Concentration gradients in evaporating binary droplets probed by spatially resolved Raman and NMR spectroscopy.

Understanding the evaporation process of binary sessile droplets is essential for optimizing various technical processes, such as inkjet printing or heat transfer. Liquid mixtures whose evaporation and wetting properties may differ significantly from those of pure liquids are particularly interesting. Concentration gradients may occur in these binary droplets. The challenge is to measure concentration gradients without affecting the evaporation process. Here, spectroscopic methods with spatial resolution can discriminate between the components of a liquid mixture. We show that confocal Raman microscopy and spatially resolved NMR spectroscopy can be used as complementary methods to measure concentration gradients in evaporating 1-butanol/1-hexanol droplets on a hydrophobic surface. Deuterating one of the liquids allows analysis of the local composition through the comparison of the intensities of the C­H and C­D stretching bands in Raman spectra. Thus, a concentration gradient in the evaporating droplet was established. Spatially resolved NMR spectroscopy revealed the composition at different positions of a droplet evaporating in the NMR tube, an environment in which air exchange is less pronounced. While not being perfectly comparable, both methods­confocal Raman and spatially resolved NMR experiments­show the presence of a vertical concentration gradient as 1-butanol/1-hexanol droplets evaporate.

XUV pump-XUV probe transient absorption spectroscopy at FELs.

The emergence of ultra-intense extreme-ultraviolet (XUV) and X-ray free-electron lasers (FELs) has opened the door for the experimental realization of non-linear XUV and X-ray spectroscopy techniques. Here we demonstrate an experimental setup for an all-XUV transient absorption spectroscopy method for gas-phase targets at the FEL. The setup combines a high spectral resolving power of E/ΔE ≈ 1500 with sub-femtosecond interferometric resolution, and covers a broad XUV photon-energy range between approximately 20 and 110 eV. We demonstrate the feasibility of this setup firstly on a neon target. Here, we intensity- and time-resolve key aspects of non-linear XUV-FEL light-matter interactions, namely the non-resonant ionization dynamics and resonant coupling dynamics of bound states, including XUV-induced Stark shifts of energy levels. Secondly, we show that this setup is capable of tracking the XUV-initiated dissociation dynamics of small molecular targets (oxygen and diiodomethane) with site-specific resolution, by measuring the XUV transient absorption spectrum. In general, benefitting from a single-shot detection capability, we show that the setup and method provides single-shot phase-locked XUV pulse pairs. This lays the foundation to perform, in the future, experiments as a function of the XUV interferometric time delay and the relative phase, which enables advanced coherent non-linear spectroscopy schemes in the XUV and X-ray spectral range.

XUV-Initiated Dissociation Dynamics of Molecular Oxygen (O2).

We performed a time-resolved spectroscopy experiment on the dissociation of oxygen molecules after the interaction with intense extreme-ultraviolet (XUV) light from the free-electron laser in Hamburg at Deutsches Elektronen-Synchrotron. Using an XUV-pump/XUV-probe transient-absorption geometry with a split-and-delay unit, we observe the onset of electronic transitions in the O2+ cation near 50 eV photon energy, marking the end of the progression from a molecule to two isolated atoms. We observe two different time scales of 290 ± 53 and 180 ± 76 fs for the emergence of different ionic transitions, indicating different dissociation pathways taken by the departing oxygen atoms. With regard to the emerging opportunities of tuning the central frequencies of pump and probe pulses and of increasing the probe-pulse bandwidth, future pump-probe transient-absorption experiments are expected to provide a detailed view of the coupled nuclear and electronic dynamics during molecular dissociation.

Noise effects and the impact of detector responses on the characterization of extreme ultraviolet attosecond pulses.

We employ numerical simulations to study the effects of noise on the reconstruction of the duration and satellite intensity ratio for transform-limited single and double pulses of 200 as duration. The forms of noise we implement are delay jitters between the attosecond pulse and the near-IR laser field, energy resolution of the photoelectron detector, and Poisson noise in streaking spectrograms with different count levels. We use the streaking method to characterize the pulse and the extended ptychographic iterative engine retrieval algorithm to reconstruct the pulse from the simulated streaking spectrogram. We found that, for practical purposes, when implementing a combination of all three mentioned noise contributions, the attosecond pulse duration will be overestimated when the photoelectron count level is low. Furthermore, the satellite pulse amplitude of the attosecond double pulse can be retrieved within 10% accuracy.

Attosecond precision in delay measurements using transient absorption spectroscopy.

Accessing attosecond (as) dynamics directly in the time domain has been achieved by several pioneering experiments over the course of the last decade. Extreme ultraviolet (XUV) group delays and, later, ionization time delays on the order of a few attoseconds have been extracted by photoemission or high-harmonic spectroscopy. Here, we present and benchmark an approach based on attosecond transient absorption spectroscopy to quantify deliberately induced delays by employing resonant photoexcitation of three XUV transitions with a precision of less than 5 as. While here we quantify the sensitivity to these delays via a chirp on the attosecond pulse by using thin-foil metallic filters, the method enables future studies of attosecond delays probed through resonant excitations.

Strong-Field Extreme-Ultraviolet Dressing of Atomic Double Excitation.

We report on the experimental observation of a strong-field dressing of an autoionizing two-electron state in helium with intense extreme-ultraviolet laser pulses from a free-electron laser. The asymmetric Fano line shape of this transition is spectrally resolved, and we observe modifications of the resonance asymmetry structure for increasing free-electron-laser pulse energy on the order of few tens of Microjoules. A quantum-mechanical calculation of the time-dependent dipole response of this autoionizing state, driven by classical extreme-ultraviolet (XUV) electric fields, evidences strong-field-induced energy and phase shifts of the doubly excited state, which are extracted from the Fano line-shape asymmetry. The experimental results obtained at the Free-Electron Laser in Hamburg (FLASH) thus correspond to transient energy shifts on the order of a few meV, induced by strong XUV fields. These results open up a new way of performing nonperturbative XUV nonlinear optics for the light-matter interaction of resonant electronic transitions in atoms at short wavelengths.

Nonlinear Coherence Effects in Transient-Absorption Ion Spectroscopy with Stochastic Extreme-Ultraviolet Free-Electron Laser Pulses.

We demonstrate time-resolved nonlinear extreme-ultraviolet absorption spectroscopy on multiply charged ions, here applied to the doubly charged neon ion, driven by a phase-locked sequence of two intense free-electron laser pulses. Absorption signatures of resonance lines due to 2p-3d bound-bound transitions between the spin-orbit multiplets ^{3}P_{0,1,2} and ^{3}D_{1,2,3} of the transiently produced doubly charged Ne^{2+} ion are revealed, with time-dependent spectral changes over a time-delay range of (2.4±0.3) fs. Furthermore, we observe 10-meV-scale spectral shifts of these resonances owing to the ac Stark effect. We use a time-dependent quantum model to explain the observations by an enhanced coupling of the ionic quantum states with the partially coherent free-electron laser radiation when the phase-locked pump and probe pulses precisely overlap in time.

Stability of Evaporating Droplets on Chemically Patterned Surfaces.

The stability of water droplets on striped surfaces exposing regions of different wettability is studied experimentally, numerically, and based on a scaling model. Different values of the stripe widths and different contact angle contrasts between the hydrophilic and hydrophobic stripes are considered. The boundary between the contact angle contrasts leaving the droplets intact and those leading to droplet breakup is computed numerically. The minimum contrast for which breakup occurs increases with increasing hydrophobic contact angle. The existence of an unstable and a stable regime is confirmed experimentally. In the unstable regime, when approching droplet breakup, a configuration with two liquid fingers on the hydrophilic stripes connected by a capillary bridge on the hydrophobic stripe is found. For decreasing volumes, the width of this capillary bridge decreases until a critical value is reached at which the droplet breaks up. The critical width depends on the ratio of the hydrophilic and the hydrophobic stripe width. A simple scaling model is presented with which the critical width can be predicted. According to the model, the droplet becomes unstable when the increasing Laplace pressure inside the bridge can no longer be balanced by the pressure inside the liquid fingers on the hydrophilic stripes.

Time-resolved four-wave-mixing spectroscopy for inner-valence transitions.

Noncollinear four-wave-mixing (FWM) techniques at near-infrared (NIR), visible, and ultraviolet frequencies have been widely used to map vibrational and electronic couplings, typically in complex molecules. However, correlations between spatially localized inner-valence transitions among different sites of a molecule in the extreme ultraviolet (XUV) spectral range have not been observed yet. As an experimental step toward this goal, we perform time-resolved FWM spectroscopy with femtosecond NIR and attosecond XUV pulses. The first two pulses (XUV-NIR) coincide in time and act as coherent excitation fields, while the third pulse (NIR) acts as a probe. As a first application, we show how coupling dynamics between odd- and even-parity, inner-valence excited states of neon can be revealed using a two-dimensional spectral representation. Experimentally obtained results are found to be in good agreement with ab initio time-dependent R-matrix calculations providing the full description of multielectron interactions, as well as few-level model simulations. Future applications of this method also include site-specific probing of electronic processes in molecules.

In vivo contact force measurements and correlation with left atrial anatomy during catheter ablation of atrial fibrillation.

AIMS: Lesion formation during catheter ablation crucially depends on catheter-tissue contact. We sought to evaluate the impact of anatomical characteristics of the left atrium (LA) and the pulmonary veins (PVs) on contact force (CF) measurements. METHODS AND RESULTS: An anatomical map of the LA was obtained in 25 patients prior to catheter ablation of atrial fibrillation. Contact force (operator blinded) and local bipolar electrogram amplitudes (EGM) were measured in eight pre-defined segments around the PVs. After unblinding, points with low CF (≤5 g) were corrected to CF >5 g, and the distance between points was measured. In a pre-procedural computed tomography of the heart, LA volume as well as sizes and circumferences of the PV ostia were measured and correlated to CF measurements. Four hundred and twenty-six points in eight pre-defined LA locations were assessed. Low CF (<5 g) was found in 25.0% (43.5%) of points superior, 33.3% (66.7%) anterior, 32.1% (44.4%) inferior, and 15.5% (15.9%) posterior to the right (left) PVs. The mean distance after correction was 5.8 ± 3.4 mm. Local bipolar electrogram amplitudes between low- and high-CF points did not differ (1.21 ± 1.54 vs. 1.13 ± 1.3 mV, P = ns). The mean CF at the left PVs was significantly lower than at the right PVs (7.91 ± 3.74 vs. 13.95 ± 6.34 g, P < 0.001), with the lowest CF anterior to the left PVs (5.2 ± 3.6 g). Contact force measurements did not correlate to LA volume, size, and circumference of the PVs. CONCLUSION: Contact force during LA mapping significantly differs according to the location within the LA. These differences are independent of LA volume and anatomy of the PV ostia.

Haemodynamic vector personalization of a quadripolar left ventricular lead used for cardiac resynchronization therapy: use of surface electrocardiogram and interventricular time delays.

AIMS: The choice of left ventricular pacing configurations (LVPCs) of quadripolar leads used for cardiac resynchronization therapy (CRT) affects haemodynamic response and thus may be a tool for device optimization. The value of surface electrocardiograms and interventricular time delays (IVDs) for optimization is unknown. METHODS AND RESULTS: Sixteen patients implanted with a CRT device with a quadripolar LV lead underwent invasive testing of LV dP/dt. QRS durations at baseline (bl) and during biventricular pacing (biv) were measured using different LVPCs (total of 141 LVPCs; 8.8 per patient). Variations in QRS duration during biv were calculated for each patient (ΔQRS) and, when compared with intrinsic QRS duration, for all LVPCs (ΔQRSLVPC). Interventricular time delays between the poles of the LV lead were obtained from intracardiac electrograms. ΔIVD was calculated as IVDmax - IVDmin. Parameters were correlated with LV dP/dt. ΔQRS and ΔQRSLVPC both significantly correlated with LV dP/dt (P < 0.01). Correlation was found for patients with ischaemic (P < 0.001) and non-ischaemic cardiomyopathy (P < 0.05), and for patients with bl QRS duration >168 ms (P < 0.001), but not <168 ms (P = ns). The LVPC with shortest QRS duration also yielded maximal LV dP/dt in 6 of 16 patients (37.5%), and was equal or better in LV dP/dt in 12 of 16 patients (75%). ΔIVD neither correlated with ΔQRS nor ΔLV dP/dt. CONCLUSION: ΔQRS predicts the maximal value of vector personalization in the individual. Reductions in QRS width, but not IVDs, correlate with acute haemodynamic response. Intraindividually, in 75% of patients, the LVPC with the shortest QRS duration gives equal or superior haemodynamic results when compared with the LVPC with longest QRS duration.

Sensitive Identification of Asymmetries and Neuromuscular Deficits in Lower Limb Function in Early Multiple Sclerosis.

BACKGROUND: In the early stages of multiple sclerosis (MS), there are no objective sensitive functional assessments to identify and quantify early subclinical neuromuscular deficits and lower limb strength asymmetries during complex movements. Single-countermovement jumps (SLCMJ), a maximum single leg vertical jump, on a force plate allow functional evaluation of unilateral lower limb performance in performance diagnostics and could therefore provide early results on asymmetries in MS. OBJECTIVE: Objective evaluation of early lower limb neuromuscular deficits and asymmetries in people with multiple sclerosis (pwMS) using SLCMJ on a force plate. METHODS: A study was conducted with pwMS (N = 126) and healthy controls (N = 97). All participants performed 3 maximal SLCMJs on a force plate. Temporal, kinetic, and power jump parameters were collected. The Expanded Disability Status Scale (EDSS) was performed on all participants. A repeated measures analysis of covariance (ANCOVA) with age, Body-Mass-Index, and gender as covariates was used. RESULTS: PwMS with normal muscle strength according to the manual muscle tests showed significantly reduced SLCMJ performance compared to HC. In both groups, jumping performance differed significantly between the dominant and non-dominant leg, with higher effect size for pwMS. A significant interaction effect between leg dominance and group was found for propulsive time, where the pwMS showed an even higher difference between the dominant and non-dominant leg compared to HC. Furthermore, there was a significant small correlation between leg asymmetries and EDSS in pwMS. CONCLUSION: The study shows that the SLCMJ on a force plate is suitable for the early detection of subclinical lower limb neuromuscular deficits and strength asymmetries in MS.

The Association of Age, Sex, and BMI on Lower Limb Neuromuscular and Muscle Mechanical Function in People with Multiple Sclerosis.

(1) Background: The countermovement jump (CMJ) on a force plate could be a sensitive assessment for detecting early lower-limb muscle mechanical deficits in the early stages of multiple sclerosis (MS). CMJ performance is known to be influenced by various anthropometric, physiological, and biomechanical factors, mostly investigated in children and adult athletes. Our aim was to investigate the association of age, sex, and BMI with muscle mechanical function using CMJ to provide a comprehensive overview of lower-limb motor function in people with multiple sclerosis (pwMS). (2) Methods: A cross-sectional study was conducted with pwMS (N = 164) and healthy controls (N = 98). All participants performed three maximal CMJs on a force plate. Age, sex, and BMI were collected from all participants. (3) Results: Significant age, sex, and BMI effects were found for all performance parameters, flight time, and negative and positive power for pwMS and HC, but no significant interaction effects with the group (pwMS, HC) were detected. The highest significant effects were found for sex on flight time (η2 = 0.23), jump height (η2 = 0.23), and positive power (η2 = 0.13). PwMS showed significantly lower CMJ performance compared to HC in middle-aged (31-49 years), with normal weight to overweight and in both women and men. (4) Conclusions: This study showed that age, sex, and BMI are associated with muscle mechanical function in pwMS and HC. These results may be useful in developing reference values for CMJ. This is a crucial step in integrating CMJ into the diagnostic assessment of people with early MS and developing individualized and effective neurorehabilitative therapy.

From sunrise to sunset: Exploring landscape preference through global reactions to ephemeral events captured in georeferenced social media.

Events profoundly influence human-environment interactions. Through repetition, some events manifest and amplify collective behavioral traits, which significantly affects landscapes and their use, meaning, and value. However, the majority of research on reaction to events focuses on case studies, based on spatial subsets of data. This makes it difficult to put observations into context and to isolate sources of noise or bias found in data. As a result, inclusion of perceived aesthetic values, for example, in cultural ecosystem services, as a means to protect and develop landscapes, remains problematic. In this work, we focus on human behavior worldwide by exploring global reactions to sunset and sunrise using two datasets collected from Instagram and Flickr. By focusing on the consistency and reproducibility of results across these datasets, our goal is to contribute to the development of more robust methods for identifying landscape preference using geo-social media data, while also exploring motivations for photographing these particular events. Based on a four facet context model, reactions to sunset and sunrise are explored for Where, Who, What, and When. We further compare reactions across different groups, with the aim of quantifying differences in behavior and information spread. Our results suggest that a balanced assessment of landscape preference across different regions and datasets is possible, which strengthens representativity and exploring the How and Why in particular event contexts. The process of analysis is fully documented, allowing transparent replication and adoption to other events or datasets.

YBX1 mediates translation of oncogenic transcripts to control cell competition in AML.

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

Measuring the frequency chirp of extreme-ultraviolet free-electron laser pulses by transient absorption spectroscopy.

High-intensity ultrashort pulses at extreme ultraviolet (XUV) and x-ray photon energies, delivered by state-of-the-art free-electron lasers (FELs), are revolutionizing the field of ultrafast spectroscopy. For crossing the next frontiers of research, precise, reliable and practical photonic tools for the spectro-temporal characterization of the pulses are becoming steadily more important. Here, we experimentally demonstrate a technique for the direct measurement of the frequency chirp of extreme-ultraviolet free-electron laser pulses based on fundamental nonlinear optics. It is implemented in XUV-only pump-probe transient-absorption geometry and provides in-situ information on the time-energy structure of FEL pulses. Using a rate-equation model for the time-dependent absorbance changes of an ionized neon target, we show how the frequency chirp can be directly extracted and quantified from measured data. Since the method does not rely on an additional external field, we expect a widespread implementation at FELs benefiting multiple science fields by in-situ on-target measurement and optimization of FEL-pulse properties.

XUV-beamline for attosecond transient absorption measurements featuring a broadband common beam-path time-delay unit and in situ reference spectrometer for high stability and sensitivity.

Measuring bound-state quantum dynamics, excited and driven by strong fields, is achievable by time-resolved absorption spectroscopy. Here, a vacuum beamline for spectroscopy in the attosecond temporal and extreme ultraviolet (XUV) spectral range is presented, which is a tool for observing and controlling nonequilibrium electron dynamics. In particular, we introduce a technique to record an XUV absorption signal and the corresponding reference simultaneously, which greatly improves the signal quality. The apparatus is based on a common beam path design for XUV and near-infrared (NIR) laser light in a vacuum. This ensures minimal spatiotemporal fluctuations between the strong NIR laser and the XUV excitation and reference beams, while the grazing incidence optics enable broadband spectral coverage. The apparatus combines high spectral and temporal resolution together with an increase in sensitivity to weak absorption signatures by an order of magnitude. This opens up new possibilities for studying strong-field-driven electron dynamics in bound systems on their natural attosecond time scale.

Pronounced effects of HERG-blockers E-4031 and erythromycin on APD, spatial APD dispersion and triangulation in transgenic long-QT type 1 rabbits.

BACKGROUND: Prolongation of action potential duration (APD), increased spatial APD dispersion, and triangulation are major factors promoting drug-induced ventricular arrhythmia. Preclinical identification of HERG/IKr-blocking drugs and their pro-arrhythmic potential, however, remains a challenge. We hypothesize that transgenic long-QT type 1 (LQT1) rabbits lacking repolarizing IKs current may help to sensitively detect HERG/IKr-blocking properties of drugs. METHODS: Hearts of adult female transgenic LQT1 and wild type littermate control (LMC) rabbits were Langendorff-perfused with increasing concentrations of HERG/IKr-blockers E-4031 (0.001-0.1 µM, n=9/7) or erythromycin (1-300 µM, n=9/7) and APD, APD dispersion, and triangulation were analyzed. RESULTS: At baseline, APD was longer in LQT1 than in LMC rabbits in LV apex and RV mid. Erythromycin and E-4031 prolonged APD in LQT1 and LMC rabbits in all positions. However, erythromycin-induced percentaged APD prolongation related to baseline (%APD) was more pronounced in LQT1 at LV base-lateral and RV mid positions (100 µM, LQT1, +40.6 ± 9.7% vs. LMC, +24.1 ± 10.0%, p<0.05) and E-4031-induced %APD prolongation was more pronounced in LQT1 at LV base-lateral (0.01 µM, LQT1, +29.6 ± 10.6% vs. LMC, +19.1 ± 3.8%, p<0.05) and LV base-septal positions. Moreover, erythromycin significantly increased spatial APD dispersion only in LQT1 and increased triangulation only in LQT1 in LV base-septal and RV mid positions. Similarly, E-4031 increased triangulation only in LQT1 in LV apex and base-septal positions. CONCLUSIONS: E-4031 and erythromycin prolonged APD and increased triangulation more pronouncedly in LQT1 than in LMC rabbits. Moreover, erythromycin increased APD dispersion only in LQT1, indicating that transgenic LQT1 rabbits could serve as sensitive model to detect HERG/IKr-blocking properties of drugs.

Vector selection of a quadripolar left ventricular pacing lead affects acute hemodynamic response to cardiac resynchronization therapy: a randomized cross-over trial.

BACKGROUND: A suboptimal left ventricular (LV) pacing site may account for non-responsiveness of patients to cardiac resynchronization therapy (CRT). The vector selection of a novel quadripolar LV pacing lead, which was mainly developed to overcome technical issues with stimulation thresholds and phrenic nerve capture, may affect hemodynamic response, and was therefore assessed in this study. (German Clinical Trials Register DRKS00000573). METHODS AND RESULTS: Hemodynamic effects of a total of 145 LVPCs (9.1 per patient) of CRT devices with a quadripolar LV lead (Quartet™, St. Jude Medical) were assessed in 16/20 consecutive patients by invasive measurement of LV+dP/dtmax at an invasively optimized AV-interval in random order. Optimal (worst) LVPCs per patient were identified as those with maximal (minimal) %change in LV+dP/dtmax (%ΔLV+dP/dtmax) as compared to a preceding baseline. LV+dP/dtmax significantly increased in all 145 LVPCs (p<0.0001 compared to baseline) with significant intraindividual differences between LVPCs (p<0.0001). Overall, CRT acutely augmented %ΔLV+dP/dtmax by 31.3% (95% CI 24%-39%) in the optimal, by 21.3% (95% CI: 15%-27%) in the worst and by 28.2% (95% CI: 21%-36%) in a default distal LVPC. This resulted in an absolute additional acute increase in %ΔLV+dP/dtmax of 10.0% (95% CI: 7%-13%) of the optimal when compared to the worst (p<0.0001), and of 3.1% (95% CI: 1%-5%) of the optimal when compared to the default distal LVPC (p<0.001). Optimal LVPCs were not programmable with a standard bipolar lead in 44% (7/16) of patients. CONCLUSION: The pacing configuration of a quadripolar LV lead determinates acute hemodynamic response. Pacing in the individually optimized configuration gives rise to an additional absolute 10% increase in %ΔLV+dP/dtmax when comparing optimal and worst vectors.