Coulomb explosion imaging of small polyatomic molecules with ultrashort x-ray pulses

Ultrashort x-ray pulses from free-electron lasers can efficiently charge up and trigger the full fragmentation of molecules. By coincident detection of up to five ions resulting from rapid Coulomb explosion of highly charged iodomethane, we show that the full three-dimensional equilibrium geometry of this prototypical polyatomic system can be determined from the measured ion momenta with the help of a charge buildup model. Supported by simulations of how the ion momenta would reflect specific changes in molecular bond lengths and angles, we demonstrate that Coulomb-explosion imaging with ultrashort x-ray pulses is a promising technique for recording movies of multidimensional nuclear wave packets, including hydrogen motions

X-ray multiphoton-induced Coulomb explosion images complex single molecules

Following structural dynamics in real time is a fundamental goal towards a better understanding of chemical reactions. Recording snapshots of individual molecules with ultrashort exposure times is a key ingredient towards this goal, as atoms move on femtosecond (10-15 s) timescales. For condensed-phase samples, ultrafast, atomically resolved structure determination has been demonstrated using X-ray and electron diffraction. Pioneering experiments have also started addressing gaseous samples. However, they face the problem of low target densities, low scattering cross sections and random spatial orientation of the molecules. Therefore, obtaining images of entire, isolated molecules capturing all constituents, including hydrogen atoms, remains challenging. Here we demonstrate that intense femtosecond pulses from an X-ray free-electron laser trigger rapid and complete Coulomb explosions of 2-iodopyridine and 2-iodopyrazine molecules. We obtain intriguingly clear momentum images depicting ten or eleven atoms, including all the hydrogens, and thus overcome a so-far impregnable barrier for complete Coulomb explosion imaging—its limitation on molecules consisting of three to five atoms. In combination with state-of-the-art multi-coincidence techniques and elaborate theoretical modelling, this allows tracing ultrafast hydrogen emission and obtaining information on the result of intramolecular electron rearrangement. Our work represents an important step towards imaging femtosecond chemistry via Coulomb explosion

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis

Resonance-enhanced x-ray multiple ionization of a polyatomic molecule

Extremely high charge states of atoms and molecules can be created when they are irradiated by intense x-ray pulses. At certain x-ray photon energies, electron ejection from atoms can be drastically enhanced by transient resonances created during the sequential ionization process. Here we report on the observation of such resonance effects in a molecule, CH3I, and show the photon-energy-dependent shift of resonance-induced structures in ion charge state distributions. By comparing the ion charge state distribution of CH3I with that from ionization of atomic xenon, molecule-specific features are observed, which can be attributed to ultrafast intramolecular charge rearrangement. In addition, we experimentally demonstrate that the charge-rearrangement-enhanced x- ray ionization of molecules, previously found with hard x rays, also plays a role in the soft x-ray regime

Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88

The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook whole-genome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi