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Register a new userSimulations of particle tracking in the oligociliated mouse node and implications for left-right symmetry breaking mechanics
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The concept of internal anatomical asymmetry is familiar; usually in humans the heart is on the left and the liver is on the right, however how does the developing embryo know to produce this consistent laterality? Symmetry breaking initiates with left-right asymmetric cilia-driven fluid mechanics in a small fluid-filled structure called the ventral node in mice. However the question of what converts this flow into left-right asymmetric development remains unanswered. A leading hypotheses is that flow transports morphogen containing vesicles within the node, the absorption of which results in asymmetrical gene expression. To investigate how vesicle transport might result in the situs patterns observed in wildtype and mutant experiments, we extend the open source Stokes flow package, NEAREST, to consider the hydrodynamic and Brownian motion of particles in a mouse model with flow driven by one, two, and 112 beating cilia. Three models for morphogen-containing particle released are simulated to assess their compatibility with observed results in oligociliated and wildtype mouse embryos: uniformly random release, localised cilium stress induced release, and localised release from motile cilia themselves. Only the uniformly random release model appears consistent with the data, with neither localised-release model resulting in significant transport in the oligociliated embryo.
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Recent 3D organ reconstitution studies show that a group of stem cells can establish a body axis and acquire different fates in a spatially organized manner. How such symmetry breaking happens in the absence of external spatial cues, and how developmental circuits are built to permit this is largely unknown. Here, we review spontaneous symmetry breaking phenomena in organoids, and hypothesize underlying patterning mechanisms that involve interacting diffusible species. Recent theoretical advances offer new directions beyond the prototypical Turing model. Experiments guided by theory will allow us to predict and control organoid self-organization.
Thromboembolic complications remain a central issue in management of patients on mechanical circulatory support. Despite the best practices employed in design and manufacturing of modern ventricular assist devices, complexity and modular nature of these systems often introduces internal steps and crevices in the flow path which can serve as nidus for thrombus formation. Thrombotic potential is influenced by multiple factors including the characteristics of the flow and surface chemistry of the biomaterial. This study explored these elements in the setting of blood flow over a micro-crevice using a multi-constituent numerical model of thrombosis. The simulations reproduced the platelet deposition patterns observed experimentally and elucidated the role of flow, shear rate, and surface chemistry in shaping the deposition. The results offer insights for design and operation of blood-contacting devices.
We derive analytic necessary and sufficient conditions for the vacuum stability of the left-right symmetric model by using the concepts of copositivity and gauge orbit spaces. We also derive the conditions sufficient for successful symmetry breaking and the existence of a correct vacuum. We then compare results obtained from the derived conditions with those from numerical minimization of the scalar potential. Finally, we discuss the renormalization group analysis of the scalar quartic couplings through an example study that satisfies vacuum stability, perturbativity, unitarity and experimental bounds on the physical scalar masses.
Left-right symmetry at high energy scales is a well-motivated extension of the Standard Model. In this paper we consider a typical minimal scenario in which it gets spontaneously broken by scalar triplets. Such a realization has been scrutinized over the past few decades chiefly in the context of collider studies. In this work we take a complementary approach and investigate whether the model can be probed via the search for a stochastic gravitational wave background induced by the phase transition in which $SU(3)_C times SU(2)_L times SU(2)_R times U(1)_{B-L}$ is broken down to the Standard Model gauge symmetry group. A prerequisite for gravitational wave production in this context is a first-order phase transition, the occurrence of which we find in a significant portion of the parameter space. Although the produced gravitational waves are typically too weak for a discovery at any current or future detector, upon investigating correlations between all relevant terms in the scalar potential, we have identified values of parameters leading to observable signals. This indicates that, given a certain moderate fine-tuning, the minimal left-right symmetric model with scalar triplets features another powerful probe which can lead to either novel constraints or remarkable discoveries in the near future. Let us note that some of our results, such as the full set of thermal masses, have to the best of our knowledge not been presented before and might be useful for future studies, in particular in the context of electroweak baryogenesis.
Aminopropyl modified mesoporous SiO2 nanoparticles, MCM-41 type, have been synthesized by the co-condensation method from tetraethylorthosilicate (TEOS) and aminopropyltriethoxysilane (APTES). By means of modifying TEOS/APTES ratio we have carried out an in-depth characterization of the nanoparticles as a function of APTES content. Surface charge and nanoparticles morphology were strongly influenced by the amount of APTES and particles changed from hexagonal to bean-like morphology insofar APTES increased. Besides, the porous structure was also affected, showing a contraction of the lattice parameter and pore size, while increasing the wall thickness. These results bring about new insights about the nanoparticles formation during the co-condensation process. The model proposed herein considers that different interactions stablished between TEOS and APTES with the structure directing agent have consequences on pore size, wall thickness and particle morphology. Finally, APTES is an excellent linker to covalently attach active targeting agents such as folate groups. We have hypothesized that APTES could also play a role in the biological behavior of the nanoparticles. So, the internalization efficiency of the nanoparticles has been tested with cancerous LNCaP and non-cancerous preosteoblast-like MC3T3-E1 cells. The results indicate a cooperative effect between aminopropylsilane presence and folic acid, only for the cancerous LNCaP cell line.
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