抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Optical frequency combs provide equidistant frequency markers in the infrared, visible and ultraviolet, and can be used to link an unknown optical frequency to a radio or microwave frequency reference. Since their inception, frequency combs have triggered substantial advances in optical frequency metrology and precision measurements and in applications such as broadband laser-based gas sensing and molecular fingerprinting. Early work generated frequency combs by intra-cavity phase modulation; subsequently, frequency combs have been generated using the comb-like mode structure of mode-locked lasers, whose repetition rate and carrier envelope phase can be stabilized. Here we report a substantially different approach to comb generation, in which equally spaced frequency markers are produced by the interaction between a continuous-wave pump laser of a known frequency with the modes of a monolithic ultra-high-Q microresonator via the Kerr nonlinearity. The intrinsically broadband nature of parametric gain makes it possible to generate discrete comb modes over a 500-nm-wide span (approximately 70 THz) around 1,550 nm without relying on any external spectral broadening. Optical-heterodyne-based measurements reveal that cascaded parametric interactions give rise to an optical frequency comb, overcoming passive cavity dispersion. The uniformity of the mode spacing has been verified to within a relative experimental precision of 7.3 x 10(-18). In contrast to femtosecond mode-locked lasers, this work represents a step towards a monolithic optical frequency comb generator, allowing considerable reduction in size, complexity and power consumption. Moreover, the approach can operate at previously unattainable repetition rates, exceeding 100 GHz, which are useful in applications where access to individual comb modes is required, such as optical waveform synthesis, high capacity telecommunications or astrophysical spectrometer calibration.

Optical frequency comb generation from a monolithic microresonator

(b) Write out the equations for the time dependence of ρ11, ρ22, ρ12 and ρ21 assuming that a light field interaction V = -μ12Ee iωt + c.c. couples only levels |1> and |2>, and that the excited levels exhibit spontaneous decay. (8 marks) (c) Under steady-state conditions, find the ratio of populations in states |2> and |3>. (3 marks) (d) Find the slowly varying amplitude ̃ ρ 12 of the polarization ρ12 = ̃ ρ 12e iωt . (6 marks) (e) In the limiting case that no decay is possible from intermediate level |3>, what is the ground state population ρ11(∞)? (2 marks) 2. (15 marks total) In a 2-level atom system subjected to a strong field, dressed states are created in the form |D1(n)> = sin θ |1,n> + cos θ |2,n-1> |D2(n)> = cos θ |1,n> sin θ |2,n-1>

The Quantum Theory of Light

The series of precisely spaced, sharp spectral lines that form an optical frequency comb is enabling unprecedented measurement capabilities and new applications in a wide range of topics that include precision spectroscopy, atomic clocks, ultracold gases, and molecular fingerprinting. A new optical frequency comb generation principle has emerged that uses parametric frequency conversion in high resonance quality factor (Q) microresonators. This approach provides access to high repetition rates in the range of 10 to 1000 gigahertz through compact, chip-scale integration, permitting an increased number of comb applications, such as in astronomy, microwave photonics, or telecommunications. We review this emerging area and discuss opportunities that it presents for novel technologies as well as for fundamental science.

http://science.sciencemag.org/content/sci/332/6029/555.full.pdf

Microresonator-Based Optical Frequency Combs

High-harmonic generation by focusing a femtosecond laser onto a gas is a well-known method of producing coherent extreme-ultraviolet (EUV) light. This nonlinear conversion process requires high pulse intensities, greater than 10(13) W cm(-2), which are not directly attainable using only the output power of a femtosecond oscillator. Chirped-pulse amplification enables the pulse intensity to exceed this threshold by incorporating several regenerative and/or multi-pass amplifier cavities in tandem. Intracavity pulse amplification (designed not to reduce the pulse repetition rate) also requires a long cavity. Here we demonstrate a method of high-harmonic generation that requires no extra cavities. This is achieved by exploiting the local field enhancement induced by resonant plasmons within a metallic nanostructure consisting of bow-tie-shaped gold elements on a sapphire substrate. In our experiment, the output beam emitted from a modest femtosecond oscillator (100-kW peak power, 1.3-nJ pulse energy and 10-fs pulse duration) is directly focused onto the nanostructure with a pulse intensity of only 10(11) W cm(-2). The enhancement factor exceeds 20 dB, which is sufficient to produce EUV wavelengths down to 47 nm by injection with an argon gas jet. The method could form the basis for constructing laptop-sized EUV light sources for advanced lithography and high-resolution imaging applications.

High-harmonic generation by resonant plasmon field enhancement

We demonstrate highly efficient cavity ringdown spectroscopy in which a broad-bandwidth optical frequency comb is coherently coupled to a high-finesse optical cavity that acts as the sample chamber. 125,000 optical comb components, each coupled into a specific longitudinal cavity mode, undergo ringdown decays when the cavity input is shut off. Sensitive intracavity absorption information is simultaneously available across 100 nanometers in the visible and near-infrared spectral regions. Real-time, quantitative measurements were made of the trace presence, the transition strengths and linewidths, and the population redistributions due to collisions and the temperature changes for molecules such as C2H2, O2, H2O, and NH3.

http://science.sciencemag.org/content/sci/311/5767/1595.full.pdf

Broadband Cavity Ringdown Spectroscopy for Sensitive and Rapid Molecular Detection

We demonstrate the generation of phase-coherent frequency combs in the vacuum utraviolet spectral region. The output from a mode-locked laser is stabilized to a femtosecond enhancement cavity with a gas jet at the intracavity focus. The resulting high-peak power of the intracavity pulse enables efficient high-harmonic generation by utilizing the full repetition rate of the laser. Optical-heterodyne-based measurements reveal that the coherent frequency comb structure of the original laser is fully preserved in the high-harmonic generation process. These results open the door for precision frequency metrology at extreme ultraviolet wavelengths and permit the efficient generation of phase-coherent high-order harmonics using only a standard laser oscillator without active amplification of single pulses.

Phase-Coherent Frequency Combs in the Vacuum Ultraviolet via High-Harmonic Generation inside a Femtosecond Enhancement Cavity

Broad-bandwidth, high-spectral-resolution optical detection of human breath has identified multiple important biomarkers correlated with specific diseases and metabolic processes. This optical-frequency-comb-based breath analysis system comes with excellent performance in all criteria: high detection sensitivity, ability to identify and distinguish a large number of analytes, and simultaneous, real-time information processing. We demonstrate a minimum detectable absorption of 8×10-10 cm-1, a spectral resolution of 800 MHz, and 200 nm of spectral coverage from 1.5 to 1.7 µm where strong and unique molecular fingerprints exist for many biomarkers. We present a series of breath measurements including stable isotope ratios of CO2, breath concentrations of CO, and the presence of trace concentrations of NH3 in high concentrations of H2O.

/pdf/cavity-enhanced-optical-frequency-comb-spectroscopy-4ui7rf0jp3.pdf

Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis

We present a high-power optical parametric oscillator-based frequency comb in the mid-infrared wavelength region using periodically poled lithium niobate. The system is synchronously pumped by a 10-W femtosecond Yb:fiber laser centered at 1.07 um and is singly resonant for the signal. The idler (signal) wavelength can be continuously tuned from 2.8 to 4.8 um (1.76 to 1.37 um) with a simultaneous bandwidth as high as 0.3 um and a maximum average idler output power of 1.50 W. We also demonstrate the performance of the stabilized comb by recording the heterodyne beat with a narrow-linewidth diode laser. This OPO is an ideal source for frequency comb spectroscopy in the mid-IR.

Phase-stabilized, 1.5-W frequency comb at 2.8 to 4.8 micron

To date, researchers have identified over 1000 different compounds contained in human breath. These molecules have both endogenous and exogenous origins and provide information about physiological processes occurring in the body as well as environment-related ingestion or absorption of contaminants1,2. While the presence and concentration of many of these molecules are poorly understood, many 'biomarker' molecules have been correlated to specific diseases and metabolic processes. Such correlations can result in non-invasive methods of health screening for a wide variety of medical conditions. In this article we present human breath analysis using an optical-frequency-comb-based trace detection system with excellent performance in all criteria: detection sensitivity, ability to identify and distinguish a large number of biomarkers, and measurement time. We demonstrate a minimum detectable absorption of 8 x 10-10 cm-1, a spectral resolution of 800 MHz, and 200 nm of spectral coverage from 1.5 to 1.7 micron where strong and unique molecular fingerprints exist for many biomarkers. We present a series of breath measurements including stable isotope ratios of CO2, breath concentrations of CO, and the presence of trace concentrations of NH3 in high concentrations of H2O.

Michael J. Thorpe

Papers

Broadband Cavity Ringdown Spectroscopy for Sensitive and Rapid Molecular Detection

Phase-Coherent Frequency Combs in the Vacuum Ultraviolet via High-Harmonic Generation inside a Femtosecond Enhancement Cavity

Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis

Phase-stabilized, 1.5-W frequency comb at 2.8 to 4.8 micron

Human breath analysis via cavity-enhanced optical frequency comb spectroscopy