Research on Optimization Design of Fully Parameterized Pump-Jet Propulsion

A pump-jet propulsion system is composed of rotor, stator, and duct. The stator has the front stator type and the rear stator type; the conduit also has the acceleration conduit and the deceleration conduit two forms. It is difficult to design and evaluate the performance of a pump-jet propulsion system because of its complex structure and many changes in component parameters. Due to the limitation of time and cost in the design process of the pump-jet propulsion system, it is difficult to find the optimal scheme in the design space. However, under the guidance of an optimization algorithm, the automatic optimization method can fill the design space with a large number of design schemes. In this paper, the geometry reconstruction technique, hydraulic performance evaluation technique and optimization technique of the pump-jet propulsion system are combined to realize the automation of the whole design process. Firstly, the geometric modeling of the pump-jet propulsion system is completed by a full parametric modeling method, and then the hydrodynamic performance of the pump-jet propulsion system is calculated based on the numerical simulation technique. The radial parameters in the fully parametric configuration of the pump-jet propulsion system were selected as the optimization design variables, and the hydro-dynamic performance was optimized as the objective function. Finally, the pump-jet propulsion system optimization design system was constructed by using the global intelligent optimization algorithm. This study provides a theoretical basis and technical guidance for numerical calculation and configuration optimization design of pump-jet propulsion system. View Full-Tex

Acoustofluidic Assembly of 3D Neurospheroids to Model Alzheimer’s Disease

Neuroinflammation plays a central role in the progression of many neurodegenerative diseases such as Alzheimer's disease, and challenges remain in modeling the complex pathological or physiological processes. Here, we report an acoustofluidic method that can rapidly construct 3D neurospheroids and inflammatory microenvironments for modeling microglia-mediated neuroinflammation in Alzheimer's disease. By incorporating a unique contactless and label-free acoustic assembly, this cell culture platform can assemble dissociated embryonic mouse brain cells into hundreds of uniform 3D neurospheroids with controlled cell numbers, composition (e.g. neurons, astrocytes, and microglia), and environmental components (e.g. amyloid-β aggregates) in hydrogel within minutes. Moreover, this platform can maintain and monitor the interaction among neurons, astrocytes, microglia, and amyloid-β aggregates in real-time for several days to weeks, after the integration of a high-throughput, time-lapse cell imaging approach. We demonstrated that our engineered 3D neurospheroids can represent the amyloid-β neurotoxicity, which is one of the main pathological features of Alzheimer's disease. Using this method, we also investigated the microglia migratory behaviors and activation in the engineered 3D inflammatory microenvironment at a high throughput manner, which is not easy to achieve in 2D neuronal cultures or animal models. Along with the simple fabrication and setup, the acoustofluidic technology is compatible with conventional Petri dishes and well-plates, supports the fine-tuning of the cellular and environmental components of 3D neurospheroids, and enables the high-throughput cellular interaction investigation. We believe our technology may be widely used to facilitate 3D in vitro brain models for modeling neurodegenerative diseases, discovering new drugs, and testing neurotoxicity

Ex situ perfusion fixation for brain banking: a technical report

Perfusion fixation is a well-established technique in animal research to improve preservation quality in the study of many tissues, including the brain. There is a growing interest in using perfusion to fix postmortem human brain tissue to achieve the highest fidelity preservation for downstream high-resolution morphomolecular brain mapping studies. Numerous practical barriers arise when applying perfusion fixation in brain banking settings, including the large mass of the organ, degradation of vascular integrity and patency prior to the start of the procedure, and differing investigator goals sometimes necessitating part of the brain to be frozen. As a result, there is a critical need to establish a perfusion fixation procedure in brain banking that is flexible and scalable. This technical report describes our approach to developing an ex situ perfusion fixation protocol. We discuss the challenges encountered and lessons learned while implementing this procedure. Routine morphological staining and RNA in situ hybridization data show that the perfused brains have well-preserved tissue cytoarchitecture and intact biomolecular signal. However, it remains uncertain whether this procedure leads to improved histology quality compared to immersion fixation. Additionally, ex vivo magnetic resonance imaging (MRI) data suggest that the perfusion fixation protocol may introduce imaging artifacts in the form of air bubbles in the vasculature. We conclude with further research directions to investigate the use of perfusion fixation as a rigorous and reproducible alternative to immersion fixation for the preparation of postmortem human brains

Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing

Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons

Prevalent presence of periodic actin-spectrin-based membrane skeleton in a broad range of neuronal cell types and animal species

Actin, spectrin, and associated molecules form a periodic, submembrane cytoskeleton in the axons of neurons. For a better understanding of this membrane-associated periodic skeleton (MPS), it is important to address how prevalent this structure is in different neuronal types, different subcellular compartments, and across different animal species. Here, we investigated the organization of spectrin in a variety of neuronal- and glial-cell types. We observed the presence of MPS in all of the tested neuronal types cultured from mouse central and peripheral nervous systems, including excitatory and inhibitory neurons from several brain regions, as well as sensory and motor neurons. Quantitative analyses show that MPS is preferentially formed in axons in all neuronal types tested here: Spectrin shows a long-range, periodic distribution throughout all axons but appears periodic only in a small fraction of dendrites, typically in the form of isolated patches in subregions of these dendrites. As in dendrites, we also observed patches of periodic spectrin structures in a small fraction of glial-cell processes in four types of glial cells cultured from rodent tissues. Interestingly, despite its strong presence in the axonal shaft, MPS is disrupted in most presynaptic boutons but is present in an appreciable fraction of dendritic spine necks, including some projecting from dendrites where such a periodic structure is not observed in the shaft. Finally, we found that spectrin is capable of adopting a similar periodic organization in neurons of a variety of animal species, including Caenorhabditis elegans, Drosophila, Gallus gallus, Mus musculus, and Homo sapiens

Long-range guidance of spinal commissural axons by netrin1 and sonic hedgehog from midline floor plate cells

An important model for axon pathfinding is provided by guidance of embryonic commissural axons from dorsal spinal cord to ventral midline floor plate (FP). FP cells produce a chemoattractive activity, comprised largely of netrin1 (FP-netrin1) and Sonic hedgehog (Shh), that can attract the axons at a distance in vitro. netrin1 is also produced by ventricular zone (VZ) progenitors along the axons’ route (VZ-netrin1). Recent studies using region-specific netrin1 deletion suggested that FP-netrin1 is dispensable and VZ-netrin1 sufficient for netrin guidance activity in vivo. We show that removing FP-netrin1 actually causes guidance defects in spinal cord consistent with long-range action (i.e., over hundreds of micrometers), and double mutant analysis supports that FP-netrin1 and Shh collaborate to attract at long range. We further provide evidence that netrin1 may guide via chemotaxis or haptotaxis. These results support the model that netrin1 signals at both short and long range to guide commissural axons in spinal cord.Z.W. was supported by the Kavli Neural Systems Institute at The Rockefeller University. S.M. was supported by a Keidanren Ishizaka Memorial Foundation fellowship. S.T. was supported by fellowship funds from the Agency for Science, Technology and Research, Singapore (A∗STAR). N.R. was supported by a post-doctoral fellowship from the Shelby White – Leon Levy Foundation. Work performed in the M.T.-L. laboratory was supported by The Rockefeller University and Stanford University, work performed in the A.C. laboratory was supported by a grant from the Agence Nationale de la Recherche (ANR-14-CE13-0004-01), and work performed in the F.C. laboratory was supported by the Canadian Institutes of Health Research (CIHR FDN334023), the Fonds de Recherche du Québec - Santé (FRQS), and the Canada Foundation for Innovation (CFI 33768). F.C. holds the Canada Research Chair in Developmental Neurobiology.Peer reviewe

Research on ship motion characteristics in a cross sea based on computational fluid dynamics and potential flow theory

ABSTRACTThe motion response of a ship in a cross sea is studied based on computational fluid dynamics. Firstly, according to the established numerical pool, and based on the Reynolds-averaged Navier–Stokes equations and the re-normalisation group K–ϵ turbulence model, the free surface is treated by the volume of fluid(VOF) method, and a numerical simulation method is established. The wave results obtained by the numerical simulation are compared with theoretical waves to verify the reliability of the method. Then, considering the DTMB5415 ship model, a prediction method for the ship’s motion in a cross sea is established by using an overlapping mesh and VOF technology. The influence of a cross sea on ship motion performance under different wave direction angles, different wave heights and for different periods is analyzed. In addition, a method is also established for studying the ship’s motion response based on potential flow theory, and it is found that ships sailing under superimposed waves will exhibit the phenomenon of beat vibration. Finally, by comparing the results obtained by the two methods, the consistency of the two methods is verified, which provides a strong basis for the safety assessment of ships in cross seas

Engineering Heterogeneous Tumor Models for Biomedical Applications

Abstract Tumor tissue engineering holds great promise for replicating the physiological and behavioral characteristics of tumors in vitro. Advances in this field have led to new opportunities for studying the tumor microenvironment and exploring potential anti‐cancer therapeutics. However, the main obstacle to the widespread adoption of tumor models is the poor understanding and insufficient reconstruction of tumor heterogeneity. In this review, the current progress of engineering heterogeneous tumor models is discussed. First, the major components of tumor heterogeneity are summarized, which encompasses various signaling pathways, cell proliferations, and spatial configurations. Then, contemporary approaches are elucidated in tumor engineering that are guided by fundamental principles of tumor biology, and the potential of a bottom‐up approach in tumor engineering is highlighted. Additionally, the characterization approaches and biomedical applications of tumor models are discussed, emphasizing the significant role of engineered tumor models in scientific research and clinical trials. Lastly, the challenges of heterogeneous tumor models in promoting oncology research and tumor therapy are described and key directions for future research are provided

Noninvasive prenatal diagnosis targeting fetal nucleated red blood cells

Abstract Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD. Graphical Abstrac

Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

SUMMARY During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR), and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots