Resonant Multi-Photon Ionization Experiments on Neon Monomers and Dimers Augmented by Pulse Intensity and Wavelength Diagnostics

This thesis deals with experiments on resonant multi-photon double ionization of Neon monomers and dimers. Experiments were carried out at the reaction microscope beamline of the XUV free-electron laser FLASH2. Employing the variable gap undulators of FLASH2, the photon energy was scanned over the 2s-2p resonance in ionic Ne+ at 26:9 eV, where resonance-enhanced sequential ionization and single-photon laser-enabled Auger decay (spLEAD) is expected for monomers and Interatomic Coulombic Decay (ICD) for dimers. As FLASH2 operates in SASE mode, which leads to large statistical fluctuations, post-analysis of single-shot diagnostics was developed and performed. The pulse energy was monitored through a photocurrent on the final focusing mirror and the photon energy with an electron spectrometer. Through single-shot analysis of the pulse-energy better insight into the power scaling of the ionization rates could be gained

"Wet-to-Dry" Conformational Transition of Polymer Layers Grafted to Nanoparticles in Nanocomposite

The present communication reports the first direct measurement of the conformation of a polymer corona grafted around silica nano-particles dispersed inside a nanocomposite, a matrix of the same polymer. This measurement constitutes an experimental breakthrough based on a refined combination of chemical synthesis, which permits to match the contribution of the neutron silica signal inside the composite, and the use of complementary scattering methods SANS and SAXS to extract the grafted polymer layer form factor from the inter-particles silica structure factor. The modelization of the signal of the grafted polymer on nanoparticles inside the matrix and the direct comparison with the form factor of the same particles in solution show a clear-cut change of the polymer conformation from bulk to the nanocomposite: a transition from a stretched and swollen form in solution to a Gaussian conformation in the matrix followed with a compression of a factor two of the grafted corona. In the probed range, increasing the interactions between the grafted particles (by increasing the particle volume fraction) or between the grafted and the free matrix chains (decreasing the grafted-free chain length ratio) does not influence the amplitude of the grafted brush compression. This is the first direct observation of the wet-to-dry conformational transition theoretically expected to minimize the free energy of swelling of grafted chains in interaction with free matrix chains, illustrating the competition between the mixing entropy of grafted and free chains, and the elastic deformation of the grafted chains. In addition to the experimental validation of the theoretical prediction, this result constitutes a new insight for the nderstanding of the general problem of dispersion of nanoparticles inside a polymer matrix for the design of new nanocomposites materials

Ion-lithium collision dynamics studied with an in-ring MOTReMi

We present a novel experimental tool allowing for kinematically complete studies of break-up processes of laser-cooled atoms. This apparatus, the 'MOTReMi', is a combination of a magneto-optical trap (MOT) and a Reaction Microscope (ReMi). Operated in an ion-storage ring, the new setup enables to study the dynamics in swift ion-atom collisions on an unprecedented level of precision and detail. In first experiments on collisions with 1.5 MeV/amu O$^{8+}$-Li the pure ionization of the valence electron as well as ionization-excitation of the lithium target has been investigated

A distinct M2 macrophage infiltrate and transcriptomic profile decisively influence adipocyte differentiation in lipedema

Lipedema is a chronic and progressive adipose tissue disorder, characterized by the painful and disproportionate increase of the subcutaneous fat in the lower and/or upper extremities. While distinct immune cell infiltration is a known hallmark of the disease, its role in the onset and development of lipedema remains unclear. To analyze the macrophage composition and involved signaling pathways, anatomically matched lipedema and control tissue samples were collected intra-operatively from gender- and BMI-matched patients, and the Stromal Vascular Fraction (SVF) was used for Cytometry by Time-of-Flight (CyTOF) and RNA sequencing. The phenotypic characterization of the immune component of lipedema versus control SVF using CyTOF revealed significantly increased numbers of CD163 macrophages. To gain further insight into this macrophage composition and molecular pathways, RNA sequencing of isolated CD11b+ cells was performed. The analysis suggested a significant modification of distinct gene ontology clusters in lipedema, including cytokine-mediated signaling activity, interleukin-1 receptor activity, extracellular matrix organization, and regulation of androgen receptor signaling. As distinct macrophage populations are known to affect adipose tissue differentiation and metabolism, we evaluated the effect of M2 to M1 macrophage polarization in lipedema using the selective PI3Kγ inhibitor IPI-549. Surprisingly, the differentiation of adipose tissue-derived stem cells with conditioned medium from IPI-549 treated SVF resulted in a significant decreased accumulation of lipids in lipedema versus control SVF. In conclusion, our results indicate that CD163+ macrophages are a critical component in lipedema and re-polarization of lipedema macrophages can normalize the differentiation of adipose-derived stem cells in vitro evaluated by the cellular lipid accumulation. These data open a new chapter in understanding lipedema pathophysiology and may indicate potential treatment options

Target electron ionization in Li2+-Li collisions: A multi-electron perspective

Target electron removal in Li2+-Li collisions at 2290 keV/amu is studied experimentally and theoretically for ground and excited lithium target configurations. It is shown that in outer-shell ionization a single-electron process plays the dominant part. However, the K-shell ionization results are more difficult to interpret. According to our calculations, the process is shown to be strongly single-particle like. On one hand, a high resemblance between theoretical single-particle ionization and exclusive inner-shell ionization is demonstrated, and contributions from multi-electron processes are found to be weak. On the other hand, it is indicated by the discrepancy between experimental and single-particle theoretical results that multi-electron processes involving ionization from the outer-shell may play a crucial role

Ion-Lithium Collision Dynamics Studied with a Laser-Cooled In-Ring Target

We present a novel experimental tool allowing for kinematically complete studies of break-up processes of laser-cooled atoms. This apparatus, the \u27MOTReMi,\u27 is a combination of a magneto-optical trap (MOT) and a reaction microscope (ReMi). Operated in an ion-storage ring, the new setup enables us to study the dynamics in swift ion-atom collisions on an unprecedented level of precision and detail. In the inaugural experiment on collisions with 1.5MeV/amu O8 +-Li the pure ionization of the valence electron as well as the ionization-excitation of the lithium target was investigated

MicroRNA Dysregulation in the Spinal Cord following Traumatic Injury

Spinal cord injury (SCI) triggers a multitude of pathophysiological events that are tightly regulated by the expression levels of specific genes. Recent studies suggest that changes in gene expression following neural injury can result from the dysregulation of microRNAs, short non-coding RNA molecules that repress the translation of target mRNA. To understand the mechanisms underlying gene alterations following SCI, we analyzed the microRNA expression patterns at different time points following rat spinal cord injury

Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders

BACKGROUND AND OBJECTIVES: To evaluate the long-term safety and efficacy of tocilizumab (TCZ), a humanized anti-interleukin-6 receptor antibody in myelin oligodendrocyte glycoprotein-IgG-associated disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). METHODS: Annualized relapse rate (ARR), Expanded Disability Status Scale score, MRI, autoantibody titers, pain, and adverse events were retrospectively evaluated in 57 patients with MOGAD (n = 14), aquaporin-4 (AQP4)-IgG seropositive (n = 36), and seronegative NMOSD (n = 7; 12%), switched to TCZ from previous immunotherapies, particularly rituximab. RESULTS: Patients received TCZ for 23.8 months (median; interquartile range 13.0-51.1 months), with an IV dose of 8.0 mg/kg (median; range 6-12 mg/kg) every 31.6 days (mean; range 26-44 days). For MOGAD, the median ARR decreased from 1.75 (range 0.5-5) to 0 (range 0-0.9; p = 0.0011) under TCZ. A similar effect was seen for AQP4-IgG+ (ARR reduction from 1.5 [range 0-5] to 0 [range 0-4.2]; p < 0.001) and for seronegative NMOSD (from 3.0 [range 1.0-3.0] to 0.2 [range 0-2.0]; p = 0.031). During TCZ, 60% of all patients were relapse free (79% for MOGAD, 56% for AQP4-IgG+, and 43% for seronegative NMOSD). Disability follow-up indicated stabilization. MRI inflammatory activity decreased in MOGAD (p = 0.04; for the brain) and in AQP4-IgG+ NMOSD (p < 0.001; for the spinal cord). Chronic pain was unchanged. Regarding only patients treated with TCZ for at least 12 months (n = 44), ARR reductions were confirmed, including the subgroups of MOGAD (n = 11) and AQP4-IgG+ patients (n = 28). Similarly, in the group of patients treated with TCZ for at least 12 months, 59% of them were relapse free, with 73% for MOGAD, 57% for AQP4-IgG+, and 40% for patients with seronegative NMOSD. No severe or unexpected safety signals were observed. Add-on therapy showed no advantage compared with TCZ monotherapy. DISCUSSION: This study provides Class III evidence that long-term TCZ therapy is safe and reduces relapse probability in MOGAD and AQP4-IgG+ NMOSD

Study of excitation transfer Li(3D → 3P) occurring in optical collisions with rare gas atoms experimentally

By selective optical excitation of collision pairs and observation of the reemitted fluorescence information is obtained on the role of the molecular channels involved in inelelastic collisions. As an example case we have studied experimentally the Li($\rm 3D\rightarrow3P$) excitation transfer in Li(3D)X systems with $X=\rm Ne$, Ar by means of the optical collision process ${\rm Li(2P)} + X + h \nu \rightarrow {\rm Li}X(3{\rm D}\Lambda)\rightarrow {\rm Li(3P, 3D)} + X$ where ${\rm Li}X(3{\rm D}\Lambda)$ collision molecules dissociate into Li(3P, 3D) atoms following laser excitation $h\nu$ of ${\rm Li(2P)}+X$ pairs. For this purpose we measured the Li 3P/3D population ratio by the fluorescence from these levels as function of the laser detuning $\Delta\nu$ from the Li(2P-3D) transition and the rare gas pressure, and determined from this the 3P/3D excitation ratio $B(\Delta\nu)$ for single collision conditions. The experiments were performed using two step cw laser excitation of gaseous mixtures ${\rm Li}+X$ at temperatures around 600 K in the detuning range $|\Delta\nu|\leq 100$ cm-1. The $B(\Delta\nu)$ profiles obtained display strong blue-red wing asymmetries both for $\rm Li^*Ne$ and $\rm Li^*Ar$. This reflects different dissociation probabilities from the ${\rm 3D}\Sigma$ or ${\rm 3D}(\Pi,\Delta)$ states that are initially prepared by blue wing or red wing excitation, respectively. The results are qualitatively discussed in terms of new ab initio potentials for the two systems