 electrograms recorded from the body surface. Information obtained in this way might be helpful for the treatment of arrhythmias, to assess the effect of drugs on conduction in the heart and to assess electrical stability of the heart.

Time-resolved holography with photoelectrons.

Ionization is the dominant response of atoms and molecules to intense laser fields and is at the basis of several important techniques, such as the generation of attosecond pulses that allow the measurement of electron motion in real time. We present experiments in which metastable xenon atoms were ionized with intense 7-micrometer laser pulses from a free-electron laser. Holographic structures were observed that record underlying electron dynamics on a sublaser-cycle time scale, enabling photoelectron spectroscopy with a time resolution of almost two orders of magnitude higher than the duration of the ionizing pulse.

Longitudinal arrhythmogenic remodelling in a mouse model of longstanding pressure overload.

INTRODUCTION: Sudden arrhythmogenic cardiac death is a major cause of mortality in patients with congestive heart failure due to adverse electrical remodelling. To establish whether abnormal conduction is responsible for arrhythmogenic remodelling in progressed stages of heart failure, we have monitored functional, structural and electrical remodelling in a murine model of heart failure, induced by longstanding pressure overload. METHODS: Mice were subjected to transverse aortic constriction (TAC; n=18) or sham operated (n=19) and monitored biweekly by echocardiography and electrocardiography. At the 16-week endpoint, electrical mapping was performed to measure epicardial conduction velocity and susceptibility to arrhythmias. Finally, tissue sections were stained for Cx43 and fibrosis. RESULTS: In TAC mice, fractional shortening decreased gradually and was significantly lower compared with sham at 16 weeks. Left ventricular hypertrophy was significant after six weeks. TAC mice developed PQ prolongation after 12 weeks, QT prolongation after 16 weeks and QRS prolongation after two weeks. Right ventricular conduction velocity was slowed parallel to fibre orientation. In 8/18 TAC hearts, polymorphic ventricular tachyarrhythmias were provoked and none in sham hearts. TAC mice had more interstitial fibrosis than sham. Immunohistology showed that Cx43 levels were similar but highly heterogeneous in TAC mice. All parameters were comparable in TAC mice with and without arrhythmias, except for Cx43 heterogeneity, which was significantly higher in arrhythmogenic TAC mice. CONCLUSION.: Chronic pressure overload resulted in rapid structural and electrical remodelling. Arrhythmias were related to heterogeneous expression of Cx43. This may lead to functional block and unstable reentry, giving rise to polymorphic ventricular tachyarrhythmias. (Neth Heart J 2010;18:509-15.).

Fever-triggered ventricular arrhythmias in Brugada syndrome and type 2 long-QT syndrome.

The risk for lethal ventricular arrhythmias is increased in individuals who carry mutations in genes that encode cardiac ion channels. Loss-of-function mutations in SCN5A, the gene encoding the cardiac sodium channel, are linked to Brugada syndrome (BrS). Arrhythmias in BrS are often preceded by coved-type ST-segment elevation in the right-precordial leads V1 and V2. Loss-of-function mutations in KCNH2, the gene encoding the cardiac ion channel that is responsible for the rapidly activating delayed rectifying potassium current, are linked to long-QT syndrome type 2 (LQT-2). LQT-2 is characterised by delayed cardiac repolarisation and rate-corrected QT interval (QTc) prolongation. Here, we report that the risk for ventricular arrhythmias in BrS and LQT-2 is further increased during fever. Moreover, we demonstrate that fever may aggravate coved-type ST-segment elevation in BrS, and cause QTc lengthening in LQT-2. Finally, we describe molecular mechanisms that may underlie the proarrhythmic effects of fever in BrS and LQT-2. (Neth Heart J 2010;18:165-9.).

The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium.

Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P < 0.05), indicating decreased sodium channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel disease.

Infrared spectroscopy and structures of cobalt carbonyl cations, Co(CO)n+ (n = 1-9).

Cobalt carbonyl cations of the form Co(CO)(n)(+) (n = 1-9) are produced in a molecular beam by laser vaporization in a pulsed nozzle source. These ions, and their corresponding "argon-tagged" analogues, Co(CO)(n)(Ar)(m)(+), are studied with mass-selected infrared photodissociation spectroscopy in the carbonyl stretching region. The number of infrared-active bands, their frequency positions, and their relative intensities provide distinctive patterns allowing determination of the geometries and electronic structures of these complexes. Co(CO)(5)(+) has a completed coordination sphere, consistent with its expected 18-electron stability, and it has the same structure (D(3h) trigonal bipyramid) as its neutral isoelectronic analog Fe(CO)(5). The carbonyl stretches in Co(CO)(5)(+) are less red-shifted than those in Fe(CO)(5) because of charge-induced reduction in the pi back-bonding. Co(CO)(1-4)(+) complexes have triplet ground states, but the spin changes to a singlet for the Co(CO)(5)(+) complex.

Differences in distribution of fibrosis in the ventricles underlie dominant arrhythmia vulnerability of the right ventricle in senescent mice.

Mutations that are supposed to affect right (RV) and left ventricular (LV) electrophysiology equally, often reveal dominant conduction slowing and arrhythmia vulnerability in RV. In this study we investigated the mechanism of dominant arrhythmia vulnerability of RV in senescent mice. We performed epicardial ventricular activation mapping on adult and senescent Langendorff perfused hearts. Longitudinal and transversal conduction velocity, as well as arrhythmia inducibility were determined. Subsequently, hearts were processed for immunohisto-chemistry and Picro Sirius Red staining. Senescent mice revealed decreased conduction velocity, increased aniso-tropic ratio and reduced excitation wavelength in RV, but not in LV. Arrhythmias were mainly induced in RV of senescent hearts. No arrhythmias were induced in adult hearts. Immunohistochemistry revealed that the amount of Connexin 43 and cardiac sodium channel Nav1 .5 were equally decreased, and that collagen content was equally increased in senescent RV and LV. However, patches of replacement fibrosis were found throughout the RV wall, but only in the sub-endocardium and mid-myocardium of LV. The study shows that the dominant arrhythmia vulnerability in RV of senescent mice is caused by the distribution of replacement fibrosis which involves the entire RV but only part of the LV. (Neth Heart J 2008;16:356-8.).

Adrenergic regulation of conduction velocity in cultures of immature cardiomyocytes.

During cardiac maturation, increased exposure of the heart to circulating catecholamines correlates with increased conduction velocity and growth of the heart. We used an in vitro approach to study the underlying mechanisms of adrenergic stimulation induced changes in conduction velocity. By combining functional measurements and molecular techniques, we were able to demonstrate that the increased conduction velocity after beta-adrenergic stimulation is probably not caused by changes in intercellular coupling. Instead, RT-PCR experiments and action potential measurements have shown an increased excitability that may well explain the observed increase in conduction velocity. Apart from being relevant to cardiac maturation, our findings are relevant in the context of stem cells and cardiac repair. Preconditioning of stem cell derived cardiomyocytes may help to enhance electrical maturation of de novo generated cardiomyocytes and consequently reduce their proarrhythmogenic potential. (Neth Heart J 2008;16:106-9.).