Femtosecond response of polyatomic molecules to ultra-intense hard X-rays.

X-ray free-electron lasers enable the investigation of the structure and dynamics of diverse systems, including atoms, molecules, nanocrystals and single bioparticles, under extreme conditions. Many imaging applications that target biological systems and complex materials use hard X-ray pulses with extremely high peak intensities (exceeding 1020 watts per square centimetre). However, fundamental investigations have focused mainly on the individual response of atoms and small molecules using soft X-rays with much lower intensities. Studies with intense X-ray pulses have shown that irradiated atoms reach a very high degree of ionization, owing to multiphoton absorption, which in a heteronuclear molecular system occurs predominantly locally on a heavy atom (provided that the absorption cross-section of the heavy atom is considerably larger than those of its neighbours) and is followed by efficient redistribution of the induced charge. In serial femtosecond crystallography of biological objects-an application of X-ray free-electron lasers that greatly enhances our ability to determine protein structure-the ionization of heavy atoms increases the local radiation damage that is seen in the diffraction patterns of these objects and has been suggested as a way of phasing the diffraction data. On the basis of experiments using either soft or less-intense hard X-rays, it is thought that the induced charge and associated radiation damage of atoms in polyatomic molecules can be inferred from the charge that is induced in an isolated atom under otherwise comparable irradiation conditions. Here we show that the femtosecond response of small polyatomic molecules that contain one heavy atom to ultra-intense (with intensities approaching 1020 watts per square centimetre), hard (with photon energies of 8.3 kiloelectronvolts) X-ray pulses is qualitatively different: our experimental and modelling results establish that, under these conditions, the ionization of a molecule is considerably enhanced compared to that of an individual heavy atom with the same absorption cross-section. This enhancement is driven by ultrafast charge transfer within the molecule, which refills the core holes that are created in the heavy atom, providing further targets for inner-shell ionization and resulting in the emission of more than 50 electrons during the X-ray pulse. Our results demonstrate that efficient modelling of X-ray-driven processes in complex systems at ultrahigh intensities is feasible.

Characterizing the multi-dimensional reaction dynamics of dihalomethanes using XUV-induced Coulomb explosion imaging.

Site-selective probing of iodine 4d orbitals at 13.1 nm was used to characterize the photolysis of CH2I2 and CH2BrI initiated at 202.5 nm. Time-dependent fragment ion momenta were recorded using Coulomb explosion imaging mass spectrometry and used to determine the structural dynamics of the dissociating molecules. Correlations between these fragment momenta, as well as the onset times of electron transfer reactions between them, indicate that each molecule can undergo neutral three-body photolysis. For CH2I2, the structural evolution of the neutral molecule was simultaneously characterized along the C-I and I-C-I coordinates, demonstrating the sensitivity of these measurements to nuclear motion along multiple degrees of freedom.

Investigating charge-up and fragmentation dynamics of oxygen molecules after interaction with strong X-ray free-electron laser pulses.

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

Pulse Energy and Pulse Duration Effects in the Ionization and Fragmentation of Iodomethane by Ultraintense Hard X Rays.

The interaction of intense femtosecond x-ray pulses with molecules sensitively depends on the interplay between multiple photoabsorptions, Auger decay, charge rearrangement, and nuclear motion. Here, we report on a combined experimental and theoretical study of the ionization and fragmentation of iodomethane (CH_{3}I) by ultraintense (∼10^{19} W/cm^{2}) x-ray pulses at 8.3 keV, demonstrating how these dynamics depend on the x-ray pulse energy and duration. We show that the timing of multiple ionization steps leading to a particular reaction product and, thus, the product's final kinetic energy, is determined by the pulse duration rather than the pulse energy or intensity. While the overall degree of ionization is mainly defined by the pulse energy, our measurement reveals that the yield of the fragments with the highest charge states is enhanced for short pulse durations, in contrast to earlier observations for atoms and small molecules in the soft x-ray domain. We attribute this effect to a decreased charge transfer efficiency at larger internuclear separations, which are reached during longer pulses.

Study of Quasielastic Barrier Distributions as a Step towards the Synthesis of Superheavy Elements with Hot Fusion Reactions.

The excitation functions for quasielastic scattering of ^{22}Ne+^{248}Cm, ^{26}Mg+^{248}Cm, and ^{48}Ca+^{238}U are measured using a gas-filled recoil ion separator. The quasielastic barrier distributions are extracted for these systems and are compared with coupled-channel calculations. The results indicate that the barrier distribution is affected dominantly by deformation of the actinide target nuclei, but also by vibrational or rotational excitations of the projectile nuclei, as well as neutron transfer processes before capture. From a comparison between the experimental barrier distributions and the evaporation residue cross sections for Sg (Z=106), Hs (108), Cn (112), and Lv (116), it is suggested that the hot fusion reactions take advantage of a compact collision, where the projectile approaches along the short axis of a prolately deformed nucleus. A new method is proposed to estimate the optimum incident energy to synthesize unknown superheavy nuclei using the barrier distribution.

Evidence of Extreme Ultraviolet Superfluorescence in Xenon.

We present a comprehensive experimental and theoretical study on superfluorescence in the extreme ultraviolet wavelength regime. Focusing a free-electron laser pulse in a cell filled with Xe gas, the medium is quasi-instantaneously population inverted by 4d-shell ionization on the giant resonance followed by Auger decay. On the timescale of ∼10 ps to ∼100 ps (depending on parameters) a macroscopic polarization builds up in the medium, resulting in superfluorescent emission of several Xe lines in the forward direction. As the number of emitters in the system is increased by either raising the pressure or the pump-pulse energy, the emission yield grows exponentially over four orders of magnitude and reaches saturation. With increasing yield, we observe line broadening, a manifestation of superfluorescence in the spectral domain. Our novel theoretical approach, based on a full quantum treatment of the atomic system and the irradiated field, shows quantitative agreement with the experiment and supports our interpretation.

48Ca+249Bk fusion reaction leading to element Z = 117: long-lived α-decaying 270Db and discovery of 266Lr.

The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-µs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."

²¹³Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience.

PURPOSE: Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as (90)Y/(177)Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with (213)Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. METHODS: Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with (90)Y/(177)Lu-DOTATOC were treated with an intraarterial infusion of (213)Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of (213)Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and (68)Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. RESULTS: The biodistribution of (213)Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. CONCLUSION: TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses.

Time-resolved measurement of interatomic coulombic decay in Ne2.

The lifetime of interatomic Coulombic decay (ICD) [L. S. Cederbaum et al., Phys. Rev. Lett. 79, 4778 (1997)] in Ne2 is determined via an extreme ultraviolet pump-probe experiment at the Free-Electron Laser in Hamburg. The pump pulse creates a 2s inner-shell vacancy in one of the two Ne atoms, whereupon the ionized dimer undergoes ICD resulting in a repulsive Ne+(2p(-1))-Ne+(2p(-1)) state, which is probed with a second pulse, removing a further electron. The yield of coincident Ne+-Ne2+ pairs is recorded as a function of the pump-probe delay, allowing us to deduce the ICD lifetime of the Ne2(+)(2s(-1)) state to be (150±50) fs, in agreement with quantum calculations.

Isotope effects in dynamics of water isotopologues induced by core ionization at an x-ray free-electron laser.

Dynamical response of water exposed to x-rays is of utmost importance in a wealth of science areas. We exposed isolated water isotopologues to short x-ray pulses from a free-electron laser and detected momenta of all produced ions in coincidence. By combining experimental results and theoretical modeling, we identify significant structural dynamics with characteristic isotope effects in H2O2+, D2O2+, and HDO2+, such as asymmetric bond elongation and bond-angle opening, leading to two-body or three-body fragmentation on a timescale of a few femtoseconds. A method to disentangle the sequences of events taking place upon the consecutive absorption of two x-ray photons is described. The obtained deep look into structural properties and dynamics of dissociating water isotopologues provides essential insights into the underlying mechanisms.

Production and decay of the heaviest nuclei (293,294)117 and (294)118.

Two years after the discovery of element 117, we undertook a second campaign using the (249)Bk+(48)Ca reaction for further investigations of the production and decay properties of the isotopes of element 117 on a larger number of events. The experiments were started in the end of April 2012 and are still under way. This Letter presents the results obtained in 1200 hours of an experimental run with the beam dose of (48)Ca of about 1.5×10(19) particles. The (249)Bk target was irradiated at two energies of (48)Ca that correspond to the maximum probability of the reaction channels with evaporation of three and four neutrons from the excited (297)117. In this experiment, two decay chains of (294)117 (3n) and five decay chains of (293)117 (4n) were detected. In the course of the long-term work, (249)Cf-the product of decay of (249)Bk (330 d)-is being accumulated in the target. Consequently, in the present experiment, we also detected a single decay of the known isotope (294)118 that was produced during 2002-2005 in the reaction (249)Cf((48)Ca,3n)(294)118. The obtained results are compared with the data from previous experiments. The experiments are carried out in the Flerov Laboratory of Nuclear Reactions, Joint Institute for Nuclear Research, using the heavy-ion cyclotron U400.

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.

Photon-recoil imaging: Expanding the view of nonlinear x-ray physics.

Addressing the ultrafast coherent evolution of electronic wave functions has long been a goal of nonlinear x-ray physics. A first step toward this goal is the investigation of stimulated x-ray Raman scattering (SXRS) using intense pulses from an x-ray free-electron laser. Earlier SXRS experiments relied on signal amplification during pulse propagation through dense resonant media. By contrast, our method reveals the fundamental process in which photons from the primary radiation source directly interact with a single atom. We introduce an experimental protocol in which scattered neutral atoms rather than scattered photons are detected. We present SXRS measurements at the neon K edge and a quantitative theoretical analysis. The method should become a powerful tool in the exploration of nonlinear x-ray physics.

Radiotoxicity of bismuth-213 bound to membranes of monolayer and spheroid cultures of tumor cells.

Monoclonal antibody 13A to murine CD44 was used to bind the alpha-particle emitter 213Bi to cell surfaces of cultured EMT-6 or Line 1 tumor cells. Data on kinetics and saturation of binding, cell shape and nuclear size were used to calculate the absorbed dose to the nuclei. Treatment of monolayer cells with [213Bi]MAb 13A produced a classical exponential survival curve with no apparent shoulder. Microdosimetry analyses indicated that 1.4-1.7 Gy produced a 37% surviving fraction (D0). Multicellular spheroids were shown to bind [213Bi]MAb 13A mainly on the outer cell layer. Relatively small amounts of activity added to the spheroids resulted in relatively large absorbed doses. The result was that 3-6-fold less added radioisotope was necessary to kill similar fractions of cells in spheroids than in monolayer cells. These data are consistent with the interpretation that the alpha particles from a single 213Bi atom bound to one cell can penetrate and kill adjacent cells. Flow cytometry was used to sort cells originating from the periphery or from the interior of spheroids. Cells from the outside of the [213Bi]MAb 13A exposed spheroids had a lower surviving fraction per administered activity than cells from the interior. Cells were killed efficiently in spheroids up to 20-30 cells in diameter. The data support the hypothesis that alpha-particle emitters should be very efficient at killing cells in micrometastases of solid tumors.

Comparison of 225actinium chelates: tissue distribution and radiotoxicity.

The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N""-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.

Combination vascular targeted and tumor targeted radioimmunotherapy.

Rat MAb 201B, which binds to murine thrombomodulin, can deliver up to 50% of the injected dose of attached radioisotopes to the lung vascular endothelium. We have shown previously that intravenous injection of about 30 microCi of 213Bi-MAb 201B, which delivers about 15 Gy of alpha irradiation to the lung, is capable of eradicating small lung colonies (500-1000 cells) of the mammary tumor line, EMT-6. Larger tumors (> 5000 cells) were not completely cured by this vascular targeted radioimmunotherapy (VT-RAIT) approach. We reasoned that VT-RAIT might make the lung vessels serving the tumor cells more permeable, allowing MAb targeted to the tumor cells to extravasate more readily and mediate more efficient standard radioimmunotherapy (RAIT). Distribution experiments with the tumor targeted MAb 13A (RAIT MAb), following VT-RAIT, did not demonstrate a large increase in tumor uptake; however, microautoradiography did indicate that MAb 13A was distributed more evenly throughout the tumor when administered after VT-RAIT. Therapy experiments on lung tumors of approximately 5000 cells each, combining 213Bi-MAb 201B (VT-RAIT) with 213Bi-MAb 13A (RAIT) 24 hours later, resulted in a better outcome (3 cured/10 at risk) than for control groups: RAIT only (0/10), VT-RAIT only (1/10), or no therapy (0/10). RAIT therapy delivered 48 hours after VT-RAIT had no apparent benefit. 213Bi-MAb 201B VT-RAIT followed by 90Y-MAb 13A Fab' RAIT showed only a slight improvement in tumor cures (2/10) over that in control groups: (0/9), (0/10), (0/10), respectively. These results suggest that optimal timing, dosage, and choice of MAb for RAIT should enhance the double MAb therapy approach significantly.

Projection pursuit nonparametric regression applied to field counts of the aphid Macrosiphum euphorbiae (Homoptera: Aphididae) on tomato crops in greenhouses.

The number of plants that sampling requires in aphid population studies often exceeds one hundred. Thus, only quick and nondestructive methods can be used to sample this pest in a reasonable time interval. We propose a visual method for estimating the density of the aphid Macrosiphum euphorbiae (Thomas) on tomato plants reared in greenhouses. After approximately 1min of visual observation plants can be assigned to abundance classes, the boundaries of which are roughly the powers of square root 10. Precise counts were collected simultaneously on sets of reference plants from the same greenhouse. Projection pursuit nonparametric regression was then used to provide unbiased estimates of aphid densities from the abundance classes and several easily gathered explanatory variables. The robustness of the method was evaluated by testing the models on the complementary data sets from plants in which the aphid densities were precisely counted. In both single and twin-row cultural conditions, for the reference and complementary data sets, the order of magnitude of the error was less than one class rank per plant. The investigation time was reduced by approximately 10-fold compared with the exact counting method. This easy-to-teach field method could be useful in large-scale population surveys and for optimizing integrated pest management strategies.

[Quantitative studies of the elimination of Salmonellae by biological wastewater treatment]. / Quantitative Untersuchungen zur Elimination von Salmonellen durch biologische Abwasserbehandlung.

The wastewater pretreatment plant of Braunschweig works as a conventional, one step activated sludge plant without primary settling tanks. There were about 37,000 m3 per day of effluent during our investigations. During some months daily quantitative determinations of salmonellae were performed in the raw wastewater, in the activated sludge, and in the effluent. The mean concentrations of salmonellae were in the raw wastewater 2 X 10(5)/l and in the effluent after 11h of aeration and then settling 2 X 10(4) cells/l. The concentrations of salmonellae varied about the factor 10(3) (limits 10(2) to 10(5)). A small peak in the spring, a big peak in the late summer, and a week pattern were observed. The most salmonellae were adsorbed to unsoluble flocs of sludge, about 30-35% of the salmonellae only were found freely in the water and from that about 60% were concentrated round the flocs. Therefore, one step of settling removes about 90% of all salmonellae. In generally terms, the settling seems to be the most important step of removal of salmonellae from wastewater. Furthermore, the rate of removal is depending of the concentration. High concentrations of salmonellae cause a strong reduction and conversely. An immediate removal of salmonellae was observed in about 60%, however, there was a propagation of salmonellae in 30% of all samples, especially under conditions of low aeration, in an anaerobic environment, respectively.