Paradise Lost: Astronomy, Scepticism, Perspective

Recent breakthroughs in Milton studies have demonstrated that the cosmological frame of Paradise Lost is not the Ptolemaic cosmos but most likely the infinite multiverse, and critics were wrong to think that Milton had chosen the geocentric model to accommodate his Christian epic. My thesis builds on this new understanding of Milton’s cosmology and re-examines three interpretational problems in Paradise Lost. Two of them are from the astronomical dialogue in book eight: God’s derisive laughter at astronomers who endeavor to “save appearances” and Raphael’s admonishment to Adam that he “be lowly wise.” The third concerns a group of Milton’s epic similes with added human perspectives. The most famous is the careful ploughman simile in book four. My general argument is that Milton’s epistemological scepticism, rooted in his infinitist cosmology, is our key to understand all three interpretational problems. In this thesis I connect Milton to Nicholas of Cusa and Michel de Montaigne, but distinguish him from Francis Bacon. The body of the thesis includes four chapters. Chapter one places Raphael’s astronomical talk in the context of early modern debates between sceptics and realists on the nature of astronomy as a science that “saves appearances.” Chapter two shows that Cusanus is our best guide to understand Milton’s epistemological scepticism. Chapter three reads Raphael’s “be lowly wise” as a well-deliberated solution to the problem between reason and faith in Milton’s time. Chapter four interprets the epic similes with added human beings in light of Milton’s own discussion of similitude in the Art of Logic

Unified Chinese License Plate Detection and Recognition with High Efficiency

Recently, deep learning-based methods have reached an excellent performance on License Plate (LP) detection and recognition tasks. However, it is still challenging to build a robust model for Chinese LPs since there are not enough large and representative datasets. In this work, we propose a new dataset named Chinese Road Plate Dataset (CRPD) that contains multi-objective Chinese LP images as a supplement to the existing public benchmarks. The images are mainly captured with electronic monitoring systems with detailed annotations. To our knowledge, CRPD is the largest public multi-objective Chinese LP dataset with annotations of vertices. With CRPD, a unified detection and recognition network with high efficiency is presented as the baseline. The network is end-to-end trainable with totally real-time inference efficiency (30 fps with 640p). The experiments on several public benchmarks demonstrate that our method has reached competitive performance. The code and dataset will be publicly available at https://github.com/yxgong0/CRPD

Bluetongue virus capsid protein VP5 perforates membranes at low endosomal pH during viral entry.

Bluetongue virus (BTV) is a non-enveloped virus and causes substantial morbidity and mortality in ruminants such as sheep. Fashioning a receptor-binding protein (VP2) and a membrane penetration protein (VP5) on the surface, BTV releases its genome-containing core (VP3 and VP7) into the host cell cytosol after perforation of the endosomal membrane. Unlike enveloped ones, the entry mechanisms of non-enveloped viruses into host cells remain poorly understood. Here we applied single-particle cryo-electron microscopy, cryo-electron tomography and structure-guided functional assays to characterize intermediate states of BTV cell entry in endosomes. Four structures of BTV at the resolution range of 3.4-3.9 Å show the different stages of structural rearrangement of capsid proteins on exposure to low pH, including conformational changes of VP5, stepwise detachment of VP2 and a small shift of VP7. In detail, sensing of the low-pH condition by the VP5 anchor domain triggers three major VP5 actions: projecting the hidden dagger domain, converting a surface loop to a protonated β-hairpin that anchors VP5 to the core and stepwise refolding of the unfurling domains into a six-helix stalk. Cryo-electron tomography structures of BTV interacting with liposomes show a length decrease of the VP5 stalk from 19.5 to 15.5 nm after its insertion into the membrane. Our structures, functional assays and structure-guided mutagenesis experiments combined indicate that this stalk, along with dagger domain and the WHXL motif, creates a single pore through the endosomal membrane that enables the viral core to enter the cytosol. Our study unveils the detailed mechanisms of BTV membrane penetration and showcases general methods to study cell entry of other non-enveloped viruses

Game and Balance Multicast Architecture Algorithms for Sensor Grid

We propose a scheme to attain shorter multicast delay and higher efficiency in the data transfer of sensor grid. Our scheme, in one cluster, seeks the central node, calculates the space and the data weight vectors. Then we try to find a new vector composed by linear combination of the two old ones. We use the equal correlation coefficient between the new and old vectors to find the point of game and balance of the space and data factorsbuild a binary simple equation, seek linear parameters, and generate a least weight path tree. We handled the issue from a quantitative way instead of a qualitative way. Based on this idea, we considered the scheme from both the space and data factor, then we built the mathematic model, set up game and balance relationship and finally resolved the linear indexes, according to which we improved the transmission efficiency of sensor grid. Extended simulation results indicate that our scheme attains less average multicast delay and number of links used compared with other well-known existing schemes

Empagliflozin inhibits coronary microvascular dysfunction and reduces cardiac pericyte loss in db/db mice

BackgroundCoronary microvascular dysfunction (CMD) is a pathophysiological feature of diabetic heart disease. However, whether sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the cardiovascular system by alleviating CMD is not known.ObjectiveWe observed the protective effects of empagliflozin (EMPA) on diabetic CMD.Materials and methodsThe mice were randomly divided into a db/db group and a db/db + EMPA group, and db/m mice served as controls. At 8 weeks of age, the db/db + EMPA group was given empagliflozin 10 mg/(kg⋅d) by gavage for 8 weeks. Body weight, fasting blood glucose and blood pressure were dynamically observed. Cardiac systolic and diastolic function and coronary flow reserve (CFR) were detected using echocardiography. The coronary microvascular structure and distribution of cardiac pericytes were observed using immunofluorescence staining. Picrosirius red staining was performed to evaluate cardiac fibrosis.ResultsEmpagliflozin lowered the increased fasting blood glucose levels of the db/db group. The left ventricular ejection fraction, left ventricular fractional shortening, E/A ratio and E/e′ ratio were not significantly different between the three groups. CFR was decreased in the db/db group, but EMPA significantly improved CFR. In contrast to the sparse and abnormal expansion of coronary microvessels observed in the db/db group, the number of coronary microvessels was increased, and the capillary diameter was decreased in the db/db + EMPA group. The number and microvascular coverage of cardiac pericytes were reduced in the db/db mice but were improved by EMPA. The cardiac fibrosis was increased in db/db group and may alleviate by EMPA.ConclusionEmpagliflozin inhibited CMD and reduced cardiac pericyte loss in diabetic mice

Salvianolic acid B plays an anti-obesity role in high fat diet-induced obese mice by regulating the expression of mRNA, circRNA, and lncRNA

Background Adipose tissue plays a central role in obesity-related metabolic diseases such as type 2 diabetes. Salvianolic acid B (Sal B), a water-soluble ingredient derived from Salvia miltiorrhiza, has been shown to reduce obesity and obesity-related metabolic diseases by suppressing adipogenesis. However, the role of Sal B in white adipose tissue (WAT) is not yet clear. Methods Illumina Hiseq 4000 was used to study the effects of Sal B on the expression of long non-coding RNA (lncRNA) and circular RNA (circRNA) in epididymal white adipose tissue induced by a high fat diet in obese mice. Results RNA-Seq data showed that 234 lncRNAs, 19 circRNAs, and 132 mRNAs were differentially expressed in WAT under Sal B treatment. The up-regulated protein-coding genes in WAT of the Sal B-treated group were involved in the insulin resistance pathway, while the down-regulated genes mainly participated in the IL-17 signaling pathway. Other pathways may play an important role in the formation and differentiation of adipose tissue, such as B cell receptor signaling. Analysis of the lncRNA–mRNA network provides potential targets for lncRNAs in energy metabolism. We speculate that Sal B may serve as a potential therapeutic approach for obesity

Dynamics of ammonia oxidizers and denitrifiers in response to compost addition in black soil, Northeast China

Organic fertilizer application could have an impact on the nitrogen cycle mediated by microorganisms in arable soils. However, the dynamics of soil ammonia oxidizers and denitrifiers in response to compost addition are less understood. In this study, we examined the effect of four compost application rates (0, 11.25, 22.5 and 45 t/ha) on soil ammonia oxidizers and denitrifiers at soybean seedling, flowering and mature stage in a field experiment in Northeast China. As revealed by quantitative PCR, compost addition significantly enhanced the abundance of ammonia oxidizing bacteria (AOB) at seedling stage, while the abundance of ammonia oxidizing archaea was unaffected across the growing season. The abundance of genes involved in denitrification (nirS, nirK and nosZ) were generally increased along with compost rate at seedling and flowering stages, but not in mature stage. The non-metric multidimensional scaling analysis revealed that moderate and high level of compost addition consistently induced shift in AOB and nirS containing denitrifers community composition across the growing season. Among AOB lineages, Nitrosospira cluster 3a gradually decreased along with the compost rate across the growing season, while Nitrosomonas exhibited an opposite trend. Network analysis indicated that the complexity of AOB and nirS containing denitrifiers network gradually increased along with the compost rate. Our findings highlighted the positive effect of compost addition on the abundance of ammonia oxidizers and denitrifiers and emphasized that compost addition play crucial roles in shaping their community compositions and co-occurrence networks in black soil of Northeast China

Aberrant Dynamic Functional Connectivity of Posterior Cingulate Cortex Subregions in Major Depressive Disorder With Suicidal Ideation

Accumulating evidence indicates the presence of structural and functional abnormalities of the posterior cingulate cortex (PCC) in patients with major depressive disorder (MDD) with suicidal ideation (SI). Nevertheless, the subregional-level dynamic functional connectivity (dFC) of the PCC has not been investigated in MDD with SI. We therefore sought to investigate the presence of aberrant dFC variability in PCC subregions in MDD patients with SI. We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 31 unmedicated MDD patients with SI (SI group), 56 unmedicated MDD patients without SI (NSI group), and 48 matched healthy control (HC) subjects. The sliding-window method was applied to characterize the whole-brain dFC of each PCC subregion [the ventral PCC (vPCC) and dorsal PCC (dPCC)]. In addition, we evaluated associations between clinical variables and the aberrant dFC variability of those brain regions showing significant between-group differences. Compared with HCS, the SI and the NSI groups exhibited higher dFC variability between the left dPCC and left fusiform gyrus and between the right vPCC and left inferior frontal gyrus (IFG). The SI group showed higher dFC variability between the left vPCC and left IFG than the NSI group. Furthermore, the dFC variability between the left vPCC and left IFG was positively correlated with Scale for Suicidal Ideation (SSI) score in patients with MDD (i.e., the SI and NSI groups). Our results indicate that aberrant dFC variability between the vPCC and IFG might provide a neural-network explanation for SI and may provide a potential target for future therapeutic interventions in MDD patients with SI