Co-Emergence of Specialized Endothelial Cells from Embryonic Stem Cells.

A well-formed and robust vasculature is critical to the health of most organ systems in the body. However, the endothelial cells (ECs) forming the vasculature can exhibit a number of distinct functional subphenotypes like arterial or venous ECs, as well as angiogenic tip and stalk ECs. In this study, we investigate the in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs). Using our staged induction methods and chemically defined mediums, highly angiogenic EC subpopulations, as well as less proliferative and less migratory EC subpopulations, are derived. Furthermore, the EC subphenotypes exhibit distinct surface markers, gene expression profiles, and positional affinities during sprouting. While both subpopulations contained greater than 80% VE-cad+/CD31+ cells, the tip/stalk-like EC contained predominantly Flt4+/Dll4+/CXCR4+/Flt-1- cells, while the phalanx-like EC was composed of higher numbers of Flt-1+ cells. These studies suggest that the tip-specific EC can be derived in vitro from stem cells as a distinct and relatively stable EC subphenotype without the benefit of its morphological positioning in the sprouting vessel

Divergent Effects of PERK and IRE1 Signaling on Cell Viability

Protein misfolding in the endoplasmic reticulum (ER) activates a set of intracellular signaling pathways, collectively termed the Unfolded Protein Response (UPR). UPR signaling promotes cell survival by reducing misfolded protein levels. If homeostasis cannot be restored, UPR signaling promotes cell death. The molecular basis for the switch between prosurvival and proapoptotic UPR function is poorly understood. The ER-resident proteins, PERK and IRE1, control two key UPR signaling pathways. Protein misfolding concomitantly activates PERK and IRE1 and has clouded insight into their contributions toward life or death cell fates. Here, we employed chemical-genetic strategies to activate individually PERK or IRE1 uncoupled from protein misfolding. We found that sustained PERK signaling impaired cell proliferation and promoted apoptosis. By contrast, equivalent durations of IRE1 signaling enhanced cell proliferation without promoting cell death. These results demonstrate that extended PERK and IRE1 signaling have opposite effects on cell viability. Differential activation of PERK and IRE1 may determine life or death decisions after ER protein misfolding

The Concept and Applications of a Dual Energy Storage Ring

A dual energy electron storage ring configuration is initially proposed as an electron cooler to cool the ion beam in a collider. It consists of two energy loops, the electron beam in the high energy loop undergoes the synchrotron radiation damping to obtain the desired beam property and the beam in the low energy loop is for cooling of the ion beam. The two different energy loops are connected by an energy recovery linac. A lattice design of such a dual energy storage ring has been completed and beam stability conditions are established. We performed numerical simulations to demonstrate the beam qualities and evaluated the cooling performance. In this paper, we present the study results and discuss possible applications of such a concept in many physics research and medical fields

Mandarin Lombard Flavor Classification

The Lombard effect refers to individuals' unconscious modulation of vocal effort in response to variations in the ambient noise levels, intending to enhance speech intelligibility. The impact of different decibel levels and types of background noise on Lombard effects remains unclear. Building upon the characteristic of Lombard speech that individuals adjust their speech to improve intelligibility dynamically based on the self-feedback speech, we propose a flavor classification approach for the Lombard effect. We first collected Mandarin Lombard speech under different noise conditions, then simulated self-feedback speech, and ultimately conducted the statistical test on the word correct rate. We found that both SSN and babble noise types result in four distinct categories of Mandarin Lombard speech in the range of 30 to 80 dBA with different transition points

OFAR: A Multimodal Evidence Retrieval Framework for Illegal Live-streaming Identification

Illegal live-streaming identification, which aims to help live-streaming platforms immediately recognize the illegal behaviors in the live-streaming, such as selling precious and endangered animals, plays a crucial role in purifying the network environment. Traditionally, the live-streaming platform needs to employ some professionals to manually identify the potential illegal live-streaming. Specifically, the professional needs to search for related evidence from a large-scale knowledge database for evaluating whether a given live-streaming clip contains illegal behavior, which is time-consuming and laborious. To address this issue, in this work, we propose a multimodal evidence retrieval system, named OFAR, to facilitate the illegal live-streaming identification. OFAR consists of three modules: Query Encoder, Document Encoder, and MaxSim-based Contrastive Late Intersection. Both query encoder and document encoder are implemented with the advanced OFA encoder, which is pretrained on a large-scale multimodal dataset. In the last module, we introduce contrastive learning on the basis of the MaxiSim-based late intersection, to enhance the model's ability of query-document matching. The proposed framework achieves significant improvement on our industrial dataset TaoLive, demonstrating the advances of our scheme

EMALG: An Enhanced Mandarin Lombard Grid Corpus with Meaningful Sentences

This study investigates the Lombard effect, where individuals adapt their speech in noisy environments. We introduce an enhanced Mandarin Lombard grid (EMALG) corpus with meaningful sentences , enhancing the Mandarin Lombard grid (MALG) corpus. EMALG features 34 speakers and improves recording setups, addressing challenges faced by MALG with nonsense sentences. Our findings reveal that in Mandarin, female exhibit a more pronounced Lombard effect than male, particularly when uttering meaningful sentences. Additionally, we uncover that nonsense sentences negatively impact Lombard effect analysis. Moreover, our results reaffirm the consistency in the Lombard effect comparison between English and Mandarin found in previous research

A comparative study of Grid and Natural sentences effects on Normal-to-Lombard conversion

Grid sentence is commonly used for studying the Lombard effect and Normal-to-Lombard conversion. However, it's unclear if Normal-to-Lombard models trained on grid sentences are sufficient for improving natural speech intelligibility in real-world applications. This paper presents the recording of a parallel Lombard corpus (called Lombard Chinese TIMIT, LCT) extracting natural sentences from Chinese TIMIT. Then We compare natural and grid sentences in terms of Lombard effect and Normal-to-Lombard conversion using LCT and Enhanced MAndarin Lombard Grid corpus (EMALG). Through a parametric analysis of the Lombard effect, We find that as the noise level increases, both natural sentences and grid sentences exhibit similar changes in parameters, but in terms of the increase of the alpha ratio, grid sentences show a greater increase. Following a subjective intelligibility assessment across genders and Signal-to-Noise Ratios, the StarGAN model trained on EMALG consistently outperforms the model trained on LCT in terms of improving intelligibility. This superior performance may be attributed to EMALG's larger alpha ratio increase from normal to Lombard speech

A power-flow emulator approach for resilience assessment of repairable power grids subject to weather-induced failures and data deficiency

A generalised uncertainty quantification framework for resilience assessment of weather-coupled, repairable power grids is presented. The framework can be used to efficiently quantify both epistemic and aleatory uncertainty affecting grid-related and weather-related factors. The power grid simulator has been specifically designed to model interactions between severe weather conditions and grid dynamic states and behaviours, such as weather-induced failures or delays in components replacements. A resilience index is computed by adopting a novel algorithm which exploits a vectorised emulator of the power-flow solver to reduce the computational efforts. The resilience stochastic modelling framework is embedded into a non-intrusive generalised stochastic framework, which enables the analyst to quantify the effect of parameters imprecision. A modified version of the IEEE 24 nodes reliability test system has been used as representative case study. The surrogate-based model and the Power-Flow-based model are compared, and the results show similar accuracy but enhanced efficiency of the former. Global sensitivity of the resilience index to increasing imprecision in parameters of the probabilistic model has been analysed. The relevance of specific weather/grid uncertain factors is highlighted by global sensitivity analysis and the importance of dealing with imprecision in the information clearly emerges

Nuclear Factor Erythroid 2-Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates multiple biologic processes, including hepatic lipid metabolism. Estrogen exerts actions affecting energy homeostasis, including a liver fat-lowering effect. Increasing evidence indicates the crosstalk between these two molecules. The aim of this study was to evaluate whether Nrf2 modulates estrogen signaling in hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) was induced in wild-type and Nrf2-null mice fed a high-fat diet and the liver fat-lowering effect of exogenous estrogen was subsequently assessed. We found that exogenous estrogen eliminated 49% and 90% of hepatic triglycerides in wild-type and Nrf2-null mice with NAFLD, respectively. This observation demonstrates that Nrf2 signaling is antagonistic to estrogen signaling in hepatic fat metabolism; thus, Nrf2 absence results in striking amplification of the liver fat-lowering effect of estrogen. In addition, we found the association of trefoil factor 3 and fatty acid binding protein 5 with the liver fat-lowering effect of estrogen. In summary, we identified Nrf2 as a novel and potent inhibitor of estrogen signaling in hepatic lipid metabolism. Our finding may provide a potential strategy to treat NAFLD by dually targeting Nrf2 and estrogen signaling

Design of the Proposed Low Energy Ion Collider Ring at Jefferson Lab

The polarized Medium energy Electron-Ion Collider (MEIC) envisioned at Jefferson Lab will cover a range of center-of-mass energies up to 65 GeV. The present MEIC design could also allow the accommodation of low energy electron-ion collisions (LEIC) for additional science reach. This paper presents the first design of the low energy ion collider ring which is converted from the large ion booster of MEIC. It can reach up to 25 GeV energy for protons and equivalent ion energies of the same magnetic rigidity. An interaction region and an electron cooler designed for MEIC are integrated into the low energy collider ring, in addition to other required new elements including crab cavities and ion spin rotators, for later reuse in MEIC itself. A pair of vertical chicanes which brings the low energy ion beams to the plane of the electron ring and back to the low energy ion ring are also part of the design