The synthesis and biochemical and pharmacological evaluation of gamma-aminobutyric acid antagonists

Y-Aminobutyrio acid has been shown to be a major inhibitory neurotransmitter in the central nervous system (CNS). This study is concemed with the examination of a number of GABA antagonists in two in vitro assay systems. A series of cage-structured compounds including bicyolic phosphate esters (2,6,7,-Trioxa-l-phosphabicyclo (2,2,2,) octan-l-oxides with suitable 4-substituents) have been shown to be potent a GABA antagonists. These compounds do not act directly on the postsysnaptio GABA receptor site but probably at the same site as another potent GABA antagonist piorotoxinin. It has been shown that the substituent group on the bridge-head on the 4-carbon atom in the molecule plays a very important role in the toxic potency and GABA antagonistic properties of these compounds. A very bulky and branched substituent caused a great increase in potency. This property was utilised in the synthesis of a series of these compounds. The binding of radiolabelled ligands (both agonists and antagonists) to synaptic membrane fractions can be utilised as a convenient assay for the study of GABA receptors. Such assays using frozen--thawed rat brain synaptosomal membranes has been demonstrated to be stereospecific and saturable using (3H)-GABA, the potent GABA agonist (3H)-muscimol also with GABA antagonists using (3H)-bicuculline methobromide and (3H)-dihydropicrotoxinin. Utilising these methods a number of agonists and antagonists have been examined to evaluate their ability to displace the stereospecific binding. The synthesised GABA antagonists have also been used to evaluate their properties on the depolarising effect of on the rat superior cervical ganglion in comparison to results obtained by known GABA, antagonists. The bicyclic phosphate esters were shown to be very toxic when administered to mammals causing seizures and death, this effect being attributed to the antagonism of GABA in the CNS. They were shown to be potent inhibitors of GABA in the superior cervical ganglion. In binding studios with (3H)-muscimol they did not displace any of the bound agonist and also were shown not to displace bound (3H)-dihydropicrotoxinin. The results obtained in this study have been discussed and compared with structure-activity relationships to other compounds of similar structure

Reaching for the Cap and Gown: Progress Toward Success Boston's College Completion Goals for Graduates of the Boston Public Schools

A new report, prepared for Mayor Martin J. Walsh and the Success Boston college completion initiative, shows a remarkable increase in both the percentage and the number of Boston Public Schools graduates who complete college within six years. The report also examines college completion for students with Success Boston coaches, a major intervention launched by the Boston Foundation and its partners, including the Boston Public Schools, in 2009. Success Boston, a citywide multi-sector college completion initiative, was launched in 2008 in response to a report that found that only 35% of the BPS Class of 2000 graduates who enrolled in college earned a degree within seven years of graduating high school. The initiative is guided by the Boston Public Schools, the Boston Foundation, UMass Boston, Bunker Hill Community College, and the Boston Private Industry Council, along with dozens of colleges, universities, and nonprofit organizations. Among the initiative's ambitious goals was pushing members of the BPS Class of 2009 to a 52%six-year college completion rate. Today's report, "Reaching for the Cap and Gown: Progress Toward Success Boston's College Completion Goals for Graduates of the Boston Public Schools," finds that the six-year college completion rate of first-year college enrollees from the BPS Class of 2009 was 51.3%--within one percentage point of the 52% goal set in 2008. Equally impressive is the gain in the number of BPS graduates completing college within six years of high school graduation--1,314 from the Class of 2009, compared to 735 from the Class of 2000, the equivalent of a 79% increase. The study also finds that college completion, at 54.7%, is even higher than the goal for students who enrolled in the fall immediately after graduating from high school

Dynamics of probability density functions for decaying passive scalars in periodic velocity fields

The probability density function (PDF) for a decaying passive scalar advected by a deterministic, periodic, incompressible fluid flow is numerically studied using a variety of random and coherent initial scalar fields. We establish the dynamic emergence at large Péclet num-bers of a broad-tailed PDF for the scalar initialized with a Gaussian random measure, and further explore a rich parameter space involv-ing scales of the initial scalar field and the geometry of the flow. We document that the dynamic transition of the PDF to a broad tailed distribution is similar for shear flows and time-varying non-sheared flows with positive Lyapunov exponent, thereby showing that chaos in the particle trajectories is not essential to observe intermittent scalar signals. The role of the initial scalar field is carefully explored. The long time PDF is sensitive to the scale of the initial data. For shear flows we show that heavy-tailed PDFs appear only when the initial field has sufficiently small-scale variation. We also connect geometric features of the scalar field with the shape of the PDFs. We docu-ment that the PDF is constructed by a subtle balance between spatial regions of strong and weak shear in conjunction with the presence of 1 To appear: Physics of Fluids small-scale scalar variation within the weak shear regions. For cellular flows we document a lack of self-similarity in the PDFs when periodic time dependence is present, in contrast to the self-similar decay for time independent flow. Finally we analyze the behavior of the PDFs for coherent initial fields and the parametric dependence of the vari-ance decay rate on the Péclet number and the initial wavenumber of the scalar field. 2

TANF/Welfare Client Decline and Community Context in the Rural South, 1997-2000

This article examines the extent to which declines in welfare rolls relate to five major dimensions of community: (1) local demographic composition, (2) local labor market conditions, (3) local civic capacity, (4) local spatial characteristics, and (5) changes in local economic opportunities. Results based on data from the Mississippi Department of Human Services indicate that demographically, economically, and socially advantaged communities were more likely to experience high declines in welfare rolls. Rurality was associated with lower likelihood of high declines in welfare rolls across Mississippi counties. Clearly, a combination of a stronger local economy and social support in a local area increases the likelihood of larger decline in welfare rolls. The analysis presented in this article suggests that there is substantial local variation in the decline in welfare rolls that is associated with local economic and social conditions. The success of welfare reform policies clearly hinge on local conditions. What this analysis cannot reveal is the extent to which decline in welfare rolls is the result of recipients marrying, finding good jobs, or simply running up against time limits imposed by the welfare reform legislation

Getting to the Finish Line: College Enrollment and Graduation

Presents data from a longitudinal study of the Boston public school system's class of 2000 -- how many had enrolled in college, had graduated, and remained enrolled as of 2007, by gender, race/ethnicity, and types of college and high school attended

Dynamics of probability density functions for decaying passive scalars in periodic velocity fields

The probability density function (PDF) for a decaying passive scalar advected by a deterministic, periodic, incompressible fluid flow is numerically studied using a variety of random and coherent initial scalar fields. We establish the dynamic emergence at large Péclet numbers of a broad-tailed PDF for the scalar initialized with a Gaussian random measure, and further explore a rich parameter space involving scales of the initial scalar field and the geometry of the flow. We document that the dynamic transition of the PDF to a broad-tailed distribution is similar for shear flows and time-varying nonsheared flows with positive Lyapunov exponent, thereby showing that chaos in the particle trajectories is not essential to observe intermittent scalar signals. The role of the initial scalar field is carefully explored. The long-time PDF is sensitive to the scale of the initial data. For shear flows we show that heavy-tailed PDFs appear only when the initial field has sufficiently small-scale variation. We also connect geometric features of the scalar field with the shape of the PDFs. We document that the PDF is constructed by a subtle balance between spatial regions of strong and weak shear in conjunction with the presence of small-scale scalar variation within the weak shear regions. For cellular flows we document a lack of self-similarity in the PDFs when periodic time dependence is present, in contrast to the self-similar decay for time independent flow. Finally, we analyze the behavior of the PDFs for coherent initial fields and the parametric dependence of the variance decay rate on the Péclet number and the initial wavenumber of the scalar field

Interactive influences of ozone and climate on streamflow of forested watersheds

The capacity of forests to mitigate global climate change can be negatively influenced by tropospheric ozone that impairs both photosynthesis and stomatal control of plant transpiration, thus affecting ecosystem productivity and watershed hydrology. We have evaluated individual and interactive effects of ozone and climate on late season streamflow for six forested watersheds (38–970 000 ha) located in the Southeastern United States. Models were based on 18–26 year data records for each watershed and involved multivariate analysis of interannual variability of late season streamflow in response to physical and chemical climate during the growing season. In all cases, some combination of ozone variables significantly improved model performance over climate-only models. Effects of ozone and ozone × climate interactions were also consistently negative and were proportional to variations in actual ozone exposures, both spatially across the region and over time. Conservative estimates of the influence of ozone on the variability (R2) of observed flow ranged from 7% in the area of lowest ozone exposure in West Virginia to 23%in the areas of highest exposure in Tennessee. Our results are supported by a controlled field study using free-air concentration enrichment methodology which indicated progressive ozone-induced loss of stomatal control over tree transpiration during the summer in mixed aspen-birch stands. Despite the frequent assumption that ozone reduces tree water loss, our findings support increasing evidence that ozone at near ambient concentrations can reduce stomatal control of leaf transpiration, and increase water use. Increases in evapotranspiration and associated streamflow reductions in response to ambient ozone exposures are expected to episodically increase the frequency and severity of drought and affect flow-dependent aquatic biota in forested watersheds. Regional and global models of hydrologic cycles and related ecosystem functions should consider potential interactions of ozone with climate under both current and future warmer and ozone-enriched climatic conditions