The determination of the infrared radiative lifetimes of a vibrationally excited neutral molecule using stimulated-emission-pumping, molecular-beam time-of-flight.

The authors present a new experimental method for measurement of collision-free infrared radiative lifetimes for single quantum states of a vibrationally excited sample. This method provides a more direct route to the infrared Einstein A coefficients than has been previously possible. Results for NO(X (2) Pi upsilon=21 and upsilon=7) are presented. Comparison to results of ab initio calculations shows excellent agreement. A controversy regarding the relative intensities of first overtone and fundamental emission intensities in NO is laid to rest. The most complete least squares analysis of existing data was carried out to derive the electric dipole moment function (EDMF) to an accuracy of +/-0.02 D between 0.9 and 1.7 Angstrom

EUV ionization of pure He nanodroplets: Mass-correlated photoelectron imaging, Penning ionization and electron energy-loss spectra

The ionization dynamics of pure He nanodroplets irradiated by EUV radiation is studied using Velocity-Map Imaging PhotoElectron-PhotoIon COincidence (VMI-PEPICO) spectroscopy. We present photoelectron energy spectra and angular distributions measured in coincidence with the most abundant ions He+, He2+, and He3+. Surprisingly, below the autoionization threshold of He droplets we find indications for multiple excitation and subsequent ionization of the droplets by a Penning-like process. At high photon energies we evidence inelastic collisions of photoelectrons with the surrounding He atoms in the droplets

Penning ionization of doped helium nanodroplets following EUV excitation

Helium nanodroplets are widely used as a cold, weakly interacting matrix for spectroscopy of embedded species. In this work we excite or ionize doped He droplets using synchrotron radiation and study the effect onto the dopant atoms depending on their location inside the droplets (rare gases) or outside at the droplet surface (alkali metals). Using photoelectron-photoion coincidence imaging spectroscopy at variable photon energies (20-25 eV), we compare the rates of charge-transfer to Penning ionization of the dopants in the two cases. The surprising finding is that alkali metals, in contrast to the rare gases, are efficiently Penning ionized upon excitation of the (n=2)-bands of the host droplets. This indicates rapid migration of the excitation to the droplet surface, followed by relaxation, and eventually energy transfer to the alkali dopants

Visualizing Nanoscale Dynamics with Time-resolved Electron Microscopy

The large number of interactions in nanoscale systems leads to the emergence of complex behavior. Understanding such complexity requires atomic-resolution observations with a time resolution that is high enough to match the characteristic timescale of the system. Our laboratory’s method of choice is time-resolved electron microscopy. In particular, we are interested in the development of novel methods and instrumentation for high-speed observations with atomic resolution. Here, we present an overview of the activities in our laboratory

In Situ Melting and Revitrification as an Approach to Microsecond Time-Resolved Cryo-Electron Microscopy

Proteins typically undergo conformational dynamics on the microsecond to millisecond timescale as they perform their function, which is much faster than the time-resolution of cryo-electron microscopy and has thus prevented real-time observations. Here, we propose a novel approach for microsecond time-resolved cryo-electron microscopy that involves rapidly melting a cryo specimen in situ with a laser beam. The sample remains liquid for the duration of the laser pulse, offering a tunable time window in which the dynamics of embedded particles can be induced in their native liquid environment. After the laser pulse, the sample vitrifies in just a few microseconds, trapping particles in their transient configurations, so that they can subsequently be characterized with conventional cryo-electron microscopy. We demonstrate that our melting and revitrification approach is viable and affords microsecond time resolution. As a proof of principle, we study the disassembly of particles after they incur structural damage and trap them in partially unraveled configurations

Collective Autoionization in Multiply-Excited Systems: A novel ionization process observed in Helium Nanodroplets

Free electron lasers (FELs) offer the unprecedented capability to study reaction dynamics and image the structure of complex systems. When multiple photons are absorbed in complex systems, a plasma-like state is formed where many atoms are ionized on a femtosecond timescale. If multiphoton absorption is resonantly-enhanced, the system becomes electronically-excited prior to plasma formation, with subsequent decay paths which have been scarcely investigated to date. Here, we show using helium nanodroplets as an example that these systems can decay by a new type of process, named collective autoionization. In addition, we show that this process is surprisingly efficient, leading to ion abundances much greater than that of direct single-photon ionization. This novel collective ionization process is expected to be important in many other complex systems, e.g. macromolecules and nanoparticles, exposed to high intensity radiation fields

Real-time dynamics of the formation of hydrated electrons upon irradiation of water clusters with extreme ultraviolet light

Free electrons in a polar liquid can form a bound state via interaction with the molecular environment. This so-called hydrated electron state in water is of fundamental importance e.g.~in cellular biology or radiation chemistry. Hydrated electrons are highly reactive radicals that can either directly interact with DNA or enzymes, or form highly excited hydrogen (H∗) after being captured by protons. Here, we investigate the formation of the hydrated electron in real-time employing XUV femtosecond pulses from a free electron laser, in this way observing the initial steps of the hydration process. Using time-resolved photoelectron spectroscopy we find formation timescales in the low picosecond range and resolve the prominent dynamics of forming excited hydrogen states

Repurposing HLA genotype data of renal transplant patients to prevent severe drug hypersensitivity reactions

Introduction: Specific alleles in human leukocyte antigens (HLAs) are associated with an increased risk of developing drug hypersensitivity reactions induced by abacavir, allopurinol, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, or flucloxacillin. Transplant patients are genotyped for HLA as a routine practice to match a potential donor to a recipient. This study aims to investigate the feasibility and potential impact of repurposing these HLA genotype data from kidney transplant patients to prevent drug hypersensitivity reactions.Methods: A cohort of 1347 kidney transplant recipients has been genotyped in the Leiden University Medical Center (LUMC) using next-generation sequencing (NGS). The risk alleles HLA-A*31:01, HLA-B*15:02, HLA-B*15:11, HLA-B*57:01, and HLA-B*58:01 were retrieved from the NGS data. Medical history, medication use, and allergic reactions were obtained from the patient's medical records. Carrier frequencies found were compared to a LUMC blood donor population.Results: A total of 13.1% of transplant cohort patients carried at least one of the five HLA risk alleles and therefore had an increased risk of drug-induced hypersensitivity for specific drugs. HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, and HLA-B*58:01 were found in carrier frequencies of 4.61%, 1.19%, 4.46%, and 3.35% respectively. No HLA-B*15:11 carrier was found. In total nine HLA-B*57:01 carriers received flucloxacillin and seven HLA-B*58:01 carriers within our cohort received allopurinol.Discussion: Our study shows that repurposing HLA genotype data from transplantation patients for the assignment of HLA risk alleles associated with drug hypersensitivity is feasible. The use of these data by physicians while prescribing drugs or by the pharmacist when dispensing drugs holds the potential to prevent drug hypersensitivity reactions. The utility of this method was highlighted by 13.1% of the transplant cohort patients carrying an actionable HLA allele. </p

Evolution and ion kinetics of a XUV-induced nanoplasma in ammonia clusters

High-intensity extreme ultraviolet (XUV) pulses from a free-electron laser can be used to create a nanoplasma in clusters. In Ref. [Michiels et al. PCCP, 2020; 22: 7828-7834] we investigated the formation of excited states in an XUV-induced nanoplasma in ammonia clusters. In the present article we expand our previous study with a detailed analysis of the nanoplasma evolution and ion kinetics. We use a time-delayed UV laser as probe to ionize excited states of H and H$_2^+$ in the XUV-induced plasma. Employing covariance mapping techniques, we show that the correlated emission of protons plays an important role in the plasma dynamics. The time-dependent kinetic energy of the ions created by the probe laser is measured, revealing the charge neutralization of the cluster happens on a sub-picosecond timescale. Furthermore, we observe ro-vibrationally excited molecular hydrogen ions H$_2^{+*}$ being ejected from the clusters. We rationalize our data through a qualitative model of a finite-size non-thermal plasma

A possible role for HLA-G in development of uteroplacental acute atherosis in preeclampsia

HLA-G, a non-classical HLA molecule expressed by extravillous trophoblasts, plays a role in the maternal immune tolerance towards fetal cells. HLA-G expression is regulated by genetic polymorphisms in the 3' untranslated region (3'UTR). Low levels of HLA-G in the maternal circulation and placental tissue are linked to preeclampsia. Our objective was to investigate whether variants of the 3'UTR of the HLA-G gene in mother and fetus are associated with acute atherosis, a pregnancy specific arterial lesion of the decidua basalis that is prevalent in preeclampsia. Paired maternal and fetal DNA samples from 83 normotensive and 83 preeclamptic pregnancies were analyzed. We sequenced the part of the HLA-G 3'UTR containing a 14-bp insertion/deletion region and seven single nucleotide polymorphisms (SNPs). Associations with acute atherosis were tested by logistic regression. The frequency of heterozygosity for the 14-bp polymorphism (Ins/Del) and the +3142 SNP (C/G) variant in the fetus are associated with acute atherosis in preeclampsia (66.7 % vs. 39.6 %, p = 0.039, and 69.0 % vs. 43.4 %, p = 0.024). Furthermore, the fetal UTR-3 haplotype, which encompasses the 14-bp deletion and the +3142G variant, is associated with acute atherosis in preeclampsia (15 % vs. 3.8 %, p = 0.016). In conclusion, HLA-G polymorphisms in the fetus are associated with acute atherosis. We hypothesize that these polymorphisms lead to altered HLA-G expression in the decidua basalis, affecting local feto-maternal immune tolerance and development of acute atherosis