Prediction of tissue-of-origin of early stage cancers using serum miRNomes.

BACKGROUND: Noninvasive detection of early stage cancers with accurate prediction of tumor tissue-of-origin could improve patient prognosis. Because miRNA profiles differ between organs, circulating miRNomics represent a promising method for early detection of cancers, but this has not been shown conclusively. METHODS: A serum miRNA profile (miRNomes)-based classifier was evaluated for its ability to discriminate cancer types using advanced machine learning. The training set comprised 7931 serum samples from patients with 13 types of solid cancers and 5013 noncancer samples. The validation set consisted of 1990 cancer and 1256 noncancer samples. The contribution of each miRNA to the cancer-type classification was evaluated, and those with a high contribution were identified. RESULTS: Cancer type was predicted with an accuracy of 0.88 (95% confidence interval [CI] = 0.87 to 0.90) in all stages and an accuracy of 0.90 (95% CI = 0.88 to 0.91) in resectable stages (stages 0-II). The F1 score for the discrimination of the 13 cancer types was 0.93. Optimal classification performance was achieved with at least 100 miRNAs that contributed the strongest to accurate prediction of cancer type. Assessment of tissue expression patterns of these miRNAs suggested that miRNAs secreted from the tumor environment could be used to establish cancer type-specific serum miRNomes. CONCLUSIONS: This study demonstrates that large-scale serum miRNomics in combination with machine learning could lead to the development of a blood-based cancer classification system. Further investigations of the regulating mechanisms of the miRNAs that contributed strongly to accurate prediction of cancer type could pave the way for the clinical use of circulating miRNA diagnostics.

Evaluation of polarized terahertz waves generated by Cherenkov phase matching.

We report terahertz (THz) wave generation by satisfying Cherenkov phase-matching condition in both s and p polarizations. A dual-wavelength optical parametric oscillator is constructed from two potassium titanium oxide phosphate crystals pumped by a frequency-doubled Nd:YAG laser. By rotating the orientation of both a lithium niobate crystal (LiNbO3) and the polarization of the pump waves, the polarization of the THz wave changes. Due to the difference in the refractive index and absorption, the output power for p polarization is one tenth that for s polarization. A tuning range from 0.2 to 6.5 THz is obtained for s polarization, and from 0.2 to 4.2 and 5.4 to 6.9 THz for p polarization. The extraction efficiency is improved by changing the angle of prism for p polarization, and a large phase change occurs at total internal reflection. Consequently, p-polarized THz waves are optimal for spectroscopic applications.

THz-wave sensing via pump and signal wave detection interacted with evanescent THz waves.

We report a novel sensing technique that uses an evanescent terahertz (THz) wave, without detecting the THz wave directly. When a THz wave generated by Cherenkov phase matching via difference frequency generation undergoes total internal reflection, the evanescent THz wave is subject to a phase change and an amplitude decrease. The reflected THz wave, under the influence of the sample, interferes with the propagating THz wave and the changing electric field of the THz wave interacts with the electric field of the pump waves. We demonstrate a sensing technique for detecting changes in the electric field of near-infrared light, transcribed from changes in the electric field of a THz wave.

Broadband THz-wave generation by satisfying the noncollinear phase-matching condition with a reflected signal beam.

We demonstrated broadband terahertz (THz) wave generation by satisfying the noncollinear phase-matching condition with a reflected signal beam. We constructed a dual-wavelength optical parametric oscillator with two potassium titanium oxide phosphate crystals pumped by a frequency-doubled Nd:YAG laser. The collinear pump and signal waves were irradiated into a lithium niobate crystal. The pump and the signal waves were reflected at the crystal surface. Because the pump and the signal waves have a finite beam diameter, when the reflected signal wave and unreflected pump wave were irradiated at the correct angle, the noncollinear phase-matching condition was satisfied. By changing the incident angle to the crystal, broadband THz-wave generation with a range of over 0.2-7.2 THz was achieved.

Cherenkov phase matched THz-wave generation with surfing configuration for bulk lithium nobate crystal.

We demonstrated a Cherenkov phase matched THz-wave generation with surfing configuration for bulk lithium niobate crystal. THz-wave output was enhanced about 50 times by suppressing phase mismatching for THz-wave propagation direction. The suppression was achieved by combining two pumping waves with dual wavelength with finite angle, and THz-frequency was controllable by changing the angle within 2.5 degrees range. Higher frequency THz-wave generation at around 4.0 THz was successfully obtained by the method.

Extremely frequency-widened terahertz wave generation using Cherenkov-type radiation.

Terahertz (THz) wave generation based on nonlinear frequency conversion is promising way for realizing a tunable monochromatic bright THz-wave source. Such a development of efficient and wide tunable THz-wave source depends on discovery of novel brilliant nonlinear crystal. Important factors of a nonlinear crystal for THz-wave generation are, 1. High nonlinearity and 2. Good transparency at THz frequency region. Unfortunately, many nonlinear crystals have strong absorption at THz frequency region. The fact limits efficient and wide tunable THz-wave generation. Here, we show that Cherenkov radiation with waveguide structure is an effective strategy for achieving efficient and extremely wide tunable THz-wave source. We fabricated MgO-doped lithium niobate slab waveguide with 3.8 microm of thickness and demonstrated difference frequency generation of THz-wave generation with Cherenkov phase matching. Extremely frequency-widened THz-wave generation, from 0.1 to 7.2 THz, without no structural dips successfully obtained. The tuning frequency range of waveguided Cherenkov radiation source was extremely widened compare to that of injection seeded-Terahertz Parametric Generator. The tuning range obtained in this work for THz-wave generation using lithium niobate crystal was the widest value in our knowledge. The highest THz-wave energy obtained was about 3.2 pJ, and the energy conversion efficiency was about 10(-5) %. The method can be easily applied for many conventional nonlinear crystals, results in realizing simple, reasonable, compact, high efficient and ultra broad band THz-wave sources.

Cherenkov phase-matched monochromatic THzwave generation using difference frequency generation with a lithium niobate crystal.

We demonstrated a Cherenkov phase-matching method for monochromatic THz-wave generation using the difference frequency generation process with a lithium niobate crystal, which resulted in high conversion efficiency and wide tunability. We successfully generated monochromatic THz waves across the range 0.2-3.0 THz. We obtained efficient energy conversion in the low frequency region below 0.5 THz, and achieved a flat tuning spectrum by varying the pumping wavelength during THz-wave tuning.