Tidelocked

A sci-fi novella about a hostile world and the edge of humanity

Design patterns for the development of electronic health record-driven phenotype extraction algorithms

AbstractBackgroundDesign patterns, in the context of software development and ontologies, provide generalized approaches and guidance to solving commonly occurring problems, or addressing common situations typically informed by intuition, heuristics and experience. While the biomedical literature contains broad coverage of specific phenotype algorithm implementations, no work to date has attempted to generalize common approaches into design patterns, which may then be distributed to the informatics community to efficiently develop more accurate phenotype algorithms.MethodsUsing phenotyping algorithms stored in the Phenotype KnowledgeBase (PheKB), we conducted an independent iterative review to identify recurrent elements within the algorithm definitions. We extracted and generalized recurrent elements in these algorithms into candidate patterns. The authors then assessed the candidate patterns for validity by group consensus, and annotated them with attributes.ResultsA total of 24 electronic Medical Records and Genomics (eMERGE) phenotypes available in PheKB as of 1/25/2013 were downloaded and reviewed. From these, a total of 21 phenotyping patterns were identified, which are available as an online data supplement.ConclusionsRepeatable patterns within phenotyping algorithms exist, and when codified and cataloged may help to educate both experienced and novice algorithm developers. The dissemination and application of these patterns has the potential to decrease the time to develop algorithms, while improving portability and accuracy

Characterization and regulation of MT1‐MMP cell surface‐associated activity

Quantitative assessment of MT1‐MMP cell surface‐associated proteolytic activity remains undefined. Presently, MT1‐MMP was stably expressed and a cell‐based FRET assay developed to quantify activity toward synthetic collagen‐model triple‐helices. To estimate the importance of cell surface localization and specific structural domains on MT1‐MMP proteolysis, activity measurements were performed using a series of membrane‐anchored MT1‐MMP mutants and compared directly with those of soluble MT1‐MMP. MT1‐MMP activity (kcat/KM) on the cell surface was 4.8‐fold lower compared with soluble MT1‐MMP, with the effect largely manifested in kcat. Deletion of the MT1‐MMP cytoplasmic tail enhanced cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin‐like domain negatively impacted KM and increased kcat. Overall, cell surface localization of MT1‐MMP restricts substrate binding and protein‐coupled motions (based on changes in both kcat and KM) for catalysis. Comparison of soluble and cell surface‐bound MT2‐MMP revealed 12.9‐fold lower activity on the cell surface. The cell‐based assay was utilized for small molecule and triple‐helical transition state analog MMP inhibitors, which were found to function similarly in solution and at the cell surface. These studies provide the first quantitative assessments of MT1‐MMP activity and inhibition in the native cellular environment of the enzyme.MT1‐MMP was stably expressed and a cell‐based FRET assay developed to quantify activity toward synthetic collagen‐model triple‐helices. Activity measurements were performed using a series of membrane‐anchored MT1‐MMP mutants and compared directly with those of soluble MT1‐MMP. Cell surface localization of MT1‐MMP was found to restrict substrate binding and protein‐coupled motions for catalysis. Small molecule and triple‐helical transition state analog MMP inhibitors were found to function similarly in solution and at the cell surface.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150520/1/cbdd13450.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150520/2/cbdd13450_am.pd

The Woody Guthrie Centennial Bibliography

This bibliography updates two extensive works designed to include comprehensively all significant works by and about Woody Guthrie. Richard A. Reuss published A Woody Guthrie Bibliography, 1912–1967 in 1968 and Jeffrey N. Gatten\u27s article “Woody Guthrie: A Bibliographic Update, 1968–1986” appeared in 1988. With this current article, researchers need only utilize these three bibliographies to identify all English-language items of relevance related to, or written by, Guthrie

Resolving Inconsistencies in Plato: the Problem of Socratic Wisdom in the Apology and the Charmides

In the Apology Plato ascribes to Socrates a kind of knowledge that distinguishes him from others, viz., the knowledge that in truth he is worthless in respect of knowledge. Furthermore, the cultivation of this ‘Socratic wisdom’ is presented by Plato as necessary for anyone wishing to pursue the examined life, the only life worth living for a human being, and therefore as something that we all should seek to acquire. In the Charmides, however, Socrates argues at length to the conclusion that such knowledge is neither possible nor, even if it were possible, of any use. This apparent contradiction in Platonic doctrine is the problem of Socratic wisdom in the Apology and the Charmides. The thesis first constructs the problem of Socratic wisdom from the text of the two dialogues. It then considers various strategies in the long tradition of Platonic scholarship by which proposals have been made to resolve this and other inconsistencies in Plato. These strategies are assessed and reasons are given for preferring a recent approach called the ‘double dialogue’ reading of Plato, which treats his works not primarily as vehicles for publishing his doctrines, but as philosophical challenges for the reader. The thesis then conducts a double dialogue reading of the second half of the Charmides and demonstrates how this way of reading Plato provides a resolution to the problem of Socratic wisdom. The resolution lies in showing how, in the Charmides, Plato issues a challenge to the reader to address the inadequacies of the model of knowledge that underlies the apparent success of the dialogue’s refutation of Socratic wisdom. Thus, not only is the problem of Socratic wisdom resolved, but the double dialogue strategy of reading Plato is validated for further employment in resolving other inconsistencies in Plato.Greek Philosoph

Resolving inconsistencies in Plato : the problem of Socratic wisdom in the Apology and the Charmides

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Airborne behaviour monitoring using Gaussian processes with map information

This paper proposes an airborne behaviour monitoring methodology of ground vehicles based on a statistical learning approach with domain knowledge given by road map information. To monitor and track the moving ground target using UAVs aboard a moving target indicator, an interactive multiple model (IMM) filter is firstly applied. {\color{red}The IMM filter consists of an on-road moving mode using a road-constrained filter and an off-road moving mode using a conventional filter.} Mode probability is also calculated from the IMM filter, and it provides deviation of the vehicle from the road. Then, a novel hybrid algorithm for anomalous behaviour recognition is developed using a Gaussian process regression on velocity profile along the one-dimensionalised position of the vehicle, as well as the deviation of the vehicle. To verify the feasibility and benefits of the proposed approach, a numerical simulation is performed using realistic car trajectory data in a city traffic