Radiation Reaction and Gravitational Waves at Fourth Post-Minkowskian Order

We obtain the total impulse in the scattering of non-spinning binaries in general relativity at fourth Post-Minkowskian order, i.e. ${\cal O}(G^4)$, including linear, nonlinear, and hereditary radiation-reaction effects. We derive the total radiated spacetime momentum as well as the associated energy flux. The latter can be used to compute gravitational-wave observables for generic (un)bound orbits. We employ the ("in-in") Schwinger-Keldysh worldline effective field theory framework in combination with modern "multi-loop" integration techniques from collider physics. The complete results are in agreement with various partial calculations in the Post-Newtonian/Minkowskian expansion.Comment: 6 pages + Refs + Supplemental. 1 figure and 1 table. 1 computer-readable ancillary fil

Optogenetics and electron tomography for structure-function analysis of cochlear ribbon synapses

Ribbon synapses of cochlear inner hair cells (IHCs) are specialized to indefatigably transmit sound information at high rates. To understand the underlying mechanisms, structure-function analysis of the active zone (AZ) of these synapses is essential. Previous electron microscopy studies of synaptic vesicle (SV) dynamics at the IHC AZ used potassium stimulation, which limited the temporal resolution to minutes. Here, we established optogenetic IHC stimulation followed by quick freezing within milliseconds and electron tomography to study the ultrastructure of functional synapse states with good temporal resolution in mice. We characterized optogenetic IHC stimulation by patch-clamp recordings from IHCs and postsynaptic boutons revealing robust IHC depolarization and neurotransmitter release. Ultrastructurally, the number of docked SVs increased upon short (17–25 ms) and long (48–76 ms) light stimulation paradigms. We did not observe enlarged SVs or other morphological correlates of homotypic fusion events. Our results indicate a rapid recruitment of SVs to the docked state upon stimulation and suggest that univesicular release prevails as the quantal mechanism of exocytosis at IHC ribbon synapses

Enrichment of Omnivorous Cercozoan Nanoflagellates from Coastal Baltic Sea Waters

Free-living nano-sized flagellates are important bacterivores in aquatic habitats. However, some slightly larger forms can also be omnivorous, i.e., forage upon both bacterial and eukaryotic resources. This hitherto largely ignored feeding mode may have pronounced implications for the interpretation of experiments about protistan bacterivory. We followed the response of an uncultured group of omnivorous cercozoan nanoflagellates from the Novel Clade 2 (Cerc_BAL02) to experimental food web manipulation in samples from the Gulf of Gdańsk (Southern Baltic Sea). Seawater was either prefiltered through 5 µm filters to exclude larger predators of nanoflagellates (F-treatment), or prefiltered and subsequently 1∶10 diluted with sterile seawater (F+D-treatment) to stimulate the growth of both, flagellates and bacteria. Initially, Cerc_BAL02 were rapidly enriched under both conditions. They foraged on both, eukaryotic prey and bacteria, and were highly competitive at low concentrations of food. However, these omnivores were later only successful in the F+D treatment, where they eventually represented almost one fifth of all aplastidic nanoflagellates. By contrast, their numbers stagnated in the F-treatment, possibly due to top-down control by a concomitant bloom of other, unidentified flagellates. In analogy with observations about the enrichment of opportunistically growing bacteria in comparable experimental setups we suggest that the low numbers of omnivorous Cerc_Bal02 flagellates in waters of the Gulf of Gdańsk might also be related to their vulnerability to grazing pressure

Mechanisms of Hsp90 regulation

Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated

Molekulare Physiologie der Bändersynapse

Durch Ca2+-Einstrom hervorgerufene Exocytose in den inneren Haarzellen (IHZ) der Cochlea ist ein kritischer Schritt für die Wahrnehmung von Geräuschen. In dieser Arbeit wurde mit Hilfe von knock-out-Mäusen die Regulierung von Ca2+-Kanälen in IHZ der Maus durch die CaV(beta)2 Ca2+-Kanaluntereinheit und durch Calcium binding protein 4 (CaBP4) untersucht. Es wurde aufgeklärt, welche CaV(beta)-Untereinheiten in IHZ exprimiert werden und gezeigt, dass CaV(beta)2 hier die wichtigste Ca2+-Kanaluntereinheit in IHZ der Maus ist. Sie ist wichtig für die Funktion der Ca2+-Kanäle und reguliert deren Inaktivierung. Weiterhin reguliert sie die Anzahl an funktionalen Ca2+-Kanälen, wahrscheinlich indem sie die Beförderung der CaV(alpha)1D-Untereinheit zur Zellmembran fördert, und beeinflusst so Sekretion und Entwicklung. Die gestörte Entwicklung von CaV(beta)2-/- Haarzellen resultiert unter anderem in einer Störung der Expression von K+-Kanälen des BK-Typs, die sich in reduzierter Expression und fehlender Aggregation dieser Kanäle auswirkt. Weiterhin wurde gezeigt, dass CaBP4 in IHZs so gut wie keine Rolle spielt. Es wird vorgeschlagen, dass stattdessen CaBP1 das wichtigste CaBP in IHZs darstellt

Radiation-Reaction in the Effective Field Theory Approach to Post-Minkowskian Dynamics

We extend the Post-Minkowskian (PM) effective field theory (EFT) approach to incorporate conservative and dissipative radiation-reaction effects in a unified framework. This is achieved by implementing the Schwinger-Keldysh "in-in" formalism and separating conservative and non-conservative terms according to the formulation in [1210.2745], which we show promotes Feynman's $i0$-prescription and cutting rules to a prominent role at the classical level. The resulting integrals, involving both Feynman and retarded propagators, can be bootstrapped to all orders in the velocity via differential equations with boundary conditions including potential and radiation modes. As a paradigmatic example we provide an ab initio derivation of the classical solution to the scattering problem in general relativity to ${\cal O}(G^3)$. For the sake of completeness, we also reproduce the leading order radiation-reaction effects in classical electrodynamics.Comment: 20+10 pages. TikZ figure

Radiation-reaction in the Effective Field Theory approach to Post-Minkowskian dynamics

Abstract We extend the Post-Minkowskian (PM) effective field theory (EFT) approach to incorporate conservative and dissipative radiation-reaction effects in a unified framework. This is achieved by implementing the Schwinger-Keldysh “in-in” formalism and separating conservative and non-conservative terms according to the formulation in [1], which we show promotes Feynman’s i0-prescription and cutting rules to a prominent role at the classical level. The resulting integrals, involving both Feynman and retarded propagators, can be bootstrapped to all orders in the velocity via differential equations with boundary conditions including potential and radiation modes. As a paradigmatic example we provide an ab initio derivation of the classical solution to the scattering problem in general relativity to O $$\mathcal{O}$$ (G 3). For the sake of completeness, we also reproduce the leading order radiation-reaction effects in classical electrodynamics

Radiation-Reaction in the Effective Field Theory Approach to Post-Minkowskian Dynamics

We extend the Post-Minkowskian (PM) effective field theory (EFT) approach to incorporate conservative and dissipative radiation-reaction effects in a unified framework. This is achieved by implementing the Schwinger-Keldysh 'in-in' formalism and separating conservative and non-conservative terms according to the formulation in [1210.2745], which we show promotes Feynman's $i0$-prescription and cutting rules to a prominent role at the classical level. The resulting integrals, involving both Feynman and retarded propagators, can be bootstrapped to all orders in the velocity via differential equations with boundary conditions including potential and radiation modes. As a paradigmatic example we provide an ab initio derivation of the classical solution to the scattering problem in general relativity to ${\cal O}(G^3)$. For the sake of completeness, we also reproduce the leading order radiation-reaction effects in classical electrodynamics

Emerging approaches for restoration of hearing and vision

Impairments of vision and hearing are highly prevalent conditions limiting the quality of life and presenting a major socioeconomic burden. For long, retinal and cochlear disorders have remained intractable for causal therapies, with sensory rehabilitation limited to glasses, hearing aids, and electrical cochlear or retinal implants. Recently, the application of gene therapy and optogenetics to eye and ear has generated hope for a fundamental improvement of vision and hearing restoration. To date, one gene therapy for the restoration of vision has been approved and undergoing clinical trials will broaden its application including gene replacement, genome editing, and regenerative approaches. Moreover, optogenetics, i.e. controlling the activity of cells by light, offers a more general alternative strategy. Over little more than a decade, optogenetic approaches have been developed and applied to better understand the function of biological systems, while protein engineers have identified and designed new opsin variants with desired physiological features. Considering potential clinical applications of optogenetics, the spotlight is on the sensory systems. Multiple efforts have been undertaken to restore lost or hampered function in eye and ear. Optogenetic stimulation promises to overcome fundamental shortcomings of electrical stimulation, namely poor spatial resolution and cellular specificity, and accordingly to deliver more detailed sensory information. This review aims at providing a comprehensive reference on current gene therapeutic and optogenetic research relevant to the restoration of hearing and vision. We will introduce gene-therapeutic approaches and discuss the biotechnological and optoelectronic aspects of optogenetic hearing and vision restoratio