19 research outputs found

    Podcast PD

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    Reports of police corruption are becoming more and more common in American media. In this podcast, we will discuss the distrust between the police and the community, some of the causes of the problem, and will address ways to resolve it. Throughout the duration of the podcast, we will provide the viewpoint of both sides and try to explain why they feel the way they do. To get the community’s input, our group decided to poll random students across campus to get a better understanding on their view of the police state in the US. For the police’s side, we decided to interview an officer for his input on why these controversial stories are being displayed all over the media, and asked what he thinks should be done to improve the relationship between the two parties. By including the thoughts of the opposing sides, as well as using data from some of the instances reported in the media, we hope that our listeners will gain a better understanding of the issue and proactively try to improve the relationship between the community and the police

    Generalized Cross-Validation as a Method of Hyperparameter Search for MTGV Regularization

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    The concept of generalized cross-validation (GCV) is applied to modified total generalized variation (MTGV) regularization. Current implementations of the MTGV regularization rely on manual (or semi-manual) hyperparameter optimization, which is both time-consuming and subject to bias. The combination of MTGV-regularization and GCV allows for a straightforward hyperparameter search during regularization. This significantly increases the efficiency of the MTGV-method, because it limits the number of hyperparameters, which have to be tested and, improves the practicality of MTGV regularization as a standard technique for inversion of NMR signals. The combined method is applied to simulated and experimental NMR data and the resulting reconstructed distributions are presented. It is shown that for all data sets studied the proposed combination of MTGV and GCV minimizes the GCV score allowing an optimal hyperparameter choice

    Molecular changes in the postmortem parkinsonian brain

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    Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease. Although PD has a relatively narrow clinical phenotype, it has become clear that its etiological basis is broad. Post-mortem brain analysis, despite its limitations, has provided invaluable insights into relevant pathogenic pathways including mitochondrial dysfunction, oxidative stress and protein homeostasis dysregulation. Identification of the genetic causes of PD followed the discovery of these abnormalities, and reinforced the importance of the biochemical defects identified post-mortem. Recent genetic studies have highlighted the mitochondrial and lysosomal areas of cell function as particularly significant in mediating the neurodegeneration of PD. Thus the careful analysis of post-mortem PD brain biochemistry remains a crucial component of research, and one that offers considerable opportunity to pursue etiological factors either by ‘reverse biochemistry’ i.e. from defective pathway to mutant gene, or by the complex interplay between pathways e.g. mitochondrial turnover by lysosomes. In this review we have documented the spectrum of biochemical defects identified in PD post-mortem brain and explored their relevance to metabolic pathways involved in neurodegeneration. We have highlighted the complex interactions between these pathways and the gene mutations causing or increasing risk for PD. These pathways are becoming a focus for the development of disease modifying therapies for PD. Parkinson's is accompanied by multiple changes in the brain that are responsible for the progression of the disease. We describe here the molecular alterations occurring in postmortem brains and classify them as: Neurotransmitters and neurotrophic factors; Lewy bodies and Parkinson's-linked genes; Transition metals, calcium and calcium-binding proteins; Inflammation; Mitochondrial abnormalities and oxidative stress; Abnormal protein removal and degradation; Apoptosis and transduction pathways

    Molecular Dynamics of Ionic Liquids from Fast-Field Cycling NMR and Molecular Dynamics Simulations.

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    Understanding the connection between the molecular structure of ionic liquids and their properties is of paramount importance for practical applications. However, this connection can only be established if a broad range of physicochemical properties on different length and time scales is already available. Even then, the interpretation of the results often remains ambiguous due to the natural limits of experimental approaches. Here we use fast-field cycling (FFC) to access both translational and rotational dynamics of ionic liquids. These combined with a comprehensive physicochemical characterization and MD simulations provide a toolkit to give insight into the mechanisms of molecular mechanics. The FFC results are consistent with the computer simulation and conventional physicochemical approaches. We show that curling of the side chains around the positively charged cationic core is essential for the properties of ether-functionalized ionic liquids, and we demonstrate that neither geometry nor polarity alone are sufficient to explain the macroscopic properties
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