Genomic diversity of Epstein-Barr virus genomes isolated from primary nasopharyngeal carcinoma biopsy samples.

UNLABELLED: Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. IMPORTANCE: This study established a sequencing workflow from EBV DNA capture and sequencing to de novo assembly and contig joining. We reported eight newly sequenced EBV genomes isolated from primary NPC biopsy specimens and revealed the sequence diversity on a whole-genome level among these EBV isolates. At least two lineages of EBV strains are observed, and recombination among these lineages is inferred. Our study has demonstrated the value of, and provided a platform for, genome sequencing of EBV.

Mode-locked ultrashort pulse generation from on-chip normal dispersion microresonators.

We describe generation of stable mode-locked pulse trains from on-chip normal dispersion microresonators. The excitation of hyperparametric oscillation is facilitated by the local dispersion disruptions induced by mode interactions. The system is then driven from hyperparametric oscillation to the mode-locked state with over 200 nm spectral width by controlled pump power and detuning. With the continuous-wave-driven nonlinearity, the pulses sit on a pedestal, akin to a cavity soliton. We identify the importance of pump detuning and wavelength-dependent quality factors in stabilizing and shaping the pulse structure, to achieve a single pulse inside the cavity. We examine the mode-locking dynamics by numerically solving the master equation and provide analytic solutions under appropriate approximations.

Esophageal squamous cell carcinoma (ESCC): advance in genomics and molecular genetics.

Esophageal cancer is aggressive and has poor prognosis. Esophageal squamous cell carcinoma (ESCC) is histologically the most prevalent type of esophageal cancer and ranked as the sixth leading cause of cancer death worldwide. In recent years, cancer has been widely regarded as genetic disease, as well as epigenetic abnormalities including DNA methylation, histone deacetylation, chromatin remodeling, gene imprinting and noncoding RNA regulation. In this review, we will provide a general overview of genes, proteins and microRNAs that are involved in the development of ESCC, which aims to enhance our understanding of molecular mechanisms implicated in ESCC development and progression.

Design of an ultra-compact electro-absorption modulator comprised of a deposited TiN/HfO2/ITO/Cu stack for CMOS backend integration.

An ultra-compact electro-absorption (EA) modulator operating around 1.55-µm telecom wavelengths is proposed and theoretically investigated. The modulator is comprised of a stack of TiN/HfO2

Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.

Poor human-to-human transmission of influenza A H5N1 virus has been attributed to the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of the human upper respiratory tract, and thus to the presumed inability of the virus to replicate efficiently at this site. We now demonstrate that ex vivo cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected with H5N1 viruses in spite of an apparent lack of these receptors.

Phase modulation in horizontal metal-insulator-silicon-insulator-metal plasmonic waveguides.

An extremely compact Si phase modulator is proposed and validated, which relies on effective modulation of the real part of modal index of horizontal metal-insulator-Si-insulator-metal plasmonic waveguides by a voltage applied between the metal cover and the Si core. Proof-of-concept devices are fabricated on silicon-on-insulator substrates using standard complementary metal-oxide-semiconductor technology using copper as the metal and thermal silicon dioxide as the insulator. A modulator with a 1-µm-long phase shifter inserted in an asymmetric Si Mach-Zehnder interferometer exhibits 9-dB extinction ratio under a 6-V/10-kHz voltage swing. Numerical simulations suggest that high speed and low driving voltage could be achieved by shortening the distance between the Si core and the n(+)-contact and by using a high-κ dielectric as the insulator, respectively.

Silicon nitride based plasmonic components for CMOS back-end-of-line integration.

Silicon nitride waveguides provide low propagation loss but weak mode confinement due to the relatively small refractive index contrast between the Si3N4 core and the SiO2 cladding. On the other hand, metal-insulator-metal (MIM) plasmonic waveguides offer strong mode confinement but large propagation loss. In this work, MIM-like plasmonic waveguides and passive devices based on horizontal Cu-Si3N4-Cu or Cu-SiO2-Si3N4-SiO2-Cu structures are integrated in the conventional Si3N4 waveguide circuits using standard CMOS backend processes, and are characterized around 1550-nm telecom wavelengths using the conventional fiber-waveguide-fiber method. The Cu-Si3N4(~100 nm)-Cu devices exhibit ~0.78-dB/µm propagation loss for straight waveguides, ~38% coupling efficiency with the conventional 1-µm-wide Si3N4 waveguide through a 2-µm-long taper coupler, ~0.2-dB bending loss for sharp 90° bends, and ~0.1-dB excess loss for ultracompact 1 × 2 and 1 × 4 power splitters. Inserting a ~10-nm SiO2 layer between the Si3N4 core and the Cu cover (i.e., the Cu-SiO2(~10 nm)-Si3N4(~100 nm)-SiO2(~10 nm)-Cu devices), the propagation loss and the coupling efficiency are improved to ~0.37 dB/µm and ~52% while the bending loss and the excess loss are degraded to ~3.2 dB and ~2.1 dB, respectively. These experimental results are roughly consistent with the numerical simulation results after taking the influence of possible imperfect fabrication into account. Ultracompact plasmonic ring resonators with 1-µm radius are demonstrated with an extinction ratio of ~18 dB and a quality factor of ~84, close to the theoretical prediction.

Theoretical investigation of ultracompact and athermal Si electro-optic modulator based on Cu-TiO2-Si hybrid plasmonic donut resonator.

An ultracompact silicon electro-optic modulator operating at 1550-nm telecom wavelengths is proposed and analyzed theoretically, which consists of a Cu-TiO(2)-Si hybrid plasmonic donut resonator evanescently coupled with a conventional Si channel waveguide. Owing to a negative thermo-optic coefficient of TiO(2) (~-1.8 × 10(-4) K(-1)), the real part of effective modal index of the curved Cu-TiO(2)-Si hybrid waveguide can be temperature-independent (i.e., athermal) if the TiO(2) interlayer and the beneath Si core have a certain thickness ratio. A voltage applied between the ring-shaped Cu cap and a cylinder metal electrode positioned at the center of the donut,--which makes Ohmic contact to Si, induces a ~1-nm-thick free-electron accumulation layer at the TiO(2)/Si interface. The optical field intensity in this thin accumulation layer is significantly enhanced if the accumulation concentration is sufficiently large (i.e., > ~6 × 10(20) cm(-3)), which in turn modulates both the resonance wavelengths and the extinction ratio of the donut resonator simultaneously. For a modulator with the total footprint inclusive electrodes of ~8.6 µm(2), 50-nm-thick TiO(2), and 160-nm-thick Si core, FDTD simulation predicts that it has an insertion loss of ~2 dB, a modulation depth of ~8 dB at a voltage swing of ~6 V, a speed-of-response of ~35 GHz, and a switching energy of ~0.45 pJ/bit, and it is athermal around room temperature. The modulator's performances can be further improved by optimization of the coupling strength between the bus waveguide and the donut resonator.

Components for silicon plasmonic nanocircuits based on horizontal Cu-SiO2-Si-SiO2-Cu nanoplasmonic waveguides.

We report systematic results on the development of horizontal Cu-SiO2-Si-SiO2-Cu nanoplasmonic waveguide components operating at 1550-nm telecom wavelengths, including straight waveguides, sharp 90° bends, power splitters, and Mach-Zehnder interferometers (MZIs). Owing to the relatively low loss for propagating (~0.3 dB/µm) and for 90° sharply bending (~0.73 dB/turn), various ultracompact power splitters and MZIs are experimentally realized on a silicon-on-insulator (SOI) platform using standard CMOS technology. The demonstrated splitters exhibit a relatively low excess loss and the MZIs exhibit good performance such as high extinction ratio of ~18 dB and low normalized insertion loss of ~1.7 dB. The experimental results of these devices agree well with those predicted from numerical simulations with suitable Cu permittivity data.

Performance of ultracompact copper-capped silicon hybrid plasmonic waveguide-ring resonators at telecom wavelengths.

Ultracompact Cu-capped Si hybrid plasmonic waveguide-ring resonators (WRRs) with ring radii of 1.09-2.59 µm are fabricated on silicon on insulator substrates using standard complementary metal-oxide-semiconductor technology and characterized over the telecom wavelength range of 1.52-1.62 µm. The dependence of the spectral characteristics on the key structural parameters such as the Si core width, the ring radius, the separation gap between the ring and bus waveguides, and the ring configuration is systematically studied. A WRR with 2.59-µm radius and 0.250-µm nominal gap exhibits good performances such as normalized insertion loss of ~0.1 dB, extinction ratio of ~12.8 dB, free spectral range of ~47 nm, and quality factor of ~275. The resonance wavelength is redshifted by ~4.6 nm and an extinction ratio of ~7.5 dB is achieved with temperature increasing from 27 to 82°C. The corresponding effective thermo-optical coefficient (dn(g)/dT) is estimated to be ~1.6 × 10(-4) K(-1), which is contributed by the thermo-optical effect of both the Si core and the Cu cap, as revealed by numerical simulations. Combined with the compact size and the high thermal conductivity of Cu, various effective thermo-optical devices based on these Cu-capped plasmonic WRRs could be realized for seamless integration in existing Si electronic-photonic integrated circuits.

Effect of cladding layer and subsequent heat treatment on hydrogenated amorphous silicon waveguides.

Although intrinsic hydrogenated amorphous silicon (a-Si:H) wire waveguides clad with normal SiO(2) layers have low propagation loss of 2.7 ± 0.1 dB/cm for transverse electric (TE) mode in the 1550-nm range, the transparency degrades when interfaced with other dielectrics (e.g., air) and/or exposed to elevated temperatures due to degradation of surface passivation in the a-Si:H waveguides. The thermal stability of a-Si:H wire waveguides with various cladding layers is systematically investigated, showing that the a-Si:H wire waveguides are stable at annealing temperature lower than ~350°C, while they degrade quickly when annealed at a higher temperature. It indicates that the thermal stability is mainly determined by the annealing temperature rather than the annealing time, which may be attributed to quick evolution of weakly bonded hydrogen in the a-Si:H waveguides. A thin Si(3)N(4) intercladding layer between SiO(2) cladding and a-Si:H waveguide core may degrade transparency due to N-H bond absorption and is of no benefit to the thermal stability, thus its overall effect on the a-Si:H waveguides is detrimental.

A nano-opto-mechanical pressure sensor via ring resonator.

This paper reports a nano-opto-mechanical pressure sensor based on nano-scaled ring resonator. The pressure is measured through the output spectrum shift which is induced via mechanical deformation of the ring resonator. The sensitivity as high as 1.47 pm/kPa has been experimentally achieved which agrees with numerical prediction. Due to the strong variation of sensitivity with different ring radius and thickness of the diaphragm, the pressure sensor can be used to form an array structure to detect the pressure distribution in highly accurate measurement with low-cost advantages. The nano-opto-mechanical pressure sensor has potential applications such as shear stress displacement detection, pressure wave detector and pressure mapping etc.

Theoretical investigation of silicide Schottky barrier detector integrated in horizontal metal-insulator-silicon-insulator-metal nanoplasmonic slot waveguide.

An ultracompact integrated silicide Schottky barrier detector (SBD) is designed and theoretically investigated to electrically detect the surface plasmon polariton (SPP) propagating along horizontal metal-insulator-silicon-insulator-metal nanoplasmonic slot waveguides at the telecommunication wavelength of 1550 nm. An ultrathin silicide layer inserted between the silicon core and the insulator, which can be fabricated precisely using the well-developed self-aligned silicide process, absorbs the SPP power effectively if a suitable silicide is chosen. Moreover, the Schottky barrier height in the silicide-silicon-silicide configuration can be tuned substantially by the external voltage through the Schottky effect owing to the very narrow silicon core. For a TaSi(2) detector with optimized dimensions, numerical simulation predicts responsivity of ~0.07 A/W, speed of ~60 GHz, dark current of ~66 nA at room temperature, and minimum detectable power of ~-29 dBm. The design also suggests that the device's size can be reduced and the overall performances will be further improved if a silicide with smaller permittivity is used.

Silicon-based horizontal nanoplasmonic slot waveguides for on-chip integration.

Horizontal metal/insulator/Si/insulator/metal nanoplasmonic slot waveguide (PWG), which is inserted in a conventional Si wire waveguide, is fabricated using the standard Si-CMOS technology. A thin insulator between the metal and the Si core plays a key role: it not only increases the propagation distance as the theoretical prediction, but also prevents metal diffusion and/or metal-Si reaction. Cu-PWGs with the Si core width of ~134-21 nm and ~12-nm-thick SiO2 on each side exhibit a relatively low propagation loss of ~0.37-0.63 dB/µm around the telecommunication wavelength of 1550 nm, which is ~2.6 times smaller than the Al-counterparts. A simple tapered coupler can provide an effective coupling between the PWG and the conventional Si wire waveguide. The coupling efficiency as high as ~0.1-0.4 dB per facet is measured. The PWG allows a sharp bending. The pure bending loss of a Cu-PWG direct 90° bend is measured to be ~0.6-1.0 dB. These results indicate the potential for seamless integration of various functional nanoplasmonic devices in existing Si electronic photonic integrated circuits (Si-EPICs).

Thermo-optical tunable planar ridge microdisk resonator in silicon-on-insulator.

In this work, we design and demonstrate planar ridge microdisk resonators in silicon-on-insulator, which assemble the advantages of microring and microdisk resonators. The dependences of resonator optical modes on the slab thickness and the waveguide-to-resonator coupling gap are investigated. The highest Q-factor obtained is ~4 × 10(5). Using the thermo-optical effect, we attain a resonance wavelength tuning efficiency of ~66.5 pm/mW. We also compare the transmission spectra measured by using wavelength-scanning method and voltage-scanning method and show potential application for the adopted voltage-scanning method.

Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous cell carcinoma.

E-cadherin is a well-documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa degradation fragment, known as soluble E-cadherin (s-Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s-Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s-Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s-Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s-Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026-1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation.

An optical neural chip for implementing complex-valued neural network.

Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.

Theoretical investigation of silicon MOS-type plasmonic slot waveguide based MZI modulators.

In this paper, a Mach-Zehnder silicon nanoplasmonic electro-optic modulator is proposed and theoretically analyzed. It is composed of horizontal metal-SiO2-Si-metal plasmonic slot waveguides for phase shifting and ultracompact V-shape splitter/combiner to link the plasmonic slot waveguides and the conventional Si dielectric waveguides. The proposed modulator can be directly integrated into existing Si electronic photonic integrated circuits (EPICs) and be fabricated using standard Si complementary metal-oxide-semiconductor (CMOS) technology. The modulator's parameters are optimized through systematic 2-dimensional numerical simulations. For a modulator with 3-µm-long Ag-SiO2(2 nm)-Si(50 nm)-Ag phase shifter and 0.35-µm-long splitter/combiner operating at 1.55-µm wavelength, simulation shows an insertion loss of ~-8 dB, an extinction ratio of ~7.3 dB - with a switching voltage of ~5.6 V, and a bandwidth of ~500 GHz. A possible approach to reduce the switching voltage is addressed.

Low-loss amorphous silicon wire waveguide for integrated photonics: effect of fabrication process and the thermal stability.

Hydrogenated amorphous silicon (a-Si:H) wire waveguides were fabricated by plasma-enhanced chemical vapor deposition and anisotropic dry etching. With the optimized fabrication process, the propagation losses of as low as 3.2 ± 0.2 dB/cm for the TE mode and 2.3 ± 0.1 dB/cm for the TM mode were measured for the 200 nm (height) × 500 nm (width) wire waveguides at 1550 nm using the standard cutback method. The loss becomes larger at shorter wavelength (~4.4 dB/cm for TE and ~5.0 dB/cm for TM at 1520 nm) and smaller at longer wavelength (~1.9 dB/cm for TE and ~1.4 dB/cm for TM at 1620 nm). With the waveguide width shrinking from 500 nm to 300 nm, the TM mode loss keeps almost unchanged whereas the TE mode loss increases, indicating that the predominant loss contributor is the waveguide sidewall roughness, similar to the crystalline silicon waveguides. Although the a-Si:H and the upper cladding SiO2 were both deposited at 400°C, the propagation loss of the fabricated a-Si:H wire waveguides starts to increase upon furnace annealing under atmosphere at a temperature larger than 300°C: ~13-15 dB/cm after 400°C/30 min annealing and >70 dB/cm after 500°C/30 min annealing, which can be attributed to hydrogen out-diffusion. Even higher temperature (i.e., >600°C) annealing leads to the propagation loss approaching to the polycrystalline silicon counterparts (~40-50 dB/cm) due to onset of a-Si:H solid-phase crystallization.

The observation of super-long range surface plasmon polaritons modes and its application as sensory devices.

In this communication, we will describe one unique phenomenon and the potential application of it. In this work, the dispersion relation of an air-silver-silicon-silver-fluid (air-Ag-Si-Ag-fluid) five-layer slab is analyzed theoretically, in which the super-long range surface plasmon polaritons (SPP) modes, whose energy penetrates deeply into the fluid, are found with their losses being extremely small and sensitive to the change of the fluid refractive index when operating near their interspace cut-off regions, where the dispersion curves are non-continuous. By applying this phenomenon in detecting the fluid refractive index change, a SPP sensor based on intensity measurement is proposed. It is a waveguide structure with an Ag-Si-Ag slab together with a flow cell filled with the detecting fluid. It is found that a large scale of linear detection (e.g., 0.08, for 1550 nm ~1.33 to 1.41) with high resolution (e.g., 7.9 × 10(-6) Refractive Index Units) can be achieved for a very short device, which is 200 µm.