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.

Advancing Care for Head and Neck Cancers in a Multidisciplinary Tumour Board in the East.

Managing head and neck cancers is an excellent example of the importance of teamwork, with head and neck surgeons, clinical oncologists, radiologists, pathologists and other allied health professionals specialised in this disease site working together. The reliable imaging and dedicated pretreatment work-up entailing the comprehensive anatomical description of tumour involvement by the radiologists, the expertise of surgeons in performing en-bloc gross tumour resection, the uneventful speedy postoperative rehabilitation and recovery by the speech therapists and nutritionists, as well as the dedicated treatment planning of clinical oncologists in delivering precise preoperative or postoperative (chemo)radiotherapy to maximise the therapeutic potentials are the pillars of treatment success. A multidisciplinary tumour board involving all of these key players is essential to provide the highest level of recommendation based on evidence-based medicine and to bring patients new hopes and the best chance of cure. This review illustrates the seamless collaborative teamwork within a well-established multidisciplinary tumour board in managing one of the most intractable cancers in the East, taking enlightenment and inspiration from the West.

Gastric Cancer - From Aetiology to Management: Differences Between the East and the West.

Gastric cancers are highly prevalent in both the East and the West, although they differ in aetiology and prognostic outcome. Management of gastric cancer from screening to definitive treatment varies substantially between Eastern and Western countries and regions, owing to numerous factors, including government incentives to carry out population-wide screening programmes to detect early disease, differences in clinical and biological tumour behaviours and responsiveness to treatment, patient accessibility to effective treatment, etc. This review highlights and contrasts the differences in tumour aetiology and histology, as well as the management approaches between the East and the West, which gives important insights and inspirations on future international multicentre research collaboration to combat this dreadful malignancy.

Microring resonator-assisted Fourier transform spectrometer with enhanced resolution and large bandwidth in single chip solution.

Single chip integrated spectrometers are critical to bring chemical and biological sensing, spectroscopy, and spectral imaging into robust, compact and cost-effective devices. Existing on-chip spectrometer approaches fail to realize both high resolution and broad band. Here we demonstrate a microring resonator-assisted Fourier-transform (RAFT) spectrometer, which is realized using a tunable Mach-Zehnder interferometer (MZI) cascaded with a tunable microring resonator (MRR) to enhance the resolution, integrated with a photodetector onto a single chip. The MRR boosts the resolution to 0.47 nm, far beyond the Rayleigh criterion of the tunable MZI-based Fourier-transform spectrometer. A single channel achieves large bandwidth of ~ 90 nm with low power consumption (35 mW for MRR and 1.8 W for MZI) at the expense of degraded signal-to-noise ratio due to time-multiplexing. Integrating a RAFT element array is envisaged to dramatically extend the bandwidth for spectral analytical applications such as chemical and biological sensing, spectroscopy, image spectrometry, etc.

Effects of Salivary Mg on Head and Neck Carcinoma via TRPM7.

Magnesium (Mg) has been known to play vital roles in regulating growth and various metabolic processes. In recent years, the association between Mg and tumorigenesis has raised more and more attention. However, the effects of Mg on the progression of head and neck carcinoma (HNC), as well as the mechanism behind it, remain undefined. In this study, the roles of Mg in tumorigenic activities were tested in CAL27 and FaDu cells as well as in a xenograft tumor model in nude mice. We demonstrated that a moderate increase in extracellular Mg contributed to the proliferation, migration, and invasion of 2 HNC cell lines, while the addition of Mg in drinking water promoted the growth of xenograft tumors in mice without altering their serum Mg levels. Moreover, TRPM7, a major Mg transporter, was shown to be essential for the tumorigenic activities of HNC and the Mg-induced promotive effects on HNC cells and was further shown to be associated with the activation of AKT/mTOR (mammalian target of rapamycin) signaling. In a preliminary clinical study, we determined the Mg ion concentrations in the stimulated saliva from 72 patients with nasopharynx carcinoma and 12 healthy individuals. Our data revealed that the salivary Mg levels of subjects with nasopharynx carcinoma were significantly higher than those of the healthy controls. This is correlated with our finding showing TRPM7 to be overexpressed in tumor tissues harvested from 9 patients with HNC. Therefore, we can conclude that salivary Mg level, within a certain range, could act as a risk factor for the progression of HNC, which involves the activation of AKT/mTOR signaling pathways through the TRPM7 channel. The control of salivary Mg level and the intervention of TRPM7 should not be ignored during the study of HNC.

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, the potential of using EPCs in tissue engineering as an angiogenic source has been extensively explored. Concomitantly, the impact of EPCs on various diseases, such as diabetes, cancer, and cardiovascular diseases, has been studied. Within the limitations of the current knowledge, this review attempts to delineate the concept of EPCs in a sequential manner from the speculative history to a definitive presence (origin, sources of EPCs, isolation, and identification) and significance of these EPCs. Additionally, this review is aimed at serving as a guide for investigators, identifying potential research gaps, and summarizing our current and future prospects regarding EPCs.

Smooth and flat phase-locked Kerr frequency comb generation by higher order mode suppression.

High-Q microresonator is perceived as a promising platform for optical frequency comb generation, via dissipative soliton formation. In order to achieve a higher quality factor and obtain the necessary anomalous dispersion, multi-mode waveguides were previously implemented in Si3N4 microresonators. However, coupling between different transverse mode families in multi-mode waveguides results in periodic disruption of dispersion and quality factor, and consequently causes perturbation to dissipative soliton formation and amplitude modulation to the corresponding spectrum. Careful choice of pump wavelength to avoid the mode crossing region is thus critical in conventional Si3N4 microresonators. Here, we report a novel design of Si3N4 microresonator in which single-mode operation, high quality factor, and anomalous dispersion are attained simultaneously. The novel microresonator is consisted of uniform single-mode waveguides in the semi-circle region, to eliminate bending induced mode coupling, and adiabatically tapered waveguides in the straight region, to avoid excitation of higher order modes. The intrinsic quality factor of the microresonator reaches 1.36 × 10(6) while the group velocity dispersion remains to be anomalous at -50 fs(2)/mm. With this novel microresonator, we demonstrate that broadband phase-locked Kerr frequency combs with flat and smooth spectra can be generated by pumping at any resonances in the optical C-band.

Post-radiation Plasma Epstein-Barr Virus DNA and Local Clinical Remission After Radical Intensity-modulated Radiation Therapy for Nasopharyngeal Carcinoma.

AIMS: We studied if post-radiation plasma Epstein-Barr virus (EBV) DNA predicted local clinical remission after radical intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma. MATERIALS AND METHODS: Patients with non-metastatic nasopharyngeal carcinoma with baseline and serial plasma EBV DNA were treated with radical IMRT ± adjunct chemotherapy. Eight weeks after IMRT, they had plasma EBV DNA and routine six-site random nasopharyngeal biopsies on the same day. A repeat biopsy was carried out every 2 weeks if residual tumours were noted in previous biopsies until 12 weeks after IMRT when local persistence was defined. Correlation of undetectable plasma EBV DNA with local clinical remission was carried out. RESULTS: Two hundred and sixty patients with serial plasma EBV DNA completed IMRT, after a median follow-up of 3.1 years. Only one (0.4%) suffered from local persistence. Area under the curve values of receiver operating characteristics of undetectable plasma EBV DNA for negative biopsy at 8 weeks and local persistence were 0.642 and 0.439, respectively. They increased to 0.856 (P = 0.007) and 0.952 (P = 0.119), respectively, when combined with age <65 years and T1/T2 stage. CONCLUSIONS: Post-treatment plasma EBV DNA was not useful to predict local clinical remission in this study, probably because of excellent local control after IMRT. However, it may serve as a reference for high-risk patients treated with older radiation techniques.

A low-phase-noise 18 GHz Kerr frequency microcomb phase-locked over 65 THz.

Laser frequency combs are coherent light sources that simultaneously provide pristine frequency spacings for precision metrology and the fundamental basis for ultrafast and attosecond sciences. Recently, nonlinear parametric conversion in high-Q microresonators has been suggested as an alternative platform for optical frequency combs, though almost all in 100 GHz frequencies or more. Here we report a low-phase-noise on-chip Kerr frequency comb with mode spacing compatible with high-speed silicon optoelectronics. The waveguide cross-section of the silicon nitride spiral resonator is designed to possess small and flattened group velocity dispersion, so that the Kerr frequency comb contains a record-high number of 3,600 phase-locked comb lines. We study the single-sideband phase noise as well as the long-term frequency stability and report the lowest phase noise floor achieved to date with -130 dBc/Hz at 1 MHz offset for the 18 GHz Kerr comb oscillator, along with feedback stabilization to achieve frequency Allan deviations of 7 × 10(-11) in 1 s. The reported system is a promising compact platform for achieving self-referenced Kerr frequency combs and also for high-capacity coherent communication architectures.

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.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

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

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.

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.

Manual contouring based volumetric evaluation for colorectal cancer with liver limited metastases: a comparison with RECIST.

BACKGROUND: To compare response evaluation criteria in solid tumours (RECIST) and volumetric evaluation (VE) for colorectal cancer with liver-limited metastasis. PATIENTS AND METHODS: VE of liver metastases was performed by manual contouring before and after chemotherapy on 45 pairs of computed tomography (CT) images in 36 patients who suffered from metastatic colorectal cancer (mCRC) with liver metastasis only. Cohen kappa was used to compare the agreement between VE and RECIST. Pearson correlation was performed for their comparison after cubic root transformation of the aggregate tumor volumes. Logistic regression was done to identify clinical and radiographic factors to account for the difference which may be predictive in overall response (OR). RESULTS: There were 16 partial response (PR), 23 stable disease (SD) and 6 progressive disease (PD) cases with VE, and 14 PR, 23 SD and 8 PD with RECIST. VE demonstrated good agreement with RECIST (κ=0.779). Discordant objective responses were noted in 6 pairs of comparisons (13.3%). Pearson correlation also showed excellent correlation between VE and RECIST (r2=0.966, p<0.001). Subgroup analysis showed that VE was in slightly better agreement with RECIST for enlarging lesions than for shrinking lesions (r2=0.935 and r2=0.780 respectively). No factor was found predictive of the difference in OR between VE and RECIST. CONCLUSIONS: VE exhibited good agreement with RECIST. It might be more useful than RECIST in evaluation shrinking lesions in cases of numerous and conglomerate liver metastases.

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.

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.

Microelectromechanical Maltese-cross metamaterial with tunable terahertz anisotropy.

Dichroic polarizers and waveplates exploiting anisotropic materials have vast applications in displays and numerous optical components, such as filters, beamsplitters and isolators. Artificial anisotropic media were recently suggested for the realization of negative refraction, cloaking, hyperlenses, and controlling luminescence. However, extending these applications into the terahertz domain is hampered by a lack of natural anisotropic media, while artificial metamaterials offer a strong engineered anisotropic response. Here we demonstrate a terahertz metamaterial with anisotropy tunable from positive to negative values. It is based on the Maltese-cross pattern, where anisotropy is induced by breaking the four-fold symmetry of the cross by displacing one of its beams. The symmetry breaking permits the excitation of a Fano mode active for one of the polarization eigenstates controlled by actuators using microelectromechanical systems. The metamaterial offers new opportunities for the development of terahertz variable waveplates, tunable filters and polarimetry.