A large aperture reflective wave-plate for high-intensity short-pulse laser experiments

We report on a reflective wave-plate system utilizing phase-shifting mirrors (PSM) for a continuous variation of elliptical polarization without changing the beam position and direction. The scalability of multilayer optics to large apertures and the suitability for high-intensity broad-bandwidth laser beams make reflective wave-plates an ideal tool for experiments on relativistic laser-plasma interaction. Our measurements confirm the preservation of the pulse duration and spectrum when a 30-fs Ti:Sapphire laser beam passes the system

Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens

Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.</p

Reduction of X-ray generation in high-intensity laser ion acceleration

In this paper, we report on measurements of bremsstrahlung in laser ion acceleration experiments from ultra-thin, polymer-based target foils. The influence of laser polarization on the generated γ radiation, the maximum achievable proton energy and the total proton number is investigated. A clear benefit in terms of γ radiation reduction by the use of circular polarized light can be observed. At the same time, the total number of accelerated protons was increased

Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant

Background: Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma. Methods: To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/c.427G>A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations. Results: p.A143T patients suffering from stroke/transient ischemic attacks had slightly decreased residual GLA activities, and/or increased lyso-Gb3 levels, suspecting FD. However, most male p.A143T patients presented with significant residual GLA activity (similar to 50 % of reference), which was associated with normal lyso-Gb3 levels. Additionally, p.A143T patients showed less severe FD-typical symptoms and absent FD-typical renal and cardiac involvement in comparison to FD patients with other missense mutations. Two tested female p.A143T patients with stroke/TIA did not show skewed X chromosome inactivation. No accumulation of neurologic events in family members of p.A143T patients with stroke/transient ischemic attacks was observed. Conclusions: We conclude that GLA p.A143T seems to be most likely a neutral variant or a possible modifier instead of a disease-causing mutation. Therefore, we suggest that p.A143T patients with stroke/transient ischemic attacks of unknown etiology should be further evaluated, since the diagnosis of FD is not probable and subsequent ERT or chaperone treatment should not be an unreflected option

Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease

Background: The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines. Methods: Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed. Results: Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-naive females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-naive females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were similar to 8 years younger than females with normal lyso-Gb3 levels. Conclusion: The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females