Technical variation in feature measurements, such as gene expression and locus accessibility, is a key challenge of large-scale single-cell genomic datasets. We show that this technical variation in ...both scRNA-seq and scATAC-seq datasets can be mitigated by analyzing feature detection patterns alone and ignoring feature quantification measurements. This result holds when datasets have low detection noise relative to quantification noise. We demonstrate state-of-the-art performance of detection pattern models using our new framework, scBFA, for both cell type identification and trajectory inference. Performance gains can also be realized in one line of R code in existing pipelines.
Neural networks such as variational autoencoders (VAE) perform dimensionality reduction for the visualization and analysis of genomic data, but are limited in their interpretability: it is unknown ...which data features are represented by each embedding dimension. We present siVAE, a VAE that is interpretable by design, thereby enhancing downstream analysis tasks. Through interpretation, siVAE also identifies gene modules and hubs without explicit gene network inference. We use siVAE to identify gene modules whose connectivity is associated with diverse phenotypes such as iPSC neuronal differentiation efficiency and dementia, showcasing the wide applicability of interpretable generative models for genomic data analysis.
Secondary lymphoid organs (SLOs) are an important target for mRNA delivery in various applications. While the current delivery method relies on the drainage of nanoparticles to lymph nodes by ...intramuscular (IM) or subcutaneous (SC) injections, an efficient mRNA delivery carrier for SLOs-targeting delivery by systemic administration (IV) is highly desirable but yet to be available. In this study, we developed an efficient SLOs-targeting carrier using phosphatidylserine (PS), a well-known signaling molecule that promotes the endocytic activity of phagocytes and cellular entry of enveloped viruses. We adopted these biomimetic strategies and added PS into the standard four-component MC3-based LNP formulation (PS-LNP) to facilitate the cellular uptake of immune cells beyond the charge-driven targeting principle commonly used today. As a result, PS-LNP performed efficient protein expression in both lymph nodes and the spleen after IV administration. In vitro and in vivo characterizations on PS-LNP demonstrated a monocyte/macrophage-mediated SLOs-targeting delivery mechanism.
Pufferfish swim and maneuver with a multi-fin system including dorsal, anal, caudal, and pectoral fins, which presents sophisticated ventures in biomimetic designs of underwater vehicles. ...Distinguished from those ‘typical’ fish with streamlined body shape and body-caudal fin (BCF) undulations, pufferfish adopt non-streamlined plump body shape and rely on the oscillations and interplay of fins to achieve high performance maneuvering. Aiming at unveiling novel mechanisms associated with multi-fin kinematics and hydrodynamic performance in pufferfish swimming, we carried out an integrated study by combining measurement and digitizing of multi-fin kinematics and three-dimensional deformations and computational fluid dynamic (CFD) modeling of steady swimming. We constructed a realistic multi-fin kinematic model to mimic motions and deformations of the dorsal, anal, and caudal fins. We further built up a CFD model of the pufferfish with a realistic body and multi-fin geometry to evaluate the hydrodynamic performance of its multi-fin system. Our results demonstrate that in pufferfish steady swimming, caudal, dorsal and anal fin rays oscillate while performing significantly passive bending and twist deformations but show a noticeable out-of-phase feature, leading to neutralizing rotational forces and hence suppressing yaw motion, particularly at fast swimming. Numerical simulation suggests that the caudal median fin plays a key role in thrust generation while the dorsal and anal fins also provide a considerable contribution.
•Pufferfish swim andmaneuver with a multi-fin system including dorsal, anal, caudal, and pectoralfins.•We carried out anintegrated study of measurement and digitizing of multi-fin kinematics and 3Ddeformations and CFD modeling of steady swimming•Our results indicate that caudal, dorsal and anal fin rays oscillatewith passive deformations, capable of sustaining stable fast swimming.•The caudal median fin plays a key role in thrust generation whilethe dorsal and anal fins also provide a considerable contribution.
Peanut (Arachis hypogaea), a vital oil and food crop globally, is susceptible to web blotch which is a significant foliar disease caused by Phoma arachidicola Marasas Pauer&Boerema leading to ...substantial yield losses in peanut production. Calcium treatment has been found to enhance plant resistance against pathogens. This study investigates the impact of exogenous calcium on peanut resistance to web blotch and explores its mechanisms. Greenhouse experiments revealed that exogenous calcium treatment effectively enhanced resistance to peanut web blotch. Specifically, amino acid calcium and sugar alcohol calcium solutions demonstrated the best induced resistance effects, achieving reduction rates of 61.54% and 60% in Baisha1016, and 53.94% and 50% in Luhua11, respectively. All exogenous calcium treatments reduced malondialdehyde (MDA) and relative electrical conductivity (REC) levels in peanut leaves, mitigating pathogen-induced cell membrane damage. Exogenous calcium supplementation led to elevated hydrogen peroxide (H.sub.2O.sub.2) content and superoxide anion (O.sub.2.sup.*-) production in peanut leaves, facilitating the accumulation of reactive oxygen species (ROS) crucial for plant defense responses. Amino acid calcium and sugar alcohol calcium treatments significantly boosted activities of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) in peanut leaves. Activation of these antioxidant enzymes effectively scavenged excess ROS, maintaining ROS balance and mitigating cellular damage. In summary, exogenous calcium treatment triggered ROS production, which was subsequently eliminated by the activation of antioxidant enzymes, thereby reducing cell membrane damage and inducing defense responses against peanut web blotch.
Although therapies of cancer are advancing, it remains challenging for therapeutics to reach the sites of metastasis, which accounts for majority of cancer associated death. In this study, we have ...developed a strategy that guides an anti-programmed cell death-ligand 1 (aPDL1) antibody to accumulate in metastatic lesions to promote anti-tumour immune responses. Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects.
Progress in atomic fountains at LNE-SYRTE Guena, J.; Abgrall, M.; Rovera, D. ...
IEEE transactions on ultrasonics, ferroelectrics, and frequency control,
03/2012, Volume:
59, Issue:
3
Journal Article, Conference Proceeding
Peer reviewed
We give an overview of the work done with the Laboratoire National de Metrologie et d'Essais-Systemes de Reference Temps-Espace (LNE-SYRTE) fountain ensemble during the last five years. After a ...description of the clock ensemble, comprising three fountains, FO1, FO2, and FOM, and the newest developments, we review recent studies of several systematic frequency shifts. This includes the distributed cavity phase shift, which we evaluate for the FO1 and FOM fountains, applying the techniques of our recent work on FO2. We also report calculations of the microwave lensing frequency shift for the three fountains, review the status of the blackbody radiation shift, and summarize recent experimental work to control microwave leakage and spurious phase perturbations. We give current accuracy budgets. We also describe several applications in time and frequency metrology: fountain comparisons, calibrations of the international atomic time, secondary representation of the SI second based on the 87 Rb hyperfine frequency, absolute measurements of optical frequencies, tests of the T2L2 satellite laser link, and review fundamental physics applications of the LNE-SYRTE fountain ensemble. Finally, we give a summary of the tests of the PHARAO cold atom space clock performed using the FOM transportable fountain.
Liquid metals show unparalleled advantages in printable circuits, flexible wear, drug carriers, and electromagnetic shielding. However, the efficient and large-scale preparation of liquid metal ...nanodroplets (LM NDs) remains a significant challenge. Here, we propose a simple and efficient method for the large-scale preparation of stable eutectic gallium indium nanodroplets (EGaIn NDs). We compared different preparation methods and found that droplets with smaller particle sizes could quickly be produced using a shaking technique. The size of EGaIn NDs produced using this technique can reach 200 nm in 30 min and 100 nm in 240 min. Benefiting from the simple method, various surfactants can directly modify the surface of the EGaIn NDs to stabilize the prepared droplets. In addition, we discovered that shaking in an ice bath produced spherical nanodroplets, and after shaking for 30 min in a non-ice bath, rod-shaped gallium oxide hydroxide (GaOOH) appeared. Furthermore, the EGaIn NDs we produced have excellent stability—after storage at room temperature for 30 days, the particle size and morphology change little. The excellent stability of the produced EGaIn NDs provides a wider application of liquid metals in the fields of drug delivery, electromagnetic shielding, conductive inks, printed circuits, etc.
Energy performance contracting (EPC) as a market instrument has been effective in promoting energy efficiency worldwide, but it has encountered many insurmountable obstacles in rural energy ...management. In this study, based on the characteristics of energy management in rural areas, three EPC modes are designed and tested in 24,000 rural households. The test results show that two adapted EPC modes of local government involvement and energy payment directly from the national grid can effectively overcome the barriers encountered in the traditional EPC modes and work well under the economic and social environmental conditions in rural areas. The key to the adaptation of the traditional EPC modes is the introduction of the local government as the third party. Participation of the third party can effectively reduce and remove the barriers and risks and increase the mutual trust between the clients (households) and the energy service companies (ESCOs). Based on the testing results, this study suggests that governmental departments should formulate relevant EPC policies and technical guidelines within the rural context. This research recommends that farmers should not manage their energy services by themselves and it is suggested to out-contracting ESCOs by applying the modes developed and tested by this paper.
•Adapted EPC modes are well-functioning within the rural context.•Participation of local authorities can overcome EPC barriers in rural energy management.•EPC in rural energy management is mainly driven by policies in China.•Participation of a third party can overcome barriers to EPC projects.
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