The PD-1/PD-L1 Axis: An Immune-Mediated Mechanism of Chemoresistance in Cancer

The ability of tumour cells to avoid immune destruction (immune escape) and their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. The interaction between specific molecules on the surface of tumour cells with their corresponding receptors on immune effector cells can result in inhibition of these effector cells, consequently allowing tumour cells to evade the host’s anti-tumour immune response. The interaction of the Programmed Death Ligand 1 (PD-L1) on the surface of tumour cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors, and is a specific example of an immune escape mechanism tumour cells use to avoid immune destruction. Clinically, antibodies capable of blocking the PD-1/PD-L1 interaction have demonstrated significant therapeutic benefit, and are currently being used to help bolster patients’ immune response against malignant cells in a variety of cancer types. Here we show that the PD-1/PD-L1 interaction also leads to tumour cell resistance to conventional chemotherapeutic agents. Incubation of PD-L1-expressing human and mouse tumour cells with PD-1-expressing Jurkat T cells or purified recombinant PD-1 resulted in tumour cell resistance to doxorubicin and docetaxel. Interference with the PD-1/PD-L1 interaction using blocking anti-PD-1 or anti-PD-L1 antibody or shRNA-mediated gene silencing resulted in attenuation of PD-1/PD-L1-mediated drug resistance. Moreover, inhibition of the PD-1/PD-L1 signalling axis using anti-PD-1 antibody enhanced the effect of doxorubicin chemotherapy to inhibit 4T1 tumour cell metastasis in an in vivo mouse model of mammary carcinoma. These findings indicate that blockade of the PD-1/PD-L1 axis may be a useful approach to immunosensitize and chemosensitize tumours in cancer patients and provide a rationale for the use of anti-PD-1/PD-L1 antibodies as adjuvants to chemotherapy.

Quality factor assessment of subwavelength resonant cavities at FIR frequencies

Subwavelength resonators at FIR are presented and studied. The structures consist of 1D cavities formed between a metallized (silver) surface and a metamaterial surface comprising a periodic array of silver patches on a silver-backed silicon substrate. The concept derives from recent discoveries of artificial magnetic conductors (AMC). By studying the currents excited on the metamaterial surface by a normally incident plane wave, the nature of the emerging resonant phenomena and the physical mechanism underlying the AMC operation are investigated. Full wave simulations, based on finite element method and time-domain transmission line modelling technique, have been carried out to demonstrate the effective AMC boundary condition and prove the possibilities for subwavelength cavities. The quality factor of the resonant cavities is assessed as a function of the cavity profile. It is demonstrated that the quality factor drops to about 1/8 of the half-wavelength value for lambda/8 resonant cavity.

Design Method for Circularly Polarized Fabry-Perot Cavity Antennas

A new class of circularly polarized (CP) Fabry-Perot cavity antennas is introduced that maintain the simplicity of a linearly polarized primary feed and a single cavity structure. The proposed antennas employ a double-sided partially reflective surface (PRS), which allows independent control of the magnitude and phase responses for the reflection and transmission coefficients. In conjunction with an anisotropic high-impedance surface (HIS) ground plane, this arrangement allows for the first time a single cavity antenna to produce a specified gain in CP from a linearly polarized primary source. A design procedure for this class of antennas is introduced. The method exploits a simple ray optics model to calculate the magnitude and phase of the electric field in the cavity upon plane wave excitation. Based on this model, analytical expressions are derived, which enforce the resonance condition for both polarizations at a predetermined PRS reflectivity (and hence predetermined antenna gain) together with a 90 degrees differential phase between them. The validity of the concept is confirmed by means of an example entailing an antenna with gain of approximately 21 dB at 15 GHz. Full-wave simulation results and experimental testing on a fabricated prototype are presented and agree well with the theoretical predictions.

Helium Gas Purity Monitor based on Low Frequency Acoustic Resonance

Monitoring gas purity is an important aspect of gas recovery stations where air is usually one of the major impurities. Purity monitors of Katherometric type ate commercially available for this purpose. Alternatively, we discuss here a helium gas purity monitor based on acoustic resonance of a cavity at audio frequencies. It measures the purity by monitoring the resonant frequency of a cylindrical cavity filled with the gas under test and excited by conventional telephone transducers fixed at the ends. The use of the latter simplifies the design considerably. The paper discusses the details of the resonant cavity and the electronic circuit along with temperature compensation. The unit has been calibrated with helium gas of known purities. The unit has a response time of the order of 10 minutes and measures the gas purity to an accuracy of 0.02%. The unit has been installed in our helium recovery system and is found to perform satisfactorily.

基于偏振度检测的光纤电流传感方案

本文提出了一种将光学谐振腔中多次来回反射所产生的法拉第旋转积累效应转化为光学信号偏振度变化的光纤电流传感方案。这种方案的主要优点是可以克服环境等因素的扰动带来偏振态变化所产生的影响。文中对所提出方案的特性进行了简单的理论分析和模拟计算，并给出了相应的实验结果验证。

室温下稳定的多波长掺铒光纤激光器的研究

通过在线形谐振腔中引入一段缠绕在压电陶瓷上的单模光纤作为正弦相位调制器，使得激射波长的损耗不固定，抑制由于掺铒光纤的均匀展宽效应引起的模式竞争，从而避免了在室温下不稳定的单波长激射，实现了多波长掺铒光纤激光器的稳定输出。为了获得平坦的多波长输出，在谐振腔里使用了一个损耗峰位于1530nm处的长周期光纤光栅，以获得较为平坦的增益谱。通过两个3dB耦合器制成的反射型梳状滤波器的滤波作用，实验中观察到稳定的多波长激射，相邻波长间隔约为0．45nm。中心9个波长的输出功率平坦度为10dB，边模抑制比大于25dB。

Scalable Methods for Deterministic Integration of Quantum Emitters in Photonic Crystal Cavities

We investigated four unique methods for achieving scalable, deterministic integration of quantum emitters into ultra-high Q{V photonic crystal cavities, including selective area heteroepitaxy, engineered photoemission from silicon nanostructures, wafer bonding and dimensional reduction of III-V quantum wells, and cavity-enhanced optical trapping. In these areas, we were able to demonstrate site-selective heteroepitaxy, size-tunable photoluminescence from silicon nanostructures, Purcell modification of QW emission spectra, and limits of cavity-enhanced optical trapping designs which exceed any reports in the literature and suggest the feasibility of capturing- and detecting nanostructures with dimensions below 10 nm. In addition to process scalability and the requirement for achieving accurate spectral- and spatial overlap between the emitter and cavity, these techniques paid specific attention to the ability to separate the cavity and emitter material systems in order to allow optimal selection of these independently, and eventually enable monolithic integration with other photonic and electronic circuitry.

We also developed an analytic photonic crystal design process yielding optimized cavity tapers with minimal computational effort, and reported on a general cavity modification which exhibits improved fabrication tolerance by relying exclusively on positional- rather than dimensional tapering. We compared several experimental coupling techniques for device characterization. Significant efforts were devoted to optimizing cavity fabrication, including the use of atomic layer deposition to improve surface quality, exploration into factors affecting the design fracturing, and automated analysis of SEM images. Using optimized fabrication procedures, we experimentally demonstrated 1D photonic crystal nanobeam cavities exhibiting the highest Q/V reported on substrate. Finally, we analyzed the bistable behavior of the devices to quantify the nonlinear optical response of our cavities.

频率分辨光学开关法测量飞秒脉冲

阐述了频率分辨光学开关法测量飞秒脉冲的原理，详细分析了模式尺寸效应和非线性效应对飞秒脉冲测量的影响。构建了一台用于飞秒脉冲测量的二次谐波-频率分辨光学开关装置，利用该装置对谐振腔输出的飞秒脉冲及压缩后的脉冲进行了测量。得到了飞秒脉冲的时间宽度及光谱宽度、电场及其相位在时域和频域的详细信息。谐振腔直接输出脉冲的时间宽度为56 fs，光谱宽度为27 nm，时间带宽积为0.686，算法中的最小误差为0.001792。脉冲压缩后的测量结果为27 fs，光谱宽度为92 nm，时间带宽积为1.27，算法误差为0.00

机载测深激光雷达千赫兹全固态激光器设计及特性研究

将千赫兹高功率全固态Nd：YAG激光器的增益介质当作厚透镜处理，使用矩阵的方法对等效热透镜腔进行分析。采用多条半导体激光列阵侧向紧凑抽运结构设计，提高了增益介质光抽运的均匀性。根据实际抽运功率，通过模拟计算，设计了平凸非稳腔。选择的凸面全反镜的最佳曲率半径有效地补偿了增益介质热透镜效应，激光器实现了动态稳腔运转，激光脉冲能量输出斜度效率大于13％，光束发散角优于1.3mrad。

激光二极管端面抽运Nd∶YVO_4板条激光器及其热效应

激光器中激光介质采用板条状几何结构可以极大地降低它的热效应,但仍然需要进一步分析其影响,进而优化激光器效率。利用有限元分析方法分析了部分端面抽运的混合腔板条激光器中激光介质的热效应,计算的热透镜焦距与实测结果基本相符。分析了热效应对模式匹配的影响,分析结果对于优化激光器效率、改进谐振腔设计具有一定的参考价值。并在分析的基础上进行了混合腔实验,抽运功率为110 W时,获得连续输出激光功率41.5 W,光-光转换效率约38%,斜效率达58.8%,M2因子为非稳腔方向M2x=1.59,稳定腔方向M2y=1.55。

高功率共振腔增强型光电探测器研究进展

共振腔增强型光电探测器(RCE-PD)作为一种新型光电探测器,具有高量子效率、高响应度和波长选择性等优点,成为目前光纤通信领域中最为重要的探测器之一.在数字和模拟光传输系统中,高功率探测器由于具有高信噪比、低插入损耗等优点,在国际上越来越受到重视.综述了这两种探测器的基本结构、发展状况,展望了其发展前景等.指出高功率共振腔增强型光电探测器将是今后最有发展前途的探测器.

Eigenmode confinement in semiconductor microcavity lasers with an equilateral triangle resonator

We analyze the mode behaviors for semiconductor lasers with an equilateral triangle resonator by deriving the mode field distribution and the eigenvalue equation. The eigenvalue equation shows that the longitudinal mode wavelength interval is equivalent to that of a Fabry-Perot cavity with the cavity length of 1.5a, where a is the side length of the equilateral triangle resonator. The transverse waveguiding is equivalent to as a strip waveguide with the width of root 3a/ 2, and the number of transverse modes supported by the resonator is limited by the total reflection condition on the sides of the equilateral triangle. Semiconductor microcavity laser with an equilateral triangle resonator is suitable to realize single mode operation, and the mode wavelength can be adjusted by changing the side length.

高性能硅基锗光电探测器的研制

在信息产业、生物医学等科技领域越来越受关注的今天，新型光电子、光通信科技必将以更快的速度发展。Si基光电子集成采用成熟价廉的微电子加工工艺，将光学器件与多种功能的微电子电路集成，是实现光通信普及发展和光互连的有效途径。Si基光电探测器是Si基光通信系统的关键器件之一。随着近年来Si基Ge材料外延技术的突破性进展，Si基Ge光电探测器因为兼顾了Si基光电子集成和对光通讯波段(1.31和1.55μm)的高效探测，成为了当今研究的一大热点。
    半导体光电探测器的性能与其结构密切相关。PIN型光电探测器是最常见的探测器，可以普遍应用于光通讯光互连系统；雪崩光电二极管(APD)因为具有较高的响应度和内部增益，在实现单光子探测方面具备很大的优越性，适用于当今迅猛发展的生物光子学和量子信息学；共振腔增强型的光电探测器(RCE-PD)，集波长选择器、高速光信号接收器于一体，而且具备共振增强作用、高饱和功率输出等特点，是局域网、光纤入户和现代波分复用(Wavelength-Division Multiplexing,WDM)系统光通信网络的一种优选方案；波导结构探测器(Waveguide-PD)可以解除探测器的响应带宽和量子效率之间的矛盾，而且其结构特点更易于实现与调制器等光波导器件的集成，是片上光互连的首选探测器。
    本论文围绕高性能Si基Ge光电探测器这一研究目标，开展了多种结构的光电探测器的研制，包括PIN型PD的研制及其优化、吸收区与倍增区分离结构(SACM)的Ge-on-Si APD、RCE-PD和Waveguide-PD，主要研究结果如下：

1.                成功研制了PIN型Ge-on-Si光电探测器，器件在-1V外加偏压下暗电流密度为46.6mA/cm2，在1.31μm和1.55μm波长下器件的量子效率分别为40%和17%；然后改进了实验方法，在制作器件之前将Ge-on-Si材料在850℃条件下快速退火1分钟，从而改善材料质量，器件的暗电流密度降低至4mA/cm2，这是目前国际上报道的最好结果之一。

2.                研制出了PIN型Ge-on-SOI光电探测器，在1.31μm和1.55μm波长的量子效率分别为62%和25%。在-3V外加偏压下，器件的3dB带宽为12.6GHz。25μm直径器件，3dB带宽更是达到了13.4GHz。同时，制作了均匀性很好的1×4探测器阵列，单个器件的3dB带宽达13.3GHz。

3.                在国际上首次研究了硅基锗光电探测器的高饱和特性。在-1V和-2V外加偏压下，探测器的1-dB小信号压缩电流分别为22mA和40mA,相应的光功率分别为67.5mW和110.5mW。

4.                成功研制了吸收区和倍增区分离的Si基Ge雪崩光电二极管，器件的穿通电压Vpt约为29V，击穿电压Vbd(暗电流等于100μA时的电压)为39.5V。在击穿电压附近，如39V时，SACM-Ge-on-Si APD的增益为40。

5.                解决了背面ICP深刻蚀工艺难题，成功制备了中心波长在1.55μm，量子效应高达62%的共振腔增强型Si基Ge光电探测器。

Dissipative Chaos in Semiconductor Superlattices

We consider the motion of ballistic electrons in a miniband of a semiconductor superlattice (SSL) under the influence of an external, time-periodic electric field. We use the semi-classical balance-equation approach which incorporates elastic and inelastic scattering (as dissipation) and the self-consistent field generated by the electron motion. The coupling of electrons in the miniband to the self-consistent field produces a cooperative nonlinear oscillatory mode which, when interacting with the oscillatory external field and the intrinsic Bloch-type oscillatory mode, can lead to complicated dynamics, including dissipative chaos. For a range of values of the dissipation parameters we determine the regions in the amplitude-frequency plane of the external field in which chaos can occur. Our results suggest that for terahertz external fields of the amplitudes achieved by present-day free electron lasers, chaos may be observable in SSLs. We clarify the nature of this novel nonlinear dynamics in the superlattice-external field system by exploring analogies to the Dicke model of an ensemble of two-level atoms coupled with a resonant cavity field and to Josephson junctions.

Chamber investigations of atmospheric mercury oxidation chemistry

Mercury is a potent neurotoxin even at low concentrations. The unoxidised metal has a high vapour pressure and can circulate through the atmosphere, but when oxidised can deposit and be accumulated through the food chain. This work aims to investigate the oxidation processes of atmospheric Hg0(g). The first part describes efforts to make a portable Hg sensor based on Cavity Enhanced Absorption Spectroscopy (CEAS). The detection limit achieved was 66 ngm−3 for a 10 second averaging time. The second part of this work describes experiments carried out in a temperature controlled atmospheric simulation chamber in the Desert Research Institute, Reno, Nevada, USA. The chamber was built around an existing Hg CRDS system that could measure Hg concentrations in the chamber of<100 ngm−3 at 1 Hz enabling reactions to be followed. The main oxidant studied was bromine, which was quantified with a LED based CEAS system across the chamber. Hg oxidation in the chamber was found to be mostly too slow for current models to explain. A seven reaction model was developed and tested to find which parameters were capable of explaining the deviation. The model was overdetermined and no unique solution could be found. The most likely possibility was that the first oxidation step Hg + Br →HgBr was slower than the preferred literature value by a factor of two. However, if the more uncertain data at low [Br2] was included then the only parameter that could explain the experiments was a fast, temperature independent dissociation of HgBr some hundreds of times faster than predicted thermolysis or photolysis rates. Overall this work concluded that to quantitatively understand the reaction of Hg with Br2, the intermediates HgBr and Br must be measured. This conclusion will help to guide the planning of future studies of atmospheric Hg chemistry.