Charged particle beam transport in a flying focus pulse with orbital angular momentum.

We demonstrate the capability of flying focus (FF) laser pulses with ℓ=1 orbital angular momentum (OAM) to transversely confine ultrarelativistic charged particle bunches over macroscopic distances while maintaining a tight bunch radius. A FF pulse with ℓ=1 OAM creates a radial ponderomotive barrier that constrains the transverse motion of particles and travels with the bunch over extended distances. As compared with freely propagating bunches, which quickly diverge due to their initial momentum spread, the particles cotraveling with the ponderomotive barrier slowly oscillate around the laser pulse axis within the spot size of the pulse. This can be achieved at FF pulse energies that are orders of magnitude lower than required by Gaussian or Bessel pulses with OAM. The ponderomotive trapping is further enhanced by radiative cooling of the bunch resulting from rapid oscillations of the charged particles in the laser field. This cooling decreases the mean-square radius and emittance of the bunch during propagation.

Investigations of the Copper Peptide Hepcidin-25 by LC-MS/MS and NMR.

Hepcidin-25 was identified as the main iron regulator in the human body, and it by binds to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as the ATCUN (amino-terminal Cu(II)- and Ni(II)-binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the complex formed between hepcidin-25 and copper could reveal insight into its biological role. The present work focuses on metal-bound hepcidin-25 that can be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25 achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry (MS/MS), high-resolution mass spectrometry (HRMS)) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a three-dimensional (3D) model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

Multi-GeV electron-positron beam generation from laser-electron scattering.

The new generation of laser facilities is expected to deliver short (10 fs-100 fs) laser pulses with 10-100 PW of peak power. This opens an opportunity to study matter at extreme intensities in the laboratory and provides access to new physics. Here we propose to scatter GeV-class electron beams from laser-plasma accelerators with a multi-PW laser at normal incidence. In this configuration, one can both create and accelerate electron-positron pairs. The new particles are generated in the laser focus and gain relativistic momentum in the direction of laser propagation. Short focal length is an advantage, as it allows the particles to be ejected from the focal region with a net energy gain in vacuum. Electron-positron beams obtained in this setup have a low divergence, are quasi-neutral and spatially separated from the initial electron beam. The pairs attain multi-GeV energies which are not limited by the maximum energy of the initial electron beam. We present an analytical model for the expected energy cutoff, supported by 2D and 3D particle-in-cell simulations. The experimental implications, such as the sensitivity to temporal synchronisation and laser duration is assessed to provide guidance for the future experiments.

QED cascade with 10 PW-class lasers.

The intensities of the order of 1023-24 W/cm2 are required to efficiently generate electron-positron pairs in laser-matter interaction when multiple laser beam collision is employed. To achieve such intense laser fields with the upcoming generation of 10 PW laser beams, focusing to sub-micron spot size is required. In this paper, the possibility of pair production cascade development is studied for the case of a standing wave created by two tightly focused colliding laser pulses. Even though the stronger ponderomotive force expels the seed particles from the interaction volume when a tightly focused laser beam is used, tight focusing allows to achieve cascade pair production due to the higher intensity in the focal spot. Optimizing the target density can compensate the expulsion by the ponderomotive force and lower the threshold power required for cascade pair production. This will in principle allow to produce pairs with 10 PW-class laser facilities which are now under construction and will become accessible soon.

Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates.

A series of new thiophene-based guanylhydrazones (iminoguanidines) were synthesized in high yields using a straightforward two-step procedure. The antifungal activity of compounds was evaluated against a wide range of medicaly important fungal strains including yeasts, molds, and dermatophytes in comparison to clinically used drug voriconazole. Cytotoxic properties of compounds were also determined using human lung fibroblast cell line and hemolysis assay. All guanylhydrazones showed significant activity against broad spectrum of clinically important species of Candida spp., Aspergillus fumigatus, Fusarium oxysporum, Microsporum canis and Trichophyton mentagrophytes, which was in some cases comparable or better than activity of voriconazole. More importantly, compounds 10, 11, 13, 14, 18 and 21 exhibited excellent activity against voriconazole-resistant Candida albicans CA5 with very low minimal inhibitory concentration (MIC) values <2 µg mL(-1). Derivative 14, bearing bromine on the phenyl ring, was the most effective compound with MICs ranging from 0.25 to 6.25 µg mL(-1). However, bis-guanylhydrazone 18 showed better selectivity in terms of therapeutic index values. In vivo embryotoxicity on zebrafish (Danio rerio) showed improved toxicity profile of 11, 14 and 18 in comparison to that of voriconazole. Most guanylhydrazones also inhibited C. albicans yeast to hyphal transition, essential for its biofilm formation, while 11 and 18 were able to disperse preformed Candida biofilms. All guanylhydrazones showed the equal potential to interact with genomic DNA of C. albicans in vitro, thus indicating a possible mechanism of their action, as well as possible mechanism of observed cytotoxic effects. Tested compounds did not have significant hemolytic effect and caused low liposome leakage, which excluded the cell membrane as a primary target. On the basis of computational docking experiments using both human and cytochrome P450 from Candida it was concluded that the most active guanylhydrazones had minimal structural prerequisites to interact with the cytochrome P450 14α-demethylase (CYP51). Promising guanylhydrazone derivatives also showed satisfactory pharmacokinetic profile based on molecular calculations.