Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies. Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development

Study of a periodic spectral fluctuation existing in a fibered optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS)

A special periodic spectral fluctuation is observed during the study of a fibered high sensitivity optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS) for the measurement of trace gas. This spectral fluctuation is different from some phenomenon observed in former OF-CEAS which contain a resonant cavity with V-shaped configuration, such as the etalon effect and the spectral ripple effect. To reveal why this phenomenon happens and how it works, a series of hypothesis are proposed and tested, and the results show that the multi-beam interference of resonance light at the input mirror of the resonant cavity is the main reason for this phenomenon. Based on the multi-beam interference theory, a mathematical modeling of this phenomenon is built, and the theoretical analyses agree well with the experimental results. Some methods to eliminate this phenomenon are proposed and implemented, and the 1σ noise equivalent absorption coefficient of 7.6 × 10− 10 cm− 1 Hz-1/2 is attained with this robust and compact OF-CEAS system

Application of Near-Infrared Optical Feedback Cavity Enhanced Absorption Spectroscopy (OF-CEAS) to the Detection of Ammonia in Exhaled Human Breath

The qualitative and quantitative analysis to trace gas in exhaled human breath has become a promising technique in biomedical applications such as disease diagnosis and health status monitoring. This paper describes an application of a high spectral resolution optical feedback cavity enhanced absorption spectroscopy (OF-CEAS) for ammonia detection in exhaled human breath, and the main interference of gases such as CO2 and H2O are approximately eliminated at the same time. With appropriate optical feedback, a fibered distributed feedback (DFB) diode laser emitting at 1531.6 nm is locked to the resonance of a V-shaped cavity with a free spectral range (FSR) of 300 MHz and a finesse of 14,610. A minimum detectable absorption coefficient of αmin = 2.3 × 10−9 cm−1 is achieved in a single scan within 5 s, yielding a detection limit of 17 ppb for NH3 in breath gas at low pressure, and this stable system allows the detection limit down to 4.5 ppb when the spectra to be averaged over 16 laser scans. Different from typical CEAS with a static cavity, which is limited by the FSR in frequency space, the attainable spectral resolution of our experimental setup can be up to 0.002 cm−1 owing to the simultaneous laser frequency tuning and cavity dither. Hence, the absorption line profile is more accurate, which is most suitable for low-pressure trace gas detection. This work has great potential for accurate selectivity and high sensitivity applications in human breath analysis and atmosphere sciences

Resolver Decoding Method Using Hilbert Transform and ATO

Resolvers are widely used in electric vehicles, trains, and other harsh fields because of their robustness. However, the resolver outputs two orthogonal analog signals, which make the resolver decoding either high hardware cost or poor decoding accuracy. A noise robust resolver decoding method using Hilbert transform and angle-tracking observer (ATO) is proposed in this paper. Firstly, Hilbert transform is employed to obtain the modular envelopes of resolver signals. Next, the modular envelopes are filtered, and their quadrants are recognized by the polarity relation of the resolver signals and the modular envelope extreme point. Then, the ideal demodulating signals are gained through the linearization of the envelope zero point. Finally, the improved ATO is used to obtain the rotor angle by iteratively calculating the demodulating signal. The effectiveness of the proposed method is verified by experiments under various rotor speed conditions and compared with other methods in noise immunity. The results show that the proposed method can control the decoding error within 0.5° when the SNR is 30 dB, which provides a high-precision and low-cost decoding scheme for practical applications

Asymmetric Etalon Effect in Fold-Type Optical Feedback Cavity-Enhanced Absorption Spectroscopy

To further improve the performance of cavity-enhanced spectroscopy systems, a high-quality U-cavity system was established. In the process of the experiment, an asymmetric ripple effect, which is different from the previous etalon effect, was found, which seriously affects the performance of the spectral system. This unique phenomenon mainly manifests in the different amplitudes of the fluctuations of the spectral curves measured by the folding mirror and the end mirror in the U-cavity system. Based on multi-beam interference theory, we analyzed the characteristics of the transmission spectrum of each mirror in the presence of the etalon effect at the end mirror, and obtained the following conclusions: for the U-cavity system, the strength of the etalon effect of each mirror is inversely proportional to its transmission loss value, that is, the larger the loss, the smaller the ripple of the transmission spectrum, and vice versa. In order to eliminate this effect, the most effective way is to eliminate the etalon effect caused by the light feedback of the end mirror. After improving the system, the minimum detectable absorption coefficient of αmin=8.33×10−9cm−1 is obtained with this U-shape Optical Feedback Cavity-Enhanced Absorption Spectroscopy. These works are valuable references for the design of folded Cavity-Enhanced Absorption Spectroscopy systems and have potential for laser wavelength calibration and measurement of a mirror’s reflectance

A He-Ne gas laser with tunable wavelength and stable output intensity based on photon tunneling

In this paper, we report on a wavelength modulation He-Ne gas laser with stable output intensity. Wavelength modulation of the laser is achieved by modulating the length of the resonator cavity. And photon tunneling is used to change the loss of the cavity, namely, to modulate the laser output intensity. Then, the closed-loop feedback control technique is adopted to ensure the output intensity is stable when the laser wavelength is being modulated. Photon tunneling shows a significant control effect on the output light intensity of the laser. Finally, compared to a laser without feed-back control, the output stability of the wavelength modulation laser with feed-back control is an order higher in magnitude than that of the former, as average standard deviation of the output intensity decreases to a thirtieth of the original. In addition longitudinal mode characteristics and beam quality of the laser is measured. The measuring results show that it has two longitudinal modes and an excellent beam quality as the value of M2 factor is 1.029

Self-supervised learning disentangled group representation as feature

A good visual representation is an inference map from observations (images) to features (vectors) that faithfully reflects the hidden modularized generative factors (semantics). In this paper, we formulate the notion of "good" representation from a group-theoretic view using Higgins' definition of disentangled representation, and show that existing Self-Supervised Learning (SSL) only disentangles simple augmentation features such as rotation and colorization, thus unable to modularize the remaining semantics. To break the limitation, we propose an iterative SSL algorithm: Iterative Partition-based Invariant Risk Minimization (IP-IRM), which successfully grounds the abstract semantics and the group acting on them into concrete contrastive learning. At each iteration, IP-IRM first partitions the training samples into two subsets that correspond to an entangled group element. Then, it minimizes a subset-invariant contrastive loss, where the invariance guarantees to disentangle the group element. We prove that IP-IRM converges to a fully disentangled representation and show its effectiveness on various benchmarks. Codes are available at https://github.com/Wangt-CN/IP-IRM.Comment: Accepted by NeurIPS 2021 (Spotlight

Migrasomes and tetraspanins in hepatocellular carcinoma: current status and future prospects

In recent years, many studies have attempted to clarify the formation, structure and biological function of migrasomes, which are defined as specialized organelles formed by the tips and intersections of Retraction Fibrils during cell migration. It has confirmed that migrasomes were involved in various critical biological processes and diseases, and has became a new research hotspot. In this paper, we reviewed the formation and biological functions of migrasomes, explored the relationship between migrasomes, tetraspanins and hepatocellular carcinoma and discussed the potential applications of migrasomes in hepatocellular carcinoma