Explore the vast range of titles available.

Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson’s Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebrospinal fluid (CSF) compared to age-matched healthy controls. However, it is unknown whether peripheral immune cells in the CSF of individuals with PD also exhibit decreased levels of RGS10. Utilizing the Michael J. Fox Foundation Parkinson’s Progression Markers Initiative (PPMI) study we found that RGS10 levels are decreased in the CSF of individuals with PD compared to healthy controls and prodromal individuals. As RGS10 levels are decreased in the CSF and circulating peripheral immune cells of individuals with PD, we hypothesized that RGS10 regulates peripheral immune cell responses to chronic systemic inflammation (CSI) prior to the onset of neurodegeneration. To test this, we induced CSI for 6 weeks in C57BL6/J mice and RGS10 KO mice to assess circulating and CNS-associated immune cell responses. We found that RGS10 deficiency synergizes with CSI to induce a bias for inflammatory and cytotoxic cell populations, a reduction in antigen presentation machinery in peripheral blood immune cells, as well as in and around the brain that is most notable in males. These results highlight RGS10 as an important regulator of the systemic immune response to CSI and implicate RGS10 as a potential contributor to the development of immune dysregulation in PD.

Regulator of G-protein signaling 10 (RGS10), a key homeostatic regulator of immune cells, has been implicated in multiple diseases associated with aging and chronic inflammation including Parkinson's Disease (PD). Interestingly, subjects with idiopathic PD display reduced levels of RGS10 in subsets of peripheral immune cells. Additionally, individuals with PD have been shown to have increased activated peripheral immune cells in cerebral spinal fluid (CSF) compared to age-matched healthy controls. However, it is unknown whether CSF-resident peripheral immune cells in individuals with PD also exhibit decreased levels of RGS10. Therefore, we performed an analysis of RGS10 levels in the proteomic database of the CSF from the Michael J. Fox Foundation Parkinson's Progression Markers Initiative (PPMI) study. We found that RGS10 levels are decreased in the CSF of individuals with PD compared to healthy controls and prodromal individuals. Moreover, we find that RGS10 levels decrease with age but not PD progression and that males have less RGS10 than females in PD. Importantly, studies have established an association between chronic systemic inflammation (CSI) and neurodegenerative diseases, such as PD, and known sources of CSI have been identified as risk factors for developing PD; however, the role of peripheral immune cell dysregulation in this process has been underexplored. As RGS10 levels are decreased in the CSF and circulating peripheral immune cells of individuals with PD, we hypothesized that RGS10 regulates peripheral immune cell responses to CSI prior to the onset of neurodegeneration. To test this, we induced CSI for 6 weeks in C57BL6/J mice and RGS10 KO mice to assess circulating and CNS-associated peripheral immune cell responses. We found that RGS10 deficiency synergizes with CSI to induce a bias for inflammatory and cytotoxic cell populations, a reduction in antigen presentation in peripheral blood immune cells, as well as in and around the brain that is most notable in males. These results highlight RGS10 as an important regulator of the systemic immune response to CSI and implicate RGS10 as a potential contributor to the development of immune dysregulation in PD.

As modern hydrodynamic codes increase in sophistication, the availability of realistic test problems becomes increasingly important. In gas dynamics, one common unrealistic aspect of most test problems is the ideal gas assumption, which is unsuited to many real applications, especially those involving high pressure and speed metal deformation. Our work considers the collapsing cavity and converging shock test problems, showing to what extent the ideal gas assumption can be removed from their specification. It is found that while most materials simply do not admit simple (i.e. scaling) solutions in this context, there are infinite-dimensional families of materials which do admit such solutions. We characterize such materials, derive the appropriate ordinary differential equations, and analyze the associated nonlinear eigenvalue problem. It is shown that there is an inherent tension between boundedness of the solution, boundedness of its derivatives, and the entropy condition. The special case of a constant-speed cavity collapse is considered and found to be heuristically possible, contrary to common intuition. Finally, we give an example of a concrete non-ideal collapsing cavity scaling solution based on a recently proposed pseudo-Mie-Gruneisen equation of state.

Previous work has shown that the one-dimensional (1D) inviscid compressible flow (Euler) equations admit a wide variety of scale-invariant solutions (including the famous Noh, Sedov, and Guderley shock solutions) when the included equation of state (EOS) closure model assumes a certain scale-invariant form. However, this scale-invariant EOS class does not include even simple models used for shock compression of crystalline solids, including many broadly applicable representations of Mie-Gr\"uneisen EOS. Intuitively, this incompatibility naturally arises from the presence of multiple dimensional scales in the Mie-Gr\"uneisen EOS, which are otherwise absent from scale-invariant models that feature only dimensionless parameters (such as the adiabatic index in the ideal gas EOS). The current work extends previous efforts intended to rectify this inconsistency, by using a scale-invariant EOS model to approximate a Mie- Gr\"uneisen EOS form. To this end, the adiabatic bulk modulus for the Mie-Gr\"uneisen EOS is constructed, and its key features are used to motivate the selection of a scale-invariant approximation form. The remaining surrogate model parameters are selected through enforcement of the Rankine-Hugoniot jump conditions for an infinitely strong shock in a Mie-Gr\"uneisen material. Finally, the approximate EOS is used in conjunction with the 1D inviscid Euler equations to calculate a semi-analytical, Guderley-like imploding shock solution in a metal sphere, and to determine if and when the solution may be valid for the underlying Mie-Gr\"uneisen EOS.

We extend Guderley's problem of finding a self-similar scaling solution for a converging cylindrical or spherical shock wave from the ideal gas case to the case of flows with an arbitrary equation of state closure model, giving necessary conditions for the existence of a solution. The necessary condition is a thermodynamic one, namely that the adiabatic bulk modulus, \\(K_S\\), of the fluid be of the form \\(pf(\\rho)\\) where \\(p\\) is pressure, \\(\\rho\\) is mass density, and \\(f\\) is an arbitrary function. Although this condition has appeared in the literature before, here we give a more rigorous and extensive treatment. Of particular interest is our novel analysis of the governing ordinary differential equations (ODEs), which shows that, in general, the Guderley problem is always an eigenvalue problem. The need for an eigenvalue arises from basic shock stability principles -- an interesting connection to the existing literature on the relationship between self-similarity of the second kind and stability. We also investigate a special case, usually neglected by previous authors, where assuming constant shock velocity yields a reduction to ODEs for every material, but those ODEs never have a bounded, differentiable solution. This theoretical work is motivated by the need for more realistic test problems in the verification of inviscid compressible flow codes that simulate flows in a variety of non-ideal gas materials.