Mutual control of x-rays and nuclear transitions

In the course of this Thesis the mutual control between x-rays and nuclear transitions is investigated theoretically. In the first Part, we study the nuclear photoexcitation with the highly brilliant and coherent x-ray free-electron lasers (XFELs). Apart from amplifying the direct resonant interaction with nuclear transitions, the super-intense XFEL can produce new states of matter like cold, high-density plasmas where secondary nuclear excitation channels may come into play, e.g., nuclear excitation by electron capture (NEEC). Our results predict that in the case of 57Fe targets secondary NEEC can be safely neglected, whereas it is surprisingly the dominating contribution (in comparison to the direct photoexcitation) for the XFEL-induced 93mMo isomer triggering. Based on these case studies, we elaborate a general set of criteria to identify the prevailing excitation channel for a certain nuclear isotope. These criteria may be most relevant for future nuclear resonance experiments at XFEL facilities. On the opposite frontier, the interplay between single x-ray photons and nuclear transitions offer potential storage and processing applications for information science in their most compact form. In the second Part of this Thesis, we show that nuclear forward scattering off 57Fe targets can be employed to process polarization-encoded single x-rays via timed magnetic field rotations. Apart from the realization of logical gates with x-rays, the polarization encoding is used to design an x-ray quantum eraser scheme where the interference between scattering paths can be switched off and on in a controlled manner. Such setups may advance time-energy complementarity tests to so far unexplored paramater regimes, e.g., to the domain of x-ray quanta

Cost-effective aperture arrays for SKA Phase 1: single or dual-band?

An important design decision for the first phase of the Square Kilometre Array is whether the low frequency component (SKA1-low) should be implemented as a single or dual-band aperture array; that is, using one or two antenna element designs to observe the 70-450 MHz frequency band. This memo uses an elementary parametric analysis to make a quantitative, first-order cost comparison of representative implementations of a single and dual-band system, chosen for comparable performance characteristics. A direct comparison of the SKA1-low station costs reveals that those costs are similar, although the uncertainties are high. The cost impact on the broader telescope system varies: the deployment and site preparation costs are higher for the dual-band array, but the digital signal processing costs are higher for the single-band array. This parametric analysis also shows that a first stage of analogue tile beamforming, as opposed to only station-level, all-digital beamforming, has the potential to significantly reduce the cost of the SKA1-low stations. However, tile beamforming can limit flexibility and performance, principally in terms of reducing accessible field of view. We examine the cost impacts in the context of scientific performance, for which the spacing and intra-station layout of the antenna elements are important derived parameters. We discuss the implications of the many possible intra-station signal transport and processing architectures and consider areas where future work could improve the accuracy of SKA1-low costing.Comment: 64 pages, 23 figures, submitted to the SKA Memo serie

Direct and secondary nuclear excitation with x-ray free-electron lasers

The direct and secondary nuclear excitation produced by an x-ray free electron laser when interacting with a solid-state nuclear target is investigated theoretically. When driven at the resonance energy, the x-ray free electron laser can produce direct photoexcitation. However, the dominant process in that interaction is the photoelectric effect producing a cold and very dense plasma in which also secondary processes such as nuclear excitation by electron capture may occur. We develop a realistic theoretical model to quantify the temporal dynamics of the plasma and the magnitude of the secondary excitation therein. Numerical results show that depending on the nuclear transition energy and the temperature and charge states reached in the plasma, secondary nuclear excitation by electron capture may dominate the direct photoexcitation by several orders of magnitude, as it is the case for the 4.8 keV transition from the isomeric state of $^{93}$Mo, or it can be negligible, as it is the case for the 14.4 keV M\"ossbauer transition in $^{57}\mathrm{Fe}$. These findings are most relevant for future nuclear quantum optics experiments at x-ray free electron laser facilities.Comment: 17 pages, 7 figures; minor corrections made; accepted by Physics of Plasma

Non-muscle (NM) myosin heavy chain phosphorylation regulates the formation of NM myosin filaments, adhesome assembly and smooth muscle contraction

KEY POINTS: Non-muscle (NM) and smooth muscle (SM) myosin II are both expressed in smooth muscle tissues, however the role of NM myosin in SM contraction is unknown. Contractile stimulation of tracheal smooth muscle tissues stimulates phosphorylation of the NM myosin heavy chain on Ser1943 and causes NM myosin filament assembly at the SM cell cortex. Expression of a non-phosphorylatable NM myosin mutant, NM myosin S1943A, in SM tissues inhibits ACh-induced NM myosin filament assembly and SM contraction, and also inhibits the assembly of membrane adhesome complexes during contractile stimulation. NM myosin regulatory light chain (RLC) phosphorylation but not SM myosin RLC phosphorylation is regulated by RhoA GTPase during ACh stimulation, and NM RLC phosphorylation is required for NM myosin filament assembly and SM contraction. NM myosin II plays a critical role in airway SM contraction that is independent and distinct from the function of SM myosin. ABSTRACT: The molecular function of non-muscle (NM) isoforms of myosin II in smooth muscle (SM) tissues and their possible role in contraction are largely unknown. We evaluated the function of NM myosin during contractile stimulation of canine tracheal SM tissues. Stimulation with ACh caused NM myosin filament assembly, as assessed by a Triton solubility assay and a proximity ligation assay aiming to measure interactions between NM myosin monomers. ACh stimulated the phosphorylation of NM myosin heavy chain on Ser1943 in tracheal SM tissues, which can regulate NM myosin IIA filament assembly in vitro. Expression of the non-phosphorylatable mutant NM myosin S1943A in SM tissues inhibited ACh-induced endogenous NM myosin Ser1943 phosphorylation, NM myosin filament formation, the assembly of membrane adhesome complexes and tension development. The NM myosin cross-bridge cycling inhibitor blebbistatin suppressed adhesome complex assembly and SM contraction without inhibiting NM myosin Ser1943 phosphorylation or NM myosin filament assembly. RhoA inactivation selectively inhibited phosphorylation of the NM myosin regulatory light chain (RLC), NM myosin filament assembly and contraction, although it did not inhibit SM RLC phosphorylation. We conclude that the assembly and activation of NM myosin II is regulated during contractile stimulation of airway SM tissues by RhoA-mediated NM myosin RLC phosphorylation and by NM myosin heavy chain Ser1943 phosphorylation. NM myosin II actomyosin cross-bridge cycling regulates the assembly of membrane adhesome complexes that mediate the cytoskeletal processes required for tension generation. NM myosin II plays a critical role in airway SM contraction that is independent and distinct from the function of SM myosin

Molecular Mechanisms for the Mechanical Modulation of Airway Responsiveness

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The smooth muscle of the airways is exposed to continuously changing mechanical forces during normal breathing. The mechanical oscillations that occur during breathing have profound effects on airway tone and airway responsiveness both in experimental animals and humans in vivo and in isolated airway tissues in vitro. Experimental evidence suggests that alterations in the contractile and mechanical properties of airway smooth muscle tissues caused by mechanical perturbations result from adaptive changes in the organization of the cytoskeletal architecture of the smooth muscle cell. The cytoskeleton is a dynamic structure that undergoes rapid reorganization in response to external mechanical and pharmacologic stimuli. Contractile stimulation initiates the assembly of cytoskeletal/extracellular matrix adhesion complex proteins into large macromolecular signaling complexes (adhesomes) that undergo activation to mediate the polymerization and reorganization of a submembranous network of actin filaments at the cortex of the cell. Cortical actin polymerization is catalyzed by Neuronal-Wiskott–Aldrich syndrome protein (N-WASP) and the Arp2/3 complex, which are activated by pathways regulated by paxillin and the small GTPase, cdc42. These processes create a strong and rigid cytoskeletal framework that may serve to strengthen the membrane for the transmission of force generated by the contractile apparatus to the extracellular matrix, and to enable the adaptation of smooth muscle cells to mechanical stresses. This model for the regulation of airway smooth muscle function can provide novel perspectives to explain the normal physiologic behavior of the airways and pathophysiologic properties of the airways in asthma

Vasodilator Stimulated Phosphoprotein (VASP) Regulates Actin Polymerization and Contraction in Airway Smooth Muscle by a Vinculin-dependent Mechanism

Vasodilator-stimulated phosphoprotein (VASP) can catalyze actin polymerization by elongating actin filaments. The elongation mechanism involves VASP oligomerization and its binding to profilin, a G-actin chaperone. Actin polymerization is required for tension generation during the contraction of airway smooth muscle (ASM); however, the role of VASP in regulating actin dynamics in ASM is not known. We stimulated ASM cells and tissues with the contractile agonist acetylcholine (ACh) or the adenylyl cyclase activator, forskolin (FSK), a dilatory agent. ACh and FSK stimulated VASP Ser157 phosphorylation by different kinases. Inhibition of VASP Ser157 phosphorylation by expression of the mutant VASP S157A in ASM tissues suppressed VASP phosphorylation and membrane localization in response to ACh, and also inhibited contraction and actin polymerization. ACh but not FSK triggered the formation of VASP-VASP complexes as well as VASP-vinculin and VASP-profilin complexes at membrane sites. VASP-VASP complex formation and the interaction of VASP with vinculin and profilin were inhibited by expression of the inactive vinculin mutant, vinculin Y1065F, but VASP phosphorylation and membrane localization were unaffected. We conclude that VASP phosphorylation at Ser157 mediates its localization at the membrane, but that VASP Ser157 phosphorylation and membrane localization are not sufficient to activate its actin catalytic activity. The interaction of VASP with activated vinculin at membrane adhesion sites is a necessary prerequisite for VASP-mediated molecular processes necessary for actin polymerization. Our results show that VASP is a critical regulator of actin dynamics and tension generation during the contractile activation of ASM

The role of affect regulation in the treatment of people who have committed sexual offences

Affect regulation problems have been found to play an important role in the onset of problematic behavior, such as sexual abuse. The role of emotion and maladaptive coping has become relevant in both research and treatment interventions. Forensic treatments have been strongly influenced by conceptualizations of affect regulation that emphasize the control of emotional experience and expression. For a long time, emotions were treated as less important than cognition. However, the view of emotion as an adaptive resource and meaning system is now emerging in the forensic literature. General psychotherapy research has shown that improved affect regulation and deeper experiencing is associated with better outcomes in psychotherapy. These findings, in combination with the role of emotions in behavioral and relational functioning, are leading to a shift in forensic treatment approaches. In this paper, we review the literature on affect regulation in treatment programs for individuals who have committed sexual offences. The implications of this work for forensic practice will be considered. Finally, Emotion-Focused Therapy will be presented as a promising therapeutic approach for forensic treatment programs to promote clients' emotional engagement and processing, and to improve treatment outcomes

Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle

Rho kinase (ROCK), a RhoA GTPase effector, can regulate the contraction of airway and other smooth muscle tissues. In some tissues, ROCK can inhibit myosin regulatory light chain (RLC) phosphatase, which increases the phosphorylation of myosin RLC and promotes smooth muscle contraction. ROCK can also regulate cell motility and migration by affecting F‐actin dynamics. Actin polymerization is stimulated by contractile agonists in airway smooth muscle tissues and is required for contractile tension development in addition to myosin RLC phosphorylation. We investigated the mechanisms by which ROCK regulates the contractility of tracheal smooth muscle tissues by expressing a kinase inactive mutant of ROCK, ROCK‐K121G, in the tissues or by treating them with the ROCK inhibitor, H‐1152P. Our results show no role for ROCK in the regulation of non‐muscle or smooth muscle myosin RLC phosphorylation during contractile stimulation in this tissue. We find that ROCK regulates airway smooth muscle contraction by mediating activation of the serine‐threonine kinase, Pak, to promote actin polymerization. Pak catalyzes paxillin phosphorylation on Ser273 and coupling of the GIT1‐βPIX‐Pak signaling module to paxillin, which activates the GEF activity βPIX towards cdc42. Cdc42 is required for the activation of Neuronal Wiskott‐Aldrich Syndrome protein (N‐WASp), which transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. Our results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle