University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Implications of Deltatheridium specimens for early marsupial history

Abstract: We describe here two new specimens of the mammal Deltatheridium pretrituberculare from the Late Cretaceous period of Mongolia. These specimens provide information on tooth replacement in basal therian mammals and on lower jaw and basicranial morphology. Deltatheroidans, known previously from isolated teeth, partial rostra and jaws from the late Cretaceous of Asia1,2,3,4 and possibly North America5,6, have been identified variously as eutherians1,7,8, as basal metatherians (the stem-based clade formed by marsupials and their extinct relatives)3,9,10,11, or as an outgroup to both eutherians and metatherians2,12,13,14,15. Resolution of these conflicting hypotheses and understanding of the early evolution of the therian lineage have been hampered by a sparse fossil record for basal therians. The new evidence supports metatherian affinities for deltatheroidans and allows a comprehensive phylogenetic analysis of basal metatherians and marsupials. The presence of specialized marsupial patterns of tooth replacement and cranial vascularization in Deltatheridium and the basal phylogenetic position of this taxon indicate that these features are characteristic of Metatheria as a whole. Other morphological transformations recognized here secure the previously elusive diagnosis of Metatheria3,14,15. The new specimens of Deltatheridium illustrate the effectiveness of fairly complete fossil specimens in determining the nature of early evolutionary events.

Automating Biomedical Data Science Through Tree-Based Pipeline Optimization

Abstract: Over the past decade, data science and machine learning has grown from a mysterious art form to a staple tool across a variety of fields in academia, business, and government. In this paper, we introduce the concept of tree-based pipeline optimization for automating one of the most tedious parts of machine learning—pipeline design. We implement a Tree-based Pipeline Optimization Tool (TPOT) and demonstrate its effectiveness on a series of simulated and real-world genetic data sets. In particular, we show that TPOT can build machine learning pipelines that achieve competitive classification accuracy and discover novel pipeline operators—such as synthetic feature constructors—that significantly improve classification accuracy on these data sets. We also highlight the current challenges to pipeline optimization, such as the tendency to produce pipelines that overfit the data, and suggest future research paths to overcome these challenges. As such, this work represents an early step toward fully automating machine learning pipeline design.

T-Cell Apoptosis and Suppression of T-Cell Receptor/CD3-ζ by Fas Ligand-Containing Membrane Vesicles Shed from Ovarian Tumors

Abstract: Purpose: The accumulation of shed plasma membrane vesicles in the peripheral circulation is unique to cancer. Because these membrane fragments (MFs) express biologically active components, such as Fas ligand (FasL), the objective of this study was to define the link between the presence of shed membrane vesicles, apoptosis, and suppression of T-cell receptor/CD3-ζ expression in T lymphocytes of patients with ovarian cancer. Experimental Design: MF shedding was measured chromatographically in sera from women with ovarian cancer ( n = 11) and, as controls, non-cancer-bearing females ( n = 9) and women with benign ovarian disease ( n = 4). FasL associated with these shed fragments was assayed by Western immunoblots, whereas HLA class I expression was defined by slot-blotting. The effect of shed MFs on CD3-ζ expression was evaluated using a T-cell bioassay, and apoptosis of circulating T cells was measured by a cell-death ELISA and electrophoretic analysis of caspase-3. Results: MFs were undetectable in control sera, and their levels were significantly elevated in sera from women with ovarian cancer. These tumor-derived MFs expressed 41-kDa FasL and HLA class I antigens. In co-incubation experiments, dose-dependent suppression of T-cell receptor/CD3-ζ expression by MFs was observed. Decreases in ζ expression correlated with the level of FasL in MFs but not with the level of HLA. The suppression of CD3-ζ by MFs appeared to be linked to the induction of apoptosis and caspase-3 within T cells. Conclusion: Our results suggest that FasL associated with tumor-derived MFs is responsible for apoptosis of T lymphocytes and a concomitant loss of ζ-chain expression in patients with ovarian carcinoma.