A method is introduced that allows one to measure normal-ordered moments of the displaced photon-number operator up to higher orders, without the need of photon-number resolving detectors. It is ...based on unbalanced homodyne correlation measurements, with the local oscillator being replaced by a displaced dephased laser. The measured moments yield a simple approximation of quasiprobabilities, representing the full quantum state. Quantum properties of light are efficiently certified through normal-ordered observables directly accessible by our method, which is illustrated for a weakly squeezed vacuum and a single-photon-added thermal state.
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Measures of quantum properties are essential to understanding the fundamental differences between quantum and classical systems as well as quantifying resources for quantum technologies. Here, two ...broad classes of bosonic phase-space functions, which are filtered versions of the Glauber-Sudarshan P function, are compared with regard to their ability to uncover nonclassical effects of light through their negativities. Gaussian filtering of the P function yields the family of s-parametrized quasiprobabilities, while more powerful regularized nonclassicality quasiprobabilities are obtained by non-Gaussian filtering. A method is proposed to directly sample such phase-space functions for the restricted case of phase-independent quantum states from balanced homodyne measurements. This overcomes difficulties of previous approaches that manually append uniformly distributed optical phases to the measured quadrature data. We experimentally demonstrate this technique for heralded single- and two-photon states using balanced homodyne detection with varying efficiency. The s-parametrized quasiprobabilities, which can be directly sampled, are non-negative for detection efficiencies below 0.5. By contrast, we show that significant negativities of non-Gaussian filtered quasiprobabilities uncover nonclassical effects for arbitrarily low efficiencies.
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Variations in the fat mass and obesity-associated (FTO) gene are linked to obesity. However, the underlying neurobiological mechanisms by which these genetic variants influence obesity, behavior, and ...brain are unknown. Given that Fto regulates D2/3R signaling in mice, we tested in humans whether variants in FTO would interact with a variant in the ANKK1 gene, which alters D2R signaling and is also associated with obesity. In a behavioral and fMRI study, we demonstrate that gene variants of FTO affect dopamine (D2)-dependent midbrain brain responses to reward learning and behavioral responses associated with learning from negative outcome in humans. Furthermore, dynamic causal modeling confirmed that FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic predisposition alters reward processing not only in obesity, but also in other disorders with altered D2R-dependent impulse control, such as addiction. Significance statement: Variations in the fat mass and obesity-associated (FTO) gene are associated with obesity. Here we demonstrate that variants of FTO affect dopamine-dependent midbrain brain responses and learning from negative outcomes in humans during a reward learning task. Furthermore, FTO variants modulate the connectivity in a basic reward circuit of meso-striato-prefrontal regions, suggesting a mechanism by which genetic vulnerability in reward processing can increase predisposition to obesity.
Actions performed by others are mostly not observed in isolation, but embedded in sequences of actions tied together by an overarching goal. Therefore, preceding actions can modulate the observer's ...expectations in relation to the currently perceived action. Ventrolateral prefrontal cortex (vlPFC), and inferior frontal gyrus (IFG) in particular, is suggested to subserve the integration of episodic as well as semantic information and memory, including action scripts. The present fMRI study investigated if activation in IFG varies with the effort to integrate expected and observed action, even when not required by the task. During an fMRI session, participants were instructed to attend to short videos of single actions and to deliver a judgment about the actor's current goal. We manipulated the strength of goal expectation induced by the preceding action, implementing the parameter "goal-relatedness" between the preceding and the currently observed action. Moreover, since objects point to the probability of certain actions, we also manipulated whether the current and the preceding action shared at least one object or not. We found an interaction between the two factors goal-relatedness and shared object: IFG activation increased the weaker the goal-relatedness between the preceding and the current action was, but only when they shared at least one object. Here, integration of successive action steps was triggered by the re-appearing (shared) object but hampered by a weak goal-relatedness between the actually observed manipulation. These findings foster the recently emerging view that IFG is enhanced by goal-related conflicts during action observation.
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The Target Absorbers for Neutrals (TANs) represent one of the most radioactive regions in the Large Hadron Collider. Seven 40cm long fused silica rods with different dopant specifications, ...manufactured by Heraeus, were irradiated in one of the TANs located around the ATLAS experiment by the Beam RAte of Neutrals (BRAN) detector group. This campaign took place during Run 2 p＋p data taking, which occurred between 2016 and 2018. This paper reports a complete characterization of optical transmission per unit length of irradiated fused silica materials as a function of wavelength (240 nm–1500 nm), dose (up to 18 MGy), and level of OH and H2 dopants introduced in the manufacturing process. The dose delivered to the rods was estimated using Monte Carlo simulations performed by the CERN FLUKA team.
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A matrix of synthetic fused silica samples with OH contents from 30 to 1300
ppm and of a fictive temperature from 1000 to 1300
°C has been characterized regarding their thermal expansion with high ...precision. The thermal expansion increases with fictive temperature and drops with OH content. Although fictive temperature and OH are coupled due to the influence of OH on the relaxation of the network, an independent influence of the OH content on thermal expansion has been observed. This may provide a deeper insight into the impact of impurities incorporated into the fused silica network.
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•Investigation of creep-fatigue behavior of X20CrMoV12-1 from 300 °C to 600 °C in dependence of atmosphere.•Validation of the K-concept for application of damage tolerance concepts in flexibly ...operated power plants with consideration of the microstructural peculiarities of ferritic-martensitic steels.•Investigation of steam oxidation impact on the transition from fatigue to creep-fatigue interaction.•Analysis of the impact of different evaluation concepts on results and subsequent interpretation.•Detailed microstructural investigation of the cracking mechanisms.
In this study the impact of frequency or rather hold time and atmosphere on the transition from fatigue dominated crack growth to creep fatigue of the ferritic/martensitic steel X20CrMoV12-1 was investigated from 300 °C−600 °C. This temperature range is most important for power plants operated in a flexible manner. Due to the increased share of renewable sources of energy, modern thermal power plants must be operated in a flexible manner to compensate fluctuating power supply from renewables. More damaging loading scenarios, including frequent start-up and shut-down cycles as well as load fluctuations, occur much more frequently than in the past as a consequence. Fatigue damage becomes more and more important, while creep damage reduces due to shorter full power operation durations. Furthermore, loss of passivation by fatigue induced cracking and delamination of protective oxide layers may constitute strong interdependencies of increased cyclic operation and steam oxidation resistance. This results in the necessity for a innovative surveillance concepts including operation mode dependent inspection intervals of thermal power plants. Application of a damage tolerance concept, based on fracture mechanics, can help to improve remaining life assessment of existing and fatigue tolerant design of future power plants. In order to develop codes for flexibly operated components, based on damage tolerance analysis by linear elastic fracture mechanics, its validity range and especially its limitation have to be evaluated first. The study has shown that the transition from pure fatigue to creep fatigue interaction begins at 500 °C and 3.33 × 10−3 Hz (300 s hold time). Furthermore this transition was found to be independent from steam atmosphere. The corresponding fracture mechanisms were investigated in detail.
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10.
High-concentration protein formulations: How high is high? Garidel, Patrick; Kuhn, Alexander B.; Schäfer, Lars V. ...
European journal of pharmaceutics and biopharmaceutics,
October 2017, 2017-Oct, 2017-10-00, 20171001, Volume:
119
Journal Article
Peer reviewed
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High-concentration protein formulation (HCPF) is a term that is used to describe protein formulations, mostly monoclonal antibody (mAb) drugs, at high protein concentration. The ...concentration is rarely defined, with typical ranges varying between 50 and 150mg/ml for mAbs. The term HCPF is meant to include and express specific solution properties of formulations that are prone to appear at high protein concentrations such as high viscosity, high opalescence, phase separation, gel formation or the increased propensity for protein particle formation. Thus the term HCPF can be understood as a descriptor of protein formulations, usually at high protein (monoclonal antibody) concentrations, which have specific solution, stability and colloidal properties that differ from formulations at low protein concentration (e.g. at 10mg/ml).
The current paper highlights in brief the development challenges that might occur for high-concentration protein/monoclonal antibody formulations. In particular, the maximum concentration regimes achievable in HCPF remained unclear. Based on geometrical considerations involving packing of monoclonal antibodies in a lattice we map out a maximum concentration range that might be theoretically achievable. Different geometrical assumptions and packing models are compared and their relevance is critically discussed, in particular concerning the influence of the physicochemical properties of the monoclonal antibodies on their solubility, which is neglected in the simple geometrical model. According to our estimates, monoclonal antibody concentration above 500mg/ml will be very challenging to achieve. Our results have implications for setting up realistic drug product development strategies and for preparing convincing drug target product profiles for development.
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