549 research outputs found

    Model AI Assignments 2018

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    The Model AI Assignments session seeks to gather and disseminate the best assignment designs of the Artificial Intelligence (AI) Education community. Recognizing that assignments form the core of student learning experience, we here present abstracts of seven AI assignments from the 2018 session that are easily adoptable, playfully engaging, and flexible for a variety of instructor needs. Assignment specifications and supporting resources may be found at http://modelai.gettysburg.edu

    Lagrangian perspective on the origins of Denmark Strait Overflow

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    Author Posting. Ā© American Meteorological Society, 2020. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 50(8), (2020): 2393-2414, doi:10.1175/JPO-D-19-0210.1.The Denmark Strait Overflow (DSO) is an important contributor to the lower limb of the Atlantic meridional overturning circulation (AMOC). Determining DSO formation and its pathways is not only important for local oceanography but also critical to estimating the state and variability of the AMOC. Despite prior attempts to understand the DSO sources, its upstream pathways and circulation remain uncertain due to short-term (3ā€“5 days) variability. This makes it challenging to study the DSO from observations. Given this complexity, this study maps the upstream pathways and along-pathway changes in its water properties, using Lagrangian backtracking of the DSO sources in a realistic numerical ocean simulation. The Lagrangian pathways confirm that several branches contribute to the DSO from the north such as the East Greenland Current (EGC), the separated EGC (sEGC), and the North Icelandic Jet (NIJ). Moreover, the model results reveal additional pathways from south of Iceland, which supplied over 16% of the DSO annually and over 25% of the DSO during winter of 2008, when the NAO index was positive. The southern contribution is about 34% by the end of March. The southern pathways mark a more direct route from the near-surface subpolar North Atlantic to the North Atlantic Deep Water (NADW), and needs to be explored further, with in situ observations.This work was financially supported by the U.S. National Science Foundation under Grant Numbers OAC-1835640, OCE-1633124, OCE-1433448, and OCE-1259210

    Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia

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    Anhedoniaā€”defined as loss of interest or pleasureā€”is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcersā€”activities with the potential to be positive experiencesā€”is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individualā€™s unique set of ā€˜likedā€™ and ā€˜dislikedā€™ activity words. A negative correlation was observed between anhedonia and the number of ā€˜likedā€™ activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward ā€˜dislikedā€™ activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD

    Three-dimensional Structure of L-2-Haloacid Dehalogenase from Xanthobacter autotrophicus GJ10 Complexed with the Substrate-analogue Formate

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    The L-2-haloacid dehalogenase from the 1,2-dichloroethane degrading bacterium Xanthobacter autotrophicus GJ10 catalyzes the hydrolytic dehalogenation of small L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids. Its crystal structure was solved by the method of multiple isomorphous replacement with incorporation of anomalous scattering information and solvent flattening, and was refined at 1.95-ƅ resolution to an R factor of 21.3%. The three-dimensional structure is similar to that of the homologous L-2-haloacid dehalogenase from Pseudomonas sp. YL (1), but the X. autotrophicus enzyme has an extra dimerization domain, an active site cavity that is completely shielded from the solvent, and a different orientation of several catalytically important amino acid residues. Moreover, under the conditions used, a formate ion is bound in the active site. The position of this substrate-analogue provides valuable information on the reaction mechanism and explains the limited substrate specificity of the Xanthobacter L-2-haloacid dehalogenase.

    Hyperglycemia-related advanced glycation end-products is associated with the altered phosphatidylcholine metabolism in osteoarthritis patients with diabetes

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    To test whether type 2 diabetic patients have an elevated level of advanced glycation end-products (AGEs) and responsible for altered phosphatidylcholine metabolism, which we recently found to be associated with osteoarthritis (OA) and diabetes mellitus (DM), synovial fluid (SF) and plasma samples were collected from OA patients with and without DM. Hyperglycemia-related AGEs including methylglyoxal (MG), free methylglyoxal-derived hydroimidazolone (MG-H1), and protein bound N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL) levels were measured in both SF and plasma samples using liquid chromatography coupled tandem mass spectrometry methodology. The correlation between these AGEs and phosphatidylcholine acyl-alkyl C34:3 (PC ae C34:3) and C36:3 (PC ae C36:3) were examined. Eighty four patients with knee OA, including 46 with DM and 38 without DM, were included in the study. There was no significant difference in plasma levels of MG, MG-H1, CML, and CEL between OA patients with and without DM. However, the levels of MG and MG-H1, but not CML and CEL in SF were significantly higher in OA patients with DM than in those without (all p ā‰¤0.04). This association strengthened after adjustment for age, body mass index (BMI), sex and hexose level (p<0.02). Moreover, the levels of MG-H1 in SF was negatively and significantly correlated with PC ae C34:3 (Ļ = -0.34; p = 0.02) and PC ae C36:3 (Ļ = -0.39; P = 0.03) after the adjustment of age, BMI, sex and hexose level. Our data indicated that the production of non-protein bound AGEs was increased within the OA-affected joint of DM patients. This is associated with changes in phosphatidylcholine metabolism and might be responsible for the observed epidemiological association between OA and DM

    Recessive Inheritance of Congenital Hydrocephalus With Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3

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    Background: ATP1A3 encodes the Ī±3 subunit of the Na+/K+ ATPase, a fundamental ion-transporting enzyme. Primarily expressed in neurons, ATP1A3 is mutated in several autosomal dominant neurological diseases. To our knowledge, damaging recessive genotypes in ATP1A3 have never been associated with any human disease. Atp1a3 deficiency in zebrafish results in hydrocephalus; however, no known association exists between ATP1A3 and human congenital hydrocephalus (CH). / Methods: We utilized whole-exome sequencing (WES), bioinformatics, and computational modeling to identify and characterize novel ATP1A3 mutations in a patient with CH. We performed immunohistochemical studies using mouse embryonic brain tissues to characterize Atp1a3 expression during brain development. / Results: We identified two germline mutations in ATP1A3 (p. Arg19Cys and p.Arg463Cys), each of which was inherited from one of the patientā€™s unaffected parents, in a single patient with severe obstructive CH due to aqueductal stenosis, along with open schizencephaly, type 1 Chiari malformation, and dysgenesis of the corpus callosum. Both mutations are predicted to be highly deleterious and impair protein stability. Immunohistochemical studies demonstrate robust Atp1a3 expression in neural stem cells (NSCs), differentiated neurons, and choroid plexus of the mouse embryonic brain. / Conclusion: These data provide the first evidence of a recessive human phenotype associated with mutations in ATP1A3, and implicate impaired Na+/K+ ATPase function in the pathogenesis of CH

    Identification of disease-causing genes using microarray data mining and gene ontology

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    Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers
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