A Compact Representation for Bayesian Neural Networks By Removing Permutation Symmetry

Bayesian neural networks (BNNs) are a principled approach to modeling predictive uncertainties in deep learning, which are important in safety-critical applications. Since exact Bayesian inference over the weights in a BNN is intractable, various approximate inference methods exist, among which sampling methods such as Hamiltonian Monte Carlo (HMC) are often considered the gold standard. While HMC provides high-quality samples, it lacks interpretable summary statistics because its sample mean and variance is meaningless in neural networks due to permutation symmetry. In this paper, we first show that the role of permutations can be meaningfully quantified by a number of transpositions metric. We then show that the recently proposed rebasin method allows us to summarize HMC samples into a compact representation that provides a meaningful explicit uncertainty estimate for each weight in a neural network, thus unifying sampling methods with variational inference. We show that this compact representation allows us to compare trained BNNs directly in weight space across sampling methods and variational inference, and to efficiently prune neural networks trained without explicit Bayesian frameworks by exploiting uncertainty estimates from HMC.Comment: Accepted at NeurIPS 2023 Workshop on Unifying Representations in Neural Models; 4 pages + appendi

Case report of a Li-Fraumeni syndrome-like phenotype with a de novo mutation in <i>CHEK2</i>

BACKGROUND: Cases of multiple tumors are rarely reported in China. In our study, a 57-year-old female patient had concurrent squamous cell carcinoma, mucoepidermoid carcinoma, brain cancer, bone cancer, and thyroid cancer, which has rarely been reported to date. METHODS: To determine the relationship among these multiple cancers, available DNA samples from the thyroid, lung, and skin tumors and from normal thyroid tissue were sequenced using whole exome sequencing. RESULTS: The notable discrepancies of somatic mutations among the 3 tumor tissues indicated that they arose independently, rather than metastasizing from 1 tumor. A novel deleterious germline mutation (chr22:29091846, G->A, p.H371Y) was identified in CHEK2, a Li–Fraumeni syndrome causal gene. Examining the status of this novel mutation in the patient's healthy siblings revealed its de novo origin. CONCLUSION: Our study reports the first case of Li–Fraumeni syndrome-like in Chinese patients and demonstrates the important contribution of de novo mutations in this type of rare disease

Detection and analysis of human papillomavirus (HPV) DNA in breast cancer patients by an effective method of HPV capture

Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16(HPV16) was detected in 1/7, 1/7, 1/7and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer

Mining bone metastasis related key genes of prostate cancer from the STING pathway based on machine learning

BackgroundProstate cancer (PCa) is the second most prevalent malignant tumor in male, and bone metastasis occurs in about 70% of patients with advanced disease. The STING pathway, an innate immune signaling mechanism, has been shown to play a key role in tumorigenesis, metastasis, and cancerous bone pain. Hence, exploring regulatory mechanism of STING in PCa bone metastasis will bring novel opportunities for treating PCa bone metastasis.MethodsFirst, key genes were screened from STING-related genes (SRGs) based on random forest algorithm and their predictive performance was evaluated. Subsequently, a comprehensive analysis of key genes was performed to explore their roles in prostate carcinogenesis, metastasis and tumor immunity. Next, cellular experiments were performed to verify the role of RELA in proliferation and migration in PCa cells, meanwhile, based on immunohistochemistry, we verified the difference of RELA expression between PCa primary foci and bone metastasis. Finally, based on the key genes to construct an accurate and reliable nomogram, and mined targeting drugs of key genes.ResultsIn this study, three key genes for bone metastasis were mined from SRGs based on the random forest algorithm. Evaluation analysis showed that the key genes had excellent prediction performance, and it also showed that the key genes played a key role in carcinogenesis, metastasis and tumor immunity in PCa by comprehensive analysis. In addition, cellular experiments and immunohistochemistry confirmed that overexpression of RELA significantly inhibited the proliferation and migration of PCa cells, and RELA was significantly low-expression in bone metastasis. Finally, the constructed nomogram showed excellent predictive performance in Receiver Operating Characteristic (ROC, AUC = 0.99) curve, calibration curve, and Decision Curve Analysis (DCA) curve; and the targeted drugs showed good molecular docking effects.ConclusionIn sum, this study not only provides a new theoretical basis for the mechanism of PCa bone metastasis, but also provides novel therapeutic targets and novel diagnostic tools for advanced PCa treatment

Are climate warming and enhanced atmospheric deposition of sulfur and nitrogen threatening tufa landscapes in Jiuzhaigou National Nature Reserve, Sichuan, China?

Massive deposition of calcium carbonate in ambient temperature waters (tufa) can form magnificent tufa landscapes, many of which are designated as protected areas. However, tufa landscapes in many areas are threatened by both local anthropogenic activities and climate change. This study, for the first time, posed the question whether the tufa landscape degradation (characterized by tufa degradation and increased biomass of green algae) in Jiuzhaigou National Nature Reserve of China is partially caused by regional air pollution and climate warming. The results indicate that wet deposition (including rain and snow) polluted by anthropogenic SO2, NOx, and NH3 emissions dissolves exposed tufa and may considerably reduce tufa deposition rate and even cause tufa dissolution within shallow waters. These effects of wet deposition on tufa enhanced as pH of wet deposition decreased from 8.01 to 5.06. Annual Volume Weighted Mean concentration of reactive nitrogen (including NH4+ and NO3-) in wet deposition (26.1 μmol L-1) was 1.8 times of the corresponding value of runoff (14.8 μmol L-1) and exceeded China's national standard of total nitrogen in runoff for nature reserves (14.3 μmol L-1), indicating a direct nitrogen fertilization effect of wet deposition on green algae. As water temperature is the major limiting factor of algal growth in Jiuzhaigou and temperature in the top layer (0-5 cm) of runoff (depth < 1 m, no canopy coverage of trees and shrubs) was significantly higher at the sites with increased biomass of green algae (p < 0.05), climate warming in this region would favor algal growth. In sum, this study suggests that climate warming and enhanced sulfur and nitrogen deposition have contributed to the current degradation of tufa landscape in Jiuzhaigou, but in order to quantify the contributions, further studies are needed, as many other anthropogenic and natural processes also influence tufa landscape evolution

Identification of a hypoxia-suppressed lncRNA RAMP2-AS1 in breast cancer

Hypoxia is a critical feature of solid tumors and exerts crucial roles in cancers, including breast cancer. However, the detailed relationship between lncRNA-miRNA-mRNA triple network and hypoxia in breast cancer is still indistinct. In this study, a series of in silico analyses and online databases or tools were employed to establish a hypoxia-related lncRNA-miRNA-mRNA network in breast cancer based on competing endogenous RNA mechanism at single-cell resolution. RAMP2-AS1 was, eventually, identified as the most potential lncRNA, which was significantly negatively associated with hypoxia in breast cancer. Compared with normal controls, RAMP2-AS1 was markedly downregulated in breast cancer. Moreover, survival analysis revealed favorable prognostic values of RAMP2-AS1 in total or in specific clinicopathological breast cancer patients. Next, miR-660-5p, miR-2277-5p and miR-1301-3p, upregulated and possessed poor prognostic values in breast cancer, were identified as three potential downstream miRNAs of RAMP2-AS1. Then, the most potential downstream hypoxia-related genes (ATM and MYH11) of RAMP2-AS1/miRNA axis in breast cancer were screened out. Intriguingly, in vitro experiments confirmed that RAMP2-AS1 was a hypoxia-suppressed lncRNA and miR-660-5p/ATM was a potential downstream axis of RAMP2-AS1 in breast cancer. Collectively, our current data elucidated a key hypoxia-suppressed lncRNA RAMP2-AS1 and its possible miRNA-mRNA regulatory mechanism in breast cancer

The statistical results of different methods on the PNIFECGDB.

The statistical results of different methods on the PNIFECGDB.</p

The block diagram of the extracted FECG signal de-noising using the proposed nonlinear ANC.

The output is an estimation of the FECG component of channel 1.</p

Evaluation Criteria for Implementation of a Sustainable Sanitation and Wastewater Treatment System at Jiuzhaigou National Park, Sichuan Province, China

The administration of Jiuzhaigou National Park in Sichuan Province, China, is in the process of considering a range of upgrades to their sanitation and wastewater treatment systems. Their case history involves an ongoing series of engineering design flaws and management failures. The administration of the Park identified sustainability, environmental protection, and education goals for their sanitation and wastewater treatment system. To meet the goal of sustainability, environmental and economic concerns of the Park’s administration had to be balanced with socio-cultural needs. An advanced reconnaissance method was developed that identified reasons for previous failures, conducted stakeholder analysis and interviews, determined evaluation criteria, and introduced innovative alternatives with records of successful global implementations. This evaluation also helped the Park to better define their goals. To prevent future failures, the administration of the Park must commit to a balanced and thorough evaluation process for selection of a final alternative and institute effective long-term management and monitoring of systems. In addition, to meet goals and achieve energy efficient, cost-effective use of resources, the Park must shift their thinking from one of waste disposal to resource recovery. The method and criteria developed for this case study provides a framework to aid in the successful implementation of sanitation projects in both underdeveloped and developed areas of the world, incorporating socio-cultural values and resource recovery for a complex group of stakeholders

Constraining the Water Cycle Model of an Important Karstic Catchment in Southeast Tibetan Plateau Using Isotopic Tracers (2H, 18O, 3H, 222Rn)

Understanding the connectivity between surface water and groundwater is key to sound geo-hazard prevention and mitigation in a waterscape such as the Jiuzhaigou Natural World Heritage Site in the southeast Tibetan Plateau, China. In this study, we used environmental isotope tracers (2H, 18O 3H, and 222Rn) to constrain a water cycle model including confirming hydrological pathways, connectivity, and water source identification in the Jiuzhaigou catchments. We established the local meteoric water line (LMWL) based on the weekly precipitation isotope sampling of a precipitation station. We systematically collected water samples from various water bodies in the study area to design the local water cycle model. The regional water level and discharge changes at one month after the earthquake indicated that there was a hydraulic connection underground across the local water divide between the Rize (RZ) river in the west and Zechawa (ZCW) lake in the east by the &delta;18O and &delta;2H measurements. We employed an end-member mixing model to identify and quantify Jiuzhaigou runoff-generating sources and their contributions, and we found that the average contributions of precipitation and groundwater to the surface runoff in the catchments are about 30% and 70%, respectively. The two branches of the Shuzheng (SZ) trunk were recharged by 62 &plusmn; 19% from the ZCW lake and 38 &plusmn; 19% from the RZ river, which was consistent with the fractions calculated by the actual discharge volume. 222Rn mass balance analyses were employed to estimate the water exchange between groundwater and river, which further confirmed this estimate. 222Rn concentrations and 3H contents showed that the groundwater had a short residence time and it was moderate precipitation, thought the contribution of groundwater to the river was 70%, according to the different tracers. A three-dimensional conceptual model of the water cycle that integrated the regional hydrological and geological conditions was established for the catchments