Heterogenous treatment effects: secrets for a reliable treat-to-target trial?

No abstract available

Pulsations as a Driver for LBV Variability

Among the most spectacular variable stars are the Luminous Blue Variables (LBVs), which can show three types of variability. The LBV phase of evolution is poorly understood, and the driving mechanisms for the variability are not known. The most common type of variability, the S Dor instability, occurs on timescales of tens of years. During an S Dor outburst, the visual magnitude of the star increases, while the bolometric magnitude stays approximately constant. In this work, we investigate pulsation as a possible trigger for the S Dor type outbursts. We calculate the pulsations of envelope models using a nonlinear hydrodynamics code including a time-dependent convection treatment. We initialize the pulsation in the hydrodynamic model based on linear non-adiabatic calculations. Pulsation properties for a full grid of models from 20 to 85 M$_{\odot}$ were calculated, and in this paper we focus on the few models that show either long-period pulsations or outburst-like behaviour, with photospheric radial velocities reaching 70-80 km/s. At the present time, our models cannot follow mass loss, so once the outburst event begins, our simulations are terminated. Our results show that pulsations alone are not able to drive enough surface expansion to eject the outer layers. However, the outbursts and long-period pulsations discussed here produce large variations in effective temperature and luminosity, which are expected to produce large variations in the radiatively driven mass-loss rates.Comment: 9 pages, 10 figures, accepted for publication in MNRA

Inhomogeneous systematic signals in cosmic shear observations

We calculate the systematic errors in the weak gravitational lensing power spectrum which would be caused by spatially varying calibration (i.e. multiplicative) errors, such as might arise from uncorrected seeing or extinction variations. The systematic error is fully described by the angular two-point correlation function of the systematic in the case of the 2D lensing that we consider here. We investigate three specific cases: Gaussian, ``patchy'' and exponential correlation functions. In order to keep systematic errors below statistical errors in future LSST-like surveys, the spatial variation of calibration should not exceed 3% rms. This conclusion is independently true for all forms of correlation function we consider. The relative size the E- and B-mode power spectrum errors does, however, depend upon the form of the correlation function, indicating that one cannot repair the E-mode power spectrum systematics by means of the B-mode measurements.Comment: 8 pages, 3 figures. Changes reflect PRD published versio

Efficiency of energy funneling in the photosystem II supercomplex of higher plants

The investigation of energy transfer properties in photosynthetic multi-protein networks gives insight into their underlying design principles.Here, we discuss excitonic energy transfer mechanisms of the photosystem II (PS-II) C$_2$S$_2$M$_2$ supercomplex, which is the largest isolated functional unit of the photosynthetic apparatus of higher plants.Despite the lack of a decisive energy gradient in C$_2$S$_2$M$_2$, we show that the energy transfer is directed by relaxation to low energy states. C$_2$S$_2$M$_2$ is not organized to form pathways with strict energetic downhill transfer, which has direct consequences on the transfer efficiency, transfer pathways and transfer limiting steps. The exciton dynamics is sensitive to small structural changes, which, for instance, are induced by the reorganization of vibrational coordinates. In order to incorporate the reorganization process in our numerical simulations, we go beyond rate equations and use the hierarchically coupled equation of motion approach (HEOM). While transfer from the peripherical antenna to the proteins in proximity to the reaction center occurs on a faster time scale, the final step of the energy transfer to the RC core is rather slow, and thus the limiting step in the transfer chain. Our findings suggest that the structure of the PS-II supercomplex guarantees photoprotection rather than optimized efficiency.Comment: 23 pages, 6 figure

Exciton-phonon information flow in the energy transfer process of photosynthetic complexes

Non-Markovian and non-equilibrium phonon effects are believed to be key ingredients in the energy transfer in photosynthetic complexes, especially in complexes which exhibit a regime of intermediate exciton-phonon coupling. In this work, we utilize a recently-developed measure for non-Markovianity to elucidate the exciton-phonon dynamics in terms of the information flow between electronic and vibrational degrees of freedom. We study the measure in the hierarchical equation of motion approach which captures strong system-bath coupling effects and non-equilibrium molecular reorganization. We propose an additional trace-distance measure for the information flow that could be extended to other master equations. We find that for a model dimer system and the Fenna-Matthews-Olson complex that non-Markovianity is significant under physiological conditions.Comment: 4 pages, 2 figure

Epigenetics and immunometabolism in diabetes and aging

Significance: A strong relationship between hyperglycemia, impaired insulin pathway and cardiovascular disease in type 2 diabetes (T2D) is linked to oxidative stress and inflammation. Immunometabolic pathways link these pathogenic processes and pose important potential therapeutic targets. Recent Advances: The link between immunity and metabolism is bi-directional and includes the role of inflammation in the pathogenesis of metabolic disorders such as T2D, obesity, metabolic syndrome and hypertension as well as the role of metabolic factors in regulation of immune cell functions. Low-grade inflammation, oxidative stress, balance between superoxide and nitric oxide, and the infiltration of macrophages, T cells, B cells in insulin-sensitive tissues, leads to metabolic impairment and accelerated ageing. Critical Issues: Inflammatory infiltrate and altered immune cell phenotype precede development of metabolic disorders. Inflammatory changes are tightly linked to alterations in metabolic status and energy expenditure and are controlled by epigenetic mechanisms. Future directions: A better comprehension of these mechanistic insights is of utmost importance to identify novel molecular targets. Here, we describe a complex scenario of epigenetic changes and immunometabolism linking to diabetes and aging-associated vascular disease

Perivascular adipose tissue inflammation in vascular disease

Perivascular adipose tissue (PVAT) plays a critical role in the pathogenesis of cardiovascular disease. In vascular pathologies, perivascular adipose tissue increases in volume and becomes dysfunctional, with altered cellular composition and molecular characteristics. PVAT dysfunction is characterized by its inflammatory character, oxidative stress, diminished production of vaso-protective adipocyte-derived relaxing factors and increased production of paracrine factors such as resistin, leptin, cytokines (IL-6 and TNF-α) and chemokines [RANTES (CCL5) and MCP-1 (CCL2)]. These adipocyte-derived factors initiate and orchestrate inflammatory cell infiltration including primarily T cells, macrophages, dendritic cells, B cells and NK cells. Protective factors such as adiponectin can reduce NADPH oxidase superoxide production and increase NO bioavailability in the vessel wall, while inflammation (e.g. IFN-γ or IL-17) induces vascular oxidases and eNOS dysfunction in the endothelium, vascular smooth muscle cells and adventitial fibroblasts. All of these events link the dysfunctional perivascular fat to vascular dysfunction. These mechanisms are important in the context of a number of cardiovascular disorders including atherosclerosis, hypertension, diabetes and obesity. Inflammatory changes in PVAT's molecular and cellular responses are uniquely different from classical visceral or subcutaneous adipose tissue or from adventitia, emphasizing the unique structural and functional features of this adipose tissue compartment. Therefore, it is essential to develop techniques for monitoring the characteristics of PVAT and assessing its inflammation. This will lead to a better understanding of the early stages of vascular pathologies and the development of new therapeutic strategies focusing on perivascular adipose tissue

Environment-assisted quantum transport in ordered systems

Noise-assisted transport in quantum systems occurs when quantum time-evolution and decoherence conspire to produce a transport efficiency that is higher than what would be seen in either the purely quantum or purely classical cases. In disordered systems, it has been understood as the suppression of coherent quantum localisation through noise, which brings detuned quantum levels into resonance and thus facilitates transport. We report several new mechanisms of environment-assisted transport in ordered systems, in which there is no localisation to overcome and where one would naively expect that coherent transport is the fastest possible. Although we are particularly motivated by the need to understand excitonic energy transfer in photosynthetic light-harvesting complexes, our model is general---transport in a tight-binding system with dephasing, a source, and a trap---and can be expected to have wider application

Path integral Monte Carlo with importance sampling for excitons interacting with an arbitrary phonon bath

The reduced density matrix of excitons coupled to a phonon bath at a finite temperature is studied using the path integral Monte Carlo method. Appropriate choices of estimators and importance sampling schemes are crucial to the performance of the Monte Carlo simulation. We show that by choosing the population-normalized estimator for the reduced density matrix, an efficient and physically-meaningful sampling function can be obtained. In addition, the nonadiabatic phonon probability density is obtained as a byproduct during the sampling procedure. For importance sampling, we adopted the Metropolis-adjusted Langevin algorithm. The analytic expression for the gradient of the target probability density function associated with the population-normalized estimator cannot be obtained in closed form without a matrix power series. An approximated gradient that can be efficiently calculated is explored to achieve better computational scaling and efficiency. Application to a simple one-dimensional model system from the previous literature confirms the correctness of the method developed in this manuscript. The displaced harmonic model system within the single exciton manifold shows the numerically exact temperature dependence of the coherence and population of the excitonic system. The sampling scheme can be applied to an arbitrary anharmonic environment, such as multichromophoric systems embedded in the protein complex. The result of this study is expected to stimulate further development of real time propagation methods that satisfy the detailed balance condition for exciton populations.Comment: 16 pages, 5 figure