3 resultados para Gap junction
em Duke University
Resumo:
Empirical studies of education programs and systems, by nature, rely upon use of student outcomes that are measurable. Often, these come in the form of test scores. However, in light of growing evidence about the long-run importance of other student skills and behaviors, the time has come for a broader approach to evaluating education. This dissertation undertakes experimental, quasi-experimental, and descriptive analyses to examine social, behavioral, and health-related mechanisms of the educational process. My overarching research question is simply, which inside- and outside-the-classroom features of schools and educational interventions are most beneficial to students in the long term? Furthermore, how can we apply this evidence toward informing policy that could effectively reduce stark social, educational, and economic inequalities?
The first study of three assesses mechanisms by which the Fast Track project, a randomized intervention in the early 1990s for high-risk children in four communities (Durham, NC; Nashville, TN; rural PA; and Seattle, WA), reduced delinquency, arrests, and health and mental health service utilization in adolescence through young adulthood (ages 12-20). A decomposition of treatment effects indicates that about a third of Fast Track’s impact on later crime outcomes can be accounted for by improvements in social and self-regulation skills during childhood (ages 6-11), such as prosocial behavior, emotion regulation and problem solving. These skills proved less valuable for the prevention of mental and physical health problems.
The second study contributes new evidence on how non-instructional investments – such as increased spending on school social workers, guidance counselors, and health services – affect multiple aspects of student performance and well-being. Merging several administrative data sources spanning the 1996-2013 school years in North Carolina, I use an instrumental variables approach to estimate the extent to which local expenditure shifts affect students’ academic and behavioral outcomes. My findings indicate that exogenous increases in spending on non-instructional services not only reduce student absenteeism and disciplinary problems (important predictors of long-term outcomes) but also significantly raise student achievement, in similar magnitude to corresponding increases in instructional spending. Furthermore, subgroup analyses suggest that investments in student support personnel such as social workers, health services, and guidance counselors, in schools with concentrated low-income student populations could go a long way toward closing socioeconomic achievement gaps.
The third study examines individual pathways that lead to high school graduation or dropout. It employs a variety of machine learning techniques, including decision trees, random forests with bagging and boosting, and support vector machines, to predict student dropout using longitudinal administrative data from North Carolina. I consider a large set of predictor measures from grades three through eight including academic achievement, behavioral indicators, and background characteristics. My findings indicate that the most important predictors include eighth grade absences, math scores, and age-for-grade as well as early reading scores. Support vector classification (with a high cost parameter and low gamma parameter) predicts high school dropout with the highest overall validity in the testing dataset at 90.1 percent followed by decision trees with boosting and interaction terms at 89.5 percent.
Resumo:
The six-layered neuron structure in the cerebral cortex is the foundation for human mental abilities. In the developing cerebral cortex, neural stem cells undergo proliferation and differentiate into intermediate progenitors and neurons, a process known as embryonic neurogenesis. Disrupted embryonic neurogenesis is the root cause of a wide range of neurodevelopmental disorders, including microcephaly and intellectual disabilities. Multiple layers of regulatory networks have been identified and extensively studied over the past decades to understand this complex but extremely crucial process of brain development. In recent years, post-transcriptional RNA regulation through RNA binding proteins has emerged as a critical regulatory nexus in embryonic neurogenesis. The exon junction complex (EJC) is a highly conserved RNA binding complex composed of four core proteins, Magoh, Rbm8a, Eif4a3, and Casc3. The EJC plays a major role in regulating RNA splicing, nuclear export, subcellular localization, translation, and nonsense mediated RNA decay. Human genetic studies have associated individual EJC components with various developmental disorders. We showed previously that haploinsufficiency of Magoh causes microcephaly and disrupted neural stem cell differentiation in mouse. However, it is unclear if other EJC core components are also required for embryonic neurogenesis. More importantly, the molecular mechanism through which the EJC regulates embryonic neurogenesis remains largely unknown. Here, we demonstrated with genetically modified mouse models that both Rbm8a and Eif4a3 are required for proper embryonic neurogenesis and the formation of a normal brain. Using transcriptome and proteomic analysis, we showed that the EJC posttranscriptionally regulates genes involved in the p53 pathway, splicing and translation regulation, as well as ribosomal biogenesis. This is the first in vivo evidence suggesting that the etiology of EJC associated neurodevelopmental diseases can be ribosomopathies. We also showed that, different from other EJC core components, depletion of Casc3 only led to mild neurogenesis defects in the mouse model. However, our data suggested that Casc3 is required for embryo viability, development progression, and is potentially a regulator of cardiac development. Together, data presented in this thesis suggests that the EJC is crucial for embryonic neurogenesis and that the EJC and its peripheral factors may regulate development in a tissue-specific manner.
Resumo:
Terrestrial ecosystems, occupying more than 25% of the Earth's surface, can serve as
`biological valves' in regulating the anthropogenic emissions of atmospheric aerosol
particles and greenhouse gases (GHGs) as responses to their surrounding environments.
While the signicance of quantifying the exchange rates of GHGs and atmospheric
aerosol particles between the terrestrial biosphere and the atmosphere is
hardly questioned in many scientic elds, the progress in improving model predictability,
data interpretation or the combination of the two remains impeded by
the lack of precise framework elucidating their dynamic transport processes over a
wide range of spatiotemporal scales. The diculty in developing prognostic modeling
tools to quantify the source or sink strength of these atmospheric substances
can be further magnied by the fact that the climate system is also sensitive to the
feedback from terrestrial ecosystems forming the so-called `feedback cycle'. Hence,
the emergent need is to reduce uncertainties when assessing this complex and dynamic
feedback cycle that is necessary to support the decisions of mitigation and
adaptation policies associated with human activities (e.g., anthropogenic emission
controls and land use managements) under current and future climate regimes.
With the goal to improve the predictions for the biosphere-atmosphere exchange
of biologically active gases and atmospheric aerosol particles, the main focus of this
dissertation is on revising and up-scaling the biotic and abiotic transport processes
from leaf to canopy scales. The validity of previous modeling studies in determining
iv
the exchange rate of gases and particles is evaluated with detailed descriptions of their
limitations. Mechanistic-based modeling approaches along with empirical studies
across dierent scales are employed to rene the mathematical descriptions of surface
conductance responsible for gas and particle exchanges as commonly adopted by all
operational models. Specically, how variation in horizontal leaf area density within
the vegetated medium, leaf size and leaf microroughness impact the aerodynamic attributes
and thereby the ultrane particle collection eciency at the leaf/branch scale
is explored using wind tunnel experiments with interpretations by a porous media
model and a scaling analysis. A multi-layered and size-resolved second-order closure
model combined with particle
uxes and concentration measurements within and
above a forest is used to explore the particle transport processes within the canopy
sub-layer and the partitioning of particle deposition onto canopy medium and forest
oor. For gases, a modeling framework accounting for the leaf-level boundary layer
eects on the stomatal pathway for gas exchange is proposed and combined with sap
ux measurements in a wind tunnel to assess how leaf-level transpiration varies with
increasing wind speed. How exogenous environmental conditions and endogenous
soil-root-stem-leaf hydraulic and eco-physiological properties impact the above- and
below-ground water dynamics in the soil-plant system and shape plant responses
to droughts is assessed by a porous media model that accommodates the transient
water
ow within the plant vascular system and is coupled with the aforementioned
leaf-level gas exchange model and soil-root interaction model. It should be noted
that tackling all aspects of potential issues causing uncertainties in forecasting the
feedback cycle between terrestrial ecosystem and the climate is unrealistic in a single
dissertation but further research questions and opportunities based on the foundation
derived from this dissertation are also brie
y discussed.