Meaning and compositionality as statistical induction of categories and constraints

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009."September 2009." Cataloged from PDF version of thesis.Includes bibliographical references (p. 191-201).What do words and phrases mean? How do we infer their meaning in a given context? How do we know which sets of words have sensible meanings when combined, as opposed to being nonsense? As language learners and speakers, we can solve these problems starting at a young age, but as scientists, our understanding of these processes is limited. This thesis seeks to address these questions using a computational approach. Bayesian modeling provides a method of combining categories and logical constraints with probabilistic inference, yielding word and phrase meanings that involve graded category memberships and are governed by probabilistically inferred structures. The Bayesian approach also allows an investigation to separately identify the prior beliefs a language user brings to a particular situation involving meaning-based inference (e.g., learning a word meaning or identifying which objects an adjective applies to within a given context), and to identify what the language user can infer from the context. This approach therefore provides the foundation also for investigations of how different prior beliefs affect what a language user infers in a given situation, and how prior beliefs can develop over time. Using a computational approach, I address the following questions: (1) How do people generalize about a word's meaning from limited evidence? (2) How do people understand and use phrases, particularly when some of the words in those phrases depend on context for interpretation? (3) How do people know and learn which combinations of predicates and noun phrases can sensibly be combined and which are nonsensical?(cont.) I show how each of these topics involves the probabilistic induction of categories, and I examine the constraints on inference in each domain. I also explore which of these constraints may themselves be learned.by Lauren A. Schmidt.Ph.D

Marek's Disease Virus VP22: Subcellular Localization and Characterization of Carboxyl Terminal Deletion Mutations

AbstractMarek's disease virus (MDV) is an alphaherpesvirus that causes T cell lymphoma and severe immunosuppression in chickens. The MDV UL49 gene, which encodes the tegument viral protein 22 (VP22), has been expressed as a green fluorescent protein (GFP) fusion protein in chicken embryonic fibroblasts to examine its subcellular localization. As with both human herpesvirus 1 and bovine herpesvirus 1VP22-GFP fusion proteins, the MDV VP22-GFP product binds to microtubules and heterochromatin. In addition, the MDV protein also binds to the centrosomes. During mitosis, VP22-GFP binds to sister chromatids, but dissociates from the centrosomes and the microtubules of the mitotic spindle. A series of VP22 carboxy terminal truncation mutants were constructed to define regions responsible for these binding properties. These mutants identified separable domains or motifs responsible for binding microtubules and heterochromatin

A New Volcanic Stratospheric Sulfate Aerosol Forcing Emulator (EVA_H): Comparison With Interactive Stratospheric Aerosol Models

Idealized models or emulators of volcanic aerosol forcing have been widely used to reconstruct the spatiotemporal evolution of past volcanic forcing. However, existing models, including the most recently developed Easy Volcanic Aerosol (EVA; Toohey et al., doi: 10.5194/gmd‐2016‐83), (i) do not account for the height of injection of volcanic SO urn:x-wiley:jgrd:media:jgrd55987:jgrd55987-math-0001; (ii) prescribe a vertical structure for the forcing; and (iii) are often calibrated against a single eruption. We present a new idealized model, EVA_H, that addresses these limitations. Compared to EVA, EVA_H makes predictions of the global mean stratospheric aerosol optical depth that are (i) similar for the 1979–1998 period characterized by the large and high‐altitude tropical SO urn:x-wiley:jgrd:media:jgrd55987:jgrd55987-math-0002 injections of El Chichón (1982) and Mount Pinatubo (1991); (ii) significantly improved for the 1998–2015 period characterized by smaller eruptions with a large variety of injection latitudes and heights. Compared to EVA, the sensitivity of volcanic forcing to injection latitude and height in EVA_H is much more consistent with results from climate models that include interactive aerosol chemistry and microphysics, even though EVA_H remains less sensitive to eruption latitude than the latter models. We apply EVA_H to investigate potential biases and uncertainties in EVA‐based volcanic forcing data sets from phase 6 of the Coupled Model Intercomparison Project (CMIP6). EVA and EVA_H forcing reconstructions do not significantly differ for tropical high‐altitude volcanic injections. However, for high‐latitude or low‐altitude injections, our reconstructed forcing is significantly lower. This suggests that volcanic forcing in CMIP6 last millenium experiments may be overestimated for such eruptions

A new volcanic stratospheric sulfate aerosol forcing emulator (EVA_H): Comparison with interactive stratospheric aerosol models.

Idealized models or emulators of volcanic aerosol forcing have been widely used to reconstruct the spatio‐temporal evolution of past volcanic forcing. However, existing models, including the most recently developed Easy Volcanic Aerosol (EVA, Toohey et al. (2016): i) do not account for the height of injection of volcanic SO2; ii) prescribe a vertical structure for the forcing; and iii) are \NEW{often} calibrated against a single eruption. We present a new idealized model, EVA_H, that addresses these limitations. Compared to EVA, EVA_H makes predictions of the global mean stratospheric aerosol optical depth that are: i) similar for the 1979‐1998 period characterized by the large and high‐altitude tropical SO2 injections of El Chichón (1982) and Mt. Pinatubo (1991); ii) significantly improved for the 1998‐2015 period characterized by smaller eruptions with a large variety of injection latitudes and heights. Compared to EVA, the sensitivity of volcanic forcing to injection latitude and height in EVA_H is much more consistent with results from climate models that include interactive aerosol chemistry and microphysics, even though EVA_H remain less sensitive to eruption latitude than the latter models. We apply EVA_H to investigate potential biases and uncertainties in EVA‐based volcanic forcing datasets from phase 6 of the Coupled Model Intercomparison Project (CMIP6). EVA and EVA_H forcing reconstructions do not significantly differ for tropical high‐altitude volcanic injections. However, for high‐latitude or low altitude injections, our reconstructed forcing is significantly lower. This suggests that volcanic forcing in CMIP6 last millenium experiments may be overestimated for such eruptions.Includes NERC

Molecular-Genetic Mapping of Zebrafish Mutants with Variable Phenotypic Penetrance

Forward genetic screens in vertebrates are powerful tools to generate models relevant to human diseases, including neuropsychiatric disorders. Variability in phenotypic penetrance and expressivity is common in these disorders and behavioral mutant models, making their molecular-genetic mapping a formidable task. Using a ‘phenotyping by segregation’ strategy, we molecularly map the hypersensitive zebrafish houdini mutant despite its variable phenotypic penetrance, providing a generally applicable strategy to map zebrafish mutants with subtle phenotypes

Quantifying Cerebral Contributions to Pain beyond Nociception

Cerebral processes contribute to pain beyond the level of nociceptive input and mediate psychological and behavioural influences. However, cerebral contributions beyond nociception are not yet well characterized, leading to a predominant focus on nociception when studying pain and developing interventions. Here we use functional magnetic resonance imaging combined with machine learning to develop a multivariate pattern signature—termed the stimulus intensity independent pain signature-1 (SIIPS1)—that predicts pain above and beyond nociceptive input in four training data sets (Studies 1–4, N¼137). The SIIPS1 includes patterns of activity in nucleus accumbens, lateral prefrontal and parahippocampal cortices, and other regions. In cross-validated analyses of Studies 1–4 and in two independent test data sets (Studies 5–6, N¼46), SIIPS1 responses explain variation in trial-by-trial pain ratings not captured by a previous fMRI-based marker for nociceptive pain. In addition, SIIPS1 responses mediate the pain-modulating effects of three psychological manipulations of expectations and perceived control. The SIIPS1 provides an extensible characterization of cerebral contributions to pain and specific brain targets for interventions

Mice with cisplatin and oxaliplatin-induced painful neuropathy develop distinct early responses to thermal stimuli

<p>Abstract</p> <p>Background</p> <p>Cisplatin has been in use for 40 years for treatment of germ line and other forms of cancer. Oxaliplatin is approved for treatment of metastatic colorectal cancer. Thirty to forty percent of cancer patients receiving these agents develop pain and sensory loss. Oxaliplatin induces distinctive cold-associated dysesthesias in up to 80% of patients.</p> <p>Results</p> <p>We have established mouse models of cisplatin and oxaliplatin-induced neuropathy using doses similar to those used in patients. Adult male C57BL6J mice were treated with daily intraperitoneal injection for 5 days, followed by 5 days of rest, for two cycles. Total cumulative doses of 23 mg/kg cisplatin and 30 mg/kg oxaliplatin were used. Behavioral evaluations included cold plate, von Frey, radiant heat, tail immersion, grip strength and exploratory behavior at baseline and at weekly intervals for 8 weeks. Following two treatment cycles, mice in the cisplatin and oxaliplatin treatment groups demonstrated significant mechanical allodynia compared to control mice. In addition, the cisplatin group exhibited significant thermal hyperalgesia in hind paws and tail, and the oxaliplatin group developed significant cold hyperalgesia in hind paws.</p> <p>Conclusion</p> <p>We have therefore established a model of platinum drug-induced painful peripheral neuropathy that reflects the differences in early thermal pain responses that are observed in patients treated with either cisplatin or oxaliplatin. This model should be useful in studying the molecular basis for these different pain responses and in designing protective therapeutic strategies.</p