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Optical atomic clocks represent the state of the art in the frontier of modern measurement science. In this article a detailed review on the development of optical atomic clocks that are based on trapped single ions and many neutral atoms is provided. Important technical ingredients for optical clocks are discussed and measurement precision and systematic uncertainty associated with some of the best clocks to date are presented. An outlook on the exciting prospect for clock applications is given in conclusion.

With the recent production of polar molecules in the quantum regime [1,2], long-range dipolar interactions are expected to facilitate the understanding of strongly interacting many-body quantum systems and to realize lattice spin models [3] for exploring quantum magnetism. In atomic systems, where interactions require wave function overlap, effective spin interactions on a lattice can be realized through superexchange; however, the coupling is relatively weak and limited to nearest-neighbor interactions [4][5][6]. In contrast, dipolar interactions exist even in the absence of tunneling and extend beyond nearest neighbors. This allows coherent spin dynamics to persist even for gases with relatively high entropy and low lattice filling. While measured effects of dipolar interactions in ultracold molecular gases have thus far been limited to the modification of inelastic collisions and chemical reactions [7,8], we now report the first observation of dipolar interactions of polar molecules pinned in a three-dimensional optical lattice. We realize a lattice spin model where spin is encoded in rotational states of molecules that are prepared and probed by microwaves. This interaction arises from the resonant exchange of rotational angular momentum between two molecules and realizes a spin-exchange interaction. The dipolar interactions are apparent in the evolution of the spin coherence, where we observe clear oscillations in addition to an overall decay of the coherence. The frequency of these oscillations, the strong dependence of the spin coherence time on the lattice filling factor, and the effect of a multi-pulse sequence designed to reverse dynamics due to two-body exchange interactions all provide clear evidence of dipolar interactions. Furthermore, we demonstrate the suppression of loss in weak lattices due to a quantum Zeno mechanism [9]. Measurements of these tunneling-induced losses allow us to independently determine the lattice filling factor. The results reported here comprise an initial exploration of the behavior of many-body spin models with direct, long-range spin interactions and lay the groundwork for future studies of many-body dynamics in spin lattices.

During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

SUMMARY Development of cancer has been linked to chronic inflammation, particularly via interleukin-23 (IL-23) and IL-17 signaling pathways. However, the cellular source of IL-17 and underlying mechanisms by which IL-17-producing cells promote human colorectal cancer (CRC) remain poorly defined. Here, we demonstrate that innate γδT (γδT17) cells are the major cellular source of IL-17 in human CRC. Microbial products elicited by tumorous epithelial barrier disruption correlated with inflammatory dendritic cell (inf-DC) accumulation and γδT17 polarization in human tumors. Activated inf-DCs induced γδT17 cells to secrete IL-8, tumor necrosis factor alpha, and GM-CSF with a concomitant accumulation of immunosuppressive PMN-MDSCs in the tumor. Importantly, γδT17 cell infiltration positively correlated with tumor stages and other clinicopathological features. Our study uncovers an inf-DC-γδT17-PMN-MDSC regulatory axis in human CRC that correlates MDSC-meditated immunosuppression with tumor-elicited inflammation. These findings suggest that γδT17 cells might be key players in human CRC progression and have the potential for treatment or prognosis prediction.

Recently there has been a remarkable synergy between the technologies of precision laser stabilization and mode-locked ultrafast lasers. This has resulted in control of the frequency spectrum produced by mode-locked lasers, which consists of a regular comb of sharp lines. Thus such a controlled mode-locked laser is a ''femtosecond optical frequency comb generator.'' For a sufficiently broad comb, it is possible to determine the absolute frequencies of all of the comb lines. This ability has revolutionized optical frequency metrology and synthesis. It has also served as the basis for the recent demonstrations of atomic clocks that utilize an optical frequency transition. In addition, it is having an impact on time-domain applications, including synthesis of a single pulse from two independent lasers. In this Colloquium, we first review the frequency-domain description of a mode-locked laser and the connection between the pulse phase and the frequency spectrum in order to provide a basis for understanding how the absolute frequencies can be determined and controlled. Using this understanding, applications in optical frequency metrology and synthesis and optical atomic clocks are discussed. This is followed by a brief overview of how the comb technology is affecting and will affect time-domain experiments. CONTENTS I. Introduction 325 II. Time-and Frequency-Domain Pictures of a Mode-Locked Laser 326 A. Introduction to mode-locked lasers 326 B. Frequency spectrum of a mode-locked laser 327 C. Determining absolute optical frequencies with octave spanning spectra 328 D. Femtosecond optical frequency comb generator 329 E. Cross correlation: Time-domain measurement of f 0 330 III. Metrology and Optical Clocks Using Mode-Locked Lasers 331 A. Measurement of absolute optical frequency 331 B. Optical atomic clock 332 C. Optical frequency synthesizer 334 IV. Other Applications of Femtosecond Combs 335 A. Carrier-envelope phase coherence 336 B. Timing synchronization of mode-locked lasers 336 C. Phase lock between two mode-locked lasers 337 D. Extreme nonlinear optics 339 E. Coherent control 339 V. Summary 339 Acknowledgments 339 References 340

We demonstrate a great simplification in the long-standing problem of measuring optical frequencies in terms of the cesium primary standard. An air-silica microstructure optical fiber broadens the frequency comb of a femtosecond laser to span the optical octave from 1064 to 532 nm, enabling us to measure the 282 THz frequency of an iodine-stabilized Nd:YAG laser directly in terms of the microwave frequency that controls the comb spacing. Additional measurements of established optical frequencies at 633 and 778 nm using the same femtosecond comb confirm the accepted uncertainties for these standards.

We propose a new light source based on having alkaline-earth atoms in an optical lattice collectively emit photons on an ultra-narrow clock transition into the mode of a high Q-resonator. The resultant optical radiation has an extremely narrow linewidth in the mHz range, even smaller than that of the clock transition itself due to collective effects. A power level of order 10 −12 W is possible, sufficient for phase-locking a slave optical local oscillator. Realizing this light source has the potential to improve the stability of the best clocks by two orders of magnitude.PACS numbers: 42.50. Nn, 06.30.6v, 37.10.Jk, 37.30.+i, 46.62.Eh Time and frequencies are the quantities that we can measure with the highest accuracy by far. From this fact derives the importance of clocks and frequency standards for many applications in technology and fundamental science. Some applications directly relying on atomic clocks are GPS, synchronization of data and communication networks, precise measurements of the gravitational potential of the earth, radio astronomy, tests of theories of gravity, and tests of the fundamental laws of physics.With the advent of octave spanning optical frequency combs [1,2] it has become feasible to use atomic transitions in the optical domain to build atomic clocks. Optical clocks based on ions [3] and ultracold neutral atoms confined in optical lattices [4] have recently demonstrated a precision of about 1 part in 10 15 at one second and a total fractional uncertainty of 10 −16 [4] or below [3], surpassing the primary cesium microwave standards [5,6].The state-of-the-art optical atomic clocks do not achieve the full stability that is in principle afforded by the atomic transitions on which they are founded. These transitions could have natural line-Qs of order 10 18 , exceeding the fractional stability of the clocks by a factor of ∼ 100. The main obstacle that prevents us from reaping the full benefit of the ultra-narrow clock transitions is the linewidth of the lasers used to interrogate these transitions. These lasers are stabilized against carefully designed passive high-Q cavities and achieve linewidths < 1 Hz, making them the most stable coherent sources of radiation. It is mainly the thermal noise of the reference cavity mirrors that prevent a further linewidth reduction [7] and substantially reducing this noise is hard [8].An elegant solution to these problems would be to directly extract light emitted from the ultra-narrow clock transition [9]. That light could then be used as an optical phase reference, circumventing the need for an ultra stable reference cavity. Unfortunately, the fluorescence light emitted on a clock transition is too weak for practical applications. For instance, for 10 6 fully inverted 87 Sr atoms the power of the spontaneously emitted light is of the order of 10 −16 W.The key observation that motivates this work is that if we could coerce the ensemble of atoms to emit the energy stored in them collectively rather than individually, the resulting power of order 10 −...