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"de Boer, Jan"
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Well-being in contemporary society
This anthology examines the practical role of well-being in contemporary society. It discusses developments such as globalization, consumerism and the rapid innovation and use of new and emerging technologies and focuses on the significant impact of these developments on the well-being of people living today.
Book
Holographic order from modular chaos
A
bstract
We argue for an exponential bound characterizing the chaotic properties of modular Hamiltonian flow of QFT subsystems. In holographic theories, maximal modular chaos is reflected in the local Poincare symmetry about a Ryu-Takayanagi surface. Generators of null deformations of the bulk extremal surface map to
modular scrambling modes
— positive CFT operators saturating the bound — and their algebra probes the bulk Riemann curvature, clarifying the modular Berry curvature proposal of arXiv:1903.04493.
Journal Article
Spheroid culture as a tool for creating 3D complex tissues
► Spheroids improve the relevance of in vitro results. ► Spheroids serve as biological models of native tissues or engineered solutions. ► Spheroids are used as building blocks to form tissues. ► Spheroids in concert with other aggregated cell shapes allow for complex tissue architecture studies.
3D cell culture methods confer a high degree of clinical and biological relevance to in vitro models. This is specifically the case with the spheroid culture, where a small aggregate of cells grows free of foreign materials. In spheroid cultures, cells secrete the extracellular matrix (ECM) in which they reside, and they can interact with cells from their original microenvironment. The value of spheroid cultures is increasing quickly due to novel microfabricated platforms amenable to high-throughput screening (HTS) and advances in cell culture. Here, we review new possibilities that combine the strengths of spheroid culture with new microenvironment fabrication methods that allow for the creation of large numbers of highly reproducible, complex tissues.
Journal Article
A non-renormalization theorem for chiral primary 3-point functions
A
bstract
In this note we prove a non-renormalization theorem for the 3-point functions of 1/2 BPS primaries in the four-dimensional
SYM and chiral primaries in two dimensional
SCFTs. Our proof is rather elementary: it is based on Ward identities and the structure of the short multiplets of the superconformal algebra and it does not rely on superspace techniques. We also discuss some possible generalizations to less supersymmetric multiplets.
Journal Article
Genetic Components of Root Architecture Remodeling in Response to Salt Stress
Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies. Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and multivariate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.
Journal Article
An open source machine learning framework for efficient and transparent systematic reviews
To help researchers conduct a systematic review or meta-analysis as efficiently and transparently as possible, we designed a tool to accelerate the step of screening titles and abstracts. For many tasks—including but not limited to systematic reviews and meta-analyses—the scientific literature needs to be checked systematically. Scholars and practitioners currently screen thousands of studies by hand to determine which studies to include in their review or meta-analysis. This is error prone and inefficient because of extremely imbalanced data: only a fraction of the screened studies is relevant. The future of systematic reviewing will be an interaction with machine learning algorithms to deal with the enormous increase of available text. We therefore developed an open source machine learning-aided pipeline applying active learning: ASReview. We demonstrate by means of simulation studies that active learning can yield far more efficient reviewing than manual reviewing while providing high quality. Furthermore, we describe the options of the free and open source research software and present the results from user experience tests. We invite the community to contribute to open source projects such as our own that provide measurable and reproducible improvements over current practice.
It is a challenging task for any research field to screen the literature and determine what needs to be included in a systematic review in a transparent way. A new open source machine learning framework called ASReview, which employs active learning and offers a range of machine learning models, can check the literature efficiently and systemically.
Journal Article
On local and integrated stress-tensor commutators
A
bstract
We discuss some general aspects of commutators of local operators in Lorentzian CFTs, which can be obtained from a suitable analytic continuation of the Euclidean operator product expansion (OPE). Commutators only make sense as distributions, and care has to be taken to extract the right distribution from the OPE. We provide explicit computations in two and four-dimensional CFTs, focusing mainly on commutators of components of the stress-tensor. We rederive several familiar results, such as the canonical commutation relations of free field theory, the local form of the Poincaré algebra, and the Virasoro algebra of two-dimensional CFT. We then consider commutators of light-ray operators built from the stress-tensor. Using simplifying features of the light sheet limit in four-dimensional CFT we provide a direct computation of the BMS algebra formed by a specific set of light-ray operators in theories with no light scalar conformal primaries. In four-dimensional CFT we define a new infinite set of light-ray operators constructed from the stress-tensor, which all have well-defined matrix elements. These are a direct generalization of the two-dimensional Virasoro light-ray operators that are obtained from a conformal embedding of Minkowski space in the Lorentzian cylinder. They obey Hermiticity conditions similar to their two-dimensional analogues, and also share the property that a semi-infinite subset annihilates the vacuum.
Journal Article
Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans
The sterol regulatory element binding proteins (SREBPs) are transcription factors that govern cholesterol and fatty acid metabolism. We recently identified SPRING as a post-transcriptional regulator of SREBP activation. Constitutive or inducible global ablation of
Spring
in mice is not tolerated, and we therefore develop liver-specific
Spring
knockout mice (LKO). Transcriptomics and proteomics analysis reveal attenuated SREBP signaling in livers and hepatocytes of LKO mice. Total plasma cholesterol is reduced in male and female LKO mice in both the low-density lipoprotein and high-density lipoprotein fractions, while triglycerides are unaffected. Loss of
Spring
decreases hepatic cholesterol and triglyceride content due to diminished biosynthesis, which coincides with reduced very-low-density lipoprotein secretion. Accordingly, LKO mice are protected from fructose diet-induced hepatosteatosis. In humans, we find common genetic
SPRING
variants that associate with circulating high-density lipoprotein cholesterol and ApoA1 levels. This study positions SPRING as a core component of hepatic SREBP signaling and systemic lipid metabolism in mice and humans.
Hendrix et al show that absence of hepatic Spring dramatically lowers levels of lipids in the liver and plasma in mice, and protects from development of diet-induced steatosis. In line, genetic variation in SPRING is associated with lipid levels in humans.
Journal Article
Osteoinductive ceramics as a synthetic alternative to autologous bone grafting
Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of \"smart\" biomaterials.
Journal Article
Probing typical black hole microstates
A
bstract
We investigate the possibility that the geometry dual to a typical AdS black hole microstate corresponds to the extended AdS-Schwarzschild geometry, including a region spacelike to the exterior. We argue that this region can be described by the mirror operators, a set of state-dependent operators in the dual CFT. We probe the geometry of a typical state by considering state-dependent deformations of the CFT Hamiltonian, which have an interpretation as a one-sided analogue of the Gao-Jafferis-Wall traversable wormhole protocol for typical states. We argue that the validity of the conjectured bulk geometry requires that out-of-time-order correlators of simple CFT operators on typical pure states must exhibit the same chaotic effects as thermal correlators at scrambling time. This condition is related to the question of whether the product of operators separated by scrambling time obey the Eigenstate Thermalization Hypothesis. We investigate some of these statements in the SYK model and discuss similarities with state-dependent perturba- tions of pure states in the SYK model previously considered by Kourkoulou and Maldacena. Finally, we discuss how the mirror operators can be used to implement an analogue of the Hayden-Preskill protocol.
Journal Article