Observational estimates of the initial power spectrum at small scale from Lyman-α\alpha absorbers

We present a new method of measuring the power spectrum of initial perturbations to an unprecedently small scale of $\sim$ 10$h^{-1}$ kpc. We apply this method to a sample of 4500 Ly-$\alpha$ absorbers and recover the cold dark matter (CDM) like power spectrum at scales $\geq 300h^{-1}$kpc with a precision of $\sim$ 10%. However at scales $\sim 10 - 300 h^{-1}$kpc the measured and CDM--like spectra are noticeable different. This result suggests a complex inflation with generation of excess power at small scales. The magnitude and reliability of these deviations depend also upon the possible incompleteness of our sample and poorly understood process of formation of weak absorbers. Confirmation of the CDM--like shape of the initial power spectrum or detection of its distortions at small scales are equally important for widely discussed problems of physics of the early Universe, galaxy formation, and reheating of the Universe. Our method links the observed mass function of absorbers with the correlation function of the initial velocity field and therefore it avoids the Nyquist restrictions limiting the investigations based on the smoothed flux or density fields. The physical model of absorbers adopted here asserts that they are formed in the course of both linear and nonlinear adiabatic or shock compression of dark matter (DM) and gaseous matter. At scales $\geq 1h^{-1}$Mpc all characteristics of the DM component and, in particular, their redshift distribution are found to be consistent with theoretical expectations for Gaussian initial perturbations with a CDM--like power spectrum.Comment: 22 pages, 10 figure

Multiorder coherent Raman scattering of a quantum probe field

We study the multiorder coherent Raman scattering of a quantum probe field in a far-off-resonance medium with a prepared coherence. Under the conditions of negligible dispersion and limited bandwidth, we derive a Bessel-function solution for the sideband field operators. We analytically and numerically calculate various quantum statistical characteristics of the sideband fields. We show that the multiorder coherent Raman process can replicate the statistical properties of a single-mode quantum probe field into a broad comb of generated Raman sidebands. We also study the mixing and modulation of photon statistical properties in the case of two-mode input. We show that the prepared Raman coherence and the medium length can be used as control parameters to switch a sideband field from one type of photon statistics to another type, or from a non-squeezed state to a squeezed state and vice versa.Comment: 12 pages, 7 figures, to be published in Phys. Rev.

Modular assembly of proteins on nanoparticles

Generally, the high diversity of protein properties necessitates the development of unique nanoparticle bio-conjugation methods, optimized for each different protein. Here we describe a universal bio-conjugation approach which makes use of a new recombinant fusion protein combining two distinct domains. The N-terminal part is Glutathione S-Transferase (GST) from Schistosoma japonicum, for which we identify and characterize the remarkable ability to bind gold nanoparticles (GNPs) by forming gold–sulfur bonds (Au–S). The C-terminal part of this multi-domain construct is the SpyCatcher from Streptococcus pyogenes, which provides the ability to capture recombinant proteins encoding a SpyTag. Here we show that SpyCatcher can be immobilized covalently on GNPs through GST without the loss of its full functionality. We then show that GST-SpyCatcher activated particles are able to covalently bind a SpyTag modified protein by simple mixing, through the spontaneous formation of an unusual isopeptide bond

Correction: S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Mesenchymal stem cells: from experiment to clinic

There is currently much interest in adult mesenchymal stem cells (MSCs) and their ability to differentiate into other cell types, and to partake in the anatomy and physiology of remote organs. It is now clear these cells may be purified from several organs in the body besides bone marrow. MSCs take part in wound healing by contributing to myofibroblast and possibly fibroblast populations, and may be involved in epithelial tissue regeneration in certain organs, although this remains more controversial. In this review, we examine the ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we update their opposing qualities of being less immunogenic and therefore tolerated in a transplant situation, yet being able to contribute to xenograft models of human tumour formation in other contexts. However, such observations have not been replicated in the clinic. Recent studies showing the clinical safety of MSC in several pathologies are discussed. The possible opposing powers of MSC need careful understanding and control if their clinical potential is to be realised with long-term safety for patients

A Temporal Gate for Viral Enhancers to Co-opt Toll-Like-Receptor Transcriptional Activation Pathways upon Acute Infection

Viral engagement with macrophages activates Toll-Like-Receptors (TLRs) and viruses must contend with the ensuing inflammatory responses to successfully complete their replication cycle. To date, known counter-strategies involve the use of viral-encoded proteins that often employ mimicry mechanisms to block or redirect the host response to benefit the virus. Whether viral regulatory DNA sequences provide an opportunistic strategy by which viral enhancer elements functionally mimic innate immune enhancers is unknown. Here we find that host innate immune genes and the prototypical viral enhancer of cytomegalovirus (CMV) have comparable expression kinetics, and positively respond to common TLR agonists. In macrophages but not fibroblasts we show that activation of NFκB at immediate-early times of infection is independent of virion-associated protein, M45. We find upon virus infection or transfection of viral genomic DNA the TLR-agonist treatment results in significant enhancement of the virus transcription-replication cycle. In macrophage time-course infection experiments we demonstrate that TLR-agonist stimulation of the viral enhancer and replication cycle is strictly delimited by a temporal gate with a determined half-maximal time for enhancer-activation of 6 h; after which TLR-activation blocks the viral transcription-replication cycle. By performing a systematic siRNA screen of 149 innate immune regulatory factors we identify not only anticipated anti-viral and pro-viral contributions but also new factors involved in the CMV transcription-replication cycle. We identify a central convergent NFκB-SP1-RXR-IRF axis downstream of TLR-signalling. Activation of the RXR component potentiated direct and indirect TLR-induced activation of CMV transcription-replication cycle; whereas chromatin binding experiments using wild-type and enhancer-deletion virus revealed IRF3 and 5 as new pro-viral host transcription factor interactions with the CMV enhancer in macrophages. In a series of pharmacologic, siRNA and genetic loss-of-function experiments we determined that signalling mediated by the TLR-adaptor protein MyD88 plays a vital role for governing the inflammatory activation of the CMV enhancer in macrophages. Downstream TLR-regulated transcription factor binding motif disruption for NFκB, AP1 and CREB/ATF in the CMV enhancer demonstrated the requirement of these inflammatory signal-regulated elements in driving viral gene expression and growth in cells as well as in primary infection of neonatal mice. Thus, this study shows that the prototypical CMV enhancer, in a restricted time-gated manner, co-opts through DNA regulatory mimicry elements, innate-immune transcription factors to drive viral expression and replication in the face of on-going pro-inflammatory antiviral responses in vitro and in vivo and; suggests an unexpected role for inflammation in promoting acute infection and has important future implications for regulating latency

Embedding artificial intelligence in society: looking beyond the EU AI master plan using the culture cycle

The European Union (EU) Commission’s whitepaper on Artificial Intelligence (AI) proposes shaping the emerging AI market so that it better reflects common European values. It is a master plan that builds upon the EU AI High-Level Expert Group guidelines. This article reviews the masterplan, from a culture cycle perspective, to reflect on its potential clashes with current societal, technical, and methodological constraints. We identify two main obstacles in the implementation of this plan: (i) the lack of a coherent EU vision to drive future decision-making processes at state and local levels and (ii) the lack of methods to support a sustainable diffusion of AI in our society. The lack of a coherent vision stems from not considering societal differences across the EU member states. We suggest that these differences may lead to a fractured market and an AI crisis in which different members of the EU will adopt nation-centric strategies to exploit AI, thus preventing the development of a frictionless market as envisaged by the EU. Moreover, the Commission aims at changing the AI development culture proposing a human-centred and safety-first perspective that is not supported by methodological advancements, thus taking the risks of unforeseen social and societal impacts of AI. We discuss potential societal, technical, and methodological gaps that should be filled to avoid the risks of developing AI systems at the expense of society. Our analysis results in the recommendation that the EU regulators and policymakers consider how to complement the EC programme with rules and compensatory mechanisms to avoid market fragmentation due to local and global ambitions. Moreover, regulators should go beyond the human-centred approach establishing a research agenda seeking answers to the technical and methodological open questions regarding the development and assessment of human-AI co-action aiming for a sustainable AI diffusion in the society

Continental break-up of the South China Sea stalled by far-field compression

The outcome of decades of two-dimensional modelling of lithosphere deformation under extension is that mechanical coupling between the continental crust and the underlying mantle controls how a continent breaks apart to form a new ocean. However, geological observations unequivocally show that continental break-up propagates in the third dimension at rates that do not scale with the rate of opening. Here, we perform three-dimensional numerical simulations and compare them with observations from the South China Sea to show that tectonic loading in the direction of propagation exerts a first-order control on these propagation rates. The simulations show that, in the absence of compression in that direction, continental break-up propagates fast, forming narrow continental margins independently of the coupling. When compression is applied, propagation stagnates, forming V-shaped oceanic basins and wide margins. Changes in out-of-plane loading therefore explain the alternation of fast propagation and relative stagnation. These new dynamic constraints suggest that the west-to-east topographic gradient across the Indochinese Peninsula prevented continental break-up propagation through the 1,000-km-wide continental rift of the central and west basin of the South China Sea, until the direction of stretching changed 23 million years ago, resulting in bypassing and acceleration of continental break-up propagation