129 research outputs found
The Problematic Business of Living Itself : David Mamet\u27s Devolving Theater
Get PDFDavid Mamet\u27s ’style is remarkably minimal; there is little in the way of stage direction and his dialogue is often a staccato vernacular. At the same time, within the apparently loose frameworks of his plays lie the seeds of their own destruction: Mamet makes up for the lack of obvious, literal stage direction with the subtle downward spiral of the plot; the coarse frankness of the language depicts worlds nearly devoid of - or at least rapidly losing - their sense of morality or whatever implicit ideas and ideals are central to maintaining the appearance of the status quo. Whether the characters are academics, businessmen, or thieves, Mamet possesses them communicate his fundamental lack of faith in all of humanity, a fate inextricably linked with what he sees as poor choices and values, a fate from which we may never recover. The overall effect of this world view is Mamet\u27s signature brand of what I have termed Devolving Theater, in which the unraveling of the circumstances within the plays themselves lead the characters perpetually downward, away from any sense of resolution or absolution. To this end, the purpose of this thesis is to explore in-depth the devolution in the plays of David Mamet, focusing specifically on three of his plays: A Life in the Theatre (1977), Oleanna (1992), and Romance (2005). I will be focusing on character relationships and the use of language, as these are the areas in which the devolution is manifested
Chronic Stress Prevents Cortico-Accumbens Cue Encoding and Alters Conditioned Approach
Get PDFChronic stress impairs the function of multiple brain regions and causes severe hedonic and motivational deficits. One brain region known to be susceptible to these effects is the PFC. Neurons in this region, specifically neuronal projections from the prelimbic region (PL) to the nucleus accumbens core (NAcC), have a significant role in promoting motivated approach. However, little is known about how activity in this pathway changes during associative learning to encode cues that promote approach. Less is known about how activity in this pathway may be altered by stress. In this study, an intersectional fiber photometry approach was used in male Sprague Dawley rats engaged in a Pavlovian autoshaping design to characterize the involvement of the PL-NAcC pathway in the typical acquisition of learned approach (directed at both the predictive cue and the goal), and its potential alteration by stress. Specifically, the hypothesis that neural activity in PL-NAcC would encode a Pavlovian approach cue and that prior exposure to chronic stress would disrupt both the nature of conditioned approach and the encoding of a cue that promotes approach was tested. Results of the study demonstrated that the rapid acquisition of conditioned approach was associated with cue-induced PL-NAcC activity. Prior stress both reduced cue-directed behavior and impaired the associated cortical activity. These findings demonstrate that prior stress diminishes the task-related activity of a brain pathway that regulates approach behavior. In addition, the results support the interpretation that stress disrupts reward processing by altering the incentive value of associated cues
Chikungunya Outbreak Risks after the 2014 Outbreak, Dominican Republic.
Get PDFThe 2014 chikungunya outbreak in the Dominican Republic resulted in intense local transmission, with high postoutbreak seroprevalence. The resulting population immunity will likely minimize risk for another large outbreak through 2035, but changes in population behavior or environmental conditions or emergence of different virus strains could lead to increased transmission
Current and emerging developments in subseasonal to decadal prediction
Get PDFWeather and climate variations of subseasonal to decadal timescales can have enormous social, economic and environmental impacts, making skillful predictions on these timescales a valuable tool for decision makers. As such, there is a growing interest in the scientific, operational and applications communities in developing forecasts to improve our foreknowledge of extreme events. On subseasonal to seasonal (S2S) timescales, these include high-impact meteorological events such as tropical cyclones, extratropical storms, floods, droughts, and heat and cold waves. On seasonal to decadal (S2D) timescales, while the focus remains broadly similar (e.g., on precipitation, surface and upper ocean temperatures and their effects on the probabilities of high-impact meteorological events), understanding the roles of internal and externally-forced variability such as anthropogenic warming in forecasts also becomes important.
The S2S and S2D communities share common scientific and technical challenges. These include forecast initialization and ensemble generation; initialization shock and drift; understanding the onset of model systematic errors; bias correct, calibration and forecast quality assessment; model resolution; atmosphere-ocean coupling; sources and expectations for predictability; and linking research, operational forecasting, and end user needs. In September 2018 a coordinated pair of international conferences, framed by the above challenges, was organized jointly by the World Climate Research Programme (WCRP) and the World Weather Research Prograame (WWRP). These conferences surveyed the state of S2S and S2D prediction, ongoing research, and future needs, providing an ideal basis for synthesizing current and emerging developments in these areas that promise to enhance future operational services. This article provides such a synthesis
The Somatic Genomic Landscape of Glioblastoma
Get PDFWe describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer
climpred: weather and climate forecast verification in python
No full text&lt;p&gt;Predicting subseasonal to seasonal weather and climate yields numerous benefits for economic and environmental decision-making.&lt;br&gt;Forecasters verify the forecast quality of models by initializing large sets of retrospective forecasts to predict past variations and phenomena in hindcast studies.&lt;/p&gt;&lt;p&gt;Quantifying prediction skill for multi-dimensional geospatial model output is computationally expensive and a difficult coding challenge. The large datasets require parallel and out-of-memory computing to be analyzed efficiently. Further, aligning the many forecast initializations with differing observational products is a straight-forward, but exhausting and error-prone exercise for researchers.&lt;/p&gt;&lt;p&gt;To simplify and standardize forecast verification across scales from hourly weather to decadal climate forecasts, we built &lt;em&gt;climpred&lt;/em&gt;: a python package for computationally efficient and methodologically consistent verification of ensemble prediction models. We rely on the &lt;em&gt;python&lt;/em&gt; software ecosystem developed by the open &lt;em&gt;pangeo&lt;/em&gt; geoscience community. We leverage &lt;em&gt;NetCDF&lt;/em&gt; metadata using &lt;em&gt;xarray&lt;/em&gt; and out-of-core computation parallelized with &lt;em&gt;dask&lt;/em&gt; to scale analyses from a laptop to supercomputer.&lt;/p&gt;&lt;p&gt;With &lt;em&gt;climpred&lt;/em&gt;, researchers can assess forecast quality from a large set of metrics (including &lt;em&gt;cprs&lt;/em&gt;, &lt;em&gt;rps&lt;/em&gt;, &lt;em&gt;rank_histogram&lt;/em&gt;, &lt;em&gt;reliability&lt;/em&gt;, &lt;em&gt;contingency&lt;/em&gt;, &lt;em&gt;bias&lt;/em&gt;, &lt;em&gt;rmse&lt;/em&gt;, &lt;em&gt;acc&lt;/em&gt;, ...) in just a few lines of code:&lt;/p&gt;&lt;p&gt;hind = xr.open_dataset('initialized.nc')&lt;br&gt;obs = xr.open_dataset('observations.nc')&lt;br&gt;he = climpred.HindcastEnsemble(hind).add_observations(obs)&lt;br&gt;# he = he.remove_bias(how='basic_quantile',&lt;br&gt;# &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; train_test_split='unfair',&amp;#160;&lt;br&gt;# &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; alignment='same_verif')&lt;br&gt;he.verify(metric='rmse',&lt;br&gt;&amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; comparison='e2o',&lt;br&gt;&amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; alignment='same_verif',&lt;br&gt;&amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; dim='init',&lt;br&gt;&amp;#160; &amp;#160; &amp;#160; &amp;#160; &amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160;&amp;#160; reference=['persistence', 'climatology'])&lt;br&gt;&lt;br&gt;This simplified and standardized process frees up resources to tackle the large process-based unknowns in predictability research. Here, we perform a live and interactive multi-model comparison removing bias with different methodologies from NMME project hindcasts and compare against persistence and climatology reference forecasts.&lt;/p&gt;&lt;p&gt;&lt;img src=&quot;https://contentmanager.copernicus.org/fileStorageProxy.php?f=gnp.55bc62bebed162677891461/sdaolpUECMynit/22UGE&amp;app=m&amp;a=0&amp;c=f1bcc77dd44d983258ee3946a8c5b41e&amp;ct=x&amp;pn=gnp.elif&amp;d=1&quot; alt=&quot;&quot; width=&quot;487&quot; height=&quot;113&quot;&gt;&lt;/p&gt;&lt;p&gt;Documentation: https://climpred.readthedocs.io&lt;/p&gt;&lt;p&gt;Repository: https://github.com/pangeo-data/climpred&lt;/p&gt;&lt;p&gt;Reference paper: Brady, Riley X. and Aaron Spring (Mar. 2021). &amp;#8220;Climpred: Verification of Weather and Climate Forecasts&amp;#8221;. en. Journal of Open Source Software 6.59, p. 2781. https://joss.theoj.org/papers/10.21105/joss.02781&lt;/p&gt;</jats:p
Establishing a Framework to Transition High Frequency Oscillations to Routine Clinical Care in Patients with Focal Epilepsy
No full textHigh frequency oscillations (HFOs), characteristic oscillations observable using electroencephalography (EEG), are a promising and specific marker of the epileptogenic zone (EZ). However, there remain several obstacles to the implementation of HFOs as a prospective tool in the treatment of epilepsy. The identification of HFOs lacks universal standards and demands large time commitments from epileptologists. Therefore, this work involved the implementation and validation of novel frameworks for identifying HFOs, and for evaluating these HFOs as markers of the EZ.
An epoched framework was implemented to facilitate the visual identification of HFOs, through which poor reliability was observed between reviewers. Furthermore, it was found that the temporal efficiency of visually evaluating HFOs within the epoched framework marked a substantial improvement over previously reported evaluation times. Using generalizability theory, it was then extended to determine effective methods of achieving highly reliable visual HFO evaluations, which included averaging ratings from at least 12 visual reviewers, or employing a training paradigm to increase the correlation of the ratings across reviewers. A novel surrogate marker (uGIC) of HFO activity was implemented and found to be correlated with HFOs detected algorithmically at low or high thresholds, all of which were found to be markers of the seizure onset zone overall.
A retrospective framework was implemented to improve the accuracy of delineating the margins of resection with respect to EEG electrodes. A deformable method of image co-registration and a hybrid method of estimating electrode shift were shown to more effectively compensate for post-surgical shifts in brain anatomy. Resecting the uGIC or detected HFOs were found to have a positive effect on seizure freedom. Notably, the inclusion of lower-threshold oscillations was beneficial in facilitating the visual evaluation of HFOs, and in the identification of the EZ.
Together, the findings of the studies undertaken herein provide a comprehensive framework to serve as the basis for transitioning high frequency oscillations to a feasible and meaningful part of the routine pre-surgical work-up in patients with focal epilepsy
- …
