Guidelines for developing optical clocks with 10−1810^{-18} fractional frequency uncertainty

There has been tremendous progress in the performance of optical frequency standards since the first proposals to carry out precision spectroscopy on trapped, single ions in the 1970s. The estimated fractional frequency uncertainty of today's leading optical standards is currently in the $10^{-18}$ range, approximately two orders of magnitude better than that of the best caesium primary frequency standards. This exceptional accuracy and stability is resulting in a growing number of research groups developing optical clocks. While good review papers covering the topic already exist, more practical guidelines are needed as a complement. The purpose of this document is therefore to provide technical guidance for researchers starting in the field of optical clocks. The target audience includes national metrology institutes (NMIs) wanting to set up optical clocks (or subsystems thereof) and PhD students and postdocs entering the field. Another potential audience is academic groups with experience in atomic physics and atom or ion trapping, but with less experience of time and frequency metrology and optical clock requirements. These guidelines have arisen from the scope of the EMPIR project "Optical clocks with $1 imes 10^{-18}$ uncertainty" (OC18). Therefore, the examples are from European laboratories even though similar work is carried out all over the world. The goal of OC18 was to push the development of optical clocks by improving each of the necessary subsystems: ultrastable lasers, neutral-atom and single-ion traps, and interrogation techniques. This document shares the knowledge acquired by the OC18 project consortium and gives practical guidance on each of these aspects

Varying constants, Gravitation and Cosmology

Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. It is thus of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We thus detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit

Guidelines for developing optical clocks with 10-18 fractional frequency uncertainty

There has been tremendous progress in the performance of optical frequency standards since the first proposals to carry out precision spectroscopy on trapped, single ions in the 1970s. The estimated fractional frequency uncertainty of today's leading optical standards is currently in the 10−18 range, approximately two orders of magnitude better than that of the best caesium primary frequency standards. This exceptional accuracy and stability is resulting in a growing number of research groups developing optical clocks. While good review papers covering the topic already exist, more practical guidelines are needed as a complement. The purpose of this document is therefore to provide technical guidance for researchers starting in the field of optical clocks. The target audience includes national metrology institutes (NMIs) wanting to set up optical clocks (or subsystems thereof) and PhD students and postdocs entering the field. Another potential audience is academic groups with experience in atomic physics and atom or ion trapping, but with less experience of time and frequency metrology and optical clock requirements. These guidelines have arisen from the scope of the EMPIR project "Optical clocks with 1×10−18 uncertainty" (OC18). Therefore, the examples are from European laboratories even though similar work is carried out all over the world. The goal of OC18 was to push the development of optical clocks by improving each of the necessary subsystems: ultrastable lasers, neutral-atom and single-ion traps, and interrogation techniques. This document shares the knowledge acquired by the OC18 project consortium and gives practical guidance on each of these aspects.EU/Horizon2020/EMPIR/E

The Advancement of Biomaterials in Regulating Stem Cell Fate.

Stem cells are well-known to have prominent roles in tissue engineering applications. Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can differentiate into every cell type in the body while adult stem cells such as mesenchymal stem cells (MSCs) can be isolated from various sources. Nevertheless, an utmost limitation in harnessing stem cells for tissue engineering is the supply of cells. The advances in biomaterial technology allows the establishment of ex vivo expansion systems to overcome this bottleneck. The progress of various scaffold fabrication could direct stem cell fate decisions including cell proliferation and differentiation into specific lineages in vitro. Stem cell biology and biomaterial technology promote synergistic effect on stem cell-based regenerative therapies. Therefore, understanding the interaction of stem cell and biomaterials would allow the designation of new biomaterials for future clinical therapeutic applications for tissue regeneration. This review focuses mainly on the advances of natural and synthetic biomaterials in regulating stem cell fate decisions. We have also briefly discussed how biological and biophysical properties of biomaterials including wettability, chemical functionality, biodegradability and stiffness play their roles