Cannibalism hinders growth: Cannibal Dark Matter and the S8S_8 tension

Many models of dark matter have been proposed in attempt to ease the $S_8$ tension between weak lensing and CMB experiments. One such exciting possibility is cannibalistic dark matter (CanDM), which has exothermal number-changing interactions allowing it to stay warm far into its non-relativistic regime. Here we investigate the cosmological implications of CanDM and how it impacts CMB anisotropies and the matter power spectrum, by implementing the model within a linear Einstein-Boltzmann solver. We show that CanDM suppresses the small scale matter power spectrum in a way very similar to light Warm Dark Matter or Hot Dark Matter. However, unlike in those models, the suppression may happen while the CanDM model still remains compatible with CMB constraints. We put strong constraints on the interaction strength of CanDM as a function of its abundance for both constant and temperature-dependent thermally-averaged cross sections. We find that the CanDM model can easily solve the $S_8$ tension (but has no impact on the Hubble tension). Indeed, it can accommodate values of $S_8$ of the order of 0.76 while being compatible with CMB+BAO data. However, as long as the $S_8$ tension remains moderate, the overall $\chi^2$ improvement is relatively small given the number of extra free parameters, and the CanDM model is not significantly preferred.Comment: 28 pages, 14 figures, 2 tables. Comments are welcome (we don't bite

Cosmological constraints on multi-interacting dark matter

The increasingly significant tensions within $\Lambda$CDM, combined with the lack of detection of dark matter (DM) in laboratory experiments, have boosted interest in non-minimal dark sectors, which are theoretically well-motivated and inspire new search strategies for DM. Here we consider, for the first time, the possibility of DM having simultaneous interactions with photons, baryons, and dark radiation (DR). We have developed a new and efficient version of the Boltzmann code CLASS that allows for one DM species to have multiple interaction channels. With this framework we reassess existing cosmological bounds on the various interaction coefficients in multi-interacting DM scenarios. We find no clear degeneracies between these different interactions and show that their cosmological effects are largely additive. We further investigate the possibility of these models to alleviate the cosmological tensions, and find that the combination of DM-photon and DM-DR interactions can at the same time reduce the $S_8$ tension (from $2.3\sigma$ to $1.2\sigma$) and the $H_0$ tension (from $4.3\sigma$ to $3.1\sigma$). The public release of our code will pave the way for the study of various rich dark sectors.Comment: 41 pages, 8 figures, 5 tables. Comments are welcom

Evaluating the feasibility of Cas9 overexpression in 3T3-L1 cells for generation of genetic knock-out adipocyte cell lines

Cell lines recapitulating physiological processes can represent alternatives to animal or human studies. The 3T3-L1 cell line is used to mimic adipocyte function and differentiation. Since transfection of 3T3-L1 cells is difficult, we used a modified 3T3-L1 cell line overexpressing Cas9 for a straightforward generation of gene knock-outs. As an example, we intended to generate 3T3-L1 cell lines deficient for adhesion G protein-coupled receptors Gpr64/Adgr2 and Gpr126/Adgr6 using the CRISPR/Cas approach. Surprisingly, all the generated knock-out as well as scramble control cell lines were unresponsive to isoprenaline in respect to adiponectin secretion and lipolysis in contrast to the wild type 3T3-L1 cells. We, therefore, analysed the properties of these stable Cas9-overexpressing 3T3-L1 cells. We demonstrate that this commercially available cell line exhibits dysfunction in cAMP signalling pathways as well as reduced insulin sensitivity independent of gRNA transfection. We tried transient transfection of plasmids harbouring Cas9 as well as direct introduction of the Cas9 protein as alternate approaches to the stable expression of this enzyme. We find that transfection of the Cas9 protein is not only feasible but also does not impair adipogenesis and, therefore, represents a preferable alternative to achieve genetic knock-out

News from the Swampland -- Constraining string theory with astrophysics and cosmology

Our current best guess for a unified theory of gravitation and quantum field theory (string theory) generically predicts a set of requirements for a consistently quantized theory, the Swampland criteria. Refined versions of these criteria have recently been shown to be in mild tension with cosmological observations. We summarize the status of the current impact of and constraints on the Swampland conjectures from cosmology, and subject a variety of dark energy quintessence models to recently released cosmological datasets. We find that instead of tightening the tension, the new data allows for slightly more freedom in the Swampland criteria. We further demonstrate that if there is no theoretical argument made to prevent interactions of the moduli fields with the electromagnetic sector, a novel fine-tuning argument arises from the extremely tight current constraints on such interactions. Finally, we conclude with a cautionary tale on model-independent reconstructions of the Swampland criteria from expansion rate data.Comment: 35 pages, 20 figures, 4 tables. All comments are welcome! [v2: Added citations, corrected eq. 2.6

Runaway dilaton models: improved constraints from the full cosmological evolution

One of the few firm predictions of string theory is the existence of a massless scalar field coupled to gravity, the dilaton. In its presence, the value of the fundamental constants of the universe, such as the fine-structure constant, will vary with the time-dependent vacuum expectation value of this field, in direct violation of the Einstein Equivalence Principle. The \emph{runaway dilaton} proposed by Damour, Piazza, and Veneziano provides a physically motivated cosmological scenario which reconciles the existence of a massless dilaton with observations, while still providing non-standard and testable predictions. Furthermore, the field can provide a natural candidate for dynamical dark energy. While this model has been previously constrained from local laboratory experiments and low-redshift observations, we provide here the first full self-consistent constraints, also including high redshift data, in particular from the cosmic microwave background. We consider various possible scenarios in which the field could act as quintessence. Despite the wider parameter space, we make use of recent observational progress to significantly improve constraints on the model's coupling parameters, showing that order unity couplings (which would be natural in string theory) are ruled out.Comment: Published in Phys. Rev.

Protein-peptide association kinetics beyond the seconds timescale from atomistic simulations

Understanding and control of structures and rates involved in protein-ligand binding are es- sential for drug design. Unfortunately, atomistic molecular dynamics (MD) simulations cannot di- rectly sample the excessively long residence and rearrangement times of tightly binding complexes. Here we exploit the recently developed multi-ensemble Markov model framework to compute full protein-peptide kinetics of the oncoprotein fragment 25−109Mdm2 and the nano-molar inhibitor peptide PMI. Using this system, we report, for the first time, direct estimates of kinetics beyond the seconds timescales using simulations of an all-atom MD model, with high accuracy and pre- cision. These results only require explicit simulations on the sub-milliseconds timescale and are tested against existing mutagenesis data and our own experimental measurements of the dissoci- ation and association rates. The full kinetic model reveals an overall downhill but rugged binding funnel with multiple pathways. The overall strong binding arises from a variety of conformations with different hydrophobic contact surfaces that interconvert on the milliseconds timescale.Funding is acknowledged by European Commission (ERC StG “pcCells” to F.N.), Deutsche Forschungsgemeinschaft (SFB 1114/C3, SFB 740/D7, and TRR 186/A12 to F.N. and SFB 1114/A4 to F.N. and T.W.). J.C. is a Wellcome Trust Senior Research Fellow (WT 095195MA). J.S. is a Marie Sklodowska-Curie Internationally outgoing fellow. M.D.C. is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) studentship

Humanity on the move: Unlocking the transformative power of cities

The momentum of urbanization and its impacts are so massive that we must face up to this trend. In view of the existing cognitive, technical, economic and institutional path dependencies, a policy of business as usual – i.e. an unstructured, quasi-automatic urbanization – would lead to a non-sustainable ‘world cities society’. Only if cities and urban societies are sufficiently empowered can they make use of the opportunities for sustainability and successfully follow the urban transformation pathways. The success or failure of the Great Transformation will be decided in the cities. The WBGU discusses the relevant conditions for the success of this transformation in this report

Der Umzug der Menschheit: Die transformative Kraft der Städte

Die Wucht der derzeitigen Urbanisierungsdynamik und ihre Auswirkungen sind so groß, dass sich weltweit Städte, Stadtgesellschaften, Regierungen und Internationale Organisationen diesem Trend stellen müssen. Ein „Weiter so wie bisher“, würde ohne gestaltende Urbanisierungspolitik zu einer nicht-nachhaltigen Welt-Städte-Gesellschaft führen. Nur wenn Städte und Stadtgesellschaften ausreichend handlungsfähig werden, können sie ihre Kraft für eine nachhaltige Entwicklung entfalten: In den Städten wird sich entscheiden, ob die Große Transformation zur Nachhaltigkeit gelingt. In diesem Buch werden die Erfolgsbedingungen dafür diskutiert