3,629 research outputs found
Deep Learning for Case-Based Reasoning through Prototypes: A Neural Network that Explains Its Predictions
Deep neural networks are widely used for classification. These deep models
often suffer from a lack of interpretability -- they are particularly difficult
to understand because of their non-linear nature. As a result, neural networks
are often treated as "black box" models, and in the past, have been trained
purely to optimize the accuracy of predictions. In this work, we create a novel
network architecture for deep learning that naturally explains its own
reasoning for each prediction. This architecture contains an autoencoder and a
special prototype layer, where each unit of that layer stores a weight vector
that resembles an encoded training input. The encoder of the autoencoder allows
us to do comparisons within the latent space, while the decoder allows us to
visualize the learned prototypes. The training objective has four terms: an
accuracy term, a term that encourages every prototype to be similar to at least
one encoded input, a term that encourages every encoded input to be close to at
least one prototype, and a term that encourages faithful reconstruction by the
autoencoder. The distances computed in the prototype layer are used as part of
the classification process. Since the prototypes are learned during training,
the learned network naturally comes with explanations for each prediction, and
the explanations are loyal to what the network actually computes.Comment: The first two authors contributed equally, 8 pages, accepted in AAAI
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Feasible Activity and Travel Time Allocations with a Discrete Choice Model: An Exploratory Study
An exploratory study using a discrete choice framework for time-use allocations is described. Instead of treating time use as continuous and dependent, it is treated as discrete and independent. By doing this, the restriction that the consumption bundle must lie on the boundary of the budget set can be enforced. Using responses collected from the 1996 travel survey for the San Francisco Bay Area, estimation of the model results is a good fit in terms of adjusted R2. This suggests that a discrete choice framework of time allocation to activities and travel is a worthwhile effort that certainly needs further investigation
Feasible Activity and Travel Time Allocations with a Discrete Choice Model: An Exploratory Study
An exploratory study using a discrete choice framework for time-use allocations is described. Instead of treating time use as continuous and dependent, it is treated as discrete and independent. By doing this, the restriction that the consumption bundle must lie on the boundary of the budget set can be enforced. Using responses collected from the 1996 travel survey for the San Francisco Bay Area, estimation of the model results is a good fit in terms of adjusted R2. This suggests that a discrete choice framework of time allocation to activities and travel is a worthwhile effort that certainly needs further investigation
An analysis of Apc5p/Fob1p interactions in yeast : implications for extended lifespan
Aging is a universal biological phenomenon in all living cells. Questions regarding how cells age are beginning to be answered. Thus, great biological interest and practical importance leading to interventions rest on uncovering the molecular mechanism of aging. This would ultimately delay the aging process while maintaining the physical and mental strengths of youth. The conservation of metabolic and signaling pathways between yeast and humans is remarkably high, leading to the expectation that aging mechanisms are also common across evolutionary boundaries. By utilizing the budding yeast, Saccharomyces cerevisiae, one of the best characterized model systems for studying aging, the span in knowledge between yeast and human aging can possibly be bridged. Evidence is accumulating that a genetic program exists for lifespan determination. Model organisms expressing mutations in single specific genes live longer with increased resistance to stress and cancer development. Mutations that accelerate aging in yeast affect the activity of the APC (Anaphase-Promoting Complex). Our finding that the APC is critical for longevity provides us with a potential central mechanism controlling lifespan determination. The APC is required for mitotic progression and genomic stability in presumably all eukaryotes by targeting regulatory proteins, such as cyclin B (Clb2p in yeast) for degradation. The key feature defining the APC as a central mediator of lifespan is the fact that multiple signaling pathways regulate APC activity and many of these pathways influence lifespan. For example, Snf1 and PKA have antagonistic effects on the APC and on lifespan. Thus, it is intriguing to speculate that the APC may link these signaling pathways to downstream targets controlling longevity. Our hypothesis states that the APC targets a protein that reduces lifespan for ubiquitin-dependent degradation. The results from our two-hybrid screen utilizing Apc5p as bait are consistent with this hypothesis, as Fob1p was isolated as an Apc5p binding partner. The FOB1 gene is located on chromosome IV and the well-known molecular function of FOB1 is the creation of a unidirectional block in replication of rDNA. Fob1p binds to the rDNA locus and overall stalls progression of the replication fork, which increases rDNA recombination and the production of toxic extrachromosomal rDNA circles (ERCs). The FOB1 deletion (fob1∆) mutant confers reduced rDNA recombination, and an increased lifespan of more than 50% compared to WT (wild type) cells.In this study, we expanded on the molecular mechanisms controlling lifespan through a genetic approach, and found that Fob1p was targeted by the APC for degradation in order to prolong lifespan. By utilizing the yeast two-hybrid approach, we confirmed the Apc5p-Fob1p interaction, and determined that the C-terminal half of Fob1p was required for the interaction with Apc5p. BLAST search analysis revealed sequence similarity with the Fob1p C-terminus that was shared with many other proteins from yeast to humans. We speculate that this shared domain may serve as an APC interaction domain employed across evolutionary boundaries. A genetic interaction analysis revealed the influence of FOB1 on the APC, and the cell. For example, deletion of FOB1 increased lifespan in apc5CA and apc10∆ mutant cells and partially suppressed the temperature sensitive (ts) growth of apc10∆ cells. On the other hand, increased FOB1 expression reduced the lifespan of WT and cells and was toxic to apc mutants, particularly the more severe apc mutants, apc10∆ and cdc16-1. Interestingly, overexpression of SIR2, which prolongs lifespan and acts antagonistically with Fob1p, was toxic to WT cells, but suppressed apc5CA ts defects, especially when FOB1 was deleted. These observations suggest that accumulation of Fob1p is harmful to yeast cells, especially when the APC is compromised. This notion was borne out when a cell cycle and steady state analysis of Fob1p revealed that Fob1p was an unstable protein, which was stabilized in apc5CA cells. Taken together, the work presented in this thesis supports a model whereby Fob1p is targeted for degradation by the APC in order to prolong lifespan in yeast. In conclusion, the extreme evolutionarily conserved nature of the APC and the Fob1p C-terminal sequence homology observed in human proteins strongly suggests that the mechanism discovered here could be directing human lifespan
Dinitrosyl formation as an intermediate stage of the reduction of NO in the presence of MoO_3
We present first-principles calculations in the framework of
density-functional theory and the pseudopotential approach, aiming to model the
intermediate stages of the reduction of NO in the presence of MoO(010). In
particular, we study the formation of dinitrosyl, which proves to be an
important intermediate stage in the catalytic reduction. We find that the
replacement of an oxygen of MoO by NO is energetically favorable, and that
the system lowers further its energy by the formation of (NO). Moreover,
the geometry and charge distribution for the adsorbed dinitrosyl indicates a
metal-oxide mediated coupling between the two nitrogen and the two oxygen
atoms. We discuss the mechanisms for the dinitrosyl formation and the role of
the oxide in the reaction.Comment: 6 pages, 4 figs, RevTeX. To be published in J. Chem. Phy
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Absorptive transport of amino acids by the rat colon.
The capacity of the colon to absorb microbially produced amino acids (AAs) and the underlying mechanisms of AA transport are incompletely defined. We measured the profile of 16 fecal AAs along the rat ceco-colonic axis and compared unidirectional absorptive AA fluxes across mucosal tissues isolated from the rat jejunum, cecum, and proximal colon using an Ussing chamber approach, in conjunction with 1H-NMR and ultra-performance liquid chromatography-mass spectrometry chemical analyses. Passage of stool from cecum to midcolon was associated with segment-specific changes in fecal AA composition and a decrease in total AA content. Simultaneous measurement of up to 16 AA fluxes under native luminal conditions, with correction for endogenous AA release, demonstrated absorptive transfer of AAs across the cecum and proximal colon at rates comparable (30-80%) to those across the jejunum, with significant Na+-dependent and H+-stimulated components. Expression profiling of 30 major AA transporter genes by quantitative PCR revealed comparatively high levels of transcripts for 20 AA transporters in the cecum and/or colon, with the levels of 12 exceeding those in the small intestine. Our results suggest a more detailed model of major apical and basolateral AA transporters in rat colonocytes and provide evidence for a previously unappreciated transfer of AAs across the colonic epithelium that could link the prodigious metabolic capacities of the luminal microbiota, the colonocytes, and the body tissues.NEW & NOTEWORTHY This study provides evidence for a previously unappreciated transfer of microbially generated amino acids across the colonic epithelium under physiological conditions that could link the prodigious metabolic capacities of the luminal microbiota, the colonocytes, and the body tissues. The segment-specific expression of at least 20 amino acid transporter genes along the colon provides a detailed mechanistic basis for uniport, heteroexchange, Na+-cotransport, and H+-cotransport components of colonic amino acid absorption
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