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The extraordinary desiccation resistance of the opportunistic human pathogen Acinetobacter baumannii is a key to its survival and spread in medical care units. The accumulation of compatible solute such as glutamate, mannitol and trehalose contributes to the desiccation resistance. Here, we have used osmolarity as a tool to study the response of cells to low water activities and studied the role of a potential inorganic osmolyte, K+, in osmostress response. Growth of A. baumannii was K+-dependent and the K+-dependence increased with the osmolarity of the medium. After an osmotic upshock, cells accumulated K+ and K+ accumulation increased with the salinity of the medium. K+ uptake was reduced in the presence of glycine betaine. The intracellular pools of compatible solutes were dependent on the K+ concentration: mannitol and glutamate concentrations increased with increasing K+ concentrations whereas trehalose was highest at low K+. After osmotic upshock, cells first accumulated K+ followed by synthesis of glutamate; later, mannitol and trehalose synthesis started, accompanied with a decrease of intracellular K+ and glutamate. These experiments demonstrate K+ uptake as a first response to osmostress in A. baumannii and demonstrate a hierarchy in the time-dependent accumulation of K+ and different organic solutes.
The HADES experiment at GSI has recently provided data on the flow coefficients v1,..., v4 for protons in Au+Au reactions at Elab = 1.23 AGeV (or √sNN = 2.4 GeV). This data allows to estimate the shear viscosity over entropy density ratio, η/s at low energies via a coarse graining analysis of the UrQMD transport simulations of the flow harmonics in comparison to the experimental data. By this we can provide for the first time an estimate of η/s ≈ 0.65 ± 0.15 (or (8 ± 2)(4π)−1) at such low energies.
The paper proposes a variation of simulation for checking and proving contextual equivalence in a non-deterministic call-by-need lambda-calculus with constructors, case, seq, and a letrec with cyclic dependencies. It also proposes a novel method to prove its correctness. The calculus’ semantics is based on a small-step rewrite semantics and on may-convergence. The cyclic nature of letrec bindings, as well as nondeterminism, makes known approaches to prove that simulation implies contextual equivalence, such as Howe’s proof technique, inapplicable in this setting. The basic technique for the simulation as well as the correctness proof is called pre-evaluation, which computes a set of answers for every closed expression. If simulation succeeds in finite computation depth, then it is guaranteed to show contextual preorder of expressions.
Often adopting a feminist perspective, the sociological literature on migrant domestic services (MDS) does not make explicit which feminist paradigm it speaks from. This article situates this literature within ongoing debates in feminist theory, in particular the tension between materialist and poststructuralist approaches. Then, it discusses the empirical relevance of each of those two paradigms on the example of the results of original research into the personalization of employment relationships in MDS.
The contribution proposes a new way of making sense of the diversity of feminist theories, distinguishing between modern and postmodern approaches. Indeed, since the 1980s, feminist theory in the US and Western Europe has undergone a ‘postmodern turn’, which renders previous typologies much less up-to-speed with recent developments in the field. Then, the article examines which paradigms are implicit in the sociological literature on MDS. Initially, personalization in MDS was mainly seen in materialist terms, as a way to maximize the quantity and quality of labour (including emotional labour) extracted from domestic workers. The emergence of postmodern approaches in feminist theory set off a progressive shift in MDS literature. First, this literature showed that personalization also fulfils identity functions for employers and
workers, then it widened its focus to include the affective dimensions of domestic labour (not to be confused with emotional labour). The final section shows how modern and postmodern feminist approaches can be combined within a single research, on the example of original research on personalization in MDS in Belgium and Poland. In particular, the contribution shows that the distinction between material functions of personalization on the one hand, and its emotional/identity functions on the other is not empirically operative. Indeed, migrant domestic workers generally use emotional/identity categories to frame material questions, and vice versa. This final part shows that, rather than representing incompatible approaches, modern and postmodern feminisms complete each other, in this case showing a fuller image of personalization processes in MDS.
A new method of event characterization based on Deep Learning is presented. The PointNet models can be used for fast, online event-by-event impact parameter determination at the CBM experiment. For this study, UrQMD and the CBM detector simulation are used to generate Au+Au collision events at 10 AGeV which are then used to train and evaluate PointNet based architectures. The models can be trained on features like the hit position of particles in the CBM detector planes, tracks reconstructed from the hits or combinations thereof. The Deep Learning models reconstruct impact parameters from 2-14 fm with a mean error varying from -0.33 to 0.22 fm. For impact parameters in the range of 5-14 fm, a model which uses the combination of hit and track information of particles has a relative precision of 4-9% and a mean error of -0.33 to 0.13 fm. In the same range of impact parameters, a model with only track information has a relative precision of 4-10% and a mean error of -0.18 to 0.22 fm. This new method of event-classification is shown to be more accurate and less model dependent than conventional methods and can utilize the performance boost of modern GPU processor units.
Amide proton transfer-chemical exchange saturation transfer (APT-CEST) imaging provides important information for the diagnosis and monitoring of tumors. For such analysis, complete coverage of the brain is advantageous, especially when registration is performed with other magnetic resonance (MR) modalities, such as MR spectroscopy (MRS). However, the acquisition of Z-spectra across several slices via multislice imaging may be time-consuming. Therefore, in this paper, we present a new approach for fast multislice imaging, allowing us to acquire 16 slices per frequency offset within 8 s. The proposed fast CEST-EPI sequence employs a presaturation module, which drives the magnetization into the steady-state equilibrium for the first frequency offset. A second module, consisting of a single CEST pulse (for maintaining the steady-state) followed by an EPI acquisition, passes through a loop to acquire multiple slices and adjacent frequency offsets. Thus, the whole Z-spectrum can be recorded much faster than the conventional saturation scheme, which employs a presaturation for each single frequency offset. The validation of the CEST sequence parameters was performed by using the conventional saturation scheme. Subsequently, the proposed and a modified version of the conventional CEST sequence were compared in vitro on a phantom with different T1 times and in vivo on a brain tumor patient. No significant differences between both sequences could be found in vitro. The in vivo data yielded almost identical MTRasym contrasts for the white and gray matter as well as for tumor tissue. Our results show that the proposed fast CEST-EPI sequence allows for rapid data acquisition and provides similar CEST contrasts as the modified conventional scheme while reducing the scanning time by approximately 50%.
A new artificial regulatory system for essential genes in yeast is described. It prevents translation of target mRNAs upon tetracycline (tc) binding to aptamers introduced into their 5'UTRs. Exploiting direct RNA–ligand interaction renders auxiliary protein factors unnecessary. Therefore, our approach is strain independent and not susceptible to interferences by heterologous expressed regulatory proteins. We use a simple PCR-based strategy, which allows easy tagging of any target gene and the level of gene expression can be adjusted due to various tc aptamer-regulated promoters. As proof of concept, five differently expressed genes were targeted, two of which could not be regulated previously. In all cases, adding tc completely prevented growth and, as shown for Nop14p, rapidly abolished de novo protein synthesis providing a powerful tool for conditional regulation of yeast gene expression.
The Education Against Tobacco (EAT) network delivers smoking prevention advice in secondary schools, typically using the mirroring approach (i.e., a "selfie" altered with a face-aging app and shared with a class). In November 2017, however, the German assembly of EAT opted to expand its remit to include nursing students. To assess the transferability of the existing approach, we implemented it with the self-developed face-aging app "Smokerface" (=mixed − methods approach) in six nursing schools. Anonymous questionnaires were used to assess the perceptions of 197 students (age 18–40 years; 83.8% female; 26.4% smokers; 23.3% daily smokers) collecting qualitative and quantitative data for our cross-sectional study. Most students perceived the intervention to be fun (73.3%), but a minority disagreed that their own animated selfie (25.9%) or the reaction of their peers (29.5%) had motivated them to stop smoking. The impact on motivation not to smoke was considerably lower than experienced with seventh graders (63.2% vs. 42.0%; notably, more smokers also disagreed (45.1%) than agreed (23.5%) with this statement. Agreement rates on the motivation not to smoke item were higher in females than in males and in year 2–3 than in year 1 students. Potential improvements included greater focus on pathology (29%) and discussing external factors (26%). Overall, the intervention seemed to be appealing for nursing students
According to the inflationary theory of cosmology, most elementary particles in the current universe were created during a period of reheating after inflation. In this work we self-consistently couple the Einstein-inflaton equations to a strongly coupled quantum field theory (QFT) as described by holography. We show that this leads to an inflating universe, a reheating phase and finally a universe dominated by the QFT in thermal equilibrium.
This paper studies constrained portfolio problems that may involve constraints on the probability or the expected size of a shortfall of wealth or consumption. Our first contribution is that we solve the problems by dynamic programming, which is in contrast to the existing literature that applies the martingale method. More precisely, we construct the non-separable value function by formalizing the optimal constrained terminal wealth to be a (conjectured) contingent claim on the optimal non-constrained terminal wealth. This is relevant by itself, but also opens up the opportunity to derive new solutions to constrained problems. As a second contribution, we thus derive new results for non-strict constraints on the shortfall of inter¬mediate wealth and/or consumption.
Vegetation responds to drought through a complex interplay of plant hydraulic mechanisms, posing challenges for model development and parameterization. We present a mathematical model that describes the dynamics of leaf water-potential over time while considering different strategies by which plant species regulate their water-potentials. The model has two parameters: the parameter λ describing the adjustment of the leaf water potential to changes in soil water potential, and the parameter Δψww describing the typical ‘well-watered’ leaf water potentials at non-stressed (near-zero) levels of soil water potential. Our model was tested and calibrated on 110 time-series datasets containing the leaf- and soil water potentials of 66 species under drought and non-drought conditions. Our model successfully reproduces the measured leaf water potentials over time based on three different regulation strategies under drought. We found that three parameter sets derived from the measurement data reproduced the dynamics of 53% of an drought dataset, and 52% of a control dataset [root mean square error (RMSE) < 0.5 MPa)]. We conclude that, instead of quantifying water-potential-regulation of different plant species by complex modeling approaches, a small set of parameters may be sufficient to describe the water potential regulation behavior for large-scale modeling. Thus, our approach paves the way for a parsimonious representation of the full spectrum of plant hydraulic responses to drought in dynamic vegetation models.
The upcoming commissioning of the superconducting (SC) continuous wave Helmholtz linear accelerators first of series cryomodule is going to demand precise alignment of the four internal SC cavities and two SC solenoids. For optimal results, a beam-based alignment method is used to reduce the misalignment of the whole cryomodule, as well as its individual components. A symmetric beam of low transverse emittance is required for this method, which is to be formed by a collimation system. It consists of two separate plates with milled slits, aligned in the horizontal and vertical direction. The collimation system and alignment measurements are proposed, investigated, and realized. The complete setup of this system and its integration into the existing environment at the GSI High Charge State Injector are presented, as well as the results of the recent reference measurements.
As a centerpiece of antigen processing, the ATP-binding cassette transporter associated with antigen processing (TAP) became a main target for viral immune evasion. The herpesviral ICP47 inhibits TAP function, thereby suppressing an adaptive immune response. Here, we report on a thermostable ICP47-TAP complex, generated by fusion of different ICP47 fragments. These fusion complexes allowed us to determine the direction and positioning in the central cavity of TAP. ICP47-TAP fusion complexes are arrested in a stable conformation, as demonstrated by MHC I surface expression, melting temperature, and the mutual exclusion of herpesviral TAP inhibitors. We unveiled a conserved region next to the active domain of ICP47 as essential for the complete stabilization of the TAP complex. Binding of the active domain of ICP47 arrests TAP in an open inward facing conformation rendering the complex inaccessible for other viral factors. Based on our findings, we propose a dual interaction mechanism for ICP47. A per se destabilizing active domain inhibits the function of TAP, whereas a conserved C-terminal region additionally stabilizes the transporter. These new insights into the ICP47 inhibition mechanism can be applied for future structural analyses of the TAP complex.
Derived from a biophysical model for the motion of a crawling cell, the evolution system(⋆){ut=Δu−∇⋅(u∇v),0=Δv−kv+u, is investigated in a finite domain Ω⊂Rn, n≥2, with k≥0. Whereas a comprehensive literature is available for cases in which (⋆) describes chemotaxis-driven population dynamics and hence is accompanied by homogeneous Neumann-type boundary conditions for both components, the presently considered modeling context, besides yet requiring the flux ∂νu−u∂νv to vanish on ∂Ω, inherently involves homogeneous Dirichlet boundary conditions for the attractant v, which in the current setting corresponds to the cell's cytoskeleton being free of pressure at the boundary. This modification in the boundary setting is shown to go along with a substantial change with respect to the potential to support the emergence of singular structures: It is, inter alia, revealed that in contexts of radial solutions in balls there exist two critical mass levels, distinct from each other whenever k>0 or n≥3, that separate ranges within which (i) all solutions are global in time and remain bounded, (ii) both global bounded and exploding solutions exist, or (iii) all nontrivial solutions blow up. While critical mass phenomena distinguishing between regimes of type (i) and (ii) belong to the well-understood characteristics of (⋆) when posed under classical no-flux boundary conditions in planar domains, the discovery of a distinct secondary critical mass level related to the occurrence of (iii) seems to have no nearby precedent. In the planar case with the domain being a disk, the analytical results are supplemented with some numerical illustrations, and it is discussed how the findings can be interpreted biophysically for the situation of a cell on a flat substrate.
Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion.
Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for γ-tests recorded.
Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2%/2 mm γ-fail rate of 1.6% with adaptation and 15.2% without adaptation (p < 0.001). For all prostate the mean 2%/2 mm γ-fail rate was 1.4% with adaptation and 17.3% without adaptation (p < 0.001). The difference between the four systems was small with an average 2%/2 mm γ-fail rate of <3% for all systems with adaptation for lung and prostate.
Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.
The article, which summarizes key findings of my German book ‘Die Gemeinfreiheit. Begriff, Funktion, Dogmatik’ (‘The Public Domain: Theory, Func-tion, Doctrine’), asks whether there are any provisions or principles under Ger-man and EU law that protect the public domain from interference by the legisla-ture, courts and private parties. In order to answer this question, it is necessary to step out of the intellectual property (IP) system and to analyze this body of law from the outside, and – even more important – to develop a positive legal conception of the public domain as such. By giving the public domain a proper doctrinal place in the legal system, the structural asymmetry between heavily theorized and protected IP rights on the one hand and a neglected public do-main on the other is countered. The overarching normative purpose is to devel-op a framework for a balanced IP system, which can only be achieved if the public domain forms an integral part of the overall regulation of information.
The prediction of protein–ligand interactions and their corresponding binding free energy is a challenging task in structure-based drug design and related applications. Docking and scoring is broadly used to propose the binding mode and underlying interactions as well as to provide a measure for ligand affinity or differentiate between active and inactive ligands. Various studies have revealed that most docking software packages reliably predict the binding mode, although scoring remains a challenge. Here, a diverse benchmark data set of 99 matched molecular pairs (3D-MMPs) with experimentally determined X-ray structures and corresponding binding affinities is introduced. This data set was used to study the predictive power of 13 commonly used scoring functions to demonstrate the applicability of the 3D-MMP data set as a valuable tool for benchmarking scoring functions.
Correlation functions provide information on the properties of mesons in vacuum and of hot nuclear matter. In this work, we present a new method to derive a well-defined spectral representation for correlation functions. Combining this method with the quark gap equation and the inhomogeneous Bethe–Salpeter equation in the rainbow-ladder approximation, we calculate in-vacuum masses of light mesons and the electrical conductivity of the quark–gluon plasma. The analysis can be extended to other observables of strong-interaction systems.