Nesterov smoothing for sampling without smoothness

We study the problem of sampling from a target distribution in $\mathbb{R}^d$ whose potential is not smooth. Compared with the sampling problem with smooth potentials, this problem is much less well-understood due to the lack of smoothness. In this paper, we propose a novel sampling algorithm for a class of non-smooth potentials by first approximating them by smooth potentials using a technique that is akin to Nesterov smoothing. We then utilize sampling algorithms on the smooth potentials to generate approximate samples from the original non-smooth potentials. We select an appropriate smoothing intensity to ensure that the distance between the smoothed and un-smoothed distributions is minimal, thereby guaranteeing the algorithm's accuracy. Hence we obtain non-asymptotic convergence results based on existing analysis of smooth sampling. We verify our convergence result on a synthetic example and apply our method to improve the worst-case performance of Bayesian inference on a real-world example

Expression, Purification and Activity Study of Amuc_1100

Objective: To construct prokaryotic expression vector of Amuc_1100 gene, the ELP (ELSTIN-LIKE PROTEIN) is used as purification label to express fusion with the target protein and detect the biological activity of recombinant protein at cell level and animal level. Methods: the recombinant plasmid pET28a-Amuc_1100-ELP is designed and synthesized, and transformed into e. coli competent cell bl21 (de3) to induce expression. The recombinant egg was isolated and purified by the reversible phase change cycling (ITC) characteristic of ELP10 white. At the cellular level, PBMCs cells from mice were extracted to detect the expression level of IL-10. At the animal level, obese mice induced by gastric gavage with high fat detected the improvement effect of the protein on mouse metabolism. Results: The recombinant protein with the expected molecular weight of 60 kDa was expressed by E.coli expression system. After circulating through ITC, the recombinant protein with high purity was obtained. The protein increased the expression level of IL-10 in PBMCs cells, and significantly improved the obesity and metabolic disorders induced by high-fat diet in mice. Conclusion: The recombinant protein expression plasmid pET28a-Amuc_1100-ELP was successfully constructed. After expression and purification, the recombinant protein expression plasmid has high purity and has 15 biologically active recombinant protein. This study laid a foundation for the industrial production and clinical application of Amuc_1100

Metamemory judgments have dissociable reactivity effects on item and interitem relational memory

Making metamemory judgments reactively changes item memory itself. Here we report the first investigation of reactive influences of making judgments of learning (JOLs) on interitem relational memory-specifically, temporal (serial) order memory. Experiment 1 found that making JOLs impaired order reconstruction. Experiment 2 observed minimal reactivity on free recall and negative reactivity on temporal clustering. Experiment 3 demonstrated a positive reactivity effect on recognition memory, and Experiment 4 detected dissociable effects of making JOLs on order reconstruction (negative) and forced-choice recognition (positive) by using the same participants and stimuli. Finally, a meta-analysis was conducted to explore reactivity effects on word list learning and to investigate whether test format moderates these effects. The results show a negative reactivity effect on interitem relational memory (order reconstruction), a modest positive effect on free recall, and a medium-to-large positive effect on recognition. Overall, these findings imply that even though making metacognitive judgments facilitates item-specific processing, it disrupts relational processing, supporting the item-order account of the reactivity effect on word list learning. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

A Novel Iron Transporter SPD_1590 in Streptococcus pneumoniae Contributing to Bacterial Virulence Properties

Streptococcus pneumoniae, a Gram-positive human pathogen, has evolved three main transporters for iron acquisition from the host: PiaABC, PiuABC, and PitABC. Our previous study had shown that the mRNA and protein levels of SPD_1590 are significantly upregulated in the ΔpiuA/ΔpiaA/ΔpitA triple mutant, suggesting that SPD_1590 might be a novel iron transporter in S. pneumoniae. In the present study, using spd1590-knockout, -complemented, and -overexpressing strains and the purified SPD_1590 protein, we show that SPD_1590 can bind hemin, probably supplementing the function of PiuABC, to provide the iron necessary for the bacterium. Furthermore, the results of iTRAQ quantitative proteomics and cell-infection studies demonstrate that, similarly to other metal-ion uptake proteins, SPD_1590 is important for bacterial virulence properties. Overall, these results provide a better understanding of the biology of this clinically important bacterium

The accuracy of soluble urokinase-type plasminogen activator receptor for the diagnosis of neonatal sepsis: a meta-analysis

BackgroundNeonatal sepsis is one of the major causes of morbidity and mortality in newborns. However, atypical clinical manifestations and symptoms make the early diagnosis of neonatal sepsis a challenge. Relatively high-serum soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated as a diagnostic biomarker for adult sepsis. Therefore, the meta-analysis is intended to explore the diagnostic value of suPAR for neonatal sepsis.MethodsThe PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, China Biological Medicine Disk, and Wanfang databases were retrieved from inception to 31 December 2022 to collect diagnostic accuracy studies about suPAR for neonatal sepsis. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies using the quality assessment of diagnostic accuracy studies-2 (QUADAS-2) tool. Then, a meta-analysis was performed using Stata 15.0 software.ResultsA total of six articles involving eight studies were included. The results of the meta-analysis showed that the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.89 [95%CI (0.83–0.93)], 0.94 [95%CI (0.77–0.98)], 14 [95%CI (3.5–55.2)], 0.12 [95%CI (0.08–0.18)], and 117 [95%CI (24–567)], respectively. The area under the curve (AUC) of summary receiver operator characteristic (SROC) curves was 0.92 [95%CI (0.90–0.94)]. Sensitivity analysis confirmed the stability of the results, and publication bias was not observed. Fagan’s nomogram results demonstrated the clinical availability of the findings.ConclusionCurrent evidence suggests that suPAR has potential diagnostic value for neonatal sepsis. Owing to the limited quality of the included studies, more high-quality studies are needed to verify the above conclusion

HBV infection-induced liver cirrhosis development in dual-humanized mice with human bone mesenchymal stem cell transplantation

疾病动物模型是现代医学发展的基石，尤其是重大、突发传染病暴发时，适宜的疾病动物模型可为及时发现病原体、制定防控策略提供强大保障，原创的疾病动物模型已成为衡量一个国家生物医药科研水平的标志。我校夏宁邵教授团队和浙江大学附属第一医院李君教授团队历经5年的协同攻关，终于建立了国际上首个高度模拟人类乙肝病毒（HBV）自然感染诱发的慢乙肝肝硬化小鼠模型。厦门大学公共卫生学院袁伦志博士生、浙江大学医学院附属第一医院江静博士和厦门大学公共卫生学院刘旋博士生为该论文共同第一作者。厦门大学夏宁邵教授、浙江大学附属第一医院李君教授和厦门大学程通副教授为该论文共同通讯作者。【Abstract】Objective： Developing a small animal model that accurately delineates the natural history of hepatitis B virus (HBV) infection and immunopathophysiology is necessary to clarify the mechanisms of host-virus interactions and to identify intervention strategies for HBV-related liver diseases. This study aimed to develop an HBV-induced chronic hepatitis and cirrhosis mouse model through transplantation of human bone marrow mesenchymal stem cells (hBMSCs). Design： Transplantation of hBMSCs into Fah -/- Rag2 -/- IL-2Rγc -/- SCID (FRGS) mice with fulminant hepatic failure (FHF) induced by hamster-anti-mouse CD95 antibody JO2 generated a liver and immune cell dual-humanized (hBMSC-FRGS) mouse. The generated hBMSC-FRGS mice were subjected to assessments of sustained viremia, specific immune and inflammatory responses and liver pathophysiological injury to characterize the progression of chronic hepatitis and cirrhosis after HBV infection. Results： The implantation of hBMSCs rescued FHF mice, as demonstrated by robust proliferation and transdifferentiation of functional human hepatocytes and multiple immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and immune cell lineages, including B cells, T cells, NK cells, dendritic cells (DCs) and viremia and specific immune and inflammatory responses and showed progression to chronic hepatitis and liver cirrhosis at a frequency of 55% after 54 weeks. Conclusion： This new humanized mouse model recapitulates the liver cirrhosis induced by human HBV infection, thus providing research opportunities for understanding viral immune pathophysiology and testing antiviral therapies in vivo.this work was supported by the national Science and technology Major Project (grant nos. 2017ZX10304402, 2017ZX10203201 and 2018ZX09711003-005-003), the national natural Science Foundation of china(grant nos. 81672023, 81571818 and 81771996), the Scientific research Foundation of the State Key laboratory of Molecular Vaccinology and Molecular Diagnostics (grant no 2016ZY005), Zhejiang Province and State's Key Project of the research and Development Plan of china (grant nos 2017c01026 and 2016YFc1101304/3).该研究获得了传染病防治国家科技重大专项、新药创制国家科技重大专项和国家自然科学基金的资助