Hybrid transmission of PS-GS4QAM and QPSK data in the form of a PS-16QAM mm-wave signal enabled by optical asymmetrical dual-SSB modulation.

The independent optical dual-single-sideband (dual-SSB) signal generation and detection can be achieved by an optical in-phase/quadrature (I/Q) modulator and one single photodiode (PD). The dual-SSB signal is able to carry two different information. After PD detection, the optical dual-SSB signal can be converted into an electrical millimeter-wave (mm-wave) signal. Therefore, the optical dual-SSB signal generation and detection technique can be employed in the radio-over-fiber (RoF) system to achieve higher system spectral efficiency and reduce system architecture complexity. However, the I/Q modulator's nonideal property results in the amplitude imbalance of the optical dual-SSB signal, and then the crosstalk can occur. Moreover, after PD detection, the generated mm-wave signal based on the optical dual-SSB modulation has a relatively low signal-to-noise ratio (SNR), which restricts the system performance. In this paper, we propose an optical asymmetrical dual-SSB signal generation and detection scheme based on the probabilistic shaping (PS) technology, to decrease the influence of the optical dual-SSB signal's amplitude imbalance and to enhance the system performance in the scenario of the limited SNR. The dual-SSB in our scheme is composed of the left sideband (LSB) in probabilistic-shaping geometric-shaping 4-ary quadrature amplitude modulation (PS-GS4QAM) format and the right sideband (RSB) in quadrature phase-shift keying (QPSK) format. The transmitter digital signal processing (DSP) generates a dual-SSB signal to drive the optical I/Q modulator. The I/Q modulator implements an electrical-to-optical conversion and generates an optical dual-SSB signal. After PD detection, the optical dual-SSB signal is converted into a PS-16QAM mm-wave signal. In our simulation, compared with the normal 16QAM scenario, the PS-16QAM scenario exhibits a ∼1.2 dB receiver sensitivity improvement at the hard-decision forward error correction (HD-FEC) threshold of 3.8×10-3. Therefore, in our experiment, based on the PS technology, we design a dual-SSB signal including a 5 Gbaud LSB-PS-GS4QAM at -15 GHz and a 5 Gbaud RSB-QPSK at 20 GHz. After 5 km standard single-mode fiber (SSMF) transmission and PD detection, the dual-SSB signal is converted into a 5 Gbaud PS-16QAM mm-wave signal at 35 GHz. Then, the generated PS-16QAM signal is sent into a 1.2 m single-input-single-output (SISO) wireless link. In the DSP at the receiver end, the dual-SSB signal can be recovered from the mm-wave signal, and the PS-GS4QAM and QPSK data carried by the dual-SSB signal can be separated. The bit error rates (BERs) of the LSB-PS-GS4QAM and the RSB-QPSK in our experiment can be below the HD-FEC threshold of 3.8×10-3. The results demonstrate that our scheme can tolerate the I/Q modulator's nonideal property and performs well in the scenario of a relatively low SNR.

Simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated high-order QAM signals enabled by bandpass delta-sigma modulation.

The application of dual vector millimeter-wave (mm-wave) signals in radio-over-fiber (RoF) systems represents a significant opportunity to enhance spectrum efficiency, transmission capacity, and access flexibility. In addition, facing the increasingly intricate application scenarios, the comprehensive exploitation of high-order quadrature-amplitude-modulation (QAM) signals with hybrid single-carrier (SC) and orthogonal-frequency-division-multiplexing (OFDM) modulation is also vital to rich systematic connotation. Based on bandpass delta-sigma modulation (BP-DSM) and heterodyne detection, we propose what we believe to be a novel scheme for the simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated high-order QAM signals. The innovation lies in the modulation-agnostic nature, accommodating both SC-modulated and OFDM-modulated vector radio-frequency (RF) signals. The BP-DSM is utilized to digitize two independent SC-modulated and OFDM-modulated high-order QAM signals into relatively simple sequences at the transmitter side. With the aid of an optical I/Q modulator, we can integrate both signals after BP-DSM to generate the desired optical quadrature-phase-shift keying (QPSK) signal carrying both information of two original high-order QAM signals. Facilitated by heterodyne detection and a single photodetector (PD), our scheme attains prowess in the detection of both SC-modulated and OFDM-modulated high-order signals. Based on our proposed scheme, we experimentally demonstrate the simultaneous wireless mm-wave transmission of both SC-modulated and OFDM-modulated 512QAM signals at 30-GHz mm-wave band, demonstrating bit-error-rates (BERs) below the hard decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 after transmission over 10-km single-mode fiber (SMF) link and 1-m wireless link. In addition, we further investigate the performance impact between SC-modulated and OFDM-modulated high-order QAM signals, and experiment results indicate that the impact is virtually negligible. Moreover, the performance of the generated QPSK mm-wave signal is transparent to the QAM modulation formats of both SC-modulated and OFDM-modulated signals in our proposed scheme.

Dual high-order QAM-modulated mm-wave signal transmission in the Q-band enabled by simple IM/DD architecture and bandpass delta-sigma modulation.

The intensity-modulation (IM)/direct-detection (DD) systems have been proven effective and low-cost due to their simple system architecture. However, the Mach-Zehnder modulator (MZM) of the IM/DD systems only reserves its driving signal intensity. Therefore, the IM/DD systems are generally unable to transmit vector signals and have a restricted spectrum efficiency and channel capacity. Similarly, the radio-over-fiber (RoF) transmission systems based on IM/DD are limited by their simple architecture and generally cannot transmit high-order quadrature amplitude modulation (QAM) signals, which hinders the improvement of their spectrum efficiency. To address the challenges, we propose a novel, to the best of our knowledge, scheme to simultaneously transmit the dual independent high-order QAM-modulated millimeter-wave (mm-wave) signals in the RoF system with a simple IM/DD architecture, enabled by precoding-based optical carrier suppression (OCS) modulation and bandpass delta-sigma modulation (BP-DSM). The dual independent signals can carry different information, which increases channel capacity and improves spectrum efficiency and system flexibility. Based on our proposed scheme, we experimentally demonstrate the dual 512-QAM mm-wave signal transmission in the Q-band (33-50 GHz) under three different scenarios: 1) dual single-carrier (SC) signal transmission, 2) dual orthogonal-frequency-division-multiplexing (OFDM) signal transmission, and 3) hybrid SC and OFDM signal transmission. We achieve high-fidelity transmission of dual 512-QAM vector signals over a 5 km single-mode fiber (SMF) and a 1-m single-input single-output (SISO) wireless link operating in the Q-band, with the bit error rates (BERs) of all three scenarios below the hard decision forward error correction (HD-FEC) threshold of 3.8 × 10-3. To the best of our knowledge, this is the first time dual high-order QAM-modulated mm-wave signal transmission has been achieved in a RoF system with a simple IM/DD architecture.

Dual vector millimeter-wave signal generation based on optical carrier suppression modulation and direct detection with one photodetector.

We propose a novel, to the best of our knowledge, scheme for dual vector millimeter-wave (mm-wave) signal generation and transmission, based on optical carrier suppression (OCS) modulation, precoding, and direct detection by a single-ended photodiode (PD). At the transmitter side, two independent vector radio frequency (RF) signals with precoding, generated via digital signal processing (DSP), are used to drive an in-phase/quadrature (I/Q) modulator operating at the optical OCS modulation mode to simultaneously generate two independent frequency-doubling optical vector mm-wave signals, which can reduce the bandwidth requirement of transmitter's components and enhance spectral efficiency. With the aid of the single-ended PD and subsequent DSP at the receiver side, two independent frequency-doubling vector mm-wave signals can be separated and demodulated without data error. Based on our proposed scheme, we experimentally demonstrate the generation, transmission, and detection of 2-Gbaud 30-GHz quadrature-phase-shift-keying (QPSK) and 2-Gbaud 46-GHz QPSK signals over 10-km single-mode fiber-28 (SMF-28) and 1-m wireless transmission. The results indicate that the bit-error ratio (BER) of the dual vector mm-wave signals can each reach the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.

Photonic-aided W-band dual-vector RF signal generation and detection enabled by bandpass delta-sigma modulation and heterodyne detection.

We propose a photonic-aided dual-vector radio-frequency (RF) signal generation and detection scheme enabled by bandpass delta-sigma modulation and heterodyne detection. With the aid of the bandpass delta-sigma modulation, our proposed scheme is transparent to the modulation format of the dual-vector RF signals and can support the generation, wireless transmission, and detection of both single-carrier (SC) and orthogonal-frequency-division-multiplexing (OFDM) vector RF signals with high-level quadrature-amplitude-modulation (QAM) modulation. With the aid of the heterodyne detection, our proposed scheme can support up to W-band (75-110 GHz) dual-vector RF signal generation and detection. For the validation of our proposed scheme, we experimentally demonstrate the simultaneous generation of a SC-64QAM signal at 94.5 GHz and a SC-128QAM signal at 93.5 GHz and their error-free high-fidelity transmission over a 20-km single-mode fiber 28 (SMF-28) and a 1-m single-input single-output (SISO) wireless link at the W-band. To the best of our knowledge, this is the first time that delta-sigma modulation has been introduced into a W-band photonic-aided fiber-wireless integration system to achieve flexible and high-fidelity dual-vector RF signal generation and detection.

An injectable superior depot of Telratolimod inhibits post-surgical tumor recurrence and distant metastases.

The clinical success of Toll-like receptor (TLR) agonists is based on their capacity to efficiently mobilize both innate and adaptive immunity. However, rapid distribution of TLR agonists into the systemic circulation may result in systemic cytokine storms. Telratolimod (Tel) is a TLR 7/8 agonist whose structure has a hydrophobic long chain that helps to prolong its release. Despite this, the phase I study of Tel showed cytokine release syndromes in 3/35 patients. Herein, we designed an injectable phase transition gel (PGE) that served as a superior drug depot for fatty acid-modified drugs. PGE further minimized the systemic drug exposure of Tel and the possible cytokine storms. In vivo studies demonstrated that Tel@PGE facilitated the recruitment of effector CD8+ T lymphocytes (T cells) and the polarization of myeloid-derived suppressor cells (MDSCs) and immunosuppressive M2-like macrophages to tumoricidal antigen-presenting cells. The reshaping of the tumor microenvironment (TME) by Tel@PGE elicited systematic immune responses to significantly prevent B16F10 or 4T-1 tumor postoperative recurrence and metastasis. Therefore, this platform of Tel is expected to provide a clinically available option for effective postoperative combined therapy. STATEMENT OF SIGNIFICANCE: A series of prodrugs or conjugates containing hydrophobic blocks were designed to achieve sustained release at the injection site by reducing the water solubility. However, this strategy sometimes failed short of expectations. Thus, we constructed a biocompatible and biodegradable injectable phase transition gel (PGE) with superior release properties that can be injected subcutaneously into the surgery site. In the long-lasting treatment, the melanoma and breast cancer immunotherapeutic effect significantly enhanced and the risk of cancer metastasis and relapse was reduced. Crucially, for some immune agonists, a superior release control can significantly reduce adverse effects which was decisive for the availability of the drugs.

ClickGene: an open cloud-based platform for big pan-cancer data genome-wide association study, visualization and exploration.

Tremendous amount of whole-genome sequencing data have been provided by large consortium projects such as TCGA (The Cancer Genome Atlas), COSMIC and so on, which creates incredible opportunities for functional gene research and cancer associated mechanism uncovering. While the existing web servers are valuable and widely used, many whole genome analysis functions urgently needed by experimental biologists are still not adequately addressed. A cloud-based platform, named CG (ClickGene), therefore, was developed for DIY analyzing of user's private in-house data or public genome data without any requirement of software installation or system configuration. CG platform provides key interactive and customized functions including Bee-swarm plot, linear regression analyses, Mountain plot, Directional Manhattan plot, Deflection plot and Volcano plot. Using these tools, global profiling or individual gene distributions for expression and copy number variation (CNV) analyses can be generated by only mouse button clicking. The easy accessibility of such comprehensive pan-cancer genome analysis greatly facilitates data mining in wide research areas, such as therapeutic discovery process. Therefore, it fills in the gaps between big cancer genomics data and the delivery of integrated knowledge to end-users, thus helping unleash the value of the current data resources. More importantly, unlike other R-based web platforms, Dubbo, a cloud distributed service governance framework for 'big data' stream global transferring, was used to develop CG platform. After being developed, CG is run on an independent cloud-server, which ensures its steady global accessibility. More than 2 years running history of CG proved that advanced plots for hundreds of whole-genome data can be created through it within seconds by end-users anytime and anywhere. CG is available at http://www.clickgenome.org/.

A quantitative method for assessing smoke associated molecular damage in lung cancers.

BACKGROUND: While tobacco exposure is the cause of the vast majority of lung cancers, an important percentage arise in lifetime never smokers. Documenting the precise extent of tobacco induced molecular changes may be of importance. Also, the contribution of environmental tobacco smoke (ETS) is difficult to assess. METHODS: We developed and validated a quantitative method to assess the extent of tobacco related molecular damage by combing the most characteristic changes associated with tobacco smoke, the tumor mutation burden (TMB) and type of molecular changes present in lung cancers. Using maximum entropy (MaxEnt) as a classifier, we developed a F score. F score values >0 were considered to show evidence of tobacco related molecular damage, while values ≤0 were considered to lack evidence of tobacco related molecular damage. Compared to the stated patient tobacco exposure histories, the F scores had sensitivity, specificity and accuracy values of 85-87%. Using this method, we analyzed public data sets of lung adenocarcinoma (LUAD), lung squamous cell (LUSC) and small cell lung cancer (SCLC). RESULTS: Less than 10% of LUSCs and SCLCs had negative F scores, while 27% to 35% of LUADs had positive scores. The F score showed a highly significant downward trend when LUADs were subdivided into the following categories: ever, reformed ≤15 years, reformed >15 years and never smokers. Most of the examined bronchial carcinoids (a lung cancer type not associated with smoke exposure) had negative F scores. In addition, most LUADs with EGFR mutations had negative F scores, while almost all with KRAS mutations had positive scores. CONCLUSIONS: We have established and validated a quantitative assay that will be of use in assessing the presence and degree of smoke associated molecular damage in lung cancers arising in ever and never smokers.

Genome-wide copy number variation pattern analysis and a classification signature for non-small cell lung cancer.

The accurate classification of non-small cell lung carcinoma (NSCLC) into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) is essential for both clinical practice and lung cancer research. Although the standard WHO diagnosis of NSCLC on biopsy material is rapid and economic, more than 13% of NSCLC tumors in the USA are not further classified. The purpose of this study was to analyze the genome-wide pattern differences in copy number variations (CNVs) and to develop a CNV signature as an adjunct test for the routine histopathologic classification of NSCLCs. We investigated the genome-wide CNV differences between these two tumor types using three independent patient datasets. Approximately half of the genes examined exhibited significant differences between LUAD and LUSC tumors and the corresponding non-malignant tissues. A new classifier was developed to identify signature genes out of 20 000 genes. Thirty-three genes were identified as a CNV signature of NSCLC. Using only their CNV values, the classification model separated the LUADs from the LUSCs with an accuracy of 0.88 and 0.84, respectively, in the training and validation datasets. The same signature also classified NSCLC tumors from their corresponding non-malignant samples with an accuracy of 0.96 and 0.98, respectively. We also compared the CNV patterns of NSCLC tumors with those of histologically similar tumors arising at other sites, such as the breast, head, and neck, and four additional tumors. Of greater importance, the significant differences between these tumors may offer the possibility of identifying the origin of tumors whose origin is unknown.