Variable Temporal Length Training for Action Recognition CNNs.

Most current deep learning models are suboptimal in terms of the flexibility of their input shape. Usually, computer vision models only work on one fixed shape used during training, otherwise their performance degrades significantly. For video-related tasks, the length of each video (i.e., number of video frames) can vary widely; therefore, sampling of video frames is employed to ensure that every video has the same temporal length. This training method brings about drawbacks in both the training and testing phases. For instance, a universal temporal length can damage the features in longer videos, preventing the model from flexibly adapting to variable lengths for the purposes of on-demand inference. To address this, we propose a simple yet effective training paradigm for 3D convolutional neural networks (3D-CNN) which enables them to process videos with inputs having variable temporal length, i.e., variable length training (VLT). Compared with the standard video training paradigm, our method introduces three extra operations during training: sampling twice, temporal packing, and subvideo-independent 3D convolution. These operations are efficient and can be integrated into any 3D-CNN. In addition, we introduce a consistency loss to regularize the representation space. After training, the model can successfully process video with varying temporal length without any modification in the inference phase. Our experiments on various popular action recognition datasets demonstrate the superior performance of the proposed method compared to conventional training paradigm and other state-of-the-art training paradigms.

Invasive pneumococcal diseases in Chinese children: a multicentre hospital-based active surveillance from 2019 to 2021.

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

The endoplasmic reticulum stress-related genes and molecular typing predicts prognosis and reveals characterization of tumor immune microenvironment in lung squamous cell carcinoma.

BACKGROUND: Endoplasmic reticulum stress (ERS) acts critical roles on cell growth, proliferation, and metastasis in various cancers. However, the relationship between ERs and lung squamous cell carcinoma (LUSC) prognoses still remains unclear. METHODS: The consensus clustering analysis of ERS-related genes and the differential expression analysis between clusters were investigated in LUSC based on TCGA database. Furthermore, ERS-related prognostic risk models were constructed by LASSO regression and Cox regression analyses. Then, the predictive effect of the risk model was evaluated by Kaplan-Meier, Cox regression, and ROC Curve analyses, as well as validated in the GEO cohort. According to the optimal threshold, patients with LUSC were divided into high- and low- risk groups, and somatic mutations, immune cell infiltration, chemotherapy response and immunotherapy effect were systematically analyzed. RESULTS: Two ERS-related clusters were identified in patients with LUSC that had distinct patterns of immune cell infiltration. A 5-genes ERS-related prognostic risk model and nomogram were constructed and validated. Kaplan-Meier curves and Cox regression analysis showed that ERS risk score was an independent prognostic factor (p < 0.001, HR = 1.317, 95% CI = 1.159-1.496). Patients with low-risk scores presented significantly lower TIDE scores and significantly lower IC50 values for common chemotherapy drugs such as cisplatin and gemcitabine. CONCLUSION: ERS-related risk signature has certain prognostic value and may be a potential therapeutic target and prognostic biomarker for LUSC patients.

Mediation of metabolic syndrome in the association between long-term exposure to particulate matter and incident cardiovascular disease: Evidence from a population-based cohort in Chengdu.

BACKGROUND: Particulate matter (PM) exposure has been linked with cardiovascular disease (CVD) and metabolic syndrome (MetS), the latter characterized by concurrent multiple metabolic disorders. As a result, the mechanisms assumption from PM to CVD through MetS have emerged, thus requiring further epidemiological evidence. This cohort study aimed to assess whether MetS mediates the associations of PM with CVD risk. METHODS: This study included 14,195 participants from the Chengdu cohort of the China Multi-Ethnic Cohort (CMEC) study in 2018. The primary outcome of incident CVD diagnoses was identified using matched hospital records from the Health Information Center of Sichuan Province. Residence-specific levels of PM with aerodynamic diameters of ≤ 1 µm (PM1), ≤ 2.5 µm (PM2.5), and ≤ 10 µm (PM10) were estimated by spatiotemporal models. Causal mediation analyses were applied to evaluate the indirect effect of MetS. RESULTS: Increased exposure levels to PM were significantly associated with MetS and CVD. Mediation analyses indicated that the associations between PM exposure and CVD were mediated by MetS, with the proportion of multiple mediations being 19.3%, 12.1%, and 13.5% for PM1, PM2.5, and PM10, respectively. Further moderated mediation analyses suggested that male, overweight individuals, alcohol drinkers, and those suffering from indoor air pollution may experience more significant adverse effects from PM exposure on CVD via MetS than others. CONCLUSIONS: Our findings suggest that MetS partially mediates the association between long-term exposure to PM and CVD. These mediation effects appear to be amplified by demographic characteristics and unhealthy lifestyles.

Ambient particulate matter and in-hospital case fatality of acute myocardial infarction: A multi-province cross-sectional study in China.

The acute myocardial infarction (AMI) outcomes have been extensively linked with ambient particulate matter (PM). However, whether a smaller particle has greater impact and the consequent attributable burden associated with PM of different sizes remain unclear. We conducted a multi-province cross-sectional study among AMI patients using the inpatient discharge datasets from four Chinese provinces (Shanxi, Sichuan, Guangxi, and Guangdong) from 2014 to 2019. Ambient PM exposure for each patient was assessed using the ChinaHighAirPollutants dataset. We employed the mixed-effects logistic regression models to evaluate the association of PM of different sizes (PM1, PM2.5, PM10) on in-hospital case fatality. The potential reducible fractions in in-hospital case fatality were estimated through counterfactual analyses. Of 177,749 participants, 125,501 (70.6 %) were male and the in-hospital case fatality rate was 4.9%. For short-term (7-day average) exposure, the odds ratios (ORs) for PM1, PM2.5, and PM10 (per 10 µg/m3) were 1.052 (95 % confidence interval [CI], 1.032-1.071), 1.026 (95 % CI, 1.014-1.037), and 1.016 (95% CI, 1.008-1.024), respectively. The estimated ORs for long-term exposure (annual average) were 1.303 (95 % CI, 1.252-1.356) for PM1, 1.209 (95 % CI, 1.178-1.241) for PM2.5, 1.157 (95 % CI, 1.134-1.181) for PM10. Short-term exposure to PM1 showed the highest potential reducible fraction (8.5 %, 95 % CI, 5.0-11.7 %), followed by PM2.5 and PM10, while the greatest potential reducible fraction of long-term exposure was observed in PM10 (30.9 %, 95 % CI, 27.2-34.4%), followed by PM2.5 and PM1. In summary, PM with smaller size had a more pronounced impact on in-hospital AMI case fatality, with PM1 exhibiting greater effects than PM2.5 and PM10. Substantial health benefits for AMI patients could be achieved by mitigating ambient PM exposure.

Measuring low-value care in hospital discharge records: evidence from China.

Background: Plenty of efforts have been made to reduce the use of low-value care (the care that is not expected to provide net benefits for patients) across the world, but measures of low-value care have not been developed in China. This study aims to develop hospital discharge records-based measures of low-value surgical procedures, evaluate their annual use and associated expenditure, and analyze the practice patterns by characterizing its temporal trends and correlations across rates of different low-value procedures within hospitals. Methods: Informed by evidence-based lists including Choosing Wisely, we developed 11 measures of low-value surgical procedures. We evaluated the count and proportion of low-value episodes, as well as the proportion of expenditure and medical insurance payouts for these episodes, using hospital discharge records in Sichuan Province, China during a period of 2016-2022. We compared the count and expenditure detected by different versions of these measures, which varied in sensitivity and specificity. We characterized the temporal trends in the rate of low-value surgical procedures and estimated the annual percent change using joint-point regression. Additionally, we calculated the Spearman correlation coefficients between the risk-standardized rates of low-value procedures which were estimated by multilevel models adjusting for case mix across hospitals. Findings: Low-value episodes detected by more specific versions of measures accounted for 3.25% (range, 0.11%-71.66%), and constituted 6.03% (range, 0.32%-84.63%) and 5.90% (range, 0.33%-82.86%) of overall expenditure and medical insurance payouts, respectively. The three figures accounted for 5.90%, 8.41%, and 8.38% in terms of more sensitive versions of measures. Almost half of the low-value procedures (five out of eleven) experienced an increase in rates during the period of 2016-2022, with four of them increasing over 20% per year. There was no significant correlation across risk-standardized rates of different low-value procedures within hospitals (mean r for pairwise, 0.03; CI, -0.02, 0.07). Interpretation: Despite overall low-value practices detected by the 11 developed measures was modest, certain clinical specialties were plagued by widespread low-value practices which imposed heavy economic burdens for the healthcare system. Given the pervasive and significant upward trends in rates of low-value practices, it has become increasingly urgent to reduce such practices. Interventions in reducing low-value practices in China would be procedure-specific as practice patterns of low-value care varied by procedures and common drivers of low-value practices may not exist. Funding: The National Science Foundation of China (72074163), Taikang Yicai Public Health and Epidemic Control Fund, Sichuan Science and Technology Program (2022YFS0052 and 2021YFQ0060), and Sichuan University (2018hhf-27 and SKSYL201811).

Estimation of the distribution patterns of heavy metal in soil from airborne hyperspectral imagery based on spectral absorption characteristics.

Though soil is widely known as one of the most valuable resources for the world, its quality is going to be lower because of unsustainable economic development and social progress. Therefore, it is important for us to monitor and evaluate the quality of soil, especially its heavy metal contents which is too scarce to identify in soil spectra easily but poisonous enough to affect human health in a long run. Most of the existing estimation methods have based the characteristic bands on statistical analysis to a large extent, which is hard to accurately explain the retrieval mechanism. In this paper, the absorption characteristics of heavy metal are studied based on the soil spectra, and the distribution pattern is mapped in a large-scale continuous space, for environmental monitoring and further decision support. Taking Yitong County, China as the study area. After spectra continuum removal, the heavy metal contents were estimated by 11 features including the absorption depth, absorption area, and band ratio around 2200 nm, which showed the best performance. For arsenic (As), the best model yields Rp2 value of 0.8474, and the RMSEP value is 36.1542 (mg/kg). It is concluded that As is adsorbed by organic matter, clay minerals, and iron/manganese oxides in soil, and the adsorption of As by first two components is greater than that of the last. For airborne spectra after continuum removal, combining the spectral absorption characteristic parameters and the highly correlated bands is more accurate than using the spectral absorption characteristic parameters or bands alone. AdaBoost is presented for the heavy metal estimation, and the fitting ability of the method is found to be stronger than that of the traditional classical methods, with the Rp2 values of 0.6242 and the RMSEP value of 43.6481 (mg/kg). In summary, these results will provide a prospective basis for the rapid estimation of soil heavy metals, the risk assessment of soil heavy metals and soil environmental monitoring in a large scale.

Incidence, prevalence, and comorbidities of chronic pancreatitis: A 7-year population-based study.

BACKGROUND: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to reduced quality of life and shortened life expectancy. Population-based estimates of the incidence, prevalence, and comorbidities of CP in China are scarce. AIM: To characterize the incidence, prevalence, and comorbidities of CP in Sichuan Province, China, with population-based data. METHODS: Data on CP from 2015 to 2021 were obtained from the Health Information Center of Sichuan Province. During the study period, a total of 38090 individuals were diagnosed with CP in Sichuan Province. The yearly incidence rate and point prevalence rate (December 31, 2021) of CP were calculated. The prevalence of comorbid conditions in CP patients was estimated. The annual number of CP-related hospitalizations, hospital length of stay, and hospitalization costs for CP were evaluated. Yearly incidence rates were standardized for age by the direct method using the permanent population of Sichuan Province in the 2020 census as the standard population. An analysis of variance test for the linearity of scaled variables and the Cochran-Armitage trend test for categorical data were performed to investigate the yearly trends, and a two-sided test with P < 0.05 was considered statistically significant. RESULTS: The 38090 CP patients comprised 23280 males and 14810 females. The mean age of patients at CP diagnosis was 57.83 years, with male patients (55.87 years) being younger than female patients (60.11 years) (P < 0.001). The mean incidence rate of CP during the study period was 6.81 per 100000 person-years, and the incidence of CP increased each year, from 4.03 per 100000 person-years in 2015 to 8.27 per 100000 person-years in 2021 (P < 0.001). The point prevalence rate of CP in 2021 was 45.52 per 100000 individuals for the total population, with rates of 55.04 per 100000 individuals for men and 35.78 per 100000 individuals for women (P < 0.001). Individuals aged 65 years or older had the highest prevalence of CP (113.38 per 100000 individuals) (P < 0.001). Diabetes (26.32%) was the most common comorbidity in CP patients. The number of CP-related hospitalizations increased from 3739 in 2015 to 11009 in 2021. The total costs for CP-related hospitalizations for CP patients over the study period were 667.96 million yuan, with an average of 17538 yuan per patient. CONCLUSION: The yearly incidence of CP is increasing, and the overall CP hospitalization cost has increased by 1.4 times during the last 7 years, indicating that CP remains a heavy health burden.

A space-confined strategy towards stable α/ß-Bi2O3 heterojunction anode for high-energy aqueous battery.

It is very necessary to design a high-capacity and stable Bi2O3 anode for nickel-bismuth (Ni//Bi) batteries. In this work, a stable α- and ß- phase Bi2O3 heterojunction nanocomposite (α/ß - Bi2O3) was successfully prepared via a simple "space-confined" strategy and it was used as a superior anode for nickel-bismuth (Ni//Bi) battery. The α/ß-Bi2O3 obtained by using MCM-41 as a space-confined template possesses a stable structure and enhanced charge transfer capability. Such superior traits vest the designed α/ß-Bi2O3 electrode with high specific capacity (235 mAh g-1 at 1 A g-1), extraordinary rate performance (137 mAh g-1 at 40 A g-1, and ∼58% capacity retention vs 1 A g-1), and excellent cyclic durability (75% capacity retention after 5000 cycles). Such performances are far superior to that of mono-phase α-Bi2O3 and ß-Bi2O3 electrodes. Furthermore, an excellent Ni//Bi battery with outstanding energy density (∼155 Wh kg-1) and long cycle life was assembled using the obtained α/ß-Bi2O3 electrode and a NiC2O4 electrode as anode and cathode, respectively (NiC2O4//α/ß-Bi2O3). This work opens a new alternative strategy for the rational design of efficient electrodes for reliable aqueous rechargeable batteries.

Influenza-associated neurologic complications in children from an H3N2 outbreak in Shenzhen, China during COVID-19 lockdown.

OBJECTIVES: To identify the characteristics of influenza-associated neurologic complications (INCs) in children from a recent H3N2 outbreak in Shenzhen, China during COVID-19 lockdown. METHODS: A retrospective cohort study of INCs in children hospitalized with H3N2 infection was conducted. RESULTS: From June 01, 2022 to July 01, 2022, 513 children with H3N2 infection were hospitalized and 97 developed INCs. Of the 18 patients with encephalopathy/encephalitis, 13 were previously healthy. Three developed acute necrotizing encephalopathy and two died. Of the 63 patients with febrile seizures, 55 (87%) had simple febrile seizures. Of the 14 patients with an exacerbation of seizure with underlying epilepsy, the seizure symptoms occurred mostly within 24 hours of disease onset (13/14). The comparison of the three groups (encephalopathy/encephalitis, febrile seizure and exacerbation of seizure with underlying epilepsy) reported no significant differences in sex, pre-existing neurologic diseases, vaccination rate, white blood cell count, C-reactive protein, procalcitonin, blood glucose, lactic acid, or duration of fever. The influenza vaccination rates were generally low (22% vs 32% vs 21%). Patients with encephalopathy/encephalitis had a higher rate of elevated alanine aminotransferase (28% vs 3% vs 0, P = 0.005). CONCLUSION: H3N2-related neurologic complications in children mainly occur early in the disease course. Most patients were previously healthy and unvaccinated against influenza. Elevated alanine aminotransferase is more common in encephalopathy/encephalitis.

Developmental regulators moonlighting as transposons defense factors.

BACKGROUND: The germline perpetuates genetic information across generations. To maintain the integrity of the germline, transposable elements in the genome must be silenced, as these mobile elements would otherwise engender widespread mutations passed on to subsequent generations. There are several well-established mechanisms that are dedicated to providing defense against transposable elements, including DNA methylation, RNA interference, and the PIWI-interacting RNA pathway. OBJECTIVES: Recently, several studies have provided evidence that transposon defense is not only provided by factors dedicated to this purpose but also factors with other roles, including in germline development. Many of these are transcription factors. Our objective is to summarize what is known about these "bi-functional" transcriptional regulators. MATERIALS AND METHODS: Literature search. RESULTS AND CONCLUSION: We summarize the evidence that six transcriptional regulators-GLIS3, MYBL1, RB1, RHOX10, SETDB1, and ZBTB16-are both developmental regulators and transposable element-defense factors. These factors act at different stages of germ cell development, including in pro-spermatogonia, spermatogonial stem cells, and spermatocytes. Collectively, the data suggest a model in which specific key transcriptional regulators have acquired multiple functions over evolutionary time to influence developmental decisions and safeguard transgenerational genetic information. It remains to be determined whether their developmental roles were primordial and their transposon defense roles were co-opted, or vice versa.

SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA turnover pathway that depends on the endonuclease SMG6. Here, we show that SMG6 is essential for male germ cell differentiation in mice. Germ-cell conditional knockout (cKO) of Smg6 induces extensive transcriptome misregulation, including a failure to eliminate meiotically expressed transcripts in early haploid cells, and accumulation of NMD target mRNAs with long 3' untranslated regions (UTRs). Loss of SMG6 in the male germline results in complete arrest of spermatogenesis at the early haploid cell stage. We find that SMG6 is strikingly enriched in the chromatoid body (CB), a specialized cytoplasmic granule in male germ cells also harboring PIWI-interacting RNAs (piRNAs) and the piRNA-binding protein PIWIL1. This raises the possibility that SMG6 and the piRNA pathway function together, which is supported by several findings, including that Piwil1-KO mice phenocopy Smg6-cKO mice and that SMG6 and PIWIL1 co-regulate many genes in round spermatids. Together, our results demonstrate that SMG6 is an essential regulator of the male germline transcriptome, and highlight the CB as a molecular platform coordinating RNA regulatory pathways to control sperm production and fertility.

Progression of the pluripotent epiblast depends upon the NMD factor UPF2.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that degrades RNAs harboring in-frame stop codons in specific contexts. Loss of NMD factors leads to embryonic lethality in organisms spanning the phylogenetic scale, but the mechanism remains unknown. Here, we report that the core NMD factor, UPF2, is required for expansion of epiblast cells within the inner cell mass of mice in vivo. We identify NMD target mRNAs in mouse blastocysts - both canonical and alternatively processed mRNAs - including those encoding cell cycle arrest and apoptosis factors, raising the possibility that NMD is essential for embryonic cell proliferation and survival. In support, the inner cell mass of Upf2-null blastocysts rapidly regresses with outgrowth and is incompetent for embryonic stem cell derivation in vitro. In addition, we uncovered concordant temporal- and lineage-specific regulation of NMD factors and mRNA targets, indicative of a shift in NMD magnitude during peri-implantation development. Together, our results reveal developmental and molecular functions of the NMD pathway in the early embryo.

Association between hospital characteristics and 30-day mortality of patients hospitalized for acute myocardial infarction in Sichuan, China.

OBJECTIVE: Because acute myocardial infarction (AMI) is a major cause of death, China faces the challenge of improving its quality of care. This study provides context-specific evidence of association between 30-day mortality and hospital characteristics in China to extend the understanding of hospitalized AMI patients. METHODS: We conducted a retrospective cohort study of 67,619 hospitalized AMI patients at 372 tertiary and secondary hospitals in Sichuan, China, between January 1, 2018 and December 31, 2020. Using a hierarchical logistic regression model to control risk factors, we explored relationships among 30-day mortality, hospital level, AMI volume, and percutaneous coronary intervention (PCI) timeliness. Locally weighted scatterplot smoothing was used to observe the trends of 30-day mortality with increased AMI volume and PCI timeliness. RESULTS: After risk factor adjustment, the 30-day mortality model demonstrated that a lower hospital level and smaller AMI volume were associated with higher 30-day mortality (medium-volume: OR = 1.511, 95% CI (1.195, 1.910); small-volume: OR = 1.636, 95% CI (1.277, 2.096); other tertiary: OR = 1.190, 95% CI (1.037, 1.365); secondary: OR = 1.524, 95% CI (1.289, 1.800)). Similarly, 30-day mortality was higher for patients at hospitals with a low PCI timeliness (low timeliness: OR = 1.318, 95% CI (1.079, 1.610)). Scatterplot smoothing showed hospital 30-day mortality first reduced quickly and gradually stabilized with increased AMI volume and PCI timeliness. CONCLUSION: Patients admitted to tertiary grade A hospitals, large-volume hospitals, and high- or medium-timeliness hospitals were more likely to survive at 30 days. Policymakers should focus on improving the outcomes at hospitals without these characteristics.

Mitochondrial genome undergoes de novo DNA methylation that protects mtDNA against oxidative damage during the peri-implantation window.

Mitochondrial remodeling during the peri-implantation stage is the hallmark event essential for normal embryogenesis. Among the changes, enhanced oxidative phosphorylation is critical for supporting high energy demands of postimplantation embryos, but increases mitochondrial oxidative stress, which in turn threatens mitochondrial DNA (mtDNA) stability. However, how mitochondria protect their own histone-lacking mtDNA, during this stage remains unclear. Concurrently, the mitochondrial genome gain DNA methylation by this stage. Its spatiotemporal coincidence with enhanced mitochondrial stress led us to ask if mtDNA methylation has a role in maintaining mitochondrial genome stability. Herein, we report that mitochondrial genome undergoes de novo mtDNA methylation that can protect mtDNA against enhanced oxidative damage during the peri-implantation window. Mitochondrial genome gains extensive mtDNA methylation during transition from blastocysts to postimplantation embryos, thus establishing relatively hypermethylated mtDNA from hypomethylated state in blastocysts. Mechanistic study revealed that DNA methyltransferase 3A (DNMT3A) and DNMT3B enter mitochondria during this process and bind to mtDNA, via their unique mitochondrial targeting sequences. Importantly, loss- and gain-of-function analyses indicated that DNMT3A and DNMT3B are responsible for catalyzing de novo mtDNA methylation, in a synergistic manner. Finally, we proved, in vivo and in vitro, that increased mtDNA methylation functions to protect mitochondrial genome against mtDNA damage induced by increased mitochondrial oxidative stress. Together, we reveal mtDNA methylation dynamics and its underlying mechanism during the critical developmental window. We also provide the functional link between mitochondrial epigenetic remodeling and metabolic changes, which reveals a role for nuclear-mitochondrial crosstalk in establishing mitoepigenetics and maintaining mitochondrial homeostasis.

Regulation of both transcription and RNA turnover contribute to germline specification.

The nuanced mechanisms driving primordial germ cells (PGC) specification remain incompletely understood since genome-wide transcriptional regulation in developing PGCs has previously only been defined indirectly. Here, using SLAMseq analysis, we determined genome-wide transcription rates during the differentiation of embryonic stem cells (ESCs) to form epiblast-like (EpiLC) cells and ultimately PGC-like cells (PGCLCs). This revealed thousands of genes undergoing bursts of transcriptional induction and rapid shut-off not detectable by RNAseq analysis. Our SLAMseq datasets also allowed us to infer RNA turnover rates, which revealed thousands of mRNAs stabilized and destabilized during PGCLC specification. mRNAs tend to be unstable in ESCs and then are progressively stabilized as they differentiate. For some classes of genes, mRNA turnover regulation collaborates with transcriptional regulation, but these processes oppose each other in a surprisingly high frequency of genes. To test whether regulated mRNA turnover has a physiological role in PGC development, we examined three genes that we found were regulated by RNA turnover: Sox2, Klf2 and Ccne1. Circumvention of their regulated RNA turnover severely impaired the ESC-to-EpiLC and EpiLC-to-PGCLC transitions. Our study demonstrates the functional importance of regulated RNA stability in germline development and provides a roadmap of transcriptional and post-transcriptional regulation during germline specification.

Nonsense-mediated RNA decay: an emerging modulator of malignancy.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that selectively degrades RNAs harbouring truncating mutations that prematurely terminate translation, including nonsense, frameshift and some splice-site mutations. Recent studies show that NMD shapes the mutational landscape of tumours by selecting for mutations that tend to downregulate the expression of tumour suppressor genes but not oncogenes. This suggests that NMD can benefit tumours, a notion further supported by the finding that mRNAs encoding immunogenic neoantigen peptides are typically targeted for decay by NMD. Together, this raises the possibility that NMD-inhibitory therapy could be of therapeutic benefit against many tumour types, including those with a high load of neoantigen-generating mutations. Complicating this scenario is the evidence that NMD can also be detrimental for many tumour types, and consequently tumours often have perturbed NMD. NMD may suppress tumour generation and progression by degrading subsets of specific normal mRNAs, including those encoding stress-response proteins, signalling factors and other proteins beneficial for tumours, as well as pro-tumour non-coding RNAs. Together, these findings suggest that NMD-modulatory therapy has the potential to provide widespread therapeutic benefit against diverse tumour types. However, whether NMD should be stimulated or repressed requires careful analysis of the tumour to be treated.

Moving Vehicle Detection for Remote Sensing Video Surveillance With Nonstationary Satellite Platform.

With satellite platforms gazing at a target territory, the captured satellite videos exhibit local misalignment and local intensity variation on some stationary objects that can be mistakenly extracted as moving objects and increase false alarm rates. Typical approaches for mitigating the effect of moving cameras in moving object detection (MOD) follow domain transformation technique, where the misalignment between consecutive frames is restricted to the image planar. However, such technique cannot properly handle satellite videos, as the local misalignment on them is caused by the varying projections from the 3D objects on the Earth's surface to 2D image planar. In order to suppress the effect of moving satellite platform in MOD, we propose a Moving-Confidence-Assisted Matrix Decomposition (MCMD) model, where foreground regularization is designed to promote real moving objects and ignore system movements with the assistance of a moving-confidence score estimated from dense optical flows. For solving the convex optimization problem in MCMD, both batch processing and online solutions are developed in this study, by adopting the alternating direction method and the stochastic optimization strategy, respectively. Experimental results on the videos captured by SkySat and Jilin-1 show that MCMD outperforms the state-of-the-art techniques with improved precision by suppressing effect of nonstationary satellite platforms.